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Biomedical subjects

M Simonson

Publications and source records attributed to M Simonson.

17 recordsLinked to original sources
PubMed1998

GATA-6 induces p21(Cip1) expression and G1 cell cycle arrest.

GATA transcription factors represent a family of highly conserved zinc finger proteins with tissue-specific expression patterns. Previous studies have shown that GATA-6 is expressed in vascular smooth muscle cells (VSMCs) and rapidly down-regulated when VSMCs are induced to proliferate. Here we investigated whether the GATA-6 transcription factor can modulate cellular proliferation. Transient transfection with a GATA-6 expression vector inhibited S-phase entry in VSMCs and in mouse embryonic fibroblasts (MEFs) lacking both p53 alleles. The GATA-6-induced growth arrest correlated with a marked increase in the expression of the general cyclin-dependent kinase (Cdk) inhibitor p21. In contrast to p53-deficient MEFs and VSMCs, MEFs null for both p21 alleles were refractory to the GATA-6-induced growth inhibition. These data demonstrate that elevated GATA-6 expression can promote the quiescent phenotype in VSMCs.

Animals↗
PubMed1997

Bcl-2 inhibits c-fos induction by calcium.

Transient elevation of cytosolic Ca2+ induces the expression of a variety of genes involved in cell growth and transformation, including the early response gene c-fos. Previously, we reported that Bcl-2 inhibits the transient elevation of cytosolic Ca2+ induced by thapsigargin (TG), a selective inhibitor of the endoplasmic reticulum-associated Ca2+-ATPase. Therefore, to determine if the effect of Bcl-2 on cytosolic Ca2+ elevation modulates Ca2+ signaling, we investigated the induction of c-fos by TG in WEHI7.2 mouse lymphoma cells, control transfectants (WEHI7.2-neo), and transfectants that stably express a high level of Bcl-2 (W.Hb12 and W.Hb15). TG induced 20-fold elevation of c-fos mRNA in WEHI7.2 and WEHI7.2-neo cells, but c-fos mRNA induction by TG was only fivefold in W.Hb12 and W.Hb15 cells. In contrast, phorbol 12-myristate acetate induced marked c-fos mRNA elevation in both WEHI7.2 and W.Hb12 cells, indicating that the inhibitory effect of Bcl-2 is selective for induction of c-fos by Ca2+. To measure c-fos promoter activity, WEHI7.2 and W.Hb12 cells were transiently transfected with a c-fos promoter-luciferase reporter plasmid. TG induced c-fos promoter activity in WEHI7.2 cells, but not in W.Hb12 cells. In WEHI7.2 cells, the signal for c-fos induction by TG was cytosolic Ca2+ elevation, as the increase in both c-fos mRNA level and promoter activity were prevented by lowering extracellular Ca2+ concentration, a condition that inhibits cytosolic Ca2+ elevation by reducing the TG-mobilizable Ca2+ pool. In summary, the findings indicate that Bcl-2 regulates Ca2+ signaling.

Animals↗
PubMed1991

Effects of endothelin on cultured human and rat glomerular mesangial cells.

Figure 5 summarizes our results and the data in the literature with regard to both short-term signalling and long-term signalling induced by endothelin. Short-term signalling, which induces vasoconstriction, is undoubtedly mediated by multiple signals including increments of cytosolic calcium, stimulation of protein kinase C and alkalinization of the cytosol. Endothelin also activates negative feedback pathways including arachidonate release with the synthesis of vasorelaxant prostaglandins and potentiation, in a prostaglandin-dependent manner, of beta-adrenergic-stimulated adenylate cyclase. Long-term signalling is less well understood and may depend not only on phospholipase activation with subsequent changes of calcium and protein kinase C but also stimulation of other protein kinases which phosphorylate key intermediates. Endothelin stimulates the transient appearance of protooncogenes that might play a role in the induction of cellular proliferation.

Animals↗
PubMed1986

Glomerular prostaglandins, angiotensin II, and nonsteroidal anti-inflammatory drugs.

The glomerulus can, in part, regulate its own flow and filtration characteristics, both of which are determinants of the glomerular filtration rate. This occurs in part as the result of interactions between vasoconstrictors, e.g., angiotensin II (AII), and the vasodilatory prostaglandins E2 or I2. It is well accepted that these prostaglandins modulate the constrictor effects of AII on systemic and renal vasculature. Experimental data accumulated from micropuncture studies, analyses of isolated glomeruli in vitro, and glomerular mesangial cell cultures also support the hypothesis that AII-stimulated production of vasodilatory prostaglandins attenuates AII-induced constriction at the glomerular level as well. These studies help to explain the deleterious actions of nonsteroidal anti-inflammatory drugs on glomerular filtration in clinical conditions associated with a decreased effective blood volume and, therefore, activation of AII and other neurohormonal constrictors. These results have also furthered our understanding of the role of prostaglandins in maintaining renal function in human and experimental renal diseases that may be associated with enhanced hormonal constrictor activity.

Angiotensin II↗
PubMed1985

L-phenylalanine.

Explore the source record for details and available documents.

Antidepressive Agents, Tricyclic↗
PubMed1981

Body image in obese adults.

Data were gathered on 38 obese women and 16 obese men attending a weight-reduction programme and on an equal number of normal weight controls, regarding accuracy of perception of body width in 4 regions, as well as attitudes towards body size. Obese subjects, particularly women, tended to overestimate body width and to dislike their bodies, but neither of these factors predicted success in losing weight. Age of onset of obesity was not related to degree of adult obesity or to accuracy of estimation of body width.

Adult↗
PubMed1980

Differential antianxiety response to caloric intake between normal and obese subjects.

Obese subjects (N = 152) attending a weight reduction clinic and controls (N = 62) rated numerous aspects of their psychological state using analogue scales before and after a standard liquid meal. Prior to the meal, the only difference in psychological state between the groups was that the obese subjects had higher scores than controls on the questions relating to their self-perception of "fatness." Following the meal, the obese subjects, including some previously obese (now normal weight) subjects, reported a decrease in "anxiety" as reflected by significant changes in premeal to postmeal scores on 5 anxiety-related questions. Control subjects tested in two separate groups, one demographically matched and one nonmatched, did not experience this "antianxiety" effect, but reported postmeal increases in feelings of "fatness" and "sexual arousal" as compared with the obese subjects.

Adult↗
PubMed1979

Attitudes toward obesity and the obese among professionals.

Negative attitudes toward obese patients by health professionals have been attributed to termination of weight reducing attempts. This study measured attitudes concerning the obese held by professional participants in a continuing education conference on causes and treatment of obesity. Substantial variation was found on items comprising obesity-related belief dimensions: (a) Disparaging image of the obese; (b) causes of obesity; and (c) ways to lose weight. Evidence is presented for the association among measures of these dimensions. While background and educational characteristics and conditions of practice were not related to such attitudes, the professional's personal experience with successful weight reduction was the best predictor of favorable attitudes.

Attitude of Health Personnel↗