Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Cinnamyl alcohol dehydrogenase (CAD) underlies the orange lemma trait and lignin reduction in barley30805ENKazuhiroSatoInstitute of Plant Science and Resources, Okayama UniversityMahoMoritaInstitute of Plant Science and Resources, Okayama UniversityNamiYamajiInstitute of Plant Science and Resources, Okayama UniversityRinkaKakoGraduate School of Agricultural Science, Setsunan UniversityTomokazuUshijimaGraduate School of Agricultural Science, Setsunan UniversityHiroshiHisanoInstitute of Plant Science and Resources, Okayama UniversityBarley (Hordeum vulgare L.) is one of the world’s major cereal crops and is widely used for feed, brewing, and food. Reducing lignin content in barley grain and straw is beneficial for improving forage digestibility and enhancing the efficiency of bioethanol production. The orange lemma mutation―characterized by orange pigmentation of husks and nodes―has long been associated with altered lignin metabolism; however, its genetic basis has remained unclear. We show that Cinnamyl Alcohol Dehydrogenase (CAD) is the causal gene underlying the orange lemma phenotype in barley. Genetic mapping using a ‘Haruna Nijo’ × ‘L053’ F₂ population and the Barley 50 K SNP array defined a candidate region on chromosome 6H containing the CAD gene. Sequence analysis revealed that all orange lemma mutants, including both naturally occurring and EMS-induced lines, carried nucleotide changes in the CAD gene, resulting in amino acid substitutions or premature stop codons. Furthermore, CRISPR/Cas9-mediated knockout of CAD in the cultivar ‘Golden Promise’ reproduced the orange lemma phenotype, providing functional validation. The knockout plants also showed significantly lower lignin content than wild-type plants. These findings resolve a long-standing question regarding the genetic basis of the orange lemma trait and demonstrate that disruption of CAD alters lignin accumulation in barley. This work provides a valuable genetic resource for breeding barley cultivars with improved biomass utilization for feed and bioenergy applications.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1058-83882026MIT/TFE family transcription factors, Mitf and Tfec, redundantly promote pigment cell differentiation and retinal epithelium pigmentation in teleosts115ENJamesListerDepartment of Human and Molecular Genetics and Massey Cancer Center, Virginia Commonwealth University School of MedicineKeisukeSugiwakaDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityTetsuakiKimuraDepartment of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic BiologyRiekoTanakaWorld Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical GardensMakotoGodaInstitute of Photonics Medicine, Hamamatsu University School of MedicineHikaruKobayashiDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityChikakoInoueR&D Fish Breeding Group, Regional Fish Institute, Ltd.Kawilarang W. A.MasengiFaculty of Fisheries and Marine Science, Sam Ratulangi UniversityKazunoriYamahiraTropical Biosphere Research Center, University of the RyukyusKiyoshiNaruseDepartment of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic BiologySatoshiAnsaiUshimado Marine Institute, Graduate School of Natural Science and Technology, Okayama UniversityRobert N.KelshDepartment of Life Sciences, University of BathMasahikoHibiDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityHisashiHashimotoDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityBackground: Transcription factors of the MIT/TFE family―mitfa, mitfb, and tfec―play essential roles in specifying pigment cells derived from neural crest cells in vertebrates. In teleosts, which possess multiple pigment cell types, these factors exhibit partially redundant but largely distinct functions across different pigment lineages. We previously reported that the combined loss of mitfa and mitfb leads to a complete absence of melanophores, xanthophores, and leucophores in medaka.<br>
Results: Here, we describe newly generated hypomorphic alleles of mitfa and mitfb, which result in delayed melanophore development. Using these hypomorphic mutants in combination with a newly generated null allele of tfec, we show that Tfec can partially compensate for the loss of Mitfa and Mitfb in melanophore, xanthophore, and leucophore differentiation. Consistent with previous findings in zebrafish, loss of tfec alone results in the complete absence of iridophores. Importantly, simultaneous null mutations in all three genes cause a complete loss of all four chromatophore types and lead to defective pigmentation of the retinal pigmented epithelium (RPE), which is not derived from the neural crest in both Oryzias species and in zebrafish. Using an RPE-specific marker, we further show that the RPE is specified and structurally intact but fails to melanize.<br>
Conclusions: These findings indicate that the redundant functions of Mitfa, Mitfb, and Tfec are not only essential for the specification of diverse pigment cell types but also critical for RPE pigmentation.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2475-03282026Biological Resectability in Colorectal Liver Metastases: A Nomogram‐Based Continuous Risk Model to Define Borderline DiseaseENYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Medical Development Field, Okayama UniversityTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruKojimaDepartment of Surgery, Okayama Saiseikai General HospitalTakeshiKoujimaDepartment of Surgery, Himeji Red Cross HospitalTatsuoMatsudaDepartment of Surgery, Tenwakai Matsuda HospitalDaisukeSatohDepartment of Surgery, Hiroshima Citizens HospitalMasaruInagakiDepartment of Surgery, National Hospital Organization Fukuyama Medical CenterKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Resectability in colorectal liver metastases (CRLM) is traditionally defined by technical feasibility; however, a biologically based definition of borderline resectable disease has not been established. We evaluated the prognostic impact of KRAS mutation and developed a model for biological risk stratification.<br>
Methods: This multi-institutional retrospective study included 584 patients undergoing initial hepatectomy for CRLM. The impact of KRAS mutation was assessed according to primary tumor sidedness and tumor burden score (TBS). A nomogram predicting overall survival (OS) was constructed using independent prognostic factors and compared with established clinical risk scores.<br>
Results: KRAS mutation was identified in 36.8% of patients and was associated with worse OS (median survival: 47.3 vs. 70.6 months, p = 0.0006) and recurrence-free survival. This adverse impact was observed in left-sided tumors but not in right-sided tumors. TBS stratified prognosis in KRAS wild-type but not in mutant cases, suggesting that tumor biology may outweigh morphology. A nomogram incorporating KRAS status, TBS, CA19-9, primary nodal status, and extrahepatic disease demonstrated improved discriminatory ability compared with conventional models and stratified recurrence patterns, including extrahepatic recurrence.<br>
Conclusions: The prognostic impact of KRAS mutation depends on tumor sidedness and is independent of tumor morphology. Our nomogram provides a continuous biological risk assessment and may facilitate biological risk stratification and support future refinement of the concept of biologically borderline resectable CRLM.No potential conflict of interest relevant to this article was reported.American Society for MicrobiologyActa Medica Okayama2165-04971492026Combinations of long terminal repeat and tax protein substitutions influence bovine leukemia virus transmission through altered viral productivitye0086926ENHironobuMurakamiSchool of Veterinary Medicine, Azabu UniversityReiichiroSatoGraduate School of Medicine and Veterinary Medicine, University of MiyazakiJumpeiUchiyamaDepartment of Infectious Diseases, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuyukiSogawaSchool of Life and EnvironmentaScience, Azabu UniversityHirohoIshidaSchool of Veterinary Medicine, Azabu UniversityMakotoNagaiSchool of Veterinary Medicine, Azabu UniversityBovine leukemia virus (BLV) infection imposes a substantial economic burden on the global cattle industry. Although proviral load (PVL) in blood influences transmission, the effects of viral genetic variations, including the high viral production-associated long terminal repeat (LTR) substitution at nucleotide position 175 (LTR175), on herd-level dynamics remain unclear. This study investigated the effects of specific substitutions on the regulation of viral productivity and transmission. Longitudinal monitoring of a single farm (herd size: 50–68 cows; 438 samples collected) over a 7-year period revealed that viral strains carrying cytosine at LTR175 (LTR175C) significantly increased in frequency, becoming dominant over wild-type strains carrying thymidine. In contrast, amino acid substitutions in the Tax protein at positions 69 (Tax69) and 73 (Tax73) modified viral transactivation independent of LTR175. Structural modeling via AlphaFold2 predicted that Tax69 and Tax73 mutations alter protein properties, suggesting modulation of transactivation activity. Consistent with this prediction, in vitro assays confirmed that the substitutions modified viral production by regulating transactivation independent of LTR175. Moreover, high viral-productivity haplotypes containing LTR175C and Tax73Q (glutamine at amino acid residue 73) exhibited a transmission advantage within the herd, even when host PVL levels were not significantly elevated. These findings suggest that cellular-level viral productivity is one of the key determinants of transmission fitness. Overall, this study revealed a regulatory interaction between the LTR and Tax protein that optimizes viral spread and highlights the need for control strategies that account for viral genetic substitutions.No potential conflict of interest relevant to this article was reported.American Society for MicrobiologyActa Medica Okayama0066-48046912025Genomic epidemiology and genetic characteristics of clinical Campylobacter species cocirculating in West Bengal, India, 2019, using whole genome analysise01108-24ENDaichiMoritaDepartment of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityAsish KumarMukhopadhyayDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesGoutamChowdhuryDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesFumitoMaruyamaSection of Microbial Genomics and Ecology, The IDEC Institute, Hiroshima UniversityMiyukiKandaDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityYukiYamamotoDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityHidetoshiTaharaDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityPiyaliMukherjeeDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesMainakBardhanDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesTakanoriKumagaiDepartment of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityKeiKitaharaCollaborative Research Centre of Okayama University for Infectious Diseases at ICMR-NICEDShin-IchiMiyoshiCollaborative Research Centre of Okayama University for Infectious Diseases at ICMR-NICEDShantaDuttaDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesTeruoKurodaDepartment of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityCampylobacter species are the most common pathogens responsible for foodborne gastroenteritis worldwide. India is a region with frequent diarrheal infections and a high level of Campylobacter infection incidence, but the detailed genomic information is limited. This study aimed to characterize 112 isolates of Campylobacter from diarrhea patients at two hospitals in Kolkata, West Bengal, by whole genome analysis. The Campylobacter isolates consisted of 90 C. jejuni, 20 C. coli, and 2 C. lari isolates. Multilocus sequence typing analysis revealed that the largest sequence type (ST) populations were ST-2131 in C. jejuni and ST-830 in C. coli and seven novel STs were found in C. jejuni and one in C. coli. Notably, ST-2131, which is rarely seen elsewhere, was positive for a sialylated LOS-related gene (wlaN +neuA + cstIII) associated with Guillain-Barré syndrome. Antibiotic resistance factors predicted from the genome sequence included blaOXA variants (58.9%), tet(O) (54.5%), tet(W) (0.9%), ant(6)-Ia (0.9%), mutation in GyrA (T86I, T86I+D90N, T86I+P104S, T86I+D90N+P104S) (79.5%), and mutation in 23S rRNA (A2075G) (12.5%). In addition to the high drug resistance of Campylobacter in Kolkata, Campylobacter pathogens were circulating that may be associated with Guillain-Barré syndrome. This study indicates the importance of genomic analysis in the surveillance of pathogens, which provides genomic information on genetic diversity, virulence mechanisms, and determinants of antimicrobial resistance.