Increased frequency of HLA-A1 and -B8 in association with total lack, but not with deficiency of serum IgA

HLA-A, B, C typing was performed on 37 unrelated healthy blood donors with selective deficiency (<0.05 g/l) or total lack (<0.00002 g/l) of serum IgA. A significant increase in HLA-B8 and A1 antigen frequency was found in the 15 individuals with lack of serum IgA. This was not observed among those 22, who had only deficiency of serum IgA (0.00002–0.05 g/l). The HLA antigen frequencies were compared to those of 900 randomly selected healthy blood donors.
Increased frequency of HLA-A1 and B8 in association with total lack of serum IgA, but not with deficiency has not been demonstrated before. On the basis of this result it seems conceivable that lack of serum IgA may be caused by a different, perhaps genetically determined, mechanism that IgA deficiency.     

Association Between Cardiorespiratory Fitness and Risk of Heart Failure: A Meta-Analysis

BackgroundEvidence emerges that cardiorespiratory fitness (CRF) might be implicated in the development of heart failure (HF). This meta-analysis aimed to quantify the association between CRF exposed at baseline and HF risk with dose–response analysis and to assess whether CRF changes over time are correlated with alterations in HF risk.Methods and ResultsCohort studies that assessed the association between CRF and risk of HF in subjects without baseline HF were included. Study-specific multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Ten studies from 8 articles were included, enrolling 8987 incident HF cases from 154,598 participants. The RR of HF per 1-metabolic equivalent (MET) higher CRF at baseline was 0.82 (95% CI 0.80–0.84) in the overall population. The RRs were similar in men (0.82, 95% CI 0.80–0.85) and women (0.81, 95% CI 0.78–0.84), and remained minorly changed in patients with existing diabetes, hypertension, or cardiovascular disease at entry. No evidence of a nonlinear relationship between CRF at baseline and risk of HF was observed (P_nonlinearity = .18). The RR of HF per 1-MET increase in CRF over time was 0.79 (95% CI 0.67–0.93), and the measurement of CRF provided incremental value to the prediction of HF beyond conventional models.ConclusionsHigh or increased CRF resulted in reduced risk of HF in a dose-dependent manner, supporting the necessity to increase CRF to prevent HF in clinical practice.     

Cyclic disulfide analogues of the complement component C3a Synthesis and conformational investigations

The flexible C-terminal region of the anaphylatoxic peptide C3a was reported to contain the receptor binding site. To elucidate the receptor binding conformation of the C-terminus, as well as to examine a synthetic approach to potential C3a-antagonists, 26 cyclic disulfide bridged C3a analogues were synthesized. Solid phase peptide synthesis was performed on different polymeric supports by individual peptide synthesis, with Fmoc strategy, and simultaneous multiple peptide synthesis, using Boc and Fmoc strategies. Both strategies gave open-chain peptides in comparable yields. Syntheses using the Boc strategy employed the HF-labile 4(methoxy)benzyl group (Mob) for β-thiol protection of cysteine; in contrast, the TFA-stable protecting groups, acetamidomethyl (Acm) and trityl (Trt), were chosen for syntheses employing Fmoc strategy. Ring closure reactions by iodine oxidation were carried out starting from protected (Acm/Acm, Trt/Acm) or unprotected dithiols. The resulting cyclic C3a analogues were characterized by HPLC, amino acid analysis, and FAB-MS. Conformational investigations using CD spectroscopy and theoretical structural investigations by means of molecular dynamics calculations revealed that slight variations in sequence result in pronounced conformational consequences. The potential of cyclic C3a analogues to activate or to desensitize guinea pig platelets, a standard test system for biological activities of anaphylatoxic peptides like C3a, revealed relatively low activities for cyclic peptides (<0.1% C3a activity). N-terminal acylation with cationic, arginine-rich sequences like YRRGR- led to amplified biological effects. Three of the synthesized peptides, namely CAALCLAR (P1), YRRGR°CGGLCLAR (P5) and YRRGRAhx°CGGLCLAR (P8), point in the direction of C3a antagonists.     

EXPLAINED VARIATION FOR LOGISTIC REGRESSION

Different measures of the proportion of variation in a dependent variable explained by covariates are reported by different standard programs for logistic regression. We review twelve measures that have been suggested or might be useful to measure explained variation in logistic regression models. The definitions and properties of these measures are discussed and their performance is compared in an empirical study. Two of the measures (squared Pearson correlation between the binary outcome and the predictor, and the proportional reduction of squared Pearson residuals by the use of covariates) give almost identical results, agree very well with the multiple R² of the general linear model, have an intuitively clear interpretation and perform satisfactorily in our study. For all measures the explained variation for the given sample and also the one expected in future samples can be obtained easily. For small samples an adjustment analogous to R²_adj in the general linear model is suggested. We discuss some aspects of application and recommend the routine use of a suitable measure of explained variation for logistic models.     

Cryotherapy for lentigo maligna

Eleven patients, 10 with lentigo maligna (LM) and one with lentigo maligna melanoma (LMM), were treated with cryotherapy. The symptoms cleared in all patients except one with LM. There were recurrences in four patients and three cleared with further treatment.