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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 469 records · Page 26Linked to original sources
PubMed1994

[Management of newborn life-threatening distress at birth. Study of the experience at a university maternity ward].

Care given to 1,425 consecutive new-born infants in a University Maternity Ward was screened for high-risk pregnancies. The characteristics of the new-borns retained for study resulted from this choice. Life-threatening distress, defined as the need for respiratory assistance beyond the third minute of life, was observed in 6% of cases. Distress had been predicted 30 minutes before birth in only 42% of cases. In 56.5%, the signs of distress occurred outside "normal" working hours and immediate care was given by the mid-wife in 36% of cases. Despite progress in fetal medicine, these findings would suggest that life-threatening distress at birth is often unpredicted and occurs at a non-negligible rate. This would emphasize the need of training the entire obstetrical team, especially the mid-wives in care the for new-borns.

Acute Disease↗
PubMed1994

[Pregnancy in patients with heart valve prosthesis. Retrospective study apropos of 40 pregnancies].

In order to be able to offer pregnant artificial heart valve patients a practical management approach enabling reduction of maternal and fetal risks, the authors evaluated 40 pregnancies in 24 women. Thirty one valves had been inserted prior to these pregnancies: 24 mechanical valves and 7 biological valves. Different types of anticoagulation regimens were used in 32 pregnancies, while 8 took place without the use of anticoagulants (biological valves in sinus rhythm). From a clinical standpoint, almost all these pregnancies brought to term took place without cardiac decompensation. They resulted in the birth of 26 live infants, including one premature. One child was born at term with a phocomelia-type malformation and two were stillborn. There were five therapeutic abortions and six spontaneous abortions. There were four cases of thromboses of the artificial valve, three of which occurred in patients on heparin (dose of 5,000 IU/12 h). Three massive thromboses required emergency valve replacement surgery. There were also three embolic accidents, including one which regressed totally in a few hours. Two hemorrhagic complications occurred with subcutaneous heparin during the post-partum period. In practice, we feel that: when a young woman wishing to become pregnant requires valve replacement, a biological device is preferable; oral anticoagulants are contra-indicated during the first three months of pregnancy; the dose of 5,000 IU/12 h of heparin is insufficient to prevent thrombo-embolic accidents; when a mechanical valve is already implanted, the sequential treatment protocol of subcutaneous heparin--oral anticoagulant--subcutaneous heparin, with an initial dose of heparin of 5,000 IU/12 h then adjusted on the basis of APTT, is the best choice.

Adult↗
PubMed1994

Measles vaccine failures: lack of sustained measles-specific immunoglobulin G responses in revaccinated adolescents and young adults.

The measles-specific antibody responses of seronegative adolescents and young adults were evaluated after revaccination. Of 1650 previously vaccinated healthy volunteers between the ages of 10 and 30 years, 4.4% were found to be seronegative for measles antibodies and 9.9% had equivocal titers. Seronegative volunteers were revaccinated to measles and followed serially for development of measles-specific IgG. Of 43 subjects followed for at least 1 year, only 58% developed and maintained positive antibody titers; 12% never developed positive titers and 30% initially developed titers that fell below positive levels within 1 year. The peak titers achieved by those subjects who responded transiently were lower than those achieved by subjects who developed sustained responses. Thus even after the recommended two dose schedule of the current measles vaccine, some adolescents and young adults lack protective titers of measles-specific antibody.

Adolescent↗
PubMed1994

[Effects of an educational campaign on cardiovascular risk factors in a French town (Epernon, study town). Methods and preliminary results: prevalence and level of risk factors].

The authors report the methods and preliminary findings of a study scheduled to last 5 years, which aims to evaluate cardiovascular risk factor changes in response to an education program. The population sample consisted of 961 subjects, from Epernon itself (the study town) and from two control towns. The assessment criteria were reported at the beginning of the study and then again after 2 and 5 years. They consisted of an analysis of medical events and of biomedical and dietary data and a detailed analysis of behavior with regard to health and socio-economic variables. Preliminary data show that the samples were similar in Epernon and the control towns and also comparable to some French epidemiological data. There is a striking difference between the percentage of subjects aware of their blood pressure (65.5%) and blood cholesterol (13.4%) levels.

Adult↗
PubMed1993

Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion.