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8012026Time Course of the Development and Loss of Delta-9-tetrahydrocannabinol Tolerance: Effects on Hypothermia and Spontaneous Locomotor Activity in Mice4754ENYukiomiEguchiDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversitySoichiroUshioDepartment of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKeiichiIrieDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityYutaYamashitaDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityMiyuEguchiDepartment of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityTakafumiNakanoDepartment of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKenichiMishimaDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityOriginal Article10.18926/AMO/70072Deregulation of cannabis use is gradually expanding in Europe and the United States. However, the biological processes driving tolerance to delta-9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component of cannabis, remain unclear. Thus, this study aimed to investigate the mechanisms and time course of tolerance development and loss to Δ9-THC in mice. Male ICR mice (7 weeks old) were administered Δ9-THC once daily for 3 days and then divided into three groups according to the washout period (3-, 10-, and 17-day washout groups). After each washout, changes in body temperature and locomotor activity were measured following re-exposure to Δ9-THC. Furthermore, the mRNA expression levels of CB1 and CB2 receptors in the brain were evaluated using real-time PCR. On day 1, significant hypothermia and reduced spontaneous locomotor activity were observed in the Δ9-THC-treated mice compared with the vehicle-treated mice. Tolerance to the hypothermic and locomotor-suppressing effects of Δ9-THC developed on days 2 and 3, respectively, and dissipated after 3 and 11 days of washout, respectively. These differences in the rates of tolerance development and recovery may reflect distinct underlying mechanisms. No significant changes in receptor mRNA expression were observed. These findings highlight the complexity of Δ9-THC tolerance and its potential implications for long-term cannabis use.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2772-7076142025Genetic variability in Neisseria meningitidis strains isolated in a Japanese hospital100511ENKazuyoshiGotohDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesShinnosukeFukushimaDepartment of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalShumaTsujiDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalOsamuMatsushitaDepartment of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjectives: 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.<br>
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).<br>
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.<br>
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.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1465-36215542025Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review313326ENYutaKubotaDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityMasanoriKawanoDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityTatsuyaIwasakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityIchiroItonagaDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityNobuhiroKakuDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityToshifumiOzakiDepartment of Orthopaedic Surgery , Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroTanakaDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityIn 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.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1464-672226112025Comparative Genomic Analysis Identifies FleQ and GcbB as Virulence-Associated Factors in Pseudomonas syringae pv. tabaci Strainse70168ENMuhammad TaufiqHidayatGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKeiYoshiokaFaculty of Agriculture, Okayama UniversityTakafumiNishimuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityShutaAsaiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySachikoMasudaCenter for Sustainable Resource Science, RIKEN-TRIPKenShirasuCenter for Sustainable Resource Science, RIKEN-TRIPNanamiSakataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMikihiroYamamotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshiteruNoutoshiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKazuhiroToyodaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukiIchinoseGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidenoriMatsuiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPseudomonas syringae pv. tabaci (Pta) is an important plant pathogen, which causes wildfire disease in Nicotiana species. However, the genetic basis underlying strain-level differences in virulence remains largely unresolved. To address this, we performed a comparative genomic analysis between a highly virulent strain Pta6605 and a less virulent strain Pta7375. Despite high overall genome similarity, we identified key single-nucleotide polymorphisms, including premature stop-codon mutations in seven open reading frames in Pta7375. Notably, point mutations in two regulatory genes, such as fleQ, which encodes a transcription factor essential for flagellar biogenesis and biofilm formation, and gcbB, which encodes a GGDEF domain-containing diguanylate cyclase responsible for cyclic dimeric guanosine monophosphate (c-di-GMP) synthesis, were implicated in virulence disparity. Functional analyses using deletion and locus replacement mutants in the Pta6605 background revealed that the disruption of fleQ markedly reduced motility, flagellin production, c-di-GMP accumulation, biofilm formation and virulence level mirroring the Pta7375 phenotype. The gcbB replacement mutant showed reduced disease symptom development, although c-di-GMP levels remained comparable to the Pta6605 wild type. Locus replacement between strains confirmed that a point mutation in fleQ was the primary driver of reduced motility and flagellin expression in Pta7375. These findings indicate that the reduced virulence of Pta7375 is associated with impaired regulation of flagella-related genes and disruption of the FleQ-mediated c-di-GMP signalling, underscoring the value of comparative genomics in disentangling the complex regulatory networks that govern virulence in plant pathogens.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0385-240752102025Biologics and Small‐Molecule Therapies in Netherton Syndrome: A Comprehensive Review14831493ENShinMorizaneDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyukiMukaiDepartment of Immunology and Molecular Genetics, Kawasaki Medical SchoolKoSunagawaDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen‐ichiHasuiDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAnriMoritaDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHayatoNomuraDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMamoruOuchidaDepartment of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNetherton syndrome (NS) is a rare congenital ichthyosis caused by loss-of-function mutations in the SPINK5 gene, leading to defective expression of the serine protease inhibitor LEKTI. Dysregulated epidermal protease activity results in impaired skin barrier function and chronic inflammation, accompanied by complex immune profiles. NS patients commonly show activation of the inflammatory axis, centered on IL-17 and IL-36, in the skin and blood, and show a psoriasis-like shift to Th17. Conversely, the immune profile differs depending on the clinical type, with ichthyosis linearis circumflexa type characterized by complement activation and Th2-type allergic responses, and scaly erythroderma type characterized by a type I IFN signature and Th9-type allergic responses. While symptomatic treatments such as emollients and topical corticosteroids have been the mainstay of care, recent advances have opened new therapeutic avenues involving biologic agents and oral small-molecule immunomodulators. This review provides a comprehensive overview of the current clinical landscape and future directions of biologics (e.g., dupilumab, secukinumab, ustekinumab) and small-molecule therapies (e.g., JAK inhibitors such as tofacitinib, baricitinib, and upadacitinib) in the treatment of NS. Though evidence remains limited to case reports and small series, preliminary data suggest that cytokine-targeted interventions―particularly those inhibiting IL-4, IL-13, IL-17, IL-36, and JAK pathways―may offer tangible clinical benefits. Well-designed clinical trials and mechanistic investigations are crucial to establishing their place in NS management.No potential conflict of interest relevant to this article was reported.Elsevier B.V.Acta Medica Okayama0304-41651869122025The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center130860ENTakumiBabaLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterGoUenoLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterChikaOheLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterShukuSajiStructural Biology Division, Japan Synchrotron Radiation Research InstituteSachikoYamamotoStructural Biology Division, Japan Synchrotron Radiation Research InstituteMasakiYamamotoLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterHiroshiNakagawaMaterials Sciences Research Center, Japan Atomic Energy AgencyNobuoOkazakiNeutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS)MamoruOuchidaDepartment of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIoriKawasaki-OhmoriSection of Developmental Physiology and Pathology, Faculty of Education, Okayama UniversityKoheiTakeshitaLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterThioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats.No potential conflict of interest relevant to this article was reported.Walter de Gruyter GmbHActa Medica Okayama2081-69361612025Age-related behavioural abnormalities in C57BL/6.KOR–Apoe shl miceENHiroshiUenoDepartment of Medical Technology, Kawasaki University of Medical WelfareYuTakahashiDepartment of Psychiatry, Kawasaki Medical SchoolSachikoMoriDepartment of Psychiatry, Kawasaki Medical SchoolErikoKitanoDepartment of Psychiatry, Kawasaki Medical SchoolShinjiMurakamiDepartment of Psychiatry, Kawasaki Medical SchoolKentaWaniDepartment of Psychiatry, Kawasaki Medical SchoolTetsujiMiyazakiDepartment of Psychiatry, Kawasaki Medical SchoolYosukeMatsumotoDepartment of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotoiOkamotoDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityTakeshiIshiharaDepartment of Psychiatry, Kawasaki Medical SchoolSpontaneously hyperlipidaemic (Apoeshl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoeshl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer’s disease (AD). To understand whether Apoeshl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoeshl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoeshl mice to investigate the behavioural abnormalities associated with ageing in Apoeshl mice. In this study, 7-month-old Apoeshl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoeshl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoeshl mice showed decreased anxiety-like behaviour. Moreover, Apoeshl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoeshl mice changes with age. However, 11-month-old Apoeshl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoeshl mice can be used to investigate the function of ApoE in the central nervous system.