HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells.

The highly invasive behavior of glioblastoma cells contributes to the morbidity and mortality associated with these tumors. The integrin-mediated adhesion and migration of glioblastoma cells on brain matrix proteins is enhanced by stimulation with growth factors, including platelet-derived growth factor (PDGF). As focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, has been shown to promote cell migration in various other cell types, we analysed its role in glioblastoma cell migration. Forced overexpression of FAK in serum-starved glioblastoma cells plated on recombinant (rec)-osteopontin resulted in a twofold enhancement of basal migration and a ninefold enhancement of PDGF-BB-stimulated migration. Both expression of mutant FAK(397F) and the downregulation of FAK with small interfering (si) RNA inhibited basal and PDGF-stimulated migration. FAK overexpression and PDGF stimulation was found to increase the phosphorylation of the Crk-associated substrate (CAS) family member human enhancer of filamentation 1 (HEF1), but not p130CAS or Src-interacting protein (Sin)/Efs, although the levels of expression of these proteins was similar. Moreover downregulation of HEF1 with siRNA, but not p130CAS, inhibited basal and PDGF-stimulated migration. The phosphorylated HEF1 colocalized with vinculin and was associated almost exclusively with 0.1% Triton X-100 insoluble material, consistent with its signaling at focal adhesions. FAK overexpression promoted invasion through normal brain homogenate and siHEF1 inhibited this invasion. Results presented here suggest that HEF1 acts as a necessary and specific downstream effector of FAK in the invasive behavior of glioblastoma cells and may be an effective target for treatment of these tumors.

A cross-sectional study of dietary patterns with glucose intolerance and other features of the metabolic syndrome.

Previous epidemiological studies have demonstrated relationships between individual nutrients and glucose intolerance and type 2 diabetes, but the association with the overall pattern of dietary intake has not previously been described. In order to characterize this association, 802 subjects aged 40-65 years were randomly selected from a population-based sampling frame and underwent a 75 g oral glucose-tolerance test. Principal component analysis was used to identify four dietary patterns explaining 31.7% of the dietary variation in the study cohort. These dietary patterns were associated with other lifestyle factors including socio-economic group, smoking, alcohol intake and physical activity. Component 1 was characterized by a healthy balanced diet with a frequent intake of raw and salad vegetables, fruits in both summer and winter, fish, pasta and rice and low intake of fried foods, sausages, fried fish, and potatoes. This component was negatively correlated with central obesity, fasting plasma glucose, 120 min non-esterified fatty acid and triacylglycerol, and positively correlated with HDL-cholesterol. It therefore appears to be protective for the metabolic syndrome. Component 1 was negatively associated with the risk of having undiagnosed diabetes, and this association was independent of age, sex, smoking and obesity. The findings support the hypothesis that dietary patterns are associated with other lifestyle factors and with glucose intolerance and other features of the metabolic syndrome. The results provide further evidence for the recommendation of a healthy balanced diet as one of the main components of chronic disease prevention.

Seasonal consumption of salad vegetables and fresh fruit in relation to the development of cardiovascular disease and cancer.

