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Biomedical subjects

S Mayer

Publications and source records attributed to S Mayer.

At least 73 records · Page 4Linked to original sources
PubMed1996

A sensitive proliferation assay to determine the specific T cell response against HLA-A2.1-binding peptides.

A proliferation assay to detect a specific T cell response against HLA class I-binding peptides is reported. To establish the specificity and sensitivity of the assay we used a synthetic peptide derived from the CMV glycoprotein B containing the HLA-A2.1 ligand motif. Lymphocyte proliferation was measured following culture of PBMC in the presence or absence of peptide by BrdU uptake. Differing culture conditions were compared (cell number, time in culture, peptide concentration, +/- IL-2). A peptide-specific response was detected in 11 of 23 HLA-A2-positive and CMV IgG-positive donors (47.8%), and in 4 of 36 HLA-A2-positive and CMV IgG-negative donors (11.1%, p = 0.019) tested under optimized conditions. None of 22 HLA-A2-negative individuals tested showed a peptide-specific response and the reproducibility was high. Peptide-specific IFN-gamma-secreting T cells could be demonstrated in responding donors with the ELISPOT assay. This proliferation assay may be suitable for monitoring induction of a specific T cell response against known HLA class I-binding peptides following vaccination with tumor or viral antigens.

Antibodies, Viral↗
PubMed1996

Quantitative determination of heparinoid mimetics in human and rat plasma by micellar electrokinetic chromatography.

The investigated new class of heparinoid mimetics are spaced persulfated carbohydrates designed to increase the success rate of angioplasty and bypass surgery by preventing restenosis without increasing the risk of bleeding. Due to the presence of sulfate groups, these compounds are highly charged and, for preclinical kinetic investigations only small sample volumes of rat plasma were available. Therefore, capillary electrophoresis (CE) was applied. A bioanalytical method based on micellar elektrokinetic chromatography (MEKC) with UV-detection was developed for the selective quantitation of heparinoid mimetics (e.g., Ro 48-0843, Ro 48-3151, Ro 47-6199 and Ro 48-8722) in plasma. Using this method, only small volumes of plasma were required, which could be introduced directly into the separation capillary after 1:1 dilution with 100 mM aqueous sodium dodecyl sulfate (SDS). For increased sample throughput, an additional ultrafiltration step was performed after SDS-dilution of the plasma sample, improving both reproducibility and robustness of the method considerably. The sensitivity of the new method (3 micrograms/ml) was sufficient to follow plasma levels in pharmacokinetic studies. The practicability of this easy and rapid assay was demonstrated by the analysis of more than 350 plasma samples from pharmacokinetic studies performed in rats.

Animals↗
PubMed1996

On the pressure and flow-rate distributions in tree-like and arterial-venous networks.

A solution algorithm yielding the pressure and flow-rate distributions for steady flow in an arbitrary, tree-like network is provided. Given the tree topology, the conductance of each segment and the pressure distribution at the boundary nodes, the solution is obtained from a simple recursion based on perfect Gauss elimination. An iterative solution method using this algorithm is suggested to solve for the pressure and flow-rate distributions in an arbitrary diverging-converging (arterial-venous) network consisting of two tree-like networks which are connected to each other at the capillary nodes. A number of special solutions for tree-like networks are obtained for which the general algorithm is either simplified or can be replaced by closed form solutions of the pressure and flow-rate distributions. These special solutions can also be obtained for each tree of diverging-converging networks having particular topologies and conductance distributions. Sample numerical results are provided.

Algorithms↗
PubMed1995

Unified enantioselective capillary chromatography on a Chirasil-DEX stationary phase. Advantages of column miniaturization.

Immobilized Chirasil-DEX (mono-6-O-octamethylenepermethyl-beta-cyclodextrin chemically linked to dimethylpolysiloxane) can be employed as a versatile chiral stationary phase in chromatography. The chiral polymer has a long lifetime and is configurationally and thermally stable. The concept of unified enantioselective chromatography has been demonstrated for the enantiomer separation of hexobarbital by gas chromatography, supercritical fluid chromatography, liquid chromatography and capillary electrochromatography on a single open-tubular column (1 m x 50 microns I.D.) coated with Chirasil-DEX. The advantages of miniaturization in contemporary chromatographic enantiomer separation are demonstrated. Chirasil-DEX coated on porous silica is also useful for enantiomer separation in high-performance liquid chromatography.

