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N V Costrini

Publications and source records attributed to N V Costrini.

14 recordsLinked to original sources
PubMed1983

Epidermal growth factor-urogastrone receptors in normal human liver and primary hepatoma.

Epidermal growth factor-urogastrone (EGF-URO) receptors have been demonstrated in rodent liver and modulation of ligand binding during transformation has been shown in a variety of study systems. A patient presented with a resectable primary hepatoma arising in a histologically normal liver. We carried out ligand binding studies using 125I-EGF and homogenates or plasma membrane preparations of normal and hepatoma tissues. EGF-URO receptors were demonstrated in normal human liver; half-maximal binding occurred at 2.5 X 10(-9) M 125I-EGF. Binding decreased in association with hepatoma formation. These results provide initial evidence that EGF-URO receptors exist in human liver and that ligand binding changes accompany hepatoma formation in man.

Carcinoma, Hepatocellular↗
PubMed1982

The chief medical residency: a description and recommendations.

Individuals occupying the position of chief medical resident have the opportunity to influence significantly the quality and tenor of medical education and medical practice. To assess the status of the position, the authors surveyed chief medical residents completing their tenure in 1980. These residents distributed their time among administrative (41 percent), teaching (35 percent), patient care (21 percent), and research (3 percent) activities. They reported that their experience was quite positive. However, overall satisfaction was significantly negatively correlated with percentage of time spent performing administrative tasks. The percentage of time chief medical residents allocate to administration has increased during the past decade, while time spent teaching and delivering patient care has decreased. Based upon this survey, recommendations for improved utilization of the time and talents of these individuals are presented.

Education, Medical↗
PubMed1981

Lectin-induced inhibition of nerve growth factor binding by receptors of sympathetic ganglia.

Nerve growth factor (NGF) initiates a pleiotypic response in numerous tissues derived from the neural crest by binding to specific plasma membrane receptors. In sympathetic ganglia this receptor has been characterized as a highly asymmetric, minimally hydrophobic, intrinsic membrane protein with a molecular weight of 135,000 (Costrini et al., 1979b). To further characterize this moiety we assessed the effects of lectins on 125I-NGF specific binding to preparations of particulate and nonionic detergent-extracted microsomal receptors of rabbit superior cervical ganglia (SCG). Concanavalin A (Con A) and wheat germ agglutinin (WGA), but not soybean agglutinin or Ulex europaeus 1, induced a concentration-related, carbohydrate-specific decrease in 125I-NGF binding. Following Con A exposure, 125I-NGF specific decrease in 125I-NGF binding. Following Con A exposure, 125I-NGF specific binding to particulate SCG receptors was maximally reduced to 23% of control values. WGA similarly reduced NGF binding to particulate microsomal receptors to 37% of control values. Scatchard analysis of growth factor binding following Con A exposure indicated that this lectin effect was principally due to a sixfold reduction in maximum receptor affinity. Lectin-associated impairment of NGF binding was also demonstrated by using a Triton X-100 solubilized receptor preparation. These results provide evidence that the high-affinity-state NGF receptor of SCG is a glycoprotein containing N-acetylglucosamine and alpha-D-mannopyranoside residues. These residues are probably located in close proximity to the growth factor binding region of the NGF receptor.

Animals↗
PubMed1979

Reduction by reserpine of the accumulation of retrogradely transported [125I]nerve growth factor in sympathetic neurons.

Experiments were carried out to determine if stimuli which augment preganglionic nerve activity to sympathetic neurons, and thereby cause trans-synaptic induction, increase the retrograde transport of nerve growth factor (NGF). It was found that nerve activity had no effect on retrograde transport of [125I]NGF. It was found, however, that reserpine decreased retrograde transport of [125I]NGF and this inhibition was characterized. Reserpine decreased the maximal accumulation of intravenously administered [125I]NGF in superior cervical ganglia (SCG) by about 60%. It also caused a distinct shift in the time course of accumulation so that maximal accumulation was seen 12 h after [125I]NGF injection rather than at 9 h as in control animals. Reserpine had no effect on retrograde transport in sensory neurons. Dose--response curves showed that maximal inhibition occurred with doses of reserpine of 2.5 mg/kg i.p. and that reserpine was not able to completely block transport at any dose. The maximal inhibition of retrograde transport was achieved within 30 min of reserpine administration and inhibitory activity was unchanged for 36 h. The ability of sympathetic neurons to transport [125I]NGF subsequently recovered and was normal 96 h after reserpine administration. The inhibitory effect of reserpine appears to be due to an action at or very near to the nerve terminal since it was effective at reducing NGF transport at very low doses (0.33 microgram) when co-administered directly into the eye with [125I]NGF. An action of reserpine at the nerve terminal was further suggested by the inability of reserpine to affect transport if the drug was given 4 h after [125I]NGF administration. Based upon these data, it is suggested that there may be two pools of retrogradely transported NGF and that only more rapidly turning over pool is reserpine-sensitive. This pool may represent the retrogradely moving synaptic vesicles or some derivative of the vesicles.

Animals↗
PubMed1979

Physical properties of the detergent-extracted nerve growth factor receptor of sympathetic ganglia.

The nerve growth factor (NGF) receptor from microsomes of adult rabbit superior cervical ganglia has been solubilized with Triton X-100 and sodium deoxycholate. The physical properties of the detergent-extracted NGF receptor were assessed by Sepharose 6B chromatography and sucrose density gradient ultracentrifugation studies in H2O and D2O. The predominant form of the NGF receptor has a Stokes radius of 71 A, a partial specific volume of 0.74 ml/g, a sedimentation coefficient of 4.3 S, and a frictional ratio of 1.8. From these parameters, it can be calculated that the NGF receptor in Triton X-100 is a minimally hydrophobic, highly asymmetric, intrinsic membrane protein with a molecular weight of approximately 135,000. A form of the receptor with a sedimentation coefficient of 10.4 S was occasionally seen which appears to represent an aggregated form of the 4.3 S moiety.