OBJECTIVE: To investigate the protective association between seasonality of consumption of fresh fruit or salad vegetables and cancer and cardiovascular disease (CVD) development. DESIGN AND SETTING: Face-to-face interviews, including a food frequency questionnaire, were conducted on 1489 men and 1900 women, aged 35-75 years, who were respondents in the British Health and Lifestyle Survey 1984/85 (HALS1). CVD and cancer morbidity and mortality were determined from the 1991/92 British Health and Lifestyle Survey (HALS2) and by NHS Register 'flagging'. RESULTS: Risk was assessed by odds ratio (OR) for trend per frequency category. In men, frequent winter salad vegetable consumption was more closely protective than that in summer for cancer (winter OR=0.79 [0.62-0.99], P=0.045, summer OR=0.83 [0.69-1.01], NS) and CVD (winter OR=0.85 [0.72-1.00], P=0.049, summer OR=0.95 [0.82-1.10], NS). Fresh fruit consumption showed no significant protection. In women, frequent salad vegetable consumption at any season was significantly protective of CVD (winter OR=0.76 [0.65-0.89], P<0.001, summer OR=0.76 [0.65-0.89], P<0.001), although not of cancer. Frequent fresh fruit consumption in women was significantly protective of CVD (winter OR=0.84 [0.74-0.94], P=0.004, summer OR=0.85 [0.74-0.97], P=0.014) but not quite significant, and only in winter, for cancer (winter OR=0.87 [0.76-1.00], P=0.052, summer OR=0.88 [0.75-1.02], P=0.097). Maintenance of salad vegetable consumption from summer to winter, to within one frequency category, was associated with further protection for cancer in men (P=0.050) and CVD in women (P=0.024). CONCLUSIONS: Diets high in fresh fruit and salad vegetables appear protective against cancer and CVD. It is important to take into account the seasonality of consumption in estimating and establishing significance of risk.

Frequent salad vegetable consumption is associated with a reduction in the risk of diabetes mellitus.

This cross-sectional study was undertaken to investigate the association between the reported frequency of consumption of vegetables and fruits, the choice of staple carbohydrate, and glucose intolerance. One thousand one hundred twenty-two subjects aged 40-64 years in a population-based study underwent an oral glucose tolerance test, and their food consumption was assessed using a food-frequency questionnaire. The crude prevalence of undiagnosed non-insulin-dependent diabetes mellitus (NIDDM) was 4.5%, and that of impaired glucose tolerance (IGT) 16.8%. The age-standardized prevalence rates were 2.3 and 11.2%, respectively. Frequent consumption of vegetables throughout the year was inversely associated with the risk of having NIDDM (odds ratio [OR] = 0.16; 95% confidence interval [CI] = 0.04-0.69). This association was maintained after adjustment for age, gender, and family history. Vegetable consumption during the summer months had a much weaker inverse association with the risk of having NIDDM that failed to reach statistical significance. A nonsignificant inverse association between frequent consumption of fruits and NIDDM was observed. Frequent self-reported pasta and rice consumption was associated with a reduction in the risk of having IGT and NIDDM. (OR = 0.62, 95% CI = 0.44-0.87, and OR = 0.51, 95% CI = 0.27-0.99, respectively) but this relationship was not independent of age. Whether these associations reflect specific effects of particular nutrients or are a reflection of the patterning of lifestyle factors remains to be determined.

The development of cardiovascular disease in relation to anthropometric indices and hypertension in British adults.

