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Biomedical subjects

D Rabin

Publications and source records attributed to D Rabin.

At least 37 records · Page 2Linked to original sources
PubMed1986

Single dose responses to the gonadotropin-releasing hormone agonist analogue [(imBz 1)-D-His6,Pro9-NEt]GnRH.

The agonist analogue of gonadotropin-releasing hormone (GnRH), [(imBz1)-D-His6,Pro9-NEt]GnRH, has a potency 200 times that of the native hormone in vitro. In single dose studies in man, this analogue resulted in 2- to 4-fold elevation of LH and FSH, and demonstrated a prolonged duration of activity. [(imBz1)-D-His6,Pro9-NEt]GnRH appears to be safe and, as with other analogues of GnRH, may have application to clinical medicine.

Adult↗
PubMed1986

Single subcutaneous doses of a luteinizing hormone-releasing hormone antagonist suppress serum gonadotropin and testosterone levels in normal men.

The ability of single doses of a LHRH antagonist [Ac-delta 3Pro1, 4F-D-Phe2, D-Trp3,6]LHRH (4F-antagonist) to suppress serum gonadotropin and testosterone levels was studied in six normal men. The 4F-antagonist was given sc at four doses: 40, 80, 160, and 320 micrograms/kg body weight. Serum immunoreactive LH, FSH, and testosterone and bioactive LH were measured at intervals for the subsequent 18 h. Serum LH decreased rapidly by (mean +/- SE) 39.7 +/- 2.7%, 41.6 +/- 5.4%, 45.5 +/- 4.7%, and 45.3 +/- 5.4% after each of the four doses. The mean number of LH pulses and their amplitude decreased after each dose and remained suppressed for at least 6 h. After each of the four doses, mean serum FSH levels decreased by 20.0 +/- 4.1%, 33.8 +/- 6.8%, 25.8 +/- 3.6%, and 33.3 +/- 5.7%, and mean serum testosterone levels decreased by 47.7 +/- 7.3%, 55.6 +/- 10.5%, 58.2 +/- 10.8%, and 76.0 +/- 6.0%. Serum testosterone remained low for at least 18 h after the two higher doses. LH bioactivity and the ratio of bioactive LH to immunoreactive LH decreased in all subjects, especially after higher doses of the 4F-antagonist. No side effects or adverse reactions occurred after 4F-antagonist administration, and toxicology studies were negative. These results demonstrate that a single sc injection of this potent LHRH antagonist inhibits the pituitary-gonadal axis in normal men.

Adult↗
PubMed1986

Simultaneous panic and depressive disorder: response to antidepressant treatments.

Recent publications have stressed the relevance of the simultaneous panic disorder and major depressive disorder (MDD) diagnosis from various aspects, including clinical, therapeutic and prognostic, incidence of family psychopathology, and biologic differences. Treatment outcome measures (Hamilton Depression Rating Scale scores and treatment response) were compared in two groups of patients; one group had MDD alone (N = 8) and the other had simultaneous panic disorder and MDD (N = 8). Patients with MDD alone responded significantly better to antidepressant treatment.

Adult↗
PubMed1985

Suppression of plasma testosterone leads to an increase in serum total and high density lipoprotein cholesterol and apoproteins A-I and B.

Men have lower high density lipoprotein (HDL) and higher low density lipoprotein (LDL) levels than women. To dynamically evaluate the role of endogenous testosterone on the lipoprotein profile, eight normal men received a long-acting gonadotropin releasing hormone analog (LHRHA) for 10 weeks by SC injection. Plasma testosterone levels were acutely lowered below 1 ng/ml after 4 weeks of LHRHA treatment and remained depressed at this level for the duration of administration of the analog. There were prompt increases in total cholesterol [baseline vs. peak (milligrams per dl) mean +/- SEM, 177 +/- 18 vs. 208 +/- 22; P less than 0.005], apoprotein B (apo B; 69 +/- 12 vs. 97 +/- 13; P less than 0.05), HDL-cholesterol (23 +/- 2 vs. 33 +/- 2; P less than 0.005), and apo A-I (80 +/- 7 vs. 112 +/- 5; P less than 0.005), but not in apo A-II (40 +/- 3 vs. 40 +/- 4; P = NS) levels. The peaks occurred after 10 weeks of treatment and were followed by a fall in these values after discontinuing LHRHA. These changes were largely prevented in a second study (six men) in which LHRHA was administered together with im testosterone enanthate, which was given every 2 weeks. These results show that suppression of endogenous testosterone leads to increases in HDL and LDL, demonstrating that testosterone has an important effect on lipoprotein metabolism and plays a key role in defining the lipoprotein profile in men.

Adult↗
PubMed1984

Evaluation of provocative tests in suspected medullary carcinoma of the thyroid:heterogeneity of calcitonin responses to calcium and pentagastrin.

