Search PubMed⌕ Search

Biomedical subjects

S Weber

Publications and source records attributed to S Weber.

At least 181 records · Page 10Linked to original sources

Spontaneous mutations in the human immunodeficiency virus type 1 gag gene that affect viral replication in the presence of cyclosporins.

Human immunodeficiency virus type 1 mutants that are resistant to inhibition by cyclosporins arise spontaneously in vitro during propagation in a HeLa-CD4+ cell line in the presence of a nonimmunosuppressive analog of cyclosporin A. Interestingly, the phenotype of all of the mutants examined is drug resistant and drug dependent, with both cyclosporin A and its analog. Four independently isolated mutants have been analyzed genetically by construction of recombinant proviruses in the NL4-3 parental strain background and subsequent testing of the chimeric viruses in HeLa cells. The cyclosporin-resistant, cyclosporin-dependent phenotype consistently transfers with a 1.3-kb fragment of gag, within which the four mutants share one of two possible single amino acid exchanges in a proline-rich stretch in the capsid domain of Pr55gag. These mutants provide the first evidence that mutations in human immunodeficiency virus type 1 gag confer resistance to cyclosporins; however, replication is conditional on the presence of the drug. In the T-cell line CEM, replication of the recombinant mutant viruses is also cyclosporin dependent. The drug-dependent replication in HeLa cells is stringent, and in the absence of cyclosporin only revertant viruses with the parental phenotype grow out of cultures infected with cyclosporin-dependent virus. In at least one isolate examined, the revertant phenotype appears to be due to suppressor mutations near the proline-rich region.

Amino Acid Sequence↗

The effects of relaxation exercises on anxiety levels in psychiatric inpatients.

The purpose of this study was to investigate the effects of relaxation exercises on anxiety levels in an inpatient general psychiatric unit. The conceptual framework used was holism. A convenience sample of 39 subjects was studied. Anxiety levels were measured prior to and post interventions with the state portion of the State-Trait Anxiety Inventory. Progressive muscle relaxation, meditative breathing, guided imagery, and soft music were employed to promote relaxation. A significant reduction in anxiety level was obtained on the post-test. The findings of this study can be incorporated by holistic nurses to help reduce anxiety levels of general psychiatric inpatients by using relaxation interventions.

Adult↗

[Treatment of myocardial infarction: from the reading of publishing work to everyday prescription].

Many therapeutic trials have demonstrated an improvement in the prognosis of myocardial infarction. The practitioner, before changing his prescribing habits, should pose questions to which the authors propose answers. The prescriber should check that the new treatment has been adequately validated by verifying the quality of the therapeutic studies (classical, mega trials such as ISIS or GISSI, metaanalysis). He should also check that a trial population is representative of his own patients (ethnic and social factors, high percentages of patients actually included in the trial compared with those eligible for inclusion). He should insure that his own conditions of practice (patient follow-up, delays and quality of specialised intervention) would provide the same benefit-risk ratio as in the clinical trial. Finally, by analysing patients subgroups or even better, factorial subgroups, and above all, the mode of action of the drugs, he should check that the new treatment may be associated with already established therapeutic modalities. In conclusion, nothing can replace case by case clinical judgment in the application of the results of the literature to everyday practice.

Clinical Trials as Topic↗

[Physiopathology of unstable angina].

The majority of cases of unstable angina and myocardial infarction have a common origin: rupture of an atheromatous plaque complicated by intracoronary thrombosis. The nature of these "high risk" plaques is now well known: they are excentric, moderately severe lesions, the voluminous lipid centres of which are covered only by a thin unstable fibrous layer. The triggering factor of the rupture of an unstable plaque may be an increase in wall stress (spastic vasoconstriction, rise in blood pressure), and/or an inflammatory or haemorrhagic phenomenon within the plaque itself. Once the plaque has ruptured, the outcome to unstable angina or myocardial infarction is determined by two factors: the size and rapidity of constitution of the thrombus and the quality of the collateral circulation.

Angina, Unstable↗

[Prescription of heparin in the acute phase of myocardial infarction: expected and observed benefits...].

