Intracellular targeting of signalling proteins. Introduction.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
S Ley
Publications and source records attributed to S Ley.
[Contrast media enhanced three dimensional MR angiography of the pulmonary arteries in patients with chronic recurrent pulmonary embolism--comparison with selective intra-arterial DSA].
PURPOSE: This study compares contrast-enhanced 3D-MR angiography (MRA) of the pulmonary arteries with selective intra-arterial DSA in patients with chronic thromboembolic pulmonary hypertension. MATERIALS AND METHODS: 20 patients preoperatively underwent a contrast-enhanced 3D-MRA of the pulmonary arteries at 1.5 T using the phased-array body coil. For MRA, we used a 3D-Flash-sequence after bolus timing. 2 radiologists analyzed the acquired image material in consensus with respect to the detection of central thromboembolic material and the visualization of the pulmonary arterial tree. Finally, the MR angiograms were compared with selective DSA images using surgical findings as the definitive standard. RESULTS: MRA demonstrated central thromboembolic material, vessel cut-offs and abnormal proximal-to-distal tapering in all patients. Compared to DSA, MRA depicted the pulmonary vessels up to the segmental level in all cases, it was inferior to DSA in delineation of the subsegmental arteries (sensitivity 87%, specificity 100%). The central beginning of the thromboembolic occlusions seen at MRA corresponded to the beginning of the deobliteration procedure during pulmonary thromboendarterectomy in every case. CONCLUSIONS: Contrast-enhanced 3D-MRA of the pulmonary arteries enables the reliable detection of central thromboembolic material in patients with CTPEH. It also allows identification of those patients who may be treated surgically.
Adult↗
[Measles, mumps, German measles].
Explore the source record for details and available documents.
Child↗
Isoforms of 14-3-3 protein can form homo- and heterodimers in vivo and in vitro: implications for function as adapter proteins.
14-3-3 proteins play a role in many cellular functions: they bind to and regulate several proteins which are critical for cell proliferation and differentiation. 14-3-3 proteins exist as dimers, and in this study we have shown that diverse 14-3-3 proteins can form both homo- and heterodimers in vitro (by cross-linking studies) and in vivo (by coimmunoprecipitation and Western blot analysis); this interaction is mediated solely through the N-terminal domain of the proteins. The composition of 14-3-3 dimers within a cell may play a key part in the role of this family of proteins as modulators or adapters which facilitate the interaction of distinct components of signalling pathways.
14-3-3 Proteins↗
Influenza surveillance: experiences from establishing a sentinel surveillance system in Germany.
OBJECTIVES: Before and during peak influenza periods there is increased morbidity from other respiratory tract disorders. Sentinel networks of primary care physicians can be very effective in the early detection of influenza epidemics and the German network, the Arbeitsgemeinschaft Influenza (AGI), began its work in this area in 1992. METHODS: Data are transmitted weekly from the doctor's computer via Btx to a central computer. The numerator is the weekly number of acute respiratory infections (ARI) in five age groups and the denominator is the weekly number of patient consultations. Data on hospitalisation, mortality, and days of sick leave from work or school are also collected. Swabs for influenza specimens are collected in 30 physicians' offices each Monday and sent to three reference centres. FINDINGS: During the last recording period, from week 46 1993 to week 15 1994, 411 physicians' offices participated in the network. For 16 to 22 weeks, more than 60% of the participants transmitted data. During both the 1992-93 and 1993-94 influenza seasons, peaks were observed in the rate of ARI. There was a corresponding increase in sick leave from work and school. Rates for hospitalisation and deaths due to influenza showed no peaks during either season. CONCLUSIONS: Although the German sentinel network for influenza experienced some technical problems in the first year, it was possible to solve these. Reporting rates were very satisfactory in the second year. The network will now be expanded to include 750 physicians in order to receive 600 weekly reports and obtain a solid baseline for an early warning system.
Adolescent↗
[Pertussis vaccination for older children. Information from the Federal Health Department].
Explore the source record for details and available documents.
