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Biomedical subjects

J M Sullivan

Publications and source records attributed to J M Sullivan.

At least 19 recordsLinked to original sources
PubMed1998

Regulation of the readily releasable vesicle pool by protein kinase C.

Modulation of the size of the readily releasable vesicle pool has recently come under scrutiny as a candidate for the regulation of synaptic strength. Using electrophysiological and optical measurement techniques, we show that phorbol esters increase the size of the readily releasable pool at glutamatergic hippocampal synapses in culture through a protein kinase C (PKC)-dependent mechanism. Phorbol ester activation of PKC also increases the rate at which the pool refills. These results identify two powerful ways that activation of the PKC pathway may regulate synaptic strength by modulating the readily releasable pool of vesicles.

Electric Stimulation↗
PubMed1998

Apoptosis.

Apoptosis is a process of cell suicide, the mechanisms of which are encoded in the genomes of all higher eukaryotes. The mechanisms involved in apoptosis suggest that the process is based on a viral defense originally developed in primitive multicelled eukaryotes and that the fundamental execution platform of the process involves 1) inhibition of protein synthesis at the level of translation initiation, 2) proteolysis specifically involving degradation of DNA repair mechanisms, and 3) polynucleotide degradation. In mammals this execution platform is regulated by a complex molecular signaling system that includes feedback mechanisms tending toward activation of all elements of the execution platform if only one element is initially engaged. Tissue ischemia and reperfusion activate elements of the apoptosis system, which thus represents a therapeutic target for emerging treatment approaches to preserve cellular integrity in critical organs such as the heart and brain.

Animals↗
PubMed1997

Effect on survival of estrogen replacement therapy after coronary artery bypass grafting.

We examined the relation between postmenopausal estrogen placement therapy (ERT) and survival in 1,098 women who underwent coronary artery bypass grafting (CABG). Patients were selected for the study if their age was > or = 55 years at the time of preoperative coronary angiography or if they had previously undergone bilateral oophorectomy. Life-table analysis was used to compare survival after surgery in 92 women who received ERT and 1,006 women who did not. Five-year survival was 98.8% in the estrogen users and 82.3% in the non-users. Ten-year survival was 81.4% in the users and 65.1% in the nonusers (p = 0.0001 by Lee Desu test). The women who did not take estrogen were significantly older (p < 0.001), had more vessels with significant stenosis (p = 0.033), lower ejection fractions (p = 0.051), and more prior myocardial infarctions (p = 0.054). However, a Cox proportional-hazards model selected the number of coronary arteries narrowed (RR 1.43, p < 0.0001), estrogen use (RR 0.38, p = 0.001), left main coronary stenosis (RR 1.83, p = 0.001), and diabetes mellitus (RR 1.57, p = 0.003) as the significant independent predictors of survival. These data suggest that ERT improves survival significantly after CABG in postmenopausal women with coronary artery disease.

Case-Control Studies↗
PubMed1997

Effect of brain ischemia and reperfusion on the localization of phosphorylated eukaryotic initiation factor 2 alpha.

Postischemic brain reperfusion is associated with a substantial and long-lasting reduction of protein synthesis in selectively vulnerable neurons. Because the overall translation initiation rate is typically regulated by altering the phosphorylation of serine 51 on the alpha-subunit of eukaryotic initiation factor 2 (eIF-2 alpha), we used an antibody specific to phosphorylated eIF-2 alpha [eIF-2(alpha P)] to study the regional and cellular distribution of eIF-2(alpha P) in normal, ischemic, and reperfused rat brains. Western blots of brain postmitochondrial supernatants revealed that approximately 1% of all eIF-2 alpha is phosphorylated in controls, eIF-2(alpha P) is not reduced by up to 30 minutes of ischemia, and eIF-2(alpha P) is increased approximately 20-fold after 10 and 90 minutes of reperfusion. Immunohistochemistry shows localization of eIF-2(alpha P) to astrocytes in normal brains, a massive increase in eIF-2(alpha P) in the cytoplasm of neurons within the first 10 minutes of reperfusion, accumulation of eIF-2(alpha P) in the nuclei of selectively vulnerable neurons after 1 hour of reperfusion, and morphology suggesting pyknosis or apoptosis in neuronal nuclei that continue to display eIF-2(alpha P) after 4 hours of reperfusion. These observations, together with the fact that eIF-2(alpha P) inhibits translation initiation, make a compelling case that eIF-2(alpha P) is responsible for reperfusion-induced inhibition of protein synthesis in vulnerable neurons.

