University of Düsseldorf

About: University of Düsseldorf is a education organization based out in Düsseldorf, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 25225 authors who have published 49155 publications receiving 1946434 citations.

Infections in patients with rheumatoid arthritis treated with biologic agents.

Abstract: Objective To estimate the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis (RA) who start treatment with a biologic agent, and to compare these rates with those in patients with RA who receive conventional treatment Methods Patients enrolled in the German biologics register between May 2001 and September 2003 were included Treating rheumatologists assessed adverse events and serious adverse events All adverse events and serious adverse events experienced within 12 months after study entry were analyzed Propensity score methods were applied to estimate which part of a rate increase was likely to be attributable to differences in patient characteristics Results Data were available for 512 patients receiving etanercept, 346 patients receiving infliximab, 70 patients receiving anakinra, and 601 control patients treated with disease-modifying antirheumatic drugs The total number of adverse events per 100 patient-years was 226 (95% confidence interval [95% CI] 187–272) among patients receiving etanercept, 283 (95% CI 231–347) among patients receiving infliximab, and 68 (95% CI 50–94) among controls (P < 00001) Significant differences in the rate of serious adverse events were also observed For patients receiving etanercept, those receiving infliximab, and controls, the total numbers of serious adverse events per 100 patient-years were 64 (95% CI 45–91), 62 (95% CI 40–95), and 23 (95% CI 13–39), respectively (P = 00016) After adjusting for differences in the case patient mix, the relative risks of serious adverse events were 22 (95% CI 09–54) for patients receiving etanercept and 21 (95% CI 08–55) for patients receiving infliximab, compared with controls Conclusion Patients treated with biologic agents have a higher a priori risk of infection However, our data suggest that this risk is increased by treatment with tumor necrosis factor inhibitors

HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3

Abstract: HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. HDL binding to scavenger receptor-BI has been shown to activate eNOS, although the responsible HDL entities and signaling pathways have remained enigmatic. Here we show that HDL stimulates NO release in human endothelial cells and induces vasodilation in isolated aortae via intracellular Ca2+ mobilization and Akt-mediated eNOS phosphorylation. The vasoactive effects of HDL could be mimicked by three lysophospholipids present in HDL: sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and lysosulfatide (LSF). All three elevated intracellular Ca2+ concentration and activated Akt and eNOS, which resulted in NO release and vasodilation. Deficiency of the lysophospholipid receptor S1P3 (also known as LPB3 and EDG3) abolished the vasodilatory effects of SPC, S1P, and LSF and reduced the effect of HDL by approximately 60%. In endothelial cells from S1P3-deficient mice, Akt phosphorylation and Ca2+ increase in response to HDL and lysophospholipids were severely reduced. In vivo, intra-arterial administration of HDL or lysophospholipids lowered mean arterial blood pressure in rats. In conclusion, we identify HDL as a carrier of bioactive lysophospholipids that regulate vascular tone via S1P3-mediated NO release. This mechanism may contribute to the vasoactive effect of HDL and represent a novel aspect of its antiatherogenic function.

Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity

Abstract: Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances1,2. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation3,4,5,6, a key regulator of gene expression and molecular phenotype7. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10−7, range P = 9.2 × 10−8 to 6.0 × 10−46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10−6, range P = 5.5 × 10−6 to 6.1 × 10−35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07–2.56); P = 1.1 × 10−54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.

Impaired Memory Retrieval after Psychosocial Stress in Healthy Young Men

Abstract: Glucocorticoids (GCs) are known to modulate memory in animals and humans. One popular model suggests that stress or GC treatment enhances memory consolidation while impairing delayed memory retrieval. Studies in humans have documented that treatment with GCs impairs delayed memory retrieval. Similar alterations after exposure to stress have not been observed thus far. In the present study, 19 young healthy male subjects were exposed to either a standardized psychosocial laboratory stressor (Trier Social Stress Test) or a control condition in a crossover manner. After both treatments, retrieval of a word list (learned 24 h earlier) containing 10 neutral, 10 negative, and 10 positive words was tested. The stressor induced a significant increase in salivary free cortisol and a decrease in mood. Memory retrieval (free recall) was significantly impaired after the stress condition. Follow-up analysis revealed that negative and positive words (i.e., emotionally arousing words) were affected, whereas no effect was observed for neutral words. No changes were detected for cued recall, working memory, or attention. The present study thus demonstrates that psychosocial stress impairs memory retrieval in humans and suggests that emotionally arousing material is especially sensitive to this effect.

Going, Going, ...Gone? The Decline of Party Membership in Contemporary Europe

Abstract: This article offers an overview of levels of party membership in European democ- racies at the end of the first decade of the twenty-first century and looks also at changes in these levels over time, comparing party membership today with figures from both 1980 and the late 1990s. While relying primarily on the direct and individual membership figures as reported by the parties themselves, the fit of the data with survey data is explored and it is concluded that the two perform well in terms of convergent validity.The differences between large and small democracies are examined, as well as old and new democracies, and it is found that levels of party membership are related to both the size and age of the democratic polity in question. Finally, the implications of the patterns observed in the membership data are discussed, and it is suggested that membership has now reached such a low ebb that it may no longer constitute a relevant indicator of party organisational capacity. This article offers an overview and initial analysis of the levels of party mem- bership in European democracies at the end of the first decade of the twenty- first century, and discusses the implications of changes in party membership for our understanding of models of party organisation. The first two sections provide a broad comparison of the data on party membership in European democracies and analyse changes in membership over time, comparing con- temporary levels with those from both 1980 and the late 1990s, and exploring variations in national patterns. In the third section, we discuss some of the implications of the patterns that we observe in the membership data and suggest that membership has now reached such a low ebb that it may no longer constitute a relevant indicator of party organisational capacity. Alternatively, if membership continues to be regarded as offering a meaningful gauge of party organisational strength, we might then conclude that party organisations have reached such a low ebb that the formal organisational level is itself no longer a relevant indicator of party capacity. In presenting an overview of the levels of party membership in European democracies at the end of the first decade of the twenty-first century, our 24