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Biomedical subjects

J Foreman

Publications and source records attributed to J Foreman.

104 records · Page 6Linked to original sources

Selenium and immune functions in humans.

Earlier animal experiments have shown that selenium depletion may decrease immune functions. In this human study, 40 volunteers from a population with low serum selenium concentrations were supplemented with selenium or placebo for 11 weeks. Blood samples were drawn at intervals for analysis of selenium status and immune function. At the end of the supplementation period, plasma selenium levels were 74 ng/ml in the placebo group and 169 ng/ml in the supplemented group. The improvement in selenium status was associated with a 57% increase in the activity of platelet glutathione peroxidase in the group supplemented with selenium, but there was no increase in the activity of this enzyme in the placebo-treated subjects. Immune function was measured in vitro by tests of lymphocyte and granulocyte activity. Intracellular killing of Staphylococcus aureus by granulocytes was slightly lower in the placebo group than in the selenium group at the end of the supplementation period (77.2 compared to 85.2%; P less than 0.05). No significant changes were observed in phagocytosis, chemotactic factor generation, antibody or leukocyte migration inhibitory factor production by lymphocytes, or proliferative responses to phytohemagglutinin or concanavalin A. These results suggest that the selenium deficiency of the order found in Finland and some other areas of the world has little, if any, influence on the immune functions measured in this study.

Adult↗

Developmental pattern of cystine transport in isolated rat renal tubules.

Isolated renal cortical tubule fragments from rats ranging in age from less than 48 h to 15 weeks were used to examine the pattern of cystine uptake with development. Immature tubules took up cystine with a faster initial rate than mature tubules and did not reach a steady state by 60 min. By eight weeks of age, the timed uptake of cystine began to approach a steady state and between 8 and 11 weeks the uptake pattern achieved its adult form of reaching a steady state by 30 min of incubation. Analysis of the intracellular metabolism of the cystine taken up by the newborn tubules revealed that the majority had been reduced to cysteine with the formation of small amounts of reduced glutathione. Cystine entered the renal cortical tubule cell from the newborn via two saturable transport systems similar to the mature animal. The kinetic parameters of initial uptake of these two transport systems were similar in the mature and newborn animal except for a higher maximum transport velocity for the low Km, low capacity system in the newborn. Lysine inhibited cystine uptake by newborn tubules and this inhibition appeared to occur on the low Km, low capacity transport system similar to the adult. Cystine uptake was sodium dependent with an apparent affinity for sodium of 36 mequiv./l. From this data, the physiologic cystinuria of the immature animal does not appear to be refeable to a lower rate of influx as previously observed with the cortical slice. Other mechanisms should be sought to explain this phenomenon of immaturity.

Aging↗

Metabolism of normal and ischemically injured rabbit kidneys during perfusion for 48 hours at 10 C.

We report a study of the effects of perfusate composition on the 5'-adenine nucleotides of rabbit kidneys perfused continuously at 10 C for 24 or 48 hr. It was found that when glucose was the sole energy source and the pO2 was approximately 150 mm Hg, the total high-energy phosphate content was reduced to one-half and total adenine nucleotides to one-third after 48-hr perfusion of freshly isolated kidneys. At this pO2 the supplementation of glucose of additional energy substrates had no effect on adenine nucleotide reserves, but the inclusion of hypoxanthine did have a positive effect, although not sufficient to restore normal levels. Increasing the pO2 to approximately 650 mm Hg however, in combination with the provision of energy substrates and hypoxanthine, produced adenine nucleotide levels very close to normal after 48 hr of perfusion. Study of metabolites in the perfusate suggested that significant glycolysis occurred when the pO2 was 150 mm Hg: it was stimulated by caprylate and inhibited by raising the pO2 to 650 mm Hg. Kidneys exposed to 60 min of warm ischemia before perfusion had severely depleted adenine nucleotide levels (less than one-fifth of normal) but after 48-hr perfusion with hypoxanthine, energy substrates, and a high pO2, the total adenine nucleotides were restored to normal and only the ATP to ADP ratio was significantly less than that observed in kidneys perfused for 48 hr without prior warm ischemia. Study of metabolites in the perfusate suggested that a burst of aerobic respiration occurred after a lag period of 20 hr in these kidneys. It is clear that a remarkable recovery of adenine nucleotides can occur during perfusion, under appropriate conditions, of kidneys damaged by warm ischemia.

Adenosine Diphosphate↗

The incidence of contrast medium induced acute tubular necrosis following arteriography.

Twenty-one patients slated for high-dose arteriography were studied to investigate the impact of predisposing medical conditions upon contrast medium induced acute renal failure. The study suggests that predisposing medical conditions are the most important factor determining the incidence of acute renal failure and the probability, speed, and degree of recovery of renal function. Patients with diabetes mellitus incur the highest risk of contrast medium induced acute renal failure. A dose relationship is also suggested. Contrast medium doses containing more than 100 g of iodine uniformly produced acute tubular necrosis in patients with predisposing medical conditions. Conversely, contrast medium doses containing less than 80 g of iodine produced clinically manifest acute renal failure in only one of 14 patients with predisposing medical conditions. Subclinical levels of acute renal failure were recognized in a large number of patients by routine measurement of radionuclide filtration fractions, serum creatinine levels, and urine osmolality and sodium concentration.

Acute Kidney Injury↗

Studies of the cyanogen bromide fragments of the apoprotein of human serum low density lipoproteins.

The apoprotein of human serum low density lipoproteins was reduced and carboxymethylated and then cleaved by cyanogen bromide (CNBr). The peptides which were produced from this cleavage (90% yield, based upon loss of methionine) were resolved by SDS polyacrylamide gel electrophoresis into 10 major bands, each having an amino acid composition very similar to that of intact reduced and carboxymethylated LDL apoprotein. The fractionation of the CNBr fragments by preparative gel filtration was dependent upon the nature of the eluting solvent. NH4OH and SDS solvents eluted all of the material in the void volume. In 6 M guanidinium chloride solvents several peaks were, however, resolved, each having an amino acid composition similar to that of the unfractionated products. Whereas no NH2-terminal was detected in reduced and carboxylmethylated LDL apoprotein, automated Edman degradation of the protein following treatment with CNBr revealed the presence of several NH2-termini. The results suggest that LDL apoprotein may be made of segments of, at least, very similar amino acid composition and that both the protein itself and derivative fragments have a great tendency to aggregate even in denaturing solvents.

Amino Acids↗