摘要:

In our studies of metabolic control mechanisms in skeletal muscle from rhesus fetus we have determined the tissue levels of the metabolic intermediates and cofactors of the glycolytic pathway and have calculated the mass-action ratios for each reaction. Skeletal muscle from rhesus fetuses (Macaco mulatto), 90–155 days of gestational age, and from adult rhesus monkeys was used in these experiments.The apparent equilibrium constants for hexokinase and phosphofructokinase (PFK) in these tissues were over 1,000 times larger than the massaction ratios at all ages studied; the corresponding values for pyruvate kinase were more than 800 times different. The data suggest that these three enzymes are rate-limiting for fetal skeletal muscle as early as 54% of gestation. The next step was to study some of the numerous factors that modify these nonequilibrium reactions. Increasing the ATP concentration had a marked effect on the PFK activity of both fetal and adult muscle, first increasing and then inhibiting enzyme activity. At maximum PFK activity, the amount of fructose-6-PO4(F6P) phosphorylated per mg of protein was 2–3 times greater in the two fetal than in the adult series. At a concentration of 0.3 mM, citrate decreased PFK activity of the 100-day fetal muscle; a further decrease occurred at 1.2 mM citrate. At a citrate level of 0.3 mM, the addition of inorganic phosphate (P1) or cyclic AMP returned PFK activity to the uninhibited levels (pH 7.0). Relief of ATP inhibition of F6P phosphorylation with P1and cyclic AMP was also observed at pH 7.0 in extracts of 100-day fetal skeletal muscle.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

Pulmonary superoxide dismutase (SOD) activity was determined for various groups of human fetuses, infants, and adults. Enzyme activity was found to increase with age from a low of 17 ± 1 units/nig DNA in fetal lung to 49 ± 6 units/nig DNA in infant lung and finally to 110.2 ± 14.8 units/mg DNA in adult lung (P<0.05). No difference in lung SOD activity was demonstrated between normal infants and those with idiopathic respiratory distress/hyaline membrane disease (IRDS/HMD). No significant differences in SOD activity were found among all the samples of infant blood. Adult blood samples, however, contained significantly greater SOD activity both in terms of heme concentration and volume of whole blood (P<0.05). SOD activity in lung tissue from both rats and rabbits was also found to increase with age from a low value in fetal animals to a maximum activity in adults (P<0.05). Exposure of New Zealand White rabbits, prematurely delivered by caesarian section, to 80% oxygen for 24 hr resulted in a 42% increase in lung SOD activity. Similarly, 7-day-old Sprague-Dawley rats exposed to 85% oxygen for 24 hr showed a 43% increase in pulmonary SOD activity. No increase in pulmonary SOD was observed when adult rats were exposed to 85% oxygen for 24 hr. The effect of hyperoxia on SOD activity in excised lung was investigated. Rat lung, incubated in either heparinized whole blood or in plasma and exposed to 100% oxygen, showed a 30% increase in SOD activity after 2 hr. This capacity of lung tissue to respond to hyperoxiain vitrowith increased SOD activity was age dependent. The maximum increase in SOD activity was seen with lungs from 10–12-day-old rats. The oxygen-stimulated increase in lung SOD activity disappeared at about 19–20 days of age.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

The 3-day-old rat has a high basal level of phosphoenolpyruvate carboxykinase (PEPCK), the activity of which is not increased upon starvation. The lower basal activity of the enzyme in 19-day-old rat liver can, however, be stimulated by starvation. Serum glucose levels increased from 3 days to 19 days of age, with a decrease to adult levels. Liver glycogen concentration increased from 3 days to 19 days of age, with no additional increase observed at 3 months. There was a decrease with age in the specific activity of liver glycogen (from [14C]alanine and [14C]leucine). In fed rats given [14C]alanine, [14CO2expiration tended to decrease with age. The14CO2production from [14C]leucine was less than that from alanine, and also decreased with age. Three-day-old rats showed no change in serum glucose when starved for 4 hr. On the other hand, 19-day-old rats responded with a decrease in serum glucose; although the adult animal's basal level of serum glucose was less than that of the 19-day-old rats, starvation for 15 hr also caused a significant decrease. There was no statistically significant difference in liver glycogen concentration between the fed and starved 3-day-old animals. Liver glycogen concentration in the 19-day-old adult rats was affected, however, by starvation. The 3-day-old rat showed no significant change in incorporation of labeled amino acids into liver glycogen during starvation. Starvation resulted in a tremendous increase in the specific activity of hepatic glycogen in the 19-day-old and adult rats. Starvation decreased the percentage of labeled amino acid expired as14CO2. The proportion expired also decreased with age. Urinary nitrogen concentration increased significantly between 3 and 19 days of age. Starvation produced differential effects in the animals, with no change being observed in either the 3-day or adult rats; a decrease was observed in the 19-day-old animals. Urinary nitrogen concentration was measured in adult carbohydrate- deprived rats and was significantly higher than control values. These rats had a high gluconeogenic rate, reflected in the increased urinary nitrogen concentration. The young rat is at the mercy of a continuous supply of substrate in that it has a limited capacity for directing substrate flow within the liver in response to dietary changes.SpeculationThe relatively high dietary protein requirement for the neonatal rat may be a reflection of the utilization of amino acids not only for protein synthesis, but also for energy, as well as the need to conserve nitrogen as a source of nucleic acids for hyperplastic growth.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

