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Establishment of new procedure for botulism including bioterrorism, and application of botulinum toxin to the treatment

Research Project

Project/Area Number 19390126
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  Okayama University, 大学院・医歯薬学総合研究科, 教授 (00002262)

Co-Investigator(Kenkyū-buntansha) YOKOTA Kenji  岡山大学, 大学院・保健学研究科, 准教授 (00243460)
AYADA Kiyoshi  岡山大学, 大学院・医歯薬学総合研究科, 助教 (00379835)
SAKAGUCHI Yoshihiko  岡山大学, 大学院・医歯薬学総合研究科, 助教 (70403491)
YAMAMOTO Yumiko  岡山大学, 大学院・医歯薬学総合研究科, 助教 (20403496)
ARIMITSU Hideyuki  藤田保健衛生大学, 医学部, 講師 (40367701)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2007: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Keywords病原性 / 感染免疫 / 疫学 / 遺伝 / 分類 / 診断 / 構造・生理 / 細菌 / 感染症 / 蛋白質 / 医療・福祉 / 食品
Research Abstract

ボツリヌス菌や毒素、抗毒素抗体の検出方法と毒素の治療への応用を検討した。菌の検出法としては、A~F型毒素遺伝子を増幅できるPCRを開発した。毒素の検出法としてはイムノクロマト法を開発したが、現在、改良中である。抗体の検出法としては、毒素の一部を結合させたカラムを用いて抗体を濃縮して検出する方法を開発した。治療への応用としては、三叉神経痛と前立腺肥大症に適用できることをとラットを用いて実証した。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (56 results)

All 2009 2008 2007 Other

All Journal Article (30 results) (of which Peer Reviewed: 30 results) Presentation (17 results) Book (4 results) Patent(Industrial Property Rights) (5 results)

  • [Journal Article] Botulinum toxin type A (150 kDa) decreases exaggerated neurotransmitter release from trigerminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction2009

    • Author(s)
      Kitamura Y, Matsuka Y, Spigelman I, Ishihara Y, Yamamoto Y, Sonoyama W, Kuboki T, and Oguma K
    • Journal Title

      Neuroscience 159

      Pages: 1422-29

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the HA3 subcomponent of Clostridium botulinum type C progenitor toxin2009

    • Author(s)
      Nakamura T, Kotani M, Tonozuka T, Ide A, Oguma K, Nishikawa A
    • Journal Title

      J Mol Biol. 385

      Pages: 1193-206

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the HA3 subcomponent of Clostridium botulinum type Cprogenitor toxin.2009

    • Author(s)
      Nakamura T
    • Journal Title

      J Mol Biol 385

      Pages: 1193-1206

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Botulinum. toxin type A (150 kDa)decreases, exaggerated neurotransmitter release from trigerminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction.2009

    • Author(s)
      Kitamura Y
    • Journal Title

      Neuroscience 159

      Pages: 1422-1429

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular analysis of an extrachromosomal element encoding the C2 toxin genediscovered in Clostridium botulinum type c.2009

    • Author(s)
      Sakaguchi Y
    • Journal Title

      J Bacteriol (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of purified newly developed botulinm neurotoxin type A in rat prostate.2009

    • Author(s)
      Nishiyama Y
    • Journal Title

      Urology (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular properties of each subcomponent in Clostridium botulinum type B haemagglutinin complex2008

    • Author(s)
      Arimitsu H, Sakaguchi Y, Lee JC, Ochi S, Tsukamoto K, Yamamoto Y, Ma S, Tsuji T, and Oguma K
    • Journal Title

      Microb Pathog. 45

      Pages: 142-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption2008

    • Author(s)
      Matsumura T, Jin Y, Kabumoto Y, Takegahara Y, Oguma K, Lencer WI, and Fujinaga Y
    • Journal Title

      Cell Microbiol. 10

      Pages: 355-364

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin2008

    • Author(s)
      Nakamura T, Tonozuka T, Idea A, Yuzawa T, Oguma K and Nishikawa A
    • Journal Title

      J. Mol Biol. 376

      Pages: 854-867

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sugar-binding sites of the HA1 subcomponent of Clostridiumbotulinum type Cprogenitor toxin.2008

    • Author(s)
      Nakaraura T
    • Journal Title

      J. Mol Biol 376

      Pages: 854-867

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption.2008

    • Author(s)
      Matsumura T
    • Journal Title

      Cell Microbiol 10

      Pages: 355-364

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular properties of each subcomponent in Clostridium botulinum type Bhaemagglutinin complex.2008

