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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 595 records · Page 33Linked to original sources

[Performance of routine Doppler studies for screening of the fetus in de uterus in the 3d trimester of pregnancy].

We did screening Doppler investigations of the foetus circulation during the third trimester of pregnancy, and established reference curves for Resistance and Pulsatility Indexes of the umbilical and middle cerebral as well as for the ratios of these indexes. We compared these indexes in groups of fetuses with different characteristics at birth. It turned out that low birth-weight, or the presence of dips in the fetal heart rate during labor is associated with some distinctive anomalies of the measured indexes compared with the control group with a normal birth-weight and no deceleration during labor.

Adult↗

[Search for emboligenic heart disease in case of ischemic cerebral accidents].

The demonstration of a cardiac source of systemic embolism in patients who have suffered a cerebral ischemic event may have important therapeutic implications. This explains the large demand for echocardiography and Holter monitoring in these patients. The frequency of cerebral embolism of cardiac origin, the simplification of the diagnostic approach by non-invasive investigations and the precision of ultrasound techniques explains the tendency towards the indiscriminate generalisation of this attitude. However, the large number of potential patients for investigation, the limited facilities of investigation and the incertitude over the responsibility of certain cardiac abnormalities with respect to the context and age, are arguments in favour of a more selective investigative approach. The keystone of diagnosis is careful history taking and clinical examination with interpretation of the ECG and chest X-ray. Three clinical situations may then be identified: 1) A cardiac abnormality known to be highly embolic is diagnosed from the outset (e.g. mitral stenosis, valve prosthesis, endocarditis, myocardial infarction). The diagnostic work-up is no longer etiological: echocardiography may show intracardiac thrombi or a valvular vegetation, reinforcing the causal relationship, but the complementary investigations are mainly useful for evaluation the cardiac disease and for deciding on curative or preventive therapy. 2) A cardiac abnormality is diagnosed but its responsibility is doubtful due to its high prevalence and low embolic potential. This is the case of patients with mitral valve prolapse, mitral annular calcification, calcific aortic stenosis and VVI pacing. Complementary investigations are not discriminative for the etiological diagnosis of the cerebral embolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

Stabilizing effect of organic solvents on oxyhemoglobin.

The role of hemoglobin solutions as oxygen carriers in biotechnology are numerous, such as in the oxygen supply to biocatalysts or in the preparation of blood substitutes. However, the major barrier to the successful use of hemoglobin in biological and medical engineering is the autoxidation of heme iron during preparation, storage, and utilization. Fifty-six solvents, chosen among the group of Parker's classification, were studied with regard to the autoxidation kinetics of oxyhemoglobin under nondenaturant conditions. Among these solvents 27 present a concentration range in which the autoxidation rates were reduced compared to autoxidation in water. Three groups of solvent have been observed: one exhibiting only a destabilizing effect regardless of the solvent proportion, a second showing a strong stabilizing effect (k(H2O)/k(solvent) greater than 20) and a third showing a low stabilization (k(H2O)/k(solvent) less than 20). The most effective stabilizing solvents were glycerol, glycols, and alcohols. The effect of hydroorganic solvents could be explained by taking into account the globin solvation by water molecules. The solvents that enhance the structure of the water and form few hydrophobic interactions with globin prevent oxyhemoglobin autoxidation.

Humans↗

Adherence of Pasteurella multocida isolated from pigs and relationship with capsular type and dermonecrotic toxin production.

