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Intravital Analysis of Oxidative Stress During Organ Circulatory Failure

Research Project

Project/Area Number 63440033
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionDepartment of Internal Medicine, School of Medicine, Keio University

Principal Investigator

TSUCHIYA Masaharu  MD Professor, 医学部・消化器内科, 教授 (60051124)

Co-Investigator(Kenkyū-buntansha) SUEMATSU Makoto  Instructor, 医学部・消化器内科, 助手 (00206385)
MIURA Soichiro  Associate Professor, 医学部・消化器内科, 講師 (50138012)
朴沢 重成  慶應義塾大学, 医学部・消化器内科, 助手 (40181482)
Project Period (FY) 1988 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 1990: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1988: ¥9,500,000 (Direct Cost: ¥9,500,000)
Keywordsoxygen radicals / digital imaging / photonic intensifier / microcirculation / chemiluminescence / dichlorofluorescin diacetate / ischemia / oxidative stress / 虚血 / 化学発光 / dichlorofluorescin / digital image processor / 血小板活性化因子(PAF) / 微小循環障害
Research Abstract

This project was aimed to establish the methodology to investigate microtopography of oxygen radical formation in microcirculatory units. Recent development of digital imaging photonic microscopy has made it possible to analyze spatial and temporal alterations of oxyradical generation during tissue injury. Luminol-dependent photonic imaging revealed granulocyte-mediated oxidative stress during microvascular damage induced by platelet-activating factor or endotoxin. Our data also demonstrated that the interface between venular indothelium and sticking granulocytes may be the most critical site of oxidant-dependent cellular damage. We have developed another new method to visualize intracellular oxidative stress in the isolated perfused rat liver using digital imaging microfluorography and a hydroperoxide-sensitive fluorescence dye, dichlorofluorescin diacetate. In the experimental model of carbon tetrachloride-induced hepatic injury, the method has revealed that cytochrome P450-dependent oxidant formation takes place predominantly in pericentral regions, preceding cell death at the same area. The current technique will provide a useful method to investigate the microtopograp hy of organ microcirculatory oxidative stress associated with xenobiotic metabolism or circulatory failure.

Report

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

    (57 results)

All Other

All Publications (57 results)