    • Author(s)
      Arimitsu H
    • Journal Title

      Microb Pathog 45

      Pages: 142-149

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin.2008

    • Author(s)
      Nakamura T.
    • Journal Title

      J. Mol Biol. 376

      Pages: 854-867

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption.2008

    • Author(s)
      Matsumura T.
    • Journal Title

      Cell Microbiol. 10

      Pages: 355-364

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary X-ray analysis of the HA3 component of Clostridium botulinum type C progenitor toxin2007

    • Author(s)
      Nakamura T, Tonozuka T, Kotani M, Kanae Obata K, Oguma K and Nishikawa A
    • Journal Title

      Acta Cryst. F63

      Pages: 1038-1040

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical application of Clostridium botulinum type A neurotoxin purified by a simple procedure for patients with urinary incontinence caused by refractory detrusor overactivity2007

    • Author(s)
      Lee JC, Yokoyama T, Hwang HJ, Arimitsu H, Yamamoto Y, Kawasaki M, Takigawa T, Takeshi K, Nishikawa A, Kumon H, and Oguma K
    • Journal Title

      FEMS Immunol. Med. Microbiol. 51

      Pages: 201-211

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of nicking the C-terminal region of the Clostridium botulinum serotype D neurotoxin heavy chain on its toxicity and molecular properties2007

    • Author(s)
      Suzuki T, Kouguchi H, Watanabe T, Hasegawa K, Yoneyama T, Niwa K, Nishikawa A, Lee JC, Oguma K, Ohyama T
    • Journal Title

      Protein J. 26

      Pages: 173-181

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cterminal half fragment (50 kDa) of heavy chain components of Clostridium botulinum type C and D neurotoxins can be used as an effective vaccine2007

    • Author(s)
      Lee JC, Hwang HJ, Sakaguchi Y, Yamamoto Y, Arimitsu H, Tsuji T, Watanabe T, Ohyama T, Tsuchiya T, and Oguma K
    • Journal Title

      Microbiol. Immunol 51

      Pages: 445-455

    • NAID

      10020280881

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of structural genes for Clostridium botulinum type C neurotoxin-converting phage particles2007

    • Author(s)
      Hwang HJ, Lee JC, Yamamoto Y, Sarker MR, Tsuchiya T, Oguma K
    • Journal Title

      FEMS Microbiol. Lett. 270

      Pages: 82-89

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human milk SIgA binds to botulinum type B 16S toxin and limits toxin adherence on T84 cells2007

    • Author(s)
      Matsumura T, Fujinaga Y, Jin Y, Kabumoto Y, Oguma K
    • Journal Title

      Biochem. Biophysic Res. Communi. 352

      Pages: 867-872

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Binding properties of Clostridium botulinum type C progenitor toxin to mucins. Biochim2007

    • Author(s)
      Nakamura T, Takada N, Tonozuka T, Sakano Y, Oguma K, and Nishikawa A
    • Journal Title

      Biophys. Acta. 1770

      Pages: 551-555

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Binding properties of Clostridium botulinum type C progenitor toxin to mucins.2007

    • Author(s)
      Nakamura T.
    • Journal Title

      Biochim. Biophys. Acta. 1770

      Pages: 551-555

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human milk SIgA binds to botulinum type B 16S toxin and limits toxin adherence on T84 cells.2007

    • Author(s)
      Matsumura T.
    • Journal Title

      Biochem. Biophysic Res. Communi. 352

      Pages: 867-872

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of structural genes for Clostridium botulinum type C neurotoxin-converting phage particles.2007

    • Author(s)
      Hwang HJ.
    • Journal Title

      FEMS Microbiol. Lett. 270

      Pages: 82-89

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [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.2007

    • Author(s)
      Lee JC.
    • Journal Title

      Microbiol. Immunol. 51

      Pages: 445-455

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of nicking the C-terminal region of the Clostridium botulinum serotype D neurotoxin heavy chain on its toxicity and molecular properties.2007

    • Author(s)
      Suzuki T.
    • Journal Title

      Protein J. 26

      Pages: 173-181

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical application of Clostridium botulinum type A neurotoxin purified by a simple procedure for patients with urinary incontinence caused by refractory detrusor overactivity.2007

    • Author(s)
      Lee JC.
    • Journal Title

      FEMS Immunol. Med. Microbiol. 51

      Pages: 201-211

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary X-ray analysis of the HA3 component of Clostridium botulinum type C progenitor toxin.2007

