Biomedical subjects
D M Styne
Publications and source records attributed to D M Styne.
Growth hormone treatment for short stature.
Fifteen short but otherwise normal children, 4.3 to 15.5 years old, with heights greater than 3 S.D. below the mean value for age, growth rates less than or equal to 5.0 cm per year, and normal serum levels of immunoreactive growth hormone in response to provocative stimuli (peak greater than or equal to 10 ng per milliliter) were treated with intramuscular injections of pituitary growth hormone (0.1 U per kilogram) three times weekly for six months, as were 14 children with documented growth hormone deficiency. In all the latter children growth rate increased by more tan 2.0 cm per year during treatment. In 6 of the 14 short normal children who remained prepubertal, growth rate also increased, by 2.2 to 4.2 cm per year during treatment; four of these children had normal base-line serum somatomedin C concentrations. In both short normal children and children with growth hormone deficiency, the increment in serum somatomedin C concentrations after 4 or 10 daily injections of growth hormone correlated with bone age but not with later growth or growth hormone levels. Among the short normal children, those who responded to growth hormone were younger and had a greater delay in bone age and a slower pretreatment growth rate than the nonresponders. These observations suggest that a dose of growth hormone comparable to that used for the treatment of hypopituitarism increases growth rate in some short normal children.
Interactions of a monoclonal antibody to the insulin receptor with receptors for insulin-like growth factors.
A monoclonal antibody to the human insulin receptor was tested for its ability to inhibit the binding of 125I-insulin-like growth factor I (IGF-I) and 125I-insulin-like growth factor II (IGF-II) to their receptors in human placenta membranes and cultured human IM-9 lymphocytes. In both placenta membranes and IM-9 cells, the antibody progressively inhibited the binding of 125I-IGF-I to its receptor with a potency that was 300-fold less than its ability to inhibit the binding of 125I-insulin to its own receptor. In contrast, in human placenta membranes, this antibody inhibited the binding of 125I-IGF-II to its receptor only slightly. These studies indicate, therefore, that this monoclonal antibody binds preferentially to the insulin receptor but also crossreacts to a lesser extent with the IGF-I receptor.
Hormone ontogeny in the ovine fetus. XVI. Plasma immunoreactive somatomedin C/insulin-like growth factor I in the fetal and neonatal lamb and in the pregnant ewe.
The basic somatomedins [SMC/insulin-like growth factor I (IGF-I)] and the neutral somatomedins (multiplication-stimulating activity/IGF-II) exhibit different patterns during pregnancy and ontogeny. We have adapted a specific RIA for SMC/IGF-I to study the pattern of change of this growth factor in fetal, neonatal, and adult sheep plasma. Acid-ethanol extraction of the samples was performed to minimize the interference of the somatomedin-binding proteins in the RIA. Results are expressed in terms of a neonatal lamb reference plasma with an arbitrarily assigned potency of 1 U/ml (equivalent to 500 ng/ml purified human IGF-I). In chronically catheterized fetal and neonatal lambs, plasma SMC/IGF-I rose from 0.14 +/- 0.02 U/ml before 100 days of gestational age (term 147 days) to 0.22 +/- 0.01 U/ml between 101 and 144 days. In neonates (1-33 days), the mean plasma concentration of SMC/IGF-I was 0.93 +/- 0.07 U/ml. In adult sheep, plasma SMC/IGF-I was twice as high in rams as in nonpregnant ewes (0.88 +/- 0.06 vs. 0.44 +/- 0.03 U/ml); in pregnant ewes plasma SMC/IGF-I did not change significantly between the second and the last third of gestation and was always higher than the fetal levels. The rise in fetal plasma SMC/IGF-I around 100 days of gestation parallels the rise in fetal GH and PRL concentrations. The discrepancy between the present results and earlier reports based on bioassays and radioreceptor assays may be due to the presence of high circulating concentrations of IGF-II-like peptides in the ovine fetus. The striking sex difference in the plasma concentrations of SMC/IGF-I in adult sheep suggests that SMC/IGF-I generation or disposition is influenced by sex steroids.
Endocrine, histological, and biochemical studies of adrenocorticotropin-producing islet cell carcinoma of the pancreas in childhood with characterization of proopiomelanocortin.
