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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 397 records · Page 22Linked to original sources
PubMed1996

Acute toxicity of selected pesticides to the estuarine shrimp Leander tenuicornis (Decapoda:Palaemonidae).

The shrimp Leander tenuicornis is abundant in southeastern Queensland intertidal marsh pools and was chosen as an indicator species for toxicological studies with pesticides. Acute toxicity to this crustacean of temephos and 3 pesticide compounds under evaluation for registration in Australia (Bacillus thuringiensis var. israelensis, s-methoprene, and pyriproxyfen) was tested in 96-h laboratory trials. Temephos was the most toxic compound, with a median lethal concentration (LC50) of 0.01 ppm (0.33 times the estimated field concentration [EFC] for a 15-cm-deep pool). s-Methoprene was the least toxic compound, with an LC50 of 14.32 ppm (1,790 times the EFC). Bacillus thuringiensis var. israelensis and pyriproxyfen produced LC50 values of 60.9 x 10(6) ITU (176 times the EFC) and 0.098 ppm (12.25 times the EFC), respectively.

Animals↗
PubMed1995

Src homologous and collagen (Shc) protein binds to F-actin and translocates to the cytoskeleton upon nerve growth factor stimulation in PC12 cells.

Immunoprecipitates of metabolically labeled PC12 cells consistently contained a 43-kDa protein that was associated with Shc, a signal-transducing protein with a single SH2 domain. Following affinity chromatography with immobilized recombinant glutathione S-transferase (GST)-Shc fusion protein, the 43-kDa protein was identified as actin by mass spectrometry and immunoblotting. Cosedimentation experiments using purified actin and GST-Shc showed that Shc binds directly to F-actin, confirming Shc-actin interaction in vivo. Various GST-truncated Shc fusion proteins were prepared and used in actin cosedimentation assays. Constructs containing the SH2 and collagen homology domains were not precipitated, and those containing the amino-terminal domain were. Thus, Shc-actin interactions do not occur in the region of tyrosine phosphorylation and leave the SH2 domain free to bind to other tyrosine-phosphorylated molecules. Although the major pool of Shc in unstimulated PC12 cells is soluble, two other pools are associated with the cytoskeleton and the submembranous cytoskeleton. Upon nerve growth factor stimulation, approximately 50% of the soluble Shc translocates to both cytoskeleton environments within 2 min, decreasing thereafter. When cells were pretreated with cytochalasin D, a drug that disrupts actin filaments, Shc translocation to the cytoskeleton was abolished. However, in the submembranous fraction, the Shc level was elevated in resting cells following cytochalasin D treatment. The kinetics of translocation, compared to mitogen-activated protein kinase activation, and the nature of the Shc-actin interaction suggest that the cytoskeletal association of Shc, induced by growth factors, may be related to membrane ruffling and actin fiber reorganization.

Actins↗
PubMed1995

The GDC in a muddle.

Explore the source record for details and available documents.

Dentist-Patient Relations↗
PubMed1995

2 A crystal structure of an extracellular fragment of human CD40 ligand.

BACKGROUND: The CD40 ligand (CD40L) is a member of the tumor necrosis factor (TNF) family of proteins and is transiently expressed on the surface of activated T cells. The binding of CD40L to CD40, which is expressed on the surface of B cells, provides a critical and unique pathway of cellular activation resulting in antibody isotype switching, regulation of apoptosis, and B cell proliferation and differentiation. Naturally occurring mutations of CD40L result in the clinical hyper-IgM syndrome, characterized by an inability to produce immunoglobulins of the IgG, IgA and IgE isotypes. RESULTS: We have determined the crystal structure of a soluble extracellular fragment of human CD40L to 2 A resolution and with an R factor of 21.8%. Although the molecule forms a trimer similar to that found for other members of the TNF family, such as TNF alpha and lymphotoxin-alpha, and exhibits a similar overall fold, there are considerable differences in several loops including those predicted to be involved in CD40 binding. CONCLUSIONS: The structure suggests that most of the hyper-IgM syndrome mutations affect the folding and stability of the molecule rather than the CD40-binding site directly. Despite the fact that the hyper-IgM syndrome mutations are dispersed in the primary sequence, a large fraction of them are clustered in space in the vicinity of a surface loop, close to the predicted CD40-binding site.

