Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat diaphragms were treated with calcium ionophore, A23187, for 60 min at 37 degrees C, and twitch, tetanus and their derivatives were studied on the basis of the active state concept. Results were than compared with those of human dystrophic muscle. Like dystrophic muscle, maximum tetanic force and maximum velocity of tetanus development were markedly reduced. Changes in twitch parameters, which tend to appear in an early stage of muscular dystrophy, were not noted after the treatment with this ionophore, except alterations relating to prolongation of the active state. Twitch/tetanus ratio was thus increased, while it was decreased in dystrophic muscle. Isoproterenol-induced change of twitch was normally seen in the A23187-treated muscle, while dystrophic muscle responded to catecholamine in a manner different from control. Therefore, the muscle treated with calcium ionophore is not wholly similar to dystrophic muscle.
 ...
PMID:Contractile and chemosensitive properties of muscle treated with calcium ionophore A23187. Comparison with dystrophic muscle. 679 24

Dystrophin is a 427-kDa protein localized adjacent to the sarcolemma in skeletal muscle. Its physiological role remains uncertain, although its absence is known to cause muscular dystrophy. In this study, the function of dystrophin was investigated using the dystrophin-deficient mdx mouse. Control and mdx animals at 2, 5, and 13 wk of age (n = 8-11/age) were compared to evaluate in situ gastrocnemius-plantaris-soleus muscle contractile, endurance, and excitability properties at nondegenerated, degenerated, and regenerated stages, respectively. Twitch and tetanic tensions expressed per gram of muscle mass were lower in mdx muscle only at 5 wk. Fatigue produced during successive contractions at 2, 10, and 20 Hz did not differ between the two groups at 2 and 5 wk but was lower in mdx muscle at 13 wk. This was not attributed to differences in mitochondria, since cytochrome-c oxidase activity was similar in mdx and control muscle. Contractile properties of control and mdx muscle became faster with age, and at 13 wk the time to peak twitch tension was shorter in mdx muscle relative to control, whereas the half-relaxation times did not differ. Mass action potential area (M wave), an index of muscle excitability, was not significantly different between mdx and control muscle at 2 or 5 wk but was greater in mdx muscle at 13 wk. Thus, in this weight-bearing muscle group, the lack of dystrophin has only a moderate impact in modifying muscle function relative to contractile properties, fatigability, or excitability.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Performance and excitability of mdx mouse muscle at 2, 5, and 13 wk of age. 777 42

Contraction tension and kinetics of the peroneus longus muscle were studied in dogs with the Duchenne homologue, golden retriever muscular dystrophy (GRMD), in advance of evaluating localized therapies such as myoblast transplantation. Absolute and both muscle- and body-weight-corrected twitch tension in GRMD dogs were low compared to normal litter mates at 3 months of age (p < 0.0005 for all). Tetanic tension was affected similarly. However, whereas absolute values were still reduced at 6 months (p < 0.0005 for twitch and 0.005 for tetany), twitch and tetanic tension corrected for either muscle or body weight was not statistically different, suggesting that the peroneus longus may be relatively spared in GRMD. Post-tetanic potentiation was more pronounced in GRMD versus normal dogs at both 3 (p < 0.0001) and 6 (p < 0.01) months. The degree of positive staircase at 3 months of age did not differ. Twitch contraction and relaxation times were dramatically prolonged, and there was concomitant sustained electrical activity, at, or before, 6 months of age in some severely affected dogs. Relatively few carriers were evaluated at these ages, but their values were similar to those of normal dogs. Apparent sparing of the peroneus longus muscle may limit application of this technique to evaluation of therapies administered early in life or in combination with toxins. Treatment to alter changes in contraction kinetics could also be assessed.
 ...
PMID:Contraction tension and kinetics of the peroneus longus muscle in golden retriever muscular dystrophy. 806

