Retinoids induce Fas(CD95) ligand cell surface expression via RARgamma and nur77 in T cells

Cells from the CD4+ murine T hybridoma line IP-12-7 enter the apoptotic suicide program via the Fas ligand (FasL)/Fas-mediated pathway upon TCR stimulation. This stimulus regulates the sensitization of the Fas death pathway and the cell surface appearance of preformed FasL. The apoptosis is dependent on new mRNA and protein synthesis and involves up-regulation of nur77.Two groups of nuclear receptors for retinoic acids (RA) have been identified: retinoic acid receptors (RAR) and retinoid X receptors. IP-12-7 cells express RARalpha and RARgamma. Here we show that,in the IP-12-7 T cells, RA also induced the expression and DNA binding of nur77, and the cell surface appearance of FasL. The induction was mediated via RARgamma. Despite the induced expression of cell surface FasL, only two structurally related RARgamma-selective compounds, CD437 and CD2325, initiated apoptosis in these cells. The lack of apoptosis induction by natural RA was related to the inability of RARgamma to sensitize the Fas death-pathway. Cell surface FasL, however, was able to induce cell death in Fas-bearing target cells. Natural RA also induced the expression of FasL in phytohemagglutinin-activated peripheral murine T cells. It is proposed that therapeutically administered RA might induce apoptosis in Fas-sensitive cells via induction of FasL expression in activated Tcells.     

Identical abnormality of the short arm of chromosome 18 in two Philadelphia-positive chronic myelocytic leukemia patients with erythroblastic transformation,resulting in duplication of BCR-ABL1 fusion

Two patients with Ph-positive chronic myelocytic leukemia in erythroblastic transformation and rearrangement of the short arm of chromosome 18 are reported. Fluorescence in situ hybridization studies showed that the 18p rearrangement resulted from translocation of the main part of chromosome 22 long arm to 18p, including BCR-ABL1 fusion. The 18p abnormality resulted, thus, in loss of 18p and duplication of BCR-ABL1 in both patients. The possible relation to the erythroblastic type of blastic phase is briefly discussed. In addition an apparently intact germline ABL1 gene was duplicated and inserted into chromosome 6 at band p21 in one of these patients.     

Noninvasive fluorescent study in situ and in real time of glucose effects on the pharmacokinetic of calcein

This study was undertaken to compare the effect of glucose injection on the pharmacokinetic behavior of a soluble dye in normal and tumoral tissues. The measurements were done using a noninvasive fluorescent spectroscopy in situ and in real time. The experiments were performed on three groups of animals with calcein as a soluble pH-insensitive fluorescent dye combined or not with glucose. Glucose solution was injected 5 or 30 min before calcein. Fluorescence emission intensity was recorded on normal and tumor tissues with an optical multichannel analyzer. Calcein concentration was also measured in blood using repetitive blood sampling. In the control group (without glucose injection), calcein is rapidly cleared from the blood, with a slow tissue clearance. Fluorescence of normal tissue was higher than fluorescence measured in tumor tissue. When glucose is injected 5 min before calcein, there was a rapid increase of tissue fluorescence followed by a plateau remaining during the whole experiment. No difference between tumor and normal tissue fluorescence intensity was observed. When glucose was injected 30 min before calcein, the plateau phase was reduced to 50 min in normal tissue. Tumor tissue fluorescence displays no distinct plateau phase. These results clearly showed the effect of glucose injection in situ and in real time, by a noninvasive method, on the pharmacokinetic of a soluble dye in a tumor tissue compared to a normal tissue. Differences between blood compartment and tissues kinetic profiles were also clearly demonstrated.     

Pre- and postnatal depression and coping: a comparative approach

BACKGROUND: The assessment of perinatal depressions and coping style. Methods: With depression scales (EPDS, GHQ.12) and Carver's BriefCope, the authors compared the prevalence rates of pre and postnatal depression in a cohort of 277 French women. RESULTS: Their work revealed very high levels of prenatal depression (almost 20%) and less important but nonetheless sizeable rates (11%) of postnatal depression, making such perinatal depressions a major public health concern. The coping styles proposed in Carver's public health BriefCope questionnaire make it possible to significantly differentiate during these two periods between depressive women and their non-depressed counterparts. CONCLUSIONS: This enables us to underline factors of risk and protection suggesting the importance of setting up compensatory and preventive systems and evaluating their pertinence in the framework of future research.     

Transvaginal sonography and rectal endoscopic sonography for the assessment of pelvic endometriosis: a preliminary comparison

BACKGROUND: Endometriosis and possible rectal involvement are difficult to assess by physical examination. Previous studies have shown the diagnostic value of magnetic resonance imaging and rectal endoscopic sonography (RES) in this setting, but not that of transvaginal sonography (TVS). The aims of this study were to compare the accuracy of TVS and RES for the diagnosis of pelvic endometriosis, and to compare the results with histological findings. PATIENTS AND METHODS: In a prospective study, 30 consecutive patients referred with clinical signs of endometriosis underwent TVS and RES; the images were interpreted blindly with regard to physical findings. RESULTS: Endometriosis was confirmed histologically in 28 (93%) of the 30 patients. Endometriomas were also present in 67% of cases. For the diagnosis of uterosacral endometriosis, the sensitivity, specificity, and positive and negative predictive values of TVS and RES were 75 and 75%, 83 and 67, 95 and 90%, and 45 and 40% respectively. For the diagnosis of rectosigmoid endometriosis, the sensitivity, specificity, and positive and negative predictive values of TVS and RES were 95 and 82%, 100 and 88%, 100 and 95%, and 89 and 64% respectively. CONCLUSION: Despite the large proportion of our patients who had intestinal endometriosis, representing a possible source of bias, our results suggest that TVS is as efficient as RES for detecting posterior pelvic endometriosis and should therefore be used as the first-line examination.     

