Fibrinogen: a possible link between social class and coronary heart disease.

Mortality from coronary heart disease in civil servants in the lowest grade of employment has been found to be about three times that of men in the highest grade of employment. As part of an investigation of this finding several haemostatic variables were measured in a sample of 29 men in lower grades of employment and 45 men in higher grades. There was a significant difference in plasma fibrinogen concentrations between men in lower grades of employment and those in higher grades (mean 3.39 g/l v 2.95 g/l, respectively; p less than 0.01) but not in other haemostatic variables. Multiple regression analyses showed significant independent associations of fibrinogen concentration with smoking (p less than 0.05) and grade of employment (p less than 0.05). The size of the observed difference between the grades of employment was similar to that between those dying of coronary heart disease or surviving during longitudinal study; it may therefore be an important part of the mechanism underlying social class differences in coronary heart disease. The statistical relation between fibrinogen concentrations and other characteristics that may be concerned in the aetiology of coronary heart disease was examined. A summary measure of job stress was significantly related to fibrinogen concentration (p less than 0.01) and made a substantial contribution to explaining the differences between grades of employment. Behaviour type and a score of physical activity were not significantly related to fibrinogen concentration.     

Pressor reactions to psychological stress and prediction of future blood pressure: data from the Whitehall II Study.

OBJECTIVE--To examine whether reactions of blood pressure to psychological stress predict future blood pressure. DESIGN--Blood pressure was recorded at a medical screening examination after which pressor reactions to a psychological stress task were determined. Follow up measurement of blood pressure was undertaken, on average, 4.9 years later. SETTING--20 civil service departments in London. SUBJECTS--1003 male civil servants aged between 35 and 55 years at entry to the study. MAIN OUTCOME MEASURE--Blood pressure at follow up screening. RESULTS--Reactions of systolic blood pressure to stress correlated positively with systolic blood pressure at follow up screening (r = 0.22, P < 0.01). The dominant correlate of follow up blood pressure was blood pressure at initial screening (r = 0.60; P < 0.01 between initial and follow up systolic blood pressure; r = 0.59, P < 0.01 between initial and follow up diastolic blood pressure). Stepwise multiple regression analysis indicated that reactions to the stressor provided minimal prediction of follow up blood pressure over and above that afforded by blood pressure at initial screening. In the case of follow up systolic blood pressure, systolic reactions to stress accounted for only 1% of follow up variance; systolic blood pressure at initial screening accounted for 34%. With regard to diastolic blood pressure at follow up, the independent contribution from diastolic reactions to stress was less than 1%. CONCLUSION--Pressor reactions to psychological stress provide minimal independent prediction of blood pressure at follow up. Measurement of reactivity is not a useful clinical index of the course of future blood pressure.     

Ecological analysis of collectivity of alcohol consumption in England: importance of average drinker.

OBJECTIVE: To assess whether the average consumption of alcohol is associated with the prevalence of heavy drinking, problem drinking, and abstention in England. DESIGN: Ecological analysis using data from a cross sectional household based survey of English adults. SUBJECTS: Random sample of 32,333 adults from the English population who participated in the 1993 and 1994 health surveys for England. MAIN OUTCOME MEASURES: Association, expressed as the correlation coefficient, between the regional mean and median alcohol consumption and the regional prevalence of heavy drinking, problem drinking, and abstention. RESULTS: Mean consumption of alcohol in light to moderate drinkers was strongly positively associated with the prevalence of heavy drinking (r = 0.75 in men and r = 0.62 in women for drinking more than 21 and 14 units per week respectively). A similar association was found between median consumption and prevalence of heavy drinking. Abstention was not significantly associated with mean consumption in drinkers (r = 0.08 for men and r = -0.29 for women). Both the median and mean consumption in drinkers were positively associated with the prevalence of problem drinking as defined by the CAGE questionnaire on alcohol use (r = 0.53 for men and r = 0.42 for women for the association with mean consumption). CONCLUSION: Factors that increase the average consumption of alcohol in the population may result in an increase in the prevalence of heavy drinking and related problems.     

Biological and computational evaluation of resveratrol inhibitors against Alzheimer’s disease

It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates β-secretase (BACE-1) expression and beta amyloid levels, thereby propagating oxidative stress and increasing neuronal injury. A series of resveratrol derivatives, known to be inhibitors of oxidative stress-induced neuronal cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous time-resolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory and BACE-1 inhibitory activity of resveratrol derivatives was statistically significant, supporting the notion that BACE-1 may act as pivotal mediator of neuronal cell oxytosis. Four of the biologically evaluated resveratrol analogs demonstrated considerably higher activity than resveratrol in either assay. The discovery of some “hits” led us to initiate detailed docking studies associated with Molecular Dynamics in order to provide a plausible explanation for the experimental results and understand their molecular basis of action.     