Before the advent of thrombolysis, heparin was widely used in the acute phase of myocardial infarction. Its prescription was based on trials, often of criticable methodology, some of which showed a reduction in hospital mortality and others a reduction in the incidence of reinfarction, left ventricular thrombi or venous thromboembolism. A better understanding of physiopathology and the development of emergency methods of myocardial reperfusion (pharmacological or mechanical) showed that the real objective of management of acute myocardial infarction should be reopening of the occluded artery and the maintenance of its patency. Reocclusion which occurs in 20% of cases in associated with increased hospital morbidity and mortality. Heparin, which limits the paradoxial increase of thrombin after thrombolysis significantly decreases this risk. Two reference trials on the benefits of heparin in association with thrombolysis, GISSI-2 and ISIS-3, demonstrated a significant reduction in the 7 day mortality but no significant reduction in the 35 day mortality. The poor quality of the anticoagulation protocol, especially in patients receiving rtPA, explains these disappointing results. Thus, it has now been clearly established that heparin, even though it increases the number of bleeding complications should be associated early and at an appropriate dosage with all thrombolytic regimes or mechanical reperfusion methods used during acute myocardial infarction. Apart from the embolic complications or ventricular thrombosis, this anticoagulation only seems to be justified during the first 48 hours.

Anticoagulants↗

[Treatment of unstable angina].

Adequate treatment of unstable angina, initiated soon enough in the setting of a coronary care unit, avoids evolution towards myocardial infarction in more than 90% of the patients. Treatment consists of a combination of anti-thrombotic and anti-ischemic therapies. Oral beta-adrenergic blockers and intravenous nitrates represent the usual anti-ischemic treatment; calcium antagonists will be prescribed as an adjunct therapy if the response is insufficient or if a vasospastic mechanism is suspected. Anti-thrombotic treatment usually consists of a combination of low dose aspirin and intravenous heparin. Twelve hours are usually sufficient to titrate this medical regimen and to assess its efficacy; if myocardial ischaemia persists or recurs despite this therapy, urgent coronary angiography and subsequent revascularization are warranted. Usually ischaemia is adequately controlled by medical therapy, elective coronary angiography is nevertheless useful to screen high risk patients (left main and severe three-vessel disease) needing coronary artery bypass graft. In most cases however revascularization, by surgery or angioplasty, will be considered only if ischaemia at rest or induced by exercise, recurs despite optimal medical treatment.

Adrenergic beta-Antagonists↗

Light-generated nuclear quantum beats: a signature of photosynthesis.

Light-induced radical pairs in deuterated and deuterated plus 15N-substituted Synechococcus lividus cyanobacteria have been studied by transient EPR following pulsed laser excitation. Nuclear quantum beats are observed in the transverse electron magnetization at lower temperatures. Model calculations for the time profiles, evaluated at the high-field emissive maximum of the spectrum, indicate assignment of these coherences to nitrogen nuclei in the primary donor. Thorough investigation of the nuclear modulation patterns can provide detailed information on the electronic structure of the primary donor, providing insight into the mechanism of the primary events of plant photosynthesis.

Journal Article↗

Suitability of the ruffe (Gymnocephalus cernua [L.]) for investigations on activity of hepatic enzymes induced by xenobiotics.

Activity measurements of enzymes catalyzing (i) the oxidation of xenobiotics (phase I) and (ii) the conjugation of metabolites produced in phase I (phase II) were carried out in ruffe to test its suitability for biological monitoring. Ruffe typically lives in the lower regions of rivers and in estuaries where monitoring is of particular interest for estimating the amount of pollutants introduced into the sea. The flounder, already examined for this purpose, is used as reference organism. In ruffe, the enzymatic activity (7-ethoxycoumarin-O-deethylase (ECOD) and 7-ethoxyresorufin-O-deethylase (EROD)) increased with the contamination of the river toward Hamburg whereas in flounder it did not. The absence of a correlation between induction of the enzymatic activity in flounder and environmental contamination is attributed to the higher readiness of the flounder to migrate. Therefore, mixed function oxygenase activity found in flounders may not represent the inducing capacity of the local concentrations of xenobiotics. Since ECOD activity in ruffe was 5 to 20 times higher compared to the flounder, histopathological findings of investigations of the liver tissue were considered. Destruction or pathological changes of the endoplasmatic reticulum (where ECOD and EROD are located) is often reported in flounder but not in the ruffe, which may influence the expression of some enzymatic activities. The enzymatic activity of the phase II enzyme glutatione-S-transferase, which is considered to have a protective function in the cell against damages, caused by reactive metabolites, was more induced in ruffe than in flounder. Thus the ruffe may be less subjected to cell injury.

