A survey on the use of mouthguards and associated oral injuries in athletics.
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Adolescent↗
Biomedical subjects
D Alexander
Publications and source records attributed to D Alexander.
FK506 and cyclosporin A each inhibit antigen-specific signaling in the T cell line 171 in the absence of a calcium signal.
Antigen-specific signal transduction leading to IL2 induction and secretion in the T cell line 171 is augmented by association of p56lck with CD4. Although no change in cytoplasmic calcium level ([Ca2+]i) was detectable during antigen-specific signal transduction of 171-CD4+ cells, IL2 induction was inhibited by FK506 and CsA. Since these drugs are thought to act selectively by inhibiting calcineurin, a calcium-calmodulin-dependent protein phosphatase associated with activation of the IL2 promoter, we considered the possibility that calcineurin is constitutively active in 171 cells. However, we found no evidence for this because PMA failed to supplement any putatively active calcineurin to induce IL2 secretion. We suggest that IL2 secretion induced by antigen presentation to TCR/CD4/p56lck requires an FK506 and cyclosporin A-sensitive step which may be independent of calcium signaling. Rapamycin did not inhibit IL2 secretion induced by TCR/CD4/p56lck, emphasizing the specific action of FK506 and cyclosporin A.
Amino Acid Sequence↗
HIV testing, counseling, and prophylaxis after sexual assault.
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AIDS Serodiagnosis↗
The CD45 tyrosine phosphatase regulates specific pools of antigen receptor-associated p59fyn and CD4-associated p56lck tyrosine in human T-cells.
A newly isolated T-cell line (CB1) derived from a T-acute lymphoblastic leukaemia (T-ALL) patient contained cells (40% of total) which did not express the CD45 phosphotyrosine phosphatase. The cells were sorted into CD45- and CD45+ populations and shown to be clonal in origin. T-cell receptor (TCR) cross-linking or coligation of the TCR with its CD4/CD8 co-receptors induced tyrosine phosphorylation and calcium signals in CD45+ but not in CD45- cells. Unexpectedly, whole cell p56lck and p59fyn tyrosine kinase activities were not reduced in CD45- compared to CD45+ cells. A novel technique was therefore developed to isolated specific pools of aggregated receptors expressed at the cell surface, together with their associated tyrosine kinases. Using this technique it was shown that cell surface CD4-p56lck kinase activity was 78% lower in CD45- than in CD45+ cells. Phosphorylation of TCR zeta- and gamma-chains occurred in TCR immunocomplexes from CD45+ but not CD45- cells, despite comparable levels of p59fyn and TCR proteins. Furthermore, TCR-associated tyrosine kinase activity towards an exogenous substrate was 84% lower in CD45- than in CD45+ cells. Addition of recombinant p59fyn to TCR immunocomplexes isolated from CD45-cells restored the phosphorylation of the TCR zeta- and gamma-chains. Our results demonstrate that CD45 selectively regulates the pools of p59fyn and p56lck kinases which are associated with the TCR and CD4 at the cell surface. Activation by CD45 of these receptor-associated kinase pools correlates with the ability of the TCR and its coreceptors to couple to intracellular signalling pathways.
CD4 Antigens↗
Adolescents and young adults: overview.
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Adolescent↗
FK 506 and cyclosporin each block antigen-induced T cell receptor signalling that is dependent on CD4 co-receptor and operates in the absence of detectable cytoplasmic calcium fluxes.
The T cell hybridoma "171", which lacks CD4 but expresses T cell receptor (TCR) for hen egg white lysozyme, requires introduction of wild-type CD4 for antigen-mediated induction and secretion of interleukin-2 (IL-2). Mutant CD4, which fails to associate with the tyrosine kinase p56lck does not support IL-2 secretion, suggesting that a role of CD4 is to bring cytoplasmic p56lck into alignment for signal transduction to the IL-2 promotor. Using 171, 171-CD4 (wild-type) and 171-CD4 (mutant), we found that IL-2 secretion was inhibited by FK 506 and cyclosporin but not by rapamycin. However, this inhibition was not associated with calcium fluxes since no change in cytoplasmic free calcium levels ([Ca]i; resting level 80 nM) was detectable during antigen stimulation of the 171 or 171-CD4 cells. Thus, although FK 506 and cyclosporin inhibited calcium-dependent signalling to the IL-2 promoter via inhibition of the protein phosphatase calcineurin, it is possible that IL-2 induction via TCR/CD4 requires an FK 506 (and cyclosporin) sensitive step which is independent of cytoplasmic calcium changes.
