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Biomedical subjects

M J Lewis

Publications and source records attributed to M J Lewis.

340 records · Page 19Linked to original sources
PubMedDate not supplied

The cardiac endothelium: cardioactive mediators.

Endothelial cells within the heart release a number of substances that modulate myocardial contractile function. These agents include nitric oxide, endothelin, prostanoids, adenylpurines, and other substances that have so far been characterized only in bioassay studies. A notable feature of many of these agents is that they influence contractile behavior predominantly by modifying cardiac myofilament properties rather than altering cytosolic Ca2+ transients. A consequence of this subcellular action is often a disproportionate effect on myocardial relaxation and diastolic tone. The paracrine modulation of cardiac myocyte function by endothelial cell factors is likely to be an important mechanism contributing to the overall regulation of cardiac contractile function, both physiologically and in pathological states.

Animals↗
PubMedDate not supplied

Naloxone suppression and morphine enhancement of voluntary wheel-running activity in rats.

This study examines the effects of the opioid receptor antagonist, naloxone, and the agonist, morphine, on voluntary wheel-running activity (WR) in rats. Male Sprague-Dawley rats were given 1-h access to a running wheel under non-deprived conditions. Naloxone injections (1.0, 0.5, or 0.25 mg/kg, ip), administered immediately before access to running wheels, dose-dependently suppressed WR. In another experiment, subjects were given 6-h access to running wheels under nondeprived conditions for 5 consecutive days. Morphine injections (2.0 mg/kg, sc) were found to increase WR after an initial suppression. These data demonstrate that naloxone inhibits WR, while morphine both suppresses and enhances WR depending on time and dose. These are in agreement with data on other behaviors that indicate that endogenous opioid systems play a major role in the mediation of motivational behaviors.

Animals↗
PubMedDate not supplied

The nature of endothelium-derived vascular relaxant factor.

The existence of endothelium-derived vascular relaxant factor (EDRF) was postulated by Furchgott and colleagues when they observed that acetylcholine paradoxically relaxed preconstricted aortic strip preparations by an endothelium-dependent mechanism. This phenomenon has since been demonstrated in different blood vessels and mammalian species and it can be elicited by several other agents. EDRF has been thought to be a humoral agent, a lipoxygenase derivative and possibly a free radical. In the study reported here, by using aortic preparations from the rabbit, alone and in cascade experiments with isolated perfused coronary preparations, we demonstrate definitively that EDRF is a humoral agent. It is released from unstimulated aortic preparations containing endothelium, its release can be stimulated for prolonged periods by acetylcholine, and it is not a lipoxygenase derivative or free radical but an unstable compound with a carbonyl group at or near its active site.

Acetylcholine↗
PubMedDate not supplied

Heat shock factor is regulated differently in yeast and HeLa cells.

When cells are exposed to elevated temperatures, transcription of a small set of genes, the heat-shock genes, is activated. This response is mediated by a short DNA sequence, the heat-shock element (HSE), which is thought to be the binding site for a specific transcription factor. Studies with Drosophila show that this protein binds to HSEs only in heat-shocked cells, suggesting that changes in factor binding are responsible for gene activation. We have investigated the properties of HSE-binding proteins from yeast and HeLa cells. In HeLa cells, binding activity is present only after heat shock. In contrast, control and heat-shocked yeast cells yield the same amount of HSE-binding activity; however, the mobility of protein-HSE complexes on polyacrylamide gels is altered following heat shock. This mobility difference can be significantly reduced by treatment of crude extracts with phosphatase. We propose that the yeast heat-shock factor binds constitutively to DNA but only activates transcription after heat-induced phosphorylation.

Gene Expression Regulation↗
PubMedDate not supplied

Comparison of Polar 810s and an ambulatory ECG system for RR interval measurement during progressive exercise.

