Linkage relations of locus for X-borne type of Charcot-Marie-Tooth muscular atrophy and that for Xg blood groups. (1/1234)

The locus for the X-borne type of Charcot-Marie-Tooth muscular atrophy is not close to the Xg locus and probably not within direct measurable distance of it.  (+info)

Motor nerve conduction velocity in spinal muscular atrophy of childhood. (2/1234)

The ulnar and posterior tibial conduction velocities were measured in 29 children with spinal muscular atrophy, 14 of whom had the servere form of the disease. The ulnar nerve velocity was slow in 12 of the 14 severely affected infants, but normal or fast in 11 of 14 children less severely affected. The corresponding results for the posterior tibial nerve were slow velocities in 11 of 12 infants in the severe group and normal or fast in all 11 infants less severely affected. The difficulty in distinguishing infantile spinal muscular atrophy from peripheral neuropathy is emphasized.  (+info)

Formation of polyglutamine inclusions in non-CNS tissue. (3/1234)

Huntington's disease (HD) is one of a class of inherited progressive neurodegenerative disorders that are caused by a CAG/polyglutamine repeat expansion. We have previously generated mice that are transgenic for exon 1 of the HD gene carrying highly expanded CAG repeats which develop a progressive movement disorder and weight loss with similarities to HD. Neuronal inclusions composed of the exon 1 protein and ubiquitin are present in specific brain regions prior to onset of the phenotype, which in turn occurs long before specific neurodegeneration can be detected. In this report we have extended the search for polyglutamine inclusions to non-neuronal tissues. Outside the central nervous system (CNS), inclusions were identified in a variety of post-mitotic cells. This is consistent with a concentration-dependent nucleation and aggregation model of inclusion formation and indicates that brain-specific factors are not necessary for this process. To possibly gain insights into the wasting that is observed in the human disease, we have conducted a detailed analysis of the timing and progression of inclusion formation in skeletal muscle and an investigation into the cause of the severe muscle atrophy that occurs in the mouse model. The formation of inclusions in non-CNS tissues will be particularly useful with respect to in vivo monitoring of pharmaceutical agents selected for their ability to prevent polyglutamine aggregation in vitro, without the requirement that the agent can cross the blood-brain barrier in the first instance.  (+info)

Dominant hereditary inclusion-body myopathy gene (IBM3) maps to chromosome region 17p13.1. (4/1234)

We recently described an autosomal dominant inclusion-body myopathy characterized by congenital joint contractures, external ophthalmoplegia, and predominantly proximal muscle weakness. A whole-genome scan, performed with 161 polymorphic markers and with DNA from 40 members of one family, indicated strong linkage for markers on chromosome 17p. After analyses with additional markers in the region and with DNA from eight additional family members, a maximum LOD score (Zmax) was detected for marker D17S1303 (Zmax=7.38; recombination fraction (theta)=0). Haplotype analyses showed that the locus (Genome Database locus name: IBM3) is flanked distally by marker D17S945 and proximally by marker D17S969. The positions of cytogenetically localized flanking markers suggest that the location of the IBM3 gene is in chromosome region 17p13.1. Radiation hybrid mapping showed that IBM3 is located in a 2-Mb chromosomal region and that the myosin heavy-chain (MHC) gene cluster, consisting of at least six genes, co-localizes to the same region. This localization raises the possibility that one of the MHC genes clustered in this region may be involved in this disorder.  (+info)

Atrophy of the posterior cricoarytenoid muscle as an indicator of recurrent laryngeal nerve palsy. (5/1234)