OBJECTIVE: To examine the predictive ability of simple anthropometric indices for the development of cardiovascular disease (CVD) over seven years in British adults, and the influence of hypertension on these associations. DESIGN: Longitudinal study of the development of CVD (morbidity or mortality) over a seven year period in a random stratified sample of British adults who were respondents in the 1984-1985 Health and Lifestyle Survey (HALS1) and who were seen again in 1991-1992 (HALS2) or who had died by then. METHODS: Face-to-face interviews at HALS1 and HALS2 recorded socio-demographic, health and lifestyle details followed by measurements of height, weight, waist circumference and blood pressure (BP). The quintiles of body mass index (BMI), waist circumference, waist: height ratio (WHTR) and height were calculated for those aged between 35 and 75 y, at HALS1. Dates and causes of death were recorded. Logistic regression was used to estimate the odds ratios (OR) of developing CVD in 1284 men and 1570 women, aged 35-75 y who were free of known CVD, cancer and diabetes at HALS1. RESULTS: By HALS2, 316 respondents in the qualifying population had developed CVD, 114 of whom were dead. There were linear trends in the development of CVD (adjusted for age and smoking) for all the men from the lowest to the highest quintile of WHTR (P = 0.034), but not for waist circumference (P = 0.095), or BMI (P > 0.2). Excluding the hypertensive men increased the significance of the trend for WHTR (P = 0.005) and waist circumference (P = 0.027). The significant interactions with hypertension for WHTR (P < 0.001), waist circumference (P = 0.006) and BMI (P = 0.044) showed that there was an increasing incidence of CVD with increasing adiposity in non-hypertensive men but, in men with treated hypertension, although the overall incidence of CVD was higher, the relationship with adiposity was inverse. In the women, there were no significant linear trends for waist circumference, WHTR or BMI. Quintile estimates were more consistent with J-shaped curves with the lowest risk in the second quintile. Excluding the hypertensive women, increased the significance of these trends. In normotensive women, there was a significant quadratic trend (P = 0.039) for the association between the incidence of CVD and the quintiles of waist circumference, but no associations for WHTR or BMI. For waist circumference there was weak evidence of an interaction with hypertension (P = 0.053). CONCLUSIONS: For the men, indices involving waist circumference, particularly WHTR, had stronger linear associations with the log odds of CVD development than BMI. The interactions with hypertension were significant for WHTR, waist circumference and also BMI. In women, none of the indices was linearly associated with the log odds of CVD development, but there was a significant J-shaped curve for waist circumference and evidence of an interaction with hypertension. These results suggest that studies in which hypertensives are included, but in which possible hypertension interactions are overlooked, important hypertensive-specific associations between anthropometric indices and CVD development may be masked. Men on anti-hypertensive medication with the lowest central adiposity, experienced higher short-term CVD risk than those with greater central adiposity.

Association of anthropometric indices with elevated blood pressure in British adults.

OBJECTIVE: To investigate which of six anthropometric indices was most strongly associated with elevated blood pressure and frank hypertension in a representative population sample of young and middle-aged British adults. SUBJECTS: A representative random sample of British adults (2712 men and 3279 women) aged between 18 and 64y, who were resident in England, Scotland and Wales, were studied in the 1984-85 Health and Lifestyle Survey. MEASUREMENTS: Following an interview where demographic, health and lifestyle details were recorded, measurements of height, weight and waist and hip circumference were made by a nurse at a home visit, where blood pressure and medication to control blood pressure were also recorded. BMI and the ratios of waist circumference to height (WHTR) and waist circumference to hip (WHR) were calculated. Respondents with a blood pressure above 140 mm Hg (systolic) and/or 90 mm Hg (diastolic) or who were being treated for hypertension were classified as having elevated blood pressure. RESULTS: For men and women aged 18-39 and 40-64 y the prevalence of elevated blood pressure increased across the quintiles of BMI, weight, waist, WHTR and WHR was P < 0.001 for each, with waist and WHTR having the highest odds ratios. Waist and height adjusted for each other were independently related to the prevalence of elevated blood pressure in 40-64 y old men and women. Height, on its own, was inversely related (P < 0.05) only in the 40-64 y old men. The age adjusted partial correlations between systolic and diastolic blood pressure measurements and the measurements of BMI, weight, waist, WHTR and WHR were close and significant, P < 0.001 for each. The ranking and significance of the correlations were hardly affected by excluding the treated hypertensives. CONCLUSIONS: The prevalence of elevated blood pressure was associated with quintiles of BMI, waist, WHTR, WHR and weight, with WHTR and WHR having the highest odds ratios. Waist and height were independently related to the prevalence of elevated blood pressure.

Associations between off-label feed additives and farm size, veterinary consultant use, and animal age.

