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Matrix metalloproteinase activation in bacterial pathogenesis

Research Project

Project/Area Number 09470077
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionKumamoto University

Principal Investigator

MAEDA Hiroshi  Kumamoto University School of Medicine, Professor, 医学部, 教授 (90004613)

Co-Investigator(Kenkyū-buntansha) MIYAMOTO Yoichi  Kumamoto University School of Medicine, Research Associate, 医学部, 助手 (20295132)
SAWA Tomohiro  Kumamoto University School of Medicine, Research Associate, 医学部, 助手 (30284756)
AKAIKE Takaaki  Kumamoto University School of Medicine, Associate Professor, 医学部, 助教授 (20231798)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥7,100,000 (Direct Cost: ¥7,100,000)
Keywordsbacterial protease / MMP / bacterial pathogenesis / NO / free radicals / peroxynitrite / bacterial invasion / ブラジキニン / 敗血症
Research Abstract

Matrix metalloproteases (MMPs) are secreted by numerous mammalian cells as inactive proenzymes (proMMPs). After activation they are involved in tissue remodeling and facilitate cancer metastasis. In view of microbial infection and inflammation, two distinct proMMPs, proMMP-8 with 85 kDa and proMMP-9 with 92-kDa, known to be secreted by human polymorphonuclear leukocytes, are of special interest. Macrophages as well as fibroblasts can also produce proMMP-1 with 52 kDa and proMMP-9 known as progelatinases which cleave denatured collagen preferentially. We have previously reported that microbial proteases can activate various endogenous protease cascade systems of the infected hosts. Among them, we studied the kinin (or bradykinin) generating cascade most extensively and demonstrated processing of Hageman factor to its active form or prekallikrein to kallikrein or direct generation of kinin from kininogen, and activation of the clotting cascade involving factors XII, X, II, etc. In the pr … More esent study, we further found that human MMPs can be processed from proMMP to their active forms by two new and unique mechanisms: Firstly, by bacterial proteases such as Pseudomonas elastase and Vibrio cholerae protease, which cleave off the N-terminal autoinhibitory domain (so-called cysteine switch) from proMMPs. The second mechanism depends on free radical generation by activated polymorphonuclear leukocytes. In this case, peroxynitrite (ONOOィイD1-ィエD1) or nitrogen dioxide radical (NOィイD22ィエD2), the reaction products of either superoxide (OィイD3-(/)2ィエD3) or molecular oxygen (OィイD22ィエD2) and nitric oxide (NO), are the key reactants. Both OィイD3-(/)2ィエD3 and NO are generated by activated macrophages and leukocytes as a result of immunologic responses involving various proinflammatory cytokines. NOィイD22ィエD2 or ONOOィイD1-ィエD1 seems to interact with a single cysteine residue in the propeptide autoinhibitory domain or so-called cysteine switch of proMMPs thus transforming proMMPs to their active conformation. Furthermore, we found a quite unique and novel MMP activation mechanism: Specifically, peroxynitrite-mediated MMP activation is remarkably potentiated by glutathione (GSH), in which nitrated GSH (NOィイD22ィエD2-GS) produced by peroxynitrite appears to be directly involved in the MMP activation. It is thus concluded that bacterial proteases and free radical species such as NO derived from host's inflammatory responses may contribute to the bacterial pathogenesis via activation of MMP activation particularly during bacterial intrusion into the host. Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (81 results)

All Other

All Publications (81 results)