We have used quantitative zymography to measure levels of the type IV collagenases matrix metalloproteinase (MMP)-9 and MMP-2 in 42 biopsies of transitional cell carcinoma and in 7 biopsies of normal bladder. Mean levels of MMP-9 were significantly higher in tumor compared with normal samples (P = 0.08). Levels of MMP-9 and active MMP-2 increased with tumor grade (test for trend, P = 0.002 and P = 0.05, respectively). Levels of MMP-9 and activated MMP-2 were also higher in invasive tumors than in superficial ones (P = 0.001 and P = 0.008, respectively). In situ hybridization studies showed that the mRNAs for both MMP-2 and MMP-9 were located chiefly in the stroma rather than epithelial tumor cells and were concentrated at the interface between the two tissues.

Carcinoma, Transitional Cell↗
PubMed1993

Fatty acid acylation of RNase A using reversed micelles as microreactors.

A water soluble protein, RNAse A, was fatty-acylated using AOT reversed micelles in 2,2,4-trimethyl pentane as microreactors and myristoyl chloride as reagent. Artificial attachment of lipid molecules to this protein was performed for different hydration degrees by changing Wo = [water]/ [AOT], the parameter which controls the microreactor size. The chemically modified protein was monitored using reverse phase HPLC and characterized by HPLC, free amino groups titration, and electrophoresis. An RNase A/myristoyl chloride ratio of 1:4 (mol/mol) at Wo = 7 was found to give 60% of modified protein.

Acylation↗
PubMed1993

Monoclonal anti-idiotypic antibodies as functional internal images of enzyme active sites: production of a catalytic antibody with a cholinesterase activity.

Monoclonal antibody 9A8 was selected by immunizing mice with AE-2, a monoclonal antibody directed against the active site of acetylcholinesterase. In accordance with the idiotypic network theory, monoclonal anti-idiotypic antibody 9A8 displayed internal-image properties of the original immunogen, the acetylcholinesterase active site. Hydrolysis of acetylthiocholine and related esters of thiocholine by 9A8 follows saturation kinetics and kinetic parameters were determined. The hydrolytic activity is characterized by a lowered kcat value (81 s-1) and an increased Km value (0.6 mM) when compared with the original enzyme. However, the rate acceleration (kcat/kuncat = 4.15 x 10(8) remains higher than for the esterase activities usually described for catalytic antibodies directed against transition-state analogs. The 9A8 activity exhibits a relaxation of specificity toward both substrates and inhibitors. This specificity does not correspond to a known enzymatic activity. The anti-idiotypic approach should be valuable for producing different structural and functional copies of the same enzyme active site. This should allow further insights into structure-activity relationships. Furthermore, use of chemically modified enzymes as immunogens may result in anti-idiotypic antibodies with catalytic activities not found in the native enzymes.

Acetylcholinesterase↗
PubMed1993

Coronary artery vasomotion in cardiac transplant patients with normal coronary angiograms.

In 18 consecutive transplant patients with normal coronary angiograms and without calcium blocker therapy, and in 20 controls, we measured the diameters of the left anterior descending artery using quantitative coronary angiography. Measurements were effected on the frames recorded 5 min or more after intravenous administration of 0.4 mg methylergometrine, and 2 min after subsequent 2 mg bolus intracoronary isosorbide dinitrate administration. The arterial vasodilatory capacity was defined as the ratio of the difference of the largest and smallest arterial diameters and the smallest diameter. We observed normal vasoconstriction of the different coronary arterial segments. Coronary arterial diameter decrease from basal state was about 8% and was more pronounced at the distal segments of the left anterior descending artery. There was no difference of vasodilatory capacity between transplant patients and controls for the proximal and middle portion of the left anterior descending artery, while the difference was highly significant for the distal portion. In eight patients, the decrease of the vasodilatory capacity was beyond the lower limit of the normal range of values. The significance of those quantitative angiographic abnormalities is still unproven. They could be due to early vasomotor capacity blunting after transplantation and to late structural alterations of distal coronary vessels in cardiac transplant patients.

Adult↗
PubMed1993

Evolutionary relationships between yeast and bacterial homoserine dehydrogenases.

The Saccharomyces cerevisiae HOM6 gene, encoding homoserine dehydrogenase (EC 1.1.1.3) was cloned and its nucleotide sequence determined. The yeast homoserine dehydrogenase shows extensive homology to the homoserine dehydrogenase domains of the two aspartokinase-homoserine dehydrogenases from Escherichia coli as well as to the homoserine dehydrogenases from Gram positive bacteria. Sequence alignment reveals that the yeast enzyme is the smallest homoserine dehydrogenase known, owing to the absence of a C-terminal domain endowed with the L-threonine allosteric response in Gram positive bacteria. Accordingly, the S. cerevisiae enzyme appears to be a naturally occurring feedback resistant homoserine dehydrogenase. Our results indicate that homoserine dehydrogenase was originally an unregulated enzyme and that feedback control acquisition occurred twice during evolution after the divergence between Gram positive and Gram negative bacteria.

