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Biomedical subjects

D Levy

Publications and source records attributed to D Levy.

At least 307 records · Page 17Linked to original sources
PubMed1990

Reconstitution of the immunopurified 49-kDa sodium-dependent bile acid transport protein derived from hepatocyte sinusoidal plasma membranes.

Reconstitution, using phosphatidylcholine liposomes in conjugation with immunological purification procedures, has been used to establish directly the identity of the hepatocyte Na(+)-dependent bile acid transport protein. Octyl glucoside-solubilized sinusoidal plasma membranes were shown to form proteoliposomes exhibiting taurocholate transport properties which were similar to those of plasma membrane vesicles, namely, Na(+)-dependence and marked inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and by taurochenodeoxycholate. Proteoliposomes formed from plasma membrane proteins depleted of the putative 49-kDa bile acid transport protein by immunoprecipitation with monoclonal antibody 25D-1, which specifically recognizes this protein (Ananthanarayanan, M., von Dippe, P., and Levy, D. (1988) J. Biol. Chem. 263, 8338-8343), showed a 94% reduction in mediated transport capacity. Proteoliposomes containing total membrane protein also demonstrated Na(+)-dependent alanine transport. The addition of taurochenodeoxycholate or the removal of the 49-kDa protein by monoclonal antibody 25D-1 immunoprecipitation had no effect on the uptake of alanine, thus confirming the specificity of these procedures. When only the immunoprecipitated 48-kDa protein was used in the reconstitution system, a 2200% increase of taurocholate uptake was observed. These results definitively establish that this 49-kDa sinusoidal membrane protein is the sole essential component of the Na(+)-dependent bile acid transport system.

Animals↗
PubMed1990

Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study.

A pattern of left ventricular hypertrophy evident on the electrocardiogram is a harbinger of morbidity and mortality from cardiovascular disease. Echocardiography permits the noninvasive determination of left ventricular mass and the examination of its role as a precursor of morbidity and mortality. We examined the relation of left ventricular mass to the incidence of cardiovascular disease, mortality from cardiovascular disease, and mortality from all causes in 3220 subjects enrolled in the Framingham Heart Study who were 40 years of age or older and free of clinically apparent cardiovascular disease, in whom left ventricular mass was determined echocardiographically. During a four-year follow-up period, there were 208 incident cardiovascular events, 37 deaths from cardiovascular disease, and 124 deaths from all causes. Left ventricular mass, determined echocardiographically, was associated with all outcome events. This relation persisted after we adjusted for age, diastolic blood pressure, pulse pressure, treatment for hypertension, cigarette smoking, diabetes, obesity, the ratio of total cholesterol to high-density lipoprotein cholesterol, and electrocardiographic evidence of left ventricular hypertrophy. In men, the risk factor-adjusted relative risk of cardiovascular disease was 1.49 for each increment of 50 g per meter in left ventricular mass corrected for the subject's height (95 percent confidence interval, 1.20 to 1.85); in women, it was 1.57 (95 percent confidence interval, 1.20 to 2.04). Left ventricular mass (corrected for height) was also associated with the incidence of death from cardiovascular disease (relative risk, 1.73 [95 percent confidence interval, 1.19 to 2.52] in men and 2.12 [95 percent confidence interval, 1.28 to 3.49] in women). Left ventricular mass (corrected for height) was associated with death from all causes (relative risk, 1.49 [95 percent confidence interval, 1.14 to 1.94] in men and 2.01 [95 percent confidence interval, 1.44 to 2.81] in women). We conclude that the estimation of left ventricular mass by echocardiography offers prognostic information beyond that provided by the evaluation of traditional cardiovascular risk factors. An increase in left ventricular mass predicts a higher incidence of clinical events, including death, attributable to cardiovascular disease.

Blood Pressure↗
PubMed1990

Expression of the bile acid transport protein during liver development and in hepatoma cells.

