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Biomedical subjects

J Oyama

Publications and source records attributed to J Oyama.

At least 37 records · Page 2Linked to original sources

The unresponsiveness of the immune system of the rat to hypergravity.

The immune response in rats exposed to simulated hypergravity (2.1 G and 3.1 G) by chronic centrifugation was assessed. Rats were immunized with sheep red blood cells (SRBC), either on the day of initial exposure to hypergravity (hyper-G), or after being centrifuged for 28 d and remaining on the centrifuge thereafter. Pair-fed and ad libitum fed noncentrifuged controls were used. Although there were some alterations in leukocyte counts, hyper-G did not systematically affect the primary or secondary anti-SRBC response, hematocrits, or the sizes of the liver, spleen, kidneys, thymus, or adrenal glands. The immune system is thus remarkably homeostatic under hypergravity conditions which do affect other physiologic parameters.

Adaptation, Physiological↗

Hypergravity effects on litter size, nursing activity, prolactin, TSH, T3, and T4 in the rat.

Hypergravity (HG) adapted rats were tested for mating ability, gestational time, fetal and newborn mortality, and nursing performances. Plasma and pituitary PRL and TSH and plasma T3 T4 were determined during 48 h peripartum. No difference was noticed in mating ability and gestation time. The number of fetuses was reduced in the HG rats (1 G- 12.9 +/- 0.5, 2.16 G-10.5 +/- 0.4, 3.14 G-9.4 +/- 0.5). None of the 3.14 G rats nursed their young, all of which were cannibalized. Of the 2.16 G rats, 50% nursed their pups, of which only half survived to weaning. The initial pituitary PRL of HG rats was lower than 1 G, but it increased postpartum, while the plasma PRL, which was very low, continued to decrease. Only postpartum was there a difference in plasma PRL between rats that previously nursed and those which did not nurse at 2.16 G. HG rats had lower T3 levels, indicating a hypermetabolic state during the peripartum, which worsened their normal relative hypothyroid state of pregnancy. Our conclusions are that exposure of pregnant rats to HG above 3 G has a lethal effect on the fetuses and newborns. Maternal PRL and T3 changes are possible reasons for this.

Adaptation, Physiological↗

Effects of simulated increased gravity on the rate of aging of rats: implications for the rate of living theory of aging.

Ever since Pearl proposed the rate of living theory of aging numerous studies have demonstrated its validity in poikilotherms. In mammals, however, satisfactory experimental demonstration is still lacking because an externally imposed increase of basal metabolic rate of these animals (e.g. by placement in the cold) is usually accompanied by general homeostatic disturbance and stress. The present study was based on the finding that rats exposed to slightly increased gravity are able to adapt with little chronic stress but at a higher level of basal metabolic expenditure (increased 'rate of living'). The rate of aging of 17-mth-old rats that had been exposed to 3.14 times normal gravity in an animal centrifuge for 8 mth was larger than of controls as shown by apparently elevated lipofuscin content in heart and kidney, reduced numbers and increased size of mitochondria of heart tissue, and inferior liver mitochondria respiration (reduced 'efficiency': 20% larger ADP: 0 ratio, P less than 0.01; reduced 'speed': 8% lower respiratory control ratio, P less than 0.05). On the other hand, steady-state food intake per day per kg body weight, which is presumably proportional to 'rate of living' or specific basal metabolic expenditure, was about 18% higher than in controls (P less than 0.01) after an initial 2-mth adaptation period. Finally, though half of the centrifuged animals lived only a little shorter than controls (average about 343 vs. 364 days on the centrifuge, difference statistically nonsignificant), the remaining half (longest survivors) lived on the centrifuge an average of 520 days (range 483-572) compared to an average of 574 days (range 502-615) for controls, computed from onset of centrifugation, or 11% shorter (P less than 0.01). Therefore, these results show that a moderate increase of the level of basal metabolism of young adult rats adapted to hypergravity compared to controls in normal gravity is accompanied by a roughly similar increase in the rate of organ aging and reduction of survival, in agreement with Pearl's rate of living theory of aging, previously experimentally demonstrated only in poikilotherms.

