Close phenotypic and functional similarities between human and murine alphabeta T cells expressing invariant TCR alpha-chains

Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expressing V alpha14+ TCR alpha-chains with highly conserved invariant junctional sequences and able to secrete Th2 cytokines when exposed to CD1+ stimulator cells. In humans, alphabeta T cells carrying invariant V alpha24+ TCR alpha-chains highly homologous to those expressed by murine NK1.1 cells have been recently described. Here we show that these cells (referred to as V alpha24inv T cells) and murine NK1.1+ alphabeta T cells resemble each other in several ways. First, like their murine counterparts, T cells expressing high levels of V alpha24inv TCRs can be either CD4- CD8- double negative (DN) or CD4+, but they never express heterodimeric CD8 molecules. Second, most V alpha24inv T cells are brightly stained by NKRP1-specific mAb but not by mAb directed against other type II transmembrane proteins of the NK complex. Third, DN and particularly CD4+ V alpha24inv T cells are greatly enriched for IL-4 producers. The concomitant expression of highly conserved TCRs of a particular set of NK markers and of Th2 cytokines in human and murine alphabeta T cells suggests a coordinate acquisition of these phenotypic and functional properties. Furthermore, the relatively high frequency of human V alpha24inv T cells, which are presently shown to represent on average 1/500 PBL, and the high interindividual variations of the size of this cell subset under physiologic conditions go for a major role played by alphabeta T cells carrying invariant TCR in a large array of immune responses.     

Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis

Utilizing cultured lenses from normal and homozygous glutathione peroxidase (GSHPx-1) knockout mice and inhibitors for GSSG Reductase (GSSG Red), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and catalase (Cat), 3-aminotriazole (3-AT), the ability to degrade H2O2 was examined at two H2O2 concentrations, 300 microM and 80 microM. It was found that GSHPx-1 contributed about 15% to the H2O2 degradation. The Cat contribution was concentration dependent being about 30% at 300 microM H2O2 and approximately 8% to 15% at 80 microM H2O2. GSH loss measured as nonprotein thiol (NP-SH) was shown to be linked to most of the remaining H2O2 degradation accounting for about 54% to 72% of the H2O2 degradation at 300 microM and 80 microM, respectively. However, based on evaluation of the ability of GSH to nonenzymatically degrade H2O2, it can only account for about 36% at 300 microM and 19% at 80 microM H2O2 of the observed lens H2O2 degradation. It is, therefore, concluded that lens GSH must be involved in other reactions either directly or indirectly related to H2O2 degradation.     

Suburethral sling urethropexy: a vaginal approach

The present study investigated the effects of ethanol withdrawal after its chronic administration on endogenous opioid systems in the nucleus accumbens of rats. An in situ hybridization study showed an increase in the prodynorphin mRNA level at 24 and 48 h (by 189 and 146%, respectively) after ethanol withdrawal, whereas the proenkephalin mRNA level remained unchanged. Furthermore, after a 48 h withdrawal period, the level of alpha-neoendorphin (alphaNEO), a prodynorphin-derived peptide, was significantly decreased (by 48%), that effect being associated with the enhancement of the K+-stimulated release of that peptide from nucleus accumbens slices. At 96 h after ethanol withdrawal, only the basal release of alphaNEO was elevated, while other parameters returned to the control level. Our data indicate that after 48 h of ethanol withdrawal, prodynorphin neurons are highly activated. The increased supply of endogenous kappa opioid receptor agonists in the nucleus accumbens at that time may promote aversive states during ethanol withdrawal.     

Outcome of transplantation for standard-risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

One hundred and eighty-one consecutive patients with standard-risk leukaemia were transplanted with HLA-identical sibling grafts depleted of lymphocytes using counter-flow centrifugation. In 116 patients, standard conditioning was intensified by the addition of anthracyclines. Multivariate analysis revealed significantly more acute GVHD > or = grade 2 and a trend towards more chronic GVHD in patients conditioned with the addition of anthracyclines. For all patients the risk for chronic GVHD, but not for acute GVHD increased with a higher number of T cells in the graft. The projected 5-year probability of relapse was significantly lower in the group of patients conditioned with anthracyclines; 26% versus 52% (P = 0.015). In multivariate analysis the addition of anthracyclines to the conditioning regimen was the only significant factor contributing to a lower probability of relapse. The projected 5-year probability of leukaemia-free survival [LFS] in the patients conditioned with and without the addition of anthracyclines was 56% and 36%, respectively (P = 0.004). In multivariate analysis the addition of anthracyclines to the conditioning regimen correlated significantly with a lower number of mixed chimaeras in patients at 6 and 12 months after BMT. Mixed chimaerism at 6 months after transplantation did not significantly correlate with a higher incidence of relapse in further follow-up. In contrast, mixed chimaerism at 12 months after BMT was significantly associated with higher relapse rate. We conclude that the addition of anthracyclines to the conditioning regimen improves outcome of BMT using T-cell-depleted grafts.     