Data from the United States National Swine Survey collected by the National Animal Health Monitoring System were used to describe the use of feed additives in swine feeds. Data were collected from 710 farms. The concentration of feed additives expressed in grams per ton of complete feed was described by stage of production, and the use of feed additives above the labeled treatment levels (i.e. off-label) was identified. Of the 3328 feeds, about 79% contained feed additives used in the labeled manner. For all classes of pigs, the prevalence of labeled feed additive use was greater than 75%. Penicillin was used according to its label most often, followed by apramycin, bacitracin, tetracyclines, lincomycin, and tylosin. Carbadox had the highest prevalence of off-label use. Of the 699 feeds that included feed additives in an off-label manner, about 57% included additives at greater than the recommended concentrations or were fed to an incorrect class of pig. About 56% of the feeds had off-label combinations of additives. Small farms were more likely to use rations with no feed additives than intermediate or large farms (P < 0.001). Of those farms using feed additives, the odds of a small farm using all feed additives in the labeled manner was 7.7 times that of an intermediate or large farm (P < 0.0001). After controlling for herd size, producers who used a veterinary consultant were 2.1 times more likely to use feeds with feed additives (P < 0.0001).

Effect of ankle orthoses on functional performance for individuals with recurrent lateral ankle sprains.

Ankle orthoses are commonly used for protection against initial ankle sprain injuries and for protection against reinjury. The purpose of this study was to compare the effects of the DonJoy Ankle Ligament Protector (ALP) and the Aircast Sport-Stirrup (AS) on the functional performance tasks of a 40-meter sprint, a figure-of-eight run, and standing vertical jump. Subjects were 14 males and nine females who reported a history of two or more lateral ankle sprains of the same ankle and no sprains of the contralateral ankle. Each subject performed all functional tasks on the first test day with both ankles unbraced and with the recurrently sprained ankle braced with one of the two orthoses. Each subject returned for testing on a second day and performed all tasks with both ankles unbraced and with the other orthosis on the recurrently sprained ankle. Subjects also rated the orthoses for comfort and support. Analysis of variance indicated that braced data were not significantly different than unbraced data and that data for the two orthoses did not differ significantly for any of the functional performance tasks. Seventy-four percent of the subjects reported the AS was more comfortable than the ALP, and 61% of the subjects indicated that the AS provided more support than the ALP. Neither orthosis had an effect on functional performance. The results may assist clinicians in selecting either of these orthoses for use in protection against ankle sprain injury.

Longitudinal dietary changes between 1984-5 and 1991-2 in British adults: association with socio-demographic, lifestyle and health factors.

The study aimed to examine dietary changes and their associations with demographic, lifestyle and health variables in a random sample of British adults. The Health and Lifestyle Survey of 1984-5 (HALS1) identified four main dietary components by principal component analysis from food frequency data. Comparison of the HALS1 dietary component scores with those of the follow-up survey of 1991-2 (HALS2) for the same individuals revealed increases on component 1 (high weightings for fresh fruit, salads, 'brown' bread, fruit juice and green vegetables but low weightings for chips, fried food and processed meat). There were substantial decreases on component 2 (high weightings for puddings/pies, cake, potatoes, biscuits, preserves, pulses and meat), small increase on component 3 (high weightings for crisps, soft drinks and chips) and increases on component 4 (high weightings for confectionery, biscuits and cake and low weightings for vegetables of all kinds). Except for women on component 3 the changes were all significant, P < 0.001. Unadjusted score changes were smallest in elderly respondents for all components. Differences in score changes between groups were based on an analysis of covariance adjusting for the HALS1 score. On component 1 the largest score increases were associated with non-manual groups, improvements in lifestyle and good health. For component 2 the greatest changes in score were associated with changes in household size, smoking habit and heavy drinking. Score increases on component 3 were also associated with heavy drinking, whilst the largest rises on component 4 were amongst the non-manual, the non-drinkers and the non-smokers and, for women only, those who had few malaise symptoms or who lived in Scotland. The results show that there have been overall dietary changes and that changes have been associated with longitudinal alterations in socio-demographic, lifestyle and health circumstances.

Cigarette smoking is not associated with hyperinsulinemia: evidence against a causal relationship between smoking and insulin resistance.