1. We have used fetal rats to study the following aspects of the development of hemopoiesis: (a) content of hemopoietic stem cells in fetal bone marrow, liver, and peripheral blood and (b) origin of hemopoietic cells in the developing mammalian bone marrow.2. In the studies we utilized the diffusion chamber technique to study the content of stem cells committed to granulopoiesis. The number of myelopoietic stem cells in liver peripheral blood and in “bone marrow” of 18-day-old rats is nearly identical. Since in “bone marrow” a considerable number of peripheral blood cells are present in the vessels at that time, whereas extravascular cells consist only of mesenchymal cells, one might assume that these periph- eral blood cells give rise to granulocytic precursors in the cultures. Morphologically these cells are “blast” cells and lymphocytes.3. Based on cell labeling indices of radioautograms, derived from continuous infusion of pregnant rats with [3H]thymidine, it could be shown that in the perichondral area mesenchymal cells of the fetus and newborn have a slow rate of DNA turnover whereas “bone marrow” cells are in an active state of profileration.4. In further support of this it was also shown that injections of hydroxyurea (an agent which destroys cells in DNA synthesis) has virtually no effect on perichondral mesenchymal cells whereas “bone marrow” cells were completely hlocked in their ability to sup- port myelopoietic differentiation in the diffusion chamber implants.5. The conclusions would therefore be that (a)local perichondral cells, i.e., mesenchymal cells, do not contribute to marrow hemo- poiesis, (b)matrix cells of the developing bone marrow cannot reconstitute hemopoiesis, and (c)hemopoietic bone marrow cells develop from migrating peripheral “stem cells,” one of the sources being the liver.SpeculationThe development of mammalian bone marrow hemopoiesis is initiated by circulating blood stem cells. The blood receives the stem cells at this time of development mainly from the liver. The morphology of the expanding stem cell population in embryogenesis varies between small mononuclearlymphocyte-like cells and “blast” cells.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

The present studies in the newborn sheep were undertaken to further clarify the mechanism or mechanisms responsible for the early increases in serum thyroid hormone concentrations in the newborn as well as the significance of these changes to newborn nonshivering thermogenesis. Six groups of animals were studied to determine the influence of neonatal cooling, cord cutting, and the effects of thyrotropin-releasing hormone (TRH) and triiodothyronine (T3) injections.Group Inewborns were delivered into room air with immediate cord cutting.Group IIanimals were delivered into room air and cord cutting was delayed 60 min.Group IIIanimals were delivered into a 39° water bath and maintained for 60 min with the umbilical cord intact; the cord was cut at the time of removal from the water bath.Group IVanimals were handled similarly togroup IIIanimals except that cord cutting was delayed 60 min after removal from the water bath.Group VandVInewborns were handled similarly togroup IVanimals except that TRH (group V) or T3 (group IV) was injected at the time of removal from the water bath. Deep rectal temperature and serum free fatty acids (FFA), thyroxfoe (T4), and T3 concentrations were measured in all newborns; FFA was measured as an index of catecholamine release. Serum thyroid-stimulating hormone (TSH) was measured in newborns fromgroups IandII.The results indicate that the newborn lamb responds to pat turition similarly to the human newborn. There are marked increases in mean serum T3 (50–242 ng/100 ml) and FFA levels (245–744 μEq/liter) during the first 60 min with only a transient fall in body temperature (39.1 ° to 37.4°), indicating effective nonshivering thermogenesis. Serum T4 concentrations do not increase significantly during this time. Warming in the water bath (groups IIIandIV) prevented the FFA and T3 responses, indicating that parturitionper seis not the stimulus to these events. Delayed cord cutting (groups IIandIV) produced marked hypothermia (to 35.6 and 34.4°), and the increases in serum FFA and T3 concentrations were not observed until the cord was cut.Mean baseline serum TSH concentrations were 4.7 and 5.3 μU/ml, respectively, ingroups IandIIanimals and increased modestly to peak values at 30–60 min whether or not the umbilical cord was cut. TRH (group VI) did not increase serum T3 levels during the firs 60 min, but a significant 4-hr response (to 336 ng/100 ml) was observed. T3 (group VI) did not stimulate the FFA or thermogenic responses directly, but significantly augmented both responses to cord cutting. In addition, there was a significant correlation between serum FFA or T3 concentrations 60 min after cord cutting and minimal rectal temperature (r= 0.53 and 0.71, respectively;P<0.005).The present results indicate that in the newborn sheep: (l) umbilical cord cutting, rather than cooling, stimulates FFA release, T3 production, and nonshivering thermogenesis; (2) that the early T3 response is not mediated via TRH and TSH, but probably represents increased peripheral monodeiodination of T4 to T3; and (3) catecholamine and T3 probably both play a significant role in newborn nonshivering thermogenesis.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