  • [Publications] T Okamoto, et al.: "Activation of human matrix metalloproteinases by various bacterial protenases"J. Biol. Chem.. 272. 6059-6066 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] t. Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxide and peroxynitrite: A novel mechanism for procollagenase activation involving nitric oxide"Arch. Biochem. Biophys.. 342. 261-274 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Umezawa, et al.: "Induction of nitric oxide synthesis and xanthine oxidase and their role in the antimicrobial mechanism agauinst Salmonella typhimurium in mice"Infect. Immun.. 65. 2932-2940 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Maruo, et al.: "Generation of anaphylatoxins through proteolytic processing of C3 and C5 by house dust mite protease"J. Allergy Clin. Immunol.. 100. 253-260 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 岡本竜哉、他: "一酸化窒素および反応性窒素酸化物によるヒト好中球コラゲナーゼの活性化機構"磁気共鳴と医学. 8. 147-150 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Akaike, et al.: "Free radicals in viral pathogenesis: Molecular mechanisms involving superoxide and NO"Proc. Soc. Exp. Biol. Med.. 217. 64-73 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Maruo, et al.: "Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist"Infect. Immun.. 66. 866-869 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J. Wu, et al.: "modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitoe, and a nitric oxide scavenger"Cancer Res.. 58. 159-165 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Maeda, et al.: "human matrix metalloprotease activation by insults of bacterial infection involving proteases and free radicals"Biol. Chem.. 379. 193-200 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 丸尾圭志、他: "バクテリア感染とカリクレイン・キニン系"炎症と免疫. 6. 490-495 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Inoue, et al: "Nitrosothiol formation catalyzed by ceruloplasmin: Omplication for cytoprotective mechanism in vivo"J. Biol. Chem. 274. 27069-27075 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Maeda, et al.: "Kallikrein-kinin in infection and cancer"Immunopharmacology. 43. 115-128 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 岡本竜哉、他: "マトリックスメタロプロテアーゼ(MMP)の活性化機構"生化学. 71. 1387-1401 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Miyamoto, et al.: "Novel functions of human α_1-protease inhibitor after S-nitrosylation: Inhibition of cysteine protease and antibacterial activity"Biochem. Biophys. Res. Commun.. 267. 918-923 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Akaike, et al.: "Viral mutation accelerated by nitric oxide production during infection in vivo"FASEB J.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Maeda and T. Akaike: "Protease Inhibitors: novel therapeutic application and Development (ed. N. Marcready)"International Business Communications, Inc., southborogh. 33 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Maeda, et al.: "medical Aspects of Proteases and protease Inhibitor (eds. N. Katunuma, H. Fritz andj. Travis)"11 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 赤池孝章、岡本竜哉: "A群レンサ球の毒素と病原性(渡辺治雄、清水可方編)"(株)近代出版(東京). 10 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Akaike and H. Maeda: "Nitric Oxide (ed. L.J. Ignarro)"Academic Press, San Diego (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Okamoto, et al.: "Activation of human matrix metalloproteinases by various bacterial proteinases"J. Biol. Chem.. 272. 6059-6066 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxide and peroxynitrite: A novel mechanism for procollagenase activation involving nitric oxide."Arch. Bjochem. Biophys.. 342. 261-274 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Umezawa, et al.: "Induction of nitric oxide synthesis and xanthine oxidase and their role in the antimicrobial mechanism against Salmonella typhimurium in mice"Infect, lmmun.. 65. 2932-2940 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Maruo, et al.: "Generation of anaphylatoxin through proteolytic processing of C3 and C5 by house dust mite protease."J. Allergy Clin. Immunl.. 100. 253-260 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Akaike, et al.: "Free radicals in viral pathogenesis: Molecular mechanisms involving superoxide and NO"Proc, Soc, Exp, Biol. Med.. 217. 64-73 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Maruo, et al.: "Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist"Infect, lmmun.. 66. 866-869 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Maeda, et al.: "Human matrix metalloprotease activation by insults of bacterial infection involving proteases and free radicals"Biol. Chem.. 379. 193-200 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J. Wu, et al.: "Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger"Cancer Res.. 58. 159-165 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Inoue, et al.: "Nitrosothiol formation catalyzed by ceruloplasmin: Implication for cytoprotective mechanism in vivo"J. Biol. Chem.. 274. 27069-27075 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Fujii, et al.: "Role of nitric oxide in pathogenesis of herpes simplex virus encephalitis in rats."Virology,. 