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0040-575213792024Mutations in starch BRANCHING ENZYME 2a suppress the traits caused by the loss of ISOAMYLASE1 in barley212ENRyoMatsushimaInstitute of Plant Science and Resources, Okayama UniversityHiroshiHisanoInstitute of Plant Science and Resources, Okayama UniversityJune-SikKimInstitute of Plant Science and Resources, Okayama UniversityRoseMcNellyJohn Innes Centre, Norwich Research ParkNaoko F.OitomeDepartment of Biological Production, Akita Prefectural UniversityDavidSeungJohn Innes Centre, Norwich Research ParkNaokoFujitaDepartment of Biological Production, Akita Prefectural UniversityKazuhiroSatoInstitute of Plant Science and Resources, Okayama UniversityThe genetic interactions among starch biosynthesis genes can be exploited to alter starch properties, but they remain poorly understood due to the various combinations of mutations to be tested. Here, we isolated two novel barley mutants defective in starch BRANCHING ENZYME 2a (hvbe2a-1 and hvbe2a-2) based on the starch granule (SG) morphology. Both hvbe2a mutants showed elongated SGs in the endosperm and increased resistant starch content. hvbe2a-1 had a base change in HvBE2a gene, substituting the amino acid essential for its enzyme activity, while hvbe2a-2 is completely missing HvBE2a due to a chromosomal deletion. Further genetic crosses with barley isoamylase1 mutants (hvisa1) revealed that both hvbe2a mutations could suppress defects in endosperm caused by hvisa1, such as reduction in starch, increase in phytoglycogen, and changes in the glucan chain length distribution. Remarkably, hvbe2a mutations also transformed the endosperm SG morphology from the compound SG caused by hvisa1 to bimodal simple SGs, resembling that of wild-type barley. The suppressive impact was in competition with floury endosperm 6 mutation (hvflo6), which could enhance the phenotype of hvisa1 in the endosperm. In contrast, the compound SG formation induced by the hvflo6 hvisa1 mutation in pollen was not suppressed by hvbe2a mutations. Our findings provide new insights into genetic interactions in the starch biosynthetic pathway, demonstrating how specific genetic alterations can influence starch properties and SG morphology, with potential applications in cereal breeding for desired starch properties.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0167-594X16712024Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review201210ENYasuhitoKegoyaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoheiInoueDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyoMizutaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesFumiyoHigakiDepartment of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKanaWashioDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinichiroKoizumiDepartment of Neurosurgery, Hamamatsu University School of MedicineKazuhikoKurozumiDepartment of Neurosurgery, Hamamatsu University School of MedicineJojiIshidaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKentaroFujiiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNorioYamamotoDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshihiroTanakaDivision of Epidemiology, Graduate School of Public Health, Shizuoka Graduate University of Public HealthIsaoDateDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesIntroduction 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.<br>
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.<br>
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.<br>
Conclusions In this study, MI-positive cases had a worse prognosis compared with MI-negative cases.No potential conflict of interest relevant to this article was reported. Japanese Society for Lymphoreticular Tissue ResearchActa Medica Okayama1346-42806412024Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders19ENTakeshiOkataniDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMidori FilizNishimuraDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYuriaEgusaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesSayakoYoshidaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYoshitoNishimuraDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAsamiNishikoriDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesTadashiYoshinoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMethotrexate (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.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0013-95806372022Novel animal model of combined generalized and focal epilepsye80e85ENIoriOhmoriSection of Developmental Physiology and Pathology, Faculty of Education, Okayama UniversityMamoruOuchidaDepartment of Molecular Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasakazuShinoharaDivision of Epidemiology, Kobe University Graduate School of MedicineKiyokaKobayashiOtsuka PharmaceuticalSaekoIshidaDivision of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, University of TokyoTomojiMashimoDivision of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, University of TokyoThioredoxin, encoded by Txn1, is a critical antioxidant that protects against oxidative damage by regulating the dithiol/disulfide balance of interacting proteins. We recently discovered the Adem rat, an epileptic rat harboring the Txn1-F54L mutation, characterized by wild running and vacuolar degeneration in the midbrain. This study aimed to characterize the classification of epilepsy in Adem rats. We performed simultaneous video-electroencephalographic recordings, magnetic resonance imaging, neurotransmitter measurements using gas chromatography–mass spectrometry (GC-MS), and immunohistochemistry. Adem rats exhibited absence, tonic, and focal seizures. The type of epilepsy was classified as combined generalized and focal epilepsy. Neurotransmitters in the midbrain and cortex were measured at 3 weeks of age, when neuronal cell death occurs in the midbrain. The results of GC-MS ruled out the dominance of the excitatory system in the midbrain and cortex of Adem rats. Activation of astrocytes and microglia was more pronounced at 5 weeks of age, at which time epileptic seizures occurred frequently. The underlying pathology in Adem rats remains unknown. However, glial cell activation and inflammation may play a significant role in the occurrence of epilepsy.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7732023Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma323330ENKeigoMakinoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroFujiiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJojiIshidaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuichiro HiranoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasukiSurugaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKanaWashioDepartments of Pediatrics, Okayama University HospitalKenjiNishidaDepartments of Pathology, Okayama University HospitalHiroyukiYanaiDepartments of Pathology, Okayama University HospitalShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalIsaoDateDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/65502In 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.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0969-99611752022Thioredoxin deficiency increases oxidative stress and causes bilateral symmetrical degeneration in rat midbrain105921ENIoriOhmoriSection of Developmental Physiology and Pathology, Faculty of Education, Okayama UniversityMamoruOuchidaDepartment of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirohikoImaiDepartment of Systems Science, Kyoto University Graduate School of InformaticsSaekoIshidaDivision of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of TokyoShinyaToyokuniDepartment of Pathology and Biological Responses, Nagoya University Graduate School of MedicineTomojiMashimoDivision of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of TokyoThioredoxin, encoded by Txn1, acts as a critical antioxidant in the defense against oxidative stress by regulating the dithiol/disulfide balance of interacting proteins. The role of thioredoxin in the central nervous system (CNS) is largely unknown. A phenotype-driven study of N-ethyl-N-nitrosourea-mutated rats with wild-running seizures revealed the importance of Txn1 mutations in CNS degeneration. Genetic mapping identified Txn1-F54L in the epileptic rats. The insulin-reducing activity of Txn1-F54L was approximately one-third of that of the wild-type (WT). Bilateral symmetrical vacuolar degeneration in the midbrain, mainly in the thalamus and the inferior colliculus, was observed in the Txn1-F54L rats. The lesions displayed neuronal and oligodendrocytic cell death. Neurons in Txn1-F54L rats showed morphological changes in the mitochondria. Vacuolar degeneration peaked at five weeks of age, and spontaneous repair began at seven weeks. The TUNEL assay showed that fibroblasts derived from homozygotes were susceptible to cell death under oxidative stress. In five-week-old WT rats, energy metabolism in the thalamus was significantly higher than that in the cerebral cortex. In conclusion, in juvenile rats, Txn1 seems to play an essential role in reducing oxidative stress in the midbrains with high energy metabolism.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7642022Genomic Profiling of a Case of Glioneuronal Tumor with Neuropil-like Islands473477ENNobushigeTsuboiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJojiIshidaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeShimazuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisanoriEdakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsuhitoUnedaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroFujiiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoKurozumiDepartment of Neurosurgery, Hamamatsu University School of MedicineDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalHiroyukiYanaiDepartment of Pathology, Okayama University HospitalIsaoDateDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report/10.18926/AMO/63907Glioneuronal tumor with neuropil-like islands (GNTNI) is a very rare subtype of glioneuronal tumor. We present a case of a 62-year-old man with GNTNI. Two adjacent lesions in the left parietal lobe were removed by left parietal craniotomy. The histological findings were glial cell proliferation and scattered rosettes consisting of synaptophysin-positive and NeuN-positive cells, leading to the diagnosis of GNTNI. Target sequencing revealed a genetic alteration similar to glioblastoma, IDH-wild type, which suggested adjuvant therapies. There are few previous reports on the treatment of this disease, and the patient should be followed carefully.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7562021Pulmonary Enteric Adenocarcinoma Harboring a BRAF G469V Mutation759762ENDaiShimizuDepartment of Thoracic Surgery, Okayama University HospitalHiromasaYamamotoDepartment of Thoracic Surgery, Okayama University HospitalKazuhikoShienDepartment of Thoracic Surgery, Okayama University HospitalKoheiTaniguchiDepartment of Diagnostic Pathology, Okayama University HospitalKentarohMiyoshiDepartment of Thoracic Surgery, Okayama University HospitalKeiNambaDepartment of Thoracic Surgery, Okayama University HospitalKumiMesakiDepartment of Thoracic Surgery, Okayama University HospitalSeiichiroSugimotoDepartment of Thoracic Surgery, Okayama University HospitalJunichiSohDepartment of Thoracic Surgery, Okayama University HospitalMasaomiYamaneDepartment of Thoracic Surgery, Okayama University HospitalShinichiToyookaDepartment of Thoracic Surgery, Okayama University HospitalCase Report/10.18926/AMO/62819Pulmonary 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.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7542021Two Types of Polyp Shape Observed in the Stomach of Patients with Peutz-Jeghers Syndrome471477ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsuyaToyokawaDepartment of Gastroenterology, Fukuyama Medical CenterKazuhiroMatsuedaDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalShinichiroHoriDepartment of Endoscopy, Shikoku Cancer CenterMasaoYoshiokaDepartment of Internal Medicine, Okayama Saiseikai General HospitalYukiMoritouDepartment of Internal Medicine, Hiroshima City Hiroshima Citizens HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotowoMizunoDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/62399The 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.