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Biomedical subjects

D Levy

Publications and source records attributed to D Levy.

At least 289 records · Page 16Linked to original sources
PubMed1992

Echocardiographic left ventricular hypertrophy: clinical characteristics. The Framingham Heart Study.

Recent data suggest that echocardiographic left ventricular (LV) hypertrophy is associated with increased cardiovascular morbidity and mortality. Based upon application of sex-specific echocardiographic criteria for LV hypertrophy, the clinical characteristics of 863 subjects with and 4097 subjects without LV hypertrophy are examined. Subjects with LV hypertrophy are older, more obese, have higher blood pressure, and are more likely to have pre-existing coronary artery disease. In addition subjects with LV hypertrophy have a higher prevalence of reduced echocardiographic fractional shortening. We conclude that subjects with echocardiographic LV hypertrophy are at high risk for cardiovascular disease complications by virtue of their clinical profile. Additional investigation of the benefits of therapeutic interventions directed toward the prevention or regression of LV hypertrophy is warranted.

Adolescent↗
PubMed1992

Partial characterization of a familial B lymphosarcoma with a thymic localization in cattle.

We recently described an original epidemiological form of bovine leukosis in cattle. In the young female offspring of one bull, more than 3% of animals developed a thymic lymphoblastic lymphosarcoma. Of these, 31 cases, together with a lymphoid cell line established from one of the tumours, were phenotypically characterized. Characterization was done using a large combination of well clustered monoclonal antibodies, and monoclonal antibodies prepared in our laboratory by immunizing mice either with bovine normal lymphocytes or with tumour thymic cells. The thymic tumours and the cell line did not express any T lymphoid antigens but they did express some B lymphoid markers. The phenotype of the tumour cells was CD45+/-, CD44+/- TdT+, class II-DR+/-, CD19+/-, CD21-, Ig- and HBM 57+ (recognizing the mb-1 chains of the B-cell receptor). The cell line expressed a more mature phenotype: TdT-, CD45-, CD44+, class II-DR+, CD19+, CD21+/- and sIgG+. These results allow us to consider these tumours as B-cell derived. These B lymphosarcomas with a thymic localization are reminiscent of a human mediastinal non-lymphoblastic lymphoma reported as a primary mediastinal clear cell lymphoma. The possibility of a thymic or extrathymic origin for this B lymphosarcoma is discussed.

Animals↗
PubMed1991

Influence of contemporary versus 30-year blood pressure levels on left ventricular mass and geometry: the Framingham Heart Study.

To determine whether long-term blood pressure levels correlate with left ventricular mass, echocardiographic measurements were performed in 152 men and 299 women who were participants in the Framingham Heart Study. All subjects were free of obesity and cardiovascular and pulmonary disease, were not taking antihypertensive medications and had echocardiographic studies that were adequate for estimating left ventricular mass. Thirty-year average systolic blood pressure was correlated with left ventricular mass (corrected for height) (r = 0.27, p less than 0.001 in men; r = 0.31, p less than 0.001 in women). Multivariate linear regression analyses taking into account age and body mass index showed 30-year average systolic blood pressure to be a significant independent predictor of left ventricular mass (p less than 0.01 in men and women). Systolic blood pressure at echocardiography was not independently associated with left ventricular mass when 30-year systolic blood pressure was entered into the multivariate model. The prevalence of left ventricular hypertrophy was associated with 30-year average systolic blood pressure (odds ratio for every 20-mm Hg increase in blood pressure: 3.20, p less than 0.05 in men; 3.27, p less than 0.001 in women). The increase in left ventricular mass associated with 30-year average systolic blood pressure reflected changes in left ventricular wall thickness but not in left ventricular internal dimension. Thirty-year average diastolic blood pressure was also correlated with left ventricular mass but to a lesser degree than was systolic blood pressure (r = 0.18, p less than 0.05 in men; r = 0.18, p less than 0.01 in women).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study.

