Project/Area Number |
16591045
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
|
Research Institution | Fukushima Medical University School of Medicine |
Principal Investigator |
SUZUKI Hitoshi Fukushima Medical University School of Medicine, Pediatrics, Professor, 医学部, 教授 (80045682)
|
Co-Investigator(Kenkyū-buntansha) |
SUZUKI Junzo Fukushima Medical University School of Nursing, Professor, 看護学部, 教授 (20171217)
HOSOYA Mitsuaki Fukushima Medical University School of Medicine, Pediatrics, Associate Professor, 医学部, 講師 (80192318)
KAWASAKI Yukihiko Fukushima Medical University School of Medicine, Pediatrics, Associate Professor, 医学部, 講師 (00305369)
ISOME Masato Fukushima Medical University School of Medicine, Pediatrics, Research Associate, 医学部, 助手 (00363747)
|
Project Period (FY) |
2004 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | IgA nephropathy / Hyper IgA(HIGA) mice / Coxsackie B4 Virus / コクサッキーウイルスB4 / 内皮細胞障害 / カーボン粒子 |
Research Abstract |
Objective. In order to clarify the pathogenetic role of viral infection in chronic glomerulonephritis, we examined the renal effects of Coxsackie B4 virus (CB4), a very common human enteric pathogen, in hyper IgA (HIGA) mice. Methods. Experiment 1 : Seventy-five mice in the injected group were inoculated intravenously with live CB4 virus (Group A) and inactivated (Group B) CB4 virus once a month from 1 to 12 months of age. Mice in the control group (Group C) were inoculated with vehicle. The kidneys were extirpated from 5 mice of each group sacrificed with time for measurement of proteinuria, cytokines and serum IgA levels, as well as and histological evaluation. Experiment 2 : Sixty mice in the injected group were inoculated intravenously with carbon or live (Group 1) or inactivated (Group 2) Cox.B4 virus once at 6 weeks of age. Mice in the control group (Group 3) were inoculated with vehicle. The kidneys were extirpated from 5 mice of each group sacrificed with time after inoculation
… More
for histological evaluation. Results. 1)On IF examination, mesangial IgA deposition was more frequently found in Group A than in Groups B and C, and CB4 RNA was detected in mesangial lesions of glomeruli in Group A. On LM examination, the scores for PCNA-positive cells and alpha-SMA-positive cells from 10 weeks to 20 weeks were higher in Group A than in Groups B and C. Matrix scores were higher in Group A than in Groups B and C. 2)On EM examination, swelling and detachment of endothelial cells from 3 hours to 5 days was more frequently found in Group a than in Groups b and c. 4)Serum IFN-gamma concentration increased from 10 weeks to 40 weeks in Group A and IgA levels did not differ among three groups. 5) Many carbon particles were present in peripheral and central zones of the mesangium from 5 to 10 days in Group 1 compared to Groups 2 and 3. Conclusion : These results suggest that CB4 provokes exacerbation of renal pathological findings in HIGA mice via endothelial injury, IFN-gamma production and dysfunction of the mesangial pathway. Less
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