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1340-28382832021Chromosome-scale genome assembly of the transformation-amenable common wheat cultivar ‘Fielder’dsab008ENKazuhiroSatoInstitute of Plant Science and Resources, Okayama UniversityFumitakaAbeInstitute of Crop Science, NAROMartinMascherLeibniz Institute of Plant Genetics and Crop Plant Research (IPK) GaterslebenGeorgHabererPlant Genome and Systems Biology (PGSB), Helmholtz Center Munich, German Research Center for Environmental HealthHeidrunGundlachPlant Genome and Systems Biology (PGSB), Helmholtz Center Munich, German Research Center for Environmental HealthManuelSpannaglPlant Genome and Systems Biology (PGSB), Helmholtz Center Munich, German Research Center for Environmental HealthKentaShirasawaKazusa DNA Research InstituteSachikoIsobeKazusa DNA Research InstituteWe have established a high-quality, chromosome-level genome assembly for the hexaploid common wheat cultivar ‘Fielder’, an American, soft, white, pastry-type wheat released in 1974 and known for its amenability to Agrobacterium tumefaciens-mediated transformation and genome editing. Accurate, long-read sequences were obtained using PacBio circular consensus sequencing with the HiFi approach. Sequence reads from 16 SMRT cells assembled using the hifiasm assembler produced assemblies with N50 greater than 20 Mb. We used the Omni-C chromosome conformation capture technique to order contigs into chromosome-level assemblies, resulting in 21 pseudomolecules with a cumulative size of 14.7 and 0.3 Gb of unanchored contigs. Mapping of published short reads from a transgenic wheat plant with an edited seed-dormancy gene, TaQsd1, identified four positions of transgene insertion into wheat chromosomes. Detection of guide RNA sequences in pseudomolecules provided candidates for off-target mutation induction. These results demonstrate the efficiency of chromosome-scale assembly using PacBio HiFi reads and their application in wheat genome-editing studies.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1471-90536232021Mutations in a Golden2-Like Gene Cause Reduced Seed Weight in Barley albino lemma 1 Mutants447457ENShinTaketaInstitute of Plant Science and Resources, Okayama UniversityMomokoHattoriInstitute of Plant Science and Resources, Okayama UniversityTsuneakiTakamiInstitute of Plant Science and Resources, Okayama UniversityEikoHimiInstitute of Plant Science and Resources, Okayama UniversityWataruSakamotoIInstitute of Plant Science and Resources, Okayama UniversityThe albino lemma 1 (alm1) mutants of barley (Hordeum vulgare L.) exhibit obvious chlorophyll-deficient hulls. Hulls are seed-enclosing tissues on the spike, consisting of the lemma and palea. The alm1 phenotype is also expressed in the pericarp, culm nodes and basal leaf sheaths, but leaf blades and awns are normal green. A single recessive nuclear gene controls tissue-specific alm1 phenotypic expression. Positional cloning revealed that the ALM1 gene encodes a Golden 2-like (GLK) transcription factor, HvGLK2, belonging to the GARP subfamily of Myb transcription factors. This finding was validated by genetic evidence indicating that all 10 alm1 mutants studied had a lesion in functionally important regions of HvGLK2, including the three alpha-helix domains, an AREAEAA motif and the GCT box. Transmission electron microscopy revealed that, in lemmas of the alm1.g mutant, the chloroplasts lacked thylakoid membranes, instead of stacked thylakoid grana in wild-type chloroplasts. Compared with wild type, alm1.g plants showed similar levels of leaf photosynthesis but reduced spike photosynthesis by 34%. The alm1.g mutant and the alm1.a mutant showed a reduction in 100-grain weight by 15.8% and 23.1%, respectively. As in other plants, barley has HvGLK2 and a paralog, HvGLK1. In flag leaves and awns, HvGLK2 and HvGLK1 are expressed at moderate levels, but in hulls, HvGLK1 expression was barely detectable compared with HvGLK2. Barley alm1/Hvglk2 mutants exhibit more severe phenotypes than glk2 mutants of other plant species reported to date. The severe alm1 phenotypic expression in multiple tissues indicates that HvGLK2 plays some roles that are nonredundant with HvGLK1.No potential conflict of interest relevant to this article was reported.Public Library ScienceActa Medica Okayama1932-62031642021Lack of collagen alpha 6(IV) chain in mice does not cause severe-to-profound hearing loss or cochlear malformation, a distinct phenotype from nonsyndromic hearing loss with COL4A6 missense mutatione0249909ENShaoyingTangDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoYonezawaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukihideMaedaDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMitsuakiOnoDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroMaebaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyusukeMomotaDepartment of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasukoTomonoDivision of Molecular and Cell Biology, Shigei Medical Research InstituteToshitakaOohashiDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCongenital hearing loss affects 1 in every 1000 births, with genetic mutations contributing to more than 50% of all cases. X-linked nonsyndromic hereditary hearing loss is associated with six loci (DFNX1-6) and five genes. Recently, the missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6, encoding the basement membrane (BM) collagen alpha 6(IV) chain, was shown to be associated with X-linked congenital nonsyndromic hearing loss with cochlear malformation. However, the mechanism by which the COL4A6 mutation impacts hereditary hearing loss has not yet been elucidated. Herein, we investigated Col4a6 knockout (KO) effects on hearing function and cochlear formation in mice. Immunohistochemistry showed that the collagen alpha 6(IV) chain was distributed throughout the mouse cochlea within subepithelial BMs underlying the interdental cells, inner sulcus cells, basilar membrane, outer sulcus cells, root cells, Reissner's membrane, and perivascular BMs in the spiral limbus, spiral ligament, and stria vascularis. However, the click-evoked auditory brainstem response analysis did not show significant changes in the hearing threshold of Col4a6 KO mice compared with wild-type (WT) mice with the same genetic background. In addition, the cochlear structures of Col4a6 KO mice did not exhibit morphological alterations, according to the results of high-resolution micro-computed tomography and histology. Hence, loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation, which differs from humans with the COL4A6 missense mutation c.1771G>A, p.Gly591Ser. Therefore, the deleterious effects in the auditory system caused by the missense mutation in COL4A6 are likely due to the dominant-negative effects of the alpha 6(IV) chain and/or alpha 5 alpha 6 alpha 5(IV) heterotrimer with an aberrant structure that would not occur in cases with loss of gene expression.No potential conflict of interest relevant to this article was reported.Spandidos PublicationsActa Medica Okayama2049-94341352020Panel‑based next‑generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings46ENHisashiIshidaDepartment of Pediatrics/Pediatric Hematology and Oncology, Okayama University HospitalAkihiroIguchiDepartment of Pediatrics, Hokkaido University HospitalMichinoriAoeDivision of Medical Support, Okayama University HospitalRitsuoNishiuchiDepartment of Pediatrics, Kochi Health Sciences CenterTakehiroMatsubaraDivision of Biobank, Center for Comprehensive Genomic Medicine, Okayama University HospitalDaiKeinoDepartment of Pediatrics, St. Marianna University School of Medicine HospitalMasashiSanadaClinical Research Center, National Hospital Organization Nagoya Medical CenterAkiraShimadaDepartment of Pediatrics/Pediatric Hematology and Oncology, Okayama University HospitalAcute 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.No potential conflict of interest relevant to this article was reported.IOP PublishingActa Medica Okayama1755-13074652020Animal Biotechnology Roles in Livestock Production012001ENHiroakiFunahashiDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityCurrently, meat and milk productions are significantly increasing especially in Asia. The supply of these products is vital to people's health and well-being, whereas the efficiency of beef production appears to be still lower than other meat productions. Improvements in the quality and functionality of their livestock products, as well as their production efficiency, are required for further production. Animal biotechnologies have contributed to genetic improvement, genetic diversity maintenance of domestic animals, etc. Basic animal biotechnologies, such as artificial insemination and embryo transfer, have been well established and applied as powerful tools for genetic improvement of livestock. In the applications of artificial insemination techniques, the use of sexed semen has been now widely spread, and also efforts are also made in the development of the technology using a small amount of sperm. For embryo transfer, several types of vitrification technologies have been applied to improve pregnancy rates and contributed to the international/domestic supply of livestock embryos. Conventional animal biotechnologies, such as in vitro fertilization and intracellular sperm injection, have been applied to not only livestock production and also human-assisted reproductive medicine. For in-vitro production of embryos in domestic animals, currently, oocytes have been collected from medium or large follicles (3-6 mm or larger in diameter) of ovaries. Although the oocytes derived from small follicles (less than 3 mm in diameter) exist more on the surface of ovaries, the developmental competence of the oocytes has been known to be significantly lower than those from medium follicles. If we could improve the competence of oocytes derived from small follicles significantly, we may be able to increase the number of female gamete resources for in vitro embryo production. Also, the development of techniques for producing transgenic and cloned animals has greatly contributed to the creation of pharmaceuticals and organs for xenotransplantation. Recently, furthermore, genome editing technologies, such as combined use of CRISPR/Cas9 and PiggyBac, have been developed and have made it possible to correct specific parts of the genome and introduce mutations by homologous recombination. In this review, I would like to discuss the application and progress of the above biotechnologies, including our recent research results.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7442020Recurrence of Solitary Fibrous Tumor/Hemangiopericytoma Could Be Predicted by Ki-67 Regardless of Its Origin335343ENYumikoYamamotoDepartment of Diagnostic Pathology, Kochi UniversityYoshihiroHayashiDepartment of Equipment of Support Planning Office, Kochi UniversityIchiroMurakamiDepartment of Diagnostic Pathology, Kochi UniversityOriginal Article10.18926/AMO/60372Since 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.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2076-2607862020Lanthanide-Dependent Methanol and Formaldehyde Oxidation inMethylobacterium aquaticumStrain 22A822ENPatchaYanpiratInstitute of Plant Science and Resources, Okayama UniversityYukariNakatsujiInstitute of Plant Science and Resources, Okayama UniversityShotaHiragaInstitute of Plant Science and Resources, Okayama UniversityYoshikoFujitaniInstitute of Plant Science and Resources, Okayama UniversityTerumiIzumiInstitute of Plant Science and Resources, Okayama UniversitySachikoMasudaInstitute of Plant Science and Resources, Okayama UniversityRyojiMitsuiDepartment of Biochemistry, Faculty of Science, Okayama University of ScienceTomoyukiNakagawaThe United Graduate School of Agricultural Science, Gifu UniversityAkioTaniInstitute of Plant Science and Resources, Okayama UniversityLanthanides (Ln) are an essential cofactor for XoxF-type methanol dehydrogenases (MDHs) in Gram-negative methylotrophs. The Ln(3+)dependency of XoxF has expanded knowledge and raised new questions in methylotrophy, including the differences in characteristics of XoxF-type MDHs, their regulation, and the methylotrophic metabolism including formaldehyde oxidation. In this study, we genetically identified one set of Ln(3+)- and Ca2+-dependent MDHs (XoxF1 and MxaFI), that are involved in methylotrophy, and an ExaF-type Ln(3+)-dependent ethanol dehydrogenase, among six MDH-like genes inMethylobacterium aquaticumstrain 22A. We also identified the causative mutations in MxbD, a sensor kinase necessary formxaFexpression andxoxF1repression, for suppressive phenotypes inxoxF1mutants defective in methanol growth even in the absence of Ln(3+). Furthermore, we examined the phenotypes of a series of formaldehyde oxidation-pathway mutants (fae1,fae2,mchin the tetrahydromethanopterin (H4MPT) pathway andhgdin the glutathione-dependent formaldehyde dehydrogenase (GSH) pathway). We found that MxaF produces formaldehyde to a toxic level in the absence of the formaldehyde oxidation pathways and that either XoxF1 or ExaF can oxidize formaldehyde to alleviate formaldehyde toxicity in vivo. Furthermore, the GSH pathway has a supportive role for the net formaldehyde oxidation in addition to the H4MPT pathway that has primary importance. Studies on methylotrophy inMethylobacteriumspecies have a long history, and this study provides further insights into genetic and physiological diversity and the differences in methylotrophy within the plant-colonizing methylotrophs.