1992 Fiscal Year Final Research Report Summary
Studies on pathogenesis and progression of primary biliary cirrhosis with special reference to analysis of autoimmune responses to biliary tract cytoskeleton.
| Project/Area Number |
02670318
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
ODA Masaya Sch.of Med. Keio Univ., Dept.of Int.Med. Assist.Prof., 医学部, 専任講師 (20129381)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Kanji Sch.of Med. Keio Univ., Dept. of Int.Med. Assistant, 医学部, 助手 (40193247)
FUNATSU Kazuo Sch.of Med. Kieo Univ., Dept.of Int.Med. Assist. Prof., 医学部, 非常勤講師 (00129644)
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| Project Period (FY) |
1990 – 1992
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| Keywords | primary biliary cirrhosis / bile duct destruction / anti-cytokeratin subclass CK1 antibody / immunoperoxidase method / HLA-DR / ICAM-1 / LFA-1 / long term UDCA therapy |
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| Research Abstract |
Transmission electron microscopy revealed that intermediate filaments (IF) are diffusely present in the cytoplasm of bile duct epithelium, whereas microfilaments (actin filametns : AF) are located in the subplasmalemmal region. Acoording to the indirect immunofluorescent method, anti-IF (cytokeratin : CK) antibody proved by the specific immunofluorescence for IF in PtK_2 cultured cells and anti-AF antibody proved by that for AF in _3T_3 cultured cells were detected in sera of all patients with primary biliary cirrhosis (PBC). CK derived from PtK_2 cells were divided into subclass CK1(52kD) and CK2(45kD) by SDS-PAGE.Monoclonal antibodies were produced against CK1 and CK2 respectively. By the sandwich inhibition ELISA, anti-CK1 antibody titers in sera of PBC patients were proved to be significantly higher than those in patients with other liver disease, demonstrating the highest degrees on the stage I-II of PBC showing the most prominent morphological features of chronic non-suppurative destructive cholangitis (CNSDC) by liver biopsy and the lowest degrees on the stage IV hardly showing CNSDC.By long term ursodeoxycholic acid (UDCA). anti-CK1 and anti-M2 (pyruvate dehydrogenase) antibody titers were significantly reduced in sera of symptomatic and asymptomatic PBC patients, implying that UDCA therapy may affect the autoimmune abnormalities in PBC.A decrease in anti-CK1 antibody titers by UDCA therapy would reflect an improvement in pathological state of PBC.By the indirect immunoperoxidase antibody method, it was revealed that not only HLA-DR but also intercellular adhesiom molecule (ICAM)-1 are most strongly expressed on the outer surfaces of the plasma membranes of bile duct epithelial cells. Furthermore CD4 and CD8-positive cells expressed on cell surface by lymphocyte function-associated antigen(LFA)-1 were found to be infiltrated particularly around bile ducts, making direct contant with the ICAM-1-positive bile duct epithelial cells.
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[Publications] Ishii, K., Oda, M., Watanabe, M., Azuma, T., Yokomori, H., Nishizaki, Y., Nishida, J., Inoue, J., Kaneko, H.and Tsuciya, M.: "Electron microscopic cytochemicalcharacterization of rat liver bile canalicuil in lithocholic acid-induced cholestasis." J.Clin. electron Microscopy. 23. 723-724 (1990)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ishii, K., Oda, M., Watanabe, N., Nishida, J., Inoue, J., Kaneko, H., Kazemoto, S.and Tsuchiya, M.: "Different effects between taurolithocholate and sulfated lithocholate on the bile canalicular motilities and ultrastructures in isolated rat hepatocytes." J.Clin. Electron Microscopy. 24. 609-610 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Oda, M., Kaneko, H., Azuma, T., Ishii, K., Komatsu, H., Nishizaki, Y., Nishida, J., Nakamura, M.and Tsuchiya, M.: "Differences in anti-cytokeratin subclass antibody-related immune abnormalities between primary biliary cirrhosis and primay sclerosing cholangitis." Gastroenterology. 100. A782 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Oda, M., Kaneko, H., Azuma, T., Kazemoto, S., Kaneko, K., Nakamura, M.and Tsuchiya, M.: "Differences in anti-cytokeratin subclass antibody formation related to bile duct destruction between symptomatic and asymptomatic primary biliary cirrhosis." Gastroenterology. 102. A863 (1992)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Oda, M., Kaneko, H., Azuma, T., Kazemoto, S., Yokomori, H., Ishii, K., Komatsu, H., Fujiwara, T.and Tsuchiya, M.: "Heterogeneity of cytoskeletal distribution in intrahepatic biliary tract and cytoskeletal antibodies in primary biliary cirrhosis." J.Clin. Electron Microscopy. 25. 397-398 (1992)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Oda, M., Kaneko, H., Kazemoto, So., Ishii, K., Yokomori, H., Azuma, T., Nakamura, M.and Tsuchiya, M.: "Long term ursodexycholic acid therapy reduces anti-cytokeratin subclass antibody formation related to bile duct destruction in primary biliary cirrhosis." Gastroenterology. 104. A966 (1993)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kaneko, H., Oda, M., Yokomori, H., Kazemoto, S., Kamegaya, Y., Komatsu, H., and Tsuchiya, M.: "Immunohistochemical microscopic analysis of bile duct destruction in primary biliary cirrhosis : Involvement of intercellular adhesion molecules." Int. Hepatol. Commun.(in press).
Description
「研究成果報告書概要(欧文)」より
