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)

There are some studies demonstrating the skeletal muscle degeneration associated with the degeneration of Z band and appearance of nemaline rods in experimental animals of the simulation model for spaceflight but not in human heart tissues. In the present study, therefore, we investigated the pathological changes or degeneration in left auricular heart muscles obtained during operations of mitral valves replacement using both electron and light microscopies. The degeneration of Z band even in the myofibrils of comparatively little damaged cell was found. Furthermore, nemaline rods were detected in most of the heart muscle cells. These results suggest that the existence of nemaline rods is involved in the cell injury in the heart muscle of patients with heart disease without nemaline myopathy. Further study is necessary to know whether the similar pathological findings are observed not only in the skeletal muscle but also in the cardiac muscle in experimental animals of the simulation model for spaceflight or in a prolonged spaceflight.
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PMID:Nemaline rod and degeneration of Z band of muscle cell in weightlessness at spaceflight. 1154 52

We report the molecular genetic abnormalities of a patient with GSD IIId presenting with progressive myopathy and cardiopathy leading to a fatal outcome. We identified two independent deletions including a 4 bp deletion (117-1120) and a 98 bp deletion (1135-1232) in cDNA. Sequencing of the genomic DNA of the corresponding region revealed a 4 bp deletion in exon 10; however, the other 98 bp deletion corresponding to exon 11, which was deleted in cDNA, was present in genomic DNA. We therefore concluded that skipping of exon 11 occurred in the cDNA of the patient. Intron/exon boundary analysis of the skipped exon 11 revealed no mutation in the consensus splice-site sequence. If normal splicing had occurred, a stop codon would have appeared within exon II due to frameshift mutation. The mechanism of exon skipping observed in our patient is as yet unknown, and it is still not clear whether intraexonal mutation of the preceding exon can influence splice-site selection. It is possible that a unique exon skipping occurred, preventing the appearance of a stop codon in our patient.
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PMID:Novel exon 11 skipping mutation in a patient with glycogen storage disease type IIId. 1175 81

In the seventies thyrotoxic heart accounted for 3% of all hospitalized cardiac patients and was found on average in 30% of all cases of hyperthyroidism. It presented most frequently by tachyfibrillation and resistant cardiac decompensation. It affected men four times as frequently as women. The incidence correlated with age, toxic nodose goitre, but its development did not correlate with concurrent thyrotoxic rhizomyelic myopathy nor with the extent of deviation of thyroid laboratory parameters (T4, T3, indexes FT4). At present the incidence of thyrotoxic heart declined due to early detection and more adequate diagnosis and treatment of hyperthyroidism, as well as due to the decline of oligosymptomatic toxic nodose goitres even in old age due to preventive iodization of table salt. However, there was an increase of hyperthyroidism induced by amiodarone and other iodine preparations (X-ray contrast materials) associated with primary heart disease and arrhythmias. (Up to 2% of amiodarone treated patients). The ratio of so-called real subclinical thyrotoxicoses in the development of thyrotoxic heart is negligible. Isolated reduction of TSH in hospital screening is a frequent finding but is conditioned most frequently by: a) the 1st stage of the low thyroxin syndrome, b) the 1st stage of subacute thyroiditis, c) the influence of various drugs (iodine preparations, overdosage of T4 substitution, pharmacotherapy with glucocorticoids, dopamine etc.), d) methodical artefacts, e) natural pulsed secretion of TSH etc. Hospital screening of hyperthyroidism and thyrotoxic heart even in older people above 60 years by T4 and/or TSH (2nd generation equipment) is not effective because it is detected in 20% of current hospital admissions and in 60% of those admitted to intensive care unitpathologic values of T4 and/or TSH most frequently without non-thyroid causes (stages of the low thyroxin syndrome) are recorded. This hospital screening has a satisfactory sensitivity but low specificity and in a large number of people calls for further diagnostic steps. Therefore it is more suitable only after clinical examination of the patient to confirm suspected hyperthyroidism to examine FT4 and TSH (IRMA 3rd generation) or possibly supplement FT3 and other aimed tests.
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PMID:[Cor thyreotoxicum. Part I--new findings about its etiopathogenesis and diagnosis. Overview of problems based on 35 years' experience]. 1185 86

