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Biomedical subjects

D Rabinowitz

Publications and source records attributed to D Rabinowitz.

At least 55 records · Page 3Linked to original sources
PubMed1978

Glucose metabolism in intact man: the responsiveness of splanchnic and peripheral tissues to insulin.

Man controls his blood sugar concentration within rather narrow limits, despite wide latitude in the content and timing of meals. Man does not eat constantly; rather, he alternates between periods of "feasting" and "fasting." It is a useful generalization that the metabolic environment is altered such that forces promoting substrate storage are dominant during the postprandial period and forces that encourage substrate mobilization are prominent during food-free intervals. In this report, we shall primarily examine the role of insulin, the hormone of carbon storage, in maintaining glucose homeostasis during a 24-hr period. In particular, we wish to highlight (A) possible important differences in the dose response curves of insulin in splanchnic and peripheral tissues and (B) the modulating influences of hyperglycemia and glucagon on insulin's effects across the splanchnic bed.

Adipose Tissue↗
PubMed1978

Induction of spermatogenesis in hypogonadotrophic hypogonadism.

A young male who presented with isolated bihormonal gonadotrophin deficiency is described, Basal levels of LH and FSH were low and there was no response to clomiphene citrate or LHRH. The remaining anterior pituitary function was intact. The administration of a combination of human menopausal gonadotrophin and human chorionic gonadotrophin caused testicular maturation with spermatogenesis and full androgenization. The patient was able to father a child.

Adult↗
PubMed1978

Persistent stimulatory effect of glucagon on glucose production despite downregulation.

The rise and subsequent return to basal of glucose production (Ra) during a constant glucagon infusion ("downregulation") has suggested to some workers that glucagon's effects are evanescent. To examine whether glucagon displays persistent biological activity even after downregulation, 6 healthy males received an 8 hour infusion of somatostatin and glucagon, with 3H-3-glucose to measure glucose turnover. Ra rose from 2.8 +/- 0.3 to 4.2 +/- 0.3 mg/kg . min at 90 minutes, returned to basal levels at 150 minutes, and remained at this level for the ensuing 330 minutes. Six additional subjects received an 8 hour somatostatin infusion, with glucagon administered concomitantly for the first 5 hours. Glucagon withdrawal at 5 hours produced an immediate decline in Ra from 1.8 +/- 0.2 to 0.9 +/- 0.2 mg/kg . min. Thus, even after downregulation the maintenance of basal Ra is dependent on circulating glucagon.

Adolescent↗
PubMed1978

Characterization of the human chorionic gonadotrophin fractions in pregnancy urine.

The human chorionic gonadotrophin (hCG) preparation (ca. 3000 IU/mg) from pooled pregnancy urine has been fractionated using anion-exchange and gel exclusion chromatography. The various fractions, many of which were heterogeneous, were assayed using radioimmunoassay (RIA) and a testicular radio-receptor assay (RRA). Three fractions were obtained with potencies between 9000 and 20 000 IU/mg); five fractions were characterized by potencies between 1000 and 6000 IU/mg; and four fractions exhibited low potencies (less than 500 IU/mg). A linear relationship between RRA and RIA potency (P) was found to exist for the various fractions: In(PRRA) = 1.14 In(PRIA) - 1.67. The major fractions, which exhibited various potencies, were further characterized by amino acid and carbohydrate analysis. Urine was collected from an individual at various times of gestation, and the hCG fraction was concentrated by benzoic acid and ethanol precipitation. Ion-exchange chromatography of the hCG fraction yielded multiple immunoreactive components throughout pregnancy; thus the observed heterogeneity in the commercial preparation does not appear to result from processing pooled urine from numerous donors. Also, heterogeneity was observed in an individual donor whose urine was not treated with the benzoic acid and alcohol fractionation scheme. It seems indisputable that individual urinary hCG is heterogenous, and this does not appear to reflect isolation artefacts.

Amino Acids↗
PubMed1978

Pituitary and adrenal function in normal women after treatment with Lergotrile mesylate.

We studied the effects of a dopaminergic agonist, 2-chloro-6-methyl-ergoline-8-beta-acetonitrile methanesulfonate (LERGOTRILE mesylate), on the pituitary and adrenal function of five normal women. No changes were observed in basal serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH) and cortisol levels, in LH and FSH levels after luteinizing hormone-releasing hormone (LH-RH) stimulation, or in GH and cortisol levels during insulin-induced hypoglycemia. Lergotrile treatment produced a fall in basal prolactin and thyrotropin (TSH) levels and there was dissociation in the responses of the women to thyrotropin-releasing hormone: attenuation of TSH release, but retention of prolactin release.

