There may be a continued risk for recurrent ischemic lesions in the weeks following the clinically symptomatic stroke. Future studies are needed to investigate whether MRI-defined ischemic lesion recurrences predict subsequent clinical recurrence and thus may be a potential surrogate endpoint in stroke secondary prevention trials.
Nuclear receptor corepressor (N-CoR) is a critical regulator of neural stem cell differentiation. Nuclear localization of N-CoR is a feature of undifferentiated neural stem cells and cytoplasmic translocation of N-CoR leads to astrocytic differentiation. Comparative proteomic analysis of microdissected glioblastoma multiforme (GBM) specimens and matched normal glial tissue reveals increased expression of N-CoR in GBM. In GBM primary cell cultures, tumor cells with nuclear localization of N-CoR demonstrate an undifferentiated phenotype, but are subject to astroglial differentiation upon exposure to agents promoting phosphorylation of N-CoR and its subsequent translocation to the cytoplasm. Treatment of glioma cell lines with a combination of retinoic acid and low-dose okadaic acid decreases the corepressor effect of N-CoR and has a striking synergistic effect on growth inhibition. The identification of N-CoR in GBM provides insights into the tumorigenesis process and supports the development of differentiation-based therapeutic strategies.
We studied 60 patients with multiple system atrophy and autonomic failure and 60 control subjects matched for age, sex and race. Their psychosocial history, pedigree and occupation were obtained by personal interview. An inventory of autonomic and neurologic symptoms was obtained from 148 first-degree relatives of the patients and 80 controls by a self-administered questionnaire. Patients with multiple system atrophy had significantly more potential exposures to metal dusts and fumes, plastic monomers and additives, organic solvents, and pesticides than the control population. The potential exposures were determined in most subjects by their reported usual occupation. Clinical symptoms of multiple system atrophy were reported by a significantly larger group of patients' relatives than controls. These findings are possibly consistent with the hypothesis that multiple system atrophy develops as a result of a genetically determined selective vulnerability in the nervous system. Specific neuronal systems may become targets for environmental insults or toxins, and the disease state may occur when ageing neuronal systems can no longer sustain functional capacity. This preliminary study supports the need to further explore possible environmental, occupational, and familial contributions to the aetiology of multiple system atrophy.
Background: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have neuroprotective effects in experimental stroke models and are commonly prescribed in clinical practice. The aim of this study was to determine if patients taking statins before hospital admission for stroke had an improved clinical outcome.
Rising counts of circulating CD4+CD28- cells are associated with an increasing risk of stroke recurrence and death, in addition to an observed association with prior stroke. Expansion of this T-cell subset presumably represents a biomarker and possibly a contributory pathogenic mechanism of recurrent stroke and death after ischemic stroke.
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