Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of energy in muscle from long-chain fatty acid oxidation is dependent upon the presence of carnitine. An abnormally low level of muscle carnitine, as seen in patients with the carnitine deficiency syndrome, results in marked muscle weakness. Muscle from 83 consecutive patients undergoing diagnostic muscle biopsy was assayed for carnitine. Carnitine levels (mean +/- SEM, expressed as nmoles carnitine per mg noncollagen protein) in muscle from patients with Duchenne dystrophy (8.1 +/- 1.7) and possible Becker dystrophy (10.6 +/- 3.0) were significantly (P less than 0.001) different from histologically normal muscle (24.0 +/- 1.4). Carnitine levels in patients with limb-girdle dystrophy (16.1 +/- 3.1) and polymyositis/dermatomyositis (16.6 +/- 3.2) were also low, although not as low as in Duchenne dystrophy. Carnitine levels from patients with denervation atrophy (22.1 +/- 3.6), nonspecific fiber atrophy (21.3 +/- 1.3), and a group of miscellaneous neuromuscular diseases (20.4 +/- 1.4) were not significantly different from histologically normal muscle. The low values of carnitine seen in Duchenne dystrophy and a group of possible Becker dystrophy patients may be a nonspecific effect, related to severe muscle damage.
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PMID:Muscle carnitine levels in neuromuscular disease. 92 14

Five billion normal myoblasts were injected into each of 21 Duchenne muscular dystrophy (DMD) boys aged 6-14 yr to assess the feasibility, safety, and efficacy of the Phase II myoblast transfer therapy (MTT). The Phase II study was designed to strengthen muscles of both lower limbs. Forty-eight intramuscular injections transferred the myoblasts into 22 major muscles at 55.6 x 10(6)/mL in 10 min under general anesthesia. Eleven boys had received 8 million myoblasts each 1 yr ago in the Phase I MTT. In the Phase II study, eight of them had their myoblasts subcultured from reserves frozen 1 yr ago. The donor myoblasts for each of the remaining boys were cultured from satellite cells derived from a 1-g muscle biopsy of a normal male who might or might not be histocompatible with the recipient. The immunosuppressant cyclosporine (Cy) is being administered to recipients for 6 mo after MTT to facilitate donor cell survival. There was no evidence of an adverse reaction to MTT or Cy as determined by serial laboratory evaluations including electrolytes, creatinine, and urea. Early objective functional tests using the KinCom Robotic Dynamometer were conducted on 13 subjects aged 6 to 13 before MTT and at 3 mo after MTT. Of the 69 muscle groups (knee extensors, knee flexors, plantar flexors) tested for isometric force generation in these subjects, 43% showed mean increase of 41.3% +/- 5.9 SEM, 38% showed no change, and 19% showed continuous force reduction of 23.4% +/- 3.1 SEM. The remaining subjects await the 3-mo post-MTT evaluation. The results indicate that 1) MTT is safe; 2) MTT increases muscle strength in DMD: 81% of the muscles tested showed either increase in strength or did not show continuous loss of strength; 3) more than 5 billion myoblasts can be cultured from 1 g normal muscle biopsy, providing unprecedented numbers of cells for MTT; 4) myoblasts, frozen over 1 yr, retain the ability to proliferate from 10 million to 5 billion, and to form normal myofibers; 5) injections of 5 billion myoblasts have not provoked any immunological rejection symptoms in the Phase II subjects, 11 of whom received 8 million myoblasts in the Phase I MTT a year ago; 6) it is safe to perform multiple injections of myoblasts into lower limb muscles without formation of emboli; and 7) donor cell rejection by the recipient can be prevented with Cy when properly managed.
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PMID:Feasibility, safety, and efficacy of myoblast transfer therapy on Duchenne muscular dystrophy boys. 134 95

