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)

A classical case of myxedema, demonstrating the typical Hoffmann syndrome (muscle weakness, hypertrophy, pseudomyotonic phenomena) and the usual rise in serum creatine phosphokinase (CPK), is discussed. Assuming that there is a CPK loss in the muscle fiber, the pseudomyotonic phenomena may be due to an increase in ADP, which in turn inhibits the calcium pump. Furthermore, light-microscopic and electron-microscopic findings are reported.
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PMID:Myxedema myopathy: a case report. 61 16

A new method of isolating human sebaceous and apocrine sweat glands by the repeated dissection of skin biopsies with scissors is described. The success of the technique is attributed to a line of weakness between the investing capsule and the surrounding connective tissue which parts under shear forces. The glands are judged to be viable by: (i) light and electron microscopy; (ii) ATP, ADP and AMP contents of 148.8 +/- 30.3, 30.6 +/- 4.7 and 14.9 +/- 4.7 pmol (mean +/- s.e.m.) for sebaceous glands and 310.2 +/- 34.1, 90.35 +/- 16.3 and 40.1 +/- 11.8 pmol (mean +/- s.e.m.) for apocrine sweat glands, which gave energy charges of 0.84 and 0.81, respectively; and (iii) a rate of sebaceous gland lipogenesis of 39.7 +/- 3.7 pmol glucose incorporated into lipid/gland/h (mean +/- s.e.m.).
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PMID:The isolation of human sebaceous glands and apocrine sweat glands by shearing. 394 36

A new method of isolating human eccrine sweat glands by the repeated dissection of skin biopsies with scissors is described. The success of the technique is attributed to a potential line of weakness between the investing capsule and the surrounding connective tissue, which parts under shear forces. The yield is 20-50 glands per biopsy (5 cm X 0.5 cm). The glands are judged to be viable by: (i) light and electron microscopy; (ii) ATP, ADP and AMP contents of 81.0 +/- 12.7, 13.8 +/- 3.3 and 3.8 +/- 1.0 pmol/gland, respectively (mean +/- S.E.M.), which gave an energy charge of 0.90; (iii) the 28-fold rise in cyclic GMP content and the sevenfold rise in cyclic AMP content effected by treatment for 2 min with 10(-5) M-acetylcholine and for 10 min with 10(-5) M-isoprenaline, respectively; (iv) the rate of [3H]leucine uptake into protein; and (v) the concentration of Neutral Red by the collecting duct. Glands were maintained for 7 days on polycarbonate filters floating on RPMI 1640 tissue-culture medium. After this time the ATP, ADP and AMP contents were 63.2 +/- 7.3, 8.5 +/- 2.2 and 3.5 +/- 0.8 pmol/gland, respectively (mean +/- S.E.M.), which gave an energy charge of 0.90. During maintenance a dilatation of the intercellular spaces developed in both secretory coil and collecting duct. Following maintenance there was a significant rise in the rate of [3H]leucine uptake into protein. Maintained glands demonstrated a fivefold greater accumulation of cyclic AMP in response to isoprenaline than did freshly isolated glands, but there was no comparable maintenance hypersensitivity of cyclic GMP to acetylcholine. This pattern of adrenergic, but not cholinergic, maintenance hypersensitivity matches the known lack of denervation hypersensitivity of human eccrine sweat glands to acetylcholine in vivo.
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PMID:Biochemical and ultrastructural studies of human eccrine sweat glands isolated by shearing and maintained for seven days. 609 35

1. The contractile force, phosphorus metabolite levels, intracellular pH and myosin isoforms were compared in isolated soleus and extensor digitorum longus (EDL) muscles from young (6 month old) and aged (28 month old) mice, at 23 degrees C. 2. The isometric force per unit cross-sectional area was significantly lower by 21 +/- 5% in soleus muscles from aged mice compared to those from young mice (mean +/- S.E.M., n = 11 and 9 respectively). 3. The EDL muscle contained twice as much total creatine and phosphocreatine as the soleus, 1.7 times as much ATP, and 0.4 times the inorganic phosphate (Pi) per unit weight. The intracellular pH and free ADP levels were not significantly different between these muscle types. 4. There was no significant difference in resting metabolite levels between young and old EDL or soleus despite the difference in mechanical strength. 5. Examination of the expression of myosin isoforms by non-denaturing gel electrophoresis has shown that the percentage of each isoform does not change with respect to age; thus, if there is an atrophic process occurring, it is not fibre type specific. 6. We have determined that neither the Pi levels nor the intracellular pH can explain the differences seen in muscle strength with age. There is also no correlation between muscle weakness and any of the other metabolites responsible for energy transduction (phosphocreatine, ATP or ADP).
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PMID:Neither changes in phosphorus metabolite levels nor myosin isoforms can explain the weakness in aged mouse muscle. 824 80

