start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=5 article-no= start-page=2308 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. en-copyright= kn-copyright= en-aut-name=MatsudaYoshihiro en-aut-sei=Matsuda en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakezakiDaiki en-aut-sei=Takezaki en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoYuma en-aut-sei=Sakamoto en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BabaNobuyasu en-aut-sei=Baba en-aut-mei=Nobuyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IsekiMasanori en-aut-sei=Iseki en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShiomiTatsushi en-aut-sei=Shiomi en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Kawasaki Medical School kn-affil= affil-num=9 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= en-keyword=psoriasis kn-keyword=psoriasis en-keyword=obesity kn-keyword=obesity en-keyword=aerobic exercise kn-keyword=aerobic exercise en-keyword=imiquimod kn-keyword=imiquimod en-keyword=high-fat diet kn-keyword=high-fat diet END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=dmm052605 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Congenital intestinal atresia (IA) is a birth defect characterised by the absence or closure of part of the intestine. Although genetic factors are implicated, mechanistic understanding has been hindered by the lack of suitable animal models. Here, we describe a medaka (Oryzias latipes) mutant, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, that develops IA during embryogenesis. Positional cloning identified a nonsense mutation in mypt1, encoding myosin phosphatase target subunit 1. Mutant embryos exhibited ectopic accumulation of F-actin and phosphorylated myosin regulatory light chain (Mrlc) in the intestinal epithelium, consistent with disrupted actomyosin regulation. These cytoskeletal abnormalities were accompanied by epithelial disorganisation, without notable alterations in cell proliferation, motility or apoptosis. Inhibition of myh11a, encoding smooth muscle (SM) myosin heavy chain, ameliorated the IA phenotype, whereas blebbistatin treatment completely rescued the defect, suggesting a non-contractile role prior to SM maturation. Together, these findings demonstrate that mypt1 loss disrupts intestinal morphogenesis through actomyosin dysregulation. Given the recent clinical identification of IA associated with MYPT1 variants, this medaka model offers a valuable platform to investigate the developmental and molecular basis of MYPT1-associated IA in humans. en-copyright= kn-copyright= en-aut-name=KobayashiDaisuke en-aut-sei=Kobayashi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UrasakiAkihiro en-aut-sei=Urasaki en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraTetsuaki en-aut-sei=Kimura en-aut-mei=Tetsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuoKazuhiko en-aut-sei=Matsuo en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YokoiHayato en-aut-sei=Yokoi en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakashimaShigeo en-aut-sei=Takashima en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitagawaTadao en-aut-sei=Kitagawa en-aut-mei=Tadao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KageTakahiro en-aut-sei=Kage en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaritaTakanori en-aut-sei=Narita en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=JindoTomoko en-aut-sei=Jindo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KinoshitaMasato en-aut-sei=Kinoshita en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NaruseKiyoshi en-aut-sei=Naruse en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakajimaYoshiro en-aut-sei=Nakajima en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShigetaMasaki en-aut-sei=Shigeta en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakakiShinichiro en-aut-sei=Sakaki en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueSatoshi en-aut-sei=Inoue en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SabaRie en-aut-sei=Saba en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamadaKei en-aut-sei=Yamada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YokoyamaTakahiko en-aut-sei=Yokoyama en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshikawaYuji en-aut-sei=Ishikawa en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ArakiKazuo en-aut-sei=Araki en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SagaYumiko en-aut-sei=Saga en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TakedaHiroyuki en-aut-sei=Takeda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YashiroKenta en-aut-sei=Yashiro en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=2 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=3 en-affil=Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology kn-affil= affil-num=4 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=5 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=6 en-affil=Graduate School of Agricultural Science, Tohoku University kn-affil= affil-num=7 en-affil=Institute for Glyco-core Research (iGCORE)/Life Science Research Centre, Gifu University kn-affil= affil-num=8 en-affil=Program in Environmental Management, Graduate School of Agriculture, Kindai University kn-affil= affil-num=9 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=10 en-affil=Laboratory of Molecular Biology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University kn-affil= affil-num=11 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=13 en-affil=Laboratory of Bioresources, National Institute for Basic Biology kn-affil= affil-num=14 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=15 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=16 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=17 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=18 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=19 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=20 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=21 en-affil=Research Centre for Radiation Protection, National Institute of Radiological Sciences kn-affil= affil-num=22 en-affil=Research Center for Aquatic Breeding, National Research Institute of Aquaculture, Fisheries Research Agency kn-affil= affil-num=23 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=24 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=25 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= en-keyword=Intestinal atresia kn-keyword=Intestinal atresia en-keyword=Mypt1 kn-keyword=Mypt1 en-keyword=Disease model kn-keyword=Disease model en-keyword=Actomyosin regulation kn-keyword=Actomyosin regulation en-keyword=Intestinal development kn-keyword=Intestinal development END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=3 article-no= start-page=329 end-page=336 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevalence and Modifiable Risk Factors of Dementia in People With Down Syndrome: Cross‐Sectional Study of Japan in Collaboration With the Intellectual Diversity for Goodness Research Consortium (INDIGO‐2019) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: People with Down syndrome (DS) have a strong genetic predisposition to Alzheimer's disease (AD). However, the clinical burden and associated risk factors in diverse, non-Western populations remain less understood. This study aimed to investigate the prevalence of dementia in Japanese adults with DS and to identify modifiable clinical factors associated with dementia.
Methods: This cross-sectional multicentre study surveyed 133 adults with DS (mean age 50.1?years) residing in 45 welfare facilities across Japan in 2019. Dementia was diagnosed by a consensus panel of physicians using established criteria (DSM-5, ICD-10, DC-LD) after comprehensive assessments, including the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-J). Logistic regression analysis was performed to identify factors independently associated with dementia.
Results: Forty-six participants (34.6%) were diagnosed with dementia. The prevalence rose sharply with age: 0% in their 30s, 30.8% in their 40s, 31.6% in their 50s and 65.5% in their 60s. After adjusting for covariates, older age, female sex, dyslipidaemia and visual impairment were independently associated with dementia.
Conclusions: This study, the largest of its kind in Asia, confirms a high prevalence of dementia in institutionalized Japanese adults with DS. Crucially, this study is the first to identify dyslipidaemia and visual impairment as independent and potentially modifiable risk factors in this population. These findings highlight tangible targets for clinical interventions aimed at mitigating dementia risk in people with DS. en-copyright= kn-copyright= en-aut-name=TakenoshitaShintaro en-aut-sei=Takenoshita en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueTomokazu en-aut-sei=Inoue en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurozumiTaku en-aut-sei=Kurozumi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuwanoRyozo en-aut-sei=Kuwano en-aut-mei=Ryozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuemitsuShigeru en-aut-sei=Suemitsu en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso kn-affil= affil-num=4 en-affil=Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso kn-affil= affil-num=7 en-affil=Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family Alterations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH-wt), is a highly aggressive brain tumor with a poor prognosis. Alterations in the fibroblast growth factor receptor (FGFR) gene family?such as FGFR::TACC fusions and FGFR1 mutations?have emerged as potential therapeutic targets; however, their clinical and genetic features in GBM, IDH-wt remain unclear. We analyzed 1076 GBM, IDH-wt cases using comprehensive genomic profiling data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. FGFR alterations were detected in 8.0% of patients, including FGFR::TACC fusions (3.3%) and FGFR1 mutations (2.9%). The FGFR::TACC fusion-positive group was older at diagnosis and showed higher frequencies of TERT promoter mutation and MDM2 amplification, and lower frequencies of EGFR amplification and TP53 mutation, compared with the fusion-negative group. The FGFR1 mutation-positive group was enriched for ATRX, NF1, and PIK3CA mutations and had significantly fewer TERT promoter and PTEN mutations, compared with the mutation-negative group. No significant differences in overall survival were observed, although both groups tended to have longer median overall survival compared with their respective negative groups. This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies. en-copyright= kn-copyright= en-aut-name=KegoyaYasuhito en-aut-sei=Kegoya en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkemachiRyosuke en-aut-sei=Ikemachi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiuraMako en-aut-sei=Kamiura en-aut-mei=Mako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=copy number alteration kn-keyword=copy number alteration en-keyword=FGFR kn-keyword=FGFR en-keyword=glioblastoma kn-keyword=glioblastoma en-keyword=single-nucleotide variant kn-keyword=single-nucleotide variant END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=1 article-no= start-page=98 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic and phenotypic identities of Staphylococcus coagulans isolated from pustules of dogs with superficial bacterial folliculitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Staphylococcus coagulans, formerly called Staphylococcus schleiferi subsp. coagulans is the second most common isolate from skin lesions of dogs with superficial bacterial folliculitis (SBF). However, the clinical significance of S. coagulans in pustules of canine SBF remains uncertain. This study aimed to investigate the prevalence and genotypic and phenotypic diversity of S. coagulans isolated from pustules in two dogs with SBF.
Results Two dogs with SBF were included in this study. S. schleiferi/coagulans was isolated as the sole organism from three pustules in case #1, whereas it coexisted with S. pseudintermedius in two of seven pustules in case #2. S. pseudintermedius was the sole organism in the remaining five pustules in case #2. Whole genome sequences revealed that all isolates tested were annotated as S. coagulans. The isolates from the same pustules exhibited identical genotypic and phenotypic profiles, indicating clonal multiplication. S. coagulans isolated from different pustules exhibited similar yet distinct genotypic and phenotypic profiles.
Conclusions S. coagulans with identical genetic and phenotypic profiles can be identified as the sole pathogen or coexist with S. pseudintermedius in the pustules of the same dogs with SBF. en-copyright= kn-copyright= en-aut-name=OsumiTakafumi en-aut-sei=Osumi en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShinomiyaYuuki en-aut-sei=Shinomiya en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WanganuttaraThamonwan en-aut-sei=Wanganuttara en-aut-mei=Thamonwan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImanishiIchiro en-aut-sei=Imanishi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimazakiYotaro en-aut-sei=Shimazaki en-aut-mei=Yotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IyoriKeita en-aut-sei=Iyori en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyodaYoichi en-aut-sei=Toyoda en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IdeKaori en-aut-sei=Ide en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishifujiKoji en-aut-sei=Nishifuji en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=2 en-affil=Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=3 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=5 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=6 en-affil=1sec Co. Ltd. kn-affil= affil-num=7 en-affil=1sec Co. Ltd. kn-affil= affil-num=8 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=9 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= en-keyword=Staphylococcus coagulans kn-keyword=Staphylococcus coagulans en-keyword=Staphylococcus pseudintermedius kn-keyword=Staphylococcus pseudintermedius en-keyword=Dog kn-keyword=Dog en-keyword=Superficial bacterial folliculitis kn-keyword=Superficial bacterial folliculitis en-keyword=Antimicrobial susceptibility kn-keyword=Antimicrobial susceptibility en-keyword=Disk diffusion test kn-keyword=Disk diffusion test END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=02 article-no= start-page=113 end-page=125 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Clinical genetics in comitant strabismus and idiopathic superior oblique muscle palsy kn-title=斜視の遺伝子研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=共同性斜視は遺伝要因と環境要因からなる多因子疾患で、内斜視と外斜視に大別される。遺伝要因は家族歴、一卵性双生児の表現型一致率から推定され、環境要因には妊娠・分娩時の低酸素状態がある。一方、遺伝要因がある非共同性（麻痺性）斜視として上斜筋腱低形成を呈する特発性上斜筋麻痺がある。遺伝統計学の連鎖解析を使って、内斜視と外斜視の小家系群で4番染色体MGST2を疾患感受性遺伝子候補と同定し、MGST2ノックアウトマウスを作成した。小動物用MRIで解析すると、そのホモ接合体では野生型と比べて眼球形状が有意に横長で体積が大きいことを見出した。次いで遺伝統計学別法の全ゲノム関連解析を内斜視、外斜視、特発性上斜筋麻痺を対象として行った。Infinium Asian Screening Array-24 v1.0でSNPを決めた内斜視253検体、外斜視356検体、上斜筋麻痺102検体を疾患群とした。対照集団としては、バイオバンクジャパン (BBJ) の疾患群とは違うアレイ(OmniExpress)でSNPを決めた182,476検体「BBJ (180K)」、疾患群と同じアレイでSNPを決めたBBJの53409検体「BBJ (ASA)」および長浜コホート3570検体を使った。３対照集団との比較で共通して検出された遺伝子は、上斜筋麻痺群で神経細胞移動に関与するDAB1であった。最も大きい対照集団「BBJ (180K)」との比較では内斜視、外斜視、上斜筋麻痺を含む疾患群全体で眼発生に関与するRARB (retinoic acid receptor β) が検出された。斜視関連遺伝子は眼球形態に関与する可能性がある。特発性上斜筋麻痺は共同性斜視とは独立した疾患と理解されるが、共通の遺伝基盤もあるかもしれない。 en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name=松尾俊彦 kn-aut-sei=松尾 kn-aut-mei=俊彦 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 en-keyword=双生児調査 kn-keyword=双生児調査 en-keyword=斜視頻度 kn-keyword=斜視頻度 en-keyword=家族歴 kn-keyword=家族歴 en-keyword=全ゲノム関連解析 kn-keyword=全ゲノム関連解析 en-keyword=連鎖解析 kn-keyword=連鎖解析 END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=12 article-no= start-page=102845 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Whole-genome sequencing and in vitro characterization of a disseminated ST398 Staphylococcus aureus infection: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Staphylococcus aureus potentially causes systemic infections such as disseminated abscesses and bloodstream infections, leading to high mortality rates. We herein describe a case of disseminated muscle abscesses caused by sequence type (ST) 398 methicillin-sensitive S. aureus (MSSA), along with in vitro investigation results for potential pathogenic factors. A 67-year-old healthy woman was admitted to our hospital with complaints of systemic body pain. Blood cultures identified MSSA and contrast-enhanced computed tomography revealed multiple muscle abscesses extending from her neck to her soles. She received antibiotic treatment with intravenous cephazolin and underwent repeated surgical drainage, and was finally discharged. Notably, the MSSA strain exclusively affected her muscle tissues, prompting us to perform genetic analysis to uncover the underlying reason. Short-read genome analysis revealed the isolate to be ST398, harboring chp and scn genes known for immune evasion from human immunity. However, no other known pathogenic factors were identified despite rigorous assays for biofilm formation, surface and cell wall proteins, protease production, and hyaluronidase activity. ST398 S. aureus is commonly isolated from livestock, and her prior experience of being flooded could be related to the disease onset. The present case underscores the possibility of severe ST398 MSSA infections in humans, even in the absence of direct animal exposure. en-copyright= kn-copyright= en-aut-name=SazumiYosuke en-aut-sei=Sazumi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatoAtsushi en-aut-sei=Kato en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KutsunoShoko en-aut-sei=Kutsuno en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HisatsuneJunzo en-aut-sei=Hisatsune en-aut-mei=Junzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugaiMotoyuki en-aut-sei=Sugai en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=9 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=10 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=11 en-affil=Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Staphylococcus aureus kn-keyword=Staphylococcus aureus en-keyword=Sequence type 398 kn-keyword=Sequence type 398 en-keyword=Disseminated infection kn-keyword=Disseminated infection en-keyword=Immune evasion cluster gene kn-keyword=Immune evasion cluster gene END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=12 article-no= start-page=102853 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and molecular characteristics of urinary catheter-associated Pseudomonas aeruginosa prostatic infection: A case series of four postoperative nosocomial infections en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudomonas aeruginosa is a causative pathogen of nosocomial catheter-associated urinary tract infections (CAUTI), but prostate involvement, including prostatitis and prostatic abscess, is rare. The clinical characteristics of P. aeruginosa-associated CAUTI with prostatic lesions, as well as the contribution of genetic backgrounds remain unclear. We describe four cases of urinary catheter-associated prostatic infection caused by P. aeruginosa following postoperative catheterization. All patients developed fever within 10 days after surgery, and three of the four patients developed bacteremia. Three patients were diagnosed with prostatic abscess by contrast-enhanced computed tomography or magnetic resonance imaging, while one case presented with prostatitis without abscess formation. Prostate-specific antigen levels were elevated over 20 ng/mL in all three measured cases. All patients were treated successfully with prolonged antibiotic therapy (28?39 days) without surgical drainage. Notably, all three abscess cases were successfully managed with fluoroquinolone-based combination therapy, highlighting its potential role in the management of prostatic abscesses. Three of four isolates were submitted for molecular investigations. All isolates harbored exoT and exoY, whereas exoU was absent. Biofilm-associated genes were detected in two cases, but not in the remaining case. Our findings suggested that P. aeruginosa strains carrying T3SS genes (exoT and exoY) potentially develop prostatic infections, independent of biofilm-associated genes. Host and iatrogenic factors, such as catheter manipulation, may play more critical roles in the development of prostatic pathology than strain-specific determinants. Assessment of prostate-specific antigen levels and early imaging may facilitate appropriate diagnosis and effective management when P. aeruginosa is detected as a cause of CAUTI. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SanoTakayuki en-aut-sei=Sano en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashimotoTakashige en-aut-sei=Kashimoto en-aut-mei=Takashige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University kn-affil= affil-num=3 en-affil=Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Pseudomonas aeruginosa kn-keyword=Pseudomonas aeruginosa en-keyword=Catheter-associated urinary tract infection kn-keyword=Catheter-associated urinary tract infection en-keyword=Prostatic abscess kn-keyword=Prostatic abscess en-keyword=Type III secretion system kn-keyword=Type III secretion system END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genotype?Phenotype Correlations of Li?Fraumeni Syndrome in Japan Children's Cancer Group LFS20 Study Cohort en-subtitle= kn-subtitle= en-abstract= kn-abstract=Li?Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline pathogenic variants in the TP53 gene. With the increasing use of multi-gene panel testing, TP53 variants have been identified in individuals who do not meet established TP53 testing criteria, such as the Chompret criteria. The term “attenuated LFS” has been proposed for some of these cases, particularly those with adult-onset cancer. We analyzed participants of the Japanese nationwide prospective clinical trial of the cancer surveillance program (Japan Children's Cancer Group LFS-20), along with clinical information including their family histories, to better understand their genotypic and phenotypic characteristics. We identified 32 distinct TP53 variants from 41 families (45 participants), including four missense variants with conflicting classifications of pathogenicity in ClinVar. Among these families, 36 (88%) met the LFS criteria (hereafter referred to as “LFS” in contrast to attenuated LFS), while 5 (12%) were classified as attenuated LFS. Including 30 additional family members carrying the same variant, we analyzed 75 individuals with TP53 variants. Of these, 40 with LFS and 6 with attenuated LFS had cancer. Multiple primary cancers occurred in 22 individuals (21 LFS, 1 attenuated LFS). LFS-core tumors accounted for 66% (58/88) of cancers in the LFS group and 63% (5/8) in the attenuated LFS group; of note, all core tumors in the attenuated group were limited to breast cancer. Hotspot missense variants were detected in 11 of 36 LFS families and in none of 5 attenuated LFS families, and non-hotspot null variants were found in 14 and 1, respectively. Our study revealed genotype?phenotype correlations in several respects. UMIN-CTR: UMIN000045855. en-copyright= kn-copyright= en-aut-name=YamazakiFumito en-aut-sei=Yamazaki en-aut-mei=Fumito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakanoYoshiko en-aut-sei=Nakano en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SanadaMasashi en-aut-sei=Sanada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurahashiHiroki en-aut-sei=Kurahashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyaiShunsuke en-aut-sei=Miyai en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UekiArisa en-aut-sei=Ueki en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeYuko en-aut-sei=Watanabe en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaDaisuke en-aut-sei=Hasegawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KarakawaShuhei en-aut-sei=Karakawa en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SaitoAkiko M. en-aut-sei=Saito en-aut-mei=Akiko M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=InoueEisuke en-aut-sei=Inoue en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoMotohiro en-aut-sei=Kato en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HattoriHiroyoshi en-aut-sei=Hattori en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pediatrics, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=3 en-affil=Department of Advanced Diagnosis, Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=4 en-affil=Division of Molecular Genetics, Center for Medical Science, Fujita Health University kn-affil= affil-num=5 en-affil=Division of Molecular Genetics, Center for Medical Science, Fujita Health University kn-affil= affil-num=6 en-affil=Department of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=7 en-affil=Department of Pediatric Oncology, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, St. Luke's International Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=13 en-affil=Showa Medical University Research Administration Center, Showa Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=15 en-affil=Department of Clinical Genetics, NHO Nagoya Medical Center kn-affil= en-keyword=cancer predisposition kn-keyword=cancer predisposition en-keyword=genotype?phenotype correlations kn-keyword=genotype?phenotype correlations en-keyword=hotspot variants kn-keyword=hotspot variants en-keyword=Li?Fraumeni syndrome kn-keyword=Li?Fraumeni syndrome en-keyword=TP53 kn-keyword=TP53 END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=e71586 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experience and Insight Into Genetic Diagnosis of Infective Aortic Aneurysm en-subtitle= kn-subtitle= en-abstract= kn-abstract=Culture-negative infected aneurysms possibly occur in various clinical situations, including prior antibiotic exposure. Accurate microbial identification is crucial for an optimal antimicrobial strategy. 16S ribosomal RNA gene sequence analysis would provide a useful tool for precise bacterial identification. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujimoriTakumi en-aut-sei=Fujimori en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=4 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= en-keyword=16S rRNA kn-keyword=16S rRNA en-keyword=culture-negative kn-keyword=culture-negative en-keyword=Enterobacter hormaechei kn-keyword=Enterobacter hormaechei en-keyword=infected aneurysm kn-keyword=infected aneurysm END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=100511 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic variability in Neisseria meningitidis strains isolated in a Japanese hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Neisseria meningitidis is a significant pathogen causing invasive meningococcal disease, posing clinical and public health concerns worldwide. This study aimed to investigate the genetic characteristics of N. meningitidis clinical isolates at Okayama University Hospital in Japan.
Methods: Between 2018 and 2023, five clinical strains were isolated, of which three were subjected to the antimicrobial susceptibility testing and whole genetic analysis using MiSeq platform (Illumina, San Diego, CA, USA).
Results: One non-groupable isolate, belonging to sequence types (STs)-11026 (ST-32 complex), exhibited non-susceptibility to penicillin G, with a five-mutation pattern (F504L, A510V, I515V, H541N, and I566V) in the penA amino acid sequence and additional mutations (XXXIV and N513Y) characteristic of a mosaic penA gene. The other two isolates, ST-1655 (ST-23 complex) with serogroup Y and ST-2057 with serogroup B, were susceptible to penicillin G, neither of which contained the five-mutation pattern. Levofloxacin resistance was observed in two isolates carrying the T91I mutation in the gyrA protein.
Conclusion: Our findings suggest the presence of antimicrobial-resistant N. meningitidis in Japan, underscoring the necessity for continuous local surveillance. Additional research is crucial for clarifying the ongoing spread of resistance mechanisms and for establishing effective countermeasures to reduce the clinical burden of invasive meningococcal disease. en-copyright= kn-copyright= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Invasive meningococcal disease kn-keyword=Invasive meningococcal disease en-keyword=Drug-resistant gene kn-keyword=Drug-resistant gene en-keyword=Genome sequence kn-keyword=Genome sequence END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=3 article-no= start-page=126 end-page=131 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A survey of college students' knowledge and awareness of hereditary cancer kn-title=遺伝性腫瘍に関する大学生の知識と意識調査 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　Genomic information plays a critical role in the diagnosis and treatment of various diseases, as well as in the management of asymptomatic individuals. This study assessed the knowledge and understanding of genetics and hereditary cancer among college students who received cancer education in Japan. The study subjects were students from fields such as education, medicine, law, and economics who participated during the period from February to December 2023. The students attended in-person lectures on genomic medicine, and they were then asked to complete an anonymous survey via Google Forms. Over 90％ of the participants reported understanding the content of the lectures, and >80％ indicated that they found the lecture's content understandable at a junior high school level. Over 60％ felt that the appropriate time to begin such education would be in late elementary or junior high school. These results indicate a high level of acceptance of hereditary cancer education among young people. However, challenges remain in their understanding of the roles of genetic factors in cancer development and the mechanisms by which inheritance and phenotype are manifested. The relevant educational programs need to be further refined and strengthened. en-copyright= kn-copyright= en-aut-name=SogawaReimi en-aut-sei=Sogawa en-aut-mei=Reimi kn-aut-name=十川麗美 kn-aut-sei=十川 kn-aut-mei=麗美 aut-affil-num=1 ORCID= en-aut-name=WadaTakahito en-aut-sei=Wada en-aut-mei=Takahito kn-aut-name=和田敬仁 kn-aut-sei=和田 kn-aut-mei=敬仁 aut-affil-num=2 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name=平沢晃 kn-aut-sei=平沢 kn-aut-mei=晃 aut-affil-num=3 ORCID= en-aut-name=KumamotoKensuke en-aut-sei=Kumamoto en-aut-mei=Kensuke kn-aut-name=隈元謙介 kn-aut-sei=隈元 kn-aut-mei=謙介 aut-affil-num=4 ORCID= en-aut-name=OhmoriIori en-aut-sei=Ohmori en-aut-mei=Iori kn-aut-name=大守伊織 kn-aut-sei=大守 kn-aut-mei=伊織 aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Clinical Genetics and Genomic Medicine, Kagawa University Hospital kn-affil=香川大学医学部附属病院　臨床遺伝ゲノム診療科 affil-num=2 en-affil=Department of Genomic Medicine, Kyoto University Graduate School of Medicine kn-affil=京都大学大学院医学研究科　ゲノム医療学 affil-num=3 en-affil=Department of Clinical Genomic Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域　臨床遺伝医療学 affil-num=4 en-affil=Department of Clinical Genetics and Genomic Medicine, Kagawa University Hospital kn-affil=香川大学医学部附属病院　臨床遺伝ゲノム診療科 affil-num=5 en-affil=Special Needs Education, Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域　特別支援教育 en-keyword=遺伝性腫瘍 (hereditary cancer) kn-keyword=遺伝性腫瘍 (hereditary cancer) en-keyword=ゲノム教育 (genome education) kn-keyword=ゲノム教育 (genome education) en-keyword=市民教育 (public education) kn-keyword=市民教育 (public education) en-keyword=学校教育 (school education) kn-keyword=学校教育 (school education) END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251117 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Profiling of Pediatric Solid Tumors With a Dual DNA/RNA Panel: JCCG-TOP2 Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=To develop an optimized genomic medicine platform for pediatric cancers, a nationwide cancer genome profiling project was conducted from January 2022 to February 2023 in collaboration with the Japan Children's Cancer Group. This prospective observational study analyzed matched blood and FFPE tumor samples from patients aged 0?29?years with solid tumors. Genomic analysis used the TOP2 hybrid capture?enrichment system, targeting 737 and 455 genes in the DNA and RNA panels, along with allele-specific genome copy number alterations. A total of 210 patients from 50 institutions were enrolled across Japan (median age, 8?years; range, 0?25). Of these, 154 (77%) were enrolled at diagnosis or during/after initial treatment and 56 (27%) at disease progression or relapse. The TOP2 findings had great benefits in clarifying the diagnosis of pediatric solid tumors. Among the 204 patients with genomic results, 147 (72%) had potentially actionable findings, including diagnostic, prognostic, and therapeutic findings in 111 (54%), 61 (30%), and 64 (31%), respectively. Oncogenic fusions were noted in 45 (23%) patients. A copy number alteration was identified in at least one genomic region in 170 (83%) patients. Two patients exhibited a high tumor mutation burden. Seventeen (8%) patients harbored a germline pathogenic/likely pathogenic variant in cancer-predisposing genes. This study highlighted the feasibility of implementing a nationwide precision medicine platform and the clinical utility of the TOP2 system for pediatric cancers. The results support the integration of genomic data into the standard clinical care of pediatric patients with cancer, both at diagnosis and at relapse. en-copyright= kn-copyright= en-aut-name=TaoKayoko en-aut-sei=Tao en-aut-mei=Kayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiokaTakako en-aut-sei=Yoshioka en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoMiho en-aut-sei=Kato en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KomatsuKazuyuki en-aut-sei=Komatsu en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujimotoShinichi en-aut-sei=Tsujimoto en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakamotoKenichi en-aut-sei=Sakamoto en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanimuraKazuki en-aut-sei=Tanimura en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiyamaMinako en-aut-sei=Sugiyama en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SekiguchiMasahiro en-aut-sei=Sekiguchi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoYoshiko en-aut-sei=Nakano en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YatabeYasushi en-aut-sei=Yatabe en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshidaAkihiko en-aut-sei=Yoshida en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkitaHajime en-aut-sei=Okita en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HiratoJunko en-aut-sei=Hirato en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KohashiKenichi en-aut-sei=Kohashi en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TanakaYukichi en-aut-sei=Tanaka en-aut-mei=Yukichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KohsakaShinji en-aut-sei=Kohsaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KuboTakashi en-aut-sei=Kubo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SunamiKuniko en-aut-sei=Sunami en-aut-mei=Kuniko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HirataMakoto en-aut-sei=Hirata en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TsutsumiShuichi en-aut-sei=Tsutsumi en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=AburataniHiroyuki en-aut-sei=Aburatani en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KohKatsuyoshi en-aut-sei=Koh en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HirayamaMasahiro en-aut-sei=Hirayama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KarakawaShuhei en-aut-sei=Karakawa en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TerashitaYukayo en-aut-sei=Terashita en-aut-mei=Yukayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=FujisakiHiroyuki en-aut-sei=Fujisaki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=YagiTakeshi en-aut-sei=Yagi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=YonedaAkihiro en-aut-sei=Yoneda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MochizukiShinji en-aut-sei=Mochizuki en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=ShichinoHiroyuki en-aut-sei=Shichino en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SuzukiTatsuya en-aut-sei=Suzuki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TakimotoTetsuya en-aut-sei=Takimoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=IchimuraKoichi en-aut-sei=Ichimura en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OgawaChitose en-aut-sei=Ogawa en-aut-mei=Chitose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=MatsumotoKimikazu en-aut-sei=Matsumoto en-aut-mei=Kimikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=IchikawaHitoshi en-aut-sei=Ichikawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=KatoMotohiro en-aut-sei=Kato en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= affil-num=1 en-affil=Department of Pediatrics, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Pathology, National Center for Child Health and Development kn-affil= affil-num=3 en-affil=Department of Childhood Cancer Data Management, National Center for Child Health and Development kn-affil= affil-num=4 en-affil=Department of Pediatrics, Hamamatsu University School of Medicine kn-affil= affil-num=5 en-affil=Department of Pediatrics, Yokohama City University kn-affil= affil-num=6 en-affil=Department of Pediatrics, Shinshu University School of Medicine kn-affil= affil-num=7 en-affil=Department of Pediatrics, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Diagnostic Pathology, National Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Diagnostic Pathology, National Cancer Center Hospital kn-affil= affil-num=14 en-affil=Department of Pathology, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Pathology, Public Tomioka General Hospital kn-affil= affil-num=16 en-affil=Department of Pathology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=17 en-affil=Department of Pathology, Kanagawa Children's Medical Center kn-affil= affil-num=18 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=19 en-affil=Department of Clinical Genomics, National Cancer Center Research Institute kn-affil= affil-num=20 en-affil=Department of Laboratory Medicine, National Cancer Center Hospital kn-affil= affil-num=21 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=22 en-affil=Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo kn-affil= affil-num=23 en-affil=Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo kn-affil= affil-num=24 en-affil=Department of Hematology and Oncology, Saitama Children's Medical Center kn-affil= affil-num=25 en-affil=Department of Pediatrics, Mie University Graduate School of Medicine kn-affil= affil-num=26 en-affil=Department of Pediatrics, Hiroshima University Hospital kn-affil= affil-num=27 en-affil=Department of Pediatrics, Hokkaido University Hospital kn-affil= affil-num=28 en-affil=Department of Pediatric Hematology and Oncology, Osaka City General Hospital kn-affil= affil-num=29 en-affil=Okinawa Prefectural Nanbu Medical Center & Children's Medical Center kn-affil= affil-num=30 en-affil=Department of Pediatric Surgery, National Center for Child Health and Development kn-affil= affil-num=31 en-affil=Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=32 en-affil=Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security kn-affil= affil-num=33 en-affil=Department of Hematology, National Cancer Center Hospital kn-affil= affil-num=34 en-affil=Department of Childhood Cancer Data Management, National Center for Child Health and Development kn-affil= affil-num=35 en-affil=Department of Pathology, Kyorin University Faculty of Medicine kn-affil= affil-num=36 en-affil=Department of Pediatrics, National Cancer Center Hospital kn-affil= affil-num=37 en-affil=Children's Cancer Center National Center for Child Health and Development kn-affil= affil-num=38 en-affil=Department of Clinical Genomics, National Cancer Center Research Institute kn-affil= affil-num=39 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= en-keyword=genomic medicine kn-keyword=genomic medicine en-keyword=integrative diagnosis kn-keyword=integrative diagnosis en-keyword=molecularly targeted therapy kn-keyword=molecularly targeted therapy en-keyword=multigene panel kn-keyword=multigene panel en-keyword=pediatric cancers kn-keyword=pediatric cancers END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=1908 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Streptococcus mutans strains possessing genes encoding collagen-binding proteins in the Japanese population en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Streptococcus mutans harbors collagen-binding protein genes, namely cnm and cbm, which are implicated in its virulence and pathogenicity in both oral and extraoral infections. Although both genes were initially identified in S. mutans isolated from Japanese populations, their geographical prevalence, distribution, and genetic relatedness within Japan remain largely unexplored. This study investigates the prevalence of S. mutans strains carrying cnm and cbm genes across Japan, correlates these findings with clinical data, and analyzes the genetic relatedness of cnm-positive and cnm-negative strains using multilocus sequence typing (MLST).
Methods Dental plaque specimens were collected from 1248 individuals from eight Japanese cities (Hiroshima, Fukuoka, Nagasaki, Niigata, Okayama, Osaka, Tokushima, and Tokyo) and plated on selective medium for S. mutans isolation. S. mutans was confirmed in 523 subjects by colony morphology and PCR using species-specific primers, and the presence of the cnm and cbm genes was determined by PCR with gene-specific primers. Demographic (age, sex) and oral examination (caries prevalence, caries experience, number of teeth) data were recorded. MLST was employed to genotype selected cnm-positive and cnm-negative S. mutans strains to assess their clonal relationships.