Animals↗
PubMed1997

Doctorally-prepared nurses: different practice settings, different views.

Nurse researchers in academic and clinical settings have the ultimate goal of improving nursing care while balancing the demands of education, their institution, research, and nursing service. The setting shapes the focus of research, the choice of research models, and the parameters of the position. The setting also influences available resources and the services rendered to the institution and the community. The functions of doctorally-prepared nurses in academic and clinical settings are compared. A better understanding of the functions of nurses in each setting could lead to better informed employment choices and improved collaborative efforts.

Education, Nursing, Graduate↗
PubMed1996

Estrogen replacement therapy.

For decades, observers have noted that women lose their natural resistance to coronary disease following menopause. It is now known that this increase in coronary risk is due to the loss of the protective effect of estrogen. Although still somewhat controversial, estrogen replacement therapy appears to offer significant cardioprotective benefits to postmenopausal women. These benefits extend to women with a history of coronary artery disease as well as to those without. The exact mechanism by which estrogen confers protection is not known, although the primary focus has been on estrogen's effect on serum lipids. Estrogen reduces total cholesterol levels and low-density-lipoprotein cholesterol levels and increases levels of high-density lipoproteins. Recent data suggest that estrogen may also have a beneficial effect on lipoprotein (a), a less studied lipid fraction, and may affect lipid metabolism in the blood-vessel wall. Numerous studies are under way to define better the risks and benefits of estrogen replacement therapy. Until more is known, the decision to recommend estrogen replacement therapy must be made on an individual basis.

Coronary Disease↗
PubMed1996

The clinical aspects of estrogen and the cardiovascular system.

Extensive epidemiologic and postmortem studies have identified a link between menopause and cardiovascular disease. The relation is especially strong in surgically menopausal women who do not receive estrogen replacement. More than 30 observational studies and one small randomized, controlled clinical trial have provided evidence that estrogen replacement reduces cardiovascular risk by approximately 50%. Four studies that used coronary arteriography to document the presence of coronary atherosclerosis have provided some of the most compelling evidence that estrogen replacement reduces cardiovascular risk in postmenopausal women. One study of survival in women undergoing coronary arteriography found that the greatest improvement in total mortality took place in those women with substantial coronary stenosis; less benefit was observed in those without disease. Angiographic studies have also confirmed the importance of high-density lipoprotein cholesterol in mediating the effect of estrogen and the beneficial effect of estrogen on endothelial function. Although the addition of progestins to estrogen attenuates estrogen's effect on high-density lipoprotein cholesterol, limited observational daa have suggested that the cardioprotective effect is not reduced.

Cardiovascular Diseases↗
PubMed1996

Estrogens, menopause, and coronary artery disease.

The incidence of cardiovascular disease increases after menopause as women age. Estrogen-replacement therapy has been found to reduce cardiovascular risk by about 50% in over 30 observational studies. Part of the beneficial effect appears to be due to a reduction of LDL cholesterol and an increase in HDL cholesterol. Another important mechanism is related to the effect of estrogen on endothelial function. In making a decision to use estrogen-replacement therapy, the benefits must be weighed against the risks of endometrial and breast cancer.

Aged↗
PubMed1996

Practical aspects of preventing and managing athersclerotic disease in post-menopausal women.

