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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.

Research Project

Project/Area Number 02670318
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKeio University

Principal Investigator

ODA Masaya  Sch.of Med. Keio Univ., Dept.of Int.Med. Assist.Prof., 医学部, 専任講師 (20129381)

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)
Project Period (FY) 1990 – 1992
Keywordsprimary biliary cirrhosis / bile duct destruction / anti-cytokeratin subclass CK1 antibody / immunoperoxidase method / HLA-DR / ICAM-1 / LFA-1 / long term UDCA therapy
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.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 織田正也: "原発性胆汁性肝硬変の発生機構における抗cytokeratin subclass抗体の意義とUDCA療法の胆汁酸分画に及ぼす影響" 肝臓. 32(12). 1195-1197 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masaya Oda: "Heterogeneity of cytoskeletal distribution in intrahepatic biliary tract and cytoskeletal antibodies in primary biliary cirrhosis" J.Clin.Electron Mcioscopy. 24(5-6). 397-398 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masaya Oda: "Differences in anti-cytokeratin subclass antibody formation related to bile duct destruction between symptomatic and asymptomatic primary biliary cirrhosis" Gastroenterology. 102(4). A863 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 金子 博: "原発性胆汁性肝硬変のUDCA長期療法における抗cytokeratin subclass CK1,抗M2抗体価の意義" 肝臓. 33(3). 54 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 織田正也: "原発性胆汁性肝硬変における肝内胆管サイトスケルトン抗体の形成とその意義" 日本臨床免疫学会会誌. 15(6). 572-585 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroshi Kaneko: "Immunohistochemical microscopic analysis of bile duct destruction in primary biliary cirrhosis:Involvement of intercellular adhesion molecules" International Hepatology Communications. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 織田正也: "自己免疫性肝疾患,その概念・病態と治療の進歩(原発性胆汁性肝硬変における抗サイトスケルトン抗体)" 日本医学館, 7 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 織田正也: "肝臓病up date(原発性胆汁性肝硬変の病因,病態研究の変遷と問題点)" 中外医学社, 10 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1995-03-27  

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