An evolutionary approach to pain.
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Biomedical subjects
Publications and source records attributed to G C Pitts.
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The effect of nutritional perturbations upon growth and catch-up growth in mass in the rat have been reevaluated by interpretation of published data. The earlier described cellular mechanisms involved were prematurely reported to be invalid. Hypertrophy and hyperplasia have been separately assessed by employing studies providing DNA content of the body or organs permitting calculation of number of "DNA units" and mean size of the units. Changes in unit number and size accounted for reported changes in gross mass. Perturbation during the periods of gestation and/or nursing decreased or increased the number of units without changing the size of the units, and in these cases the change in body or organ mass persisted into maturity. Perturbation during adulthood changed size of the units without changing their number, and in these cases catch-up occurred. Post-weaning was a transitional period with perturbation sometimes changing unit number after which the change persisted and sometimes unit size after which catch-up occurred. Failure in most cases of DNA unit number and unit size to change simultaneously led to speculations about the mechanisms involved. Besides perturbations resulting from experimental interventions, the rat is influenced also by circumstances with unpredictable nutritional impact encountered during the ontogeny of free-living individuals, for example, interactions between pups and mother and between siblings. Presumably the generalizations arrived at above also apply in these cases.
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Changes in rat body composition (15 components) associated with changes in level of physical activity (cage restraint, ad libitum activity in living cages, and ad libitum wheel running), age at initiation of regimen (22 days-16 wk), sex, and diet (chow and 60% fat) are evaluated. Running regimen initiation at 7 wk of age or younger is associated with a decrease in the fat-free body mass (FFBM) in males and an increase in females. Initiation at 11 wk or older does not change FFBM. Both reduce body fatness in either sex. Age altered the mass of 11 components, diet altered the mass of 10 components, and activity altered the mass of 8 components, and there were 6 interactions between the experimental variables. The significance of interactions in general is discussed. Our data together with those of other investigators indicate that the responses to volitional wheel running and forced treadmill running are similar, but data from swimming rats may not be comparable in some cases.
Five male rats were exposed to 18.5 days of weightlessness in the Soviet mission COSMOS 1129 (flight group) and killed after reentry. They were immediately dissected into three major body subdivisions: musculoskeletal system, skin, and pooled viscera analyzed for fat, water, solids, and six elements. These results, expressed as percentages of the fat-free body or its components, were compared with two groups of terrestrial controls: one subjected to a flight simulation in a spacecraft mock-up and the other under standard vivarium conditions. Relative to the control groups the flight group showed 1) a reduced fraction of total body water, 2) a net shift of body water from skin to viscera, 3) a marked diminution in fraction of extracellular water in the fat-free body, 4) a marked reduction in fraction of bone mineral, 5) no change in the quantity of stored fat or adrenal masses, and 6) a net increase in total muscle mass as indicated by total body creatine, protein, and body cell mass.
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Female weanling rats were chronically centrifuged at 4.15 g with controls at terrestrial gravity. Samples of 6 to 10 rats were sacrificed for body composition studies at 0, 28, 63, 105, 179 and 308 days of centrifugation and 57 days after centrifugation ended. The centrifuged group had a significantly lower mature body mass than the controls (251 vs 318 g) but the rate of approach to the mature values was the same in both groups. Retirement to 1 g on the 60th day resulted in complete recovery. Masses of muscle, bone, skin, CNS, heart, kidneys, body water and body fat were changed in the centrifuged group. However, an analysis of the growth in mass of individual components relative to growth of the total fat-free compartment revealed that only skin (which increased in mass) was responding to centrifugation per se.
Both new and published data (rats, mice, and human beings) on three parameters--fat mass, fat-free body mass (FFBM), and total body mass in some cases--are evaluated. Steady state values of the parameters are analyzed for changes in response to specific perturbing agents and for their frequency distributions. Temporal sequences of values on individuals are examined for evidence of regulatory responses. The results lead to the hypothesis that the FFBM is regulated, but probably not as a unit, and that mass of fat is regulated with a high priority near the range extremes but with a much lower priority in the mid-range. Properties and advantages of such a mechanism are discussed.
Four regimens: high-fat diet, exercised (I); chow, exercised (II); high-fat sedentary (III); and chow, sedentary (IV) were initiated in 35-day-old male rats. Growth was exponential in I and II and exponential progressing to rectilinear in III and IV. The exponential model predicted the decreasing rank order in asymptotic weight to be: III, IV, I, II. Body composition data (9 components) showed rank order in masses of fat and the fat-free body mass compartment (FFBM) to be the same as for asymptotic live weight. The rectilinear growth mode probably reflected fat accretion. High-fat diet increased and treadmill exercise decreased FFBM, the latter being reversible. These effects depended on regimen initiations by the 5-7th wk of age. During growth, masses of H2O, muscle, and skin increased as functions of body size; bone as a function of age; and heart, liver, gut, testevity, and diet. Growth in body size was expressed more precisely with FFBM, instead of live weight, as the index of size.
Body composition studied as a function of acceleration (1-4.7 G) in mice and rats showed fat-free body mass (FFBM) to be a predictable function of G-force while corroborating the known lability of body fat. Of nine studied components of FFBM only skeletal muscle, liver and heart contributed to the observed changes induced by delta G. (Body water /FFBM) was independent of delta G. When FFBM (as a percentage of 1 G controls) was plotted against G for mice, rats and monkeys (1-4.7 G) and men (0-1 G), the mass of the fat-free compartment passed through a maximum at 1 G. The data distribution in the figure suggested possible effects of body size and of age.
Female rats approximately 6 mo old were chronically centrifuged for up to 30 days at 2.76 G or 3.18 G and sacrificed at intervals for body-composition study. Both fat and the fat-free body mass (FFBM) were reduced during the 1st wk of centrifugation, with the fat showing considerably more variation both within and between groups. The FFBM was reduced below control level to the same extent in rats fed commercial chow, a high-fat diet, or a high-protein diet or in rats prefasted to produce a body-mass deficit at the start of centrifugation. There were no centrifugation-associated changes in body water content. It was concluded that body fat showed no evidence of regulation, FFBM is regulated at any constant level of acceleration between 1 and 4.15 G, and the change in FFBM induced by a change in acceleration is probably not regulated.
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This brief review leads to the following conclusions: (i) Inversion or clinostat rotation of frogs' eggs demonstrated a critical period of enhanced gravity-sensitivity prior to the first cleavage. These results were corroborated by centrifugation studies which localized the period of maximal sensitivity at approximately 20 minutes post-fertilization. (ii) Eggs of various invertebrates suspended in aqueous solution proved capable of normal development following brief ultracentrifugation. (iii) Among fly larvae, grasshopper nymphs, turtles, mice, rats and chickens, growth rates were inversely related to G-force and maximal chronic acceleration tolerated was inversely related to body size. (iv) Body composition data demonstrated the importance of separately evaluating fat and the fat-free portion of the body in studies of the effect of acceleration on growth in homeotherms. (v) The attempt to evaluate the effect of weightlessness on development of frogs' eggs in Biosatellite 2 was inconclusive for technical reasons.
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