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101.
Del Bo R Crimi M Sciacco M Malferrari G Bordoni A Napoli L Prelle A Biunno I Moggio M Bresolin N Scarlato G Pietro Comi G 《Neurobiology of aging》2003,24(6):829-838
The ageing process is associated with the accumulation of somatic mutations of mitochondrial DNA (mtDNA). The aged human skeletal muscle tissue presents a mosaic of fibers when stained histochemically for cytochrome c oxidase (COX) activity with a proportion of COX negative fibers. Given the potential relevance of any alteration in the mtDNA control region for replication, we analysed the correlation between the presence of mutations and their degree of heteroplasmy and the COX phenotype in individual muscle fibers of aged healthy donors.A region of the mtDNA D-loop was cloned from single fiber-derived DNA and multiple clones were analysed. This strategy showed that a high level of mutational burden is present in all fibers and that several types of mtDNA rearrangements are detectable: recurrent (A189G, T408A and T414G) and rare point mutations, length variations affecting the homopolymeric tract and the (CA)(n) repeat and macrodeletions. The aggregate mutational load in the D-loop region correlated with the single fiber COX phenotype, suggesting that the cumulative burden of multiple, individually rare, mtDNA alterations might functionally impair the mitochondrial genetic machinery. 相似文献
102.
Crimi M Del Bo R Galbiati S Sciacco M Bordoni A Bresolin N Comi GP 《European journal of human genetics : EJHG》2003,11(11):896-898
Mitochondrial (mt)DNA alterations cause cellular energy failure and respiratory chain dysfunction. Single large-scale rearrangements represent the most common mtDNA mutations and are responsible for very variable clinical manifestations. Here, we show an increased frequency of the A12308G substitution, a common polymorphism used to define the European mtDNA haplogroup U, in mitochondrial patients carrying mtDNA single macrodeletion. In this group of patients, A12308G substitution is associated with a higher relative risk of developing pigmentary retinal degeneration, short stature, dysphasia-dysarthria and cardiac conduction defects. MtDNA haplotype might modulate the clinical expression of mitochondrial encephalomyopathies due to mtDNA macrodeletions. 相似文献
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Telephone interviews were conducted with 500 primary care physicians, drawn from a stratified random sample of internists, family practitioners, pediatricians, general practitioners, and OB/GYN physicians. Respondents were asked to report their experience treating AIDS patients and to estimate the percentage of their patients they felt were at high risk for HIV infection. Nineteen questions designed to assess practices and attitudes towards AIDS and HIV-related issues were asked. Results suggest that physicians underestimate their patients' level of risk for HIV infection and are not taking adequate drug use and sexual histories. The level of concern for personal risk of infection was high, although a strong ethical obligation to treat HIV patients was expressed. Physicians also expressed support for mandatory reporting and contact tracing, although this diminished as contact with HIV patients increased. 相似文献
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Two young adult dizygotic twins with high schooling suffered two strokes at the ages of 26 and 30 years. On the first occasion, Case 2 suffered a stroke only a few months after Case 1; on the second occasion, Case 1 suffered a second stroke a few months after Case 2. In Case 1, lesions were mainly localized to the left cerebellar hemisphere in both stroke episodes. Case 2 suffered lesions localized to the right cerebellar hemisphere in the first stroke episode, and multiple lesions in both cerebellar hemispheres and the vermis, right pons and left thalamus during the second stroke episode. Seven years after the second stroke, despite full recovery of motor functions, the patients still show mild, yet selective, linguistic deficits (syntactic comprehension deficits, mild agrammatism, reading and writing disorders) without speech disturbances. They also present with selective dysfunctions in visuospatial short-term memory. Language disorders are ascribed to a dysfunction of the cerebellum in Case 1, while in Case 2 a dysfunction of the cerebellum and the thalamus is considered as both structures are part of the so-called 'frontal lobe system', which supports language generation. Visuospatial short-term memory disorders are attributed to an impaired ability to appreciate the organizing structure of the visual task and to poor planning strategies, which are in turn ascribed to cerebellar lesions. The role of the cerebellum in cognitive and linguistic functions is discussed. 相似文献
109.
Conti G Rostami A Scarpini E Baron P Galimberti D Bresolin N Contri M Palumbo C De Pol A 《Experimental neurology》2004,187(2):350-358
The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell-axon relationship causing axonal damage and regulating endoneurial cell life and death. 相似文献
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