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Biomedical subjects

B Posner

Publications and source records attributed to B Posner.

At least 19 recordsLinked to original sources

Octreotide inhibits insulin-like growth factor-I hepatic gene expression in the hypophysectomized rat: evidence for a direct and indirect mechanism of action.

Somatostatin and somatostatin analogs are known to interact with the GH-insulin-like growth factor (IGF)-I axis by inhibiting GH secretion and consequently hepatic IGF-I production. Indirect evidence suggests that octreotide, a somatostatin analog, reduces serum IGF-I levels relatively more than expected from GH reduction, implying a GH-independent pathway of action. To study the role of octreotide in the regulation of IGF-I production, independently of endogenous GH, we used the hypophysectomized (hypox) rat to measure hepatic IGF-I expression and also employed cultured rat hepatocytes to examine whether octreotide has any direct effect on the production of IGF-I. Forty male hypox Sprague-Dawley rats were randomized into 4 groups to receive daily injections for 3 days of either saline, human GH (hGH) (100 g), octreotide (100 g twice), or both hGH (100 g) and octreotide (100 g twice). GH stimulated serum IGF-I levels to 104 +/- 10 micrograms/liter as compared to saline (26 +/- 2 micrograms/liter). Octreotide alone had no effect, but combining octreotide and hGH significantly reduced the hGH-induced rise in the IGF-I levels (52 +/- 6 micrograms/liter). The relative expression of hepatic IGF-I in the rats treated with hGH increased by 4-fold compared to that in the saline-treated rats. Octreotide administered simultaneously with hGH potently blocked the hGH-induced IGF-I expression to control levels. In cultured hepatocytes, IGF-I mRNA levels maximally stimulated by combining bGH and glucagon were significantly inhibited in the presence of octreotide at low concentrations (0.3 and 3 ng/ml) by 25% and 45%, respectively. In contrast, high concentrations of octreotide (30 and 300 ng/ml) had no significant effect on IGF-I mRNA abundance. We conclude that: 1) octreotide inhibits IGF-I serum levels and hepatic gene expression in the hypox rat; and 2) octreotide can inhibit partially the direct effects of GH and glucagon on hepatic IGF-I production.

Animals

Insulin and the efficacy of total parenteral nutrition.

This study examined the effect of insulin on the efficacy of total parenteral nutrition (TPN). Patients were randomized to receive either crystalline zinc insulin (CZI) in each liter of TPN solution (insulin group) or no additional insulin (control group). The efficacy of TPN was evaluated by measuring body composition at 2-wk intervals. In malnourished patients the body cell mass (BCM) increased significantly with 2 wk of TPN both with and without additional insulin. The rate of change of BCM was correlated to the total caloric intake, serum insulin concentration, age, and nutritional state. The resulting multiple linear regression demonstrated that the restoration of a depleted BCM was directly related to the caloric intake, plasma insulin concentration, and degree of malnutrition and was inversely related to age. The addition of insulin to TPN solutions increases the rate at which a malnourished state is corrected.

Adult

Catecholamine-secreting paraganglioma of glomus jugulare region.

A 43-year-old woman had clinical and biochemical evidence of a secreting paraganglioma of the glomus jugulare region. Catecholamine secretion was exacerbated during embolization of the tumor before surgery and resulted in a life-threatening vasomotor attack. Preoperatively, pharmacologic blockade of excessive catecholamine secretion with prazocin controlled her blood pressure, tachycardia, and symptoms. The tumor was resected and its catecholamine content measured. This case is reported to stress the importance of adequate preoperative assessment of patients with paragangliomas of the head and neck. The extreme rarity of catecholamine-secreting tumors of this region should not lead us to underestimate the morbidity and mortality of such patients undergoing surgery or any other invasive procedure whether the diagnosis is confirmed or only suspected.

Adult

Effect of chronically elevated androgen or estrogen on the glucose tolerance test and insulin response in female rhesus monkeys.

Insulin concentrations, in response to an intravenous glucose bolus after a 24-hour fast, have been studied in female rhesus monkeys in which the circulating levels of androstenedione and testosterone or estrone and estradiol have been increased for as long as 4 1/2 years. No significant differences were observed in the basal insulin or C-peptide concentrations in the androgen or estrogen-treated animals compared with each other or with normal cycling, nontreated control animals. The insulin and C-peptide responses to intravenous glucose were similar in control and androgen-treated monkeys. Compared with both the control and androgen-treated monkeys, the responses of the estrogen-treated monkeys tended to be lower but were not significantly different. The glucose disappearance rate after the intravenous glucose bolus was not significantly different in androgen and control monkeys but was significantly slower during the initial 30 minutes in the estrogen-treated monkeys compared with both the control and androgen-treated monkeys. These studies suggest that chronically elevated androgen levels in the mature female subhuman primate do not lead to insulin resistance or overt glucose intolerance.

