| Project/Area Number |
05454175
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | Kanazawa University |
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Principal Investigator |
NAKAMURA Yasuni Kanazawa University School of Medicine, Professor, 医学部, 教授 (10115256)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Motoko Kanazawa University School of Medicine, Assistant, 医学部, 助手 (10251943)
HOSO Masahiro Kanazawa University School of Medicne, Assistant, 医学部, 助手 (20219182)
SAITO Katsuhiko Kanazawa University School of Medicine, Assistant Professor, 医学部, 講師 (10205635)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1993: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | vanishing bile duct syndrome / primary biliary cirrhosis / primary sclerosing cholangitis / biliary epithelium / cellular adhesion molecules / cytokines / cell culture / immunopathology / 原発性胆汁性肝硬変 / 細胞接着因子 / コラーゲンゲル / HLA-DR / アポトーシス / 肝内胆管消失症候群 / ミトコンドリア抗体 / 胆管周囲血管叢 / 第八因子 / アレルギー / 感染性胆管障害 |
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| Research Abstract |
Vanishing bile duct syndrome was examined immunopathologically with emphasis on etiology and pathogenesis. 1. Among this syndrome in Japan, primary biliary cirrhosis was most frequent, and the next was primary sclerosing cholangitis. Graft-versus-host disease related to bone marrow transplantation and drug-induced bile duct loss were also occasionally encoutered. 2. In primary biliary cirrhosis, pyruvate dehydrogenase complex E2 on mitochondrial inner membrane was regarded as an autoantigen. Immunohistochemical study using monoclonal antibody disclosed that this complex was aberrantly expressed outside mitochondria, suggesting molecular mimicry pathogenesis of this disease. 3. Peribiliary vascular plexus, a system of blood supply to the bile ducts, was involved immunologically in primary biliary cirrhosis and makedly diminished in primary sclerosing cholangitis. These changes may be related to their pathogenesis. 4. Around the damaged bile ducts of primary biliary cirrhosis, abnormal e
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xpression of abhesion molecules such as ICAM-1 and VCAM-1 on the endothelial cells and adso bile duct epithelium, were found. Marked infiltration of CD4 and CD8 positive lymphoid cells were also found around these ducts. These abnomal microenviroments may be involved in the pathogenesis of primary biliary cirrhosis. 5. Selective culture of biliary tree was methodologically established, using collagen gel. By this method, it was found that addition of cytokines such as INF-gamma induced abnormal expression of HLA-DR or HLA-A,B,C on cultured bile duct epithelium. Further analysis of biological phenomenon of ductal epitelium of vanishing bile duct syndrome will be expected. 6. Combination of hepatotoxic drugs and immunomodulation created pecular bile duct damages in experimental models, presenting biliary cell necrosis and apoptosis. The latter finding were also found in damaged bile ducts in vanishing bile duct syndrome, suggesting that our animal models could be applied to the evaluation of human vanishing bile duct syndrome. Less
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