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Biomedical subjects

D Alexander

Publications and source records attributed to D Alexander.

At least 73 records · Page 4Linked to original sources

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↗

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↗

98.6 degrees F.

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Body Temperature↗

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↗

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↗

Characterization of the hepatitis C virus E2/NS1 gene product expressed in mammalian cells.

Truncated and full-length versions of the hepatitis C virus protein domain encoding a presumptive envelope glycoprotein designated E2/NS1 were stably expressed in CHO cell lines. Characterization of the processing events involved in the maturation of E2/NS1 revealed that a high-mannose form resident in the endoplasmic reticulum was the most abundant form detected intracellularly. The ionophore carboxyl cyanide m-chlorophenyl-hydrazone was used to show that the E2/NS1 glycoprotein resided in the endoplasmic reticulum. The full-length form of E2/NS1 appeared to be cell-associated and could not be detected as a secreted product. C-terminal truncated molecules could be detected in the extracellular media as fully processed glycoproteins containing terminal sialic acid additions. These truncated glycoproteins are predicted to be biologically relevant targets of the host immune response and are therefore potential subunit vaccine candidates.

Animals↗

The role of CD45 in T-cell activation--resolving the paradoxes?

CD45 is one of the most abundant transmembrane glycoproteins expressed on the surface of haematopoietic cells. Despite the striking advances of the past few years in the understanding of the actions of CD45 at a molecular level, several paradoxes remain. This article argues that these paradoxes are more apparent than real, and suggests that CD45 plays a key role on the T-cell surface in regulating coupling of the antigen-receptor complex to intracellular signalling pathways.

CD3 Complex↗

Evidence for the indirect utilization of glucose for the synthesis of hepatic glycogen in man.

1. This study was designed to test the hypothesis that three-carbon intermediates can be used in the 'indirect' pathway of glycogen synthesis in human liver (i.e. a route additional to the use of glucose by the 'direct' pathway). 2. After an overnight fast, 13 patients were given an infusion of 20% (w/v) glucose before elective abdominal operation. All received a 2.5 g bolus of 2220 kBq of selectively 3H- and 14C-labelled glucose before removal of a 1 g biopsy of liver. 3H and 14C were determined in purified glycogen as well as in glucose and lactate from samples of peripheral blood. 3. The ratio and specific activities of 3H and 14C in glycogen were found to be significantly lower than those in administered glucose. By calculation, 7-74% of glycogen repletion occurred by indirect pathways and not all of this was from the glucose supplied. 4. This study suggests that the operation of a direct pathway in man is not exclusive and that significant repletion of hepatic glycogen occurs by an indirect route.

Adult↗

One hundred requests for predictive testing for Huntington's disease.

In Grampian region, the first 100 requests for predictive testing for Huntington's disease have been analysed. Forty-five presymptomatic predictive test results have been given, eleven families have made a decision to undergo prenatal exclusion tests, and so far eleven pregnancies have been investigated using chorion villus biopsy. This paper presents the protocol used and a descriptive analysis of those receiving results, those choosing to leave the programme, and those unable to complete it because of an unsuitable family structure or unco-operative relatives.

Adult↗

Analysis of strike-through contamination in saturated sterile dressings.

The method of saturating gauze sponges directly in their wrapper was tested to determine strike-through contamination. Contamination occurred in 100% of the uncoated-wrapper sponges, regardless of exposure to Staphylococcus epidermidis or Escherichia coli. Among coated-wrapper sponges, 80% exposed to Staphylococcus epidermidis and 20% exposed to Escherichia coli demonstrated strike-through contamination. Coated-wrapper sponges had a significantly lower rate of contamination than uncoated-wrapper sponges when exposed to Escherichia coli. Occurrence of contamination of all sponges was significantly higher from Staphylococcus epidermidis. The findings render the popular practice of saturating gauze sponges in their wrapper unacceptable.

Bandages↗

Differential tissue regulation of insulin-like growth factor binding proteins in experimental diabetes mellitus in the rat.

The expression and regulation of IGF-I is tissue-specific in diabetes mellitus in the rat. These studies were designed to examine if similar tissue specificity exists for IGF-BPs in the diabetic milieu. Diabetes mellitus was induced by a single i.p. injection of STZ (100 mg/kg body weight). Rats were treated with either vehicle--insulin, vanadate, or phlorizin for 7-14 days. Tissues were analyzed for IGF-BPs by ligand blotting and by affinity cross-linking and immunoprecipitation. In liver tissue from nondiabetic control rats, multiple forms of IGF-BPs were noted, ranging from 48,000 to 25,000 M(r). In diabetic rat liver tissue, the 25,000-M(r) form was unchanged, whereas the higher M(r) forms (48,000-42,000 M(r)) were decreased, and the 30,000-M(r) form was increased. Insulin therapy of diabetic rats decreased all forms to below control levels. In the kidney tissue of control rats, faint IGF-BP bands were seen at 30,000 and 25,000 M(r). In diabetic rat kidney tissue, the 30,000-M(r) form again was increased (as in liver) and restored to control levels with insulin therapy. In contrast, only a 30,000-M(r) band was seen in control pituitary tissue, which was slightly increased in the diabetic rats and also was decreased below control levels by insulin. In hypothalamus and cerebral cortex tissue, bands at 30,000 and 25,000 M(r) were noted, and neither was altered by diabetes or insulin treatment. Treatment of diabetic rats with vanadate and phlorizin resulted in comparable blood glucose levels, which were only slightly higher than those achieved with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