A serum factor was demonstrated in normal individuals which (1) enhances the incorporation of L-[3H]fucose into cultured human skin fibroblasts, (2) is nondialyzable, (3) is heat labile at 50°, (4) is present in the noneuglobulin fraction, and (5) appears to be deficient in serum from patients with cystic fibrosis. The specific activity of L-[3H]fucose incorporated into skin fibroblasts from normal individuals in the presence of serum from 12 control subjects was 3,337 ± 168 cpm/mg protein in contrast to 2,294 ± 172, the activity obtained either in the presence of serum from 10 age-matched patients with cystic fibrosis or in the absence of serum. These differences were significant atP<0.001. In comparison, no significant difference was detected in the amount of L-[3H]fucose incorporated into skin fibroblasts derived from normal individuals and patients with cystic fibrosis. The plasma membrane of cultured skin fibroblasts derived from patients with cystic fibrosis appears to be grossly unaltered in its protein and L-fucose labeling pattern.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

The intracellular content and proportional distribution of B12(cobalamin) derivatives in fibroblasts cultured from patients with various forms of methylmalonic aciduria, as well as from normal control subjects, has been determined by a two-dimensional chromatobioautographic technique. Each line of fibroblasts was grown in the presence of four concentrations of cobalamin, ranging from the 0.04–0.07 pmol/ml contained in the basal medium to 74 pmol/ml (100 ng/ml), added in form of hydroxocobalamin (OHCBI). Control cells grown in the basal medium contained substantial proportions of both methylcobalamin (MeCbl) and adenosyl-cobalamin (AdoCbl), with the former predominating. As increasing concentrations of OH-CBI were added to the growth medium, the total cellular cobalamin content increased without marked changes in the relative proportions of MeCbl, AdoCbl, and OHCbl. Three different patterns were discernable in the cobalamin distributions of the cells cultured from patients with methylmalonic aciduria (Table 1 and Fig. 1).

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

In eight infants and children who had recovered from proteinenergy malnutrition (PEM), muscle mass was estimated by measuring creatine turnover by an isotope dilution technique using [15N]creatine, creatine concentration, and urinary creatinine output. Creatine turnover varied from 1.5 to 2.6% of the muscle creatine pool per day and muscle creatine concentration ranged from 1.7 to 3.9 μg/μg muscle DNA. Muscle mass was between 15% and 37% of total body weight. The results indicate that daily creatinine output is not a reliable indicator of muscle mass in children who have recently recovered from severe PEM.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

Chromosomes were studied in 74-hr lymphocyte cultures from seven patients with Down's syndrome and from 12 hematologically and karyotypically normal control subjects. Six were studied before and six after chickenpox infection.In Down's syndrome, the number of breaks per cell was 0.083 ± 0.036 immediately after chickenpox infection; this was significantly greater than the number of breaks before infection, 0.03 ± 0.008, and also significantly greater than the number of breaks, 0.046 ± 0.023, observed in control children with chickenpox. Therefore, chromosomes from patients with Down's syndrome were significantly more sensitive to breakage after chickenpox infection than those from control subjects.The incidence of chromosome breaks in Down's syndrome 1 month after chickenpox infection fell to the level observed in the preinfection range. The present results showed that the difference between the observed and the expected values for breakage in special regions of chromosome was not significant, but that chromosome breakage was random.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

A possible regulatory role of insulin in the development of ketosis in newborn and suckling rats was inrestigated. The average plasma concentration of total ketone bodies measured at birth was 0.414 ± 0.037 μmol/ml. Within 24 hr after birth the level of ketones had increased to 4 times its initial value. The 3-to 4-fold increase in plasma ketones was maintained during the first 5 days of life but started to decline thereafter. Plasma insulin of newborn rats at birth (62 ± 8 μU/ml) was comparable to that of fed adult rats (85 ± 10 μU/ml). The levels decreased to 28 μU/ml on the first day of life and stayed low throughout the suckling period despite a tendency to increase at the time close to weaning. The capacities for ketone production in liver homogenates of suckling rats were inversely related to the levels of insulin. Administration of insulin (0.125 mU/g body weight, im) and glucose (1.75 mg/g body weight, ip) both suppressed plasma ketone bodies in suckling rats. Insulin administration increased plasma insulin but failed to decrease plasma glucose. Injection of glucose increased plasma insulin and glucose. Neither insulin nor glucose treatment changed the plasma levels of free fatty acids. These data suggest that a limited availability of insulin permits a high rat of ketogenesis and hence induced ketosis in newborn and suckling rats.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID