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Michael Sinnreich

Publications and source records attributed to Michael Sinnreich.

10 recordsLinked to original sources
PubMed2006

Lariat branch point mutation in the dysferlin gene with mild limb-girdle muscular dystrophy.

The authors report a genotype-phenotype correlation in a limb-girdle muscular dystrophy 2B family. Two severely affected sisters were homozygous for a dysferlin null mutation. Their mildly affected compound heterozygous mother harbored, in addition to one null allele, an in-frame exon-skipping allele caused by a novel lariat branch point mutation. The dysferlin molecule arising from the latter allele appeared to partially complement the null mutation, likely accounting for the mother's mild phenotype.

Aged↗
PubMed2005

Diabetic neuropathies. Classification, clinical features, and pathophysiological basis.

Diabetes mellitus is associated with a wide spectrum of neuropathy syndromes, ranging from a mild asymptomatic distal sensory neuropathy to a severe disabling radiculoplexus neuropathy. As the pathophysiology of these separate conditions is better understood, classification of the various phenotypes becomes important because of treatment implications. Here we provide a short summary of the history of the classification of diabetic neuropathies and try to describe the most common forms classified according to their presumed pathophysiology. We have tried to include epidemiological data where available, as well as histopathology of nerve in several diabetic neuropathies.

Diabetic Neuropathies↗
PubMed2004

Isoform-specific expression of the Coxsackie and adenovirus receptor (CAR) in neuromuscular junction and cardiac intercalated discs.

BACKGROUND: The Coxsackie and adenovirus receptor (CAR) has a restricted expression pattern in the adult. In skeletal muscle, although CAR is expressed in immature fibers, its transcript levels are barely detectable in mature muscle. This is in contrast to the robust expression observed in the heart. However, both heart and skeletal muscle are susceptible to infection with the Coxsackie B virus which utilizes primarily CAR for cellular internalization. The specific point of viral entry in skeletal and heart muscle remains unknown. RESULTS: Using antibodies directed against the extracellular and the cytoplasmic domains of CAR, we show CAR in normal human and mouse skeletal muscle to be a novel component of the neuromuscular junction. In cardiac muscle, CAR immunoreactivity is observed at the level of intercalated discs. We demonstrate a single isoform of CAR to be expressed exclusively at the human neuromuscular junction whereas both predominant CAR isoforms are expressed at the intercalated discs of non-diseased human heart. CONCLUSION: The localization of CAR to these important junctional complexes suggests that CAR may play both a structural and a regulatory role in skeletal and cardiac muscle, and that these complexes may serve as a point of entry for Coxsackie B virus.

Amino Acid Sequence↗
PubMed2004

Neurologic course, endocrine dysfunction and triplet repeat size in spinal bulbar muscular atrophy.

OBJECTIVE: To study the role of diabetes, gynecomastia and CAG triplet repeat size as disease modifying factors of neurologic expression in spinal bulbar muscular atrophy (SBMA, Kennedy's disease). METHODS: Twenty unrelated SBMA patients with confirmatory genetic testing were reviewed. Patterns of neurologic involvement were assessed (e.g. bulbar, asymmetric, proximal, distal, motor and sensory). Slopes of disease progression were calculated from serial quantified neurologic examinations. Patterns of neurologic involvement and course were correlated to the presence of diabetes, gynecomastia and triplet repeat size. RESULTS: Diabetes or glucose impairment occurred in nine and 11 had gynecomastia. Patterns of neurologic involvement and rates of progression did not correlate with these endocrine diseases or triplet repeat sizes. Correlation was seen between number of CAG repeats and age of onset weakness (r = -0.53, r2 = 29%, p = 0.01). CONCLUSIONS: The specific neurotoxic effect of expanded CAGs appears limited to age of onset weakness in SBMA. Although significant, only 29% of the variability in onset age could be accounted for by polyglutamine size suggesting the importance of other unidentified factors. In this series diabetes or glucose impairment was more common than previously reported and, like gynecomastia, did not correlate with size of triplet repeats, severity or patterns of neurologic involvement. Modifying factors other than diabetes, gynecomastia or triplet repeat size are suggested in disease expression.

Adult↗
PubMed2004

Prothrombin overexpressed in post-natal neurones requires blood factors for activation in the mouse brain.

Thrombin is thought to mediate, through protease-activated receptors, both protective as well as cytotoxic effects. As thrombin receptors are expressed in the CNS, an important question arises as to whether the intact nervous system is able to generate thrombin by activation of its precursor prothrombin, derived endogenously or only upon extravasation following brain injury. To address this question, transgenic mice that express C-terminally haemagglutinin tagged human prothrombin in post-mitotic neurones were generated. In situ hybridization and immunohistochemical analysis showed abundant and widespread cerebral expression of the transgene. Amidolytic assays of brain homogenates and hippocampal slice cultures demonstrated that activation of transgenic prothrombin required added factors, such as snake venom or blood components. This strongly suggests that any possible action of thrombin in the adult CNS depends on blood-derived factors that activate prothrombin. Furthermore, the results are consistent with the idea that in the non-pathological situation an as yet unidentified ligand activates thrombin receptors in the nervous system.

Age Factors↗
PubMed2003

The molecular era of myology.

This review covers, in general terms, the salient features and impact of molecular myology under the following headings: its role in providing clues for the understanding of molecular etiology and pathogenesis of genetic myopathies, its contribution to the modernization and rationalization of the classification of muscle diseases, providing means of precise diagnosis and prevention of myopathies, development of radically new cell and gene therapies, and determination of future research directions. Myology appears to be among the medical disciplines that have benefited a great deal from molecular science. This remarkable progress will hopefully translate into effective treatment capabilities in the near future.

Animals↗
PubMed2003

[Quiz case].

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Humans↗