Acetonitriles↗
PubMed1977

Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man.

To investigate the role of glucagon in regulating hepatic glucose production in man, selective glucagon deficiency was produced in four normal men by infusing somatostatin (0.9 mg/h) and regular pork insulin (150-muU/kg per min) for 2 h. Exogenous glucose was infused to maintain euglycemia. Arterial plasma glucagon levels fell by greater than 50% whereas plasma insulin levels were maintained in the range of 10-14 muU/ml. In response to these hormonal changes, net splanchnic glucose production (NSGP) fell by 75% and remained suppressed for the duration of the study. In contrast, when somatostatin alone was administered to normal men, resulting in combined insulin and glucagon deficiency (euglycemia again maintained), NSGP fell markedly but only transiently, reaching its nadir at 15 min. Thereafter, NSGP rose progressively, reaching the basal rate at 105 min. These data indicate that the induction of selective glucagon deficiency in man (with basal insulin levels maintained) is associated with a marked and sustained fall in hepatic glucose production. We conclude, therefore, that basal glucagon plays an important role in the maintenance of basal hepatic glucose production in normal man.

Adolescent↗
PubMed1977

The nature of the defect in a salt-wasting disorder in Jews of Iran.

Studies in 8 families of Iranian Jews revealed 12 patients with selective aldosterone deficiency due to a biosynthetic defect. There was a marked range in clinical severity which varied from acute salt-wasting crisis in infancy to an asymptomatic state in adults detectable only by biochemical screening. Manifestations of intermediate degrees of severity included unexplained short stature and postural hypotension. This clinical variability in the manifestations of aldosterone deficiency was not due entirely to quantitative differences in hormone secretion but also to a changing pattern of requirement throughout life in which deficiency during the first year of life had grave consequences while a similar degree of deficiency in the adult was well-tolerated, suggesting that the hormone was no longer essential. Most families came from a relatively isolated community in Isfahan with a high incidence of consanguinity and three were related. Aldosterone deficiency was due to an inborn error involving the terminal portion of the biosynthetic pathway and characterized by marked overproduction of glomerulosa zone 18-hydroxycorticosterone relative to aldosterone. The best diagnostic index was the excretory ratio of the major urinary metabolites of these steroids. This ratio, normally less than 3.0, was frequently greater than 100 in untreated patients with this defect. Plasma aldosterone was not a reliable index of the disorder since some patients achieved normal levels but at the expense of marked elevation in plasma renin activity and overproduction of precursors.

Adolescent↗
PubMed1977

Metabolic responses to the administration of angiotensin II, K and ACTH in two salt-wasting syndromes.

Metabolic responses to the administration of Angiotensin II, K and ACTH are described in two salt-wasting syndromes: hypoaldosteronism in Jews from Iran, which is characterized by an enzymic block in the conversion of 18-hydroxycorticosterone to aldosteron; and pseudohypoaldosteronism, a disorder in which aldosterone secretion is high in association with renal tubular unresponsiveness to mineralocorticoids. The response of plasma and urinary aldosterone to K and ACTH is qualitatively normal in hypoaldosteronism; however, infusion of Angiotensin II, in a dose that was pressor and elevated aldosterone levels threefold in control subjects, was only pressor in hypoaldosteronism. In pseudohypoaldosteronism, plasma and urinary aldosterone respond to Angiotensin II, K and ACTH, notwithstanding very high basal hormonal levels.

Adrenocorticotropic Hormone↗
PubMed1977

Dissociation of prolactin responsiveness to TRH and chlorpromazine in women with isolated gonadotropin deficiency.

The hormonal response to luteinizing hormone releasing hormone (LHRH) thyrotropin releasing hormone (TRH) and chlorpromazine has been evaluated in eleven female subjects with the syndrome of isolated bihormonal gonadotropin deficiency (IGD). Following LHRH, all subjects had elevations of both LH and FSH, but the gonadotropin responses were attenuated relative to those observed in normal female subjects studied in the early proliferative phase of the cycle. Similarly, peak TSH levels after TRH were significantly less in subjects with IGD relative to normal controls. Basal prolactin levels were low in the patient group. Prolactin levels following TRH increased at least two-fold in control subjects and in the group with IGD. Conversely, chlorpromazine failed to induce elevations of prolactin in eight of nine females with IGD.

