MDPIActa Medica Okayama1999-49151412022Nectin-2 Acts as a Viral Entry Mediated Molecule That Binds to Human Herpesvirus 6B Glycoprotein B160ENHirohitoOgawaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeFujikuraSchool of Veterinary Medicine, Kitasato UniversityHikaruNambaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobukoYamashitaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyukiHondaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaoYamadaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHuman herpesvirus 6B (HHV-6B) is a T-lymphotropic virus and the etiological agent of exanthem subitum. HHV-6B is present in a latent or persistent form after primary infection and is produced in the salivary glands or transmitted to this organ. Infected individuals continue to secrete the virus in their saliva, which is thus considered a source for virus transmission. HHV-6B primarily propagates in T cells because its entry receptor, CD134, is mainly expressed by activated T cells. The virus then spreads to the host's organs, including the salivary glands, nervous system, and liver. However, CD134 expression is not detected in these organs. Therefore, HHV-6B may be entering cells via a currently unidentified cell surface molecule, but the mechanisms for this have not yet been investigated. In this study, we investigated a CD134-independent virus entry mechanism in the parotid-derived cell line HSY. First, we confirmed viral infection in CD134-membrane unanchored HSY cells. We then determined that nectin cell adhesion molecule 2 (nectin-2) mediated virus entry and that HHV-6B-insensitive T-cells transduced with nectin-2 were transformed into virus-permissive cells. We also found that virus entry was significantly reduced in nectin-2 knockout parotid-derived cells. Furthermore, we showed that HHV-6B glycoprotein B (gB) interacted with the nectin-2 V-set domain. The results suggest that nectin-2 acts as an HHV-6B entry-mediated protein.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221112021Novel urinary glycan profiling by lectin array serves as the biomarkers for predicting renal prognosis in patients with IgA nephropathy3394ENChiekoKawakitaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKokiMiseDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMichihiroYoshidaCenter for Innovative Clinical Medicine, Okayama University HospitalMasaoYamadaGlycoTechnica LtdJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIn IgA nephropathy (IgAN), IgA1 molecules are characterized by galactose deficiency in O-glycans. Here, we investigated the association between urinary glycosylation profile measured by 45 lectins at baseline and renal prognosis in 142 patients with IgAN. The primary outcome was estimated glomerular filtration rate (eGFR) decline (>4 mL/min/1.73 m(2)/year), or eGFR >= 30% decline from baseline, or initiation of renal replacement therapies within 3 years. During follow-up (3.4 years, median), 26 patients reached the renal outcome (Group P), while 116 patients were with good renal outcome (Group G). Multivariate logistic regression analyses revealed that lectin binding signals of Erythrina cristagalli lectin (ECA) (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.11-7.28) and Narcissus pseudonarcissus lectin (NPA) (OR 2.32, 95% CI 1.11-4.85) adjusted by age, sex, eGFR, and urinary protein were significantly associated with the outcome, and they recognize Gal(beta 1-4)GlcNAc and high-mannose including Man(alpha 1-6)Man, respectively. The addition of two lectin-binding glycan signals to the interstitial fibrosis/tubular atrophy score further improved the model fitness (Akaike's information criterion) and incremental predictive abilities (c-index, net reclassification improvement, and integrated discrimination improvement). Urinary N-glycan profiling by lectin array is useful in the prediction of IgAN prognosis, since ECA and NPA recognize the intermediate glycans during N-glycosylation of various glycoproteins.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2297-055X82021Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)668059ENKokiMiseDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMarikoImamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiYamaguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMayuWatanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChigusaHiguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihiroKatayamaDiabetes Center, Okayama University HospitalSatoshiMiyamotoCenter for Innovative Clinical Medicine, Okayama University HospitalHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsukoNakatsukaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunEguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyukiHidaDepartment of Diabetology and Metabolism, National Hospital Organization Okayama Medical CenterTatsuakiNakatoOkayama Saiseikai General HospitalAtsuhitoToneOkayama Saiseikai General HospitalSanaeTeshigawaraOkayama Saiseikai General HospitalTakashiMatsuokaKurashiki Central HospitalShinjiKameiKurashiki Central HospitalKazutoshiMurakamiKurashiki Central HospitalIkkiShimizuThe