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排序方式: 共有1073条查询结果,搜索用时 531 毫秒
71.
OBJECTIVE: Since apoptosis is an important contributor to heart diseases in which ischemia and hypoxia are key elements, we tested the hypothesis that hypoxia predisposes neonatal rat ventricular myocytes (NRVM) to Fas-mediated apoptosis, by shifting the balance between antiapoptotic and proapoptotic proteins towards the latter. METHODS: Normoxic or hypoxic (22 h, 1% O(2)) cultured NRVM were exposed to recombinant Fas L (rFasL) for 7 h, and apoptosis measured thereafter. RESULTS: Whereas in normoxic NRVM, rFasL did not cause apoptosis measured by the TUNEL assay (4.8+/-0.5% in control versus 4.5+/-0.9% in rFasL), in hypoxic cultures rFasL increased the background apoptosis level by 100%. That Fas was functional in normoxic NRVM, despite its inability to mediate apoptosis, was evidenced by the finding that Fas activation increased the diastolic [Ca(2+)](i) levels measured by Fura 2 fluorescence, and caused arrhythmias. In support of our working hypothesis, hypoxia increased Fas expression by 200% (measured by quantitative Western blot), and the expression of the proapoptotic proteins ARTS and FADD by 323 and 250%, respectively, and decreased the expression of the antiapoptotic proteins ARC and FLIP by 90 and 60%, respectively. CONCLUSION: By upregulating Fas expression and key proapoptotic proteins, and by downregulating antiapoptotic proteins, hypoxia predisposes ventricular myocytes to Fas-induced apoptosis. 相似文献
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Y.J. Chung S. Ronsmans R.W.R. Crevel G.F. Houben R.J. Rona R. Ward A. Baka 《Regulatory toxicology and pharmacology : RTP》2012
Scientific criteria for identifying allergenic foods of public health importance (Björkstén, B., Crevel, R., Hischenhuber, C., Løvik, M., Samuels, F., Strobel, S., Taylor, S.L., Wal, J.-M., Ward, R., 2008. Criteria for identifying allergenic foods of public health importance. Regulatory Toxicology and Pharmacology 51(1), 42–52) have been further refined to incorporate an assessment of the strength of available scientific evidence (van Bilsen, J.H., Ronsmans, S., Crevel, R.W., Rona, R.J., Przyrembel, H., Penninks, A.H., Contor, L., Houben, G.F., 2011. Evaluation of scientific criteria for identifying allergenic food of public health importance. Regulatory Toxicology and Pharmacology 60, 281–289). A multi-disciplinary group was invited to critically test the refined approach. They independently evaluated selected publications on coconut, soy and/or peanut allergy, scored them using the newly developed level of evidence criteria, and debated proposed approaches for combining and utilising the scores to measure the overall impact of an allergen in public health impact assessments. The evaluation of selected publications using the modified criteria produced a relatively consistent result across the experts. These refined criteria were judged to be a way forward for the identification of allergenic foods of public health importance, and for prioritisation of allergen risk management and future data gathering. The debate to combine available evidence when assessing whether an allergenic food is of sufficient public health importance to warrant active management led to proposals on how to weight and combine evidence on allergen severity, potency and prevalence. The refined criteria facilitate a debate to find a meaningful sequence of steps to summarise the available information in relation to a food allergen. 相似文献
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Accumulation of prion protein in the brain that is not associated with transmissible disease 总被引:5,自引:0,他引:5
Piccardo P Manson JC King D Ghetti B Barron RM 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(11):4712-4717
Prion diseases or transmissible spongiform encephalopathies are characterized histopathologically by the accumulation of prion protein (PrP) ranging from diffuse deposits to amyloid plaques. Moreover, pathologic PrP isoforms (PrP(Sc)) are detected by immunoblot analysis and used both as diagnostic markers of disease and as indicators of the presence of infectivity in tissues. It is not known which forms of PrP are associated with infectivity. To address this question, we performed bioassays using human brain extracts from two cases with phenotypically distinct forms of familial prion disease (Gerstmann-Str?ussler-Scheinker P102L). Both cases had PrP accumulations in the brain, but each had different PrP(Sc) isoforms. Only one of the brains had spongiform degeneration. Tissue from this case transmitted disease efficiently to transgenic mice (Tg PrP101LL), resulting in spongiform encephalopathy. In contrast, inoculation of tissue from the case with no spongiform degeneration resulted in almost complete absence of disease transmission but elicited striking PrP-amyloid deposition in several recipient mouse brains. Brains of these mice failed to transmit any neurological disease on passage, but PrP-amyloid deposition was again observed in the brains of recipient mice. These data suggest the possible isolation of an infectious agent that promotes PrP amyloidogenesis in the absence of a spongiform encephalopathy. Alternatively, the infectious agent may be rendered nonpathogenic by sequestration in amyloid plaques, or PrP amyloid can seed amyloid accumulation in the brain, causing a proteinopathy that is unrelated to prion disease. Formation of PrP amyloid may therefore not necessarily be a reliable marker of transmissible spongiform encephalopathy infectivity. 相似文献
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Strategies for learning evidence-based practice: critically appraising clinical practice guidelines 总被引:1,自引:0,他引:1
Nurse educators have a mandate to educate our students about using an evidence-based practice approach to clinical decision making. At the Lienhard School of Nursing, Pace University, faculty have successfully integrated evidence-based practice into the family nurse practitioner curriculum. This article describes one teaching-learning strategy to help students learn how to critically appraise clinical practice guidelines using the AGREE instrument. There are several steps to the learning exercise: completing preparatory reading, obtaining the guideline that forms the focus of the assignment, working as teams, using the AGREE tool to assess the guideline's validity, and reporting team findings to the entire class. Students have found this learning activity helpful in preparing them for clinical practice. 相似文献
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Comorbidity in irritable bowel syndrome 总被引:1,自引:0,他引:1
Whitehead WE Palsson OS Levy RR Feld AD Turner M Von Korff M 《The American journal of gastroenterology》2007,102(12):2767-2776
BACKGROUND: Comorbid nongastrointestinal symptoms account for two-thirds of excess health-care costs in irritable bowel syndrome (IBS). OBJECTIVES: To determine whether IBS patients are at greater risk for specific comorbid disorders versus showing a general tendency to overreport symptoms; whether patients with inflammatory bowel disease (IBD) show patterns of comorbidity similar to IBS; whether comorbidity is explained by psychiatric disease; and whether excess comorbidity occurs in all IBS patients. METHODS: All 3,153 patients in a health maintenance organization with a diagnosis of IBS in 1994-1995 were compared to 3,153 age- and gender-matched controls, and to 571 IBD patients. All diagnoses in a 4-yr period beginning 1 yr before their index visit were categorized as gastrointestinal, psychiatric, or nongastrointestinal somatic. Nongastrointestinal somatic diagnoses were further divided into symptom-based versus biological marker-based diagnoses. RESULTS: Forty-eight of 51 symptom-based and 16 of 25 biomarker-based diagnoses were significantly more common in IBS versus controls. However, there were no unique associations. Bacterial, viral, and fungal infections and stroke were among diagnoses made more frequently in IBS. IBD patients were similar to controls. Greater somatic comorbidity was associated with concurrent psychiatric diagnosis. Only 16% of IBS patients had abnormally high numbers of comorbid diagnoses. CONCLUSIONS: Comorbidity in IBS is due to a general amplification of symptom reporting and physician consultation rather than a few unique associations; this suggests biased symptom perception rather than shared pathophysiology. Comorbidity is influenced by, but is not explained by, psychiatric illness. Excess comorbidity is present in only a subset of IBS patients. 相似文献
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