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Establishment of new procedures for botulism including bio-terrorism and for the treatment of patients with dystonia.

Research Project

Project/Area Number 17390127
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

OGUMA Keiji  Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (00002262)

Co-Investigator(Kenkyū-buntansha) YOKOTA Kenji  Okayama University Medical School, Faculty of Health Sciences, Associate Professor, 医学部, 助教授 (00243460)
AYADA Kiyoshi  Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (00379835)
KOUICHI Takeshi  Obihiro University of Agriculture and veterinary Medicine, Faculty of Animal Husbandry School of Veterinary Medicine, Professor, 畜産学部, 教授 (50396339)
ARIMITSU Hideyuki  Fujita Health University, Faculty of Medicine, Lecturer, 医学部, 講師 (40367701)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2006: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2005: ¥8,600,000 (Direct Cost: ¥8,600,000)
Keywordsbacteria / infectious disease / protein / medicine, welfare / food
Research Abstract

1. Development of vaccine and immuno-strip for detecting toxin
In order to prepare the safe and effective type C and D vaccines for animal botulism, the heavy chains (100 kDa) and their C-terminal (Hc, 50 kDa) and N-terminal (Hn, 50 kDa) half fragments were prepared as GST fusion proteins. Production level of Hc and Hn was quite higher than that of H. H and He showed good vaccine effects but that of Hn was quite low. GST fused-or GST-eliminated He preparation showed similar vaccine effect. Therfore, it was concluded that He with or without GST can be used as commercially effective vaccine. Immuno-strip method was prepared using polyclonal antisera against A, B, E, and F neurotoxins. They could detect approximately 1 ng of each toxin.
2. Development of neurotoxin preparations for treating dystonia
We found that HAI and HA3b, which are the subcomponents of HA, have adjuvant activity. Therefore, we tried to treat the patients with the neurotoxins rather than the progenitor toxins. We found that Type A and B neurotoxins can easily be purified by using a lactose gel column, and that they can be stocked in a deep freezer without reducing the toxin activity by mixing with 0.05% albumin (for type B) or 0.05% albumin plus 1% terehalose (for type A). When this preparation was used for the treatment of 18 patients with urinary incontinence caused by refractory idiopathic and neurogenic detrusor overactivity, 16 patients showed excellent improvement; it started within 1 week after injection in most cases and lasted 3 to 12 months.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (42 results)

All 2007 2006 2005 Other

All Journal Article (31 results) Book (10 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Identification of structural genes for Clostridium botulinum type Cneurotoxin-converting phage particles.2007

    • Author(s)
      Hwang HJ, et al.
    • Journal Title

      FEMS Microbiol. Lett. 270

      Pages: 82-89

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human milk SIgA binds to botulinum type B 16S toxin and limits toxin adherence on T84 cells.2007

    • Author(s)
      Matsumura T, et al.
    • Journal Title

      Biochem. Biophysic Res. Communi. 352

      Pages: 867-872

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Binding properties of Clostridium botulinum type C progenitor toxin to mucins.2007

    • Author(s)
      Nakamura T, et al.
    • Journal Title

      Biochim. Biophys. Acta. 1770

      Pages: 551-555

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 3.26 Glycoconjugates and Bacterial Infections : Botulinum Toxin.2007

    • Author(s)
      Nishikawa A, et al.
    • Journal Title

      COMPREHENSIVE GLYCOSCIENCE. Elsevier LTD.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Botulism (Botulinum Diseases)2007

    • Author(s)
      Takeshi K, et al.
    • Journal Title

      Shin-Kansenshogaku. Nippon Rinsho.

      Pages: 184-187

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human milk SIgA binds to botulinum type B 16S toxin and limits toxin adherence on T84 cells.2007

    • Author(s)
      Matsumura T( et al.
    • Journal Title

      Biochem. BioPhysic Res.Communi. 352

      Pages: 867-872

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Binding properties of Clostridinum botulinum type C progenitor toxin to mucins.2007

    • Author(s)
      Nakamura T( et al.
    • Journal Title

      Biochim.Biophys.Acta. 1770

      Pages: 551-555

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cell internalization and traffic pathway of Clostridium botulinum type C neurotoxin in HT-29 cells.2006

    • Author(s)
      Uotsu N, et al.
    • Journal Title

      Biochim. Biophys. Acta. 1763

      Pages: 120-128

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bacterial toxin and food born poisoning.2006

    • Author(s)
      Oguma K, et al.
    • Journal Title

      IDEN. NTS.

