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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An ELISA assay with monoclonal antibody (Mab 2F4) raised against human ventricular myosin heavy chains was developed and used to investigate human sera after myocardial infarction. The monoclonal antibody 2F4 was selected for its high affinity to soluble fragments of myosin heavy chains (subfragment-1) and for its appropriate tissue specificity. By including Mab 2F4 in a simple and rapid dot immunobinding assay sera from patients with acute chest pain and of persons without a history of heart disease were tested. Myosin was detected only in the sera of the patients with myocardial necrosis, confirmed by electrocardiographic data. Negative reactions in all control cases were found. The serum myosin fragments reactive with Mab 2F4 were characterized by immunoblot experiments and protein bands in the region about 43 kDa were found. It was concluded that the myocardial infarction can be demonstrated by detection of cardiac myosin heavy chain fragments in the patients' sera.
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PMID:Identification of human ventricular myosin heavy chain fragments with monoclonal antibody 2F4 in human sera after myocardial necrosis. 175 94

The presence of ventricular myosin light chains in the atria of children with congenital heart disease was demonstrated by two-dimensional polyacrylamide gel electrophoresis, peptide mapping, and Western blot analysis. Ventricular myosin light chains were present in 27% of biopsies from 91 children with different forms of congenital heart disease. Perimembranous ventricular septal defects and tetralogy of Fallot were associated with the presence of ventricular myosin light chains in 50% of patients. The presence of ventricular myosin light chains in these atria did not correlate with pressure or volume overload. Analysis of myosin heavy chain isotype in the same biopsies by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, peptide mapping, and Western blot analysis indicated that there was no detectable expression of ventricular myosin heavy chain (beta-subunit), suggesting that the genes for the myosin heavy chains and light chains are not expressed coordinately.
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PMID:Expression of ventricular myosin subunits in the atria of children with congenital heart malformations. 195 79

We have developed anticardiac myosin antibodies, especially monoclonal antibodies, for helping in the diagnosis of heart disease. Our investigations were divided into three research projects. We visualized the distribution of myosin isozymes in human atrial and ventricular myocardium by an immunofluorescence staining method using monoclonal antibodies specific for individual human cardiac myosin isozymes. We also revealed the redistribution of these cardiac myosin isozymes in an overloaded condition. The isozymic pattern of cardiac myosin was changed from the atrial type to the ventricular type in the overloaded atrium. This isozymic redistribution can be considered as physiological adaptive mechanism to meet increased cardiac work during overload. We developed a new method of imaging for myocardial infarction by single photon emission tomography using labelled monoclonal antibody specific for cardiac myosin heavy chain. Specific localization of the labelled antibody was demonstrated in the infarcted area and no accumulation of radioactivity was shown in the bone matrix as observed in 99mTc pyrophosphate images. We developed a sensitive radioimmunoassay of cardiac myosin light chain I (LCI) and demonstrated that peak serum levels of LCI in the patients with acute myocardial infarction correlated well with the left ventricular ejection fraction. Furthermore, LCI release from the infarcted myocardium was not affected by coronary reperfusion due to intracoronary thrombolysis. Thus, serial determinations of serum LCI better quantify the extent of myocardial damage even after coronary reperfusion in acute myocardial infarction.
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PMID:Applications of anticardiac myosin monoclonal antibodies in the diagnosis of heart disease. 405 38

Heart tissue destruction in chronic Chagas disease cardiopathy (CCC) may be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after Trypanosoma cruzi infection. Indirect evidence suggests that there is antigenic crossreactivity between T. cruzi and heart tissue. As there is evidence for immune recognition of cardiac myosin in CCC, we searched for a putative myosin-crossreactive T. cruzi antigen. T. cruzi lysate immunoblots were probed with anti-cardiac myosin heavy chain IgG antibodies (AMA) affinity-purified from CCC or asymptomatic Chagas disease patient-seropositive sera. A 140/116-kDa doublet was predominantly recognized by AMA from CCC sera. Further, recombinant T. cruzi protein B13--whose native protein is also a 140- and 116-kDa double band--was identified by crossreactive AMA. Among 28 sera tested in a dot-blot assay, AMA from 100% of CCC sera but only 14% of the asymptomatic Chagas disease sera recognized B13 protein (P = 2.3 x 10(-6)). Sequence homology to B13 protein was found at positions 8-13 and 1442-1447 of human cardiac myosin heavy chain. Competitive ELISA assays that used the correspondent myosin synthetic peptides to inhibit serum antibody binding to B13 protein identified the heart-specific AAALDK (1442-1447) sequence of human cardiac myosin heavy chain and the homologous AAAGDK B13 sequence as the respective crossreactive epitopes. The recognition of a heart-specific T. cruzi crossreactive epitope, in strong association with the presence of chronic heart lesions, suggests the involvement of crossreactivity between cardiac myosin and B13 in the pathogenesis of CCC.
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PMID:Autoimmunity in Chagas disease cardiopathy: biological relevance of a cardiac myosin-specific epitope crossreactive to an immunodominant Trypanosoma cruzi antigen. 753 37

