| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Background : Drug-efflux pumps are known as one of mechanisms of drug resistance in cancer cells, because of transportation of anticancer drugs out of cells, and these pumps also transport corticosteroids. Most of adult patients with minimal change nephrotic syndrome (MCNS) are steroid-responsive ; however, relapse occurs in 10 to 40% of patients with steroid-sensitive MCNS. We investigated the association between these pumps of T cells and steroid dependency in MCNS.
Methods : Eleven Japanese patients (5 males and 6 females) who showed clinical and renal immunopathological signs of primary MCNS were studied. Diagnosis of MCNS was based on a renal biopsy that showed no abnormality by light microscopic examination and the absence of immunoglobulins or complements deposits by immunofluorescence examination. All patients responded to corticosteroids (prednisolone) and proteinuria had immediately disappeared. Corticosteroids were gradually tapered and this study was performed at the time wh
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en treated doses of prednisolone were withdrawn to 10 mg daily. After then, these patients were divided into two groups ; one group consisted of patients with MCNS who had not relapsed one or more years after discontinuation of steroid therapy, and the another group consisted of patients with MCNS who had relapsed during steroid therapy. Peripheral blood mononuclear cells (PBMC) from them were incubated in rhodamine-123-added medium. Incubated PBMCs were washed and reincubated in dye-free medium with or without the presence of verapamil as the inhibitor of drug-efflux pumps. After then, reincubated cells were stained with phycoerythrin-conjugated anti-human CD3 antibody and analyzed via flow cytometer.
Results : This flow cytometric assay revealed no difference of percentages of CD3^+ cells between both groups (65.1±9.1% vs.75.5±3.0%). There was no difference of percentages of rhodamine-123^+CD3^+ cells among the CD3^+ cells measured between both groups in the presence of verapamil (97.7±0.6% vs. 95.9±0.7%). However, in the absence of verapamil, percentages of rhodamine-123^+CD3^+ cells from steroid-dependent MCNS patients (51.6±3.8%) were significantly lower than those cells from steroid-independent MCNS (83.7±2.2%).
Conclusion : T lymphocytes from steroid-dependent patients showed significantly higher dye efflux. Therefore, transportation of corticosteroids out of T lymphocytes might lead to steroid dependency, and this efflux test would be helpful for prediction of relapse. Less
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