| Project/Area Number |
12670572
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
FUJISHIMA Seitaro Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (00173419)
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| Co-Investigator(Kenkyū-buntansha) |
YOGO Yurika Department of Medicine, School of Medicine, Keio University, Instructor, 医学部, 助手 (90306712)
TATENO Hiroki Department of Medicine, School of Medicine, Keio University, Instructor, 医学部, 助手 (50286473)
HIRAOKA Yoshiki Department of Anatomy, School of Medicine, Keio University , Assistant Professor, 医学部, 講師 (80218768)
SEKINE Kazuhiko Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Instructor, 医学部, 助手 (90296715)
山崎 元靖 慶應義塾大学, 医学部, 助手 (00296716)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | chemokine / gene polymorphism / MCP-1 / interleukin-8 / NRAMP1 / 炎症性肺疾患 / sepsis / 肺線維症 / interleukin 8 / interleukin 18 / 肺結核症 |
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| Research Abstract |
1. Identifiticantion and analysis of chemokine, etc gene polymorphisms: Initially we analyzed various gene polymorphisms of a NRAMP1 gene in Japanese healthy controls and patients with pulmonary tuberculosis. Among polymorphisms analyzed, the rare combination of one and two GT repeats was more frequent in patients with pulmonary fibrosis (PF).
We then analyzed fibronectin SNPs in Japanese healthy controls and patients with pulmonary fibrosis. Although these frequency was quite different between Japanese and Caucasians, it was not different in PF patients.
By examining MCP-1 promoter -2518 SNP, we found that allele G was more frequent in Japanese, but its frequency was not different in PF patients. Plasma MCP-1 levels was not different among MCP-1 genotypes.
For IL-8 gene analysis, we searched new polymorphisms by directly sequencing 1 Kb promoter region and found that the frequency distribution of this SNP was 1:3:6 in a sepsis patient and 16:47:37 (A/A:A/T:T/T) in healthy controls.
2. Analysis of various mediator genes expression in animal models: (1) A rat model of radiation fibrosis: We analyzed the gene expressions of chemokines, MCP-1, MIP-1alpha, beta, MIP-2, lymphotactin, and fractalkine and found the augmented expression of MCP-1, TARC mRNA at four weeks after irradiation, and a slightly increased expression of MCP-1, MIP-1alpha at 8 weeks.
2) A mouse model of burn-primed sepsis and ARDS:
The 72 hour survival was 100% in no priming group and 0% in a bum primed model. The plasma cytokine increase was single-peaked in no priming group and two-peaked in burn-primed group. Furthermore, liver IL-18 content was significantly higher in burn-primed group than in sham group one week after the treatment.
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