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Biomedical subjects

M Young

Publications and source records attributed to M Young.

At least 19 recordsLinked to original sources
PubMed1979

Proteolytic activity of nerve growth factor: a case of autocatalytic activation.

Nerve growth factor is a highly specific protease that can convert plasminogen to plasmin and that can hydrolyze certain synthetic N-substituted arginine esters (e.g., Nalpha=p-toluenesulfonyl-L-arginine methyl ester (TAME); N.S. Orenstein et al. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 5497). Hydrolysis of TAME is characterized by a lag phase of lower velocity which precedes development of the steady-state maximal velcity. Kinetic analyses indicate that this behavior stems from autocatalytic activation of a nerve growth factor (NGF)-zymogen by NGF. As isolated from the mouse submandibular gland at high concentration, NGF is largely enzymically inactive. Upon high dilution, the protein undergoes autocatalytic activation with concomitant generation of full enzymic activity. The biologic significance of this unusual property of NGF is not clear, but it may serve to prevent expression of enzymic activity until the protein reaches its target cell(s) or until it recognizes its physiological substrate.

Catalysis↗
PubMed1979

Extrapyramidal side effects and increased serum prolactin following fluoxetine, a new antidepressant.

Fluoxetine (Lilly 110140) is a potent, specific serotonin (5-HT) uptake blocker which is being tested in man for antidepressant activity. One of 9 depressed patients receiving this drug developed a dystonic reaction, parkinsonian rigidity, and increased serum prolactin levels, all signs of decreased dopaminergic activity. Homovanillic acid levels also decreased in the cerebrospinal fluid of this subject. We postulate that fluoxetine, via the increase in 5-HT activity resulting from 5-HT uptake blockade, inhibited both the nigro-striatal and tubero-infundibular dopaminergic neurons. These results provide additional evidence for a linkage between serotonergic and dopaminergic neurons in man.

Adult↗
PubMed1979

Effect of clozapine on human serum prolactin levels.

The authors determined serum prolactin levels in 13 patients receiving clozapine, an antipsychotic drug that does not produce extrapyramidal side effects. Morning serum prolactin levels, 11 hours after the last dose, were not elevated during chronic treatment with clozapine in any subject despite its therapeutic effects. Serum prolactin levels were moderately increased between 90 minutes and 4 hours after administration of very high doses of oral clozapine in 4 patients but were smaller than those produced by chlorpromazine in other subjects. The authors suggest that clozapine in other subjects. The authors suggest that clozapine may achieve its antipsychotic effect differently than do classical neuroleptics and that sustained prolactin increases are not essential for antipsychotic action.

Animals↗
PubMed1979

Diethylstilbestrol and estradiol binding to serum albumin and pregnancy plasma of rat and human.

The equilibrium binding of diethylstilbestrol (DES) and 17 beta-estradiol (E2) to plasma proteins has been characterized. DES exhibits a 10- to 20-fold greater binding affinity index for bovine serum albumin and rat plasma than E2. As expected, E2 gave high values for binding to plasma from pregnant mice or rats, reflecting the presence of alpha-fetoprotein. DES bound to these samples as it did to bovine albumin and rat plasma. These results suggested that DES ineracts weakly with alpha-fetoprotein. This was verified by Scatchard plots of DES and E2 binding to rat and human pregnancy plasma. High affinity, low capacity binding was demonstrated with E2 but not with DES. The significantly lower binding of DES suggests that increased delivery of DES to the fetus may be at least partially responsible for the transplacental toxicity and carcinogenicity of DES.

Animals↗
PubMed1979

Intranuclear inclusion bodies in epithelial cells of human vas deferens.

Four different types of inclusion bodies were seen within the nucleus of the principal cells in segments of vas deferens from 40 fertile males: (1) electron-dense homogeneous bodies of various sizes (0.1--1.8 microns) and shapes, (2) granular bodies approximately 0.06--0.12 microns, (3) lipid inclusion bodies, and (4) less electron-dense, filamentous bodies. They were either membrane-bound or free within the nucleoplasm. Some membranous material was scattered within the nucleoplasm. The internal structure of nuclei containing these bodies differed from cell to cell. The nucleoplasm was composed either of dense granular elements or fine filamentous components. The aggregation and density of the ground nuclear material increased with increasing numbers of inclusion bodies. Very dense nuclei were in cells with typical features of degeneration. Frequently, extruded parts of cells or entire cells were seen within the lumen of the vas deferens.

Adult↗
PubMed1979

Behavioral epidemiology of food additives.

Behavioral toxicology in the natural environment can be considered a special branch of epidemiology. Behavioral epidemiology, because it typically relies on complex functional criteria, faces all of the problems of behavior measurement posed by uncontrollable variation, and amplified even further by chemical exposure. Many such issues arose in a study of behavioral responses to artificial food colors in children. Difficulties in employing Applied Behavioral Analysis in such a context run the gamut from selection of retrospective criteria to appropriate statistical models.

Child↗
PubMed1978

Antagonism of central histamine H1 receptors by antipsychotic drugs.

The activity of 8 widely antipsychotic drugs as antagonists of central histamine H1 receptors was determined from the inhibition of the binding of 3H-mepyramine to a membrane fraction from guinea-pig brain. The phenothiazines examined, clorpromazine, fluphenazine, thioridazine and trifluoperazine, were all potent H1 antagonists. Both alpha- and beta-flupenthixol were potent inhibitors, but butaclamol, although less potent, showed stereospecificity. Haloperidol and spiperone were markedly weaker antihistamines than the phenothiazines.

Animals↗
PubMed1978

Secretagogue-mediated discharge of nerve growth factor from granular tubules of male mouse submandibular glands: an immunocytochemical study.

Submandibular glands of male mice were stained for nerve growth factor by light microscopic immunocytochemistry. Nerve growth factor (NGF) was present in the granules of granular tubule cells, with the immunoreactive material often concentrated at the periphery of granules. Administration of the alpha-adrenergic agent, phenylephrine, to animals resulted in a marked depletion of NGF-containing granules from granular tubules. Some release also occurred following administration of the beta-adrenergic agent, isoproterenol. Cholinergic stimulation (pilocarpine) did not result in appreciable loss of immunoreactive granules from these cells. In vitro results were not as clear cut, immunocytochemically, as those obtained with intact animals. It is concluded that discharge of NGF from male mouse submandibular glands is mediated predominantly by alpha-adrenergic activation, and that this phenomenon is readily demonstrated in the intact animal.

Animals↗