Inhibition of the insulin response to glucose after treatment with cyproheptadine.
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Biomedical subjects
Publications and source records attributed to A Golander.
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The immunologic mechanisms that protect the fetus from rejection were the subject of numerous investigations. Reports showing the uterus as a favorable site of implantation focused our attention to the decidua which is the maternal tissue intimately attached to fetal structures. Explants of human decidua were cultured for periods of 24 h and incubation media tested for their immunosuppressive activity. The incubation medium of human decidua when added to cultures of human lymphocytes suppressed both their reactivity to lectins and their activity in the mixed lymphocyte reaction. The results of these experiments suggest that decidual tissue releases a soluble factor which is a potent inhibitor of cell-mediated immunity.
To study the effects of calcium on the release of human placental lactogen (hPL), placental explants were exposed to media containing lower or higher concentrations of calcium than normally available to the placenta. Explants exposed for 2 h to calcium-poor medium or medium containing either 2 mM EDTA or 2 mM EGTA released 160, 248, and 253% more hPL, respectively, than control explants. In contrast, explants exposed to medium containing higher than normal calcium concentrations released the same amounts of hPL as the control explants. At lower than normal extracellular calcium concentrations, the increased hPL release was inversely proportional to the calcium concentration. The increased release in calcium-poor medium was inhibited by subsequent exposure of the explants to medium containing calcium and was prevented by either barium or magnesium. Changes in barium or magnesium concentrations, however, had no effects on hPL release in the presence of normal extracellular calcium concentrations. Methoxyverapamil (D 600), an inhibitor of calcium flux, stimulated hPL release. Because low extracellular calcium and methoxyverapamil both inhibit calcium influx, these experiments suggest that calcium influx inhibits hPL release. The role of calcium in the regulation of hPL release therefore appears to be different from that reported in other release systems.
The immune functions were evaluated in 30 children, aged one year to 9 8/12 years, who had suffered during their early infancy from protein-calorie malnutrition (PCM) as the result of intractable diarrhea. Twelve healthy children matched for age and sex served as controls. All 42 children responded normally to intradermal injections of tuberculin and candida antigens. The reduction of nitrous blue tetrazolium (NBT) by the polymorphonuclear leucocytes (PMN) was normal. Apart from the lower concentrations of IgM in the post-PCM group--145 +/- 67 mg % as compared to 212.8 +/- 46 mg % (p less than 0.005)--no differences were noted in the other serum immunoglobulin and complement levels. The response to phytohaemagglutinins (PHA) in two different concentrations was significantly enhanced in the post-PCM group (p less than 0.05). The per cent of T cells in both groups was normal. The results of this study indicate that most immunologic parameters return to normal after a healthy nutritional status has been achieved, with the exception of some abnormalities in IgM production and lymphocyte reactivity to PHA. These need further investigation.
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To determine whether the secretion of PRL by human decidual tissue in vitro is influenced by factors which inhibit or stimulate pituitary PRL secretion, explants of decidual tissue were incubated in media containing bromocriptine, dopamine, or TRH at concentrations known to affect pituitary PRL secretion in vitro. The quantities of PRL secreted by the explants exposed to these factors were compared with amounts secreted by explants incubated in control medium. Bromocriptine in concentrations ranging from 1.5 x 10(-10) to 1.5 x 10(-7) M did not inhibit PRL secretion over a 3-day period and dopamine in concentrations ranging from 5 x 10(-5)-10(-9) M did not inhibit PRL secretion over a 4-h period. TRH in concentrations ranging from 10(-9)-10(-3) M did not stimulate PRL secretion. These results suggest that the mechanism of PRL secretion by decidual tissue in vitro is different, at least in part, from the mechanism of pituitary PRL secretion.
To determine whether human decidua and/or chorion synthesizes and secretes prolactin, explants of decidua obtained at Caesarian section and explants of chorion from the membranes separating dizygotic twins were cultured for periods of up to 6 days. The decidual explants released 366 +/- 37 ng prolactin/100 mg tissue (mean +/- S.D.) during each day in culture and incorporated 3H-labelled amino acids into immunoprecipitable prolactin. In the radioimmunoassay for prolactin, serial dilutions of incubation medium displaced 125I-labelled prolactin parallel to the displacement by pituitary prolactin and the prolactin in the medium eluted from Sephadex G-150 in a position indentical to that of pituitary prolactin. Chorionic explants released prolactin into the incubation medium during day 1 of culture only and did not incorporate 3H-labelled amino acids into prolactin. These results demonstrate that prolactin is synthesized by the decidua and not by the chorion and suggest that the decidua is the source of prolactin in amniotic fluid.
Explants of human chorion-decidual tissue obtained at delivery from normal, full-term pregnancies synthesize and secrete prolactin. This hormone is indistinguishable from pituitary prolactin by chromatographic, electrophoretic, immunologic, and receptor assay techniques. These results suggest that chorion-decidua may be the source of the large quantities of prolactin in amniotic fluid.