Adult↗
PubMed1977

Salt conservation in familial dysautonomia (Riley-Day syndrome).

In some patients with familial dysautonimia, plasma renin activity shows a paradoxical response to postural stimuli, i.e., levels of plasma renin activity are high when the patient is in the supine position and fall significantly during subsequent ambulation. Furthermore, there is no coordinated release of plasma renin activity and aldosterone. The aim of the present study was to determine whether these findings are accompanied by a disturbance of salt conservation. Six patients were studied in a summer camp while on normal and low-salt diets. Plasma and urinary aldosterone levels rose sharply and appropriately when four of the patients were placed on a low-sodium diet. In these subjects, urinary sodium output fell sharply although three of them failed to attain sodium equilibrium by the third day of the low-sodium regimen. Elevation of early morning plasma renin activity appeared to correlate with an inversion in the normal day-night rhythm in urinary volume.

Adolescent↗
PubMed1975

Chromatin-positive Klinefelter's syndrome with undetectable peripheral FSH levels.

An 18 year old phenotypic man is described with chromatin-positive Klinefelter's syndrome and undetectable peripheral human follicle stimulating hormone levels. The subject manifested chromosomal mosaicism consisting of three stem cell lines (45X; 46XY; and 47XXY). Testicular biopsy specimen showed germinal cell aplasia: the tubules were lined by Sertoli cells only, whereas the Leydig cells appeared normal. Serum human follicle stimulating hormone levels were undetectable and rose to only 5 mIU/ml after the administration of luteinizing hormone releasing hormone. Serum human luteinizing hormone varied between normal and moderately elevated values, and serum testosterone was in the low normal range. We discuss the features which distinguish this syndrome from isolated gonadotropin deficiency and from classic germinal cell aplasia. We suggest that the patient represents a new variant of Klinefelter's syndrome, with failure of human follicle stimulating hormone release secondary to prolonged hypersecretion.

Adolescent↗
PubMed1975

Alpha subunit of glycoprotein hormone: presence in peripheral serum after LHRH.

A method is described for the selective measurement of human luteinizing hormone (hLH) and alpha subunit. The assays employ highly purified tracers of hLH and of subunit of human chorionic gonadotropin (hCGalpha) and a "mixed population" of antibody: Population I (directed against determinants on beta subunit of hCG) and Population II (directed against determinants on alpha subunit of hCG). The former is present in greater concentration than the latter. When the mixed antibody is used at higher dilution (1:1.2x10(6)), Population II is effectively diluted out, and using 125I-labelled hLH as tracer, the assay recognize hLH, hCG and their beta subunits 20-50 times more sensitively than hCGalpha. When the mixed antibody is used at fivefold higher concentration, Population I is present in relative excess and acts as a "sink" for hCG, hLH and their beta subunits. Under these conditions, using 125I-hCGalpha as tracer, the assay recognize the alpha subunit 20 to 50-fold more sensitively than hLH and hCG. These assays have been employed in the study of sera which have been filtered over Sephadex G-100. Alpha subunit was detected in serum within minutes after intravenous injection of luteinizing hormone releasing hormone (LHRH) in four subjects tested.

Adolescent↗
PubMed1975

Heterogeneity of purified human pituitary luteinizing hormone: effect on hormone measurement by radioimmunoassay.

Purified preparations of human luteinizing hormone (hLH), Hartree IRC-2, and NIH LER-960, have been examined after gel filtration of unlabelled and iodinated hormone. Several peaks of radioactivity were observed corresponding to dimeric (peak I), monomeric (peak II), and sub-unit (peak III) lLH forms. The immunologic and receptor activities of each fraction have been evaluated, Receptor activity was found in peaks I and II but not in peak III. Within peak II all fractions were not equally active in the receptor assay, and maximum activity appeared to correspond to molecules with elution characteristics similar to the unlabelled molecule. All fractions of peak II were immunologically active when tested against rabbit anti-hCG in excess. Two immunoassay systems with improved specificity for hLH and hLH-alpha, respectively, have been employed to show the presence of alpha subunit in one of the hLH preparations. These data have relevance with respect to testing of immuno and receptor potencies of hLH preparations.

Animals↗