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Biomedical subjects

D Levy

Publications and source records attributed to D Levy.

At least 361 records · Page 20Linked to original sources

Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population.

To determine if sudden cardiac death shows circadian variation, the time of day of sudden cardiac deaths in the Framingham Heart Study was analyzed. Analysis was based on mortality data collected in a standardized manner for the past 38 years for each death among the 5,209 persons in the original cohort. The necessary assumptions about the cause and timing of unwitnessed deaths were made in a manner likely to diminish the possibility of detecting an increased incidence of sudden cardiac death during the morning. In the Framingham study, analyses using these assumptions reveal a significant circadian variation (p less than 0.01) in occurrence of sudden cardiac death (n = 429), with a peak incidence from 7 to 9 AM and a decreased incidence from 9 AM to 1 PM. Risk of sudden cardiac death was at least 70% higher during the peak period than was the average risk during other times of the day. Further studies are needed to confirm this finding in other populations, to collect data regarding medications and to determine activity immediately before sudden cardiac death. Investigation of physiologic changes occurring during the period of increased incidence of sudden cardiac death may provide increased insight into its causes and suggest possible means of prevention.

Adult↗

Risk of ventricular arrhythmias in left ventricular hypertrophy: the Framingham Heart Study.

The association of ventricular arrhythmias with left ventricular (LV) hypertrophy was examined in 6,218 participants in the Framingham Heart Study. Electrocardiographic (ECG) LV hypertrophy was present in 171 subjects and echocardiographic hypertrophy was detected in 869. Echocardiographic LV hypertrophy was associated with increased risk for each of 6 ventricular arrhythmia grades in men (relative risk up to 8.9, p less than 0.01), and 4 of 6 grades in women (p less than 0.05). Similarly, men with ECG LV hypertrophy were at increased risk for 4 of 6 arrhythmia grades (p less than 0.05). However, owing to low prevalence ECG LV hypertrophy was not associated with arrhythmia in women. After adjustment for age, sex, systolic blood pressure, valvular heart disease, angina pectoris and acute myocardial infarction, the association of echocardiographic but not ECG LV hypertrophy with ventricular arrhythmia remained significant (p less than 0.001). Thus, echocardiographic LV hypertrophy is more prevalent and more sensitive for ventricular arrhythmias than ECG LV hypertrophy.

Adult↗

Cholesterol and mortality. 30 years of follow-up from the Framingham study.

From 1951 to 1955 serum cholesterol levels were measured in 1959 men and 2415 women aged between 31 and 65 years who were free of cardiovascular disease (CVD) and cancer. Under age 50 years, cholesterol levels are directly related with 30-year overall and CVD mortality; overall death increases 5% and CVD death 9% for each 10 mg/dL. After age 50 years there is no increased overall mortality with either high or low serum cholesterol levels. There is a direct association between falling cholesterol levels over the first 14 years and mortality over the following 18 years (11% overall and 14% CVD death rate increase per 1 mg/dL per year drop in cholesterol levels). Under age 50 years these data suggest that having a very low cholesterol level improves longevity. After age 50 years the association of mortality with cholesterol values is confounded by people whose cholesterol levels are falling--perhaps due to diseases predisposing to death.

Adult↗

Echocardiographic criteria for left ventricular hypertrophy: the Framingham Heart Study.

Of 6,148 original cohort and offspring subjects of the Framingham Heart Study who underwent routine evaluation, a healthy group of 347 men (aged 42 +/- 12 years) and 517 women (aged 43 +/- 12 years) was identified to develop echocardiographic criteria for left ventricular (LV) hypertrophy. Healthy subjects were defined as normotensive, receiving no cardiac or antihypertensive medications, nonobese and free of cardiopulmonary disease. Echocardiographic criteria (in accordance with the American Society of Echocardiography convention) for LV hypertrophy, based on mean plus 2 standard deviations for LV mass, LV mass corrected for body surface area and LV mass corrected for height in this healthy sample are, respectively: 294 g, 150 g/m2 and 163 g/m in men and 198 g, 120 g/m2 and 121 g/m in women. Criteria based on LV mass/height result in higher prevalence rates of LV hypertrophy than LV mass/body surface area while still correcting for body size. The prevalence of LV hypertrophy in the entire study population (using LV mass/height criteria) is 16% in men and 19% in women. Until outcome guided criteria for LV hypertrophy are developed, application of sex-specific criteria based on a healthy population distribution of LV mass offer the best approach to echocardiographic diagnosis of LV hypertrophy.