256. 203-212 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Doi, et al.: "Induction of haem oxygenase-1 by nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth"Br. J. Cancer. 80. 1945-1954 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Maeda, et al.: "Free radical generation from heterocyclic amines by cytochrome b5 reductase in the presence of NADH"Cancer Letter. 143. 117-121 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Maeda, et al.: "Kallikrein-kinin in infection and cancer"Immunopharmacology. 43. 115-128 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Miyamoto, et al.: "Novel functions of human αィイD21ィエD21-protease inhibitor after S-nitrosylation: Inhibition of cysteine protease and antibacterial activity."Biochem. Biophys. Res. Commun.. 267. 918-923 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Akaike, et al.: "Viral mutation accelerated by nitric oxide production during infection in vivo"FASEB J.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Kuwahara, et al.: "Helicobacter pylori urease suppresses bacctericidal activity of peroxynitrite via carbon dioxide production"Infect. Immun.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Maeda and T. Akaike: "Bacterial proteases as pathogenic factors in view of septicemia and shock. In Protease Inhibitors: Novel Therapeutic Application and Development (ed. N. Macready)"International Business Communications, Inc. Southborough, Chapter 2.1. 1-33 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Maeda, et al.: "Activation of matrix metalloproteinases by and pathogenic implication. In Medical Aspects of Proteases and Protease Inhibitors (eds. N. Katunuma, H. Kido, H. Fritz and J. Travis)"IOS Press, Amsterdam, The Netherlands. 128-138 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Akaike and H. Maeda: "Pathophysiological effects of high-output production of nitric oxide. In Nitric Oxide (ed. L.J. Ignarro)"Academic Press, San Diego (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Fujii,et al.: "Role of nitric oxide in pathogenesis of herpes simplex virus encephalitis in rats"Virology. 256. 203-212 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Sugiura,et al.: "Role of peroxynitrite in airway microvascular hyperpermeability during late allergic phase in guinea pigs"Am. J. Respir. Crit. Care Med.. 160. 663-671 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Dio,et al.: "Induction of haem oxygenase-1 by nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth"Br. J. Cancer. 80. 1945-1954 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Inoue,et al.: "Nitrosothiol formation catalyzed by ceruloplasmin: Implication for cytoprotective mechanism in vivo"J. Biol. Chem.. 274. 27069-27075 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Iwasaki,et al.: "Combined effects of both bacteria and gastric juice on pneumonia in mice"Respur. Physiol.. 116. 201-209 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Maeda,et al.: "Kallikrein-kinin in infection and cancer"Immunopharmacology. 43. 115-128 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Miyamoto,et al.: "Novel functions of human α_1-protease inhibitor after S-nitrosylation: Inhibition of cysteine protease and antibacterial activity"Biochem. Biophys. Res. Commun.. 267. 918-923 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Sawa,et al.: "Tumor-targeting chemotherapy by a xanthine oxidase-polymer conjugate that generates oxygen-free radicals in tumor tissue"Cancer Res.. 60. 666-671 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Akaike,et al.: "Viral mutation accelerated by nitric oxide production during infection in vivo"FASEB J.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 岡本竜哉,他: "マトリックスメタロプロテアーゼ(MMP)の活性化機構"生化学. 71. 1387-1401 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Akaike, et al.: "Nitric Oxide and Infection (ed. F. C. Fang)"Plenum Publishing Co., New York. 19 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Akaike: "Guanidino Compounds (eds. M. Mori, M. Ishida and J. F. Clark)"Blackwell Science Asia, Tokyo. 5 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Akaike and H. Maeda: "Nitric Oxide (ed. L. J. Ignarro)"Academic Press, San Diego (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Maeda, et al.: "The Biology of Nitric Oxide Part 7 (eds. S. Moncada, L. Gustafsson, P. Wiklund and E. A. Higgs)"Portland Press Ltd., London (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Miyamoto, et al.: "The Biology of Nitric Oxide Part 7 (eds. S. Moncada, L. Gustafsson, P. Wiklund and E. A. Higgs)"Portland Press Ltd., London (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Akaike,et al.: "Free radicals in viral pathogenesis:Molecular mechanisms involving superoxide and NO" Proc.Soc.Exp.Biol.Med.217. 64-73 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Yoshida,et al.: "Effect of the No scavenger carboxy-PTIO on enthothelium-dependent of vasorelaxation of various blood vessels from rabbits" Life Sciences. 62. 