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Elucidation of pathogenesis and UDCA effect mechanisms in primary biliary cirrhosis

Research Project

Project/Area Number 04670407
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionINSTITUTE OF CLINICAL MEDICINE, UNIVERSITY OF TSUKUBA

Principal Investigator

MATSUZAKI Yasushi  Institute of Clinical Medicine, University of Tsukuba, Assistant Professor., 臨床医学系, 講師 (50209532)

Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsprimary biliary cirrhosis / UDCA / GVHR / cellular immunity / MHC class I / MHC calss II / autoimmune diseases / 原発性胆汁性肝硬変 / ursodeoxycholic acid / MHC classI / MHC classII / GVHD(GVHR)
Research Abstract

I summarized the results of these investigations. First, we examined the efficacy of biochemical and histology after more than 4 yrs of ursodeoxycholic acid(UDCA)treatment in primary biliary chirrhosis(PBC). Three cases show that liver histology was found to be improved, as were blood chemistry and pruritus, during short-term UDCA treatment, but histology results were slightly worse after long-term treatment despite the sustained improvement in biochemistry and pruritus. Moreover, consistent changes of MHC class I and II antigens by UDCA were not obtained. It is supposed that UDCA is not fundamental treatment, but delay the progression of the clinical stage of PBC.Second, we studied wherther the amount of soluble MHC class I antigen shows the relation between the mortality of GVHR.Our results indicates that measurement of soluble MHC calss I antigen is uesful for deciding the severity of GVHR.Third, we examined the effect of interleukin-6(IL-6) on the development of autoimmune diseases employing murine GVHR model with MHC class II disparity. Autoimmune like lesions in transgenic recipients became weakened as compared with those in non-transgenic recipients. In contrast, anti-PDH antibody in transgenic recipients were significantly higher than that of non-transgenic recipients. These results indicate that IL-6 excessively produced in vivo might regulate the progression of autoimmune diseases. In the last study, in order to elucidate the UDCA effect mechanisms, we studied the cellular immunological changes after UDCA and TUDCA treatment in MHC class II mutant mice. We could not recognize that the degree of GVHR, the expression of MHC class II, CD4/CD8 ratio and ICAM-1 between treatment group and non-treament group. In the PBC model, it is supposed that UDCA may not regulate the cellular immunity. Further studies regarding the soluble MHC calss I level and IL-6 in PBC patients, are needed.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Matsuzaki Y,et al: "Effect of long-term ursodeoxycholic acid treatment on histology,bloodchemistry and MHC expression in primary biliary cirrhosis." Gastroenterology. 102(4). A850 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsuzaki Y,et al: "Is taurine effective for treatment of painful muscle cramps in liver cirrhosis?" Ame J Gastroenterol. 88(9). 1466-1467 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsuzaki Y,et al: "Enzyme immunoassay of serum type IV collagen in anti-HCV positive chronic liver diseases." Clin Chim Acta. 221. 209-217 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsuzaki Y,et al: "Biochemical and histological changes after more than four years of treatment of ursodeoxycholic acid in primary biliary cirrhosis." J Clin Gastroenterol. 18(1). 36-41 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kimura T,et al.: "Indication of autoimmune disease by graft-versus-host reaction across MHC class II difference:modification of the lesions in IL-6 transgenic mice." Clinical & experimental immunology. 95(3). 525-530 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ikegami T,et al: "Endoscopic diagnosis of common bile duct varices by percutaneous transhepatic choledochoscopy." Gastrointestinal Endoscopy. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 松崎靖司: "原発性胆汁性肝硬変,原発性硬化性胆管炎,今月の治療,1巻,8号" 戸田剛太郎編集,総合医学社, 135(p.32-54) (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Matsuzaki, M.Doy, N.Tanaka, T.Osuga, T.Yohida, A.Honda, M.Nakano, T.Aikawa: "Effect of long-term ursodeoxycholic acid treatment on histology, bloodchemistry and MHC expression in primary biliary cirrhosis." Gastroenterology. 102(4) A850,1992. 57-1465 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsuzaki Y,Yohiga S,Sugitani T,, Shoda J,Tanaka N,Osuga T: "Enzyme immunoassay of serum type IV collagen in anti-HCV positive chronic liver diseases." Clin Chim Acta. 221. 209-217 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsuzaki Y,Tanaka N,Osuga T: "Is taurine effective for treatment of painful muscle cramps in liver cirrhosis?" Amer J Gastroenterol. 88(9). 1466-1467 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsuzaki Y,Doy M,Tanaka N,Shoda J,Osuga T,Nakano M Akikawa T: "Biochemical and histological changes after more than four years of treatment of ursodeoxycholic acid in primary biliary cirrhosis." J Clin Gastroenterol. 18(1). 36-41 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kimura T,Suzuki K,Inada S,Hayashi A,Saito H,Miyai T,Ohsugi Y,Matsuzaki Y, Tanaka N,Osuga T,Fujiwara M: "Indication of autoimmune disease by graft-versus-host reaction across MHC class II difference : modification of the lesions in IL-6 transgenic mice." Clinical & experimental immunology. 95(3). 525 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsuzaki Y,et al:"Effect of long-term ursodeoxycholic acid treatment on histology,bloodchemistry and MHC expression in primary biliary cirrhosis." Gastroenterology. 102(4). A850 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsuzaki Y,et al:"Is taurine effective for treatment of painful muscle cramps in liver cirrhosis?" Ame J Gastroenterol. 88(9). 1466-1467 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsuzaki Y,et al:"Enzyme immunoassay of serum type IV collagen in anti-HCV positive chronic liver diseases." Clin Chim Acta. 221. 209-217 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsuzaki Y,et al:"Biochemical and histological changes after more than four years of treatment of ursodeoxycholic acid in primary biliary cirrhosis." J Clin Gastroenterol. 18(1). 36-41 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kimura T,et al.:"Indication of autoimmune disease by graft-versus-host reaction across MHC class II difference:modification of the lesions in IL-6 transgenic mice." Clinical & experimental immunology. 95(3). 525-530 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ikegami T,et al:"Endoscopic diagnosis of common bile duct varices by percutaneous transhepatic choledochoscopy." Gastrointestinal Endoscopy. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松崎靖司.: "原発性胆汁性肝硬変,原発性硬化性胆管炎,今月の治療,1巻,8号" 戸田剛太郎編集,総合医学社, 135(32-54) (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松崎 靖司 他: "原発性胆汁性肝硬変の治療" Current Therapy. 10. 1817-1821 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yasushi Matsuzaki et al: "Effect of long-term ursodeoxycholic acid treatment on histology,blood chemistry and MHC expression in primary biliary cirrhosis" Gastloenterology. 102. A850- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yasushi Matsuzaki et al: "Indications and limitations of Gallstone dissolution therapy" Asian Med J. 35. 341-344 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 田中 直見 他: "胆汁酸製剤による胆石溶解療法と肝内胆汁うつ滞" メディチーナ. 29. 251-254 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 田中 直見,他: "原発性胆汁性肝硬変のウルソデオキシコール酸療法" Therapeutic Research. 12. 3072-3075 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 田中 直見,他: "原発性胆汁性肝硬変に対するウルソデオキシコール酸長期投与の肝組織改善効果とその作用機序" 肝臓. 32. 1204-1206 (1991)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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