    • Author(s)
      Nakamura T.
    • Journal Title

      Acta Cryst. F63

      Pages: 1038-1040

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effects of purified newly developed botulinum neurotoxin type A in rat prostate

    • Author(s)
      Nishiyama Y, Yokoyama T, Tomizawa K, Okamura K, Lee L. C, Matsui H, Oguma K, Nagai A, Kumon H
    • Journal Title

      Urology (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular analysis of an extrachromosomal element encoding the C2 toxin gene discovered in Clostridium botulinum type C

    • Author(s)
      Sakaguchi Y, Hayashi T, Yamamoto Y, Nakayama K, Zhang K, Ma S, Arimitsu H, and Oguma K
    • Journal Title

      J Bacteriol. (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] C 型とD型ボツリヌスC2毒素遺伝子をコードするプラスミドの解析2009

    • Author(s)
      阪口義彦、林哲也、中山恵介、山本由弥子、馬少博、橋本夕佳、張凱、小熊惠二
    • Organizer
      第82回日本細菌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] C型とD型ボツリヌスC2毒素遺伝子をコードするプラスミドの解析2009

    • Author(s)
      阪口義彦
    • Organizer
      第82回日本細菌学会総会
    • Place of Presentation
      名古屋,日本
    • Related Report
      2008 Annual Research Report
  • [Presentation] Botulinum toxin blocks neurotransmitter release from somata of rat neuropathic trigeminal ganglion neurons2008

    • Author(s)
      Yoichi, Kitamura, Yoshizo, Matsuka, Yoshihiro, Ishihara, Igor, Spigelman, Yumiko, Yamamoto, Wataru, Sonoyama, Horoshi, Kamioka, Takashi, Yamashiro, Keiji, Oguma and Takuro, Kuboki
    • Organizer
      The 6^<th> International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins
    • Place of Presentation
      Italy
    • Related Report
      2008 Final Research Report
  • [Presentation] The effect of peripheral administration of botulinum toxin type A in ratswith neuropathic pain2008

    • Author(s)
      Yoshizo Matsuka, Yoichi Kitamura, Igor Spigelman, Rahena Akther, Yumiko Yamamoto, Wataru Sonoyama, Keiji Oguma and Takuo Kuboki
    • Organizer
      The 6^<th> International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins
    • Place of Presentation
      Italy
    • Related Report
      2008 Final Research Report
  • [Presentation] ボツリヌス毒素および抗体の検出方法の開発2008

    • Author(s)
      小熊惠二, 横田憲治, 綾田潔
    • Organizer
      第82 回日本感染症学会総会
    • Place of Presentation
      島根
    • Related Report
      2008 Final Research Report
  • [Presentation] Clinical application of Clostridium botulinum type A neurotoxin purified by asimple procedure for patients with urinary incontinence caused by refractory detrusor overactivity.2008

    • Author(s)
      Oguma K
    • Organizer
      The 6th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins
    • Place of Presentation
      Italy
    • Related Report
      2008 Annual Research Report
  • [Presentation] Botulinum toxin blocks neurotransraitter release from somata of ratneuropathic trigeminal ganglion neurons.2008

    • Author(s)
      Kitamura Y
    • Organizer
      The 6th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins
    • Place of Presentation
      Italy
    • Related Report
      2008 Annual Research Report
  • [Presentation] The effect of peripheral administration of botulinum toxin type A in ratswith neuropathic pain.2008

    • Author(s)
      Matsuka Y
    • Organizer
      The 6th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins
    • Place of Presentation
      Italy
    • Related Report
      2008 Annual Research Report
  • [Presentation] C型とD型ボツリヌス菌の産生するホスホリパーゼCの酵素活性と生物活性2008

    • Author(s)
      阪口義彦
    • Organizer
      第61回日本細菌学会中国・四国支部総会
    • Place of Presentation
      愛媛,日本
    • Related Report
      2008 Annual Research Report
  • [Presentation] ボツリヌス毒素および抗体の検出方法の開発2008

    • Author(s)
      小熊恵二
    • Organizer
      第82回日本感染症学会総会
    • Place of Presentation
      島根,日本
    • Related Report
      2008 Annual Research Report
  • [Presentation] C型とD型ボツリヌスC2毒素遺伝子をコードするプラスミドの解析2008

    • Author(s)
      阪口義彦
    • Organizer
      BMB(Biochemistry and Molecular Biology)2008, 第31回日本分子生物学会年会、第81回日本生化学会大会、合同大会
    • Place of Presentation
      神戸,日本
    • Related Report
      2008 Annual Research Report
  • [Presentation] ボツリヌスC型HA1の三次構造と糖鎖への結合様式;DDSへの応用2007

