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Gene diagnoics of Sudden death and its practise

Research Project

Project/Area Number 10357004
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Public health/Health science
Research InstitutionUniversity of Tokyo

Principal Investigator

TOYO-OKA Teruhiko  University of Tokyo, Health Service Center, Professor, 保健管理センター, 教授 (00146151)

Co-Investigator(Kenkyū-buntansha) TOMARU Takanobu  Red Cross Hospital, Division of Cardiology, Chief, 循環器科, 部長 (60180163)
SHIN Wee soo  University of Tokyo, Health Service Center, Research Associate, 保健管理センター, 助手 (10211971)
SAKAMOTO Aiji  Research Institute of NCVC, Chief Investigator, 室長 (40291067)
NAKAMURA Fumitaka  University of Tokyo, Dept. of Cardiol., Research Associate, 医学部, 循環器内科・助手 (20261969)
鈴木 順一  東京大学, 保健管理センター, 講師 (50260485)
上原 誉志夫  東京大学, 保健管理センター, 助教授 (40184965)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥18,400,000 (Direct Cost: ¥18,400,000)
Fiscal Year 2000: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1998: ¥7,000,000 (Direct Cost: ¥7,000,000)
KeywordsGene / Diagnosis / Sudden death / Mitochondria / HCM / DCM / MELAS / D-loop / 遺伝子 / Dループ / 発症前診断 / 予防医学
Research Abstract

Upto last year, we have reported gene analysis of mitochondrial DNA (mtDNA) mutation. This year, we analyzed evolutional modification of the gene mutation with special reference to cardiomyopathy development. Following the routine methods of gene isolation and preparation of mtDNA from patients with HCM, DCM, other cardiac diseases and normal control subjects, In the present study, we added the gene analysis of D-loop to characterize genetic lineage of the patients after PCR amplification.
In summary, 162 cases with cardiomyopathy (HCM, 112 and DCM, 50 cases), we identified MELAS type mutation, i.e, A3243G, in 4 cases (2.5%) but found no case in 168 subjects without the cardiomyopathies. After analyzing 4 cases with MELAS-type mutation, to our surprise, 10 cases with other type cardiomyopathies and 23 subjects without cardiomyopathy, we found all subjects with these MELAS mutation segregated to one family with the common D-loop (Shin et al, Am.J.Hum.Genet.200Q). Accordingly, these results suggest the common roots of MELAS patients.

