Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne muscular dystrophy (DMD) is a severe, progressive, X-linked muscle-wasting disorder with an incidence of approximately 1/3,500 male births. Females are also affected, in rare instances. The manifestation of mild to severe symptoms in female carriers of dystrophin mutations is often the result of the preferential inactivation of the X chromosome carrying the normal dystrophin gene. The severity of the symptoms is dependent on the proportion of cells that have inactivated the normal X chromosome. A skewed pattern of X inactivation is also responsible for the clinical manifestation of DMD in females carrying X;autosome translocations, which disrupt the dystrophin gene. DMD may also be observed in females with Turner syndrome (45,X), if the remaining X chromosome carries a DMD mutation. We report here the case of a karyotypically normal female affected with DMD as a result of homozygosity for a deletion of exon 50 of the dystrophin gene. PCR analysis of microsatellite markers spanning the length of the X chromosome demonstrated that homozygosity for the dystrophin gene mutation was caused by maternal isodisomy for the entire X chromosome. This finding demonstrates that uniparental isodisomy of the X chromosome is an additional mechanism for the expression of X-linked recessive disorders. The proband's clinical presentation is consistent with the absence of imprinted genes (i.e., genes that are selectively expressed based on the parent of origin) on the X chromosome.
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PMID:Uniparental disomy of the entire X chromosome in a female with Duchenne muscular dystrophy. 898 59

Duchenne muscular dystrophy is a muscle-wasting disease accompanied by a variable, but often significant degree of mental retardation, possibly due to the absence of dystrophin. However, the function of brain type dystrophin remains insufficiently clear. With this background, in order to study the cell-specific regulation of brain type dystrophin expression in mice, we generated transgenic mice carrying the 2.1 kb 5'-fragment of the mouse brain type dystrophin gene, fused to the coding region of the bacterial lacZ gene. Three transgenic mice lines showed lacZ expression in the cerebral cortex. However, lacZ expression was not detected in the CA region of the hippocampus. These results suggest that the 2.1 kb 5'-fragment of the mouse brain type dystrophin gene contains the regulatory element required for its expression in the cerebral cortex, but not in the hippocampus.
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PMID:2.1 kb 5'-flanking region of the brain type dystrophin gene directs the expression of lacZ in the cerebral cortex, but not in the hippocampus. 909 55

We have refined the mdx mouse as a clinical model for Duchenne dystrophy. Our power estimates, primary measures, regular sacrifice intervals, and quality checks constitute a high-speed, low-cost system for preclinically testing therapies designed to slow muscle destruction in Duchenne dystrophy. Irradiated (18 Gy) and contralateral shielded anterior tibial muscles were studied in 21-day-old mdx and normal mice at the time of irradiation and 4, 8, 12, 16, and 20 weeks thereafter. Regeneration-blocked mdx (irradiated) muscle expressed muscular dystrophy as progressive wasting after a brief (4 week) period of growth. Regeneration-blocked normal muscle showed stunted growth but neither progressive wasting nor microscopic pathological changes.
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PMID:Regeneration-blocked mdx muscle: in vivo model for testing treatments. 923 93

The muscular dystrophies are a clinically and genetically heterogeneous group of skeletal muscle-wasting diseases that differ widely in their frequency and pattern of cardiac involvement. Myocardial disease manifesting predominantly as cardiomyopathy and congestive heart failure is characteristic of Duchenne and Becker muscular dystrophies and X-linked dilated cardiomyopathy, whereas conduction system abnormalities that cause heart block, arrhythmias, and sudden death are more commonly seen in limb-girdle type 1B, myotonic, and Emery-Dreifuss muscular dystrophies. Primary defects in the mechanical stabilization of the plasma membrane and signal transduction may underlie these two groups of muscular dystrophies. The identification of several new disease genes has yielded additional insights into the pathophysiology of muscular dystrophy. Molecular genetic and biochemical analyses of patient samples now permit accurate diagnosis and genotype-phenotype correlations. Ultimately, this knowledge will provide the foundation for etiology-specific gene therapy.
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PMID:Dystrophies and heart disease. 924 91

The absence of dystrophin at the muscle membrane leads to Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease that is inevitably fatal in early adulthood. In contrast, dystrophin-deficient mdx mice appear physically normal despite their underlying muscle pathology. We describe mice deficient for both dystrophin and the dystrophin-related protein utrophin. These mice show many signs typical of DMD in humans: they show severe progressive muscular dystrophy that results in premature death, they have ultrastructural neuromuscular and myotendinous junction abnormalities, and they aberrantly coexpress myosin heavy chain isoforms within a fiber. The data suggest that utrophin and dystrophin have complementing roles in normal functional or developmental pathways in muscle. Detailed study of these mice should provide novel insights into the pathogenesis of DMD and provide an improved model for rapid evaluation of gene therapy strategies.
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PMID:Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. 928 51

Dystrophin is a cytoskeletal protein of muscle fibers; its loss in humans leads to Duchenne muscular dystrophy, an inevitably fatal wasting of skeletal and cardiac muscle. mdx mice also lack dystrophin, but are only mildly dystrophic. Utrophin, a homolog of dystrophin, is confined to the postsynaptic membrane at skeletal neuromuscular junctions and has been implicated in synaptic development. However, mice lacking utrophin show only subtle neuromuscular defects. Here, we asked whether the mild phenotypes of the two single mutants reflect compensation between the two proteins. Synaptic development was qualitatively normal in double mutants, but dystrophy was severe and closely resembled that seen in Duchenne. Thus, utrophin attenuates the effects of dystrophin deficiency, and the double mutant may provide a useful model for studies of pathogenesis and therapy.
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PMID:Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy. 928 52

