Effect of dietary fatty acids on gene expression in breast cells.
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Biomedical subjects
Publications and source records attributed to J Tillotson.
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OBJECTIVE: To determine the effects of increased sympathetic nervous system activity in humoral hypertension on the regulation of surface alpha 1 adrenoceptors and signal transduction, deoxycorticosterone acetate (DOCA) salt hypertension was induced in rats and the animals killed three weeks following the initiation of hypertension. METHODS: Experiments were performed on male Sprague-Dawley rats, weighing 250-300 g, divided into two groups: DOCA-salt (n = 75), and control (n = 60). Radioligand binding studies of the alpha 1 adrenoceptors, noradrenaline stimulated phosphoinositol turnover, ADP ribosylation of 41 kD substrate by pertussis toxin, and myocardial noradrenaline content were measured in the ventricular myocardium. The expression of sarcomeric actin isoforms was examined by northern blot and hybridisation with specific oligonucleotide probes. RESULTS: The density of alpha 1 adrenoceptors was decreased by 51% in DOCA-salt treated rats. However, noradrenaline stimulated phosphoinositol turnover in myocytes from DOCA-salt hearts was not diminished. The relative quantities of pertussis toxin labelled substrates did not differ in experimental and control hearts. Myocardial noradrenaline content was reduced by 60% in DOCA-salt hearts. Northern blots on RNA extracted from hypertrophic hearts of DOCA-salt treated rats showed an upregulation of alpha skeletal actin. CONCLUSIONS: The adrenergic state present in short term DOCA-salt hypertensive hypertrophy is characterised by enhanced signal transduction via the alpha 1 adrenoceptors and the re-expression of alpha skeletal actin in enlarging myocytes.
To determine the effects of myocardial infarction-induced left ventricular failure on the regulation of surface alpha-1 adrenoreceptors and signal transduction, large infarcts were produced in rats and the animals killed seven days later. After the documentation of impaired left ventricular pump performance, radioligand binding studies of the alpha-1 adrenoreceptor, norepinephrine-stimulated phosphoinositol turnover, and ADP ribosylation of 41 kD substrate by pertussis toxin were examined in the hypertrophying unaffected myocardium. Moreover, the expression of sarcomeric actin isoforms was analyzed by Northern blots and hybridization with specific oligonucleotide probes. Alpha-1 adrenoreceptor density was found not to be altered in membranes obtained from the spared left ventricular tissue, whereas phosphoinositol turnover was increased 3.1-fold in the viable myocytes of infarcted hearts. Furthermore, pertussis toxin substrate was augmented 2.5-fold in membranes prepared from the surviving left ventricular myocardium. Finally, an upregulation of the skeletal actin isoform was detected in the tissue of the failing left ventricle. In conclusion, the possibility is raised that in the presence of severe myocardial dysfunction and ongoing reactive hypertrophy, effector pathways linked to the alpha-1 adrenoreceptor may stimulate the myocyte hypertrophic response which would tend to normalize cardiac hemodynamics. The reexpression of alpha skeletal actin may be a molecular indicator of the persistance of an overload on the myocardium.
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Nutrient intake was determined in over 8000 men of Japanese ancestry residing on the island of Oahu. Nutrient determination took place at the initial examination during the years 1965-1968. This report relates nutrient intake to the risk of developing coronary heart disease in the 10 years subsequent to the initial examination. Men who developed coronary heart disease had a lower average intake of calories, carbohydrates, starch, and vegetable protein than men who remained free of coronary heart disease. Men who developed coronary heart disease also had a higher mean intake of percentage of calories from protein, fat, saturated fatty acids, and polyunsaturated fatty acids than men who remained free of coronary heart disease. These men also had a significantly lower mean percentage of calories from carbohydrates and a higher mean ingestion of cholesterol per 1000 calories than men who remained free of coronary heart disease. In multivariate analyses including age, systolic blood pressure, serum cholesterol, cigarettes smoked per day, and physical activity index, carbohydrates, vegetable protein, percentage of calories from saturated fatty acids, and percentage of calories from polyunsaturated fatty acids are no longer significantly related to incidence.
Within-person variability of nutrient intake is examined using data on 7 consecutive days for 329 men. The variability of nutrient intake within persons differs for the nutrients examined. Some nutrients, such as starch, have small within-person components of variance and are therefore highly reliable even using a single 24-h recall. Others, such a polyunsaturated fatty acids, have large within-person components of variance and are thus less reliable. Within-person variability affects the power of a study to detect differences in nutrient intake between groups and also affects the magnitude of calculated correlation coefficients. For the least reliable nutrient it is estimated that the correlation would be attenuated to two-thirds its true size. Eating patterns in the cohort appear to be nonrandom. Using this nonrandomness of nutrient intake it may be possible to reduce the within-person component of variance using less recalls than is suggested if random eating patterns are assumed.