Ventilatory data, including timing and partitioning of ventilation, were obtained from six subjects with advanced Duchenne muscular dystrophy, aged 16 to 22 years, during polysomnography on two consecutive nights; the subjects were randomized to breathing air or oxygen. Five of the six patients developed oxygen desaturation exceeding 5 percent during rapid eye movement (REM) sleep while breathing air. Minute ventilation on air (the mean of at least six consecutive minutes) was 6.9 +/- 0.7 (SEM) L min-1 but fell, owing to decreases in both tidal volume and frequency, to 4.9 +/- 0.3 L min-1 (p less than 0.05) in slow wave sleep and to 4.5 +/- 0.6 L min-1 (p less than 0.05) in REM sleep. Similar falls were seen on oxygen. The variability of all ventilatory data was significantly greater in REM than non-REM (NREM) sleep. The mean abdominal contribution to breathing was lower than predicted for wakefulness and all sleep stages, and two subjects showed paradoxical abdominal movement in NREM sleep; a correlation (p less than 0.05) existed between the NREM abdominal (diaphragmatic) contribution and the extent of oxygen desaturation subsequently seen in REM. We conclude that although awake minute ventilation is normal in Duchenne muscular dystrophy, hypoventilation occurs in all sleep stages, and those with diaphragmatic dysfunction are especially vulnerable to oxygen desaturation during REM sleep.
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PMID:Ventilation and breathing pattern during sleep in Duchenne muscular dystrophy. 258 42

Overnight polysomnography after acclimatization was performed on 14 patients with Duchenne muscular dystrophy (mean age, 18.3 yr; mean VC, 1.24 L). Despite their lack of sleep-related symptoms and normal daytime blood gas tensions, periods of hypopnea and/or apnea (H/A) were observed in all patients (mean frequency 9.6/h; range, 3.7 to 17.0; mean duration 23.1; range of means, 16 to 36 s). In 9 patients, between 0.5 and 12.3 oxygen desaturations of greater than 5% occurred per hour, with falls from a mean SaO2 baseline of 95.4 +/- 0.6% (SEM) to a mean nadir of 74.2 +/- 3.9% (range, 58 to 90). This desaturating group (n = 9) showed longer and more frequent H/A than did the 5 nondesaturators; the proportion of REM sleep occupied by H/A was 37.7 +/- 3.8% in the desaturating group compared with only 15.1 +/- 5.1% in the remainder (p less than 0.01). The severity of sleep-disordered breathing could not be reliably predicted from daytime pulmonary function test results, and only maximal static expiratory pressure appeared significantly lower in the desaturating group. Hypopneas were associated with reduced chest wall movement in all subjects, and with chest wall paradox in one; continued submental "inspiratory" EMG activity throughout "central" apneas in 2 subjects suggested that these episodes were not truly central in origin. Sleep hypoxemia is imputed in the progression of several chronic respiratory diseases, and its prevention in Duchenne and related neuromuscular diseases may influence morbidity and mortality.
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PMID:Hypoxemia during sleep in Duchenne muscular dystrophy. 335 96

Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disease characterized by progressive weakness and severe muscle wasting. Alterations in carbohydrate metabolism are often associated with neuromuscular disorders. We performed oral glucose tolerance tests and insulin binding studies on erythrocytes from 17 DMD and 8 normal males. Furthermore, we measured insulin binding to erythrocytes from 12 normal males and from 11 mothers and 10 sisters of affected males. As a group, DMD patients had mild glucose intolerance and both fasting and postabsorptive marked hyperinsulinemia (insulin resistance). Levels of glucose and insulin, expressed as incremental areas under their respective curves, were significantly elevated in the wheelchair-ridden patients. Incremental areas of glucose (0-2 h) and insulin (0-5 h) were 42 +/- 5 mg/dl X h (mean +/- SEM) and 96 +/- 18 microU/ml X h, respectively, in normal subjects and 71 +/- 6 (P less than 0.05) and 206 +/- 30 (P less than 0.05), respectively, in the wheelchair-confined DMD patients. All of the ambulatory DMD males had normal oral glucose tolerance tests. Insulin binding to erythrocytes was 20-30% lower (P less than 0.01) in all DMD patients than in normal males appropriately matched for age and degree of sexual development. This difference in binding was a result of lower affinity of the insulin receptor in DMD erythrocytes. On the other hand, insulin binding to fibroblasts was the same in normal males and DMD patients, suggesting that the abnormality of erythrocyte binding in DMD is probably not genetically induced. Insulin binding to erythrocytes and monocytes was the same in all females studied, regardless of whether they were carriers of the DMD gene. Our results suggest that abnormal insulin binding in DMD erythrocytes is an acquired rather than genetic abnormality, but insulin binding is not helpful in the identification of carrier females. The defect in insulin binding in DMD is present before the development of insulin resistance, which occurs only in severely immobilized patients. Thus, the cause of the insulin resistance in DMD may reside at steps beyond the binding of insulin to its receptor.
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PMID:Dissociation of insulin resistance and decreased insulin receptor binding in Duchenne muscular dystrophy. 396 91

