Immunologically silent autochthonous acute hepatitis E virus infection in France

Hepatitis E is an acute and self-limiting hepatitis, and the causative agent, hepatitis E virus, is excreted in feces and orally transmitted. The disease is common in Asia and Africa, causing outbreaks or sporadic cases. In Europe, the infection is generally observed after a history of travel in an area of endemicity. We report on an autochthonous case in southwestern France in which the diagnosis was based on molecular tools rather than serological testing.     

Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defenses in that illness

OBJECTIVE: Major depression is associated with defective antioxidant defenses. Vitamin E is the major fat soluble antioxidant in the body. The aim of the present study is to examine serum vitamin E concentrations in major depressed patients versus normal volunteers. METHOD: Serum vitamin E concentrations were measured in 26 healthy volunteers and 42 major depressed patients by means of HPLC. Since vitamin E is a fat soluble vitamin, and serum vitamin E concentrations are strongly related to these of low-density-lipoprotein cholesterol (LDL-C) and triglycerides, we have adjusted the results for possible differences in these lipids. The numbers of peripheral blood leukocytes were measured. RESULTS: Patients with major depression had significantly lower serum vitamin E concentrations than healthy controls. The area under the ROC (receiver operating characteristics) curve was 83%. There were significant and negative correlations between serum vitamin E and number of total leukocytes and neutrophils. CONCLUSIONS: Major depression is accompanied by significantly lower serum vitamin E concentrations, suggesting lower antioxidant defenses against lipid peroxidation. The results could, in part, explain previous findings, which suggest increased lipid peroxidation in major depression.     

Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial

BACKGROUND: DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. PATIENTS AND METHODS: Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 x 1014 molecules) or peptides (10 versus 100 mug/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. RESULTS: The GMP process allowed to harvest about 5 x 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. CONCLUSION: The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration.     

Monosomy 9q and trisomy 16q in a case of congenital solitary infantile myofibromatosis

Although infantile myofibromatosis (IM) is the most common fibrous proliferation of infancy, many aspects of this benign lesion have not been explored. IM histogenesis is still poorly understood, despite immunohistochemical staining and ultrastructural features that suggest a myofibroblastic origin. IM diagnosis is often made difficult by the predominance of small primitive spindle cells over myofibrobasts and the presence of intravascular growth. Genetic information is scarce, with only one karyotyped case. Here we describe a case of solitary IM discovered at birth in an otherwise healthy girl. The tumor was well circumscribed, arranged in nodules and made up of ovoid cells without atypia, in a myxoid background. Immunohistochemical evaluation indicated a myofibroblastic differentiation. The cytogenetic and fluorescence in situ hybridization analyses revealed an abnormal chromosome 9, derived from an unbalanced whole-arm translocation between chromosomes 9 and 16. On both chromosomes, the breakpoints were located in the pericentric heterochromatic region. This clonal abnormality has not been reported in other tumors and is different from the chromosome 6q deletion reported in the single previous reported IM karyotype.     

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.     

Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia

The present study was designed to assess the effects of dietary leucine supplementation on muscle protein synthesis and whole body protein kinetics in elderly individuals. Twenty healthy male subjects (70 ± 1 years) were studied before and after continuous ingestion of a complete balanced diet supplemented or not with leucine. A primed (3.6 μmol kg⁻¹) constant infusion (0.06 μmol kg⁻¹ min⁻¹) of l -[1-¹³C]phenylalanine was used to determine whole body phenylalanine kinetics as well as fractional synthesis rate (FSR) in the myofibrillar fraction of muscle proteins from vastus lateralis biopsies. Whole body protein kinetics were not affected by leucine supplementation. In contrast, muscle FSR, measured over the 5-h period of feeding, was significantly greater in the volunteers given the leucine-supplemented meals compared with the control group (0.083 ± 0.008 versus 0.053 ± 0.009% h⁻¹, respectively, P < 0.05). This effect was due only to increased leucine availability because only plasma free leucine concentration significantly differed between the control and leucine-supplemented groups. We conclude that leucine supplementation during feeding improves muscle protein synthesis in the elderly independently of an overall increase of other amino acids. Whether increasing leucine intake in old people may limit muscle protein loss during ageing remains to be determined.     

Estimating relative physical workload using heart rate monitoring: a validation by whole-body indirect calorimetry

Measuring physical workload in occupational medicine is fundamental for risk prevention. An indirect measurement of total and relative energy expenditure (EE) from heart rate (HR) is widely used but it has never been validated. The aim of this study was to validate this HR-estimated energy expenditure (HREEE) method against whole-body indirect calorimetry. Twenty-four-hour HR and EE values were recorded continuously in a calorimetric chambers for 52 adult males and females (19–65 years). An 8-h working period was retained, comprising several exercise sessions on a cycloergometer at intensities up to 65% of the peak rate of oxygen uptake. HREEE was calculated with reference to cardiac reserve. A corrected HREEE (CHREEE) was also calculated with a modification to the lowest value of cardiac reserve. Both values were further compared to established methods: the flex-HR method, and the use of a 3rd order polynomial relationship to estimate total and relative EE. No significant difference was found in total EE when measured in a calorimetric chamber or estimated from CHREEE for the working period. A perfect linear and identity relationship was found between CHREEE and energy reserve values for intensities ranging from 15% to 65%. Relative physical workload can be accurately assessed from HR recordings when expressed in CHREEE between 15% to 65%, and EE can be accurately estimated using the CHREEE method.