Sakakibara Heart Institute of OkayamaKatsuhiroMiyashitaJapanese Red Cross Okayama HospitalShinichiroAndoOkayama City General Medical CenterTomokazuNunoueNunoue ClinicMichihiroYoshidaCenter for Innovative Clinical Medicine, Okayama University HospitalMasaoYamadaGlycoTechnica Ltd.KenichiShikataCenter for Innovative Clinical Medicine, Okayama University HospitalJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813212020ヘルペスウイルスの自然史と病態1317ENMasaoYamadaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.The Japanese Society of Veterinary ScienceActa Medica Okayama0916-72508182019Risk assessment for hepatitis E virus infection from domestic pigs introduced into an experimental animal facility in a medical school11911196ENHirohitoOgawaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHarukoHirayamaDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversitySatsukiTanakaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorioYataDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversityHikaruNambaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobukoYamashitaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenzoYonemitsuLaboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi UniversityKenMaedaLaboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi UniversityKatsumiMominokiDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversityMasaoYamadaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Hepatitis E virus (HEV) is known to cause zoonotic infections from pigs, wild boars and deer. Domestic pigs have been used as an experimental animal model in medical research and training; however, the risks of HEV infection from pigs during animal experiments are largely unknown. Here, we retrospectively investigated the seroprevalence and detection rates of viral RNA in 73 domestic pigs (average 34.5 kg) introduced into an animal experimental facility in a medical school during 2012-2016. We detected anti-HEV immunoglobulin G antibodies in 24 of 73 plasma samples (32.9%), though none of the samples were positive for viral RNA. Plasma samples of 18 pigs were sequentially monitored and were classified into four patterns: sustained positive (5 pigs), sustained negative (5 pigs), conversion to positive (6 pigs) and conversion to negative (2 pigs). HEV genomes were detected in 2 of 4 liver samples from pigs that were transported from the same farm during 2016-2017. Two viral sequences of the overlapping open reading frame (ORF) 2/3 region (97 bp) were identical and phylogenetically fell into genotype 3. A 459-bp length of the ORF2 region of an amplified fragment from a pig transported in 2017 was clustered with the wbJYG1 isolate (subgenotype 3b) with 91.5% (420/459 bp) nucleotide identity. Based on our results, we suggest that domestic pigs introduced into animal facilities carry a potential risk of HEV infection to researchers, trainees and facility staff. Continuous surveillance and precautions are important to prevent HEV infection in animal facilities.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812732015第56回日本臨床ウイルス学会開催報告261262ENMasaoYamadaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama0001-648913392013The engraftment and differentiation of transplanted bone marrow-derived cells in the olfactory bulb after methimazole administration951956ENYoheiNodaKazunoriNishizakiJunkoYoshinobuYorihisaOritaHidetsuguTsujigiwaMasaoYamadaConclusion: Bone marrow-derived cells can be engrafted in the olfactory bulb and a few cells can differentiate into mitral/tufted cells in the olfactory bulb. Objectives: To investigate whether bone marrow-derived cells can be engrafted into the olfactory bulb and differentiate into neurons and glial cells after methimazole administration. Methods: Bone marrow of GFP (green fluorescence protein) mice was transplanted into lethally irradiated recipient mice. Immunostaining was performed to confirm the cell types of bone marrow-derived cells expressing GFP. Results: GFP-positive cells were observed in the olfactory bulb at 2 days after methimazole administration. The number of dendritic GFP-positive cells increased up to 30 days after methimazole administration and then decreased. Double immunostaining for GFP and Iba1 or TBX21 showed that a large population of the GFP-positive cells had characteristics of microglia/macrophages and a few cells had characteristics of mitral/tufted cells.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812522013マウスインフルエンザ肺炎におけるレドックス制御蛋白チオレドキシン（TRX-1）の治療的効果109112ENMasatoYashiroHirokazuTsukaharaAkihiroMatsukawaMutsukoYamadaYosukeFujiiYoshiharuNagaokaMitsuruTsugeNobukoYamashitaToshihiroItoMasaoYamadaHiroshiMasutaniJunjiYodoiTsuneoMorishimaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama0090-34934112013Redox-Active Protein Thioredoxin-1 Administration Ameliorates Influenza A Virus (H1N1)-Induced Acute Lung Injury in Mice171181ENMasatoYashiroHirokazuTsukaharaAkihiroMatsukawaMutsukoYamadaYosukeFujiiYoshiharuNagaokaMitsuruTsugeNobukoYamashitaToshihiroItoMasaoYamadaHiroshiMasutaniObjectives: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice.
Design: Prospective animal trial.