Child↗
Comparative analysis of phosphotyrosyl polypeptides in normal and leukemic human T lymphocytes activated via CD3 or CD2.
Phosphotyrosyl polypeptides induced following CD3- or CD2- specific antibody stimulation were analysed in different human T cell lines by immunoblotting or by immunoprecipitation of 32P-labelled cell lysates using a phosphotyrosine-specific monoclonal antibody. In Jurkat cells, resting peripheral T lymphocytes, T lymphoblasts, CD8+ T lymphoblasts and a CD4+ T cell clone, CD3 stimulation induced a strong but transient tyrosine phosphorylation of at least 15 polypeptides. However, in peripheral T cells and T blasts, the kinetics of phosphorylation were considerably slower than in Jurkat cells. The pattern of phosphotyrosyl polypeptides induced by CD3 stimulation was similar, although some differences were noted between normal T cells and Jurkat, especially at the level of the extent of phosphorylation. As had been previously reported for Jurkat T cells, a qualitatively similar tyrosine phosphorylation response was induced upon CD2 or CD3 stimulation in each of the analysed T cell populations, suggesting that CD3 and CD2 share a common pathway of protein tyrosine kinase (PTK) activation. In HPB. ALL leukemia T cells (which express very low levels of CD45), both CD3 and CD2 stimulation induced only very weak protein tyrosyl phosphorylation. However, a 50 kDa polypeptide, which was part of an inducible doublet in Jurkat or normal T lymphocytes, was constitutively tyrosyl-phosphorylated in the HPB. ALL line. These results suggest that there is a common pathway of early PTK activation following CD3- or CD2-mediated stimulation in mature T cells, whether they express surface CD4 or CD8, and also that the PTK may be differently regulated in different T cell populations leading to different kinetics or intensity of tyrosyl phosphorylation.
Antigens, Differentiation, T-Lymphocyte↗
Regulation of phosphoinositide kinases in T cells. Evidence that phosphatidylinositol 3-kinase is not a substrate for T cell antigen receptor-regulated tyrosine kinases.
A phosphoinositide kinase that can phosphorylate phosphatidylinositol (PtdIns) is present in 4G10 monoclonal antibody (mAb) phosphotyrosine immunoprecipitates isolated from T cells activated via the T cell antigen receptor (TCR).CD3 complex. This PtdIns kinase is not the PtdIns 3-kinase that associates with activated protein tyrosine kinases in fibroblasts, since Western blotting and immunoprecipitation experiments with antibodies specific for the p85 alpha subunit of the PtdIns 3-kinase indicate that this polypeptide is not immunoprecipitated by the 4G10 mAb from TCR.CD3-activated Jurkat cells. Moreover, immunoprecipitated PtdIns 3-kinase isolated from T cells with p85 antibodies is inhibited when PtdIns is presented in Nonidet P-40, whereas the PtdIns kinase activity present in 4G10 mAb phosphotyrosine immunoprecipitates is enhanced in the presence of Nonidet P-40. In vitro kinase assays of PtdIns 3-kinase immunoprecipitated with p85 antibodies from T cells indicate that it associates with a serine kinase that can phosphorylate a p85 polypeptide. However, no protein tyrosine kinase activity capable of tyrosine phosphorylating p85 in vitro associates with p85 alpha immunoprecipitates in quiescent or TCR.CD3-activated T cells. These data suggest that the TCR.CD3 complex does not regulate PtdIns 3-kinase activity by a mechanism that involves protein tyrosine kinases.
Adenosine↗
The influence of chronic pain on the analgesic effects of the alpha 2-adrenoceptor agonist, xylazine, in sheep.
A comparison of the analgesic potency of the alpha 2-adrenoceptor agonist, xylazine, in control healthy sheep and sheep suffering chronic pain from footrot, indicated that the analgesic effectiveness of xylazine was significantly reduced in the animals experiencing chronic pain. This was measured by recording the threshold to a mechanically applied pressure stimulus. Furthermore, when the condition was apparently resolved, by conventional treatment over a period of 2 to 3 weeks, the decreased analgesic effectiveness of the alpha 2-agonist was still apparent although the animals were clinically cured of the footrot.
