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Simone Ohlwein Frauke Hennig Sarah Lucht Brge Schmidt Lewin Eisele Marina Arendt Ulrich Dührsen Jan Dürig Karl-Heinz Jckel Susanne Moebus Barbara Hoffmann 《Environmental health perspectives》2021,129(2)
Background: Residential exposure to air pollution (AP) has been shown to activate the immune system (IS). Although innate immune responses to AP have been studied extensively, investigations on the adaptive IS are scarce.Objectives: The aim of this study was to investigate the association between short- to long-term AP exposure and polyclonal free light chains (FLC) produced by plasma cells.Methods: We used repeated data from three examinations (: 2000–2003; : 2006–2008; and : 2011–2015) of the population-based German Heinz Nixdorf Recall cohort of initially 4,814 participants (45–75 y old). Residential exposure to total and source-specific particulate matter (PM) with an aerodynamic diameter of 10 or ( and respectively), nitrogen dioxide (), and particle number concentrations (accumulation mode; ) was estimated using a chemistry transport model with different time windows (1- to 365-d mean ± standard deviation) before blood draw. We applied linear mixed models with a random participant intercept to estimate associations between total, traffic- and industry-related AP exposures and log-transformed FLC, controlling for examination time, sociodemographic and lifestyle variables, estimated glomerular filtration rate and season.Results: Analyzing 9,933 observations from 4,455 participants, we observed generally positive associations between AP exposures and FLC. We observed strongest associations with middle-term exposures, e.g., 3.0% increase in FLC (95% confidence interval: 1.8%, 4.3%) per interquartile range increase in 91-d mean of (). Across the different pollutants, showed strongest associations with FLC, followed by and . Effect estimates for traffic-related exposures were mostly higher compared with total exposures. Although and estimates remained stable upon adjustment for PM, PM estimates decreased considerably upon adjustment for and .Discussion: Our results suggest that middle-term AP exposures in particular might be positively associated with activation of the adaptive IS. Traffic-related PM, , and showed strongest associations. https://doi.org/10.1289/EHP7164 相似文献
156.
Signaling of G protein-coupled receptors (GPCRs) is tightly regulated by coordinated phosphorylation of intracellular serine and threonine residues. Although the mechanisms of agonist-induced phosphorylation have been deciphered for many GPCRs, the regulation of their dephosphorylation remains poorly understood. Using a combination of siRNA knockdown screening and phosphosite-specific antibodies, we have recently identified the catalytic subunit β of protein phosphatase 1 (PP1β) as major constituent of the GPCR phosphatase responsible for dephosphorylation of the sst2 somatostatin receptor. However, PP1-targeting subunits specifically required for GPCR dephosphorylation have not been identified so far. Here, we show that siRNA knockdown of β-arrestin1 strongly inhibits sst2 receptor dephosphorylation. Co-immunoprecipitation experiments demonstrate that β-arrestin1 and PP1β exist as constitutive complex that mediates rapid dephosphorylation of sst2 receptors at or near the plasma membrane. By contrast, β-arrestin2 is not essential for rapid sst2 receptor dephosphorylation. Together, these findings reveal a novel scaffolding function of β-arrestin1 that facilitates efficient targeting of PP1β to phosphorylated GPCRs. 相似文献
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Heart failure (HF) affects approximately 23 million individuals worldwide and this number is increasing, due to an aging and growing population. Early detection of HF is crucial in the management of this debilitating disease. Current diagnostic methods for HF rely heavily on clinical imaging techniques and blood analysis, which makes them less than ideal for population-based screening purposes. Studies focusing on developing novel biomarkers for HF have utilized various techniques and biological fluids, including urine and saliva. Promising results from these studies imply that these body fluids can be used in evaluating the clinical manifestation of HF and will one day be integrated into a clinical workflow and facilitate HF management. 相似文献
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Pohl H Aschenbeck J Drossel R Schröder A Mayr M Koch M Rothe K Anders M Voderholzer W Hoffmann J Schulz HJ Liehr RM Gottschalk U Wiedenmann B Rösch T 《Journal of internal medicine》2008,264(4):370-378
Objective. Potential process differences between hospital and community‐based endoscopy for Barrett’s oesophagus have not been examined. We aimed at comparing adherence to guidelines and neoplasia detection rates in medical centres (MC) and community practices (CP). Design. Retrospective analysis. Setting. All histologically confirmed Barrett cases seen over a 3‐year period in six MC and 19 CP covering a third of all upper gastrointestinal endoscopies (n = 126 000) performed annually in Berlin, Germany. Main outcome measure. Rate of relevant neoplasia (high‐grade intraepithelial neoplasia or more) in both settings in relation to adherence to standards. Results. Of 1317 Barrett cases, 66% were seen in CP. CP patients had a shorter mean Barrett length (2.6 cm vs. 3.8 cm; P < 0.001) with fewer biopsies taken during an examination (2.5 vs. 4.1 for Barrett length ≤2 cm; P < 0.001). CPs also provided fewer complete esophagogastroduodenoscopy documentation (25.1% vs. 57.8%, P < 0.001). Neoplasias were found more commonly in MCs compared to CPs (9.2% vs. 0.8%; P < 0.001). However, on exclusion of all referred patients with known neoplasia (65%) or those examined for other reasons (27.5%), the detection rate at MCs decreased to 1.3%, not different from the one seen at CPs (0.8%, P = 0.43). Only 13% were found during surveillance, but 57% were diagnosed at an early stage. Conclusions. Referral bias and not better adherence to guidelines could explain the higher neoplasia prevalence in Barrett’s oesophagus at hospital centres. Despite a generally poor adherence to guidelines, most neoplasias found were at an early and potentially curable stage. 相似文献