Baseline 24-hour dietary recalls from 16,349 men ages 45-64 years who had no evidence of coronary heart disease (CHD) were obtained in three prospective studies: the Framingham Study (859 men), the Honolulu Heart Study (7272 men) and the Puerto Rico Heart Health Program (8218 men). These men were followed for up to 6 years for the first appearance of CHD or death. Men who had a greater caloric intake or a greater caloric intake per kilogram of body weight were less likely to develop CHD manifest as myocardial infarction (MI) or CHD death, even though men of greater weight were more likely to develop CHD. This may reflect the benefit of greater physical activity. Men who consumed more alcohol were less likely to develop CHD, but more likely to die of causes other than CHD, particularly in the Honolulu study. In the Honolulu and Puerto Rico studies, but not in the Framingham study, men who consumed more starch were less likely to develop MI or CHD death. There was an inverse relation between starch intake and serum cholesterol, but it was too weak to explain fully the inverse starch-CHD association. There was also no evidence that the inverse relation between starch intake and incidence of CHD in the Honolulu and Puerto Rico studies was an indirect result of differences in fat intake. While the findings suggest additional areas for research, none of them would lead to an alteration of currently recommended preventive diets that emphasize lowering fat intake, because in isocaloric diets the logical way to balance a decreased fat intake is to increase the consumption of foods containing starch.
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A study of base-line nutrient intakes of 8218 urban and rural Puerto Rican man aged 45 to 64 years was undertaken in relation to subsequent six year coronary heart disease (CHD) incidence. Urban dietary intakes were significantly higher in total fat and lower in carbohydrate, particularly starch. Average cholesterol intakes were 83 mg/day higher in urban than rural men. Urban serum cholesterol values were significantly higher than rural values. Urban men who developed myocardial infarction or CHD death had significantly lower calorie and carbohydrate intakes i.e., chiefly those derived from rice and legumes. The same association was found in the rural group but failed to reach statistical significance. A very low intake of alcohol was noted in the 73 rural CHD cases. Dietary sucrose intake showed no relationship to CHD incidence. Multivariate analysis, taking relative weight, hematocrit, blood pressure, serum cholesterol, alcohol intake, cigarette smoking, area, and age into account, demonstrated an independent inverse relation of carbohydrate intake from legumes to CHD incidence. The apparent protective effect of complex carbohydrate merits further investigation.
A standardized system for the collection and processing of dietary information in large-scale studies is described. Components of the system include interviewer and coder training, certification and continuing education, automated procedures for identifying and quantitating fat, guides for classifying and quantitating foods, system maintenance and quality control procedures, and a food table containing about 800 food items and 450 recipe items. The system is flexible enough to respond to market changes in formulation. Unique automated features make the system particularly useful in identifying and quantitating different dietary fats. These features could be modified to meet nutritional demands of other studies.
The relationship of dietary intakes to subsequent development of coronary heart disease (CHD) during a 6-year follow-up period was investigated in 7705 men of Japanese ancestry, ages 45 to 68 and living in Hawaii. Data on the intakes of calories and nutrients were obtained by 24-hr diet recall interviews at the base-line examination. An index for ingestion of traditional Japanese diet (Japanese diet score) was also calculated for each man. The men who subsequently developed myocardial infarction or died of CHD generally ate less than those who remained free of CHD, with statistically significant differences for total calories, total carbohydrate, complex carbohydrate or starch, simple carbohydrate other than sucrose, vegetable protein, alcohol, and Japanese diet score. However, when other major risk factors for CHD were taken into account, the negative association with CHD remained statistically significant only for alcohol and, to a lesser extent, total carbohydrate intakes. The lower total caloric intakes in CHD cases, largely due to decreased alcohol and carbohydrate intakes, could not be accounted for by either under-reporting of food consumption among obese men or diminished physical activity in CHD cases.
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Dietary intake information was collected on 2,426 rural and 5,828 urban men free of coronary heart disease in the Pureto Rico Heart Health Program. Serum cholesterol and triglyceride, body weights, and related parameters were measured during a detailed cardiovascular examination. There were statistically significant differences between rural and urban values with respect to lipids, relative weight, and intake of many nutrients. Rural subjects had lower lipids and relative weights. Serum cholesterol was associated with relative weight in both rural and urban areas. In the urban areas, serum cholesterol was associated with intake of total fat, saturated fatty acids, polyunsaturated fatty acids, total carbohydrate, and starch (all measured as percent of calories). It was also related to percent carbohydrate from starch and dietary cholesterol intake, even after relative weight was taken into account. The associations were of a low order, although statistically significant. The association of fasting triglycerides with some of the carbohydrate variables was statistically significant after relative weight was taken into account in the urban area. Overall, diet and relative weight can account for at most 6% of the variability in serum cholesterol observed, with at most 2.5% of the variability due diet alone.
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