(1) Biopsies from the gastrocnemius muscle of patients with Duchenne dystrophy were partitioned into a myofibrillar plus nuclear fraction, a mitochondrial fraction and a supernatant fraction. The fractions were assayed for mitochondrial enzymes and protein, in order to obtain information about the integrity of mitochondrial structure and function. Muscles from boys and adults without neuromuscular disease were treated likewise. (2) In adults, muscle possesses a significantly higher specific activity (on protein basis) of monoamine oxidase and rotenone-insenitive NADH-cytochrome c reductase (RINCR) than in boys. In childhood, monoamine oxidase activity increases with age. At the age of 5 yr, the specific activity is 50% of the adult value. RINCR activity is constant in childhood. With adolescence it increases from 20 +/- 2 (SEM) to 35 +/- 6 mumoles cytochrome c reduced per min per g protein, and it remains at this level. Palmitoyl-CoA synthetase activity remains constant with age. (3) In Duchenne dystrophy the extractable protein content from muscle is decreased to 75%. The specific activities of the matrix enzymes propionyl-CoA carboxylase and glutamate dehydrogenase are 1.8 and 2.8 times increased, the inner membrane enzyme cytochrome c oxidase is 2.8 times increased, the inner membrane enzyme cytochrome c oxidase is 2.8 times increased. Of the outer membrane enzymes RINCR is 2.0 times increased, while palmitoyl-CoA synthetase is not changed in acitivity. In Duchenne dystrophy monoamine oxidase activity also increases with age. In part this may be due to mitochondria from adipose tissue and macrophages, which are increasingly present in older patients. The specific activities of enzymes with a predominant cytosolic localisation, creatine kinase and adenylate kinase, are increased by a factor of 1.5 and 1.7. (4) The subcellular distribution of the studied enzymes in human skeletal muscle was found to be similar as in animal studies. In mitochondrial fractions from Duchenne patients the recoveries of the following enzymes are decreased: glutamate dehydrogenase (from 25 to 9%), creatine kinase (1.1-0.66%), adenylate kinase (0.44-0.22%), hexokinase (7.1-2.7%), monoamine oxidase (36-21%), RINCR (30-17%), and palmitoyl-CoA synthetase (40-21%). The recoveries of last 3 mitochondrial outer membrane enzymes in the supernatant fractions are correspondingly increased. These results indicate an increased fragility of the mitochondrial membranes in dystrophic muscles. (5) The reported changes are clearly evident in a one-year-old patient, which indicates that the mitochondria are involved early in the disease process.
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PMID:Early changes of muscle mitochondria in Duchenne dystrophy. Partition and activity of mitochondrial enzymes in fractionated muscle of unaffected boys and adults and patients. 624 85

The intercellular adhesiveness of skin fibroblasts from patients and carriers of Duchenne muscular dystrophy (DMD) and control subjects has been determined using couette viscometers. The values for 12 DMD patients (mean = 1.38, SEM = 0.1, n = 32) were significantly lower than for ten control subjects (mean = 3.17, SEM = 0.2, n = 22). According to the Lyon hypothesis, carriers of DMD should be mosaics of cells expressing the normal and DMD phenotypes, and their cultured skin fibroblasts should have intercellular adhesiveness intermediate between that for normal and DMD cells. Cells from three obligate heterozygotes and five individuals at high risk of being carriers had normal values (in both groups mean = 2.82) in contrast to artificial 1:1 mixtures of normal and DMD cells that had intermediate values (mean = 2.22, SEM = 0.2, n = 15). This unexpected finding is probably the result of "correction" of the DMD cells by normal gene product from the cells expressing the normal gene.
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PMID:A cell surface abnormality in Duchenne muscular dystrophy: intercellular adhesiveness of skin fibroblasts from patients and carriers. 685 19

