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Biomedical subjects

C N Corder

Publications and source records attributed to C N Corder.

At least 37 records · Page 2Linked to original sources

Enkephalins: immunomodulators.

Our original studies of the enkephalins were centered on behavioral stress and brain dopaminergic interactions. More recently we discovered the enkephalins to be immunomodulators as evidenced by their enhancement effects on lymphocyte blastogenesis in mice, increases in the sizes of the thymus or spleen in rodents, and prolongation of survival of BDF1 mice inoculated with attentuated L1210 cells. Finally, in studies of human blood samples from both normal volunteers and cancer patients, the enkephalins were demonstrated to stimulate active T cell rosettes and natural killer cell activities (in vitro). These studies support our hypothesis that, in stress, the enkephalins modulate the effects of steroid hormones on the immune system.

Acoustic Stimulation↗

Levels of the oxytocin-associated and vasopressin-associated neurophysins in plasma and their responses in essential hypertension.

A group of 89 individuals with essential hypertension was evaluated with several measurements including the neurophysin believed to be the human oxytocin neurophysin (OT-Np), and the human vasopressin neurophysin (VP-Np). The neurophysins are proteins synthesized within cells of the supraoptic and paraventricular nuclei in conjunction with their respective hormones oxytocin and vasopressin as part of a common precursor molecule and so may reflect the simultaneous presence in plasma of their associated hormones. A poor but statistically significant correlation was noted between levels of OT-Np and renin activity in plasma (PRA) either supine (r = 0.248) or erect (r = 0.255). Levels of OT-Np averaged 1.75 ng/ml and were inversely correlated with creatinine (r = -0.252), supine blood pressure (r = -0.450), plasma volume (r = -0.327), and 24-hour urine sodium (r = -0.313). Levels of Ot-Np could be suppressed by infusion of physiologic saline. Levels of OT-Np were lower in the volume expanded state and were positively correlated with the quantity of sodium excreted into a 24-hour urine collected after the infusion (r = 0.426) and inversely correlated with the supine systolic (r = -0.379) and supine diastolic (r = -0.455) blood pressures recorded after the infusion of saline. Oestrogen, a stimulus to the secretion of OT-Np, did not account for the elevation of OT-Np observed in the study, since mean levels of oestradiol (E2) in a subset of the patients with elevated OT-Np (E2 = 36 pg/ml) were not different from levels in subjects with lower values of OT-Np (E2 = 45 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pyruvate and lactate levels in oviducts of cycling, pregnant, and pseudopregnant mice.

Pyruvate and lactate were measured in oviducts during the first 5 days following ovulation in cycling, pregnant, and pseudopregnant mice, to determine how oviductal metabolism might change to promote the availability of these substrates to the early embryo. The postovulatory peak in ampullar pyruvate was most evident in the 12-h pregnant oviduct, 3.19 mmol . kg-1. This increase at +12 h was related to a decrease in lactate dehydrogenase (LDH) activity, compared to cycling animals, observed at this time. Although cycling animals showed a significant increase in isthmic pyruvate at +3 h, no change in isthmic pyruvate was observed in either mated group through the postovulatory period. Isthmic LDH activity was also unchanged in cycling or mated animals through this period. Ampullar lactate in both mated groups was elevated at 12 to 24 h after ovulation, a pattern similar to that seen in cycling animals. Isthmic lactate levels also increased after ovulation in all groups, but in the pregnant group the lactate remained elevated (25-28 mmol . kg-1) through 72 h, while concentrations in the cycling and pseudopregnant animals, returned to low levels (14-16 mmol . kg-1) by 48 h. The patterns of pyruvate and lactate, especially those in the pregnant animals, seem suited to providing these metabolites at levels near those required for optimal in vitro embryo growth. The +12 h ampullar pyruvate peak noted in mated animals implies a specific response to the mating stimulus. Prolongation of increased isthmic lactate levels only in pregnant animals suggests a response of the oviduct to the viable embryo.

Analysis of Variance↗

Quantitative histochemical measurement of pyruvate and lactate in mouse oviduct during the estrous cycle.

Pyruvate and lactate are important energy sources for preimplantation embryos cultured in vitro. The purpose of this study was to determine in vivo levels of these substances in mouse oviductal tissues throughout the estrous cycle. Quantitative histochemical assays were developed to analyze these metabolites in submicrogram samples of freeze-dried ampullar and isthmic oviduct. The potential for other alpha-keto acids to interfere with the pyruvate assay was assessed and found to be minimal with this procedure. The importance of the collection method in maintaining in vivo metabolite levels was demonstrated by the marked changes observed with extended anoxia or pentobarbital anesthesia. Pyruvate levels at 3 hr postovulation (2.6 mmol X kg-1 dry weight) were higher than 12 hr before ovulation or 12 to 72 hr after ovulation (1.6 to 2.2 mol X kg-1) in both ampulla and isthmus. Lactate levels were significantly increased at 12 to 24 hr in the isthmus (28 mmol X kg-1) compared to other times during the cycle (9-19 mmol X kg-1). The observed levels of these metabolites may reflect changes in oviductal metabolism, induced by the hormone pattern of the estrous cycle, that promote the availability of needed energy substrates for the early embryo.