Nitric oxide inhibits cysteine proteinases and alcohol dehydrogenase 2 of Entamoeba histolytica

Nitric oxide is involved in the neutrophil and macrophage killing of the protozoan parasite Entamoeba histolytica. In the present study, we found that cysteine proteinases, significant contributors to amebic virulence and alcohol dehydrogenase 2, an enzyme absolutely required for the survival of the parasite, are both significantly inhibited by S-nitroso-glutathione, a physiological nitric oxide donor, within the concentration range 0.5-2.0 m M.     

Linkage disequilibrium analysis of childhood-onset spinal muscular atrophy (SMA) in the French -- Canadian population

Spinal muscular atrophy (SMA) is, after Duchenne muscular dystrophy,the most common neuromuscular disorder in childhood. The generesponsible for childhood SMA has been mapped to the q11. 2– q13. 3 region of chromosome 5. We have extended ourlinkage studies of SMA In the French - Canadian population toInclude microsatellite markers at the D5S125, D5S351, D5S435,JK53CA1/ 2 and MAPI B locl. These markers span about 4 cM ofthe SMA candidate region. We observed significant evidence forlinkage between SMA and all the markers tested. The analysisof recombinant chromosomes provide evidence for the followinggenetic order: D5S125-D5S435-MAP1B-3'-JK53CA1/2 and places D5S351proximal to JK53CA1/2. Furthermore, we confirm the current localizationof the SMA gene distal to D5S435. Finally, we provide demonstrationof significant linkage disequilibrium between childhood-onsetSMA and four of the five marker loci, D5S125, D5S435, D5S351and JK53CA1/2. Analysis of SMA-region haplotypes suggests thatthere may be a predominant SMA allele that is present on about17% of SMA chromosomes in this sample of the French - Canadianpopulation. We conclude that the observed linkage disequilibriumis likely due to genetic drift among regions of Quebec, consistentwith this population's early history.     

High-intensity intermittent running training improves pulmonary function and alters exercise breathing pattern in children

We investigated the effects of short duration running training on resting and exercise lung function in healthy prepubescent children. One trained group (TrG) (n = 9; three girls and six boys; age = 9.7 ± 0.9 year) participated in 8 weeks of high-intensity intermittent running training and was compared to a control group (ContG) (n = 9; four girls and five boys; age = 10.3 ± 0.7 year). Before and after the 8-week period, the children performed pulmonary function tests and an incremental exercise test on a cycle ergometer. After the 8-week period, no change was found in pulmonary function in ContG. Conversely, an increase in forced vital capacity (FVC) (+7 ± 4% ; P = 0.026), forced expiratory volume in one second (+11 ± 6% ; P = 0.025), peak expiratory flows (+17 ± 4% ; P = 0.005), maximal expiratory flows at 50% (+16 ± 10% ; P = 0.019) and 75% (+15 ± 8% ; P = 0.006) of FVC were reported in TrG. At peak exercise, TrG displayed higher values of peak oxygen consumption (+15 ± 4% ; P<0.001), minute ventilation (+16 ± 5% ; P = 0.033) and tidal volume (+15 ± 5% ; P = 0.019) after training. At sub-maximal exercise, ventilatory response to exercise was lower (P = 0.017) in TrG after training, associated with reduced end-tidal partial oxygen pressure (P<0.05) and higher end-tidal partial carbon dioxide pressure (P = 0.026). Lower deadspace volume relative to tidal volume was found at each stage of exercise in TrG after training (P<0.05). Eight weeks of high-intensity intermittent running training enhanced resting pulmonary function and led to deeper exercise ventilation reflecting a better effectiveness in prepubescent children.     

A new species of the medicinal leech (Oligochaeta, Hirudinida, Hirudo) from Transcaucasia and an identification key for the genus Hirudo

A recent molecular phylogenetic study has suggested that the genus Hirudo contains a neglected species previously known as the orientalis coloration type of the medicinal leech Hirudo medicinalis. In this paper, the new species is formally described as Hirudo orientalis sp. n. It can most readily be identified by the grass green coloration of the dorsum, segmentally arranged pairs of black quadrangular or rounded dots on its paramarginal dorsal stripes and similarly arranged, but less regular light-colored markings on the predominantly black venter. It has medium-sized epididymes and an evenly coiled vagina. H. orientalis is known from Transcaucasia, Iran, and Uzbekistan. It is widely used in medicine as the “medicinal leech.” Very little is known about its exact distribution, specific habitat, and conservation status. The paper contains an identification key to all species of the genus Hirudo.     

Optimal detection of the progression of coronary artery disease: comparison of methods suitable for risk factor intervention trials

To assess the best method of quantitating progression of coronary disease, we studied four measurements in 114 coronary segments from 35 medically treated patients from whom angiograms were obtained 5 years apart. Only stenoses of less than 70% that were visualized in nearly identical projections on both angiograms were evaluated. Vessel edges were measured by use of catheter calibration and an automated computer algorithm yielding two "absolute dimensions" (mean and minimum diameters) and two measurements (percent stenosis and atheroma area) that required a "normal reference" diameter. The coefficient of variation for repeated segment measurements was less for mean and minimum diameter than for percent stenosis and area of atheroma. The best measure of progression of coronary disease as determined by t test comparison of different methods was the change in mean diameter over time (6.7 +/- 14.1% decrease), whether calculated on a per coronary segment or per patient basis (p less than .001). Based on this measurement and its standard deviation of progression of coronary disease in this patient subset with relatively benign disease, it is estimated that 470 patients per group would be required for an interventional study to demonstrate a 33% reduction in disease progression (207 patients for 50% reduction) at a 95% confidence level and 90% power.