Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional and histologic picture of steroid-induced myopathy was systematically examined in eight patients with chronic obstructive pulmonary disease (COPD) and compared with control patients with COPD matched for age, sex, and degree of airflow obstruction. Steroid-induced myopathy was associated with severe peripheral muscle weakness, quadriceps force being 23 +/- 14 versus 71 +/- 23% in control patients with COPD (p < 0.001). In addition, clear ventilatory muscle weakness was present. PImax was 37 +/- 15 versus 67 +/- 24% in control patients (p < 0.001 ), and PEmax averaged 34 +/- 10 versus 74 +/- 23% (p < 0.001). Vital capacity tended to be slightly reduced compared with that in control patients (69 +/- 21 versus 80 +/- 16%, p = 0.11). The only biochemical abnormalities associated to steroid-induced myopathy were a moderately increased lactic dehydrogenase level (697 +/- 301 versus 421 +/- 128 IU/L, p < 0.001) and an increased creatine excretion in 24-h urine (990 +/- 609 versus 159 +/- 219 mg/24 h, p< 0.001). On quadriceps biopsy steroid-induced myopathy was characterized by increased variation in diameter of fibers, with several angular atrophic fibers and diffuse necrotic and basophilic fibers. In addition, increased amount of connective tissue in between fibers and increased number of subsarcolemmal and central nuclei were present. On ATPase stain diffuse fiber atrophy predominantly affecting fast fibers was present, but there was no indication that atrophy was confined to type IIb fibers in contrast to conventional thinking. On follow-up, survival of patients with steroid-induced myopathy was reduced in comparison with control patients with COPD with similar degree of airflow obstruction (p < 0.025).
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PMID:Functional and histologic picture of steroid-induced myopathy in chronic obstructive pulmonary disease. 866 61

A 59-year-old woman with rheumatoid arthritis was treated with prednisone and 250 mg of chloroquine diphosphate (CQ) daily. Though there was improvement in her joint symptoms, she began to notice progressive lower limb weakness, later extending to the arms and lasting for 2 months. Electromyography showed fibrillations, polyphasic potentials and high frequency discharges. Biceps brachii biopsy showed that virtually every muscle fiber and multiple small vacuoles surrounded by a basophilic rim. There was variation in fiber diameter and some fibers were atrophic and angulated. ATPase revealed type grouping. Electron microscopy showed, in each muscle fiber, numerous concentric membranous bodies, some with curvilinear profiles, beneath the sarcolemma or among the myofibrils. Some were also observed in endothelial cells of muscle capillaries. CQ was withdrawn, but no significant regression of symptoms had been observed at the time follow-up was discontinued. The patient died of cardiac insufficiency and bronchopneumonia. The case illustrates a rare complication of CQ therapy of rheumatic conditions. It is noteworthy because the drug was administered in therapeutic doses and only for a short period. CQ is known to interfere with lysosomal function, from which presumably the membranous bodies here described originate. Improvement of neuromuscular symptoms has been reported following withdrawal of the drug.
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PMID:Chloroquine neuromyopathy. 887 64

The severe neonatal centronuclear/myotubular myopathy (XLMTM) is an X-linked disorder characterized by generalized muscle weakness, hypotonia and serious respiratory insufficiency. The gene for this disease has been assigned to the long arm of chromosome X in the Xq28 band. Ca2+ ATPase isoform-3 (ATP2B3) has also been mapped to the human Xq28 region. Moreover, it is expressed in fetal but not in adult muscle, suggesting the developmental regulation of gene transcription. These findings render the ATP2B3 gene as an interesting candidate gene for XLMTM. Four families and 7 unrelated XLMTM patients have been analysed by using cDNA and genomic probes of ATP2B3. No large deletions or duplications have been found but a new EcoRI polymorphism has been identified. In addition, the DNA of an XLMTM male deletion patient has been hybridized with the ATP2B3 gene sequences. Our results therefore support the exclusion of ATP2B3 as the causal disease gene of XLMTM. The isolation of the MTM1 gene has recently been reported by another group. However, our approach has led to the detection of a new polymorphism that is an informative marker for linkage and mutation studies in other Xq28-mapped neurological or neuromuscular disorders.
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PMID:Detection of a new polymorphism in the plasma-membrane Ca2+ ATPase isoform-3 gene and its exclusion as a candidate for X-linked myotubular myopathy (MTM1). 893

A 32 year old woman with a history of anorexia nervosa began experiencing severe muscle weakness. Proximal weakness was worse than distal and she became unable to walk. Serum creatine kinase was elevated 15-fold and EMG was consistent with a myopathic process. Muscle biopsy showed focal areas of absent staining using NADH and ATPase enzyme histochemistry. Gomori trichrome revealed many positive inclusions which were positive using immunohistochemistry for actin. Electron microscopy revealed these areas to contain cytoid bodies with Z-band streaming and disorganization of the myofibrillar network. These findings are consistent with the myopathy associated with ipecac (emetine) toxicity. A urine toxicology screen demonstrated evidence of emetine abuse, which was later admitted by the patient. Following discontinuation of the drug, the patient recovered normal muscle strength.
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PMID:Case of the month. June 1996--anorexia nervosa. 894 26

