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Biomedical subjects

J Hutt

Publications and source records attributed to J Hutt.

8 recordsLinked to original sources

Expression and function of CCAAT/enhancer binding proteinbeta (C/EBPbeta) LAP and LIP isoforms in mouse mammary gland, tumors and cultured mammary epithelial cells.

CCAAT/Enhancer binding proteins (C/EBPs) play important roles in the regulation of cell growth and differentiation. This study investigated the expression and function of C/EBPbeta isoforms in the mouse mammary gland, mammary tumors, and a nontransformed mouse mammary epithelial cell line (HC11). C/EBPbeta mRNA levels are 2-5-fold higher in mouse mammary tumors derived from MMTV/c-neu transgenic mice compared with lactating and involuting mouse mammary gland. The "full-length" 38 kd C/EBPbeta LAP ("Liver-enriched Activator Protein") isoform is the predominant C/EBPbeta protein isoform in mammary tumor whole cell lysates, however, the truncated 20 kd C/EBPbeta LIP ("Liver-enriched Inhibitory Protein") isoform is also present at detectable levels (mean LAP:LIP ratio 5.3:1). The mammary tumor C/EBPbeta LAP:LIP ratio decreases 70% (from 5.3:1 to 1.6:1) when lysate preparation is switched from a rapid whole cell lysis protocol to a multistep nuclear/cytoplasmic fractionation protocol. In contrast to mammary tumors, only the C/EBPbeta LAP isoform is detectable in the mammary gland whole cell and nuclear lysates; the truncated "LIP" isoform is undetectable regardless of isolation protocol. Ectopic over expression of C/EBPbeta LIP or C/EBPbeta LAP did not alter HC11 growth rates. However, C/EBPbeta LIP over expressing HC11 cells (LAP:LIP ratio of approximately 1:1) exhibited a consistent 2-4 h delay in G(0)/S phase transition. C/EBPbeta LIP overexpressing HC11 cells did not express beta-casein mRNA (mammary epithelial cell differentiation marker) in response to lactogenic hormones. This defect in beta-casein expression was not corrected by carrying out the differentiation protocol in the presence of an artificial extracellular matrix. These results demonstrate that the "full-length" C/EBPbeta LAP isoform is the predominant C/EBPbeta protein isoform expressed in mouse mammary gland in vivo and mouse mammary epithelial cell cultures in vitro. C/EBPbeta LIP detected in mammary tumor lysates may result from in vivo production or ex vivo isolation-induced proteolysis of C/EBPbeta LAP. Ectopic overexpression of C/EBPbeta LIP (LAP:LIP ratio of approximately 1:1) inhibits mammary epithelial cell differentiation (beta-casein expression).

Animals↗

Joined up in Wales.

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Delivery of Health Care↗

Cardiopulmonary and anesthetic effects of propofol in wild turkeys.

OBJECTIVE: To determine safety, anesthetic variables, and cardiopulmonary effects of i.v. infusion of propofol for induction and maintenance of anesthesia in wild turkeys. ANIMALS: 10 healthy, adult wild turkeys. PROCEDURE: Anesthesia was induced by i.v. administration of propofol (5 mg/kg of body weight) over 20 seconds and was maintained for 30 minutes by constant i.v. infusion of propofol at a rate of 0.5 mg/kg/min. Heart and respiratory rates, arterial blood pressures, and arterial blood gas tensions were obtained prior to propofol administration (baseline values) and again at 1, 2, 3, 4, 5, 10, 15, 20, 25, and 30 minutes after induction of anesthesia. All birds were intubated immediately after induction of anesthesia, and end-tidal CO2 concentration was determined at the same time intervals. Supplemental oxygen was not provided. RESULTS: Apnea was observed for 10 to 30 seconds after propofol administration, which induced a decrease in heart rate; however, the changes were not significant. Compared with baseline values, respiratory rate was significantly decreased at 4 minutes after administration of propofol and thereafter. Systolic, mean, and diastolic pressures decreased over the infusion period, but the changes were not significant. Mean arterial blood pressure decreased by 30% after 15 minutes of anesthesia; end-tidal CO2 concentration increased from baseline values after 30 minutes; PO2 was significantly decreased at 5 minutes after induction and thereafter; PCO2 was significantly (P < 0.05) increased after 15 minutes of anesthesia; and arterial oxygen saturation was significantly (P < 0.05) decreased at the end of anesthesia. Two male turkeys developed severe transient hypoxemia, 1 at 5 and the other at 15 minutes after induction. Time to standing after discontinuation of propofol infusion was 11 +/- 6 minutes. Recovery was smooth and unremarkable. CONCLUSION: Propofol is an effective agent for i.v. induction and maintenance of anesthesia in wild turkeys, and is useful for short procedures or where the use of inhalational agents is contraindicated.

Anesthesia, Intravenous↗

Effects of demand and decision latitude on cardiovascular reactivity among coronary-prone women and men.

According to the Job Strain Model, high demand/low decision latitude jobs may be associated with increased risk of developing coronary heart disease. In further analyses of a laboratory study, the authors hypothesized that Type A behavior and/or hostility moderate the effects of demand, decision latitude, and gender on cardiovascular reactivity, a putative mechanism for the development of coronary disease. With multiple regressions, it was found that scores on the Framingham Type A scale interacted with demand and decision latitude to affect diastolic blood pressure changes, such that Type Bs in the low demand/high decision latitude condition showed the smallest increases in diastolic blood pressure. Among men, hostility accounted significantly and positively for variance in systolic blood pressure changes in addition to that accounted for by high demand. These results suggest that coronary-prone traits may potentiate, or add to, the effects that stressful environments have on health outcomes.

Adolescent↗

The effects of task demand and decision latitude on cardiovascular reactivity to stress.

This study investigated the effects of task demand (absence or presence of time pressure) and decision latitude (choice or no choice over a task) on cardiovascular and affective responses to stressful tasks among 70 college students. Subjects also rated whether they felt under pressure and the extent to which they felt in control. Time pressure was related to elevated systolic blood pressure (SBP) responses among men and increased negative affect for both sexes. Lack of choice over the task also resulted in increased negative affect in both sexes. The least stressful condition--having a choice in the absence of time pressure--resulted in reduced negative affect. In addition to the effects of manipulated decision latitude and demand, perceptions of being in control were associated with reduced SBP among women who had a choice. Perceived control also contributed to reduced negative affect among men. These results suggest that the postulated negative effects of high demand and low decision latitude (ie, job strain) on cardiovascular health may be mediated in part by increased cardiovascular reactivity and negative affect.

Adolescent↗

Family stress and coronary risk in children.

This study examined children of 64 families for associations between a) family conflict and cohesion and b) plasma lipids, lipoproteins, and aggressiveness. Ratings of conflict and cohesion were obtained from parents. Children rated themselves on aggressiveness, one component of Type A behavior. The presence of conflict in the family was positively related to an unfavorable lipid profile (total plasma cholesterol/high-density lipoprotein cholesterol) among boys, but not girls. Family conflict predicted increased levels of aggression in girls, and in boys whose family cohesion was low. These findings suggest that stress in the family may play an important role in the development of coronary risk.

Aggression↗