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T. T. KELLER C. NAGEL H. TE VELTHUIS† V. E. A. GERDES N. J. WAREHAM‡ S. A. BINGHAM§ R. LUBEN¶ C. E. HACK P. H. REITSMA†† M. LEVI K. T. KHAW¶ S. M. BOEKHOLDT‡‡ 《Journal of thrombosis and haemostasis》2006,4(11):2391-2396
INTRODUCTION: Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS: We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS: In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION: High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals. 相似文献
3.
Williams TN; Maitland K; Phelps L; Bennett S; Peto TE; Viji J; Timothy R; Clegg JB; Weatherall DJ; Bowden DK 《QJM : monthly journal of the Association of Physicians》1997,90(12):751-757
We studied the aetiology of malnutrition in a cohort of 1511 children <
10 years old in Espiritu Santo, Vanuatu. Malnutrition was categorized using
standard anthropometric criteria as: underweight [weight-for-age (WA) Z
score < -2], wasting [weight-for-height (WH) Z < -2], or stunting
[height-for-age (HA) Z < -2]. On multiple logistic regression analysis,
the only factors significantly associated with wasting were age < 5
years [OR (95% CI) 1.8 (1.2-2.9), p = 0.01] and having suffered one or more
episodes of clinical P. vivax malaria in the 6 months preceding nutritional
assessment [OR 2.4 (1.3-4.4), p = 0.006]. The incidence of P. vivax
infection was significantly higher during the 6 months preceding assessment
in underweight vs. non-underweight children [incidence rate ratio (IRR) 2.6
(1.5-4.4), p < or = 0.0001). These groups had similar incidences of
clinical P. falciparum infection during the same period [IRR 1.1 (0.57-2.1)
p = 0.8] and of either species during the 6 months following assessment
[IRR P. vivax 1.3 (0.9- 2.0) p = 0.2; IRR P. falciparum 1.3 (0.9-1.9) p =
0.2]. In these children, P. vivax malaria was a major predictor of acute
malnutrition; P. falciparum was not. Wasting neither predisposed to nor
protected against malaria of either species. Although P. vivax malaria is
generally regarded as benign, it may produce considerable global mortality
through malnutrition.
相似文献
4.
Walker AS; Peto TE; Babiker AG; Darbyshire JH 《QJM : monthly journal of the Association of Physicians》1998,91(6):423-438
The Concorde trial compared immediate (Imm) with deferred (Def) AZT
monotherapy in asymptomatic HIV-positive participants. Haematological and
immunological markers and weight were measured throughout, and correlated
with clinical endpoints. Markers associated with disease progression (CD4
lymphocyte count and percentage, platelets, p24 antigen and beta 2
microglobulin favoured Imm: those associated with toxicity (haemoglobin,
neutrophils and white cell count) favoured Def. CD8 and total lymphocyte
count did not differ significantly between groups. In multivariate
analysis, the combination of baseline CD4, p24 antigen and beta 2m was the
best baseline predictor of disease. Including change in CD4 and beta 2m at
12 weeks, or changes over follow- up in these markers significantly
improved the fit. Markers were also incorporated into the definition of
'clinical' endpoints. Hazard ratio estimates from end-points that included
CD4 < 50 and CD4 < 25 were closest to those for AIDS or death alone,
but added very few extra events. Use of other landmark CD4 counts (100 or
greater) or relative decreases in counts (25% or more) increased the number
of events, but overestimated the effect of immediate AZT. Although AZT had
a beneficial effect on the surrogate markers of efficacy evaluated, these
changes did not predict clinical outcome, nor could the markers be usefully
incorporated into an endpoint definition.
相似文献
5.
Apoptosis and/or differentiation induction caused by the peroxisome proliferator-activated receptor gamma (PPARgamma) ligand is a promising approach to cancer therapy. The thiazolidinedione derivative MCC-555 has an apoptotic activity in human colorectal cancer cells, accompanied by up-regulation of a proapoptotic nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in a PPARgamma-independent manner. Treatment with MCC-555 resulted in the induction of NAG-1 expression and apoptosis in HCT-116 cells. Down-regulation of NAG-1 by small interfering RNA suppressed MCC-555-induced apoptosis. MCC-555 was found to affect NAG-1 mRNA stability. To further define the underlying mechanism of RNA stability affected by MCC-555, we cloned the 3'-untranslated region (3'UTR) of human NAG-1 mRNA, which contains four copies of an AU-rich element (ARE), downstream from the luciferase gene. The reporter activity was reduced to approximately 70% by inserting the 3'UTR. In addition, deletion of ARE sequences in the 3'UTR or MCC-555 treatment substantially restored activity. This effect of MCC-555 on the ARE-mediated mRNA degradation was inhibited by extracellular signal-regulated kinase (ERK) pathway inhibitors. Subsequently, rapid phosphorylation of ERK1/2 by MCC-555 treatment was detected. Moreover, ERK small interfering RNA suppressed MCC-555-induced NAG-1 expression. These results suggest that ARE sequences in the 3'UTR of the NAG-1 gene contribute to mRNA degradation and ERK1/2 phosphorylation is responsible for the stabilization of NAG-1 mRNA. These findings may provide a novel explanation for the antitumorigenic and/or proapoptotic action of MCC-555 in human colorectal cancer and the ability of pharmacologic approaches to be used against diseases caused by alterations of RNA stability. 相似文献
6.