Animals↗
Densities of Vibrio vulnificus in the intestines of fish from the U.S. Gulf Coast.
Densities of Vibrio vulnificus in the intestinal contents of various finfish, oysters, and crabs and in sediment and waters of the U.S. Gulf Coast were determined by the most probable number procedure. Species were identified by enzyme immunoassay. During the winter, densities of V. vulnificus were low, and the organism was isolated more frequently from sheepshead fish than from sediment and seawater. From April to October, V. vulnificus densities were considerably higher (2 to 5 logs) in estuarine fish than in surrounding water, sediment, or nearby oysters and crustacea. Highest densities were found in the intestinal contents of certain bottom-feeding fish (10(8)/100 g), particularly those that consume mollusks and crustaceans. Densities of V. vulnificus in fish that feed primarily on plankton and other finfish were similar to those in oysters, sediment, and crabs (10(5)/100 g). V. vulnificus was found infrequently in offshore fish. The presence of high densities of V. vulnificus in the intestines of common estuarine fish may have both ecological (growth and transport) and public health (food and wound infections) implications.
Alabama↗
A novel inhibitor of cyclin-Cdk activity detected in transforming growth factor beta-arrested epithelial cells.
Transforming growth factor beta (TGF-beta) is a potent inhibitor of epithelial cell growth. Cyclins E and A in association with Cdk2 have been shown to play a role in the G1-to-S phase transition in mammalian cells. We have studied the effects of TGF-beta-mediated growth arrest on G1/S cyclins E and A. Inhibition of cyclin A-associated kinase by TGF-beta is primarily due to a decrease in cyclin A mRNA and protein. By contrast, while TGF-beta inhibits accumulation of cyclin E mRNA, the reduction in cyclin E protein is minimal. Instead, we find that the activation of cyclin E-associated kinase that normally accompanies the G1-to-S phase transition is inhibited. A novel inhibitor of cyclin-Cdk complexes was detected in TGF-beta-treated cell lysates. Inhibition is mediated by a heat-stable protein that targets both Cdk2 and Cdc2 kinases. In G0-arrested cells, a similar inhibitor of Cdk2 kinase was detected. These data suggest the existence of an inhibitor of cyclin-dependent kinases induced under different conditions to mediate antiproliferative responses.
Animals↗
Screening alcohol abuse potential among Army reservists with the Short Michigan Alcoholism Screening Test.
The Short Michigan Alcoholism Screening Test was psychometrically useful in screening a sample of 560 reservists from a midwest general hospital unit. The most conservative estimate of alcohol abuse potential was 11.3%, with possibly 6.6% having symptoms of alcohol dependence. Comparisons with active duty military, Army, and civilian samples suggest that prevalence of abuse in the Reserve sample is similar to that of the combined military, but lower than that of the Army. Future research and policy choices are highlighted.
Alcoholism↗
Nutrient intake and haematological status of vegetarians and age-sex matched omnivores.
