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心筋細胞の文化異常と病態形式

Research Project

Project/Area Number 06274105
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionKurume University

Principal Investigator

古賀 義則  久留米大学, 医学部, 教授 (50080669)

Co-Investigator(Kenkyū-buntansha) 古川 哲史 (古川 哲央)  東京医科歯科大学, 難治疾患研究所, 助手 (80251552)
松原 弘明  関西医科大学, 講師 (10239072)
永井 良三  群馬大学, 医学部, 教授 (60207975)
杉浦 清了  東京大学, 医学部, 助手 (10272551)
堀 久枝  東京医科歯科大学, 難治疾患研究所, 助手 (80014190)
杉山 理  応用生化学研究所, 部長 (30111850)
芹澤 剛  東京大学, 医学部, 講師 (90143429)
木村 彰方  九州大学, 生体防御医学研究所, 助教授 (60161551)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥117,000,000 (Direct Cost: ¥117,000,000)
Fiscal Year 1996: ¥35,000,000 (Direct Cost: ¥35,000,000)
Fiscal Year 1995: ¥40,000,000 (Direct Cost: ¥40,000,000)
Fiscal Year 1994: ¥42,000,000 (Direct Cost: ¥42,000,000)
Keywords肥大型心筋症 / QT延長症候群 / ミトコンドリア心筋症 / サルコメア蛋白遺伝子異常 / K^+チャンネル遺伝子 / Cl^-チャンネル遺伝子 / HERG遺伝子 / インビトロ運動再構築系 / 収縮蛋白遺伝子異常 / アクチン滑り速度 / カリウムチャンネル遺伝子 / アポトーシス / チロシンキナーゼ / 心筋βミオシン重鎖遺伝子 / ミオシン調節軽鎖遺伝子 / アイチン滑り速度 / ナトリウムポンプ遺伝子
Research Abstract

本研究の目的は心筋に特異的に分化した機能蛋白の異常を分析し、その分子機構の解明を行うことである。肥大型心筋症ついては木村、堀はこれまでに報告された心筋βミオシン重鎖、トロポニンT、αトロポミオシン、ミオシン結合蛋白C以外に新たにミオシンアルカリ軽鎖、調節軽鎖、トロポニンlの遺伝子変異を見出し、また本邦に多い心尖部肥大型の一部にもサルコメア異変を発見した。古賀は遺伝子型と臨床病型の関係を検討し、ミオシン重鎖変異例は典型的臨床像を示すのに対してトロポニンT変異例は収縮不全を伴う重症例が多く、ミオシン結合蛋白C変異例は心筋病変が軽症であることを示した。杉浦はインビトロ運動再構成系を用いて遺伝子工学的に作製した変異ミオシンが収縮機能を障害し、本症の予後を規定する可能性を示した。QT延長症候群については長井はKVLQTlおよびHERG遺伝子で10種類の異変を同定し、このうち9種は日本人で新たに発見された。また変異HERGはK^+チャンネルを抑制しdominant negative機構により本症を発症させていることを示した。心筋電解質移送蛋白については松原は遅延整流型K^+チャンネルであるKv1.5をクローニングし、cAMPがその転写を増加させること、肥大心ではKv1.5の発現低下が活動電位延長に関与することを示した。古川は心筋伸展刺激活性化Cl^-チャンネルの単離・構造決定を行ない、アミノ端が伸展刺激応答に重要な部位であることを示した。ミトコンドリア心筋症については蛋白合成に関わるtRNA,rRNA遺伝子異常が予後不良なことを明らかにした。以上の様に本研究では臨床的には肥大型心筋症、QT延長症候群、ミトコンドリア心筋症の遺伝子異常を解明した。さらに分子生物学的にK^+、Cl^-チャンネル遺伝子のクローニングを行い、心筋細胞の分化異常と病態形式のメカニズムを明らかにし、これらの疾患の治療法の確立の糸口をつかむことができた。

Report

(3 results)
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (90 results)

All Other

All Publications (90 results)