OBJECTIVE: --To determine the relationship of varying degrees of obesity with left ventricular mass and geometry. DESIGN: --Survey. SETTING: --Population-based epidemiologic study. PARTICIPANTS AND METHODS: --M-mode echocardiograms, which were adequate for estimation of left ventricular mass, were obtained in 3922 healthy participants of the Framingham Heart Study. Measured height and weight were used to calculate body-mass index, a measure of obesity. RESULTS: --Body-mass index was strongly correlated with left ventricular mass. After adjusting for age and blood pressure, body-mass index remained a strong independent predictor of left ventricular mass, left ventricular wall thickness, and left ventricular internal dimension (P less than .01 for all). Body-mass index was associated with prevalence of echocardiographic left ventricular hypertrophy, particularly in subjects with a body-mass index exceeding 30 kg/m2. CONCLUSIONS: --Obesity is significantly correlated with left ventricular mass, even after controlling for age and blood pressure. The increase in left ventricular mass associated with increasing adiposity reflects increases in both left ventricular wall thickness and left ventricular internal dimension.

Adult↗
PubMed1991

Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study).

Although several reports have described early changes of cardiac structure and function in diabetic patients, controversy persists regarding the existence of a clinically distinct diabetic cardiomyopathy. To this end, sex-specific linear regression analyses were used to examine the contribution of diabetes mellitus and glucose intolerance to age-adjusted echocardiographic parameters in 1,986 men (mean age 48 years) and 2,529 women (mean age 50 years) from the original Framingham Study cohort and the Framingham Offspring Study. Subjects with evidence of cardiovascular disease at the time of echocardiogram were excluded. Diabetics had higher heart rates than nondiabetics (67.9 vs 64.0 beats/min (p = 0.002) in men, and 73.1 vs 68.3 beats/min (p = 0.004) in women). Diabetic women had increased left ventricular (LV) wall thickness (18.7 vs 17.1 mm, p less than 0.001), relative wall thickness (0.403 vs 0.377, p = 0.008), LV end-diastolic dimension (46.9 vs 45.7 mm, p = 0.03) and LV mass corrected for height (100.4 vs 82.2 g/m, p less than 0.001). Women with glucose intolerance showed similar, less significant trends (p = 0.007 for wall thickness, p less than 0.01 for LV mass). In diabetic men, fractional shortening was slightly reduced (0.355 vs 0.360, p less than 0.05). In a multivariate model that included potentially confounding factors, diabetes remained an independent contributor to LV mass (p = 0.004) and wall thickness (p = 0.008) in women. In a separate linear regression model, which assessed the association of age with LV mass, the age-coefficient for diabetic women was much higher than that for nondiabetics (13.6 vs 6.6 g/m per 10-year increment in age).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

High-resolution 13C NMR study of the topography and dynamics of methionine residues in detergent-solubilized bacteriorhodopsin.

The proton transport membrane protein bacteriorhodopsin has been biosynthetically labeled with [methyl-13C]methionine and studied by high-resolution 13C NMR after solubilization in the detergent Triton X-100. The nine methionine residues of bacteriorhodopsin give rise to four well-resolved 13C resonances, two of which are shifted upfield or downfield due to nearby aromatic residues. Methionine residues located on the hydrophilic surfaces, on the hydrophobic surface, and in the interior of the protein could be discriminated by studying the effects of papain proteolysis, glycerol-induced viscosity increase, and paramagnetic broadening by spin-labels on NMR spectra. Such data were used to evaluate current models of the bacteriorhodopsin transmembrane folding and tertiary structure. T2 and NOE measurements were performed to study the local dynamics of methionine residues in bacteriorhodopsin. For the detergent-solubilized protein, hydrophilic and hydrophobic external residues undergo a relatively large extent of side chain wobbling motion while most internal residues are less mobile. In the native purple membrane and in reconstituted bacteriorhodopsin liposomes, almost all methionine residues have their wobbling motion severely restricted, indicating a large effect of the membrane environment on the protein internal dynamics.

Amino Acid Sequence↗
PubMed1991

Relation of alcohol intake to left ventricular mass: The Framingham Study.

Alcohol has direct toxic effects on the myocardium and is associated with elevated blood pressure, but its relation to left ventricular mass independent of blood pressure level has not been assessed. Reported alcohol intake and left ventricular mass measured by echocardiography were evaluated in 1,980 men and 2,511 women 17 to 90 years of age and free of cardiovascular disease in the Framingham offspring and cohort study. The relation of reported alcohol intake to left ventricular mass was assessed by gender-specific multivariate regression analysis adjusting for age, height, body mass index, systolic blood pressure, history of hypertension and cigarette smoking. Alcohol intake was positively associated with left ventricular mass in men (p less than 0.01) but not in women (p = 0.64). When stratified by beverage type, beer and wine in both men and women and liquor in men were positively related to left ventricular mass. The lack of association of total alcohol intake to left ventricular mass in women appeared to be due to a negative association (p less than 0.01) with liquor. The strongest positive associations were with wine in men (p less than 0.001) and beer in women (p less than 0.05). Alcohol use is independently associated with left ventricular mass; this association may vary by beverage type. In persons with unexplained left ventricular hypertrophy, excessive alcohol intake should be considered.