Results Among 523 subjects possessing S. mutans (aged 3?90 years), we detected cnm-positive strains in all cities; specifically, the prevalence ranged from 5.5% in Okayama to 25.0% in Tokushima. In contrast, cbm-positive strains were less common and undetectable in some regions. Furthermore, subjects harboring cnm-positive S. mutans were significantly older (p?=?0.002) and had higher caries prevalence and experience (p? Conclusions The cnm-positive S. mutans strains are widely distributed throughout Japan and are associated with increased age and caries burden. Although core genome analysis revealed some clonal patterns, the non-uniform distribution of the non-core cnm gene is likely influenced by horizontal gene transfer, providing S. mutans with adaptive advantages irrespective of its core genetic background or serotype. en-copyright= kn-copyright= en-aut-name=OkudaMakoto en-aut-sei=Okuda en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuehiroYuto en-aut-sei=Suehiro en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LapirattanakulJinthana en-aut-sei=Lapirattanakul en-aut-mei=Jinthana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaShuhei en-aut-sei=Naka en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Matsumoto-NakanoMichiyo en-aut-sei=Matsumoto-Nakano en-aut-mei=Michiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomuraRyota en-aut-sei=Nomura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkawaRena en-aut-sei=Okawa en-aut-mei=Rena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoKazuhiko en-aut-sei=Nakano en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=2 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Faculty of Dentistry, Mahidol University kn-affil= affil-num=4 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=7 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=8 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= en-keyword=Collagen-binding protein gene kn-keyword=Collagen-binding protein gene en-keyword=cnm gene kn-keyword=cnm gene en-keyword=cbm gene kn-keyword=cbm gene en-keyword=Japan kn-keyword=Japan en-keyword=Multilocus sequence typing kn-keyword=Multilocus sequence typing en-keyword=Serotype kn-keyword=Serotype en-keyword=Streptococcus mutans kn-keyword=Streptococcus mutans END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=1720 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n?=?1808; replication cohort: n?=?207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p?=?4.60 × 10-8); this finding has been confirmed in the replication cohort (p?=?0.0068) and meta-analysis (p?=?1.08 × 10?9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p?=?0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset. en-copyright= kn-copyright= en-aut-name=NakamuraRyoichi en-aut-sei=Nakamura en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TohnaiGenki en-aut-sei=Tohnai en-aut-mei=Genki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AtsutaNaoki en-aut-sei=Atsuta en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsudaYumi en-aut-sei=Matsuda en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorimotoSatoru en-aut-sei=Morimoto en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoDaisuke en-aut-sei=Ito en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatsunoMasahisa en-aut-sei=Katsuno en-aut-mei=Masahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IzumiYuishin en-aut-sei=Izumi en-aut-mei=Yuishin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaMitsuya en-aut-sei=Morita en-aut-mei=Mitsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwataIkuko en-aut-sei=Iwata en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YabeIchiro en-aut-sei=Yabe en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakazatoTomoko en-aut-sei=Nakazato en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HattoriNobutaka en-aut-sei=Hattori en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirayamaTakehisa en-aut-sei=Hirayama en-aut-mei=Takehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KanoOsamu en-aut-sei=Kano en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TamuraAsako en-aut-sei=Tamura en-aut-mei=Asako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SuzukiNaoki en-aut-sei=Suzuki en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AokiMasashi en-aut-sei=Aoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShibuyaKazumoto en-aut-sei=Shibuya en-aut-mei=Kazumoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KuwabaraSatoshi en-aut-sei=Kuwabara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OdaMasaya en-aut-sei=Oda en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HashimotoRina en-aut-sei=Hashimoto en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=AibaIkuko en-aut-sei=Aiba en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=IshiharaTomohiko en-aut-sei=Ishihara en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=OnoderaOsamu en-aut-sei=Onodera en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=BokudaKota en-aut-sei=Bokuda en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ShimizuToshio en-aut-sei=Shimizu en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=IkedaYoshio en-aut-sei=Ikeda en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=HasegawaKazuko en-aut-sei=Hasegawa en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TanakaFumiaki en-aut-sei=Tanaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=YokotaTakanori en-aut-sei=Yokota en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KanaiKazuaki en-aut-sei=Kanai en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NotoYu-ichi en-aut-sei=Noto en-aut-mei=Yu-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=KajiRyuji en-aut-sei=Kaji en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=WatanabeHirohisa en-aut-sei=Watanabe en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KonishiTomoko en-aut-sei=Konishi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=HasegawaMikiko en-aut-sei=Hasegawa en-aut-mei=Mikiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=FukayaHozuki en-aut-sei=Fukaya en-aut-mei=Hozuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=NiwaJun-ichi en-aut-sei=Niwa en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=DoyuManabu en-aut-sei=Doyu en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=OkadaYohei en-aut-sei=Okada en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=NakamuraShiho en-aut-sei=Nakamura en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=OzawaFumiko en-aut-sei=Ozawa en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=OkanoHideyuki en-aut-sei=Okano en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=NakatochiMasahiro en-aut-sei=Nakatochi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=SobueGen en-aut-sei=Sobue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= affil-num=1 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=2 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=3 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=4 en-affil=Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=6 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Division of Neurology, Department of Internal Medicine, Jichi Medical University kn-affil= affil-num=10 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=11 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=12 en-affil=Department of Neurology, Juntendo University School of Medicine kn-affil= affil-num=13 en-affil=Department of Neurology, Juntendo University School of Medicine kn-affil= affil-num=14 en-affil=Department of Neurology, Toho University Faculty of Medicine kn-affil= affil-num=15 en-affil=Department of Neurology, Toho University Faculty of Medicine kn-affil= affil-num=16 en-affil=Department of Neurology, Mie University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Neurology, Tohoku University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neurology, Tohoku University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=20 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=21 en-affil=Department of Neurology, Vihara Hananosato Hospital kn-affil= affil-num=22 en-affil=Department of Neurology, NHO Higashinagoya National Hospital kn-affil= affil-num=23 en-affil=Department of Neurology, NHO Higashinagoya National Hospital kn-affil= affil-num=24 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=25 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=26 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=27 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=28 en-affil=Department of Neurology, Tokyo Metropolitan Neurological Hospital kn-affil= affil-num=29 en-affil=Department of Neurology, Tokyo Metropolitan Neurological Hospital kn-affil= affil-num=30 en-affil=Department of Neurology, Gunma University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Division of Neurology, NHO Sagamihara National Hospital kn-affil= affil-num=32 en-affil=Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine kn-affil= affil-num=33 en-affil=Department of Neurology and Neurological Science, NucleoTIDE and PepTIDE Drug Discovery Center (TIDE), Institute of Science Tokyo kn-affil= affil-num=34 en-affil=Department of Neurology, Fukushima Medical University School of Medicine kn-affil= affil-num=35 en-affil=Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=36 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=37 en-affil=Department of Neurology, Fujita Health University kn-affil= affil-num=38 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=39 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=40 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=41 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=42 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=43 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=44 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=45 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=46 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=47 en-affil=Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine kn-affil= affil-num=48 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel in-frame duplication variant of SOD1 in a Japanese family with familial amyotrophic lateral sclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To analyze the cases of a family with a novel in-frame duplication variant (NM_000454.5:c.357_357?+?2dup, p.Val120dup) of SOD1 and a structural model of the mutated SOD1 protein. Methods: The clinical profiles of three patients in the family were analyzed, including the neuropathological findings of the proband’s mother. Genetic analyses were conducted for three patients. cDNA and in silico structural analyses were performed to evaluate the effects of duplication variants on the structure of SOD1. Results: The clinical features of the patients included predominant involvement of the lower motor neurons, asymmetric onset of motor symptoms in the lower limbs, and a relatively rapid progression of muscular weakness and respiratory insufficiency. Neuropathological findings revealed severe loss of spinal cord motor neurons, and immunohistochemistry using an anti-misfolded SOD1 antibody revealed aggregates in the spinal cord. Genetic analyses revealed a c.357_357?+?2dup at the exon 4?intron 4 boundary of SOD1 in three patients. cDNA analysis of the proband suggested the presence of a valine (p.Val120dup) duplication in the heterozygous state, and the SOD1 transcript level showed no significant differences from those of healthy controls. In silico structural analyses predicted that p.Val120dup could affect the structure of the β-barrels and copper ion binding site of SOD1, suggesting an abnormal conformation of SOD1 that is predicted to interfere with the binding of copper ions. Conclusion: We identified a novel in-frame duplication variant in the C-terminus of β7 of SOD1. This genotype?structure?phenotype study of SOD1 provides valuable insights into disease-causing mechanisms. en-copyright= kn-copyright= en-aut-name=NakajimaMasanori en-aut-sei=Nakajima en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaruseHiroya en-aut-sei=Naruse en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RikuYuichi en-aut-sei=Riku en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaKunihiro en-aut-sei=Ueda en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraYoshitsugu en-aut-sei=Nakamura en-aut-mei=Yoshitsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshidaShimon en-aut-sei=Ishida en-aut-mei=Shimon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaTakashi en-aut-sei=Yamada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoroNaoki en-aut-sei=Moro en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KotsukiNaoki en-aut-sei=Kotsuki en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagaiKentaro en-aut-sei=Nagai en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TokushigeShin-ichi en-aut-sei=Tokushige en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UchiboriAyumi en-aut-sei=Uchibori en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OishiChizuko en-aut-sei=Oishi en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YabataHiroyuki en-aut-sei=Yabata en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrushitaniMakoto en-aut-sei=Urushitani en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IwasakiYasushi en-aut-sei=Iwasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=IchikawaYaeko en-aut-sei=Ichikawa en-aut-mei=Yaeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Division of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical University kn-affil= affil-num=8 en-affil=Division of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical University kn-affil= affil-num=9 en-affil=Department of Pathology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=10 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=12 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=13 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=14 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=15 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=16 en-affil=Department of Neurology, Shiga University of Medical Science kn-affil= affil-num=17 en-affil=Department of Neurology, Shiga University of Medical Science kn-affil= affil-num=18 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=19 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=21 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=22 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= en-keyword=Familial amyotrophic lateral sclerosis kn-keyword=Familial amyotrophic lateral sclerosis en-keyword=SOD1 kn-keyword=SOD1 en-keyword=in-frame duplication kn-keyword=in-frame duplication en-keyword=protein structure kn-keyword=protein structure en-keyword=misfolded protein kn-keyword=misfolded protein END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=4 article-no= start-page=244 end-page=249 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of New Repeat Expansion Diseases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Through a genetic study of benign adult familial myoclonus epilepsy (BAFME) type 1, TTTCA and TTTTA repeat expansions have been identified in intron 4 of SAMD12. Lengths of expanded repeats inversely correlated with age at onset of epilepsy. Gain-of-toxic function mechanisms are suggested by the presence of UUUCA-repeat-containing RNA foci. From families with BAFME who did not have repeat expansions in SAMD12, we identified expanded TTTCA and TTTTA repeats in TNRC6A and RAPGEF2. These findings indicated a strong correlation between the repeat motif and the phenotype, leading to the identification of other types of BAFME. We then conducted genetic analysis of neuronal intranuclear inclusion disease (NIID), oculopharyngeal myopathy with leukoencephalopathy (OPML), and oculopharyngodistal myopathy (OPDM). From the observation that NIID, OPML, and OPDM, in addition to fragile X-associated tremor/ataxia syndrome, have shared clinical features, a direct search for CGG repeat expansions successfully led to the identification of the causative genes. Here, I review recent studies on repeat expansions. en-copyright= kn-copyright= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama UniversityGraduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=421 end-page=429 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Thoron Inhalation and Cyclosporin A Treatment on Dextran Sulfate Sodium-Induced Oxidative Damage in Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Radon (222Rn; Rn) and thoron (220Rn; Tn) inhalation have been reported to enhance antioxidant activity in various organs. However, the effects of Tn on the colon have not been investigated. This study aimed to clarify the effects of Tn inhalation, alone and in combination with cyclosporin A (CsA), on dextran sulfate sodium (DSS)-induced colitis, and the accompanying oxidative stress, in mice. Male BALB/c mice were subjected to continuous 8-day Tn inhalation (c-Tn, 533±128 Bq/m3) or alternate-day Tn inhalation over the same period (f-Tn, 577±63Bq/m3), followed by treatment with 3% DSS and either CsA or vehicle for 7 days. Although the disease activity index (DAI) decreased significantly by day 2 in the c-Tn group, scores remained significantly higher than those in the f-Tn group. In the c-Tn group, superoxide dismutase and catalase activity in the colon were significantly elevated compared with those in sham controls. Thus, DSS-induced damage was effectively inhibited in the earlier stages by the c-Tn mode of inhalation than by the f-Tn mode. These findings suggest that continuous Tn inhalation more effectively attenuated early colitis symptoms than alternate-day inhalation, potentially through upregulation of antioxidant defenses. Tn and CsA showed no combined effects. en-copyright= kn-copyright= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaoeShota en-aut-sei=Naoe en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakenakaReiju en-aut-sei=Takenaka en-aut-mei=Reiju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanzakiNorie en-aut-sei=Kanzaki en-aut-mei=Norie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakodaAkihiro en-aut-sei=Sakoda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaokaKiyonori en-aut-sei=Yamaoka en-aut-mei=Kiyonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KataokaTakahiro en-aut-sei=Kataoka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=5 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=6 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=thoron kn-keyword=thoron en-keyword=DSS kn-keyword=DSS en-keyword=antioxidant activity kn-keyword=antioxidant activity en-keyword=CsA kn-keyword=CsA en-keyword=colon kn-keyword=colon END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=413 end-page=419 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=COVID-19 and the Risks of Migraine and Headache: A Mendelian Randomization Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Several observational studies suggested that migraine headache attacks were associated with coronavirus disease 2019 (COVID-19). We investigated genetic causal links between COVID-19 phenotypes and the development of headache and migraine, including migraine with aura (MA) and migraine without aura (MO). We conducted a two-sample Mendelian randomization (MR) analysis to estimate the genetic association in European populations. The inverse-variance weighted (IVW) method was used as the main approach in the MR analyses, together with weighted median and MR-Egger methods. We also performed a series of sensitivity tests to assess the robustness of the MR results. The MR results demonstrated that COVID-19 severity, hospitalization, and susceptibility had no causal effect on the risks of headache, migraine, MA, or MO. No horizontal pleiotropy was detected, and the results were robust as supported by the sensitivity analysis findings. Our analyses identified no casual effect of COVID-19 severity, hospitalization, or susceptibility on the risks of headache or migraine in European populations. en-copyright= kn-copyright= en-aut-name=JiangZhiyun en-aut-sei=Jiang en-aut-mei=Zhiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=XiYing en-aut-sei=Xi en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University kn-affil= en-keyword=headache kn-keyword=headache en-keyword=migraine kn-keyword=migraine en-keyword=Mendelian randomization kn-keyword=Mendelian randomization en-keyword=COVID-19 kn-keyword=COVID-19 END start-ver=1.4 cd-journal=joma no-vol=114 cd-vols= no-issue=3 article-no= start-page=117209 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular epidemiological investigation of the carbapenemase-producing Enterobacterales isolates in Okayama prefecture, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the genetic characteristics of non-IMP type carbapenemase-producing Enterobacterales isolates detected in Japan. The isolates were found to carry diverse plasmids with high sequence similarity to those previously reported in other countries, underscoring the critical imperative for comprehensive nationwide epidemiological surveillance for the silent pandemic of the nightmare pathogen. en-copyright= kn-copyright= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoMayu en-aut-sei=Sato en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueYasurou en-aut-sei=Inoue en-aut-mei=Yasurou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakitaSayaka en-aut-sei=Sakita en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FudeyasuTomoko en-aut-sei=Fudeyasu en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Laboratory, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Laboratory, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Laboratory, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Clinical Laboratory, Microbiology Division, Tsuyama Chuo Hospital kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Carbapenemase-producing Enterobacterales kn-keyword=Carbapenemase-producing Enterobacterales en-keyword=New Delhi metallo-β-lactamase kn-keyword=New Delhi metallo-β-lactamase en-keyword=Klebsiella pneumoniae carbapenemase kn-keyword=Klebsiella pneumoniae carbapenemase en-keyword=Genomic surveillance kn-keyword=Genomic surveillance END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=23 article-no= start-page=3413 end-page=3418 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Prompt Diagnosis of Ascites and Dramatic Effect of Alectinib for Advanced Lung Adenocarcinoma Harboring EML4-ALK Fusion en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 75-year-old never-smoker woman presented with dyspnea and loss of appetite. A mass was identified in the left upper lobe of the lung, and the patient was referred to our hospital. Despite the diagnosis of lung adenocarcinoma via bronchoscopy, anaplastic lymphoma kinase (ALK) immunostaining was negative. Rapid weight gain and abdominal distension caused by ascites prompted fluid testing using the AmoyDx? Pan Lung Cancer PCR Panel. EML4-ALK fusion was confirmed, and alectinib therapy was initiated immediately. The tumor size had decreased significantly, and the patient was discharged on day 34. This case highlights the necessity of multiplex genetic testing even when ALK immunostaining is negative. en-copyright= kn-copyright= en-aut-name=BabaTakahiro en-aut-sei=Baba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuokaHiromi en-aut-sei=Matsuoka en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KyakunoMio en-aut-sei=Kyakuno en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshinagaYusuke en-aut-sei=Yoshinaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakeguchiTetsuya en-aut-sei=Takeguchi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraMiho en-aut-sei=Fujiwara en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamadaKotaro en-aut-sei=Yamada en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraEri en-aut-sei=Nakamura en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Medical Support, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Medical Support, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Geriatric Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=lung adenocarcinoma kn-keyword=lung adenocarcinoma en-keyword=EML4-ALK kn-keyword=EML4-ALK en-keyword=AmoyDx? Pan Lung Cancer PCR Panel kn-keyword=AmoyDx? Pan Lung Cancer PCR Panel en-keyword=alectinib kn-keyword=alectinib END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=4 article-no= start-page=313 end-page=326 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review en-subtitle= kn-subtitle= en-abstract= kn-abstract=In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes. en-copyright= kn-copyright= en-aut-name=KubotaYuta en-aut-sei=Kubota en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawanoMasanori en-aut-sei=Kawano en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwasakiTatsuya en-aut-sei=Iwasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItonagaIchiro en-aut-sei=Itonaga en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakuNobuhiro en-aut-sei=Kaku en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaKazuhiro en-aut-sei=Tanaka en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery , Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= en-keyword=NTRK fusion-positive sarcoma kn-keyword=NTRK fusion-positive sarcoma en-keyword=larotrectinib kn-keyword=larotrectinib en-keyword=entrectinib kn-keyword=entrectinib en-keyword=infantile fibrosarcoma kn-keyword=infantile fibrosarcoma en-keyword=NTRK-rearranged spindle cell neoplasms kn-keyword=NTRK-rearranged spindle cell neoplasms END start-ver=1.4 cd-journal=joma no-vol=2025 cd-vols= no-issue=1 article-no= start-page=e240121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adult hypophosphatasia presenting with recurrent acute joint pain en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5′-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms. en-copyright= kn-copyright= en-aut-name=YoshidaHayao en-aut-sei=Yoshida en-aut-mei=Hayao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiTakaaki en-aut-sei=Murakami en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgawaAtsubumi en-aut-sei=Ogawa en-aut-mei=Atsubumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunouchiTakashi en-aut-sei=Sunouchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HidakaNaoko en-aut-sei=Hidaka en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoNobuaki en-aut-sei=Ito en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurakamiHiromi en-aut-sei=Murakami en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawasakiHidenori en-aut-sei=Kawasaki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakajimaKatsumi en-aut-sei=Nakajima en-aut-mei=Katsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YabeDaisuke en-aut-sei=Yabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamamotoTaizo en-aut-sei=Yamamoto en-aut-mei=Taizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Diabetes and Endocrinology, Shiga General Hospital kn-affil= affil-num=2 en-affil=Department of Diabetes and Endocrinology, Shiga General Hospital kn-affil= affil-num=3 en-affil=Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Division of Nephrology and Endocrinology, The University of Tokyo Hospital kn-affil= affil-num=5 en-affil=Division of Nephrology and Endocrinology, The University of Tokyo Hospital kn-affil= affil-num=6 en-affil=Osteoporosis Center, The University of Tokyo Hospital kn-affil= affil-num=7 en-affil=Department of Genomic Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Genomic Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Diabetes and Endocrinology, Shiga General Hospital kn-affil= affil-num=11 en-affil=Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Diabetes and Endocrinology, Shiga General Hospital kn-affil= en-keyword=hypophosphatasia kn-keyword=hypophosphatasia en-keyword=genetic disorders kn-keyword=genetic disorders en-keyword=bone kn-keyword=bone END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome. en-copyright= kn-copyright= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiTatsuro en-aut-sei=Yamaguchi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataKeiji en-aut-sei=Hirata en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaMasayoshi en-aut-sei=Yamada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumamotoKensuke en-aut-sei=Kumamoto en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaYasuki en-aut-sei=Akiyama en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshimaruKei en-aut-sei=Ishimaru en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKoichi en-aut-sei=Okamoto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawasakiYuko en-aut-sei=Kawasaki en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KomineKeigo en-aut-sei=Komine en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakamotoAkira en-aut-sei=Sakamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShibataYoshiko en-aut-sei=Shibata en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShimamotoYusaku en-aut-sei=Shimamoto en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShimodairaHideki en-aut-sei=Shimodaira en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SekineShigeki en-aut-sei=Sekine en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakaoAkinari en-aut-sei=Takao en-aut-mei=Akinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakaoMisato en-aut-sei=Takao en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakamizawaYasuyuki en-aut-sei=Takamizawa en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakeuchiYoji en-aut-sei=Takeuchi en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TanabeNoriko en-aut-sei=Tanabe en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ChinoAkiko en-aut-sei=Chino en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=ChoHourin en-aut-sei=Cho en-aut-mei=Hourin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=DoiSatoru en-aut-sei=Doi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=NakajimaTakeshi en-aut-sei=Nakajima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamoriSakiko en-aut-sei=Nakamori en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakayamaYoshiko en-aut-sei=Nakayama en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NagasakiToshiya en-aut-sei=Nagasaki en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HasumiHisashi en-aut-sei=Hasumi en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=BannoKouji en-aut-sei=Banno en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=HinoiTakao en-aut-sei=Hinoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=FujiyoshiKenji en-aut-sei=Fujiyoshi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HorimatsuTakahiro en-aut-sei=Horimatsu en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=MasudaKenta en-aut-sei=Masuda en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=MiguchiMasashi en-aut-sei=Miguchi en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=MizuuchiYusuke en-aut-sei=Mizuuchi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=MiyakuraYasuyuki en-aut-sei=Miyakura en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=MutohMichihiro en-aut-sei=Mutoh en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=YoshiokaTakahiro en-aut-sei=Yoshioka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=TanakaShinji en-aut-sei=Tanaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SakamotoKazuhiro en-aut-sei=Sakamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SakamakiKentaro en-aut-sei=Sakamaki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ItabashiMichio en-aut-sei=Itabashi en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=TomitaNaohiro en-aut-sei=Tomita en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=SugiharaKenichi en-aut-sei=Sugihara en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=AjiokaYoichi en-aut-sei=Ajioka en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= affil-num=1 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=2 en-affil=Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=3 en-affil=Department of Surgery 1, University of Occupational and Environmental Health kn-affil= affil-num=4 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Genome Medical Science and Medical Genetics, Faculty of Medicine, Kagawa University kn-affil= affil-num=6 en-affil=Department of Surgery 1, University of Occupational and Environmental Health kn-affil= affil-num=7 en-affil=Division of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science kn-affil= affil-num=9 en-affil=College of Nursing, University of Hyogo kn-affil= affil-num=10 en-affil=Department of Medical Oncology, Tohoku University Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Himawari-No-Kai (Sunflower Association), a Patient Advocacy Group for Individuals and Families Affected By Lynch Syndrome kn-affil= affil-num=14 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Division of Medical Oncology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University kn-affil= affil-num=16 en-affil=Department of Pathology, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=19 en-affil=Department of Colorectal Surgery, National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=22 en-affil=Department of Surgery, Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=23 en-affil=Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=24 en-affil=Endoscopy Center, Tokyo Medical University Hospital kn-affil= affil-num=25 en-affil=Harmony Line (Association for Patients and Families With Familial Adenomatous Polyposis) kn-affil= affil-num=26 en-affil=Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute kn-affil= affil-num=27 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=28 en-affil=Department of Pediatrics, Shinshu University School of Medicine kn-affil= affil-num=29 en-affil=Department of Gastroenterological Surgery, Saitama Cancer Center kn-affil= affil-num=30 en-affil=Department of Urology, Yokohama City University kn-affil= affil-num=31 en-affil=Center of Maternal -Fetal/Neonatal Medicine, Hiroshima University Hospital kn-affil= affil-num=32 en-affil=Department of Clinical and Molecular Genetics, Hiroshima University Hospital kn-affil= affil-num=33 en-affil=Department of Surgery, Kurume University School of Medicine kn-affil= affil-num=34 en-affil=Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital kn-affil= affil-num=35 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=36 en-affil=Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital kn-affil= affil-num=37 en-affil=Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=38 en-affil=Department of Colon and Pelvic Surgery, Cancer Prevention and Genetic Counseling, Tochigi Cancer Center kn-affil= affil-num=39 en-affil=Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=40 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=41 en-affil=JA Onomichi General Hospital kn-affil= affil-num=42 en-affil=Koshigaya Municipal Hospital kn-affil= affil-num=43 en-affil=Faculty of Health Data Science, Juntendo University kn-affil= affil-num=44 en-affil=Saiseikai Kazo Hospital kn-affil= affil-num=45 en-affil=Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=46 en-affil=Division of Cancer Treatment , Toyonaka Municipal Hospital kn-affil= affil-num=47 en-affil=Institute of Science Tokyo kn-affil= affil-num=48 en-affil=Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=Hereditary colorectal cancer kn-keyword=Hereditary colorectal cancer en-keyword=Guidelines kn-keyword=Guidelines en-keyword=Familial adenomatous polyposis kn-keyword=Familial adenomatous polyposis en-keyword=Lynch syndrome kn-keyword=Lynch syndrome END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative Analysis of a Dual DNA?RNA Panel and a DNA-Only Panel for Sarcoma: Real-World Data From a Nationwide Genomic Database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Next-generation sequencing-based comprehensive cancer genomic profiling is promising in cancer management; however, most studies rely on tumor-only DNA panels from single institutions. In 2023, Japan introduced an insurance-covered cancer genomic profiling test?the GenMine TOP Cancer Genome Profiling System?a dual DNA?RNA panel with matched tumor?normal testing. This study evaluated its utility compared to a conventional DNA-only test (FoundationOne CDx) in managing sarcoma patients using a nationwide genetic profiling database provided by the Center for Cancer Genomics and Advanced Therapeutics. This study included 1046 patients registered between August 2023 and October 2024. The dual DNA?RNA test identified significantly more fusion genes (20.3% vs. 7.4%, p?A Variant en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives
Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges.
Methods
We describe 2 of 3 individuals carrying the homozygous c.254T >A variant in EIF2B2 identified at our hospital, excluding 1 previously reported case.1 Genetic analyses were performed using whole-genome sequence or whole-exome sequence analysis, and detected variants were confirmed by direct nucleotide sequence analysis. Brain MRI findings and clinical features were reviewed for the 2 individuals along with other cases in the literature with the same variant.
Results
A 69-year-old woman presented with recurrent transient dizziness and secondary amenorrhea. MRI of the brain revealed small T2-hyperintense lesions confined to the subcortical white matter with hyperintensities on diffusion-weighted images and mildly elevated apparent diffusion coefficient values. A 28-year-old woman presented with transient dizziness and secondary amenorrhea. MRI of the brain showed mild T2-hyperintense lesions in the cerebral white matter with frontal predominance.
Discussion
This report highlights the clinically mild cases of VWM with subtle abnormalities on brain MRI who had the homozygous c.254T >A in EIF2B2, further expanding the clinical spectrum of VWM and underscoring the importance of genetic assessments in the diagnosis of individuals with mild clinical and MRI findings. en-copyright= kn-copyright= en-aut-name=KakumotoToshiyuki en-aut-sei=Kakumoto en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokimuraRyo en-aut-sei=Tokimura en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboyamaYoko en-aut-sei=Tsuboyama en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HayashiYasufumi en-aut-sei=Hayashi en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataAtsushi en-aut-sei=Iwata en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaMeiko Hashimoto en-aut-sei=Maeda en-aut-mei=Meiko Hashimoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimizuJun en-aut-sei=Shimizu en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GonoiWataru en-aut-sei=Gonoi en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=478 cd-vols= no-issue= article-no= start-page=123708 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=CST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words). en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiomiKazutaka en-aut-sei=Shiomi en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoRyoji en-aut-sei=Goto en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuromiYumiko en-aut-sei=Kuromi en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsudaNozomu en-aut-sei=Matsuda en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanaiKazuaki en-aut-sei=Kanai en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurokawaRyo en-aut-sei=Kurokawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NomotoJunko en-aut-sei=Nomoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TanakaMasaki en-aut-sei=Tanaka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=8 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=9 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=14 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=15 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=16 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=17 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=CST3 kn-keyword=CST3 en-keyword=Cystatin-C kn-keyword=Cystatin-C en-keyword=Leukodystrophy kn-keyword=Leukodystrophy en-keyword=Leukoencephalopathy kn-keyword=Leukoencephalopathy en-keyword=Middle cerebellar peduncle kn-keyword=Middle cerebellar peduncle en-keyword=MCP kn-keyword=MCP END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=INF2-Related Charcot?Marie?Tooth Disease in a Japanese Cohort: Genetic and Clinical Insights en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: INF2 mutations cause focal segmental glomerulosclerosis (FSGS) and Charcot?Marie?Tooth disease (CMT). Accurate genetic diagnosis is critical, as INF2-related FSGS is typically resistant to immunotherapy yet rarely recurs after transplantation, and its associated neuropathy can mimic treatable immune-mediated disorders such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
Methods: We performed a multicenter study investigating 3329 Japanese patients with inherited peripheral neuropathies/CMT who underwent gene panel sequencing or whole-exome analysis between 2007 and 2024. Clinical data, including electrophysiological assessments, were obtained from the patients' medical records.
Results: We identified six pathogenic INF2 variants in eight patients, all of which were located within the diaphanous inhibitory domain. Structural modeling revealed clustering of variants near the diaphanous autoregulatory domain-binding pocket, which is critical for INF2 autoinhibition. Clinically, all cases were sporadic, with a median age at neurological onset of 9?years. All patients exhibited lower limb weakness, and 6/8 (75%) had sensory disturbances. All patients also developed kidney dysfunction, with 7/8 (88%) progressing to end-stage renal disease at a median age of 15?years. Furthermore, all patients showed demyelinating neuropathy, and 2/8 (25%) received immunotherapy due to suspected immune-mediated neuropathy.
Conclusion: Although INF2 variants are a rare cause of CMT in Japan, they should be considered in pediatric patients with demyelinating neuropathy and early-onset proteinuria, even in the absence of a family history. Blood and urine tests assessing renal dysfunction can provide guidance for appropriate genetic testing. en-copyright= kn-copyright= en-aut-name=YanoChikashi en-aut-sei=Yano en-aut-mei=Chikashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AndoMasahiro en-aut-sei=Ando en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiguchiYujiro en-aut-sei=Higuchi en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuanJun‐Hui en-aut-sei=Yuan en-aut-mei=Jun‐Hui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimuraAkiko en-aut-sei=Yoshimura en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HobaraTakahiro en-aut-sei=Hobara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatomoRisa en-aut-sei=Nagatomo en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KojimaFumikazu en-aut-sei=Kojima en-aut-mei=Fumikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiramatsuYu en-aut-sei=Hiramatsu en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NozumaSatoshi en-aut-sei=Nozuma en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraTomonori en-aut-sei=Nakamura en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakiyamaYusuke en-aut-sei=Sakiyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimuraTakashi en-aut-sei=Kimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiyazakiAyako en-aut-sei=Miyazaki en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KinjoChinatsu en-aut-sei=Kinjo en-aut-mei=Chinatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YokochiKenji en-aut-sei=Yokochi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamanakaNanami en-aut-sei=Yamanaka en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsudaNozomu en-aut-sei=Matsuda en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SuichiTomoki en-aut-sei=Suichi en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HanaokaYoshiyuki en-aut-sei=Hanaoka en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KojimaHaruka en-aut-sei=Kojima en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TodoKenichi en-aut-sei=Todo en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TakashimaHiroshi en-aut-sei=Takashima en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=8 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=9 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=10 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=11 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=12 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=13 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neurology, Hyogo Medical University kn-affil= affil-num=16 en-affil=Department of Clinical Genetics, Hyogo Medical University kn-affil= affil-num=17 en-affil=Department of Clinical Genetics, Hyogo Medical University kn-affil= affil-num=18 en-affil=Department of Pediatrics, Toyohashi Municipal Hospital kn-affil= affil-num=19 en-affil=Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Neurology, Fukushima Medical University School of Medicine kn-affil= affil-num=21 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Kurashiki Central Hospital kn-affil= affil-num=23 en-affil=Department of Neurology, Tokyo Women's Medical University kn-affil= affil-num=24 en-affil=Department of Neurology, Tokyo Women's Medical University kn-affil= affil-num=25 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=27 en-affil=Department of Neurology, The University of Tokyo Hospital kn-affil= affil-num=28 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=Charcot-Marie- Tooth disease kn-keyword=Charcot-Marie- Tooth disease en-keyword=focal segmental glomerulosclerosis kn-keyword=focal segmental glomerulosclerosis en-keyword=INF2 kn-keyword=INF2 en-keyword=inherited peripheral neuropathies kn-keyword=inherited peripheral neuropathies en-keyword=neuropathy kn-keyword=neuropathy END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=11 article-no= start-page=102658 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pathophysiology and Therapeutic Needs in Nonobstructive Hypertrophic Cardiomyopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypertrophic cardiomyopathy (HCM) affects individuals worldwide with an estimated prevalence of over 1 in 500 individuals. Nonobstructive HCM accounts for approximately 30% to 70% of cases, is extremely heterogeneous, and is associated with a notable degree of morbidity, including daily life limitations, ventricular tachyarrhythmias, progression to heart failure, and atrial fibrillation. No approved pharmaceutical therapies target the pathophysiology of nonobstructive HCM, although several clinical trials are underway. This narrative review provides a comprehensive overview of nonobstructive HCM, focusing on epidemiology, natural history, genetics, pathophysiology, clinical manifestations, diagnosis, burden of disease, and current treatments and ongoing clinical trials. en-copyright= kn-copyright= en-aut-name=DesaiMilind Y. en-aut-sei=Desai en-aut-mei=Milind Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MauriziNiccolo en-aut-sei=Maurizi en-aut-mei=Niccolo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BiaginiElena en-aut-sei=Biagini en-aut-mei=Elena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=CharronPhilippe en-aut-sei=Charron en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FernandesFabio en-aut-sei=Fernandes en-aut-mei=Fabio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Gonz?lez-L?pezEsther en-aut-sei=Gonz?lez-L?pez en-aut-mei=Esther kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=van HaelstPaul L. en-aut-sei=van Haelst en-aut-mei=Paul L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaugaaKristina Hermann en-aut-sei=Haugaa en-aut-mei=Kristina Hermann kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KramerChristopher M. en-aut-sei=Kramer en-aut-mei=Christopher M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MederBenjamin en-aut-sei=Meder en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MichelsMichelle en-aut-sei=Michels en-aut-mei=Michelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OwensAnjali en-aut-sei=Owens en-aut-mei=Anjali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ElliottPerry en-aut-sei=Elliott en-aut-mei=Perry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=HCM Center, Department of Cardiovascular Medicine, Cleveland Clinic kn-affil= affil-num=2 en-affil=Cardiomyopathy Unit, Careggi University Hospital kn-affil= affil-num=3 en-affil=Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna kn-affil= affil-num=4 en-affil=European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart) kn-affil= affil-num=5 en-affil=InCor, Faculdade de Medicina da Universidade de S?o Paulo kn-affil= affil-num=6 en-affil=Puerta de Hierro Majadahonda University Hospital, Health Research Institute of the Puerta de Hierro Majadahonda-Segovia de Arana University Hospital (IDIPHISA) kn-affil= affil-num=7 en-affil=Cardiovascular Division, Department of Medicine, University of Virginia Health kn-affil= affil-num=8 en-affil=Cardiovascular Division, Department of Medicine, University of Virginia Health kn-affil= affil-num=9 en-affil=Cardiovascular Division, Department of Medicine, University of Virginia Health kn-affil= affil-num=10 en-affil=Department of Internal Medicine III, Institute for Cardiomyopathies, University of Heidelberg kn-affil= affil-num=11 en-affil=European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart) kn-affil= affil-num=12 en-affil=Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=UCL Institute of Cardiovascular Science and St Bartholomew’s Hospital kn-affil= en-keyword=heart failure kn-keyword=heart failure en-keyword=hypertrophic cardiomyopathy kn-keyword=hypertrophic cardiomyopathy en-keyword=nonobstructive kn-keyword=nonobstructive END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=19 article-no= start-page=9347 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: From Sarcomere to Clinic en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by unexplained left ventricular hypertrophy, often resulting from pathogenic variants of sarcomeric protein genes. Conventional treatments, such as the use of beta blockers or calcium channel blockers, focus on symptomatic control but do not address the underlying hypercontractility at the sarcomere level. Recent advances in molecular understanding have led to the development of cardiac myosin inhibitors that directly modulate sarcomeric function by reducing myosin?actin cross-bridge formation and adenosine triphosphatase (ATPase) activity. Mavacamten and aficamten have shown promising results in phase 2 and 3 clinical trials, improving symptoms, exercise capacity, and left ventricular outflow tract gradients in patients with obstructive HCM. This review summarizes the current understanding of HCM pathophysiology, diagnostic strategies, and conventional treatments with a focus on the mechanisms of action of myosin inhibitors, clinical evidence supporting their use, and future directions for improvement. We also discuss their potential applications in non-obstructive HCM and the importance of precision medicine guided by genetic profiling. en-copyright= kn-copyright= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkumuraTakahiro en-aut-sei=Okumura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoSeiya en-aut-sei=Kato en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoueKenji en-aut-sei=Onoue en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuboToru en-aut-sei=Kubo en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KouzuHidemichi en-aut-sei=Kouzu en-aut-mei=Hidemichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YanoToshiyuki en-aut-sei=Yano en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InomataTakayuki en-aut-sei=Inomata en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Advanced Cardiovascular Therapeutics, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Pathology, Saiseikai Fukuoka General Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Nara Medical University kn-affil= affil-num=5 en-affil=Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University kn-affil= affil-num=6 en-affil=Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=hypertrophic cardiomyopathy kn-keyword=hypertrophic cardiomyopathy en-keyword=myosin inhibitors kn-keyword=myosin inhibitors en-keyword=sarcomere kn-keyword=sarcomere en-keyword=mavacamten kn-keyword=mavacamten en-keyword=aficamten kn-keyword=aficamten en-keyword=heart failure kn-keyword=heart failure END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=e72549 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimization of Preemptive Therapy for Cytomegalovirus Infections With Valganciclovir Based on Therapeutic Drug Monitoring: Protocol for a Phase II, Single-Center, Single-Arm Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Valganciclovir (VGCV) is the first-line drug for preemptive therapy of cytomegalovirus (CMV) infections. However, even when administered at the dose specified in the package insert, there is significant interindividual variability in the plasma concentrations of ganciclovir (GCV). In addition, correlations have been reported between the area under the concentration?time curve and therapeutic efficacy or adverse events. Therefore, therapeutic drug monitoring (TDM) can be used to improve the efficacy and safety of preemptive VGCV therapy.
Objective: This study aims to evaluate whether the dosage adjustment of VGCV based on TDM in patients undergoing preemptive therapy for CMV infections is associated with the successful completion rate of treatment without severe hematological adverse effects.
Methods: This phase II, single-center, single-arm trial aims to enroll 40 patients admitted at the Department of Rheumatology and Clinical Immunology, Kobe University Hospital, who will receive oral VGCV as preemptive therapy for CMV infections. Participants will begin treatment with VGCV at the dose recommended in the package insert, with subsequent dose adjustments based on weekly TDM results. The primary end point will be the proportion of patients who achieve CMV antigenemia negativity within 3 weeks without severe hematological adverse events. The secondary end points will include weekly changes in CMV antigen levels, total VGCV dose, and duration of preemptive therapy. For safety evaluation, the occurrence, type, and severity of VGCV-related adverse events will be analyzed. Additionally, this study will explore the correlations between the efficacy and safety of preemptive therapy and the pharmacokinetic parameters of GCV, CMV-polymerase chain reaction values, and nudix hydrolase 15 (NUDT15) genetic polymorphisms. The correlation between GCV plasma concentrations obtained from regular venous blood and blood concentrations will be examined using dried blood spots.
Results: This study began with patient recruitment in September 2024, with 5 participants enrolled as of June 16, 2025. The target enrollment is 40 participants, and the anticipated study completion is set for July 2027.
Conclusions: This is the first study to investigate the impact of TDM intervention in patients receiving VGCV as preemptive therapy. The findings are postulated to provide valuable evidence regarding the utility of TDM in patients receiving VGCV as preemptive therapy.
Trial Registration: Japan Registry of Clinical Trials jRCTs051240080; https://jrct.mhlw.go.jp/latest-detail/jRCTs051240080
International Registered Report Identifier (IRRID): DERR1-10.2196/72549 en-copyright= kn-copyright= en-aut-name=TamuraNaoki en-aut-sei=Tamura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoharaKotaro en-aut-sei=Itohara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaYo en-aut-sei=Ueda en-aut-mei=Yo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaneToshiyasu en-aut-sei=Sakane en-aut-mei=Toshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SaegusaJun en-aut-sei=Saegusa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=3 en-affil=Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=5 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Technology, Kobe Pharmaceutical University kn-affil= affil-num=8 en-affil=Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=valganciclovir kn-keyword=valganciclovir en-keyword=ganciclovir kn-keyword=ganciclovir en-keyword=cytomegalovirus kn-keyword=cytomegalovirus en-keyword=therapeutic drug monitoring kn-keyword=therapeutic drug monitoring en-keyword=preemptive therapy kn-keyword=preemptive therapy en-keyword=dried blood spots kn-keyword=dried blood spots END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=e70104 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adequacy evaluation of 22‐gauge needle endoscopic ultrasound‐guided tissue acquisition samples and glass slides preparation for successful comprehensive genomic profiling testing: A single institute experience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: This study aimed to evaluate the successful sequencing rate of Foundation One CDx (F1CDx) using small tissue samples obtained with a 22-gauge needle (22G) through endoscopic ultrasound-guided fine needle acquisition (EUS-TA) and to propose guidelines for tissue quantity evaluation criteria and proper slide preparation in clinical practice.
Methods: Between June 2019 and April 2024, 119 samples of 22G EUS-TA collected for F1CDx testing at Himeji Red Cross Hospital were retrospectively reviewed. Tissue adequacy was only assessed based on tumor cell percentage (?20%). The procedure stopped when white tissue fragments reached 20 mm during macroscopic on-site evaluation. The specimens were prepared using both ‘tissue preserving sectioning’ to retain tissue within formalin-fixed paraffin-embedded blocks and the ‘thin sectioning matched needle gauge and tissue length’ method with calculation to ensure minimal unstained slides for the 1 mm3 sample volume criterion. Tissue area from HE slides and sample volume were measured, and F1CDx reports were analyzed.
Results: Of 119 samples, 108 (90.8%) were suitable for F1CDx. Excluding the cases not submitted for testing, in the 45 cases where F1CDx was done using 22G EUS-TA samples, eight (17.8%) had a sum of tissue area tissue of 25 mm2 or greater in the HE-stained sample. However, all cases met the F1CDx 1 mm3 volume criterion by submitting > 30 unstained slides per sample. As a result, 43 of 45 cases (95.6%) were successfully analyzable.
Conclusions: The 22G EUS-TA needle is an effective tool for providing the sufficient tissue volume required for F1CDx. en-copyright= kn-copyright= en-aut-name=NagataniTami en-aut-sei=Nagatani en-aut-mei=Tami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WaniYoji en-aut-sei=Wani en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakataniMasahiro en-aut-sei=Takatani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FushimiSoichiro en-aut-sei=Fushimi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriShinichiro en-aut-sei=Hori en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KaiKyohei en-aut-sei=Kai en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkazakiTetsuya en-aut-sei=Okazaki en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TaniokaMaki en-aut-sei=Tanioka en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=5 en-affil=Division of Medical Support, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=7 en-affil=Department of Genetic Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=8 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=12 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biliary tract cancer kn-keyword=biliary tract cancer en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=endoscopic ultrasound-guided fine needle aspiration kn-keyword=endoscopic ultrasound-guided fine needle aspiration en-keyword=endoscopic ultrasound-guided fine needle biopsy kn-keyword=endoscopic ultrasound-guided fine needle biopsy en-keyword=pancreatic cancer kn-keyword=pancreatic cancer END start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=2 article-no= start-page=473 end-page=479.e1 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.
Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the interferon signature for neonatal screening and to gain insight into presymptomatic state of neonates with inborn errors of immunity (IEIs).
Methods: DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs as well as from neonates with viral infections, including some samples obtained during the presymptomatic neonatal period, were examined by nontargeted proteome analyses. Expression of interferon-stimulated genes (ISGs) was evaluated and a DBS-interferon signature was defined. Differential expression/pathway analysis was also performed.
Results: The ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z scores for these as the DBS-interferon signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high interferon signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus?like pathways.
Conclusion: Upregulation of the interferon pathway exists already at birth?not only in neonates with type I interferonopathy but also in other IEIs, including CGD. en-copyright= kn-copyright= en-aut-name=NihiraHiroshi en-aut-sei=Nihira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaDaisuke en-aut-sei=Nakajima en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IzawaKazushi en-aut-sei=Izawa en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawashimaYusuke en-aut-sei=Kawashima en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShibataHirofumi en-aut-sei=Shibata en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonnoRyo en-aut-sei=Konno en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashiguchiMotoko en-aut-sei=Higashiguchi en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoTakayuki en-aut-sei=Miyamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nishitani-IsaMasahiko en-aut-sei=Nishitani-Isa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiejimaEitaro en-aut-sei=Hiejima en-aut-mei=Eitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HondaYoshitaka en-aut-sei=Honda en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsubayashiTadashi en-aut-sei=Matsubayashi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaTakashi en-aut-sei=Ishihara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwataNaomi en-aut-sei=Iwata en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhwadaYoko en-aut-sei=Ohwada en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomotakiSeiichi en-aut-sei=Tomotaki en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaiMasahiko en-aut-sei=Kawai en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MurakamiKosaku en-aut-sei=Murakami en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhnishiHidenori en-aut-sei=Ohnishi en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshimuraMasataka en-aut-sei=Ishimura en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OkadaSatoshi en-aut-sei=Okada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YamashitaMotoi en-aut-sei=Yamashita en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MorioTomohiro en-aut-sei=Morio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HoshinoAkihiro en-aut-sei=Hoshino en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KaneganeHirokazu en-aut-sei=Kanegane en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ImaiKohsuke en-aut-sei=Imai en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakamuraYasuko en-aut-sei=Nakamura en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NonoyamaShigeaki en-aut-sei=Nonoyama en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UchiyamaToru en-aut-sei=Uchiyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OnoderaMasafumi en-aut-sei=Onodera en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=IshikawaTakashi en-aut-sei=Ishikawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawaiToshinao en-aut-sei=Kawai en-aut-mei=Toshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TakitaJunko en-aut-sei=Takita en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NishikomoriRyuta en-aut-sei=Nishikomori en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OharaOsamu en-aut-sei=Ohara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=YasumiTakahiro en-aut-sei=Yasumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= affil-num=1 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University kn-affil= affil-num=15 en-affil=Department of Infection and Immunology, Aichi Children’s Health and Medical Center kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neonatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Pediatrics, Gifu University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=23 en-affil=Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=24 en-affil=Laboratory of Immunology and Molecular Medicine, Advanced Research Initiative, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=25 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=26 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=27 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=28 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=29 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=30 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=31 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=32 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=33 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=34 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=35 en-affil=Department of Pediatrics and Child Health, Kurume University School of Medicine kn-affil= affil-num=36 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=37 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= en-keyword=Inborn errors of immunity kn-keyword=Inborn errors of immunity en-keyword=interferonopathy kn-keyword=interferonopathy en-keyword=signature kn-keyword=signature en-keyword=proteome kn-keyword=proteome en-keyword=dried blood spot kn-keyword=dried blood spot en-keyword=CGD kn-keyword=CGD en-keyword=WAS kn-keyword=WAS en-keyword=newborn kn-keyword=newborn en-keyword=neonate kn-keyword=neonate END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=15 article-no= start-page=2290 end-page=2294 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and Genetic Analyses of SPG7 in Japanese Patients with Undiagnosed Ataxia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Spastic paraplegia 7 (SPG7) is an autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in SPG7. It is predominantly characterized by adult-onset slowly progressive spastic paraparesis. While SPG7 presenting with ataxia with or without spasticity is relatively common in Europe and North America, it is considered rare in Japan. This study aimed to identify SPG7 patients among those with undiagnosed ataxia within the Japanese population.
Methods We retrospectively selected 351 patients with undiagnosed ataxia, excluding those with secondary and common spinocerebellar ataxia. Whole-exome sequence analysis was conducted, and homozygosity of the identified variants was confirmed using droplet digital polymerase chain reaction (ddPCR).
Results Among the 351 patients, 2 were diagnosed with SPG7, and homozygosity was confirmed by ddPCR. Both patients carried homozygous pathogenic variants in SPG7: c.1948G>A, p.Asp650Asn, and c.1192C>T, p.Arg398Ter (NM_003119.4). Clinically, both patients presented with progressive ataxia. In addition, Patient 1 exhibited partial ophthalmoplegia and spastic paraparesis, whereas Patient 2 demonstrated cerebellar ataxia without spasticity.
Conclusion The rarity of SPG7 in Japan may be attributed to variation in the minor allele frequency of the c.1529C>T, p.Ala510Val variant, which is more prevalent in Europe and North America than in other areas. en-copyright= kn-copyright= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HinoRimi en-aut-sei=Hino en-aut-mei=Rimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujinoGo en-aut-sei=Fujino en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaiYuto en-aut-sei=Sakai en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=K. IwataNobue en-aut-sei=K. Iwata en-aut-mei=Nobue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, International University of Health and Welfare Mita Hospital kn-affil= affil-num=6 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, International University of Health and Welfare Mita Hospital kn-affil= affil-num=9 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=cerebellar ataxia kn-keyword=cerebellar ataxia en-keyword=spastic paraparesis kn-keyword=spastic paraparesis en-keyword=whole-exome sequence analysis kn-keyword=whole-exome sequence analysis en-keyword=SPG7 kn-keyword=SPG7 END start-ver=1.4 cd-journal=joma no-vol=472 cd-vols= no-issue= article-no= start-page=123486 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical, neuroimaging and genetic findings in the Japanese case series of CLCN2-related leukoencephalopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Biallelic loss-of-function variants in CLCN2 lead to CLCN2-related leukoencephalopathy (CC2L), also called leukoencephalopathy with ataxia (LKPAT). CC2L is characterized clinically by a spectrum of clinical presentations including childhood- to adult-onset mild ataxia, spasticity, cognitive decline, and vision loss as well as typical MRI findings of symmetrical high signal intensities on the DWIs/T2WIs of the middle cerebellar peduncles (MCPs). We searched for pathogenic variants of CLCN2 in a case series of undiagnosed leukoencephalopathy accompanied by MCP signs, which led to the identification of four Japanese patients with CC2L. All the patients carried at least one allele of c.61dupC (p.Leu21Profs*27) in CLCN2, including compound heterozygosity with either the novel pathogenic variant c.983 + 2 T > A or the previously reported pathogenic variant c.1828C > T (p.Arg610*). Of note, all the four previously reported cases from Japan also harbored c.61dupC, and no reports of this variant have been documented from outside Japan. The allele frequency of c.61dupC in the Japanese population is 0.002152, raising the possibility of a relatively high prevalence of CC2L in Japan. Patients in this study developed symptoms after the age of 30, and demonstrated neurological signs including cerebellar ataxia, pyramidal signs, and mild cognitive impairment, consistent with previous reports. One male patient had two children, supporting preserved fertility, and another patient had calcifications in the cerebral and cerebellar surfaces. These findings provide valuable insights into the broader clinical and genetic spectra of CC2L in the Japanese population, and emphasize the importance of considering this disease in the differential diagnoses of leukoencephalopathy with MCP signs. en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChoTakusei en-aut-sei=Cho en-aut-mei=Takusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaruseHiroya en-aut-sei=Naruse en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakiyamaYoshio en-aut-sei=Sakiyama en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SumiKensho en-aut-sei=Sumi en-aut-mei=Kensho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchioNaohiro en-aut-sei=Uchio en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatakeAkane en-aut-sei=Satake en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakiyamaYoshihisa en-aut-sei=Takiyama en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsushitaTakuya en-aut-sei=Matsushita en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Division of Neurology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, Mitsui Memorial Hospital kn-affil= affil-num=8 en-affil=Department of Neurology, Mitsui Memorial Hospital kn-affil= affil-num=9 en-affil=Department of Neurology, Fuefuki Central Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Fuefuki Central Hospital kn-affil= affil-num=11 en-affil=Department of Neurology, Kochi Medical School, Kochi University kn-affil= affil-num=12 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=13 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=14 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=15 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=16 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=17 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=Leukodystrophy kn-keyword=Leukodystrophy en-keyword=CC2L kn-keyword=CC2L en-keyword=CLCN2 kn-keyword=CLCN2 en-keyword=MCP sign kn-keyword=MCP sign END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e261 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol-voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol-voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol-voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC. en-copyright= kn-copyright= en-aut-name=KatadaChikatoshi en-aut-sei=Katada en-aut-mei=Chikatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyamaTetsuji en-aut-sei=Yokoyama en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoTomonori en-aut-sei=Yano en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHaruhisa en-aut-sei=Suzuki en-aut-mei=Haruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurueYasuaki en-aut-sei=Furue en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoKeiko en-aut-sei=Yamamoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoyamaHisashi en-aut-sei=Doyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoikeTomoyuki en-aut-sei=Koike en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaokiMasashi en-aut-sei=Tamaoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawataNoboru en-aut-sei=Kawata en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraoMotohiro en-aut-sei=Hirao en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OgataTakashi en-aut-sei=Ogata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatagiriAtsushi en-aut-sei=Katagiri en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamanouchiTakenori en-aut-sei=Yamanouchi en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KiyokawaHirofumi en-aut-sei=Kiyokawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawakuboHirofumi en-aut-sei=Kawakubo en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KonnoMaki en-aut-sei=Konno en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhashiShinya en-aut-sei=Ohashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KondoYuki en-aut-sei=Kondo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KishimotoYo en-aut-sei=Kishimoto en-aut-mei=Yo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KanoKoichi en-aut-sei=Kano en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MureKanae en-aut-sei=Mure en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HayashiRyuichi en-aut-sei=Hayashi en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IshikawaHideki en-aut-sei=Ishikawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MutoManabu en-aut-sei=Muto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Health and Promotion, National Institute of Public Health kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=6 en-affil=Division of Endoscopy, Hokkaido University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=10 en-affil=Division of Endoscopy, Shizuoka Cancer Center kn-affil= affil-num=11 en-affil=Department of Surgery, National Hospital Organization Osaka National Hospital kn-affil= affil-num=12 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=14 en-affil=Department of Medicine, Division of Gastroenterology, Showa University Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Kumamoto Regional Medical Center kn-affil= affil-num=16 en-affil=Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= affil-num=17 en-affil=Department of Surgery, Kawasaki Municipal Kawasaki Hospital kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Tochigi Cancer Center kn-affil= affil-num=19 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=20 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=22 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital kn-affil= affil-num=23 en-affil=Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine kn-affil= affil-num=24 en-affil=Department of Public Health, Wakayama Medical University School of Medicine kn-affil= affil-num=25 en-affil=Department of Head and Neck Surgery, National Cancer Center Hospital East kn-affil= affil-num=26 en-affil=Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine kn-affil= affil-num=27 en-affil=Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=28 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=alcohol kn-keyword=alcohol en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=field cancerization kn-keyword=field cancerization en-keyword=head and neck cancer kn-keyword=head and neck cancer en-keyword=JEC study kn-keyword=JEC study END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=293 end-page=297 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness of Pallidal Stimulation for Dystonic Storm and Subsequent Ssevere Posterior Reversible Encephalopathy Syndrome in a Patient with GNAO1 Variant en-subtitle= kn-subtitle= en-abstract= kn-abstract=GNAO1 variant affects primarily the brain and neurodevelopment, leading to a range of motor disorders including seizures beginning in infancy and involuntary movements such as dyskinesia and dystonia. Our patient, a 15-year-old Japanese female, began exhibiting involuntary movements at age 4. A de novo missense mutation (NM_020988.3: c.228C>G, NP_066268.1: p.(Asn76Lys)) in the GNAO1 gene was identified when the patient was 15, and during the same year she developed influenza pneumonia, accompanied by dystonic storm. She required intensive care with mechanical ventilation and underwent a tracheostomy. She also developed posterior reversible encephalopathy syndrome. Globus pallidal stimulation was administered, leading to an improvement in the dystonic storm. Early consideration of globus pallidal stimulation is recommended when treating difficult-to-manage dystonic storms. en-copyright= kn-copyright= en-aut-name=KawaiKoji en-aut-sei=Kawai en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanimotoShun en-aut-sei=Tanimoto en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaijoTomoya en-aut-sei=Saijo en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiraideTakuya en-aut-sei=Hiraide en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SaitsuHirotomo en-aut-sei=Saitsu en-aut-mei=Hirotomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Biochemistry, Hamamatsu University School of Medicine kn-affil= affil-num=8 en-affil=Department of Biochemistry, Hamamatsu University School of Medicine kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=GNAO1 variant kn-keyword=GNAO1 variant en-keyword=dystonic storm kn-keyword=dystonic storm en-keyword=globus pallidal stimulation kn-keyword=globus pallidal stimulation en-keyword=posterior reversible encephalopathy syndrome kn-keyword=posterior reversible encephalopathy syndrome END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=1 article-no= start-page=104318 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hypotheses of pathophysiological mechanisms in epileptic encephalopathies: A review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Epileptic encephalopathy (EE) is a serious clinical issue that manifests as part of developmental and epileptic encephalopathy (DEE), particularly in childhood epilepsy. In EE, neurocognitive functions and behavior are impaired by intense epileptiform electroencephalogram (EEG) activity. Hypotheses of pathophysiological mechanisms behind EE are reviewed to contribute to an effective solution for EE.
Review: Current hypotheses are as follows: 1) neuronal dysfunction based on genetic abnormalities that may affect neurocognitive functions and epilepsy separately; 2) impairment of synaptic homeostasis during sleep that may be responsible for DEE/EE with spike-and-wave activation in sleep; 3) abnormal subcortical regulation of the cerebral cortex; 4) abnormal cortical metabolism and hemodynamics with impairment of the neural network including default mode network; 5) neurotransmitter imbalance and disordered neural excitability; 6) the effects of neuroinflammation that may be caused by epileptic seizures and in turn aggravate epileptogenesis; 7) the interaction between physiological and pathological high-frequency EEG activity; etc. The causal relationship between epileptiform EEG activity and neurocognitive dysfunctions is small in DEE based on genetic abnormalities and it is largely unestablished in the other hypothetical mechanisms.
Conclusion: We have not yet found answers to the question of whether the single-central or multiple derangements are present and what seizures and intense epileptiform EEG abnormalities mean in EE. We need to continue our best efforts in both aspects to elucidate the pathophysiological mechanisms of DEE/EE and further develop epilepsy treatment and precision medicine. en-copyright= kn-copyright= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShibataTakashi en-aut-sei=Shibata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaHiroki en-aut-sei=Tsuchiya en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkiyamaMari en-aut-sei=Akiyama en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Pediatrics, Asahigawaso Rehabilitation and Medical Center kn-affil= affil-num=2 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Behavior kn-keyword=Behavior en-keyword=Childhood epilepsy kn-keyword=Childhood epilepsy en-keyword=Cognitive function kn-keyword=Cognitive function en-keyword=Developmental and epileptic encephalopathy kn-keyword=Developmental and epileptic encephalopathy en-keyword=Regression kn-keyword=Regression END start-ver=1.4 cd-journal=joma no-vol=272 cd-vols= no-issue=1 article-no= start-page=36 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic and functional analyses of SPTLC1 in juvenile amyotrophic lateral sclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. Pathogenic variants in SPTLC1, encoding a subunit of serine palmitoyltransferase, cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), and have recently been associated with juvenile ALS. SPTLC1 variants associated with ALS cause elevated levels of sphinganines and ceramides. Reports on ALS associated with SPTLC1 remain limited. This study aimed to investigate the frequency of SPTLC1 variants in ALS and relevant clinical characteristics.
