Glucocorticoids down-regulate dendritic cell function in vitro and in vivo

Exogenous glucocorticoid hormones are widely used as therapeutical agents, whereas endogenous glucocorticoids may act as physiological immunosuppressants involved in the control of immune and inflammatory responses. The optimal activation of T lymphocytes requires two distinct signals: the major histocompatibility complex-restricted presentation of the antigen and an additional co-stimulatory signal provided by the antigen-presenting cells. There is ample evidence that, among the cells able to present the antigen, the dendritic cells (DC) have the unique property to activate antigen-specific, naive T cells in vitro and in vivo, and are therefore required for the induction of primary immune responses. In this work, we tested whether glucocorticoids affected the capacity of DC to sensitize naive T cells. Our data show that, in vitro, the steroid hormone analog dexamethasone (Dex) affects the viability of DC, selectively downregulates the expression of co-stimulatory molecules on viable DC, and strongly reduces their immunostimulatory properties. In vivo, a single injection of Dex results in impaired antigen presenting function, a finding which correlates with reduced numbers of splenic DC. These results show that glucocorticoids regulate DC maturation and immune function in vitro and in vivo and suggest that this mechanism may play a role in preventing overstimulation of the immune system.     

Energy cost of running during a specific transition in duathlon]

The aim of the present study was to investigate the variability of the energy cost of running (Cr) during a simulated duathlon performed in outdoor conditions by elite duathletes. This duathlon consisted of 5 km of running, 30 km of cycling, and 5 km of running. The main result was the lack of significant difference in Cr between the two running bouts (210 +/- 10 mL d'O2.km-1.kg-1 vs. 217 +/- 10 mL d'O2.km-1.kg-1). This result is different from those observed during a triathlon, where an increase of energy cost of running bout has been reported. Furthermore, during a short-distance duathlon performed by well-trained subjects, none of the physiological (ventilation alteration, metabolic changes, or dehydration) or biomechanical factors that are classically evoked in triathlon research to explain Cr variability seem to be affected by the run-cycle-run transition. These results seem to minimize the negative effect of the cycle-to-run transition during a short-duration event in well-trained subjects.     

Differential histochemical peanut agglutinin stain in benign and malignant human prostate tumors: Relationship with prostatic specific antigen immunostain and nuclear DNA content

The histochemical binding pattern of the peanut (Arachis hypogaea) lectin (PNA) was quantitatively described by means of computer-assisted microscope analysis in 28 benign prostatic hyperplasias (BPH), 15 prostatic intraepithelial neoplasias (PIN), and 119 prostatic adenocarcinomas. PNA exhibits noninunune but selective binding to glycoproteins with β-D-galactosyl(1,3)-N-acetyl-D-galactosamine residues. We also investigated whether a relationship existed between the number of histochemical-related PNA acceptors and the histochemical prostate-specific antigen (PSA) stain intensity, and between the number of PNA receptors and DNA ploidy level. The results show that neoplastic prostate tissues and high-grade intraepithelial prostatic neoplasias (PIN2_3) exhibit a significantly higher number of PNA acceptors than benign prostatic hyperplasias and low (PIN1) grade prostatic intraepithelial neoplasias. A statistically significant correlation was observed between the number of histochemically related PNA acceptors and PSA immunostain intensity. Lastly, diploid prostatic tumors, whether benign or malignant, exhibited a significantly higher number of PNA acceptors than aneuploid ones. These results suggest that PNA acceptors play an important role in the biology of prostate tumors.     

Widespread lipoplex-mediated gene transfer to vascular endothelial cells and hemangioblasts in the vertebrate embryo.

