| Project/Area Number |
63570425
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | GUNMA UNIVERSITY |
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Principal Investigator |
TOMIZAWA Shigeru Gunma University, Dept. of Pediatrics, Assis Prof., 医学部, 講師 (90125865)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASHIMA Kanji Gunma University, Dept. of Pediatrics, Lectur, 医学部, 講師 (00164418)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1988: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | MCNS / VPF / T-lymphocyte / CD4^+cell / lymphokine / less anionic albumin / pI / GBM / CD4^+cell / less anicnic albumin / 微小変化型ネフローゼ症候群 / 血管透過性因子 / 糸球体基底膜透過性因子 / 尿中アルブミン / 陰性荷電 / 等電点電気泳動 |
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| Research Abstract |
The etiology of minimal change nephrotic syndrome(MCNS) is obscure. Several investigators have presumed that vascular permeability factor(VPF) derived from lymphocyte cultures in MCNS might be related to massive proteinuria. We already demonstrated that VPF was produced by T-lymphocytes from patients with MCNS. Furthermore, the infusion of T-lymphocyte culture supernatants from patients with MCNS into the left renal artery of rats, induced not only significant proteinuria in the rat urine but also a reduction of anionic sites in the glomerular basement membrane of the kidney in the hats. In order to determine the identity of T-lymphocyte subset in MCNS which release VPF, VPF assay of the culture supernatant of T-lymphocyte, CD4^+ cell or CD8^+ cell enriched fraction was performed. T-lymphocytes were purified by passage over a nylon wool column and separated to either CD4^+ cell or CD8^+ cell enriched fractions with monoclonal antibodies (anti-OKT4 and anti-OKT8 antibody) and a rabbit c
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omplement. VPF activity was found in either T-lymphocyte or CD4^+ cell enriched culture-supernatant. Moreover, its activity has not been inhibited by either anti-IL1 or anti-IL2 antibody. These results suggest that VPF might be different from lymphokines such as IL1 or IL2 and be produced by CD4^+ cells. Further studies are needed to clarify the correlations between VPF production of CD4^+ cells and massive proteinuria in MCNS.
Next, it is reported that pI changes of serum and urine from nephrotic patients will be one of causes of protein excretion. We purified albumin from urine and investigated the pI and glomerul; basement membrane(GBM) permeability of rat kidney by infusing of the albumin. As the results, less anionic albumin was detected in the urine from MCNS patients. After infusion of the less anionic albumin to the rat kidney, the negative charge of the rat GBM was reduced and increased protein excretion. From these results, it is presumed that less anionic albumin will neutralized the negative charge of GBM, and will enhance the protein permeability. This will be one of the mechanism of protein excretion. Less
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