Factors that exacerbate the risk of atherosclerotic plaque formation include cigarette smoking, hypertension, hypercholesterolaemia, sedentary lifestyle, and oestrogen deficiency. The potentially important role of oestrogen deficiency in this process is evidenced by the significant increase in cardiovascular risk observed in women after menopause, and in the marked reduction in cardiovascular events observed in women who take hormone replacement therapy. Oestrogen replacement therapy, through an effect on the blood vessel wall and on serum lipids, also appears to stabilize existing atherosclerotic plaques. The combination of oestrogen and progesterone reduces risk of endometrial cancer while possibly delivering the same benefits as oestrogen alone. Other measures, such as antithrombotic therapy, exercise, and smoking cessation, also contribute to reduced risk of cardiovascular disease in older women.

Coronary Artery Disease↗
PubMed1996

A 1996 update on antihypertensive agents.

Seven new classes of antihypertensive agents that are currently under development are outlined. Clinical studies of neutral endopeptidase inhibitors and angiotensin II receptor blockers are described. Experimental studies are described involving endothelin inhibitors, and clinical and experimental studies of a new multiple action antihypertensive agent, carvedilol, are presented. Studies demonstrating the efficacy of very low doses of thiazide diuretics added to other antihypertensive agents are described. A meta-analysis that found increased risk of sudden death in hypertensive patients treated with non-potassium-sparing diuretics is reported. The controversy over the use of calcium-channel blockers is reviewed, and current recommendations regarding the use of rapidly-acting nifedipine are given.

Angiotensin Receptor Antagonists↗
PubMed1996

Hemodynamic effects of aerobic vs resistance exercise.

Previous studies suggest that aerobic exercise lowers blood pressure (BP), while isometric exercise increases BP, at least transiently. The purpose of this study was to examine the hemodynamic effect of a 6-week training period of aerobic exercise or weight training. Twenty deconditioned healthy males ages 18-36, self-selected a training regimen. The aerobic group exercised 30 min/day, 4 times each week to achieve 60-80% maximal heart rate. The resistance group lifted weights at 65-80% maximal voluntary contraction; 3-4 sets of 8-12 repetitions; 3 day/week using large muscle groups. Hemodynamic measurements of heart rate, BP, venous capacitance, forearm blood flow, and vascular resistance were made at baseline and week 6 by plethysmography and analyzed by 2-way ANOVA. The groups showed no differences in baseline characteristics. A training effect was confirmed by a decrease in resting heart rate in the aerobic group (71.5 +/- 4.4 to 64.5 +/- 3.7, beats per minute, P = 0.004), and an increase in total work capacity in the weight lifting group (6231 vs 7508, P = 0.01). Forearm blood flow increased similarly in both groups, averaging 17% (3.5 +/- 0.2 vs 4.2 +/- 0.2 ml 100 g/min, P = 0.03), while forearm vascular resistance fell 19% (28.8 +/- 1.7 vs 24.3 +/- 1.7 mm Hg/ml/min 100 g, P = 0.08). The main differences between the groups after training was found in their response to isometric stress (1/3 maximal handgrip). The weight-lifting group had a greater increase of forearm blood flow and venous capacitance, less increase in systolic BP (SBP) and a greater fall of forearm vascular resistance, (P < 0.05) while the aerobic group had less increase in SBP and heart rate (P < 0.04) but no significant change of forearm hemodynamics. We conclude that both aerobic and repetitive weight programs have short term favorable effects on resting forearm BP and resistance. The exercise programs differ in altering the individual's physiologic response to subsequent isometric stress. However, exercise training of longer duration or greater intensity or frequency could alter these results.

Adult↗
PubMed1995

Three distinct structural environments of a transmembrane domain in the inwardly rectifying potassium channel ROMK1 defined by perturbation.