Previous reports of a relationship between cigarette smoking and hyperinsulinemia and insulin resistance provide an important possible mechanism by which smoking could be associated with the metabolic cardiovascular syndrome and hence with ischemic heart disease. However, few previous studies have been able to adjust for all the possible confounding factors related both to smoking and to insulin resistance. Therefore, we examined this association in a population-based cohort study of 1,122 individuals aged 40 to 65 years who underwent a 75-g oral glucose tolerance test with specific measurement of insulin, 32,33-split proinsulin, and intact proinsulin concentrations. Physical activity was quantified using the Paffenbarger questionnaire, and smoking status and alcohol consumption were determined using the Health and Lifestyle Survey questionnaire; 17.4% of the population were current smokers and 32.4% were ex-smokers. Current smoking was associated with reduced overall obesity as indicated by the body mass index (BMI) but an increase in central adiposity as measured by the waist to hip ratio (WHR). There were also significant associations between cigarette smoking and the pattern of alcohol intake and physical inactivity. In unadjusted analyses, current smoking was associated with lower fasting and 120-minute insulin and also 120-minute glucose compared with levels in nonsmokers. Adjustment for confounding by age and BMI reduced these differences, but they were increased by adjustment for central obesity. We conclude from this study that a causal relationship between cigarette smoking and insulin resistance is unlikely.

Effects of temporally varied biased and unbiased story summaries on the suggestibility of preschoolers.

Preschool children's resistance to the influence of postevent misinformation was investigated. Ninety-one preschoolers (3 years 6 months to 5 years 6 months old) were read a story about a boy's birthday party. One week later, they received 1 of 3 summary conditions containing general information (unbiased, biased, or no summary). Two weeks after the original story, they were presented with either a biased summary or no summary. The children's suggestibility was assessed by a recognition test that provided a choice between the original and postevent misinformation. Those who received an unbiased summary showed higher recognition rates than those who received a biased summary, regardless of whether the biased information had been given at the 1- or 2-week interval. Although an unbiased summary followed by biased information did not produce greater recognition rates that were found in the control group, participants who received unbiased summaries did perform above chance, suggesting that even a vague summary may help to reactivate specific memory traces, particularly when information is bimodally presented.

Undiagnosed glucose intolerance in the community: the Isle of Ely Diabetes Project.

The Isle of Ely Diabetes Project is a prospective population-based study of the aetiology and pathogenesis of Type 2 diabetes mellitus. Between 1990 and 1992, 1156 subjects aged between 40 and 65 years underwent a standard 75 g oral glucose tolerance test (OGTT). A total of 1122 individuals who were not known to have diabetes completed the test and were classified according to WHO criteria; 51 subjects (4.5%) had previously undiagnosed diabetes and 188 (16.7%) had impaired glucose tolerance. The subjects with newly diagnosed glucose intolerance were significantly older, more obese, and shorter than those with normal glucose tolerance. Blood pressure, cholesterol, triglyceride, and LDL-cholesterol concentrations were elevated and HDL-cholesterol levels were lower among those with abnormal rather than normal glucose tolerance. In multiple regression analyses stratified by gender and including age, body mass index, and the waist-hip ratio as covariates, there were significant differences between those with normal and abnormal glucose intolerance in blood pressure, triglyceride, and HDL-cholesterol, but not total or LDL-cholesterol. In both male and female subjects, height had a significant independent negative association with the plasma glucose at 120 min after administration of oral glucose (standardized beta coefficient = -0.12, p < 0.01).

Children's use of mnemonic strategies: variability in response to metamemory training.

In this study, 8- to 12-year-old children were tested to determine their level of use of a strategy for organizing lists of low-associated words into semantic groups. Then, on the basis of their scores in the strategy tests, the children were placed in either a strategic or nonstrategic group. The groups were divided into a sort-instruction training condition, in which they were told to group words so that they "go together" in some way, and a metamemory training condition, in which these instructions were supplemented by feedback, strategy reminders, and opportunities to self-test. One week later, each child's strategy use was reassessed. Children in the strategic group sorted semantically throughout training and transfer, and they showed high recall, regardless of condition. Children in the nonstrategic group showed high strategy use and recall during training, but they showed significantly more variability in recall than did the children in the strategic group. Children in the nonstrategic-metamemory condition who benefited from training were also more likely to transfer the use of the strategy than were children trained in the sort-instruction condition.