The expression of the hepatocyte Na(+)-dependent bile acid transport protein during liver development and in hepatoma cells has been characterized using a monoclonal antibody (mAb 25D-1) which specifically recognizes this 49-kDa carrier system. mAb binding studies demonstrated a greatly reduced concentration of this transport protein on the surface of hepatoma tissue culture (HTC) cells, a result consistent with the greater than 95% reduction in bile acid transport capacity when compared with normal adult hepatocytes. Immunoprecipitation procedures with 25D-1 were utilized to quantitate the presence of this transport protein in HTC cells as well as in adult hepatocytes that had been labeled with [35S]methionine or Na125I. These studies indicate that the 49-kDa transport protein is not expressed either on the surface or in any intracellular compartment in HTC cells. mAb binding to fetal cells (day 17) also indicated a greatly decreased number of transport molecules in the plasma membrane. Total cell content of this carrier protein during the next 7 weeks of liver development, as measured by immunoprecipitation, increased in a linear fashion reaching 92% of the adult level at 4 weeks after birth, which parallels the increase in transport function. These results demonstrate that bile acid transport capacity is directly related to the level of expression of this 49-kDa membrane protein.

Aging↗
PubMed1990

Association of echocardiographic left ventricular mass with body size, blood pressure and physical activity (the Framingham Study).

Left ventricular (LV) hypertrophy has been found to predispose to increased cardiovascular morbidity and mortality. To assess the clinical correlates and potential determinants of LV mass, the relation of echocardiographically determined LV mass to a variety of clinical parameters was examined in a general population. From 1979 to 1983 Framingham Heart Study participants underwent routine evaluation including medical history, physical examination and M-mode echocardiography. LV mass was determined using an anatomically validated formula that incorporates measurements of LV wall thickness and LV internal diameter. The study population consisted of 2,226 men and 2,746 women (mean age 51 years, range 17 to 90). Age, height, systolic blood pressure and body mass index (a measure of obesity) were statistically significant and independent correlates of LV mass in both sexes (p less than 0.001). In men under age 50, leisure-time physical activity was associated with LV mass (p less than 0.05), but this was not observed in women. Results from multivariate analyses in which body mass index and subscapular skinfold thickness were included suggest that lean body mass is correlated with LV mass. Maintenance of ideal body weight and normal blood pressure, weight reduction in obese persons and blood pressure control in hypertensive patients may contribute to the primary and secondary prevention of LV hypertrophy and its sequelae. Clinical interpretation of echocardiograms should include consideration of the correlates of LV mass to gain better insight into the pathogenesis of LV hypertrophy.

Age Factors↗
PubMed1990

Risk of coronary heart disease in subjects with chest discomfort: the Framingham Heart Study.

PURPOSE: To examine the risk of coronary heart disease (CHD) events in subjects of the Framingham Study reporting new chest discomfort. SUBJECTS AND METHODS: Original cohort subjects with chest discomfort were classified by their history into three groups: definite angina, possible angina, or nonanginal chest discomfort. Subjects were followed for 2 years for CHD events, including coronary insufficiency, myocardial infarction, or CHD death. RESULTS: Compared to that in subjects without chest discomfort, the relative odds of a CHD event was 3.7 (95% confidence interval [CI] 2.11, 6.60) in men with definite angina and 3.0 (95% CI 1.33, 6.69) in men with possible angina. Comparable increased CHD risk was also observed in women with definite or possible angina, with relative odds of 5.4 (95% CI 3.08, 9.30) and 2.9 (95% CI 1.13, 7.17), respectively. The increase in CHD risk associated with definite or possible angina persisted after adjustment for cardiac risk factor profile. There was no increase in risk associated with nonanginal chest discomfort. CONCLUSION: CHD risk is increased in subjects with new chest discomfort that on the basis of history is consistent with definite or possible angina, whereas CHD risk is not increased in subjects with nonanginal chest discomfort. The presence of chest discomfort and its characteristics facilitate the classification of subjects into meaningful categories that offer prognostic information beyond that provided by traditional CHD risk factors.

Adult↗
PubMed1990

Stratifying the patient at risk from coronary disease: new insights from the Framingham Heart Study.

Although cardiovascular disease remains the leading cause of death in the United States, cardiovascular disease mortality has decreased steadily during the past 2 decades. This trend is largely attributable to improved detection and management of cardiovascular risk factors, in which the Framingham Heart Study has played a major role. This article examines some of the risk factors associated with coronary heart disease, notably, advancing age, hypertension, left ventricular hypertrophy, smoking, elevated serum cholesterol, and reduced high-density lipoprotein, all of which have been investigated by the Framingham Heart Study. In addition, new data are presented from a multidimensional model of coronary heart disease. This is a novel approach that takes into account the interactions of multiple risk factors and their contribution to overall coronary heart disease risk.

Adult↗
PubMed1990

Prognostic significance of the electrocardiogram after Q wave myocardial infarction. The Framingham Study.