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama038556006462020Genomic characterization of antibiotic resistance‐encoding genes in clinical isolates of Vibrio cholerae non‐O1/non‐O139 strains from Kolkata, India: generation of novel types of genomic islands containing plural antibiotic resistance genes435444ENDaichiMoritaCollaborative Research Center of Okayama University for Infectious Diseases in India, Okayama UniversityEizoTakahashiCollaborative Research Center of Okayama University for Infectious Diseases in India, Okayama UniversityMasatomoMoritaDepartment of Bacteriology I, National Institute of Infectious DiseasesMakotoOhnishiDepartment of Bacteriology I, National Institute of Infectious DiseasesTamakiMizunoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin‐ichiMiyoshiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDevaratiDuttaDivision of Bacteriology, National Institute of Cholera and Enteric DiseasesThandavarayanRamamurthyCenter for Human Microbial Ecology, Translational Health Science and Technology InstituteGoutamChowdhuryDivision of Bacteriology, National Institute of Cholera and Enteric Diseases Asish K.MukhopadhyayDivision of Bacteriology, National Institute of Cholera and Enteric DiseasesKeinosukeOkamotoCollaborative Research Center of Okayama University for Infectious Diseases in India, Okayama UniversityNon‐O1/non‐O139 nontoxigenic Vibrio cholerae associated with cholera‐like diarrhea has been reported in Kolkata, India. However, the property involved in the pathogenicity of these strains has remained unclear. The character of 25 non‐O1/non‐O139 nontoxigenic V. cholerae isolated during 8 years from 2007 to 2014 in Kolkata was examined. Determination of the serogroup showed that the serogroups O6, O10, O35, O36, O39, and O70 were represented by two strains in each serogroup, and the remaining isolates belonged to different serogroups. To clarify the character of antibiotic resistance of these isolates, an antibiotic resistance test and the gene analysis were performed. According to antimicrobial drug susceptibility testing, 13 strains were classified as drug resistant. Among them, 10 strains were quinolone resistant and 6 of the 13 strains were resistant to more than three antibiotics. To define the genetic background of the antibiotic character of these strains, whole‐genome sequences of these strains were determined. From the analysis of these sequences, it becomes clear that all quinolone resistance isolates have mutations in quinolone resistance‐determining regions. Further research on the genome sequence showed that four strains possess Class 1 integrons in their genomes, and that three of the four integrons are found to be located in their genomic islands. These genomic islands are novel types. This indicates that various integrons containing drug resistance genes are spreading among V. cholerae non‐O1/non‐O139 strains through the action of newly generated genomic islands.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7422020Identification of a Novel ACVRL1 Gene Mutation (c.100T>A, p.Cys34Ser) in a Japanese Patient with Possible Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease)165169ENHiroshiUmemuraDivision of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of MedicineKatsuhiro MiuraDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of MedicineHiromuNaruseDivision of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of MedicineYoshihiroHattaDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of MedicineMasamiTakeiDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of MedicineTomohiroNakayamaDivision of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of MedicineCase Report/10.18926/AMO/58276 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.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama22144269212019Clinical and genetic aspects of mild hypophosphatasia in Japanese patients100515ENKatsuyukiYokoiDepartment of Pediatrics, Fujita Health University School of MedicineYokoNakajimaDepartment of Pediatrics, Fujita Health University School of MedicineYasukoShinkaiDivision of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health UniversityYoshimiSanoDepartment of Plastic Surgery, Division of Pediatric Dentistry & Orthodontics, Fujita Health University of MedicineMototakaImamuraDepartment of Plastic Surgery, Division of Pediatric Dentistry & Orthodontics, Fujita Health University of MedicineTomoyukiAkiyamaDepartment of Child Neurology, Okayama University HospitalTetsushiYoshikawaDepartment of Pediatrics, Fujita Health University School of MedicineTetsuyaItoDepartment of Pediatrics, Fujita Health University School of MedicineHirokiKurahashiDivision of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health UniversityBackground: 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.<br/>
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.<br/>
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.<br/>
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.No potential conflict of interest relevant to this article was reported.BlackwellActa Medica Okayama0013-95804932007Rasmussen encephalitis associated with SCN1A mutation521526ENIoriOhmoriDepartments of Cellular Physiology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama UniversityMamoruOuchidaDepartments of Molecular Genetics, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama UniversityKatsuhiroKobayashiDepartments of Child Neurology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshimiJitsumoriTakushiInoueDepartments of Child Neurology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama UniversityKenjiShimizuDepartments of Molecular Genetics, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama UniversityHidekiMatsuiDepartments of Cellular Physiology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama UniversityYokoOhtsukaDepartments of Child Neurology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihiroMaegakiDivision of Child Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University Mutations in the SCN 1 A gene, encoding the neuronal voltage-gated sodium channel alpha1 subunit, cause SMEI, GEFS+, and related epileptic syndromes. We herein report the R1575C-SCN 1 A mutation identified in a patient with Rasmussen encephalitis. R1575C were constructed in a recombinant human SCN 1 A and then heterologously expressed in HEK293 cells along with the human beta1 and beta2 sodium channel accessory subunits. Whole-cell patch-clamp recording was used to define biophysical properties. The R1575C channels exhibited increased channel availability and an increased persistent sodium current in comparison to the wild-type. These defects of electrophysiological properties can result in neuronal hyperexitability. The seizure susceptibility allele may influence the pathogenesis of Rasmussen encephalitis in this case.No potential conflict of interest relevant to this article was reported.Elsevier ScienceActa Medica Okayama092012111051-22013Inhalation of 10% carbon dioxide rapidly terminates Scn1a mutation-related hyperthermia-induced seizures220224ENIoriOhmoriDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiichiroHayashiDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHaijiaoWangDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMamoruOuchidaDepartment of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaohiroFujitaDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakushiInoueDepartment of Child Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyukiMichiueDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeiichiNishikiDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidekiMatsuiDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The aim of this study was to assess the anticonvulsant effect of carbon dioxide (CO2) on Scn1a mutation-related febrile seizures. We examined physiological changes in the blood gas levels after the induction of hyperthermia-induced seizures (HISs), which were associated with the Scn1a missense mutation. We determined the efficacy of inhalation of 5% or 10% CO2 to treat HISs. HISs were evoked in Scn1a mutant and wild-type (WT) rats by hot water baths. To determine the anticonvulsant effect of CO2 inhalation, rats were placed in a chamber filled with air or mixed gas containing 5% CO2 or 10% CO2 for 3 min, immediately after the induction of HISs. We also analyzed the blood gas levels at the end of inhalation of CO2. Hot water bathing induced a significant reduction in the partial pressure of CO2 (pCO2) and respiratory alkalosis in the WT and Scn1a mutant rats. HISs were evoked in 100% of the Scn1a mutant rats within 5 min, but in none of the WT rats. The Scn1a mutant rats demonstrated a higher HISs susceptibility associated with respiratory alkalosis than the WT rats. Inhalation of 10% CO2 shortened the seizure duration from 62.6±12.1 s to 15.5±1.0 s. Blood gas analysis after the inhalation of 10% CO2 demonstrated an elevated pCO2 level and respiratory acidosis. Inhalation of 10% CO2 demonstrated a potent and fast-acting anticonvulsant effect against HISs.No potential conflict of interest relevant to this article was reported.Cell PressActa Medica Okayama221112472852019Genome-Edited Triple-Recessive Mutation AltersSeed Dormancy in Wheat13621369ENFumitakaAbeDivision of Wheat and Barley Research, Institute of Crop Science, NAROEmdadulHaqueDivision of Wheat and Barley Research, Institute of Crop Science, NAROHiroshiHisanoInstitute of Plant Science and Resources, Okayama UniversityTsuyoshiTanakaDivision of Basic Research, Institute of Crop Science, NAROYokoKamiyaKihara Institute for Biological Research, Yokohama City UniversityMasafumiMikamiGraduate School of Nanobioscience, Yokohama City UniversityKanakoKawauraKihara Institute for Biological Research, Yokohama City UniversityMasakiEndoDivision of Applied Genetics, Institute of Agrobiological Sciences, NAROKazumitsuOnishiDepartment of Agro-Environmental Science, Obihiro University of Agriculture and Veterinary MedicineTakeshiHayashiDivision of Basic Research, Institute of Crop Science, NAROKazuhiroSatoInstitute of Plant Science and Resources, Okayama University1Common wheat has three sets of sub-genomes, making mutations difficult to observe, especially for traits controlled by recessive genes. Here, we produced hexaploid wheat lines with loss of function of homeoalleles of Qsd1, which controls seed dormancy in barley, by Agrobacterium-mediated CRISPR/Cas9. Of the eight transformed wheat events produced, three independent events carrying multiple mutations in wheat Qsd1 homeoalleles were obtained. Notably, one line had mutations in every homeoallele. We crossed this plant with wild-type cultivar Fielder to generate a transgene-free triple-recessive mutant, as revealed by Mendelian segregation. The mutant showed a significantly longer seed dormancy period than wild-type, which may result in reduced pre-harvest sprouting of grains on spikes. PCR, southern blotting, and whole-genome shotgun sequencing revealed that this segregant lacked transgenes in its genomic sequence. This technique serves as a model for trait improvement in wheat, particularly for genetically recessive traits, based on locus information from diploid barley.