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)

A wide-range complex of biochemical techniques was used to study metabolic processes in workers exposed to cobalt and ethanol. In practically healthy workers were found laboratory manifestations of hepato-biliary irritations, hyperpermeability of the hepatocytes' cytoplasmic membrane, cholestasis syndrome, initial manifestations of muscular dystrophy and minor signs of atherosclerosis risks. The biochemical shifts were like those in alcoholism cases. It was suggested that, under the existing technological conditions of cobalt-containing hard-facing alloys' powder processing, the action of ethanol increased the toxic effect of cobalt.
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PMID:[Metabolic status in workers engaged in the production of cobalt-containing powder compositions of hard alloys]. 179 96

A number of active oxygen species are likely implicated in the etiology or manifestation of several pathological conditions, including aging, arthritis, carcinogenesis, atherosclerosis, and muscular dystrophy. Ascorbate plays a key role in protecting cells against oxidative damage. Paradoxically, in the presence of Fe3+ or Cu2+, ascorbate can promote the generation of the same reactive oxygen species (.OH, O2-, H2O2, and ferryl ion) it is known to destroy. This prooxidant activity derives from the ability of ascorbate to reduce Fe3+ or Cu2+ to Fe2+ or Cu+, respectively, and to reduce O2 to O2-. and H2O2. Damage to nucleic acid and proteins results from the binding of either Fe2+ or Cu+ to metal binding sites on these macromolecules followed by reaction of the metal complexes with H2O2; this leads to the production of active oxygen species that attack functional groups at or near the metal binding sites.
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PMID:Ascorbic acid and oxidative inactivation of proteins. 196 58

This is a clinical report of a rare case of Charcot-Marie-Tooth disease associated with dilated cardiomyopathy. A seventy-seven-year-old Japanese male first visited our outpatient clinic with a ten-year history of muscular weakness in his bilateral lower extremities and gait disturbance characterized by classical features of peroneal muscular atrophy and inverted champagne bottle legs. Biopsy findings of the m. quadriceps femoris and the n. gastrocnemius revealed clustered atrophy of myofibrils and segmental demyelinization mingled with remyelinization. Because of his other problem of dilated cardiomyopathy, he had been treated with salt restriction, digitalis, diuretics and vasodilators, until his third hospitalization, when he developed terminal stage of severe congestive heart failure. Despite our intensive cardiac care, the patient died because of profound pump failure. Autopsy findings disclosed a remarkably dilated left ventricular chamber and an increased total heart weight of 600 grams. Grossly, the cross sectional view of the left ventricle revealed diffuse, but not homogenous fibrosis that was most prominent in the posterior wall. On light microscopic examination, the left ventricular myocardium revealed diffusely scattered muscular degeneration interlaced with fibrosis. Although large epicardial coronary arteries revealed only mild intimal atheromatous thickening, most of the small intramuscular coronary arteries were free from atherosclerosis. Neither diabetic nor amyloid lesions could be detected. It has been well known that cardiomyopathy is often associated with various forms of muscular dystrophy and Friedreich's ataxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Charcot-Marie-Tooth disease associated with dilated cardiomyopathy: an autopsy case report]. 204 12

This article reviews the available data on the role of the peroxisome in the growth, differentiation and degeneration of mammalian tissues. Developmental progressions of peroxisomes are described, along with the influence of inhibitors of peroxisomal enzymes, peroxisome proliferators and morphogenetic agents on the ontogeny of experimental animals. The role of the peroxisome in protecting tissues from damage by oxygen free radicals is also described, as is the changing role of the peroxisome in the ageing animal. Amongst the degenerative diseases which have been associated with free radical damage are cancer, atherosclerosis, muscular dystrophy, rheumatoid arthritis and the senile degeneration of brain function. In all these conditions, the major characteristics of molecular damage have been considered, along with the particular role of the peroxisome in alleviating these effects. Proposals for further research into peroxisomal function during ontogeny and the degenerative changes associated with ageing are developed, and the possibility of palliative treatments discussed.
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PMID:On the role of the peroxisome in ontogeny, ageing and degenerative disease. 756 65

