1992 Fiscal Year Annual Research Report

肝壊死-再生の病態連繋機構に関する研究

Research Project

Project/Area Number	04304038
Research Institution	Gifu University
Principal Investigator	武藤泰敏岐阜大学, 医学部, 教授 (20010069)
Co-Investigator(Kenkyū-buntansha)	沖田極山口大学, 医学部, 教授 (70107738) 鎌田武信大阪大学, 医学部, 教授 (80028399) 和気健二郎東京医科歯科大学, 医学部, 教授 (00046963) 黒川清東京大学, 医学部, 教授 (30167390) 水戸廸郎旭川医科大学, 教授 (60000981)
Keywords	細胞障害性T細胞 / 細胞外マトリックス / 肝細胞増殖仰制因子 / TGF-β / 肝微小循環 / 接着分子 / 肝細胞多層集合体 / 伊東細胞
Research Abstract	1.肝壊死の免疫学的機構:(1)C型肝炎ウイルスコア抗原を認識する細胞障害性T細胞をC型肝炎者から誘導でき、これは内因性に発現する抗原も認識することが判明した。(2)サイトカインによる肝細胞障害には活性酸素の関与が示唆された。2.細胞外マトリックス:ラット肝障害モデルでは、肝小葉内のヘパラン硫酸プロテオグリカン(PG)は肝壊死の進行とともに染色性が低下し、再生とともに回復したが、コンドロイチン硫酸PGは一過性の染色性増強の後に再生とともに染色性が低下し、PGと再生との関連が明らかにされた。3.肝細胞増殖因子(HGF)ならびに阻害因子:HGFはNa^+/H^+antiporter活制化により細胞内pHの上昇がもたらされることが示された。また、HGFレセプターであるc-Metの肝再生時の動態が明らかとなった。一方、肝細胞増殖仰制作用を有するTGF-βを分離肝細胞に添加すると、その除去後にEGFを加えても肝細胞の増殖作用が阻止されることが示された。さらに劇症肝炎患者血中の新たな肝再生仰制因子の精製が進められた。4.動物モデルの作製:肝壊死と肝再生障害を認める動物モデルが作製され、その機序として再生肝細胞に対する特異的な障害活性を有する細胞群の存在による可能性が示され、接着分子との関連についての実験的な検討がおこなわれた。また四塩化炭素による肝壊死後には星細胞を含む肉芽腫形成がみられ、肝線維化との関連が報告された。5.肝微小循環動態:収縮性蛋白を豊富に持つ伊東細胞が肝類洞の血流を調節している可能性が示唆された。6.ハイブリッド型人工肝臓:人工基質材料(PVLA)上で細胞間マトリックスを有する三次元的生着形態を有する肝細胞多層集合体が形成され、これは肝細胞の特異的機能を長期間にわたって維持しえた。また、アルギン酸カルシウム被包化肝細胞の腹腔内移植によりD-galによる急性肝不全の発症が阻止し得、その機序として網内系を介することが示された。

Research Products

(38 results)

All Other

All Publications (38 results)