Report

(4 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Shin WS, Tanaka M, Suzuki J, Toyo-ok T.: "A homoplamic mitochondrial DNA mutation with characteristic D-loop sequence as a risk factor cardioselective expression of myopathy"Am. J. Hum. Gen.. 67. 1617-1620 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Xi H, Shin WS, Suzuki J, et al.: "Dystrophin disruption might be related to myocardial cell apoptosis caused by isoproterenol"J. Cardiovasc. Pharmacol.. 36(Suppl.2). S25-S29 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang Y, Chen J, Wang Y, et al.: "Crucial role type 1, but not type 3, inositol 1,4,5-trisphosphate IP_3 receptors in IP_3-induced Ca^<2+> capacitative Ca^<2+> entry and proliferation of A7r5 vascular smooth muscle cells"Circ. Res.. 88. 202-209 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawada T, Sakamoto A, Nakazawa M, et al.: "Morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy"Biochem. Biophys. Res. Commun.. 284. 431-435 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toyo-oka T.: "Long-and short-term cross talk between endothelial cells and vascular smooth muscle cells mediated by nitric oxide"Jpn. Heart J. 2001. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawada T, Nakazawa M, Sakamoto A, et al.: "Long-term rescue of hereditrary form of dilated cardiomyopathy by rAAV vector-mediated somatic gene therapy"Proc. Natl. Acad. Sci., USA. 99. 901-906 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shin WS, Toyo-oka T.: "Coculture of endothelial cells and vascular smooth muscle cells"Humana Press (London).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shin W.S., Tanaka M., Suzuki J., Toyo-oka T.: "A homoplamic mitochondrial DNA mutation with characteristic D-loop sequence as a risk factor cardioselective expression of myopathy"Am. J. Hum. Gen.. 67. 1617-1620 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Xi H., Shin W.S., Suzuki J., et al.: "Dystrophin disruption might be related to myocardial cell apoptosis caused by isoproterenol"J. Cardiovasc. Pharmacol.. 36 (Suppl. 2). S25-S29 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang Y., Chen J., Wang Y., et al.: "Crucial role of type 1, but not type 3, inositol 1,4,5-trisphosphate IP_3 receptors in IP_3-induced Ca^<2+> release, capacitative Ca^<2+> entry, and proliferation of A7r5 vascular smooth muscle cells"Circ. Res.. 88. 202-209 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawada T., Sakamoto A., Nakazawa M,. et al.: "Morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy"Biochem. Biophys. Res. Commun.. 284. 431-435 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toyo-oka T.: "Long- and short-term cross talk between ehdothelial cells and vascular smooth muscle cells mediated by nitric oxide"Jpn. Heart J.. (In press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawada T., Nakazawa M., Sakamoto A., et al.: "Long-term rescue of hereditrary form of dilated cardiomyopathy by rAAV vector-mediated somatic gene therapy"Proc. Natl. Acad. Sci., USA. 99. 901-906 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shin W.S. and Toyo-oka T.: "Cocultiire of endothelial cells and vascular smooth muscle cells"Humana Press (London).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hikiji H et al.,: "Peroxynitrite production by TNF-α and IL-1β."Am.J.Physiol.. 278. E1031-E1037 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wang YP et al.,: "Autocrine action and its underlying mechanism…"J.Biol.Chem.. 275. 28739-28749 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shin WS et al.,: "A homoplamic mitochondrial DNA mutation…"Am.J.Hum.Gen.. 67. 1617-1620 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xi H et al.,: "Dystrophin disruption might be related to ……"J.Cardiovasc.Pharmacol.. 36. S25-S29 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki J et al.,: "Screening and/or follow-up with…"Radiology. 6. 189-197 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wang YP et al.,: "Crucial role of type 1, but not type 3,…"Circ.Res.. 88. 202-209 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki J, et al.: "Morphological onset and early diagnosis in apical hypertrophic cardiomyopathy ; a long-term analysis with nuclear magnetic resonance imaging"J. Am. Coll. Cardiol.. 33:. 146-151 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawada T, et al.: "Precise identification of gene-products in hearts after in vivo gene transfection, using Sendai virus-coated proteoliposomes"Biochem. Biophys. Res. Commun.. 259. 408-413 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirawa N, et al.: "Long-tern inhibition of renin-angiotensin system sustainains memory function in aged Dahl rats"Hypertension. 34:. 496-502 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Asano M, et al.: "Eicosapentaenoic acid inhibits vasopressin-activated Ca^<2+> influx and cell proliferation in rat aortic smooth muscle cell line"Eur. J. Phamacol.. 379;. 199-209 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawada T. et al.: "Strain- and age-dependent loss of sarcoglycan complex in cardiomyopathic hamstar hearts and its reexpression by δ-sarcoglycan gene transfer in vivo"F. E. B. S. Lett.. 458;. 405-8, (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawaguchi H, et al.: "Apoptotic cell death in acute myocardial injury induced by isoproterenol is mediated by nitric oxide"J. Cardiovasc. Pharmacol.. 34(Suppl.4);. S25-8, (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagoshi H.et al.: "Prostaglandin D2 inhibits inducible nitric oxide synthaseexpression in rat vascular smooth muscle." Circ.Res.82. 204-209 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamazaki T.et al.: "Transient hypertension in male adolescents when measured by women." Heart. 79. 104-105 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimamoto R.et al.: "Measuring the diameter of coronary arteries on MR angiograms using spatia profile curbes." Am.J.Roent.170. 889-893 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uehara H.et al.: "A hypertensive father,but not hypertensive mother,determines blood pressure in normotensive male offspring through body mass index." J Human Hyperten.12. 441-445 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki J.et al.: "Morphological onset and early diagnosis inapical hypertrophic cardiomyopathy" J Am Coll Cardiol. 33. 146-151 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawada T.et al.: "In vivo Gene Supplementation for the Therapy of Cardiomyopathy." J Card Failure. (in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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