Methods We analyzed whole-exome and whole-genome sequence data from 40 probands with familial ALS and 413 patients with sporadic ALS without previously identified causative variants. Reverse transcription polymerase chain reaction (RT-PCR) analysis and droplet digital PCR (ddPCR) were used to assess splicing and mosaicism, respectively. Plasma sphingolipid levels were quantified to analyze biochemical consequences.
Results The heterozygous c.58G>A, p.Ala20Thr variant was identified in a 21-year-old Japanese female patient presenting with symmetric weakness which slowly progressed over 15 years. RT-PCR analysis showed no splice defects. Plasma sphingolipid levels in the patient were significantly increased compared to her asymptomatic parents. ddPCR revealed that the asymptomatic father harbored a mosaic variant with 17% relative mutant allele abundance in peripheral blood leukocytes.
Conclusions We identified a pathogenic c.58G>A, p.Ala20Thr SPTLC1 variant in a patient with juvenile ALS, likely inherited from an asymptomatic parent with mosaicism. Lipid analysis results are consistent with previous findings on SPTLC1-associated ALS. Further studies are necessary to determine the clinical effect of mosaic variants of SPTLC1. en-copyright= kn-copyright= en-aut-name=OkuboSo en-aut-sei=Okubo en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaruseHiroya en-aut-sei=Naruse en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SudoAtsushi en-aut-sei=Sudo en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EsakiKayoko en-aut-sei=Esaki en-aut-mei=Kayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatakeWataru en-aut-sei=Satake en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GreimelPeter en-aut-sei=Greimel en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShingaiNanoka en-aut-sei=Shingai en-aut-mei=Nanoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OyaYasushi en-aut-sei=Oya en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshikawaTakeo en-aut-sei=Yoshikawa en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Biotechnology and Life Sciences, Faculty of Biotechnology and Life Sciences, Sojo University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Laboratory for Cell Function Dynamics, RIKEN Centre for Brain Sciences kn-affil= affil-num=10 en-affil=Division of Applied Life Science, Graduate School of Engineering, Sojo University kn-affil= affil-num=11 en-affil=Department of Neurology, National Center of Neurology and Psychiatry kn-affil= affil-num=12 en-affil=Laboratory of Molecular Psychiatry, RIKEN Center for Brain Science kn-affil= affil-num=13 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=Juvenile amyotrophic lateral sclerosis kn-keyword=Juvenile amyotrophic lateral sclerosis en-keyword=SPTLC1 kn-keyword=SPTLC1 en-keyword=Sphingolipids kn-keyword=Sphingolipids en-keyword=Mosaicism kn-keyword=Mosaicism END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=6 article-no= start-page=1008 end-page=1016 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240422 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: Lynch syndrome (LS) is a dominantly inherited syndrome characterized by an increased risk for LS associated tumors such as colorectal cancer (CRC) and gastric cancer (GC). However, the clinical benefit of surveillance for GC remains unclear while it has already been recommended for CRC. This study aimed to elucidate the clinical features of GC in Japanese individuals with LS, and the risk of developing multiple GCs to build regional-tailored surveillance programs in LS patients with GC.
Methods: Data on Japanese individuals with LS were retrospectively collected from a single institution. The clinical features of GC, including the cumulative risk of multiple GCs, were analyzed.
Results: Among 96 individuals with LS (MLH1/MSH2/MSH6, 75:20:1), 32 GC lesions were detected in 15 individuals with LS (male/female, 11:4). The median age at initial GC diagnosis was 52.7?y (range: 28?71). Histological examination revealed a predominance of intestinal type (19/24: 87.5%). Moreover, the majority of the GC lesions (82%) were determined to have high-frequency of microsatellite instability. The cumulative risk of individuals with LS developing GC at 70?y was 31.3% (MLH1 36.1%, MSH2 18.0%). Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20?y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively.
Conclusion: Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC. en-copyright= kn-copyright= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=van SchaikThijs A. en-aut-sei=van Schaik en-aut-mei=Thijs A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoYumiko en-aut-sei=Sato en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuganoKokichi en-aut-sei=Sugano en-aut-mei=Kokichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkagiKiwamu en-aut-sei=Akagi en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Genetic Medicine, Kyoundo Hospital, SSasaki Foundation kn-affil= affil-num=8 en-affil=Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center kn-affil= affil-num=9 en-affil=Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= en-keyword=cumulative risk kn-keyword=cumulative risk en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=Japanese individuals kn-keyword=Japanese individuals en-keyword=Lynch syndrome kn-keyword=Lynch syndrome en-keyword=multiple gastric cancers kn-keyword=multiple gastric cancers END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002112 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(?) Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(?) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses. en-copyright= kn-copyright= en-aut-name=HughesHolly R. en-aut-sei=Hughes en-aut-mei=Holly R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BallingerMatthew J. en-aut-sei=Ballinger en-aut-mei=Matthew J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BaoYiming en-aut-sei=Bao en-aut-mei=Yiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BlasdellKim R. en-aut-sei=Blasdell en-aut-mei=Kim R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BrieseThomas en-aut-sei=Briese en-aut-mei=Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrignoneJulia en-aut-sei=Brignone en-aut-mei=Julia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CarreraJean Paul en-aut-sei=Carrera en-aut-mei=Jean Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=De ConinckLander en-aut-sei=De Coninck en-aut-mei=Lander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=de SouzaWilliam Marciel en-aut-sei=de Souza en-aut-mei=William Marciel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=D?rrwaldRalf en-aut-sei=D?rrwald en-aut-mei=Ralf kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ErdinMert en-aut-sei=Erdin en-aut-mei=Mert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FooksAnthony R. en-aut-sei=Fooks en-aut-mei=Anthony R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ForbesKristian M. en-aut-sei=Forbes en-aut-mei=Kristian M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Freitas-Ast?aJuliana en-aut-sei=Freitas-Ast?a en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=GarciaJorge B. en-aut-sei=Garcia en-aut-mei=Jorge B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=GeogheganJemma L. en-aut-sei=Geoghegan en-aut-mei=Jemma L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GrimwoodRebecca M. en-aut-sei=Grimwood en-aut-mei=Rebecca M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HorieMasayuki en-aut-sei=Horie en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HyndmanTimothy H. en-aut-sei=Hyndman en-aut-mei=Timothy H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohneReimar en-aut-sei=Johne en-aut-mei=Reimar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KlenaJohn D. en-aut-sei=Klena en-aut-mei=John D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KooninEugene V. en-aut-sei=Koonin en-aut-mei=Eugene V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KostygovAlexei Y. en-aut-sei=Kostygov en-aut-mei=Alexei Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=LetkoMichael en-aut-sei=Letko en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LiJun-Min en-aut-sei=Li en-aut-mei=Jun-Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=LiuYiyun en-aut-sei=Liu en-aut-mei=Yiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=MartinMaria Laura en-aut-sei=Martin en-aut-mei=Maria Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MullNathaniel en-aut-sei=Mull en-aut-mei=Nathaniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NazarYael en-aut-sei=Nazar en-aut-mei=Yael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=NowotnyNorbert en-aut-sei=Nowotny en-aut-mei=Norbert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NunesM?rcio Roberto Teixeira en-aut-sei=Nunes en-aut-mei=M?rcio Roberto Teixeira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=?klandArnfinn Lodden en-aut-sei=?kland en-aut-mei=Arnfinn Lodden kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=RubbenstrothDennis en-aut-sei=Rubbenstroth en-aut-mei=Dennis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=RussellBrandy J. en-aut-sei=Russell en-aut-mei=Brandy J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SchottEric en-aut-sei=Schott en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SeifertStephanie en-aut-sei=Seifert en-aut-mei=Stephanie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SenCarina en-aut-sei=Sen en-aut-mei=Carina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ShedroffElizabeth en-aut-sei=Shedroff en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=SironenTarja en-aut-sei=Sironen en-aut-mei=Tarja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=SmuraTeemu en-aut-sei=Smura en-aut-mei=Teemu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=TavaresCamila Prestes Dos Santos en-aut-sei=Tavares en-aut-mei=Camila Prestes Dos Santos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=TeshRobert B. en-aut-sei=Tesh en-aut-mei=Robert B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=TilstonNatasha L. en-aut-sei=Tilston en-aut-mei=Natasha L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=TordoNo?l en-aut-sei=Tordo en-aut-mei=No?l kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=VasilakisNikos en-aut-sei=Vasilakis en-aut-mei=Nikos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=WangFei en-aut-sei=Wang en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=WhitmerShannon L.M. en-aut-sei=Whitmer en-aut-mei=Shannon L.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=WolfYuri I. en-aut-sei=Wolf en-aut-mei=Yuri I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=XiaHan en-aut-sei=Xia en-aut-mei=Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=YeGong-Yin en-aut-sei=Ye en-aut-mei=Gong-Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=YeZhuangxin en-aut-sei=Ye en-aut-mei=Zhuangxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=YurchenkoVyacheslav en-aut-sei=Yurchenko en-aut-mei=Vyacheslav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=ZhaoMingli en-aut-sei=Zhao en-aut-mei=Mingli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= affil-num=1 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=2 en-affil=Biological Sciences, Mississippi State University kn-affil= affil-num=3 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Consejo Nacional de Investigaciones Cient?ficas y T?cnicas (CONICET) and Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=5 en-affil=CSIRO Health and Biosecurity kn-affil= affil-num=6 en-affil=Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University kn-affil= affil-num=7 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=8 en-affil=Instituto Conmemorativo Gorgas de Estudios de la Salud kn-affil= affil-num=9 en-affil=Division of Clinical and Epidemiological Virology, KU Leuven kn-affil= affil-num=10 en-affil=Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky kn-affil= affil-num=11 en-affil=Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=12 en-affil=QAAFI, The University of Queensland kn-affil= affil-num=13 en-affil=Robert Koch Institut kn-affil= affil-num=14 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=15 en-affil=Animal and Plant Health Agency (APHA) kn-affil= affil-num=16 en-affil=Department of Biological Sciences, University of Arkansas kn-affil= affil-num=17 en-affil=Embrapa Cassava and Fruits kn-affil= affil-num=18 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=19 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=20 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=21 en-affil=Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University kn-affil= affil-num=22 en-affil=School of Veterinary Medicine, Murdoch University kn-affil= affil-num=23 en-affil=German Federal Institute for Risk Assessment kn-affil= affil-num=24 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=25 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=26 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=27 en-affil=University of Ostrava kn-affil= affil-num=28 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=29 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=30 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=31 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=32 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=33 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=34 en-affil=Department of Natural Sciences, Shawnee State University kn-affil= affil-num=35 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=36 en-affil=College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health kn-affil= affil-num=37 en-affil=Universidade Federal do Par? kn-affil= affil-num=38 en-affil=Pharmaq Analytiq kn-affil= affil-num=39 en-affil=Institute of Diagnostic Virology, Friedrich-Loeffler-Institut kn-affil= affil-num=40 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=41 en-affil=Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science kn-affil= affil-num=42 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=43 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=44 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=45 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=46 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=47 en-affil=Integrated Group of Aquaculture and Environmental Studies, Federal University of Paran? kn-affil= affil-num=48 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=49 en-affil=Department of Microbiology and Immunology, Indiana University School of Medicine kn-affil= affil-num=50 en-affil=Institut Pasteur kn-affil= affil-num=51 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=52 en-affil=University of Queensland kn-affil= affil-num=53 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=54 en-affil=North Carolina State University kn-affil= affil-num=55 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=56 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=57 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=58 en-affil=Institute of Insect Sciences, Zhejiang University kn-affil= affil-num=59 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=60 en-affil=University of Ostrava kn-affil= affil-num=61 en-affil=Department of Pathobiology and Population Sciences, Royal Veterinary College kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=International Consensus Histopathological Criteria for Subtyping Idiopathic Multicentric Castleman Disease Based on Machine Learning Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder classified into three recognized clinical subtypes?idiopathic plasmacytic lymphadenopathy (IPL), TAFRO, and NOS. Although clinical criteria are available for subtyping, diagnostically challenging cases with overlapping histopathological features highlight the need for an improved classification system integrating clinical and histopathological findings. We aimed to develop an objective histopathological subtyping system for iMCD that closely correlates with the clinical subtypes. Excisional lymph node specimens from 94 Japanese iMCD patients (54 IPL, 28 TAFRO, 12 NOS) were analyzed for five key histopathological parameters: germinal center (GC) status, plasmacytosis, vascularity, hemosiderin deposition, and “whirlpool” vessel formation in GC. Using hierarchical clustering, we visualized subgroups and developed a machine learning-based decision tree to differentiate the clinical subtypes and validated it in an external cohort of 12 patients with iMCD. Hierarchical cluster analysis separated the IPL and TAFRO cases into mutually exclusive clusters, whereas the NOS cases were interspersed between them. Decision tree modeling identified plasmacytosis, vascularity, and whirlpool vessel formation as key features distinguishing IPL from TAFRO, achieving 91% and 92% accuracy in the training and test sets, respectively. External validation correctly classified all IPL and TAFRO cases, confirming the reproducibility of the system. Our histopathological classification system closely aligns with the clinical subtypes, offering a more precise approach to iMCD subtyping. It may enhance diagnostic accuracy, guide clinical decision-making for predicting treatment response in challenging cases, and improve patient selection for future research. Further validation of its versatility and clinical utility is required. en-copyright= kn-copyright= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SumiyoshiRemi en-aut-sei=Sumiyoshi en-aut-mei=Remi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UjiieHideki en-aut-sei=Ujiie en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaharaYuri en-aut-sei=Kawahara en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KogaTomohiro en-aut-sei=Koga en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UekiMasao en-aut-sei=Ueki en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LaczkoDorottya en-aut-sei=Laczko en-aut-mei=Dorottya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OksenhendlerEric en-aut-sei=Oksenhendler en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawakamiAtsushi en-aut-sei=Kawakami en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=6 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=9 en-affil=School of Information and Data Sciences, Nagasaki University kn-affil= affil-num=10 en-affil=Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania kn-affil= affil-num=11 en-affil=Department of Clinical Immunology, H?pital Saint-Louis kn-affil= affil-num=12 en-affil=Center for Cytokine Storm Treatment and Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Myeloma Center, University of Arkansas for Medical Sciences kn-affil= affil-num=14 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=15 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=clinical subtype kn-keyword=clinical subtype en-keyword=histopathological criteria kn-keyword=histopathological criteria en-keyword=idiopathic multicentric castleman disease kn-keyword=idiopathic multicentric castleman disease en-keyword=lymphoproliferative disease kn-keyword=lymphoproliferative disease en-keyword=machine-learning kn-keyword=machine-learning END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recent progress in oculopharyngodistal myopathy research from clinical and genetic viewpoints en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oculopharyngodistal myopathy (OPDM) is a rare muscular disorder characterized by ocular symptoms, pharyngeal symptoms, facial weakness, and distal predominant limb muscle weakness. The cause of the disease was unknown for a long time. Recently, however, it has been reported that expansions of CGG or CCG repeats in LRP12, LOC642361/NUTM2B-AS1, GIPC1, NOTCH2NLC, RILPL1, and ABCD3 are the causes of the disease. Cases sometimes present with neurological symptoms, and the clinical spectrum of diseases caused by expansions of CGG or CCG repeats has been proposed to be called FNOP-spectrum disorder after the names of fragile X-associated tremor/ataxia syndrome, neuronal intranuclear inclusion disease, oculopharyngeal myopathy with leukoencephalopathy, and OPDM. In this article, the recent progress in the field of OPDM is reviewed, and remaining issues in OPDM are discussed. en-copyright= kn-copyright= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=oculopharyngodistal myopathy kn-keyword=oculopharyngodistal myopathy en-keyword=CGG repeat kn-keyword=CGG repeat en-keyword=CCG repeat kn-keyword=CCG repeat en-keyword=repeat motif?phenotype correlation kn-keyword=repeat motif?phenotype correlation en-keyword=FNOP-spectrum disorder kn-keyword=FNOP-spectrum disorder END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=147 end-page=155 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunometabolic Regulation of Innate Immunity in Systemic Lupus Erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pathogens or their components can induce long-lasting changes in the behavior of innate immune cells, a process analogous to “training” for future threats or environmental adaptation. However, such training can sometimes have unintended consequences, such as the development of autoimmunity. Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease characterized by the production of autoantibodies and progressive organ damage. Innate immunity plays a central role in its pathogenesis, contributing through impaired clearance of apoptotic cells, excessive type I interferon production, and dysregulated formation of neutrophil extracellular traps. Recent studies have revealed that metabolites and nucleic acids derived from mitochondria, a crucial energy production site, directly regulate type I interferon and anti-inflammatory cytokine production. These insights have fueled interest in targeting metabolic pathways as a novel therapeutic approach for SLE, offering promise for improving long-term patient outcomes. en-copyright= kn-copyright= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=systemic lupus erythematosus kn-keyword=systemic lupus erythematosus en-keyword=interferon kn-keyword=interferon en-keyword=tricarboxylic acid cycle kn-keyword=tricarboxylic acid cycle en-keyword=innate immune memory kn-keyword=innate immune memory en-keyword=trained immunity kn-keyword=trained immunity END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=e70793 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Gastric cancer (GC) in younger patients often exhibits aggressive behavior and a poorer prognosis than that in older patients. Although the clinical differences may stem from oncogenic gene variations, it is unclear whether genetic differences exist between these groups. This study compared the genetic profiles of early- and late-onset GC and evaluated their impact on treatment outcomes.
Methods: We analyzed genetic data from 1284 patients with GC in the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, comparing early-onset (<= 39 years; n = 143) and late-onset (>= 65 years; n = 1141) groups. The influence of TP53 mutations on the time to treatment failure (TTF) with platinum-based chemotherapy and the sensitivity of cancer cells with different TP53 mutation sites to oxaliplatin were assessed in vitro.
Results: Early- and late-onset GC showed distinct genetic profiles, with fewer neoantigen-associated genetic changes observed in early-onset cases. In particular, TP53 has distinct mutation sites; R175H and R273 mutations are more frequent in early- and late-onset GC, respectively. The R175H mutation showed higher sensitivity to oxaliplatin in vitro, consistent with the longer TTF in early-onset patients (17.3 vs. 7.0 months, p = 0.013) when focusing on the patients with TP53 mutations.
Conclusion: Genomic differences, particularly in TP53 mutation sites, between early- and late-onset GC support the need for age-specific treatment strategies. en-copyright= kn-copyright= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirosunaKensuke en-aut-sei=Hirosuna en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OzatoToshiki en-aut-sei=Ozato en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=early-onset gastric cancer kn-keyword=early-onset gastric cancer en-keyword=oxaliplatin kn-keyword=oxaliplatin en-keyword=TP53 kn-keyword=TP53 END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=6 article-no= start-page=2713 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Involvement of a Novel Variant of FGFR1 Detected in an Adult Patient with Kallmann Syndrome in Regulation of Gonadal Steroidogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism. en-copyright= kn-copyright= en-aut-name=SoejimaYoshiaki en-aut-sei=Soejima en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaguchiMarina en-aut-sei=Kawaguchi en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoKoichiro en-aut-sei=Yamamoto en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaMiho en-aut-sei=Yasuda en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UedaKeigo en-aut-sei=Ueda en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataNahoko en-aut-sei=Iwata en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=fibroblast growth factor receptor 1 (FGFR1) kn-keyword=fibroblast growth factor receptor 1 (FGFR1) en-keyword=gynecomastia kn-keyword=gynecomastia en-keyword=Kallmann syndrome (KS) kn-keyword=Kallmann syndrome (KS) en-keyword=osteoporosis and steroidogenesis kn-keyword=osteoporosis and steroidogenesis END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=10 article-no= start-page=1241 end-page=1252 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword “TAFRO” to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO. en-copyright= kn-copyright= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PiersonSheila K. en-aut-sei=Pierson en-aut-mei=Sheila K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwakiNoriko en-aut-sei=Iwaki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawanoMitsuhiro en-aut-sei=Kawano en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraNaoya en-aut-sei=Nakamura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IzutsuKoji en-aut-sei=Izutsu en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiKengo en-aut-sei=Takeuchi en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshizakiKazuyuki en-aut-sei=Yoshizaki en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OksenhendlerEric en-aut-sei=Oksenhendler en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=3 en-affil=Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=4 en-affil=Hematology/Respiratory Medicine, Kanazawa University Graduate School of Medical Science kn-affil= affil-num=5 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Rheumatology, Kanazawa University Graduate School of Medical Science kn-affil= affil-num=7 en-affil=Department of Pathology, Tokai University School of Medicine kn-affil= affil-num=8 en-affil=Department of Hematology, National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Organic Fine Chemicals, Institute of Scientific and Industrial Research, Osaka University kn-affil= affil-num=14 en-affil=Department of Clinical Immunology, H?pital Saint-Louis kn-affil= affil-num=15 en-affil=Myeloma Center, University of Arkansas for Medical Sciences kn-affil= affil-num=16 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=2 article-no= start-page=376 end-page=382 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of pancreatic ductal adenocarcinoma growing within the pancreatic duct mimicking an intraductal tubulopapillary neoplasm en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein report a case of pancreatic ductal adenocarcinoma (PDAC) that developed within the pancreatic duct and was initially diagnosed as an intraductal tubulopapillary neoplasm (ITPN). A 76-year-old man presented with weight loss and main pancreatic duct dilation. The imaging studies revealed a 30-mm hypovascular tumor within the main duct of the pancreatic head. An endoscopic examination with a biopsy revealed high-grade atypical epithelial cells with immunostaining patterns suggestive of ITPN. Following robot-assisted pancreaticoduodenectomy, postoperative pathology revealed conflicting features: nodular/cribriform infiltrations typical of ITPN and non-lobular replacement with scattered infiltrations characteristic of PDAC. A comprehensive genomic profiling test detected KRAS and TP53 mutations, leading to the final diagnosis of PDAC (fT3N1aM0, stage IIB). The patient received adjuvant S-1 chemotherapy and remained recurrence-free for 15 months post-surgery. This case highlights the diagnostic challenges of differentiating intraductal pancreatic tumors and demonstrates the utility of integrating genetic testing with conventional diagnostic modalities for an accurate diagnosis and appropriate treatment selection. en-copyright= kn-copyright= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishidaKenji en-aut-sei=Nishida en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pathology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pathology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=Pancreatic intraductal neoplasms kn-keyword=Pancreatic intraductal neoplasms en-keyword=Pancreatic carcinoma kn-keyword=Pancreatic carcinoma en-keyword=Intraductal tubulopapillary neoplasm kn-keyword=Intraductal tubulopapillary neoplasm en-keyword=Genetic testing kn-keyword=Genetic testing END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=1 end-page=7 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endothelial Cell Polarity in Health and Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Endothelial cell polarity is fundamental to the organization and function of blood vessels, influencing processes such as angiogenesis, vascular stability, and response to shear stress. This review elaborates on the molecular mechanisms that regulate endothelial cell polarity, focusing on key players like the PAR polarity complex and Rho family GTPases. These pathways coordinate the front?rear, apical?basal and planar polarity of endothelial cells, which are essential for the proper formation and maintenance of vascular structures. In health, endothelial polarity ensures not only the orderly development of blood vessels, with tip cells adopting distinct polarities during angiogenesis, but also ensures proper vascular integrity and function. In disease states, however, disruptions in polarity contribute to pathologies such as coronary artery disease, where altered planar polarity exacerbates atherosclerosis, and cancer, where disrupted polarity in tumor vasculature leads to abnormal vessel growth and function. Understanding cell polarity and its disruption is fundamental not only to comprehending how cells interact with their microenvironment and organize themselves into complex, organ-specific tissues but also to developing novel, targeted, and therapeutic strategies for a range of diseases, from cardiovascular disorders to malignancies, ultimately improving patient outcomes. en-copyright= kn-copyright= en-aut-name=ThihaMoe en-aut-sei=Thiha en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HikitaTakao en-aut-sei=Hikita en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=blood vessel kn-keyword=blood vessel en-keyword=endothelial cell kn-keyword=endothelial cell en-keyword=cell polarity kn-keyword=cell polarity en-keyword=atherosclerosis kn-keyword=atherosclerosis en-keyword=cancer kn-keyword=cancer END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=2 article-no= start-page=835 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pathophysiology of Group 3 Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary hypertension associated with lung diseases and/or hypoxia is classified as group 3 in the clinical classification of pulmonary hypertension. The efficacy of existing selective pulmonary vasodilators for group 3 pulmonary hypertension is still unknown, and it is currently associated with a poor prognosis. The mechanisms by which pulmonary hypertension occurs include hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, a decrease in pulmonary vascular beds, endothelial dysfunction, endothelial-to-mesenchymal transition, mitochondrial dysfunction, oxidative stress, hypoxia-inducible factors (HIFs), inflammation, microRNA, and genetic predisposition. Among these, hypoxic pulmonary vasoconstriction and subsequent pulmonary vascular remodeling are characteristic factors involving the pulmonary vasculature and are the focus of this review. Several factors have been reported to mediate vascular remodeling induced by hypoxic pulmonary vasoconstriction, such as HIF-1 alpha and mechanosensors, including TRP channels. New therapies that target novel molecules, such as mechanoreceptors, to inhibit vascular remodeling are awaited. en-copyright= kn-copyright= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TayaSatoshi en-aut-sei=Taya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurodaKazuhiro en-aut-sei=Kuroda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatanosakaYuki en-aut-sei=Katanosaka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pharmacy, Kinjo Gakuin University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=group 3 pulmonary hypertension kn-keyword=group 3 pulmonary hypertension en-keyword=hypoxic pulmonary vasoconstriction kn-keyword=hypoxic pulmonary vasoconstriction en-keyword=pulmonary vascular remodeling kn-keyword=pulmonary vascular remodeling END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=2 article-no= start-page=102575 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and microbiological characteristics of high-level daptomycin-resistant Corynebacterium species: A systematic scoping review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections.
Methods: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including “Corynebacterium”, “Daptomycin", and "Resistance”, in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ?256 μg/mL, were deemed eligible for this review.
Results: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8 %), and prosthetic device-associated infections accounted for 66.7 % of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71 %?100 %) within 24 h of incubation, compared to other Corynebacterium strains.
Conclusion: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Corynebacterium kn-keyword=Corynebacterium en-keyword=Daptomycin kn-keyword=Daptomycin en-keyword=High-level daptomycin resistance kn-keyword=High-level daptomycin resistance en-keyword=pgsA2 kn-keyword=pgsA2 END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue=8 article-no= start-page=881 end-page=896 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD. en-copyright= kn-copyright= en-aut-name=KambaraYui en-aut-sei=Kambara en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunihiroMari en-aut-sei=Kunihiro en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OyamaTadashi en-aut-sei=Oyama en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoAyame en-aut-sei=Sato en-aut-mei=Ayame kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PeltierDaniel en-aut-sei=Peltier en-aut-mei=Daniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ReddyPavan en-aut-sei=Reddy en-aut-mei=Pavan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshinobuMaeda en-aut-sei=Yoshinobu en-aut-mei=Maeda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical School kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Microbiology and Genetics, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Simon Cancer Center, Indiana University School of Medicine kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=17 en-affil=Division of Blood Transfusion, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=20 en-affil=Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine kn-affil= affil-num=21 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=42 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genotypes and phenotypes of neurofibromatosis type 1 patients in Japan: A Hereditary Tumor Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype?phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care. en-copyright= kn-copyright= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiTetsuya en-aut-sei=Okazaki en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukanoChika en-aut-sei=Fukano en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OsumiRisa en-aut-sei=Osumi en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoFumino en-aut-sei=Kato en-aut-mei=Fumino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UrakawaYusaku en-aut-sei=Urakawa en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Genetic Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=8 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=20 article-no= start-page=e70288 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=New Anti-Angiogenic Therapy for Glioblastoma With the Anti-Depressant Sertraline en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aims: Anti-angiogenic therapies prolong patient survival in some malignancies but not glioblastoma. We focused on the relationship between the differentiation of glioma stem like cells (GSCs) into tumor derived endothelial cells (TDECs) and, anti-angiogenic therapy resistance. Especially we aimed to elucidate the mechanisms of drug resistance of TDECs to anti-angiogenic inhibitors and identify novel anti-angiogenic drugs with clinical applications.
Results: The mouse GSCs, 005, were differentiated into TDECs under hypoxic conditions, and TDECs had endothelial cell characteristics independent of the vascular endothelial growth factor (VEGF) pathway. In vivo, inhibition of the VEGF pathway had no anti-tumor effect and increased the percentage of TDECs in the 005 mouse model. Novel anti-angiogenic drugs for glioblastoma were evaluated using a tube formation assay and a drug repositioning strategy with existing blood-brain barrier permeable drugs. Drug screening revealed that the antidepressant sertraline inhibited tube formation of TDECs. Sertraline was administered to differentiated TDECs in vitro and 005 mouse models in vivo to evaluate genetic changes by RNA-Seq and tumor regression effects by immunohistochemistry and MRI. Sertraline reduced Lama4 and Ang2 expressions of TDEC, which play an important role in non-VEGF-mediated angiogenesis in tumors. The combination of a VEGF receptor inhibitor axitinib, and sertraline improved survival and reduced tumor growth in the 005 mouse model.
Conclusion: Collectively, our findings showed the diversity of tumor vascular endothelial cells across VEGF and non-VEGF pathways led to anti-angiogenic resistance. The combination of axitinib and sertraline can represent an effective anti-angiogenic therapy for glioblastoma with safe, low cost, and fast availability. en-copyright= kn-copyright= en-aut-name=TsuboiNobushige en-aut-sei=Tsuboi en-aut-mei=Nobushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UnedaAtsuhito en-aut-sei=Uneda en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SurugaYasuki en-aut-sei=Suruga en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoYuji en-aut-sei=Matsumoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHideki en-aut-sei=Matsui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KurozumiKazuhiko en-aut-sei=Kurozumi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurosurgery, Hamamatsu University School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= en-keyword=anti-angiogenic therapy kn-keyword=anti-angiogenic therapy en-keyword=antidepressant sertraline kn-keyword=antidepressant sertraline en-keyword=drug repositioning kn-keyword=drug repositioning en-keyword=glioblastoma kn-keyword=glioblastoma en-keyword=tumor derived endothelial cells kn-keyword=tumor derived endothelial cells END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=1 article-no= start-page=1 end-page=11 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tectal glioma: clinical, radiological, and pathological features, and the importance of molecular analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tectal glioma (TG) is a rare lower grade glioma (LrGG) that occurs in the tectum, mainly affecting children. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. We conducted a retrospective review of cases clinically diagnosed as TG and treated at our institute between January 2005 and March 2023. Six cases were identified and the median age was 30.5 years. Four patients underwent biopsy and two patients underwent tumor resection. Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. The integrated diagnosis, according to the fifth edition of the World Health Organization Classification of Tumours of the central nervous system, included two cases of PA and one case each of diffuse high-grade glioma; diffuse midline glioma H3 K27-altered; glioblastoma; and circumscribed astrocytic glioma. Among the three patients who underwent molecular evaluation, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation. en-copyright= kn-copyright= en-aut-name=ImotoRyoji en-aut-sei=Imoto en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiranoShuichiro en-aut-sei=Hirano en-aut-mei=Shuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KemmotsuNaoya en-aut-sei=Kemmotsu en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SurugaYasuki en-aut-sei=Suruga en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KegoyaYasuhito en-aut-sei=Kegoya en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InoueYohei en-aut-sei=Inoue en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UmedaTsuyoshi en-aut-sei=Umeda en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HokamaMadoka en-aut-sei=Hokama en-aut-mei=Madoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SatomiKaishi en-aut-sei=Satomi en-aut-mei=Kaishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IchimuraKoichi en-aut-sei=Ichimura en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Pathology, Kyorin University Faculty of Medicine kn-affil= affil-num=17 en-affil=Department of Brain Disease Translational Research, Juntendo University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Tectal glioma kn-keyword=Tectal glioma en-keyword=Lower grade glioma kn-keyword=Lower grade glioma en-keyword=KRAS kn-keyword=KRAS en-keyword=H3 K27M kn-keyword=H3 K27M en-keyword=Molecular analysis kn-keyword=Molecular analysis END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=5 article-no= start-page=377 end-page=386 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic Efficacy of the Albumin Grade in Patients with Hepatocellular Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously found that “albumin grade”, formerly called the “ALBS grade,” demonstrated significant capability for prognostic stratification in hepatocellular carcinoma (HCC) patients treated with lenvatinib. The purpose of the present study was to compare the performance of the albumin grade with that of the modified albumin-bilirubin (mALBI) grade in predicting overall survival of HCC patients with different BCLC stages and treatment types. We enrolled 7,645 Japanese patients newly diagnosed with HCC using the Akaike information criteria (AIC), likelihood ratio, and C-index in different Barcelona Clinic Liver Cancer (BCLC) stages and treatments. The albumin grade showed similar and slightly better performance than the mALBI grade for BCLC stage 0 and A and especially for patients who underwent curative surgery and ablation. In patients treated with transcatheter arterial chemoembolization, molecular targeted agents, and the best supportive care, the mALBI grade had better performance than the albumin grade. However, the differences of the indices were very small in all scenarios. Overall, the albumin grade was comparable in efficacy to the mALBI grade, showing particular benefit for patients with early-stage HCC. en-copyright= kn-copyright= en-aut-name=HiranoYuichi en-aut-sei=Hirano en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KariyamaKazuya en-aut-sei=Kariyama en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraokaAtsushi en-aut-sei=Hiraoka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShiotaShohei en-aut-sei=Shiota en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WakutaAkiko en-aut-sei=Wakuta en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaSatoshi en-aut-sei=Yasuda en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToyodaHidenori en-aut-sei=Toyoda en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsujiKunihiko en-aut-sei=Tsuji en-aut-mei=Kunihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HatanakaTakeshi en-aut-sei=Hatanaka en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KakizakiSatoru en-aut-sei=Kakizaki en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NaganumaAtsushi en-aut-sei=Naganuma en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TadaToshifumi en-aut-sei=Tada en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ItobayashiEi en-aut-sei=Itobayashi en-aut-mei=Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshikawaToru en-aut-sei=Ishikawa en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaNoritomo en-aut-sei=Shimada en-aut-mei=Noritomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakaguchiKoichi en-aut-sei=Takaguchi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TsutsuiAkemi en-aut-sei=Tsutsui en-aut-mei=Akemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NaganoTakuya en-aut-sei=Nagano en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ImaiMichitaka en-aut-sei=Imai en-aut-mei=Michitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NakamuraShinichiro en-aut-sei=Nakamura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KumadaTakashi en-aut-sei=Kumada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=Real-Life Practice Experts for HCC (RELPEC) Study Group in Japan en-aut-sei=Real-Life Practice Experts for HCC (RELPEC) Study Group in Japan en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=4 en-affil=Gastroenterology Center, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital kn-affil= affil-num=9 en-affil=Center of Gastroenterology, Teine Keijinkai Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Saiseikai Maebashi Hospital kn-affil= affil-num=11 en-affil=Department of Clinical Research, NHO Takasaki General Medical Center kn-affil= affil-num=12 en-affil=Department of Gastroenterology, NHO Takasaki General Medical Center kn-affil= affil-num=13 en-affil=Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Asahi General Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Saiseikai Niigata Hospital kn-affil= affil-num=16 en-affil=Division of Gastroenterology and Hepatology, Otakanomori Hospital kn-affil= affil-num=17 en-affil=Department of Hepatology, Kagawa Prefectural Central Hospital kn-affil= affil-num=18 en-affil=Department of Hepatology, Kagawa Prefectural Central Hospital kn-affil= affil-num=19 en-affil=Department of Hepatology, Kagawa Prefectural Central Hospital kn-affil= affil-num=20 en-affil=Department of Gastroenterology, Niigata Cancer Center Hospital kn-affil= affil-num=21 en-affil=Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=22 en-affil=Department of Nursing, Gifu Kyoritsu University kn-affil= affil-num=23 en-affil= kn-affil= en-keyword=albumin grade kn-keyword=albumin grade en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=modified albumin-bilirubin grade kn-keyword=modified albumin-bilirubin grade END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=5 article-no= start-page=371 end-page=376 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phenotypic and Genetic Characteristics of Carbapenemase-Producing Enterobacterales Isolates at Okayama University Hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 μg/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control. en-copyright= kn-copyright= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiMakoto en-aut-sei=Miyoshi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=I Putu Bayu Mayura en-aut-sei=I Putu Bayu Mayura en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Clinical Microbiology, Faculty of Medicine, Udayana University kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=carbapenemase-producing enterobacterales kn-keyword=carbapenemase-producing enterobacterales en-keyword=carbapenemase-resistant enterobacterales kn-keyword=carbapenemase-resistant enterobacterales en-keyword=Silent pandemic kn-keyword=Silent pandemic en-keyword=whole genome sequence kn-keyword=whole genome sequence END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=3 article-no= start-page=271 end-page=279 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202406 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Humidified High-Flow Nasal Cannula Oxygen Therapy with a Pulmonary Infection Control Window as a Ventilation Switching Indication in Combination with Atomizing Inhalation of Terbutaline on the Lung Function of Patients with Acute Exacerbation of COPD en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated how humidified high-flow nasal cannula oxygen therapy (HFNC) with a pulmonary infection control (PIC) window as a ventilation switching indication in combination with atomizing inhalation of terbutaline affects the lung function of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We examined 140 hospitalized AECOPD patients randomized to control and observation groups. Conventional supportive therapy and invasive mechanical ventilation with tracheal intubation were conducted in both groups, with a PIC window as the indication for ventilation switching. Noninvasive positive pressure ventilation (NIPPV) plus atomizing inhalation of terbutaline was used in the control group. In the observation group, HFNC combined with atomizing inhalation of terbutaline was used. Compared to the control group, after 48-hr treatment and treatment completion, the observation group had significantly increased levels of lung function indicators (maximal voluntary ventilation [MVV] plus forced vital capacity [FVC], p<0.05) and oxygen metabolism indicators (arterial oxygen partial pressure [PaO2], arterial oxygen content [CaO2], and oxygenation index, p<0.05). The comparison of the groups revealed that the levels of airway remodeling indicators (matrix metalloproteinase-2 [MMP-2], tissue inhibitor of metalloproteinase 2 [TIMP-2] plus MMP-9) and inflammatory indicators (interferon gamma [IFN-γ] together with interleukin-17 [IL-17], IL-10 and IL-4) were significantly lower after 48 h of treatment as well as after treatment completion (both p<0.05). These results demonstrate that HFNC with a PIC window as the indication for ventilation switching combined with atomizing inhalation of terbutaline can relieve the disorder of oxygen metabolism and correct airway hyper-reactivity. en-copyright= kn-copyright= en-aut-name=YeMengjiao en-aut-sei=Ye en-aut-mei=Mengjiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhangRenwei en-aut-sei=Zhang en-aut-mei=Renwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Respiratory and Critical Care Medicine, Tiantai Hospital of Traditional Chinese Medicine kn-affil= affil-num=2 en-affil=Department of Respiratory and Critical Care Medicine, Tiantai Hospital of Traditional Chinese Medicine kn-affil= en-keyword=chronic obstructive pulmonary disease kn-keyword=chronic obstructive pulmonary disease en-keyword=inhalation kn-keyword=inhalation en-keyword=oxygen therapy kn-keyword=oxygen therapy en-keyword=pulmonary function kn-keyword=pulmonary function en-keyword=ventilation kn-keyword=ventilation END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=5 article-no= start-page=e0302537 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240521 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The use of artificial intelligence in induced pluripotent stem cell-based technology over 10-year period: A systematic scoping review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Stem cell research, particularly in the domain of induced pluripotent stem cell (iPSC) technology, has shown significant progress. The integration of artificial intelligence (AI), especially machine learning (ML) and deep learning (DL), has played a pivotal role in refining iPSC classification, monitoring cell functionality, and conducting genetic analysis. These enhancements are broadening the applications of iPSC technology in disease modelling, drug screening, and regenerative medicine. This review aims to explore the role of AI in the advancement of iPSC research.
Methods
In December 2023, data were collected from three electronic databases (PubMed, Web of Science, and Science Direct) to investigate the application of AI technology in iPSC processing.
Results
This systematic scoping review encompassed 79 studies that met the inclusion criteria. The number of research studies in this area has increased over time, with the United States emerging as a leading contributor in this field. AI technologies have been diversely applied in iPSC technology, encompassing the classification of cell types, assessment of disease-specific phenotypes in iPSC-derived cells, and the facilitation of drug screening using iPSC. The precision of AI methodologies has improved significantly in recent years, creating a foundation for future advancements in iPSC-based technologies.
Conclusions
Our review offers insights into the role of AI in regenerative and personalized medicine, highlighting both challenges and opportunities. Although still in its early stages, AI technologies show significant promise in advancing our understanding of disease progression and development, paving the way for future clinical applications. en-copyright= kn-copyright= en-aut-name=VoQuan Duy en-aut-sei=Vo en-aut-mei=Quan Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IdaToshihiro en-aut-sei=Ida en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Faculty of Medicine, Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Faculty of Medicine, Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Medicine, Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Medicine, Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=10 article-no= start-page=e174618 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro -tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph -circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC. en-copyright= kn-copyright= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShanQuisheng en-aut-sei=Shan en-aut-mei=Quisheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MizukawaNobuyoshi en-aut-sei=Mizukawa en-aut-mei=Nobuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IidaSeiji en-aut-sei=Iida en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Universit kn-affil= affil-num=6 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=3 article-no= start-page=169 end-page=174 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recent advances in CGG repeat diseases and a proposal of fragile X-associated tremor/ataxia syndrome, neuronal intranuclear inclusion disease, and oculophryngodistal myopathy (FNOP) spectrum disorder en-subtitle= kn-subtitle= en-abstract= kn-abstract=While whole genome sequencing and long-read sequencing have become widely available, more and more focuses are on noncoding expanded repeats. Indeed, more than half of noncoding repeat expansions related to diseases have been identified in the five years. An exciting aspect of the progress in this field is an identification of a phenomenon called repeat motif?phenotype correlation. Repeat motif?phenotype correlation in noncoding repeat expansion diseases is first found in benign adult familial myoclonus epilepsy. The concept is extended in the research of CGG repeat expansion diseases. In this review, we focus on newly identified CGG repeat expansion diseases, update the concept of repeat motif?phenotype correlation in CGG repeat expansion diseases, and propose a clinical concept of FNOP (fragile X-associated tremor/ataxia syndrome, neuronal intranuclear inclusion disease, and oculopharyngodistal myopathy)-spectrum disorder, which shares clinical features and thus probably share some common disease pathophysiology, to further facilitate discussion and progress in this field. en-copyright= kn-copyright= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=151 end-page=161 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors. en-copyright= kn-copyright= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmoriToshinori en-aut-sei=Omori en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiuKazuhisa en-aut-sei=Sugiu en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MochizukiYusuke en-aut-sei=Mochizuki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DemiyaKoji en-aut-sei=Demiya en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=soft-tissue sarcoma kn-keyword=soft-tissue sarcoma en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=BCL-xL kn-keyword=BCL-xL END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=7 article-no= start-page=1298 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation en-subtitle= kn-subtitle= en-abstract= kn-abstract=A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features. en-copyright= kn-copyright= en-aut-name=OhsawaKumiko en-aut-sei=Ohsawa en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GionYuka en-aut-sei=Gion en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SawadaKeisuke en-aut-sei=Sawada en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashiMorihiro en-aut-sei=Higashi en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokuhiraMichihide en-aut-sei=Tokuhira en-aut-mei=Michihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaruJun-Ichi en-aut-sei=Tamaru en-aut-mei=Jun-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences kn-affil= affil-num=6 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=7 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=8 en-affil=Department of Hematology, Japan Community Health Care Organization Saitama Medical Center kn-affil= affil-num=9 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=10 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=classic Hodgkin lymphoma kn-keyword=classic Hodgkin lymphoma en-keyword=methotrexate kn-keyword=methotrexate en-keyword=immunodeficiency kn-keyword=immunodeficiency en-keyword=programmed cell death-ligand 1 kn-keyword=programmed cell death-ligand 1 en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis END start-ver=1.4 cd-journal=joma no-vol=167 cd-vols= no-issue=1 article-no= start-page=201 end-page=210 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs.
Methods We searched Medline through the PubMed database using two search terms: “G34” and “glioma”, between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan?Meier curves and logistic regression.
Results A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs.
