Genome-Wide Scan on Total Serum IgE Levels Identifies FCER1A as Novel Susceptibility Locus

High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85×10−20 and 7.08×10−19 in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78×10−4 and P = 1.95×10−3). The “top” SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28×10−7−4.46×10−8) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels

Preparation of an affinity chromatographic system for the separation of ADP binding proteins

[4-(3-Bromoacetylpyridinio)-butyl]adenosine pyrophosphate as a structural analog of NAD+ reacts covalently with the sulfhydryl groups of thiopropyl agarose. 10-20 μmol can be bound to 1 ml gel. Stabilization of the insoluble coenzym e is attained by treatment with sodium boro hydride (NaBH4). This complex when applied to column chromatography, allow s the separation of various dehydrogenases as a result of their different complex stability coefficients. Alcohol dehydrogenase from liver, lactate dehydrogenase, and adenylate kinase, which all bind to the ADP-analog residues of the gel matrix, can thus be separated by different salt gradients. Alcohol dehydrogenase from yeast, however, does not form a complex and can easily be eluted from the column with phosphate buffer. Glyceraldehyde-3 phosphate and aldehyde dehydrogenases can be eluted by the addition of NAD+ or NADH to the buffer. The uncharged 1,4-dihydropyridin ring of the reduced coenzyme produces a more stable complex with the dehydrogenases than the oxidized form

Comparison of methods for measuring atmospheric deposition of arsenic, cadmium, nickel and lead

International audienc

Estimating the Fraction of First-Year Hemodialysis Deaths Attributable to Potentially Modifiable Risk Factors: Results from the DOPPS.

PURPOSE: Mortality among first-year hemodialysis (HD) patients remains unacceptably high. To address this problem, we estimate the proportions of early HD deaths that are potentially preventable by modifying known risk factors. METHODS: We included 15,891 HD patients (within 60 days of starting HD) from 21 countries in the Dialysis Outcomes and Practice Patterns Study (1996-2015), a prospective cohort study. Using Cox regression adjusted for potential confounders, we estimated the fraction of first-year deaths attributable to one or more of twelve modifiable risk factors (the population attributable fraction, AF) identified from the published literature by comparing predicted survival based on risk factors observed vs counterfactually set to reference levels. RESULTS: The highest AFs were for catheter use (22%), albumin 10,000/μL. AFs for ferritin, calcium, and PTH were 10 mg/L was 21% in facilities where it was routinely measured. CONCLUSION: A substantial proportion of first-year HD deaths could be prevented by successfully modifying a few risk factors. Highest priorities should be decreasing catheter use and limiting malnutrition/inflammation whenever possible

Estimating the fraction of first-year hemodialysis deaths attribuable to potentially modifiable risk factors: results from the DOPPS

Diffusé sur CD-RO

Dermal and pulmonary absorption of propan-1-ol and propan-2-ol from hand rubs.

International audienceBACKGROUND: It has been shown that nontoxic concentrations of ethanol are absorbed after hand hygiene using ethanol-based hand rubs. This study investigated whether absorption of propan-1-ol and propan-2-ol from commercially available hand rubs results in measurable concentrations after use. METHODS: The pulmonary and dermal absorption of propanol during hand rubs was investigated. Rubs contained 70% (w/w) propan-1-ol, 63.14% (w/w) propan-2-ol, or 45% (w/w) propan-2-ol in combination with 30% (w/w) propan-1-ol. RESULTS: Peak median blood levels were 9.15 mg/L for propan-1-ol and 5.3 mg/L for propan-2-ol after hygienic hand rubs and 18.0 mg/L and 10.0 mg/L, respectively, after surgical hand rubs. Under actual surgical conditions, the highest median blood levels were 4.08 mg/L for propan-1-ol and 2.56 mg/L for propan-2-ol. The same procedure performed with prevention of pulmonary exposure through the use of a gas-tight mask resulted in peak median blood levels of 1.16 mg/L of propan-1-ol and 1.74 mg/L of propan-2-ol. CONCLUSION: Only minimal amounts of propanols are absorbed through the use of hand rubs. Based on our experimental data, the risk of chronic systemic toxic effects caused by hand rubs is likely negligible. However, our study did not evaluate the consequences of long-term daily and frequent use of hygienic hand rubs

The german AD Registry Treatgermany: Results from an interim data analysis on baseline charesteristics, comorbidities and treatment history

Heratizadeh A, Haufe E, Stoelzl D, et al. The german AD Registry Treatgermany: Results from an interim data analysis on baseline charesteristics, comorbidities and treatment history. In: ABSTRACTS from 11 th George Rajka International Symposium on Atopic Dermatitis April 19–20, 2021 Seoul, Korea. Acta Dermato-Venereologica. Vol 101. Uppsala: Society for Publication of Acta Dermato-Venereologica ; 2021: 24-25