• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Factors Associated with Insufficient Liver Regeneration in Fulminant Hepatic Failure

Research Project

Project/Area Number 01480223
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionUniversity of Tokyo

Principal Investigator

FUJIWARA Kenji  University of Tokyo, Faculty of Medicine, Lecturer., 医学部・附属病院, 講師 (80101088)

Co-Investigator(Kenkyū-buntansha) 持田 智  東京大学, 医学部・附属病院, 医員 (20219968)
富谷 智明  東京大学, 医学部・附属病院, 医員 (90227637)
名越 澄子  東京大学, 医学部・附属病院, 医員
平田 啓一  東京大学, 医学部・附属病院, 医員 (50199064)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1989: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordsfulminant hepatitis / liver regeneration / intravascular coagulation / macrophage / ornithine decarboxylase / plasma membrane / cultured hepatocyte / polyamine / ポリアミン代謝 / オルニシン脱炭酵素 / 分子生物学 / 肝再生促進因子
Research Abstract

The aim of this project is to find factors associated with insufficient liver regeneration in fulminant hepatic failure. The following results have been obtained.
1) In massive hepatic necrosis induced in rats by a hepatotoxin, fibrin deposition in the hepatic sinusoids was seen in association with endothelial cell destruction. Such massive hepatic necrosis was also observed when rats received endotoxin following hepatic macrophage activation by administration of killed Corynebacterium parvum or after partial hepatectomy.
2) When rats received putrescine essential for liver regeneration following partial hepatectomy, hepatic DNA synthesis was enhanced with increased hepatic putrescine content, Insulin. glucagon or epidermal growth factor increased hepatic putrescine content through enhancing mRNA content and/or altering posttranscriptional regulation of ornithine decarboxylase, the key enzyme of polyamine production, thus suggesting that polyamine metabolism in the liver after partial hepatectomy may provide a useful tool for evaluation of action sites of hepatotrophic factors.
3) Rat plasma membrane was found to have both stimulatory and inhibitory factors for DNA synthesis by rat hepatocytes in primary culture in the presence of epidermal growth factor or hepatocytes growth factor. The stimulatory factor seemed to be protein in character.
4) In rats with massive hepatic necrosis secondary to fibrin deposition in the hepatic sinusoids, prothrombin time was negatively correlated with hepatic DNA synthesis. The necrosis was attenuated by treatment with anticoagulant infusion. When plasma membrane was obtained from rats given a hepatotoxin, its stimulatory potential for liver proliferation almost disappeared. Circulatory disturbance in the liver and loss of such stimulatory potential of liver plasma membrane may contribute to insufficient liver regeneration in fulminant hepatic failure.

Report

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

    (65 results)

All Other

All Publications (65 results)