Aging↗

Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity.

Rats adapted to hypergravity by continuous centrifugation at 4.15 g for 7 mo exhibit increased glucose uptake at lower plasma insulin levels than weight-matched control animals following oral glucose administration. To assess insulin sensitivity of specific tissues, glucose uptake by perfused skeletal muscle and liver from year-old hypergravic rats was compared with perfused tissue from weight-matched control rats (2.5-mo-old). The results show that metabolic clearance of glucose by skeletal muscle from hypergravic rats ws not significantly greater than control muscle when perfused in the absence of insulin (10.6 vs. 8.1 microliter.min-1.g muscle-1) but was twofold faster (23.0 vs. 9.5) at perfusate insulin levels of 35 microunits/ml. Conversely, glucose uptake by hypergravic livers was significantly decreased (P less than 0.001) compared with control livers (10.3 vs. 27.8) at perfusate insulin levels of 40 microunits/ml. These findings suggest that skeletal muscle rather than liver is the tissue primarily responsible for enhanced sensitivity to insulin observed in older rats adapted to hypergravity.

Adaptation, Physiological↗

Effect of chronic centrifugation on the cross-sectional shape of long bones in dogs.

Alterations in cross-sectional shape at midlength of the femur, tibia, and humerus of 16 male Beagle dogs exposed for 6 months to either 2.1 g or 2.6 g by centrifugation were analysed by the area moment correlation coefficient, as defined by AMTMANN and POTULSKI (1981). As shown by variance analysis the cross-sectional shape differences between bones are highly significant, while the treatment effects are only significant at a 5% level. While the femur and the tibia are almost alike in the shape of their whole sectional area and cortical surface, they differ in the shape of their marrow cavity. The most oval cross sections were found in the humerus. In femur and humerus the shape of the whole sectional area, the marrow cavity and the cortical surface tend to be more oval in the centrifuged animals than in the controls. In the tibial cross sections the opposite is the case. A significant interaction "Gravity X Bone" was found for the shape of the marrow cavity.

Analysis of Variance↗

Insulin binding and glucose uptake of adipocytes in rats adapted to hypergravitational force.

Rats were exposed to 4.15 g for 1 yr and weight and age matched, and lean noncentrifuged rats were used as control groups. Rats exposed to chronic hypergravity (hypergravic rats) were found to show lower ambient insulin levels, greater food intake with smaller body weight gain, and decreased size of isolated adipocytes. The ability of adipocytes from the hypergravic rats to bind insulin was increased. With Scatchard analysis, both number and affinity of receptors were increased. In contrast to the increased binding, glucose transport was found to be decreased in adipocytes from these animals. However, when the data were expressed as a percentage of maximal effect, the half maximal insulin effect for both the hypergravic and lean control groups was produced at an insulin concentration of 0.23 +/- 0.02 ng/ml, which was lower than the insulin concentration of 0.31 +/- 0.02 ng/ml for the weight-matched control group (P less than 0.05). This increased insulin sensitivity in the hypergravic group was accounted for by an increased number of receptors.

Adaptation, Physiological↗

Rat growth during chronic centrifugation.

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.

Adipose Tissue↗

RBC-51Cr half-life and albumin turnover in growing beagle dogs during chronic radial acceleration.

The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control animals. Albumin-125I and autologous RBC-51Cr preparations were injected into all dogs at day 82 of the centrifugation period and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifuged groups, one with a normal half-life of 27 +/- 1 S.E.M. d, and one with a significantly ( less than 0.01) shorter half-life of 15 +/- 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as yet unknown mechanism to affect RBC population kinetics.

Acceleration↗

Abnormal canine bone development associated with hypergravity exposure.

