Biosynthesis of prostaglandins and thromboxanes in fetal tissues.
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Biomedical subjects
Publications and source records attributed to S Solomon.
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1. Post-natal development of single nephron glomerular filtration rate, superficial proximal tubular length, nephron number and kidney weight have been studied in Sprague Dawley and in Wistar rats. 2. Superficial tubular length is a non-linear function of body weight or age. There seems to be a rapid growth until animals weigh about 150 g in Wistar rats. In this strain, growth is slower thereafter. This difference is not as evident in Sprague Dawley rats. 3. Nephron numbers increase over the same period at which rapid tubular growth occurs. 4. Sprague Dawley rats have somewhat fewer, but longer, proximal tubules than do Wistar rats. 5. In all animals weighing more than 100 g, SNGFR is linearly related to weight. For younger, smaller Sprague Dawley rats, the same linearity holds over the age range studied--older than 20 days of age. In Wistar rats, SNGFR relative to weight is less in young animals. 6. By relating SNGFR to total kidney GFR, evidence is obtained that maturation of renal function also involves a greater increase in filtration by superficial than by juxtamedullary nephrons.
A simple procedure for the preparation of beta-N-acetylhexosaminidase (EC 3.2.1.52), free from other glycosidases, from commercial bovine serum albumin is described. It has been fractionated into three peaks on a DEAE-cellulose column. The Km and V values for 4-methylumbelliferyl-beta-D-N-acetylglucosaminide (4MU-gluNAc), 4-methvlumbelliferyl-beta-D-N-acetylgalactosaminide (4MU-galNAc), p-nitrophenyl-beta-D-N-acetylglucosaminide, and p-nitrophenyl-beta-D-N-acetylgalactosaminide for each was established. The inhibition by several structural analogues on 4MU-gluNAc and 4MU-galNAc hydrolysis by the enzyme present in peak 1 was investigated.
alpha-Fetoprotein and the synthesis of heme associated with hemoglobin were measured simultaneously in short-term cultures of human fetal liver cells to correlate the relationship of alpha-fetoprotein to erythroid cell function. Both synthetic processes decreased exponentially during the first 5 days of culture. The use of media supplemented with different batches of fetal calf serum and porcine portal vein serum indicated that the optimal conditions for the production of alpha-fetoprotein were different from those required for the synthesis of heme associated with hemoglobin. Moreover, the alpha-fetoprotein-producing cells could be separated from erythroid cells after velocity sedimentation in Ficoll gradients. Although it is well known that erythropoiesis and alpha-fetoprotein production occur simultaneously during ontogenesis, alpha-fetoprotein itself (0.01-100 micron g/ml) did not stimulate heme synthesis in liver erythroid cells. Erythropoietin did not stimulate alpha-fetoprotein production. It is concluded that there is no cause-effect relationship between alpha-fetoprotein production and erythroid cell fuction in human fetal liver cells and that the two processes occur independently in different cell types.
Uptake of p-aminohippurate (PAH) by rat kidney slices was optimal at a pH of around 7.3 when incubation temperature was 37 degrees C. At 25 degrees C, however, optimal pH was increased to about 7.5. When the uptake was evaluated as a function of the OH/H ratio of the medium, it was found that optimal uptake is at a constant OH/H. Data showing the same characteristics of OH/H dependence were also observed for phenol red. Passive uptake of PAH was pH independent. Efflux rates for PAH also showed the pH optimal which was identical to that of uptake. At both 25 and 37 degrees C the Km appeared to be independent of pH while the maximum rate of active influx. An optimal OH/H ratio determines maximal velocity and this ratio is fixed and independent of temperature.
Prolactin was shown to activate adenylate cyclase in broken cellular enzyme preparations from rat renal medulla. Likewise, vasopresin was effective on this enzyme system. Parathyroid hormone was similarly active in the renal cortex. The simultaneous administration of vasopressin and prolactin to medullary kidney slices did not result in an additive effect in stimulating medullary adenyl cyclase. Audioradiographic techniques revealed a selective and prolonged localization of intravenously injected 125I-prolactin to the thick limb of the loop of Henle, the distal tubule and the collecting duct. It is concluded that prolactin activates medullary adenylate cyclase, and may do so by occupying ADH receptors.