Analgesia↗
Variation in the analgesic effects of xylazine in different breeds of sheep.
Explore the source record for details and available documents.
Analgesia↗
Defects in signal transduction caused by a T cell receptor beta chain substitution.
An antigen-specific T-T hybridoma was mutagenized with ethylmethane sulfonate and negatively selected by anti-Ly-6 antibody-induced growth inhibition. One of the mutants generated, M4/8, had lost surface expression of a T cell receptor (TcR) V beta 8 epitope detected on the surface of the parental cell line. However, the mutant cell line did express high levels of TcR heterodimer as detected with a pan-specific anti-TcR antibody. CD3 epsilon, Ly-6 and Thy-1 were expressed at levels similar to the wild-type parental cell line. Analysis of the surface TcR/CD3 complexes by immunoprecipitation and two-dimension gel electrophoresis confirmed that the major discernable difference between the wild-type and mutant TcR/CD3 complexes resided in the TcR beta chain. The parental cell line had the potential to express two TcR heterodimers, V alpha V beta 1 and V alpha V beta 8, as determined by Northern blot analysis. Co-modulation experiments suggested that both types of receptors were expressed. However, the V alpha V beta 8 receptor was the predominant form. In contrast, the mutant M4/8 cell line did not synthesize V beta 8 mRNA and, thus, only the V alpha V beta 1 TcR was synthesized. Despite the normal surface expression of TcR/CD3 complex, the M4/8 mutant cell line did not produce interleukin 2 (IL 2) in response to antigen or soluble anti-CD3 epsilon monoclonal antibody (mAb). Furthermore, it responded poorly to concanavalin A, phytohemagglutinin and anti-Ly-6 mAb. Cross-linking of the stimulatory antibodies partially restored the IL 2 response to anti-CD3 epsilon or anti-Ly-6 to wild-type levels. Phorbol ester and ionomycin stimulated a full IL 2 response in the M4/8 cell line, demonstrating that the defect in the decreased signaling in the mutant did not result from a defect in the IL 2 gene program. In conclusion, these data suggested that the pairing of alpha/beta heterodimer not only determined antigen/MHC specificity but also the signaling efficiency of the TcR/CD3 complex.
Antigens, Differentiation, T-Lymphocyte↗
Structure of the T-cell antigen receptor: evidence for two CD3 epsilon subunits in the T-cell receptor-CD3 complex.
The T-cell antigen receptor (TCR) consists of heterodimeric glycoproteins (TCR alpha beta or gamma delta) that demonstrate homology with immunoglobulins. Noncovalently associated with the alpha beta (or gamma delta) heterodimer are at least five nonvariant proteins (CD3-gamma, -delta, -epsilon, -zeta, and -eta), which together comprise the TCR-CD3 complex. The stoichiometry of the antigen receptor has been assumed to be either alpha beta gamma delta epsilon zeta zeta or alpha beta gamma delta epsilon zeta eta. In this paper we provide several lines of evidence that support the notion that the mature TCR-CD3 complex on the cell surface contains two CD3-epsilon polypeptide chains. Transfection of two murine T cell-T cell hybridomas with the human DNA encoding CD3-epsilon protein demonstrated that both murine and human CD3-epsilon chains were present within the same TCR-CD3 complex. Analysis of thymocytes isolated from transgenic mice that expressed high copy numbers of the human CD3-epsilon gene showed that the heterologous human CD3-epsilon subunits were coexpressed with murine CD3-epsilon in the same TCR-CD3 complex. Since CD3-epsilon was shown to form disulfide-linked homodimers both in human and murine T cells, the two CD3-epsilon subunits present in the TCR-CD3 complex were in direct contact with one another. The presence of two CD3-epsilon polypeptide chains in close proximity to one another in the TCR-CD3 complex may have important implications for its assembly and its signal transduction mechanisms.
Animals↗