Amino Acid Sequence↗
PubMed1995

Fibrinogen after coronary angioplasty as a risk factor for restenosis.

BACKGROUND: Fibrinogen is a risk factor for cardiovascular disease and is related to the severity of coronary atherosclerosis. Its role in restenosis after coronary angioplasty remains unknown. Although platelets and thrombosis contribute to the pathogenesis of restenosis, few clinical data are available concerning the relations between restenosis and proteins of the coagulation and fibrinolytic systems. METHODS AND RESULTS: In 107 consecutive patients undergoing coronary angioplasty, we measured plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, and fibrinogen before and immediately after angioplasty and at a 6-month follow-up. The individual changes of intraluminal diameter were measured by quantitative coronary angiography, and patients were classified according to four definitions of restenosis: (1) a final stenosis > 50%, (2) a loss of minimal luminal diameter during the follow-up period greater than the measurement variability in our laboratory (> 0.52 mm), (3) a loss of at least 50% of the gain in luminal diameter achieved by angioplasty, and (4) the combination of definitions 1 and 2. The relations between coagulation variables and each definition of restenosis were assessed univariately; then with the clinical variables included, the relations were analyzed multivariately. Angiographic follow-up was obtained in 92% of patients with a primary success of angioplasty. Global restenosis rates were 38%, 43%, 48%, and 30% for definitions 1 through 4, respectively. Plasma levels of t-PA antigen and PAI-1 antigen were not associated with any of the four definitions of restenosis. Multivariate analysis demonstrated that von Willebrand factor measured immediately after angioplasty predicted restenosis according to definitions 2 and 3. Fibrinogen measured within 6 months of follow-up was significantly increased in all restenosis groups of the four definitions. Patients with a fibrinogen concentration > 3.5 g/L at follow-up had higher restenosis rates than patients with a concentration < 3.5 g/L: 55% versus 22% (P = .001), 68% versus 31% (P = .002), 63% versus 37% (P = .01), and 74% versus 26% (P = .002) for definitions 1 through 4, respectively. The loss index was lower (P = .003) and the net gain higher (P = .03) in patients with a fibrinogen level < 3.5 g/L. There was a significant correlation between fibrinogen level and angiographic loss index (r = .41; P < .0001). Multivariate analysis confirmed that the fibrinogen level predicted restenosis with all definitions. CONCLUSIONS: An independent relation exists between von Willebrand factor measured immediately after angioplasty and restenosis defined by the degree of intraluminal renarrowing. An elevated fibrinogen level during follow-up is a strong biochemical predictor of restenosis. Therefore, fibrinogen should be considered at least as an independent marker of restenosis and perhaps as a common risk factor for both spontaneous coronary atherosclerosis and postangioplasty restenosis, which is an accelerated form of atherosclerosis.

Angioplasty, Balloon, Coronary↗
PubMed1995

Identification of the yeast methionine biosynthetic genes that require the centromere binding factor 1 for their transcriptional activation.

The yeast Centromere binding factor I (Cbf1) belongs to the family of the DNA binding factors that recognize the consensus sequence CACGTG. Phenotypic studies of cells lacking Cbf1 revealed that this factor is actually involved in two cellular processes; the fidelity of the chromosomal segregation and the metabolism of sulfur amino acids. However, the function of Cbf1 in the regulation of the sulfur amino acid metabolism is now a matter of controversy in literature with conflicting reports about its binding to the CACGTG sequences found upstream to the methionine biosynthetic genes. To provide a reliable basis for the functional analysis of Cbf1, we present an analysis of the transcription of the methionine biosynthesic genes in cells lacking Cbf1. Our results prove that Cbf1 is indeed involved in the transcriptional regulation of the sulfur amino acid metabolism.

Base Sequence↗
PubMed1995

Chromatographic resolution of an intracellular calcium influx factor from thapsigargin-activated Jurkat cells. Evidence for multiple activities influencing calcium elevation in Xenopus oocytes.

