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Biomedical subjects

S Weber

Publications and source records attributed to S Weber.

At least 19 recordsLinked to original sources
PubMed1992

[Vasomotricity of normal and atheromatous coronary arteries].

In order to fulfil, at any time, the myocardium requirements for oxygen and energy, the coronary circulation must be able of extremely intense and rapid vasodilation. This circulation undoubtedly is the body's regional circulation that "works" in the most difficult anatomical and physiological conditions. Coronary vasomotricity is regulated by three different systems operating synchronously. Metabolism-mediated vasodilatation, with adenosine as principal mediator, essentially concerns the small-caliber intramyocardial arterioles and is the predominant regulatory system in normal subjects. Nervous regulation (sympathetic and parasympathetic systems) exclusively concerns the wide, epicardial coronary arteries; it plays a modest, but non-negligible, role in normal subjects but becomes very important in patients with stenosis of the epicardial coronary arteries. Endothelium-mediated regulation, discovered about 10 years ago, seems to play a crucial role. Under the influence of haemodynamic and humoral stimuli, the endothelium synthesizes and releases substances which stimulate the underlying vascular smooth muscle. Nitric oxide (NO), or EDFR1, is the best known, but not the only messenger of vasodilatation; beside its relaxant effect on the smooth muscle, it exerts a potent platelet antiaggregating action. The functioning of these regulatory systems is deeply perturbed by atheroma of the coronary arteries: in addition to the fixed haemodynamic obstacle due to atheromatous stenosis, there is a diffuse decrease of endothelial functions and a rise in sensitivity to nervous vasoconstrictor stimuli.

Animals↗
PubMed1992

Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function.

BACKGROUND: Bronchial hyperresponsiveness to cholinergic stimuli such as the inhalation of methacholine is common in patients with impaired left ventricular function. Such hyperresponsiveness is best explained by cholinergic vasodilation of blood vessels in the small airways, with extravasation of plasma due to high left ventricular filling pressure. Because this vasodilation may be prevented by the inhalation of the vasoconstrictor agent methoxamine, we studied the effect of methoxamine on exercise performance in patients with chronic left ventricular dysfunction. METHODS: We studied 19 patients with a mean left ventricular ejection fraction of 22 +/- 4 percent and moderate exertional dyspnea. In the first part of the study, we performed treadmill exercise tests in 10 patients (group 1) at a constant maximal workload to assess the effects of 10 mg of inhaled methoxamine on the duration of exercise (a measure of endurance). In the second part of the study, we used a graded exercise protocol in nine additional patients (group 2) to assess the effects of inhaled methoxamine on maximal exercise capacity and oxygen consumption. Both studies were carried out after the patients inhaled methoxamine or placebo given according to a randomized, double-blind, crossover design. RESULTS: In group 1, the mean (+/- SD) duration of exercise increased from 293 +/- 136 seconds after the inhalation of placebo to 612 +/- 257 seconds after the inhalation of methoxamine (P = 0.001). In group 2, exercise time (a measure of maximal exercise capacity) increased from 526 +/- 236 seconds after placebo administration to 578 +/- 255 seconds after methoxamine (P = 0.006), and peak oxygen consumption increased from 18.5 +/- 6.0 to 20.0 +/- 6.0 ml per minute per kilogram of body weight (P = 0.03). CONCLUSIONS: The inhalation of methoxamine enhanced exercise performance in patients with chronic left ventricular dysfunction. However, the improvement in the duration of exercise at a constant workload (endurance) was much more than the improvement in maximal exercise capacity assessed with a progressive workload. These data suggest that exercise-induced vasodilation of airway vessels may contribute to exertional dyspnea in such patients. Whether or not inhaled methoxamine can provide long-term benefit in patients with heart failure will require further study.

Administration, Inhalation↗
PubMed1992

Specific low-affinity recognition of major histocompatibility complex plus peptide by soluble T-cell receptor.

The T-cell receptor is necessary and sufficient for recognition of peptides presented by major histocompatibility complex molecules. Other adhesion molecules, like CD4 or CD8, play an auxiliary role in antigen recognition by T cells. Here we analyse T-cell receptor (TCR) binding using a soluble rather than a cell-bound receptor molecule. A TCR-immunoglobulin chimaera is constructed with the variable and the first constant regions of both the TCR alpha- and beta-chains linked to the immunoglobulin light-chain constant regions. This soluble TCR is expressed, assembled and secreted as an alpha beta heterodimer by a myeloma cell line transfected with the recombinant genes. Furthermore, the soluble TCR is biologically active: it specifically inhibits antigen-dependent activation of the relevant T-cell clones and thus discriminates between proper and irrelevant peptides presented by major histocompatibility complex molecules.

Animals↗
PubMed1992

[The effective antibacterial spectrum of sulfacetamide].

