Biomedical subjects

L Schwarcz

Publications and source records attributed to L Schwarcz.

4 recordsLinked to original sources

PubMed2001

Utilization of new technologies in drug trials and discovery.

It has become widely accepted that individual genetic variation is a prime determinant in both disease susceptibility and toxic response to therapeutic agents and xenobiotics. Emerging genetic sequence data and phenotype association studies are expected to enable disease risk prediction and guide subsequent therapeutic approaches in individual cases. However, making a good match between an individual genetic profile, disease risk prediction, and appropriate therapeutic intervention will require genotyping many polymorphic sites in large numbers of genes or single nucleotide polymorphism sites throughout the genome. Additionally, each polymorphism will have to be associated with a phenotype. Presumably, a composite phenotype may be predicted by integrating anticipated contributions from each polymorphism contributing to the complex genotype. Methods for executing such large-scale genotyping studies are rapidly evolving and becoming available. DNA microarray technology applied in hybridization-based genotyping assays is particularly well suited to respond to the accelerating pace of polymorphism discovery and the associated demand for highly parallel genotyping capability.

Base Sequence↗

PubMed1998

Two-dimensional parallel array technology as a new approach to automated combinatorial solid-phase organic synthesis

An automated, 96-well parallel array synthesizer for solid-phase organic synthesis has been designed and constructed. The instrument employs a unique reagent array delivery format, in which each reagent utilized has a dedicated plumbing system. An inert atmosphere is maintained during all phases of a synthesis, and temperature can be controlled via a thermal transfer plate which holds the injection molded reaction block. The reaction plate assembly slides in the X-axis direction, while eight nozzle blocks holding the reagent lines slide in the Y-axis direction, allowing for the extremely rapid delivery of any of 64 reagents to 96 wells. In addition, there are six banks of fixed nozzle blocks, which deliver the same reagent or solvent to eight wells at once, for a total of 72 possible reagents. The instrument is controlled by software which allows the straightforward programming of the synthesis of a larger number of compounds. This is accomplished by supplying a general synthetic procedure in the form of a command file, which calls upon certain reagents to be added to specific wells via lookup in a sequence file. The bottle position, flow rate, and concentration of each reagent is stored in a separate reagent table file. To demonstrate the utility of the parallel array synthesizer, a small combinatorial library of hydroxamic acids was prepared in high throughput mode for biological screening. Approximately 1300 compounds were prepared on a 10 μmole scale (3-5 mg) in a few weeks. The resulting crude compounds were generally >80% pure, and were utilized directly for high throughput screening in antibacterial assays. Several active wells were found, and the activity was verified by solution-phase synthesis of analytically pure material, indicating that the system described herein is an efficient means for the parallel synthesis of compounds for lead discovery. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗

PubMed1996

Deconvolution of combinatorial libraries for drug discovery: experimental comparison of pooling strategies.

An experimental evaluation of several different pooling strategies for combinatorial libraries was conducted using a library of 810 compounds and an enzyme inhibition assay (phospholipase A2). The library contained compounds with varying degrees of activity as well as inactive compounds. The compounds were synthesized in groups of three and pooled together in various formats to realize different pooling strategies. With one exception, all iterative deconvolution strategies and position scanning resulted in identification of the same compound. The results are in good agreement with the predicted outcome from theoretical and computational methods. These data support the tenet that active compounds for pharmaceutically relevant targets can be successfully identified from combinatorial libraries organized in mixtures.

Drug Evaluation, Preclinical↗

PubMed1987

Gender differences in the relationship between hostility and the type A behavior pattern.

A group of 97 male and 111 female undergraduates completed the Jenkins Activity Survey, the Framingham Type A Scale, the Adjective Checklist Type A Scale, the Spielberger State-Trait Anxiety Inventory, and the Buss-Durkee Hostility Inventory. A factor analysis revealed three dimensions: Anger-Emotionality, Anger-Aggression, and Residual Pattern A. All Type A measures loaded highly on the Type A factor, with the Jenkins Activity Survey loading the highest. The Framingham Type A Scale was related to Anger-Emotionality, the Adjective Checklist Type A Scale was related to Anger-Aggression, and the Jenkins Activity Survey was related to neither of the anger dimensions. Women scored higher than men on Anger-Emotionality and the Guilt, Resentment, and Irritability subscales and lower than men on the Assaultiveness subscale. Women showed higher correlations between Type A and the Guilt subscale, and men between Type A and the Suspiciousness subscale. We conclude that Type A is a multidimensional construct that manifests itself differently in men and women.

Adult↗