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Studies of pathogenesis in Farber disease-cloning of the DNA and study of signal transduction system

Research Project

Project/Area Number 09670805
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionOsaka University

Principal Investigator

INUI Koji  Osaka University Medical School, Associate Peofessor, 医学部, 助教授 (90175208)

Co-Investigator(Kenkyū-buntansha) NISHIGAKI Toshinori  Osaka University Medical School, Assistant Peofessor, 医学部, 助手 (20283749)
OKADA Shintaro  Osaka University Medical School, Peofessor, 医学部, 教授 (30028609)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsFarber disease / ceramidase / mutation analysis / apoptosis / cytokins / 遺伝子異常 / フポトーシス
Research Abstract

Farber disease is a rare autosomal recessive sphingolipidosis caused by a deficiency of acid ceramidase, a lysosomal enzyme that normally catalyzes the hydrolysis of ceramide to sphingosine and free fatty acids.The disease is clinically characterized by swollen joints with limitation of movements, disseminated subcutaneous nodules, particularly in the joints and over pressured points, hoarseness, and progressive cachexia.Recently the mode of ceramide action and the regulation of its production have attracted great attention impart due to the emerging role of ceramide as an intracellular effector molecule in apoptosis.It is possible that at least some of the pathologic events in Farber disease are related to second messenger functions.We have recently diagnosed two patients with type II Farber disease due to the reduced enzymatic activity of ceramidase and accumulation of ceramide after feeding of radiolabelled serin.cDNA analysis of these patients disclosed V369I/V97E and homogygous mutation of V96 del, respectively.These mutations were confirmed in expression studies in COS I cells.Increased secreations of cytokins including IL-2, -6, and TNF- alpha, not detected in skin fibroblasts from control and Farber disease, and ceramide did not induced cytokin productions.The removed nodules showed increased level of ceramide and macrophage infiltrations.However, immunostainig of Fas, bcl-2, and IL-6 showed negative.Tunel method did not show significant positive staining and no DNA ladder was not detected in extracted DNA from nodules.These evidence suggest that apoptosis did not occur in the nodules.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Sakai N et al.: "Human galactocerebrosidase gene : promoter..." Biochem Biophys Acta. 1395. 62-67 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fu L et al.: "Molecular heterogeneity of Krabbe disease" J Inherit Meta Dis. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mohri I et al.: "A case of Kearns-Syre syndrome" J Neurol Sci. 158. 106-109 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taniike M et al.: "Suppressed LIDP-galactose : ceramide..." J Neurosci Res. 51. 536-540 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takiyama et al.: "Molecular form and subcellular..." Brain Dev. 19. 126-130 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Manoj et al.: "Haplotype and mutation analysis..." Am J Hum Genet. 60. 1423-1429 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 乾 幸治: "小児科学 Krabbe病" 医学書印, 2 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 乾 幸治: "小児内科 小児筋疾患の展望" 東京医学社, 3 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sakai N et al.: "Human galactocerebrosidase gene ; promoter ・・・" Biochem Biophys Acta. 1395. 62-67 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fu L et al.: "Molecular heterogeneity of krabbe disease" J Inherit Meta Dis. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mohri I et al.: "A case of kearns - Syre syndrome ・・・" J Neurol Sci. 158. 106-109 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Taniike M et al.: "Suppressed UDP - galactose ; ceramide" J Neurosci Res. 51. 536-540 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takiyama et al.: "Molecular form and subcellular ・・・" Brain Dev. 19. 126-130 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Manoj et al.: "Haplotype and mutation analysis ・・・" Am J Hum Genet. 60. 1423-1429 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 乾幸治: "小児科学 Krabbe 病" 医学書院, 2 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 乾幸治: "小児内科 小児筋疾患の展望" 東京医学社, 3 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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