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Analyses, using toxin fragment, of disturbances in autonomic nervous system in tetanus intoxication, a possible major cause of tetanus death

Research Project

Project/Area Number 60480164
Research Category

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

Allocation TypeSingle-year Grants
Research Field 細菌学
Research InstitutionOsaka University

Principal Investigator

MATSUDA Morihiro  Research Institute for Microbial Diseases, Osaka University, 微生物病研究所, 教授 (20029771)

Co-Investigator(Kenkyū-buntansha) SUGIMOTO Hisashi  Medical School, Osaka University, 医学部, 講師 (90127241)
OZUTSUMI Kunihiro  Research Institute for Microbial Diseases, Osaka University, 微生物病研究所, 助手 (00144519)
SUGIMOTO Nakaba  Research Institute for Microbial Diseases, Osaka University, 微生物病研究所, 助手 (20142317)
HIRAI Toshihiro  Research Institute for Microbial Diseases, Osaka University, 微生物病研究所, 助手 (50029790)
Project Period (FY) 1985 – 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1986: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1985: ¥5,900,000 (Direct Cost: ¥5,900,000)
KeywordsTetanus toxin / Toxin fragment / Tetanus intoxication / Tetanus / 自律神経系 / 致死原因 / 自律神経系活動異常
Research Abstract

Fragments(A-B and C) of tetanus toxin were highly purified from mildly papain-digested toxin by HPLC-gel permeation and adsorption column chromatograpies. Fragment A-B preparation(200 <mu> g), further purified by affinity chromatography using anti-fragment C antibody as ligand, had no spastic toxicity which is typical for tetanus toxin, nor blocked neuromuscular transmission in rat, but showed definite, atypical toxicity("flaccid paralysis" or "weakness") when injected intramuscularly or intravenously into mice and killed them in 2-4 days. Unlike whole toxin, purified fragment A-B, blocked both inhibitory and excitatory synapses almost at the same time after injection into cat spinal cord. Toxin injected intramuscularly or intravenously into mice did not elicit hypertension but remarkable hypotension one to half day before death. Purified fragment A-B showed similar activity in mice. Toxin(0.64-2.6 ng) injected intravenously into rat, unlike toxin injected intramuscularly, elicited abnormal hypertension and subsequent death. Intracerebroventicular injection of toxin into rat gave more reproducible effects than intravenous injection. Immunocytochemical studies by indirect fluorescent technique showed localizatin of toxin in border between area postrema and nucleus solitarius in medulla oblongata. Further exact studies are being carried out using mouse monoclonal anti-bodies against toxin fragments. Toxin injected intravenously into rabbits (first 0.3 <mu> g and then 30 <mu> g 7 days later) showed remarkable fluctuations in blood pressure having repeated hypotensive phases resembling those in severe cases of tetanus patients. Control of blood pressure in these rabbits was attempted by intravenous administration of epinephine under total spinal anaesthesia. The method was successfully applied to treatment of tetanus patients.

Report

(1 results)
  • 1986 Final Research Report Summary
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Ozutsumi,K.: Appl.Environ.Microbiol.49. 939-943 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Ozutsumi,K.: Proc.7th Int.Conf.on Tetanus. 49-56 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 小堤国広: 日本細菌学雑誌. 41. 243 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Matsuda,M.: Proc.8th Int.Conf.on Tetanus. (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Ozutsumi,K.: Toxicon. 25. (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takano,K.: Naunyn Schmiedebergs Arch.Pharmacol.(1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Simpson,L.L.: "Structure of tetanus toxin In Clostridial Neurotoxins" Academic Press,New York, 500 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Ozutsumi, K.: "Rapid, simplified method for production and purification of tetanus toxin." Appl. Environ. Microbiol.49. 939-943 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Ozutsumi, K.: "Rapid and simplified method of tetanus toxin and toxin fragments determined by HPLC." Proc. 7th Int. Conf. on Tetanus. 49-56 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Matsuda, M.: "Biological activities of fragments of tetanus toxin." Proc. 8th Int. Conf. on Tetanus. in press (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Ozutsumi, K.: "Isolation and purification of fragments derived from papain-treated tetanus toxin by high performance liquid chromatogaphy." Toxicon. 25. to be submitted (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takano, K.: "Effect of fragment A-B of tetanus toxin on the transmission of motoneurone in the spinal cord." Naunyn Schmiedebergs Arch. Pharmacol.to be submitted (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Ozutsumi, K.: "Abnormal blood pressure in rats intoxicated by tetanus toxin." Nihon Saikingaku Zasshi. 41. 243 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Simpson, L.L.: Academic Press, New York. Structure of tetanus toxin In Clostridial Neurotoxins, 500 pages in press (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary

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Published: 1987-03-31   Modified: 2016-04-21  

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