  • [Publications] 古賀義則他: "肥大型心筋症の遺伝子異常と病態・治療" 循環器専門医. 4. 5-14 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koyanagi T,et al: "DNA typing of HLA class II genes in Japanese patients with rheumatic heart disease" J Mol Cell Cardiol. 28. 1349-1353 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koga Y,et al: "Clinical manifestations of hypertrophic cardiomyopathy with mutations in the cardiac heta-myosin heavy chain gene or cardiac troponin T gene" J Cardiac Failure. 2. S97-S103 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamada H,et al: "Dystroglycan is a dual receptor for agrin and laminin-2 in Schwann cell membrane" J Biol Chem. 271. 23418-23423 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kitaoka M,et al: "Differential expressions of collagen type IV,III and I during the development of invasive tropoblasts in rats" Developmental Dynamics. 207. 319-331 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mizuta T,et al: "Characterization of monoclonal antibodies recognizing human merosin and their use in affinity purification of native" Hybrydoma. 15. 373-378 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sata M,et al: "Coupling between myosin ATPase cycle and creatinin kinase cycle facilitates cardiac actomyosin sliding in vitro : A clue to mechanical dysfunction during myocardial ischemia" Circulation. 93. 310-317 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugiura S,et al: "Different cardiac myosin isoform exhibit equal force-generating ability in vitro" Biochim Biophys Acta. 1273. 73-76 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujita S,et al: "Characterization of mutant myosins of Dictiostelium Discoideum equivalent to human hypertrophic cardiomyopathy mutants" J Clin Invest. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Arai M,et al: "Sarcoplasmic reticulum genes are upregulated in mild cardiac hypertrophy but downregulated in severe cardiac hypertrophy induced by pressure overload" J Mol Cell Cardiol. 28. 1583-1590 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Watanabe,M et al: "Structure and characterization of the 5'-flanking region of the mouse smooth muscle myosin heavy chain (SM1/2) gene" Circ Res. 78. 978-989 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suzaki,T et al: "Preferential differentiation of P19 mouse embryonal carcinoma cells into smooth muscle cells ; Use of retinoic acid and antisense against the central nervous system-specific POU transcription factor Brn-2" Circ Res. 78. 395-404 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sawada Y,et al: "Co-elevation of brain natriuretic peptide and proprotein-processing endoprotease fuin after myocardial infarction in rats" FEBS Letters. 400. 177-182 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka T,et al: "Four novel KVLQl and four novel HERG mutations in familial long QT syndrome" Circulation. 95. 565-567 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mori Y,et al: "Gll3 cell-specific expression of Kv 1.5 gene,Regulation by a silencer containing dinucleotide repititive element" J Biol Chem. 270. 27788-27796 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Furukawa T,et al: "Functional linkage of the cardiac ATP-sensitive K^+ channel to the actin cytoskeleton" Pflugers Archives. 431. 504-512 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 中島忠 他: "QT延長症候群の原因遺伝子とその機能" 呼吸と循環. 45. 121-128 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hayakawa M,et al: "Age-related extensive fragmentation of mitochondrial DNA into minicircles" Biochem Biophys Res Commun. 226. 369-377 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugiyama S,et al: "Effects of ubiquinone enriched diet on deterioration of mitochondrial respiratory function caused by fried beef derived mutagenic factors in rats" Biochem Mol Biol Int. 40. 305-314 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koga Y, et al: "Disappearance of giant negative T waves in patients with the Japanese form of apical hypertrophy" J Am Coll Cardiol. 26. 1672-1678 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishi H, et al: "A myosin missense mutation, not a null allele, cauyses familial hyperprophic cardiomyopathy" Circulation. 91. 2911-2915 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishi H, et al: "DNA typing of HLA class II genes in Japanese patients with dilated cardiomyopathy" J Mol Cell Cardiol. 27. 2385-2392 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 古賀義則他: "肥大型心筋症の遺伝子異常と病態・治療" 循環器専門医. 4. 5-14 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamada H, et al: "Secretion of laminin α2 chain in cerebrospinal fluid" FEBS Letters. 376. 37-40 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sata M, et al: "A new in vitro motility assay technique to evaluate calcium aensitivity of the cardias contractile protein" Pflugers Arch. 429. 443-445 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sata M, et al: "MCI-154 increasres Ca2^+ sensitivity of reconstituted thin filament. A study using a novel in vitro motility assay technique" Circ Res. 76. 626-633 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sugiura S, et al: "Force-velosity relations of rat cardiac myosin isozymes sliding on agal cell actin cables in vitro" Biophy Biochim Acta. 1231. 69-75 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sata M, et al: "Pimobendan directly sensitizes reconstituted thin filament to slide on cardiac myosin" Eur J Pharmacol. 290. 55-59 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sata M, et al: "Phosphocreatinine shuttle provides optimal condition for mechanical interaction of cardiac actomyosin" Circulation. 93. 310-317 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kurihara Y, et al: "Aortic arch malformation and ventricular septal defect in mice deficient in endothelin-1" J Clin Invest. 96. 293-300 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takewaki S, et al: "Activation of Na^+-H^+ antiporter (NHE-1) gene expression during growth, hypertrophy and proliferation of the rabbit cardio-vascular system" J Mol Cell Cardiol. 27. 729-742 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okamoto E, et al: "Diversity of the synthetic-state smooth muscle cells ptoliferating in mechanically and hemodynamically injured arteries" Lab Invest. 74. 120-128 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mori Y, et al: "GH3 cell-specific expression of Kv 1.5 gene, Regulation by a silencer containing dinucleotide repititive element" J Biol Chem. 270. 27788-27796 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mori Y, et al: "The transcription of a mammalian voltage-gated potassium channel is regulated by cAMP in a cell-spesific manner" J Biol Chem. 268. 26482-26493 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsubara H, et al: "Shaker-related potasium channel, Kv 1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv 1.5 genes in myocardial development and hypertrophy" J Clin Invest. 92. 1659-1666 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsubara H, et al: "Pretranslational mechanisms determine the type of potassium channels expressed in the rat skiletal and cardiac muscles" J Biol Chem. 266. 13324-13328 (1991)