Hyaline bodies are rare subsarcolemmal aggregates in type 1 fibers of the skeletal muscle, stain pale pink with hematoxylin-eosin and pale green with the modified Gomori trichrome, and lack reactivity for glycogen and oxidative enzymes. We report clinical findings of autosomal-dominant hyaline body myopathy in seven members in four generations and muscle biopsy findings in two of them. Slowly progressive muscle weakness and atrophy developed with scapuloperoneal distribution; age at onset was from the first to the fifth decade. Muscle biopsy showed subsarcolemmal hyaline bodies in approximately 20% of type 1 fibers. Hyaline bodies showed myofibrillar ATPase activity after acid pre-incubation. Immunohistochemically, they stained intensely with myosin heavy chain (slow), but not with myosin heavy chain (fast). Ultrastructurally, they consisted of granules sometimes in linear array, filaments, and amorphous materials. These findings suggest that hyaline bodies may be products of degeneration of myosin heavy chain (slow).
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PMID:Autosomal dominant hyaline body myopathy presenting as scapuloperoneal syndrome: clinical features and muscle pathology. 900 27

Energy intake profoundly influences many endocrine axes which in turn play a central role in development. The specific influence of a short period of mild hypothyroidism, similar to that induced by undernutrition, in regulating muscle development has been assessed in a large mammal during early postnatal life. Hypothyroidism was induced by providing methimazole and iopanoic acid in the feed of piglets between 4 and 14 d of age, and controls were pair-fed to the energy intake of their hypothyroid littermates. Thyroid status was evaluated, and myofibre differentiation and cation pump concentrations were then assessed in the following functionally distinct muscles: longissimus dorsi (l. dorsi), soleus and rhomboideus. Reductions in plasma concentrations of thyroxine (T4; 32%, P < 0.01), triiodothyronine (T3; 48%, P < 0.001), free T3 (58%, P < 0.001) and hepatic 5'-monodeiodinase (EC 1.11.1.8) activity (74%, P < 0.001) occurred with treatment. Small, although significant, increases in the proportion of type I slow-twitch oxidative fibres occurred with mild hypothyroidism, in l. dorsi (2%, P < 0.01) and soleus (7%, P < 0.01). Nuclear T3-receptor concentration in l. dorsi of hypothyroid animals compared with controls increased by 46% (P < 0.001), a response that may represent a homeostatic mechanism making muscle more sensitive to low levels of circulating thyroid hormones. Nevertheless, Na+, K(+)-ATPase (EC 3.6.1.37) concentration was reduced by 15-16% in all muscles (l. dorsi P < 0.05, soleus P < 0.001, rhomboideus P < 0.05), and Ca(2+)-ATPase (EC 3.6.1.38) concentration was significantly reduced in the two slow-twitch muscles: by 22% in rhomboideus (P < 0.001) and 23% in soleus (P < 0.05). It is concluded that during early postnatal development of large mammals a period of mild hypothyroidism, comparable with that found during undernutrition, induces changes in myofibre differentiation and a down-regulation of cation pumps in skeletal muscle. Such changes would result in slowness of movement and muscle weakness, and also reduce ATP hydrolysis with a concomitant improvement in energetic efficiency.
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PMID:Role of thyroid hormones in early postnatal development of skeletal muscle and its implications for undernutrition. 901 53

Female Wistar rats were treated orally for 5 days with 80 mg/kg body weight of 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ), a microsomal Ca2+ ATPase inhibitor. Motor endplates of the lumbrical muscles were examined by light and electron microscopy. There was a decrease in body weight in the treated rats from the first day after administration, and toxic signs appeared after the third day, such as adoption of a prone position, salivation, lacrymation, and an abnormal gait and/or muscle weakness. No remarkable macroscopic or light microscopic changes were noted in the lumbrical muscles as well as other peripheral nerves of hind legs of the treated rats killed 1 day after the last DTBHQ treatment. Ultrastructurally, neurotoxicity characterized by loss of synaptic vesicles and mitochondria in the motor endplates, and by destruction of the motor terminals was detected in the lumbrical muscles of the treated rats. These results strongly indicate that DTBHQ targets the motor endplates in the rat lumbrical muscles and suggest that the resultant damage is responsible for the appearance of neurological signs, such as an abnormal gait and loss of muscle control.
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PMID:Ultrastructural changes in motor endplates of the lumbrical muscles of rats induced by a microsomal Ca2+ ATPase inhibitor, 2,5-di(tert-butyl)-1,4-hydroquinone. 945 84