The prognostic value of abnormalities on the electrocardiogram (ECG) present 1 year after initial myocardial infarction (MI) is examined in relation to reinfarction and coronary death throughout 32 years (mean, 10.1 years) of follow-up in the Framingham Heart Study. Resting 12-lead ECGs were available in 251 survivors (190 men and 61 women) of clinically recognized Q wave MI. The ECG reverted to normal in 31 (12.4%) cases and was abnormal but without Q waves in 37 (14.7%). Q waves persisted without other significant abnormalities in 108 (43.0%) and with other abnormalities in 75 (29.9%) cases. Electrocardiographic abnormalities at follow-up were more common in women and in those persons whose initial MI was anterior as compared with inferior. Nonspecific T wave, ST segment changes, and electrocardiographic left ventricular hypertrophy on the ECG before or after MI were powerful predictors (p less than 0.01) of coronary death. The relation of these residual post-MI electrocardiographic findings to reinfarction and coronary death was assessed by Cox regression analysis. The follow-up electrocardiographic status was unrelated to the risk of subsequent reinfarction. Subjects who lost Q wave evidence of MI but whose ECG continued to show evidence of repolarization abnormalities, left ventricular hypertrophy, or blocked intraventricular conduction were at a 3.5-fold increased risk (p less than 0.01) of coronary death as compared with those reverting to a normal ECG. Persons with a persistent Q wave MI accompanied by these abnormalities were at a 2.7-fold excess risk (p = 0.01) of coronary death as compared with those with a normalized ECG. These findings remained significant when considering age and standard coronary risk factors. The presence of other electrocardiographic abnormalities without persistent Q waves yields a worse prognosis than a Q wave persisting alone. The prognostic value of a follow-up ECG with abnormalities other than a persistent Q wave MI also remained after considering the effects of left ventricular hypertrophy and cardiac enlargement on x-ray, functional classification, and diuretic usage. Specific electrocardiographic abnormalities present before infarction, however, were potent indicators of long-term prognosis prognosis and diminished the importance of the follow-up ECG. Although survival after initial MI is improved only if the ECG reverts to normal, information on electrocardiographic abnormalities before MI can be especially useful in evaluating long-term risk.

Cohort Studies↗
PubMed1990

Determinants of sensitivity and specificity of electrocardiographic criteria for left ventricular hypertrophy.

Numerous electrocardiographic criteria, which are largely dependent on fixed voltage thresholds, have been proposed for the diagnosis of left ventricular hypertrophy (LVH). Electrocardiographic criteria for LVH were examined in 4,684 subjects of the Framingham Heart Study who underwent echocardiographic study for LVH. Echocardiographic LVH was detected in 290 men (14.2%) and 465 women (17.6%). Electrocardiographic features of LVH were present in 2.9% of men (60/2,042) and 1.5% of women (39/2,642). The overall sensitivity of the electrocardiographic diagnosis of LVH was 6.9%, whereas specificity was 98.8%. Sensitivity of the electrocardiogram (ECG) for LVH was marginally lower in women than in men (5.6% vs. 9.0%, p = 0.075). Obesity was inversely associated with sensitivity (p less than 0.05, both sexes combined, sex-adjusted). Smoking was also inversely related to sensitivity (p = 0.001, both sexes combined, sex-adjusted). In contrast, sensitivity of the ECG increased with age (p less than 0.001, both sexes combined, sex-adjusted). These findings suggest that electrocardiographic detection of LVH can be improved by incorporating information about noncardiac factors that impact on electrocardiographic sensitivity for LVH, presumably by attenuating QRS voltage. New strategies that take into consideration sex, age, smoking status, and obesity might improve the sensitivity of the ECG without diminishing specificity.

Age Factors↗
PubMed1990

Natural history of progressive ischemic stroke in a population treated with heparin.

Data on the acute natural history of progressive stroke with or without heparin treatment are limited. To define the acute course of patients treated with heparin for progressive stroke, we examined the charts of 69 such patients identified through the Cornell Neurology Database from October 1979 to June 1985. Analysis included determining whether further clinical deterioration or hemorrhagic complications were associated with readily identifiable clinical or laboratory variables. Twenty-five patients (36%) continued to deteriorate while receiving heparin, another two (3%) worsened due to intracerebral hemorrhage, and a total of 10 patients (14%) had bleeding complications. No clinical features or heparin dosing regimens distinguished the patients likely to benefit from heparin. Clinical progression or hemorrhage did not correlate with the level of anticoagulation as measured by the average heparin dose per day or the mean partial thromboplastin time. Without unequivocal evidence demonstrating heparin's ineffectiveness for progressive stroke, many clinicians managing such patients will continue to use heparin. Our results suggest that this decision should not be governed by such clinical features as a patient's age or sex or by the vascular distribution of the stroke. Furthermore, frequent measurement of and overzealous efforts to adjust the partial thromboplastin time may be unnecessary since it does not correlate with outcome.