Pasteurella multocida can often be isolated from pneumonic lungs in pigs. There is little information about the pathogenesis of this infection. Attachment of microorganisms to eucaryotic cells is considered to be a prerequisite for colonization of the host in the pathogenesis of bacterial infections. Forty-seven P multocida strains isolated from pigs in France, and belonging to capsular type A or D were tested for their ability to agglutinate human erythrocytes, and to adhere to tracheal and lung cells. Each isolate was tested for dermonecrotic toxin production. Adherent strains were further observed by electron microscopy to look for attachment structure. Only type A strains agglutinated human O erythrocytes, but no relationship was observed between hemagglutination and dermonecrotic toxin production. The results of the adherence tests showed a greater affinity (P less than 0.05) of type A strains for lung cells (50% were adherent, whereas only 20% of type D strains were adherent) but did not reveal any correlation between adherence and the presence of dermonecrotic toxin. Microscope observations showed that these P multocida strains did not possess any pili-like structures. In conclusion, by means of the adherence test we were able to demonstrate a stronger adherence of type A strains and this adherence did not seem to be related to pili-like structures.

Animals↗

[Results of surgery in mitral valve insufficiency with impaired left ventricular function].

This cooperative study (8 French Cardiology Departments) was undertaken to determine the postoperative outcome of patients with pure, chronic, non-ischemic mitral regurgitation and poor left ventricular function (ejection fraction less than 50%). Seventy-three patients, 48 males and 25 females with a mean age of 55.5 +/- 12.1 years were included. Fifty-eight patients were in Class III or IV of the NYHA Classification. The average cardiothoracic ratio was 0.59 +/- 0.07. Forty-six patients were in atrial fibrillation. The average ejection fraction was 43 +/- 5 per cent (end systolic volume: 97.8 +/- 37.9 ml/m2; end diastolic volume: 175.2 +/- 67.6 ml/m2). Sixty-one patients underwent prosthetic mitral valve replacement and 12 had a Carpentier valvuloplasty. Two patients died after the operation and 20 died during follow-up (average 48.1 +/- 27.6 months), giving a 5 year actuarial survival rate of 69.6 per cent. In the long-term, fifteen per cent of patients were in NYHA Class III or IV. A multivariate Cox analysis showed that the only predictive factors of a poor outcome were age and female sex. These results of surgery for mitral regurgitation with moderate to severely altered left ventricular function were relatively good, but this study does not allow evaluation of the evolution of patients with mitral regurgitation and very poor left ventricular function (no patients with ejection fraction less than 25%).

Actuarial Analysis↗

[Myocardial involvement in 2 women, carriers of Duchenne de Boulogne muscular dystrophy].

Duchenne muscular dystrophy is the commonest genetic muscular disease. The prognosis, which depends on cardiac involvement, is poor. In boys, this takes the form of a hypokinetic cardiomyopathy particularly affecting the postero-lateral wall of the left ventricle which then dilates. The recent identification of the gene which transmits the disease on the X chromosome and of the coded protein, dystrophin, has improved our understanding of the disease. We report two cases of isolated cardiac involvement in two female carriers of the disease, classically thought to be unaffected. They presented with apparently idiopathic dilated cardiomyopathies. These cases show that Duchenne muscular dystrophy is an original example of a genetically determined diffuse muscular disease with cardiac involvement.

Adult↗

[Dystrophic aortic insufficiency: influence of dilatation of the ascending aorta on secondary outcome].

This cooperative study recensed 89 cases of patients operated for aortic regurgitation in whom the dystrophic process was confirmed on anatomical (thin, translucent valves without symphysis, multilation or sclerosis) and histological criteria (mucinous infiltration). They included 81 men (91%) and the average age was 52 +/- 14 years. The valvular degeneration was part of a generalised dystrophy of elastic tissue in 8 patients (6 "formes frustes" of Marfan's syndrome, 2 Lobstein's syndrome). The patients were divided into 2 groups according to the diameter of the ascending aorta measured by echocardiography and/or aortography. In Group 1 (n = 40), the aorta was not dilated (diameter less than 40 mm) whereas in Group 2 (n = 49), the diameter of the ascending aorta was dilated (40-55 mm) but not aneurysmal (loss of parallelism of the aortic walls). The two groups were comparable before surgery with respect to age, sex, functional class, degree of left ventricular dilatation, left ventricular ejection fraction and presence of associated coronary disease). There were no differences in the operative parameters but aortic parietal biopsy (n = 35) revealed clear signs of cystic medianecrosis more often in Group 2 than in Group 1 (14/25 versus 1/10, p less than 0.05). No operative procedure was performed on the ascending aorta during aortic valve replacement. One operative death occurred in each group. After an average follow-up of 4 years, there was a higher mortality in Group 2: the actuarial 7 year survival rate being 74% in Group 1 and 54% in Group 2. This was explained by a higher incidence of ascending aortic complications. Only 1 patient in Group 1 developed an aneurysm of the ascending aorta requiring reoperation compared to 14 patients in Group 2, 8 of whom were reoperated (p less than 0.01). These results suggest that non-aneurysmal dilatation of the ascending aorta in patients with dystrophic aortic regurgitation is a poor prognostic factor because of the high incidence of secondary aortic parietal complications (aneurysm, dissection).