Emery-Dreifuss muscular dystrophy is an X-linked neuromuscular disorder caused by defects in the STA gene on Xq28, which codes for a nuclear protein named emerin. Affected patients usually present in early adolescence with scapulo-peroneal muscle weakness and wasting, and contractures of the tendo Achilles, elbows and paraspinal muscles, resulting in spine rigidity. We present here a case of Emery-Dreifuss muscular dystrophy with an unusually severe, early presentation. He presented at 2.5 years with predominantly proximal weakness and mild equinovarus deformity of the right foot. Serum creatine kinase activity was elevated (1994 IU/I) and a muscle biopsy at the age of 4 years showed marked dystrophic abnormalities. Normal expression of dystrophin, and no detectable deletion in the corresponding gene, excluded a diagnosis of Duchenne muscular dystrophy. Similarly, normal expression of alpha-sarcoglycan made a limb-girdle muscular dystrophy caused by a defect in a sarcoglycan unlikely. Several years later, examination of the proband's maternal cousin, aged 14 years, suggested Emery-Dreifuss muscular dystrophy. This was confirmed in both affected boys by the absence of emerin in muscle and leucocytes, and identification of a mutation in exon 4 of the STA gene. Carrier status in both mothers was also confirmed by mutational and protein analysis. Emery-Dreifuss muscular dystrophy should therefore be considered in the differential diagnosis of cases of early onset muscular dystrophy, even in the absence of the typical clinical features.
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PMID:Early presentation of X-linked Emery-Dreifuss muscular dystrophy resembling limb-girdle muscular dystrophy. 960 59

In many patients with neuromuscular diseases, respiratory failure is mainly caused by alveolar hypoventilation in their terminal stages. Malnutrition is one of the common and serious problems in patients with chronic respiratory failure. Energy consumption for breathing is remarkably high in respiratory compromised patients, causing subsequent increase of total energy expenditure. However, most patients have limited capacity of oral intake. Nutritional depletion is associated with wasting of respiratory muscles, impairment of respiratory drive, alteration of respiratory pattern, and pathological change of pulmonary parenchyma. These indicate that nutritional and ventilatory support is very important in these patients. However, overfeeding also may have detrimental influence on respiratory failure. We experienced a Duchenne muscular dystrophy (DMD) patient on noninvasive positive pressure ventilation (NIPPV) who developed hypercapnia after total parenteral nutrition (TPN). Analysis of clinical course of this patient revealed that there is a significant correlation between PaCO2 and caloric intake. Excess carbohydrate intake can precipitate fat synthesis which induces over-production of carbon dioxide (CO2). Since NIPPV doesn't have a closed circuit, there are some difficulties in respiratory management, such as air leakage to stomach and mouth, and airway obstruction. Failure to optimize NIPPV setting against increased CO2 load might cause hypercapnia in this patient. These suggest that evaluation of energy expenditure and design of nutritional program are essential to avoid hypercapnia due to nutritional support.
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PMID:[Excess caloric intake induced severe hypercapnia in a patient with Duchenne muscular dystrophy on noninvansive positive pressure ventilation]. 1007 34

Duchenne muscular dystrophy (DMD) is an inherited muscle-wasting disease caused by the absence of a muscle cytoskeletal protein, dystrophin. We have previously shown that utrophin, the autosomal homologue of dystrophin, is able to compensate for the absence of dystrophin in a mouse model of DMD; we have therefore undertaken a detailed study of the transcriptional regulation of utrophin to identify means of effecting its up-regulation in DMD muscle. We have previously isolated a promoter element lying within the CpG island at the 5' end of the gene and have shown it to be synaptically regulated in vivo. In this paper, we show that there is an alternative promoter lying within the large second intron of the utrophin gene, 50 kb 3' to exon 2. The promoter is highly regulated and drives transcription of a widely expressed unique first exon that splices into a common full-length mRNA at exon 3. The two utrophin promoters are independently regulated, and we predict that they respond to discrete sets of cellular signals. These findings significantly contribute to understanding the molecular physiology of utrophin expression and are important because the promoter reported here provides an alternative target for transcriptional activation of utrophin in DMD muscle. This promoter does not contain synaptic regulatory elements and might, therefore, be a more suitable target for pharmacological manipulation than the previously described promoter.
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PMID:A second promoter provides an alternative target for therapeutic up-regulation of utrophin in Duchenne muscular dystrophy. 1057 Jan 92

To determine whether whole body protein kinetics are altered in Duchenne muscular dystrophy (DMD), six 9 +/- 1-year-old children with DMD and five weight and height matched controls, received intravenous infusion of L-[1-(13)C]leucine and L-[2-(15)N]glutamine in the post-absorptive state. Glutamine rate of appearance was approximatly 24% lower in DMD boys than in controls (321 +/- 22 vs 425 +/- 37 micromol kg(-1)h(-1), P< 0.05) resulting from a 32% decrease in glutamine de novo synthesis (230 +/- 21 vs 340 +/- 34 micromol kg(-1)h(-1), P< 0.05). Whereas there was no difference between groups in estimates of protein degradation and synthesis, leucine oxidation rate was 44% higher in DMD boys than in controls (23 +/- 2 vs 16 +/- 2 micromol kg(-1)h(-1), P< 0.05). The data suggest that the dramatic mucle mass loss observed in DMD boys is associated with a) significant protein wasting, since increased leucine oxidation reflects a more negative whole body leucine balance, and b) a significant decrease in glutamine availability in the postabsorptive state. Glutamine might therefore be a 'conditionally essential' amino-acid in DMD.
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PMID:Is glutamine a 'conditionally essential' amino acid in Duchenne muscular dystrophy? 1063 22


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