Adolescent↗
PubMed1991

Duration of the QT interval and total and cardiovascular mortality in healthy persons (The Framingham Heart Study experience).

The baseline electrocardiograms of 5,125 original subjects of the Framingham Heart Study were measured to examine the relation of the QT interval corrected for heart rate (QTc) to risk of total mortality, sudden cardiac death, and death due to coronary artery disease over a 30-year follow-up period. Quintiles of QTc (seconds) less than or equal to 0.36, 0.36 to 0.38, 0.39 to 0.40, 0.41 to 0.43 and greater than or equal to 0.44 were studied in relation to these outcomes. There were no significant differences in the risk of total mortality, sudden cardiac death or death due to coronary artery disease according to QTc. A similar lack of significant association between QTc and these 3 outcomes was observed among all persons studied and in the 2 sexes after using a multiple regression analysis to control for several potentially confounding characteristics including age, gender, cigarette smoking, serum total cholesterol, systolic systemic blood pressure and Framingham relative weight. The results of this study fail to demonstrate an association between baseline QTc and overall mortality, and deaths due to sudden cardiac events or coronary artery disease in a large population-based cohort of essentially healthy persons in whom pathologic forms of QTc prolongation are uncommon.

Adult↗
PubMed1991

Butyrylcholinesterase and acetylcholinesterase prophylaxis against soman poisoning in mice.

Human butyrylcholinesterase (BChE, EC 3.1.1.8) or acetylcholinesterase (AChE, EC 3.1.1.7) from fetal bovine serum (FBS), administered i.v. in mice, sequestered at approximately 1:1 stoichiometry the highly toxic anti-ChE organophosphate, 1,2,2-trimethylpropyl methyl-fluorophosphonate (soman). A quantitative linear correlation was demonstrated between blood-ChE levels and the protection conferred by exogeneously administered ChE. Results presented here demonstrate that either human BChE or FBS-AChE is an effective prophylactic measure sufficient to protect mice from multiple LD50S of soman without the administration of post-treatment supportive drugs.

Acetylcholinesterase↗
PubMed1991

Effect of an in vivo immunostimulant treatment on PMN functions: interaction with antibiotics in vitro.

The in vivo effect of immunostimulant treatment, bacterial ribosomes together with membranal proteoglycans (three tablets and three sprays daily during 4 days) in combination or not with in vitro amoxicillin or josamycin (range 5-50 micrograms/ml), has been studied on three related functions of polymorphonuclear cells (PMN) isolated from human blood: adhesion, spontaneous and oriented migration. The immunostimulant treatment always induces an increase of the three parameters. A positive effect of high concentrations of amoxicillin could be also observed on adhesion and gives rise to a great additional impact by associating it with immunostimulant treatment (control: 8.26 PMN/field; assay: 51.55 PMN/field). Spontaneous and oriented migration are not very altered by in vitro antibiotics. A very significant decrease of chemotaxis has been only observed with 50 microgram/ml of josamycin. However, the immunostimulant treatment compensates for this negative effect. The real increase in PMN activation produced by the immunostimulant treatment might extend its indications beyond prevention during antibiotherapy, for example in the acute phase of respiratory infections.

Adjuvants, Immunologic↗
PubMed1991

Clinical significance of left ventricular hypertrophy: insights from the Framingham Study.

Left ventricular hypertrophy (LVH) is a cardiac end-organ response to increased pressure or volume load. For the past 40 years the electrocardiogram (ECG) has been used in the Framingham Heart Study for the detection of LVH. There is an increased risk of developing coronary heart disease following the appearance of LVH on the ECG. ECG LVH also carries a high risk for mortality. The overall risk of mortality in subjects with ECG LVH exceeds that following myocardial infarction. Over the past three decades there has been a significant decline in prevalence of ECG LVH concomitant with increased utilization of antihypertensive drug therapy. The recent introduction of echocardiography into the Framingham Heart Study has resulted in the development of new echocardiographic criteria for LVH. Echocardiographic LVH is more prevalent than ECG LVH. Corresponding prevalence rates for these two methods (per 1,000) are 174 vs. 24, respectively. Ambulatory ECG monitoring documents an association of echocardiographic LVH with increased risk for ventricular arrhythmias. Data from Framingham and elsewhere suggest that echocardiographically defined LVH is an important predictor of risk for cardiovascular disease morbidity and mortality. The extent to which prevention or regression of LVH, in response to antihypertensive drug therapy will alter the substantial risks associated with this condition, awaits additional investigation.