The manifestations of fatigue, as observed by reductions in the ability to produce a given force or power, are readily apparent soon after the initiation of intense activity. Moreover, following the activity, a sustained weakness may persist for days or even weeks. The mechanisms responsible for the impairment in performance are various, given the severe strain imposed on the multiple organ systems, tissues and cells by the activity. At the level of the muscle cell, ATP utilization is dramatically accelerated in an attempt to satisfy the energy requirements of the major processes involved in excitation and contraction namely sarcolemmal Na+/K+ exchange, sarcoplasmic reticulum Ca2+ sequestration and actomyosin cycling. In an attempt to maintain ATP levels, high-energy phosphate transfer, glycolysis and oxidative phosphorylation are recruited. With intense activity, ATP production rates are unable to match ATP utilization rates, and reductions in ATP occur accompanied by accumulation of a range of metabolic by-products such as hydrogen ions, inorganic phosphate, AMP, ADP and IMP. Selective by-products are believed to disturb Na+/K+ balance, Ca2+ cycling and actomyosin interaction, resulting in fatigue. Cessation of the activity and normalization of cellular energy potential results in a rapid recovery of force. This type of fatigue is often referred to as metabolic. Repeated bouts of high-intensity activity can also result in depletion of the intracellular substrate, glycogen. Since glycogen is the fundamental fuel used to sustain both glycolysis and oxidative phosphorylation, fatigue is readily apparent as cellular resources are exhausted. Intense activity can also result in non-metabolic fatigue and weakness as a consequence of disruption in internal structures, mediated by the high force levels. This type of impairment is most conspicuous following eccentric muscle activity; it is characterized by myofibrillar disorientation and damage to the cytoskeletal framework in the absence of any metabolic disturbance. The specific mechanisms by which the high force levels promote muscle damage and the degree to which the damage can be exacerbated by the metabolic effects of the exercise remain uncertain. Given the intense nature of the activity and the need for extensive, high-frequency recruitment of muscle fibres and motor units in a range of synergistic muscles, there is limited opportunity for compensatory strategies to enable performance to be sustained. Increased fatigue resistance would appear to depend on carefully planned programmes designed to adapt the excitation and contraction processes, the cytoskeleton and the metabolic systems, not only to tolerate but also to minimize the changes in the intracellular environment that are caused by the intense activity.
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PMID:Mechanisms of muscle fatigue in intense exercise. 923 50

An important adverse effect of corticosteroid treatment is respiratory muscle weakness with diaphragm muscle wasting, but little is known about the underlying pathophysiological processes involved. In order to differentiate between the effects of nutrition depletion and corticosteroids on diaphragm muscle metabolism, a study was performed to investigate the effects of triamcinolone (TR) for 2 weeks and of chronic undernutrition in a pair-weight (PW) group on the structure and energy metabolism of the diaphragm in male Wistar rats compared with a free-fed (FF) group. Diaphragm mass was reduced in TR and PW rats to a similar degree, but the extent of type-IIx/b atrophy was more pronounced in TR rats than in PW rats. No myopathic features were observed after either treatment. ATP in absolute terms as well as the ATP/ADP ratio, total adenine nucleotides, the phosphocreatine (PCr) level and the ratio between PCr and creatine (PCr/Cr) were decreased in the diaphragm of both TR and PW rats. In contrast to the PW group, the total Cr pool was reduced and pyruvate and lactate levels were elevated in the diaphragm of the TR group compared with the FF group. In conclusion, the results of this study indicate that severe undernutrition causes a decrease in muscle energy status resulting in a new metabolic equilibrium, while chronic low-dose TR treatment (0.25 mg/kg per day i.m.) causes a decrease in muscle energy status together with a mismatch between glycolysis and oxidative metabolism.
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PMID:Different effects of corticosteroid-induced muscle wasting compared with undernutrition on rat diaphragm energy metabolism. 1098 6