7-Alkoxycoumarin O-Dealkylase↗

Thrombocytopenia-adapted in vitro bleeding test assesses platelet function in thrombocytopenic patients.

Platelet counts do not always reflect the true bleeding risk in chronically thrombocytopenic patients, and the posttransfusion platelet increments do not necessarily demonstrate that therapeutic efficacy. There are no easy and reliable tests yet permitting the determination of platelet function in thrombocytopenic patients. The in-vitro bleeding test (IVBT) with the Thrombostat 4000 proved to be a very sensitive and specific test for the detection of platelet disorders. In order to become suitable for the investigation of thrombocytopenic blood with platelet count between 5 x 10(9)/L and 50 x 10(9)/L, special modifications were necessary. We report on the evaluation of two thrombocytopenia-adapted modifications (TP-IVBT 150/120), first with blood of healthy donors made thrombocytopenic (three experiments with six blood samples each of different platelet concentrations and identical hematocrit) and then in a clinical study on 77 thrombocytopenic patients (69 with bone marrow hypoplasia, eight with autoimmune thrombocytopenia) receiving 267 platelet transfusions. The patients were followed over 15 days on average (1-67 days) by daily examinations (total 1,285 observation days). Most TP-IVBT measurements were carried out in triplicate, using the modification with the 120-microns filter (TP-IVBT 120) because it proved to be superior to the other modification. Additionally, cell counts, hematocrit, body temperature, platelet volume, platelet distribution width, expression of CD 36, 41a, 42b on platelets, Simplate bleeding time, and detailed analysis of bleeding signs were performed for the calculation of a bleeding score. There was a close correlation between TP-IVBT and platelet counts with thrombocytopenic normal blood (r2 = 0.81-0.94). This indicated the suitability of this test modification to examine platelet function in thrombocytopenic patients. The clinical study showed that the TP-IVBT helped at least to determine the platelet-related bleeding risk in thrombocytopenic patients. It allowed differentiation between hypoplastic and autoimmune thrombocytopenia in most cases. In addition, significant differences in platelet function of various diseases and of different bone marrow regeneration could be demonstrated. The TP-IVBT is well-suited for the control of platelet transfusion efficacy and may replace the in-vivo bleeding time in most cases. On the other hand, the test still shows too much of a variation and involves too much labor and cost for routine application.

Bleeding Time↗

Mast cells.

Explore the source record for details and available documents.

Animals↗

Decay kinetics of N,N,N',N'-tetramethylbenzidine photocations in frozen micellar solution of cetyltrimethylammonium bromide.

After UV irradiation of rapidly frozen solutions of N,N,N',N'-tetramethylbenzidine (TMB) in dilute aqueous micellar cetyltrimethylammonium bromide at 80 K, the ESR signal corresponding to the TMB+ cation was detected indicating photoionization. This signal was monitored as a function of time at various temperatures between 80 K and 260 K. On a timescale of a few days the signal decayed to a plateau value that was stable for months. Two distinct second-order processes for the decay from the initial to the plateau value were observed: one prevailing at low temperatures with an activation energy of 0.6 kJ/mol, and one prevailing at T > 220 K with an activation energy of 13 kJ/mol. By means of spin probe investigations the latter process was shown to be connected with a local softening of the region adjacent to the micellar surface.

Benzidines↗

An epitope of elongation factor Tu is widely distributed within the bacterial and archaeal domains.

A monoclonal antibody (MAb), MAb 900, which detects a 43-kDa protein present on Escherichia coli was found. Subsequently, more than 90 organisms, belonging to either the bacterial, archaeal, or eucaryal domain, were tested for reactivity to this MAb. Of the bacterial and archaeal domains, almost all species proved to be positive, whereas all organisms from the eucaryal domain gave negative results. The 43-kDa protein was purified by affinity chromatography and subsequently analyzed by microsequencing methods. Two peptide sequences which showed a high degree of homology (> 99%) to the prokaryotic elongation factor Tu (EF-Tu) were obtained. Western blot (immunoblot) analysis using both purified EF-Tu and EF-Tu domains confirmed that the unknown protein was EF-Tu. The panbacterial distribution of EF-Tu, which is present in large amounts in every prokaryotic cell, renders this protein a good candidate for a diagnostic approach. In consequence, we have used the anti-EF-Tu MAb 900 to design both a dot blot assay and an enzyme-linked immunosorbent assay. From either blood culture, urine, or gall-bladder fluid, bacterial contamination could be detected. The sensitivity of these tests is currently 10(4) bacteria per ml.