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7342019Dynamic Reorganization of Microtubule and Glioma Invasion285297ENYoshihiroOtaniDepartment of Neurosurgery, The University of Texas Health Science Center at HoustonTomotsuguIchikawaDepartment of Neurosurgery, Kagawa Prefectural Central HospitalKazuhikoKurozumiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIsaoDateDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesReview/10.18926/AMO/56930 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.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7332019Improvement 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 Movement255262ENDaisukeSekiDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryNobuoTakeshitaDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryMasahiroSeiryuDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryToruDeguchiDivision of Orthodontics, The Ohio State University College of DentistryTerukoTakano-YamamotoDepartment of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido UniversityCase Report10.18926/AMO/56869 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.No potential conflict of interest relevant to this article was reported.Elsevier ScienceActa Medica Okayama15671348542017Characterization of Vibrio cholerae O1 strains that trace the origin of Haitian-like genetic traits4753ENPriyankaGhoshDivision of Bacteriology, National Institute of Cholera and Enteric DiseasesDhirendraKumarMaharishi Valmiki Infectious Diseases HospitalGoutamChowdhuryDivision of Bacteriology, National Institute of Cholera and Enteric DiseasesPuneetaSinghMaharishi Valmiki Infectious Diseases HospitalProsenjitSamantaDivision of Bacteriology, National Institute of Cholera and Enteric DiseasesShantaDuttaDivision of Bacteriology, National Institute of Cholera and Enteric DiseasesT.RamamurthyDivision of Bacteriology, National Institute of Cholera and Enteric DiseasesN. C.SharmaMaharishi Valmiki Infectious Diseases HospitalPreetySinhaDepartment of Zoology, A.N. CollegeYogendraPrasadDepartment of Animal Science, MJP Rohilkhand UniversitySumioShinodaCollaborative Research Center of Okayama University for Infectious Diseases at NICEDAsish K.MukhopadhyayDivision of Bacteriology, National Institute of Cholera and Enteric Diseases Vibrio cholerae O1 is the etiological agent of the severe diarrheal disease cholera. The bacterium has recently been causing outbreaks in Haiti with catastrophic effects. Numerous mutations have been reported in V. cholerae O1 strains associated with the Haitian outbreak. These mutations encompass among other the genes encoding virulence factors such as the pilin subunit of the toxin-co-regulated pilus (tcpA), cholera toxin B subunit (ctxB), repeat in toxins (rtxA), and other genes such as the quinolone resistance-determining region (QRDR) of gyrase A (gyrA), rstB of RS element along with the alteration in the number of repeat sequences at the promoter region of ctxAB. Given the numerous genetic changes in those Haitian isolates, we decided to investigate the possible origins of those variations in the Indian subcontinent. Thus, we determined the genetic traits among V. cholerae O1 strains in Delhi, India. A total of 175 strains isolated from cholera patients during 2004 to 2012 were analysed in the present study. Our results showed that all the tested strains carried Haitian type tcpA (tcpACIRS) and variant gyrA indicating their first appearance before 2004 in Delhi. The Haitian variant rtxA and ctxB7 were first detected in Delhi during 2004 and 2006, respectively. Interestingly, not a single strain with the combination of El Tor rtxA and ctxB7 was detected in this study. The Delhi strains carried four heptad repeats (TTTTGAT) in the CT promoter region whereas Haitian strains carried 5 such repeats. Delhi strains did not have any deletion mutations in the rstB like Haitian strains. Overall, our study demonstrates the sequential accumulation of Haitian-like genetic traits among V. cholerae O1 strains in Delhi at different time points prior to the Haitian cholera outbreak.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7312019The Role of Kallikrein-Related Peptidases in Atopic Dermatitis16ENShinMorizaneDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesReview10.18926/AMO/56452 Excessive protease activity is a characteristic abnormality that affects the epidermal barrier in patients with atopic dermatitis (AD). Kallikrein-related peptidases (KLKs) are excessively expressed in AD lesions, and it is suggested that the abnormal action of KLKs is involved in the skin barrier dysfunction in AD. In other words, overexpressed KLKs disrupt the normal barrier function, and due to that breakdown, external substances that can become antigens of AD easily invade the epidermis, resulting in dermatitis, coupled with the induction of Th2 cytokines. Further investigations are required to elucidate the role of KLKs in AD; this knowledge could contribute to the design of new therapeutic and prophylactic drugs for AD.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7232018Analysis of All 34 Exons of the SPINK5 Gene in Japanese Atopic Dermatitis Patients275282ENShinMorizaneDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMamoruOuchidaDepartment of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoSunagawaDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSaekoSugimotoDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMinaKobashiDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruSugiharaDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHayatoNomuraDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhideTsujiNishigawara Dermatology ClinicAtsushiSatoSato Dermatology ClinicYoshihiroMiuraMiura Dermatology ClinicHiroakiHattoriHattori Dermatology and Allergy ClinicKotaroTadaTada Dermatology ClinicWook-KangHuhDr. Huh's Dermatology ClinicAkemiSenoDepartment of Dermatology, Mitoyo General HospitalKeijiIwatsukiDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article/10.18926/AMO/56073 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.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama1617461529342018MexEF-OprN multidrug efflux pump transporter negatively controls N-acyl-homoserine lactone accumulation in pseudomonas syringae pv. Tabaci 6605111ENTakahiroSawadaGraduate School of Environmental and Life ScienceOkayama UniversityMihoEguchiGraduate School of Environmental and Life ScienceOkayama UniversitySeiyaAsakiFaculty of AgricultureOkayama UniversityRyotaKashiwagiFaculty of AgricultureOkayama UniversityKousukeShimomuraFaculty of AgricultureOkayama UniversityFumikoTaguchiGraduate School of Environmental and Life ScienceOkayama UniversityHidenoriMatsuiGraduate School of Environmental and Life ScienceOkayama UniversityMikihiroYamamotoGraduate School of Environmental and Life ScienceOkayama UniversityYoshiteruNoutoshiGraduate School of Environmental and Life ScienceOkayama UniversityKazuhiroToyodaGraduate School of Environmental and Life ScienceOkayama UniversityYukiIchinoseGraduate School of Environmental and Life ScienceOkayama University Our previous studies revealed that flagellar-motility-defective mutants such as ∆fliC of Pseudomonas syringae pv. tabaci 6605 (Pta6605) have remarkably reduced production of N-acyl-homoserine lactones (AHL), quorum-sensing molecules. To investigate the reason of loss of AHL production in ∆fliC mutant, we carried out transposon mutagenesis. Among approximately 14,000 transconjugants, we found 11 AHL production-recovered (APR) strains. In these APR strains, a transposon was inserted into either mexE or mexF, genes encoding for the multidrug efflux pump transporter MexEF-OprN, and mexT, a gene encoding a putative transcriptional activator for mexEF-oprN. These results suggest that MexEF-OprN is a negative regulator of AHL production. To confirm the negative effect of MexEF-OprN on AHL production, loss- and gain-of-function experiments for mexEF-oprN were carried out. The ∆fliC∆mexF and ∆fliC∆mexT double mutant strains recovered AHL production, whereas the mexT overexpressing strain abolished AHL production, although the psyI, a gene encoding AHL synthase, is transcribed as wild type. Introduction of a mexF or mexT mutation into another flagellar-motility- and AHL production-defective mutant strain, ∆motCD, also recovered the ability to produce AHL. Furthermore, introduction of the mexF mutation into other AHL production-defective mutant strains such as ∆gacA and ∆aefR also recovered AHL production but not to the ∆psyI mutant. These results indicate that MexEF-OprN is a decisive negative determinant of AHL production and accumulation.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812922017家族性大腸腺腫症術後20年後に小腸癌を発症した1例111114ENYuusakuSugiharaDepartment of Gastroenterology and Hepatology, Okayama University HospitalSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKeitaHaradaDepartment of Gastroenterological Surgery, Okayama University HospitalShihoTakashimaDepartment of Gastroenterology and Hepatology, Okayama University HospitalDaisukeTakeiDepartment of Gastroenterological Surgery, Okayama University HospitalToshihiroInokuchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalMasahiroTakaharaDepartment of Gastroenterology and Hepatology, Okayama University HospitalSakikoHiraokaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYoshikoMoriDivision of Endoscopy, Okayama University HospitalHiroyukiKishimotoDivision of Endoscopy, Okayama University HospitalTakeshiNagasakaDivision of Endoscopy, Okayama University HospitalHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University HospitalA 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.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812722015基底膜ツールキットとしてのXV/XVV型コラーゲン遺伝子の機能103109ENToshitakaOohashiNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812632014膣後壁合併切除を伴う会陰アプローチが有用であった直腸巨大GISTの１切除例217221ENKazuhideIwakawaManabuNishieNaoyukiTokunagaHideakiMiyasoHiromiIwagakiWe report a case of giant rectal gastrointestinal stromal tumor (GIST) successfully resected by abdominoperineal resection combined with posterior vaginal wall resection. Our patient was a 79-year-old woman had been diagnosed as having von Recklinghausen disease at the age of 30 years. In 2006, a computed tomography (CT) scan revealed a tumor originating from the posterior wall of the rectum. In June 2010, she was admitted to our hospital with the chief complaint of bloody stool. A CT scan revealed a giant tumor that had increased to 9cm in size. Colonoscopy demonstrated a submucosal tumor, which was subsequently diagnosed by biopsy as a GIST. Due to the patient's continuous bleeding and abdominal pain, an emergent abdominoperineal resection was performed at that time. The tumor, which measured 8×9cm, was immunohistochemically positive for c-kit and CD34. Concomitant resection of the posterior wall of the vagina via the perineal approach provided a wide area to expose the tumor for a safe operation. The patient has been well with no sign of recurrence since the operation. This procedure is recommended as a useful approach for giant rectal GISTs or rectal cancer with invasion of the posterior pelvic wall.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812512013予後不良な経過をたどったBRAF遺伝子変異を伴うStage W大腸癌の１例4750ENRyoInadaTakeshiNagasakaKiyotoTakeharaMasahiroSugiharaYoshikoMoriYuzoUmedaNobuhitoKubotaTatsuyaMorikawaYoshitakaKondoFutoshiUnoYuSadamoriTakahitoYagiToshiyoshiFujiwara A 79-year-old woman visited a previous hospital with a complaint of general fatigue. The patient was diagnosed with cecal cancer with multiple liver metastases and lymph node metastases on colonoscopy, abdominal ultrasonography and CT scan, and was referred to our division for treatment. Based on the diagnosis of non-curative colonic cancer, we planned to perform systematic chemotherapy after local surgical treatment. We performed an ileocecal resection, and the specimen showed poorly differentiated adenocarcinoma with mutation in the BRAF oncogene. After the surgical treatment, the tumor grew rapidly and the patient died from cancer on the 19th postoperative day without having the opportunity to undergo chemotherapy.