[Publications] Yasutoshi Muto: "Fulminant Hepatitis-Is the Survival Improving?" Gastroenterol Jpn. 27. 142-144 (1992)
[Publications] Yoshihide Ishiki: "Direct Evidence that Hepatocyte Growth Facter is a Hepatotrohic Factor for Liver Regeneration and has a Potent Antihepatitis Effect in Vivo" Hepatology. 16. 1227-1235 (1992)
[Publications] Nobuo Murakami: "Chenges in Brain Momoamine Metabolism in Rats with Acute Ischemic Hepatic Failure Under Artificial Cardiopulmonary Management" Gastroenterol Jpn. 27. 191-198 (1992)
[Publications] Yoichiro Ito: "Pathophysiological Role of Intestinal Fiora in the Developmens of Hepatic Encephalopathy,with Special Reference to Floral Alteration Induced by Antinicrobial Agents" Microbial Ecol Health Dis. 5. 1-13 (1992)
[Publications] S.Kasai: "Beneficial Effect of Hepatocyte Transplantation on Hepatic Failure" Transplantation Proceedings. 26. 2990-2992 (1993)
[Publications] Takeshi Kugumiya: "Investigation of Dynamic Behaveors of Asialoglycoprotein Receptors of Hepatocytes Using a Latex Probe Whose Surface Was Coated With Lactose-Carrying Polystytene" J.Bioactive Compatible Polym. 7. 337-345 (1192)
[Publications] 小林明: ""肝細胞の分化・増殖を制御するアシアロ糖タンパクモデル接着基質の設計とその応用"" 人工臓器. 21(3). 1060-1064 (1992)
[Publications] Akira Kobyashi: "¨Control of Adhesion and Detechment of Parenchymal Liver Cells Using Lactose-Carrying Polystyrene as Substratum¨" J.Biomater.Sci.Polymer Ed. 3. 499-508 (1992)
[Publications] Seishiro Tobe: "¨Receptor-Mediated Formation of Multilayer Aggregates of Primary Cultured Adult Rat Hepatocytes on Lactose-Substituted Polyrene¨" Biochim Biophys Res Commun. 184. 225-230 (1992)
[Publications] 赤池敏宏: ""ハイブリッド人工肝臓の実用化への展望と課題"" 日本外科学会雑誌92,. 1272-1275 (1991)
[Publications] H.Yamada: "Furgher Purification and Characterization of Inhibitor of DNA Synthesis in Rat Hepatocyets from Blood of Fulminant Hepatic Failure Patients" Hepatology. 16. 179A (1992)
[Publications] 山田春木: "劇症肝炎患者血中の呼再生仰制物質-HPLCを用いた部分精製" 肝臓. 33. 238 (1992)
[Publications] M.Goto: "Hepatic Tissus Oxygenation as a Predictive Indication of Ishemic-reperfusion Liver Injury" Hepatology. 15. 432-437 (1992)
[Publications] 大井手弘純: "伊東細胞・細胞骨格と収縮" 肝胆膵. 24. 915-920 (1992)
[Publications] 和気健二郎: "網内系学説と現在の肝類洞壁細胞像" 日本網内系学会会誌. 32. 3-11 (1992)
[Publications] 和気健二郎: "肝類洞壁の構造" 肝胆膵. 24. 833-838 (1992)
[Publications] Ekapot Bhunchet: "Role of Mesenchymal Cell Population in Porcine Serum-Induced Rat Liver Fibrogenesis" Hepatology. 16. 1452-1473 (1992)
[Publications] Shinichi Kakumu: "Localization of Intrehepatic Interleukin 6 in Patients with Acute and Chronic Liver Disease" J Clin Pathol. 45. 408-411 (1992)
[Publications] Shinichi Kakumu: "Effects of Transtorming Growth Factor Veta I Against Inhibitory Action of Interferon on DNA Synthesis and Viral Replication in Hepatitis B Virus-transfected Cells" J Med Virol. 38. 62-66 (1992)
[Publications] A Kaneko: "Intracellular Calcium as a Second Messenger for Human Hepatocyte Growth Factor in Hepatocyte" Hepatology. 15. 1173-1178 (1992)
[Publications] Y Tanaka: "Epidermal Growth Facter Induces Dose-dependent Calcium Oscillations in Single Fura-2-loaded Hepatocytes" Hepatology. 16. 479-486 (1992)
[Publications] A Kaneko: "Changes in Serum Hepatocyte Growth Factor Levels After Transcatheter Aterial Embolezation and Partial Hepatectomy" The American Journal of Gastroenterology. 87. 1014-1017 (1992)
[Publications] N Yuki: "Improved Serodiagnosis of Chronic Hepatitis C in Japan by a Second-genaration Enzyme-linked Immunosorbent Assay" J.Med.Virol. 37. 237-240 (1992)
[Publications] H Hagiwara: "Detection of Hepatitis C Virus RNA in Serum of Patients with Chronic Hepatitis C Treated with Interferon-α" Hepatology. 15. 37-41 (1992)
[Publications] 辻孝夫: "鑑別診断のすすめ方" 臨床と研究. 69. 1033-1038 (1992)
[Publications] 辻孝夫: "高齢者の肝炎、肝硬変" 老年消化器病. 4. 11-18 (1992)
[Publications] 辻孝夫: "C型慢性肝炎と漢方薬" 医学のあゆみ. 161. 352-354 (1992)
[Publications] 辻孝夫: "B型肝炎" 総合臨床. 41. 1545-1547 (1992)
[Publications] M Kawaguchi: "Combination of Epidermal Growth Factor and Insulin is Required for Multicellular Spheroid Formation of Rat Hepatocytes in Primary Culture" Acta Med Okayama. 46. 195-201 (1992)
[Publications] 森健治: "各種肝疾患における血清中Thrombomodulinの臨床的意義-急性肝不全を中心として-" 肝臓. 33. 147-152 (1992)
[Publications] 萱野幸三: "急性肝障害における血清TNF-αの臨床的検討" 肝臓. 33. 213-218 (1992)
[Publications] K Kayano: "Detection of Proliterating Hepatocytes by Immunohistochemical Staining for Proliferating Cell Nuclear Antigen (PCNA) in Patients with Acute Hepatic Failure" Liver. 12. 132-136 (1992)
[Publications] 水戸廸郎編: "肝再生をめぐる基礎と臨床" 東洋出版, 103 (192)
[Publications] R Williams編: "Acute Liver Failure,Improved Understanding and Better Therapy" Smithkline Beacham Pharmacenticals UK, 114 (1991)
[Publications] Kenjiro Wake: "Molecular and Cell Biology of Liver Fibrogenesis" Kiuwer Academic Publishers(Dordrecht/Boston/London), -555 (1992)
[Publications] 岸江孝男: "マクロファージ実験マニュアル" 講談社サイエンティフィク, -250 (1992)
[Publications] 辻孝夫: "臓器と免疫" 文永堂出版, 978 (1992)
[Publications] Takao Tsuji: "Immune Response and Interferon Treatment in Viral Hepatitis" Nankodo, 117 (1992)

