| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
(1) To clarify the clinical characteristics of trichosporonosis, the questionnairing was conducted on 32 hospitals in Kumamoto. The results of the questionnaire was that 6 cases of trichosporonosis were found and all cases had neutropenia and underlying disease.
(2) Detection of Trichosporon in clinical specimen (sputum and urine) was made possible by PCR method.
(3) We produced disseminated trichosporonosis in a neutropenic murine model with clinical and environmental isolates of Trichosporon asahii, identified by DNA relatedness. We then assessed the efficacy of granulocyte colony-stimulating factor (G-CSF ; 30-100 mug/kg.day) and granulocytemacrophage colony-stimulating factor (GM-CSF ; 0.8-2 mug/kg.day). The administration of G-CSF,either before or after infection, improved the survival rate from less than 25% up to 100% (p<0.05). Effects of G-CSF on organ clearance and histological examinations were most remarkable in the lungs. The levels of tumor necrosis factor-a (TNF-alpha) in bronchoalveolar lavage fluid (BALF) of neutropenic, non-immunosuppressed and G-CSF pre-treated mice were 6.0 <plus-minus> 0.6*10^4,1.3 <plus-minus> 0.4*10^2 and 18 <plus-minus> 6 ng/ml, respectively, at 24 h after infection. Immunohistologically, alveolar macrophages proved to be the main source of TNF-alpha in BALF.GM-CSF increased neutrophil counts less significantly than did G-CSF and increased the lethality (p<0.05) with a high level of TNF-alpha in BALF.Expecting to inhibit TNF-alpha, we administrated anti-TNF-alpha intraperitoneally at the dose completely inhibiting TNF-alpha in plasma, but the TNF-alpha in BALF and also the lethality increased. Though the number of neutrophils appeared to be the most critical, the opposite effects of G-CSF and GM-CSF suggest that other host defense mechanisms, such as TNF-alpha overproduction in the lungs, has a role in trichosporonosis.
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