Setting: Research laboratory.
Subjects: Nine-week-old male C57BL/6 mice inoculated with H1N1.
Intervention: The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day -1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days 1, 1, and 3.
Measurements and Main Results: Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-a and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-a and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice.
Conclusions: Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans. (Crit Care Med 2013; 41:171-181)No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X4511991Reactivatable latency of three avirulent strains of herpes simplex virus type 1 after intranasal inoculation in mice.4347ENYujiroAraoAtsushiHatanoMasaoYamadaFumioUnoShiroNiiArticle10.18926/AMO/32214<p>In order to elucidate the mechanism of latent infection of herpes simplex virus (HSV), reactivatable latency of three avirulent strains (SKO-1B, -GCr Miyama, SKa) of HSV type 1 was comparatively examined in a mouse latency model. The SKO-1B strain showed high rate of virus reactivation from explanted trigeminal ganglia without n-butyrate enhancement, while the other two strains showed a very low rate of virus reactivation in the absence of n-butyrate. In the presence of n-butyrate, however, the rate of the -GCr Miyama strain jumped to a comparable level with that of SKO-1B, although the rate of SKa remained at a low level. A more precise follow-up experiment changing the virus dose highlighted the difference of the ability to reactivate from the latent state between SKO-1B and -GCr Miyama. Virus titer in trigeminal ganglia during acute phase, infectivity to cell lines of neural origin, and susceptibility to acyclovir and phosphonoacetate were assayed to know the reasons for the variation in the ability of reactivatable latency among these strains. It was concluded that the reduced infectivity to neural cells, and limited ability of reactivatable latency shown by the SKa strain could mainly be attributed to the deficiency of thymidine kinase activity.</P></p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X4521991Neurovirulent strains of herpes simplex virus type 1 are not necessarily competent for reactivatable latency.117121ENYujiroAraoAtsushiHatanoMasaoYamadaFumioUnoShiroNiiArticle10.18926/AMO/32190<p>Ability of two neurovirulent strains (F and +GC (LPV) Miyama) of herpes simplex virus type 1 (HSV-1) to establish and maintain reactivatable latency in trigeminal ganglia (TG) was compared after intranasal inoculation of mice. The +GC (LPV) Miyama strain showed a very low rate of virus reactivation in explant cultures of TG, while the F strain showed a high rate of reactivation. These data indicate that neurovirulent strains of HSV-1 are not always competent for reactivatable latency, although most virulent strains of HSV-1 thus far reported were competent for reactivatable latency.</P></p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5822004Induction and prevention of virus-associated malignant lymphoma by serial transmission of EBV-related virus from cynomolgus by blood transfusion in rabbits.6774ENTirtha RajKoiralaKazuhikoHayashiZaishunJinSachiyoOnodaTakehiroTanakaWakakoOdaKoichiIchimuraNobuyaOharaTakashiOkaMasaoYamadaTadashiYoshinoOkayama UniversityArticle10.18926/AMO/32097<p>Epstein-Barr virus (EBV)-related herpesvirus (Si-IIA-EBV) was serially transmitted for 3 passages from rabbit to rabbit of the opposite sex by blood transfusion, which subsequently induced virus-associated rabbit lymphomas. The virus could be transmitted by transfusion with 15-20 ml of whole blood (7/7) or irradiated blood (1/6) from the EBV-related virus-infected rabbits, but there was no transmission with transfusion of cell-free plasma (0/6) from the infected rabbits. Passive anti-EBV-VCA IgG (x 20 approximately x 10) titers decreased during the first 1-2 weeks in the transfused rabbits. The virus-transmitted rabbits showed a gradual increase in antibody titers ranging from peak titers of x 640 to x 2560 after 3 weeks of transfusion. The recipient origin of malignant lymphoma that developed in the first rabbit transfused by infected blood was confirmed by chromosomal analysis. This rabbit model thus shows that EBV-related herpesvirus is serially transmissible by blood transfusion and that transmission can not be completely prevented by irradiation of blood, but removal of blood cells is the best way to prevent transmission of EBV-related virus. Therefore, this animal model provides a convenient in vivo system for studies of the prevention and therapy of transfusion-related transmission of EBV and EBV-associated lymphoproliferative diseases in immunocompromised human beings.</p>No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155811312001新興感染症115116ENNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama1983Replication of herpes simplex virus in two cell systems derived from rhesus monkeysENNo potential conflict of interest relevant to this article was reported.