  • [Publications] Fujiwara K.: "Activated Kupffer Cells as a Factor of Massive Hepatic Necrosis after Liver Resection." HepatoーGastroenterology. 37. 194-197 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Mochida S.: "Provocation of Massive Hepatic Necrosis by Endotoxin after Partial Hepatectomy in Rats." Gastroenterology. 99. 771-777 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hirata K.: "Possible Contribution of Protein Kinase C Activation to Priming for DNA Synthesis Induced by Epidermal Growth Factor with Insulin and its Inhibition by Plasma Membrane in Primary Cultured Rat Hepatocytes." Biochem.Biophys.Res.Comm.171. 1093-1098 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fujiwara K.: "Insulin and Glucagon Therapy of Acute Hepatic Failure." Dig.Dis.Sci.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohno A.: "Ruffle Formation in the Evaluation of stimulatory State of Hepatic Macrophages in Rats." Liver.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yamada S.: "Evidence for Enhanced Function of Hepatic Macrophages after Longーterm Ethanol Feeding in Rats." Liver.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Mochida S.: "Method for in situ Evaluation of Superoxide Production by Pulmonary Macrophages in the Rat." Acta Pathol.Jpn.41. 217-220 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Mochida S.: "In situ detection of Lipid Peroxidation in Rat Hepatocytes." Gastroenterology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Mochida S.: "Gutーderived Substances in Activation of Hepatic Macrophages after Partial Hepatectomy in Rats." J.Hepatology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tomiya T.: "Ornithine Decarboxylase Induction in Partial Hepatectomized Rat Liver and Modes of its Stimulation by Glucagon and Insulin." J.Biochem.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nogoshi S.: "Stimulation of Putrescine Production by Epidermal Growth Factor in Rat Liver after Partial Hepatectomy." Hepatology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tomiya T.: "Significance of Serum Human Hepatocyte Growth Factor Levels in Patients with Hepatic Failure." Hepatology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hirata K.: "Rat Liver Plasma Membrane has Both Stimulatory and InhibitoryFactors for DNA Synthesis by Primary Cultured Rat HePatocytes in the Presence of Edidermal Growth Factor and Insulin." Biochem.Biophys.Res.Comm.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] FUJIWARA K, OGATA I, OKA H: "Reciprocal Changes in Serum Albumin and Alpha-fetoprotein Levels in the Recovery Course of Acute Viral Hepatitis Stimulated by Glucagon and Insulin Therapy : Analysis of a Double Blind Controlled Trial." Gastroenterol. Jpn.24 :. 143-148 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] TOMIYA T, HAYASHI S, OGATA I, FUJIWARA K: "Plasma Alpha2-Plasmin Inhibitor-Plasmin Complex and FDP-D-Dimer in Fulminantheaptic Failure." Thromb. Res.53. 253-260 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] TOMIYA T, FUJIWARA K.: "Inhibition of Thrombin Generation in Fulminant Hepatic Failure by Treatment with Antithrombin III" Biomed. Prog.3. 39-40 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] HIRATA K, OGATA I, OHTA Y, FUJIWARA K.: "Hepatic Sinusoidal Cell Destruction in the Development of Intravascular Coagulation in Acute Liver Failure of Rats." J. Pathol. 158. 157-165 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] YAMADA S, OGATA I, HIRATA K, MOCHIDA S, TOMIYA T, FUJIWARA K.: "Intravascular Coagulation in Development of Massive Hepatic Necrosis Induced by Corynebacterium Parvum and Endotoxin in Rats." Scand. J. Gastroenterol.24. 293-298 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] MOCHIDA S, OGATA I, OHTA Y, YAMADA S, FUJIWARA K.: "In Situ evaluation of Stimulatory State of Hepatic Macrophage Based on Their Ability to Produce Superoxide Anions in Rats." J. Pathol.158. 67-71 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] SATO Y, FUJIWARA K, OGATA I, TOMIYA T, TOMIYA T, OKA H.: "Additive Stimulation of Hepatic Putrescine Production by Glucagon and Insulin after Partial Hepatectomy in Rats." Life Sci.41. 77-83 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] FUJIWARA K, OGATA I, MOCHIDA S, YAMADA S, HIRATA K, TOMIYA T, OHTA Y: "Activated Kupffer Cells as a Factor of Massive Hepatic Necrosis after Liver Resection." Hepato-Gastroenterology,. 37. 194-197 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] MOCHIDA S, OGATA I, HIRATA K, OHTA Y, YAMADA S, FUJIWARA K.: "Provocation of Massive Hepatic Necrosis by Endotoxin after Partial Hepatectomy in Rats." Gastroenterology. 99. 