1992 Fiscal Year Annual Research Report

肝壊死-再生の病態連繋機構に関する研究

Principal Investigator

武藤 泰敏 岐阜大学, 医学部, 教授 (20010069)

Research Products

[Publications] Yasutoshi Muto: "Fulminant Hepatitis-Is the Survival Improving?" Gastroenterol Jpn. 27. 142-144 (1992)

[Publications] Yoshihide Ishiki: "Direct Evidence that Hepatocyte Growth Facter is a Hepatotrohic Factor for Liver Regeneration and has a Potent Antihepatitis Effect in Vivo" Hepatology. 16. 1227-1235 (1992)

[Publications] Nobuo Murakami: "Chenges in Brain Momoamine Metabolism in Rats with Acute Ischemic Hepatic Failure Under Artificial Cardiopulmonary Management" Gastroenterol Jpn. 27. 191-198 (1992)

[Publications] Yoichiro Ito: "Pathophysiological Role of Intestinal Fiora in the Developmens of Hepatic Encephalopathy,with Special Reference to Floral Alteration Induced by Antinicrobial Agents" Microbial Ecol Health Dis. 5. 1-13 (1992)

[Publications] S.Kasai: "Beneficial Effect of Hepatocyte Transplantation on Hepatic Failure" Transplantation Proceedings. 26. 2990-2992 (1993)

[Publications] Takeshi Kugumiya: "Investigation of Dynamic Behaveors of Asialoglycoprotein Receptors of Hepatocytes Using a Latex Probe Whose Surface Was Coated With Lactose-Carrying Polystytene" J.Bioactive Compatible Polym. 7. 337-345 (1192)