Conclusions In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. en-copyright= kn-copyright= en-aut-name=KegoyaYasuhito en-aut-sei=Kegoya en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYohei en-aut-sei=Inoue en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KoizumiShinichiro en-aut-sei=Koizumi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KurozumiKazuhiko en-aut-sei=Kurozumi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoNorio en-aut-sei=Yamamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanakaYoshihiro en-aut-sei=Tanaka en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurosurgery, Hamamatsu University School of Medicine kn-affil= affil-num=8 en-affil=Department of Neurosurgery, Hamamatsu University School of Medicine kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Division of Epidemiology, Graduate School of Public Health, Shizuoka Graduate University of Public Health kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Diffuse hemispheric gliomas, H3 G34-mutation kn-keyword=Diffuse hemispheric gliomas, H3 G34-mutation en-keyword=Midline invasion kn-keyword=Midline invasion en-keyword=Frontal lobe kn-keyword=Frontal lobe en-keyword=Gross total resection kn-keyword=Gross total resection END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=1 article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders en-subtitle= kn-subtitle= en-abstract= kn-abstract=Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/ lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary. en-copyright= kn-copyright= en-aut-name=OkataniTakeshi en-aut-sei=Okatani en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EgusaYuria en-aut-sei=Egusa en-aut-mei=Yuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaSayako en-aut-sei=Yoshida en-aut-mei=Sayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=methotrexate-associated lymphoproliferative disorders kn-keyword=methotrexate-associated lymphoproliferative disorders en-keyword=other iatrogenic immunodeficiency-associated lymphoproliferative disorders kn-keyword=other iatrogenic immunodeficiency-associated lymphoproliferative disorders en-keyword=lymphoproliferative disorders arising in immune deficiency/dysregulation kn-keyword=lymphoproliferative disorders arising in immune deficiency/dysregulation en-keyword=NOTCH1 kn-keyword=NOTCH1 END start-ver=1.4 cd-journal=joma no-vol=186 cd-vols= no-issue= article-no= start-page=4189 end-page=4203.e22 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thrombopoietin (THPO or TPO) is an essential cytokine for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation. Here, we report the 3.4 ? resolution cryoelectron microscopy structure of the extracellular TPO-TPO receptor (TpoR or MPL) signaling complex, revealing the basis for homodimeric MPL activation and providing a structural rationalization for genetic loss-of-function thrombocytopenia mutations. The structure guided the engineering of TPO variants (TPOmod) with a spectrum of signaling activities, from neutral antagonists to partial- and super-agonists. Partial agonist TPOmod decoupled JAK/STAT from ERK/AKT/CREB activation, driving a bias for megakaryopoiesis and platelet production without causing significant HSC expansion in mice and showing superior maintenance of human HSCs in vitro. These data demonstrate the functional uncoupling of the two primary roles of TPO, highlighting the potential utility of TPOmod in hematology research and clinical HSC transplantation. en-copyright= kn-copyright= en-aut-name=TsutsumiNaotaka en-aut-sei=Tsutsumi en-aut-mei=Naotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasoumiZahra en-aut-sei=Masoumi en-aut-mei=Zahra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JamesSophie C. en-aut-sei=James en-aut-mei=Sophie C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TuckerJulie A. en-aut-sei=Tucker en-aut-mei=Julie A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WinkelmannHauke en-aut-sei=Winkelmann en-aut-mei=Hauke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GreyWilliam en-aut-sei=Grey en-aut-mei=William kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PictonLora K. en-aut-sei=Picton en-aut-mei=Lora K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MossLucie en-aut-sei=Moss en-aut-mei=Lucie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WilsonSteven C. en-aut-sei=Wilson en-aut-mei=Steven C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CaveneyNathanael A. en-aut-sei=Caveney en-aut-mei=Nathanael A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=JudeKevin M. en-aut-sei=Jude en-aut-mei=Kevin M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GatiCornelius en-aut-sei=Gati en-aut-mei=Cornelius kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=PiehlerJacob en-aut-sei=Piehler en-aut-mei=Jacob kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HitchcockIan S. en-aut-sei=Hitchcock en-aut-mei=Ian S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GarciaK. Christopher en-aut-sei=Garcia en-aut-mei=K. Christopher kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=3 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=4 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=5 en-affil=Department of Biology/Chemistry and Center of Cellular Nanoanalytics, Osnabr?ck University kn-affil= affil-num=6 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=7 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= affil-num=8 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=9 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= affil-num=10 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= affil-num=11 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= affil-num=12 en-affil=Department of Structural Biology, Stanford University School of Medicine kn-affil= affil-num=13 en-affil=Department of Biology/Chemistry and Center of Cellular Nanoanalytics, Osnabr?ck University kn-affil= affil-num=14 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=15 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= en-keyword=thrombopoietin kn-keyword=thrombopoietin en-keyword=TpoR kn-keyword=TpoR en-keyword=c-MPL kn-keyword=c-MPL en-keyword=structure kn-keyword=structure en-keyword=cryo-EM kn-keyword=cryo-EM en-keyword=signaling kn-keyword=signaling en-keyword=JAK-STAT kn-keyword=JAK-STAT en-keyword=mTOR kn-keyword=mTOR en-keyword=hematopoiesis kn-keyword=hematopoiesis en-keyword=ligand engineering kn-keyword=ligand engineering END start-ver=1.4 cd-journal=joma no-vol=194 cd-vols= no-issue=5 article-no= start-page=e63525 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiological characteristics of skeletal growth in neonates and infants with achondroplasia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH. en-copyright= kn-copyright= en-aut-name=MiyaharaDaisuke en-aut-sei=Miyahara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AgoYuko en-aut-sei=Ago en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FutagawaNatsuko en-aut-sei=Futagawa en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiguchiYousuke en-aut-sei=Higuchi en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriwakeTadashi en-aut-sei=Moriwake en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaHiroyuki en-aut-sei=Tanaka en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Orthopedics, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Orthopedics, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Iwakuni Clinical Center, National Hospital Organization kn-affil= affil-num=10 en-affil=Department of Pediatrics, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bone development kn-keyword=bone development en-keyword=dwarfism kn-keyword=dwarfism en-keyword=growth kn-keyword=growth en-keyword=infant kn-keyword=infant en-keyword=radiography kn-keyword=radiography END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=843 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ligneous periodontitis exacerbated by Beh?et’s disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C?>?T: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia.
We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity.
Case presentation This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C?>?T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Beh?et's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated.
Conclusions Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C?>?T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions. en-copyright= kn-copyright= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiAnna en-aut-sei=Hirai en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IdeguchiHidetaka en-aut-sei=Ideguchi en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoFumino en-aut-sei=Kato en-aut-mei=Fumino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OgawaTatsuo en-aut-sei=Ogawa en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakadoiTakato en-aut-sei=Nakadoi en-aut-mei=Takato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Clinical Genomic Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Ligneous periodontitis kn-keyword=Ligneous periodontitis en-keyword=Plasminogen deficiency kn-keyword=Plasminogen deficiency en-keyword=PLG kn-keyword=PLG en-keyword=Behcet's disease kn-keyword=Behcet's disease en-keyword=Gingival hyperplasia kn-keyword=Gingival hyperplasia END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=589 end-page=593 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cochlear Implantation in the Poorer-Hearing Ear Is a Reasonable Choice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Choosing the optimal side for cochlear implantation (CI) remains a major challenge because of the lack of evidence. We investigated the choice of the surgery side for CI (i.e., the better- or poorer-hearing ear) in patients with asymmetric hearing. Audiological records of 74 adults with a unilateral hearing aid who had undergone surgery at Okayama University Hospital were reviewed. The definition of ‘better-hearing ear’ was the aided ear, and the unaided ear was considered the poorer-hearing ear. We performed a multiple regression analysis to identify potential predictors of speech recognition performance after unilateral CI in the patients. Fifty-two patients underwent CI in the poorer-hearing ear. The post-Ci bimodal hearing rate was far higher in the poorer-ear group (77.8% vs. 22.2%). A multivariate analysis revealed that prelingual hearing loss and the patient’s age at CI significantly affected the speech recognition outcome (beta coefficients: 24.6 and ?0.33, 95% confidence intervals [11.75-37.45] and [?0.58 to ?0.09], respectively), but the CI surgery side did not (?6.76, [?14.92-1.39]). Unilateral CI in the poorer-hearing ear may therefore be a reasonable choice for adult patients with postlingual severe hearing loss, providing a greater opportunity for postoperative bimodal hearing. en-copyright= kn-copyright= en-aut-name=OmichiRyotaro en-aut-sei=Omichi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KariyaShin en-aut-sei=Kariya en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaedaYukihide en-aut-sei=Maeda en-aut-mei=Yukihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaKunihiro en-aut-sei=Fukushima en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaYuko en-aut-sei=Kataoka en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugayaAkiko en-aut-sei=Sugaya en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishizakiKazunori en-aut-sei=Nishizaki en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medial University kn-affil= affil-num=3 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Hayashima Clinic of Otolaryngology and Dermatology kn-affil= affil-num=5 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cochlear implantation kn-keyword=cochlear implantation en-keyword=poorer hearing ear kn-keyword=poorer hearing ear en-keyword=better hearing ear kn-keyword=better hearing ear en-keyword=hearing aids kn-keyword=hearing aids en-keyword=speech recognition kn-keyword=speech recognition END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=20 article-no= start-page=15450 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children. en-copyright= kn-copyright= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EitokuTakahiro en-aut-sei=Eitoku en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=biomarker kn-keyword=biomarker en-keyword=coronary artery lesions kn-keyword=coronary artery lesions en-keyword=Kawasaki disease kn-keyword=Kawasaki disease en-keyword=multisystem inflammatory syndrome in children kn-keyword=multisystem inflammatory syndrome in children en-keyword=nitric oxide kn-keyword=nitric oxide en-keyword=nitrosative stress kn-keyword=nitrosative stress en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=systemic inflammation kn-keyword=systemic inflammation en-keyword=vascular endothelial dysfunction kn-keyword=vascular endothelial dysfunction END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=517 end-page=525 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer. en-copyright= kn-copyright= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimotoKosaku en-aut-sei=Morimoto en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TerasawaHiroyuki en-aut-sei=Terasawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamazakiTatsuhiro en-aut-sei=Yamazaki en-aut-mei=Tatsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=BRCA kn-keyword=BRCA en-keyword=FOLFIRINOX kn-keyword=FOLFIRINOX en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=progression-free survival kn-keyword=progression-free survival en-keyword=pathogenic variant kn-keyword=pathogenic variant END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=7 article-no= start-page=739 end-page=753 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mixed Response to Cancer Immunotherapy is Driven by Intratumor Heterogeneity and Differential Interlesion Immune Infiltration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some patients experience mixed response to immunotherapy, whose biological mechanisms and clinical impact have been obscure. We obtained two tumor samples from lymph node (LN) metastatic lesions in a same patient. Whole exome sequencing for the both tumors and single-cell sequencing for the both tumor-infiltrating lymphocytes (TIL) demonstrated a significant difference in tumor clonality and TILs' characteristics, especially exhausted T-cell clonotypes, although a close relationship between the tumor cell and T-cell clones were observed as a response of an overlapped exhausted T-cell clone to an overlapped neoantigen. To mimic the clinical setting, we generated a mouse model of several clones from a same tumor cell line. Similarly, differential tumor clones harbored distinct TILs, and one responded to programmed cell death protein 1 (PD-1) blockade but the other did not in this model. We further conducted cohort study (n = 503) treated with PD-1 blockade monotherapies to investigate the outcome of mixed response. Patients with mixed responses to PD-1 blockade had a poor prognosis in our cohort. Particularly, there were significant differences in both tumor and T-cell clones between the primary and LN lesions in a patient who experienced tumor response to anti-PD-1 mAb followed by disease progression in only LN metastasis. Our results underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome.
Significance: Several patients experience mixed responses to immunotherapies, but the biological mechanisms and clinical significance remain unclear. Our results from clinical and mouse studies underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome. en-copyright= kn-copyright= en-aut-name=MorinagaTakao en-aut-sei=Morinaga en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaxNicolas en-aut-sei=Sax en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaKazuo en-aut-sei=Yamashita en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OharaYuuki en-aut-sei=Ohara en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuwataTakeshi en-aut-sei=Kuwata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YukamiHiroki en-aut-sei=Yukami en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawazoeAkihito en-aut-sei=Kawazoe en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShitaraKohei en-aut-sei=Shitara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmedaYoshiyasu en-aut-sei=Umeda en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KawaharaYu en-aut-sei=Kawahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KiniwaYukiko en-aut-sei=Kiniwa en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=EnokidaTomohiro en-aut-sei=Enokida en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TaharaMakoto en-aut-sei=Tahara en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HasegawaYoshinori en-aut-sei=Hasegawa en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=NishikawaHiroyoshi en-aut-sei=Nishikawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=2 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=3 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=KOTAI Biotechnologies Inc kn-affil= affil-num=6 en-affil=KOTAI Biotechnologies Inc kn-affil= affil-num=7 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=8 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=10 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=11 en-affil=Department of Pathology, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Genetic Medicineand Services, National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=14 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=15 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=16 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=17 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=18 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=19 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=20 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=21 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=22 en-affil=Department of Dermatology, Shinshu University School of Medicine kn-affil= affil-num=23 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=24 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=26 en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=27 en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=28 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=29 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=30 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=31 en-affil=Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center kn-affil= affil-num=32 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=4 article-no= start-page=395 end-page=405 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=?0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=?0.258, t=?2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=?0.247, p=0.019) and antipsychotic treatment duration (ρ=?0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia. en-copyright= kn-copyright= en-aut-name=PavlovicMarko en-aut-sei=Pavlovic en-aut-mei=Marko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BabicDragan en-aut-sei=Babic en-aut-mei=Dragan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RastovicPejana en-aut-sei=Rastovic en-aut-mei=Pejana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArapovicJurica en-aut-sei=Arapovic en-aut-mei=Jurica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MartinacMarko en-aut-sei=Martinac en-aut-mei=Marko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JakovacSanja en-aut-sei=Jakovac en-aut-mei=Sanja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BarbaricRomana en-aut-sei=Barbaric en-aut-mei=Romana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=University Hospital Center Mostar, University of Mostar kn-affil= affil-num=2 en-affil=University Hospital Center Mostar, University of Mostar kn-affil= affil-num=3 en-affil=University Hospital Center Mostar, University of Mostar kn-affil= affil-num=4 en-affil=University Hospital Center Mostar, University of Mostar kn-affil= affil-num=5 en-affil=Health Care Center Mostar, University of Mostar kn-affil= affil-num=6 en-affil=University Hospital Center Mostar, University of Mostar kn-affil= affil-num=7 en-affil=University Hospital Center Mostar, University of Mostar kn-affil= en-keyword=tumor necrosis factor-alpha kn-keyword=tumor necrosis factor-alpha en-keyword=schizophrenia kn-keyword=schizophrenia en-keyword=psychopathology kn-keyword=psychopathology en-keyword=immune system kn-keyword=immune system END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=4 article-no= start-page=365 end-page=370 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=GATA4 rs61277615, rs73203482, and rs35813172 in Newborns with Transposition of the Great Arteries en-subtitle= kn-subtitle= en-abstract= kn-abstract=Congenital heart disease is the most common malformative pathology in newborns, with a worldwide incidence at 0.4-5%. We investigated the possible relationship between variations in nucleotide sequences and specific cardiac malformations in the GATA-binding factor 4 (GATA4) exon 1 region by using Sanger sequencing. Forty-four newborns from a third-level neonatal intensive care unit who were diagnosed with nonsyndromic, ductal-dependent congenital heart disease (i.e., transposition of the great arteries or ductal-dependent coarctation of the aorta) were enrolled. Their DNA was extracted using commercial methods and tested using the multiplex ligation-dependent probe amplification (MLPA) technique. The Sanger sequencing for GATA4 exon 1 in the newborns’ DNA identified rs61277615, rs73203482, and rs35813172 variants not reported in the ClinVar archive of human variations in newborns previously diagnosed with transposition of the great arteries (n=5) and coarctation of the aorta (n=1). The identification of these novel variants in newborns with transposition of the great arteries or ductal-dependent coarctation of the aorta may be the first step in determining the variants’ contribution to the occurrence of congenital heart disease. However, these results may be inconclusive, since the observed variants within GATA4 gene were not previously reported. en-copyright= kn-copyright= en-aut-name=MoldovanElena en-aut-sei=Moldovan en-aut-mei=Elena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=B?nescuClaudia en-aut-sei=B?nescu en-aut-mei=Claudia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CucereaManuela en-aut-sei=Cucerea en-aut-mei=Manuela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoldovanValeriu en-aut-sei=Moldovan en-aut-mei=Valeriu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GozarLiliana en-aut-sei=Gozar en-aut-mei=Liliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Pu?ca?iuLucian en-aut-sei=Pu?ca?iu en-aut-mei=Lucian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Pediatric Intensive Care Unit, Cardiovascular and Transplant Emergency Institute of T?rgu Mure? kn-affil= affil-num=2 en-affil=George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T?rgu Mure? kn-affil= affil-num=3 en-affil=George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T?rgu Mure? kn-affil= affil-num=4 en-affil=T?rgu Mure? County Emergency Clinical Hospital kn-affil= affil-num=5 en-affil=George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T?rgu Mure? kn-affil= affil-num=6 en-affil=George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T?rgu Mure? kn-affil= en-keyword=transposition of the great arteries kn-keyword=transposition of the great arteries en-keyword=ductal-dependent coarctation of the aorta kn-keyword=ductal-dependent coarctation of the aorta en-keyword=GATA4 kn-keyword=GATA4 en-keyword=MLPA kn-keyword=MLPA en-keyword=Sanger sequencing kn-keyword=Sanger sequencing END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=3 article-no= start-page=323 end-page=330 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases. en-copyright= kn-copyright= en-aut-name=MakinoKeigo en-aut-sei=Makino en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiranoShuichiro en-aut-sei=Hirano en-aut-mei=Shuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SurugaYasuki en-aut-sei=Suruga en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishidaKenji en-aut-sei=Nishida en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Pediatrics, Okayama University Hospital kn-affil= affil-num=8 en-affil=Departments of Pathology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Departments of Pathology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=pediatric brain tumor kn-keyword=pediatric brain tumor en-keyword=genome-wide DNA methylation kn-keyword=genome-wide DNA methylation en-keyword=MYCN kn-keyword=MYCN END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=3 article-no= start-page=255 end-page=262 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Prevalence of Antimicrobial Resistance in Okayama from a National Database between 2018 and 2021 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Antimicrobial resistance is an emerging global threat that must be addressed using a multidisciplinary approach. This study aimed to raise awareness of high-level antimicrobial-resistant (AMR) pathogens in Japan by comparing their recent prevalences among prefectures, particularly Okayama. Data for the isolation proportions of meropenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae, and levofloxacin-resistant E. coli and K. pneumoniae were collected from the Japan Nosocomial Infections Surveillance, a national database sponsored by the Japanese Ministry of Health, Labour, and Welfare, between 2018 and 2021. The average isolated proportions of the seven AMR pathogens were higher in Okayama compared to other prefectures: the worst (19.9%) was meropenem-resistant P. aeruginosa, the sixth worst (57.2%) was methicillin-resistant S. aureus, the eighth worst (3.3%) was vancomycin-resistant E. faecium, the second (37.8%) and fifth worst (17.6%) were cefotaxime-resistant E. coli and K. pneumoniae, respectively, and the fourth (49.9%) and third worst (8.7%) were levofloxacin-resistant E. coli and K. pneumoniae, respectively. Our study highlights the notably high prevalences of representative AMR pathogens in Okayama, suggesting the need for fundamental infection prevention and control by healthcare professionals, promoting antimicrobial stewardship, and educating undergraduates and postgraduates in Okayama. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=antimicrobial stewardship kn-keyword=antimicrobial stewardship en-keyword=epidemiology kn-keyword=epidemiology en-keyword=infection prevention and control kn-keyword=infection prevention and control en-keyword=Japan Nosocomial Infections Surveillance kn-keyword=Japan Nosocomial Infections Surveillance END start-ver=1.4 cd-journal=joma no-vol=178 cd-vols= no-issue= article-no= start-page=1 end-page=10 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored.
Materials and methods: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined.
Results: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity.
Conclusion: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME. en-copyright= kn-copyright= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirabaeAtsuko en-aut-sei=Hirabae en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakadaKenji en-aut-sei=Takada en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KumonHiromi en-aut-sei=Kumon en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=17 en-affil=Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University kn-affil= affil-num=18 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=EGFR mutation kn-keyword=EGFR mutation en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=Antitumor immunity kn-keyword=Antitumor immunity en-keyword=Non-inflamed tumor kn-keyword=Non-inflamed tumor en-keyword=Ad-SGE-REIC kn-keyword=Ad-SGE-REIC en-keyword=Gene therapy kn-keyword=Gene therapy en-keyword=PD-1 kn-keyword=PD-1 END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=1 article-no= start-page=57 end-page=64 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development, Disappearance, and Clinical Course of Melanosis Coli: Sex Differences in the Progression of Severity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Melanosis coli (MC) is an acquired colorectal disorder visualized as colonic mucosa pigmentation. Disease severity is confirmed based on MC depth, shape, and coloration, although the clinical course is not fully understood. This study sought to clarify characteristics of MC development and disappearance and to investigate its clinical course and severity. Contributors to MC grade progression were explored. This study reviewed MC cases discovered via colonoscopy at a single institution over a 10-year period. Of all 216 MC cases, 17 developing and 10 disappearing cases were detected. Anthranoid laxative use was a key factor: 29.4% of the developing cases had used such agents before the initial MC diagnosis, whereas 40% of disappearing cases had discontinued anthranoids prior to detection of MC disappearance. Among 70 grade I cases, progression to grade II occurred in 16 cases during a mean follow-up of 3.67±2.1 years (rate of progression=22.8%). Males more commonly showed progressive than stable grade I cases, and the probability of progression was higher for male than for female cases. An association between anthranoid administration and MC presence was presumed, and grade I MC was found to progress in severity over 5 years. en-copyright= kn-copyright= en-aut-name=KatsumataRyo en-aut-sei=Katsumata en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ManabeNoriaki en-aut-sei=Manabe en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MonobeYasumasa en-aut-sei=Monobe en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AyakiMaki en-aut-sei=Ayaki en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuehiroMitsuhiko en-aut-sei=Suehiro en-aut-mei=Mitsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujitaMinoru en-aut-sei=Fujita en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamadaTomoari en-aut-sei=Kamada en-aut-mei=Tomoari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawamotoHirofumi en-aut-sei=Kawamoto en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HarumaKen en-aut-sei=Haruma en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center kn-affil= affil-num=2 en-affil=Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center kn-affil= affil-num=3 en-affil=Pathology, Kawasaki Medical School General Medical Center kn-affil= affil-num=4 en-affil=Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center kn-affil= affil-num=5 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center kn-affil= affil-num=6 en-affil=Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center kn-affil= affil-num=7 en-affil=Health Care Medicine, Kawasaki Medical School General Medical Center kn-affil= affil-num=8 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center kn-affil= affil-num=9 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center kn-affil= en-keyword=melanosis kn-keyword=melanosis en-keyword=sex characteristics kn-keyword=sex characteristics en-keyword=laxatives kn-keyword=laxatives en-keyword=colorectal neoplasms kn-keyword=colorectal neoplasms en-keyword=colonoscopy kn-keyword=colonoscopy END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=1 article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevalence of Inducible Macrolide, Lincosamide, and Streptogramin B (inducible MLSB) Resistance in Clindamycin-Susceptible Staphylococcus aureus at Okayama University Hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Inducible resistance to the macrolide, lincosamide, and streptogramin B (iMLSB) antibiotic family is a latent mechanism for antimicrobial resistance in Staphylococcus aureus. We here investigated the frequency and genotypic profiles of iMLSB resistance in clindamycin (CLDM)-susceptible S. aureus isolated in Okayama University Hospital from June 2020 to June 2021. We phenotypically screened the iMLSB resistance via D-zone test and performed PCR testing for the erythromycin ribosomal methylase (erm) genes: ermA and ermC. Among 432 CLDM-susceptible S. aureus isolates, 138 (31.9%) exhibited an iMLSB-resistance phenotype, with methicillinresistant S. aureus isolates (MRSA; 61 isolates: 58.6%) exhibiting higher positivity than methicillin-sensitive S. aureus isolates (MSSA; 77 isolates: 23.5%) (p<0.001). Male patients had a higher frequency of iMLSB resistance than females (OR [95%CI]: 1.8 [1.2-2.8]; p=0.007). Genotypically, ermA predominated in both MSSA (70.1%) and MRSA (86.9%) compared to ermC (14.3% in MSSA and 11.5% in MRSA). A single strain of MRSA possessed both ermA and ermC, while 12 (15.6%) MSSA isolates were negative for both ermA and ermC, suggesting the presence of other genetic mechanisms. Collectively, these results show that approximately 33% of CLDM-susceptible S. aureus isolates at our university hospital exhibited iMLSB resistance, predominantly caused by ermA in both MSSA and MRSA. en-copyright= kn-copyright= en-aut-name=NaharLutfun en-aut-sei=Nahar en-aut-mei=Lutfun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NadaTakahiro en-aut-sei=Nada en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=clindamycin kn-keyword=clindamycin en-keyword= erm kn-keyword= erm en-keyword=D-zone test kn-keyword=D-zone test en-keyword=inducible MLSB kn-keyword=inducible MLSB END start-ver=1.4 cd-journal=joma no-vol=478 cd-vols= no-issue=8 article-no= start-page=1779 end-page=1790 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC. en-copyright= kn-copyright= en-aut-name=MatsumotoJun en-aut-sei=Matsumoto en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimotoAnzu en-aut-sei=Nishimoto en-aut-mei=Anzu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatariShogo en-aut-sei=Watari en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UekiHideo en-aut-sei=Ueki en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShiromizuShoya en-aut-sei=Shiromizu en-aut-mei=Shoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataNaohiro en-aut-sei=Iwata en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KajizonoMakoto en-aut-sei=Kajizono en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiyoshiMasachika en-aut-sei=Fujiyoshi en-aut-mei=Masachika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AriyoshiNoritaka en-aut-sei=Ariyoshi en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Urology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=4 en-affil=Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pharmacy, Tottori University Hospital kn-affil= affil-num=11 en-affil=Department of Pharmaceuticals Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Urology, Faculty of Medicine, Shimane University kn-affil= affil-num=14 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Genetic variant kn-keyword=Genetic variant en-keyword=Polymorphism kn-keyword=Polymorphism en-keyword=Renal cell carcinoma kn-keyword=Renal cell carcinoma en-keyword=Survival kn-keyword=Survival en-keyword=UDP-glucuronosyltransferase kn-keyword=UDP-glucuronosyltransferase END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=58 end-page=60 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel ABCD1 mutation detected in a symptomatic female carrier of adrenoleukodystrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=X-linked adrenoleukodystrophy (ALD) is a major peroxisomal disorder, in which abnormal accumulation of very long-chain fatty acids (VLCFA) caused by ABCD1 gene mutation results in damage to the peripheral and central nervous system and adrenal gland. While affected male patients with ALD present severe neurological symptoms, some female carriers slowly develop spastic gait and urinary incontinence. We report a case of a symptomatic female ALD carrier with a novel ABCD1 gene mutation. She has developed progressive gait disturbance since age 40, and her father and sister had similar symptoms. When admitted to our hospital at age 66, blood analysis showed slight increase of VLCFA, and DNA analysis of ABCD1 gene revealed a novel heterozygous missense mutation (c.1700 A>C, p.Gln567Pro). The genetic testing for ABCD1 gene can be considered in female patients over middle age presenting spastic gait, because female ALD carriers tend to be symptomatic beyond age 60. en-copyright= kn-copyright= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TairaYuki en-aut-sei=Taira en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiRyo en-aut-sei=Sasaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TadokoroKoh en-aut-sei=Tadokoro en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShimozawaNobuyuki en-aut-sei=Shimozawa en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Genomics Research, Life Science Research Center, Gifu university kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=adrenoleukodystrophy kn-keyword=adrenoleukodystrophy en-keyword=symptomatic female carriers kn-keyword=symptomatic female carriers en-keyword=spastic paraplegia kn-keyword=spastic paraplegia en-keyword=ABCD1 kn-keyword=ABCD1 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=673 end-page=678 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Handling of Germline Findings in Clinical Comprehensive Cancer Genomic Profiling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Patients found to have presumed germline pathogenic variants (PGPVs) during comprehensive genomic profiling (CGP) require genetic counseling (GC) referrals. We retrospectively investigated the outcomes of patients with PGPVs. Among 159 patients who underwent CGP, we recommended GC for the 16 patients with PGPVs (3 with [FG group] and 13 without [G Group] a family/personal history of hereditary cancer) as well as for the 8 patients with no PGPVs, but a history (F group); 2 (67%), 5 (38%), and 3 (38%) patients received GC in the FG, G, and F groups, respectively. Germline testing results were positive in 1 and 2 patients of the FG and G groups, respectively. Among the patients recommended for GC, 58% did not receive GC due to lack of interest, poor performance status, or death. CGP contributes to the identification of germline variants in patients without a history of hereditary cancer. However, the proportion of patients who undergo GC should be improved. en-copyright= kn-copyright= en-aut-name=Okazawa-SakaiMika en-aut-sei=Okazawa-Sakai en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoYasuko en-aut-sei=Yamamoto en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkamuraMiki en-aut-sei=Okamura en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyawakiSatoko en-aut-sei=Miyawaki en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishinaTomohiro en-aut-sei=Nishina en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeharaKazuhiro en-aut-sei=Takehara en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HyodoIchinosuke en-aut-sei=Hyodo en-aut-mei=Ichinosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhsumiShozo en-aut-sei=Ohsumi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cancer Genomic Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hereditary Tumors, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Cancer Genomic Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Cancer Genomic Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Department of Clinical Research Center, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Cancer Genomic Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=11 en-affil=Department of Hereditary Tumors, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=12 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=hereditary cancer kn-keyword=hereditary cancer en-keyword=germline findings kn-keyword=germline findings en-keyword=presumed germline pathogenic variant(s) kn-keyword=presumed germline pathogenic variant(s) en-keyword=genetic counseling kn-keyword=genetic counseling END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=661 end-page=671 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001?3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01). en-copyright= kn-copyright= en-aut-name=AbeYuko en-aut-sei=Abe en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashiwabaraKosuke en-aut-sei=Kashiwabara en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsurutaniJunji en-aut-sei=Tsurutani en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitadaMasahiro en-aut-sei=Kitada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiMasato en-aut-sei=Takahashi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoHiroaki en-aut-sei=Kato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KikawaYuichiro en-aut-sei=Kikawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakataEiko en-aut-sei=Sakata en-aut-mei=Eiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HasegawaYoshie en-aut-sei=Hasegawa en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SaitoTsuyoshi en-aut-sei=Saito en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IwasaTsutomu en-aut-sei=Iwasa en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakashimaTsutomu en-aut-sei=Takashima en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AiharaTomohiko en-aut-sei=Aihara en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MukaiHirofumi en-aut-sei=Mukai en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine surgery, Kawasaki Medical School Hospital kn-affil= affil-num=3 en-affil=Clinical Research Promotion Center, University of Tokyo Hospital kn-affil= affil-num=4 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=5 en-affil=Breast Disease Center, Asahikawa Medical University Hospital kn-affil= affil-num=6 en-affil=Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=7 en-affil=Department of Breast Surgery, Teine Keijinkai Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgery, Kansai Medical University Hospital kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Niigata City General Hospital kn-affil= affil-num=10 en-affil=Department of Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=11 en-affil=Department of Breast Surgery, Hachinohe City Hospital kn-affil= affil-num=12 en-affil=Department of Breast Surgery, Japanese Red Cross Saitama Hospital kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Breast Center, Aihara Hospital kn-affil= affil-num=16 en-affil=Department of Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=17 en-affil=Breast Oncology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=18 en-affil=Department of Breast and Endocrine surgery, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Breast surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=20 en-affil=Department of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=metastatic breast cancer kn-keyword=metastatic breast cancer en-keyword=taxane-induced peripheral neuropathy kn-keyword=taxane-induced peripheral neuropathy en-keyword=chemotherapy-induced peripheral neuropathy kn-keyword=chemotherapy-induced peripheral neuropathy en-keyword=nab-paclitaxel kn-keyword=nab-paclitaxel en-keyword=single nucleotide polymorphism kn-keyword=single nucleotide polymorphism END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=5 article-no= start-page=489 end-page=502 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Insights into Mesenchymal Signatures in Glioblastoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma (GBM) is a fatal primary malignant brain tumor in adults. Despite decades of research, the prognosis for GBM patients is still disappointing. One major reason for the intense therapeutic resistance of GBM is inter- and intra-tumor heterogeneity. GBM-intrinsic transcriptional profiling has suggested the presence of at least three subtypes of GBM: the proneural, classic, and mesenchymal subtypes. The mesenchymal subtype is the most aggressive, and patients with the mesenchymal subtype of primary and recurrent tumors tend to have a worse prognosis compared with patients with the other subtypes. Furthermore, GBM can shift from other subtypes to the mesenchymal subtype over the course of disease progression or recurrence. This phenotypic transition is driven by diverse tumor-intrinsic molecular mechanisms or microenvironmental factors. Thus, better understanding of the plastic nature of mesenchymal transition in GBM is pivotal to developing new therapeutic strategies. In this review, we provide a comprehensive overview of the current understanding of the elements involved in the mesenchymal transition of GBM and discuss future perspectives. en-copyright= kn-copyright= en-aut-name=MatsumotoYuji en-aut-sei=Matsumoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchikawaTomotsugu en-aut-sei=Ichikawa en-aut-mei=Tomotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurozumiKazuhiko en-aut-sei=Kurozumi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Hamamatsu University Hospital kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=glioma kn-keyword=glioma en-keyword=glioblastoma kn-keyword=glioblastoma en-keyword=mesenchymal subtype kn-keyword=mesenchymal subtype en-keyword=mesenchymal transition kn-keyword=mesenchymal transition en-keyword=heterogeneity kn-keyword=heterogeneity END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=11 article-no= start-page=1578 end-page=1581 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High frequency of extended-spectrum beta-lactamase-producing Enterobacteriaceae carriers at a Japanese long-term care hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Long-term care hospitals (LTCHs) are at a high risk for the inflow and spread of antimicrobial resistance (AMR) pathogens. However, owing to limited laboratory resources, little is known about the extent to which AMR organisms are endemic.

Methods: We performed active surveillance for carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in newly admitted patients at Marugame Medical Center, a nearly 200-bedded LTCH located in Kagawa, Japan. From August to December 2021, we tested stool samples from patients wearing diapers and confirmed the genetic variants using specific PCR assays. We also collected clinical variables and compared them between AMR carriers and non-carriers.

Results: Stool samples were collected from 75 patients, with a median age of 84 years. CRE strain was not detected, but 37 strains of ESBL-E were isolated from 32 patients (42.7%). During the study period, 4.9% of in-hospital patients (37 per 756 patients) were identified to be ESBL-E carriers in the routine microbiological processing, suggesting that active surveillance detected approximately 9-fold more ESBL-E carriers. The bla(CTM-M-9) group was the most common (38.5%), followed by the bla(TEM) (26.9%). The clinical backgrounds of the ESBL-E non-carriers and carriers were not significantly different.

Conclusion: Our active screening demonstrated that nearly half of the patients hospitalized or transferred to a Japanese LTCH were colonized with ESBL-E. We highlight the enforcement of universal basic infection prevention techniques at LTCHs where patients carrying AMR pathogens gather. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnishiYuji en-aut-sei=Onishi en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinoharaNatsumi en-aut-sei=Shinohara en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokuyasuMayumi en-aut-sei=Tokuyasu en-aut-mei=Mayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImanishiAki en-aut-sei=Imanishi en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaharLutfun en-aut-sei=Nahar en-aut-mei=Lutfun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Clinical Laboratory, Marugame Medical Center kn-affil= affil-num=3 en-affil=Clinical Laboratory, Marugame Medical Center kn-affil= affil-num=4 en-affil=Department of Nursing, Marugame Medical Center kn-affil= affil-num=5 en-affil=Department of Nursing, Marugame Medical Center kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Aging society kn-keyword=Aging society en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Carbapenem-resistant Enterobacteriaceae kn-keyword=Carbapenem-resistant Enterobacteriaceae en-keyword=Extended-spectrum beta-lactamase kn-keyword=Extended-spectrum beta-lactamase en-keyword=Infection prevention and control kn-keyword=Infection prevention and control END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=4 article-no= start-page=479 end-page=483 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Liquid Biopsy Revealed HBOC Pedigree and Led to Medical Management Among the Relatives en-subtitle= kn-subtitle= en-abstract= kn-abstract=A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient’s daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance. en-copyright= kn-copyright= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SogawaReimi en-aut-sei=Sogawa en-aut-mei=Reimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasuokaKayoko en-aut-sei=Hasuoka en-aut-mei=Kayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UrakawaYusaku en-aut-sei=Urakawa en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KochiMariko en-aut-sei=Kochi en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Nursing, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Center for Comprehensive Genomic Medicine, Okayama University Hospital Biobank, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=hereditary breast and ovarian cancer (HBOC) kn-keyword=hereditary breast and ovarian cancer (HBOC) en-keyword=BRCA 1 kn-keyword=BRCA 1 en-keyword=presumed germline pathogenic variants (PGPV) kn-keyword=presumed germline pathogenic variants (PGPV) en-keyword=germline findings kn-keyword=germline findings en-keyword=cancer precision medicine kn-keyword=cancer precision medicine END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=4 article-no= start-page=399 end-page=408 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gene Expression Profiling between Patient Groups with High and Low Ki67 Levels after Short-term Preoperative Aromatase Inhibitor Treatment for Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=According to a recent report, a low Ki67 level after short-term preoperative hormone therapy (post-Ki67) might suggest a more favorable prognosis compared with a high post-Ki67 level in patients with hormone receptorpositive/human epidermal growth factor 2-negative (HR+/HER2?) breast cancer with high levels of Ki67. This study aimed to evaluate the pre-treatment genetic differences between these two patient groups. Forty-five luminal B-like patients were stratified into two groups, namely, a group with high (H→H) and one with low (H→L) Ki67 levels after short-term preoperative aromatase inhibitor (AI) treatment. We compared pre-treatmentgene expression profiles between the two groups. In gene level analysis, there was no significant difference between the two groups by the class comparison test. In pathway analysis, five metabolism-related gene sets were significantly upregulated in the H→L group (p?0.05). In the search for novel targets, five genes (PARP, BRCA2, FLT4, CDK6, and PDCD1LG2) showed significantly higher expression in the H→H group (p?0.05). Several metabolism-related pathways were associated with sensitivity to AI. In the future, it will be necessary to seek out new therapeutic strategies for the poor prognostic group with high post-Ki67. en-copyright= kn-copyright= en-aut-name=KajiwaraYukiko en-aut-sei=Kajiwara en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamotoTakayuki en-aut-sei=Iwamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhuYidan en-aut-sei=Zhu en-aut-mei=Yidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KochiMariko en-aut-sei=Kochi en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=short-term hormone therapy kn-keyword=short-term hormone therapy en-keyword=gene expression profiling kn-keyword=gene expression profiling en-keyword=Ki-67 kn-keyword=Ki-67 en-keyword=targeted therapy kn-keyword=targeted therapy END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=4 article-no= start-page=359 end-page=371 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Systemic lupus erythematosus (SLE) is a potentially fatal systemic autoimmune disease, and its etiology involves both genetic and environmental factors such as sex hormone imbalance, genetic predisposition, epigenetic regulation, and immunological factors. Dysregulation of microRNA (miRNA) is suggested to be one of the epigenetic factors in SLE. miRNA is a 22-nucleotide single-stranded noncoding RNA that contributes to post-transcriptional modulation of gene expression. miRNA targeting therapy has been suggested to be useful for the treatment of cancers and other diseases. Gene knockout and miRNA targeting therapy have been demonstrated to improve SLE disease activity in mice. However, these approaches have not yet reached the level of clinical application. miRNA targeting therapy is limited by the fact that each miRNA has multiple targets. In addition, the expression of certain miRNAs may differ among cell tissues within a single SLE patient. This limitation can be overcome by targeted delivery and chemical modifications. In the future, further research into miRNA chemical modifications and delivery systems will help us develop novel therapeutic agents for SLE. en-copyright= kn-copyright= en-aut-name=Hiramatsu-AsanoSumie en-aut-sei=Hiramatsu-Asano en-aut-mei=Sumie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=systemic lupus erythematosus kn-keyword=systemic lupus erythematosus en-keyword=miRNA kn-keyword=miRNA en-keyword=miRNA targeting therapy kn-keyword=miRNA targeting therapy END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=3 article-no= start-page=323 end-page=328 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of a Solitary Cortical Tuber with No Other Manifestations of Tuberous Sclerosis Complex Mimicking Focal Cortical Dysplasia Type II with Calcification en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case. en-copyright= kn-copyright= en-aut-name=HosomotoKakeru en-aut-sei=Hosomoto en-aut-mei=Kakeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiKoji en-aut-sei=Kawai en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkazakiYosuke en-aut-sei=Okazaki en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoYuki en-aut-sei=Hyodo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibataTakashi en-aut-sei=Shibata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Diagnostic Pathology,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cortical tuber kn-keyword=cortical tuber en-keyword=epilepsy kn-keyword=epilepsy en-keyword=focal cortical dysplasia kn-keyword=focal cortical dysplasia en-keyword=transmantle sign kn-keyword=transmantle sign en-keyword=tuberous sclerosis complex kn-keyword=tuberous sclerosis complex END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=228 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adenomatoid mesothelioma arising from the diaphragm: a case report and review of the literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Adenomatoid mesothelioma is a rare subtype of malignant mesothelioma that can be confused with adenomatoid tumors, which are classified as benign. The clinical features and optimal management of adenomatoid mesothelioma have not been elucidated in the literature. In this report, we present an extremely rare case of adenomatoid mesothelioma that developed on the peritoneal surface of the diaphragm as well as a literature review of adenomatoid mesothelioma in the abdominal cavity. Case presentation The patient was a 61-year-old Japanese woman who had undergone resection of a malignant peripheral nerve sheath tumor of the hand 18 years prior. She was diagnosed with clinical stage I lung adenocarcinoma on follow-up chest radiography. Simultaneously, a 20-mm enhancing nodule with slow growth on the right diaphragm was detected on contrast-enhanced computed tomography. She presented no specific clinical symptoms. At this point, the lesion was suspected to be a hypervascular tumor of borderline malignancy, such as a solitary fibrous tumor. After a left upper lobectomy for lung adenocarcinoma, she was referred to our department, and laparoscopic tumor resection was performed. Adenomatoid tumors were also considered based on the histopathological and immunohistochemical analyses, but we made the final diagnosis of adenomatoid mesothelioma using the results of the genetic profile. The patient remains alive, with no recurrence noted 6 months after surgery. Conclusion We encountered a valuable case of adenomatoid mesothelioma of peritoneal origin. There are some previously reported cases of adenomatoid mesothelioma and adenomatoid tumors that may need to be recategorized according to the current classification. It is important to accumulate and share new findings to clarify the clinicopathological characteristics and genetic status of adenomatoid mesothelioma. en-copyright= kn-copyright= en-aut-name=KawabeKenta en-aut-sei=Kawabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoHiroki en-aut-sei=Sato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitanoAkiko en-aut-sei=Kitano en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KumanoKenjiro en-aut-sei=Kumano en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KagouraMasaaki en-aut-sei=Kagoura en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Center for Graduate Medical Education, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= en-keyword=Adenomatoid mesothelioma kn-keyword=Adenomatoid mesothelioma en-keyword=Adenomatoid tumor kn-keyword=Adenomatoid tumor en-keyword=Mesothelial tumor kn-keyword=Mesothelial tumor en-keyword=Diaphragm kn-keyword=Diaphragm en-keyword=Peritoneal kn-keyword=Peritoneal END start-ver=1.4 cd-journal=joma no-vol=132 cd-vols= no-issue=7 article-no= start-page=e140869 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202241 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tankyrase represses autoinflammation through the attenuation of TLR2 signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dysregulation of Toll-like receptor (TLR) signaling contributes to the pathogenesis of autoimmune diseases. Here, we provide genetic evidence that tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, negatively regulates TLR2 signaling. We show that mice lacking tankyrase in myeloid cells developed severe systemic inflammation with high serum inflammatory cytokine levels. We provide mechanistic evidence that tankyrase deficiency resulted in tyrosine phosphorylation and activation of TLR2 and show that phosphorylation of tyrosine 647 within the TIR domain by SRC and SYK kinases was critical for TLR2 stabilization and signaling. Last, we show that the elevated cytokine production and inflammation observed in mice lacking tankyrase in myeloid cells were dependent on the adaptor protein 3BP2, which is required for SRC and SYK activation. These data demonstrate that tankyrase provides a checkpoint on the TLR-mediated innate immune response. en-copyright= kn-copyright= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DimitriouIoannis D. en-aut-sei=Dimitriou en-aut-mei=Ioannis D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=La RoseJose en-aut-sei=La Rose en-aut-mei=Jose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LimMelissa en-aut-sei=Lim en-aut-mei=Melissa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CamilleriSusan en-aut-sei=Camilleri en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LawNapoleon en-aut-sei=Law en-aut-mei=Napoleon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AdissuHibret A. en-aut-sei=Adissu en-aut-mei=Hibret A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TongJiefei en-aut-sei=Tong en-aut-mei=Jiefei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoranMichael F. en-aut-sei=Moran en-aut-mei=Michael F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ChruscinskiAndrzej en-aut-sei=Chruscinski en-aut-mei=Andrzej kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HeFang en-aut-sei=He en-aut-mei=Fang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SadaKen-ei en-aut-sei=Sada en-aut-mei=Ken-ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=RottapelRobert en-aut-sei=Rottapel en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Princess Margaret Cancer Centre, University Health Network, University of Toronto kn-affil= affil-num=3 en-affil=Princess Margaret Cancer Centre, University Health Network, University of Toronto kn-affil= affil-num=4 en-affil=Princess Margaret Cancer Centre, University Health Network, University of Toronto kn-affil= affil-num=5 en-affil=Centre for Modeling Human Disease, Toronto Centre for Phenogenomics kn-affil= affil-num=6 en-affil=Centre for Modeling Human Disease, Toronto Centre for Phenogenomics kn-affil= affil-num=7 en-affil=Labcorp Early Development Laboratories Inc. kn-affil= affil-num=8 en-affil=Program in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics kn-affil= affil-num=9 en-affil=Program in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics kn-affil= affil-num=10 en-affil=Multi-Organ Transplant Program, University Health Network kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Princess Margaret Cancer Centre, University Health Network, University of Toronto kn-affil= END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=203 end-page=215 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression. en-copyright= kn-copyright= en-aut-name=MasudaTomoya en-aut-sei=Masuda en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoYuuri en-aut-sei=Hashimoto en-aut-mei=Yuuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IedaTakeshi en-aut-sei=Ieda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Oncolys BioPharma Inc. kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=EMT kn-keyword=EMT en-keyword=TGF-β kn-keyword=TGF-β en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=E1A kn-keyword=E1A END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=137 end-page=143 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changes in Plasma Clozapine Levels after Smoking Cessation in Japanese Inpatients with Schizophrenia: A Retrospective Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although reported for Caucasians, changes in plasma clozapine levels after smoking cessation in East Asians remain unclear. We here investigated plasma clozapine levels before and after smoking cessation in Japanese inpatients with schizophrenia. We conducted a retrospective chart review of 14 inpatients with schizophrenia who were being treated with clozapine between June 1, 2019, and July 31, 2019 and who were smokers as of July 1, 2019, the day on which a smoking ban was instituted in the tertiary public psychiatric hospital. The primary outcome was individual differences in plasma clozapine levels between before and after the smoking ban, which were compared using paired t-tests. The mean plasma clozapine level was significantly increased, by 213.4 ng/mL (95% CI 119.9-306.8; p<0.01) or 53.2%. Four of the 14 inpatients experienced clinically significant side effects, such as myoclonus, drooling, and amnesia, due to the development of high plasma clozapine levels. Our findings indicated that close monitoring of plasma clozapine levels before and after smoking cessation and prior dose adjustment of clozapine may be necessary, to prevent a significant risk of developing high plasma clozapine levels, even in Japanese patients. en-copyright= kn-copyright= en-aut-name=TsukaharaMasaru en-aut-sei=Tsukahara en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SoRyuhei en-aut-sei=So en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YadaYuji en-aut-sei=Yada en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KodamaMasafumi en-aut-sei=Kodama en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KishiYoshiki en-aut-sei=Kishi en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamadaNorihito en-aut-sei=Yamada en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Psychiatry, Okayama Psychiatric Medical Center kn-affil= affil-num=2 en-affil=Department of Psychiatry, Okayama Psychiatric Medical Center kn-affil= affil-num=3 en-affil=Department of Psychiatry, Okayama Psychiatric Medical Center kn-affil= affil-num=4 en-affil=Department of Psychiatry, Okayama Psychiatric Medical Center kn-affil= affil-num=5 en-affil=Department of Psychiatry, Okayama Psychiatric Medical Center kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Asian kn-keyword=Asian en-keyword=clozapine kn-keyword=clozapine en-keyword=schizophrenia kn-keyword=schizophrenia en-keyword=smoking kn-keyword=smoking END start-ver=1.4 cd-journal=joma no-vol=387 cd-vols= no-issue=15 article-no= start-page=70 end-page=74 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20184 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Familial and sporadic chronic progressive degenerative parietal ataxia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background & objective: Parietal ataxia has been mainly reported as a consequence of acute ischemic stroke, while degenerative parietal ataxia has not been reported. Methods: We investigated clinical characteristics, neuroimaging data, and genetic analysis of patients with cerebellar ataxia plus parietal atrophy. Results: We identified seven patients, including five patients from two families, with chronic progressive cerebellar ataxia due to degenerative parietal atrophy but not stroke. Age at onset of ataxia was 57.6 +/- 6.9 years. All patients showed chronic progressive cerebellar ataxia with severity of ataxic gait > limb ataxia > dysarthria. Patients showed no cognitive dysfunction, muscle weakness, or parkinsonism, and only two patients showed mild sensory disturbances. The seven patients showed lateralized limb ataxia with greater contralateral parietal lobe atrophy by magnetic resonance imaging, and hypoperfusion by single photon emission computed tomography, without any abnormal cerebellar pathology (i.e., crossed cerebellar diaschisis). Pathogenic mutations in the microtubule-associated protein tau gene were not found using two single nucleotide polymorphisms. Conclusions: This is the first description showing unique clinical features of familial and sporadic chronic progressive degenerative parietal ataxia. en-copyright= kn-copyright= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurataTomoko en-aut-sei=Kurata en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoKota en-aut-sei=Sato en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IkeuchiTakeshi en-aut-sei=Ikeuchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KitaguchiMasataka en-aut-sei=Kitaguchi en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=2 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=3 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=4 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=5 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=6 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=7 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=8 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=9 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Molecular Genetics, Bioresource Science Branch, Center of Bioresource, Brain Research Institute Niigata University kn-affil= affil-num=11 en-affil=Department of Neurology, Baba Memorial Hospital kn-affil= affil-num=12 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= en-keyword=parietal ataxia kn-keyword=parietal ataxia en-keyword=parietal lobe atrophy kn-keyword=parietal lobe atrophy en-keyword=crossed cerebellar diaschisis kn-keyword=crossed cerebellar diaschisis en-keyword=MAPT kn-keyword=MAPT END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=41 end-page=49 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Urinary Protein-to-creatinine Ratios Predict Recurrence in Pediatric and Young Adult Cases of Minimal Change Nephrotic Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=High-dose steroids are required for the treatment of minimal change nephrotic syndrome (MCNS), especially for episodes of recurrence. Predicting and avoiding recurrence can help reduce the steroid dose, but prediction is currently difficult. We herein examined whether changes in laboratory data, especially the urinary protein- to-creatinine ratio (UTP/UCr), can predict clinical recurrence. We also assessed differences in clinical features between children and young adults. We included 36 patients with MCNS; for each case, we retrospectively studied laboratory data during stable remission and pre-recurrence, with the “stable” period defined as all but the 6 weeks before recurrence, and pre-recurrence defined as the 4±2 weeks before recurrence. UTP/UCr, serum albumin, etc. were measured every 5 years during stable periods. We divided patients into cohorts by age at recurrence, < 15 years and ? 15 years, and compared stable and pre-recurrence values for the two groups. UTP/UCr values during stable periods tended to be higher in younger patients. UTP/UCr and serum albumin showed statistically significant changes during pre-recurrence periods, but only in those aged ? 15 years. Thus, clinical features of recurrence differed depending on age. Signs of recurrence can be confirmed via UTP/UCr or serum albumin several weeks before recurrence in patients ? 15 years. en-copyright= kn-copyright= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyaiTakayuki en-aut-sei=Miyai en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AyaKunihiko en-aut-sei=Aya en-aut-mei=Kunihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=minimal change nephrotic syndrome kn-keyword=minimal change nephrotic syndrome en-keyword=recurrence kn-keyword=recurrence en-keyword= urinary protein to creatinine ratio kn-keyword= urinary protein to creatinine ratio END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=98 end-page=101 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of a heterozygous ABCC6 mutation showing recurrent ischemic strokes and intracranial hemorrhages en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mutations in the ATP-binding cassette subfamily C member 6 (ABCC6) gene are responsible for pseudoxanthoma elasticum (PXE). PXE is a rare genetic metabolic disease with autosomal recessive inheritance that shows ectopic mineralization in skin, eyes and blood vessels, and causes cerebrovascular disease. There are few reports of intracranial hemorrhages in patients with the ABCC6 mutation. We report the first Japanese case with a heterozygous ABCC6 mutation displaying recurrent ischemic strokes and intracranial hemorrhages. We propose that the ABCC6 mutation may be one cause of neurovascular diseases with a family history. en-copyright= kn-copyright= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaharaYuko en-aut-sei=Kawahara en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoteYoshio en-aut-sei=Omote en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiYoshiaki en-aut-sei=Takahashi en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoNamiko en-aut-sei=Matsumoto en-aut-mei=Namiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkegamiKen en-aut-sei=Ikegami en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UemuraMasahiro en-aut-sei=Uemura en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=13 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=ATP-binding cassette subfamily C member 6 (ABCC6) kn-keyword=ATP-binding cassette subfamily C member 6 (ABCC6) en-keyword=neurovascular diseases kn-keyword=neurovascular diseases en-keyword=pseudoxanthoma elasticum (PXE) kn-keyword=pseudoxanthoma elasticum (PXE) END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=1 article-no= start-page=29 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. Here, we demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo.