Animals↗
PubMed1979

Binding characteristics and apparent molecular size of detergent solubilized nerve growth factor receptor of sympathetic ganglia.

Nerve growth factor (NGF), a hormone-like regulator of sympathetic neuron ontogeny and metabolism affects its target cells initially by associating with specific plasma membrane receptors. We have solubilized the NGF receptor of adult rabbit superior cervical ganglia (SCG) with the nonionic detergent Triton X-100. The high-affinity equilibrium binding constant of the detergent-extracted receptor is 2-8 x 10(-10) M. Gel chromatography of the receptor or the 125I-labeled NGF receptor complex on a column of Sepharose 6B indicated, in both cases, a single component of an apparent hydrodynamic radius of 71 +/- 5 A. In parallel investigations, we have confirmed the similarity between the hydrodynamic size of the NGF receptor of rabbit SCG and that of the insulin receptor of IM-9 lymphocytes evaluated by similar methods.

Animals↗
PubMed1977

Effect of insulin, glucose, and controlled diabetes mellitus on human jejunal function.

The effects of serum insulin concentration, serum glucose concentration, and of insulin-dependent diabetes mellitus on human jejunal glucose, Na, and H2O absorption were assessed. Triple-lumen perfusion studies were carried out in 20 nondiabetic and 9 insulin-requiring diabetic male volunteers. In seven normal subjects, sequential elevation of serum insulin concentrations from 20 muU/ml to 50 and 100 muU/ml for 2 h each, with maintenance of constant serum glucose levels, failed to significantly alter glucose, Na, and H2O absorption. Absorption of glucose, Na, and H2O was similar when the serum glucose concentration was maintained at 125 and at 250 mg/100 ml. Glucose absorption results during 26 perfusion studies in 20 control subjects were compared with results obtained during 20 perfusion studies in 9 diabetic subjects. Glucose concentrations in isotonic perfusates were 25, 40, or 75 mM. Na and H2O absorption rates were similar in both groups. Regression lines relating glucose load or geometric mean study segment glucose concentration to glucose absorption were also comparable. These results indicate that insulin-requiring diabetics absorb glucose, Na, and H2O normally.

Adult↗
PubMed1971

Relative effects of pregnancy, estradiol, and progesterone on plasma insulin and pancreatic islet insulin secretion.

Influences of estrogen and progesterone on the development of hyperinsulinemia and augmented pancreatic islet insulin secretion during pregnancy were assessed in this study. Groups of female rats were injected subcutaneously for 21 days with varying daily dosages of estradiol benzoate or progesterone in oil. On day 21, pancreatic islets were isolated by a collagenase method. Total insulin secretion was measured after 90-min incubations of 10 islets in buffered medium containing glucose. Higher physiologic dosages of estradiol or progesterone, singly or in combination, significantly increased islet secretion above values of untreated control rats and were comparable to augmented islet responses of term, 3-wk pregnant rats. Diameter and protein content of islets obtained from steroid-treated and pregnant rats exceeded control measurements in these instances. However, 2-hr preincubations of control islets with 1 or 10 mug/ml of either steroid did not influence subsequent glucose-stimulated insulin output. In related studies, plasma insulin responses during 30 min intravenous glucose tolerance tests were significantly above control responses in term-pregnant rats and animals receiving comparable dosages of steroids for 3 wk. Unlike pregnancy or progesterone treatment, estradiol administration alone or with progesterone significantly lowered postchallenge plasma glucose concentrations. These results indicate that estradiol and progesterone contribute to enhanced islet insulin secretion and plasma insulin responses to glucose administration during pregnancy. This change is not acutely produced but can be related to hypertrophy of islets following chronic hormonal administration. Although the data do not distinguish between direct and indirect beta-cytotrophic effects of these sex steroids, metabolic actions of estradiol and progesterone may differ, since estrogen treatment lowers plasma glucose curves following the induction of hyperinsulinemia.

Animals↗
PubMed1971

Plasma insulin disturbances in primary hyperparathyroidism.

Plasma insulin dynamics were evaluated in 10 patients with primary hyperparathyroidism before and after parathyroidectomy and correction of hypercalcemia. Before surgery fasting plasma insulin concentrations and insulin responses to administered glucose, tolbutamide, and glucagon were significantly greater than postoperative values. Hyperinsulinemia was not associated with altered glucose curves during glucose or glucagon tolerance tests, but a relatively greater insulin response to tolbutamide resulted in an increased hypoglycemic effect following its administration. The glucose-lowering action of intravenous insulin was slightly impaired before treatment. Intramuscular injections of parathormone to six normal men for 8 days induced mild hypercalcemia and hypophosphatemia and reproduced augmented plasma insulin responses to oral glucose and intravenous tolbutamide. 4-hr intravenous infusions of calcium to another group of six normal men raised serum calcium concentrations above 11 mg/100 ml. This did not alter glucose or insulin curves during oral glucose tolerance but markedly accentuated insulin responses to tolbutamide and potentiated its hypoglycemic effect. When highly purified parathormone was incubated with isolated pancreatic islets of male rats, glucose-stimulated insulin secretion was unaffected. These findings suggest that chronic hypercalcemia of hyperparathyroidism sustains a form of endogenous insulin resistance that necessitates augmented insulin secretion to maintain plasma glucose homeostasis. This state is insufficient to oppose tolbutamide-induced hypoglycemia because of an additional direct, selective enhancement of hypercalcemia on pancreatic beta cell responsiveness to the sulfonylurea. The possible direct role of parathormone in these events has not been established.

Adenoma↗