Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protease inhibitor leupeptin decreases protein degradation in rat skeletal and cardiac muscle incubated in vitro, while protein synthesis remains unaltered. Leupeptin also lowers protein breakdown in denervated rat muscles and affected muscles from mice with hereditary muscular dystrophy. Leupeptin may thus be useful in retarding tissue atrophy. Since homogenates of leupeptin-treated muscles had decreased cathepsin B activity, this lysosomal protease may play a role in protein turnover in normal and diseased muscles.
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PMID:Leupeptin, a protease inhibitor, decreases protein degradation in normal and diseased muscles. 62 52

Electrocardiographic abnormalities were identified in 63 (84%) of 75 patients with Duchenne's progressive muscular dystrophy. A tall R wave over V1 with an abnormal R/S ratio was seen in 64% of the patients, a deep and narrow Q wave greater than 4 mm over leads I, V5, and V6 in 44%, sinus tachycardia in 32% and right axis deviation in 16%. Other ECG abnormalities included an abnormal PV1 index in 14% of patients and a short P-R interval in 6%. Ultrastructural characteristics of the heart were determined for two patients with characteristic electrocardiographic abnormalities. Common to both hearts was a total loss of thick as well as thin myofilaments, which gave a "moth-eaten" appearance to the myofiber. This feature, combined with preservation of the transverse tubular system, formed the most characteristic ultrastructural finding and was seen most consistently in the posterobasal area of the left ventricle. Alterations of Z-band material; accumulation of mitochondria, occasionally containing electron-dense bodies and showing loss or discontinuity of cristae; dilatation of sarcoplasmic reticulum with striking ectasia of cisternae; depletion of glycogen particles; a paucity of lipoid or lipochrome granules; and the absence of virus-like particles were other consistent ultrastructural features. Comparison of skeletal and cardiac muscle disclosed identical subcellular changes. These observations support the contention that the distinctive ECG pattern associated with Duchenne's dystrophy results from multifocal degenerative changes involving myocardium, predominantly the posterobasal region of the left ventricle and the posterior papillary muscle.
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PMID:An ultrastructural basis for electrocardiographic alterations associated with Duchenne's progressive muscular dystrophy. 63 32

The presence of taurine, a non-essential amino acid, in nerve and muscle has been previously associated with inhibition of activity in the central nervous system, with the etiology of epileptogenic foci, and with the muscle weakness of muscular dystrophy. We present here data showing a small and probably insignificant effect of taurine on neuromuscular transmission per se, but significant hyperpolarization of the membrane potential in both taurine-incubated and taurine-loaded muscles. In addition, we found that taurine reduces the time course of the muscle action potential. The results are interpreted in terms of neuromuscular transmission and excitation-contraction coupling consequent to these phenomena. This interpretation is compatable with the hypothesis that taurine is involved in the genesis of muscular dystrophy where the membrane potential is depolarized. Our results and interpretation can also explain the anti-arrhythmic action of taurine on cardiac muscle.
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PMID:Excitability modulation by taurine. Transmembrane measurements of neuromuscular transmission. 107 44

In a previous study, the efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) which takes place from isolated mouse skeletal muscle was shown to be significantly reduced by pretreatment of the intact animal with diethylstilbestrol (DES). This compound is known to reduce the high serum enzymes present in patients with Duchenne's muscular dystrophy (DMD). Glucocorticoids also reduce the serum enzymes in DMD. The purpose of this study was to determine if pretreatment with the glucocorticoid, prednisolone, also lowered the efflux from isolated mouse skeletal and cardiac muscle. The results of these studies show that prednisolone pretreatment lowers the enzyme efflux from isolated skeletal muscle, but not from heart. There is an optimal dose which produces this reduction, which if exceeded, augments the efflux. Thus two agents are now known which lower the efflux of CPK and LDH from isolated skeletal muscle. These same two agents lower the high serum enzymes in DMD. This suggests, but does not prove, that the mechanism by which these agents lower the serum enzymes in DMD is by reducing enzyme efflux from skeletal muscle.
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PMID:Effect of pretreatment with prednisolone on enzyme efflux from isolated skeletal and heart muscle. 119 19

Duchenne's muscular dystrophy (DMD), which affects 1/3500 live male births, involves a progressive degeneration of skeletal and cardiac muscle, leading to early death. The protein dystrophin is lacking in DMD and present, but defective, in the allelic, less severe, Becker muscular dystrophy and is also missing in the mdx mouse. Experiments on the mdx mouse have suggested two possible therapies for these myopathies. Implantation of normal muscle precursor cells (mpc) into mdx skeletal muscle leads to the conversion of dystrophin-negative fibres to -positive, with consequent improvement in muscle histology. Direct injection of dystrophin cDNA into skeletal or cardiac muscle also gives rise to dystrophin-positive fibres. Although both appear promising, there are a number of questions to be answered and refinements to be made before either technique could be considered possible as treatments for myopathies in man.
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PMID:Cell transplantation and gene therapy in muscular dystrophy. 136 21

Duchenne's muscular dystrophy (DMD), which affects one in 3,500 males, causes progressive myopathy of skeletal and cardiac muscles and premature death. One approach to treatment would be to introduce the normal dystrophin gene into diseased muscle cells. When pure plasmid DNA is injected into rodent skeletal or cardiac muscle, the cells express reporter genes. We now show that a 12-kilobase full-length human dystrophin complementary DNA gene and a 6.3-kilobase Becker-like gene can be expressed in cultured cells and in vivo. When the human dystrophin expression plasmids are injected intramuscularly into dystrophin-deficient mdx mice, the human dystrophin proteins are present in the cytoplasm and sarcolemma of approximately 1% of the myofibres. Myofibres expressing human dystrophin contain an increased proportion of peripheral nuclei. The results indicate that transfer of the dystrophin gene into the myofibres of DMD patients could be beneficial, but a larger number of genetically modified myofibres will be necessary for clinical efficacy.
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PMID:Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. 188 32

