1990 Fiscal Year Final Research Report Summary
Studies on Pathogenesis of Intrahepatic Cholestasis - Analysis of Ca^<++>- Calmodulin-Actomyosin System.
| Project/Area Number |
62570335
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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) |
FUNATSU Kazuo Sch. of Med. Keio Univ., Dept. of Int. Med. Assist. Prof., 医学部, 非常勤講師 (00129644)
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| Project Period (FY) |
1987 – 1989
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| Keywords | intrahepatic cholestasis / canalicular contraction / actin filaments / intracytoplasmec Ca^<++> / calmodulin / primary biliary cirrhosis / anticytokeratin antibody / HLA-DR |
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| Research Abstract |
In an attempt to elucidate the pathogenesis of intrahepatic cholestasis due to bile secretory impairment, the cytoskeletal system in the intrahepatic bilary tract was investigated in vivo and in vitro by immunofluorescence and immunoelectron microscopy using an experimental model of acute intrahepatic cholestasis and liver biopsy specimens obtained from patients with acute intrahepatic cholestasis. The ultrastructural distribution of intracytoplamic free calcium ions (Ca^<++>) and its alterations were revealed by digital image analysis of the electron micrographs obtained by the potassium antimonate method. Bile canalicular contractions were analysed by time-lapse cinematography. It has been probed that the existence of intracytoplasmic Ca^<++>, Ca^<++>-binding protein calmodulin, and Ca^<++>-Mg^<++>-ATPase is essential for the control of actin filaments-mediated bile canalicular contractions. The depletion of these three factors resulted in the disturbances of bile canalicular contrac
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tions, i. e. the paralytic dilatation of bile canaliculli, causing stagnation of bile in the canaliclus network leading to intrahepatic cholestasis.
Anti-intermediate filaments (IF) and anti-actin filaments (AF) were determined in sera of patients with primary biliary cirrhosis (PBC) by immunofluorescence and immunoperoxidase method using the monolayer-culutured cell lines, _3T_3 and PtK_2. It has been considered that anti-IF antibody is formed against the IF derived from the bile duct epithelium as a result of bile duct destruction, while anti-IF antibody is formed mainly against the AF derived from the luminal site of bile duct epithelium at stage I of PBC and is further formed against the AF from pericanalicular region after the stage II. Immunofluorescence and immunoperoxidase microscopy revealed the aberrant expression of HLA-DR within the intrahepatic bile duct epithelium in the biopsy speciments from patients with PBC. It is strongly suggested that cytotoxic T cells may recognize this HLA-DR and react with the bile duct epithelium, leading to the destruction of bile duct in PBC. Less
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[Publications] Oda, M., Komatsu, H., Honda, K., Kaneko, K., Azuma, T., Ishii, M., Tsukada, N., Nakamura, M., Funatsu, K., Fujiwara, T. and Tsuchiya, M.: "Intrahepatic distribution of laminin and its producing cells in carbon tetrachloride-induced liver cirrhosis - An immunofluorescence and immunoelectron microscopic study -." J. Clin. Electron Microscopy. 20. 560-561 (1987)
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「研究成果報告書概要(欧文)」より
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[Publications] Oda, M., Watanabe, N., Azuma, T., Nishizaki, Y., Nishida, J., Inoue, J. and Tsuchiya, M: "Electron microscopic changes of intrahepatocellular calcium ion distribution in bile canalicular contractions - digital image analysis combined with fura-2 fluorescence-." Hepatology. 10. 635 (1989)
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「研究成果報告書概要(欧文)」より
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[Publications] Oda, M., Funatsu, K., Watanabe, N., Azuma, T., Nishizaki, Y., Yokomori, H., Ueno, M., Nakamura, M., Tsuchiya, M. and Phillips, M. J.: "An experimental model for acute intrahepatic cholestasis in humans - Electron microscopic and cytochemical study -." J. Clin. Electron Microscopy. 22. 593-594 (1989)
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「研究成果報告書概要(欧文)」より
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[Publications] Watanabe, N., Miyairi, M., Suyama, K., Oshio, C., Oda, M. and Tsuchiya, M.: "Effects of taurolithocholate on the bile canalicular motilities in isolated rat hepatocytes." J. Clin. Electron Microscopy. 22. 738-739 (1989)
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「研究成果報告書概要(欧文)」より
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[Publications] Ishii, K., Oda, M., Azuma, T., Nishizaki, Y., Yokomori, H., Nishida, J., Inoue, J., Watanabe, N., and Tsuchiya, M.: "Differences in changes of individual serum bile acids between primary sclerosing cholangitis and primary biliary cirrhosis." Hepatology. 12. 414 (1990)
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「研究成果報告書概要(欧文)」より
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[Publications] Oda, M., Azuma, T., Watanabe, N., Nishizaki, Y., Nishida, J., Ishii, K., Suzuki, H., Komatsu, H., Tsukada, N. and Tsuchiya, M.: "Regulatory mechanisms of the hepatic microcirculation - Involvement of the contraction and dilatation of sinusoids and sinusoidal endothelial fenestrae -." Progress in Applied Microcirculation. Vol. 15. 103-128 (1990)
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「研究成果報告書概要(欧文)」より