      Pages: 143-153

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Application of botulinum neurotoxin to medical treatment.2006

    • Author(s)
      Oguma K, et al.
    • Journal Title

      Igaku no Ayumi. Ishiyaku Shuppann. 216

      Pages: 251-252

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cell internalization and traffic pathway of Clostridinum botulinum type C neurotoxin iin HT-29 cells.2006

    • Author(s)
      Uotsu N( et al.
    • Journal Title

      Biochim.Biophys.Acta. 1763

      Pages: 120-128

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The genome sequence of Clostridium botulinum type C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny.2005

    • Author(s)
      Sakaguchi Y, et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA. 102

      Pages: 17472-17477

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Production of Anti-neurotoxin antibody is enhanced by two subcomponents, HA1 and HA3b, of Clostridium botulinum type B 16S toxin-hemagglutinin.2005

    • Author(s)
      Lee J, et al.
    • Journal Title

      Microbiol. 151

      Pages: 3739-3747

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Characterization of the interaction between subunits of the botulinum toxin complex produced by serotype D through tryptic susceptibility of the isolated components and complex forms.2005

    • Author(s)
      Suzuki T, et al.
    • Journal Title

      Microbiol. 151

      Pages: 1475-1483

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The genome sequence of Clostridium botulinum type C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny2005

    • Author(s)
      Sakaguchi Y, et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA. 102

      Pages: 17472-17477

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Production of Anti-neurotoxin antibody is enhanced by two subcomponents, HA1 and HA3b, of Clostridium botulinum type B 16S toxin-hemagglutinin.2005

    • Author(s)
      Lee JC, et al.
    • Journal Title

      Microbiol. 151

      Pages: 3739-3747

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Botulinum diseases and Immunity.2005

    • Author(s)
      Oguma K.
    • Journal Title

      Nihon Iji Shinpo. No. 4212

      Pages: 95-97

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Invasive-mechanism of botulinum toxin into epithelical cells of the small intestine.2005

    • Author(s)
      Nishikawa A, et al.
    • Journal Title

      Tousa Kagaku no Shintenkai. NTS.

      Pages: 188-193

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sugar chain and therapy (Botulism and sugar chain).2005

    • Author(s)
      Nishikawa A, et al.
    • Journal Title

      Idenshi Igaku. Medical Do.

      Pages: 239-243

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Characterization of the interaction between subunits of the botulinum toxin complex produced by serotype D through tryptic susceptibility of the isolated components and complex forms.2005

    • Author(s)
      Suzuki T
    • Journal Title

      Microbiol. 151

      Pages: 1475-1483

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Production of Anti-neurotoxin antibody is enhanced by two subcomponents, HA 1 and HA3b, of Clostridium botulinum type B 16S toxin- hemagglutinin.2005

    • Author(s)
      Lee J
    • Journal Title

      Microbiol. 151

      Pages: 3739-3747

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The genome sequence of Clostridium botulinum type C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny.2005

    • Author(s)
      Sakaguchi Y
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 102

      Pages: 17472-17477

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ボツリヌス毒素の遺伝子および構造と機能に関する研究(浅川賞受賞論文)2005

    • Author(s)
      小熊 惠二
    • Journal Title

      日本細菌学雑誌 60

      Pages: 521-531

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of Nicking the C-terminal Region of the Clostridium botulinum Serotype D Neurotoxin Heavy Chain on its Toxicity and Molecular Properties.

    • Author(s)
      Suzuki T, et al.
    • Journal Title

      Protein J. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] C terminal half fragment (50 kDa) of heavy chain components of Clostridium botulinum type C and D neurotoxins can be used as an effective vaccine.