Myoadenylate deaminase deficiency is the most common metabolic disorder of skeletal muscle in the Caucasian population, affecting approximately 2% of all individuals. Although most deficient subjects are asymptomatic, some suffer from exercise-induced myalgia suggesting a causal relationship between a lack of enzyme activity and muscle function. In addition, carriers of this derangement in purine nucleotide catabolism may have an adaptive advantage related to clinical outcome in heart disease. The molecular basis of myoadenylate deaminase deficiency in Caucasians has been attributed to a single mutant allele characterized by double C to T transitions at nucleotides +34 and +143 in mRNA encoded by the AMPD1 gene. Polymerase chain reaction-based strategies have been developed to specifically identify this common mutant allele and are considered highly sensitive. Consequently, some laboratories preferentially use this technique over other available diagnostic tests for myoadenylate deaminase deficiency. We previously identified a G468-T mutation in one symptomatic patient who was only heterozygous for the common AMPD1 mutant allele. In this report, nine additional individuals with this compound heterozygous genotype are revealed in a survey of 48 patients with documented deficiency of skeletal muscle adenosine monophosphate deaminase and exercise-induced myalgia. Western blot analysis of leftover biopsy material from one of these individuals does not detect any immunoreactive myoadenylate deaminase polypeptide. Baculoviral expression of the G468-T mutant allele produces a Q156H substitution enzyme exhibiting labile catalytic activity. These combined results demonstrate that the G468-T transversion is dysfunctional and further indicate that AMPD1 alleles harboring this mutation contribute to the high incidence of partial and complete myoadenylate deaminase deficiency in the Caucasian population. Consequently, genetic tests for abnormal AMPD1 expression designed to diagnose patients with metabolic myopathy, and to evaluate genetic markers for clinical outcome in heart disease should not be based solely on the detection of a single mutant allele.
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PMID:A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population. 1211 80

A caesarean section was indicated in a 29-year-old parturient affected by a muscular deficit in myophosphorylase responsible for a type V glycogen storage disease (McArdle disease). This metabolic myopathy had been diagnosed two years previously, whereas the patient already suffered from a hereditary form of dilated cardiomyopathy. The muscular disease was invalidating on the functional level with exercise intolerance. The cardiopathy was little symptomatic but the dysfunction of the left ventricle worsened during the pregnancy with an ejection fraction calculated to 43%. In this case, we report the realization of a general anaesthesia in a patient who had epidural anaesthesia for a previous caesarean section.
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PMID:[Anesthesia for cesarean section in a patient with McArdle disease and hereditary dilated cardiomyopathy]. 1213 96

Patients with Cushing's syndrome can rarely present with systolic heart failure as the mainstay feature. In these patients, heart failure is usually secondary to left ventricular hypertrophy (LVH) and not to dilated cardiopathy. We herewith report a patient with Cushing's syndrome, who presented with systolic ventricular failure secondary to dilated myocardiopathy and signs of proximal myopathy as predominant features. All symptoms regressed after successful treatment.
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PMID:Dilated cardiomyopathy as a presenting feature of Cushing's syndrome. 1271 23

Patients with hyperthyroidism usually present with symptoms of hypermetabolism with or without goitre and/or eye signs. Occasionally, however, the chief complaints are not immediately suggestive of hyperthyroidism. Patients with hyperthyroidism are described who presented with such atypical manifestations as periodic muscular paralysis, myasthenia, myopathy, encephalopathy, psychosis, angina pectoris, atrial fibrillation, heart failure without underlying heart disease, skeletal demineralization, pretibial myxedema, unilateral eye signs, and pitting edema of the ankles.
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PMID:ATYPICAL MANIFESTATIONS OF HYPERTHYROIDISM. 1417 5