Caveolae are small invaginations of the plasma membrane found in many cell types, and caveolins are integral membrane proteins that form the framework of caveolae. In the past several years, research on caveolae has developed explosively, and caveolae and/or caveolins have been shown to play many important roles in cell physiology: in particular, they are thought to be related to signal transduction, cholesterol transport, endocytosis and tumor suppression. On the other hand, some studies have suggested that another membrane domain called rafts is also involved in the same processes, and some confusion remains concerning the relationship between these two domains. Abnormalities in caveolae and/or caveolins have been found in various diseases, including cancer, atherosclerosis, muscular dystrophy and the Alzheimer's disease, which may make this domain a new focus for pharmacological research. This review will focus on the cell biology of caveolae, caveolins and rafts, and then summarize the implications of these findings for clinical studies.
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PMID:Cell biology of caveolae and its implication for clinical medicine. 1091 16

Caveolae, plasma membrane invaginations that serve as membrane organizing centers, are found in most cell types, but are enriched in adipocytes, endothelial cells, and myocytes. Three members of the caveolin family (Cav-1, -2, and -3) are essential for the formation of caveolae. Specialized motifs in the caveolin proteins function to recruit lipids and proteins to caveolae for participation in intracellular trafficking of cellular components and operation in signal transduction. Mutations in the gene encoding CAV-1 are associated with the development and progression of breast cancers, whereas mutations in the CAV-3 gene result in Rippling Muscle Disease and a form of Limb-Girdle Muscular Dystrophy. The generation of caveolin-null mice has confirmed the essential role of these proteins in caveolae biogenesis and in the pathophysiology of diverse tissues. Caveolin-null mice provide new animal models for studying the pathogenesis of a number of human diseases, including cancer, diabetes, atherosclerosis, restrictive lung disease and pulmonary fibrosis, cardiomyopathy, muscular dystrophy, and bladder dysfunction.
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PMID:The biology of caveolae: lessons from caveolin knockout mice and implications for human disease. 1499 53

Nuclear factor-kappaB (NF-kappaB) is a major transcription factor that plays an essential role in several aspects of human health including the development of innate and adaptive immunity. The dysregulation of NF-kappaB is associated with many disease states such as AIDS, atherosclerosis, asthma, arthritis, cancer, diabetes, inflammatory bowel disease, muscular dystrophy, stroke, and viral infections. Recent evidence also suggests that the dysfunction of NF-kappaB is a major mediator of some human genetic disorders. Appropriate regulation and control of NF-kappaB activity, which can be achieved by gene modification or pharmacological strategies, would provide a potential approach for the management of NF-kappaB related human diseases. This review summarizes the current knowledge of the physiological and pathophysiological functions of NF-kappaB and its possible role as a target of therapeutic intervention
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PMID:Nuclear factor-kappaB: its role in health and disease. 1517 63

Diseases due to mutations in the lamin A/C gene (LMNA) are highly heterogeneous, including neuromuscular and cardiac dystrophies, lipodystrophies, and premature ageing syndromes. In this study we characterized the neuromuscular and cardiac phenotypes of patients bearing the heterozygous LMNA R482W mutation, which is the most frequent genotype associated with the familial partial lipodystrophy of the Dunnigan type (FPLD). Fourteen patients from two unrelated families, including 10 affected subjects, were studied. The two probands had been referred for lipoatrophy and/or diabetes. Lipodystrophy, exclusively observed in LMNA-mutated patients, was of variable severity and limited to postpubertal subjects. Lipodystrophy and metabolic disturbances were more severe in women, even if an enlarged neck was a constant finding. The severity of hypertriglyceridemia and hirsutism in females was related to that of insulin resistance. Clinical muscular alterations were only present in LMNA-mutated patients. Clinical and histological examination showed an invalidating, progressive limb-girdle muscular dystrophy in a 42-yr-old woman that had been present since childhood, associated with a typical postpubertal FPLD phenotype. Six of eight adults presented the association of calf hypertrophy, perihumeral muscular atrophy, and a rolling gait due to proximal lower limb weakness. Muscular histology was compatible with muscular dystrophy in one of them and/or showed a nonspecific excess of lipid droplets (in three cases). Immunostaining of lamin A/C was normal in the six muscular biopsies. Surprisingly, calpain 3 expression was undetectable in the patient with the severe limb-girdle muscular dystrophy, although the gene did not reveal any molecular alterations. At the cardiac level, cardiac septal hypertrophy and atherosclerosis were frequent in FPLD patients. In addition, a 24-yr-old FPLD patient had a symptomatic second degree atrioventricular block. In conclusion, we showed that most lipodystrophic patients affected by the FPLD-linked LMNA R482W mutation show muscular and cardiac abnormalities. The occurrence and severity of the myopathic and lipoatrophic phenotypes varied and were not related. The muscular phenotype was evocative of limb girdle muscular dystrophy. Cardiac hypertrophy and advanced atherosclerosis were frequent. FPLD patients should receive careful neuromuscular and cardiac examination whatever the underlying LMNA mutation.
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PMID:Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities. 1553 79