    • Related Report
      1995 Annual Research Report
  • [Publications] Furukawa T, et al: "Molecular cloning and characterization of a novel truncated form (CIC-2) of CIC-2 (CIC-2G) in rabbit heart" FEBS Letters. 375. 56-62 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Furukawa T, et al: "Negative charges that share important elements of function in cloned cardiac K^+ channel (Kv 1.5)" Heart Vessels. Suppl 9. 14-16 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Furukawa T, et al: "Functional linkage of the cardiac ATP-sensitive K^+ channel to the actin cytoskeleton" Pfluger Arch. in press. (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamane T, et al: "4-Aminopyridine block oa the noninactivating cloned K^+ channel Kv 1.5 expressed in Xenopus oocytes" Am J Physiol. 269. H556-H564 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 古川哲史: "肥大心筋におけるK^+チャネル変調-電気生理学的検討-" 心電図. 15. S-2-38-S-2-53 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 平岡昌和、沢登徹、古川哲史: "虚血病態におけるATP感受性Kチャネルの開口の役割" Japancsc Circulation Journal. 58. 1225-1231 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ozawa T, et al: "Mitochondrial DNA mutations and survival rate" Lancet. 345. 189- (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ozawa T, et al: "Genotype and phenotype of severe mitochondrial cardiomyopathy: a recipient of heart transplantation and the genetic control" Biochem Biophys Res Commun. 207. 613-620 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Murakami T, et al: "Different adaptation to endurance training between heart and gastrocnemius muscle mitochondria in rats" Biochem Mol Biol Int. 36. 285-290 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sugiyama S, et al: "Preservation of mitochondrial respiratory function by coenzyme Q10 in aged rat skeletal muscle" Biochem Mol Biol Int. 37. 1111-1120 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hayakawa M, et al: "Mitochondrial DNA minicircles, lacking replication origins, exist in the cardiac muscle of a young normal subject" Biochem Biophys Res Comm. 215. 952-960 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamada K, et al: "Early appearance of age-associated deterioration in mitochondrial function of diaphragm and heart in rats treated with doxorubicin" Exp Gerontol. 30. 581-593 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirozane T, et al: "Experimental graft coronary artery disease in a murine heterotopic cardiac transplant model" Circulation. 91. 386-392 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sato M, et al: "Inotropic agent vesnarinone inhibits cytokine production and Eselectin expression in human umbilical vein endothelial cells" J Moll Cell Cardiol. 27. 2265-2273 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsumori A, et al: "Dilated cardiomyopathy associated with hepatitis C virus infection" Circulation. 92. 2519-2525 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirozane T, et al: "Beneficial effect of amrinone on murine cardiac allograft survial" Clin Exp Immunol. 102. 186-191 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Furukawa Y, et al: "The angiotensin II receptor antagonist TCV-116 reduces graft coronary artery disease and preserves graft status in a murine model" Circulation. 93. 333-339 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watkins H, et al: "Mutations in the genes for cardiac troponin T and alphatropomyosin in hypertrophic cardiomyopathy" New Eng J Med. 332. 1058-1064 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Honda H, et al: "Expression of p210bcr/abl by metallothionein promotor induced T- cell leukemia in transgenic mice" Blood. 85. 2853-2861 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Honda H, et al: "Increasred tyrosine-phosphorylation of 55KDa proteins in β-actin/tec transgenic mice" Biochem Biophys Res Commun. 206. 287-293 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamagata T, et al: "Of the GATA-binding proteins, only GATA4 selectively regulates human IL-5 promotor in IL-6 producing cells which express multiple GATA-binding proteins" Mol Cell Biol. 15. 3830-3839 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 古賀義則他: "第24回日本医学会総会会誌(II)-肥大型心筋症診療の進歩" 第24回日本医学会総会, 2 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kimura A, et al: "Cardiac Development and Gene Regulation - Genetic approaches to identification of a novel gene responsible for familial hypertrophic cardiomyopathy" Excerpta Medica, 18 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sugiura S, et al: "Cardiac Energetics: From Emax to Pressure-Volume Area - Kinetic property of cardiac myosin in vitro" Kluwer Academic Publishers, 11 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 杉山 理: "第24回日本医学会総会会誌(I)-ミトコンドリア心筋症" 第24回日本医学会総会, 1 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Koga Y,et al: "Therapeutic management of dilated cardiomyopathy" Cardiovascular Drugs and Therapy. 8. 83-88 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 古賀義則: "肥大型心筋症における心機能障害" 心臓. 26(Suppl2). 