Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Cardiological findings in athletes are often similar to those observed in clinical cases. Electrocardiographic and cardiac imaging abnormalities as well as physical findings may be the same in both of these groups. Bradycardia and rhythm disturbances are the most common abnormalities in athletes. Most athletes with abnormal electrocardiograms are asymptomatic and numerous investigators have failed to detect heart disease in association with such electrocardiograms. In contrast to cardiac dysfunction observed in clinical cases, enhanced or normal ventricular systolic and diastolic function have been reported in athletes. In endurance athletes, this is associated with very high values for maximal aerobic power (VO2max). Absolute and body size-normalised cardiac dimensions in most athletes do not approach values from chronic disease states, and may not exceed echocardiographic normal limits. In addition, pathological and physiological enlargement appear to be biochemically and functionally different. Myosin ATPase enzyme expression and calcium metabolism are different in rats with pathologically or physiologically induced enlargement. The reported biochemical differences underlie systolic and diastolic dysfunction in pathological enlargement. Conversely, trained rodents and humans have demonstrated enhanced systolic and diastolic function. It is important to note that cardiac enlargement observed in athletes is the result of normal adaptation to physical conditioning and/or hereditary influences. Conversely, pathological changes result from disease processes which can lead in turn to reduced function, morbidity and mortality. Since the mid 1970s echocardiography has been used to compare cardiac dimensions in male endurance- and resistance-trained athletes. A sport-specific profile of eccentric and concentric enlargement has been documented in endurance and resistance athletes, respectively. Subsequent studies of athletes have examined factors such as age, sex and degree of competitive success to determine their contribution to these sport-specific cardiac profiles. Unique athletic subgroups have also been analysed and have included ballet dancers, rowers, basketball players and triathletes. However, there is a paucity of data on cardiac dimensions in female athletes. Finally, physical conditioning studies have also examined echocardiographic dimensions before and after endurance and resistance training. Significant enlargement of internal dimensions, wall thickness or left ventricular mass have been reported but such increases are relatively small and by no means universal. Several conflicting explanations for enlarged cardiac dimensions appear in the literature. Chronic volume and pressure haemodynamic overloading during physical conditioning has been proposed to explain eccentric and concentric cardiac enlargement in endurance- and resistance-trained athletes respectively. However, twin studies suggest that hereditary factors may be important determinants of cardiac dimensions and/or the degree of cardiac adaptability to physical conditioning.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The 'athletic heart syndrome'. A critical review. 182 49

A sensitive and highly specific ELISA assay was developed to determine the anti-myosin humoral immune response (AMA) in various heart diseases: acute viral myocarditis, infective endocarditis, acute myocardial infarction, and valve and coronary bypass surgery. The mean study entry AMA titer of each patient group was already significantly increased compared with age matched controls. During further follow-up (90 d) all the groups except for endocarditis showed a significant increase of AMA titer compared with their entry titer. Anti-myosin antibody titer were higher after cardiac surgery than after myocardial infarction or inflammatory heart disease. These results suggest that anti-myosin immune response is not limited to infectious processes in which the pathogen induces antibodies which cross-react with heart constituents but is merely caused by direct cardiac injury. Myosin as a major compound of heart cellular proteins turned out to be a good candidate to trigger immune response after cardiac injury.
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PMID:Anti-myosin humoral immune response following cardiac injury. 249 42