Androstenedione

Receptors for insulin-like growth factors in rabbit articular and growth plate chondrocytes in culture.

Receptors for the insulin-like peptide ILAs have been identified in cultured rabbit chondrocytes. The cell-ILAs interaction is a time-dependent, reversible and saturable process. The cell-bound radioactive material appears as intact hormone. Insulin-like growth factor II (IGFII) is as potent as ILAs in competing for 125I-ILAs binding, whereas insulin-like growth factor I is somewhat less potent. Insulin does not affect ILAs binding. Our results suggest that the cultured chondrocytes possess a common receptor for the somatomedin peptides and that insulin, which is able to stimulate sulfate incorporation into proteoglycans, acts through an insulin receptor distinct from the somatomedin site. In growth plate chondrocytes the specific binding of 125I-ILAs is ten times lower than in articular cells in culture, whereas the sulfation activity of ILAs, at all concentrations studied, is 2.5-3 times lower in growth plate than in articular chondrocytes. The total binding of 125I-ILAs is higher to a particulate cell fraction than to intact cultured cells, by a factor of 10 for the growth plate cells, and by a factor of 2 for the articular cells. These findings suggest a poor accessibility of the hormone to the receptor sites of the growth plate chondrocytes in cultures, which are known to be surrounded by a thick matrix.

Animals

Development of growth hormone receptors in rabbit and lamb liver after hypophysectomy.

The prolactin receptors of rat liver are pituitary-dependent, and previous studies have shown that prolactin itself plays a role in inducing and maintaining their presence. This study tried to determine if hepatic growth hormone (GH) receptors are comparably dependent on the pituitary. Young 47-day and older 116-day old rabbits were either hypophysectomized (H) or sham-operated (S). Hypophysectomy completely arrested the growth of the older rabbits but only reduced it by 50 p. 100 in the young ones. After 21 days, the specific binding (sb) of 125I-labelled human GH (hGH) to liver membranes was measured in H and S animals. The sb of hGH in H rabbits compared to S animals (older, young) was 14.9 p. 100 in older H rabbits and 45.5 p. 100 in young H animals. Similar studies in lambs showed that the sb of hGH in H lambs (compared to S animals) was 23.9 p. 100. When some H lambs were treated with 1 mg/kg of oGH or bGH 3 times per week, the sb of hGH was significantly increased to 56.1 p. 100 of the S levels. All changes in sb reflected changes in receptor number, as shown by the dose response binding curves. This study demonstrates that hepatic GH receptors in both the rabbit and the lamb are pituitary-dependent. The level in rabbits is correlated with the growth rate. Since GH receptor levels were partially restored in GH-treated lambs, it is possible that GH plays a role in inducing its own receptors.

Animals

Seminal fluid prolactin: studies in normal subjects and in hypergonadotropic oligospermia.

A sensitive radioimmunoassay was developed for the determination of seminal plasma prolactin levels. Prolactin added to normal or oligospermic seminal plasma was fully recoverable, indicating that the seminal plasma of oligospermic patients did not contain interfering substances. A gradient between seminal plasma blood serum prolactin was found in 54 health fertile subjects. No gradient was demonstrable among 13 infertile oligospermic patients who had normal levels of serum testosterone and luteinizing hormone but elevated levels of follicle-stimulating hormone.

Follicle Stimulating Hormone

Increased plasma somatomedin reactivity in chronic renal failure as determined by acid gel filtration and radioreceptor assay.

Plasma Somatomedin (SM) reactivity has been determined in patients with chronic renal failure and in normal children by radioreceptor assay (RRA) following acid gel filtration on Sephadex G-100. Total small molecular weight SM reactivity was obtained by the summation of all values between Kav 0.55 to 0.75. The mean SM reactivity (+/-SE) for the renal failure group (N = 9) was 154 +/- 10 ng/ml and for the normal subjects (N = 9) was 91 +/- 5 ng/ml (p less than .001). The renal failure group also had significantly increased mean levels of insulin, GH and PRL, but individual increases were not always concordant. Our data reveal that small molecular weight SM reactivity as determined by RRA of column eluates is increased in chronic renal failure compared to normal controls. Thus SM reactivity is not low in chronic renal failure, supporting the suggestion that peripheral antagonism to SM action contributes to the growth failure observed in these patients.

Adolescent

[Culture of normal and pathological human growth cartilage. Action of vitamin D derivatives and somatomedin].

Chondrocytes from normal cartilage of a 2 month old child have been cultured. In vitro the cells maintained their morphological identity and synthesised proteoglycans with electrophoretic properties similar to those synthesised by cartilage in vivo. Sulphation was stimulated by vitamin D metabolites and by somatomedin. This technique has been used to study biopsies of abnormal cartilage.

Cartilage, Articular

Two days richer.

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Adult

The party.

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Arizona