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Disturbed Oxygen Metabolism Induced by Perturbation of Microcirculation.

Research Project

Project/Area Number 01480226
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionJuntendo University School of Medicine (1990)
Osaka University (1989)

Principal Investigator

SATO Nobuhiro  Juntendo Univ. Gastroenterology Professor, 医学部, 教授 (90028358)

Co-Investigator(Kenkyū-buntansha) KATAYAMA Kazuhiro  Ohsaka Univ. Gastroenterology, 医学部・附属病院, 医員(平成元年度)
SAKAKI Yutaka  Ohsaka Univ. Gastroenterology, 医学部・附属病院, 医員(平成元年度)
YOSHIHARA Harumasa  Ohsaka Univ. Gastroenterology, 医学部, 助手 (70230795)
KAWANO Sunao  Ohsaka Univ. Gastroenterology, 医学部, 助手(平成元年度) (60133138)
福井 弘幸  大阪大学, 医学部附属病院, 医員
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1990: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1989: ¥4,200,000 (Direct Cost: ¥4,200,000)
Keywordsmicrocirculation / alcoholic liver disease / biomedical engineering / protooncogene / liver regeneration / tissue oxygenation / liver transplantation / hypoxia / 薬剤性肝障害 / 肝移値 / ヒポキシア / 肝微小循環 / 肝血流 / 肝酸素化 / 白血球 / 虚血性肝障害
Research Abstract

There is an increasing body of evidence that the disturbance of microcirculation in hepatic lobules is involved in the pathogenesis of a wide variety of lever damage. Among them are alcohol-and drug-induced damage and liver injury caused by ischemia-reperfusion process, which occurs in case of major liver surgery including liver transplantation. To investigate the mechanisms of these liver damages and of liver regeneration process, we applied the medical-engineering technology and molecular biological techniques. For analyzing the hepatic microcirculation, we developed an in vivo super-magnified video microscopy system which allows us to monitor sinusoidal blood cell flow velocity and regional cellular oxygenation. Ethanol causes severe microcirculatory disturbances in midzone of hepatic lobule which could account for later tissue damage. CC1_4 and galactosamine also induced a microcirculatory change of the hepatic lobules which preceeded the liver damage. Microciroulatory disorder also plays an important role in liver transplantation. during regeneration of the liver following drug-induced liver damage. Expression of the protooncogenes and their products is specifically enhanced in parallel with increased DNA replication. Zonal heterogeneity of c-Ha-ras gane expression was evident, and a higher number of gene products was detected in the pericentral (PC) region than in periportal (PP) region after CC1_4-treatment, which caused a severe structural damage and microcirculatory disorder in PC region. Protein kinase C, an important protein in signal transduction, also shows heterogeneous activation (more in PC than in PP) during liver regeneration, which might trigger cellular functions and proliferation and mediate the biological action of hepatotrophic factors. In conclusion, the microcirculatory disorder has a role in pathogenesis and repair process of alcohol-and drug-induced liver damage and following liver transplantation.