Skeletal muscle involvement, or myopathy, has been a recognized feature of systemic sclerosis (SSc). We studied retrospectively 302 Japanese patients with SSc to elucidate the clinical and laboratory features in scleroderma patients developing skeletal myopathy during their clinical course. Forty-three patients (14%) developed skeletal myopathy during their course of the disease. The mean age of the patients who developed skeletal myopathy was significantly lower than that of those who did not. The ratio of male to female was significantly higher in the myopathic patients. The patients with diffuse cutaneous SSc were more likely to develop myopathy than those with limited cutaneous SSc. The prevalences of heart involvement, pulmonary fibrosis, diffuse pigmentation of the skin, and contracture of phalanges were significantly greater in those with skeletal myopathy than in those without. None of the patients with skeletal myopathy had anticentromere antibody. These findings suggested that the SSc patients with severe internal organ involvement, such as pulmonary fibrosis and heart disease, and some other complications were prone to develop skeletal myopathy during their clinical course of the disease.
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PMID:Clinical and laboratory features of scleroderma patients developing skeletal myopathy. 1532 44

A subset of patients harboring mutations in the dystrophin gene suffer from X-linked dilated cardiomyopathy (XLCM), a familial heart disease that is not accompanied by any clinical signs of skeletal muscle myopathy. As the muscle (M) isoform of dystrophin is not expressed in these patients, the absence of skeletal muscle symptoms has been attributed to expression of the brain (B) and cerebellar Purkinje (CP) isoforms of dystrophin in skeletal, but not cardiac, muscles of XLCM patients. The compensatory mechanism of dystrophin B and CP promoter upregulation is not known but it has been suggested that the dystrophin muscle enhancer from intron 1, DME-1, may be important in this activity. Previous studies have shown that the presence of the DME-1 is essential for a significant increase in dystrophin B and CP promoter activity in skeletal muscle cells in culture. Here, we demonstrate that the mouse dystrophin CP promoter drives expression of a lacZ reporter gene specifically to the cerebellar Purkinje cell layer but not to skeletal or cardiac muscle of transgenic mice. However, if the mouse counterpart of DME-1 is present in the transgene construct, the dystrophin CP promoter is now activated in skeletal muscle, but not in cardiac muscle. Our findings provide in vivo evidence for the importance of the dystrophin muscle enhancer sequences in activating the dystrophin CP promoter in skeletal muscle. Furthermore, they provide support for the model in which muscle enhancers, like DME-1, activate the dystrophin B and CP promoters in skeletal muscle, but not in cardiac muscle, of XLCM patients.
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PMID:The mouse dystrophin muscle enhancer-1 imparts skeletal muscle, but not cardiac muscle, expression onto the dystrophin Purkinje promoter in transgenic mice. 1538 45

Timothy syndrome (TS) is a multisystem disorder that causes syncope and sudden death from cardiac arrhythmias. Prominent features include congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. All TS individuals have syndactyly (webbing of fingers and toes). We discovered that TS resulted from a recurrent, de novo cardiac L-type calcium channel (CaV1.2) mutation, G406R. G406 is located in alternatively spliced exon 8A, encoding transmembrane segment S6 of domain I. Here, we describe two individuals with a severe variant of TS (TS2). Neither child had syndactyly. Both individuals had extreme prolongation of the QT interval on electrocardiogram, with a QT interval corrected for heart rate ranging from 620 to 730 ms, causing multiple arrhythmias and sudden death. One individual had severe mental retardation and nemaline rod skeletal myopathy. We identified de novo missense mutations in exon 8 of CaV1.2 in both individuals. One was an analogous mutation to that found in exon 8A in classic TS, G406R. The other mutation was G402S. Exon 8 encodes the same region as exon 8A, and the two are mutually exclusive. The spliced form of CaV1.2 containing exon 8 is highly expressed in heart and brain, accounting for approximately 80% of CaV1.2 mRNAs. G406R and G402S cause reduced channel inactivation, resulting in maintained depolarizing L-type calcium currents. Computer modeling showed prolongation of cardiomyocyte action potentials and delayed afterdepolarizations, factors that increase risk of arrhythmia. These data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of TS.
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PMID:Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. 1586 12


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