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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
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1990: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
KeywordsNucleation / Bile salt micelle / Vesicle / Discoidal particle / Apolipoproten A-1 / Prostaglandin / Mucin / Cholesterol gallstone / 胆汁脂質 / コレステロ-ル結晶析出 / アラキドン酸 / ムチン / モルモット / 胆汁 / コレステロール胆石 / 人皮胆汁 / 胆汁酸 / コレステロール結晶析出時間胆汁蛋白
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.

Report

(4 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [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
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Susumu Tazuma: "The role of bile acids in extracorporeal shockーwave lithotripsy(ESWL)of gallstone patients." Shock Waves. (1991)

    • Related Report
      1990 Annual Research Report
  • [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)

    • Related Report
      1990 Annual Research Report
  • [Publications] 田妻 進: "プレ-リ-ドッグにおけるコレステロ-ル胆石形成に及ぼすコレステロ-ル合成律速酵素阻害剤の影響" 日本消化器病学会雑誌. 88. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 峠 誠司: "過飽和人口胆汁におけるコレステロ-ル結晶析出におよぼすアポ蛋白Aー1の抑制機序" 肝臓. 32. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 佐川 広: "胆汁酸の膜障害性に関する研究(第一報)ーヒト赤血球膜を用いてー" 胆道. 5. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 梶山 梧朗: "COMMON DISEASE SERIES 13 “胆石症"ー食事と胆石" 南江堂, 5 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 田妻 進: "臨床胆汁酸研究の進歩1990" 医事出版, (1991)

    • Related Report
      1990 Annual Research Report
  • [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)

    • Related Report
      1989 Annual Research Report
  • [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)

    • Related Report
      1989 Annual Research Report
  • [Publications] Susumu Tazuma: "Effect of ursodeoxycholic acid administration on nucleation time in human gallbladder bile" Gastroenterology. 97. 173-178 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kazunobu Koide: "Effect of CS-514,a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase,on cholesterol gallstone formation in hamster" Biochimica et Biophysica Acta. 1005. 65-71 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 田妻進: "特集:体外衝撃波胆石破砕療法の現状ー胆石溶解療法無効例に対する体外衝撃波療法ー" 胆と膵. 11. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 田妻進: "Methyl tert-butyl ether(MTBE)によるコレステロ-ル胆石直接溶解療法の基礎的検討および臨床応用" 胆道. 4. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 梶山梧朗: "COMMON DISEASE SERIES 13“胆石症"ー食事と胆石" 南江堂, 5 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 梶山梧朗: "血清脂質異常の臨床" 永井書店, (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 梶山梧朗: 臨床医薬. 4. 191-200 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 田妻進: 日本消化器病学会雑誌. 85. 2271 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 田妻進: 日本消化器病学会雑誌. 85. 1530-1535 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Susumu Tazuma: Gastroenterology. inpress (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Susumu Tazuma: Am J Physiol. 255. G745-G751 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 水野重樹: 日本臨床代謝学会記録. XXV. 230-231 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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