Ventilatory function and winter fresh fruit consumption in a random sample of British adults.

The relation between ventilatory function and the reported frequency of consumption of fresh fruit and fruit juice was studied among 1502 lifelong non-smokers and 1357 current smokers aged 18-69 with no history of chronic respiratory disease. Forced expiratory volume in one second (FEV1) was assessed by turbine spirometry. As winter fruit consumption was more widely dispersed than summer consumption and few subjects ate fruit more frequently in the winter, winter fruit consumption was taken as an indicator of habitual (year round) consumption. After adjustment for sex, age, height, cigarette consumption, region of residence, and household socioeconomic group, FEV1 was associated with winter fruit consumption. The mean adjusted FEV1 among those who never drank fresh fruit juice and ate fresh fruit less than once a week during the winter was 78 ml lower (95% confidence interval 24-132 ml) than the mean for the other subjects. A similar difference was found in all age-sex groups and among both current smokers and lifelong non-smokers. Antioxidant and other actions of vitamin C may protect against pulmonary emphysema, or reduce bronchoconstrictor responses to environmental pollutants.

Height and glucose tolerance in adult subjects.

In a prospective study concerning the pathogenesis of impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus, 346 subjects with no clinical history of diabetes were given a standard 75 g oral glucose tolerance test. The expected positive associations between 120-min plasma glucose concentration and age and body mass index were observed in both sexes and between 120-min plasma glucose and waist/hip ratio in male subjects. An unexpected negative correlation was found between 120-min plasma glucose and height in both sexes (r = -0.23, (95% confidence interval, -0.38 - -0.07) p less than 0.007 for male subjects and r = -0.24, (-0.37 - -0.11) p less than 0.006 for female subjects). These negative associations with height remained significant after controlling for age and body mass index in male subjects but not in female subjects. In the latter a highly significant negative relationship of height with age was recorded (r = -0.33, (-0.45 - -0.20) p less than 0.0001). Comparison between individuals with impaired glucose tolerance and control subjects matched for sex, age and body mass index showed that subjects with impaired glucose tolerance are significantly shorter. Mean (+/- SEM) height in the male subjects with impaired glucose tolerance (n = 29) was 173.4 +/- 1.1 cm vs 176.9 +/- 1.3 cm in control subjects, p = 0.02. In the female subjects (n = 39) mean (+/- SEM) height was 159.4 +/- 1.0 cm vs 162.4 +/- 1.0 cm in control subjects, p = 0.02. The negative relationship between height and glucose tolerance is a new epidemiological observation which has not been previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Some regional variations in dietary patterns in a random sample of British adults.

Comparison was made of the reported frequency of consumption or choice of 30 food items by 8860 adults in the 11 standard regions of Great Britain, with the use of log-linear analysis to allow for the age, sex, social class and smoking habit variations between the regions. The South-East was taken as the base region against which the others were compared. The number of food items for which there were significant differences from the South-East were Scotland 23, North 25, North-West and Yorkshire/Humberside 20, Wales 19, West Midlands 15, East Midlands 10, East Anglia 8, South-West 7 and Greater London 9. Overall the findings confirm a North/South trend in relation to eating habits, even when demographic and smoking-habit variations are taken into account, with the frequent consumption of many fruit and vegetable products being much less common and of several high-fat foods (chips, processed meats and fried food) more common in Scotland, Wales and the northern part of England. In most regions there was a significantly lower frequency of consumption of fresh fruit, fruit juice, 'brown' bread, pasta/rice, poultry, skimmed/semi-skimmed milk, light desserts and nuts, and a higher consumption of red meat, fish and fried food than in the South-East.