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31.
Lyons B 《Australian family physician》1999,28(3):209-215
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Summary Dystrophin, the protein product of the gene responsible for X-linked muscular dystrophies, shares structural features with the cytoskeletal proteins spectrin and -actinin. Like spectrin, it is localized at the cytoplasmic surface of the sarcolemma and is particularly concentrated in the subsynaptic region of the neuromuscular junction.Mdx mice have a profound deficiency of dystrophin and develop a necrotizing myopathy in the first weeks of life. Abnormalities of the neuromuscular junction, including a redistribution of postsynaptic molecules and reduction in synaptic folding, are also observed. We have studied these mice to see whether the lack of dystrophin has a specific effect on the structure and function of their neuromuscular junctions.Using a fore-limb muscle from 8 week oldmdx mice we confirm the previously described postsynaptic structural changes and in addition show that many nerve terminals are abnormally complex. We demonstrate that these structural abnormalities are found exclusively at neuromuscular junctions on regenerated muscle fibres. Despite these structural abnormalities, miniature endplate potential frequency, the quantal content of endplate potentials, the amplitude and time course of miniature endplate currents and the number of acetylcholine receptors at the postsynaptic membrane are normal inmdx mice of this age. We conclude that in themdx mouse the absence of dystrophin from the postsynaptic membrane has little direct effect on the function of the neuromuscular junction but that degeneration and regeneration of muscle fibres leads to remodelling of both its pre- and postsynaptic components. 相似文献
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Malignant transformation of a Hürthle cell tumor: case report and survey of the literature 总被引:1,自引:0,他引:1
R J McDonald S Y Wu J L Jensen L N Parker K P Lyons E M Moran W H Blahd 《Journal of nuclear medicine》1991,32(6):1266-1269
Hürthle cell carcinoma is a relatively uncommon type of well-differentiated thyroid carcinoma. Its diagnosis has been controversial due to the difficulty in separating Hürthle cell adenoma from Hürthle cell carcinoma, thus the term Hürthle cell tumor is often used to describe both lesions. The present case of anaplastic giant-cell carcinoma in an 81-yr-old woman arose in a Hürthle cell tumor. This case illustrates the propensity of Hürthle cell tumor to undergo "malignant transformation" and argues for a more aggressive approach to such tumors. 相似文献
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The effect of family status and schizotypy on electrophysiologic measures of attention and semantic processing. 总被引:3,自引:0,他引:3
M Kimble M Lyons B O'Donnell P Nestor M Niznikiewicz R Toomey 《Neuropsychopharmacology》2000,47(5):402-412
BACKGROUND: Disturbances in both attention and language are central to the phenomenology of the schizophrenia spectrum disorders. The purpose of this study was to investigate the relative contributions of two factors, family status and schizotypy, on electrophysiologic measures of attention and semantic processing in family members of individuals with schizophrenia. METHODS: Fifteen first-degree relatives of individuals with schizophrenia and 15 comparison subject controls participated in diagnostic evaluations, an assessment of schizotypy, and two event-related potential (ERP) paradigms. The first paradigm was an auditory P300 "oddball" task designed to assess attentional functioning. The second was an N400 sentence paradigm particularly sensitive to language processing. RESULTS: Both relatives and individuals higher in schizotypy, but not their respective comparison groups, showed reductions in P300 amplitude. In the N400 paradigm, individuals higher in schizotypy, but not relatives, showed a reduced N400 effect. There were no differences in latency for either group on either component. CONCLUSIONS: The results suggest that both family status and schizotypal presentation independently contribute to disturbances in electrophysiologic measures sensitive to attention and language. Whereas higher levels of schizotypy appear to be associated with disturbances in both attention and language processing, family membership appears to place individuals at risk for attentional deficits alone. 相似文献
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Manoj Kumar Reddy Somagutta Nishat Shama Maria Kezia Lourdes Pormento Ravi Pankajbhai Jagani Ngaba Neguemadji Ngardig Klodin Ghazarian Greta Mahmutaj Khaled El-Faramawy Ashwini Mahadevaiah Molly Sanjay Jain 《Reumatologia》2022,60(1):63
Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality. 相似文献
39.
Identification
of RAD51–BRCA2 Inhibitors Using N-Acylhydrazone-Based
Dynamic Combinatorial Chemistry
Greta Bagnolini Beatrice Balboni Fabrizio Schipani Dario Gioia Marina Veronesi Francesca De Franco Cansu Kaya Ravindra P. Jumde Jose Antonio Ortega Stefania Girotto Anna K. H. Hirsch Marinella Roberti Andrea Cavalli 《ACS medicinal chemistry letters》2022,13(8):1262
RAD51 is an ATP-dependent recombinase, recruited by BRCA2 to mediate DNA double-strand breaks repair through homologous recombination and represents an attractive cancer drug target. Herein, we applied for the first-time protein-templated dynamic combinatorial chemistry on RAD51 as a hit identification strategy. Upon design of N-acylhydrazone-based dynamic combinatorial libraries, RAD51 showed a clear templating effect, amplifying 19 N-acylhydrazones. Screening against the RAD51–BRCA2 protein–protein interaction via ELISA assay afforded 10 inhibitors in the micromolar range. Further 19F NMR experiments revealed that 7 could bind RAD51 and be displaced by BRC4, suggesting an interaction in the same binding pocket of BRCA2. These results proved not only that ptDCC could be successfully applied on full-length oligomeric RAD51, but also that it could address the need of alternative strategies toward the identification of small-molecule PPI inhibitors. 相似文献
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