Polysaccharide of Pneumocystis carinii cyst wall as a new target for therapy
Polysaccharide of Pneumocystis carinii cyst wall as a new target for therapy
批准号:
04557022
负责人:
MATSUMOTO Yoshitsugu
金额:
$4.22万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
财政年份:
1992
资助国家:
日本
项目状态:
已结题
起止时间:
1992 至 1993
中文摘要
肺孢子虫肺炎是免疫功能低下患者,特别是艾滋病患者中最常见和最严重的机会性感染。批准的治疗仅限于喷他脒和叶酸合成抑制剂,但这些药物在艾滋病患者中显示出很高的不良反应率,强调迫切需要额外的有效治疗<4-7>。然而,由于缺乏对这种寄生虫细胞特征的了解,进展受到了阻碍。该研究表明,用β-1,3-葡聚糖昆布五糖水解酶体外处理卡氏肺孢子虫包囊导致包囊壁溶解和苯胺蓝染色的损失,苯胺蓝染色是一种选择性地显示β-1,3-葡聚糖的染料。此外,在类固醇治疗的大鼠中,给予β-1,3-葡聚糖生物合成抑制剂--刺桐素A,可影响囊肿壁形成,抑制囊肿成熟,并预防严重肺炎。因此,这项研究不仅证明β-1,3-葡聚糖(酵母葡聚糖)是一种主要的囊壁成分,是寄生虫在大鼠体内生长所不可或缺的,而且还提出了一种治疗人类肺孢子虫病的新策略。
英文摘要
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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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)
Matsumoto, Y. 和 Yamada, Y.:“aculeacin A(一种 β-1, 3-葡聚糖抑制剂)与甲氧苄氨嘧啶-磺胺甲恶唑联合预防大鼠实验性卡氏肺孢子虫肺炎的功效。”
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通讯作者:
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)
Yoshitsugu Matsumoto:“卡氏肺孢子虫肺炎治疗药物的开发 - 靶向细胞壁多糖”《医学史》165. 853 (1993)。
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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)
Takashi Kuramochi:“葡聚糖合成抑制剂对 SCID 小鼠实验性卡氏肺囊虫肺炎的预防作用”,《日本寄生虫学杂志》41(增刊)。
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M.T.Cushion: "Recent Advances in the Biology of Pneumocystis carinii" The Journal of Medical and Veterinary Mycology. in press. (1994)
M.T.Cushion:“卡氏肺囊虫生物学的最新进展”《医学和兽医真菌学杂志》。
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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)
Yoshitsugu Matsumoto:“联合使用葡聚糖合成抑制剂阿库莱星 A 和 ST 组合预防卡氏肺孢子虫肺炎的实验”《日本寄生虫学杂志》41(补充)。
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共 12 条
Epidemiology and pathlogy of leishmaniasis in Old world.
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批准号:23256001
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项目类别:Grant-in-Aid for Scientific Research (A)
-
资助金额:$29.12万
-
财政年份:2011
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负责人:MATSUMOTO Yoshitsugu
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依托单位:
Epidemiology of human visceral leishmaniasis (Kala-azar) in Old World
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批准号:19256001
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项目类别:Grant-in-Aid for Scientific Research (A)
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资助金额:$26.29万
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财政年份:2007
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负责人:MATSUMOTO Yoshitsugu
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依托单位:
Studies on atypical cutaneous leishmaniasis in Sri Lanka
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批准号:16406007
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$6.4万
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财政年份:2004
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负责人:MATSUMOTO Yoshitsugu
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依托单位:
Development of vaccine and diagnosis targeted on Leishmania amastigotes specific protein
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批准号:13557020
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$3.71万
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财政年份:2001
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负责人:MATSUMOTO Yoshitsugu
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依托单位:
Epidemiology and Control of Leishmaniasis in Central Eurasia ; A new epidemic in association with irrigation of deserts
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批准号:10041190
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项目类别:Grant-in-Aid for Scientific Research (A).
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资助金额:$16.51万
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财政年份:1998
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负责人:MATSUMOTO Yoshitsugu
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依托单位:
Epidemiology and Control of Leishmaniasis in Cetral Eurasia ; A new epidemic in association with irrigation of deserts
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批准号:08041169
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项目类别:Grant-in-Aid for international Scientific Research
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资助金额:$8.38万
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财政年份:1996
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负责人:MATSUMOTO Yoshitsugu
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依托单位:
Development of live vaccine used transgenic Leishmania parasite
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批准号:08456149
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$4.74万
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财政年份:1996
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负责人:MATSUMOTO Yoshitsugu
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依托单位:
Immunological and Genetical Heterogeneity of Pneumocystis carinii
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批准号:05670223
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$1.34万
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财政年份:1993
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负责人:MATSUMOTO Yoshitsugu
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依托单位:
海外基金