  • [Publications] M.Suematsu,et.al.,: "Luminolーdependent photoemission from single neutrophil stimulated by phorbol ester and calcium ionophore" Biochem.Biophys.Res.Commun.155. 106-111 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M.Suematsu,et.al.: "Effects of serine protease inhibitors on oxyradical burst from phagocytizing neutrophils" J.Biolum.Chemilum.4. 531-534 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M.Suematsu,et.al.: "In vivo visualization of oxyradicalーdependent photoemission during endotheliumーgranulocyte interaction in microcirculatory beds treated with plateletーactivating factor" J.Biochem.106. 355-360 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M.Suematsu,et.al.: "Intralobular heterogneity of carbon tetrachlorideーinduced oxidative stress in perfused rat liver visualized by digital fluorescence microscopy" Lab.Invest.64. 167-173 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M.Suematst,et.al.: "Microtopographic analysis of axidative stress in organ microcirculatory units" Adv.Exp.Biol.Med.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M.Suematsu,et.al: "Midzonal oxidative stress preceding cell death in hypoperfused rat liver" J.Clin.Invest.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tsuchiya,M.,et.al.: "Free Radicals in Digestive Diseases" Elsevier,Amsterdam, 244 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tsuchiya,M.,et.al.: "Proceeding of the VIth International Congress for Mucosal Immunology" Elsevier,Amsterdam, (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tsuchiya, M., Suematsu, M., Miura, S., Suzuki, M., Yamakawa, H.: "Les aspects microcirculatoires du phenomene de Reilly." Bull. Acad. Natle. Med. 172. 409-419 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suzuki, M., Suematsu, M., Miura, S., Oshio, C., Oda, M., Tsuchiya, M.: "Microcirculatory disturbances in endotoxin-induced disseminated intravascular coagulation-The effect of heparin and gabexate mesilate on locomotive and metabolic changes of neutrophils." Adv. Exp. Med. Biol.242. 161-175 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Oda, M., Nakamura, M., Honda, K., Komatsu, H., Kaneko, K., Azuma, T., Suematsu, M., Yonei, Y., Watanabe, N., Tsuchiya, M.: "Alterations in gastric mucosal microvascular endothelium in a stress condition. -relevance to gastric ulcerogenesis." Adv. Exp. Med. Biol.242. 161-175 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kitahora, T., Suzuki, K., Asakura, H., Yoshida, T., Suematsu, M., Watanabe, M., Aiso, S., Tsuchiya, M.: "Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease." Dig. Dis. Sci.33. 951-955 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Miura, S., Tanaka, S., Suematsu, M., Suzuki, M., Houzawa, S., Nagata, H., Asakura, H., Tsuchiya, M.: "Movement analysis of lymphocyte migration to Peyer's patches of the intestine." Gastrointestinal Function, Vol. 6, eds. Tsuchiya, M., et al.Excerpta Medica, Tokyo. 87-102 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kurose, I., Maruyama, K., Suzuki, M., Azuma, T., Suematsu, M., Miura, S., Okazaki, I., Oda, M., Tsuchiya, M.: "Oxyradical mediated activation of tissue-type plasminogen activator in the rat acute gastric mucosal injury." Microcirculation annual 1988, eds. Tsuchiya, M., et al.Nihon Igakukan, Tokyo. 71-72 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suzuki, M., Suematsu, M., Miura, S., Houzawa, S., Nagata, H., Morishita, T., Tsuchiya, M.: "Neutrophil -related capillary obstruction during gastric mucosal injury-Dynamic analysis using acridine orange-labelled neutrophils." Microcirculation annual 1988, eds. Tsuchiya, M., et al.Nihon Igakukan-kan, Tokyo. 101-102 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Oda, M., Watanabe, N., Komatsu, H., Suematsu, M., Kaneko, K., Azuma, T., Nishizaki, Y., Nakamura, M., Fujiwara, T., Tsuchiya, M.: "Electron microscopic demonstration of free calcium in the capillary endothelium in comparison with computarized image analysis using fura-2" AM. J. Clin. Electron Microscopy. 21. 5-6 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suematsu, M., Miura, S., Suzuki, M., Nagata, H., Morishita, T., Oshio, C., Tsuchiya, M.: "5-1ipoxygenase inhibitor (AA-861) attenuates neutrophil-mediated oxidative stress on the venular endothelium in endotoxemia." J. Clin. Lab. Immunol.25. 41-45 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suematsu, M., Oshio, C., Miura, S., Suzuki, M., Houzawa, S., Tsuchiya, M.: "Luminol-dependent photoemission from single neutrophil stimulated by phorbol ester and calcium ionjphorerole of degranulation and myelperoxidase." Biochhm. Biophys. Res. Commun.155. 106-111 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suzuki, M., Suematsuz, M., Miura, S., Houzawa, S., Nagata, H., Morishita, T., Osa, M., Tsuchiya, M.: "Neutrophil-mediated oxidative stress during acute gastric mucosal injury." Medical, Biochemical and chemical Aspects of Free Radicals, eds. Hayaishi, O., et al.Elsevier, Amsterdam. 1433-1436 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sumatsu, M., Suzuki, M., Kuratsuji, T., Oshio, C., Miura, S., Nagata, H., Morishita, T., Tsuchiya, M.: "Real-time visualization of luminol-dependent chemiluminescence from single neutrophil." Medical, Biochemical and Chemical Aspects of Free Radicals, eds. Hayaishi, O., et al.Elsevire, Amsterdam. 891-894 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suematsu, M., Oshio, C., Kurose, I., Miura, S., Asako, H., Sekizuka, E., Houzawa, S,, Nagata, H., Tsuchiya, M: "Profeie analysis of oxyradical diffusion from a single neutrophil using photonic image intensifier microscopy" Cytoprotection and Cytobiology Vol. 6, eds. Nagamachi, Y., et al .Cytomedica London. 321-326 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suematsu, M., Suzuki, M., Nagata, H., Miura, S., Houzawa, S., Morishita, T., Tsuchiya, M.: "Role of neutrophil-mediated oxidative stress in acute gatric mucosal injury induced by microvascular derangement." Free Radicals in Digestive Diseases, eds. Tsuchiya, M., et al.Eiseveer, Amsterdam. 