Monte Carlo and analytical calculation of proton pencil beams for computerized treatment plan optimization

Proton pencil beams in water, in a format suitable for treatment planning algorithms and covering the radiotherapy energy range (50-250 MeV), have been calculated using a modified version of the Monte Carlo code PTRAN. A simple analytical model has also been developed for calculating proton broad-beam dose distributions which is in excellent agreement with the Monte Carlo calculations. Radial dose distributions are also calculated analytically and narrow proton pencil-beam dose distributions derived. The physical approximations in the Monte Carlo code and in the analytical model together with their limitations are discussed. Examples showing the use of the calculated set of proton pencil beams as input to an existing photon treatment planning algorithm based on biological optimization are given for fully 3D scanned proton pencil beams; these include intensity modulated beams with range shift and scanning in the transversal plane.     

Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat

Acute, monophasic experimental allergic encephalomyelitis (EAE) in the Lewis rat shows pathological similarities to the human disease multiple sclerosis (MS). Rats that recover from EAE are essentially resistant to disease reinduction, unlike MS in which relapses are frequently associated with common bacterial and viral infections. As macrophage-derived interleukin (IL)-12 is a critical component of innate resistance to bacterial infection and appears to directly activate encephalitogenic T cells in vivo, the ability of this cytokine to reinduce paralysis in EAE was examined. Paralytic disease was exacerbated by intraperitoneal IL-12 administration and could be reinduced up to 1 week after recovery from the primary clinical episode. Concomitant with worsening of initial clinical signs and relapse was an increase in the ratio of macrophages to T cells in brain stem perivascular cuffs and the expression of inducible nitric oxide synthase in cells with both macrophage and microglial morphology. These findings suggest that IL-12 may contribute to macrophage-mediated disease exacerbation and relapse in patients with MS.     

Short cue presentations encourage advance task preparation: A recipe to diminish the residual switch cost.

In the task-switching literature, it has frequently been demonstrated that although advance task preparation reduces the switch cost, it never really eliminates the switch cost. This remaining residual switch cost received much attention, and it has been argued that advance preparation is restricted in nature. In the present study, the role of task-cue presentation in the establishment of the residual switch cost was investigated. In 4 experiments, the cue was removed during the preparation interval, and it was hypothesized that this would encourage participants to complete advance task preparation. The results of all 4 experiments provided support for this hypothesis: When the cue was presented for a short time and then removed, the residual switch cost completely disappeared. This was found for different cue types. Furthermore, Experiment 3 demonstrated that it was not the presence of the cue itself but merely differences in advance task preparation that caused the effects. This suggests that advance task preparation is not as restricted in nature as previously assumed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ultrastructure of a bio-electrolytic methanogenic/methanotrophic granular biofilm for the complete degradation of tetrachloroethylene in contaminated groundwater.

The electrolytical methanogenic/methanotrophic coupling (eMaMoC) process was tested in a laboratory-scale single-stage reactor for the treatment of tetrachloroethene (PCE)-contaminated waters. A water electrolysis cell was placed directly in the effluent recirculation loop for the supply of both O2 and H2 to the system: H2 serving as the electron donor for both carbonate reduction into CH4 and reductive dechlorination. The concurrent presence of O2 and CH4 could be used by the methanotrophs for co-metabolically oxidising the chlorinated intermediates left over by the anaerobic transformation of PCE. At a PCE inlet of 33-52 microM and a hydraulic residence time (HRT) of 5.6 days, PCE reductive dechlorination to dichloroethene (DCE) was over 95% with a maximum DCE mineralisation of 83%. Fluorescence in situ hybridisation with 16S rRNA probes related to type I and type II methanotrophic bacteria were utilised to localise the methanotrophic communities in the anaerobic/aerobic granules. It evidenced that with operational time, along with increasing oxygenation rate, methanotrophic communities were specifically colonising onto the outermost layer of the anaerobic/aerobic granule.