Adult↗

Echocardiographically determined left ventricular structural and functional correlates of complex or frequent ventricular arrhythmias on one-hour ambulatory electrocardiographic monitoring.

The associations between 6 echocardiographic measurements and ventricular arrhythmias on 1-hour ambulatory electrocardiograms were evaluated in 3,348 subjects of the Framingham Heart Study who were free of symptomatic coronary artery disease, congestive heart failure and valvular heart disease and were not receiving diuretic drugs or other blood pressure or cardiac medications. Age-adjusted estimates of association between echocardiographic measurements of left ventricular (LV) structure and function and complex or frequent (Lown grade 2 or greater) ventricular arrhythmia were computed using logistic regression. In this bivariate model only LV internal diameter (systolic and diastolic) and fractional shortening were associated with arrhythmia in both sexes (p less than 0.01). When all variables were entered into a multivariate model, only age and systolic LV internal diameter remained independently associated with arrhythmia (p less than 0.001). Thus, LV chamber size and function are important predictors of risk for ventricular arrhythmia. Systolic LV internal diameter, which reflects both functional and structural information, is the only measurement independently predictive of arrhythmia risk in persons free of apparent heart disease.

Adult↗

Wheat germ agglutinin (WGA): a bovine T lymphocyte marker.

Bovine peripheral blood lymphocytes (PBL) were examined for their ability to bind wheat germ agglutinin (WGA). This lectin labelled 43.8% +/- 11.95 of bovine PBL, whereas peanut agglutinin (PNA), a T cell marker, bound 59.4% +/- 8.67 cells, and surface immunoglobulin (SLG)-bearing cells constituted 24.15% +/- 8.47 of PBL. After panning fractionation of B (Slg+) and T (PNA+) lymphocytes. WGA labelled 89 to 97% of the enriched T cell population (80/87% PNA+; 2-4% Slg+) but only 6 to 8% of the enriched B cell population (85-91% Slg+; 5-7% PNA+).

Animals↗

Bovine leukemia virus replicates in sheep B lymphocytes under a T cell released factor.

In order to determine which cell supports BLV replication in experimentally infected sheep, peripheral blood lymphocytes (PBL) were separated into purified B and T populations by a panning technique. Our data demonstrate that viral replication takes place only in B lymphocytes. However, PHA, a T cell mitogen, is necessary for BLV replication both in PBL and enriched surface immunoglobulin bearing cells, whereas B cell mitogens have no effect on viral replication. Altogether, these results suggest that BLV activation in enriched B lymphocytes is dependent on the presence of residual T cells, and occurs through a T cell interaction, probably mediated by a soluble factor. This possibility was confirmed by the fact that the conditioned medium from cultures of BLV-free sheep T lymphocytes greatly enhances viral production by infected B lymphocytes. Our data favor the hypothesis that BLV multiplication occurs through the regular activation mechanisms of the immune system.

Animals↗

Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element.

A human gene encoding an interferon-induced 15-kDa protein has been isolated from a genomic library. The gene appears to be single-copy and is composed of two exons, the first of which contains the ATG translation initiation codon. In vitro nuclear run-on assays showed that the transcription rate of the gene is stimulated after interferon treatment. To analyze transcriptional regulatory sequences, we constructed recombinant plasmids for use in transient transfection assays of HeLa cells. Constructs containing 115 nucleotides 5' to the transcription initiation site were found to be fully inducible by interferon. Assays of deletion mutants identified a critical element for interferon induction located between -115 and -96, just upstream of the "CCAAT box." Moreover, a DNA fragment including this region can confer interferon inducibility on a heterologous promoter (thymidine kinase) when cloned in either orientation upstream of the gene or downstream of the gene. These are properties characteristic of an enhancer element that is active only after treatment with interferon. This regulatory sequence may be shared by a group of interferon-induced genes, since a very similar sequence is present within the functional region near the RNA start site of another interferon-induced gene.

Amino Acid Sequence↗

Left ventricular hypertrophy and risk of cardiac failure: insights from the Framingham Study.

