[Diseases and their treatment in concentration camps along the River Kwai].
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Biomedical subjects
Publications and source records attributed to G Bras.
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A multivariable statistical model for predicting the duration of life of rats permitted to select their own diets was evaluated prospectively. With information relating to pre-adult dietary habits and growth responses, the predicted length of life for an individual closely matched the observed life span; the average absolute error was 11%. This suggests that, even under normal feeding conditions, the diet/growth history is an important factor bearing on death rate. In general, an early adult death age is associated with a high food intake prior to adulthood particularly when coupled with a high efficiency of food utilization during the post-puberty period, a rapid growth rate and early attainment of mature weight. Deviations from this pattern serve to increase the duration of life of the individual.
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The dietary and growth histories of noninbred male Charles River COBS rats permitted freedom of dietary choice throughout life were analyzed to determine the conditions associated with the spontaneous occurrence of anterior pituitary gland tumors (PT). The animals were allowed to regulate their protein intake apart from energy intake. Multivariable models were derived distinguishing rats that develop PT from those remaining free of tumors throughout life. Conventional fixed diet studies suggested that the quantity and quality of the diet consumed would be the best explanatory variables. However, body weight-related variables were found to be more important. The interacting, time-related conditions conductive to a high probability of PT occurrence included an unusually high growth rate associated with a high level of conversion of the food consumed into body mass during early life and a high intake of protein relative to body weight during early adult life. The accuracy in identifying rats with PT was even greater if mature body weight was included as an explanatory variable.
The mature body weight of outbred CD-Crl:COBS CD(SD)BR male rats permitted to select their own diets throughout life was shown to correlate linearly with the frequency of spontaneous tumors. In an analysis of the dietary practices of these animals, a multifactorial model was derived--for which prepuberty and early post-puberty data only were used--that accounted for a large proportion of the variance in mature weight. The level of food or calorie intake proved less informative than the following: the interactive effects of food intake relative to body weight, the proportion of protein and carbohydrate constituents in the diet, the intake of each of these components, and, particularly, the efficiency with which the diet consumed was used for growth during early postweaning life. In a prospective study of other rats maintained on a similar feeding regimen, the model was found to be an accurate predictor of mature weight. Several of the explanatory factors necessary for estimation of body weight also contributed to tumor susceptibility. Nonetheless, both dietary and body weight-related factors in a specific time-related sequence were required to explain variation in spontaneous tumor susceptibility.
The association between the age at death of rats that develop spontaneous tumors and their early life dietary practices and growth responses was investigated. The data were obtained from outbred male Charles River CD Crl:COBS CD (SD)BR rats maintained for life on a self-selection dietary regimen that permitted them to regulate their protein intake apart from energy intake. A series of multivariable models was derived, after the rats were grouped by tumor type, that accurately accounted for the age of death of the individuals in each class. The models that explain the variance in death age of rats that develop tumors also differed from the combination of factors for rats that do not develop tumors but succumb to other age-related diseases. Although dietary protein and measures of growth are ubiquitous features in these models, no one set of idealized conditions for longevity can be proposed.
A complete life history was obtained of the dietary practices, growth responses, and diseases of outbred male Charles River COBS rats permitted to select their own diets. Simple correlation analyses proved inadequate for detecting an association between any single factor at any age and tumor development. A multifactorial model showed that animals that developed tumors could be distinguished from those that did not, solely on the basis of age- or weight-specific information prior to maturity. The combination of variables that maximize the probability of a neoplasm is: 1. a high absolute protein intake shortly after weaning, 2. a high degree of efficiency in converting consumed food into body mass at the time the individual enters puberty, 3. a high level of protein intake relative to body weight during the early adult period and concomitantly, 4. a high level of food intake, and 5. a rapid growth rate during early postnatal life so that comparatively less time is required to attain a specified body weight than a subsequent weight increment. The opposite set of conditions reduces the probability of neoplasm occurrence, which is even further minimized if the proportion of protein in the diet in early postweaning life and the absolute intake of protein during the early adult period are relatively high. Differences in temporal-specific dietary practices and growth responses accounted for differences in the tissue origin of the tumors.
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Protease I, a periplasmic endopeptidase from Escherichia coli has been further purified by a modified procedure. While the purified protein consists of a single polypeptide chain of about 21000 daltons, its molecular weight in dilute salt solution was estimated to be near 43000, suggesting that the enzyme has a marked tendency to dimerize. It has only one disulphide bond and is very sensitive to urea. In agreement with previous evidence of a chymotrypsin-like specificity, hydrolytic assays of various p-nitrophenyl esters of N-substituted amino acids showed that phenylalanine and tyrosine derivatives are the best substrates for the enzyme. The Km(app) for N-benzoyloxycarbonyl-L-tyrosin-p-nitrophenyl ester at pH 7.5 In 100 mM sodium phosphate buffer at 25 degrees C was found to be 0.2 mM. In contrast to chymotrypsin, protease I is unable to hydrolyse N-acetyl-L-phenylalanine ethyl ester and its tyrosine analogue. Moreover, the enzyme appears devoid of amidase activity and exhibits a low activity upon polypeptides. At 37 degrees C, it cleaves the carboxymethylated B-chain of bovine insulin at four points: Phe25-Tyr26, Phe24-Phe25, Leu15-Tyr16 and Ser9-His10. From a detailed study of peptides bonds hydrolyzed, it was concluded that protease I has a stringent requirement for both residues forming the scissile bond, and appears to possess an extended hydrophobic binding site.
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