Swabs of the anterior eye segment of 180 eyes (145 patients) taken in the time period between August 1, 1989 until August 30, 1989 were sent to an external, independent microbiological institute in order to verify in-vitro antibacterial properties of marketed sulfacetamide containing drugs. MIC test was performed with isolated pathogenic bacterial strains without knowledge of the underlying diagnosis. It was shown that sulfacetamide is able to inhibit the growth of all isolated strains. Depending on the type of bacteria concentrations of 0.006 up to 6.4% sodium sulfacetamide proved to be effective. Simultaneously, all patients were treated with sulfacetamide containing ointment and/or eye drops 4 times daily for maximum of 14 days. With swabs taken at intervals of 7 and 14 days no bacterial growth was detected.

Bacteria↗
PubMed1992

Expression of chimeric neo-Rev response element sequences interferes with Rev-dependent HIV-1 Gag expression.

Recombinant plasmids containing reiterated human immunodeficiency virus type 1 (HIV-1) Rev response element (RRE) sequences were constructed to suppress Rev-dependent HIV-1 Gag expression. The mammalian expression vectors pMAMneo containing one, three, or six repeats of the RRE sequence were cotransfected with a HIV-1 HTLV-IIIB proviral DNA into HeLa cells. All three RRE expression plasmids reduced replication of HIV-1 with similar efficacy. Furthermore, the chimeric expression vector pCMV neoRRE6 x ----(containing six copies of the RRE sequence) was used to establish HeLa cell lines constitutively expressing RRE. A plasmid encoding a Rev-dependent HIV-1 p24 Gag protein was cotransfected with the wild-type Rev expression plasmid into three different RRE-expressing HeLa cell lines. p24 Gag protein production in the culture supernatants of the HeLaneoRRE cells was compared with two neo-expressing cell lines. Although all cell lines (HeLaneoRRE, HeLaneo) displayed similar transfection efficiencies, p24 Gag protein synthesis was markedly reduced in the RRE-expressing cell lines in comparison to the control cells.

Base Sequence↗
PubMed1992

[The bronchial arteries and their anastomoses with the coronary arteries].

We studied bronchial arteries (BA) and their anastomoses with coronary arteries in 53 adult subjects (30 female and 23 male, mean age 82) and one 2 month old child. Each subject had 1 to 4 BAs, born from an area on the anterior side of the descending aorta measuring less than 2 cm in diameter in 62 percent of the cases and never exceeding 4 cm in the other cases. In 6 cases BAs vascularize the left auricle; more than half of all cases had an anastomose with the coronary arteries: 11 with the right coronary artery and 9 with the left one. These anastomoses preserve the vascularization of the carina after a cardio-pulmonary transplantation. The may have a function of vascular supply in some coronarian patients and the study of associated coronary pathology gives confirmation of it in one fourth of the cases.

Aged↗
PubMed1992

[Mechanism of cellular action of nitrate derivatives].

Nitrate derivatives have to undergo metabolic activation in the smooth muscle cell or in the plasma with a sulflydryl radical. This transformation results in the formation of nitric oxide and/or S-nitrosothiols. These products stimulate an enzyme, the soluble guanylate cyclase in the sarcoplasm of the smooth muscle cell; giving rise to the formation of intracellular cyclic GMP from GTP. The cyclic GMP activates a kinase protein which in turn activates a number of other protein enzymes involved in the recaptation of calcium by the sarcoplasmic reticulum and in the extrusion of calcium from the cell. In addition, cyclic GMP reduces the level of phosphorylation of the myosin light chain, thereby reducing the sensitivity of the contractile proteins to intracellular calcium. All these phenomena cause smooth muscle relaxation so explaining most of the vasodilator effect of nitrate derivatives.

Cyclic GMP↗
PubMed1992

[Isosorbide dinitrate in the treatment of coronary insufficiency].

The improvement of our understanding of the pharmacology of nitrate derivatives has allowed rationalisation of their use in the treatment of coronary artery disease. The comprehension of the evolution of the sensitivity of the vessel wall to nitrate vasodilatation with time has enabled definition of a rhythm of administration which preserves therapeutic efficacy: a daily therapeutic window of 8 to 10 hours. The introduction of new galenic forms (slow release oral preparations and transdermal patches) facilitates the practical application of the "optimal" pharmacokinetic profile. A single daily dose of slow release ISDN is effective in controlled trials versus placebo in the treatment of chronic stable angina. Many clinical trials have also shown the synergy of the anti-anginal effects of ISDN and betablockers, both in single dose studies and during prolonged administration. These therapeutic windows are not adapted to the treatment of acute coronary insufficiency (unstable angina, myocardial infarction); however, it has recently been shown that the use of small, fixed doses of intravenous ISDN over a 3 day period is usually adequate for controlling acute coronary insufficiency and is not associated with the phenomenon of tolerance.

Adrenergic beta-Antagonists↗
PubMed1992

[Doppler echocardiographic evaluation of vasodilator treatments in patients with cardiac insufficiency. Contribution to the combination of isosorbide dinitrate and captopril].