The incidence of congestive heart failure (CHF), derived from more than 30 years of follow-up, is examined by electrocardiogram (ECG) and radiography in relation to cardiac hypertrophy. Cardiac failure occurred in 485 of 5,209 subjects participating in the Framingham Study. Hypertension was the dominant predisposing factor for both cardiac hypertrophy and cardiac failure. The ECG pattern of left ventricular hypertrophy (ECG-LVH) heralded serious cardiovascular disease of all varieties, but risk ratios were two- to fivefold greater for the development of CHF in men and women (ages 35-64 years) than for any other sequelae. Risk of CHF in those with ECG-LVH exceeded that for unrecognized ECG patterns at myocardial infarction (ECG-MI). The ECG pattern of left ventricular hypertrophy, characterized by increased voltage unaccompanied by a repolarization abnormality, carried a decreased risk, chiefly reflecting the severity of coexistent hypertension. The independent contribution of ECG-LVH with accompanying repolarization changes to the risk of CHF was equal in the two sexes and persisted with advancing age. The ECG pattern of left ventricular hypertrophy was more strongly associated with occurrence of CHF than was radiographic enlargement, and contributed to the risk of CHF (taking radiographic heart size into account). Echocardiographic evidence of LVH (ECHO-LVH) was more common in subjects with CHF than was ECG-LVH, occurring in 63% of women and 77% of men with CHF, and LVH was the most frequently observed echocardiographic finding. Cardiac hypertrophy was found to be an ominous harbinger of cardiac failure, particularly when it was manifested on an ECG with repolarization abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Development of leukemia and lymphosarcoma induced by bovine leukemia virus in sheep: a hematopathological study.

The hematological and neoplastic disorders induced in sheep by experimental bovine leukemia virus (BLV) infection are described. Seventeen of 19 BLV-inoculated sheep developed a marked increase in peripheral blood lymphocytes by 36 months after the intraperitoneal injection of peripheral blood lymphocytes from a BLV-infected cow. This increase correlated with an increase in the number of circulating B lymphocytes as demonstrated by the presence of surface immunoglobulins (SIg) and a high cell proliferative response to lipopolysaccharide and was considered to be a persistent B cell lymphocytosis. Lymphosarcoma developed in five BLV-infected sheep between 19 and 38 months postinoculation and was preceded in four out of five of these cases by an elevation in peripheral blood lymphocytes which began 4 to 26 months before death due to lymphosarcoma. The majority of tumor cells in all lymphosarcoma cases were of the centroblastic type, and in two cases in which the presence of SIg was assayed, the majority of tumor cells were SIg-positive. Thus, BLV-induced lymphosarcoma in sheep seems to be a B lymphocyte-derived tumor.

Animals↗

The spectrum of left ventricular hypertrophy in a general population sample: the Framingham Study.

To assess the prevalence, characteristics, and correlates of echocardiographically determined left ventricular hypertrophy (echo LVH) in a free-living population, 510 men and 855 women from the original Framingham cohort (age 59 to 90 years) were studied by M-mode echocardiography. Offspring and offspring spouses (1718 men and 1892 women; age 17 to 75 years) were similarly studied. The severity of echo LVH, as reflected by left ventricular mass indexed to body surface area, ranged from 101 g/m2 (women) and 132 g/m2 (men) to more than 400 g/m2. The prevalence of electrocardiographically assessed LVH increased proportionately with increased echocardiographic left ventricular mass. Women with echocardiographic left ventricular mass indexes exceeding 200 g/m2 were three to four times more likely to have electrocardiographic LVH than men with similar elevations of echocardiographic left ventricular mass index. The prevalence of echo LVH ranged from 6.6% in the younger (offspring study) women to 33% in the older (original cohort) women (8.6% and 23.7%, respectively, for men) and included a spectrum of forms--eccentric-dilated, eccentric-nondilated, concentric, and disproportionate septal thickness--which varied in prevalence in the various age-sex groups. Each of these forms of echo LVH was associated with higher systolic blood pressures at the time of echocardiographic examination and over the previous 30 years when compared with blood pressures of Framingham subjects without echo LVH.

Adult↗

Electrocardiographic changes with advancing age. A cross-sectional study of the association of age with QRS axis, duration and voltage.

In order to examine the electrocardiographic (ECG) changes which occur with advancing age we defined an apparently healthy reference population derived from prospectively followed subjects of the Framingham Heart Study. Healthy subjects were clinically free of hypertension, coronary artery disease, congestive heart failure and valve disease and were not taking antihypertensive or other cardiac medications. ECG tracings were analyzed by the IBM Bonner (V2) program. Mean values and correlations with age for PR duration, QRS duration and axis, S wave voltage V1 and R wave voltage V5 are presented. With advancing age in men there is a narrowing of QRS, a leftward QRS axis shift, and a loss of S V1 and R V5 amplitude. In women only a leftward QRS axis shift is associated with advancing age. These changes should be considered in defining normal age- and sex-specific reference values. These findings underscore theoretical limitations of commonly-used criteria for the ECG diagnosis of conditions such as left ventricular hypertrophy.

