Serum cholesterol and long-term death rates from suicide, accidents, or violence. Seven Countries Study Group.
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Biomedical subjects
Publications and source records attributed to A Keys.
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There is significant variation in metabolic rate in humans, independent of differences in body size, body composition, age, and gender. Although it has been generally held that the normal human "set-point" body temperature is 37 degrees C, these interindividual variations in metabolic rate also suggest possible variations in body temperature. To examine the possibility of correlations between metabolic rate and body temperature, triplicate measurements of oral temperatures were made before and after measurement of 24-h energy expenditure in a respiratory chamber in 23 Pima Indian men. Fasting oral temperatures varied more between individuals than can be attributed to methodological errors or intraindividual variation. Oral temperatures correlated with sleeping (r = 0.80, P < 0.0001), and 24-h (r = 0.48, P < 0.02) metabolic rates adjusted for differences in body size, body composition, and age. Similarly, in the 32 Caucasian men of the Minnesota Semi-Starvation Study, oral temperature correlated with adjusted metabolic rate, and the interindividual differences in body temperature were maintained throughout semistarvation and refeeding. These results suggest that a low body temperature and a low metabolic rate might be two signs of an obesity-prone syndrome in humans.
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From over forty independently isolated potato lines transformed with wild-type and promoter-mutated T-cyt genes, a number of lines were selected for examination of phenotypic changes in growth and development for plants grown in soil in a controlled environment. The three lines chosen for most detailed examination showed a wide spectrum of phenotypic changes. In comparisons with control potato cv. Désirée, the plants of one line had a two- to three-fold increase in biomass production during early vegetative growth, advanced senescence and a shortened plant life-span. Another line showed abnormal cellulytic senescence. In two lines there were increases in tuber numbers and more skewed tuber size distributions which correlated with reduced shoot apical dominance and shortened dormancy of the stored tubers. None of the lines showed altered timing of onset of tuberization or flowering, although tuberization was consistently delayed when expressed as a function of increasing total plant weight. A hypothesis is proposed to explain the diverse phenotypes which postulates that (1) T-cyt transformation causes enhanced sensitivity to cytokinins in specific types of shoot cells which are already targets for regulation by normal root-derived cytokinins; (2) two distinct types of shoot target cells are present, one in shoot meristems and one in leaves; (3) the two types can acquire enhanced sensitivity, either separately or in combination depending on the particular T-cyt transformation event. The scope for using the transformed plants in subsequent physiological, biochemical and molecular studies, aimed at examining the molecular basis of the model or selected consequences of T-cyt transformation in altering regulation of potato plant growth and development, is discussed. The attention is drawn to the possible involvement at the subcellular level of sucrose phosphate synthase in mediating the phenotypic effects caused by T-cyt transformation.
STUDY OBJECTIVE: The aims were (1) to compare all cause mortality in population samples of different cultures; and (2) to cross predict fatal event by risk functions involving risk factors usually measured in cardiovascular epidemiology. DESIGN: The study was a 25 year prospective cohort study. The prediction of all cause mortality was made using the multiple logistic equation as a function of 12 risk factors; the prediction of months lived after entry examination was made by the multiple linear regression using the same factors. POPULATION SAMPLES: There were five cohorts of men aged 40-59 years, from Finland (two cohorts, 1677 men), from The Netherlands (one cohort, 878 men), and from Italy (two cohorts, 1712 men). SETTING: The Finnish cohorts came from geographically defined rural areas, the Dutch cohort from a small town in central Holland, and the Italian cohorts from rural villages in northern and central Italy. MEASUREMENTS AND MAIN RESULTS: All cause mortality was highest in Finland (557 per 1000), and lower in The Netherlands (477) and in Italy (475). The solutions of the multiple logistic function showed the significant and almost universal predictive role of certain factors, with rare exceptions. These were age, blood pressure, cigarette smoking, and arm circumference (the latter with a negative relationship). Similar results were obtained when solving a multiple linear regression equation predicting the number of months lived after entry examination as a function of the same factors. The prediction of fatal events in each country, using the risk functions of the others, produced limited errors, the smallest one being -2% and the largest +11%. When solving the logistic model in the pool of all the cohorts with the addition of dummy variables for the identification of nationality, it also appeared that only a small part of the mortality differences between countries is not explained by 12 available risk factors. CONCLUSIONS: A small set of risk factors seems to explain the intercohort differences of 25 year all cause mortality in population samples of three rather different cultures.