Report

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

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Sato N: "Characterization of hepatic hemodynamics in cirrhosis and noncirrhticsーEffect of glucagon infusion.ー" Scan J Gastroenterol. 24. 223-230 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Lieber CS: "Impaired oxygen utilization.A new mechanism for the hepatotoxicity of ethanol in subーhuman primates." J Clin Invest. 83. 1682-1690 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sasaki Y: "Cellular analysis of cーHaーrasーgene expression in rat liver after CCl_4 administration." Hepatology. 10. 494-500 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sasaki Y: "Heterogenous activation of protein kinase C during rat liver regeneration induced by carbon tetrachloride administration." FEBS LETTERS. 254. 59-65 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kurosawa K: "Transport of glutathione across the mitochondrial membranes." Biochemical and Biophysical Research communications. 167. 367-372 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 柏木 徹: "^<123>IーIMP直腸内投与による下腸間膜静脈血流の肝内分布に関する検討" 日消誌. 87. 1520-1524 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 肱岡 泰三: "アルコ-ル代謝と肝┣D2" 「アルコ-ル代謝と肝研究会」編(東洋出版), 240 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 林 紀夫: "細胞レベルからみた消化器の機能" 「谷内昭、永森静志」編(日本医学館), 360 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sato N, Kawano S, Matsumura T, Meren H, Yoshihara H, et al.: "Characterization of hepatic hemodynamics in cirrhotics and non-cirrhotics -Effect of glucagon infusion." Scand J Gestroenterol. 24. 223-230 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukui H, Sato N, Kawano S, Yoshihara H, Hijioka T, et al.: "Hepatic microcirculatory insufficiency and hypoxia after ethanol load." Gastroenterology. 96. 162 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tsujii S, Sato N, Kawano S, Hayashi N, Tsujii M, et al.: "Evaluation of oxygen metabolism in digestive organs using computer-assisted electronic endoscopy." Gastroenterology. 96. 517 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hijioka T, Sato N, Matsumura T, Yoshihara H, Fukui H, et al.: "Role of vasoconstriction in disturbed microcirculation of the liver after etanol load." Gastroenterology. 96. 608 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yuki T, Yoshitoku K, Nakagawa Y, Okanoue T, Fukui H, et al.: "Effect of coenzyme Q10 (CoQ10) on the hepatic lipid peroxidation and mitochondrial damage n alcohol-treated rats." Gastroenterology. 96. 675 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Badr MZ, Ganey PE, Yoshihara H, Kauffman FC, Thurman RG.: "Hepatotoxicity of menadione predominantes in oxygen-rich zones of the liver lobule." J Pharmacol Exp Ther. 248. 1317-1322 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Lieber CS, Baraona E, Hernandez-Munoz R, Kubota S, Sato N, et al.: "Impaired oxygen utilization. A new mechanism for the hepatotoxicity of ethanol in sub-human primates." J Clin Invest. 83. 1682-1690 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Katayama K, Hayashi N, Sasaki Y, Kasahara A, et al.: "Detection of hepatitis B virus X gene protein and antibody in type B chronic liver disease." Gastoenterology. 97. 990-998 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sasaki Y, Hayashi N, Morita Y, Ito T, Kasahara A, Sato N et al.: "Cellular analysis of c-Ha-ras gene expression in rat liver after CC1_4 administration." Hepatology. 10. 494-500 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sasaki Y, Hayashi N, Ito T, Fusamoto H, Sato N, Kamada T.: "Heterogeneous activation of protein kinasa C during rat liver regeneration induced by carbon tetrachloride administration." Febs Letters. 254. 59-65 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ishibashi K, Nishikawa A, Hayashi N, Kasahara A, Sato N, et al.: "N-acetylglucosaminyltransferase III in human serum, and hepatoma tissues : increased activity in liver cirrhosis and hepatoma patients." Clinica Chimica Acta. 185. 325-332 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yuki N, Hayashi N, Katayama K, Kasahara A, et al.: "Quantitative analysis of pre-S1 and pre-S2 in relation to HBsAg expression." Hepatology. 11. 38-43 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tsuji S, Kawano S, Sato N, Kamada T.: "Mucosal blood flow stasis and hypoxemia as the pathogenesis of acute gastric mucosal injury : Role of endogenous leukotriens and prostaglandins." J Clin Gastroenterol. 12(Supple 1). 85-91 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kurosawa K, Hayashi N, Sato N, Kamada T, Tagawa K.: "Transport of glutathione across the mitochondrial membranes." Biochemcal and Biophysical Research Communications. 167. 367-372 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kurosawa K, Shibata H, Hayashi N, Sato N, Kamada T, et al.: "Kinetics of hydroperoxide degradation by DADP-glutathione system in mitochondria." J Biochem. 108. 9-16 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yuki N: "Quantitative analysis of preーSi in relation to HBsAg expression." Hepatology. 11. 38-43 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tsuji S: "Mucosal blood flow stasis and hypoxemis as the pathogenesis of acute gastric mucosal injury:Role of endogenous leukotriens and prostaglandins." J Clin Gastroenterol. 12. S85-S91 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kurosawa K: "Transport of glutathione across the mitochondrial membeanes." Biochemical Biophysical Research Communications. 167. 367-372 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kurosawa K: "Kinetics of hydroperoxide degrandation by NADPーglutathione system in mitochondria." J Biochem. 108. 9-16 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 柏木 徹: " ^<123>IーIMP直腸内投与による下腸間膜静脈血流の肝内分布に関する検討" 日消誌. 87. 1520-1524 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 柏木 徹: " ^<123>Iーindoamphetamine十二指腸内投与による上腸間静脈血液のportsystemic ahunt index測定" 日消誌. 87. 1578-1578 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 林 紀夫: "細胞レベルからみた消化器の機能" 谷内昭、永森静志編(日本医学館), 360 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 川野 淳: "消化性潰痒治療ー今日と未来ー" 佐藤信紘,鎌田悌輔,小味渕智雄編(裕文社), 220 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nobuhiro Sato: "Characterization of hepatic hemodynamics in cirrhotics and non-cirrhotics" Scand.J.Gastroenterol.24. 223-230 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Taizo Hijioka: "Ethanol-induced hepatic hypoxia due to disturbed microcirculation of the liver" American J.Physiology.

    • Related Report
      1989 Annual Research Report
  • [Publications] Yutaka Sasaki: "Cellular analysis of c-Ha-ras gene expression in rat liver after CCl_4 administration" Hepatology. 10. 494-500 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yutaka Sasaki: "Heterogenous activation of protein kinase C during rat liver regeneration induced by carbon tetrachloride administration" FEBS Lett.254. 59-65 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Charles S.Lieber: "Impaired oxygen utilization-A new mechanism for the hepatotoxicity of ethanol in sub-human primates" J.Clin.Invest.83. 1682-1690 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 佐藤信紘,福井弘幸: "肝微小循環ーその障害とアルコ-ル性肝障害のinitiation機序についてー" 日本バイオレオロジ-学会誌. 3. 176-182 (1989)

    • Related Report
      1989 Annual Research Report

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

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