The aim of the present paper was to study the myopathic bone both from the morphological and structural viewpoints. To this end, samples from 8 patients affected by different neuromuscular diseases (DMD, SMA and CMD) have been examined. Thus, by SEM analysis a quantitative reduction of the trabeculae and an increase in porosity of the myopathic bone were found and also, by diffractometric analysis, the presence of pathologic crystalline phases (beta-TCP and beta-TCP-Mg).
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PMID:Morphological and structural characteristics of the myopathic bone. 812 10

We investigated the usefulness of the plasma concentration of brain natriuretic peptide (BNP) for evaluating cardiac function in patients with Duchenne muscular dystrophy (DMD). The plasma BNP concentration was measured by immunoradiometric assay in 55 patients with DMD and in 34 healthy subjects. Cardiac function was evaluated by the cardiothoracic ratio (CTR) on chest roentgenogram, left ventricular end-diastolic dimension (LVDd) and fractional shortening (FS) on echocardiogram, and the ratio of ejection time to pre-ejection period (ET/PEP) on mechanocardiogram. The function of skeletal muscle was evaluated in terms of the disability of lower limb function, serum creatine kinase (CK) activity and % vital capacity (% VC). The plasma concentration of BNP was increased in patients with DMD (32.7 +/- 14.8 pg/ml, mean +/- SEM) compared with that in normal subjects (4.3 +/- 0.5 pg/ml). Two of the DMD patients had symptoms of heart failure, with markedly increased plasma BNP concentrations. The other DMD patients with increased plasma BNP concentrations showed abnormal cardiac function but no symptoms of heart failure. In addition, in patients with DMD, the plasma BNP concentration showed significant positive correlations with CTR and LVDd (p < 0.01), and negative correlations with ET/PEP and FS (p < 0.01). In severe DMD patients who had advanced disability and decreased CK activity, the plasma BNP concentration tended to be elevated. There was no significant correlation between the plasma BNP concentration and % VC. These findings suggest that the plasma BNP concentration is useful for evaluating cardiac dysfunction, whether manifest or latent, in patients with DMD, in whom accurate evaluation of cardiac function by conventional methods is difficult due to severe muscle atrophy and deformity of the thorax.
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PMID:[Estimation of cardiac function by plasma concentration of brain natriuretic peptide in patients with Duchenne muscular dystrophy]. 868 97

In an experimental animal exercise model we tested whether daily administration of prednisone prevents the development of mechanically induced muscle fibre damage. Six-week-old rats were treated with different doses of prednisone ranging from 1 to 50 mg/kg body weight per day or with placebo, for 8 days. On day 6 of treatment the rats were forced to run for 2 h on a level treadmill. Two days after exercise morphological damage in the soleus muscles was quantified using light microscopy and a semi-automatic image analysis system. Creatine kinase (CK) activity was measured before exercise (day 5) and directly after exercise (day 6). The expression of dystrophin in a placebo group and in a group that received 5 mg prednisone/kg body weight per day with and without performing exercise was studied with Western blotting. The effect of prednisone on fibre type distribution was determined with an antibody against fast myosin and the effect of prednisone on the proliferative activity of muscle satellite cells was studied using bromodeoxyuridine (BrdU) immunohistochemistry. Exercise-induced muscle fibre damage varied in a dose-dependent way. In the placebo group the mean (SEM) damaged muscle fibre area was 4% (1%). The groups that received low doses of prednisone, 1 or 2.5 mg/kg per day, showed a similar level of muscle damage. However, with 5 mg prednisone/kg per day the amount of muscle fibre damage [mean (SEM)] was significantly reduced to 1.4% (0.5%) (P <or= 0.05, Student's t-test). High doses of prednisone had no protective effect. Directly after exercise the CK activity was increased two-fold, except in the group that received 50 mg prednisone/kg body weight per day. No changes in the amount of dystrophin were found after densitometric analysis of the Western blots. Prednisone did not affect the fibre distribution or the labelling index of satellite cells. We conclude that prednisone, given in an appropriate dose, protects muscle fibres against the development of mechanically induced damage, possibly by stabilizing the muscle fibre membranes. This action may explain the beneficial effect of prednisone observed in Duchenne muscular dystrophy patients.
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PMID:Prednisone can protect against exercise-induced muscle damage. 874 Oct 82


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