Caveolae are vesicular organelles (50-100-nm in diameter) that are particularly abundant in cells of the cardiovascular system, including endothelial cells, smooth muscle cells, macrophages, cardiac myocytes and fibroblasts. In these cell types, caveolae function both in protein trafficking and signal transduction, as well as in cholesterol homeostasis. Caveolins are the structural proteins that are both necessary and sufficient for the formation of caveolae membrane domains. Caveolins 1 and 2 are co-expressed in most cell types, while the expression of caveolin-3 is muscle-specific. Thus, endothelial cells and fibroblasts are rich in caveolins 1 and 2, while cardiac myocytes and skeletal muscle fibers express caveolin-3. In contrast, smooth muscle cells express all three caveolins (Cav-1, -2, and -3). Mechanistically, caveolins interact with a variety of downstream signaling molecules, including Src-family tyrosine kinases, p42/44 mitogen activated protein (MAP) kinase, and endothelial nitric oxide synthase (eNOS), and hold these signal transducers in the inactive conformation until activation by an appropriate stimulus. In many ways, caveolins serve both to compartmentalize and regulate signaling. Recent studies using caveolin-deficient mouse models dramatically show that caveolae and caveolins play a prominent role in various human patho-biological conditions, especially those related to the cardiovascular system. These disease phenotypes include: atherosclerosis, cardiac hypertrophy, cardiomyopathy, pulmonary hypertension, and neointimal hyperplasia (smooth muscle cell proliferation). In addition, caveolins play a significant role in other disease phenotypes, such as cancer, diabetes, bladder dysfunction, and muscular dystrophy, as we discuss in this review. Thus, caveolin-deficient mice will serve as important new animal models to dissect the intricate role of caveolae and caveolins in the pathogenesis of human diseases.
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PMID:The Caveolin genes: from cell biology to medicine. 1576 30

Laminopathies are a group of diseases due to mutations of type A-lamins, a group of proteins lining the inner aspect of cell nuclei. These diseases illustrate the complexity of the genotype-phenotype relationship characteristic of same genetic diseases. Since the discovery of the causal role of LMNA gene mutations in the genesis of Emery Dreifuss muscular dystrophy in 1999, no less than eight other diseases have been associated with mutations of this same gene! The tissue-specific nature of the clinical manifestations, contrasting with the ubiquitous expression of these proteins, has incited much research concerning the physiological role of lamins, considered to be much broader than the structural function initially put forward. Certain laminopathies, which combine insulin resistance, android distribution of adipose tissue, dyslipidemia, early atherosclerosis, and hepatic steatosis, appear very similar though more severe to the frequent dysmetabolism syndrome. The relationships of laminopathies with accelerated aging syndrome, Hutchinson-Gilford progeria, or progeroid syndromes, which are also related to A/C lamin anomalies, could provide new avenues of research on the pathogenesis of the metabolic syndrome. In addition, clinicians have to be aware of atypical and milder forms of laminopathies, that require specific investigations and molecular screening of relatives allowing an adequate medical management.
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PMID:[Laminopathies: lipodystrophies, insulin resistance, syndromes of accelerated ageing... and others]. 1598 90


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