Chronic centrifugation of 85- to 92-day-old Beagles at 2.0 X g and 2.6 X g for 26 weeks during the time of active skeletal growth caused skeletal abnormalities in the radius and the ulna of ten of 11 dogs. The pattern of change mimicked that found in naturally occurring and experimentally induced premature distal ulnar physeal closure or delayed growth at this physis. Minimal changes in bone density were detected by sensitive photon absorptiometric techniques. Skeletal abnormalities also were found in five of the six cage-control dogs, although the run-control dogs were radiographically normal.

Animals↗

Effect of chronic centrifugation on bone density of the dog.

Sixteen male Beagle dogs, 293 to 509 days old, were exposed almost continuously for 3 months to 2.0 G on a 7.9m radius centrifuge. The dogs were maintained on the centrifuge by means of a specially designed, automated waste disposal and life support system. Bone density was measured by a 125I Profile Scanner in the anterior, medial posterior and lateral cortex of the femoral mid-shaft. As compared to mean density in the femora of normal gravity controls, centrifuged dogs showed a 0.8% (P less than 0.05) lower mean linear absorption in their femora. However, the regression of density on the square-root of cross-sectional area/pi differs very significantly in the animals living at earth gravity and those living at hypergravity. Thin hypergravic bones are denser, thick hypergravic ones are less dense than the corresponding ones of normal gravity controls.

Animals↗

Studies on the erythron and the ferrokinetic responses in beagles adapted to hypergravity.

Red cell survival, ferrokinetics, and hematologic parameters were investigated in Beagle dogs exposed to chronic hypergravity (2.6 Gx). Ineffective erythropoiesis, red cell mass, plasma volume, and 51 Cr elution were significantly increased; maximum 59Fe incorporation was decreased; and there was no change in the mean erythrocyte life span following autologous injection of 51Cr-labeled red cells and 59Fe-labeled transferrin. Red cell count, Fcells, total body hemoglobin (Hb), susceptability to osmotic lysis, and differential reticulocyte count were increased. White blood cell count, venous blood %Hb, mean cell volume, mean cell Hb, mean cell Hb concentration, and serum iron were decreased. No changes were observed for body mass, mg Fe per g Hb, iron binding capacity, percent saturation of iron carrying capacity, or the electrophoretic mobility of purified Hb. This study indicated that chronic exposure to hypergravity induced changes in red cell size, volume, total mass, and membrane permeability.

Adaptation, Physiological↗

Effect of chronic centrifugation on bone density of the rat.

Alterations in density of the femur of female Sprague-Dawley rats exposed to chronic centrifugation of 2.76 G for 810 days were studied. The density was measured by photon absorptiometry, using a 125I Profile Scanner. The photon absorption measurements were taken: (1) on bone sections from the midshaft of the femur in the anterior, posterior, medial and lateral cortex with the beam path parallel to the shaft axis, and (2) on the femur near the midshaft with the beam path perpendicular to the shaft axis. The latter were correlated with the cross-sectional area in the midshaft. Compared with femora of age-matched rats (age controls) and of rats having body masses comparable to the centrifuged group (weight controls), kept under earth gravity, the chronically centrifuged animals showed no average no significant differences in photon absorption (density) in the four positons in midshaft. The absorption measurements perpendicular to the shaft axis in all groups differ significant differences between the centrifuged group and the control groups. When cross-sections of equal size are compared, the density of the rat femora is clearly higher in the centrifuged animals than in the control groups. In contrast, the age and weight controls do not differ significantly in density. The results suggest that the increased stress in the rat femora due to centrifugation is reflected in an increased bone density.

Absorption↗

The effects of centrifugation on the morphology of the lateral vestibular nucleus in the rat: a light and electron microscopic study.