Carbohydrate Sequence↗
PubMed1995

Lipid profile with paternal history of coronary heart disease before age 40.

Serum lipids were measured in children and their parents from 40 families in which the father had a myocardial infarction or coronary heart disease (CHD) before age 40 years. The relationship between physical activity and serum lipid concentrations in the children was also evaluated. Twenty six men had one or more abnormal lipid value (in mmol/l): total venous cholesterol (TVC) > 6.24, triglycerides < 2.55, low density lipoprotein cholesterol (LDL-C) > 4.42, or high density lipoprotein cholesterol (HDL-C) < 0.91. There were 15 spouses with significant hyperlipidaemia (values above). In the 107 children examined, TVC mean (SD) was 4.68 (1.17), triglycerides 1.4 (0.8), LDL-C 3.0 (1.0), and HDL-C 1.18 (0.28). Altogether 42% of the children had significant hyperlipidaemia. No significant correlation was found between the degree of physical activity of the children and their LDL-C and TVC concentrations. However, a significant positive correlation was found between the degree of physical activity and HDL-C and a significant negative one with triglyceride concentrations. It is concluded that screening the progeny of young CHD patients is highly productive in identifying young people at excessive risk for future CHD. The data also suggest that promoting high degrees of activity among these children may have a positive influence on risk factors for adult onset CHD.

Adolescent↗
PubMed1995

Transcranial Doppler ultrasonography in cerebral arteriovenous malformations. Diagnostic sensitivity and association of flow velocity with spontaneous hemorrhage and focal neurological deficit.

BACKGROUND AND PURPOSE: We sought to investigate (1) the sensitivity of transcranial Doppler ultrasonography (TCD) for diagnosis of cerebral arteriovenous malformations (AVMs) and (2) the association of feeding artery flow velocity profiles with spontaneous hemorrhage and focal neurological deficit in AVM patients. METHODS: We examined 114 consecutive AVM patients prospectively by TCD; 22 non-AVM patients with acute cerebral hemorrhage and 52 normal subjects served as controls. To estimate the association of blood flow velocity patterns in feeding arteries with spontaneous hemorrhage and focal neurological deficit, the total group of AVM subjects was divided into patients with and without a history of bleeding and also into those with and without clinical signs of "steal" (focal deficit unrelated to hemorrhage). RESULTS: Sensitivity for large and medium-sized AVMs was high (> 80%), whereas 62% of small AVMs were missed. TCD was also highly sensitive (80%) in a group of five AVM patients with acute hemorrhage. Flow velocity profiles were not related to spontaneous hemorrhage (mean velocity, 111 cm/s in patients with hemorrhage versus 114 cm/s in patients without hemorrhage; P = .65) or clinical signs of steal (mean velocity, 111 cm/s versus 113 cm/s in patients with and without steal, respectively; P = .89). CONCLUSIONS: We concluded that (1) TCD is highly sensitive for large and medium-sized AVMs; (2) in acute cerebral hemorrhage TCD may help to differentiate AVM from non-AVM bleeds; (3) the predictive value of TCD findings for clinical sequelae of AVMs remains undetermined; and (4) the concept of hemodynamic steal in AVMs is not supported by TCD data.

Adult↗
PubMed1994

Enantiomer separation using mobile and immobile cyclodextrin derivatives with electromigration.

The principle of electrochromatography is applied to enantiomer separation with wall-coated capillaries of 50 microns (ID). As chiral stationary phase an immobilized polysiloxane containing chemically bonded monokis-6-O-octamethylene-permethyl-cyclodextrin (beta- or gamma-Chirasil-Dex) was used. The results are compared with the conventional method of adding cyclodextrin derivatives as chiral pseudostationary phase to the running buffer.

Buffers↗
PubMed1994

Attitudinal, circadian, circumstantial, and subject selection explanations of shiftwork effects on health.

The competing explanations for adverse health symptoms commonly observed in night-shift workers can be divided into "correlational" and "causational" groups. This study monitored health claims and costs over 3 years for all shifts in seven industrial plants and administered a survey canvassing a range of behavioral and attitudinal dimensions. Shift workers differed from day workers in symptomatology and health claims, and, in their feelings of support from management, safety attitudes, and practices, felt support from friends and family, alcohol and tobacco use, and other dimensions. Because shiftwork was associated with adverse health effects but these other measured dimensions were not, the explanation that health effects are due to shiftwork itself rather than to its attitudinal or demographic correlates is supported.

Adult↗
PubMed1993

Patent problems.

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Animals↗
PubMed1993

In vitro and in vivo irreversible plasma protein binding of beclobric acid enantiomers.

Acyl glucuronides are known to be labile conjugates, which undergo hydrolysis and bind irreversibly to proteins. The lipid-regulating agent (+/-)-beclobrate is immediately converted to the free acid after oral administration. Further metabolism leads to formation of the corresponding diastereomeric acyl glucuronides. Beclobric acid glucuronides were quantified by indirect measurement with an HPLC method based on chiral fluorescent derivatization of the carboxylic acid and subsequent normal-phase chromatography. The renal clearance of unchanged drug is low, with almost all drug excreted into urine as glucuronic acid conjugates. Beclobric acid glucuronide is also detectable in plasma. In vitro degradation studies with beclobric acid glucuronide (at a concentration of 5 microM in 150 mM phosphate buffer pH 7.4) exhibited a minor tendency for acyl migration and hydrolysis, i.e., a higher stability than has been observed for the acyl glucuronides of most other drugs. The in vitro degradation half-lives of the two beclobric acid beta-1-O-acyl glucuronides were 22.7 and 25.7 h. After incubation with pooled plasma and human serum albumin in buffer pH 7.4 irreversible binding was measured in vitro. No significant difference between the two enantiomers was detected with respect to the magnitude of in vitro irreversible binding. In 3 healthy male volunteers the extent of irreversible binding of both beclobric acid enantiomers to plasma proteins was investigated after single and multiple oral doses of racemic beclobrate (100 mg once daily). Irreversible binding of both enantiomers was observed in all volunteers. The adduct densities for (-)- and (+)-beclobric acid after single 100 mg beclobrate doses were 0.147 x 10(-4) and 0.177 x 10(-4) mol/mol protein. Multiple dosing increased irreversible binding 3- to 4-fold.

Benzhydryl Compounds↗
PubMed1993

Predictability of the covalent binding of acidic drugs in man.

Although metabolism via glucuronide conjugation has generally been considered a detoxification route for carboxylic acids, the newly discovered chemical reactivity of these conjugates, leading to covalent binding with proteins, is consistent with the toxicity observed for drugs containing the carboxylic acid moiety. Here we report that degradation rates (intramolecular rearrangement and hydrolysis) for 9 drug glucuronide metabolites show an excellent correlation (r2 = 0.995) with the extents of drug covalent binding to albumin in vitro. Furthermore, this binding capacity is predictable based on chemical structure of the acid and depends on the degree of substitution at the carbon alpha to the carboxylic acid. The in vivo covalent binding in humans for these drugs is also predictable (r2 = 0.873) when the extent of adduct formation is corrected for the measured plasma glucuronide concentrations. These results suggest that the structure of a carboxylic acid drug may predict the degree to which the corresponding acyl glucuronides will form covalent adducts that probably/possibly lead to toxicity. This information could be a useful adjunct in drug design.

Animals↗
PubMed1993

Pharmacokinetics of beclobric acid enantiomers and their conjugates after single and multiple oral dosage of racemic beclobrate.

The chiral lipid regulating agent beclobrate (CAS 55937-99-0), which was marketed as racemate, is - like clofibrate - rapidly hydrolyzed to beclobric acid immediately after absorption. Pharmacokinetic data were only available for the total concentration, but not for the two enantiomers. Therefore, the pharmacokinetics of (-)- and (+)-beclobric acid were studied in 8 healthy male volunteers after a single 100 mg dose of rac-beclobrate and under steady state conditions, i.e. after repetitive dosage of 100 mg beclobrate once daily for 8 days. After oral administration unchanged beclobrate was not detected in plasma. Distinct differences were found in the pharmacokinetic parameters of the two beclobric acid enantiomers. The maximum plasma concentrations and the AUC values of the (+)-enantiomer exceeded those of the (-)-enantiomer nearly 2 fold. Beclobric acid, the active metabolite, is converted to an acyl glucuronide. The diastereomeric glucuronides were detected in the plasma of all volunteers, but the differences in the pharmacokinetics were not as evident as for beclobric acid enantiomers. A comparison of the measured steady-state beclobric acid enantiomer concentration and those simulated on the basis of the parameters (open two-compartment model) obtained for a single beclobrate dose showed that the accumulation factor is slightly but nevertheless significantly higher than predicted.

Adolescent↗