OBJECTIVE: The study was designed to investigate the nutritional intake and haematological status of adult vegetarians. DESIGN: Cross-sectional comparison of vegetarians and age/sex-matched omnivores. SETTING: Free-living community subjects. SUBJECTS: Fifty vegetarians were recruited by local advertisement. Each vegetarian selected their own age/sex-matched 'friend' control. OUTCOME MEASURES: Each subject completed a 12 day dietary record. Haemoglobin, red cell indices, and serum ferritin, B12 and folate were measured. RESULTS: Protein, saturated fat and vitamin D intake were significantly lower in the vegetarians, particularly in the vegans. Dietary fibre was higher in the vegetarians, and intake of calcium and zinc was similar. Mean (SD) iron intake in the vegetarians and vegans of 16.8 (4.8) mg/day was significantly greater than that of the omnivores: 14.6 (4.3) mg/day (P = 0.02). All the iron consumed by the vegetarians was non-haem; for the omnivores 10% was haem iron. Serum ferritin concentrations were significantly lower in male vegetarians than omnivores; mean (SD): 36.6 (36.0) and 105.4 (78.7) ng/ml, respectively, P < 0.01; and significantly more had values below 12 ng/ml (P < 0.001), despite having higher iron intakes which exceeded the Recommended Nutrient Intake (RNI). Female vegetarians also had lower ferritin concentrations than omnivores; mean (SD) 13.6 (7.5) compared to 33.6 (54.3) ng/ml, P < 0.01, but similar numbers of women had values below 12 ng/ml (42% and 39%). The vegans all had B12 intakes below the RNI; and 35% of the long-term vegetarians and vegans had serum vitamin B12 concentrations below the reference range. CONCLUSION: Although the vegetarians had diets nearer to the recommended diet with a lower fat and salt content, a significant number need advice to improve their haematological status. Recommended intakes of iron may also need to be higher for vegetarians, particularly men.
Adult↗
An athlete dying young. Arrythmogenic right ventricular dysplasia.
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Adipose Tissue↗
Increased tolerance to two oomycete pathogens in transgenic tobacco expressing pathogenesis-related protein 1a.
Expression of pathogenesis-related protein 1a (PR-1a), a protein of unknown biochemical function, is induced to high levels in tobacco in response to pathogen infection. The induction of PR-1a expression is tightly correlated with the onset of systemic acquired resistance (SAR), a defense response effective against a variety of fungal, viral, and bacterial pathogens. While PR-1a has been postulated to be involved in SAR, and is the most highly expressed of the PR proteins, evidence for its role is lacking. In this report, we demonstrate that constitutive high-level expression of PR-1a in transgenic tobacco results in tolerance to infection by two oomycete pathogens, Peronospora tabacina and Phytophthora parasitica var. nicotianae.
Oomycetes↗
Analysis of medical treatment at a field hospital following Hurricane Andrew, 1992.
STUDY OBJECTIVE: To determine what medical care was required of a special operations response team by a community devastated by a major hurricane. STUDY DESIGN: Retrospective analysis of 1,544 patient encounter forms generated at a field hospital set up in Homestead, Florida, after Hurricane Andrew in August 1992 and staffed by the special operations response team from Forsyth County, North Carolina. TYPE OF PARTICIPANTS: All persons presenting for treatment. RESULTS: One thousand two hundred three adult patients and 336 pediatric patients were seen by the special operations response team. Only five of the injuries treated were due directly to the hurricane, whereas 285 of the treated injuries were sustained during clean-up activities. Most of the care provided was routine medical care denied the citizens due to the loss of their physicians' offices and clinics. Supplies of tetanus toxoid, antibiotics, and insulin were depleted in 24 hours. Resupplying these items and acquiring other medication to refill prescriptions constituted a pressing problem. CONCLUSION: The primary function of medical personnel responding to an area hit by a major hurricane will be to provide general medical care. Any trauma encountered will be primarily due to clean-up activities and not due to the hurricane itself. Responding medical personnel should plan on providing their own food and water for the first 72 hours and be well stocked with antibiotics, tetanus toxoid, and insulin.
Adult↗
From the National Institutes of Health.
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Alcoholism↗
Does co-aggregation of the CD45 and CD3 antigens inhibit T cell antigen receptor complex-mediated activation of phospholipase C and protein kinase C?