Adult↗
PubMed1990

Interferon-dependent transcriptional activation: signal transduction without second messenger involvement?

Two specific macromolecular interactions are known to underlie the demonstrated transcriptional stimulation of different sets of genes incident to the binding of different polypeptide ligands to cells. The initial polypeptide-receptor interaction is widely recognized to be specific. It is also well established that the binding of specific transcription factors to well-defined DNA sites activates specific genes. In this paper, we suggest that a third, equally specific protein-protein interaction links the first two specific interactions and ensures the high specificity required in these pathways. We propose that a receptor-recognition protein is required to recognize the bound receptor. This receptor-recognition protein might itself be part of a transcription factor or might interact directly with a transcription factor that would thereby be activated and translocated to the nucleus to participate in gene activation. According to this hypothesis, no global changes in second messenger concentrations are necessary, and the enzymatic properties of the receptor-recognition protein(s) need not be specified. Phosphorylations of, or by, receptor-bound proteins would not, of course, be excluded. But such modifications during ligand-mediated signal transduction would not depend on global second messenger changes. This model is derived from studies of the proteins involved in interferon (IFN)-stimulated gene transcription. It is now established that interferon-alpha (IFN alpha) activates a multisubunit transcription factor in the cell cytoplasm, and that this factor then moves to the nucleus to activate a set of IFN-stimulated genes.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA-Binding Proteins↗
PubMed1990

The fat embolism syndrome. A review.

While fat embolism occurs in most (more than 90%) patients with traumatic injury, the fat embolism syndrome (FES) occurs in only 3%-4% of patients with long-bone fractures. FES involves multiple organ systems and can cause a devastating clinical deterioration within hours. The major clinical features of FES include hypoxia, pulmonary edema, central nervous system depression, and axillary or subconjunctive petechiae. Improvements have been made in supporting the respiratory compromise and adult respiratory distress syndrome that these patients develop. Aggressive measures to improve the pulmonary function, i.e., positive pressure ventilation and effective fluid management, are important and expedite fixation of bone fractures.

Embolism, Fat↗
PubMed1989

Cardiovascular risk factors in the elderly.

The relation of total plasma cholesterol to the incidence of coronary heart disease (CHD) was one of the first findings of the Framingham Heart Study. The Framingham data established that a 1% increase in total cholesterol produced a 2% increase in CHD incidence. This relation has now been shown to apply to persons aged 60 to 70 years as well as to younger persons. The risk of CHD associated with various factors, including total cholesterol, low- and high-density lipoprotein and triglyceride levels, uric acid, blood glucose level, fibrinogen level and hypertensive blood pressure, is discussed with particular reference to the elderly. New data from the Framingham group show that increased left ventricular mass may be a significant risk factor for CHD, particularly among the elderly.

Adult↗
PubMed1989

Cardiovascular risk factors and graded treadmill exercise endurance in healthy adults: The Framingham Offspring Study.

To help describe the association between exercise endurance and cardiovascular risk factor profiles, 2,606 young and middle-aged healthy adults in the Framingham Offspring Study were given submaximal treadmill tests. For both men and women, exercise endurance was inversely related to resting heart rate (p less than 0.001), body mass index (p less than 0.001), systolic blood pressure (p less than 0.001) and blood glucose (p less than 0.01), and positively related to high density lipoprotein (HDL) cholesterol (p less than 0.05). In men, cigarette smoking (p less than 0.05), high levels of total cholesterol (p less than 0.01) and very low density lipoprotein (VLDL) cholesterol (p less than 0.001) were also associated with poor exercise endurance. After adjusting for age, resting heart rate and body mass index, significant independent associations persisted for HDL cholesterol (p less than 0.05) in both sexes and for systolic blood pressure, VLDL cholesterol, blood glucose and cigarette smoking in men (p less than 0.05). Risk factors associated with overt cardiovascular disease in older individuals are also associated with poor exercise endurance in those who are younger and asymptomatic.

Adolescent↗