Hepatitis E in the south west of France in individuals who have never visited an endemic area

A total of 431 consecutive patients from the Midi Pyrenees area with acute hepatitis with unknown etiology in 2001-2002 were tested for the presence of immunoglobulin G-class (IgG) anti-hepatitis E virus (HEV) antibodies. Forty-six (10.7%) had anti-HEV IgG, and the results were questionable for a further 17 (3.9%). Real time PCR based on TaqMan detection was used to identify HEV genome fragments in the serum of patients with positive or questionable anti-HEV serology. HEV RNA was found in 25.4% of cases. All amplification products were sequenced and analyzed. Phylogenetic analysis revealed that all the strains were genotype 3. In conclusion, virological and epidemiological data indicate that genotype 3 viruses are circulating in the south west part of France (Midi-Pyrenees) in patients with acute hepatitis and who have not visited recently areas in which HEV is endemic.     

Location and morphology of chloride cells during the post-embryonic development of the european sea bass,Dicentrarchus labrax

Location and morphology of chloride cells were studied in the sea bass ( Dicentrarchus labrax) from hatching to the juvenile stage to determine the development of the adult osmoregulatory function as seen in adult fish. During the studied developmental sequence changes were observed in the location, number, size and structure of these cells, that were studied by microscopy (light, scanning electron, transmission electron and confocal) and immunocytochemistry. Chloride cells were found on the tegument and on the gills. They were present on the tegument already at hatching, before the development of the gills. Their density as well as their association in multicellular complexes decreased during the postembryonic development. In old larvae and in juveniles, cutaneous chloride cells were associated with the fins, the developing scales and the lateral line. Gills developed gradually during the prelarval stage and the gill arches were present at mouth opening. At that time chloride cells were already numerous on the gill arches. In older larvae, during the progressive development of the gill filaments, chloride cells were numerous on these structures and formed multicellular complexes. Several stages in the differentiation of these cells were studied, including the development of the tubulovesicular system at the end of the prelarval stage, as well as the stratification appearance of the cytoplasm that was concomitant with the considerable development of the tubular system and its association with the endoplasmic reticulum during the larval period. The involvement of different epithelia in the osmoregulatory process during the postembryonic development of this species, as well as the role of chloride cells during successive developmental stages, is discussed.     

Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant splicing of several genes has been reported to contribute to some symptoms of DM1, but the cause of muscle weakness in DM1 and elevated Ca2+ concentrations in cultured DM muscle cells is unknown. Here, we investigated the alternative splicing of mRNAs of two major proteins of the sarcoplasmic reticulum, the ryanodine receptor 1 (RyR1) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 1 or 2. The fetal variants, ASI(-) of RyR1 which lacks residue 3481-3485, and SERCA1b which differs at the C-terminal were significantly increased in skeletal muscles from DM1 patients and the transgenic mouse model of DM1 (HSA(LR)). In addition, a novel variant of SERCA2 was significantly decreased in DM1 patients. The total amount of mRNA for RyR1, SERCA1 and SERCA2 in DM1 and the expression levels of their proteins in HSA(LR) mice were not significantly different. However, heterologous expression of ASI(-) in cultured cells showed decreased affinity for [3H]ryanodine but similar Ca2+ dependency, and decreased channel activity in single-channel recording when compared with wild-type (WT) RyR1. In support of this, RyR1-knockout myotubes expressing ASI(-) exhibited a decreased incidence of Ca2+ oscillations during caffeine exposure compared with that observed for myotubes expressing WT-RyR1. We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle.     

TRIO amplification and abundant mRNA expression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer

Studies by comparative genome hybridization have suggested that 5p amplification is related to tumor progression in urinary bladder cancer. In this study seven genes (TAS2R, ADCY2, DNAH5, CTNND2, TRIO, ANKH, and MYO10) located to 5p15.31-5p15.1 were analyzed by fluorescence in situ hybridization using a tissue microarray containing samples from tumors and cell lines with known 5p amplification by comparative genome hybridization. Amplification frequency was highest for TRIO, which maps to 5p15.2 and encodes a protein with a putative role in cell-cycle regulation. To further investigate the role of TRIO amplification in bladder cancer, a tissue microarray containing samples from 2317 bladder tumors was used for fluorescence in situ hybridization analysis. TRIO amplification was strongly associated with invasive tumor phenotype, high tumor grade, and rapid tumor cell proliferation (Ki67 LI) (P < 0.0001 each). Only 7 of 456 pTaG1/G2 tumors (1.5%) but 62 of 485 pT1-4 carcinomas (12.8%) had TRIO amplification. TRIO amplification was not associated with poor prognosis. Using a frozen bladder tumor tissue microarray RNA in situ hybridization confirmed that TRIO is up-regulated in amplified tumors. It is concluded that TRIO up-regulation through amplification has a potential role in bladder cancer progression.     

Tumor antigens and antigen-presenting capacity in breast cancer.