Ambulatory heart rate monitors and clinical electrocardiographic (ECG) devices are capable of measuring the length of consecutive cardiac periods (RR intervals). The aim of the study was to assess the agreement between the Polar 810s heart rate monitor (Polar) and the Reynolds digital ambulatory ECG using Pathfinder software version 8.4 (Reynolds v8.4) during cycle ergometry. For this purpose, eight subjects completed incremental cycling exercise that began at 60 W and increased by 30 W each 2-minute period until volitional fatigue. Simultaneous recording of the ECG (Reynolds Pathfinder), RR interval (Polar), and respiratory parameters (Metamax 3B) were undertaken at rest and throughout the exercise period. No significant differences were found in RR intervals measured by Polar and Reynolds v8.4 at any relative intensity. Polar and Reynolds v8.4 displayed strong linear relationships at all relative intensities (r2=0.927 to 0.998). Bland and Altman analyses between Polar and Reynolds v8.4 consistently demonstrated minimal bias in absolute RR interval (<0.10 ms) and the limits of agreement for group differences in RR interval and heart rate were less than +/- 10 ms and +/- 2 beats.min (-1) for all relative intensities, respectively. Power spectral analysis provided similar results for both systems in all bandwidths studied during rest and low intensity exercise. However, significant differences and large relative limits of agreement (>100 % of mean of paired means) were identified in UF at intensities > 40 % VO2max, HF at intensities > 60 % VO2max and LF during exercise at 80-100 % VO2max. These findings demonstrate that RR intervals and heart rate measurements obtained using Polar and Reynolds v8.4 are in good agreement. However, caution should be exercised when interpreting spectral analysis of RR interval data derived from different acquisition systems during physical activity.

Adult↗
PubMedDate not supplied

Half-life of digoxin in myocardium after stopping maintenance treatment.

The rate of decline of digoxin level in myocardium was estimated from operative samples of atrial and ventricular tissue from 40 patients undergoing cardiac surgery 1-20 days after maintenance digoxin treatment was stopped. Linear regression of myocardial log concentration-time curves for the group as a whole gave half-lives of 2.9 and 3.1 days in ventricular and atrial myocardium, respectively. Serum concentrations of digoxin were measured twice in each patient in this study: once while receiving treatment and once at the time of operation. Analysis of the 22 pairs of serum samples in which the second sample contained measurable levels of digoxin gave an estimated half-life of 2.3 days. The serum half-life was shorter than either the ventricular or the atrial myocardial half-life when data were analysed by unpaired statistics. Considering data only from those patients in whom the serum half-life was measured, to allow comparison by paired statistics, estimated ventricular and atrial half-lives were 1.5 and 1.3 days, respectively, which are significantly less than the respective serum half-lives of 2.3 and 2.1 days. Relatively slow clearance of digoxin from myocardium received further, anecdotal support from its demonstration in one patient 20 days after treatment was stopped.

Adult↗
PubMedDate not supplied

Differences in basal endothelium-derived relaxing factor activity in different artery types.

Mechanical responses and calcium influx were measured in order to compare basal endothelium-derived relaxing factor (EDRF) activity in isolated preparations of rabbit aorta, rat aorta, and dog coronary artery. EDRF activity was characterized by endothelium-dependent mechanical relaxation and reduction of 45Ca influx which could be blocked by EDRF inhibitors. In resting preparations, the mechanical effects of basal EDRF were negligible in all preparations, and a small effect on calcium influx was demonstrated only in rat preparations. In agonist-constricted preparations, basal EDRF activity had only a small mechanical effect in rabbit preparations but markedly depressed constriction in rat and dog preparations; likewise, it had no demonstrable effect on calcium influx in rabbit preparations but had a marked effect in rat and dog preparations. In both resting and agonist-stimulated rabbit preparations, endothelium caused a cyclooxygenase product-dependent increase in calcium influx. Thus, basal EDRF activity has little or no effect in resting preparations and little or no effect in agonist-stimulated rabbit aorta preparations, but a marked effect in agonist-stimulated rat aorta and dog coronary preparations.

Animals↗
PubMedDate not supplied

Evaluation of three methods for improving mammography rates in a managed care plan.

INTRODUCTION: Mammography has been shown to reduce breast cancer mortality among women 50 and older. Although mammography rates are increasing nationally, this effective screening tool remains underused. This study was conducted among 395 women who were members of a network model health maintenance organization (HMO) in Philadelphia in order to determine which of three methods was most effective in increasing mammography rates: (1) a birthday card reminder only (the standard method); (2) a personalized letter from the medical director and materials promoting mammography; and (3) a multicomponent phone call incorporating a reminder, counseling, and scheduling of appointments. An additional goal was to determine whether the interventions were more or less effective depending on a woman's readiness to get a mammogram, as measured by stage of change. METHODS: Eligible women were randomized into one of three treatment groups described earlier. Mammography rates were calculated on the basis of a claims review and follow-up phone interviews after a period of six months. RESULTS: Women who received the telephone intervention were most likely to obtain a mammogram (28%); followed by the group that received the birthday card only (15%), and those who received the mailed intervention (9%). CONCLUSIONS: These results indicate that a multicomponent phone intervention is significantly effective in promoting mammography in managed health care plan members. An analysis by women's stage of change found a difference in the effectiveness of the three interventions among contemplators only.

Aged↗