Acid extracts of thapsigargin-stimulated Jurkat cells revealed both intracellular and extracellular activities stimulating Ca(2+)-dependent Cl- currents on Xenopus laevis oocytes. Chromatographic fractionation of these extracts on gel filtration separated two active fractions of M(r) approximately 600 and 400. Moreover, the M(r) 600 fraction exhibited both intracellular and extracellular activities. However, the intracellular activity was absent from extracts of unstimulated Jurkat cells, suggesting its production was stimulated by thapsigargin. The further purification of this fraction by high performance thin layer chromatography resolved a single fraction which was active only on microinjection and which required calcium entry for activation of current responses. These results suggest that a single authentic calcium influx factor can be resolved by purification from confounding activities detected in crude acid extracts.

Animals↗
PubMed1995

Evaluation of calcium influx factors from stimulated Jurkat T-lymphocytes by microinjection into Xenopus oocytes.

Acid extracts of thapsigargin-activated Jurkat cells have been shown to have intracellular activity in inducing a dose-dependent rapid chloride current upon microinjection in Xenopus laevis oocytes. The extracts act by elevation of calcium through calcium entry. The factor(s) responsible for this activity have been termed calcium influx factor (CIF) and have been found to be small, relatively polar molecules (< 1000 daltons) whose activity is abolished by alkaline phosphatase treatment and potentiated by co-injection of okadaic acid (a protein phosphatase inhibitor). CIF is produced in a time-dependent manner following thapsigargin treatment of Jurkat cells, being first elevated above basal levels by 2 min. Intracellular CIF activity is completely absent from NG115-401L neuronal cells, which lack capacitative entry. On this basis, it appears that Jurkat cells, activated by stimuli that deplete internal calcium stores, produce one or more CIF activities acting intracellularly, and Xenopus oocytes may be a powerful tool to purify and characterize CIFs.

Animals↗
PubMed1995

[Evaluation of the coronary risk in sclerotic arterial diseases of the lower limbs].

The prevalence of coronary artery disease is very high among patients with peripheral arterial disease. The fate of these patients mainly depends on their coronary risk. Most often, the evaluation of coronary risk is performed when a surgical intervention on the aorta or lower limb arteries is decided. However, the late risk, at medium and long term, of coronary disease is much higher than its immediate perioperative risk. Diagnostic work-up is complex. Symptoms of coronary insufficiency may be masked by the limited capacity to physical exercise, but remain essential indices. None of the available complementary investigations has a satisfactory predictive value. Diagnostic explorations and therapeutic decisions for coronary heart disease have to be discussed in each case, according mainly to age and symptoms, and to whether peripheral arterial surgery is required.

Arterial Occlusive Diseases↗
PubMed1995

Variation in HLA-associated risks of childhood insulin-dependent diabetes in the Finnish population: I. Allele effects at A, B, and DR loci. DiMe Study Group. Childhood Diabetes in Finland.

Variation in the risk of insulin-dependent diabetes mellitus (IDDM) across alleles at HLA-A, B, and DR loci was investigated in a population-based study of 801 families of children with newly diagnosed IDDM in Finland nationwide. Parallel analyses assessed the relative frequencies of alleles in IDDM children compared with age-matched sibling controls and with the four possible genotypes which could have been inherited from the parents. The joint effects of DR3 and DR4 alleles were investigated under dominant, recessive, and additive models of gene expression. The additive model gave the best fit, though the relative risk for DR4 homozygotes was smaller than predicted. To investigate other alleles, we fitted the standard multiplicative model for alleles at each locus. After controlling for the correlation among alleles, significantly elevated risks were found for B13, DR3, DR4, and DR14. Subjects with these alleles have more than twice the risk of IDDM as those without. Alleles A24 and B62 incurred relative risks between one and two. DR2 and DR5 were significantly negatively associated with IDDM, incurring less than half the risk. These findings support an independent role of class I antigens in the etiology of IDDM.

Adolescent↗
PubMed1995

Variation in HLA-associated risks of childhood insulin-dependent diabetes in the Finnish population: II. Haplotype effects. DiMe Study Group. Childhood Diabetes in Finland.