Anaerobiosis↗

Effects of opiate antagonists on early pregnancy and pseudopregnancy in mice.

Administration of naltrexone or the long-acting morphine antagonist chlornaltrexamine before infertile mating had no effect on the length of the resulting pseudopregnancy in mice. Naltrexone in doses of 10 to 200 mg/kg s.c. given on Days 2 or 3 of pregnancy showed no consistent effects on the maintenance of pregnancy. Multiple doses or intracerebroventricular administration of naltrexone also had no effect. Chronic infusion of naltrexone, provided by mini-osmotic pumps, from Day 1 of pregnancy had no effect on the incidence of pregnancy or the number of embryos implanted. These results suggest that endogenous opioids do not play a critical role in this prolactin-dependent physiological process.

Animals↗

Variable levels of plasma catecholamines and dopamine beta-hydroxylase in hemodialysis patients.

Plasma norepinephrine (NE), epinephrine (EPI), dopamine (DPM), dopamine beta-hydroxylase (DBH), and renin were measured in patients undergoing maintenance hemodialysis. The predialysis NE, EPI, and DPM concentrations were lower than normal at 29, 7.3 and 4.8 pg/ml, respectively. The NE level increased in the erect posture to 100 pg/ml at 30 min. Levels were also measured during the postdialysis period, and were approximately the same as in normal subjects, but lower than previously published values for patients undergoing hemodialysis. In the predialysis period, NE and renin correlated upon assumption of the upright posture. It is concluded that maintenance hemodialysis can be carried out without a major distortion of the plasma catecholamine levels.

Adult↗

Diuretic and vasoconstrictor effects of sodium orthovanadate on the isolated perfused rat kidney.

Sodium orthovanadate (vanadate) is a powerful inhibitor of (Na+,K+) adenosine triphosphatase and exhibits widespread actions on the renal and cardiovascular systems. In the present study, the effect of vanadate on the functions of the isolated perfused rat kidney was studied. The control parameters for this preparation were: glomerular filtration rate, 225 microliter/min; urine flow, 40 microliter/min; fractional sodium reabsorption, 92%; and total peripheral resistance, 765 kilo pascals/l/min. Varying concentrations of vanadate in the perfusate (0 to 32 microM) produced a dose-dependent rise in glomerular filtration rate, urine flow, total peripheral resistance and inhibition of sodium reabsorption. At higher concentrations, vanadate was nephrotoxic. Since vanadate produces simultaneous rises in glomerular filtration rate and total peripheral resistance, a postcapillary vasoconstrictor effect for the anion is postulated. Clearance of vanadate from the perfusate was determined at various concentrations of the anion in the perfusate and the reversibility of vanadate effect on the kidney was studied. In conclusion, vanadate is a potent diuretic, natriuretic and vasoconstrictor in the isolated, perfused rat kidney and is nephrotoxic at higher dose levels.

Animals↗

The effect of vanadate on human kidney potassium dependent phosphatase.

This study examined the effects of vanadate on the potassium dependent phosphatase activity present in purified human kidney microsomal (Na+ + K+)-adenosine triphosphatase. Vanadate anion inhibited the K+-dependent phosphatase at a K1 of 35 nM. This inhibition was noncompetitive with the substrate, p-nitrophenylphosphate. The inhibition by vanadate at 1 mM K+ was only 45% of the inhibition that was observed at 10 mM K+. Neither preincubation of the enzyme with vanadate, nor changing the pH of the assay from 8.2 to 7.2 had any effect on the K1 for vanadate. The inclusion of 2.5 mM isoproterenol, to complex the yanadate, reversed the inhibition, as did diluting the enzymatic reaction. Vanadate also inhibited the overall (Na+ + K+)-ATPase reaction at a K1 of 1.91 microM. This inhibition was also reversible upon inclusion of isoproterenol in the assay. Increasing the level of magnesium from 6 mM to 30 mM lowered the K1 of vanadate to 0.25 microM. The possible role of vanadate as a physiological mediator of (Na+ + k+)-atpase activity is discussed.

Humans↗

Effect of mercaptoethanol in the radioactive thin layer chromatography assay of NAD+-15-hydroxyprostaglandin in dehydrogenase.

