1993 Fiscal Year Final Research Report Summary
Polysaccharide of Pneumocystis carinii cyst wall as a new target for therapy
| Project/Area Number |
04557022
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
寄生虫学(含医用動物学）
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| Research Institution | University of Tokyo |
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Principal Investigator |
MATSUMOTO Yoshitsugu Univ.of Tokyo, Faculty of Agriculture, Associate professor, 農学部, 助教授 (00173922)
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| 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)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Pneumocystis carinii / Pneumocystis carinii pneumonia / opportunistic infection / glucan / aculeacin / therapeutic agent / AIDS / scid mouse |
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| 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.
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[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)
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