| 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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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
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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 / 抗CK1抗体 / 抗M2抗体 / 症候性PBC / 無症候性PBC / Leu 2a / actin filaments(AF) / cytokeratin(CK) / 免疫酵素抗体間接法 / Leu2a陽性細胞 / HLAーDR / ICAMー1 / 原発性胆汁性肝硬変 / 細胞傷害性T細胞 / アクチンフィラメント / 中間系フィラメント / サイトケラチン |
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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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