67-72 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Morishita, T., Nagata, H., Suematsu, M., Houzawa, S., Sawaguchi, K., Sekizuka, E., Miura, S., Oshio, C., Oda, M., Tsuchiya, M.: "Effects of microspheres on the formation of gastric ulcer." Microcirculation annual 1989, eds. Tsuchiya, M., et al.Nihon Igaku-kan, Tokyo. 89-90 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Oshiro, C., Sekizuka, E., Minamitani, H., Nagata, H., Morishita, T., Suematsu, M., Tsuchiya, M.: "Relationship between portal hypertension and intestinal lymph flow." Microcirculation annual 1989, eds. Tsuchiya, M., et al.Nihon Igaku-kan, Tokyo. 109-110 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kurose, I., Suematsu, M., Asako, H., Houazawa, S., Miura, S., Sekizuka, E., Nagata, H., Oshio, C., Tsuchiya, M.: "Visualization of oxyradical-generating sites in rat mesenteric microvascular beds treated with platelet-activating factor." Microcirculation annual 1989, eds. Tsuchiya, M., et al.Niho Igaku-kan, Tokyo. 151-152 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Okada, E., Minamitani, H., Fukuoka, Y., Sekizuka, E., Oshio, C., Suematsu, M., Tsuchiya, M.: "A new arrangement of microscopic laser doppler velocimeter for precise RBC velocity measurement." Microcirculation annual 1989, eds.Nihon Igaku-kan, Tokyo. 161-162 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suematsu, M., Kato, S., Oshio, C., Isii, H., Tsuchiya, M.: "Spatial and temporal analysis of intravital oxidative stress in organ microcirculatory system-The application of digital imaging photonic microscopy." Cell Str. Funct.14. 812 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suematsu, M., Kurose, I., Asako, H., Miura, S., Tsuchiya, M.: "visualization of oxyradical-dependent photoemission during endothelium-granulocyte interaction in microvascular beds treated with platelet-activating factor." J. Biochem.106. 355-360 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suematsu, M., Houzawa, S., Miura. S., Nagata, H., Kitahora, T., Morishita, T., Oshio. C., Tsuchiya, M .: "Effects of serine protease inhibitors on oxyradical burst from phagocytizing neutrophils-Analysis by chemiluminescence counting and its microscopic imaging." J. Biolum. Chemilum. 4. 531-534 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nagata, H., Sekizuka, E., Oshio, C., Suematsu, M., Miura, S., Houzawa, S., Morishita, T., Tsuchiya, M.: "Alteration of intestinal microcirculation during portal pressure elevation." J. Gastroenterol. Hepatol.(Supplement) 1. 117-118 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kurose, I., Miura, M., Suematsu, M., Asako, H., Serizawa, H., Ogata, H., Hibi, T., Tsuchiya, M.: "Possible involvement of fissue-type plasminogen activator in gastric ulcer formation-Biochimical evaluation using biopsy specimens from gastric mucosa." Dig. Endosc.2. 49-53 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukumura, D., Kurose, I., Miura, S., Suematsu, M., Sekizuka, E., Tashiro, H., Serizawa, H., Asako, H., Nagata, H., Tsuchiya, M.: "Intravital observation of rat interstinal microcirculatory changes induced by endothelin" Microcirculation annual 1990, eds. Tsuchiya, M., et al. Nihon Igaku-kan, Tokyo. 41-42 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Morishita, T., Sekizuka, E., Nagata, H., Houzawa, S., Miyairi, M., Suzuki, H., Suematsu, M., Oshilo, C., Tsuchiya, M.: "Microcirculatory changes of the stomach in the portal hypertension." Microcirculation annual 1990, eds. Tsuchiya, M., et al.Nihon Igaku-kan, Tokyo. 99-100 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nagata, H., Sekizuka, E., Morishita, T., Oshio, C., Houzawa, S., Suematsu, M., Miura, S., Oda, M., Tsuchiya, M.: "Effect of acute portal hypertension on microvessels of intestinal villi, submucosa and muscle in rat." Microcirculation annual 1990, eds. Tsuchiya, M., et al.Nihon Igku-kan Tokyo. 105-106 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tashiro, H., Miura, S., Serizawa, H., Yoshioka, M., Tanaka, S., Asako, H., Suematsu, M., Kurose, I., Tsuchiya, M., Kudoh, Y: "Involvement of Microcirculatory disturbance in verotoxin-induced hemorrhagic enteritis," Microcirculation annual 1990, eds. Tsuchiya, M., et al.Nihon Igaku-kan, Tokyo. 111-112 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Asako, H., Suematsu, M., Kato, S., Yanagisawa, T., Ukigai, K., Kurose, I., Suzuki, H., Tsuchiya, M.: "Real-time analysis of oxidative stress in perfused rat hepatic microcirculatory units visualized by digital imaging microscopic fluorography." Microcirculation annual 1990, eds. Tsuchiya, M., et la.Nihon Igaku-kan, Tokyo. 121-122 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suzuki, H., Suematsu, M., Sekizuka, E., Shan, Y., Asako, H., Nagata, H., Oshio, C., Miura, S., Tsuchiya, M.: Microcirculation annual 1990, eds. Tsuchiya, M., et al.Nihon Igaku-kan, Tokyo. 157-158 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suematsu, M., Kato, S., Ishii, H., Yanagisawa, T., Asako, H., Suzuki, H., Oshio, C., Tsuchiya, M.: "Intralobular heterogeneity of carbon tetrachloride-induced oxidative stress visualized by digital imaging fluorescence microscopy." Lab. Invest.64. 167- (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suematsu,M.,et.al.: "Intralobular heterogeneity of carbon tetrachlorideーinduced oxidative stress in perfused rat liver visualized by digital imaging fluorescence microscopy." Lab.Invest.64. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Suematsu,M.,et.al.: "Microtopographic analysis of oxidative stress in organ microcirculatory units" Adv.Exp.Med.Biol.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kurose,I.,et.al.,: "Involvement of superoxide anion and plateletーactivating factor in increased tissueーtype plasminogen activator during rat gastric microvascular damages" Thromb.Res.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Miura,S.,et.al.,: "Ischemic bowel necrosis induced by endothelinー1;An experimental model in rats" Digestion. 48. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Suematsu,M.,et.al.,: "Midzonal oxidative stress preceding cell death in hypoperfused rat liver" J.Clin.Invest.