Methods Three different pancreatic cancer line cells, BxPC3, PANC1, and PK8 cells were mixed with miPSCs and subcutaneously injected into immunodeficient mice. Tumors were evaluated by histological analysis and cells derived from iPSCs were isolated and selected from tumors. The isolated cells were characterized for cancer stem cell characters in vitro and in vivo as well as their responses to anticancer drugs. The impact of co-injection of iPSCs with cancer cells on transcriptome and signaling pathways of iPSCs was investigated.
Results The injection of miPSCs mixed with human pancreatic cancer cells into immunodeficient mice maintained the stemness of miPSCs and changed their phenotype. The miPSCs acquired CSC characteristics of tumorigenicity and self-renewal. The drug responses and the metastatic ability of CSCs converted from miPSCs varied depending on the microenvironment of cancer cells. Interestingly, transcriptome profiles of these cells indicated that the pathways related with aggressiveness and energy production were upregulated from the levels of miPSCs.
Conclusions
Our result suggests that cancer-inducing microenvironment in vivo could rewire the cell signaling and metabolic pathways to convert normal stem cells into CSCs. en-copyright= kn-copyright= en-aut-name=HassanGhmkin en-aut-sei=Hassan en-aut-mei=Ghmkin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumonKazuki en-aut-sei=Kumon en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZahraMaram H. en-aut-sei=Zahra en-aut-mei=Maram H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FuXiaoying en-aut-sei=Fu en-aut-mei=Xiaoying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Al KadiMohamad en-aut-sei=Al Kadi en-aut-mei=Mohamad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SalomonDavid S. en-aut-sei=Salomon en-aut-mei=David S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Medical School, Okayama University kn-affil= affil-num=3 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=8 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Mouse genetics program, Center for Cancer Research, National Cancer Institute kn-affil= affil-num=10 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Cancer stem cells kn-keyword=Cancer stem cells en-keyword=iPSCs kn-keyword=iPSCs en-keyword=Conversion kn-keyword=Conversion en-keyword=Plasticity kn-keyword=Plasticity en-keyword=Tumorigenesis kn-keyword=Tumorigenesis en-keyword=Pancreatic cancer microenvironments kn-keyword=Pancreatic cancer microenvironments END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=23 article-no= start-page=12659 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multifaceted Analysis of IL-23A-and/or EBI3-Including Cytokines Produced by Psoriatic Keratinocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Interleukin (IL) 23 (p19/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. In clinical practice, anti-IL-23Ap19 antibodies are highly effective against psoriasis. IL-39 (p19/ Epstein-Barr virus-induced (EBI) 3), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. Anti-IL-23Ap19 antibodies may bind to IL-39; also, the cytokine may contribute to the pathogenesis of psoriasis. To investigate IL23Ap19- and/or EBI3-including cytokines in psoriatic keratinocytes, we analyzed IL-23Ap19 and EBI3 expressions in psoriasis skin lesions, using immunohistochemistry and normal human epidermal keratinocytes (NHEKs) stimulated with inflammatory cytokines, using quantitative real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-electrospray tandem mass spectrometry (LC-Ms/Ms). Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-alpha, IL-17A, and interferon (IFN)-gamma, and suppressed by dexamethasone, vitamin D3, and acitretin. In ELISA and LC-Ms/Ms analyses, keratinocyte-derived IL-23Ap19 and EBI3, but not heterodimeric forms, were detected with humanized anti-IL-23Ap19 monoclonal antibodies, tildrakizumab, and anti-EBI3 antibodies, respectively. Psoriatic keratinocytes may express IL-23Ap19 and EBI3 proteins in a monomer or homopolymer, such as homodimer or homotrimer. en-copyright= kn-copyright= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TangNina en-aut-sei=Tang en-aut-mei=Nina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UrakamiHitoshi en-aut-sei=Urakami en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KajitaAi en-aut-sei=Kajita en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobashiMina en-aut-sei=Kobashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SasakuraMinori en-aut-sei=Sasakura en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaSatoru en-aut-sei=Sugihara en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=11 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=12 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=13 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= en-keyword=psoriasis vulgaris kn-keyword=psoriasis vulgaris en-keyword=interleukin (IL) 23 kn-keyword=interleukin (IL) 23 en-keyword=IL-39 kn-keyword=IL-39 en-keyword=p19 kn-keyword=p19 en-keyword=Epstein-Barr virus-induced (EBI) 3 kn-keyword=Epstein-Barr virus-induced (EBI) 3 en-keyword=tildrakizumab kn-keyword=tildrakizumab END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=48 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development.

Case presentation
A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3 '-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. Conclusions We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production. en-copyright= kn-copyright= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KochiMariko en-aut-sei=Kochi en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UrakawaYusaku en-aut-sei=Urakawa en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SogawaReimi en-aut-sei=Sogawa en-aut-mei=Reimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoFumino en-aut-sei=Kato en-aut-mei=Fumino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Okazawa-SakaiMika en-aut-sei=Okazawa-Sakai en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShinozakiKatsunori en-aut-sei=Shinozaki en-aut-mei=Katsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Division of Clinical Oncology, Hiroshima Prefecture Hospital kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=RAD51D kn-keyword=RAD51D en-keyword=Splice variant kn-keyword=Splice variant en-keyword=Leiomyosarcoma kn-keyword=Leiomyosarcoma en-keyword=Homologous recombination (HR) kn-keyword=Homologous recombination (HR) en-keyword=Cancer susceptibility kn-keyword=Cancer susceptibility en-keyword=Presumed germline pathogenic variant (PGPV) kn-keyword=Presumed germline pathogenic variant (PGPV) END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=11 article-no= start-page=e00424 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Impact of KRAS Mutation in Patients With Sporadic Nonampullary Duodenal Epithelial Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION: The genomic characterization of primary nonampullary duodenal adenocarcinoma indicates a genetic resemblance to gastric and colorectal cancers. However, a correlation between the clinical and molecular characteristics of these cancers has not been established. This study aimed to elucidate the clinicopathological features of sporadic nonampullary duodenal epithelial tumors, including their molecular characteristics and prognostic factors.
METHODS: One hundred forty-eight patients with sporadic nonampullary duodenal epithelial tumors were examined in this study. Patient sex, age, TNM stage, tumor location, treatment methods, histology, KRAS mutation, BRAF mutation, Fusobacterium nucleatum, mucin phenotype, and programmed death-ligand 1 (PD-L1) status were evaluated. KRAS and BRAF mutations, Fusobacterium nucleatum, mucin phenotype, and PD-L1 status were analyzed by direct sequencing, quantitative polymerase chain reaction, and immunochemical staining.
RESULTS: The median follow-up duration was 119.4 months. There were no deaths from duodenal adenoma (the primary disease). Kaplan-Meier analysis for duodenal adenocarcinoma showed a significant effect of TNM stage (P < 0.01). In univariate analysis of primary deaths from duodenal adenocarcinoma, TNM stage II or higher, undifferentiated, KRAS mutations, gastric phenotype, intestinal phenotype, and PD-L1 status were significant factors. In multivariate analysis, TNM stage II or higher (hazard ratio: 1.63 x 10(10), 95% confidence interval: 18.66-6.69 x 10(36)) and KRAS mutation (hazard ratio: 3.49, confidence interval: 1.52-7.91) were significant factors.
DISCUSSION: Only KRAS mutation was a significant prognostic factor in primary sporadic nonampullary duodenal adenocarcinoma in cases in which TNM stage was considered. en-copyright= kn-copyright= en-aut-name=KinugasaHideaki en-aut-sei=Kinugasa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoShumpei en-aut-sei=Yamamoto en-aut-mei=Shumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchimuraKouichi en-aut-sei=Ichimura en-aut-mei=Kouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakagawaMasahiro en-aut-sei=Nakagawa en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pathology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=8 en-affil=Department of Endoscopy, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=9 en-affil=Center for Innovative Clinical Medicine, OkayamaUniversity Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=FSO757 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year= dt-pub= dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Concordance of acquired mutations between metastatic lesions and liquid biopsy in metastatic colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: To evaluate whether PCR-reverse sequence-specific oligonucleotide can examine the concordance between liquid biopsy and metastatic lesions with acquired resistance. Materials & methods: We examined acquired mutations in chemoresistant lesions and blood obtained from four patients with RAS wildtype metastatic colorectal cancer who underwent treatment with anti-epidermal growth factor receptor antibodies. Results: In one patient, metastatic lesions harbored diverse acquired mutations in KRAS in all seven metastases; the two acquired mutations were detectable in blood collected after the patient acquired resistance. None of the other patients exhibited liquid biopsy mutations, except one, with a BRAF mutation confirmed in primary tumor and peritoneal dissemination. Conclusion: Liquid biopsy based on PCR-reverse sequence-specific oligonucleotide is a successful procedure for capturing acquired mutations with precise information on the RAS mutational spectrum. en-copyright= kn-copyright= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NyuyaAkihiro en-aut-sei=Nyuya en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToshimaToshiaki en-aut-sei=Toshima en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriYoshiko en-aut-sei=Mori en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkawakiMakoto en-aut-sei=Okawaki en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TaniokaHiroaki en-aut-sei=Tanioka en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamaguchiYoshiyuki en-aut-sei=Yamaguchi en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GoelAjay en-aut-sei=Goel en-aut-mei=Ajay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NagasakaTakeshi en-aut-sei=Nagasaka en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Oncology, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Genetics & Digestive Tract & General Surgery, Saitama Medical Center, Saitama Medical University, kn-affil= affil-num=6 en-affil=Department of Clinical Oncology, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Clinical Oncology, Kawasaki Medical School kn-affil= affil-num=11 en-affil=Department of Clinical Oncology, Kawasaki Medical School kn-affil= affil-num=12 en-affil=Department of Molecular Diagnostics & Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences kn-affil= en-keyword=Acquired mutations kn-keyword=Acquired mutations en-keyword=BRAF kn-keyword=BRAF en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=liquid biopsy kn-keyword=liquid biopsy en-keyword=PCR-rSSO kn-keyword=PCR-rSSO en-keyword=RAS kn-keyword=RAS END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=6 article-no= start-page=759 end-page=762 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pulmonary Enteric Adenocarcinoma Harboring a BRAF G469V Mutation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of lung cancer that should be differentiated from colorectal cancer metastasis. Little is known about its genetic background. An 84-year-old male with adenocarcinoma of the lung underwent left upper lobectomy. The histology of the surgical specimen was suggestive of PEAC. Gastrointestinal and colorectal fiberscopy revealed no evidence of colorectal cancer. Next-generation sequencing of the tumor identified a G469V substitution in serine/threonine-protein kinase B-raf (BRAF). Based on the higher prevalence of the G469 substitution in BRAF-mutant lung adenocarcinoma than in BRAFmutant colorectal cancer, the tumor likely originated from the lung. Identification of mutational genotype may be of some help in distinguishing PEAC from the lung metastasis of colorectal cancer. en-copyright= kn-copyright= en-aut-name=ShimizuDai en-aut-sei=Shimizu en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiKohei en-aut-sei=Taniguchi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NambaKei en-aut-sei=Namba en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MesakiKumi en-aut-sei=Mesaki en-aut-mei=Kumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Diagnostic Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=somatic mutations kn-keyword=somatic mutations en-keyword=pulmonary adenocarcinoma with enteric differentiation kn-keyword=pulmonary adenocarcinoma with enteric differentiation en-keyword=non-V600E BRAF mutation kn-keyword=non-V600E BRAF mutation en-keyword=next-generation sequencing kn-keyword=next-generation sequencing END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=6 article-no= start-page=745 end-page=750 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Non-Invasive Prenatal Genetic Testing (NIPT) Leading to Prenatal Diagnosis of Trisomy 21 Mosaicism and 18q Deletion Syndrome: Two Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=NIPT is non-definitive testing to estimate the possibility that fetuses have trisomy 21, trisomy 18, or trisomy 13. However, in NIPT-positive and indeterminate cases, rare chromosomal disease may become apparent, requiring advanced genetic considerations and counseling skills. We experienced two such cases, a trisomy 21 mosaicism case triggered by NIPT-positive status and 18q deletion syndrome triggered by NIPT-indeterminate status. These cases have two clinical implications for NIPT. First, it was revealed that trisomy mosaicism might be found in NIPT-positive cases that have lower Z-Scores than those inferred from the fraction of fetal cfDNA in the case of standard trisomy. Second, it is possible that microdeletion syndrome could be the reason for an indeterminate NIPT result. Today’s genetic counseling requires more expertise in ethics and communication as well as genetic science because NIPT can lead to totally unexpected results. en-copyright= kn-copyright= en-aut-name=HayataKei en-aut-sei=Hayata en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MishimaSakurako en-aut-sei=Mishima en-aut-mei=Sakurako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhiraAkiko en-aut-sei=Ohira en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniKazumasa en-aut-sei=Tani en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=NIPT kn-keyword=NIPT en-keyword=massively parallel sequencing kn-keyword=massively parallel sequencing en-keyword=trisomy 21 mosaicism kn-keyword=trisomy 21 mosaicism en-keyword=18q-deletion syndrome kn-keyword=18q-deletion syndrome en-keyword=genetic counseling kn-keyword=genetic counseling END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=5 article-no= start-page=549 end-page=556 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Glial Cells as Possible Targets of Neuroprotection through Neurotrophic and Antioxidative Molecules in the Central and Enteric Nervous Systems in Parkinson’s Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. The loss of nigrostriatal dopaminergic neurons produces its characteristic motor symptoms, but PD patients also have non-motor symptoms such as constipation and orthostatic hypotension. The pathological hallmark of PD is the presence of α-synuclein-containing Lewy bodies and neurites in the brain. However, the PD pathology is observed in not only the central nervous system (CNS) but also in parts of the peripheral nervous system such as the enteric nervous system (ENS). Since constipation is a typical prodromal non-motor symptom in PD, often preceding motor symptoms by 10-20 years, it has been hypothesized that PD pathology propagates from the ENS to the CNS via the vagal nerve. Discovery of pharmacological and other methods to halt this progression of neurodegeneration in PD has the potential to improve millions of lives. Astrocytes protect neurons in the CNS by secretion of neurotrophic and antioxidative factors. Similarly, astrocyte-like enteric glial cells (EGCs) are known to secrete neuroprotective factors in the ENS. In this article, we summarize the neuroprotective function of astrocytes and EGCs and discuss therapeutic strategies for the prevention of neurodegeneration in PD targeting neurotrophic and antioxidative molecules in glial cells. en-copyright= kn-copyright= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Parkinson’s disease kn-keyword=Parkinson’s disease en-keyword=astrocyte kn-keyword=astrocyte en-keyword=enteric glial cell kn-keyword=enteric glial cell en-keyword=neurotrophic factor kn-keyword=neurotrophic factor en-keyword=antioxidative molecule kn-keyword=antioxidative molecule END start-ver=1.4 cd-journal=joma no-vol=2021 cd-vols= no-issue= article-no= start-page=1 end-page=11 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of the molecular causes underlying physical abnormalities in Diamond‐Blackfan anemia patients with RPL5 haploinsufficiency en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diamond-Blackfan anemia (DBA) is a genetic disorder caused by mutations in genes encoding ribosomal proteins and characterized by erythroid aplasia and various physical abnormalities. Although accumulating evidence suggests that defective ribosome biogenesis leads to p53-mediated apoptosis in erythroid progenitor cells, little is known regarding the underlying causes of the physical abnormalities. In this study, we established induced pluripotent stem cells from a DBA patient with RPL5 haploinsufficiency. These cells retained the ability to differentiate into osteoblasts and chondrocytes. However, RPL5 haploinsufficiency impaired the production of mucins and increased apoptosis in differentiated chondrocytes. Increased expression of the pro-apoptotic genes BAX and CASP9 further indicated that RPL5 haploinsufficiency triggered p53-mediated apoptosis in chondrocytes. MDM2, the primary negative regulator of p53, plays a crucial role in erythroid aplasia in DBA patient. We found the phosphorylation level of MDM2 was significantly decreased in RPL5 haploinsufficient chondrocytes. In stark contrast, we found no evidence that RPL5 haploinsufficiency impaired osteogenesis. Collectively, our data support a model in which RPL5 haploinsufficiency specifically induces p53-mediated apoptosis in chondrocytes through MDM2 inhibition, which leads to physical abnormalities in DBA patients. en-copyright= kn-copyright= en-aut-name=FukuiYuko en-aut-sei=Fukui en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayanoSatoru en-aut-sei=Hayano en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawanabeNoriaki en-aut-sei=Kawanabe en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimadaAkira en-aut-sei=Shimada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoMegumu K. en-aut-sei=Saito en-aut-mei=Megumu K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AsakaIsao en-aut-sei=Asaka en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University kn-affil= affil-num=3 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University kn-affil= affil-num=5 en-affil=Department of Pediatric Hematology/Oncology Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Application, Center for iPS Cell Research and Application Kyoto University kn-affil= affil-num=7 en-affil=Department of Fundamental Cell Technology, Center for iPS Cell Research and Application Kyoto University kn-affil= affil-num=8 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University kn-affil= en-keyword=iPS cell kn-keyword=iPS cell en-keyword=RPL5 kn-keyword=RPL5 en-keyword=cleft lip and palate kn-keyword=cleft lip and palate en-keyword=chondrocyte kn-keyword=chondrocyte en-keyword=Diamond-Blackfan Anemia kn-keyword=Diamond-Blackfan Anemia END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=4 article-no= start-page=517 end-page=521 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Arrhythmogenic Right Ventricular Cardiomyopathy Diagnosed during Hospitalization for Cardiac Arrest en-subtitle= kn-subtitle= en-abstract= kn-abstract=Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically mediated cardiomyopathy charac-terized by progressive myocardial loss of the right ventricle and its replacement by fibrofatty tissue, causing dyskinesia, aneurysm, and/or arrhythmia. The prevalence of ARVC is estimated to be 1 in 2,000-5,000, with the condition accounting for up to 20% of sudden cardiac deaths in individuals < 35 years old. This report describes the case of 61-year-old Japanese who was diagnosed with ARVC after cardiac arrest (CA) and successful resusci-tation. After the sudden CA, the restoration of spontaneous circulation was achieved with appropriate resusci-tation, followed by the introduction of target temperature management in the intensive care unit. He was diag-nosed with ARVC based on angiography and histology results. An ICD (implantable cardioverter-defibrillator) was implanted, and he was discharged without neurological sequelae 1 month post-CA. ARVC is an important cause of sudden CA, and successfully resuscitated patients with right ventricular dilation should undergo testing to rule out ARVC. en-copyright= kn-copyright= en-aut-name=OchiMasahiko en-aut-sei=Ochi en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IidaAtsuyoshi en-aut-sei=Iida en-aut-mei=Atsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiYuka en-aut-sei=Takahashi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaMasamichi en-aut-sei=Tanaka en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoHironori en-aut-sei=Saito en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MikaneTakeshi en-aut-sei=Mikane en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukeSoichiro en-aut-sei=Fuke en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiology, Japan Red Cross Okayama Hospital kn-affil= affil-num=2 en-affil=Department of Emergency Medicine, Japan Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=Division of Pathology and Clinical Laboratories, National Cancer Center Hospital kn-affil= affil-num=4 en-affil=Department of Cardiology, Japan Red Cross Okayama Hospital kn-affil= affil-num=5 en-affil=Department of Cardiology, Japan Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency Medicine, Japan Red Cross Okayama Hospital kn-affil= affil-num=8 en-affil=Department of Cardiology, Japan Red Cross Okayama Hospital kn-affil= en-keyword=inverted T-wave kn-keyword=inverted T-wave en-keyword=right ventricular dilatation kn-keyword=right ventricular dilatation en-keyword=sudden cardiac arrest kn-keyword=sudden cardiac arrest en-keyword=sudden cardiac death kn-keyword=sudden cardiac death END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=4 article-no= start-page=471 end-page=477 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two Types of Polyp Shape Observed in the Stomach of Patients with Peutz-Jeghers Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=The characteristics of gastric polyps in patients with Peutz-Jeghers (PJ) syndrome (PJS) have not been fully investigated. The objective of this study was to reveal the endoscopic and pathologic findings of gastric polyps in patients with PJS. We reviewed 11 patients with PJS treated at 6 institutions, and summarized the endo-scopic and pathologic features of their gastric polyps. The polyps were mainly classified into 2 types: (i) soli-tary or sporadic polyps > 5 mm, reddish in color with a sessile or semi-pedunculated morphology (n = 9); and (ii) multiple sessile polyps ? 5 mm with the same color tone as the peripheral mucosa (n = 9). Patients who underwent endoscopic mucosal resection for polyps > 5 mm were diagnosed with PJ polyps (n = 2), whereas those who underwent biopsy were diagnosed with hyperplastic polyps. Polyps ? 5 mm were pathologically diagnosed as fundic gland polyps or hyperplastic polyps. This study revealed that patients with PJS present with 2 types of polyps in the stomach. Endoscopic mucosal resection of polyps > 5 mm seems necessary for the pathologic diagnosis of PJ polyps. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuedaKazuhiro en-aut-sei=Matsueda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HoriShinichiro en-aut-sei=Hori en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiokaMasao en-aut-sei=Yoshioka en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritouYuki en-aut-sei=Moritou en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MizunoMotowo en-aut-sei=Mizuno en-aut-mei=Motowo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Endoscopy, Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Peutz-Jeghers syndrome kn-keyword=Peutz-Jeghers syndrome en-keyword= esophagogastroduodenoscopy kn-keyword= esophagogastroduodenoscopy en-keyword=gastric polyps kn-keyword=gastric polyps END start-ver=1.4 cd-journal=joma no-vol=188A cd-vols= no-issue= article-no= start-page=249 end-page=252 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A novel pathogenic variant p.Asp797Val in IFIH1 in a Japanese boy with overlapping Singleton-Merten syndrome and Aicardi-Goutieres syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of permanent teeth, and aortic calcification, as well as causing Aicardi-Gouti?res (A-G) syndrome, which shows progressive encephalopathy, spastic paraplegia, and calcification of basal ganglia. Recently, patients with overlapping syndromes presenting with features of S-M syndrome and A-G syndrome were reported. However, progression of clinical features of this condition has not been fully understood. We report a Japanese boy with a novel pathogenic IFIH1 variant who presented with clinical features of S-M syndrome and A-G syndrome. en-copyright= kn-copyright= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaHiroyuki en-aut-sei=Tanaka en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FutagawaNatsuko en-aut-sei=Futagawa en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiguchiYousuke en-aut-sei=Higuchi en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=3 article-no= start-page=639 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202177 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR?mutant lung cancer with HIF?1α/TGF?α expression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osimertinib, a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with lung cancer harboring EGFR T790M; however, acquired resistance is inevitable due to genetic and epigenetic changes in cancer cells. In addition, a recent randomized clinical trial revealed that the combination of osimertinib and bevacizumab failed to exhibit superior progression?free survival compared with osimertinib alone. The present study aimed to investigate the effect of triple therapy with osimertinib, bevacizumab and cetuximab in xenograft tumors with different initial tumor volumes (conventional model, 200 mm3 and large model, 500 mm3). The results demonstrated that osimertinib significantly inhibited tumor growth in both the conventional and large models; however, maximum tumor regression was attenuated in the large model in which hypoxia?inducible factor?1α (HIF?1α) and transforming growth factor?α (TGF?α) expression levels increased. Although the combination of osimertinib and bevacizumab exerted a greater inhibitory effect on tumor growth compared with osimertinib in the conventional model, the effect of this combination therapy was attenuated in the large model. TGF?α attenuated sensitivity to osimertinib in vitro; however, this negative effect was counteracted by the combination of osimertinib and cetuximab, but not osimertinib and bevacizumab. In the large xenograft tumor model, the triple therapy induced the greatest inhibitory effect on tumor growth compared with osimertinib alone and its combination with bevacizumab. Clinical trials of the triple therapy are required for patients with lung cancer with EGFR mutations and HIF?1α/TGF?α. en-copyright= kn-copyright= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=epidermal growth factor receptor kn-keyword=epidermal growth factor receptor en-keyword=osimertinib kn-keyword=osimertinib en-keyword=bevacizumab kn-keyword=bevacizumab en-keyword=cetuximab kn-keyword=cetuximab en-keyword=hypoxia?inducible factor?1α kn-keyword=hypoxia?inducible factor?1α en-keyword=transforming growth factor?α kn-keyword=transforming growth factor?α END start-ver=1.4 cd-journal=joma no-vol=100 cd-vols= no-issue=13 article-no= start-page=e25265 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Disseminated gonococcal infection in a Japanese man with complement 7 deficiency with compound heterozygous variants A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rationale: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants.
Patient concerns: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger.
Diagnosis: Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test.
Interventions: Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient's serum, supporting that the patient has C7 deficiency with compound heterozygous variants.
Outcomes: Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela.
Lessons: DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI. en-copyright= kn-copyright= en-aut-name=KageyamaMisaki en-aut-sei=Kageyama en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaYasutaka en-aut-sei=Ueda en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhtaniKatsuki en-aut-sei=Ohtani en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukumoriYasuo en-aut-sei=Fukumori en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueNorimitsu en-aut-sei=Inoue en-aut-mei=Norimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WakamiyaNobutaka en-aut-sei=Wakamiya en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YonedaNanoka en-aut-sei=Yoneda en-aut-mei=Nanoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KimuraKeigo en-aut-sei=Kimura en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagasawaMotonori en-aut-sei=Nagasawa en-aut-mei=Motonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakagamiFutoshi en-aut-sei=Nakagami en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishiIsao en-aut-sei=Nishi en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SugimotoKen en-aut-sei=Sugimoto en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=RakugiHiromi en-aut-sei=Rakugi en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of General Medicine, Osaka University Hospital kn-affil= affil-num=2 en-affil=Department of General Medicine, Osaka University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Osaka University Hospital kn-affil= affil-num=4 en-affil=The Japanese Association for Complement Research kn-affil= affil-num=5 en-affil=Department of Molecular Genetics, Wakayama Medical University kn-affil= affil-num=6 en-affil=The Japanese Association for Complement Research kn-affil= affil-num=7 en-affil=The Japanese Association for Complement Research kn-affil= affil-num=8 en-affil=Laboratory for Clinical Investigation, Osaka University Hospital kn-affil= affil-num=9 en-affil=Laboratory for Clinical Investigation, Osaka University Hospital kn-affil= affil-num=10 en-affil=Department of General Medicine, Osaka University Hospital kn-affil= affil-num=11 en-affil=Department of General Medicine, Osaka University Hospital kn-affil= affil-num=12 en-affil=Laboratory for Clinical Investigation, Osaka University Hospital kn-affil= affil-num=13 en-affil=Department of General Medicine, Osaka University Hospital kn-affil= affil-num=14 en-affil=Department of General Medicine, Osaka University Hospital kn-affil= en-keyword=complement addition test kn-keyword=complement addition test en-keyword=complement deficiency kn-keyword=complement deficiency en-keyword=disseminated gonococcal infection kn-keyword=disseminated gonococcal infection en-keyword=genome analysis kn-keyword=genome analysis en-keyword=Neisseria gonorrhoeae kn-keyword=Neisseria gonorrhoeae en-keyword=sexually transmitted infection kn-keyword=sexually transmitted infection END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=397 end-page=402 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Metastatic Fumarate Hydratase-Deficient?like Renal Cell Carcinoma Successfully Managed by Ipilimumab plus Nivolumab en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a 62-year-old male with metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) without fumarate hydratase (FH) mutation (FH-deficient?like RCC). The International Metastatic RCC Database Consortium risk score was intermediate, and immunotherapy with nivolumab and ipilimumab (Ipi/ Nivo) was initiated. Four cycles of Ipi/Nivo and 5 cycles of nivolumab resulted in a complete response of the metastases. Hypophysitis occurred as an immune-related adverse event after four cycles of Ipi/Nivo. The prognosis of patients with FH-deficient RCC is generally poor. Few reports of FH-deficient RCC successfully treated with Ipi/Nivo have been published. Ipi/Nivo can be effective for treating FH-deficient RCC. en-copyright= kn-copyright= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakamotoAtsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuiMasao en-aut-sei=Mitsui en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatariShogo en-aut-sei=Watari en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubotaRisa en-aut-sei=Kubota en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakoTomoko en-aut-sei=Sako en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShibataRei en-aut-sei=Shibata en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Kurashiki Medical Center kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=fumarate hydratase kn-keyword=fumarate hydratase en-keyword=fumarate hydratase-deficient renal cell carcinoma kn-keyword=fumarate hydratase-deficient renal cell carcinoma en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=ipilimumab kn-keyword=ipilimumab en-keyword=nivolumab kn-keyword=nivolumab END start-ver=1.4 cd-journal=joma no-vol=557 cd-vols= no-issue= article-no= start-page=199 end-page=205 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adrenergic signaling promotes the expansion of cancer stem-like cells of malignant peripheral nerve sheath tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Malignant peripheral nerve sheath tumor (MPNST), a highly malignant tumor that arises in peripheral nerve tissues, is known to be highly resistant to radiation and chemotherapy. Although there are several reports on genetic mutations and epigenetic changes that define the pathogenesis of MPNST, there is insufficient information regarding the microenvironment that contributes to the malignancy of MPNST. In the present study, we demonstrate that adrenaline increases the cancer stem cell population in MPNST. This effect is mediated by adrenaline stimulation of beta-2 adrenergic receptor (ADRB2), which activates the Hippo transducer, YAP/TAZ. Inhibition and RNAi experiments revealed that inhibition of ADRB2 attenuated the adrenaline-triggered activity of YAP/TAZ and subsequently attenuated MPNST cells stemness. Furthermore, ADRB2-YAP/TAZ axis was confirmed in the MPNST patients’ specimens. The prognosis of patients with high levels of ADRB2 was found to be significantly worse. These data show that adrenaline exacerbates MPNST prognosis and may aid the development of new treatment strategies for MPNST. en-copyright= kn-copyright= en-aut-name=HuangRongsheng en-aut-sei=Huang en-aut-mei=Rongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakihiraShota en-aut-sei=Takihira en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshikawaSoichiro en-aut-sei=Yoshikawa en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiyamaTakeshi en-aut-sei=Hiyama en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KamiyaAtsunori en-aut-sei=Kamiya en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=MPNST kn-keyword=MPNST en-keyword=Cancer stem-like cells kn-keyword=Cancer stem-like cells en-keyword=ADRB2 kn-keyword=ADRB2 en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=231 end-page=238 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term Survival with a Rare Advanced Primary Gastrointestinal Malignant Melanoma Treated with Laparoscopic Surgery/Immune Checkpoint Inhibitor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Targeted therapies for malignant melanoma have improved patients’ prognoses. A primary gastrointestinal malignant melanoma is very rare, with no standard treatment strategy. We treated a 78-year-old Japanese female with advanced primary gastrointestinal melanoma of the descending colon and gallbladder. We administered a multidisciplinary treatment: surgical resection of the descending colon and gallbladder tumors, resection of the metastatic lymph nodes behind the pancreas head, and immune checkpoint antibody-blockade therapy (nivolumab) for ~4 years. PET/CT demonstrated no recurrent lesion for > 3 years. Multidisciplinary therapies (e.g., surgery, chemotherapy, radiotherapy, target therapy, and immune checkpoint antibody-blockade therapy) can successfully treat primary gastrointestinal malignant melanoma. en-copyright= kn-copyright= en-aut-name=EndoMotochika en-aut-sei=Endo en-aut-mei=Motochika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanoHiroaki en-aut-sei=Asano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishizakiMasahiko en-aut-sei=Nishizaki en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Surgery, Mitoyo general Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=primary gastrointestinal melanoma kn-keyword=primary gastrointestinal melanoma en-keyword=laparoscopic surgery kn-keyword=laparoscopic surgery en-keyword=immune checkpoint antibody-blockade inhibitor kn-keyword=immune checkpoint antibody-blockade inhibitor END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=205 end-page=212 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Camouflage Treatment for Skeletal Maxillary Protrusion and Lateral Deviation with Classic-Type Ehlers-Danlos Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein report the case of a 19-year-old female with a transverse discrepancy, skeletal Class II malocclusion, severe crowding with concerns of classic-type Ehlers-Danlos syndrome (EDS), aesthetics problems and functional problems. The main characteristics of classic EDS are loose-jointedness and fragile, easily bruised skin that heals with peculiar “cigarette-paper” scars. The anteroposterior and transverse skeletal discrepancies can generally be resolved by maxilla repositioning and mandibular advancement surgery following pre-surgical orthodontic treatment. However, this patient was treated with orthodontic camouflage but not orthognathic surgery because of the risks of skin bruising, poor healing and a temporomandibular disorder. A satisfactory dental appearance and occlusion were achieved after camouflage treatment with orthodontic anchor screws and the use of Class II elastics, including the preservation of the stomatognathic functions. Acceptable occlusion and dentition were maintained after a two-year retention period. This treatment strategy of orthodontic camouflage using temporary anchorage, such as anchor screws and Class II elastics, may be a viable treatment option for skeletal malocclusion patients with EDS. en-copyright= kn-copyright= en-aut-name=HoshijimaMitsuhiro en-aut-sei=Hoshijima en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawanabeNoriaki en-aut-sei=Kawanabe en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IidaSeiji en-aut-sei=Iida en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamashiroTakashi en-aut-sei=Yamashiro en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Osaka University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=asymmetry kn-keyword=asymmetry en-keyword=Class II kn-keyword=Class II en-keyword=camouflage kn-keyword=camouflage en-keyword=orthodontic anchor screw kn-keyword=orthodontic anchor screw en-keyword=Ehlers-Danlos syndrome kn-keyword=Ehlers-Danlos syndrome END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Profile of down syndrome?associated malignancies: Epidemiology, clinical features and therapeutic aspects en-subtitle= kn-subtitle= en-abstract= kn-abstract=Down syndrome (DS) is a congenital chromosomal abnormality caused by the presence of all or part of a third copy of chromosome 21 (+21). DS is frequently complicated by congenital heart or digestive tract diseases at birth. DS patients are prone to infections and have mental retardation, with dementia such as Alzheimer's disease showing in later life. Furthermore, malignancies with specific characteristics are also highly reported in DS patients compared with non-DS patients. Therefore, DS is believed to be a cancer predisposition syndrome due to the chromosomal instability. Acute myeloid leukemia (AML) and especially acute megakaryoblastic leukemia (AMKL) by French-American-British (FAB) classification are the most frequent hematological malignancies in DS patients, occurring at a rate that is 500 times higher than that in non-DS patients. Interestingly, transient abnormal myelopoiesis (TAM) is observed in approximately 10% of DS neonates with GATA1 mutations, and most TAM patients are asymptomatic and show spontaneous regression; however, about 10%?20% of TAM cases are fatal because of complications such as fetal effusion, liver fibrosis, and other complications.Acute lymphoblastic leukemia (ALL) is also associated with DS, occurring at a rate that is 20 times higher than that in non-DS patients. Furthermore, the prognosis of DS-ALL patients is poorer than that of non-DS-ALL patients. A recent genetic analysis revealed that more than half of DS-ALL cases have a mutation in the CRLF2?JAK pathway, indicating that JAK inhibitors might have a limited effect for DS-ALL patients.Notably, solid tumors such as neuroblastoma, Wilms tumor, and brain tumor, which are frequently observed in non-DS children, are rarely reported in DS children. The reason remains unknown, but it may be because of the triplication of the Down syndrome critical region 1 (DSCR1) gene on chromosome 21. In adult patients with DS, the expected age-adjusted incidence rates of solid tumors are low compared with age-matched euploid cohorts for most cancers except for testicular cancer. Although the average life expectancy of patients with DS will increase with advances in healthcare, the detailed health problems including cancer rates in older DS patients remain unknown. Therefore, these issues will be needed to be addressed in future studies. en-copyright= kn-copyright= en-aut-name=ShimadaAkira en-aut-sei=Shimada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Pediatric Hematology, Okayama University Hospital kn-affil= en-keyword=Down syndrome kn-keyword=Down syndrome en-keyword=Acute myeloid leukemia kn-keyword=Acute myeloid leukemia en-keyword=Acute megakaryoblastic leukemia kn-keyword=Acute megakaryoblastic leukemia en-keyword=Transient abnormal myelopoiesis kn-keyword=Transient abnormal myelopoiesis en-keyword=Acute lymphoblastic leukemia kn-keyword=Acute lymphoblastic leukemia en-keyword=Solid tumor kn-keyword=Solid tumor en-keyword=Cancer predisposition syndrome kn-keyword=Cancer predisposition syndrome en-keyword=GATA1 kn-keyword=GATA1 en-keyword=Down syndrome critical region 1 kn-keyword=Down syndrome critical region 1 END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=7 article-no= start-page=1033 end-page=1036 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristic Clinical Features of Werner Syndrome with a Novel Compound Heterozygous WRN Mutation c.1720+1G>A Plus c.3139-1G>C en-subtitle= kn-subtitle= en-abstract= kn-abstract=Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by mutations in the WRN gene (WRN). Most Japanese WS patients are born from a consanguineous marriage with homozygous WRN mutations. We herein report a rare WS patient born from non-consanguineous parents with compound heterozygous WRN mutations with a novel heterogeneous c.1720+1G>A substitution plus the most frequent heterogeneous c.3139-1G>C substitution among Japanese. Although the present case showed clinical characteristics common to previous Japanese WS patients, he had not developed any malignant tumors as of 43 years of age, suggesting that WS patients with this particular genetic mutation have a different phenotype than others. en-copyright= kn-copyright= en-aut-name=MatsumotoNamiko en-aut-sei=Matsumoto en-aut-mei=Namiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KishidaMasayuki en-aut-sei=Kishida en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKota en-aut-sei=Sato en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShangJingwei en-aut-sei=Shang en-aut-mei=Jingwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeAki en-aut-sei=Watanabe en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoteKoutaro en-aut-sei=Yokote en-aut-mei=Koutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakemotoMinoru en-aut-sei=Takemoto en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OshimaJunko en-aut-sei=Oshima en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama Citizen's Hospital kn-affil= affil-num=4 en-affil=Department of General Internal Medicine, Okayama Citizen's Hospital kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University kn-affil= affil-num=11 en-affil=Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University kn-affil= affil-num=12 en-affil=Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Department of Pathology, University of Washington kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=werner syndrome kn-keyword=werner syndrome en-keyword=compound heterozygous kn-keyword=compound heterozygous en-keyword=Japanese kn-keyword=Japanese END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=3 article-no= start-page=1053 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epstein-Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. EBVMCU is a unifocal mucosal or cutaneous ulcer that often occurs after local trauma in patients with immunosuppression; the patients generally have a good prognosis. It is histologically characterized by proliferating EBV-positive atypical B cells accompanied by ulcers. On the basis of conventional pathologic criteria, EBVMCU may be misdiagnosed as EBV-positive diffuse large B-cell lymphoma or other lymphomas. However, its prognosis differs from that of EBV-associated lymphomas, in that patients with EBVMCU frequently show spontaneous regression or complete remission without chemotherapy. Therefore, EBVMCU is now recognized as a low-grade malignancy or a pseudo-malignant lesion. Avoiding unnecessary chemotherapy by distinguishing EBVMCU from other EBV-associated lymphomas will reduce the burden and unnecessary harm on patients. On the basis of these facts, EBVMCU was first described as a new clinicopathological entity by the World Health Organization in 2017. In this review, we discuss the clinicopathological characteristics of previously reported EBVMCU cases, while focusing on up-to-date clinical, pathological, and genetic aspects. en-copyright= kn-copyright= en-aut-name=IkedaTomoka en-aut-sei=Ikeda en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GionYuka en-aut-sei=Gion en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=EBV-positive mucocutaneous ulcer kn-keyword=EBV-positive mucocutaneous ulcer en-keyword=clinical features kn-keyword=clinical features en-keyword=pathological features kn-keyword=pathological features en-keyword=immunosuppression kn-keyword=immunosuppression END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=5 article-no= start-page=46 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202011 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Panel?based next?generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings en-subtitle= kn-subtitle= en-abstract= kn-abstract=Acute myeloid leukemia (AML) accounts for ~20% of pediatric leukemia cases. The prognosis of pediatric AML has been improved in recent decades, but it trails that of most other types of pediatric cancer, with mortality rates of 30?40%. Consequently, newer more targeted drugs are required for incorporation into treatment plans. These newer drugs selectively target AML cells with specific gene alterations. However, there are significant differences in genetic alterations between adult and pediatric patients with AML. In the present study, inexpensive and rapid next?generation sequencing (NGS) of >150 cancer?related genes was performed for matched diagnostic, remission and relapse (if any) samples from 27 pediatric patients with AML. In this analysis, seven genes were recurrently mutated. KRAS was mutated in seven patients, NRAS was mutated in three patients, and KIT, GATA1, WT1, PTPN11, JAK3 and FLT3 were each mutated in two patients. Among patients with relapsed AML, six harbored KRAS mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (FLT3?ITD and TP53 alterations) were detected among patients who eventually relapsed, and these mutations are reported to be adverse prognostic factors for adult patients with AML. This panel?based, targeted sequencing approach may be useful in determining the genetic background of pediatric AML and improving the prediction of treatment response and detection of potentially targetable gene alterations. RAS pathway mutations were highly unstable at relapse; therefore, these mutations should be chosen as a target with caution. Incorporating this panel?based NGS approach into the clinical setting may allow for a patient?oriented strategy of precision treatment for childhood AML. en-copyright= kn-copyright= en-aut-name=IshidaHisashi en-aut-sei=Ishida en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IguchiAkihiro en-aut-sei=Iguchi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AoeMichinori en-aut-sei=Aoe en-aut-mei=Michinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiuchiRitsuo en-aut-sei=Nishiuchi en-aut-mei=Ritsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsubaraTakehiro en-aut-sei=Matsubara en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KeinoDai en-aut-sei=Keino en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SanadaMasashi en-aut-sei=Sanada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimadaAkira en-aut-sei=Shimada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pediatrics/Pediatric Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Hokkaido University Hospital kn-affil= affil-num=3 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Division of Biobank, Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, St. Marianna University School of Medicine Hospital kn-affil= affil-num=7 en-affil=Clinical Research Center, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=8 en-affil=Department of Pediatrics/Pediatric Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=leukemia kn-keyword=leukemia en-keyword=pediatric kn-keyword=pediatric en-keyword=acute myeloid leukemia kn-keyword=acute myeloid leukemia en-keyword=molecular genetics kn-keyword=molecular genetics en-keyword=precision medicine kn-keyword=precision medicine END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue= article-no= start-page=5 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Familial pancreatic cancer with PALB2 and NBN pathogenic variants: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Family history is one of the risk factors for pancreatic cancer. It is suggested that patients with pancreatic cancer who have a familial history harbor germline pathogenic variants of BRCA1 and/or BRCA2 (BRCA1/2), PALB2, or ATM. Recently, some germline variants of familial pancreatic cancers (FPCs), including PALB2, have been detected. Several countries, including Japan, perform screening workups and genetic analysis for pancreatic cancers. We have been carrying out active surveillance for FPC through epidemiological surveys, imaging analyses, and genetic analysis.