We fitted models for the main effects of alleles at the HLA-A, B, and DR loci and their haplotypes on the risk of insulin-dependent diabetes mellitus (IDDM). Empirical Bayes methods were used, assuming independent exchangeable normal priors for effects at each locus separately and for haplotype effects. A pure main effects model, pure haplotype effects model, and a combined model were fitted using Gibbs sampling. The main effects model showed that the DR locus had the largest variation in risk between alleles, followed by the B locus; significance tests for each allele in this model were in general agreement with those in the companion paper [Langholz et al. (1995) Genet Epidemiol 12:441-453], although all relative risks were shrunk toward 1.0 in the empirical Bayes analysis. The variance estimate for pure haplotype effects was substantially larger than for any of the three main effects considered in this analysis, but in the combined model, the DR locus showed larger variability than the haplotype deviations. We confirmed that haplotype A2/B56/DR4 previously reported to be common in Finnish diabetics does indeed confer unusually high risk (relative risk = 7.6, P < 0.001), but found this to be only 1.9 times higher than predicted by its component main effects (P = 0.046). All of the other haplotypes could be adequately explained by their main effects. Empirical Bayes methods provide a natural means of dealing with the problems of multiple comparisons, multicolinearity, and sparse data that complicate the analysis of HLA data.

Adolescent↗
PubMed1995

Bone progenitor cell deficits and the age-associated decline in bone repair capacity.

Aging bone shows a progressive decline in mass and strength. Previous studies have suggested that bone marrow stem cells are reduced with aging and that this could be responsible, in part, for age-associated bone deficits. We measured the number of osteoprogenitor cells present in the bone marrow from adult and aged rats as well as their ability to differentiate in vitro and to form bone in vivo. We found that the number of adherent colony-forming cells was significantly lower (65%) in marrow cells isolated from aged compared with adult rats. Furthermore, 88% of the colonies obtained from aged rats were alkaline phosphatase (AP) positive, whereas virtually all the colonies from adult rats were positive. The addition of dexamethasone to the culture medium decreased the proliferation of the adherent cells and reduced the number of colonies obtained from both adult and aged bone marrow, all of which were AP positive. No significant differences were found in the expression of certain major bone cell marker genes as a function of donor age. However, dexamethasone treatment increased expression of osteopontin (OP) by fivefold. Adult stromal cells not treated with dexamethasone and implanted subcutaneously in recipient rats exhibited about 10-fold greater formation of bone compared with cells from aged rats. In contrast, dexamethasone-treated cells exhibited high levels of bone formation, irregardless of donor age or the age of the recipient into which the cells were grafted. These studies are consistent with a deficit of osteoprogenitor cells in the bone marrow site as a contributing, perhaps correctable factor in the decline in bone repair and bone mass with age.

Aging↗
PubMed1995

Attitudes and opinions of French cardiologists towards smoking.

To assess attitudes and opinions of French cardiologists towards tobacco, a postal survey was performed in 1993 of all members of the French Society of Cardiology using a questionnaire designed by the World Health Organisation (WHO) and the International Union against tuberculosis and lung diseases (IUATLD) for health professionals. 730 cardiologists responded to the mailing. The mean age of them was 47 + or - 9 years, 84% were males. The prevalence of smoking was 27% (14% daily smokers and 13% occasionally smokers). There were more never smokers in age group < 45 than in those aged 45 and more (33% vs 21%). Of daily smokers, 42% claimed to have made a serious attempt to stop smoking, but only 16% expected to have stopped within five years of the survey. French cardiologists aged 29-45 years had a better knowledge of tobacco related respiratory and cardiovascular diseases than those over 45 years old. Only 64% (54% of daily smokers) would counsel a patient to stop smoking if he did not have a smoking related illness and did not himself raise the question. 53% thought they had sufficient knowledge to advise their patients on stopping smoking. The results compared to those of the French general practitioners survey, showed a lower prevalence of daily smokers. French cardiologists especially those aged 29-45, have a better knowledge of the risk of cardiovascular diseases. But only 64% of them would advise any smoker patients. These results also demonstrated the influence of personal smoking on the attitude of cardiologists towards smoker patients.

Adult↗