Case 1: A 27-year-old man had a fever of 38 degrees C, followed by acute onset of bilateral upper arm pain. Two days later severe muscle weakness in bilateral upper arms appeared and he was admitted to our hospital. On admission, severe atrophy of the left deltoid and mild atrophy of the right deltoid were observed, with severe muscle weakness in bilateral deltoid and mild weakness in other parts of upper extremities. Tendon reflexes were decreased in the upper extremities. Sensation was intact. CSF showed mild pleocytosis. Nerve conduction velocity was normal and electromyography showed mild NMU decrease in upper extremities. Muscle biopsy of the right deltoid one month after the onset was normal. Muscle weakness began to improve 3 months after the onset, with only mild weakness at 10 months. Case 2: A 60-year-old man had acute onset of left shoulder and upper arm pain, followed by muscle atrophy and weakness of the left upper arm. He showed marked atrophy of the left deltoid, moderate atrophy of the left biceps and left scapular region, and severe muscle weakness in the left upper arm. Deep tendon reflexes were absent in the left upper extremity. Sensation was intact. Nerve conduction velocity was normal and electromyography showed marked NMU decrease in the left upper arm. Muscle biopsy of the left biceps 4 months after the onset showed grouped atrophies on HE staining, type 2 fiber atrophies on routine ATPase staining, and many targetoid atrophic fibers on NADH-TR staining. Muscle weakness began to improve slowly 6 months after the onset, but considerable weakness persisted at 10 months. Detailed muscle biopsy findings in neuralgic amyotrophy have not been documented. Muscle biopsy of Case 2 showed marked neurogenic changes compared to Case 1, which may be associated with the difference in clinical course between the two cases.
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PMID:[Two cases of neuralgic amyotrophy]. 986 14

Muscle wasting and weakness are common features of patients with critical illnesses, and may impair their recovery. This study examines whether cytoskeletal and contractile proteins are damaged, and which proteolytic mechanisms might be involved, in the muscle fibre atrophy or necrosis associated with the acute myopathy of critically ill patients. Ninety-eight muscle biopsies were obtained by the conchotome method from 57 critically ill patients and examined morphometrically and by immunohistochemical labelling. Sequential biopsies showed a mean reduction in fibre cross-sectional areas of 3-4% per day. More intense immunolabelling for desmin was seen in the smaller fibres of 52% of the biopsies, while immunolabelling for dystrophin, actin and myosin heavy chains was maintained. Myosin ATPase activity was weak in the smaller fibres in some biopsies, and electron microscopy showed the loss of myosin filaments in atrophic fibres. These changes suggest that loss of the filamentous structure of myosin, without degradation of the immunolabelled epitopes, leads to the collapse of the intermyofibrillar desmin network. Fibres with abnormal desmin labelling showed increased cathepsin B, lysozyme and ubiquitin immunolabelling. Nine cases showed increased immunolabelling for heat shock protein 72. The changes in desmin immunolabelling were more prevalent in patients with higher APACHE II scores on admission, but were not related to other clinical features. The results indicate that fibre atrophy is associated with myosin filament depolymerization and the presence of several proteolytic enzymes. In our study, these changes occurred in patients who were critically ill but who did not receive large doses of steroids or neuromuscular blocking agents.
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PMID:Muscle fibre atrophy in critically ill patients is associated with the loss of myosin filaments and the presence of lysosomal enzymes and ubiquitin. 988 61

In recent years, genetic defects of the mitochondrial genome (mtDNA) were shown to be associated with a heterogeneous group of disorders, known as mitochondrial diseases, but the cellular events deriving from the molecular lesions and the mechanistic basis of the specificity of the syndromes are still incompletely understood. Mitochondrial calcium (Ca2+) homeostasis depends on close contacts with the endoplasmic reticulum and is essential in modulating organelle function. Given the strong dependence of mitochondrial Ca2+ uptake on the membrane potential and the intracellular distribution of the organelle, both of which may be altered in mitochondrial diseases, we investigated the occurrence of defects in mitochondrial Ca2+ handling in living cells with either the tRNALys mutation of MERRF (myoclonic epilepsy with ragged-red fibers) or the ATPase mutation of NARP (neurogenic muscle weakness, ataxia and retinitis pigmentosa). There was a derangement of mitochondrial Ca2+ homeostasis in MERRF, but not in NARP cells, whereas cytosolic Ca2+ responses were normal in both cell types. Treatment of MERRF cells with drugs affecting organellar Ca2+ transport mostly restored both the agonist-dependent mitochondrial Ca2+ uptake and the ensuing stimulation of ATP production. These results emphasize the differences in the cellular pathogenesis of the various mtDNA defects and indicate specific pharmacological approaches to the treatment of some mitochondrial diseases.
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PMID:A calcium signaling defect in the pathogenesis of a mitochondrial DNA inherited oxidative phosphorylation deficiency. 1042 22


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