| Project/Area Number |
05671077
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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 |
Digestive surgery
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| Research Institution | Sapporo Medical College School of Medicine |
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Principal Investigator |
HIRATA Koichi Sapporo Medical University School of Medicine, First Department of Surgery, Professor, 医学部, 教授 (50136959)
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| Co-Investigator(Kenkyū-buntansha) |
KATSURAMAKI Tadashi Sapporo Medical University School of Medicine, First Department of Surgery, Inst, 医学部, 助手 (50253993)
MUKAIYA Mitsuhiro Sapporo Medical University School of Medicine, First Department of Surgery, Inst, 医学部, 助手 (00253998)
KIMURA Hiromichi Sapporo Medical University School of Medicine, First Department of Surgery, Inst, 医学部, 助手 (20186331)
DENNO Ryuichi Sapporo Medical University School of Medicine, First Department of Surgery, Assi, 医学部, 講師 (40163943)
KOBAYASHI Kenji Sapporo Medical University School of Medicine, First Department of Surgery, Assi, 医学部, 講師 (30153604)
八木橋 厚仁 札幌医科大学, 医学部, 助手
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Cholestasis / Endotoxin / Macrophage / Cytokine / Kupffer cell / Hepatocyte |
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| Research Abstract |
Reactive products between lipopolysaccharide and Kupffer cells or polymorphonuclear cells were proven to have a characteristic effect on secretion of bile and on function of bile canaliculus. Experimentally, decrease of bile flow and bile acids secretion, lysosomal activations, mitochondrial disturbances and the morphological changes of bile canalidulus are confirmed. In order to clarify above phenomena, monoclonal antibodies for one fraction of culture media between lipopolysaccharide and macrophages were studied. None among several monoclonal a ntibodies gained had significant anti-effects for the functions of that fraction. The relationships between those antibodies and the well-known cytokines, i.e.IL-1, IL-6, IL-8, IL-10, TNF and PAF,were made sure and no-specific correlation was observed. Namely, this monoclonal antibody is not specific for those cytokines. Howerver, one of them has an anti-effect of hepatocyte cytotoxicity by reactive product from cultured media. In details abou
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t this antibody and antigen are in study. The administration experiment via the portal vein was observed in vivo. And also in vitro, the effect of this antibody had been compared to that of the commercial antibodies for well-known cytokines about cytotoxicity and modulationin rat hepatocytes. The highly specific phenomena could not be found in a monoclonal antibody produced in this series, therefore, the commercial antibodies were utilized in most of in vivo experiment. The pretreatments by those antibodies had significant effects of total bile flow, the changes of bile acid concentrations and the morphological changes of bile canaliculus but no effect is obseved in the posttreatment following the perfusion of reactive products.
The significant phenomena using by antibodies were observed in "in vitro" experiment than in "in vivo", on the point of views, i.e.the activation of hepatocyte lysosomal enzymes and the decrease of hepatocyte mitochondrial ATPase by the reactive products. The characteristics of an unknown monoclonal antibody and its antigan is recognized to be important and will be continued to study in this research. Less
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