| Project/Area Number |
60570337
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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 Assistant Professor, 医学部内科学, 専任講師 (20129381)
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| Co-Investigator(Kenkyū-buntansha) |
FUNATSU Kazuo Assistant Professor, 医学部内科学, 講師 (00129644)
OSHIO Chikara Instructer, 医学部内科学, 助手 (40095584)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1985: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | liver cirrhosis / hepatic microcirculation / sinusoidal endothelial fenestrae / actin filament / calcium / calmodulin / adrenergic merve / コリン作動性神経 / サイカラシンB / 超微形態 |
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| Research Abstract |
The hepatic sinusoids, the major component of the microcirculatory system in the liver, are ultrastructually characterized by the presence of the sinusoidal endoyhelial fenestras(SEF) i.e.the sieve plate-like pores and by the absence of the basement membrane beneath the sinusoidal endothelia. Actin and calmodulin (Ca -binding protein) and calcium ions(Ca ) were proved in the cytoplasm of the sinusoidal endotelium in liver tissue and in primary monolayer culture. Ttansmission electron microscopy revealed the presence of microfilaments in close association with the plasma membrane of the SEF. The in vivo and in vitro treatment with cytochalasin B caused the dilatation and fusion of the SEF with the loss of filamentous structures of actin filaments. the SEF were contracted or dilated respectively in response to a decrease in the sinusoidal blood flow induced by norepinephrine and histamine administration or to an increase by acetylcholine and isoproterenol. These endotelial responses toth
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e biogenic amines were reproduced in the primary monolayer-cultured sinusoidal endothelia. The above observation indicate that the contraction and dilatation of the SEF possibly regulated by actin filaments within the endothelium in the presence of Ca and calmodulin would contribute to the regulatory mechanism for maintaining the constant sinusoidal flow as well as the blood-hepatocyte exchange.
In carbon tetrachloride-induced liver cirrhosis,norepinephrine,histamine and endotoxin content in serum were elevated and endotoxin content in bile was also increased. The sinusoidal blood flow measured by hydrogen gas clearance method was significantly reduced. In experimental and human liver cirrhosis, the SEF were significantly reduced both in diameter and in number with the appeartance of the basement membrane beneath the sinusoidal endothelia,i.e.the capillarization of hepatic sinusoids. The decrease of the SEF in diameter and number in cirrhosis would interrupt the free transition of plasma constituents and oxygen from the sinusoids to the hepatocytes, leading to a vicious cycle in the self-perpetuation of liver cirrhosis. Less
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