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Biomedical subjects

D Goldman

Publications and source records attributed to D Goldman.

At least 325 records · Page 18Linked to original sources
PubMed1981

Ultrasensitive stain for proteins in polyacrylamide gels shows regional variation in cerebrospinal fluid proteins.

A new silver stain for electrophoretically separated polypeptides can be rapidly and easily used and can detect as little as 0.01 nanogram of protein per square millimeter. When employed with two-dimensional electrophoresis, it should permit qualitative and quantitative characterization of protein distributions in body fluids and tissues. It has been used to demonstrate regional variations in cerebrospinal fluid proteins.

Cerebrospinal Fluid Proteins↗
PubMed1981

Lectins activate lymphocyte pyruvate dehydrogenase by a mechanism sensitive to protease inhibitors.

The mitogenic lectins concanavalin A and phytohemagglutinin were found to stimulate pyruvate oxidation in rat mesenteric lymphocytes. Marked cell agglutination accompanied this response. Wheat germ agglutinin, a nonmitogenic lectin, also aggregated lymphocytes but did not cause alteration of pyruvate oxidation. Cell lysates from lectin-treated cells retained their ability to oxidize pyruvate at an elevated rate, indicating that the observed stimulation of pyruvate oxidation was not due to increased transport of labeled pyruvate into the cells. Pyruvate oxidation activity in such lysates was readily sedimented in a mitochondria-enriched cellular fraction, indicating that it reflects mitochondrial pyruvate dehydrogenase. Stimulation of this activity by lectins in intact lymphocytes was inhibited when the cells were incubated under conditions expected to inhibit trypsin-like proteases. Thus, esters of arginine, but not of alanine or tyrosine, blocked stimulation of pyruvate dehydrogenase by the lectins. The data indicate that pyruvate dehydrogenase is activated in lymphocytes treated with mitogenic lectins by a mechanism involving one or more proteolytic reactions. The similarity between the results presented here and those recently reported for insulin action on its target cells [Seals, J. R. & Czech, M. P. (1980) J. Biol. Chem. 255, 6529-6531] suggests that these systems may have similar modes of transmembrane signalling.

Animals↗
PubMed1981

Protein variations associated with Lesch-Nyhan syndrome.

Patients having Lesch--Nyhan syndrome were studied by using enzymatic, immunologic, and two-dimensional electrophoretic techniques. Four hundred proteins were analyzed on each two-dimensional electrophoretogram for positional or quantitative variation. In autoradiograms of lymphocytes stimulated with phytohemagglutinin, there were 11 quantitative differences found in all patients that were significant at the 2P less than 0.01 level. A significant quantitative difference was also found in an analysis of silver-stained gels of unstimulated lymphocytes. Patients had trace amounts of erythrocyte hypoxanthine phosphoribosyl transferase (HPRT) activity and trace or no immunoprecipitable HPRT. However, HPRT was observed in silver-stained erythrocyte electrophoretograms and in autoradiograms from phytohemagglutinin-stimulated lymphocytes. Unstimulated lymphocytes contained 65% of the control HPRT concentration. Currently, the technology of two-dimensional electrophoresis detects a fraction of the total cellular proteins and defective proteins may not show electrophoretic alterations. However, specific secondary changes in other polypeptides may be observed and, when catalogued, will serve as an aid in the diagnosis and understanding of the pathophysiology of metabolic diseases.

Blood Proteins↗
PubMed1981

Some considerations in the experimental approach to distinguishing between membrane transport and intracellular disposition of antineoplastic agents, with specific reference to fluorodeoxyuridine, actinomycin D, and methotrexate.

Analysis of the interaction between an anticancer agent and the intact cell can provide important clues to cytotoxic determinants and mechanisms of drug selectivity and resistance. This can be very useful in optimally evaluating single and multidrug regimens in test systems, designing new agents, and evaluating drug metabolism and binding to cellular target sites. This cellular pharmacokinetic approach requires very meticulous attention to experimental design, especially the time dimension chosen for study, and an appropriate framework for data analysis. This paper reviews cellular pharmacokinetic principles and experimental approaches that can be applied in "uptake studies" with cytotoxic agents, focusing, as examples, on studies from this laboratory with fluorodeoxyuridine, actinomycin D, and methotrexate.

Animals↗
PubMed1980

Two-dimensional gel electrophoresis of cerebrospinal fluid proteins.

Two-dimensional electrophoresis, with isoelectric focusing in the first dimension and sodium dodecyl sulfate/polyacrylamide gel electrophoresis in the second, has been adapted for the high-resolution analysis of cerebrospinal fluid proteins. Proteins were detected with a new, highly sensitive silver stain that made visible more than 300 polypeptides from 60 microL of spinal fluid, in highly reproducible patterns. We have mapped these patterns, noting difference between the proteins observed in spinal fluid and plasma, and have prepared a partial map of cerebrospinal fluid proteins.

Blood Proteins↗
PubMed1976

Treatment of phenothiazine-induced dyskinesia.

Previous experience indicated the possibility that a serotonin antagonist substance, was effective in relieving dyskinesia as a reaction to phenothiazine antipsychotic drugs. Since the substances used in the original observations did not become available on the United States market, a compound known to be a serotonin antagonist, cyproheptadine, which was readily available and safe, was used to treat three patients who had phenothiazine-induced dyskinesia. In these patients, cyproheptadine was definitely effective in relieving the dyskinesia over an extended period of time. Further controlled studies are required to confirm this report.

Antipsychotic Agents↗