Amino Acid Sequence↗
PubMed1993

[Tobacco smoking and cardiovascular diseases].

Epidemiological studies have shown that chronic tobacco smoking is associated with a significant increase in risks of coronary disease (chiefly myocardial infarction and sudden death), occlusive arteriopathy of the lower limbs and cerebral vascular accident. The risk is strongly augmented by the presence of other vascular risk factors such as arterial hypertension, hypercholesterolaemia, diabetes and oral contraception. Nicotine and carbon monoxide seem to play a major role in the effect of smoking on vessels. In addition to its acute haemodynamic effects, tobacco not only has an atherogenic effect (endothelial toxicity and changes in lipid profile), but it also facilitates thrombosis (by alteration of platelet functions and elevation of fibrinogen level, haematocrit level and blood viscosity) and spasm (by modification of prostaglandin metabolism and action on catecholamines). All these isolated or associated mechanisms account for clinical and evolutive manifestations or coronary or peripheral arterial lesions. The progression of female smoking partly explains the frequency of vascular pathology in young women. Recent experimental data and epidemiological studies have confirmed the responsibility of passive smoking for coronary pathology, thus justifying the measures enforced to limit the exposure of non-smokers. To cease smoking is probably the most efficient primary or secondary preventive measure, as it results in a relatively rapid decrease in the risk of complications, and notably thrombosis. No effort should be spared to obtain these results and at the same time correct other vascular risk factors.

Cardiovascular Diseases↗
PubMed1993

Three-dimensional transformation of capsids associated with genome packaging in a bacterial virus.

Three-dimensional structures of the empty procapsid and the mature capsid of the Salmonella bacteriophage P22 have been determined to a resolution of 28 A using electron cryomicroscopy and computer image processing. The coat subunits in both the structures are arranged as pentamers and hexamers on a T = 7 icosahedral lattice. The two structures display significant differences in shape, size and intersubunit interactions. The empty procapsid is spherical in contrast to the distinctly larger and polyhedral mature capsid. The empty procapsid structure exhibits holes at all the quasi sixfold positions that are absent in the mature capsid. These holes may be the exit ports for scaffolding subunits. Detailed comparisons of the two structures indicate that extensive structural changes take place during maturation in all seven quasi-equivalent subunits. These changes cause flattening of the icosahedral facets, capsid expansion and closing of the holes. This process results in a stable and impenetrable capsid that protects the bacterial genome.

Bacteriophage P22↗
PubMed1993

Reaction-diffusion coupling in a structured system: application to the quantitative simulation of endplate currents.

An approach derived from reaction-diffusion problems is introduced to describe the synaptic endplate current (EPC) at the neuromuscular junction. The model constructed borrows heavily from earlier models, but it takes into account the anisotropic distribution of the different elements participating to the generation of EPC. The transmitter acetylcholine (ACh) is released at the presynaptic membrane, diffuses through the cleft where acetylcholinesterase is homogeneously distributed and then reaches the postsynaptic surface where the receptor is located. The system is defined by a series of partial differential equations which are solved by an explicit difference method. The model predicts amplitudes and time constants in agreement with those observed experimentally, in all the conditions of inhibition of the enzyme or the receptor tested.

Acetylcholine↗
PubMed1993

Subunit conformational changes accompanying bacteriophage P22 capsid maturation.

In double-stranded DNA bacteriophages, packaging of dsDNA requires the transformation of a precursor procapsid into a mature viral capsid. Lattice expansion and release of scaffolding subunits accompanying DNA packaging. Three-dimensional structures of procapsid and mature phage lattices demonstrate that the capsid transformation involves substantial changes in subunit environment. Since this transformation occurs without subunit dissociation, it represents a transition between at least two stable subunit conformations. Using Raman spectroscopy, we have identified changes in coat protein secondary structure and side-chain environments which accompany the capsid transformation. The subunits of procapsid shells contain only 2.0 +/- 0.4% more alpha-helix and less beta-sheet than those of mature capsids; however, numerous side chains are substantially altered by the transformation, including tyrosines, tryptophans, phenylalanines, and aliphatics, which are widely distributed through the subunit sequence. We propose, therefore, that procapsid expansion is accomplished through the relative motion of coat subunit domains with little change in secondary structure. Such hinge-bending conformational transitions may couple ATP-dependent dsDNA condensation with shell expansion.