Over 60 entries in the genetic catalog have cardiomyopathy features--32 autosomal dominant, 35 autosomal recessive and X-linked. Over 40 present in, or can have survival into, adult life. Major clinicopathologic categories of these cardiomyopathic disorders included: sudden death (13 entities); cardiac conduction disturbance important feature; associated myopathy or motor dysfunction; storage diseases with cardiac involvement; cardiac amyloidoses; and, other categories. Genes, abnormality of which can cause hypertrophic cardiomyopathy (HCM), have been identified on chromosomes 1, 14 and 15, the locus on chromosome 14 involving the B-myosin heavy chain gene, but at least one unidentified locus is known to exist and there is a suggestive locus on chromosome 16, so that HCM is not a single disease but a group of disorders with clinicopatholopic similarities. To investigate these aspects of HCM in some detail, sixty-six patients with "sharply demarcated" differential myocardial fiber bundle hypertrophy (DMBH), considered to be of significant degree, from a pediatric autopsy data base of approximately 8,000 cases, were reviewed. Twenty-three of the patients died suddenly, without antecedent significant cardiac dysfunction, seven had clinical congestive heart failure of varying duration, three were stillborn, six showed evidence of aspiration of amniotic sac content (three had history of fetal distress), five had ischemic bowel disease, three (two with clinical cerebral palsy and one with Ondine's curse syndrome) had cerebral atrophy and sclerosis and one had extensive more acute encephalomalacia, and a variety of other major "causes of death" were present. Whether all infants and children with DMBH meeting the criteria used, who do not have congenital heart disease, have dominant hypertrophic cardiomyopathy (HCM) cannot be established by studies of this type, but the "concentration" of a gene or genes for HCM in pediatric autopsy series because the strong effect of HCM on life expectancy is relevant to this possibility. The data raise the question that stillbirth, fetal distress with aspiration of amniotic sac content, ischemic bowel disease and cerebral atrophy and sclerosis may be hitherto underappreciated features of HCM in childhood, and that patients with HCM may be peculiarly liable to die with certain types of septic shock, such as acute meningococcemia. In the material of this study, sudden death was statistically more frequent in females than in males in childhood (p < .029).
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PMID:Cardiomyopathy in childhood and adult life, with emphasis on hypertrophic cardiomyopathy. 783 Nov 49

A leading cause of sudden death among young athletes is the autosomal dominant genetic heart disease, familial hypertrophic cardiomyopathy (FHC). Mutations in several contractile proteins, including cardiac myosin heavy chains, have been described in families with FHC, leading to the hypothesis that FHC is a disease of the sarcomere (17). To create an animal model for this disease, five lines of transgenic mice have been produced that express a mutant myosin heavy chain in their hearts. The hearts of these mice exhibit the histopathological features seen in patients and demonstrate enlarged left ventricles. Our analysis suggests that the mutant protein acts as a dominant negative, since it constitutes only 5-10% of the total myosin in the heart. In addition, while the transgene is expressed in all chambers of the heart, only the left ventricle demonstrates pathology and enlargement, suggesting that several prominent features of the disease represent secondary responses influenced by other factors, such as hemodynamics.
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PMID:A murine model for hypertrophic cardiomyopathy. 858 73

Mutations in several muscle structural proteins (the myosin heavy chain, alpha tropomyosin, cardiac troponin T and myosin binding protein C) result in a genetically dominant heart disease, hypertrophic cardiomyopathy. Biochemical data from studies of mutant myosin suggest a dominant-negative mechanism for inheritance of this disease. The most likely primary defect is sarcomere dysfunction, which is followed by the major clinical symptoms.
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PMID:Contractile protein mutations and heart disease. 879 11