Changes in two of the elements of myocardial subcellular organelles relating to cardiac energetics, ventricular myosin isozymes and mitochondrial DNA mutations, were examined using left ventricular tissue samples obtained at autopsy from patients with ischemic heart disease. Myosin isozymes were examined in tissues from nine patients with ischemic heart disease and 12 control patients with cancer but no heart disease. Extracted myosin was separated by pyrophosphate gel electrophoresis. The relative concentration of each component was determined by densitometry. Mitochondrial DNA mutations were evaluated in tissues from ten patients with myocardial infarction and 11 control patients with cancer but no heart disease. DNA was extracted and mitochondrial DNA mutations were detected by the polymerase chain reaction. Two bands were revealed by pyrophosphate gel electrophoresis. These contained VM-A, which exhibited faster electrophoretic mobility and was present in lower concentrations, and VM-B, which had a lower mobility and a higher concentration, respectively. SDS polyacrylamide gel electrophoresis showed that these two components contained the heavy chain and light chains 1 and 2 of myosin. VM-A concentrations tended to be higher in patients with ischemic heart disease than in controls. A 7.4-kb deletion was detected between the D-loop and the ATPase 6 genes of mitochondrial DNA from the myocardium of 6 out of 10 patients with myocardial infarction. The relative amounts of the two myosin isozymes could be altered by ischemic heart disease, although the functional significance of these components is unclear. The changes in the two myosin isozymes might be an adaptive change to disordered energy metabolism, but this change was small. The myocardial mitochondrial DNA deletions in patients with myocardial infarction were thought to result from ischemic damage.
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PMID:Myocardial adaptive changes and damage in ischemic heart disease. 890 72

Myosin is a chemomechanical motor that converts chemical energy into the mechanical work of muscle contraction. More than 40 missense mutations in the cardiac myosin heavy chain (MHC) gene and several mutations in the two myosin light chains cause a dominantly inherited heart disease called familial hypertrophic cardiomyopathy. Very little is known about the biochemical defects in these alleles and how the mutations lead to disease. Because removal of the light chain binding domain in the lever arm of MHC should alter myosin's force transmission but not its catalytic function, we tested the hypothesis that such a mutant MHC would act as a dominant mutation in cardiac muscle. Hearts from transgenic mice expressing this mutant myosin are asymmetrically hypertrophied, with increases in mass primarily restricted to the cardiac anterior wall. Histological examination demonstrates marked cellular hypertrophy, myocyte disorganization, small vessel coronary disease, and severe valvular pathology that included thickening and plaque formation. Skinned myocytes and multicellular preparations from transgenic hearts exhibited decreased Ca2+ sensitivity of tension and decreased relaxation rates after flash photolysis of diazo 2. These experiments demonstrate that alterations in myosin force transmission are sufficient to trigger the development of hypertrophic cardiomyopathy.
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PMID:Cardiac myosin heavy chains lacking the light chain binding domain cause hypertrophic cardiomyopathy in mice. 1036 99

Myosin-induced autoimmune myocarditis (EAM) is a model of inflammatory heart disease initiated by CD4(+) T cells. It is a paradigm of the immune-mediated cardiac damage believed to play a role in the pathogenesis of a subset of postinfectious human cardiomyopathies. Myocarditis is induced in susceptible mice by immunization with purified cardiac myosin or specific peptides derived from cardiac myosin, or by adoptive transfer of myosin-reactive T cells. Myocarditis is induced in Lewis rats by immunization with purified cardiac myosin or by adoptive transfer of T cells stimulated by specific peptides derived from cardiac myosin. Myocarditis begins 12 to 14 days after the first immunization, and is maximal after 21 days. In addition to the protocols used to induce EAM in mice and rats, support protocols are included for preparing purified cardiac myosin using mouse or rat heart tissue, preparing purified cardiac myosin for injection, and collecting and assessing hearts by histopathological means.
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PMID:Autoimmune myocarditis. 1843 31

With age, cardiac performance declines progressively and the risk of heart disease, a primary cause of mortality, rises dramatically. As the elderly population continues to increase, it is critical to gain a better understanding of the genetic influences and modulatory factors that impact cardiac aging. In an attempt to determine the relevance and utility of the Drosophila heart in unraveling the genetic mechanisms underlying cardiac aging, a variety of heart performance assays have recently been developed to quantify Drosophila heart performance that permit the use of the fruit fly to investigate the heart's decline with age. As for the human heart, Drosophila heart function also deteriorates with age. Notably, with progressive age the incidence of cardiac arrhythmias, myofibrillar disorganization and susceptibility to heart dysfunction and failure all increase significantly. We review here the evidence for an involvement of the insulin-TOR pathway, the K(ATP) channel subunit dSur, the KCNQ potassium channel, as well as Dystrophin and Myosin in fly cardiac aging, and discuss the utility of the Drosophila heart model for cardiac aging studies.
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PMID:Drosophila as a model to study cardiac aging. 2113 Aug 61