Hemodynamic evaluation of a vasodilator drug is a difficult exercise in which Doppler echocardiography can be a useful tool. We studied the hemodynamic effect of isosorbide dinitrate (ISDN) by Doppler echocardiography in 7 patients with severe cardiac failure despite prolonged therapy with usually effective doses of captopril. The patients were evaluated before (H0) and 24 hours after treatment by ISDN (120 mg/24 hr) (H24) and 10 minutes after sublingual 0.75 mg of trinitrin (H24 + T). M mode echocardiography did not show any significant changes in chamber dimension as reported after vasodilator therapy in patients without cardiac dilation: in patients with severe left ventricular dilatation a reduction in LV filling pressures causes little if any changes in fractional shortening and ventricular dimensions. Two-dimensional echocardiography showed a reduction in end systolic volume and an increase in ejection fraction, emphasizing the superiority of this technique in cases of abnormal left ventricular function and the sensitivity of indices of systolic function to changes in afterload in these patients. Cardiac output measured by Doppler increased during the study. The maximal acceleration did not change significantly and pulmonary artery pressures were stable after administration of nitrates. ISDN caused a marked change in diastolic mitral flow patterns for which there are several explanations: an effect of ISDN on relaxation or LV compliance or on the conditions of LV filling or on both factors together. The presence of mitral regurgitation and/or atrial arrhythmia prevents the use of Doppler indices for analysis of diastolic LV function.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Evaluation of tolerance during intravenous administration of low dose of isosorbide dinitrate in the treatment of unstable angina].

The eventuality of tolerance was assessed in 19 patients with unstable angina treated by continuous intravenous infusion of 50 micrograms/min of isosorbide trinitrate (ISDN) in association with heparin and betablocker therapy. The tolerance phenomenon was evaluated by the hypotension produced by the ISDN infusion and by the amplitude of fall in blood pressure produced by an intravenous bolus of 1 mg of glyceryl trinitrate (GTN) according to the principle of crossed tolerance to the two nitrate derivatives. Under these conditions of administration, the authors observed partial attenuation of the blood pressure response to continuous ISDN infusion and absence of cross tolerance between ISDN and intravenous GTN. The co-prescription of intravenous N-acetylcysteine at a dosage of 10 g/24 hours in 10 of the 19 patients did not affect the blood pressure or the response to the GTN bolus compared with the 9 other patients who had received placebo after double-blind randomisation. The results of this study do not indicate if the maintenance of vascular sensitivity to nitrate derivatives at least for 72 hours, was related to the choice of a relatively low dose and/or the use of ISDN rather than another nitrate derivative, in particular glyceryl trinitrate. The use of intravenous ISDN at a low dose over a 3 day period in the usual conditions of prescription for unstable angina does not seem to induce a quantitatively significant phenomenon of tolerance.

Acetylcysteine↗
PubMed1991

A simple and rapid slide blot method to quantify cytokine-mRNA in small numbers of lymphocytes.

In this study we describe an in situ hybridization protocol suitable for the measurement of interleukin mRNAs in small numbers of cells in suspension. In this procedure defined numbers of such cells are coated onto defined areas of microscopic slides using LAB-TEK tissue culture chamber slides. 32P-labelled oligonucleotides are then hybridized to them in situ. Binding of the probes is measured by autoradiography using X ray film followed by densitometry (slide blot) or, as in standard in situ protocols, by exposure to photoemulsion. In experiments designed to demonstrate the specificity and feasability of this protocol, peripheral blood T cells were activated with mitogenic stimuli and oligonucleotide probes specific for IL-2, IFN-gamma, or a control probe (IL-2 random) were hybridized to them. Both lymphokine genes were found to be transcribed in two discrete phases with the first peak at 12 h and another peak 48 h after stimulation, as measured semi-quantitatively on a per cell basis using X ray film exposure. The proposed experimental protocol supports the advantages of X ray film autoradiography such as rapidity, simplicity and the objectivity of densitometric evaluation, but also permits microscopic evaluation of individual cells as performed in classical in situ hybridization protocols using photoemulsion.

Base Sequence↗
PubMed1991

Purification and cDNA sequencing of an oleate-selective acyl-ACP:sn-glycerol-3-phosphate acyltransferase from pea chloroplasts.

The soluble acyl-ACP:sn-glycerol-3-phosphate acyltransferase from chloroplasts of chilling-sensitive and -resistant plants differ in their fatty acid selectivity. Enzymes from resistant plants discriminate against non-fluid palmitic acid and select oleic acid whereas the acyltransferase from sensitive plants accepts both fatty acids. To use this difference for improving plant chilling resistance by biotechnology the gene for an oleate-selective enzyme is required. Therefore, the oleate-selective enzyme from pea seedlings was purified to apparent homogeneity. Tryptic peptides of internal origin were sequenced. Polyclonal antibodies raised in rabbits were used for an immunological screening of a pea leaf cDNA expression library in lambda gt11. A positive clone of 1800 bp was selected showing an open reading frame which codes for 457 amino acids. The deduced amino acid sequence coincides perfectly with the tryptic sequences. A tentative assignment of the processing site was made which divides the preprotein into a mature protein of 41 kDa in accordance with experimental findings and a transit peptide of 88 amino acids. At present the comparison between a selective (pea) and an unselective (squash) acyltransferase sequence does not provide a clue for recognizing the structural differences resulting in different selectivities.

1-Acylglycerophosphocholine O-Acyltransferase↗