Adult↗
PubMed1991

Microvascular A-V shunts and the growth of autologous tissue flaps in Millipore chambers.

An animal model was developed using the male Sprague-Dawley rat to establish a protocol and design criteria for the growth of autologous tissue based on a microvascular pedicle. It became apparent that growth within the chamber depended heavily on membrane porosity and the presence of the microarteriovenous shunt. Different membrane porosities ranging from 0.0, 0.25, 1.2, to 8.0 microns were evaluated (n = 48). Optimal growth occurred with the 1.2-microns and the 8.0-microns micropore Millipore. Growth within the chamber consisted of a radial deposition of collagen and neovascularization originating from the arteriovenous (A-V) anastomosis. In contrast, control chambers (no A-V anastomosis), with the preceding range in membrane porosity, experienced little to no cell growth. In addition, the majority of A-V shunts did not remain patent in chambers having 0.0-microns porosity or 0.25-microns porosity. Thus it is apparent that a strong relationship exists between membrane porosity, patency, and in situ vascularization allowing for the proliferation of cells and collagen.

Animals↗
PubMed1991

Heart rate adjustment of exercise-induced ST segment depression. Improved risk stratification in the Framingham Offspring Study.

BACKGROUND: Simple heart rate adjustment of ST segment depression during exercise (delta ST/HR index) and the pattern of ST depression as a function of heart rate during exercise and recovery (the rate-recovery loop) have been shown to improve the ability of the exercise electrocardiogram to detect the presence of coronary heart disease (CHD), but the performance of these methods for the prediction of future coronary events remains to be examined. METHODS AND RESULTS: We compared the delta ST/HR index and the rate-recovery loop with standard electrocardiographic criteria for prediction of CHD events in 3,168 asymptomatic men and women in the Framingham Offspring Study who underwent treadmill exercise electrocardiography and who, at entry, were free of clinical and electrocardiographic evidence of CHD. After a mean follow-up of 4.3 years, there were 65 new CHD events: four sudden deaths, 24 new myocardial infarctions, and 37 incident cases of angina pectoris. When a Cox proportional hazards model with adjustment for age and sex was used, a positive exercise electrocardiogram by standard criteria (greater than or equal to 0.1 mV horizontal or downsloping ST segment depression) was not predictive of new CHD events (chi 2 = 0.40, p = 0.52). In contrast, stratification according to the presence or absence of a positive delta ST/HR index (greater than or equal to 1.6 microV/beat/min) and a positive (counterclockwise) rate-recovery loop was associated with CHD event risk (chi 2 = 9.45, p less than 0.01) and separated subjects into three groups with varying risks of coronary events: high risk, when both tests were positive (relative risk 3.6; 95% confidence interval, 2.4-5.4); intermediate risk, when either the delta ST/HR index or the rate-recovery loop was positive (relative risk, 1.9; 95% confidence interval, 1.3-2.8); and low risk, when both tests were negative. After multivariate adjustment for age, sex, smoking, total cholesterol level, fasting glucose level, diastolic blood pressure, and electrocardiographic evidence of left ventricular hypertrophy, the combined delta ST/HR index and rate-recovery loop criteria remained predictive of coronary events (chi 2 = 5.45, p = 0.02). CONCLUSIONS: Heart rate adjustment of ST segment depression by the delta ST/HR index and the rate-recovery loop during exercise electrocardiography can improve prediction of future coronary events in asymptomatic men and women.

Adult↗
PubMed1991

QRS interval fails to predict coronary disease incidence. The Framingham Study.

The Framingham Study cohort of 5209 white men and women was examined to determine the long-term incidence of manifestations of new coronary heart disease as a function of QRS interval on subjects' baseline electrocardiograms (recorded at the 9th biennial examination). Over 18 years of follow-up, age-adjusted incidence of myocardial infarction, angina pectoris, and coronary death appeared unrelated to baseline QRS prolongation in both sexes, by Cox regression. Subjects with left bundle-branch block fared no worse than those with right pattern. These relations held whether or not subjects with baseline electrocardiographic abnormalities other than intraventricular block were excluded from consideration. In sum, QRS duration is an unimportant predictor of coronary disease in this Framingham population.