The binding of agonistic monoclonal antibodies (mAb) to the CD3 antigen in T cells induces a rapid increase in tyrosine phosphorylation, inositive phosphate (IP) production, a rise in intracellular calcium and protein kinase C (PKC) activation. These intracellular signals have been implicated in the control of interleukin-2 and interleukin-2R receptor gene expression, thereby regulating T cell proliferation. Previous studies have shown that co-ligation of the CD45 and CD3 antigens inhibits CD3-induced tyrosine phosphorylation, IP production, calcium signals and T cell proliferation. It has therefore been suggested that the CD45 antigen uncouples the T cell receptor (TcR) from mitogenic signal pathways. In this study co-ligation of the CD3 and CD45 antigens with precisely constructed bispecific mAb did not inhibit CD3-induced T cell proliferation, IP production, calcium signals, diacylglycerol production or PKC activation. Furthermore, co-ligation of CD3 and CD45 antigens already cross-linked with IgM mAb did not lead to inhibition of CD3-induced calcium signals. Inhibitions of CD3-induced intracellular signals were observed following co-ligation of IgG CD45 and CD3 mAb with anti-IgG (F(ab')2 fragments. However, comparable inhibitions were also noted following co-ligation of CD3 with other abundant cell-surface antigens such as CD5 and LFA-1, and inhibitions were only observed when the CD3 mAb used required cross-linking to induce signals. These results suggested that the inhibitory effects of CD45 IgG mAb were not specific and were caused by the prevention of CD3-CD3 cross-linking following CD3 antigen co-ligation with other cell surface molecules. These findings are inconsistent with a specific inhibitory role for the CD45 phosphotyrosine phosphatase in uncoupling the TcR from mitogenic signal pathways.
Antibodies, Monoclonal↗
CD45 tyrosine phosphatase-activated p59fyn couples the T cell antigen receptor to pathways of diacylglycerol production, protein kinase C activation and calcium influx.
The role of the CD45 phosphotyrosine phosphatase in coupling the T cell antigen receptor complex (TCR) to intracellular signals was investigated. CD45- HPB-ALL T cells were transfected with cDNA encoding the CD45RA+B+C- isoform. The tyrosine kinase activity of p59fyn was found to be 65% less in CD45- cells than in CD45+ cells, whereas p56lck kinase activity was comparable in both sub-clones. In CD45- cells the TCR was uncoupled from protein tyrosine phosphorylation, phospholipase C gamma 1 regulation, inositol phosphate production, calcium signals, diacylglycerol production and protein kinase C activation. Restoration of TCR coupling to all these pathways correlated with the increased p59fyn activity observed in CD45-transfected cells. Co-aggregation of CD4- or CD8-p56lck kinase with the TCR in CD45- cells restored TCR-induced protein tyrosine phosphorylation, phospholipase C gamma 1 regulation and calcium signals. Receptor-mediated calcium signals were largely due (60-90%) to Ca2+ influx, and only a minor component (10-40%) was caused by Ca2+ release from intracellular stores. Maximal CD3-mediated Ca2+ influx occurred at CD3 mAb concentrations at which inositol phosphate production was non-detectable. These results indicate that CD45-regulated p59fyn plays a critical role in coupling the TCR to specific intracellular signalling pathways and that CD4- or CD8-p56lck can only restore signal transduction coupling in CD45- cells when brought into close association with the TCR.
Biological Transport↗
Erythropoietic adaptations to endurance training.
Erythropoietic adaptations involving the oxygen dissociation curve (ODC) and erythropoietin production have been implicated in the etiology of reduced blood haemoglobin concentrations in sportspersons (known as sports anaemia). A significant increase in the half-saturation pressure indicating a right-shift in the ODC was measured in 34 male [25.8-27.4 mmHg (3.44-3.65 kPa)] and 16 female (25.8-27.7 mmHg (3.44-3.69 kPa)] trained distance runners (P less than 0.01 for both genders) after completing a standard 42-km marathon. Erythrocyte 2,3-diphosphoglycerate concentrations measured concurrently were unaltered by exercise, although consistently higher in the female compared to the male athletes (P less than 0.05). The serum erythropoietin (EPO) concentrations of 15 male triathletes (26.3 U.ml-1) were significantly lower than those of 45 male distance runners (31.6 U.ml-1; P less than 0.05). However, the mean serum EPO concentrations of male and female athletes engaged in a variety of sports were not different from those of sedentary control subjects of both sexes (26.5-35.3 U.ml-1). Furthermore, the serum EPO concentrations were unaltered after prolonged strenuous exercise in 20 male marathon runners. These data suggest that the haematological status of these endurance athletes is in fact normal and that the observed shift in the ODC, while providing a physiological advantage during exercise, has no measurable effect on the erythropoietic drive.
2,3-Diphosphoglycerate↗