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2001 Fiscal Year Final Research Report Summary

An approach to the pathogenesis of inflammatory lung diseases by establishing efficient analytical protocols for multiple mediator gene polymorphisms

Research Project

Project/Area Number 12670572
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKeio University

Principal Investigator

FUJISHIMA Seitaro  Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (00173419)

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)
Project Period (FY) 2000 – 2001
Keywordschemokine / gene polymorphism / MCP-1 / interleukin-8 / NRAMP1
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.

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Tateno H, Fujishima S, et al.: "Eotaxin and monocyte chemoattractant protein-1 in chronic eosinophilic pneumonia"Eur Respir J. 17. 962-968 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] 藤島清太郎, 佐々木淳一: "基礎傷病の有無による細菌内毒素反応の差異とcytokine産生抑制剤の効果:マウス熱傷後septic ALIモデルによる検討"第5回Acute Lung Injury研究会誌. 19-21 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Fujishima S, Gao PS, et al.: "Genetic variants of NRAMP1 and active tuberculosis in Japanese populations"Clin Genet. 58(1). 74-76 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura M, Fujishima S, et al.: "Importance of interleukin-8 in the development of reexpansion lung injury"Am J Respir Crit Care Med. 161. 1030-1036 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 大久保泰之, 藤島清太郎: "呼吸不全の病態 急性肺傷害と分子生物学 サイトカインの面から"Medical Practice. 17(12). 2035-2037 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 関根和彦, 藤島清太郎, 相川直樹: "SIRSメディエータのマーチ SIRSと抗サイトカイン療法"現代医療. 32増刊III. 133-138 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 藤島清太郎: "サイトカインと疾患 SIRS,セプシスとサイトカイン"医歯薬出版社 別冊・医学の歩み. 5 (2000)

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  • [Publications] Tateno H, Nakamura H, Mmematsu N, Amakawa K, Terashima T, Fujishima S, Luster AD, Lilly CM, Yamaguchi K: "Eotaxin and monocyte chemoattractant protein-1 in chronic eosinophilic pneumonia"Eur Respir J. 17. 962-968 (2001)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Fujishima S, Sasaki J, Yamaguchi K, Aikawa N: "Different response to endotoxin with and without prior burn insult"J fifth Acute Lung Injury. 19-21 (2001)

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  • [Publications] Aikawa N, Aoki K, Hori S, Fujishima S: "Definition, diagnosis and severity score of organ failure"Gendai Iryo. 33. 13-17 (2001)

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  • [Publications] Umeda K, Yamasawa F, Fujishima: "Acid Base Disturbance"Respiration Research. 20 (8). 795-799 (2001)

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  • [Publications] Yamazaki M, Fujishima S , Aikawa N: "Anti-cytokine strategy for shock"Rinshoi. 27 (8). 2166-2167 (2001)

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  • [Publications] Fujishima S: "Cytokine determination and SIRS severity"Kansensho-to-Kagakuryoho. 5 (6). 11-14 (2001)

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  • [Publications] Sasaki J, Fujishima S, Kobayashi K, Aikawa N: "Treatment strategy for sepsis"Gendai Iryo. 33 (3). 849-854 (2001)

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  • [Publications] Fujishima S, Gao PS, Mao XQ, Remus N, Kanda M, Enomoto T, Dake Y, Bottini N, Tabuchi M, Hasegawa N, Yamaguchi K, Tiemessen C, Hopkin JM, Shirakawa T, Kishi F: "Genetic variants of NRAMP1 and active tuberculosis in Japanese populations"Clin Genet. 58 (1). 74-76 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura M, Fujishima S, Sawafuji M, Ishizaka A, Oguma T, Soejima K, Matsubara H, Tasaka.S, Kikuchi K, Kobayashi K, Ikeda E, Sadick M, Hebert CA, Aikawa N, Kanazawa M, Yamaguchi K: "Importance of interleukin-8 in the development of reexpansion lung injury in rabbits"Am J Respir Crit Care Med. 161. 1030-1036 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Okubo Y, Fujishima S: "Acute lung injury and molecular biology, a cytokine view"Medical Practice. 17 (12). 2035-2037 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Sekine K, Fujishima S, Aikawa N: "SIRS and anti-cytokine therapy"Gendai Iryo. 32. 133-138 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Sasaki J, Fujishima S, Kobayashi K, Aikawa N: "Anti-mediator therapy for Sepsis"Therapy. 82. 588-594 (2000)

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Published: 2003-09-17  

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