Biomedical subjects

J Gastel

Publications and source records attributed to J Gastel.

3 recordsLinked to original sources

PubMed1991

The formamidine pesticides chlordimeform and amitraz decrease hepatic glutathione in mice through an interaction with alpha 2-adrenoceptors.

Recent studies have provided evidence that formamidine pesticides, such as chlordimeform (CDM; N'-4-chloro-o-tolyl-N,N-dimethylformamidine) or amitraz (AMZ; N'-2-4-(dimethylphenyl)-N-[((2,4-dimethylphenyl)imino)methyl]-N- methanimidamide) exert some of their toxic effects by an interaction with alpha 2-adrenoceptors. Since epinephrine and clonidine have been shown to decrease hepatic glutathione (GSH) by activating alpha 2-adrenoceptors, and alpha 2-antagonists partially antagonize GSH depletion and hepatotoxicity caused by bromobenzene and cocaine, we have investigated whether the formamidines would affect hepatic GSH levels in mice. Both CDM and AMZ decreased hepatic nonprotein sulfydryls (NPSH) to a maximum of about 40%, in a dose-dependent manner. The effect of AMZ was longer lasting than that of CDM. For both compounds, decrease of hepatic NPSH was antagonized by the alpha 2-antagonist yohimbine but not by the alpha 1-antagonist prazosin or the beta-antagonist propanolol. The alpha 2-agonist clonidine also caused a dose-dependent decrease of hepatic NPSH (to a maximum of 40%), which was prevented only by yohimbine. The effects of AMZ, CDM, and clonidine were not additive, suggesting that all compounds act on a common site and/or with a common mechanism. Adrenalectomy or destruction of peripheral sympathetic nerves with 6-hydroxydopamine did not alter the ability of CDM and AMZ to decrease hepatic NPSH. These results indicate that formamidine pesticides can affect the levels of hepatic GSH, possibly through a direct interaction with hepatic alpha 2-adrenoceptors.

Animals↗

PubMed1991

Synaptic regulation of immediate early gene expression in primary cultures of cortical neurons.

Neuronal stimulation can rapidly activate several immediate early genes that code for transcription factors. We have used primary cortical cultures to study the regulation of four of these genes, c-fos, c-jun, jun-B, and zif268. Immunocytochemical studies with antibodies to Jun-B, c-Jun, and c-Fos demonstrate intense staining in the nuclei of a subset of cortical neurons in mature cultures (21-25 days in vitro) but not young cultures (3-7 days in vitro). To assess whether this immunoreactivity may be induced by spontaneous synaptic activity that develops with a similar profile, we examined the effects of agents that reduce this synaptic activity. Tetrodotoxin or N-methyl-D-aspartate receptor antagonists suppress basal immunoreactivity to Jun-B and c-Fos, but not c-Jun, indicating that the basal level of c-Jun expression is not dependent on electrical activity. Picrotoxin, an agent that increases synaptic excitation indirectly by blocking inhibitory synaptic currents mediated by gamma-aminobutyric acidA receptors, markedly increases the percentage of neurons displaying immunoreactivity to c-Fos, c-Jun, Jun-B, and Zif268. Northern analysis suggests that the increases in immunostaining induced by picrotoxin are secondary to a rapid increase in mRNA for these proteins. These findings provide evidence for rapid transcriptional regulation of immediate early genes in cortical neurons by synaptic activity.

Animals↗

PubMed1989

If dancers ate their shoes: inductive reasoning with factual and counterfactual premises.

This experiment addressed the effect of precue information, which may be either familiar or novel, and either relevant or irrelevant, on the solution of inductive reasoning problems. Sixty undergraduate students each completed 216 verbal inductive reasoning problems and five psychometric ability tests. The reasoning problems were equally divided among analogies, classifications, and series completions, with half of each kind of item presented in a standard, uncued format, and half presented with a precue. With respect to internal validation, it was found that for analogies and classifications, subjects take longer to process irrelevant than relevant information if the precue is familiar, but they take longer to process relevant than irrelevant information if the precue is novel. For series completions, this relation does not hold; rather, both novelty and irrelevance add time to the processing of information, with the time for irrelevance greater than that for novelty. The utility of precues for different tasks was explored, and it was found that familiar relevant precues facilitated solution of the more difficult kinds of items (classifications and series completions), but hampered solution of the easier, more automatically solved items (analogies). With respect to external validation, it was found that the nonentrenched induction tasks overlapped with psychometric tests in terms of abilities measured, that the abilities measured were fluid rather than crystallized, and that the precued (more nonentrenched) items were better measures of fluid abilities than were the uncued items.

Adult↗