    • Related Report
      1990 Annual Research Report
  • [Publications] 末松 誠: "内毒素血症における内皮ー顆粒球相互反応とoxidative stressの生体内解析" 脈管学. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Suzuki,H.,et.al.,: "Cytoprotection & Biology vol.11." Cytomedica,London., (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Suematsu,M.,: "Effects of serine protease inhibitors on oxyradical burst from phagocytizing neutrophils." J.Biolum.Chemilum.4. 531-534 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suematsu,M.,: "In vivo visualization of oxyradical-dependent photoemission during endothelium-granulocyte interaction in microvascular beds treated with platelet-activating factor." J.Biochem.106. 355-360 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suematsu,M.,: "Platelet-activating factor and granulocyte-mediated oxidative stress-strategy for in vivo oxyradical visualization." Lipids. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suematsu,M.,: "Intralobular heterogeneity of carbon tetrachloride-induced oxidative stress in perfused rat liver visualized by digital imaging fluorescence microscopy." Lab.Invest.

    • Related Report
      1989 Annual Research Report
  • [Publications] 末松誠: "炎症メディエ-タ-による血管内皮ー顆粒球相互反応活性化と活性酸素放出反応の生体内撮像" 炎症. 10. 43-48 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 末松誠: "胃粘膜再灌流障害における血管内皮ー好中球相互反応と酸素ストレスーplatelet-activating factorの役割" 脈管学. 30. 97-101 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Tsuchiya,M.: "Free Radicals in Digestive Diseases" Elsevier,Amsterdam, 244 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Makoto,Suematsu: Biochem.Biophys.Res.Commun.155. 106-111 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Makoto,Suematsu: J.Biolum.Chemilum.(Suppl.). (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 末松誠: Therapeutic Research. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 土屋雅春: 医学のあゆみ. 147. 380-384 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 末松誠: "フリーラジカルの臨床 vol.4" 日本医学館, (1989)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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