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Biomedical subjects

E Silbergeld

Publications and source records attributed to E Silbergeld.

16 recordsLinked to original sources
PubMed2000

The N-methyl-D-aspartate neurotransmitter receptor is a mammalian brain target for the dinoflagellate Pfiesteria piscicida toxin.

Blooms of Pfiesteria piscicida, a dinoflagellate in eastern U.S. coastal rivers, are believed to secrete toxins that kill fish and produce short-term memory loss in humans. Only one or two of Pfiesteria's multiple stages secrete the toxin, and only under certain environmental conditions. Thus, neither the presence of Pfiesteria nor fish kill alone can be indicative of toxin presence. The objective of this study was to identify the mammalian molecular brain target for the toxin that is associated with decrements in memory. Seven rat brain neurotransmitter receptors were selected to study because of their reported roles in cognitive function: receptors for nicotine, muscarine, AMPA/kainate, N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid, and dopamine 1 and 2. The effects of 17 environmental and laboratory samples on radioactive ligand binding to these receptors were studied. Of the seven receptors, binding only to the NMDA receptor was inhibited by only the two Pfiesteria-containing waters (identified by PCR) that also killed fish, and not by any of the other 15 samples tested. It is suggested that inhibition of NMDA-receptor binding is the cause of memory loss in exposed humans. Thus, it could be a useful biomarker for the toxin's presence in rivers for decisions on closures and for identification of the fractions containing the toxin during its purification. Knowledge of the toxin's molecular target, and how it affects its function, also leads to suggestions for therapeutics to use in animal models.

Animals↗
PubMed1996

P53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers.

In this paper we describe a statistical analysis of the European Molecular Library p53 mutation database comparing p53 mutations occurring in breast, colorectal, liver, lung, and ovarian cancers. The analyses show that mutation hot spots vary by cancer and that base pair changes and predicted amino acid changes in the gene product vary by cancer and by codon. The analyses use relative frequencies and epidemiologic measures of effect (prevalence ratios) not applied previously to these data. The five cancers in the database with the largest sample sizes were breast (418), colorectal (398), liver (341), non-small cell lung (313), and ovarian cancers (251), for a total of 1,721 reports of p53 mutations. The five cancers varied considerably in the distribution of mutations over sites, with different hot spots in each cancer. At the six most frequently reported codon sites, we compared base pair and amino acid changes by type of cancer. The comparison of base pair changes indicated a predominance of particular base pair changes at a codon (for example, C-->T and G-->A changes at Codon 248) and their association with specific cancers (C-->T changes with colorectal cancer and G-->A changes with both colorectal and breast cancers at codon 248). Comparing predicted amino acid changes by codon and cancer was also intriguing, as in codons 175 and 273, where arginine to cysteine and arginine to histidine changes were frequent in breast, colorectal, and ovarian cancers. Variations in p53 mutational distributions by cancer may be explained by different exposures to carcinogens or by organ-specific clonal selection. Further research may be stimulated by this analysis.

Amino Acids↗
PubMed1993

A reproductive hazards research agenda for the 1990s. Research Needs Working Group.

There is substantial scientific and public concern about the potential effects of occupational and environmental toxicants on reproductive health. These effects include impaired functioning of the reproductive systems of men and women as well as a broad spectrum of developmental problems expressed in offspring. Research on reproduction and development is among the most complex undertakings in biomedical research. This complexity is due in part to the intricate biology of reproduction, the multiple targets involved (male, female, and offspring), the uncertainties in extrapolating from animal models to humans, and the problems involved in accurately characterizing exposures and outcomes in epidemiologic investigations. However, given the relatively brief history of research into toxicant-induced reproductive health effects, we have made enormous strides in our knowledge over the past decade. In particular, recent advances in reproductive biology and biotechnology and in the development of biological markers of exposure, effect, and susceptibility are greatly enhancing our ability to study cause-effect relationships. In this paper, the Research Needs Working Group proposes ways to apply existing knowledge to better protect reproductive health and suggests directions for future research. Fulfilling this challenging agenda will require responsible cooperation by labor, industry, government, individual citizens, and the scientific community. Further research and collaboration are essential to both prevent adverse reproductive and developmental outcomes and to formulate a sound scientific basis for policy making.

Communication↗
PubMed1979

Advances in the neuropharmacology of Parkinsonism.

Advances through basic research have elucidated the disturbances of neurotransmitter function in Parkinson's Dopamine has replaced acetylcholine and norepinephrine as the most studied neurotransmitter, with both conceptual and practical developments, exemplified by the hypothesis of cyclic adenosine monophosphate as a "second messenger," and new therapeutic agents. We now have rationally designed in-vitro and in-vivo tests for the evaluation of dopaminergic compounds instead of entirely empiric screening procedures. We are starting to identify different categories of dopaminergic receptors and to manipulate them selectively, with gains in understanding the physiologic input to the striatum. Crucial questions remain, including how dopamine modulates striatal output and what causes the parkinsonian degeneration of the nigrostriatal pathway. Developing knowledge on synaptic physiology and pharmacology may lead to better therapy.

Animals↗
PubMedDate not supplied

Criteria for progressive modification of neurobehavioral batteries.

Six specific issues affecting the progressive modification of neurobehavioral test batteries used in field studies of populations exposed to neurotoxicants are discussed and test review recommendations are provided addressing each issue. The issues include: (a) general test review standards, (b) comprehensive assessment, (c) tailored batteries, (d) incorporation of new tests and techniques, (e) personnel and mechanisms for review, and (f) development of a battery assessing peripheral nervous system function.

Behavior↗