We report here a method that allows fast, efficient, and low-cost screening for gene function in the vascular system of the vertebrate embryo. Through intracardiac delivery of nucleic acids optimally compacted by a specific cationic lipid, we are able to induce in vivo endothelial cell-specific gain-of-function during development of the vascular network in the chick embryo. When the nucleic acids are delivered during the period of intraembryonic hematopoiesis, aortic hemangioblasts, the forerunners of the hematopoietic stem cells known to derive from the aortic endothelium, are also labeled. Similarly, we show that siRNA could be used to induce loss-of-function in vascular endothelial cells. This gene transfer technique was also applied to the mouse embryo with a high efficiency. The present method allows large-scale analysis and may represent a new and versatile tool for functional genomics.     

Estimation of the parameters of the relationship between power and time to exhaustion from a single ramp test.

This study aimed to estimate the power/time relationship from a single ramp test (RT) assuming critical power (Pc) from ventilatory threshold (VT) and energy reserve (W') from total work during RT These estimates from single RT were compared to those from a series of 4 constant power exercises (CPT) and from a series of 4 RT. Only W' from CPT was higher than from the series of RT and from single RT using VT (p < 0.05).     

Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families

Chronic distal spinal muscular atrophy (Chronic DSMA, MIM (*)607088) is a rare autosomal recessive disorder characterized by a progressive motor weakness and muscular atrophy, predominating in the distal parts of the limbs. A form of Chronic DSMA gene has been previously mapped to chromosome 11q13 in the 10.3 cM interval defined by loci D11S1889 and D11S1321. By linkage analysis in 12 European Chronic DSMA families, we showed that a disease gene maps to chromosome 11q13.3 (Z(max)=6.66 at theta=0.00 at the DSM4 locus) and suggested that this condition is genetically homogeneous. Recombination events allowed us to reduce the genetic interval to a 2.6 cM region, telomeric to the IGHMBP2 gene, excluding this gene as the disease causing gene in Chronic DSMA. Moreover, partial linkage disequilibrium was found between three rare alleles at loci D11S1369, DSM4 and D11S4184 and the mutant chromosome in European patients. Analysis of the markers at these loci strongly suggests that most Chronic DSMA chromosomes are derived from a single ancestor. Refinement of the Chronic DSMA locus will hopefully allow to test candidate genes and lead to identification of the disease-causing mutations.     

Arrhythmogenic right ventricular cardiomyopathy versus fatty replacement of the right ventricle. An autopsy case report

We report an autopsy case of a cardiomyopathy characterized by fatty replacement of the right ventricular myocardium and compare its clinical and histologic characteristics with those of the arrhythmogenic right ventricular cardiomyopathy. A 39-year old male died suddenly in a hospital room. He had an alcoholic cirrhosis with ascitis, but the clinical examination and the biology showed no abnormalities explaining the death. Histologically, in the right ventricle, large areas of cardiomyocytes were replaced by fat, but there was no fibrosis. In contrast, fibrosis is present in association with fat in arrhythmogenic right ventricular cardiomyopathy. Fatty replacement of the right ventricle is likely to be a distinct entity. Right ventricular failure has been shown to be a possible complication. Sudden death is probably rare and is likely to occur when other arrhythmogenic factors are associated.     

Effects of swimming with a wet suit on energy expenditure during subsequent cycling.]

The aim of this study was to investigate the effects of swimming with a wetsuit on energy expenditure during subsequent cycling. Nine well-trained triathletes underwent three submaximal trials. The first trial (SC) consisted of a 750-m swim realised at a competition pace, followed by a 10-min cycling exercise at a power output corresponding to the ventilatory threshold . The two other trials were composed of the same cycling exercise, preceded either by a 750-m swim with a wetsuit (WSC) or by a cycling warm-up (Ctrl). The main results are that the WSC trial was characterised by significantly lower swimming cadence (-14%), heart rate (-11%), and lactate values (-47%) compared to the SC trial, p < 0.05. Moreover, cycling efficiency was significantly higher in the WSC trial compared to the SC trial (12.1% difference, p < 0.05). The lower relative intensity observed during swimming with a wetsuit suggest the relative importance of swimming condition on the total performance in a sprint triathlon.