The biocompatibility of nine different white cell filters was examined by analysis of complement activation in plasma specimens obtained from blood components before and after filtration. Filters for both red cell (RBC) concentrates and platelet concentrates (PCs) were tested. It was found in all of the filters tested that the postfiltration levels of complement activation products were not higher than the prefiltration levels in RBC concentrates and PCs. One exception was the filtration of multiple PCs with Imugard IG-500, in which case a rise in C3 activation products was seen. Moreover, there was a significant rise in C3 activation products, but not the terminal complement complex, when plasma was filtered through Imugard E, which contrasted with results with the other filters. High initial and storage time-dependent levels, especially of C3 activation products, were observed in the PCs, probably due to their processing at room temperature. It can be concluded that the majority of the filters tested do not activate complement. 相似文献
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8.
Luciano Fasotti Feri Kovacs Paul A.T.M. Eling Wiebo H. Brouwer 《Neuropsychological rehabilitation》2013,23(1):47-65
Following severe closed head injury, deficits in speed of information processing are common. As a result, many head-injured patients experience a feeling of “information overload” in daily tasks that once were relatively easy. Many remedial programmes have been designed that treat different aspects of attention (often including mental speed requirements) by repetitive exercises. In the present study, a different approach to slow information processing has been taken, namely Time Pressure Management (TPM). TPM consists of a set of alternative cognitive strategies that allow head-injured patients in real-life tasks to compensate for their mental slowness. In a randomised pre-training vs. post-training vs. follow-up group study, the effectiveness of TPM training was compared with concentration training in which verbal instruction was the key element. The results indicate that specific TPM strategies are learned by the experimental subjects but that both treatments improve task performance significantly for an information intake task. TPM, however, produces greater gains than concentration training and also appears to generalise to other measures of speed and memory function. 相似文献
9.
Paul Eling 《Neuropsychological rehabilitation》2013,23(2):187-190
Abstract McCarthy, R.A. &; Warrington, E.K. (1990). Cognitive neuropsychology: A clinicaf introduction. London: Academic Press. Pp. 428. ISBN 0-12481-845-5. f49.00 (hardback). ISBN 0-12481-846-3. £25.00 (paperback). Schulkin, J. (Ed.) (1990). Preoperative events. Their effects on behavior following brain damage. Hillsdale, N.J. : Lawrence Erlbaum Associates. Pp. 346. ISBN 0-8058-0021-2. £50.50. Caramazza, A. (Ed.) (1990). Cognitive neuropsychology and neurolinguistics: Advances in models of cognitive function and impairment. Hillsdale, NJ: Lawrence Erlbaum Associates. Pp. 293. ISBN 0-89859-892-3. US $64.95, £39.95. 相似文献
10.
The effect of ozone exposure on rat alveolar macrophage arachidonic acid metabolism. 总被引:1,自引:0,他引:1
Rat alveolar macrophages were prelabeled with 3H-arachidonic acid (3H-AA) and exposed to air or O3 (0.1-1.0 ppm) in vitro for 2 h. Alveolar macrophages released 3.6-fold more tritium at the 1.0 ppm exposure concentration compared with air-exposed macrophages. A significantly increased production of several 3H-AA metabolites, including 6-keto-PGF1 alpha, thromboxane B2, 12-hydroxy-5,8,10-heptadecatrienoic acid, prostaglandins E2 and D2, leukotrienes B4 and D4, and 15-hydroxyeicosatetraenoic acid was formed by macrophages exposed to 1.0 ppm O3 compared with air-exposed macrophages as determined by high performance liquid chromatography (HPLC) analysis. O3 exposure did not alter macrophage 3H-AA metabolism in response to calcium ionophore A23187. The largest tritiated peak observed in the HPLC chromatograms of O3-exposed cells was a polar complex of products that contained various phospholipids and neutral lipids (including diacylglycerol) and possibly degradation products of 3H-AA and some of its metabolites. These changes in macrophage arachidonic acid metabolism may play an important role in the lung response to O3 exposure in vivo. 相似文献