Acute renal failure induced in Charles River rats by right nephrectomy and left renal artery clamping for 70 min, constantly produced high blood urea and serum creatinine levels 24 h following the experimental procedure. The intravascular administration of propranolol in different doses persistently alleviated the severity of uremia seen on the following day. The optimum dose in this experimental set-up was 1 mg/kg/h. The mean blood urea level was 237 +/- 15.5 (SEM) mg% in the saline-treated controls and 116 +/- 16 mg% in the group treated with propranolol 1 mg/kg/h. P113 alone and prostaglandin A1 alone were not effective in alleviating the ARF. The combination of P113 and propranolol produced the same amount of alleviation in uremia as propranolol alone. The PRA was low in the propranolol-treated rats and high in the group which received both P113 and propranolol, even though alleivation of ARF was produced in both of these groups. The mechanism by which the beta-adrenergic blockade produced by propranolol alleviates the anoxic type of acute renal failure is unknown. However, it does not seem to act through the suppression of renin release from the kidney.
Plasma renin activity (PRA) of infant rats is high until some time between the 3rd and 4th week after birth. Mothers, however, return PRA to normal by 2 weeks post partum. The rate of disappearance endogenous PRA of nephrectomized rats is slower in those animals having gigh PRA than in mature rats. Disappearance curves of endogenous PRA of mothers post partum is also the same as that of normal mature females. Part of the high PRA of the neonate can thereby be the related to the lower rate of destruction. Total kidney renin content increases with age. Renal renin activity (RRA) is low only during the 1st postnatal week when expressed in terms of whole kidney weight and compared to later postnatal times. Although there are some slight differences in the means in older animals, none are statistically significant.
The effects of testosterone and 17beta-estradiol on the synthesis of fetal and adult hemoglobins have been studied using a short-term primary cell culture system of human fetal liver at midgestation. There was a significant 23% increase in incorporation of 59Fe into adult hemoglobin relative to the total after the addition of 5 X 10(-8)M testosterone. 17beta-Estradiol (10(-6)M) lowered the incorporation of 59Fe by 21%. beta-Globin chain synthesis, measured as 3H- or 14C-leucine incorporation into globin chains, was identical in control and testosterone-treated cells and only slightly lower when 17beta-estradiol was added. For this reason the observed changes in adult hemoglobin resulting from the action of testosterone and 17beta-estradiol are caused by an indirect effect either in the final hemoglobin assembly or by small changes in the gamma/alpha-chain ratio which may be undetected by the methodology used.
The role of isoproterenol in the synthesis of heme associated with hemoglobin has been studied in primary cultures of human fetal liver. This drug (10-10M) stimulated the incorporation of 59Fe into heme associated with hemoglobin in cell cultures of livers obtained from human fetuses 8 to 10 weeks gestation but was inactive in cell cultures prepared from livers of older fetuses. Isoproterenol has its optimal activity at a much earlier time in gestation than that previously reported for testosterone or erythropoietin. The interpretation of these results is that there is present a cell population in human fetal liver early in gestation with the appropriate isoproterenol-receptors and capable of erythroid differentiation after exposure to the drug.
A 64-year-old man with diffuse atherosclerosis developed an organic mental syndrome, followed by hypothalamic symptoms. Autopsy showed an old large cystic infarct involving the left temporal lobe including the hippocampus, and atrophy of the ipsilateral fornix, mammillary body, hypothalamus, mammillothalamic tract, and the anterior thalamic nucleus. The clinical deterioration and pathologic findings may be explained by anterograde transneuronal degeneration within the limbic system following the infarction.
Recent work on kidneys from hypophysectomized (hypox) rats has shown atrophy of the proximal tubules with no effects on the other parts of the nephron. We carried out experiments to determine whether the reduction of p-aminohippurate (PAH) is consistent with structural changes in the proximal tubule of hypophysectomized rats. Initial velocities of PAH uptake by renal cortical slices were found to be constant over 30 min of incubation at concentrations of PAH up to 0-5 mmol/1 for both control and hypox animals. Using kinetic analysis, it was found that both maximal velocity, Vmax, and the Michaelis constant, Km, were reduced in hypox animals, the relative reduction being similar for both parameters. Comparison between high Na (100 mmol/1) and low Na (6 mmol/1) media indicated that in both control and hypox rats, Vmax was significantly lower in low Na medium than in high Na medium, whereas Km was not changed. Efflux of PAH from pre-loaded tissue also showed a reduction in hypox animals. These results may indicate that hypophysectomy alters the capacity of PAH transport in renal cortical slices by (1) reducing the effective transport area or sites, and (2) by changing carrier-substrate affinity.