Despite theoretical obstacles associated with performing cell-based assays in high-density formats (microplates with at least 384 wells), it is becoming clear that the pharmaceutical industry is now routinely running cell-based tests in these formats. This work is revealing the weakness of established cytotoxicity end points, specifically in relation to sensitivity and reproducibility. New assay kits based on bioluminescent detection of ATP and ADP are now providing the answer to these problems.
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PMID:Cytotoxicity tests for high-throughput drug discovery. 1116 76

Magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (P-31 MRS) provide unique, quantitative data that cannot be obtained from routine laboratory tests. MRI is the method of choice for imaging of muscle abnormalities. It is also a very sensitive technique for localizing nonhomogeneous inflammation in inflammatory myopathies such as dermatomyositis, juvenile dermatomyositis, amyopathic dermatomyositis, polymyositis, and inclusion body myositis. During treatment of inflammatory myopathies, the extent and severity of inflammation may decrease at varying rates, but weakness and fatigue remain serious clinical problems. The metabolic abnormalities detected with P-31 MRS are more persistent and can be used for objective patient evaluation after the disappearance of inflammation and normalization of serum levels of muscle enzymes. With P-31 MRS, biochemical defects are quantitated, including low levels of ATP and phosphocreatine (PCr) and elevated concentrations of ADP and inorganic phosphate (Pi), which may all be related to weakness and fatigue. Thus, MRI and P-31 MRS are useful in assessing the status of patients with inflammatory myopathies during treatment with prednisone and immunosuppressive drugs.
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PMID:Utility of magnetic resonance imaging in the evaluation of patients with inflammatory myopathies. 1147 53

The interaction of the molecular chaperonin GroEL with fluorescein-labeled lysozyme in the presence of high concentrations of thiol reagent--dithiothreitol (DTT) has been studied. In case of high concentrations of DTT lysozyme loses the native conformation due to the disruption of the intramolecular disulfide bonds stabilizing its structure and effectively aggregates. It has been shown that in the presence of high concentrations of DTT and two-fold molar excess of GroEL the lysozyme tightly interacts with GroEL that essentially decreases the efficiency of its aggregation. The addition of ADP to the complex of GroEL with nonnative lysozyme noticeably decreases the interaction of the chaperonin with nonnative protein target resulting in some increase of the efficiency of its aggregation. However, the addition of the co-chaperonin GroES together with ADP (i.e. the formation of the complex of GroEL with GroES) leads to drastic weakness of the interaction of GroEL with nonnative lysozyme and the efficiency of its aggregation becomes comparable with that in the absence of GroEL.
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PMID:[Effect of ADP and GroES on interaction of molecular chaperonin GroEL with non-native lysozyme]. 1457 57

Mitochondrial myopathy, associated with muscle weakness and progressive external ophthalmoplegia, is caused by mutations in mitochondria oxidative phosphorylation genes including the heart-muscle isoform of the mitochondrial adenine nucleotide translocator (ANT1). To develop therapies for mitochondrial disease, we have prepared a recombinant adeno-associated viral vector (rAAV) carrying the mouse Ant1 cDNA. This vector has been used to transduce muscle cells and muscle from Ant1 mutant mice, which manifest mitochondrial myopathy. AAV-ANT1 transduction resulted in long-term, stable expression of the Ant1 transgene in muscle precursor cells as well as differentiated muscle fibers. The transgene ANT1 protein was targeted to the mitochondrion, was inserted into the mitochondrial inner membrane, formed a functional ADP/ATP carrier, increased the mitochondrial export of ATP and reversed the histopathological changes associated with the mitochondrial myopathy. Thus, AAV transduction has the potential of providing symptomatic relief for the ophthalmoplegia and ptosis resulting from paralysis of the extraocular eye muscles cause by mutations in the Ant1 gene.
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PMID:Adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ANT) in mouse. 1564 64


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