Case presentation
Here, we present the case of a female patient harboring pathogenic variants of PALB2 and NBN, with a family history of multiple pancreatic cancer in her younger brother, her aunt, and her father. Moreover, her father harbored a PALB2 pathogenic variant and her daughter harbored the same NBN pathogenic variant. Given the PALB2 and NBN variants, we designed surveillance strategies for the pancreas, breast, and ovary.
Conclusions
Further studies are required to develop strategies for managing FPCs to facilitate prompt diagnosis before their progression. en-copyright= kn-copyright= en-aut-name=AbeKodai en-aut-sei=Abe en-aut-mei=Kodai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UekiArisa en-aut-sei=Ueki en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UrakawaYusaku en-aut-sei=Urakawa en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitagoMinoru en-aut-sei=Kitago en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshihamaTomoko en-aut-sei=Yoshihama en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NankiYoshiko en-aut-sei=Nanki en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitagawaYuko en-aut-sei=Kitagawa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AokiDaisuke en-aut-sei=Aoki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KosakiKenjiro en-aut-sei=Kosaki en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Surgery, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Center for Medical Genetics, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Surgery, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Surgery, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Center for Medical Genetics, Keio University School of Medicine kn-affil= affil-num=10 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Hereditary pancreatic cancer kn-keyword=Hereditary pancreatic cancer en-keyword=PALB2 kn-keyword=PALB2 en-keyword=NBN kn-keyword=NBN END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=24 article-no= start-page=9504 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular Features and Clinical Management of Hereditary Gynecological Cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hereditary gynecological cancers are caused by several inherited genes. Tumors that arise in the female reproductive system, such as ovaries and the uterus, overlap with hereditary cancers. Several hereditary cancer-related genes are important because they might lead to therapeutic targets. Treatment of hereditary cancers should be updated in line with the advent of various new methods of evaluation. Next-generation sequencing has led to rapid, economical genetic analyses that have prompted a concomitant and significant paradigm shift with respect to hereditary cancers. Molecular tumor profiling is an epochal method for determining therapeutic targets. Clinical treatment strategies are now being designed based on biomarkers based on tumor profiling. Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines significantly changed the genetic testing process in 2020 to initially consider multi-gene panel (MGP) evaluation. Here, we reviewed the molecular features and clinical management of hereditary gynecological malignancies, such as hereditary breast and ovarian cancer (HBOC), and Lynch, Li-Fraumeni, Cowden, and Peutz-Jeghers syndromes. We also reviewed cancer-susceptible genes revealed by MGP tests. en-copyright= kn-copyright= en-aut-name=UekiArisa en-aut-sei=Ueki en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Center for Medical Genetics, Keio Cancer Center, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=hereditary gynecological cancer kn-keyword=hereditary gynecological cancer en-keyword=multi-gene testing kn-keyword=multi-gene testing en-keyword=tumor profiling kn-keyword=tumor profiling en-keyword=hereditary breast and ovarian cancer (HBOC) kn-keyword=hereditary breast and ovarian cancer (HBOC) en-keyword=Lynch kn-keyword=Lynch en-keyword=Li?Fraumeni kn-keyword=Li?Fraumeni en-keyword=Cowden kn-keyword=Cowden en-keyword=Peutz?Jeghers kn-keyword=Peutz?Jeghers en-keyword=syndrome kn-keyword=syndrome END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=6 article-no= start-page=545 end-page=550 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Delayed Methotrexate Elimination after Administration of a Medium Dose of Methotrexate in a Patient with Genetic Variants Associated with Methotrexate Clearance en-subtitle= kn-subtitle= en-abstract= kn-abstract=Polymorphisms in methotrexate transporter pathways have been associated with methotrexate toxicities and clearance. Recent genome-wide association studies have revealed that the SLCO1B1 T521C variant is associated with methotrexate elimination. We present a case of a pediatric patient with acute lymphoblastic leukemia who suffered from persistently high plasma methotrexate concentrations and acute kidney injuries after the admin-istration of a medium dose of methotrexate. Subsequent genetic analysis showed that he was a carrier of dys-functional genetic variants associated with methotrexate clearance. This case highlights that polymorphisms of methotrexate transporter pathways can adversely affect methotrexate elimination in a clinically significant manner. en-copyright= kn-copyright= en-aut-name=TatebeYasuhisa en-aut-sei=Tatebe en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanamitsuKiichiro en-aut-sei=Kanamitsu en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanzakiHirotaka en-aut-sei=Kanzaki en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaHisashi en-aut-sei=Ishida en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiwaraKaori en-aut-sei=Fujiwara en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimadaAkira en-aut-sei=Shimada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of pediatrics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of pediatrics, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of pediatrics, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of pediatrics, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of pediatrics, Okayama University Hospital kn-affil= en-keyword=methotrexate kn-keyword=methotrexate en-keyword=polymorphism kn-keyword=polymorphism en-keyword=drug elimination kn-keyword=drug elimination en-keyword=acute kidney injury kn-keyword=acute kidney injury en-keyword=acute lymphoblastic leukemia kn-keyword=acute lymphoblastic leukemia END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=6 article-no= start-page=531 end-page=535 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Soft Tissue Myoepithelioma of the Shoulder en-subtitle= kn-subtitle= en-abstract= kn-abstract=Soft tissue myoepitheliomas are often misdiagnosed due to their rarity. Herein, we describe a case of soft tissue myoepithelioma of the shoulder. A 72-year-old woman had a suspected sarcoma on her shoulder and under-went open biopsy. She was referred to our hospital, where the tumor was widely resected and the diagnosis of myoepithelioma was histologically confirmed. No recurrence has been observed in the 3 years since the sur-gery. Careful and prompt planning is necessary for the effective treatment of myoepithelioma. en-copyright= kn-copyright= en-aut-name=HashimotoKazuhiko en-aut-sei=Hashimoto en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraShunji en-aut-sei=Nishimura en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChikugoTakaaki en-aut-sei=Chikugo en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakinokiRyosuke en-aut-sei=Kakinoki en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkagiMasao en-aut-sei=Akagi en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, Kindai University Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Kindai University Hospital kn-affil= en-keyword=soft tissue myoepithelioma kn-keyword=soft tissue myoepithelioma en-keyword=unplanned resection kn-keyword=unplanned resection en-keyword=shoulder kn-keyword=shoulder END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=6 article-no= start-page=495 end-page=503 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antenatal Care Visits and Adverse Pregnancy Outcomes at a Hospital in Rural Western Province, Rwanda en-subtitle= kn-subtitle= en-abstract= kn-abstract=In many economically developing countries, and especially in the rural regions of sub-Saharan African coun-tries, there have been only limited investigations into the association between antenatal care (ANC) and adverse pregnancy outcomes. We obtained information on ANC and pregnancy outcomes between 2011 and 2016 from hospital files of pregnant women (n = 4,960) served at a rural hospital in Rwanda, and we examined the associa-tions between their ANC visits and the adverse pregnancy and neonatal outcomes by using univariate and mul-tivariate logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Most of the pregnant women had ? 4 ANC visits, but 39% (n = 1,911) did not have ? 3 visits before delivery. The prev-alence of low birth weight (LBW) and that of preterm birth (PTB) were 12% and 9.9%, respectively. Compared to the women who attended only one ANC visit, those who attended ? 4 ANC visits had lower risks of LBW (OR 0.20; 95%CI: 0.11-0.36) and PTB (OR 0.28; 95%CI: 0.11-0.76). Frequent ANC visits were also associ-ated with better postnatal outcomes of the newborns. Encouraging women to attend ANC visits before delivery can markedly reduce PTB-related and LBW-related complications, especially in resource-limited settings. en-copyright= kn-copyright= en-aut-name=CalliopeSimba Akintije en-aut-sei=Calliope en-aut-mei=Simba Akintije kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaTakayuki en-aut-sei=Wada en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MukakarakeMarie Goret en-aut-sei=Mukakarake en-aut-mei=Marie Goret kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MutesaLeon en-aut-sei=Mutesa en-aut-mei=Leon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoTaro en-aut-sei=Yamamoto en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Graduate School of Human Life Science, Osaka City University kn-affil= affil-num=4 en-affil=Mibilizi District Hospital kn-affil= affil-num=5 en-affil=Center for Human Genetics, College of Medicine and Health Sciences, University of Rwanda kn-affil= affil-num=6 en-affil=Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University kn-affil= en-keyword=antenatal care kn-keyword=antenatal care en-keyword=epidemiology kn-keyword=epidemiology en-keyword=low birth weight kn-keyword=low birth weight en-keyword=preterm birth kn-keyword=preterm birth en-keyword=rural kn-keyword=rural END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue= article-no= start-page=100643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Marked motor function improvement in a 32-year-old woman with childhood-onset hypophosphatasia by asfotase alfa therapy: Evaluation based on standardized testing batteries used in Duchenne muscular dystrophy clinical trials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypophosphatasia (HPP) is a rare disorder resulting from biallelic loss-of-function variants or monoallelic dominant negative variants in the ALPL gene. We herein describe the clinical outcome of a 32-year-old woman with childhood-onset HPP caused by compound heterozygous variants in ALPL. Her chief complaints were severe musculoskeletal pain, muscle weakness, and impaired daily activities necessitating assistance in housework and child-rearing in addition to a history of early tooth loss and mildly short stature. Asfotase alfa therapy produced a remarkable increase in muscle strength and daily activities and markedly reduced musculoskeletal pain. Drug efficacy was clearly demonstrated through multiple test batteries (muscle strength test using microFET?2, six-minute walking test, Stair Climb Test, rising-from-floor-time test, and number-of-steps test using Actigraph?) currently adopted as standardized evaluations in Duchenne muscular dystrophy clinical trials since no test batteries for HPP have been established to date. These tests may also be promising for the assessment of HPP. en-copyright= kn-copyright= en-aut-name=NishizawaHitomi en-aut-sei=Nishizawa en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoYoshihiko en-aut-sei=Sato en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshikawaMasumi en-aut-sei=Ishikawa en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArakawaYuko en-aut-sei=Arakawa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IijimaMari en-aut-sei=Iijima en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakanoKyoko en-aut-sei=Takano en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeAtsushi en-aut-sei=Watanabe en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KoshoTomoki en-aut-sei=Kosho en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Faculty of Health Sciences, Department of Medicine, Shinshu University kn-affil= affil-num=2 en-affil=Department of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, Matsumoto kn-affil= affil-num=3 en-affil=Center for Medical Genetics, Shinshu University Hospital kn-affil= affil-num=4 en-affil=Department of Dentistry and Oral Surgery, Shinshu University School of Medicine kn-affil= affil-num=5 en-affil=Department of Clinical Nutrition, Shinshu University Hospital kn-affil= affil-num=6 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Center for Medical Genetics, Shinshu University Hospital kn-affil= affil-num=8 en-affil=Division of Clinical Genetics, Kanazawa University Hospital kn-affil= affil-num=9 en-affil=Center for Medical Genetics, Shinshu University Hospital kn-affil= en-keyword=Hypophosphatasia kn-keyword=Hypophosphatasia en-keyword=Alkaline phosphatase kn-keyword=Alkaline phosphatase en-keyword=Genetic disease kn-keyword=Genetic disease en-keyword=Asfotase alfa kn-keyword=Asfotase alfa en-keyword=Recombinant gene therapy kn-keyword=Recombinant gene therapy en-keyword=Motor function kn-keyword=Motor function END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue= article-no= start-page=103080 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A detection method for latent circadian rhythm sleep-wake disorder en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Individuals with typical circadian rhythm sleep-wake disorders (CRSWDs) have a habitual sleep timing that is desynchronized from social time schedules. However, it is possible to willfully force synchronisation against circadian-driven sleepiness, which causes other sleep problems. This pathology is distinguishable from typical CRSWDs and is referred to here as latent CRSWD (LCRSWD). Conventional diagnostic methods for typical CRSWDs are insufficient for detecting LCRSWD because sufferers have an apparently normal habitual sleep timing.
Methods
We first evaluated the reliability of circadian phase estimation based on clock gene expression using hair follicles collected at three time points without sleep interruption. Next, to identify detection criteria for LCRSWD, we compared circadian and sleep parameters according to estimated circadian phases, at the group and individual level, between subjects with low and high Pittsburgh Sleep Quality Index (PSQI) scores. To validate the reliability of identified detection criteria, we investigated whether the same subjects could be reproducibly identified at a later date and whether circadian amelioration resulted in sleep improvement.
Findings
We successfully validated the reliability of circadian phase estimation at three time points and identified potential detection criteria for individuals with LCRSWD attributed to delayed circadian-driven sleepiness. In particular, a criterion based on the interval between the times of the estimated circadian phase of clock gene expression and getting out of bed on work or school days was promising. We also successfully confirmed the reproducibility of candidate screening and sleep improvement by circadian amelioration, supporting the reliability of the detection criteria.
Interpretation
Although several limitations remain, our present study demonstrates a promising prototype of a detection method for LCRSWD attributed to delayed circadian-driven sleepiness. More extensive trials are needed to further validate this method. en-copyright= kn-copyright= en-aut-name=AkashiMakoto en-aut-sei=Akashi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SogawaReimi en-aut-sei=Sogawa en-aut-mei=Reimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumuraRitsuko en-aut-sei=Matsumura en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishidaAtsuhiro en-aut-sei=Nishida en-aut-mei=Atsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraRino en-aut-sei=Nakamura en-aut-mei=Rino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokudaIsao T. en-aut-sei=Tokuda en-aut-mei=Isao T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NodeKoichi en-aut-sei=Node en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=The Research Institute for Time Studies, Yamaguchi University kn-affil= affil-num=2 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=The Research Institute for Time Studies, Yamaguchi University kn-affil= affil-num=4 en-affil=The Research Institute for Time Studies, Yamaguchi University kn-affil= affil-num=5 en-affil=The Research Institute for Time Studies, Yamaguchi University kn-affil= affil-num=6 en-affil=Department of Mechanical Engineering, Ritsumeikan University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Saga University kn-affil= en-keyword=Circadian rhythm sleep-wake disorder kn-keyword=Circadian rhythm sleep-wake disorder en-keyword=Circadian clock kn-keyword=Circadian clock en-keyword=Hair follicle kn-keyword=Hair follicle en-keyword=Clock gene kn-keyword=Clock gene en-keyword=Period3 kn-keyword=Period3 END start-ver=1.4 cd-journal=joma no-vol=113 cd-vols= no-issue= article-no= start-page=33 end-page=41 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6?dependent Epilepsy Than Pyridoxal 5′-Phosphate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
We aimed to demonstrate the biochemical characteristics of vitamin B6?dependent epilepsy, with a particular focus on pyridoxal 5′-phosphate and pyridoxal in the cerebrospinal fluid.
Methods
Using our laboratory database, we identified patients with vitamin B6?dependent epilepsy and extracted their data on the concentrations of pyridoxal 5′-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5′-phosphate concentrations.
Results
We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5′-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5′-phosphate concentrations were low in patients with vitamin B6?dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6?dependent epilepsy, suggestive of pyridoxal 5′-phosphate deficiency in the brain.
Conclusions
Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5′-phosphate deficiency in the brain in vitamin B6?dependent epilepsy than low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5′-phosphate homeostasis protein deficiency, which does not have known biomarkers. en-copyright= kn-copyright= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HyodoYuki en-aut-sei=Hyodo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OboshiTaikan en-aut-sei=Oboshi en-aut-mei=Taikan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImaiKatsumi en-aut-sei=Imai en-aut-mei=Katsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshiharaNaoko en-aut-sei=Ishihara en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DowaYuri en-aut-sei=Dowa en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoikeTakayoshi en-aut-sei=Koike en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoToshiyuki en-aut-sei=Yamamoto en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShibasakiJun en-aut-sei=Shibasaki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShimboHiroko en-aut-sei=Shimbo en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FukuyamaTetsuhiro en-aut-sei=Fukuyama en-aut-mei=Tetsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakanoKyoko en-aut-sei=Takano en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShirakuHiroshi en-aut-sei=Shiraku en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakeshitaSaoko en-aut-sei=Takeshita en-aut-mei=Saoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkanishiTohru en-aut-sei=Okanishi en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=BabaShimpei en-aut-sei=Baba en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KubotaMasaya en-aut-sei=Kubota en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HamanoShin-ichiro en-aut-sei=Hamano en-aut-mei=Shin-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatric Neurology, Osaka Women’s and Children’s Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological Disorders kn-affil= affil-num=6 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=7 en-affil=Department of Neurology, Gunma Children’s Medical Center kn-affil= affil-num=8 en-affil=Department of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological Disorders kn-affil= affil-num=9 en-affil=Institute of Clinical Genomics, Tokyo Women’s Medical University kn-affil= affil-num=10 en-affil=Department of Neonatology, Kanagawa Children’s Medical Center kn-affil= affil-num=11 en-affil=Clinical Institute, Kanagawa Children’s Medical Center kn-affil= affil-num=12 en-affil=Department of Pediatrics, Shinshu University kn-affil= affil-num=13 en-affil=Center for Medical Genetics, Shinshu University Hospital kn-affil= affil-num=14 en-affil=Department of Pediatrics, JA Toride Medical Center kn-affil= affil-num=15 en-affil=Department of Pediatrics, Yokohama City University Medical Center kn-affil= affil-num=16 en-affil=Department of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital kn-affil= affil-num=17 en-affil=Department of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital kn-affil= affil-num=18 en-affil=Division of Neurology, National Center for Child Health and Development kn-affil= affil-num=19 en-affil=Division of Neurology, Saitama Children’s Medical Center kn-affil= affil-num=20 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= en-keyword=ALDH7A1 kn-keyword=ALDH7A1 en-keyword=PLPBP kn-keyword=PLPBP en-keyword=PLPHP kn-keyword=PLPHP en-keyword=PROSC kn-keyword=PROSC en-keyword=Pyridoxal 5′-phosphate homeostasis protein deficiency kn-keyword=Pyridoxal 5′-phosphate homeostasis protein deficiency en-keyword=Pyridoxine-dependent epilepsy kn-keyword=Pyridoxine-dependent epilepsy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201009 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=There has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as a BRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39 years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, Lynch syndrome was suspected. However, germline multigene panel testing revealed a pathogenic BRCA2 variant rather than pathogenic variants in mismatch repair genes. In this case, with conventional genetic risk assessment, we were unable to determine whether the patient had a high risk of hereditary breast and ovarian cancer; thus, germline multigene panel testing may provide valuable information to improve disease management strategies for patients in clinical settings. Particularly, germline multigene panel testing may be useful for detecting hereditary tumor syndromes if a patient does not present with a typical family history of cancer. en-copyright= kn-copyright= en-aut-name=YoshihamaTomoko en-aut-sei=Yoshihama en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name= SuganoKokichi en-aut-sei= Sugano en-aut-mei=Kokichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaTeruhiko en-aut-sei=Yoshida en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UshiamaMineko en-aut-sei=Ushiama en-aut-mei=Mineko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UekiArisa en-aut-sei=Ueki en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkahaneTomoko en-aut-sei=Akahane en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NankiYoshiko en-aut-sei=Nanki en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakaiKensuke en-aut-sei=Sakai en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakabeTakeshi en-aut-sei=Makabe en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamagamiWataru en-aut-sei=Yamagami en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SusumuNobuyuki en-aut-sei=Susumu en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KameyamaKaori en-aut-sei=Kameyama en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakiKenjiro en-aut-sei=Kosaki en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AokiDaisuke en-aut-sei=Aoki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute kn-affil= affil-num=4 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=6 en-affil=Center for Medical Genetics, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=10 en-affil= Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=11 en-affil= Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=12 en-affil= Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Department of Pathology, Showa University Northern Yokohama Hospital kn-affil= affil-num=14 en-affil=Center for Medical Genetics, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= en-keyword=BRCA2 kn-keyword=BRCA2 en-keyword=Hereditary breast and ovarian cancer kn-keyword=Hereditary breast and ovarian cancer en-keyword=Multigene panel testing kn-keyword=Multigene panel testing en-keyword=Genetic counseling kn-keyword=Genetic counseling en-keyword=Lynch syndrome kn-keyword=Lynch syndrome END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=5 article-no= start-page=443 end-page=448 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combined Laparoscopic and CT Monitoring of the Ice-Ball Margin during Cryoablation for Renal Cell Carcinoma Associated with von Hippel-Lindau Disease: First Case en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a 47-year-old Japanese female with 10 previous treatments for multiple bilateral renal cell carcinoma (RCC) associated with von Hippel-Lindau disease. The 14-mm right lower pole renal tumor was in contact with the right ureter. Laparoscopic cryoablation was performed to protect the ureter wrapped with gauze. Computed tomography (CT) monitoring was used to confirm the precise ? 6 mm ice-ball margin. There was no local progression at 6-months post-surgery. The serum creatinine has been stable. This is apparently the first report of combined laparoscopic and CT monitoring of an ice-ball formation and its margin during cryoablation for RCC. en-copyright= kn-copyright= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomakiToshiyuki en-aut-sei=Komaki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatariShogo en-aut-sei=Watari en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KubotaRisa en-aut-sei=Kubota en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakamotoAtsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SakoTomoko en-aut-sei=Sako en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KanazawaSusumu en-aut-sei=Kanazawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil= Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=laparoscopic cryoablation kn-keyword=laparoscopic cryoablation en-keyword=multiple renal masses kn-keyword=multiple renal masses en-keyword=nephron-sparing surgery kn-keyword=nephron-sparing surgery en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=von Hippel-Lindau disease kn-keyword=von Hippel-Lindau disease END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=5 article-no= start-page=435 end-page=441 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Disseminated Fusarium fujikuroi Species Complex Infection Prior to Allogeneic Hematopoietic Stem Cell Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 53-year-old man was diagnosed with acute myeloid leukemia, which was refractory to chemotherapies. Systemic papules appeared afterward. The skin biopsies revealed filamentous fungal infection including fusariosis. Despite antifungal therapy, the infection did not resolve, because neutropenia persisted with the leukemia. He underwent hematopoietic stem cell transplantation (HSCT) to overcome the leukemia and restore normal hematopoiesis but died from fusariosis just before engraftment. Fusarium fujikuroi species complex was detected in blood cultures with poor antifungal susceptibility. Because restoring normal hematopoiesis is important in the treatment of fusariosis, HSCT might be considered for patients with persistent pancytopenia. en-copyright= kn-copyright= en-aut-name=FujishitaKeigo en-aut-sei=Fujishita en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkaSatoshi en-aut-sei=Oka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KameiKatsuhiko en-aut-sei=Kamei en-aut-mei=Katsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniKatsuma en-aut-sei=Tani en-aut-mei=Katsuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujisawaYuka en-aut-sei=Fujisawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MachidaTakuya en-aut-sei=Machida en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ImaiToshi en-aut-sei=Imai en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Medical Mycology Research Center, Chiba University kn-affil= affil-num=4 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=8 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= en-keyword=disseminated fusariosis kn-keyword=disseminated fusariosis en-keyword=Fusarium fujikuroi species complex kn-keyword=Fusarium fujikuroi species complex en-keyword=allogeneic hematopoietic stem cell transplantation kn-keyword=allogeneic hematopoietic stem cell transplantation en-keyword=acute myeloid leukemia kn-keyword=acute myeloid leukemia END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=5 article-no= start-page=427 end-page=429 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Polydactyly of the Foot Diagnosed from a Minor Nail Problem en-subtitle= kn-subtitle= en-abstract= kn-abstract=Polydactyly is one of the most common foot congenital anomalies. It is often detected immediately after birth, but the diagnosis can sometimes be delayed if the symptoms are less evident. A 2-year-old girl with a complaint of recurrent bleeding from the right toenail was diagnosed with foot polydactyly. She underwent corrective surgery, and her family was satisfied with the outcome. Although the diagnosis of polydactyly may be difficult in cases with minor nail problems, further radiographic evaluation will be needed for the improvement of the patient’s quality of life. en-copyright= kn-copyright= en-aut-name=HiraokaTomohiro en-aut-sei=Hiraoka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SenooHaruka en-aut-sei=Senoo en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamazakiYuka en-aut-sei=Yamazaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuenobuKosaku en-aut-sei=Suenobu en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Pediatrics, Ochiai Hospital kn-affil= affil-num=2 en-affil=Department of Dermatology, Ochiai Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Plastic Surgery, Okayama Medical Center kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= en-keyword=polydactyly kn-keyword=polydactyly en-keyword=hyperdactyly kn-keyword=hyperdactyly en-keyword=hexadactyly kn-keyword=hexadactyly END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=4 article-no= start-page=335 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recurrence of Solitary Fibrous Tumor/Hemangiopericytoma Could Be Predicted by Ki-67 Regardless of Its Origin en-subtitle= kn-subtitle= en-abstract= kn-abstract=Since the discovery of the NAB2-STAT6 gene fusion in 2013, solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) have been considered the same disease. STAT6 nuclear stain is approved as a highly sensitive and specific marker to diagnose SFT/HPC from other tumors with similar histology. As the next step, detection of fusion variants that may predict clinical malignancy of SFT/HPC has been attempted. However, no fusion variants with a clear relation to malignancy have been identified. In this study, the clinical and histological backgrounds of 23 Japanese patients diagnosed with SFT/HPC from 2000 to 2019 at Kochi University Hospital were examined to identify factors potentially related to recurrence. A significant relationship to recurrence was detected for mitosis ? 1/10 HPF (400×), necrosis, and Ki-67>5%. These findings indicate that a deliberate investigation of histological features such as mitosis and necrosis is crucial for the clinical observation of SFT/ HPC patients. In addition, Ki-67 was revealed to be a useful parameter to predict recurrence in SFT/HPC patients. en-copyright= kn-copyright= en-aut-name=YamamotoYumiko en-aut-sei=Yamamoto en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiYoshihiro en-aut-sei=Hayashi en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MurakamiIchiro en-aut-sei=Murakami en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Diagnostic Pathology, Kochi University kn-affil= affil-num=2 en-affil=Department of Equipment of Support Planning Office, Kochi University kn-affil= affil-num=3 en-affil=Department of Diagnostic Pathology, Kochi University kn-affil= en-keyword=solitary fibrous tumor kn-keyword=solitary fibrous tumor en-keyword=hemangiopericytoma kn-keyword=hemangiopericytoma en-keyword=Ki-67 kn-keyword=Ki-67 en-keyword=NAB2-STAT6 kn-keyword=NAB2-STAT6 en-keyword=WHO classification kn-keyword=WHO classification en-keyword=WHO grading criteria kn-keyword=WHO grading criteria en-keyword=Marseille Grading System kn-keyword=Marseille Grading System END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=4 article-no= start-page=265 end-page=274 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors Predicting a Favorable Disease Course Without Anti-TNF Therapy in Crohn’s Disease Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Determining factors that predict a favorable disease course without anti-tumor necrosis factor (TNF) agents would help establish a more cost-effective strategy for Crohn’s disease (CD). A retrospective chart review was performed for CD patients with disease durations > 10 years who had not received anti-TNF agents as first-line therapy. Patients were divided into 2 groups: those who received neither anti-TNF agents nor bowel resection (G1), and those who had received an anti-TNF agent and/or bowel resection (G2). The patient backgrounds, therapies and clinical courses were compared between the groups. A total of 62 CD patients met the inclusion criteria (males: 71%; median duration of follow-up: 19 years). Six patients were included in G1; they were significantly less likely to have upper gastrointestinal lesions than G2 (p=0.007). A multivariate analysis revealed that the significant factors for avoidance of bowel resection without anti-TNF treatment were non-stricturing and non-penetrating behaviors, and absence of upper gastrointestinal lesions at the diagnosis (hazard ratios 0.41 and 0.52; p=0.004 and 0.04, respectively). In consideration of the long treatment course of CD, patients with non-stricturing and non-penetrating behaviors and no upper gastrointestinal lesions should not be treated with anti-TNF agents as first-line therapy. en-copyright= kn-copyright= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasutomiEriko en-aut-sei=Yasutomi en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkaShohei en-aut-sei=Oka en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KinugasaHideaki en-aut-sei=Kinugasa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakaharMasahiro en-aut-sei=Takahar en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HaradaKeita en-aut-sei=Harada en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatoJun en-aut-sei=Kato en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=bDepartment of Gastroenterology, Mitsui Memorial Hospital kn-affil= en-keyword=Crohn’s disease kn-keyword=Crohn’s disease en-keyword=anti-TNF agent kn-keyword=anti-TNF agent en-keyword=upper gastrointestinal lesion kn-keyword=upper gastrointestinal lesion en-keyword=bamboo joint-like appearance kn-keyword=bamboo joint-like appearance END start-ver=1.4 cd-journal=joma no-vol=132 cd-vols= no-issue=1 article-no= start-page=25 end-page=28 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-title=岡山大学病院臨床遺伝子診療科の紹介 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name=平沢晃 kn-aut-sei=平沢 kn-aut-mei=晃 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Clinical Cenomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科　臨床遺伝子医療学 en-keyword= clinical genetics kn-keyword= clinical genetics en-keyword=cancer precision medicine kn-keyword=cancer precision medicine en-keyword=patient and public involvement kn-keyword=patient and public involvement en-keyword=hereditary tumor kn-keyword=hereditary tumor en-keyword=genetic counseling kn-keyword=genetic counseling END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=12 article-no= start-page=2437 end-page=2448 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200619 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epstein?Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P?A, p.Cys34Ser) in a Japanese Patient with Possible Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease) en-subtitle= kn-subtitle= en-abstract= kn-abstract= Hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu disease) is an autosomal dominant genetic disorder that causes frequent epistaxis, mucocutaneous telangiectasia, and visceral arteriovenous malformations. Four genes (ENG, ACVRL1, SMAD4, and GDF2) have been identified as pathogenic in HHT. We describe the case of a 50-year-old Japanese man highly suspected of having HHT due to recurrent epistaxis, mucocutaneous telangiectasia, and a family history. Genomic analysis revealed a novel missense mutation of c.100T>A, p.Cys34Ser in the patient’s ACVRL1 gene. We used 6 freeware programs to perform an in silico analysis of this mutation. The results demonstrated the mutation’s high pathogenicity. en-copyright= kn-copyright= en-aut-name=UmemuraHiroshi en-aut-sei=Umemura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiuraKatsuhiro en-aut-sei=Miura en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaruseHiromu en-aut-sei=Naruse en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HattaYoshihiro en-aut-sei=Hatta en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeiMasami en-aut-sei=Takei en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakayamaTomohiro en-aut-sei=Nakayama en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine kn-affil= affil-num=2 en-affil=Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine kn-affil= affil-num=3 en-affil=Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine kn-affil= affil-num=4 en-affil=Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine kn-affil= affil-num=5 en-affil=Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine kn-affil= affil-num=6 en-affil=Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine kn-affil= en-keyword=ACVRL1 kn-keyword=ACVRL1 en-keyword=hereditary hemorrhagic telangiectasia kn-keyword=hereditary hemorrhagic telangiectasia en-keyword=in silico analysis kn-keyword=in silico analysis en-keyword=missense mutation kn-keyword=missense mutation en-keyword=Osler-Weber- Rendu disease kn-keyword=Osler-Weber- Rendu disease END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=21 article-no= start-page=E5402 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Animal Models for Parkinson's Disease Research: Trends in the 2000s en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson's disease (PD) is a chronic and progressive movement disorder and the second most common neurodegenerative disease. Although many studies have been conducted, there is an unmet clinical need to develop new treatments because, currently, only symptomatic therapies are available. To achieve this goal, clarification of the pathology is required. Attempts have been made to emulate human PD and various animal models have been developed over the decades. Neurotoxin models have been commonly used for PD research. Recently, advances in transgenic technology have enabled the development of genetic models that help to identify new approaches in PD research. However, PD animal model trends have not been investigated. Revealing the trends for PD research will be valuable for increasing our understanding of the positive and negative aspects of each model. In this article, we clarified the trends for animal models that were used to research PD in the 2000s, and we discussed each model based on these trends. en-copyright= kn-copyright= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KamedaMasahiro en-aut-sei=Kameda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil= Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil= Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil= Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=animal model kn-keyword=animal model en-keyword=alpha-synuclein kn-keyword=alpha-synuclein en-keyword=DJ-1 kn-keyword=DJ-1 en-keyword=neurotoxin kn-keyword=neurotoxin en-keyword=Parkin kn-keyword=Parkin en-keyword=Parkinson's disease kn-keyword=Parkinson's disease en-keyword=pesticide kn-keyword=pesticide en-keyword=PINK1 kn-keyword=PINK1 en-keyword=1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine kn-keyword=1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine en-keyword=6-hydroxydopamine kn-keyword=6-hydroxydopamine END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=5 article-no= start-page=288 end-page=290 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190629 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Late presented congenital myasthenic syndrome with novel compound heterozygous CHRNE mutations mimicking seronegative myasthenia gravis en-subtitle= kn-subtitle= en-abstract= kn-abstract= We found a late presented congenital myasthenic syndrome (CMS) patient with novel CHRNE gene mutations. Although our patient has shown blepharoptosis since youth, fatigable muscle weakness began at age 71. Genetic analysis revealed novel compound heterozygous CHRNE mutations (c.1032+2T>G, c.1306_1307 delGA). His myasthenic symptoms were well managed by oral anti‐cholinesterase drug until he died at 82‐year‐old. The present case showed mild myasthenic symptoms with very late presentation and slow progression. Late presented CMS is often underdiagnosed; therefore, genetic testing is important to distinguish it from other myasthenic disease. en-copyright= kn-copyright= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsunodaKeiichiro en-aut-sei=Tsunoda en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKota en-aut-sei=Sato en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anti-cholinesterase drug kn-keyword=anti-cholinesterase drug en-keyword=the CHRNE gene kn-keyword=the CHRNE gene en-keyword=congenital myasthenic syndrome kn-keyword=congenital myasthenic syndrome en-keyword=late presentation kn-keyword=late presentation en-keyword=mimicking seronegative myasthenia gravis kn-keyword=mimicking seronegative myasthenia gravis END start-ver=1.4 cd-journal=joma no-vol=91 cd-vols= no-issue= article-no= start-page=22 end-page=31 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collagen adhesion gene is associated with blood stream infections caused by methicillin-resistant Staphylococcus aureus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. It is not clear whether genetic characteristics of the bacteria contribute to disease pathogenesis in MRSA infection. We hypothesized that whole genome analysis of MRSA strains could reveal the key gene loci and/or the gene mutations that affect clinical manifestations of MRSA infection.
Methods: Whole genome sequences (WGS) of MRSA of 154 strains were analyzed with respect to clinical manifestations and data. Further, we evaluated the association between clinical manifestations in MRSA infection and genomic information.
Results: WGS revealed gene mutations that correlated with clinical manifestations of MRSA infection. Moreover, 12 mutations were selected as important mutations by Random Forest analysis. Cluster analysis revealed strains associated with a high frequency of bloodstream infection (BSI). Twenty seven out of 34 strains in this cluster caused BSI. These strains were all positive for collagen adhesion gene (cna) and have mutations in the locus, those were selected by Random Forest analysis. Univariate and multivariate analysis revealed that these gene mutations were the predictor for the incidence of BSI. Interestingly, mutant CNA protein showed lower attachment ability to collagen, suggesting that the mutant protein might contribute to the dissemination of bacteria.
Conclusions: These findings suggest that the bacterial genotype affects the clinical characteristics of MRSA infection. (c) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. en-copyright= kn-copyright= en-aut-name=IwataYasunori en-aut-sei=Iwata en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatouKenji en-aut-sei=Satou en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FuruichiKengo en-aut-sei=Furuichi en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YonedaIkuko en-aut-sei=Yoneda en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumuraTakuhiro en-aut-sei=Matsumura en-aut-mei=Takuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YutaniMasahiro en-aut-sei=Yutani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujinagaYukako en-aut-sei=Fujinaga en-aut-mei=Yukako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaseAtsushi en-aut-sei=Hase en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaHidetoshi en-aut-sei=Morita en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhtaToshiko en-aut-sei=Ohta en-aut-mei=Toshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SendaYasuko en-aut-sei=Senda en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=Sakai-TakemoriYukiko en-aut-sei=Sakai-Takemori en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WadaTaizo en-aut-sei=Wada en-aut-mei=Taizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujitaShinichi en-aut-sei=Fujita en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MiyakeTaito en-aut-sei=Miyake en-aut-mei=Taito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YasudaHaruka en-aut-sei=Yasuda en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SakaiNorihiko en-aut-sei=Sakai en-aut-mei=Norihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KitajimaShinji en-aut-sei=Kitajima en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ToyamaTadashi en-aut-sei=Toyama en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ShinozakiYasuyuki en-aut-sei=Shinozaki en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SagaraAkihiro en-aut-sei=Sagara en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MiyagawaTaro en-aut-sei=Miyagawa en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HaraAkinori en-aut-sei=Hara en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=ShimizuMiho en-aut-sei=Shimizu en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KamikawaYasutaka en-aut-sei=Kamikawa en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IkeoKazuho en-aut-sei=Ikeo en-aut-mei=Kazuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ShichinoShigeyuki en-aut-sei=Shichino en-aut-mei=Shigeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=UehaSatoshi en-aut-sei=Ueha en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NakajimaTakuya en-aut-sei=Nakajima en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MatsushimaKouji en-aut-sei=Matsushima en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=KanekoShuichi en-aut-sei=Kaneko en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=WadaTakashi en-aut-sei=Wada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Division of Infection Control, Kanazawa University kn-affil= affil-num=2 en-affil=Faculty of Electrical and Computer Engineering, Kanazawa University kn-affil= affil-num=3 en-affil=Division of Nephrology, Kanazawa Medical University School of Medicine kn-affil= affil-num=4 en-affil=Division of Nephrology, Kanazawa University kn-affil= affil-num=5 en-affil=Department of Bacteriology, Kanazawa University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Faculty of Electrical and Computer Engineering, Kanazawa University kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=University of Tsukuba kn-affil= affil-num=11 en-affil=Division of Infection Control, Kanazawa University kn-affil= affil-num=12 en-affil=Division of Infection Control, Kanazawa University kn-affil= affil-num=13 en-affil=Division of Infection Control, Kanazawa University kn-affil= affil-num=14 en-affil=Division of Infection Control, Kanazawa University kn-affil= affil-num=15 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=16 en-affil=Department of Nephrology and Laboratory Medicine, Kanazawa University kn-affil= affil-num=17 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Division of Blood Purification, Kanazawa University kn-affil= affil-num=18 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=19 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=20 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=21 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=22 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=23 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=24 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=25 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=26 en-affil=Laboratory of DNA Data Analysis, National Institute of Genetics kn-affil= affil-num=27 en-affil=Department of Molecular Preventive Medicine, University of Tokyo kn-affil= affil-num=28 en-affil=Department of Molecular Preventive Medicine, University of Tokyo kn-affil= affil-num=29 en-affil=Department of Molecular Preventive Medicine, University of Tokyo kn-affil= affil-num=30 en-affil=Department of Molecular Preventive Medicine, University of Tokyo kn-affil= affil-num=31 en-affil=epartment of Disease Control and Homeostasis, Kanazawa University kn-affil= affil-num=32 en-affil=Division of Nephrology, Kanazawa University, Kanazawa, Japan; Department of Nephrology and Laboratory Medicine, Kanazawa University kn-affil= en-keyword=Bloodstream infection kn-keyword=Bloodstream infection en-keyword=Cna kn-keyword=Cna en-keyword=MRSA kn-keyword=MRSA en-keyword=Whole genome sequencing kn-keyword=Whole genome sequencing END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue= article-no= start-page=100515 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and genetic aspects of mild hypophosphatasia in Japanese patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from a dysfunctional tissue non-specific alkaline phosphatase enzyme (TNSALP). Although genotype-phenotype correlations have been described in HPP patients, only sparse information is currently available on the genetics of mild type HPP.
Methods: We investigated 5 Japanese patients from 3 families with mild HPP (patients 1 and 2 are siblings; patient 4 is a daughter of patient 5) who were referred to Fujita Health University due to the premature loss of deciduous teeth. Physical and dental examinations, and blood, urine and bone density tests were conducted. Genetic analysis of the ALPL gene was performed in all patients with their informed consent.
Results: After a detailed interview and examination, we found characteristic symptoms of HPP in some of the study cases. Mobile teeth or the loss of permanent teeth were observed in 2 patients, and 3 out of 5 patients had a history of asthma. The serum ALP levels of all patients were 30% below the lower limit of the age equivalent normal range. ALPL gene analysis revealed compound heterozygous mutations, including Ile395Val and Leu520Argfs in family 1, Val95Met and Gly491Arg in family 2, and a dominant missense mutation (Gly456Arg) in family 3. The 3D-modeling of human TNSALP revealed three mutations (Val95Met, Ile395Val and Gly456Arg) at the homodimer interface. Severe collisions between the side chains were predicted for the Gly456Arg variant.