DMD and BMD are now understood at the genetic, biochemical, and molecular levels. At the genetic level, both disorders result from mutations of the X-linked gene encoding dystrophin. At the biochemical level, DMD results from the deficiency of a large protein called dystrophin, whereas BMD results when dystrophin is present, though abnormal in either amount or molecular structure. To date, thousands of patients have been analyzed for mutations of the dystrophin gene in peripheral blood DNA or alterations of the dystrophin protein in muscle tissue. The severity of the clinical phenotype of these patients has been compared with their dystrophin gene mutations and corresponding dystrophin protein alterations, revealing an unexpectedly high degree of correlation. Thus, information derived from the molecular analysis (DNA or protein) of a particular patient provides a "molecular diagnosis," which is highly predictive of the clinical course that patient can be expected to follow. Because molecular diagnoses are independent of the patient's age, they provide a prognosis for the large majority of muscular dystrophy patients even before clinical symptoms of their disease become apparent. Such prognostic molecular diagnoses have proven particularly valuable when the patient is an isolated case, with no family history for the disorder. Prenatal genetic diagnosis of DMD or BMD may involve use of Southern blot or PCR techniques to search for a deletion in the DNA of at-risk fetuses or more complicated family linkage studies using intragenic and flanking RFLPs. More recently, assay of dystrophin content in fetal skeletal or cardiac muscle from at-risk abortuses has been accomplished, allowing definitive discrimination of affected and normal fetuses in cases in which deletion analyses and family DNA studies were equivocal. In utero fetal skeletal muscle biopsy for dystrophin protein assay has actually been accomplished in at least one at-risk pregnancy in which family DNA studies were uninformative. Dystrophin was present in skeletal muscle from this 20-week-old male fetus, and the pregnancy continued, resulting in the term birth of a healthy male infant. The future holds exciting opportunities for neonatal screening and treatment of these devastating neuromuscular diseases.
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PMID:Duchenne and Becker muscular dystrophies: genetics, prenatal diagnosis, and future prospects. 228 31

A 42-year-old man with limb-girdle muscular dystrophy who showed prominent cardiac involvement is described. He was treated for and diagnosed with dilated cardiomyopathy before admission. Initially, no overt feature of muscular dystrophy was evidenced, but serum enzymes were elevated. During the 2-year follow-up period, distinct features of muscular dystrophy appeared, and muscle biopsy confirmed the diagnosis. He was regarded as experiencing a sporadic occurrence. Because some patients diagnosed with and treated for dilated cardiomyopathy may have similar results, this form of muscular dystrophy should be recognized as occasionally associated with cardiac muscle disease.
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PMID:Marked cardiac involvement in limb-girdle muscular dystrophy. 235 53

In patients with Duchenne muscular dystrophy (DMD), heart failure appears in later stage of the disease due to myocardial degeneration and respiratory insufficiency, and sometimes causes death. However, there have been no adequate parameters which can be used easily to evaluate the grade of heart failure in DMD, except cardiac enlargement and pulmonary congestion observed by chest X-ray picture. Thus, we measured the plasma concentrations of atrial natriuretic peptide (ANP) in the patients with muscular dystrophy of various types, and studied a relationship between plasma ANP concentration and heart failure, expecting that it could be an index of heart failure in DMD patients. The plasma ANP concentrations in patients with DMD were 35.5 +/- 3.3pg/ml (mean +/- SE) and higher than in normal subjects (19.3 +/- 1.0pg/ml). In the patients with limb-girdle muscular dystrophy, facioscapulohumeral muscular dystrophy and neurogenic muscular atrophy, the plasma ANP concentration showed a tendency to elevate. However, no elevation of plasma ANP levels was observed in the patients with other types of muscular dystrophy. In DMD, number of the patients having a high plasma ANP concentration was increased with progress of disability grade, and decrease in serum creatine kinase activity and serum myoglobin concentration. There was a significant correlation (p less than 0.01) between plasma ANP concentration and cardiothoracic ratio or PEP/LVET, but no correlation between the concentration and respiratory failure. Immunohistochemistry of the atrial cardiac muscle of an autopsied DMD case revealed many ANP-positive atrial muscle cells, indicating the preservation of ANP-secreting function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Secretion and clinical significance of atrial natriuretic peptide in patients with muscular dystrophy]. 252 1

The degree of DNA-polyploidy of cardiac muscle cells was investigated by cytofluorometry in 4 cases of progressive muscular dystrophy (DMP) and 2 cases of myotonic dystrophy (DM), and the results were compared with those for non-dystrophic hearts of normal or increased weight. The heart muscle cells from all patients with these forms of dystrophy showed marked nuclear DNA hyperploidy reaching 16c, irrespective of cardiac hypertrophy or atrophy. In the non-dystrophic group, DNA hypertrophy corresponding to that of dystrophy was only detected in cases of marked cardiac hypertrophy exceeding a weight of 400 g. The wasting of the respiratory musculature, deformity of the thorax and cardiac muscular atrophy appeared to be the principal factors causing DNA polyploidy in patients with muscular dystrophy.
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PMID:Cytofluorometric determination of nuclear DNA in heart muscles of patients with muscular dystrophy. 253 66


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