[Publications] 小林 明: ""肝細胞の分化・増殖を制御するアシアロ糖タンパクモデル接着基質の設計とその応用"" 人工臓器. 21(3). 1060-1064 (1992)

[Publications] Akira Kobyashi: "¨Control of Adhesion and Detechment of Parenchymal Liver Cells Using Lactose-Carrying Polystyrene as Substratum¨" J.Biomater.Sci.Polymer Ed. 3. 499-508 (1992)

[Publications] Seishiro Tobe: "¨Receptor-Mediated Formation of Multilayer Aggregates of Primary Cultured Adult Rat Hepatocytes on Lactose-Substituted Polyrene¨" Biochim Biophys Res Commun. 184. 225-230 (1992)

[Publications] 赤池 敏宏: ""ハイブリッド人工肝臓の実用化への展望と課題"" 日本外科学会雑誌92,. 1272-1275 (1991)

[Publications] H.Yamada: "Furgher Purification and Characterization of Inhibitor of DNA Synthesis in Rat Hepatocyets from Blood of Fulminant Hepatic Failure Patients" Hepatology. 16. 179A (1992)

[Publications] 山田 春木: "劇症肝炎患者血中の呼再生仰制物質-HPLCを用いた部分精製" 肝臓. 33. 238 (1992)

[Publications] M.Goto: "Hepatic Tissus Oxygenation as a Predictive Indication of Ishemic-reperfusion Liver Injury" Hepatology. 15. 432-437 (1992)

[Publications] 大井手 弘純: "伊東細胞・細胞骨格と収縮" 肝胆膵. 24. 915-920 (1992)

[Publications] 和気 健二郎: "網内系学説と現在の肝類洞壁細胞像" 日本網内系学会会誌. 32. 3-11 (1992)

[Publications] 和気 健二郎: "肝類洞壁の構造" 肝胆膵. 24. 833-838 (1992)

[Publications] Ekapot Bhunchet: "Role of Mesenchymal Cell Population in Porcine Serum-Induced Rat Liver Fibrogenesis" Hepatology. 16. 1452-1473 (1992)

[Publications] Shinichi Kakumu: "Localization of Intrehepatic Interleukin 6 in Patients with Acute and Chronic Liver Disease" J Clin Pathol. 45. 408-411 (1992)

[Publications] Shinichi Kakumu: "Effects of Transtorming Growth Factor Veta I Against Inhibitory Action of Interferon on DNA Synthesis and Viral Replication in Hepatitis B Virus-transfected Cells" J Med Virol. 38. 62-66 (1992)

[Publications] A Kaneko: "Intracellular Calcium as a Second Messenger for Human Hepatocyte Growth Factor in Hepatocyte" Hepatology. 15. 1173-1178 (1992)

[Publications] Y Tanaka: "Epidermal Growth Facter Induces Dose-dependent Calcium Oscillations in Single Fura-2-loaded Hepatocytes" Hepatology. 16. 479-486 (1992)

[Publications] A Kaneko: "Changes in Serum Hepatocyte Growth Factor Levels After Transcatheter Aterial Embolezation and Partial Hepatectomy" The American Journal of Gastroenterology. 87. 1014-1017 (1992)

[Publications] N Yuki: "Improved Serodiagnosis of Chronic Hepatitis C in Japan by a Second-genaration Enzyme-linked Immunosorbent Assay" J.Med.Virol. 37. 237-240 (1992)

[Publications] H Hagiwara: "Detection of Hepatitis C Virus RNA in Serum of Patients with Chronic Hepatitis C Treated with Interferon-α" Hepatology. 15. 37-41 (1992)

[Publications] 辻 孝夫: "鑑別診断のすすめ方" 臨床と研究. 69. 1033-1038 (1992)

[Publications] 辻 孝夫: "高齢者の肝炎、肝硬変" 老年消化器病. 4. 11-18 (1992)

[Publications] 辻 孝夫: "C型慢性肝炎と漢方薬" 医学のあゆみ. 161. 352-354 (1992)