Discussion: One of the characteristic findings of this present study was a high prevalence of coexisting asthma and a high level serum IgE level. These characteristics may account for the fragility of tracheal tissues and a predisposition to asthma in patients with mild HPP. The genotypes of the five mild HPP patients in our present study series included 1) compound heterozygous for severe and hypomorphic mutations, and 2) dominant-negative mutations. All of these mutations were at the homodimer interface, but only the dominant-negative mutation was predicted to cause a severe collision effect between the side chains. This may account for varying mechanisms leading to different effects on TNSALP function. en-copyright= kn-copyright= en-aut-name=YokoiKatsuyuki en-aut-sei=Yokoi en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoko en-aut-sei=Nakajima en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinkaiYasuko en-aut-sei=Shinkai en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SanoYoshimi en-aut-sei=Sano en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImamuraMototaka en-aut-sei=Imamura en-aut-mei=Mototaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshikawaTetsushi en-aut-sei=Yoshikawa en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoTetsuya en-aut-sei=Ito en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurahashiHiroki en-aut-sei=Kurahashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=3 en-affil=Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University kn-affil= affil-num=4 en-affil=Department of Plastic Surgery, Division of Pediatric Dentistry & Orthodontics, Fujita Health University of Medicine kn-affil= affil-num=5 en-affil=Department of Plastic Surgery, Division of Pediatric Dentistry & Orthodontics, Fujita Health University of Medicine kn-affil= affil-num=6 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=9 en-affil=Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University kn-affil= en-keyword=ALPL kn-keyword=ALPL en-keyword=Dominant-negative mutations kn-keyword=Dominant-negative mutations en-keyword=Hypophosphatasia kn-keyword=Hypophosphatasia en-keyword=Premature loss of deciduous kn-keyword=Premature loss of deciduous END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=243 end-page=252 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190614 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors en-subtitle= kn-subtitle= en-abstract= kn-abstract=We recently demonstrated the generation of mouse induced tissue-specific stem (iTS) cells through transient overexpression of reprogramming factors combined with tissue-specific selection. Here we induced expandable tissue-specific progenitor (iTP) cells from human pancreatic tissue through transient expression of genes encoding the reprogramming factors OCT4 (octamer-binding transcription factor 4), p53 small hairpin RNA (shRNA), SOX2 (sex-determining region Y-box 2), KLF4 (Kruppel-like factor 4), L-MYC, and LIN28. Transfection of episomal plasmid vectors into human pancreatic tissue efficiently generated iTP cells expressing genetic markers of endoderm and pancreatic progenitors. The iTP cells differentiated into insulin-producing cells more efficiently than human induced pluripotent stem cells (iPSCs). iTP cells continued to proliferate faster than pancreatic tissue cells until days 100?120 (passages 15?20). iTP cells subcutaneously inoculated into immunodeficient mice did not form teratomas. Genomic bisulfite nucleotide sequence analysis demonstrated that the OCT4 and NANOG promoters remained partially methylated in iTP cells. We compared the global gene expression profiles of iPSCs, iTP cells, and pancreatic cells (islets >80%). Microarray analyses revealed that the gene expression profiles of iTP cells were similar, but not identical, to those of iPSCs but different from those of pancreatic cells. The generation of human iTP cells may have important implications for the clinical application of stem/progenitor cells. en-copyright= kn-copyright= en-aut-name=NoguchiHirofumi en-aut-sei=Noguchi en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Miyagi-ShiohiraChika en-aut-sei=Miyagi-Shiohira en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaYoshiki en-aut-sei=Nakashima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KinjoTakao en-aut-sei=Kinjo en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiNaoya en-aut-sei=Kobayashi en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitohIssei en-aut-sei=Saitoh en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShapiroA. M. James en-aut-sei=Shapiro en-aut-mei=A. M. James kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KinTatsuya en-aut-sei=Kin en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=2 en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=3 en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=4 en-affil=Department of Basic Laboratory Sciences, School of Health Sciences in Faculty of Medicine, University of the Ryukyus kn-affil= affil-num=5 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=6 en-affil=Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Clinical Islet Transplant Program and Department of Surgery, University of Alberta kn-affil= affil-num=9 en-affil=Clinical Islet Transplant Program and Department of Surgery, University of Alberta kn-affil= en-keyword=induced tissue-specific progenitor cells kn-keyword=induced tissue-specific progenitor cells en-keyword=iTP kn-keyword=iTP en-keyword=induced tissue-specific stem cells kn-keyword=induced tissue-specific stem cells en-keyword=iTS kn-keyword=iTS en-keyword=induced pluripotent stem cells kn-keyword=induced pluripotent stem cells en-keyword=iPSCs kn-keyword=iPSCs en-keyword=reprogramming factors kn-keyword=reprogramming factors en-keyword=pancreas kn-keyword=pancreas END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue= article-no= start-page=209 end-page=217 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CACNA1A variants may modify the epileptic phenotype of Dravet syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract= Dravet syndrome is an intractable epileptic syndrome beginning in the first year of life. De novo mutations of SCN1A, which encode the Na(v)1.1 neuronal voltage-gated sodium channel, are considered the major cause of Dravet syndrome. In this study, we investigated genetic modifiers of this syndrome. We performed a mutational analysis of all coding exons of CACNA1A in 48 subjects with Dravet syndrome. To assess the effects of CACNA1A variants on the epileptic phenotypes of Dravet syndrome, we compared clinical features in two genotype groups: 1) subjects harboring SCN1A mutations but no CACNA1A variants (n=20) and 2) subjects with SCN1A mutations plus CACNA1A variants (n=20). CACNA1A variants detected in patients were studied using heterologous expression of recombinant human Ca(v)2.1 in HEK 293 cells and whole-cell patch-clamp recording. Nine CACNA1A variants, including six novel ones, were detected in 21 of the 48 subjects (43.8%). Based on the incidence of variants in healthy controls, most of the variants seemed to be common polymorphisms. However, the subjects harboring SCN1A mutations and CACNA1A variants had absence seizures more frequently than the patients with only SCN1A mutations (8/20 vs. 0/20, p=0.002). Moreover, the former group of subjects exhibited earlier onset of seizures and more frequent prolonged seizures before one year of age, compared to the latter group of subjects. The electrophysiological properties of four of the five novel Ca(v)2.1 variants exhibited biophysical changes consistent with gain-of-function. We conclude that CACNA1A variants in some persons with Dravet syndrome may modify the epileptic phenotypes. en-copyright= kn-copyright= en-aut-name=OhmoriIori en-aut-sei=Ohmori en-aut-mei=Iori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JitsumoriYoshimi en-aut-sei=Jitsumori en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriAkiko en-aut-sei=Mori en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishikiTeiichi en-aut-sei=Nishiki en-aut-mei=Teiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhtsukaYoko en-aut-sei=Ohtsuka en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHideki en-aut-sei=Matsui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil= kn-affil= affil-num=5 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=4 article-no= start-page=367 end-page=372 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Patient with Type 3 Autoimmune Polyglandular Syndrome who Developed Systemic Lupus Erythematosus 8 years after the Diagnosis of Autoimmune Hepatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract= Eight years prior to her present admission, a 61-year-old Japanese woman was diagnosed with autoimmune hepatitis, slowly progressive insulin-dependent diabetes mellitus, and chronic thyroiditis; she had been treated with oral prednisolone (PSL). After she suddenly discontinued PSL, she newly developed systemic lupus erythematosus. A combination therapy of oral PSL and intravenous cyclophosphamide resulted in remission. She was finally diagnosed with autoimmune polyglandular syndrome (APS) type 3 (3A ,3B, 3D), complicated with four different autoimmune diseases. Since patients with type 3 APS may present many manifestations over a long period of time, they should be carefully monitored. en-copyright= kn-copyright= en-aut-name=Mifune-MoriokaTomoyo en-aut-sei=Mifune-Morioka en-aut-mei=Tomoyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=A. UchidaHaruhito en-aut-sei=A. Uchida en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeMayu en-aut-sei=Watanabe en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OuchiChihiro en-aut-sei=Ouchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiseKoki en-aut-sei=Mise en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawakitaChieko en-aut-sei=Kawakita en-aut-mei=Chieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanoYuzuki en-aut-sei=Kano en-aut-mei=Yuzuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnishiAkifumi en-aut-sei=Onishi en-aut-mei=Akifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TomaKishio en-aut-sei=Toma en-aut-mei=Kishio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WadaNozomu en-aut-sei=Wada en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IkedaFusao en-aut-sei=Ikeda en-aut-mei=Fusao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SasakiErika en-aut-sei=Sasaki en-aut-mei=Erika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SuganamiYu en-aut-sei=Suganami en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KishidaMasayuki en-aut-sei=Kishida en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of General Internal Medicine and Endocrinology, Okayama City Hospital kn-affil= affil-num=15 en-affil=Department of General Internal Medicine and Endocrinology, Okayama City Hospital kn-affil= affil-num=16 en-affil=Department of General Internal Medicine and Endocrinology, Okayama City Hospital kn-affil= affil-num=17 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=autoimmune polyglandular syndrome type 3 kn-keyword=autoimmune polyglandular syndrome type 3 en-keyword=systemic lupus erythematosus kn-keyword=systemic lupus erythematosus en-keyword=autoimmune hepatitis kn-keyword=autoimmune hepatitis en-keyword=slowly progressive insulin-dependent diabetes mellitus kn-keyword=slowly progressive insulin-dependent diabetes mellitus en-keyword=chronic thyroiditis kn-keyword=chronic thyroiditis END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=4 article-no= start-page=315 end-page=323 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Construction and Characterization of a PGN_0297 Mutant of Porphyromonas gingivalis: Evidence of the Contribution of PGN_0297 to Gingipain Activity en-subtitle= kn-subtitle= en-abstract= kn-abstract=The periodontal pathogen Porphyromonas gingivalis shows colonial pigmentation on blood agar and produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in an organism’s virulence and pigmentation. We showed previously that deletion of the PGN_0300 gene abolished the pigmentation activity and reduced the proteolytic activity of gingipains. The role of the PGN_0297 gene, which consists of an operon with the PGN_0300 gene, is unclear. Herein we examined the effect of PGN_0297 gene deletion on the pigmentation and proteolytic activities and transcriptional levels of gingipains. A PGN_0297 gene deletion mutant (ΔPGN_0297) did not exhibit the pigmentation. The proteolytic activity of the gingipains was decreased in the culture supernatant and on the cell surface of ΔPGN_0297. The mutant ΔPGN_0297 failed to attenuate Akt phosphorylation at Thr308 and Ser473, but both phosphorylations were attenuated in the wild-type and its complementation strain. The deletion of PGN_0297 gene did not substantially affect the transcriptional levels of the gingipain genes kgp, rgpA, and rgpB. Taken together, these results indicate that PGN_0297 is closely involved in the secretion and maturation of gingipains. en-copyright= kn-copyright= en-aut-name=OnoShintaro en-aut-sei=Ono en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TachibanaMasato en-aut-sei=Tachibana en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Abu Saleh Muhammad Shahriar en-aut-sei=Abu Saleh Muhammad Shahriar en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HelingWang en-aut-sei=Heling en-aut-mei=Wang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=periodontitis kn-keyword=periodontitis en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=gingipain kn-keyword=gingipain en-keyword=C-terminal domain kn-keyword=C-terminal domain en-keyword=secretion system kn-keyword=secretion system END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=4 article-no= start-page=285 end-page=297 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dynamic Reorganization of Microtubule and Glioma Invasion en-subtitle= kn-subtitle= en-abstract= kn-abstract= Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion. en-copyright= kn-copyright= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchikawaTomotsugu en-aut-sei=Ichikawa en-aut-mei=Tomotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurozumiKazuhiko en-aut-sei=Kurozumi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neurosurgery, The University of Texas Health Science Center at Houston kn-affil= affil-num=2 en-affil=Department of Neurosurgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=glioma kn-keyword=glioma en-keyword=cytoskeletons kn-keyword=cytoskeletons en-keyword=invasion kn-keyword=invasion en-keyword=microtubules kn-keyword=microtubules END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=3 article-no= start-page=273 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Nager Syndrome Diagnosed Before Birth en-subtitle= kn-subtitle= en-abstract= kn-abstract= Nager syndrome is a rare disease involving severe micrognathia and upper limb shortening. In this report, we describe a case in which micrognathia of the fetus was suspected based on the observation of upper limb shortening during detailed B mode and 3D/4D ultrasonographic observation, and combined fetal MRI and 3D-CT led to a prenatal diagnosis of Nager syndrome. Upon birth, because severe micrognathia caused airway obstruction and made it difficult to spread the larynx for intubation, effective ventilation could not be carried out and a tracheostomy was necessary. Since a differential diagnosis of Nager syndrome can be made based on the fact that micrognathia typically co-occurs with upper limb shortening, it is possible to diagnose the disease before birth and prepare for life-saving measures accordingly. en-copyright= kn-copyright= en-aut-name=HayataKei en-aut-sei=Hayata en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Masuyama Hisashi en-aut-sei=Masuyama en-aut-mei= Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Eto Eriko en-aut-sei=Eto en-aut-mei= Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuiTakashi en-aut-sei=Mitsui en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamadaShoko en-aut-sei=Tamada en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EguchiTakeshi en-aut-sei=Eguchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TaniKazumasa en-aut-sei=Tani en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhiraAkiko en-aut-sei=Ohira en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WashioYosuke en-aut-sei=Washio en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshimotoJunko en-aut-sei=Yoshimoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Nager syndrome kn-keyword=Nager syndrome en-keyword=acrofacial dysostosis kn-keyword=acrofacial dysostosis en-keyword=micrognathia kn-keyword=micrognathia en-keyword= jaw index kn-keyword= jaw index en-keyword=SF3B4 kn-keyword=SF3B4 END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=3 article-no= start-page=263 end-page=267 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sudden, Sharp Turn in an AIDS Patient’s Course Following the Onset of Fulminant Type 1 Diabetes en-subtitle= kn-subtitle= en-abstract= kn-abstract= A previously healthy 40-year-old Japanese male was urgently admitted with a 2-month history of dysphagia, 30-kg weight loss, and fever. Human immunodeficiency virus (HIV) antibodies and cytomegalovirus antigenemia were positive. Pneumocystis pneumonia and cytomegalovirus pneumonia were suspected. The patient was diagnosed with acquired immune deficiency syndrome (AIDS). Cytomegalovirus antigenemia became negative 20 days after the positive result. On hospital day 41, he experienced cardiopulmonary arrest. The clinical diagnosis was fulminant type 1 diabetes mellitus. He later developed hypoglycemia and was diagnosed with adrenal insufficiency accompanied by septic shock. He died of multiple organ failure 29 h post-admission to our ICU. en-copyright= kn-copyright= en-aut-name=ShimoyamaYuichiro en-aut-sei=Shimoyama en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UmegakiOsamu en-aut-sei=Umegaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OoiYukimasa en-aut-sei=Ooi en-aut-mei=Yukimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShigemotoSho en-aut-sei=Shigemoto en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AguiTomoyuki en-aut-sei=Agui en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KadonoNoriko en-aut-sei=Kadono en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MinamiToshiaki en-aut-sei=Minami en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Intensive Care Unit, Osaka Medical College Hospital kn-affil= affil-num=2 en-affil=Department of Intensive Care Unit, Osaka Medical College Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Osaka Medical College Hospital kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Osaka Medical College Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Osaka Medical College Hospital kn-affil= affil-num=6 en-affil=Department of Intensive Care Unit, Osaka Medical College Hospital kn-affil= affil-num=7 en-affil=Department ofAnesthesiology, Osaka Medical College Hospital kn-affil= en-keyword=fulminant type 1 diabetes mellitus kn-keyword=fulminant type 1 diabetes mellitus en-keyword=human immunodeficiency virus kn-keyword=human immunodeficiency virus en-keyword=cytomegalovirus kn-keyword=cytomegalovirus en-keyword=hypoglycemia kn-keyword=hypoglycemia END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=3 article-no= start-page=255 end-page=262 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Improvement of Open Bite and Stomatognathic Function in an Axenfeld- Rieger Syndrome Patient by Orthodontic Sectional Arch Mechanics: Clinical Considerations and the Risk of Orthodontic Tooth Movement en-subtitle= kn-subtitle= en-abstract= kn-abstract= Orthodontists need to understand the orthodontic risks associated with systemic disorders. Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder with genetic and morphological variability. The risks of orthodontic treatment in ARS patients have been unclear. Here we describe the correction of an anterior open bite in a 15-year-old Japanese female ARS patient by molar intrusion using sectional archwires with miniscrew implants. An undesirable development of external apical root resorption (EARR) was observed in all intrusive force-applied posterior teeth during the patient’s orthodontic treatment, suggesting that ARS patients have a higher risk of EARR than the general population. en-copyright= kn-copyright= en-aut-name=SekiDaisuke en-aut-sei=Seki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeshitaNobuo en-aut-sei=Takeshita en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SeiryuMasahiro en-aut-sei=Seiryu en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DeguchiToru en-aut-sei=Deguchi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Takano-YamamotoTeruko en-aut-sei=Takano-Yamamoto en-aut-mei=Teruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry kn-affil= affil-num=2 en-affil=Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry kn-affil= affil-num=3 en-affil=Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry kn-affil= affil-num=4 en-affil=Division of Orthodontics, The Ohio State University College of Dentistry kn-affil= affil-num=5 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= en-keyword=Axenfeld-Rieger syndrome kn-keyword=Axenfeld-Rieger syndrome en-keyword=external apical root resorption kn-keyword=external apical root resorption en-keyword=miniscrew implant kn-keyword=miniscrew implant en-keyword=anterior open bite kn-keyword=anterior open bite END start-ver=1.4 cd-journal=joma no-vol=51 cd-vols= no-issue=3 article-no= start-page=1040 end-page=1045 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular Characterization of High-Level-Cholera-Toxin-Producing El Tor Variant Vibrio cholerae Strains in the Zanzibar Archipelago of Tanzania en-subtitle= kn-subtitle= en-abstract= kn-abstract= Analysis of 1,180 diarrheal stool samples in Zanzibar detected 247 Vibrio cholerae O1, Ogawa strains in 2009. Phenotypic traits and PCR-based detection of rstR, rtxC, and tcpA alleles showed that they belonged to the El Tor biotype. Genetic analysis of ctxB of these strains revealed that they were classical type, and production of classical cholera toxin B (CTB) was confirmed by Western blotting. These strains produced more CT than the prototype El Tor and formed a separate cluster by pulsed-field gel electrophoresis (PFGE) analysis. en-copyright= kn-copyright= en-aut-name=NahaA. en-aut-sei=Naha en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChowdhuryG. en-aut-sei=Chowdhury en-aut-mei=G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Ghosh-BanerjeeJ. en-aut-sei=Ghosh-Banerjee en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SenohM. en-aut-sei=Senoh en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiT. en-aut-sei=Takahashi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LeyB. en-aut-sei=Ley en-aut-mei=B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ThriemerK. en-aut-sei=Thriemer en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DeenJ. en-aut-sei=Deen en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SeidleinL. V. en-aut-sei=Seidlein en-aut-mei=L. V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AliS. M. en-aut-sei=Ali en-aut-mei=S. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KhatibA. en-aut-sei=Khatib en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=RamamurthyT. en-aut-sei=Ramamurthy en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NandyR. K. en-aut-sei=Nandy en-aut-mei=R. K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NairG. B. en-aut-sei=Nair en-aut-mei=G. B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakedaY. en-aut-sei=Takeda en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MukhopadhyayA. K. en-aut-sei=Mukhopadhyay en-aut-mei=A. K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=1National Institute of Cholera and Enteric Diseases kn-affil= affil-num=2 en-affil=1National Institute of Cholera and Enteric Diseases kn-affil= affil-num=3 en-affil=1National Institute of Cholera and Enteric Diseases kn-affil= affil-num=4 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases at NICED, kn-affil= affil-num=5 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases at NICED, kn-affil= affil-num=6 en-affil=The International Vaccine Institute kn-affil= affil-num=7 en-affil=The International Vaccine Institute kn-affil= affil-num=8 en-affil=The International Vaccine Institute kn-affil= affil-num=9 en-affil=Menzies School of Health Research kn-affil= affil-num=10 en-affil=Ministry of Health and Social Welfare kn-affil= affil-num=11 en-affil=Ministry of Health and Social Welfare kn-affil= affil-num=12 en-affil=1National Institute of Cholera and Enteric Diseases kn-affil= affil-num=13 en-affil=1National Institute of Cholera and Enteric Diseases kn-affil= affil-num=14 en-affil=1National Institute of Cholera and Enteric Diseases kn-affil= affil-num=15 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases at NICED, kn-affil= affil-num=16 en-affil=1National Institute of Cholera and Enteric Diseases kn-affil= en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae en-keyword=ctxB kn-keyword=ctxB en-keyword=Cholera kn-keyword=Cholera en-keyword=PFGE kn-keyword=PFGE END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=12 article-no= start-page=5658 end-page=5672 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160407 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Physiological TLR5 expression in the intestine is regulated by differential DNA binding of Sp1/Sp3 through simultaneous Sp1 dephosphorylation and Sp3 phosphorylation by two different PKC isoforms en-subtitle= kn-subtitle= en-abstract= kn-abstract= Toll-like receptor 5 (TLR5) expression in the intestinal epithelial cells (IECs) is critical to maintain health, as underscored by multiple intestinal and extra-intestinal diseases in mice genetically engineered for IEC-specific TLR5 knockout. A gradient of expression exists in the colonic epithelial cells from the cecum to the distal colon. Intriguingly, an identical gradient for the dietary metabolite, butyrate also exists in the luminal contents. However, both being critical for intestinal homeostasis and immune response, no studies examined the role of butyrate in the regulation of TLR5 expression. We showed that butyrate transcriptionally upregulates TLR5 in the IECs and augments flagellin-induced immune responses. Both basal and butyrate-induced transcription is regulated by differential binding of Sp-family transcription factors to the GC-box sequences over the TLR5 promoter. Butyrate activates two different protein kinase C isoforms to dephosphorylate/acetylate Sp1 by serine/threonine phosphatases and phosphorylate Sp3 by ERK-MAPK, respectively. This resulted in Sp1 displacement from the promoter and binding of Sp3 to it, leading to p300 recruitment and histone acetylation, activating transcription. This is the first study addressing the mechanisms of physiological TLR5 expression in the intestine. Additionally, a novel insight is gained into Sp1/Sp3-mediated gene regulation that may apply to other genes. en-copyright= kn-copyright= en-aut-name=Bhupesh Kumar Thakur en-aut-sei=Bhupesh Kumar Thakur en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DasguptaNirmalya en-aut-sei=Dasgupta en-aut-mei=Nirmalya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaAtri en-aut-sei=Ta en-aut-mei=Atri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DasSantasabuj en-aut-sei=Das en-aut-mei=Santasabuj kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases kn-affil= affil-num=2 en-affil=Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases kn-affil= affil-num=3 en-affil=Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases kn-affil= affil-num=4 en-affil=Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases kn-affil= END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=2 article-no= start-page=181 end-page=188 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exchange Transfusion and Cytarabine for Transient Abnormal Myelopoiesis in Hydrops Fetalis en-subtitle= kn-subtitle= en-abstract= kn-abstract= Most cases of transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) resolve spontaneously; however, DS-TAM neonates with hydrops fetalis (HF) show poor clinical outcomes. We report three infants with DS-TAM and HF who were treated with exchange transfusion (ET) followed by low-dose cytarabine (LD-CA). All of them survived without developing liver failure, acute leukemia, or other serious adverse events. Our results suggest that this combination treatment with ET and LD-CA would be safe, tolerable and effective as an novel approach for DS-TAM patients with HF. en-copyright= kn-copyright= en-aut-name=OkamuraTomoka en-aut-sei=Okamura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WashioYousuke en-aut-sei=Washio en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshimotoJunko en-aut-sei=Yoshimoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniKazumasa en-aut-sei=Tani en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimadaAkira en-aut-sei=Shimada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatric Hematology/Oncology, Okayama University Hospital kn-affil= en-keyword=cytarabine kn-keyword=cytarabine en-keyword=Down syndrome kn-keyword=Down syndrome en-keyword=exchange transfusion kn-keyword=exchange transfusion en-keyword=hydrops fetalis kn-keyword=hydrops fetalis en-keyword=transient abnormal myelopoiesis kn-keyword=transient abnormal myelopoiesis END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20180927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=POLE 変異とマイクロサテライト不安定性に基づいて分類された子宮体癌の臨床的意義 kn-title=Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HarumaTomoko en-aut-sei=Haruma en-aut-mei=Tomoko kn-aut-name=春間朋子 kn-aut-sei=春間 kn-aut-mei=朋子 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=72 cd-vols= no-issue=4 article-no= start-page=423 end-page=426 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=201808 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study Design of a Phase II Clinical Trial to Assess the Efficacy and Safety of Eperisone in Japanese Type 2 Diabetes Patients with Risk and Non-risk Alleles of CDKAL1 en-subtitle= kn-subtitle= en-abstract= kn-abstract= Genetic variation in Cdk5 Regulatory Associated Protein 1-Like 1 (CDKAL1) is associated with the development of type 2 diabetes (T2D). Dysfunction of CDKAL1 impairs the translation of proinsulin, which leads to glucose intolerance. Eperisone, an antispasmodic agent, has been shown to ameliorate glucose intolerance in Cdkal1-deficient mice. We have launched a phase II clinical study to investigate the potential anti-diabetic effect of eperisone in T2D patients carrying risk or non-risk alleles of CDKAL1. The primary endpoint is the change of hemoglobin A1c (HbA1c) levels. We also examined whether the efficacy of eperisone in T2D patients is associated with CDKAL1 activity. en-copyright= kn-copyright= en-aut-name=SakakidaKourin en-aut-sei=Sakakida en-aut-mei=Kourin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WeiFan-Yan en-aut-sei=Wei en-aut-mei=Fan-Yan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SenokuchiTakafumi en-aut-sei=Senokuchi en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimodaSeiya en-aut-sei=Shimoda en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakumaTatsuyuki en-aut-sei=Kakuma en-aut-mei=Tatsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ArakiEiichi en-aut-sei=Araki en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TomizawaKazuhito en-aut-sei=Tomizawa en-aut-mei=Kazuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=The Eperisone for Diabetes with Impaired tRNA (EDIT) Study Group en-aut-sei=The Eperisone for Diabetes with Impaired tRNA (EDIT) Study Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=2 en-affil=Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=3 en-affil=Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=4 en-affil=Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=5 en-affil=Biostatics Center, Medical School, Kurume University kn-affil= affil-num=6 en-affil=Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=7 en-affil=Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=8 en-affil= kn-affil= en-keyword=diabetes kn-keyword=diabetes en-keyword= insulin secretion kn-keyword= insulin secretion en-keyword=single nucleotide polymorphism kn-keyword=single nucleotide polymorphism en-keyword=glucose kn-keyword=glucose END start-ver=1.4 cd-journal=joma no-vol=72 cd-vols= no-issue=3 article-no= start-page=275 end-page=282 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=201806 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analysis of All 34 Exons of the SPINK5 Gene in Japanese Atopic Dermatitis Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract= Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a large multidomain serine protease inhibitor that is expressed in epidermal keratinocytes. Nonsense mutations of the SPINK5 gene, which codes for LEKTI, cause Netherton syndrome, which is characterized by hair abnormality, ichthyosis, and atopy. A single nucleotide polymorphism (SNP) of SPINK5, p.K420E, is reported to be associated with the pathogenesis of atopic dermatitis (AD). We studied all 34 exons of the SPINK5 gene in Japanese 57 AD patients and 50 normal healthy controls. We detected nine nonsynonymous variants, including p.K420E; these variants had already been registered in the SNP database. Among them, p.R654H (n=1) was found as a heterozygous mutation in the AD patients, but not in the control. No new mutation was detected. We next compared the data of the AD patients with data from the Human Genetic Variation Database provided by Kyoto University; a significant difference was found in the frequency of the p.S368N genotype distribution. PolyPhen-2 and SIFT, two algorithms for predicting the functional effects of amino acid substitutions, showed significant scores for p.R654H. Therefore, R654H might be a risk factor for epidermal barrier dysfunction in some Japanese AD patients. en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugimotoSaeko en-aut-sei=Sugimoto en-aut-mei=Saeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobashiMina en-aut-sei=Kobashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiharaSatoru en-aut-sei=Sugihara en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsujiKazuhide en-aut-sei=Tsuji en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoAtsushi en-aut-sei=Sato en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiuraYoshihiro en-aut-sei=Miura en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HattoriHiroaki en-aut-sei=Hattori en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TadaKotaro en-aut-sei=Tada en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HuhWook-Kang en-aut-sei=Huh en-aut-mei=Wook-Kang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SenoAkemi en-aut-sei=Seno en-aut-mei=Akemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Nishigawara Dermatology Clinic kn-affil= affil-num=9 en-affil=Sato Dermatology Clinic kn-affil= affil-num=10 en-affil=Miura Dermatology Clinic kn-affil= affil-num=11 en-affil=Hattori Dermatology and Allergy Clinic kn-affil= affil-num=12 en-affil=Tada Dermatology Clinic kn-affil= affil-num=13 en-affil=Dr. Huh's Dermatology Clinic kn-affil= affil-num=14 en-affil=Department of Dermatology, Mitoyo General Hospital kn-affil= affil-num=15 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=atopic dermatitis kn-keyword=atopic dermatitis en-keyword=SPINK5 kn-keyword=SPINK5 en-keyword=LEKTI kn-keyword=LEKTI en-keyword=serine protease inhibitor kn-keyword=serine protease inhibitor en-keyword=epidermal barrier dysfunction kn-keyword=epidermal barrier dysfunction END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=5 article-no= start-page=433 end-page=436 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic Factors of Low-responsiveness to Hepatitis B Virus Vaccine Confirms the Importance of Human Leukocyte Antigen Class II Types in a Japanese Young Adult Population en-subtitle= kn-subtitle= en-abstract= kn-abstract= We investigated the genetic mechanisms underlying the association between human leukocyte antigen (HLA) types and the immune response to hepatitis B virus (HBV) vaccination in 84 healthy Japanese adults, and found that the HLA-DRB1＊04 and HLA-DQB1＊03 frequencies were higher in the low responders (<10 mIU/ml; n=9, 10.7%) compared to the responders (?10 mIU/ml, n=75, 89.3%). The combination of DRB1＊04 and DQB1＊03 was associated with a low response to vaccination. The DRB1＊04 and DQB1＊03 haplotypes’ frequencies were significantly higher in the low responders compared to responders. Novel candidate HLA types may be important in Japanese individuals. en-copyright= kn-copyright= en-aut-name=YukimasaNobuyasu en-aut-sei=Yukimasa en-aut-mei=Nobuyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KohamaShota en-aut-sei=Kohama en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OboshiWataru en-aut-sei=Oboshi en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoShoichi en-aut-sei=Sato en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraTakehiro en-aut-sei=Nakamura en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=3 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=4 en-affil=Clinical Laboratory, Chiba Emergency Medical Center kn-affil= affil-num=5 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= en-keyword=HBV vaccine kn-keyword=HBV vaccine en-keyword=antibody response kn-keyword=antibody response en-keyword=low-responder kn-keyword=low-responder en-keyword=HLA class II kn-keyword=HLA class II en-keyword=Japanese kn-keyword=Japanese END start-ver=1.4 cd-journal=joma no-vol=129 cd-vols= no-issue=2 article-no= start-page=111 end-page=114 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20170801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Adenocarcinoma in the jejunum 20 years after surgery for familial adenomatous polyposis kn-title=家族性大腸腺腫症術後20年後に小腸癌を発症した1例 en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 58-year-old Japanese man visited a local clinic for the evaluation of a stomachache. He was diagnosed with intestinal obstruction. His medical history included a proctocolectomy at the age of 38 years, due to familial adenomatous polyposis (FAP). He was referred to our institution, where he underwent a computed tomography examination and endoscopy of the small intestine. The pathological diagnosis was adenocarcinoma. No invasive or metastatic lesions were observed. Therefore, partial resection of the ileum with lymphadenectomy and reconstruction of the ileostomy were performed. Pathological examination revealed that the tumor was type 2, pT3 (SS) , pN1, pPM0, pDM0, pRM0, INFb, ly1, v1, pEX0, PN0. Twenty-nine days after the surgery, the patient was diagnosed with lung metastasis and he underwent lung radiofrequency ablation. We suggest that long-term follow-up is necessary for patients after surgery for FAP, because of the risk of malignant disease developing in other organs. en-copyright= kn-copyright= en-aut-name=SugiharaYuusaku en-aut-sei=Sugihara en-aut-mei=Yuusaku kn-aut-name=杉原雄策 kn-aut-sei=杉原 kn-aut-mei=雄策 aut-affil-num=1 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name=川野誠司 kn-aut-sei=川野 kn-aut-mei=誠司 aut-affil-num=2 ORCID= en-aut-name=HaradaKeita en-aut-sei=Harada en-aut-mei=Keita kn-aut-name=原田馨太 kn-aut-sei=原田 kn-aut-mei=馨太 aut-affil-num=3 ORCID= en-aut-name=TakashimaShiho en-aut-sei=Takashima en-aut-mei=Shiho kn-aut-name=高嶋志保 kn-aut-sei=高嶋 kn-aut-mei=志保 aut-affil-num=4 ORCID= en-aut-name=TakeiDaisuke en-aut-sei=Takei en-aut-mei=Daisuke kn-aut-name=竹井大介 kn-aut-sei=竹井 kn-aut-mei=大介 aut-affil-num=5 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name=井口俊博 kn-aut-sei=井口 kn-aut-mei=俊博 aut-affil-num=6 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name=高原政宏 kn-aut-sei=高原 kn-aut-mei=政宏 aut-affil-num=7 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name=平岡佐規子 kn-aut-sei=平岡 kn-aut-mei=佐規子 aut-affil-num=8 ORCID= en-aut-name=MoriYoshiko en-aut-sei=Mori en-aut-mei=Yoshiko kn-aut-name=母里淑子 kn-aut-sei=母里 kn-aut-mei=淑子 aut-affil-num=9 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name=岸本浩行 kn-aut-sei=岸本 kn-aut-mei=浩行 aut-affil-num=10 ORCID= en-aut-name=NagasakaTakeshi en-aut-sei=Nagasaka en-aut-mei=Takeshi kn-aut-name=永坂岳司 kn-aut-sei=永坂 kn-aut-mei=岳司 aut-affil-num=11 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name=岡田裕之 kn-aut-sei=岡田 kn-aut-mei=裕之 aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil=岡山大学病院　消化器内科 affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil=岡山大学病院　消化器内科 affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil=岡山大学病院　光学医療診療部 affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil=岡山大学病院　消化器内科 affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil=岡山大学病院　光学医療診療部 affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil=岡山大学病院　消化器内科 affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil=岡山大学病院　消化器内科 affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil=岡山大学病院　消化器内科 affil-num=9 en-affil=Division of Endoscopy, Okayama University Hospital kn-affil=岡山大学病院　消化管外科 affil-num=10 en-affil=Division of Endoscopy, Okayama University Hospital kn-affil=岡山大学病院　消化管外科 affil-num=11 en-affil=Division of Endoscopy, Okayama University Hospital kn-affil=岡山大学病院　消化管外科 affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil=岡山大学病院　消化器内科 en-keyword=家族性大腸腺腫症 (familial adenomatous polyposis) kn-keyword=家族性大腸腺腫症 (familial adenomatous polyposis) en-keyword=小腸癌 (jejunal cancer) kn-keyword=小腸癌 (jejunal cancer) en-keyword=小腸内視鏡検査 (small intestine endoscope) kn-keyword=小腸内視鏡検査 (small intestine endoscope) END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=3 article-no= start-page=237 end-page=239 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20161201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Biobank kn-title=バイオバンク en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MoritaMizuki en-aut-sei=Morita en-aut-mei=Mizuki kn-aut-name=森田瑞樹 kn-aut-sei=森田 kn-aut-mei=瑞樹 aut-affil-num=1 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name=豊岡伸一 kn-aut-sei=豊岡 kn-aut-mei=伸一 aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Biorepository Research and Networking, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科　クリニカルバイオバンクネットワーキング事業化研究講座 affil-num=2 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科　臨床遺伝子医療学 END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=3 article-no= start-page=183 end-page=189 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20161201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Electroencephalography：an old examination tool with a new meaning for childhood epilepsy kn-title=脳波：小児てんかんにおける古くて新しい検査 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name=小林勝弘 kn-aut-sei=小林 kn-aut-mei=勝弘 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科　発達神経病態学 en-keyword=頭皮脳波 kn-keyword=頭皮脳波 en-keyword=点頭てんかん kn-keyword=点頭てんかん en-keyword=てんかん外科 kn-keyword=てんかん外科 en-keyword=高周波振動 kn-keyword=高周波振動 en-keyword=時間・周波数分析 kn-keyword=時間・周波数分析 END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=3 article-no= start-page=165 end-page=169 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20161201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2015 Incentive Award of the Okayama Medical Association in General Medical Science (2015 Yuuki Prize) kn-title=平成27年度岡山医学会賞 総合研究奨励賞（結城賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name=藤原英晃 kn-aut-sei=藤原 kn-aut-mei=英晃 aut-affil-num=1 ORCID= affil-num=1 en-affil=University of Michigan kn-affil=ミシガン大学 END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=4 article-no= start-page=229 end-page=236 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Moyamoya Disease: A Review of Clinical Research en-subtitle= kn-subtitle= en-abstract= kn-abstract=About 5 decades have passed since the concept of moyamoya disease (MMD) was established in Japan. In that time, many clinical MMD studies have been performed from several different points of view, such as epidemiology, pathophysiology, surgical procedures, and prognosis. In addition, rapid developments in MMD genetic analysis have occurred. In light of all this activity, clinicians must continually update their knowledge of MMD in order to improve the prognosis of MMD patients. In this review article, we summarize the clinical MMD studies and introduce cutting-edge findings regarding MMD. en-copyright= kn-copyright= en-aut-name=HishikawaTomohito en-aut-sei=Hishikawa en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=clinical research kn-keyword=clinical research en-keyword=moyamoya disease kn-keyword=moyamoya disease END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=統合失調症発症に関与する危険アレルは、不良な臨床・社会転帰とも関連する kn-title=Individual risk alleles of susceptibility to schizophrenia are associated with poor clinical and social outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name=酒本真次 kn-aut-sei=酒本 kn-aut-mei=真次 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=1 article-no= start-page=13 end-page=19 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Current state of and views regarding clinical approarches to Helicobacter pylori infection kn-title=Helicobacter pylori 感染診療の現況と展望 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name=岡田裕之 kn-aut-sei=岡田 kn-aut-mei=裕之 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 消化器・肝臓内科学 en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori en-keyword=除菌療法 kn-keyword=除菌療法 en-keyword=胃癌 kn-keyword=胃癌 en-keyword=胃炎 kn-keyword=胃炎 en-keyword=MALT リンパ腫 kn-keyword=MALT リンパ腫 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20151231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=染色体不安定性をもつ胃癌におけるNetrin-1受容体群のジェネティックおよびエピジェネティック変異 kn-title=Genetic and epigenetic alterations of netrin-1 receptors in gastric cancer with chromosomal instability en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TodaKeisuke en-aut-sei=Toda en-aut-mei=Keisuke kn-aut-name=戸田桂介 kn-aut-sei=戸田 kn-aut-mei=桂介 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院 END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=8 article-no= start-page=e72214 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Calpain-2 Compensation Promotes Angiotensin II-Induced Ascending and Abdominal Aortic Aneurysms in Calpain-1 Deficient Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Objective Recently, we demonstrated that angiotensin II (AngII)-infusion profoundly increased both aortic protein and activity of calpains, calcium-activated cysteine proteases, in mice. In addition, pharmacological inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal formation localized to the ascending aorta. However, the precise functional contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA formation is not known. Similarly, a functional role of calpain in AngII-induced ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and calpain-1 genetic deficient mice, we examined the relative contribution of calpain isoforms in AngII-induced ascending and abdominal AA development. Methodology/Results To investigate the relative contribution of calpain-1 and -2 in development of AngII-induced AAs, male LDLr ?/? mice that were either calpain-1 +/+ or ?/? were fed a saturated fat-enriched diet and infused with AngII (1,000 ng/kg/min) for 4 weeks. Calpain-1 deficiency had no significant effect on body weight or blood pressure during AngII infusion. Moreover, calpain-1 deficiency showed no discernible effects on AngII-induced ascending and abdominal AAs. Interestingly, AngII infusion induced increased expression of calpain-2 protein, thus compensating for total calpain activity in aortas of calpain-1 deficient mice. Oral administration of BDA-410, a calpain inhibitor, along with AngII-infusion significantly attenuated AngII-induced ascending and abdominal AA formation in both calpain-1 +/+ and ?/? mice as compared to vehicle administered mice. Furthermore, BDA-410 administration attenuated AngII-induced aortic medial hypertrophy and macrophage accumulation. Western blot and immunostaining analyses revealed BDA-410 administration attenuated AngII-induced C-terminal fragmentation of filamin A, an actin binding cytoskeletal protein in aorta. Conclusion Calpain-2 compensates for loss of calpain-1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation in mice. en-copyright= kn-copyright= en-aut-name=SubramanianVenkateswaran en-aut-sei=Subramanian en-aut-mei=Venkateswaran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoorleghenJessica　J. en-aut-sei=Moorleghen en-aut-mei=Jessica　J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BalakrishnanAnju en-aut-sei=Balakrishnan en-aut-mei=Anju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HowattDeborah　A. en-aut-sei=Howatt en-aut-mei=Deborah　A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChishtiAthar H. en-aut-sei=Chishti en-aut-mei=Athar H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Saha Cardiovascular Research Center, University of Kentucky affil-num=2 en-affil= kn-affil=Saha Cardiovascular Research Center, University of Kentucky affil-num=3 en-affil= kn-affil=Saha Cardiovascular Research Center, University of Kentucky affil-num=4 en-affil= kn-affil=Saha Cardiovascular Research Center, University of Kentucky affil-num=5 en-affil= kn-affil=Department of Molecular Physiology and Pharmacology, Sackler School Programs in Physiology, Pharmacology, and Microbiology, Tufts University School of Medicine affil-num=6 en-affil= kn-affil=Department of Medicine and Clinical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=3 article-no= start-page=213 end-page=218 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20151201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A case report of giant ectopic pheochromocytoma conversion therapy with radioisotope therapy and chemotherapy followed by curative resection kn-title=術前内照射および化学療法が著効し,根治切除し得た巨大異所性褐色細胞腫の1例 en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 46-year-old man was found to be positive for occult blood at a medical checkup and was revealed to have a 14-cm tumor on the right side of abdominal aorta by a subsequent abdominal CT scan. The endocrinology laboratory data showed elevations in the levels of serum noradrenaline, and ectopic pheochromocytoma was suspected. The tumor was compressing the inferior vena cava and portal vein, the superior mesenteric artery and the pancreas. Since it would be difficult to cure by operation, neoadjuvant therapy was started using radioisotope therapy by I-131 metaiodobenzylguanidine (131I-MIBG) and chemotherapy (CVD therapy ; cyclophosphamide, vincristine, dacarbazine). He was treated with three courses of radioisotope therapy and 16 courses of chemotherapy, which significantly reduced the tumor size. This made radical resection possible ; we were able to avoid the merger excision of great vessels and other organs. On pathological and immunopathological findings, the tumor was diagnosed as ectopic　pheochromocytoma. Regarding the safety and curability of the treatment, neoadjuvant therapy may be useful in treating very large tumors that show invasion of other organs. en-copyright= kn-copyright= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name=安井和也 kn-aut-sei=安井 kn-aut-mei=和也 aut-affil-num=1 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name=楳田祐三 kn-aut-sei=楳田 kn-aut-mei=祐三 aut-affil-num=2 ORCID= en-aut-name=KumanoKenjiro en-aut-sei=Kumano en-aut-mei=Kenjiro kn-aut-name=熊野健二郎 kn-aut-sei=熊野 kn-aut-mei=健二郎 aut-affil-num=3 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name=田端雅弘 kn-aut-sei=田端 kn-aut-mei=雅弘 aut-affil-num=4 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name=大塚文男 kn-aut-sei=大塚 kn-aut-mei=文男 aut-affil-num=5 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name=八木孝仁 kn-aut-sei=八木 kn-aut-mei=孝仁 aut-affil-num=6 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name=藤原俊義 kn-aut-sei=藤原 kn-aut-mei=俊義 aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=4 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=6 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=7 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 en-keyword=異所性褐色細胞腫（ectopic pheochromocytoma） kn-keyword=異所性褐色細胞腫（ectopic pheochromocytoma） en-keyword=化学療法（chemo therapy） kn-keyword=化学療法（chemo therapy） en-keyword=131I-MIBG kn-keyword=131I-MIBG END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=3 article-no= start-page=187 end-page=195 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20151201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Basic and clinical research regarding vascular endothelial function kn-title=血管内皮機能を対象にした基礎および臨床医学研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name=塚原宏一 kn-aut-sei=塚原 kn-aut-mei=宏一 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 en-keyword=アルギニン代謝 kn-keyword=アルギニン代謝 en-keyword=一酸化窒素 kn-keyword=一酸化窒素 en-keyword=ガス生物学 kn-keyword=ガス生物学 en-keyword=血管内皮学 kn-keyword=血管内皮学 en-keyword=酸化ストレス kn-keyword=酸化ストレス END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=20 article-no= start-page=2131 end-page=2138 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrocardiographic Parameters and Fatal Arrhythmic Events in Patients With Brugada Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives This study aimed to determine the usefulness of the combination of several electrocardiographic markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS). Background Detection of high-/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several electrocardiographic markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear. Methods Baseline characteristics of 246 consecutive patients (236 men; mean age, 47.6 +/- 13.6 years) with a Brugada-type electrocardiogram, including 13 patients with a history of VF and 40 patients with a history of syncope episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in 1 patient were observed. Clinical/ genetic and electrocardiographic parameters were compared with VF/SCD events. Results On univariate analysis, a history of VF and syncope episodes, paroxysmal atrial fibrillation, spontaneous type 1 pattern in the precordial leads, and electrocardiographic markers of depolarization abnormalities (QRS duration >= 120 ms, and fragmented QRS [f-QRS]) and those of repolarization abnormalities (inferolateral early repolarization [ER] pattern and QT prolongation) were associated with later cardiac events. On multivariable analysis, a history of VF and syncope episodes, inferolateral ER pattern, and f-QRS were independent predictors of documented VF and SCD (odds ratios: 19.61, 28.57, 2.87, and 5.21, respectively; p < 0.05). Kaplan-Meier curves showed that the presence/ absence of inferolateral ER and f-QRS predicted a worse/better prognosis (log-rank test, p < 0.01). Conclusions The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high-and low-risk BrS patients. en-copyright= kn-copyright= en-aut-name=TokiokaKoji en-aut-sei=Tokioka en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KusanoKengo F. en-aut-sei=Kusano en-aut-mei=Kengo F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiuraDaiji en-aut-sei=Miura en-aut-mei=Daiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaseSatoshi en-aut-sei=Nagase en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KohnoKunihisa en-aut-sei=Kohno en-aut-mei=Kunihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OheTohru en-aut-sei=Ohe en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cardiovasc Med affil-num=2 en-affil= kn-affil=Natl Cerebral & Cardiovasc Ctr, Dept Cardiovasc Med affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cardiovasc Med affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cardiovasc Med affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cardiovasc Med affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cardiovasc Med affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cardiovasc Med affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cardiovasc Med affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cardiovasc Med affil-num=10 en-affil= kn-affil=Sakakibara Heart Inst Okayama en-keyword=Brugada syndrome kn-keyword=Brugada syndrome en-keyword=early repolarization kn-keyword=early repolarization en-keyword=fragmented QRS kn-keyword=fragmented QRS en-keyword=noninvasive risk assessment kn-keyword=noninvasive risk assessment en-keyword=ventricular fibrillation kn-keyword=ventricular fibrillation END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=3 article-no= start-page=187 end-page=190 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20141201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2013 Incentive Award of the Okayama Medical Association in General Medical Science (2013 Yuuki Prize) kn-title=平成25年度岡山医学会賞 総合研究奨励賞（結城賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract=受賞対象論文: Yamamoto H, Higasa K, Sakaguchi M, Shien K, Soh J, Ichimura K, Furukawa M, Hashida S, Tsukuda K, Takigawa N, Matsuo K, Kiura K, Miyoshi S, Matsuda F, Toyooka S：Novel germline mutation in the transmembrane domain of HER2 in familial lung adenocarcinomas. J Natl Cancer Inst (2014) 106, djt338 en-copyright= kn-copyright= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name=山本寛斉 kn-aut-sei=山本 kn-aut-mei=寛斉 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　呼吸器・乳腺内分泌外科学 END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=23 article-no= start-page=6495 end-page=6505 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20131201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Genetically Engineered Oncolytic Adenovirus Decoys and Lethally Traps Quiescent Cancer Stem-like