BMI, obesity, and sickness absence in the Whitehall II study

Objective: To study BMI and change in BMI from age 25 as predictors of sickness absence. Research Methods and Procedures: Data were collected from 2564 women and 5853 men, who were British civil servants (35 to 55 years) on entry to the Whitehall II study (Phase 1, 1985 to 1988). Employer's records provided annual medically certified (long, >7 days) and self‐certified (short, 1 to 7 days) spells of sickness absence. BMI at age 25 and Phase 1 were examined in relation to absences from Phase 1 to the end of 1998 (mean follow‐up, 7.0 years). Results: After adjustment for employment grade, health‐related behaviors, and health status, overweight (BMI = 25.0 to 29.9 kg/m²) and obesity (BMI > 30.0 kg/m²) at Phase 1 were significant predictors of short and long absences in both sexes; rate ratios (95% confidence intervals) ranged from 1.13 (1.05 to 1.21) to 1.51 (1.30 to 1.76) compared with a BMI of 21.0 to 22.9 kg/m². Additionally, a BMI of 23.0 to 24.9 kg/m² at Phase 1 predicted long absences in women, and underweight (BMI < 21.0 kg/m²) predicted short absences in men. Obesity at age 25 predicted long absences, and obesity at Phase 1 predicted short and long absences in both sexes. Chronic obesity was a particularly strong predictor of long absences in men, with a rate ratio of 2.61 (1.88 to 3.63). Discussion: Findings from this well‐characterized cohort suggest that the obesity epidemic in industrialized countries may result in significant increases in sickness absence. Further research is needed to determine the underlying mechanisms. Policy to reduce sickness absence needs to tackle the problem of excess weight in the working population.     

The tomato NBARC-LRR protein Prf interacts with Pto kinase in vivo to regulate specific plant immunity

Immunity in tomato (Solanum lycopersicum) to Pseudomonas syringae bacteria expressing the effector proteins AvrPto and AvrPtoB requires both Pto kinase and the NBARC-LRR (for nucleotide binding domain shared by Apaf-1, certain R gene products, and CED-4 fused to C-terminal leucine-rich repeats) protein Prf. Pto plays a direct role in effector recognition within the host cytoplasm, but the role of Prf is unknown. We show that Pto and Prf are coincident in the signal transduction pathway that controls ligand-independent signaling. Pto and Prf associate in a coregulatory interaction that requires Pto kinase activity and N-myristoylation for signaling. Pto interacts with a unique Prf N-terminal domain outside of the NBARC-LRR domain and resides in a high molecular weight recognition complex dependent on the presence of Prf. In this complex, both Pto and Prf contribute to specific recognition of AvrPtoB. The data suggest that the role of Pto is confined to the regulation of Prf and that the bacterial effectors have evolved to target this coregulatory molecular switch.     

Controlled trial of biofeedback-aided behavioural methods in reducing mild hypertension.

Employees of a large industry were screened for the presence of coronary risk factors. A total of 204 employees, aged 35-64 years, with two or more such factors (serum cholesterol concentration greater than or equal to 6.3 mmol/l (243.6 mg/100 ml), blood pressure greater than or equal to 140/90 mm Hg, and current cigarette consumption greater than or equal to 10 cigarettes a day) were randomly allocated to a biofeedback group receiving training in relaxation and management of stress or a control group. Both groups received simple health education literature. After eight weeks of training, and again eight months later, the biofeedback group showed a significantly greater fall in systolic and diastolic blood pressures than the control group (p less than 0.001). Plasma renin activity and plasma aldosterone concentration were measured in a subsample at entry to the study and again at eight weeks and eight months; both showed a greater reduction in the biofeedback compared with the control group at eight weeks'' follow-up. The greater reduction in blood pressure in the subjects in the biofeedback group compared with the control group (11.0 mm Hg systolic and 8.8 mm Hg diastolic), persisting eight months after the training, suggests that relaxation-based behavioural methods might be offered as a first-time treatment to patients with mild hypertension.     

Human cytotrophoblasts acquire aneuploidies as they differentiate to an invasive phenotype

Through an unusual differentiation process, human trophoblast progenitors (cytotrophoblasts) give rise to tumor-like cells that invade the uterus. By an unknown mechanism, invasive cytotrophoblasts exhibit permanent cell cycle withdrawal. Here, we report molecular cytogenetic data showing that approximately 20 to 60% of these interphase cells had acquired aneusomies involving chromosomes X, Y, or 16. The incidence positively correlated with gestational age and differentiation to an invasive phenotype. Scoring 12 chromosomes in flow-sorted cytotrophoblasts showed that more than 95% of the cells were hyperdiploid. Thus, aneuploidy appears to be an important component of normal placentation, perhaps limiting the proliferative and invasive potential of cytotrophoblasts within the uterus.