The objective of this study was to determine whether cardiac contractile force is altered in the dystrophin-deficient mdx mouse model of muscular dystrophy. Left atria from 12-14-week-old control and mdx mice were paced at 1 Hz in 1.25 mM external Ca2+ buffer. Twitch properties and effects of interposing intervals of 0.3 to 600 s on the force of subsequent beats (force-interval curves) were examined. Peak force and time-to-peak force were similar in both groups, but half-relaxation time was significantly prolonged in mdx heart. In control hearts, force-interval curves increased to an inflection point at about 1 s, then rose to a second peak near 60 s. In mdx heart, curves reached the early inflection more quickly, the second peak was diminished in magnitude and force was greatly depressed at long intervals. Curves were fitted to a four-parameter equation to quantify differences in shape. The parameter a, which reflects rate of rise to the first inflection, was significantly increased in mdx atria, while the parameter B, which reflects amplitude of the late peak, was significantly reduced. These differences in force production were more marked when external Ca2+ was raised to 2.5 mM. Results show contractile properties are markedly altered in atria from dystrophin-deficient mdx mice. These findings are consistent with the hypothesis that dystrophin deficiency affects cardiac contractile function, possibly through effects on SR function.
 ...
PMID:Contractile properties of myocardium are altered in dystrophin-deficient mdx mice. 890 14

A 9-year-old female presented to neurology outpatient department of our hospital with complaints of recurrent generalized tonic-clonic seizures since birth and was being treated with anticonvulsants for the same. Patient also had complaints of giddiness and episodes of momentary loss of consciousness. There was history of twitching of left hemiface and eyelid during infancy, often associated with deviation of eyes to the left and groaning. The birth history was unremarkable. Family history revealed no known consanguinity. General examination revealed no dysmorphic features. Neurological examination revealed no cognitive deficits/signs to suggest cerebellar pathology. An electroencephalogram was done in view of her recurrent seizures, which was normal. Initial laboratory work-up was normal. The patient then underwent magnetic resonance imaging (MRI) brain, acquired with a 1.5-T unit (Siemens, Erlangen, Germany). MRI brain revealed hemihypertrophy of left cerebellar hemisphere with disorganized architecture, fissural malorientation with individual folia running vertically rather than horizontally with disorganized foliation, abnormal arborization of white matter predominantly involving mid and dorsal surface of left cerebellar hemisphere and a few suspicious areas of abnormal T2-hyperintense signal in subcortical white matter. Right cerebellar hemisphere and cerebellar vermis were normal. Corpus callosum was normal. Cerebral parenchyma was normal in signal intensity pattern with normal gray-white matter differentiation. Ventricular system was normal (Figures 1 and 2). Cerebellar malformations are uncommon and are usually associated with Dandy-Walker continuum, Joubert syndrome, rhombencephalosynapsis, lissencephaly, Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, muscle-eye-brain disease, congenital cytomegalovirus infection to name a few.1,2 Isolated unilateral cerebellar hemispheric dysplasia is exceedingly rare with only a few cases previously described in English literature. Cerebellar malformations are less adequately understood entity partly because of the complex cerebellar embryology and limited histologic studies of these disorders. Genes expressed in migration and maintenance of the Purkinje cells and/or in the generation and migration of granular cells when mutated will disrupt cerebellar migration and foliation and thus cause cerebellar malformation.3-5 Cerebellum is known to be a centre for motor learning, coordination, and higher cognitive functions. Clinical presentation of cerebellar malformations is highly variable and depends on the degree of cerebellar involvement, presence of associated cerebral involvement and the underlying disorders such as muscular dystrophy if any. Patel and Barkovich suggested an imaging-based classification of cerebellar malformations and classified the malformations broadly into two types, malformations with cerebellar hypoplasia and the ones with cerebellar dysplasia. Each of these was further classified into focal and diffuse.1 Demaerel gave a classification of abnormalities of cerebellar foliation and fissuration.2 Our index case with disorganized architecture, fissural malorientation and disorganized foliation of left cerebellar hemisphere associated with normal cerebellar vermis, corpus callosum, and absence of cerebral malformation falls into Type 2 category as per the classification by Demaerel.2 Treatment depends upon the severity of symptoms and the underlying disorder in case of syndromic malformations. Generally, treatment is symptomatic and supportive. Understanding of the basics of cerebellar embryology, knowledge of the imaging features, and clinical presentation aids in the precise diagnosis of this disorder and its optimal management.
 ...
PMID:Isolated Unilateral Cerebellar Hemispheric Dysplasia: A Rare Entity. 3135 12