Two 8-yr-old children, a boy and girl, are described with Cushing's syndrome secondary to ectopic ACTH-secreting pancreatic islet cell carcinomas. The girl, seen 28 yr ago, had strong presumptive evidence of ectopic ACTH production and hypercalcemia. The boy, studied recently, had strikingly elevated concentrations of plasma ACTH (1,500 pg/ml) and beta-lipotropin (beta LPH; 2,500 pg/ml) and showed no suppression of urinary 17-hydroxycorticoids or cortisol with low and high dose dexamethasone. He had increased plasma calcitonin (257 pg/ml), glucagon (442 pg/ml), lactate dehydrogenase (497 IU/liter), and alpha-fetoprotein (5,144 pg/ml). He also had hypokalemic alkalosis with elevated plasma deoxycorticosterone (70 ng/ml) and PRA (6.9 ng/ml.h) but normal plasma aldosterone (8.2 ng/dl) and 18-hydroxycorticosterone (7.6 ng/dl). Preoperative localization of the tumor was accomplished by computed tomographic scan of the abdomen with concurrent barium enema. Cell-free translation of the tumor mRNA produced authentic proopiomelanocortin of 35,000 mol wt, indicating that the ACTH and beta LPH were produced by the tumor from a common precursor. After removal of a large amount of metastatic tissue from the boy, clinical progression of the remaining tumor was monitored by measuring plasma ACTH and beta LPH. Episodic secretion of ACTH and beta LPH was demonstrated by taking frequent plasma samples while suppressing pituitary ACTH with oral dexamethasone. Chemotherapy and radiation proved ineffective in controlling the growth of his tumor.
CT localization of occult secretory tumors in children.
Three seemingly occult secretory tumors in children (pheochromocytoma, ganglioneuroblastoma and islet cell carcinoma) were localized within the abdomen by computed tomography after other diagnostic imaging procedures had failed. The superb density resolution and tomographic formating of CT images make CT uniquely suited for the demonstration of small abdominal lesions. CT is recommended as a primary imaging modality for secretory tumors in children.
Improved recovery of somatomedin activity from plasma by prolonged formic acid extraction.
Recovery of somatomedin activity from plasma fractions was increased approximately 5-fold by prolonged extraction of isolates with formic acid. Extraction for 72 hours enhanced the yields of active peptides in the 6,000, 8,000 and > 20,000 dalton range. Yields of smaller peptides were similar following short (2 hrs) and long (72 hrs) extraction periods. Active fractions obtained after prolonged extraction possessed sulfation activity and insulin-receptor affinity comparable to somatomedin isolated during short extraction with formic acid.
Plasma glycoprotein hormone alpha-subunit in the neonate and in prepubertal and pubertal children: effects of luteinizing hormone-releasing hormone.
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Plasma glycoprotein hormone alpha-subunit in the syndrome of gonadal dysgenesis: the effect of estrogen replacement in hypergonadotropic hypogonadism.
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Normal and abnormal puberty in the female.
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Hormone ontogeny in the ovine fetus. IV. Serum somatomedin activity in the fetal and neonatal lamb and pregnant ewe: correlation with maternal and fetal growth hormone, prolactin, and chorionic somatomammotropin.
Somatomedin (SM) activity was measured by a placental membrane receptor assay using 125I-labeled somatomedin A, as radioligand in serum samples obtained from 33 ovine fetuses, 14 neonatal lambs, 8 pregnant, and 3 postpartum ewes. The mean serum concentration of SM activity in eight adult rams was 2.06 +/- 0.12 U/ml. In fetal sheep, SM activity was detected at 66 days gestation (term 147 days), in the youngest fetus studied. Before 100 days of gestation, SM was lower (P less than 0.001) in fetal sheep (1.08 +/- 0.18 U/ml) than in adult rams. In fetuses between 101 and 125 days, SM rose (P less than 0.001) to 2.64 +/- 0.32 U/ml. In late gestation fetal serum SM fell but during the neonatal period it rose to 3.38 +/- 0.3 U/ml, higher (P less than 0.01) than that in adult rams. Serum SM activity in the pregnant ewe prior to 100 days was 1.01 +/- 0.11 U/ml, increased (P less than 0.05) to 1.75 +/- 0.21 U/ml between 125 days and term, and rose further to 2.56 +/- 0.32 U/ml in the postpartum period. Maternal concentrations of serum SM in late gestation were significantly less than in the fetus. Gel chromatography of fetal, maternal, and neonatal sera indicated that over 90% of SM activity circulated in high-molecular weight form. The rise in SM activity in fetal serum between 100 and 125 days parallels the rise in fetal growth hormone and prolactin concentrations; however, in maternal serum the increase in SM activity is associated with rising maternal chorionic somatomammotropin concentrations.
Immunoreactive somatostatin and luteinizing hormone releasing hormone in median eminence synaptosomes of the rat: detection by immunohistochemistry and quantification by radioimmunoassay.
Somatostatin and LHRH were detected by radioimmunoassay in the synaptosome fraction obtained by homogenization and differential centrifugation of the rat median eminence. Both somatostatin and LHRH were demonstrated by electron microscopic immunocytochemistry in secretory granules within synaptosomes.