Very little is known about structural changes in the central nervous system following exposure to increased g forces. Sprague-Dawley rats were centrifuged at Ames Research Center at 2.76-4.15 x g for periods ranging from 4 days to 21 months. The lateral vestibular nuclei were processed for electron microscopy and examined for evidence of structural alteration as a result of centrifugation. The number of filamentous nuclear inclusions, varicosities, and relative number of axosomatic synaptic terminals containing flattened vesicles (presumed inhibitory in function) increased in centrifuged rats. Altered mitochondria also were noted in that cell bodies of Deiters' neurons. Neuroaxonal dystrophy (NAD) was found in long-term centrifuged rats and was characterized by axons filled with reticulated mitochondria. The NAD found in the lateral vestibular nuclei of centrifuged rats is different from that seen in the dorsal column nuclei of aged mice.

Animals↗

Effect of chronic centrifugation on the structural development of the musculoskeletal system of the rat.

25 female Sprague-Dawley rats were placed on a 3.66 m radius centrifuge and subsequently exposed almost continuously for 810 days to 2.76 G. Compared to normal gravity controls, the most noticeable effect of hypergravity was the inhibition of growth of the centrifuged animals. The rats exposed to hypergravity showed on average a smaller femur length (-6.5%), a smaller cross-sectional area (-7.7%, when expressed linearly, i. e. (area/pi)1/2), and smaller outer and inner cross-sectional radii (linearly -9.3% and -12.3%) at the mid-shaft of the femoral bones. The growth inhibition of 3 hind-leg muscles was on average significantly less ranging from (-3.5% to -4.1%), compared to the growth inhibition of the linear dimension of the femur. Statistically there was no difference in the slope and elevation of the regression of the square-root of the cross-sectional area divided by pi on the length of the femur between centrifuged animals and their 16 age matched controls. In the weight control group of 24 animals, comprised of 34,74, and 102 day old rats, the corresponding regression line was parallel and lower in elevation by -12.8%, compared to the line for the centrifuged and age control groups. But, compared to the regression derived from all control animals ranging from 34 to 840 days of age, the cross-sectional area at the mid-shaft of the femur was 8.4% greater in the rats exposed to 2.76 G for 810 days. The slopes of the regression of the outer radius at mid-shaft on the length of the femur were the same in the centrifuged group and in the weight and age control groups of animals. But, the regression lines differed in elevation by -4.4% on average between the centrifuged and age control animals. The line for the regression of the inner radius at the mid-shaft on the length of the femur was parallel and lower in elevation by -7.6% in the centrifuged animals compared to the line for the age controls. But, compared to all control animals living at normal gravity, the outer radius was increased by 3.0% and the inner radius was decreased by 5.7% in the animals exposed to 2.76 G for 810 days. Since the centrifuged animals were all 840 days old, while the controls were from 34 to 840 days old, only further experiments comparing centrifuged and control animals of the same age at various growth stages will be able to furnish evidence for an unambiguous bone hypertrophy. The regressions of the cube-root of body weight on length of the femur deviate significantly in the 3 groups of animals. The heavier rats of the age control group have relatively shorter femurs than the lighter animals. The opposite applies to the centrifuged and the weight control groups of rats. Although the rats on the centrifuge are markedly smaller in overall body size than the controls, they exhibit on average the same absolute muscle weights as the animals at earth gravity, if rats of the same overall body size are compared...

Animals↗

Effect of chronic centrifugation of the musculoskeletal system of the dog.

Sixteen male Beagle dogs, 293 to 509 days old, were exposed almost continuously for 3 months to 2.0 G on a 7.9 meter radius centrifuge. The dogs were maintained on the centrifuge, by means of a specially designed automated waste disposal and life support system. As compared to the mean values of normal gravity controls, centrifuged dogs showed no differences in femur length; cross-sectional area, outer and inner radii at mid-shaft of the femur; dry weights of the biceps femoris, quadriceps femoris, and gastrocnemius muscles. It was shown by analysis of covariance that chronic centrifugation has no effect on the relationship between the length and the cross-sectional dimensions at mid-shaft of the femur. Photon absorptiometry, however, revealed significant mineral content increases averaging 1.5% at 3 sites, i.e., at the 1/4, 1/2 and 3/4 length of the femur.

Animals↗