The use of mercaptoethanol in the assay of rat kidney 15-hydroxyprostaglandin dehydrogenase (PGDH) was found to have minimal effect on activity assayed with the spectrophotometric and substrate loss assays. However, mercaptoethanol appeared to inhibit PGDH when assayed by thin-layer chromatography, based upon conversion of 3H-PGE1 to 15-keto-3H-PGE1. Mercaptoethanol reacted with 15-keto-PGE1 to alter its chromatographic mobility and to suppress the U.V. absorption spectrum of 15-keto-PGE1. The implication of the use of ME in radiometric assays is discussed.

Animals↗

NAD+-15-hydroxyprostaglandin dehydrogenase distribution in rat kidney.

Rat kidney NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) was measured in zones and substructure of the rat kidney nephron. This was accomplished utilizing an assay procedure based upon determining the amount of prostaglandin E1 present before and after the reaction with the 15-hydroxyprostaglandin dehydrogenase contained in the tissue sample. The enzyme activity was assayed in freeze dried, quick frozen rat kidney sections and its distribution within the rat kidney was determined. In kidney zones, it was localized to medullary rays and inner cortex. In kidney substructure, activity was highest in collecting tubule, pars recti tubule, distal convoluted tubule and the ascending limb of Henle (14.2, 11.5, 6.4 and 9.2 mM kg-1hr-1, respectively). Activity in glomeruli, proximal convoluted tubule and small arteries was lower (2.1, 2.8 and 2.1 mM kg-1hr-1, respectively). The assay procedure was verified by established assays (spectrophotometric, fluorometric and radiometric TLC) which are often used in homogenate and purified PGDH preparations.

Animals↗

Quantitative histochemistry of the sorbitol pathway in glomeruli and small arteries of human diabetic kidney.

Recent evidence has suggested a role for the polyol pathway in pathogenesis of cell damage in diabetes Glucose may be phosphorylated to glucose-6-phosphate via hexokinase and enter glycolysis or reduced to sorbitol via aldose reductase to enter the polyol pathway. The poorly diffusible sorbitol is converted via sorbitol dehydrogenase to fructose. Hexokinase, aldose reductase and sorbitol dehydrogenase activities were measured in glomeruli (G) and small arteries (SA) taken from normal and diabetic human kidneys, Hexokinase in diabetic G was 1688, which was significantly decreased from normal, 3147 mmoles/kg-1/h-1. Alodse reductase was significantly elevated in diabetic G,56-6, compared to normal G,10-8 mmoles/kg-1/h-1. In contrast, sorbitol dehydrogenase was significantly depressed in diabetic G, 3-7 VERSUs 10-9 mmoles/kg-1/h-1. The enzymatic changes observed in diabetic G would facilitate accumulation of sorbitol and therefore could contribute to the progression of glomerulosclerosis. The activity of hexokinase was also significantly reduced in SA, whereas aldose reductase and sorbitol dehydrogenase were unchanged.

Diabetes Mellitus↗

Reversible in activation of purified (Na+ + K+)-ATPase from human renal tissue by cyclic AMP-dependent protein kinase.

Human renal (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparations which exhibited a non-linear reaction rate, contained high levels of membrane-bound cyclic AMP-dependent protein kinase, while this latter activity was much less or absent in purified preparations. A non-linear reaction rate was observed in a purified preparation of (Na+ + K+)-ATPase by reconstituting the enzyme into lipid vesicles with cyclic AMP-dependent protein kinase. The addition of cyclic AMP to the ATPase assay of these lipid vesicles inactivated the (Na+ + K+)-ATPase. The cytoplasmic fraction of the cell contained a nondialyzable factor, which prevented (or reversed) the cyclic AMP-mediated inactivation of the enzyme.

Adenosine Triphosphatases↗

The K+-dependent phosphatase from human renal tissue: its properties and time dependent inhibition by ouabain.

The K+-dependent p-nitrophenyl phosphatase activity associated with human renal (Na+ + K+)-ATPase was examined for some of its kinetic properties. ATP inhibited the K+-dependent phosphatase and raised the Km for p-nitrophenylphosphate. Stimulation of the K+-dependent phosphatase by K+ was blocked by Na+ in a noncompetitive manner. Inhibition of the K+-dependent phosphatase by ouabain was dependent upon incubation time. The apparent Kï was 2.0 micron.

Adenosine Triphosphatases↗

The multiple factors affecting plasma renin activity in essential hypertension.

Seventy-nine patients with essential hypertension were evaluated for peripheral renin activity in response to injection of 60 mg of furosemide and to upright posture. Age and supine diastolic blood pressure were found to be significant determinants of responsiveness, with contributions from sex and race. Patients with impaired responsiveness were predominantly older and female, while the group of hyperresponders was younger, male, and had significantly lower supine diastolic pressures. Aldosterone responses in relation to changes in peripheral renin activity were found to be nearly random with both furosemide and with posture. Thus, patients could be subdivided into renin subgroups, but not into parallel aldosterone subgroups. Data on four patients with primary hyperaldosteronism were discussed for comparison.

Adolescent↗