    • Author(s)
      Lee JC, et al.
    • Journal Title

      Microbiol. Immunol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of Nicking the C-terminal Region of the Clostridium botulinum Serotype D Neurotoxin Heavy Chain on its Toxicity and Molecular Properties.

    • Author(s)
      Suzuki T, et al.
    • Journal Title

      Protein J. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] C terminal half fragment (50 kDa) of heavy chain components of Clostridium botulinum type C and D neurotoxins can be used as an effective vaccine.

    • Author(s)
      Lee JC, et al.
    • Journal Title

      Microbiol. Immunol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of Nicking the C-terminal Region of the Clostridinum botulinum Serotype DNeurotoxin Heavy Chain on its Toxicity and Molecular Properties.

    • Author(s)
      Suzuki T( et al.
    • Journal Title

      Protein J. (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] C terminal half fragment (50 kDa)of heavy chain components of Clostridinum botulinum type C and D neurotoxins can be used as an effective vaccine.

    • Author(s)
      Lee JC( et al.
    • Journal Title

      Microbiol.Immunol. (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of structural genes for Clostridinum botulinum type Cneurotoxin-converting phage particles.

    • Author(s)
      Hwang HJ( et al.
    • Journal Title

      FEMS Microbiol.Lett. (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cell internalization and traffic pathway of Clostridium botulinum type C neurotoxin in HT-29 cells.

    • Author(s)
      Uotsu N
    • Journal Title

      Biochim.Biophys.Acta. (in press)

    • Related Report
      2005 Annual Research Report
  • [Book] COMPREHENSIVE GLYCOSCIENCE; 3.26 Glycoconjugates and Bacterial Infections : Botulinum Toxin2007

    • Author(s)
      A.Nishikawa et al.
    • Publisher
      Elsevier Ltd.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 四類感染症 ポツリヌス症.日本臨床(増刊号)新感染症学 下2007

    • Author(s)
      武士甲一, 他
    • Publisher
      日本臨床社.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] COMPREHENSIVE GLYCOSCIENCE; 3.26 Glycoconjugates and Bacterial Infections : Botulinum Toxin2007

    • Author(s)
      A.Nishikawa, K.0guma
    • Publisher
      Elsevier Ltd.
    • Related Report
      2006 Annual Research Report
  • [Book] 遺伝(別冊)科学は食のリスクをどこまで減らせるか第5章「病原細菌-毒素と食中毒」2006

    • Author(s)
      小熊恵二, 他
    • Publisher
      NTS
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 医学のあゆみ「ボツリヌス神経毒素製剤の臨床応用」2006

    • Author(s)
      小熊恵二, 他
    • Publisher
      医歯薬出版株式会社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 直伝(別冊)「科学は食のリスクをどこまで減らせるか」第5章「病原細菌」-毒素と食中毒2006

    • Author(s)
      小熊恵二, 武士甲一, 中野宏幸
    • Publisher
      NTS
    • Related Report
      2006 Annual Research Report
  • [Book] ハリソン内科学第2版(破傷風,ボツリヌス中毒,ガス壊疽,その他のClostridium感染症)2006

    • Author(s)
      小熊 惠二
    • Publisher
      メディカル・サイエンス・インターナショナル
    • Related Report
      2005 Annual Research Report
  • [Book] 日本医事新報No.4212.「ボツリヌス菌感染症と免疫」2005

    • Author(s)
      小熊恵二
    • Publisher
      日本医事新報社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 糖鎖科学め新展開「ボツリヌス毒素の細胞内移行機構」2005

    • Author(s)
      西河 淳, 他
    • Publisher
      NTS
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 遺伝子医学MOOK3糖鎖と病気「糖鎖と治療(ボツリヌス中毒と糖鎖)」2005

    • Author(s)
      西河 淳, 他
    • Publisher
      株式会社メデイカルドウ
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 糖結合性ポリペプチド、複合材料、及び薬剤送達システム2007

    • Inventor(s)
      小熊恵二, 西河 淳
    • Industrial Property Rights Holder
      国享大学法人岡山大学, 国立大学法人東京農工大学
    • Industrial Property Number
      2007-005265
    • Filing Date
      2007-01-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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