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Arginine has been demonstrated to be a potent stimulus to GH and PRL secretion. To determine the effect of arginine on plasma ovine placental lactogen (oPL) concentrations, arginine (50 g in 350 ml distilled water, pH 7.4) or hypertonic saline of identical volume, osmolality, and pH was infused iv over a 30-min period into nine pregnant ewes, and blood samples from chronic indwelling venous catheters were obtained at frequent intervals before and for 8 h after the infusions. After the infusion of hypertonic saline, plasma oPL concentrations (measured by homologous RIA) decreased 20--50% over 1--2 h and then returned to baseline concentrations. After the infusion of arginine, plasma oPL concentrations also decreased by 20--50% for 1--2 h. However, 2--3 h after the infusion, plasma oPL concentrations in creased 79--115% (delta = 204--700 ng/ml) over preinfusion concentrations in seven ewes and 454% (2930 ng/ml) and 1142% (2042 ng/ml) in two ewes and remained elevated for the remainder of the 8-h interval. When the amount of arginine infused was reduced from 50 to 25 g, an increase in plasma oPL concentrations occurred in only one of five ewes. Plasma oPL concentrations increased by 8--58% after infusions of 50 g alanine or glycine but did not increase after 50 g glutamic acid. The delayed oPL response to arginine suggests that the increase in plasma oPL concentrations is not caused directly by arginine but rather by changes in the synthesis, secretion, and/or degradation of oPL induced indirectly by arginine.
The concentrations of ovine placental lactogen (oPL) have been determined in maternal plasma, umbilical cord plasma, and allantoic fluid by an homologous radioimmunoassay for oPL which is sensitive to 0-1 ng hormone. Ovine placental lactogen was first detected in maternal plasma at 41-50 days of gestation and reached a peak concentration of 2547 +/- 226 (S.E.M.) ng/ml at 121-130 days in ewes with singleton gestations. The oPL concentration in cord plasma was 336-4 +/- 60-3 ng/ml and in allantoic fluid was 29-6 +/- 6-4 ng/ml. After surgical removal of the placenta, oPL disappeared from maternal plasma with a half-life of 29-1 +/- 1-3 min.
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The influence of Tuftsin, the synthetic phagocytosis-stimulating tetrapeptide (L-threonyl-L-lysyl-L-prolyl-L-arginine), on the nitrous blue tetrazolium (NBT) reduction by human polymorphonuclear leukocytes was investigated. It was found that this substance increases the NBT reduction by approximately as much as endotoxin. Other tetrapeptides do not share this property. When Tuftsin analogs are added to the cell suspension and incubated, they prevent the action of both Tuftsin and endotoxin but not of methylene blue. When washed of the analogs, the cells regain the property to be activated by both Tuftsin and endotoxin. It appears that methylene blue on one hand and Tuftsin and endotoxin on the other hand have different sites for their actions. We suggest that whereas methylene blue diffuses into the cell and acts directly upon the hexosemonophosphate shunt activation, Tuftsin and endotoxin appear to act on the cell membrane binding to specific receptors. By treating the cells with Tuftsin analogs, we probably block these receptors.
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The dynamics of prolactin release from human decidual explants were studied under basal conditions, in response to decidual prolactin-releasing factor (PRL-RF), and in response to PRL-RF in the presence of decidual prolactin release-inhibitory factor (PRL-IF) or other factors known to inhibit prolactin release in static cultures. Explants were perifused with medium at a rate of 6 ml/h, and the medium was collected at 5 min intervals. The explants released prolactin for up to 20 h without evidence of cell necrosis, with the rate of prolactin decreasing gradually from 3.9 +/- 0.1 ng/5 min during the first 2 h to 2.2 +/- 0.1 ng/5 min during the last 2 h of exposure. PRL-RF, a 23.5 KMr protein released by the placenta, stimulated a dose-dependent increase in prolactin release from the perifused explants that occurred within the first 5 min of exposure and persisted until the exposure to the releasing factor was discontinued. PRL-IF, a 35-45 K Mr protein released by the decidua, caused a dose-dependent inhibition of PRL-RF-mediated prolactin release. Dibutyryl cAMP, cholera toxin, sn-1, 2-dioctonylglycerol, PMA, and arachidonic acid, which inhibit basal prolactin release from static decidual cultures, also caused a dose-dependent inhibition of prolactin release in response to PRL-RF. In each instance, the maximal dose of the agents tested inhibited PRL-RF-mediated prolactin release by greater than 84 per cent. These results indicate that the stimulation of prolactin by PRL-RF is inhibited by PRL-IF and pharmacologic agents that inhibit basal prolactin release.(ABSTRACT TRUNCATED AT 250 WORDS)