Publications by authors named "Nichols N"

16,16-Dimethyl PGE2 (dmPGE2) has previously been shown to protect the in vivo rat liver against CCl4-induced damage. These studies were undertaken to determine if this protection could be demonstrated in vitro where factors of absorption, secretion, and blood flow are not present. Primary hepatocyte cultures were established by perfusing rat liver with collagenase.

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It has been proposed that concomitant substances of abuse may have additive or synergistic properties such that alcoholics using other substances of abuse concurrently may have a harder time giving up alcohol than alcoholics abusing only alcohol. The present study surveyed 291 alcoholics in an alcohol treatment program and 86 social drinker controls matched on age, education, SES and gender. Alcohol consumption, smoking, coffee intake, other substances of abuse.

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Previous gel filtration binding assay studies indicated that rat vascular smooth muscle cells contained corticoid receptor I and corticoid receptor II sites which could be distinguished on the basis of their relative affinities for aldosterone and dexamethasone. Ion-exchange chromatography experiments were designed to separate the two sites for further studies on their physical characteristics and role in vascular smooth muscle cell physiology. Cultured aortic cells were incubated with 5-10 nM 3H steroid alone or in the presence of 10-fold non-radioactive steroid competitor for 30 min at 37 degrees C.

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The Dahl salt-resistant substrain of Sprague-Dawley rats represents a uniform population of animals that are resistant to salt and mineralocorticoid induced hypertension. Aldosterone binding in the aortae of these rats is contrasted to that of age- and sex-matched rats of the Dahl salt-susceptible strain in an effort to identify a mechanism for resistance to salt induced hypertension. Cultured smooth muscle cells of both substrains contain two classes of aldosterone binding sites: corticoid receptor I with high affinity and low capacity, and corticoid receptor II with low affinity and high capacity.

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The relationship of tests of neuropsychological functioning to clinical ratings of participation in therapeutic activities and predictions of outcome were investigated in two groups of men alcoholics. Factor analysis of the clinical ratings confirmed the existence of three factors: cognitive, clinical improvement and interpersonal. Significant relationships were found in the first group of alcoholics (N = 52) between neuropsychological test scores and scores on each of the three factors.

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Models which define fitness in terms of per capita rate of increase of phenotypes are used to analyse patterns of individual growth. It is shown that sigmoid growth curves are an optimal strategy (i.e.

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We have compared, by two-dimensional gel electrophoresis, the effects of glucocorticoids on newly synthesized proteins of cultured cardiovascular cells (rat synthetic- and contractile-state vascular smooth muscle, rat cardiac muscle and non-muscle, and bovine endothelium) and rat hepatoma (H4) cells, as a non-cardiovascular target. In each cell type, glucocorticoids consistently affected a particular set of proteins termed the glucocorticoid domain for that target tissue. Cardiovascular cells exhibited overlapping but non-identical glucocorticoid domains; these domains varied in number of proteins, proportion of induced and repressed proteins, and overlap (extent of shared protein responses) between the various cardiovascular cell types studied.

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To analyze direct effects of steroids on the rates of synthesis (and/or degradation) of newly synthesized proteins of the rat heart, we have used high resolution two-dimensional gel electrophoresis and autoradiography. A collective steroid domain of nineteen proteins, comprising fifteen with an increased rate of synthesis and four with a decreased rate of synthesis, was consistently seen in cultures of cardiac muscle and non-muscle cells from neonatal rats following 24 h incubation with 10(-7) dexamethasone. Similarly, incubation with 10(-7) M sex steroids, mineralocorticoids, and other glucocorticoids including the highly selective compound RU26988, established the glucocorticoid-specificity of the response.

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We have investigated the domain of adrenal steroid action in a variety of mammalian cells and tissue by high resolution two-dimensional gel electrophoresis and autoradiography. Following in vivo or in vitro treatment with steroids, minced tissue or cells were pulsed with [35S]methionine, and they newly synthesized polypeptides compared with controls by visual inspection of partial protein maps. We have found a similar protein (Mr approximately 41-44K, pI approximately 6.

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Timoprazole, a substituted benzimidazole, is an antisecretory agent that inhibits gastric acid secretion by interference with (H+-K+)-ATPase. In the studies reported herein, timoprazole given orally was found to be cytoprotective for the stomach when given 30 min prior to a challenge to boiling water, ethanol, or 0.6 N HCl.

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The Fischer 344 rat strain represents a uniform population that is immune to salt induced hypertension and resistant to mineralocorticoid hypertension. We have compared aldosterone binding in aortic cells cultured from salt-resistant Fischer 344 rats to that from salt-sensitive Wistar-Kyoto controls for aldosterone binding. Aortic smooth muscle cells of both strains contain two classes of aldosterone binding sites: corticoid receptor I with high affinity and low capacity and corticoid receptor II with low affinity and high capacity.

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High circulating levels of corticosteroids are associated with elevated blood pressure and an increased incidence of vascular damage. We have used high resolution two-dimensional gel electrophoresis and autoradiography to analyse direct steroid effects on the newly synthesized proteins in bovine aortic endothelial cells. At medium concentrations of 10(-7) M, corticosteroids but not sex steroids increased the synthesis of two endothelial proteins: el (M.

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To examine the direct effects of steroids on vascular smooth muscle, we have incubated rat aortic vascular smooth muscle cells in culture either steroid-free, or with natural and synthetic corticosteroids (RU26988, dexamethasone, corticosterone, 9 alpha-fluorocortisol, aldosterone, deoxycorticosterone) or sex steroids (estradiol, 5 alpha-dihydrotestosterone). At the end of 24 h, cultures were pulsed with [35S]methionine for 2 h, the cells lysed, and patterns of incorporation of isotope into protein determined by two-dimensional gel electrophoresis and autoradiography. Neither estradiol nor 5 alpha-dihydrotestosterone altered protein synthetic profiles compared with control (steroid-free) incubations.

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Spontaneously hypertensive rats and rats made hypertensive by deoxycorticosterone-salt treatment have in common increased Na+ and K+ permeability and transport in their aortic cells. These changes may be important factors in the development of the hypertensive state and may be mediated by mineralocorticoid binding to intracellular sites in the aorta. Therefore, we examined 3H-aldosterone binding in aortic cell cultures from spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.

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