Amino Acid Sequence↗

Strategies for negotiating preemployment agreements.

Though the long-term effects of preemployment agreements on career development are unknown, these guidelines are suggestions to ensure responsible interactions among facilities, health information management students, and academic programs. Preemployment agreements meet personal, educational, professional, financial, and institutional goals. Long-term implications warrant additional study. Preemployment agreements are increasing because they mutually benefit HIM students and employers. This emerging process, however, is creating new ethical and legal dilemmas for academic programs and other involved parties. The intent of this article is to identify potential issues and dilemmas involved in student-employee negotiations and preemployment agreements. The issues and proposed guidelines may not be germane to all situations. Many successful relationships, primarily those that include the guidelines discussed here, have been negotiated. Terminology for preemployment agreements is different from terminology for financial aid. Consistent use of terminology, and knowledge regarding these agreement processes including guidelines for their appropriate use, is necessary to avoid ethical and legal problems. Exploration of the impact of preemployment agreements on future career decisions and professional development is needed.

Education, Continuing↗

Indomethacin treatment causes loss of insulin action in rats: involvement of prostaglandins in the mechanism of insulin action.

Glucose tolerance tests in rats showed that after indomethacin treatment plasma insulin levels rose five-fold higher than in untreated controls. Accordingly, the pancreatic islets of indomethacin-treated rats secreted insulin at a threefold higher rate. Glucose tolerance tests additionally showed that indomethacin treatment led to a retarded disposal of the elevated blood glucose. Both effects appear to be caused by an attenuation of the hormone responsiveness for insulin and noradrenaline (alpha-adrenoceptor action) by indomethacin. The following observations support this view: insulin and adrenaline (alpha-adrenoceptor action) lost their ability to lower cyclic adenosine monophosphate (AMP) levels in hepatocytes; the glycogen content of liver and skeletal muscle was reduced by 95% and 65%, respectively; in adipocytes the stimulation of glucose transport by insulin was reduced by 60%. These effects of indomethacin can be reversed by the addition of exogenous prostaglandin E (PGE), as elevated cyclic AMP synthesis was again sensitive to alpha-adrenergic inhibition in the liver. These results indicate a relationship between prostaglandins and insulin action. These effects of indomethacin could result from reduced synthesis of cyclic PIP (prostaglandylinositol cyclic phosphate), a proposed second messenger for insulin and alpha-adrenoceptor action, whose synthesis was decreased by indomethacin treatment and increased by the addition of exogenous PGE. Stimulation of glucose transport by cyclic PIP was unaffected by indomethacin treatment, in contrast to the stimulation by insulin. Inhibition of PGE and cyclic PIP synthesis resulted in a metabolic state comparable to insulin resistance in non-insulin-dependent diabetes mellitus.

Adipocytes↗

A contribution to the indications for platelet transfusion and determination of its therapeutic efficacy.

The platelet count does not really reflect the true bleeding risk in chronically thrombocytopenic patients. Recently, we reported on two modifications of an in vitro bleeding test (IVBT) which appeared to be suitable for the evaluation of primary non-vascular hemostatis in thrombocytopenic and anemic patients (platelets 10-50,000/microL, hct 16-30 L/L). We report on the clinical study conducted with the IVBT modification which proved to be superior. Fifty thrombocytopenic patients, 42 with bone marrow hypoplasia and 8 with autoimmune thrombocytopenia, were followed up for a total of 686 days and received 161 platelet transfusions (mainly from cell separator). The IVBT was carried out with the Thrombostat 4000 in triplicate using 120 microns filters and evaluating the occlusion time (OT). Additionally, cell count, hematocrit, body temperature, platelet volume, platelet distribution width, Simplate time and a detailed analysis of bleeding signs for the calculation of a bleeding score were performed. The IVBT modification used allowed the determination of platelet-related bleeding risk in thrombocytopenic patients. With the IVBT, significant differences in platelet function in different patients could be demonstrated which primarily reflected the underlying disease. In addition, bone marrow regeneration correlated with platelet function. From the findings of this study, the authors formulate criteria for the indication of platelet transfusion which includes platelet function as well as the platelet count. Increased individual bleeding risk factors have to be considered too. But before generalization these criteria have to be verified by a controlled prospective study.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests↗