To probe the protein environment of an ion channel, we have perturbed the structure of a transmembrane domain by substituting side chains with those of two different sizes by using site-specific mutagenesis. We have used Trp and Ala as a high- and a low-impact perturbation probe, respectively, to replace each of 18 consecutive residues within the putative second transmembrane segment, M2, of an inwardly rectifying potassium channel, ROMK1. Our rationale is that a change in the channel function as a consequence of these mutations at a particular position will reflect the structural environment of the altered side chain. Each position can then be assigned to one of three classes of environments, as grated by different levels of perturbation: very tolerant (channel functions with both Trp and Ala substitutions), tolerant (function preserved with Ala but not with Trp substitution), and intolerant (either Ala or Trp substitution destroys function). We identify the very tolerant environment as being lipid-facing, tolerant as protein-interior-facing, and intolerant as pore-facing. We observe a strikingly ordered pattern of perturbation of all three environmental classes. This result indicates that M2 is a straight alpha-helix.

Alanine↗
PubMed1995

Impact of patency of the left anterior descending coronary artery on long-term survival.

This study examines the relative importance of patency of the left anterior descending (LAD) coronary artery on long-term survival when the LAD is the only significantly narrowed coronary artery. From a cardiac disease registry of 21,786 patients, 826 medically treated patients with isolated LAD disease were identified. These patients were followed for > 5 years. Patients were divided into those with open versus those with closed arteries. With the use of univariate and multivariate analysis, the relative importance of the patency of the LAD was determined. All patients with previous anterior wall infarction were analyzed as a separate group, and those with and without a patent LAD were compared. Overall, survival was significantly better in patients with an open LAD. However, multivariate analysis of either the entire study group or the group with myocardial infarction showed that coronary artery patency was not an independent predictor of long-term survival. Analysis of patients with prior anterior myocardial infarction showed significantly improved 5-year survival in younger patients (< 70 years) who had an open (but stenosed) versus a closed LAD without angiographic collateral formation (94% vs 81%, p = 0.025). Furthermore, this survival difference was most striking in patients with left ventricular dysfunction. Survival in younger patients with an open LAD was similar to that of patients with a closed LAD with collateral formation (94% vs 92%, p = 0.55). No differences in survival were observed in the groups without infarction. This study implies that an open LAD improves long-term survival for younger patients with a previous anterior myocardial infarction and no collateral support to the ischemic or infarcted myocardium.

Coronary Disease↗
PubMed1995

In situ human obstetrical ultrasound exposimetry: estimates of derating factors for each of three different tissue models.

A specialized in vivo exposimetry system was developed to acquire transabdominal in situ ultrasound exposure quantities in obstetric patients. Under surgical conditions, the sterilized 7-element calibrated linear array hydrophone was introduced into the uterus under direct ultrasound guidance and placed in direct contact with the products of conception, usually in the saggital midplane of the uterine cavity. Twenty-five patients with empty bladders and 10 patients with full bladders were studied at gestational ages between 7 and 20 weeks. In the empty bladder condition, the sound beam traversed the anterior abdominal wall, uterus, amniotic fluid and fetal parts and in the full bladder condition, the sound beam also traversed the fluid-filled bladder. Each study was conducted with a 3 MHz, mechanical sector transducer in combination with an ATL Ultramark 4 diagnostic ultrasound imaging system. Calibration data were recorded after completion of each in vivo patient study. The acquired exposimetry data from the 35 obstetric patients were used to evaluate the appropriateness of three tissue attenuation models, viz., fixed path, homogeneous and overlying. All three tissue models yield a mean attenuation coefficient value of about a factor of 3 to 4 greater than their respective minimum values. In the case of the overlying and homogeneous tissue models, there was a statistically significant correlation between their calculated attenuation coefficients and total distance for the combined data set whereas there was no such dependency for the calculated fixed-path tissue model. In summary, any one of the three tissue models may be used to estimate in utero acoustic quantities during the first and second trimesters of human pregnancy based on this study.

Adult↗