Adult↗
PubMed1990

Evidence for proton countertransport by the sarcoplasmic reticulum Ca2(+)-ATPase during calcium transport in reconstituted proteoliposomes with low ionic permeability.

To ascertain the coupling between Ca2+ and H+ fluxes during Ca2+ transport by the Ca2(+)-pumping ATPase of the sarcoplasmic reticulum, we used well characterized reconstituted proteoliposomes. The method for the functional reconstitution of the Ca2(+)-ATPase was an extension of our recently published procedure (Rigaud, J. L., Paternostre, M. T., and Bluzat, A. (1988) Biochemistry, 27, 2677-2688). The reconstituted vesicles which sustained high Ca2+ transport activities in the absence of Ca2+ precipitating anions exhibited low ionic passive permeability. Proton fluxes generated by external acid pulses have been monitored by using the fluorescence of the pH-sensitive probe pyranine trapped inside proteliposomes. When K+ was the only permeant ion, low proton-hydroxyl passive permeability was found (permeability coefficient congruent to 5 x 10(-5) cm s-1). In the presence of Cl-1 ions, a higher proton permeability was observed, presumably due to diffusion of HCl molecules. It was further demonstrated that systematic characterization of the passive permeability is essential for understanding and controlling the ATP-dependent Ca2+ accumulation in the reconstituted liposomes. The first line of evidence for Ca2(+)-H+ countertransport during operation of the Ca2(+)-ATPase came from Ca2+ uptake measurements. The ATP-dependent Ca2+ accumulation into proteoliposomes was shown to be critically dependent upon the ionic composition of the medium and the presence of ionophores. In K2SO4 medium a very low Ca2+ uptake was obtained which was only slightly affected by the presence of valinomycin. On the contrary, Ca2+ accumulation was increased 3-4-fold in the presence of the protonophore carbonyl-cyanide-p-trifluoromethoxy phenylhydrazone, indicating that a transmembrane pH gradient was built up during Ca2+ uptake that inhibited the transport activity of the pump. Accordingly, we found that Ca2+ loading capacity increased with internal buffer capacity. Finally in KCl medium, high Ca2+ accumulation was observed even in the absence of protonophore in agreement with a rapid dissipation of the pH gradient in the presence of chloride ions. Additional evidence that the Ca2+ pump of sarcoplasmic reticulum operated as a Ca2(+)-H+ countertransport was provided by measurements of ATP-dependent intraliposomal alkalinization using entrapped 8-hydroxyl-1,3,6-pyrene trisulfonate (pyranine) and accumulation of the weak acid acetate. In K2SO4 medium, transmembrane pH gradients of about 1 pH unit were generated with kinetics parallel to those of the Ca2+ uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗
PubMed1990

Phospholipid vesicle solubilization and reconstitution by detergents. Symmetrical analysis of the two processes using octaethylene glycol mono-n-dodecyl ether.

The processes of liposome solubilization and reconstitution were studied by using n-dodecyl octaethylene glycol monoether (C12E8). The solubilization of large unilamellar liposomes prepared by reverse-phase evaporation was systematically investigated by turbidity, 31P nuclear magnetic resonance, and centrifugation experiments. The solubilization process is well described by the three-stage model previously proposed for other detergents, and our results further demonstrate the validity of some of the postulates related to this model. In stage I, the detergent distributes between the bilayers and the aqueous solution with a partition coefficient of 1.6 mM-1. In stage II, the detergent-saturated liposomes convert into mixed micelles, the conversion being complete by stage III where all the phospholipids are present as mixed micelles. The agreement between the three methods was excellent, and the results allowed quantitative determination of the effective detergent to phospholipid ratios at which the lamellar to micellar transformation begins and is complete, which amounted to 0.66 and 2.2 (mol/mol), respectively. Furthermore, compositional analysis determined from centrifugation experiments directly demonstrate that the properties of detergent-saturated liposomes and mixed micelles remain constant throughout most of stage II: the C12E8 to phospholipid ratios in the pelleted vesicles and in micelles are constant during stage II and similar to the ratios at which stage II was initiated and complete, respectively. On the other hand, bilayer formation upon detergent removal from mixed C12E8-phospholipid micelles by SM2 Bio-Beads is demonstrated to be the symmetrical opposite of bilayer solubilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Detergents↗