Myocarditis is an important cause of heart failure among adolescents and young adults. A remarkable observation is the discrepancy between the limited overt evidence of myocyte injury and the global impairment of left ventricular function. This discrepancy has stimulated suggestions that immunological mechanisms contribute to cardiac damage. We have developed two murine models of myocarditis, one elicited by cardiotropic Coxsackie B3 (CB3) virus infection and the other by cardiac myosin immunization, to better analyze the pathogenetic mechanisms responsible for immune-mediated heart-muscle disease. Both virus infection and myosin immunization produce myocardial inflammation and elicit heart-reactive antibodies which bind to the myocardium in vivo and which recognize the cardiac myosin heavy chain. Each model offers unique advantages. The virus-induced disease more closely resembles human myocarditis; myosin immunization isolates the autoimmune components of the disease since no virus infection is involved. We have also distinguished strains of mice resistant to autoimmune myocarditis (such as B10.A) from those susceptible to the autoimmune phase of disease (such as A.CA and A/J). Mice from a resistant strain to virus-or myosin-induced autoimmune heart disease develop myocardial inflammation and myosin antibodies if co-treated with tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 when infected or immunized. Thus, cytokines can modulate the outcome of cardiotropic virus infection and enhance its autoimmune sequela. We also found that blocking IL-1 receptor inhibits autoimmune myocarditis in genetically susceptible mice.
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PMID:The pathogenesis of postinfectious myocarditis. 881 Oct 68

Congenital heart disease (CHD), cardiomyopathy, and vasculopathies are common causes of mortality and morbidity in pediatrics, including the perinatal period. This article reviews evidence that single gene defects cause many of the pediatric heart diseases. Vasculopathies discussed include Marfan's syndrome, supravalvar aortic stenosis and Williams' syndrome, Alagille's syndrome, and hereditary telangiectasia, the Osler-Weber-Rendu syndrome. Genetic causes of hypertrophic cardiomyopathy caused by sarcomeric protein mutations (beta-cardiac myosin heavy chain) and of dilated cardiomyopathy secondary to structural protein deficiencies (dystrophin) are presented. Defects in proteins essential for myocardial energy production such as oxidative phosphorylation proteins and fatty acid oxidation genes that cause cardiomyopathy or sudden death are described. Gene ablation models in mice, such as RXR alpha and homeobox gene knockouts, which result in cardiac phenotypes resembling human congenital heart disease, are described. Familial types of human CHD which are being investigated for genetic causes by positional cloning methods and known cytogenetic causes of CHD, including the CATCH-22 syndrome and monosomy at 22q11, are presented. General lessons and principles derived from these new and exciting discoveries in human cardiovascular development are surmised.
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PMID:The genetic basis of pediatric cardiovascular disease. 909 Jul 81

Hypertrophic cardiomyopathy is a human heart disease characterized by increased ventricular mass, focal areas of fibrosis, myocyte, and myofibrillar disorganization. This genetically dominant disease can be caused by mutations in any one of several contractile proteins, including beta cardiac myosin heavy chain (beta MHC). To determine whether point mutations in human beta MHC have direct effects on interfering with filament assembly and sarcomeric structure, full-length wild-type and mutant human beta MHC cDNAs were cloned and expressed in primary cultures of neonatal rat ventricular cardiomyocytes (NRC) under conditions that promote myofibrillogenesis. A lysine to arginine change at amino acid 184 in the consensus ATP binding sequence of human beta MHC resulted in abnormal subcellular localization and disrupted both thick and thin filament structure in transfected NRC. Diffuse beta MHC K184R protein appeared to colocalize with actin throughout the myocyte, suggesting a tight interaction of these two proteins. Human beta MHC with S472V mutation assembled normally into thick filaments and did not affect sarcomeric structure. Two mutant myosins previously described as causing human hypertrophic cardiomyopathy, R249Q and R403Q, were competent to assemble into thick filaments producing myofibrils with well defined I bands, A bands, and H zones. Coexpression and detection of wild-type beta MHC and either R249Q or R403Q proteins in the same myocyte showed these proteins are equally able to assemble into the sarcomere and provided no discernible differences in subcellular localization. Thus, human beta MHC R249Q and R403Q mutant proteins were readily incorporated into NRC sarcomeres and did not disrupt myofilament formation. This study indicates that the phenotype of myofibrillar disarray seen in HCM patients which harbor either of these two mutations may not be directly due to the failure of the mutant myosin heavy chain protein to assemble and form normal sarcomeres, but may rather be a secondary effect possibly resulting from the chronic stress of decreased beta MHC function.
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PMID:Point mutations in human beta cardiac myosin heavy chain have differential effects on sarcomeric structure and assembly: an ATP binding site change disrupts both thick and thin filaments, whereas hypertrophic cardiomyopathy mutations display normal assembly. 910 42


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