Sex/gender bias in the management of chest pain in ambulatory care.

Cardiovascular diseases (CVD) are the main cause of death worldwide and despite a higher prevalence in men, mortality from CVD is higher among women. Few studies have assessed sex differences in chest pain management in ambulatory care. The objective of this post hoc analysis of data from a prospective cohort study was to assess sex differences in the management of chest pain in ambulatory care. We used data from the Thoracic Pain in Community cohort study that was realized in 58 primary care practices and one university ambulatory clinic in Switzerland. In total, 672 consecutive patients aged over 16 years attending a primary care practice or ambulatory care clinic with a complaint of chest pain were included between February and June 2001. Their mean age was 55.2 years and 52.5% were women. The main outcome was the proportion of patients referred to a cardiologist at 12 months follow-up. A panel of primary care physicians assessed the final diagnosis retained for chest pain at 12 months. The prevalence of chest pain of cardiovascular origin (n = 108, 16.1%) was similar for men and women (17.5% vs 14.8%, respectively, p = 0.4). Men with chest pain were 2.5 times more likely to be referred to a cardiologist than women (16.6% vs 7.4%, odds ratio: 2.49, 95% confidence interval: 1.52-4.09). After adjustment for the patients' age and cardiovascular disease risk factors, the estimates did not significantly change (odds ratio: 2.30, 95% confidence interval: 1.30-3.78). Although the same proportion of women and men present with a chest pain of cardiovascular origin in ambulatory care, there is a strong sex bias in their management. These data suggest that effort must be made to assure equity between men and women in medical care

Oocyte expression with injection of purified T7 RNA polymerase.

International audienceThe Xenopus oocyte is a widely used system for protein expression. Investigators have had the choice between two different techniques: injection into the cytoplasm of in vitro transcribed complementary RNA (cRNA) or injection into the nucleus of complementary DNA (cDNA). We report on a third expression technique that is based on the combined injection of cDNA and purified T7 RNA polymerase directly into the cytoplasm of oocytes

The Protease Inhibitor Alpha-2-Macroglobuline-Like-1 Is the p170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human

Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained unknown

Smoking offsets the metabolic benefits of parental longevity in women : the CoLaus study

Rapport de synthèse : Objectif: nous avons regardé si les sujets dont les parents vivaient plus longtemps présentaient des niveaux plus faibles de facteurs de risques cardiovasculaires, y compris pour le syndrome métabolique. Méthodes: nous avons analysé les données d'un échantillon représentatif de la population suisse (1163 hommes et 1398 femmes) âgé de 55 à 75 ans, de la ville de Lausanne. Les participants ont été stratifiés par nombre de parents (0, 1, 2) qui ont vécu jusqu'à 85 ans ou plus. Les associations entre la longévité parentale et les facteurs de risques cardiovasculaires ou les variables métaboliques associées ont été analysées au moyen de régressions linéaires multiples. Résultats: la prévalence ajustée pour l'âge du syndrome métabolique varie de 24.8%, 20.5% à 13.8% chez les femmes (P<0.05) et de 28.8%, 32.1 % à 27.6% chez les hommes (non significatif) pour 0, 1 et 2 parents à forte longévité. L'association entre la longévité parentale et la prévalence du syndrome métabolique est particulièrement forte pour les femmes qui n'ont jamais fumé. Dans ce groupe, les femmes qui ont 2 parents à forte longévité ont un BMI plus faible et un tour de taille moins grand. Chez les gens qui n'ont jamais fumé, pour les deux sexes, les niveaux moyens (95% d'intervalle de confiance) et ajustés de cholestéro-HDL étaient de 1.64(1.61-1.67), 1.67(1.65-1.70) et 1.71(1.65-1.76) mmol/L pour 0, 1 et 2 parents à forte longévité (P<0.01), respectivement. La tendance n'était pas significative chez les anciens fiuneurs et fumeurs actuels. Conclusions: la longévité parentale est associée à un meilleur profil métabolique chez les femmes, mais pas chez les hommes. Les avantages métaboliques du fait d'avoir des parents âgés sont fortement atténués par le tabagisme

Role of glycosylation and disulfide bond formation in the beta subunit in the folding and functional expression of Na,K-ATPase

Initial folding is a prerequisite for subunit assembly in oligomeric proteins. In this study, we have compared the role of co-translational modifications in the acquisition of an assembly-competent conformation of the beta subunit, the assembly of which is required for the structural and functional maturation of the catalytic Na,K-ATPase alpha subunit. Cysteine or asparagine residues implicated in disulfide bond formation or N-glycosylation, respectively, in the Xenopus beta1 subunit were eliminated by site-directed mutagenesis, and the assembly efficiency of the mutants and the functional expression of Na+,K+ pumps were studied after expression in Xenopus oocytes. Our results show that lack of each one of the two most C-terminal disulfide bonds indeed permits short term but completely abolishes long term assembly of the beta subunit. On the other hand, lack of the most N-terminal disulfide bonds allows the expression of a small number of functional Na+,K+ pumps at the cell surface. Elimination of all three but not of one or two glycosylation sites produces beta subunits that remain stably expressed in the endoplasmic reticulum, in association with binding protein but not as irreversible aggregates. The assembly efficiency of nonglycosylated beta subunits is decreased but a reduced number of functional Na+,K+ pumps is expressed at the cell surface. The lack of sugars does not influence the apparent K+ or ouabain affinity of the Na+,K+ pumps. Thus, these data show that disulfide bond formation and N-glycosylation may play important but qualitatively distinct roles in the initial folding of oligomeric protein subunits. Moreover, the results suggest that an endoplasmic reticulum degradation pathway exists, which is glycosylation-dependent

Hydrophobic C-terminal amino acids in the beta-subunit are involved in assembly with the alpha-subunit of Na,K-ATPase

To define the structural basis of oligomerization for the alpha- and beta-subunits of Na,K-ATPase, we have attempted to identify the amino acids in the C-terminus of the beta-subunit that are involved in subunit assembly. We predicted that the last 10 amino acids form a beta-strand-like structure exposing on one side a hydrophilic and on the other side a continuous hydrophobic domain. The relative importance of the two domains in assembly was probed by introducing point mutations in either domain of Xenopus beta 3-subunits and by testing the ability of these mutants to stabilize newly synthesized alpha-subunits expressed in Xenopus oocytes and to form functional alpha-beta complexes at the plasma membrane. All single and double mutants with changes at R268 and/or K272 to either uncharged or negatively charged amino acids associated with coexpressed alpha-subunits and increased the number of ouabain binding sites and Rb uptake into oocytes. On the other hand, mutations affecting the hydrophobic amino acids influenced the assembly efficiency with alpha-subunits to a variable extent. The single mutants V269N and I275N did not influence and the mutant V273N slightly affected the assembly process. On the other hand, the cellular accumulation of alpha-subunits and the expression of functional Na,K pumps was considerably reduced with the mutant F271N and totally abolished with the double mutant V269N/F271N. Finally, replacement of V269 and F271 or V273 and I275 with the less hydrophobic alanine also significantly decreased subunit assembly, which was no longer detectable after replacement of all four amino acids.(ABSTRACT TRUNCATED AT 250 WORDS