Actuarial Analysis↗

Substrate inhibition or activation kinetics of the beta-galactosidase from the extreme thermoacidophile archaebacterium Caldariella acidophila.

The kinetics of the hydrolysis of p-nitrophenyl-beta-D-galactopyranoside (pNPG) by a thermophile, beta-galactosidase, was studied at different temperatures. This enzyme was isolated from the thermophilic microorganism archaebacterium Caldariella acidophila. The hydrolysis of pNPG by beta-galactosidase does not follow Michaelis-Menten law. This enzyme is inhibited by excess substrate at low temperatures and it is activated by excess substrate at high temperatures. A minimum mechanistic model is proposed to explain the behaviour. This model assumes the binding of an additional substrate molecule on the glycosidyl enzyme intermediate. This model is in good agreement with the postulated mechanism for beta-galactosidase from Escherichia coli. The kinetic parameters are calculated at six different temperatures.

Archaea↗

Distribution of intravenously administered acidic and basic fibroblast growth factors in the mouse.

Iodinated acidic or basic fibroblast growth factor (aFGF or bFGF) were separately injected into adult mice to follow their distribution in the main organs of the animals. Iodinated FGFs intravenously injected into mice cleared from blood with a T1/2 of 30 s. They mainly bound to kidney, liver and spleen. The binding of FGFs to these organs was maintained when the latter were washed with a physiological buffer containing 0.15 M NaCl, but it was eliminated when the buffer contained 2 M NaCl. Simultaneous injections of the FGFs together with increasing doses of heparin weakened the binding of FGF to vessels in a dose-dependent manner.

Animals↗

Gene-enzyme relationship in the sulfate assimilation pathway of Saccharomyces cerevisiae. Study of the 3'-phosphoadenylylsulfate reductase structural gene.

In yeast, mutations in six different loci (MET1, MET4, MET8, MET16, MET22, and MET25) have been reported to result in the absence of 3'-phosphoadenylylsulfate (PAPS) reductase activity. In the present study, we show that MET16 is the structural gene for PAPS reductase and that the yeast and the Escherichia coli enzymes display significant similarities. Thioredoxin has been implicated in the reduction of PAPS in Saccharomyces cerevisiae as well as in E. coli. One of the generally accepted mechanisms for the action of thioredoxin as a hydrogen donor involves a redox-active sulfhydryl group in the catalytic site of PAPS reductase. However, the present study shows that the site-directed mutagenesis of the unique cysteine from PAPS reductase leads to an enzyme which remains active in vivo. This result would rather support the hypothesis of thioredoxin playing the role of a thiol carrier in the reduction of PAPS into sulfite. Strains separately mutated in the six different loci cited above were examined for the expression of different genes. A mutation in the MET4 gene abolishes transcription of both genes MET16 and MET25. In contrast, mutations in MET1, MET8, and MET25 do not impair MET16 transcription, yet strains bearing these mutations are devoid of PAPS reductase activity. To account for the latter result, we postulate that the enzymes involved in sulfate assimilation may occur as a multienzyme complex in S. cerevisiae.