44-57 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nishi H,et al: "Possible gene dose effect of a mutant cardiac β-myosin heavy chain gene on the clinical manifestation of familial hypertrophic cardiomyopathy" Biochem Biophys Res Commun. 200. 549-556 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamashita H,et al: "ADP inhibits sliding velocity of fluorescent actin filament on cardiac and skeletal myosins" Circulation Research. 74. 1027-1033 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sata M,et al: "A new in vitro motility assay technique to evaluate calcium sensitivity of the cardiac contractile proteins" Pflugers Arch. 429. 443-445 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kojima M,et al: "Angiotensin II receptor antagonist TCV 116 regresses hypertensive left ventricular hypertrophy in vivo and inhibits intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro" Circulation. 89. 2204-2211 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松原弘明 他4名: "Pretranslational mechanisms determine the type of potassium channels expressed in the rat skeletal and cardiac muscles" J.Biol.Chem.266. 13324-13328 (1991)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Furukawa al.: "Mechanism for reactivation of the ATP-sensitive K+channel by MgATP complexes in guinea-pig ventricular myocytes" Journal of Physiology(London). 479.1. 95-107 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Furukawa et al.: "Metabolic inhibition of l_<Ca,L> and l differs in feline left ventricular hypertrophy." American Journal of Physiology. 266. H1121-H1131 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Ishibashi et al.: "Molecular cloning and expression of a member of the aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells" Proceeding of National Academy of Science,USA. 91. 6269-6273 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Fushimi al.: "Functional characterization and cell immunolocalization of AQP-CD water channel in kidney collecting duct" American Journal of Physiology. 267. F573-F582 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] J.Nitta et al.: "Subcellular mechanism for Ca^<2+>-dependent enhancement of delayed rectifier K^+ current in isolatedmembrane patches of guinea-pig ventricular myocytes." Circulation Research. 74. 96-104 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kurihara Y,et al.: "Disruption of mouse endothelin-1 gene results in lethality and craniofacial anomaly in homozygotes and elevated blood pressure in heterozygotes" Nature. 368. 703-710 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tanaka T,et al: "Gene linkage analysis of Romano-Ward syndrome (RWS) in 13 Japanese families" Human Genetics. 94. 380-384 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kuro-o M,et al: "Salt-sensitive hypertension in transgenic mice overexpressing sodium-proton exchanger" Circulation Research. 76. 148-153 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松原弘明 他2名: "Regulatory mechanism for voltage-sensitive potassium channel gene in the heart" Jpn.J.Electrocardiology. 15. 25-33 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 森 泰清 他4名: "The transcription of a mammalian voltage-gated potassium channel is regulated by cAMP in a cell-specific manner" J.Biol.Chem.268. 26482-26493 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松原弘明 他5名: "Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy." J Clin Invest. 92. 1659-1666 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 古川哲史 他: "左室圧負荷により発現するイオンチャネル" 心電図. 14. 32-41 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Katsumata K,et al: "Fragmentation of human heart mitochodrial DNA associated with premature aging" Biochem Biophys Res Commun. 202. 102-110 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sato W,et al: "Cardiomyopathy and angiopathy in patients with mitochondrial myopathy, lactic acidosis and stroke-like episodes" American Heart Journal. 128. 733-741 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Murakami T,et al: "Enzymatic and genetic adaptation of soleus muscle mitochondria to physical training in rats" American J Physiology(Endocri Metab). 267. E388-E395 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ozawa T,et al: "Mitochondrial DNA mutations and survival rate" Lancet. 345. 189 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nishi H,et al: "Cardiomyopathy Update 5 - Prognosis and Treatment of Cardiomyopathy and Myocarditis" University of Tokyo Press, 10 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 西 宏文 他: "心臓病の分子医学-肥大型心筋症の遺伝子異常" 羊土社(矢崎義雄 編), 10 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shiojima I,et al: "Diastolic Relaxation of the Heart" Kluwer Academic Publisher,Boston, 8 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 杉山 理: "ミトコンドリア遺伝子変異による心筋障害とは 循環器 Now 6 心筋症・心筋炎" 南江堂(矢崎義雄、和泉 徹 編), 4 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kimura A,et al: "Developmental Mechanisms of Heart Disease" Futura Press, 8 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nagai R,et al: "The Adapted Heart" Raven Press, New York, 13 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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