[Publications] 辻 孝夫: "B型肝炎" 総合臨床. 41. 1545-1547 (1992)

[Publications] M Kawaguchi: "Combination of Epidermal Growth Factor and Insulin is Required for Multicellular Spheroid Formation of Rat Hepatocytes in Primary Culture" Acta Med Okayama. 46. 195-201 (1992)

[Publications] 森 健治: "各種肝疾患における血清中Thrombomodulinの臨床的意義-急性肝不全を中心として-" 肝臓. 33. 147-152 (1992)

[Publications] 萱野 幸三: "急性肝障害における血清TNF-αの臨床的検討" 肝臓. 33. 213-218 (1992)

[Publications] K Kayano: "Detection of Proliterating Hepatocytes by Immunohistochemical Staining for Proliferating Cell Nuclear Antigen (PCNA) in Patients with Acute Hepatic Failure" Liver. 12. 132-136 (1992)

[Publications] 水戸 廸郎編: "肝再生をめぐる基礎と臨床" 東洋出版, 103 (192)

[Publications] R Williams編: "Acute Liver Failure,Improved Understanding and Better Therapy" Smithkline Beacham Pharmacenticals UK, 114 (1991)

[Publications] Kenjiro Wake: "Molecular and Cell Biology of Liver Fibrogenesis" Kiuwer Academic Publishers(Dordrecht/Boston/London), -555 (1992)

[Publications] 岸江 孝男: "マクロファージ実験マニュアル" 講談社サイエンティフィク, -250 (1992)

[Publications] 辻 孝夫: "臓器と免疫" 文永堂出版, 978 (1992)

[Publications] Takao Tsuji: "Immune Response and Interferon Treatment in Viral Hepatitis" Nankodo, 117 (1992)

武藤泰敏岐阜大学, 医学部, 教授 (20010069)

[Publications] 小林明: ""肝細胞の分化・増殖を制御するアシアロ糖タンパクモデル接着基質の設計とその応用"" 人工臓器. 21(3). 1060-1064 (1992)

[Publications] 赤池敏宏: ""ハイブリッド人工肝臓の実用化への展望と課題"" 日本外科学会雑誌92,. 1272-1275 (1991)

[Publications] 山田春木: "劇症肝炎患者血中の呼再生仰制物質-HPLCを用いた部分精製" 肝臓. 33. 238 (1992)

[Publications] 大井手弘純: "伊東細胞・細胞骨格と収縮" 肝胆膵. 24. 915-920 (1992)

[Publications] 和気健二郎: "網内系学説と現在の肝類洞壁細胞像" 日本網内系学会会誌. 32. 3-11 (1992)

[Publications] 和気健二郎: "肝類洞壁の構造" 肝胆膵. 24. 833-838 (1992)

[Publications] 辻孝夫: "鑑別診断のすすめ方" 臨床と研究. 69. 1033-1038 (1992)

[Publications] 辻孝夫: "高齢者の肝炎、肝硬変" 老年消化器病. 4. 11-18 (1992)

[Publications] 辻孝夫: "C型慢性肝炎と漢方薬" 医学のあゆみ. 161. 352-354 (1992)

[Publications] 辻孝夫: "B型肝炎" 総合臨床. 41. 1545-1547 (1992)

[Publications] 森健治: "各種肝疾患における血清中Thrombomodulinの臨床的意義-急性肝不全を中心として-" 肝臓. 33. 147-152 (1992)

[Publications] 萱野幸三: "急性肝障害における血清TNF-αの臨床的検討" 肝臓. 33. 213-218 (1992)

[Publications] 水戸廸郎編: "肝再生をめぐる基礎と臨床" 東洋出版, 103 (192)

[Publications] 岸江孝男: "マクロファージ実験マニュアル" 講談社サイエンティフィク, -250 (1992)

[Publications] 辻孝夫: "臓器と免疫" 文永堂出版, 978 (1992)