Multiple genetic and epigenetic alterations in oncogenes and tumor suppressor genes are involved in the process of colorectal carcinogenesis. Some of the alterations have been identified as predictive and prognostic biomarkers. A mutation in the BRAF oncogene was reported to be associated with a very unfavorable prognosis in colorectal cancers. Some of the cases with rapid progression are suggested to have the BRAF oncogene mutation. According to our experience, chemotherapy before surgical treatment might improve the prognosis of cases with the BRAF mutation.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6712013Silenced Expression of NFKBIA in Lung Adenocarcinoma Patients with a Never-smoking History1924ENMasashiFurukawaJunichiSohHiromasaYamamotoKouichiIchimuraKazuhikoShienYuhoMakiTakayukiMuraokaNorimitsuTanakaTsuyoshiUenoHiroakiAsanoKazunoriTsukudaShinichiToyookaShinichiroMiyoshiOriginal Article/10.18926/AMO/49253Nuclear factor of κ-light polypeptide gene enhancer in B cells inhibitor α (NFKBIA), which is a tumor suppressor gene, was found to be silenced in lung adenocarcinomas. We examined NFKBIA expression, mutations in the EGFR and K-ras genes, and EML4-ALK fusion in 101 resected lung adenocarcinoma samples from never-smokers. NFKBIA expression was evaluated using immunohistochemistry. NFKBIA expression was negative in 16 of the 101 samples (15.8%). EGFR and K-ras mutations and EML4-ALK fusion were detected in 61 (60.5%), 1 (1.0%), and 2 (2.0%) of the 101 samples, respectively, in a completely mutually exclusive manner. Negative NFKBIA expression was observed significantly more frequently among the tumors with none of the three genetic alterations compared to those with such alterations (p＝0.009). In addition, negative NFKBIA expression was significantly more frequent among the EGFR-wild type samples compared to the EGFR-mutant samples (p＝0.013). In conclusion, NFKBIA expression was silenced in adenocarcinomas without EGFR/K-ras mutations or EML4-ALK fusion, suggesting that the silencing of NFKBIA may play an important role in the carcinogenesis of adenocarcinomas independent of EGFR/K-ras mutations or EML4-ALK fusion.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6652012Dravet Syndrome : A Genetic Epileptic Disorder369376ENMariAkiyamaKatsuhiroKobayashiYokoOhtsukaReview/10.18926/AMO/48961Dravet 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.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6622012Different Responses to 5-fluoraouracil in Mutagenicity and Gene Expression between Two Human Lymphoblastoid Cell Lines with or without TP53 Mutation119129ENHiroakiOkaMamoruOuchidaTakuyaKondoFumioMoritaKenjiShimizuOriginal Article10.18926/AMO/48262Human 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.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812412012骨形成不全症の治療6770ENHiroyukiTanakaNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812322011成人期に達したDravet症候群の長期経過に関する研究9195ENMariAkiyamaKatsuhiroKobayashiHarumiYoshinagaYokoOhtsukaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama125161998The ich1 gene of the mushroom Coprinus cinereus is essential for pileus formation in fruiting31333141ENHajimeMuraguchiTakashiKamada<p>The formation of the pileus in homobasidiomycete fungi is essential for sexual reproduction, because the pileus bears the hymenium, a layer of cells that includes the specialised basidia in which nuclear fusion, meiosis and sporulation occur. The developmental mutant ichijiku of Coprinus cinereus fails to develop a differentiated pileus at the apex of the primordial shaft, which is the basal part of the fruit-body primordia and formed in an early stage of fruit-body differentiation. Genetic analysis indicates that this phenotype is caused by a recessive mutation in a single gene (ich1). The ich1 gene was mapped to chromosome XII using restriction fragment length polymorphism markers and the marker chromosome method, and cloned by complementation using a chromosome-XII-specific cosmid library. The ich1 gene encodes a novel protein of 1,353 amino acids. The Ich1 amino-acid sequence contains nuclear targeting signals, suggesting that the Ich1 protein would function in the nucleus. Northern blot analysis indicates that the ich1 gene is specifically expressed in the pileus of the wild-type fruit-body. No ich1 mRNA was detected in the ichijiku mutant, consistent with loss of the promoter region of ich1 in the mutant genome. These data demonstrate that the ick1 gene product is essential for pileus formation.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6262008Mammalian Acatalasemia: The Perspectives of Bioinformatics and Genetic Toxicology345361ENMasanaOgataDa-HongWangKeikiOginoReview10.18926/AMO/30951<p>The molecular defects in the catalase gene, levels of m-RNA and properties of the residual catalase studied by scientists are reviewed in human (Japanese, Swiss and Hungarian) and non-human (mouse and beagle dog) acatalasemia with reference to the bioinformatics. Japanese acatalasemia-I, the G to A transition at the fifth position of intron 4 of the catalase gene, limited the correct splicing of the mRNA and synthesized trace catalase with normal properties. Hungarian acatalasemia type C showed a splicing mutation. In the Japanese acatalasemia II and the type A and B of Hungarian acatalasemia, the deletion or insertion of nucleotides was observed in the coding regions, and the frame shift altered downstream amino acid sequences and formed truncated proteins. In the Hungarian acatalasemia D, the substitution of a nucleotide in the exon was found. In mouse and beagle dog acatalasemia, the substitution of nucleotides in the coding regions was also observed. Studies of residual catalase in Swiss, mouse and beagle dog acatalasemia showed that aberrant catalase protein degrades more quickly than normal catalase in cells. The experimental research in genetic toxicology concerning the effect of oxidative stressors (nitrogen monoxide, nitrogen dioxide and so on) on Japanese acatalasemic blood and acatalasemic mice is described. The clinical features of Japanese and Hungarian acatalasemic
subjects are also described.</p>No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812212010DNA 損傷センサーATMキナーゼとChk2はＣ型肝炎ウイルスのRNA複製に必要である916ENYasuoAriumiMisaoKurokiHiromichiDansakoKenichiAbeMasanoriIkedaTakajiWakitaNobuyukiKatoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812132009Dravet 症候群患者に認められたカルシウムチャネル 機能異常を引き起こす CACNB4 遺伝子変異149156ENIoriOhmoriMamoruOuchidaNobuyoshiMimakiTeiichiNishikiKazuhitoTomizawaHidekiMatsuiNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155810341991ファンコニー貧血に自然発生する特異的染色体切断点の悪性腫瘍発生における意義235246ENKazushiroTsujiIndividuals with Fanconi anemia (FA) are susceptible to acute non-lymphocytic leukemia (ANLL) or hepetocellular carcinoma. To clarify why FA is associated with a specific type of neoplasia, we performed cytogenetic studies on somatic cells established from 4 FA patients, two of whom developed acute myelocytic leukemia (AML). A hypersensitive response to mitomycin C (MMC) was obtained in two patients but non-sensitivity in two patients with AML. Analysis of spontaneous break-points showed that the frequency of breakage in the FA patients was 4 to 5 times higher than in normal controls. Significantly more breakpoints gathered on 1p11 or q11, 1q21, 1q32, 2p11, or q11, 3p14, 3q21, 5q15, 7p11 or q11, 8q22, 9q11-12, 9q13, 11q13, 11q23, 12q13, 12q24 and 17q21 bands. Furthermore, many chromosome rearrangements involving these breakpoints were observed. Most of the breakpoints specific to FA coincided with those seen in the rearrangements of ANLL reported so far. These findings suggest that the nonrandomness of spontaneous breakpoints plays an important role in the tumorigenesis of FA.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581037-81991NIH 3T3 細胞の温熱耐性に対するケルセチンの作用 第1編 細胞の生存率からみたケルセチンの作用973981ENMasahiroKurodaYoshioHirakiShoujiKawasakiThe inhibition of thermotolerance development by quercetin was examined in NIH 3T3 cells. The cytotoxicity of quercetin increased with the increase in the concentration (10,100μg/ml) and duration (12,48,72 hours) of treatment. The cell killing effect of heat was not enhanced by quercetin (10μg/ml) itself. Quercetin (10μg/ml) inhibited the proliferation of cells for about 72 hours. Quercetin (10μg/ml) delayed the development of thermotolerance, but did not decrease the degree of maximum thermotolerance. Quercetin (10μg/ml) exibited no effect on the decay of thermotolerance.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581063-41994慢性骨髄性白血病並びに周辺疾患の分子生物学的解析429441ENNorikoSekitoChronic myelocytic leukemia (CML) is cytogentically characterized by the Philadelphia chromosome (Ph(1)) resulting from a reciprocal translocation t(9;22)(q34;q11). The breakpoints on chromosome 22 are clustered within a limted region of 5.8 kilobase (kb), termed the breakpoint cluster region (bcr). Herein the bcr rearrangement was examined to clarify the relationship between CML and related diseases. By Southern blot analysis of DNA, the bcr rearrangements were recopnized (bcr(+)) in 52 of 54 standard Ph(1)-positive (Ph(1+)) CML and all 3 variant Ph(1+)CML［46, XX, t(9;22;13)(q34;q11;q22),46, XX, t89;22)(q21;q11) and 46, XX, t(9;22)(q34;q11),inv (9)(9q22;22q13)］. The site of breakpoint within bcr was not a prognostic factor in Ph(1+)CML. On the other hand bcr rearrangements were negative (bcr(−)) in 2 juvenile CML (JCML), 3 chronic neutrophilic leukemia (CNL), 9 chronic myelomonocytic leukemia (CMML), 8 polycythemia vera (PV), 15 essential thrombocythemia (ET) and 4 myelofibrosis (MF) patients. In 5 patients with Ph(1)-negative (Ph(1−)) CML/unclassifid chronic myeloproliferative disorders (UCMPD), 2 were bcr(+) and 3 were bcr(−), which strongly suggested the existence of Ph(1−)bcr(−)CML.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581061-21994日本人におけるRBI遺伝子第17および20番イントロン内VNTRの多型性の検討および遺伝性網膜芽細胞腫における遺伝相談への応用110ENShinsukeNinomiyaRisk estimation for siblings or offspring is important in genetic counseling of patients with hereditary retinoblastoma. The RB1 gene spans approximately 200 kb in length, containing 27 exons. The use of polymorphic markers within the RB1 gene will eliminate the need of laborious specification of a mutation. The present study determined types and frequencies of VNTR polymorphisms of the 17th and 20th introns of the RB1 gene in 50 unrelated Japanese, using PCR amplification. In the 17th intron VNTR, there were 4 alleles, which ranged from 1400 by to 1550 bp. The most common allele was 1400 bp with a frequency of 73%, and the hetetozygosity rate was 46%. In the 20th intron VNTR, there were at least 9 alleles, wihch ranged from 192 bp to 240 bp. The alleles were more evenly distributed than those of the 17th intron VNTR, and the heterozygosity rate was 64%. These VNTR polymorphisms were successfully applied to the prediction of retinoblastoma and to the determination of parental origin of a chromosome deletion in 3 families with hereditary retinoblastoma. Analysis of VNTR polymorphisms within the RB1 gene proves to be practical and efficient for risk estimation in hereditary retinoblastoma.