Cells in S/G(2)/M Phases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Because chemoradiotherapy selectively targets proliferating cancer cells, quiescent cancer stem-like cells are resistant. Mobilization of the cell cycle in quiescent leukemia stem cells sensitizes them to cell death signals. However, it is unclear that mobilization of the cell cycle can eliminate quiescent cancer stem-like cells in solid cancers. Thus, we explored the use of a genetically-engineered telomerase-specific oncolytic adenovirus, OBP-301, to mobilize the cell cycle and kill quiescent cancer stem-like cells. Experimental Design: We established CD133(+) cancer stem-like cells from human gastric cancer MKN45 and MKN7 cells. We investigated the efficacy of OBP-301 against quiescent cancer stem-like cells. We visualized the treatment dynamics of OBP-301 killing of quiescent cancer stem-like cells in dormant tumor spheres and xenografts using a fluorescent ubiquitination cell-cycle indicator (FUCCI). Results: CD133(+) gastric cancer cells had stemness properties. OBP-301 efficiently killed CD133(+) cancer stem-like cells resistant to chemoradiotherapy. OBP-301 induced cell-cycle mobilization from G(0)-G(1) to S/G(2)/M phases and subsequent cell death in quiescent CD133(+) cancer stem-like cells by mobilizing cell-cycle-related proteins. FUCCI enabled visualization of quiescent CD133(+) cancer stem-like cells and proliferating CD133(-) non-cancer stem-like cells. Three-dimensional visualization of the cell-cycle behavior in tumor spheres showed that CD133(+) cancer stem-like cells maintained stemness by remaining in G(0)-G(1) phase. We showed that OBP-301 mobilized quiescent cancer stem-like cells in tumor spheres and xenografts into S/G(2)/M phases where they lost viability and cancer stem-like cell properties and became chemosensitive. Conclusion: Oncolytic adenoviralinfection is an effective mechanism of cancer cell killing in solid cancer and can be a new therapeutic paradigm to eliminate quiescent cancer stem-like cells. en-copyright= kn-copyright= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoYuuri en-aut-sei=Hashimoto en-aut-mei=Yuuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishizakiMasahiko en-aut-sei=Nishizaki en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UnoFutoshi en-aut-sei=Uno en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagasakaTakeshi en-aut-sei=Nagasaka en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HoffmanRobert M. en-aut-sei=Hoffman en-aut-mei=Robert M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=2 en-affil= kn-affil=Okayama Univ Hosp, Ctr Innovat Clin Med affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=10 en-affil= kn-affil=Oncolys BioPharma Inc affil-num=11 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=12 en-affil= kn-affil=Univ Calif San Diego, Dept Surg affil-num=13 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=3 article-no= start-page=163 end-page=170 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201406 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biallelic Disruption of the PTCH1 Gene in Multiple Basal Cell Carcinomas in Japanese Patients with Nevoid Basal Cell Carcinoma Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of the present study is to address whether the molecular pathogenesis is identical among multiple basal cell carcinomas (BCCs) present in the same nevoid basal cell carcinoma syndrome (NBCCS) patient. Patient 1 is a 61-year-old (yo) Japanese female whose clinical characteristics and findings of a genetic analysis of PTCH1 have been previously described. Patient 2 is patient 1?s 64-yo sister who also suffered from NBCCS with a single base deletion at nucleotide 2613 in exon 16 (c.2613delC) in one PTCH1 allele. Thirteen and 3 independent specimens of BCC were applied for a molecular analysis of loss of heterozygosity (LOH) in PTCH1 in patients 1 and 2, respectively. Of particular note is that all BCC specimens examined showed a loss of the wild-type allele of exon 16 in PTCH1, thus indicating that LOH results in the biallelic disruption of PTCH1 in multiple BCCs that develop in an age- and location-independent manner in the same patient. These results indicate that the germline single base deletion of PTCH1 (c.2613 delC) is a first hit and the LOH of the wild-type allele is a second hit, implying that all 16 BCCs detected in these NBCCS sisters fit the standard two-hit model. en-copyright= kn-copyright= en-aut-name=TateGenshu en-aut-sei=Tate en-aut-mei=Genshu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KishimotoKoji en-aut-sei=Kishimoto en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuyaToshiyuki en-aut-sei=Mitsuya en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Department of Pathology, Showa University Fujigaoka Hospital affil-num=2 en-affil= kn-affil=Department of Pathology, Showa University Fujigaoka Hospital affil-num=3 en-affil= kn-affil=Department of Pathology, Showa University Fujigaoka Hospital en-keyword=biallelic disruption kn-keyword=biallelic disruption en-keyword=hedgehog kn-keyword=hedgehog en-keyword=nevoid basal cell carcinoma syndrome kn-keyword=nevoid basal cell carcinoma syndrome en-keyword=Patched 1 kn-keyword=Patched 1 en-keyword=two-hit model kn-keyword=two-hit model END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=遺伝子改変した腫瘍融解アデノウイルスは静止期癌幹細胞様細胞をS/G2/M期におびきよせそこで殺傷する kn-title=A Genetically Engineered Oncolytic Adenovirus Decoys and Lethally Traps Quiescent Cancer Stem-like Cells in S/G2/M Phases en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name=矢野修也 kn-aut-sei=矢野 kn-aut-mei=修也 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=1 article-no= start-page=65 end-page=67 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=SFTS : Severe fever with thrombocytopenia syndrome kn-title=重症熱性血小板減少症候群 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WatanabeTokiko en-aut-sei=Watanabe en-aut-mei=Tokiko kn-aut-name=渡邉都貴子 kn-aut-sei=渡邉 kn-aut-mei=都貴子 aut-affil-num=1 ORCID= en-aut-name=KusanoNobuchika en-aut-sei=Kusano en-aut-mei=Nobuchika kn-aut-name=草野展周 kn-aut-sei=草野 kn-aut-mei=展周 aut-affil-num=2 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name=岩月啓氏 kn-aut-sei=岩月 kn-aut-mei=啓氏 aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=岡山大学病院　感染制御部 affil-num=2 en-affil= kn-affil=岡山大学病院　感染制御部 affil-num=3 en-affil= kn-affil=岡山大学病院　感染制御部 END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=1 article-no= start-page=55 end-page=58 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Clinical guideline for epilepsy kn-title=てんかん治療ガイドラインについて en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MorimotoNobutoshi en-aut-sei=Morimoto en-aut-mei=Nobutoshi kn-aut-name=森本展年 kn-aut-sei=森本 kn-aut-mei=展年 aut-affil-num=1 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name=阿部康二 kn-aut-sei=阿部 kn-aut-mei=康二 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=香川県立中央病院　神経内科 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経内科学 END start-ver=1.4 cd-journal=joma no-vol=97 cd-vols= no-issue=7 article-no= start-page=E1202 end-page=E1207 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Serum Vaspin Concentrations Are Closely Related to Insulin Resistance, and rs77060950 at SERPINA12 Genetically Defines Distinct Group with Higher Serum Levels in Japanese Population en-subtitle= kn-subtitle= en-abstract= kn-abstract=Context: Vaspin is an adipokine with insulin-sensitizing effects identified from visceral adipose tissues of genetically obese rats. Objective: We investigated genetic and nongenetic factors that define serum concentrations of vaspin. Design, Setting and Participants: Vaspin levels were measured with RIA in Japanese subjects with normal fasting plasma glucose (NFG; n = 259) and type 2 diabetes patients (T2D; n = 275). Single nucleotide polymorphisms (SNP) at SERPINA12 (vaspin) gene locus were discovered, and five SNP were genotyped in the subjects with varied body mass index (n = 1138). Results: The level of serum vaspin in 93% of the samples was found to vary from 0.2 to nearly 2 ng/ml in NFG subjects (n = 259) and from 0.2 to nearly 3 ng/ml in T2D patients (n = 275) (Vaspin(Low) group), whereas a significant subpopulation (7%) in both groups displayed much higher levels of 10-40 ng/ml (Vaspin(High) group). In the Vaspin(Low) group, serum vaspin levels in T2D were significantly higher than healthy subjects (0.99 +/- 0.04 vs. 0.86 +/- 0.02 ng/ml; P < 0.01). Both in T2D and genotyped Japanese population, serum vaspin levels closely correlated with homeostasis model of assessment for insulin resistance rather than anthropometric parameters. By genotyping, rs77060950 tightly linked to serum vaspin levels, i.e. CC (0.6 +/- 0.4 ng/ml), CA (18.4 +/- 9.6 ng/ml), and AA (30.5 +/- 5.1 ng/ml) (P < 2 x 10(-16)). Putative GATA-2 and GATA-3 binding consensus site was found at rs77060950. Conclusions: Serum vaspin levels were related to insulin resistance, and higher levels of serum vaspin in 7% of the Japanese population are closely linked to minor allele sequence (A) of rs77060950. (J Clin Endocrinol Metab 97: E1202-E1207, 2012) en-copyright= kn-copyright= en-aut-name=TeshigawaraSanae en-aut-sei=Teshigawara en-aut-mei=Sanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HidaKazuyuki en-aut-sei=Hida en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakatsukaAtsuko en-aut-sei=Nakatsuka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurakamiKazutoshi en-aut-sei=Murakami en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanzakiMotoko en-aut-sei=Kanzaki en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueKentaro en-aut-sei=Inoue en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TeramiTakahiro en-aut-sei=Terami en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatayamaAkihiro en-aut-sei=Katayama en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IsedaIzumi en-aut-sei=Iseda en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsushitaYuichi en-aut-sei=Matsushita en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyatakeNobuyuki en-aut-sei=Miyatake en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=McDonaldJohn F. en-aut-sei=McDonald en-aut-mei=John F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HottaKikuko en-aut-sei=Hotta en-aut-mei=Kikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci affil-num=3 en-affil= kn-affil= affil-num=4 en-affil= kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil= kn-affil= affil-num=7 en-affil= kn-affil=Kagawa Univ, Fac Med, Dept Hyg affil-num=8 en-affil= kn-affil= affil-num=9 en-affil= kn-affil= affil-num=10 en-affil= kn-affil= affil-num=11 en-affil= kn-affil= affil-num=12 en-affil= kn-affil= affil-num=13 en-affil= kn-affil=Kagawa Univ, Fac Med, Dept Hyg affil-num=14 en-affil= kn-affil=Millipore Corp, Linco Res, St Charles affil-num=15 en-affil= kn-affil=Kyoto Univ, Grad Sch Med, Evidenced Based Med Res Ctr affil-num=16 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue=1 article-no= start-page=35 end-page=39 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=An epidemiologically rare case of Vibrio vulnificus infection that occurred in October in an inland city of Japan kn-title=内陸地津山で発症した季節外れのVibrio vulnificus感染症 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　A 68-year-old man with alcohol addiction, who lived in the suburbs of Tsuyama, an inland city located in northeast Okayama prefecture, was transported to the emergency unit of the Tsuyama Central Hospital in a state of cardiopulmonary arrest (CPA). Despite rigorous systemic investigation and treatment, the patient died 2 hours after arrival. After his death, Vibrio vulnificus was isolated from his blood culture. 　Vibrio vulnificus causes fatal infection in humans, usually only in areas located close to the sea where appropriate temperature and suitable salt concentration for its growth are available. Therefore, its occurrence is epidemiologically restricted ; in Japan, the western coastal areas, especially in summers, are reported to be the high-risk regions. This is a rare case because it occurred in a city approximately 50 kilometers from both the Sea of Japan and the Pacific coast of Okayama, and at the end of October in 2011. Economic development and distribution systems have made it possible to transport various food products from coastal areas or abroad to any place in a short time, such that these infections can potentially develop in areas other than expected. We should be aware of the increasing risk of Vibrio vulnificus infection during any season and at any place, especially in patients with abnormal liver function. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name=萩谷英大 kn-aut-sei=萩谷 kn-aut-mei=英大 aut-affil-num=1 ORCID= en-aut-name=ShiotaSumiko en-aut-sei=Shiota en-aut-mei=Sumiko kn-aut-name=塩田澄子 kn-aut-sei=塩田 kn-aut-mei=澄子 aut-affil-num=2 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name=三好伸一 kn-aut-sei=三好 kn-aut-mei=伸一 aut-affil-num=3 ORCID= en-aut-name=KuroeYasutoshi en-aut-sei=Kuroe en-aut-mei=Yasutoshi kn-aut-name=黒江泰利 kn-aut-sei=黒江 kn-aut-mei=泰利 aut-affil-num=4 ORCID= en-aut-name=NojimaHiroyoshi en-aut-sei=Nojima en-aut-mei=Hiroyoshi kn-aut-name=野島宏悦 kn-aut-sei=野島 kn-aut-mei=宏悦 aut-affil-num=5 ORCID= en-aut-name=OtaniShinkichi en-aut-sei=Otani en-aut-mei=Shinkichi kn-aut-name=大谷晋吉 kn-aut-sei=大谷 kn-aut-mei=晋吉 aut-affil-num=6 ORCID= en-aut-name=SugiyamaJunichi en-aut-sei=Sugiyama en-aut-mei=Junichi kn-aut-name=杉山淳一 kn-aut-sei=杉山 kn-aut-mei=淳一 aut-affil-num=7 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name=内藤宏道 kn-aut-sei=内藤 kn-aut-mei=宏道 aut-affil-num=8 ORCID= en-aut-name=KawanishiSusumu en-aut-sei=Kawanishi en-aut-mei=Susumu kn-aut-name=川西進 kn-aut-sei=川西 kn-aut-mei=進 aut-affil-num=9 ORCID= en-aut-name=HagiokaShingo en-aut-sei=Hagioka en-aut-mei=Shingo kn-aut-name=萩岡信吾 kn-aut-sei=萩岡 kn-aut-mei=信吾 aut-affil-num=10 ORCID= en-aut-name=MorimotoNaoki en-aut-sei=Morimoto en-aut-mei=Naoki kn-aut-name=森本直樹 kn-aut-sei=森本 kn-aut-mei=直樹 aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=津山中央病院　救命救急センター affil-num=2 en-affil= kn-affil=就実大学薬学部　病原微生物学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　衛生微生物化学 affil-num=4 en-affil= kn-affil=津山中央病院　救命救急センター affil-num=5 en-affil= kn-affil=津山中央病院　救命救急センター affil-num=6 en-affil= kn-affil=津山中央病院　救命救急センター affil-num=7 en-affil= kn-affil=津山中央病院　救命救急センター affil-num=8 en-affil= kn-affil=津山中央病院　救命救急センター affil-num=9 en-affil= kn-affil=津山中央病院　救命救急センター affil-num=10 en-affil= kn-affil=津山中央病院　救命救急センター affil-num=11 en-affil= kn-affil=津山中央病院　救命救急センター en-keyword=Vibrio vulnificus kn-keyword=Vibrio vulnificus END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20120927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=バスピン血中濃度はインスリン抵抗性と相関があり、日本人にはrs77060950によって規定される血中濃度高値群が存在する kn-title=Serum Vaspin Concentrations Are Closely Related to Insulin Resistance, and rs77060950 at SERPINA12 Genetically Defines Distinct Group with Higher Serum Levels in Japanese Population en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TeshigawaraSanae en-aut-sei=Teshigawara en-aut-mei=Sanae kn-aut-name=勅使川原早苗 kn-aut-sei=勅使川原 kn-aut-mei=早苗 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=5 article-no= start-page=369 end-page=376 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dravet Syndrome : A Genetic Epileptic Disorder en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dravet syndrome (DS), or severe myoclonic epilepsy in infancy, is one of the most severe types of genetic epilepsy. It is characterized by the initial occurrence of febrile or afebrile seizures that often evolve into status epilepticus in infants with normal development, and by the subsequent appearance of myoclonic and/or atypical absence seizures as well as complex partial seizures. The key feature that characterizes DS is fever sensitivity, although photosensitivity and pattern-sensitivity are also often seen. The prognosis is unfavorable in most cases. Seizures become drug-resistant and persist, with many patients suffering from motor and cognitive impairment. Mutations of SCN1A, which encodes the voltage-gated sodium channel NaV1.1, are the most frequent genetic cause of this syndrome. SCN1A mutations and/or microchromosomal rearrangements involving SCN1A are detected in about 85% of patients. Mutations of PCDH19 have also been reported in female patients with clinical findings compatible with DS. PCDH19 mutations might account for 5% of overall DS cases. Thirty years after its first description, DS is considered as a model of channelopathy. This survey reviews recent developments in the research literature on DS, focusing on the clinical course, as well as its genetic causes. en-copyright= kn-copyright= en-aut-name=AkiyamaMari en-aut-sei=Akiyama en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsukaYoko en-aut-sei=Ohtsuka en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, and Okayama University Hospital affil-num=2 en-affil= kn-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, and Okayama University Hospital affil-num=3 en-affil= kn-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, and Okayama University Hospital en-keyword=Dravet syndrome kn-keyword=Dravet syndrome en-keyword=long-term outcome kn-keyword=long-term outcome en-keyword=SCN1A kn-keyword=SCN1A en-keyword=PCDH19 kn-keyword=PCDH19 END start-ver=1.4 cd-journal=joma no-vol=124 cd-vols= no-issue=2 article-no= start-page=137 end-page=143 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20120801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Study for the structures of the HA complexes produced by Clostridium botulinum type A mutant strain kn-title=ボツリヌスＡ型菌変異株が産生するHA複合体の構造に関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Clostridium botulinum produces seven neurotoxin (NTX) serotypes, classified from as A to G. In culture, NTX forms protein complexes by association with non-toxic components, such as nontoxic-nonhemagglutinin (NTNH) and hemagglutinins (HA1, HA2, HA3). C. botulinum serotype A produces three types of toxin complexes, M-toxin (NTX and NTNH), L-toxin (M-toxin and HAs) and LL-toxin (dimer of L-toxin). In this study, I found three HA complexes in the culture of a nontoxigenic mutant serotype A lacking ntx and ntnh expression. The HA complexes displayed similar banding patterns on SDS-PAGE, but the staining intensities of the HA1 and HA2 bands were different. In addition, their native-PAGE banding profiles exhibited different behaviors. The large-molecular-size HA complex showed the highest activity, similar to that of an L-toxin. Based on the combined results of the PAGE and gel-filtration profiles, the differences in molecular size among the three HA complexes were thought to be caused by different numbers of HA1 and HA2 molecules. This paper reports for the first time the purification and characterization of a native HA complex of serotype A, and suggests that the HA can form complex structures without NTX and NTNH. This may help in understanding the toxin complex assembly pathway. en-copyright= kn-copyright= en-aut-name=MaShaobo en-aut-sei=Ma en-aut-mei=Shaobo kn-aut-name=馬少博 kn-aut-sei=馬 kn-aut-mei=少博 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　病原細菌学 en-keyword=ボツリヌス毒素（botulinum toxin） kn-keyword=ボツリヌス毒素（botulinum toxin） en-keyword=ボツリヌス菌（Clostridium botulinum） kn-keyword=ボツリヌス菌（Clostridium botulinum） en-keyword=血球凝集素（hemagglutinin） kn-keyword=血球凝集素（hemagglutinin） en-keyword=タンパク質複合体構造（protein complex structure） kn-keyword=タンパク質複合体構造（protein complex structure） END start-ver=1.4 cd-journal=joma no-vol=124 cd-vols= no-issue=2 article-no= start-page=115 end-page=117 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20120801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Therapy for hyperthermia-induced seizures in Scn1a mutant rats kn-title=Scn1a遺伝子変異ラットを用いた抗てんかん薬の熱性けいれん抑制効果 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HayashiKeiichiro en-aut-sei=Hayashi en-aut-mei=Keiichiro kn-aut-name=林桂一郎 kn-aut-sei=林 kn-aut-mei=桂一郎 aut-affil-num=1 ORCID= en-aut-name=OhmoriIori en-aut-sei=Ohmori en-aut-mei=Iori kn-aut-name=大守伊織 kn-aut-sei=大守 kn-aut-mei=伊織 aut-affil-num=2 ORCID= en-aut-name=MatsuiHideki en-aut-sei=Matsui en-aut-mei=Hideki kn-aut-name=松井秀樹 kn-aut-sei=松井 kn-aut-mei=秀樹 aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　細胞生理学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　細胞生理学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　細胞生理学 en-keyword=febrile seizures kn-keyword=febrile seizures en-keyword=animal model kn-keyword=animal model en-keyword=Scn1a gene kn-keyword=Scn1a gene en-keyword=generalized epilepsy with febrile seizures plus kn-keyword=generalized epilepsy with febrile seizures plus en-keyword=severe myoclonic epilepsy of infancy kn-keyword=severe myoclonic epilepsy of infancy END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=2 article-no= start-page=119 end-page=129 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Different Responses to 5-fluoraouracil in Mutagenicity and Gene Expression between Two Human Lymphoblastoid Cell Lines with or without TP53 Mutation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Human lymphoblastoid TK6 and WTK-1 cells are widely used to detect mutagens in vitro. TK6 cells have wild-type TP53 alleles, while WTK-1 cells have one allele of mutated TP53. Both cells were treated with 5-fluorouracil (5-FU), and gene mutation assay and micronucleus assay were performed to clarify the differential response related to the TP53 gene status. The effects of 5-FU on gene expression were assessed by microarray and quantitative RT-PCR analyses. In WTK-1 cells, 5-FU increased the frequency of cells with micronucleus and mutation. In TK6 cells, frequency of cells with micronucleus was increased but the mutation frequency was not. The cytotoxicity induced by 5-FU was more prominent in TK6 cells than in WTK-1 cells. Analysis of gene expression showed that the genes involved in the TP53 pathway were up-regulated in TK6 cells but not in WTK-1 cells. The differential responses to 5-FU between these cell lines appeared to be due to the difference in the TP53 gene status, thus providing a molecular basis for the bioassays using these cell lines in the toxicology field. Our results indicate that the clinical efficacy of 5-FU chemotherapy may depend on the TP53 genotype. en-copyright= kn-copyright= en-aut-name=OkaHiroaki en-aut-sei=Oka en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoTakuya en-aut-sei=Kondo en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoritaFumio en-aut-sei=Morita en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimizuKenji en-aut-sei=Shimizu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Tokushima Research Center, Taiho pharmaceutical Co., Ltd. affil-num=2 en-affil= kn-affil=Department of Molecular Genetics, Okayama University Graduate School of Medicine affil-num=3 en-affil= kn-affil=Tokushima Research Center, Taiho pharmaceutical Co., Ltd. affil-num=4 en-affil= kn-affil=Tokushima Research Center, Taiho pharmaceutical Co., Ltd. affil-num=5 en-affil= kn-affil=Department of Molecular Genetics, Okayama University Graduate School of Medicine en-keyword=5-fluorouracil kn-keyword=5-fluorouracil en-keyword=TP53 kn-keyword=TP53 en-keyword=Tk mutation assays kn-keyword=Tk mutation assays en-keyword=microarray analysis kn-keyword=microarray analysis END start-ver=1.4 cd-journal=joma no-vol=124 cd-vols= no-issue=1 article-no= start-page=67 end-page=70 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20120401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Bisphosphonate treatment in osteogenesis imperfecta kn-title=骨形成不全症の治療 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TanakaHiroyuki en-aut-sei=Tanaka en-aut-mei=Hiroyuki kn-aut-name=田中弘之 kn-aut-sei=田中 kn-aut-mei=弘之 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山済生会総合病院　小児科 en-keyword=ビスフォスフォネート kn-keyword=ビスフォスフォネート en-keyword=パミドロネート kn-keyword=パミドロネート en-keyword=ゾレドロネート kn-keyword=ゾレドロネート en-keyword=骨折 kn-keyword=骨折 en-keyword=コラーゲン kn-keyword=コラーゲン END start-ver=1.4 cd-journal=joma no-vol=123 cd-vols= no-issue=3 article-no= start-page=231 end-page=235 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20111201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Japanese guidelines for the diagnosis and management of soft tissue tumor kn-title=軟部腫瘍診療ガイドライン en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MorimotoYuki en-aut-sei=Morimoto en-aut-mei=Yuki kn-aut-name=森本裕樹 kn-aut-sei=森本 kn-aut-mei=裕樹 aut-affil-num=1 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name=尾ｱ敏文 kn-aut-sei=尾ｱ kn-aut-mei=敏文 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=岡山大学病院　整形外科 affil-num=2 en-affil= kn-affil=岡山大学病院　整形外科 END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=5 article-no= start-page=315 end-page=323 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=201110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Single Nucleotide Polymorphism WRN Leu1074Phe Is Associated with Prostate Cancer Susceptibility in Chinese Subjects en-subtitle= kn-subtitle= en-abstract= kn-abstract=Deficiencies in the human DNA repair gene WRN are the cause of Werner syndrome, a rare autosomal recessive disorder characterized by premature aging and a predisposition to cancer. This study evaluated the association of WRN Leu1074Phe (rs1801195), a common missense single nucleotide polymorphism in WRN, with prostate cancer susceptibility in Chinese subjects. One hundred and forty-seven prostate cancer patients and 111 male cancer-free control subjects from 3 university hospitals in China were included. Blood samples were obtained from each subject, and the single nucleotide polymorphism WRN Leu1074Phe was genotyped by using a Snapshot assay. The results showed that WRN Leu1074Phe was associated with the risk of prostate cancer in Chinese men and that the TG/GG genotype displayed a decreased prevalence of prostate cancer compared with the TT genotype (OR＝0.58, 95%CI:0.35-0.97, p＝0.039). Through stratified analysis, more significant associations were revealed for the TG/GG genotype in the subgroup with diagnosis age <_ 72 yr (OR＝0.27, 95%CI:0.12-0.61, p＝0.002) and in patients with localized diseases (OR＝0.36, 95%CI:0.19-0.70, p＝0.003). However, no statistically significant difference was found in the subgroup with age ＞72 yr or in patients with advanced diseases. We concluded that the genetic variant Leu1074Phe in the DNA repair gene WRN might play a role in the risk of prostate cancer in Chinese subjects. en-copyright= kn-copyright= en-aut-name=WangLei en-aut-sei=Wang en-aut-mei=Lei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KakuHaruki en-aut-sei=Kaku en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangPeng en-aut-sei=Huang en-aut-mei=Peng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=XuKexin en-aut-sei=Xu en-aut-mei=Kexin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YangKai en-aut-sei=Yang en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhangJiheng en-aut-sei=Zhang en-aut-mei=Jiheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiMing en-aut-sei=Li en-aut-mei=Ming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=XieLiping en-aut-sei=Xie en-aut-mei=Liping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WangXiaofeng en-aut-sei=Wang en-aut-mei=Xiaofeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaiAkiko en-aut-sei=Sakai en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShimizuKenji en-aut-sei=Shimizu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KumonHiromi en-aut-sei=Kumon en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NaYanqun en-aut-sei=Na en-aut-mei=Yanqun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Department of Urology, Peking University People's Hospital affil-num=2 en-affil= kn-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Urology, Peking University People's Hospital affil-num=5 en-affil= kn-affil=Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University affil-num=6 en-affil= kn-affil=Department of Urology, Peking University School of Oncology, Beijing Cancer Hospital & Institute affil-num=7 en-affil= kn-affil=Department of Urology, Peking University School of Oncology, Beijing Cancer Hospital & Institute affil-num=8 en-affil= kn-affil=Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University affil-num=9 en-affil= kn-affil=Department of Urology, Peking University People's Hospital affil-num=10 en-affil= kn-affil=Department of Molecular Genetics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=11 en-affil= kn-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=12 en-affil= kn-affil=Research and Develop Center for Advanced Clinical Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=13 en-affil= kn-affil=Department of Molecular Genetics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=14 en-affil= kn-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=15 en-affil= kn-affil=Department of Urology, Peking University People's Hospital en-keyword=polymorphism kn-keyword=polymorphism en-keyword=prostatic neoplasms kn-keyword=prostatic neoplasms en-keyword=single nucleotide kn-keyword=single nucleotide en-keyword=susceptibility kn-keyword=susceptibility en-keyword=WRN kn-keyword=WRN END start-ver=1.4 cd-journal=joma no-vol=123 cd-vols= no-issue=2 article-no= start-page=91 end-page=95 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20110801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A long-term follow-up study of Dravet syndrome up to adulthood kn-title=成人期に達したDravet症候群の長期経過に関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AkiyamaMari en-aut-sei=Akiyama en-aut-mei=Mari kn-aut-name=秋山麻里 kn-aut-sei=秋山 kn-aut-mei=麻里 aut-affil-num=1 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name=小林勝弘 kn-aut-sei=小林 kn-aut-mei=勝弘 aut-affil-num=2 ORCID= en-aut-name=YoshinagaHarumi en-aut-sei=Yoshinaga en-aut-mei=Harumi kn-aut-name=吉永治美 kn-aut-sei=吉永 kn-aut-mei=治美 aut-affil-num=3 ORCID= en-aut-name=OhtsukaYoko en-aut-sei=Ohtsuka en-aut-mei=Yoko kn-aut-name=大塚頌子 kn-aut-sei=大塚 kn-aut-mei=頌子 aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　発達神経病態学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　発達神経病態学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　発達神経病態学 affil-num=4 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　発達神経病態学 en-keyword=Dravet症候群 kn-keyword=Dravet症候群 en-keyword=乳児重症ミオクロニーてんかん kn-keyword=乳児重症ミオクロニーてんかん en-keyword=予後 kn-keyword=予後 en-keyword=けいれん性てんかん重積状態 kn-keyword=けいれん性てんかん重積状態 END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=1 article-no= start-page=37 end-page=91 dt-received= dt-revised= dt-accepted= dt-pub-year=1957 dt-pub=19570131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=STUDIES ON THE RESISTANCE OF MYCOBACTERIUM TUBERCULOSIS TO STREPTOMYCIN kn-title=結核菌のストレプトマイシン耐性に関する研究 第2編 ストレプトマイシン耐性結核菌の耐性持続性並びに緩解に就いて en-subtitle= kn-subtitle= en-abstract= kn-abstract=In 1887, Kossiakoff first described the phenomenon of drug-resistance of bacteria. Recently with the wide-spread use of streptomycin and other various antibiotics in the field of therapeutics, this phenomenon of drug-resistance has become very important in clinical medicine. As to streptomycin alone, which was discovered in 1944 by Waksmann and brought the epoch-making progress to the therapy ef tuberculosis, the acquisition of resistance is one of the problems which need great precautions at the execution of streptomycin-therapy. Since 1946 when Luria and Delbr?ck first reported about the mechanism of acquisition of resistance to sulfonamide, the mechanism of acquisition of resistance to streptomycin and other antibiotics and that of reversion from it have been hotly argued. No decidedly substantiating results, however, have yet been obtained, though two confronting theories, spotaneous mutation theory and adaptation theory, are now advocated. The former is the theory which asserts that the acquisition of resistance is originated in their spontaneous mutation happening during the process of proliferation and in the selective action of drugs; this theory has nowadays many sustaining scholars. In the latter theory, the direct action of drugs to the rise of resistance is considered as the mehanism of the acquisition of resistance. Now that this phenomenon of drug-resistance is demonstrated to be the genetic variation with heredity and its mode of transmission is also clarified by Lederberg and Newcombe, it is difficult to explain the mechanism of acquisition of resistance according to the adaptation theory only. In the adaptation theory, however, refering to the idea of “Dauermodifikation” described on paramecium by Jollos in 1921, they have become to consider that antibiotics have the mutagenicity which seems to be the direct cause of the acquisition of drug-resistance. Since 1952, the author has carried out many experiments to study the essential features of streptomycin-resistant tubercle bacilli in vitro and in vivo, according to the "theory of spontaneous mutation with selection" which is supported by many researchers. The results are as follows: 1) Wolinsky reported that mutants over 0.1% of the original streptomycin-sensitive tubercle bacilli were observed on the culture media containig 1000γ/cc of streptomycin. In the present reports, the author studied the development of resistance by succesive cultures of the strains newly isolated from the tnberculosis patients who had received no or little streptomycin-therapy, and observed the spontaneous mutants over 0.1% of 0.1 mg and 1 mg of the inoculated bacilli. 2) Akiba et al. reported that, besides the spontaneous mutation, streptomycin itself had some effect on the mutation of gene. In the present work, many facts were observed which were hardly explained by “spontaneous mutation with selection” only. For example, the author also isolated one strain which seemed to be caused by such cause as that Akiba et al. reported. 3) There are many reports that the resistance of streptomycin-resistant tubercle bacilli is stable and long-lasting. The author performed many experiments in vitro and in vivo to study the development of the resistance of highly resistant strain over 1000γ/cc, of middle grade-resistant one over 100γ/cc and of low grade-resistant one under 10γ/cc. As a result of these experiments, the falling tendency of resistance was clearly observed in not only low and middle grade-resistant but also in highly resistant strains. en-copyright= kn-copyright= en-aut-name=NozakiTatsuo en-aut-sei=Nozaki en-aut-mei=Tatsuo kn-aut-name=野崎達夫 kn-aut-sei=野崎 kn-aut-mei=達夫 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部微生物学教室 END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=4 article-no= start-page=263 end-page=265 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=201008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Common Acute Lymphoblastic Leukemia Ph＋ Following Langerhans Cell Histiocytosis in a Multi-Malformed Child with INV (9) (p12;q13) (mat):Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=The occurrence of Langerhans cell histiocytosis (LCH) and another malignancy in the same patient is infrequent but has been recognized. The genetic changes that could be responsible for LCH and/or concomitant leukemia development are obscure. To the best of our knowledge, this is the first description of constitutional maternally derived inv (9) (p12;q13) in an LCH patient, and also of the development of common ALL Ph after LCH diagnosis and therapy. The potential significance of these findings [inv (9)LCHALL Ph] and their mutual relationship are unknown. Therefore, cooperative studies of large numbers of patients are needed to identify the common risk factors, if any. en-copyright= kn-copyright= en-aut-name=Paveli?Jasminka en-aut-sei=Paveli? en-aut-mei=Jasminka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=?uli?Srdjana en-aut-sei=?uli? en-aut-mei=Srdjana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=?uli?Vida en-aut-sei=?uli? en-aut-mei=Vida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Division of Molecular Medicine, Laboratory of Molecular Oncology, Ru?er Bo?kovi? Institute affil-num=2 en-affil= kn-affil=Clinical Department for Hematology, Oncology, Immunology and Medical Genetics, Clinical Hospital Center Split, Paediatric Clinic affil-num=3 en-affil= kn-affil=Clinical Department for Hematology, Oncology, Immunology and Medical Genetics, Clinical Hospital Center Split, Paediatric Clinic en-keyword=acute lymphoblastic leukemia kn-keyword=acute lymphoblastic leukemia en-keyword=genetic changes kn-keyword=genetic changes en-keyword=langerhans cell histiocytosis kn-keyword=langerhans cell histiocytosis END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=2 article-no= start-page=119 end-page=124 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=20100802 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Psycho-oncology ： An overview kn-title=精神腫瘍学概論 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name=内富庸介 kn-aut-sei=内富 kn-aut-mei=庸介 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　精神神経病態学 en-keyword=がん kn-keyword=がん en-keyword=サイコオンコロジー kn-keyword=サイコオンコロジー en-keyword=quality of life kn-keyword=quality of life en-keyword=緩和ケア kn-keyword=緩和ケア END start-ver=1.4 cd-journal=joma no-vol=135B cd-vols= no-issue=1 article-no= start-page=5 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=20050505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A functional glutathione S-transferase P1 gene polymorphism is associated with methamphetamine-induced psychosis in Japanese population en-subtitle= kn-subtitle= en-abstract= kn-abstract=Several lines of evidence suggest that oxidative stress plays a role in the mechanisms of action of methamphetamine (MAP) in the human brain. Given the role of glutathione S-transferases (GSTs) in the protection against oxidative stress, genes encoding the GSTs have been considered as candidates for association studies of MAP abuse. This study was undertaken to investigate the role of the functional polymorphism of GSTP1 gene exon 5 (Ile105Val) in the pathogenesis of MAP abuse. Genotyping for GSTP1 gene polymorphism exon 5 (Ile105Val) in 189 MAP abusers and 199 normal controls was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Association between GSTP1 gene polymorphism and clinical features (prognosis of psychosis (transient-type and prolonged-type), spontaneous relapse (positive and negative), and poly-substance abuse) of MAP abusers was evaluated. Significant differences in the frequency of both alleles (P = 0.026, odds ratio: 1.70, 95% confidence intervals (CI) 1.06-2.72) and genotypes (P = 0.029) between MAP abusers and controls were detected. In particular, a significant difference in both genotype frequency (P = 0.013) and allele frequency (P = 0.014, odds ratio: 1.84, 95% CI 1.13-2.97) between MAP abusers with psychosis (transient-type and prolonged-type) and controls was detected. Our findings suggest that the polymorphism (Ile 105Val) on exon 5 of the GSTP1 gene may contribute to a vulnerability to psychosis associated with MAP abuse in Japanese population. en-copyright= kn-copyright= en-aut-name=HashimotoTasuku en-aut-sei=Hashimoto en-aut-mei=Tasuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashimotoKenji en-aut-sei=Hashimoto en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuzakaDaisuke en-aut-sei=Matsuzaka en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimizuEiji en-aut-sei=Shimizu en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekineYoshimoto en-aut-sei=Sekine en-aut-mei=Yoshimoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshiyaInada en-aut-sei=Yoshiya en-aut-mei=Inada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataNakao en-aut-sei=Iwata en-aut-mei=Nakao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaranoMutsuo en-aut-sei=Harano en-aut-mei=Mutsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KomiyamaTokutaro en-aut-sei=Komiyama en-aut-mei=Tokutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaMitsuhiko en-aut-sei=Yamada en-aut-mei=Mitsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SoraIchiro en-aut-sei=Sora en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UjikeHiroshi en-aut-sei=Ujike en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IyoMasaomi en-aut-sei=Iyo en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Department of Psychiatry, Chiba University Graduate School of Medicine affil-num=2 en-affil= kn-affil=Department of Psychiatry, Chiba University Graduate School of Medicine affil-num=3 en-affil= kn-affil=Department of Psychiatry, Chiba University Graduate School of Medicine affil-num=4 en-affil= kn-affil=Department of Psychiatry, Chiba University Graduate School of Medicine affil-num=5 en-affil= kn-affil=Department of Psychiatry and Neurology, Hamamatsu University School of Medicine affil-num=6 en-affil= kn-affil=Department of Psychiatry, Nagoya University Graduate School of Medicine affil-num=7 en-affil= kn-affil=Department of Psychiatry, Fujita Health University School of Medicine affil-num=8 en-affil= kn-affil=Department of Neuropsychiatry, Kurume University School of Medicine affil-num=9 en-affil= kn-affil=National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry (NCNP) affil-num=10 en-affil= kn-affil=National Institute of Mental Health, NCNP affil-num=11 en-affil= kn-affil=Division of Psychobiology, Tohoku University Graduate School of Medicine affil-num=12 en-affil= kn-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry affil-num=13 en-affil= kn-affil=Department of Psychiatry, Chiba University Graduate School of Medicine en-keyword=methamphetamine kn-keyword=methamphetamine en-keyword=psychosis kn-keyword=psychosis en-keyword=drug abuse kn-keyword=drug abuse en-keyword=genetic factor; polymorphism kn-keyword=genetic factor; polymorphism END start-ver=1.4 cd-journal=joma no-vol=132B cd-vols= no-issue=1 article-no= start-page=70 end-page=73 dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=20050105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association study between brain-derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Several lines of evidence suggest that genetic factors might contribute to drug abuse vulnerability. Recent genomic scans for association demonstrated that the brain-derived neurotrophic factor (BDNF) gene was associated with drug abuse vulnerability. In this study, we analyzed association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C>T (C270T named formerly) in the noncoding region of exon V and 196G >A (val66met) in the coding region of exon XIIIA, with methamphetamine (MAP) abuse in Japan. No significant differences were found in the frequency of the genotype or allele in these two SNPs between MAP abusers and controls (132C>T in exon V: genotype, p = 0.586, allele, p = 0.594; 196G>A (val66met) in exon XIIIA: genotype, p = 0.889, allele, p = 0.713). Furthermore, there was no difference between clinical parameters (e.g. prognosis psychosis, spontaneous relapse, or poly-substance abuse) and the two SNPs of BDNF gene. These results suggest that the two SNPs (132C>T in exon V and 196G>A (val66met) in exon XIIIA) of the BDNF gene may not be associated with Japanese MAP abusers. en-copyright= kn-copyright= en-aut-name=ItohKanako en-aut-sei=Itoh en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashimotoKenji en-aut-sei=Hashimoto en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimizuEiji en-aut-sei=Shimizu en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekineYoshimoto en-aut-sei=Sekine en-aut-mei=Yoshimoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiNorio en-aut-sei=Ozaki en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InadaToshiya en-aut-sei=Inada en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaranoMutsuo en-aut-sei=Harano en-aut-mei=Mutsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwataNakao en-aut-sei=Iwata en-aut-mei=Nakao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KomiyamaTokutaro en-aut-sei=Komiyama en-aut-mei=Tokutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaMitsuhiko en-aut-sei=Yamada en-aut-mei=Mitsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SoraIchiro en-aut-sei=Sora en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakataKenji en-aut-sei=Nakata en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UjikeHiroshi en-aut-sei=Ujike en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IyoMasaomi en-aut-sei=Iyo en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil= kn-affil=Department of Psychiatry, Chiba University Graduate School of Medicine affil-num=2 en-affil= kn-affil=Department of Psychiatry, Chiba University Graduate School of Medicine affil-num=3 en-affil= kn-affil=Department of Psychiatry, Chiba University Graduate School of Medicine affil-num=4 en-affil= kn-affil=Department of Psychiatry and Neurology, Hamamatsu University School of Medicine affil-num=5 en-affil= kn-affil=Department of Psychiatry and Psychobiology, Nagoya University Graduate School of Medicine affil-num=6 en-affil= kn-affil=Department of Psychiatry and Psychobiology, Nagoya University Graduate School of Medicine affil-num=7 en-affil= kn-affil=Department of Neuropsychiatry, Kurume University School of Medicine affil-num=8 en-affil= kn-affil=Department of Psychiatry, Fujita Health University School of Medicine affil-num=9 en-affil= kn-affil=National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry affil-num=10 en-affil= kn-affil=Karasuyama Hospital, Showa University School of Medicine affil-num=11 en-affil= kn-affil=Division of Psychobiology, Tohoku University Graduate School of Medicine affil-num=12 en-affil= kn-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry affil-num=13 en-affil= kn-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry affil-num=14 en-affil= kn-affil=Department of Psychiatry, Chiba University Graduate School of Medicine en-keyword=brain-derived neurotrophic factor kn-keyword=brain-derived neurotrophic factor en-keyword=polymorphism kn-keyword=polymorphism en-keyword=drug abuse kn-keyword=drug abuse en-keyword=methamphetamine kn-keyword=methamphetamine END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=6 article-no= start-page=407 end-page=415 dt-received= dt-revised= dt-accepted= dt-pub-year=1992 dt-pub=199212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Detection of oncogene rearrangements in human non-Hodgkin's lymphomas. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Southern blot hybridization was used to detect the rearrangement and amplification of five proto-oncogenes (bcl-2, bcl-1, c-myc, c-myb and c-Ha-ras) and one tumor suppressor gene (RB-1) in 55 Japanese patients with non-Hodgkin's lymphoma; 16 with T-cell lymphomas and 39 with B-cell lymphomas (7 follicular and 32 diffuse lymphomas). Genetic abnormalities of the proto-oncogenes were detected in 7 of the 55 (13%). Genetic abnormalities of bcl-2 plus other genes were detected in 5 of 7 cases of follicular lymphoma (71%), rearrangements of bcl-2 and c-myc, rearrangement of bcl-2 and amplification of c-myb. Genetic abnormalities were observed in only three cases of diffuse lymphoma. In each of 3 cases of B-cell lymphoma, one of the genes, blc-2 mbr, bcl-2 mcr and c-myc, was rearranged respectively. The incidence of genetic abnormalities in diffuse lymphomas (6.3%) was lower than that in follicular lymphomas. None of diffuse lymphomas had double oncogene abnormality. No abnormalities were found in RB-1, bcl-1, and Ha-ras. These findings suggest that follicular lymphomas are associated with some abnormalities of oncogenes not restricted to bcl-2 that facilitate growth which may be associated with their clinical features.

en-copyright= kn-copyright= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkagiTadaatsu en-aut-sei=Akagi en-aut-mei=Tadaatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayashiKazuhiko en-aut-sei=Hayashi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiKiyoshi en-aut-sei=Takahashi en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University en-keyword=malignant lymphoma kn-keyword=malignant lymphoma en-keyword=cellular oncogenes kn-keyword=cellular oncogenes END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=4 article-no= start-page=285 end-page=293 dt-received= dt-revised= dt-accepted= dt-pub-year=1992 dt-pub=199208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anti-C100-3 antibody status, viral genomic sequences, and clinical features in chronic hepatitic patients with hepatitis C virus RNA in sera. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Since detection of hepatitis C virus RNA by the polymerase chain reaction (PCR) showed that there existed anti-C100-3 (anti-HCV) antibody negative patients infected with HCV, we attempted to find out whether there were any clinical or viral genomic differences between the anti-HCV antibody positive and negative groups. One hundred and fifty-nine patients with chronic liver diseases with hepatitis C virus RNA in their sera were selected. Anti-HCV antibody was tested for anti-C100-3 antibody by an enzyme linked immunosorbent assay. The incidence of anti-HCV antibody was 129/159. The concentration of serum gamma-globulin, the titier of ZTT, and the positive rate of the PCR with the primers of the NS3/4 region (NS3/4PCR) were significantly higher in the anti-HCV antibody positive group than in the negative group. However, the other data such as alanine aminotransferase activity or past history were not significantly different. Nucleotide sequence of the cDNA fragments of NS3/4 region amplified by the PCR did not differ significantly between isolates from anti-HCV antibody positive and negative sera. The sequences observed in the present study did not differ significantly from those reported previously. Although there remains the possibility that the variation of viral genomic sequences may cause the absence of anti-HCV antibody, these results suggested that the individual clinical backgrounds or immunoreactivity of the patients might influence the antibody development.

en-copyright= kn-copyright= en-aut-name=MoriiKazuhiko en-aut-sei=Morii en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimomuraHiroyuki en-aut-sei=Shimomura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaHiroshi en-aut-sei=Nakagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasuiToshimi en-aut-sei=Hasui en-aut-mei=Toshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiTakao en-aut-sei=Tsuji en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University en-keyword=hepatitis C virus kn-keyword=hepatitis C virus en-keyword=polymerase chain reaction kn-keyword=polymerase chain reaction en-keyword=anti-C100-3 antibody kn-keyword=anti-C100-3 antibody en-keyword=genetic variation kn-keyword=genetic variation END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=4 article-no= start-page=241 end-page=248 dt-received= dt-revised= dt-accepted= dt-pub-year=1991 dt-pub=199108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic variation of putative core gene in hepatitis C virus. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Genetic variation of hepatitis C virus was assessed. We prepared RNA fractions from 21 patients' sera which were positive for hepatitis C virus RNA, synthesized their cDNAs, and amplified fragments, 406 base pairs, encoding a putative core protein, by polymerase chain reaction. One of them, N 15, was cloned and sequenced. N 15 showed 92.4% homology at the nucleotide level and 97.0% homology at the amino acid level compared with HC-J 1 which is the first isolated clone in Japan and similar to that isolated in USA. By restriction fragment length polymorphisms analysis, 14 out of 21 patients (66.7%) showed the same pattern as N 15. No patients showed the pattern of HC-J 1. We could not find a correlation between the genetic variation and clinical features of hepatitis C virus infection. These results indicate that the region, which encodes the core protein and is believed to be relatively conserved in hepatitis C virus genome, has several variations at the nucleotide level, and the major part of hepatitis C virus in Okayama district is different from HC-J 1 and the USA clone.

en-copyright= kn-copyright= en-aut-name=FujioKozo en-aut-sei=Fujio en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimomuraHiroyuki en-aut-sei=Shimomura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiTakao en-aut-sei=Tsuji en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University en-keyword=hapatitis C virus kn-keyword=hapatitis C virus en-keyword=restriction fragment length polymorphisms kn-keyword=restriction fragment length polymorphisms en-keyword=polymerase chain reaction kn-keyword=polymerase chain reaction en-keyword=genetic variation kn-keyword=genetic variation END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=2 article-no= start-page=59 end-page=65 dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=200404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sneddon's syndrome: clinical and laboratory analysis of 10 cases. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Sneddon's syndrome is characterized by livedo reticularis and cerebrovascular lesions. We report the cases of women (mean age, 36.2 +/- 8.1 years) diagnosed with Sneddon's syndrome based on the presence of livedo reticularis and characteristic cerebrovascular findings. Seven of these patients had cerebral infarcts on cranial computed tomography scan. Antiphospholipid antibodies were positive in 6 of these cases. Three cases had abnormal levels of antithrombin III. Analyses of chromosome 6 revealed no abnormalities. In 3 of the cases, investigation of the pedigrees revealed autosomal dominant traits. Two cases had epilepsy, and 3 had migraine. One case with migraine also had myasthenia gravis. In addition, we detected inferior altudinal hemianopia in 2 cases, cognitive functional disorder in 3 and depression in 2. Based on these findings, the entire vascular, haematologic, neurologic, and dermatologic systems should be evaluated in patients diagnosed with Sneddon's syndrome.

en-copyright= kn-copyright= en-aut-name=BolayirErtugrul en-aut-sei=Bolayir en-aut-mei=Ertugrul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YilmazAbdulkerim en-aut-sei=Yilmaz en-aut-mei=Abdulkerim kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuguNesim en-aut-sei=Kugu en-aut-mei=Nesim kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ErdoganHaydar en-aut-sei=Erdogan en-aut-mei=Haydar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkyolMelih en-aut-sei=Akyol en-aut-mei=Melih kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkyuzAytekin en-aut-sei=Akyuz en-aut-mei=Aytekin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Cumhuriyet University Faculty of Medicine affil-num=2 en-affil= kn-affil=Cumhuriyet University affil-num=3 en-affil= kn-affil=Cumhuriyet University, Turkey affil-num=4 en-affil= kn-affil=Cumhuriyet University affil-num=5 en-affil= kn-affil=Cumhuriyet University, Turkey affil-num=6 en-affil= kn-affil=Cumhuriyet University, Turkey en-keyword=Sneddon’s syndrome kn-keyword=Sneddon’s syndrome en-keyword=antiphospholipid antibodies kn-keyword=antiphospholipid antibodies en-keyword=genetics kn-keyword=genetics en-keyword=cognitive functions kn-keyword=cognitive functions en-keyword=migraine kn-keyword=migraine END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=6 article-no= start-page=255 end-page=261 dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=200412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Brugada syndrome: 12 years of progression. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Brugada syndrome is increasingly being recognized in clinical medicine. What started as an electrocardiographic curiosity has become an important focus of attention for individuals working in the different disciplines related to sudden cardiac death, from basic scientists to clinical cardiac electrophysiologists. In just 12 years, since the description of the disease, clinically relevant information is continuously being provided to physicians to help protect the individuals with Brugada syndrome to the best of our ability. And this information has been gathered thanks to the effort of hundreds of basic scientists, physicians and patients who continue to give their time, effort and data to help understand how the electrocardiographic pattern may cause sudden cardiac death. There are still many unanswered questions, both at the clinical and basic field. However, with the further collection of data, the longer follow-up and the continued interest from the basic science world we will have the necessary tools to the successful unraveling of the disease.

en-copyright= kn-copyright= en-aut-name=HongKui en-aut-sei=Hong en-aut-mei=Kui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AntzelevitchCharles en-aut-sei=Antzelevitch en-aut-mei=Charles kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BrugadaPedro en-aut-sei=Brugada en-aut-mei=Pedro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BrugadaJosep en-aut-sei=Brugada en-aut-mei=Josep kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OheTohru en-aut-sei=Ohe en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BrugadaRamon en-aut-sei=Brugada en-aut-mei=Ramon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Masonic Medical Research Laboratory affil-num=2 en-affil= kn-affil=Masonic Medical Research Laboratory affil-num=3 en-affil= kn-affil=Cardiovascular Research and Teaching Institute of Aalst, affil-num=4 en-affil= kn-affil=University of Barcelona affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Masonic Medical Research Laboratory en-keyword=Brugada syndrome kn-keyword=Brugada syndrome en-keyword=suddendeath kn-keyword=suddendeath en-keyword=genetics kn-keyword=genetics END