AIMS: Cancer cells frequently express antigens capable of being recognized by the host immune system; however, any resultant immune response is often ineffective. This may be related in part to tumor-induced defects in antigen presentation. We screened for dendritic cell infiltration, tumor MHC II expression and associated lymphocytic reaction in the context of three established breast tumor antigens. METHODS: Forty primary breast tumors were evaluated by immunohistochemical techniques for expression of her2/neu, p53, and MUC1 and MHC class II molecules. Twenty-five samples were further analyzed for p53 mutations by PCR-SSCP analysis and DNA sequencing. The phenotype of tumor-infiltrating inflammatory cells was evaluated using the following markers: CD1a, MHC Class II, CD3, CD45, and CD45RO. RESULTS: Tumors with p53 mutations and overexpression, but not her2/neu or MUC1 overexpressing tumors, more frequently harbored marked CD1a+ dendritic cell infiltrates. An overall correlation between CD1a+ cell infiltrates and HLA class II expression on tumor cells (p = 0.0008) was also observed and these tumors had greater CD45RO+ lymphocytic infiltrates. CONCLUSIONS: In breast cancer, p53 mutations may present a more visible signal to the immune system and hence provide a better target for immunotherapy. Infiltrating CD1a positive cells are associated with a more dense tumor lymphocytic infiltrate and tumor cell expression of MHC II molecules.     

Hepatitis B control in Europe by universal vaccination programmes: the situation in 2001

In the nine years since the Global Advisory Group of the Expanded Programme on Immunisation (WHO) set 1997 as the target for integrating hepatitis B vaccination into national immunisation programmes worldwide, 129 countries have included hepatitis B vaccine as part of their routine infant or adolescent immunisation programmes (June 2001). By the end of 2002, 41 out of the 51 countries of the WHO European Region will be implementing universal hepatitis B immunisation. The rewards of effective implementation of the programmes in countries that started 10 years ago are becoming apparent; and their success offers an exemplary model for other countries. Some other countries, however, have difficulties to incorporate hepatitis B vaccine into universal childhood immunisation programmes, because of major economic constrains and the inability to procure a constant vaccine supply. The next decade will be characterised by expanded use of hepatitis B vaccines and the increasing efforts to sustain vaccine programmes and make the vaccine available to those countries and regions that cannot afford it. In Europe, as well as in the rest of the world, work still remains to be done to support and implement interventions that will bring us closer to the WHO goal and to eradicate hepatitis B.     

Physical activity improves gaze and posture control in the elderly

Ageing is associated with a decrease in the quality of balance regulation, in particular through dysfunctions of gaze control and postural stabilization, which results in an increased risk of falling. Conversely, the practice of physical and sporting activities has been shown to improve every level of postural regulation. This study is to assess the effects of the practice of physical activities on vestibulospinal reflex and ocular movements of visual and vestibular origins in elderly people. Gaze control and posture stabilization were evaluated in 13 healthy aged women who regularly practised physical activities and in 13 healthy aged sedentary women of a similar age, by dynamic posturographic test with electromyography, as well as electronystagmography with caloric and rotational vestibular tests, ocular saccades, smooth pursuit and optokinetic tests. The gaze and posture control performance of the active group was better; the proprioceptive and vestibular sensitivities were higher, visual detection quality was good, and reaction time was low. Regular physical activity develops or maintains the efficiency of the reflexes involved in postural control, especially through adequate neurosensorial information, which allows the central integrative structures to generate a more appropriate motor response.     

In vivo efficacy of cefotaxime and amoxicillin against penicillin-susceptible, penicillin-resistant and penicillin-cephalosporin-resistant strains of Streptococcus pneumoniae in a mouse pneumonia model

Objective: To compare cefotaxime (CTX) to amoxicillin (AMO) (usually considered the definitive therapy for penicillinsusceptible Streptococcus pneumoniae infections) in an immunocompromised mouse pneumonia model.
Methods: Three S. pneumoniae clinical isolates were used: two serotype 19 strains, a penicillin-susceptible (P^s) strain (penicillin MIC = 0.03 μ/mL) and a highly penicillin-resistant (P^r) strain (penicillin MIC = 4 μ/mL), and one serotype 23F strain, a penicillin-cephalosporin-resistant (CFTR) strain (CTX MIC = 4 μ/mL).
Results: CTX activity in this mouse model of pneumonia induced by the highly penicillin-resistant strain of S. pneumoniae was lower than expected from its low MIC against this organism. Furthermore, AMO had greater efficacy than CTX against a CFTR S. pneumoniae strain.
Conclusion: Our data suggest that there is no major difference in the in vivo efficacy of the two agents, cefotaxime and amoxicillin, against penicillin-resistant and penicillin-cephalosporin-resistant S. pneumoniae.     

Quantitation of differential sensitivity of normal marrow myeloid progenitor cells to anthracene derivatives

The effect of 3 anthracene derivatives, mitoxantrone, ametantrone, bisantrene, on 4 normal human bone marrows, was studied using the myeloid stem cell assay developed by Pike and Robinson, in order to define to what extent this test could be used to predict the relative clinical hematologic toxicity of new anticancer agents. For the 3 drugs, an exponential relationship between colony survival and drug concentration was found, but was much steeper for mitoxantrone (slope = -195.2 ± 8.8/g/ml) than for ametantrone (slope = 5.1 ± 1.0/g/ml, p0.001) and bisantrene (slope = 7.1 ± 0.3/g/ml, p0.001). The difference of slope between ametantrone and bisantrene was of borderline significance (p0.05). The ratios of concentrations inducing a 50% growth inhibition for mitoxantrone versus bisantrene and for ametantrone versus bisantrene were close to the corresponding ratios of concentrations inducing a 90% growth inhibition. The relative in vitro toxicities reproduce very well the relative myelosuppression observed in clinical trials with mitoxantrone versus bisantrene but the results were less satisfactory for the comparison of these 2 agents with ametantrone. In addition, our data suggest that, for these 3 compounds, intrinsic myeloid progenitor sensitivity is a major determinant of leukopenia.