Myosin is the chemomechanical energy transducer in striated heart muscle. The myosin cross-bridge applies impulsive force to actin while consuming ATP chemical energy to propel myosin thick filaments relative to actin thin filaments in the fiber. Transduction begins with ATP hydrolysis in the cross-bridge driving rotary movement of a lever arm converting torque into linear displacement. Myosin regulatory light chain (RLC) binds to the lever arm and modifies its ability to translate actin. Gene sequencing implicated several RLC mutations in heart disease, and three of them are investigated here using photoactivatable GFP-tagged RLC (RLC-PAGFP) exchanged into permeabilized papillary muscle fibers. A single-lever arm probe orientation is detected in the crowded environment of the muscle fiber by using RLC-PAGFP with dipole orientation deduced from the three-spatial dimension fluorescence emission pattern of the single molecule. Symmetry and selection rules locate dipoles in their half-sarcomere, identify those at the minimal free energy, and specify active dipole contraction intermediates. Experiments were performed in a microfluidic chamber designed for isometric contraction, total internal reflection fluorescence detection, and two-photon excitation second harmonic generation to evaluate sarcomere length. The RLC-PAGFP reports apparently discretized lever arm orientation intermediates in active isometric fibers that on average produce the stall force. Disease-linked mutants introduced into RLC move intermediate occupancy further down the free energy gradient, implying lever arms rotate more to reach stall force because mutant RLC increases lever arm shear strain. A lower free energy intermediate occupancy involves a lower energy conversion efficiency in the fiber relating a specific myosin function modification to the disease-implicated mutant.
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PMID:Regulatory light chain mutants linked to heart disease modify the cardiac myosin lever arm. 2334 68

Myosin-binding protein C (MyBP-C) is an accessory protein of striated muscle thick filaments and a modulator of cardiac muscle contraction. Defects in the cardiac isoform, cMyBP-C, cause heart disease. cMyBP-C includes 11 Ig- and fibronectin-like domains and a cMyBP-C-specific motif. In vitro studies show that in addition to binding to the thick filament via its C-terminal region, cMyBP-C can also interact with actin via its N-terminal domains, modulating thin filament motility. Structural observations of F-actin decorated with N-terminal fragments of cMyBP-C suggest that cMyBP-C binds to actin close to the low Ca(2+) binding site of tropomyosin. This suggests that cMyBP-C might modulate thin filament activity by interfering with tropomyosin regulatory movements on actin. To determine directly whether cMyBP-C binding affects tropomyosin position, we have used electron microscopy and in vitro motility assays to study the structural and functional effects of N-terminal fragments binding to thin filaments. 3D reconstructions suggest that under low Ca(2+) conditions, cMyBP-C displaces tropomyosin toward its high Ca(2+) position, and that this movement corresponds to thin filament activation in the motility assay. At high Ca(2+), cMyBP-C had little effect on tropomyosin position and caused slowing of thin filament sliding. Unexpectedly, a shorter N-terminal fragment did not displace tropomyosin or activate the thin filament at low Ca(2+) but slowed thin filament sliding as much as the larger fragments. These results suggest that cMyBP-C may both modulate thin filament activity, by physically displacing tropomyosin from its low Ca(2+) position on actin, and govern contractile speed by an independent molecular mechanism.
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PMID:Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism. 2447 90

Myosin filaments in muscle, carrying the ATPase myosin heads that interact with actin filaments to produce force and movement, come in multiple varieties depending on species and functional need, but most are based on a common structural theme. The now successful journeys to solve the ultrastructures of many of these myosin filaments, at least at modest resolution, have not been without their false starts and erroneous sidetracks, but the picture now emerging is of both diversity in the rotational symmetries of different filaments and a degree of commonality in the way the myosin heads are organised in resting muscle. Some of the remaining differences may be associated with how the muscle is regulated. Several proteins in cardiac muscle myosin filaments can carry mutations associated with heart disease, so the elucidation of myosin filament structure to understand the effects of these mutations has a clear and topical clinical relevance.
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PMID:Muscle myosin filaments: cores, crowns and couplings. 2850 95


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