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Polysaccharide of Pneumocystis carinii cyst wall as a new target for therapy

Research Project

Project/Area Number 04557022
Research Category

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

Allocation TypeSingle-year Grants
Research Field 寄生虫学(含医用動物学)
Research InstitutionUniversity of Tokyo

Principal Investigator

MATSUMOTO Yoshitsugu  Univ.of Tokyo, Faculty of Agriculture, Associate professor, 農学部, 助教授 (00173922)

Co-Investigator(Kenkyū-buntansha) YOKOIYAMA Shigeyuki  Asahi Chemical Industry Co., Ltd., Institute for Life Science Research, Senior I, ライフサイエンス総合研究所, 主幹研究員
KURAMOCHI Takashi  Central Institute for Experimental Animals, Investigator, 免疫研究室, 研究員 (10225253)
ITOH Mamoru  Central Institute for Experimental Animals, Investigator, 免疫研究室, 研究員 (00176364)
YAMADA Minoru  Kyoto Prefecutural Univ.of Med., Instructor, 医学部, 講師 (70106392)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1992: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsPneumocystis carinii / Pneumocystis carinii pneumonia / opportunistic infection / glucan / aculeacin / therapeutic agent / AIDS / scid mouse / 日和見感染症
Research Abstract

Pneumocystis pneumonia is the most common and most serious opportunistic infection in immunocompromised patients, particularly those with AIDS.Approved therapy is limited to pentamidine and inhibitors of folic acid synthesis, but these drugs show a high rate of adverse reactions in AIDS patients emphasizing the urgent need for additional effective therapies^<4-7>. Progress has, hawever, been hindered by lack of knowledge about this parasite's cellular characteristics. This study shows that in vitro treatment of P.carinii cysts with beta-1, 3-glucan laminaripentaohydrolase results in cyst wall lysis and loss of Aniline blue staining, a dye which selectively demonstrates 3-1, 3-glucan. Additionally, administration of aculeacin A, an inhibitor of beta-1, 3-glucan biosynthesis, affects cyst wall formation, inhibits cyst maturation, and prevents severe pneumonia in steroid-treated rats. Thus this study not only demonstrates that beta-1, 3-glucan (yeast glucan) is a major cyst wall component and indispensable for growth of the parasite in rats, but suggests a new therapeutic strategy for human pneumocystosis.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] 松本芳嗣: "ニューモシスチス・カリニ肺炎治療薬の開発-細胞壁多糖を標的として" 医学のあゆみ. 165. 853 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.T.Cushion: "Recent Advances in the Biology of Pneumocystis carinii" The Journal of Medical and Veterinary Mycology. in press. (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 松本芳嗣: "グルカン合成阻害薬aculeacin AとST合剤の併用による実験的ラット・ニューモシスチスカリニ肺炎の予防" JAPANESE JOURNAL OF PARASITOLOGY. 41(補). 116 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 倉持隆司: "SCIDマウスにおける実験的ニューモシスチス・カリニ肺炎に対するグルカン合成阻害薬の予防効果" JAPANESE JOURNAL OF PARASITOLOGY. 41(補). 116 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsumoto, Y.and Yamada, Y.: "Efficacies of aculeacin A, an inhibitor of beta-1, 3-glucan, in combination with trimethoprim-sulfamethoxazole in the prevention of experimental Pneumocystis carinii pneumonia in rats." Jpn.J.Parasitol.41(Suppl.). 116 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuramochi, T., Murakami, S., Hioki, K., Ito, M.and Matsumoto, Y.: "Inhibitors of beta-1, 3-glucan biosynthesis as prophylactic agents against experimental Pneumocystis carinii pneumonia in SCID mice." Jpn.J.Parasitol.41(Suppl.). 116 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsumoto, Y.: "Polysaccharide of Pneumocystis carinii cyst wall as a new target for therapy." J.Clin.Expt.Med.(Igaku no Ayumi). 165(12). 853 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Cushion, M.T., Harmsen, A., Matsumoto, Y., Stringer, J.R., Wakefield, A.E.and Yamada, M.: "Recent advances in the biology of Pneumocystis carinii." J.Med.Vet.Mycol.(in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 松本芳嗣: "ニューモシスチス・カリニ肺炎治療薬の開発-細胞壁多糖を標的として" 医学のあゆみ. 165. 853 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.T.Cushion,A.Harmsen,Y.Matsumoto,et.al.: "Recent Advances in the Biology of Pneumocystis carinii" The Journal of Medical and Veterinary Mycology. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松本 芳嗣,山田 稔: "グルカン合成阻害薬aculeacin AとST合剤の併用による実験的ラット・ニューモシスチス・カリニ肺炎の予防" 日本寄生虫学雑誌. 41Suppl.116 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 倉持 隆司,村上 茂,日置 恭司,伊藤 守,松本 芳嗣: "SCIDマウスにおける実験的ニューモシスチス・カリニ肺炎に対するグルカン合成阻害薬の予防効果" 日本寄生虫学雑誌. 41Suppl.116 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 松本 芳嗣: "ニューモシスチス・カリニ肺炎治療薬の開発・細胞壁多糖を標的として" 医学のあゆみ. (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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