Abnormal calcitonin secretion provides a reliable marker for the presence of medullary carcinoma of the thyroid (MCT) and its precursor form, C-cell hyperplasia (CCH). Since this tumor may be transmitted by a dominant autosomal gene, the coincidence of a sensitive marker and an easily identified "at risk" population affords an unusual opportunity for cancer prophylaxis. To evaluate the specificity and sensitivity of provocative tests used for detection of C-cell disease, we have compared the calcitonin (hCT) responses to calcium (3 mg/kg body weight over 10 minutes intravenously), pentagastrin (0.5 microgram/kg body weight), and injection of calcium (1.0 mg/kg body weight) plus pentagastrin (0.25 microgram/kg body weight) over 60 seconds in 13 patients with subsequently proven MCT or CCH and in 31 normal volunteers. The ranges of hCT observed in normals after injection of pentagastrin and combined calcium and pentagastrin were lower than those seen in all nine patients with MCT. One subject, the only MCT patient with normal basal hCT values, had a normal response to calcium whereas all others achieved supranormal levels. Basal hCT levels were normal in the four patients with CCH but the hCT response to calcium was to a value in excess of 300 pg/mL, a level exceeded by only 3 of 31 normal subjects; the hCT response to pentagastrin in CCH and in normal subjects was indistinguishable. Combined calcium and pentagastrin administration was associated with abnormal hCT responses in two of the CCH patients and in the MCT patient with a normal response to calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

A luteinizing hormone-releasing hormone agonist decreases biological activity and modifies chromatographic behavior of luteinizing hormone in man.

The effect of the luteinizing hormone-releasing hormone (LHRH) agonist, [D-Trp6,Pro9-NEth]LHRH (LHRHA), on luteinizing hormone (LH) bioactivity was assessed with a rat interstitial cell assay in four men during a 14-d treatment period. Biologic/immunologic (B/I) ratios were unchanged initially with treatment but by day 12 had fallen to levels lower than basal values. Frequent sampling on day 12 revealed blunted gonadotropin responsiveness to LHRHA and absence of spontaneous LH pulsations. Despite continued administration of LHRHA, human chorionic gonadotropin administration resulted in elevated B/I ratios and testosterone levels. Further characterization of the serum immunoreactive LH by Sephadex chromatography revealed a later elution profile during treatment with LHRHA. Thus, LHRHA appears to act, in part, by modification of the bioactivity of LH in man.

Adult↗
PubMed1984

Gonadotropin and steroid secretory patterns during chronic treatment with a luteinizing hormone-releasing hormone agonist analog in men.

LHRH agonist analogs induce hypogonadism in man but the mechanism is uncertain. To evaluate this, we treated 13 normal men with 50 micrograms/day D-Trp6,Pro9-NEt LHRH (LHRHA) for periods up to 8 weeks and measured (1) patterns of endogenous gonadotropin and testosterone secretion, (2) gonadal response to exogenous human LH infusions, and (3) gonadotropin and testosterone responses to hourly bolus doses of LHRH. Seven men were evaluated with frequent sampling for 12-h periods every 4 week during treatment with LHRHA. Before treatment, all had three to four spikes of LH in 12 h. On the first day of treatment, the response to LHRHA was tested in four of the men, and there were significant increases in LH, FSH, and testosterone. After 4 weeks, all men had dramatic decreases in mean testosterone levels and blunted or absent gonadotropin responses to acute injection of LHRHA. Mean gonadotropin levels at 4 and 8 weeks were variable; values lower than pretreatment basal levels were found in three men, while unchanged or higher values were found in the remaining four. The pulsatile pattern of LH secretion, characteristic among these men before treatment, was lost during LHRHA therapy. Forty-eight-hour constant infusion of human LH in four other analog-treated men resulted in increases in serum testosterone comparable to those in untreated men. Pulsatile administration of native sequence LHRH to two other men during chronic treatment with LHRHA failed to elicit demonstrable responses in serum gonadotropin or testosterone levels. LHRHA produced a qualitative change in the pattern of LH release from the pituitary. Mean basal LH levels varied during treatment, but the normal pulsatile pattern was diminished. The gonadotropin response to pulsatile administration of LHRH was lost during chronic treatment with LHRHA, but the Leydig cell remained responsive to exogenous human LH. Thus, the locus of action of the analog appears to be at the level of the pituitary in man.

Adult↗
PubMed1983

A characterization of the low temperature structural transition of Escherichia coli 5 S RNA by partial enzymatic digestion.

The low temperature structural transition (low leads to high) of 5 S RNA from Escherichia coli is investigated by partial digestion with ribonuclease T1. In addition to a general masking of guanines from the nuclease, differential changes of accessibility are observed when Mg2+ and salt concentrations are increased to bring about the low leads to high transition. Residue G13 becomes more exposed in the high form while residues G54, G56, G61, G72, and G83-86 become less exposed. The observed cutting rate at other sites is unchanged. A possible conformational change is discussed which could explain the observed changes in RNase T1 digestion patterns as well as the physical chemical observations.