BACKGROUND AND PURPOSE: The posterior cricoarytenoid (PCA) muscle is one of the intrinsic muscles of the larynx innervated by the recurrent laryngeal nerve. As such, recurrent laryngeal nerve palsy should not only result in paralysis of the true vocal cord or thyroarytenoid muscle but also in a similar change in the PCA muscle. The ability of CT and MR imaging to depict denervation atrophy in the PCA muscle in patients with recurrent laryngeal nerve palsy was evaluated. METHODS: Two investigators reviewed the CT and/or MR studies of 20 patients with a clinical history of vocal cord paralysis. The appearance of the PCA muscle was given a rating of 0, 1, 2, 3, or 4, with 0 being definitely normal and 4 being definitely abnormal or atrophic. Each study was also reviewed for the presence or absence of other features of vocal cord paralysis: thyroarytenoid muscle atrophy, anteromedial deviation of the arytenoid cartilage, an enlarged piriform sinus and laryngeal ventricle, and a paramedian cord. RESULTS: Atrophy of the PCA muscle was shown unequivocally in 65% of the cases and was most likely present in an additional 20%. The frequency with which other features of vocal cord paralysis were seen was as follows: thyroarytenoid atrophy, 95%; anteromedial deviation of the arytenoid cartilage, 70%; enlarged piriform sinus, 100%; enlarged laryngeal ventricle, 90%; and a paramedian cord, 100%. CONCLUSION: Atrophy of the PCA muscle may be commonly documented on CT and MR studies in patients with recurrent laryngeal nerve palsy and vocal cord paralysis, and therefore should be part of the constellation of imaging features of vocal cord paralysis. This finding is particularly useful when other imaging findings of vocal cord paralysis are absent or equivocal.  (+info)

Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. (6/1234)

The ubiquitin-proteasome proteolytic system is stimulated in conditions causing muscle atrophy. Signals initiating this response in these conditions are unknown, although glucocorticoids are required but insufficient to stimulate muscle proteolysis in starvation, acidosis, and sepsis. To identify signals that activate this system, we studied acutely diabetic rats that had metabolic acidosis and increased corticosterone production. Protein degradation was increased 52% (P < 0.05), and mRNA levels encoding ubiquitin-proteasome system components, including the ubiquitin-conjugating enzyme E214k, were higher (transcription of the ubiquitin and proteasome subunit C3 genes in muscle was increased by nuclear run-off assay). In diabetic rats, prevention of acidemia by oral NaHCO3 did not eliminate muscle proteolysis. Adrenalectomy blocked accelerated proteolysis and the rise in pathway mRNAs; both responses were restored by administration of a physiological dose of glucocorticoids to adrenalectomized, diabetic rats. Finally, treating diabetic rats with insulin for >/=24 h reversed muscle proteolysis and returned pathway mRNAs to control levels. Thus acidification is not necessary for these responses, but glucocorticoids and a low insulin level in tandem activate the ubiquitin-proteasome proteolytic system.  (+info)

Space travel directly induces skeletal muscle atrophy. (7/1234)

Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.  (+info)

Physical activity, protein intake, and appendicular skeletal muscle mass in older men. (8/1234)

BACKGROUND: Aging is associated with physical inactivity, low energy intake, and loss of skeletal muscle mass. It is not clear whether regular physical activity and adequate dietary protein intake can attenuate the loss of skeletal muscle mass. OBJECTIVE: We hypothesized that the maintenance of physical activity and dietary protein intake would attenuate the age-related decline in total appendicular skeletal muscle mass. DESIGN: Total appendicular skeletal muscle mass was determined by dual-energy X-ray absorptiometry in 44 healthy, older white men aged 49-85 y. Physical activity level was determined by using a uniaxial accelerometer over a 9-d period. Dietary protein intake was estimated from a 3-d food record. RESULTS: Aging was inversely associated with total appendicular skeletal muscle mass in older men (r = -0.43; slope: -0. 119 +/- 0.039 kg/y; P < 0.01). An effect of age on appendicular skeletal muscle mass persisted after standing height and physical activity were controlled for (r = -0.34; slope: -0.120 +/- 0.052 kg/y; P = 0.03). Furthermore, an effect of age on appendicular skeletal muscle mass persisted after standing height and dietary protein intake per kilogram body mass was controlled for (r = -0.41; slope: -0.127 +/- 0.045 kg/y; P < 0.01). CONCLUSIONS: Maintaining regular physical activity and adequate protein intake may not offset the age-related loss of appendicular skeletal muscle mass in older men. Prospective studies are needed to confirm these results and to determine whether anabolic physical activity (eg, strength training) can attenuate the age-related loss of muscle mass in the elderly.  (+info)