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Biomedical subjects

S Weber

Publications and source records attributed to S Weber.

At least 19 recordsLinked to original sources

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

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

[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

[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

[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

[Hemolytic crisis and acute kidney failure from rifampicin].

Two cases are reported of hemolytic crisis and acute anuria after intermittent rifampicin medication. Immunologic tests demonstrate that the hemolysis was of the drug-induced heteroimmune type whereas the pathogenesis of the anuria was uncertain. For both complications the prognosis is good.

Acute Kidney Injury

[Biological determination of the beta blocking activity of human serum].

A method of biological assessment of the Beta blocking activity of human serum is reported. It is based on the catecholamine response of rat myocardial cells in culture, incubated in the serum to be tested. Its advantage is that it takes into account all block-blocking substances present in the serum, not only the drug itself but also its possible active metabolites. The results obtained by this method in 10 healthy subjects after 60 mg penbutolol were compared with those given by chemical dosage and ergometry. The ergometric and biological changes were parallel from the 2nd and the 8th hour while the serum levels of the drug rapidly. This discordance could be due to the presence of an active metabolite, 4-hydroxy-penbutolol.

Adrenergic beta-Antagonists

[An attempt to analyze the state of gastric cancer control in the German Democratic Republic (author's transl)].

Starting from the records of the county cancer control offices, an attempt is made to analyze the quality of detection and treatment of gastric cancer in the G.D.R. Possibilities and results of curative treatment strongly depend upon the extent of the disease and the age of the patient at the time of diagnosis. During the period of observation (Berlin 1955--1974, county Königs Wusterhausen 1960--1974), the proportion of elderly patients (65-yrs.) increased, stage distribution remained about the same, the rate of curative operations increased a little. When comparing the situation in the capital Berlin with the district Erfurt, the city of Dresden and the rural county Königs Wusterhausen, it can be demonstrated that the quality of diagnosis and treatment in Berlin is somewhat better then in the other teritories.

Adult

Inhibited response to isoproterenol and altered action potential of beating rat heart cells by human serum in septic shock.

Human serum, obtained within 24 hours after the onset of septic shock, was evaluated for its effects on the chronotropic response of cultured rat myocardial cells to isoproterenol. Transmembrane action potential (AP) was measured in some experiments. Sera obtained after the first four to five hours, when central venous pressure (CVP) was normal or high, inhibited increased cell beats, while this property was not evidenced for samples taken soon after septic shock when CVP was low. Sera were also found to alter AP in much the same way as Sotalol, an adrenergic beta-blocking drug. These two effects were never observed with control sera obtained from healthy male adults at rest. These findings demonstrate that sera from patients in septic shock depress the beta-adrenergic response of rat myocardial cells, after the early phase of septic shock characterized by sympathoadrenergic activity. They strongly suggest the mediation of unidentified humoral factors, which might interfere in the pathogenesis of myocardial dysfunction during the intermediate phase of septic shock.

Action Potentials