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CD109 attenuates bleomycin-induced pulmonary fibrosis by inhibiting TGF-β signaling
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
A comparison of two types of contrast media used in endoscopic retrograde cholangiopancreatography: A retrospective study
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Development and validation of a new asthma questionnaire to help achieve a high level of control in school-age children and adolescents
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Hydrogen attenuates endothelial glycocalyx damage associated with partial cardiopulmonary bypass in rats
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Breach of tolerance versus burden of bile acids : Resolving the conundrum in the immunopathogenesis and natural history of primary biliary cholangitis
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi
SRPKIN-1 as an inhibitor against hepatitis B virus blocking the viral particle formation and the early step of the viral infection
Get PDF浜松医科大学博士（医学）doctoral医学系研究科New antiviral agents are needed for the treatment of hepatitis B virus (HBV) infection because currently available drugs do not completely eradicate chronic HBV in patients. Phosphorylation dynamics of the HBV core protein (HBc) regulate several processes in the HBV life cycle, including nucleocapsid formation, cell trafficking, and virus uncoating after entry. In this study, the SRPK inhibitors SPHINX31, SRPIN340, and SRPKIN-1 showed concentration-dependent anti-HBV activity. Detailed analysis of the effects of SRPKIN-1, which exhibited the strongest inhibitory activity, on the HBV replication process showed that it inhibits the formation of infectious particles by inhibiting pregenomic RNA packaging into capsids and nucleocapsid envelopment. Mass spectrometry analysis combined with cell-free translation system experiments revealed that hyperphosphorylation of the Cterminal domain of HBc is inhibited by SRPKIN-1. Further, SRPKIN-1 exhibited concentration-dependent inhibition of HBV infection not only in HepG2-hNTCP-C4 cells but also in fresh human hepatocytes (PXB cells) and in the single-round infection system. Treatment with SRPKIN-1 at the time of infection reduced the nuclease sensitivity of HBV DNA in the nuclear fraction. These results suggest that SRPKIN-1 has the potential to not only inhibit the HBV particle formation process but also impair the early stages of viral infection.doctoral thesi
Importance of eosinophilic infiltration of the colonic mucosa in ulcerative colitis patients who are refractory to maintenance therapy: A prospective, single-center study
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Eosinophilic infiltration is sometimes observed histologically in ulcerative colitis (UC), but the effect of the degree of infiltration on the treatment course for UC is not completely understood. We investigated whether short-term steroid administration in UC patients refractory to maintenance therapy, with high eosinophilic infiltration in the colonic mucosa, contributed to the clinical and endoscopic improvement. Ten patients with endoscopically active and pathologically high eosinophilic infiltration, based on pathological examination using endoscopic biopsy, were examined for the clinical background when starting steroid treatment. The clinical and endoscopic improvement before and after steroid use were assessed prospectively. The average initial steroid dosage and duration of use were 21.0 mg and 102.7 days, respectively. The mean values before and after steroid use of the clinical activity index, the Mayo endoscopic subscore, and the UC endoscopic index of severity were 2.4 and 1.0, 1.8 and 0.7, and 3.9 and 1.1, respectively. All scores improved significantly after steroid use (P=.042, P=.002, P=.002, respectively). Steroids were discontinued in all patients; no patients required steroid re-administration. There may be cases of UC with eosinophilic infiltration into the colonic mucosa and resistance to maintenance treatment, suggesting that short-term steroid administration may contribute to clinical and endoscopic improvements.doctoral thesi