Bacteriophage P22↗
PubMed1993

Combined segregation and linkage analysis of late-onset Alzheimer's disease in Duke families using Gibbs sampling.

We illustrate the use of Gibbs sampling for combined segregation and linkage analysis using late-onset families in the Duke Alzheimer's disease (AD) data set. The disease penetrance model is flexible, incorporating variable age of disease onset, sporadic cases, and unknown or uncertain ages of AD onset. Model parameters (including allele frequencies) and lod scores are estimated, and a correction for ascertainment is made. Little indication of linkage was observed for any chromosome 19 or 21 marker. However, there was strong evidence for the existence of an AD major gene under an autosomal dominant/sporadic model.

Aged↗
PubMed1993

Salt tolerance and methionine biosynthesis in Saccharomyces cerevisiae involve a putative phosphatase gene.

The progressive salinization of irrigated land poses a threat to the future of agriculture in arid regions. The identification of crucial metabolic steps in salt tolerance is important for the understanding of stress physiology and may provide the tools for its genetic engineering. In the yeast Saccharomyces cerevisiae we have isolated a gene, HAL2, which upon increase in gene dosage improves growth under NaCl and LiCl stresses. The HAL2 protein is homologous to inositol phosphatases, enzymes known to be inhibited by lithium salts. Complementation analysis demonstrated that HAL2 is identical to MET22, a gene involved in methionine biosynthesis. Accordingly, methionine supplementation improves the tolerance of yeast to NaCl and LiCl. These results demonstrate an unsuspected interplay between methionine biosynthesis and salt tolerance.

Adaptation, Physiological↗
PubMed1993

The intestine is a site of passage for potato leafroll virus from the gut lumen into the haemocoel in the aphid vector, Myzus persicae Sulz.

Four detection techniques, three of which gave reliable identification of the virus particles, were used to locate potato leafroll virus (PLRV) in the alimentary canal of its main aphid vector, Myzus persicae Sulz: immunofluorescence on cryostat sections, conventional transmission electron microscopy on ultrathin sections and immune electron microscopy with gold labeling, either prior to or after fixation-embedding. Each method clearly showed the presence of the virus in the intestine epithelium and its absence in cells of the other parts of the alimentary canal. Under the experimental conditions used, the intestinal cells seemed to be the pathway for PLRV transport from the gut lumen into the haemocoel. Electron microscopy examinations showed many virus particles close to the apical plasmalemma of the epithelial cells in the gut lumen of the intestine. Other particles were seen in shallow pit-like regions or surrounded by coated vesicles in the apical part of these cells. Thus the virus particles seemed to enter the epithelial cells of the intestine by a mechanism of endocytosis. In the cytoplasm of these cells, virions were also frequently observed in isolated--or more often aggregated--tubular vesicles. The latter could be involved in PLRV transport through the cell since they were observed fusing with different cell organelles. A few viral particles were also detected in lysosomes as well as in multivesicular bodies. Virus particles were observed between the plasmalemma and basal lamina of the intestine cells but not in the haemocoel, where probably they were quickly dispersed. Our results are discussed in relation to other reports which have shown hindgut and stomach as sites of passage from the gut lumen into the aphid's body cavity for PLRV and other circulative viruses.

Animals↗
PubMed1993

Cerebellar soluble lectin and its glycoprotein ligands in the developing brain of control and dysmyelinating mutant mice.

The levels of an endogenous lectin, the cerebellar soluble lectin (CSL) and of its endogenous glycoprotein ligands were studied using immunoblotting and affinoblotting techniques in the forebrain of quaking, shiverer and jimpy dysmyelinating mutant mice and their respective control littermates during the postnatal development. In the controls of the mutant mice, the level of CSL showed an important increase between days 5-18 then a stabilization, although at all ages the level of CSL was reduced (at least 15%) in the control littermate of the shiverer mutant. In the shiverer mutant the developmental pattern is similar to the control but was reduced by 50% as compared to the control. In the jimpy mutant an erratic development of CSL was observed which was with quasi absence of CSL at days 12 and 25. Variation of CSL levels in the quaking brain were also observed. CSL glycoprotein ligands also showed variable developmental profiles with a special persistence with ageing of CSL-binding glycoproteins in the quaking and jimpy mice. Developmental variations were also observed between the different control littermates. These results are discussed in view of developmental roles attributed to CSL and its glycoproteins ligands in cell adhesion mechanism during brain ontogenesis and especially myelination.

Aging↗