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155811432003D-バリン培地法により選択的に初代培養したラット胆管上皮細胞に対する Phospholipase A(2) の細胞増殖促進効果の解析289296ENKaoruOguraYasuhiroWatanabeChiharuHiramineToshitakaNakagawaAkiraTokiMasaakiTokudaWe hypothesized that a high level of phospholipase A(2) (PLA(2)) in bile juice works as a growth factor of biliary epithelial cells and causes hyperplastic change of the bile duct in pancreaticobiliary maljunction. in order to examine this hypothesis, we established a primary culture system of biliary epithelial cells from the extra-hepatic bile duct of rats. We successfully excluded fibroblasts from the epithelial cells using D-valine-containing medium and the single-cell cloning method. The established cells exhibited the characteristic features of rat bile duct epithelial cells. They were stained with anti-cytokeratin antibody, a marker protein of epithelial cells, were positive with PAS stain, and possessed the architectures of microvilli, tonofilament fibers and desmosomes. The effect of PLA(2) on proliferation of these cells was then examined. We clearly demonstrated that PLA(2) at nano-molar concentration (50nM, 100nM), that is, equivalent to the level of PLA(2) in the bile juice of pancreaticobiliary maljunction cases, caused a significant enhancement of epithelial cell proliferation.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155811432003癌抑制遺伝子 ING ファミリーの構造と機能253259ENMehmetGunduzNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155811812006原発性肺高血圧症の病態形成における骨形成蛋白（BMP）T型受容体の関与とその意義：肺動脈血管平滑筋細胞を用いた検討1721ENNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811932008p53 遺伝子を発現するアデノウイルスベクターを用いた肺癌の遺伝子治療229234ENToshiyoshiFujiwaraNoriakiTanakaTo determine the feasibility, safety, humoral immune response, and biological activity of multiple intratumoral injections of Ad5CMV-p53, and to characterize the pharmacokinetics of Ad5CMV-p53 in patients with advanced non-small cell lung cancer (NSCLC). Fifteen patients with histologically confirmed NSCLC and p53 mutations were enrolled into this phase I trial. Nine patients received escalating dose levels of Ad5CMV-p53 (1 × 109 to 1 × 1011 plaque-forming units[PFU]) as monotherapy once every 4 weeks. Six patients were treated on a 28-day schedule with Ad5CMV-p53 in combination with intravenous administration of cisplatin (80 mg/m2). Patients were monitored for toxicity, vector distribution, antibody formation, and tumor response. Fifteen patients received a total of 63 intratumoral injections of Ad5CMV-p53 without dose-limiting toxicity. The most common treatment-related toxicity was a transient fever. Specific p53 transgene expression was detected using reverse-transcriptase polymerase chain reaction in biopsied tumor tissues throughout the period of treatment despite of the presence of neutralizing anti-adenovirus antibody. Distribution studies revealed that the vector was detected in the gargle and plasma, but rarely in the urine. Thirteen of 15 patients were assessable for efficacy; one patient had a partial response (squamous cell carcinoma at the carina), 10 patients had stable disease, with three lasting ≥9 months, and 2 patients had progressive disease. Multiple courses of intratumoral Ad5CMV-p53 injection alone or in combination with intravenous administration of cisplatin were feasible and well tolerated in advanced NSCLC patients, and appeared to provide clinical benefit.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811922007食道扁平上皮癌の発癌過程におけるDNAメチル化の役割113117ENTatsuhiroIshiiJunMurakamiKenjiNotoharaHiromiSasamotoTakeshiKambaraYasuhiroShirakawaYoshioNaomotoMamoruOuchidaKenjiShimizuR. JassJeremyNagahideMatsubaraNoriakiTanakaNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811912007日本人Brugada症候群患者における心筋ナトリウムチャネル遺伝子 (SCN5A) の変異と多型4955ENDaijiMiuraBackground: Brugada syndrome is an inherited arrhythmogenic disease characterized by right bundle branch block pattern and ST segment elevation, leading to the change of V1 to V3 on electrocardiogram, and an increased risk of sudden cardiac death resulting from ventricular fibrillation. The sodium channel alpha 5 subunit (SCN5A) gene encodes a cardiac voltage-dependent sodium channel, and SCN5A mutations have been reported in Brugada syndrome. However, single nucleotide polymorphisms (SNPs) and gene mutations have not been well investigated in Japanese patients with Brugada syndrome.
Methods and Results: The SCN5A gene was examined in 58 patients by using PCR and the ABI 3130xl sequencer, revealing 17 SNP patterns and 13 mutations. Of the 13 mutations, 8 were missense mutations (with amino acid change), 4 were silent mutations (without amino acid change), and one case was a mutation within the splicing junction. Six of the eight missense mutations were novel mutations. Interestingly, we detected an R1664H mutation, which was identified originally in long QT syndrome.
Conclusion: We found 13 mutations of the SCN5A gene in 58 patients with Brugada syndrome. The disease may be attributable to some of the mutations and SNPs.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155812012008EGFR K-ras 遺伝子変異と DNA メチル化異常からみた肺腺癌の発癌機構711ENShinichiToyookaHiroshiDateNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2007Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via PLCγ-activated STAT1ENDaisukeHaradaThe most frequent type of rhizomelic dwarfism, achondroplasia (ACH), is caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Mutations in FGFR3 result in skeletal dysplasias of variable severity, including mild phenotypic effects in hypochondroplasia (HCH), severe phenotypic effects in thanatophoric dysplasia types I (TDI) and II (TDII), and severe but survivable phenotypic effects in severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN). To explore the molecular mechanisms that result in the different phenotypes, we investigated the kinetics of mutated versions of FGFR3. First, we assayed the phosphorylation states of the mutated FGFR3s and found that the level of phosphorylation in TDI-FGFR3 was lower than in ACH-FGFR3, although the other mutants were phosphorylated according to phenotypic severity. Second, we analyzed the duration of the phosphorylation. TDI-FGFR3 was not highly phosphorylated under ligand-free conditions, but the peak phosphorylation levels of TDI-FGFR3 and ACH-FGFR3 were maintained for 30 min after stimulation with FGF-1. Moreover, ligand-dependent phosphorylation of TDI-FGFR3, but not ACH-FGFR3, lasted for more than 8 h after FGF-1 administration. The other mutant proteins showed sustained phosphorylation independent of ligand presence. Third, we investigated the intracellular localization of the mutant proteins. Immunofluorescence analysis showed accumulations of TDII-FGFR3, SADDAN-FGFR3, and a portion of TDI-FGFR3 in the endoplasmic reticulum (ER). Based on these data, we concluded that sustained phosphorylation of FGFR3 causes chondrodysplasia, and the phenotypic severity depends on the proportion of ER-localized mutant FGFR3. In FGFR3 signaling, the transcription factor, signal transducer and activator of transcription 1 (STAT1) inhibit proliferation and induce apoptosis of chondrocytes. Here we reveal that phospholipase C gamma (PLCgamma) mediates FGFR3-induced STAT1 activation. Both PLCgamma and STAT1 were activated by FGFR3 signaling, but a dominant-negative form of PLCgamma (DN-PLCgamma) remarkably reduced STAT1 phosphorylation. Apoptosis assays revealed that the constitutively active forms of FGFR3 (TDII-FGFR3) and STAT1 (STAT1-C) induce apoptosis of chondrogenic ATDC5 cells via caspase activity. DN-PLCgamma reduced the apoptosis of ATDC5 cells expressing TDII-FGFR3, but over-expression of both DN-PLCgamma and STAT1-C induced apoptosis. Therefore, we conclude that a PLCgamma-STAT1 pathway mediates apoptotic signaling by FGFR3.No potential conflict of interest relevant to this article was reported.岡山大学資源生物科学研究所Acta Medica Okayama0916-930X211994オオムギの葉の剛毛に関する遺伝子分析6368ENKazuhiroSatoKazuyoshiTakedaThe inheritance and linkage relationship of a new hairiness trait "large trichome" was investigated in barley. Although the size of large trichome is about four times that of normal one, the character can not be recognized with the naked eye. However, it is easily identified by the roughness of leaf touch. The large trichomes develop on both sides of the leaf blades. The direction of trichome is both acropetal and basipetal. It is clearly distinguished from the extremely long trichome controlled by Pub gene. About 2,300 varieties of our Barley Germplasm Center were screened by the leaf touch to find nine varieties with large trichome. Two of them were six-rowed local variety from Pakistan, and other seven were two-rowed varieties from Europe and Japan. All of them were hulled type. Crosses of six large trichome varieties with a normal Japanese variety resulted in the large trichome type F1s, suggesting the dominant nature of the trait. The large trichome line Hokuiku 17 was crossed with various linkage testres to study the mode of inheritance and the linkage relationship of the gene. In the F2 populations, the large trichome was controlled by a single dominant gene named Ltr (large trichome), which was independentiy inherited from the following marker genes; br and gl-5 on chromosome 1; li and ν on chromosome 2; uz on chromosome 3; K and gl-3 on chromosome 4; trd on chromosome 5; ο on chromosome 6. On the other hand, from the cross between Hokuiku 17 and OUL166, Ltr was found to be linked with s and fs on chromosome 7. Although the allelism test has not been completed, the very low frequency of the large trichome type (9/2,300) indicates that the variant resulted from a recent mutation event, or the fitness of the variant is low in the natural and/or artificial selection.No potential conflict of interest relevant to this article was reported.岡山大学農学部Acta Medica Okayama0474-02543811971Studies on the Radiation Breeding in the genus Mentha : (XII) Variation in Quantitative Characters of X2 plant after Hybridization and Irradiation in Mint17ENSeirokuOnoThe present paper describes some aspects of inducing genetic variation of polygenically controlled characters following the irradiation of two mint species and their hybrids. The data for the characters studied in X2 generations were analyzed by appropriate analysis of variance. In all the cases, the mean value of the irradiated population with respect to seed size character was almost the same as that of the non-irradiated control, while the variance of the irradiated population increased. On the other hand, for endosperm quality the irradiated populations showed increase in the mean value and the variance. The results obtained in the present experiment suggest that back-ground geno-types played an important role in the manifestation of mutated characters.No potential conflict of interest relevant to this article was reported.