Amino Acid Sequence↗

The control of lipase-catalysed transesterification and esterification reaction rates. Effects of substrate polarity, water activity and water molecules on enzyme activity.

The reaction rate of two lipase-catalysed reactions, esterification and transesterification, were studied in a liquid/solid two-phase system in order to investigate the effect of water partition between the enzyme preparation and the liquid phase composed of only the reactants, i.e. without the conventional solvents. Lipase from Candida cylindracea was used for these studies. The enzyme was inactive in dehydrated systems. In the case of monoester synthesis, the reaction rate increased with increasing water activity. The reaction rates of the non-specific C. cylindracea lipase-catalysed reactions were very sensitive to the nature of the substrates in this unusual system. For instance, the transesterification reaction rate of ethyl propionate was 48 times higher with nonanol than heptanol in the case of dehydrated substrates, but only 2.2 times higher in the case of water-saturated substrates. The results presented here demonstrate the absolute necessity to consider the polarity of every substrate, because of its ability to modify the water partition between the solid phase (enzyme preparation) and the liquid phase (substrate and product), which results in drastic changes in enzyme activity. Contrary to esterification, which is known to be activated by the water produced, the rate of transesterification remained constant at the beginning of the reaction. However, when transesterification and esterification were carried out in the same liquid phase, the transesterification reaction rate was controlled by the water produced by the concomitant esterification. Activation effects of the water molecules produced during the enzymatic reaction were of exactly the same order of magnitude for both reactions.

Alcohols↗

Pattern formation in an immobilized bienzyme system. A morphogenetic model.

Experimental and theoretical studies of a reaction-diffusion model of two immobilized enzymes participating in the cellular acid-base metabolism, namely glutaminase and urease, are presented. The system shows an unstable steady state at pH 6.0, where any perturbation will drive the system towards a more alkaline or more acidic pH, owing to the autocatalytic behaviour with respect to pH exhibited by both enzymes. When diffusion is coupled to reaction by means of immobilization, different patterns of the internal pH profile appear across the membrane. If the bienzymic membrane is subjected to a perturbation at its boundaries, of the same amplitude but in opposite directions, the internal pH evolves through an asymmetric pattern to attain a nearly symmetric distribution of pH. The pH value at the final steady state is more acidic or more alkaline than the initial state according to the initial and boundary conditions. The final nearly symmetric state is attained more rapidly when less enzyme is immobilized (1.8 x 10(-4) M.s-1 as against 3.3 x 10(-4) M.s-1 of total enzyme activity in the membrane volume). The experimental results agree rather well qualitatively with numerical predictions of the model equations.

Diffusion↗

Conformational states of the bacteriophage P22 capsid subunit in relation to self-assembly.

The formation of closed icosahedral capsids from a single species of coat protein subunit requires that the subunits assume different conformations at different lattice positions. In the double-stranded DNA bacteriophage P22, formation of correctly dimensioned capsids is mediated by interaction between coat protein subunits and scaffolding protein. Raman spectroscopy has been employed to compare the conformations of coat protein subunits which have been polymerized to form capsids in the presence and absence of the of scaffolding protein display a Raman spectrum characterized by a broad amide I band centered at 1665 cm-1 with a discernible shoulder near 1653 cm-1, and a broad amide III profile centered at 1238 cm-1 but asymmetrically skewed to higher frequency. These spectral features indicate that the protein conformation in procapsid shells is rich in beta-sheet secondary structure but contains also a significant distribution of alpha-helix. When biologically active, purified subunits assemble in the absence of scaffolding protein, they form polydisperse multimers lacking the proper dimensions of procapsid closed shells. We designate these multimers as "associated subunits" (AS). The Raman spectrum of associated subunits indicates a narrower distribution of secondary structure. The associated subunits are characterized by a sharper and more intense Raman amide I band at 1666 cm-1, with no prominent amide I shoulder of lower frequency. An analogous narrowing of the Raman amide III profile is also observed for AS particles, with an accompanying shift of the amide III band center to 1235 cm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Capsid↗