203-211 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Maeda,et al.: "Human matrix metalloprotease activation by insults of bacterial infection involving ptoteases and free radicals" Biol.Chem.379. 193-200 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Wu,et al.: "Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist,a cyclooxygenase inhibitor,and a nitric oxide scavenger" Cancer Res.58. 159-165 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Maruo,et al.: "Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist" Infect.Immun.66. 866-869 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Maeda,et: "Nitric oxide and oxygen radicals in infection,inflammation and cancer" Biochemistry(Moscow). 63. 854-865 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Sato,et al.: "Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice" Am.J.Respir.Crit.Care Med. 157. 853-857 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Sawa,et al.: "Lipid peroxyl radicals from oxidized oils and heme-iron:Implication of a high-fat diet in colon carcinogenesis" Cancer Epidemiol.Biomarkers & Prevantion. 7. 1007-1012 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Yoshida,et al.: "The possible effect of nitric oxide on relaxation and noradrenaline release in the isolated rabbit urethra" Eur.J.Pharmacol.357. 213-219 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Nakatsubo,et al.: "Improved nitric oxide detection using 2,3- diaminonaphthalene and its application to the evaluation of novel nitric oxide synthase inhibitors" Biol.Pharm.Bull. 21. 1247-1250 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Doi,et al.: "Induction of heme oxygenase-1 by nitric oxide and ischemia in experimental solid tumors and implications for tumor growth" Br.J.Cancer. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Fujii,et al.: "Role of nitric oxide in pathogenesis of herpes simplex virus encephalitis in rats" Virology. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Maeda,et al.: "Free radical generation from heterocyclic amines by cytochrome b5 reductase in the presence of NADH" Cancer Letters. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Maeda,et al.: "Kallikrein-kinin in infection and cancer" Immunopharmacology. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Akaike,et al.: "Nitric Oxide and infection(ed.F.C.Fang)" Plenum Publishing Co.,New York(in press), (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] T. Okamoto, et al.: "Activation of human matrix metalloproteinases by various bacterial proteinases" J. Biol. Chem.272. 6059-6066 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H. Muranaka, et al.: "Superoxide scavenging activity of erythromycin-iron complex" Biochem. Biophys. Res. Commun.232. 183-187 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] D.C. Hooper, et al.: "Prevention of experimental allergic encephalitis by targeting nitric oxide and peroxynitrite : implications for the treament of multiple sclerosis" Proc. Natl. Acad. Scie. U.S.A. 94. 2528-2533 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K. Umezawa, et al.: "Induction of nitric oxide synthesis and xanthine oxidase and their role in the antimicrobial mechanism against Salmonella typhimurium in mice" Infect. Immun.65. 2932-2940 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K. Maruo, et al.: "Generation of anaphylatoxins through proteolytic processing of C3 and C5 by house dust mite protease" J. Allergy and Clin. Immunol.100. 253-260 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T. Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxides and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide" Arch. Biochem. Biophys.342. 253-260 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T. Akaike, et al.: "Free radicals in viral pathogenesis : Molecular mechanisms involving superoxide and NO" Proc. Soc. Exp. Biol. Med.217. 64-73 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] H. Maeda, et al.: "Human matrix metalloprotease activation by insults of bacterial infection involving proteases and free radicals" Biol. Chem.379. 193-200 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] J. Wu, et al.: "Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger" Cancer Res.58. 159-165 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K. Maruo, et al.: "Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist" Infect. Immun.66. 866-869 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] H. Maeda and T. Akaike: "Protease Inhibitors : Novel Therapeutic Application and Development (e d. N. Marcready)" International Business Communications, Inc., Southborough, 33 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H. Maeda, et al.: "Medical Aspects of Proteases and Protease Inhibitors (eds. N. Katunuma, H. Kido, H. Fritz and J. Travis)" IOS Press, Amsterdam, 11 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H. Maeda and T. Akaike: "Nitric Oxide in Transplant Rejection and Anti-tumor Defense (eds. J.L. Zweier and S.J. Lukiewicz)" Kluwer Academic Publishers, Norwell(in press), (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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