Adult↗

Purification and reconstitution of the bile acid transport system from hepatocyte sinusoidal plasma membranes.

The taurocholic acid transport system from hepatocyte sinusoidal plasma membranes has been studied using proteoliposome reconstitution procedures. Membrane proteins were initially solubilized in Triton X-100. Following detergent removal, the resultant proteins were incorporated into lipid vesicles prepared from soybean phospholipids (asolectin) using sonication and freeze-thaw procedures. The resultant proteoliposomes demonstrated Na+-dependent transport of taurocholic acid which could be inhibited by bile acids. Greatly reduced amounts of taurocholic acid were associated with the phospholipid or membrane proteins alone prior to proteoliposome formation. Membrane proteins were fractionated on an anionic glycocholate-Sepharose 4B affinity column which was prepared by coupling (3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholan-24-oyl)-N alpha-lysine to activated CH-Sepharose 4B via the epsilon-amino group of lysine resulting in the retention of a free carboxyl group. The adsorbed proteins enriched in components in the 54 kDa zone, which were originally identified by photoaffinity labeling to be components of the bile acid transport system, were also incorporated into liposomes. This vesicle system showed almost a 4-fold increase in Na+-dependent taurocholic acid uptake when compared to proteoliposomes formed from total membrane protein, as well as sensitivity to inhibition by bile acids. These results demonstrate that the bile acid carrier system can be reconstituted in proteoliposomes and that utilizing proteins in the 54 kDa zone leads to a significant enhancement in the transport capacity of the reconstituted system, consistent with the role of 54 kDa protein(s) as component(s) of the bile acid carrier system.

Animals↗

[Thoracic outlet syndrome. Value of non-invasive arterial studies].

The value of non-invasive clinical evaluation of arterial compression at thoracic outlet was evaluated in 150 normal subjects and in 103 patients operated upon (127 sides). The specificity of arm abduction manoeuvres was good for angles of 90 degrees or less. Their sensitivity was poor in forms with neurological symptoms and better in forms with vascular symptoms. In these two forms, their predictive value was excellent (congruent 90%) with angles of less than 90 degrees. Their negative predictive value was mediocre in forms with neurological symptoms. It is concluded that a positive response to manoeuvres at an angle of less than 90 degrees is a strong argument in favour of arterial compression in the thoracic outlet, but that a negative response should not rule out a diagnosis of thoracic outlet syndrome, especially when neurological symptoms are present.

Adolescent↗

Incidence of bovine leukemia virus-specific antibodies in West African cattle.

A sero-epidemiological survey of bovine leukemia virus (BLV) infection in indigenous West African cattle was undertaken using a radioimmunoassay and enzyme-linked immunosorbent assay. A high incidence of anti-BLV antibodies was found in the breeds tested and their crosses, whatever the test used. More extensive studies are needed to establish the prevalence of BLV infection in other parts of Africa; these may provide additional data on the similarities found between human and bovine leukemia viruses.

Africa, Western↗

Synthesis and in vitro properties of a powerful quaternary methylphosphonate inhibitor of acetylcholinesterase. A new marker in blood-brain barrier research.

To substantiate reported data and improve the properties of anticholinesterase drugs in blood-brain barrier (B-BB) research, 7-(methylethoxyphosphinyloxy) 1-methyl-quinolinium iodide (MEPQ) was prepared and evaluated as an inhibitor of both acetyl- and butyrylcholinesterase (AChE and BuChE, respectively) from various sources. The second-order rate constants for the inhibition of cholinesterase from eel, mice brain and horse serum at 25 degrees were found to be 5.3 X 10(8), 1.3 X 10(8) and 5.4 X 10(7) M-1 min-1 respectively. The inhibited enzyme could be reactivated by 1-methyl-2-hydroxy iminomethylpyridinium iodide (2-PAM). The two enantiomers of the racemic mixture MEPQ inhibited AChE at similar rates. Low concentrations of AChE could be determined by the residual enzyme activity and by fluorescence measurements of the leaving group, thus suggesting the application of MEPQ as a sensitive titrant of cholinesterase, as well as a potential tool in studying B-BB permeability changes.

Acetylcholinesterase↗