    • Author(s)
      小熊惠二
    • Organizer
      19年度中四国乳酸菌研究会
    • Place of Presentation
      岡山,日本
    • Year and Date
      2007-05-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] Clostridium botulinum Structure of Progenitor toxin ; struc ture and function of hemagglutinin (HA)2007

    • Author(s)
      Keiji Oguma
    • Organizer
      1^<st> U. S. - Japan Medical Biodef ense Research & Bioterrorism Symposi um USA
    • Place of Presentation
      Arlington, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Clostridium botulinum. Structure of Progenitor toxin; structure and function of hemagglutinin (HA).2007

    • Author(s)
      Keiji Oguma.
    • Organizer
      1st U.S.-Japan Medical Biodefense Research & Bioterrorism Symposium USA.
    • Place of Presentation
      Arlington, USA.
    • Related Report
      2007 Annual Research Report
  • [Presentation] C型とD型ボツリヌス菌ホスホリパーゼCの酵素活性と生物活性2007

    • Author(s)
      清水健太
    • Organizer
      第60回日本細菌学会中国・四国支部総会
    • Place of Presentation
      岡山,日本
    • Related Report
      2007 Annual Research Report
  • [Presentation] ボツリヌス症2007

    • Author(s)
      小熊 惠二
    • Organizer
      衛生微生物技術協議会第28回研究会
    • Place of Presentation
      岡山,日本
    • Related Report
      2007 Annual Research Report
  • [Presentation] Crystal structure of Clostridium botulinum type C HA3 component.2007

    • Author(s)
      Mao Kotani
    • Organizer
      第80回日本生化学会大会
    • Place of Presentation
      横浜,日本
    • Related Report
      2007 Annual Research Report
  • [Book] 臨床と微生物(Vol.135 No.4)2008

    • Author(s)
      小熊惠二
    • Publisher
      近代出版
    • Related Report
      2008 Final Research Report
  • [Book] 臨床と微生物Vol. 135 No. 42008

    • Author(s)
      小熊恵二
    • Publisher
      近代出版
    • Related Report
      2008 Annual Research Report
  • [Book] 構造生物学-ポストゲノム時代のタンパク質研究- 2.7 各種不随意運動の治療に用いられている最強の毒素 ; ボツリヌス毒素2007

    • Author(s)
      小熊惠二
    • Publisher
      共立出版
    • Related Report
      2008 Final Research Report
  • [Book] 構造生物学-ポストゲノム時代のタンパク質研究-2.7各種不随意運動の治療に用いられている最強の毒素;ボツリヌス毒素.2007

    • Author(s)
      小熊 惠二
    • Publisher
      共立出版
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] ボツリヌス毒素由来のポリペプチド及びボツリヌス毒素の検出方法2008

    • Inventor(s)
      小熊惠二
    • Industrial Property Rights Holder
      小熊惠二
    • Industrial Property Number
      2008-272678
    • Filing Date
      2008-10-23
    • Related Report
      2008 Final Research Report
  • [Patent(Industrial Property Rights)] ボツリヌス毒素由来のポリペプチドを有効成分として含む鎮痛作用を有する医薬組成物2008

    • Inventor(s)
      窪木拓男・小熊惠二
    • Industrial Property Rights Holder
      窪木拓男・小熊惠二
    • Industrial Property Number
      2008-182218
    • Filing Date
      2008-07-14
    • Related Report
      2008 Final Research Report
  • [Patent(Industrial Property Rights)] ボツリヌス毒素由来のポリペプチドを有効成分として含む鎮痛作用を有する医薬組成物2008

    • Inventor(s)
      窪木拓男 小熊恵二
    • Industrial Property Rights Holder
      窪木拓男 小熊恵二
    • Industrial Property Number
      2008-182218
    • Filing Date
      2008-07-14
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] ボツリヌス毒素由来のポリペプチド及びボツリヌス毒素の検出方法2008

    • Inventor(s)
      小熊恵二
    • Industrial Property Rights Holder
      小熊恵二
    • Industrial Property Number
      2008-272678
    • Filing Date
      2008-10-23
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] ボツリヌス毒素成分HAを核酸の細胞内導入キャリアーとして利用 する方法2007

    • Inventor(s)
      (財)科学及血清療法研究所・小熊惠二
    • Industrial Property Rights Holder
      (財)科学及血清療法研究所・小熊惠二
    • Industrial Property Number
      2007-251502
    • Filing Date
      2007-09-27
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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