Twelve cohorts of men aged 40-59 at entry, enrolled in six countries (Finland, The Netherlands, Italy, Yugoslavia, Greece and Japan), giving a total of 8,287 subjects, were examined for the measurement of cardiovascular risk factors and then followed-up for 20 years. Changes of systolic blood pressure (SBP) occurred over the first 10 years in 6,767 men and these values, computed by an integral-like procedure (Delta-SBP), were used as possible predictors of fatal events recorded in the second 10 years of follow-up. Men who had a relative increase of SBP in the first 10 years showed an excess risk of death as compared with those who had a relative decrease of SBP, after adjustment for age and entry levels of SBP. Such relative risks were greater than 1 in the cohorts pooled within each of the six countries, ranging from 1.07 to 1.79 for all causes of death and from 1.12 to 2.15 for atherosclerotic cardiovascular disease deaths (coronary, stroke and peripheral atherosclerotic disease). The Cox model was solved using the same two end-points as dependent variables and, as coviariates, six risk factors measured at entry examination (age, cigarettes smoked per day, body mass index, serum cholesterol, physical activity at work and systolic blood pressure). By adding Delta-SBP the predictive power of the models was significantly improved and the coefficients of Delta-SBP proved to be statistically significant.
Five cohorts of men ages 40-59 (Finland: 2 cohorts of 1,677 men; Netherlands: 1 cohort of 878 men; Italy: 2 cohorts of 1,712 men) were examined and evaluated for cardiovascular risk factors in 1959-1960 and subsequently followed-up for mortality over the next 25 years. Age-adjusted death rates from coronary heart disease were highest in Finland (244 per 1,000), intermediate in The Netherlands (195 per 1,000), and lowest in Italy (122 per 1,000) with a twofold range between the extremes. The Cox proportional hazards model was used for single cohorts and for the pools of national cohorts with coronary heart disease deaths as endpoints and 12 risk factors as covariates. It showed the significant and almost universal predictive value of these factors (with some rare exceptions). The most highly predictive values were age, blood pressure, total serum cholesterol, cigarette smoking, and physical activity (negative relationship). The prediction of events within each country using the risk function of the others produced errors ranging from -19% to +51%. The largest errors were those involving the Italian cohorts whose experience tended to underpredict coronary heart disease mortality elsewhere and to be overpredicted by the risk functions of the other countries. Solving a Cox model which included all the cohorts, and adding dummy variables for the identification of nationality, it appears that the relative risk, everything else being equal, is 1.49 and 1.34 for a Finnish man, compared with Italian and Dutch men, respectively.
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Twelve cohorts of men aged 40-59 for a total of 8287 individuals in six countries (Finland, the Netherlands, Italy, Yugoslavia, Greece and Japan) were examined in the late 1950s or early 1960s for the measurement of some risk factors and then followed up for mortality and causes of death through 20 years. Large differences in 20-year death rates from stroke were recorded among cohorts, with the highest levels in the pool of the Yugoslavia (67 per 1000) and Japanese cohorts (62 per 1000) and the lowest in the Dutch cohort (22 per 1000). The simple linear correlation (among cohorts) of stroke mortality on mean levels at entry of some factors showed inverse significant coefficients for systolic (-0.63) diastolic (-0.51) and mean blood pressure (-0.72), and for serum cholesterol (-0.72), whereas no significant coefficients were found for mean body mass index, mean cigarette consumption and mean physical activity. The Cox model solved for six national pools of cohorts showed that only age and mean blood pressure carry significant positive coefficients, whereas all the other available factors (cigarette consumption, serum cholesterol, body mass index, physical activity) did not approach significant levels except the negative coefficients of smoking habits in Greece.
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Some differences in the blood of farmers in Nurmijarvi, Finland, Canino, Italy, and Beltsville, Maryland in the United States apparently were associated with differences, among the areas, in the farmers' diets. Those associations suggested that diets that are high in saturated fats (Nurmijarvi) could predispose humans to develop intravascular disease. Such predisposition has been observed in experimental animals. Low levels of the parameters that are considered active in such predisposition apparently were associated with diets that were low in saturated fats (Canino) or with diets that were low in saturated and high in unsaturated fats (Beltsville). Within the limits of the experimental design, the data from the three population groups indicated that a more comprehensive study might establish a relation between diet and intravascular disease in humans.
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The effect on the fasting serum lipid levels of adding daily 291 mg of cholesterol to diets containing 3 mg of cholesterol and equal fat content, but different fatty acid composition, was tested on 12 young men. The saturated diet provided 97 g/day of a staurated oil made up of 2 parts of palm oil and 1 part of coconut oil. The polyunsatured diet provided 97 g/day of safflower oil. The cholesterol was dissolved in 40 g of either oil incorporated into a spread. A similar spread, devoid of cholesterol, was fed during the cholesterol free periods. Duration of dietary periods was 14 days. Addition of cholesterol produced a mean elevation of serum cholesterol of 9 mg/dl (SE +/- 2.1) in the presence of the saturated diet, and of 8 mg/dl (SE +/- 1.6) in the presence of the polyunsaturated diet. Both cholesterol elevations were significant (P less than 0.01) but not significantly different from each other. Substitution of the saturated diet for the polyunsatured diet caused a significant elevation of serum cholesterol which was the same when the substitution was made in the presence or in the absence of added dietary cholesterol.
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