Escherichia coli↗
PubMed1983

The effect of thyroid hormones on gluconeogenesis and forearm metabolism in man.

The present study was designed to examine the effects of excess T3 on total body glucose production and forearm exchange of glucose, amino acids, and other metabolites. Five healthy male volunteers were studied after an overnight fast, before and 7 days after the administration of 150 micrograms/day T3. Glucose production (milligrams per kg/min) was measured using a primed continuous infusion of [3-3H]glucose and gluconeogenic index (micromoles per kg/min) was measured by following the conversion of infused [14C]alanine to [14C]glucose. Blood flow across the forearm was measured using capacitance plethysmography and forearm release of substrates was determined by the Fick principle. After T3 administration, there was a 3.7-fold rise in T3 from 150 +/- 15 to 530 +/- 12 ng/dl (P less than 0.001), with no change in insulin (12 +/- 1 microU/ml pre-T3 vs. 13 +/- 2 microU/ml post-T3) and glucagon (79 +/- 5 pre-T3 vs. 84 +/- 7 pg/ml post-T3). T3 administration resulted in an increase in plasma glucose (from 83 +/- 5 to 98 +/- 5 mg/dl; P less than 0.05), net glucose uptake by the forearm (from 250 +/- 90 to 712 +/- 60 nmol/100 ml forearm tissue X min; P less than 0.005) and glucose production (1.7 +/- 0.09 to 2.2 +/- 0.08 mg/kg X min; P less than 0.005), without a change in glucose clearance (2.1 +/- 0.02 vs. 2.0 +/- 0.02 ml/kg X min); the rate of conversion of [14C]alanine to [14C]glucose increased by 30% (0.56 +/- 0.03 to 0.74 +/- 0.03 mumol/ kg X min P less than 0.005). These values were associated with a 25% increase in blood lactate to 712 +/- 69 mumol/liter (P less than 0.05) and a 131% increase in lactate release across the forearm to 434 +/- 90 (P less than 0.005). Forearm release of alanine (96 +/- 29 nmol/100 ml forearm tissue X min) and glutamine (151 +/- 41 nmol/100 ml forearm tissue X min) increased by 90% (P less than 0.005 and P = 0.04, respectively), with no change in their concentrations. Forearm release of branched chain amino acids did not change, while those of their ketoacids, alpha-ketoisocaproate (KIC) and alpha-ketoisovalerate (KIV), doubled (to 64 +/- 9 mumol/liter for KIC and 39 +/- 6 mumol/liter for KIV; P less than 0.05). These were associated with a 45% increase in the branched chain amino acid levels and a 46% rise in both KIC and KIV levels to 41 +/- 9 and 28 +/- 7 mumol/liter, respectively (P less than 0.05). There was a concurrent significant (P less than 0.05) change in the arterial levels of phenylalanine (-32%), tyrosine (-29%), threonine (-20%), glycine (-20%), and serine (-15%), without any change in their efflux across the forearm. The data indicate that a pharmacologically induced rise in T3, to levels comparable to those seen in hyperthyroidism, results in enhanced glucose production, with an increase in glucose uptake by the forearm. The former can be partially accounted for by an increase in hepatic gluconeogenesis, glycogenolysis, or possibly increased renal glucose production...

Adult↗
PubMed1983

Histamine release from a gastric carcinoid: provocation by pentagastrin and inhibition by somatostatin.

We have previously reported that flushing associated with a gastric carcinoid tumor can be provoked by pentagastrin and inhibited by either somatostatin or combined histamine H1- and H2-receptor blockade. In this report, the effects of pentagastrin and somatostatin on histamine release in a patient with a metastatic gastric carcinoid tumor were examined. Small doses of intravenous pentagastrin (0.1-0.4 micrograms) produced a dose-dependent increase in the level of circulating plasma histamine. Graded infusions of somatostatin suppressed both basal and pentagastrin-stimulated plasma histamine levels in a dose-dependent fashion. A close correlation was found between circulating plasma histamine levels and attendant changes in blood pressure and pulse rate. This study documents that pentagastrin directly evokes the release of histamine from this patient's gastric carcinoid tumor and that the release of histamine is inhibited by somatostatin. In addition, this study provides additional evidence that the primary mediator of the flushing in this patient with foregut carcinoid syndrome is histamine.

Blood Pressure↗
PubMed1983

Effects of dietary lecithin on hormonal and neurobehavioral profiles in normal subjects.

Four normal subjects received lecithin supplements sufficient to elevate serum choline levels 3-fold. Despite persistent hypercholinemia over 48 hours of close observation, no increase was observed in serum ACTH, cortisol, and insulin concentrations, or in free urinary catecholamine excretion. Screening of a large group of other pituitary and gonadal hormones also failed to reveal any influence of lecithin supplements. EEG patterns and results of psychometric tests were also unaltered.

Acetylcholine↗