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1990 Fiscal Year Final Research Report Summary

A Study on the Pathogenesis of Cholesterol Gallstone Formation : Importance of Biliary Proteins and Biliary Lipid Particles.

Research Project

Project/Area Number 63480520
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

KAJIYAMA Goro  Hiroshima University School of Medicine Professor, 医学部, 教授 (40034087)

Co-Investigator(Kenkyū-buntansha) TAZUMA Susumu  University Hospital of Hiroshima University School of Medicine, Research Assista, 医学部・附属病院, 助手 (80201614)
HORIUCHI Itaru  Hiroshima University School of Medicine, Assistant Professor, 医学部, 講師 (60157055)
Project Period (FY) 1988 – 1990
KeywordsNucleation / Bile salt micelle / Vesicle / Discoidal particle / Apolipoproten A-1 / Prostaglandin / Mucin / Cholesterol gallstone
Research Abstract

To evaluate the role of biliary proteins and biliary lipid particles in the pathogenesis of cholesterol gallstone formation, we performed an ultrastructural studies using transmission electron microscopy. Conclusions were as follow ;
1. There are three different types of lipid particle in human gallbladder bile and supersaturated model bile solutions, lecithin-cholesterol vesicle, bile salt micelle, and discoidal particle.
2. Apolipoprotein A-1, an anti-nucleating factor, stabilizes nonmicellar lipid particles by binding to discoidal particles, followed by inhibition of transformation to multilamellar liposome.
3. On the other hand, a high hepatic output of cholesterol into bile correlates a high incorporaion of linoleate and arachidonate into biliarylecithin, resulting in the induced synthesis and secretion of mucin, a pronucleating factor, by the gallbladder. This is mediated by an arachidonate-prostanoid pathway. Mucin promotes vesicular aggregation and fusion, resulting in fastnucleation.
Thus, cholesterol crystal nucleation is regulated by the balance between anti-nucleating factors and pronucleating factors. In addition, nucleation occurs from the non micellar lipid particles, i. e. vesicles, discoidal particles.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 田妻 進: "アポ蛋白Aー1によるヒト胆嚢胆汁中コレステロ-ル結晶析出抑制の作用機序に関する研究" 日本消化器病学会雑誌. 88. (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田妻 進: "胆汁中コレステロ-ル溶存性を規定する因子に関する研究 ー胆汁蛋白、特にアポ蛋白Aー1の意義に関連してー" 日本消化器病学会雑誌. 86. 1666-1672 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田妻 進: "胆汁中disc様粒子とそのrouleau formation の証明 ーコレステロ-ル結晶析出過程における役割ー" 日本消化器病学会雑誌. 86. 144- (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Susumu Tazuma: "Effect of ursodeoxycholic acid administration on nucleation time in human gallbladder bile." Gastroenterology. 97. 173-178 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田妻 進: "モルモット胆嚢における粘液糖蛋白分秘に対する16,16ーdemethyl prostaglandin E_2の影響 ー催石性に関連してー" 日本消化器病学会雑誌. 85. 2271- (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田妻 進: "ウルソデオキシコ-ル酸(UDCA)服用によるnucleation time(NT)への影響" 日本消化器病学会雑誌. 85. 1530-1535 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田妻 進: "臨床胆汁酸研究の進歩 1990" 医事出版, (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 梶山 梧朗: "血清脂質異常の臨床" 永井書店, (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Susumu Tazuma: "A study on the mechanisms where by apolipoprotein A-1 (apo A-1) inbits cholesterol crystal nucleation in human gallbladder bile." Japanese Journal of Gastroenterology. 88. (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Susumu Tazuma: "The study on factors affecting cholesterol solubility in bile : Relation to biliary proteins including apolipoprotein A-1." Japanese Journal of gastroenterology. 86. 1666-1672 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Susumu Tazuma: "Characterization of rouleau formation of disc-like particle in bile by transmission electron microscopy : Relation to cholesterol crystal nucleation." Japanese Journal of Gastroenterology. 86. 144 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Susumu Tazuma: "Effect of ursodeoxycholic acid administration on nucleation time in human gallbladder bile." Gastroenterology. 97. 173-178 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Susumu Tazuma: "Effects of 16, 16-dimethyl prostaglandin E2 on the mucous glycoprotein secretion of the gallbladder in guinea pigs : Relation to the gallstone formation." Japanese Journal of Gastroenterology. 85. 2271 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Susumu Tazuma: "Effect of ursodeoxycholic acid (UDCA) treatment on nucleation time (NT)." Japanese Journal of Gastroenterology. 85. 1530-1535 (1988)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-08-12  

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