771-777 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] HIRATA K, FUJIWARA K.: "Possible Contribution of Protein Kinase C Activation to Priming for DNA Synthesis Induced by Epidermal Growth Factor with Insulin and its Inhibition by Plasma Membrane in Primary Cultured Rat Hepatocytes." Biochem. Biophys. Res. Commun.171. 1093-1098 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] FUJIWARA K, OGATA I, SATO Y, TOMIYA T, OHTA Y, NAGOSHI S, YAMADA S, MASAKI N, TAKATSUKI K, HAYASHI S, OKA H.: "Insulin and Glucagon Therapy of Acute Hepatic Failure." Dig. Dis. Sci.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] OHNO A, HIRATA K, OHTA Y, YAMADA S, MOCHIDA S, FUJIWARA K.: "Ruffle Formation in the Evaluation of Stimulatory State of Hepatic Macrophages in Rats." Liver.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] YAMADA S, MOCHIDA S, OHNO A, HIRATA K, OGATA I, OHTA Y, FUJIWARA K.: "Evidence for Enhanced Function of Hepatic Macrophages after Long-term Ethanol Feeding in Rats." Liver.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] MOCHIDA S, OGATA I, FUJIWARA K.: "Method for in situ Evaluation of Superoxide Production by Pulmonary Macrophages in the Rat." Acta Pathol. Jpn.,.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] MOCHIDA S, MASAKI N, OHTA Y, OGATA I, MATUI Y, FUJIWARA K.: "In Situ Detection of Lipid Peroxidation in Rat Hepatocytes." Gastoenterology,.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] MOCHIDA S, OHTA Y, OGATA I, FUJIWARA K: "Gut-derived Substances in Activation of Hepatic Macrophages after Partial Hepatectomy in Rats." J. Hepatol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] TOMIYA T, SATO Y, MURAKAMI Y, NAGOSHI S, OGATA I, FUJIWARA K: "Ornithine Decarboxylase Induction in Partially Hepatectomized Rat Liver and Modes of its Stimulation by Glucagon and Insulin" J. Biohem.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] NAGOSHI S, TOMIYA T, SATO Y, OKA Y, OGATA I, FUJIWARA K: "Stimulation of Putrescine Production by Epidermal Growth Factor in Rat Liver after Partial Hepatectomy." Hepatology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] TOMIYA T, NAGOSHI S, FUJIWARA K.: "Significance of Serum Human Hepatocyte Growth Factor Levels in Patients with Hepatic Failure." Hepatology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] HIRATA K, FUJIWARA K.: "Rat Liver Plasma Membrane has Both Stimulatory and Inhibitory Factors for DNA Synthesis by Primary Cultured Rat Hepatocytes in the Presence of Epidermal Growth Factor and Insulin." Biochem Biophys. Res. Comm.,.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fujiwara K.: "Reciprocal changes in serum albumin and alphaーfetoprotein levels in the recovery course of acute viral hepatitisーstimulated by glucagon and insulin therapy:Analysis of a double blidd controlled trial." Gastroenterol.Jpn.24. 143-148 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tomiya T.: "Plasma alpha2ーplasmin inhibitorーplasmin complex and FDPーDーDimer in fulminant hepatic failure." Thrombosis Res.53. 253-260 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tomiya T.: "Increased thrombin generation in fulminant hepatic failure evaluated by plasma thrombinーantithrombin III complex levels after treatment with antithrombin III." Biomed.Progr.3. 39-40 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hirata K.: "Hepatic sinusoidal cell destruction in the development of intravascular coagulation in acute liver failure of rats." J.Pathol.158. 157-165 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamada S.: "Intravascular coagulation in the development of massive hepatic necrosis induced by Corynebacterium parvum and endotoxin in rats." Scand.J.Gastroenterol.24. 293-298 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Mochida S.: "In situ evaluation of stimulatory state of hepatic macrophage based on ability to produce superoxide anions in rats." J.Pathol.158. 67-71 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sato Y.: "Additive stimulation of hepatic putrescine production by glucagon and insulin after partial hepatectomy in rats." Life Sci.41. 77-83 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Fujiwara K.: "Activated Kupffer cells as a factor of massive hepatic necrosis after liver resection." HepatoーGastroenterology. 37. 194-197 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Mochida S.: "Provocation of massive hepatic necrosis by endotoxin after partial hepatectomy in rats." Gastroenterology. 99. 771-777 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hirata K.: "Contribution of protein kinase C activation to priming for DNA synthesis induced by epidermal growth factor with insulin and its inhibition by plasma membrane in primary cultured rat hepatocytes." Biochem.Biophys.Res.Commun.171. 1093-1098 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Fujiwara K.: "Insulin and glucagon therapy of acute hepatic failure." Dig.Dis.Sci.

