1,721,114 research outputs found
Prognostic factors in mild dystrophinopathies.
No full textAngelini C, Fanin M, Freda MP, Martinello F, Miorin M, Melacini P, Siciliano G, Pegoraro E, Rosa M, Danieli G
Regeneration in sarcoglycanopathies expression studies of sarcoglycans and other muscle proteins.
No full textI.F. 1.98
Protein and genetic diagnosis of limb girdle muscular dystrophy type 2A: The yield and the pitfalls
No full textLimb girdle muscular dystrophy type 2A (LGMD2A) is the most frequent form of LGMD worldwide. Comprehensive clinical assessment and laboratory testing is essential for diagnosis of LGMD2A. Muscle immunoblot analysis of calpain-3 is the most useful tool to direct genetic testing, as detection of calpain-3 deficiency has high diagnostic value. However, calpain-3 immunoblot testing lacks sensitivity in about 30% of cases due to gene mutations that inactivate the enzyme. The best diagnostic strategy should be determined on a case-by-case basis, depending on which tissues are available, and which molecular and/or genetic methods are adopted. In this work we survey the current knowledge, advantages, limitations, and pitfalls of protein testing and mutation detection in LGMD2A and provide an update of genetic epidemiology
Pathogenesis, clinical features and diagnosis of sarcoglycanopathies
No full textIntroduction: By reviewing the literature from the last twenty years we present an accurate assessment of the state of the art in the pathogenesis and clinical presentations of sarcoglycanopathies, as well as the progress in diagnosis and treatment. Areas covered: Sarcoglycanopathies usually have a childhood onset but they can occur in adults with a limb girdle phenotype. Four main genes are expressed in the sarcoglycan complex. Cases with beta- or delta-sarcoglycan primary deficiency often present severe cardiac and respiratory complications. A defect of nitric oxide synthase might contribute to the pathogenesis of cardiac involvement and fatigue. Neuroimaging shows that muscle involvement affects mainly proximal muscle groups, followed by fibro-fatty replacement. Expert opinion: In cases of children with high creatine kinase levels and weakness or adults with limb girdle weakness, immunolabelling of muscle biopsy with anti-sarcoglycan antibodies may suggest the diagnosis, which should be confirmed by mutation analysis in the sarcoglycan genes. New genetic technologies, such as next generation sequencing, might be useful to obtain a molecular diagnosis, which is necessary for genetic counselling
Muscle atrophy in Limb Girdle Muscular Dystrophy 2A: A morphometric and molecular study
No full textAims: The peculiar clinical features and the pathogenic mechanism related to calpain-3 deficiency (impaired sarcomere remodelling) suggest that the ubiquitin-proteasome degradation pathway may have a crucial role in Limb Girdle Muscular Dystrophy 2A (LGMD2A). We therefore investigated muscle atrophy and the role of the ubiquitin-proteasome and lysosomal-autophagic degradation pathways. Methods: We selected 25 adult male LGMD2A patients (and seven controls), classified them using clinical severity score, analysed muscle fibre size by morphometry and protein and/or transcriptional expression levels of the most important atrophy- and autophagy-related genes (MuRF1,atrogin1,LC3,p62,Bnip3). Results: Muscle fibre size was significantly lower in LGMD2A than in controls and it was significantly correlated with patients' clinical disability score recorded at the time of biopsy, suggesting that functional and structural muscle impairment are dependent. The large majority of atrophic fibres originate from a mechanism different from regeneration, as assessed by neonatal myosin immunolabelling. As compared with controls, LGMD2A muscles have higher MuRF1 (but not atrogin1) protein and MuRF1 gene expression levels, and MuRF1 protein levels significantly correlated with both muscle fibre size and clinical disability score. LGMD2A muscles have slightly increased levels of LC3-II and p62 proteins and a significant up-regulation of p62 and Bnip3 gene expression. Conclusions: In LGMD2A muscles the activation of the atrophy programme appeared to depend mainly upon induction of the ubiquitin-proteasome system and, to a lesser extent, the autophagic-lysosomal degradation pathway. © 2013 British Neuropathological Society
Multifactorial study of inflammatory myopathies. Report of 29 cases
No full textWe made a comparative clinical, immunopathological and therapeutic evaluation in 17 patients with polymyositis (PM) and 12 patients with dermatomyositis (DM), followed up at our Neuromuscular Center. DM can be distinguished by its clinical appearance and pathological changes. Current evidence suggests that it results from vasculopathy. For studying these inflammatory myopathies we used multifactorial diagnostic criteria, evaluating the therapeutic response by means of a composite clinical and functional score in a longitudinal study. In muscle biopsy specimens we characterized with monoclonal antibodies T lymphocyte subpopulations (CD4, CD8), macrophages, IgG, IgM, C1q, C3, C4 complement fractions, MHC-I, MHC-II. In PM the cell-mediated immunity was more pronounced and in sowithin muscle fibers. Our patients were treated with steroids; in resistant cases azathioprine, cyclophosphamide, plasmapheresis, high-dose intravenous immunoglobulins (ivIgG) and total body irradiation were added to the therapeutic schedule. © 1993 Masson Italia Editori
Gender difference in limb-girdle muscular dystrophy: A muscle fiber morphometric study in 101 patients
No full textAims: Limb girdle muscular dystrophies (LGMD), a genetically and clinically heterogeneous group of neuromuscular disorders, may show gender differences in the disease severity. We aimed to measure the extent of muscle fiber atrophy and evaluate possible gender differences at fiber level. Methods: We conducted a thorough morphometric analysis of muscle fiber size and fiber area in 101 muscles from patients with various forms of LGMD (43 LGMD2A, 30 LGMD2B, 21 LGMD2C-2D-2E, 7 LGMD1C) and 12 normal controls. Results: Reduced fiber size (atrophy) was pronounced in LGMD2A and LGMD2B, while LGMD1C showed a significant fiber hypertrophy. When we compared LGMD patients and controls of the same gender, males with LGMD2A and LGMD2B showed significantly higher fiber atrophy than control males, whereas female LGMD patients had similar values to female controls, suggesting a gender difference in muscle fiber atrophy. Discussion: Less recovery to disuse atrophy in men than in women has been attributed to the possibility that in women a smaller initial muscle size associated to endocrine factors could attenuate gender-specific muscle loss. The possibility that males with LGMD may be clinically more severely affected than females has been explored, but the mechanism remains elusive. © 2014 Dustri-Verlag Dr. K. Feistle
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