    • Related Report
      1990 Annual Research Report
  • [Publications] Ohno A.: "Ruffle formation in the evaluation of stimulatory state of hepatic macrophages in rats." Liver.

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamada S.: "Evidence for enhanced function of hepatic macrophages after longーterm ethanol feeding in rats." Liver.

    • Related Report
      1990 Annual Research Report
  • [Publications] Mochida S.: "Method for in situ evaluation of pulmonary macrophages' ability to produce superoxide in the rat." Acta Pathol.Jpn.

    • Related Report
      1990 Annual Research Report
  • [Publications] Mochida S.: "In situ detection of lipid peroxidation in hepatocytes." Gastroenterology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Mochida S.: "Gutーderived substances in activation of hepatic macrophages after partial hepatectomy in rats." J.Hepatol.

    • Related Report
      1990 Annual Research Report
  • [Publications] Tomiya T.: "Ornithine decarboxvlase induction in partially hepatectomized rat liver and modes of its stimulation by glucagon and insulin." J.Biochem.

    • Related Report
      1990 Annual Research Report
  • [Publications] Nagoshi S.: "Simulation of putrescine production by epidermal growth factor in rat liver after partial hepatectomy." Hepatology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Tomiya T.: "Significance of serum human hepatocyte growth factor levels in patients with hepatic failure." Hepatology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hirata K.: "Rat liver plasma membrane has both stimulatory and inhibitory factors for DNA synthesis by primary cultured rat hepatocytes in the presence of epidermal growth factor and insulin" Biochem.Biophys.Res.Commun.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hirata K.: "Rat liver plasma membrane has both stimulatory and inhibitory factors for DNA synthesis by primary cultured rat hepatocytes in the presence of epidermal growth factor and insulin" Biochem.Biophys.Res.Commun.Fujiwara K.:

    • Related Report
      1990 Annual Research Report
  • [Publications] Fujiwara K.: "Reciprocal changes in serum albumin and alpha-fetoproteir levels in the recovery course of acute vinal hepatitis stimulated by glucagon and insulin:Analysis of a double blind cohtrolled trial" Gatroenterol.Jpn.24. 143-148 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Tomiyama T.: "Plasma alpha2-plasmin inhibitor-plasmin complex and FDPD-Dimer infulminant hepatic failure" Throm.Res.53. 253-260 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yamada S.: "Intravascular coagulation in the development of massive hepatic necrosis induced by Corynebacterium parvum and endotoxin in rats" Scand.J.Gastroenterol.24. 293-298 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Hirata K.: "Hepatic sinusoidal cell destruction in the development of intravascular coagulation in acute liver failure of rats" J.Pathol.158. 157-165 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Tomiya T.: "Increased thrombin generation in fulminant hepatic failure evaluated by plasma thrombin-antithrombin III complex levels after treatment with antithrombin III" Biomed.Progr.2. 39-40 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Sato Y.: "Additive stimulation of hepatic putrescine production by glucagon and insulin after partial hepatectomy in rats" Life Sci.41. 77-83 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Mochida S.: "In situ evaluation of stimulatory state of hepatic macrophage based on ability to produce superoxide anions in rats" J.Pathol.158. 67-71 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Sakamoto K.: "Rat epidermal growth factor:purification and tissus content" Endocrinol.Jpn.36. 289-267 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Mochida S.: "Provocation of massive hepatic necrosis by endotoxin after partial hepatectomy in rats" Gastroenterology,submitted.

    • Related Report
      1989 Annual Research Report
  • [Publications] Tomiya T.: "Molecular mechanisms of ornithine decarboxylase induction in hepatecomized rat liver and action sites of glucagon and insulin in its stimulation" J.Biol.Chem.

    • Related Report
      1989 Annual Research Report
  • [Publications] Nagoshi S.: "Stimulation of putrescine production by epidermal growth factor in rat liver after partial hepatectomy" Hepatology.

    • Related Report
      1989 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi