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Biomedical subjects

L S Jacobs

Publications and source records attributed to L S Jacobs.

At least 55 records · Page 3Linked to original sources

Thyroid hormone and thyrotropin levels in patients placed on colestipol hydrochloride.

Bile acid sequestrant resins can bind T4 in vitro and in the gut. Therefore, the effect of colestipol HCl on thyroid function was studied prospectively in 17 subjects with type II hyperlipoproteinemia. Serum T4, T3, T3 resin uptake, and TSH levels were measured before and during therapy. No change in T4 levels and only small transient, but significant, decreases in T3 were noted in a minority of patients; TSH levels did not change. Small increases in T3 resin uptake were noted. We conclude that no major alterations in thyroid function occurred with colestipol therapy.

Colestipol↗

Galactorrhoea and hypogonadism associated with a radiologically-inapparent prolactin-secreting pituitary tumour.

A 38 year old man was investigated because of impotence, gynaecomastia and galactorrhoea. Hyperprolactinaemia and hypogonadism were documented. Pituitary function was otherwise normal as was tomographic examination of the sella turcica. In the absence of direct evidence of pituitary involvement (hyperprolactinaemia can suppress gonadal function) and to exclude ectopic prolactin production, venous blood was drawn at multiple sites. The highest prolactin levels were found in the superior vena cava and above, indicating an intracranial source. At transsphenoidal hypophysectomy a microadenoma was removed; tumour cells contained typical prolactin secretory granules on electron microscopy. In the light of this report the appropriateness of dividing hyperprolactinaemia into "tumourous" and "idiopathic" subgroups on the basis of sella size must be reconsidered. Functional tests do not distinguish between the subgroups although prolactin levels tend to be higher when the sella is enlarged. Only a quantitative rather than a qualitative difference may exist between the subgroups.

Adenoma↗

Thyroid function and the intraocular pressure response to topical corticosteroids.

Baseline thyroxine, thyrotropin (TSH), and triiodothyronine (T3) resin uptake levels were measured in patients classified according to their topical intraocular response to corticosteroids. Results of thyroid studies were similar in patients with primary open-angle glaucoma and noncorticosteroid responsive (NN, intraocular pressure less than 20 mmHg after six weeks of topical 0.1% dexamethasone eyedrops) subjects. Primary open-angle glaucoma was not associated with the increased prevalence of low thyroid function values. The TSH suppression induced by oral dexamethasone was similar in NN subjects and patients with primary open-angle glaucoma. Patients with primary open-angle glaucoma did not demonstrate an increased glucocorticoid sensitivity as related to thyroid function. Thus, the adenohypophysial thyrotropic cell, the major site of dexamethasone inhibition of TSH secretion, does not appear to share the enhanced corticosteroid sensitivity of the eye, the hypothalamus, and the lymphocyte in patients with primary open-angle glaucoma.

Administration, Oral↗

Binding of microtubules to pituitary secretory granules and secretory granule membranes.

Microtubules assembled in vitro were bound to purified porcine pituitary secretory granules and to isolated granule membranes. The interaction between microtubules and whole secretory granules was demonstrated by alteration in the sedimentation properties of the microtubules. Incubation of secretory granules with microtubules resulted in pelleting of microtubules which increased as a function of the number of granules added. Binding was quantitated by measurement of the tubulin remaining in the supernate after centrifugation. The interaction of secretory granules and microtubules was inhibited by nucleoside triphosphates and augmented by adenosine 5'-monophosphate and adenosine. When depolymerized protein from microtubules was incubated with secretory granules, the granules did not appear to bind the soluble tubulin dimer present in these preparations. However, the high molecular weight protein associated with microtubules was adsorbed by secretory granules during the binding process. Incubation of isolated secretory granule membranes with microtubules followed by centrifugation to density equilibrium in a discontinuous sucrose density gradient caused pelleting of the membranes, which otherwise banded higher in the gradient. The visible alteration in membrane sedimentation was confirmed by measurements of the membrane-associated magnesium-ATPase activity and by a shift in radioactivity in iodinated membrane preparations. Our data suggest a role for microtubules in the intracellular movement of secretory granules; this movement is perhaps brought about by dynein-like cross bridges which link the tubulin backbone and granule surface.

Adenosine↗

Apomorpine inhibits the prolactin but not the TSH response to thyrotropin releasing hormone.

Pretreatment of normal subjects with apomorphine, a dopamine receptor agonist, resulted in significant impairment of the subsequent prolactin (PRL) response to thyrotropin releasing hormone (TRH). The mean maximal increment of PRL was 27.9+/-2.4 ng/ml after TRH alone, and 11.9+/-3.0 ng/ml (P less than 0.001) after apomorphine plus TRH. In contrast, the.thyrotropin (TSH) response to TRH was unaffected by apomorphine (10.5+/-2.9 vs. 9.5+/-1.8 muU/ml, P greater than 0.5). These results demonstrate that dopaminergic effects are capable of inhibiting PRL responses to TRH, probably via a direct effect on the lactotrope cell. They also suggest that dopaminergic influences are not important in the regulation of TSH secretion.

Adult↗

Failure of papaverine to alter L-dopa-influenced GH and PRL secretion.

Papaverine, 150 mg BID for 2 weeks, a dose which produced marked clinical impairment in Parkinsonian patients taking L-Dopa, failed to alter L-Dopa-stimulated GH secretion or L-Dopa inhibited PRL secretion in 6 normal volunteers. Failure to demonstrate an inhibitory effect of papaverine on dopaminergic hypothalamic-pituitary systems, despite its inhibition of striatal dopaminergic pathways, may imply qualitative or quantitative functional differences between hypothalamic and striatal dopaminergic systems.

Adult↗

Plasma indolethylamine-n-methyltransferase activity and growth hormone level during sleep: a pilot study.

Polygraphic recordings and sequential growth hormone (GH) samplings were performed in eight healthy adult males. In the plasma samples from seven of the subjects, indolethylamine-N-methyltransferase (INMT) activity was also determined. Five of eight subjects showed significant fluctuation in plasma GH level, and six of seven subjects showed significant fluctuation in plasma INMT activity level. There were also significant positive correlations between plasma GH and INMT activity level during the second episode of NREM sleep stage 1 and during the third episode of NREM sleep stage 2. A significant negative correlation between plasma GH and INMT activity level during the seventh episode of sleep stage 2 and during the fifth episode of post sleep-onset wake was found. In view of a previous finding that INMT activity in the serum of psychiatric patients is positively correlated with severity of delusions, the observation that NREM sleep is associated with mental activity characterized by repetitive thoughts, and the result that GH level in plasma is increased in NREM sleep early at night, our present findings suggest the hypotheses that increased plasma INMT activity during sleep is indicative of both increased INMT activity in the central nervous system (CNS) and the activation or maintenance of NREM mental activity during sleep. Additional research will be needed in order to validate our observations and test these hypotheses.

Adult↗

Receptor-active growth hormone in Laron dwarfism.

The hepatic radioreceptor assay for hGH has been applied to the detection of hGH in the sera of patients with high growth hormone dwarfism (Laron dwarfism). Substantial quantities of receptor-active hGH were found in the sera of all 7 patients studied. In one patient, arginine infusion elicited a prompt increase in both immunoactive and receptor-active hGH. These observations suggest that circulating hGH in Laron dwarfism is biologically active and support the concept that the disease may be caused by a generalized defect in hGH receptors.

Arginine↗

Normal gestation and diminished androgen responsiveness in an untreated patient with 21-hydroxylase deficiency.

A 22-year-old woman with 21-hydroxylase deficiency but minimal clinical evidence of androgenization was studied. She had conceived twice and had borne a normal male infant without therapy of any kind. The diagnosis of 21-hydroxylase deficiency was substantiated by the findings of 17-ketosteroid and pregnanetriol excretions of 18.1 and 8.1 mg/24 hours, respectively. Adequate basal compensation was indicated by a fasting plasma cortisol of 17.5 mug/dl. Plasma ACTH (207 pg/ml), testosterone (216 ng/dl) delta4-androstenedione (649 mg/dl), progesterone (249 ng/dl) and 17alpha-hydroxyprogesterone (4820 ng/dl) were all significantly elevated.

Adrenal Hyperplasia, Congenital↗

An XX male: cytogenetic and endocrine studies.

A 3 year old black male with ambiguous genitalia had a 46, XY karyotype in a bone marrow culture and an intermediate buccal smear result, suggestive of a mosaic of chromatin positive and chromatin negative cells. Upon re-evaluation at age 15 years, he has a 30% positive buccal smear and a 46, XX karyotype in cultures of peripheral blood lymphocytes, skin fibroblasts, bone marrow, and testis. No Y-body fluorescence was detectable in interphase cells from the testicular biopsy or the various cultures. The testicular biopsy appeared similar to that of XXY males, and primary hypogonadism was documented by elevated LH (107 mIU/ml) and FSH (57 mIU/ml) levels in conjunction with low testosterone (142 ng/100 ml). Administration of hCG produced qualitatively normal acute responses of testosterone and estrogens. The cytogenetic data provide support for the theory that at least some XX males once had a Y-containing cell line which was subsequently lost.

Adolescent↗

Suppression of sleep-related prolactin secretion and enhancement of sleep-related growth hormone secretion.

Methysergide, a clinically-used blocker of serotonin receptors, was administered to 10 normal young men at a dose of 2 mg every 6 h for 48 h. After drug treatment, serum levels of growth hormone during sleep were 41.9% higher than placebo values (less than 0.001). In contrast, drug treatment was associated with a 36.4% decrease in stimulated growth hormone secretion during insulin tolerance testing (P less than 0.01). These opposite effects of methysergide suggest that different mechanisms are responsible for sleep-related and insulin-induced growth hormone secretion. Accordingly, data obtained with pharmacologic stimuli may lead to erroneous inferences regarding physiologic growth hormone control mechanisms. Administration of methysergide profoundly suppressed sleep-related prolactin secretion; overall nocturnal mean prolactin fell by 70.3% from 4.30+/-0.19 to 1.28+/-0.06 ng/ml (P less than 0.0001). It appears that serotonin may be significant modulating neurotransmitter for the control of growth hormone secretion, limiting sleep-related release, and enhancing insulin-induced release. It seems likely from these data that the role of serotonin in the control of prolactin secretion is relatively more important, since serotonin receptor blockade dramatically reduced sleep-related prolactin secretion.

Adult↗

Pituitary hormonal reserve in patients presenting hyperprolactinemia, intrasellar masses, and amenorrhea without galactorrhea.

The pituitary release of gonadotropins, prolactin, and TSH after the simultaneous intravenous administration of 50 mug LH-RH was 400 mug TRH was evaluated in 7 amenorrheic women with sellar enlargement and hyperprolactinemia. It was found that only minimal amounts of LH and FSH were released by LH-RH. All patients had elevated serum prolactin levels but TRH administration elicited negligible release of prolactin. This was in contrast to the normal TSH response to TRH in most of these women. It is concluded that intrasellar masses may be associated with hyperprolactinemia which does not necessarily cause galactorrhea and that impaired gonadotropin reserve correlates with the presence of amenorrhea.

Adult↗

Radioreceptor-inactive growth hormone associated with stimulated secretion in normal subjects.

We have previously reported systematic discrepancies between radioreceptor (RRA) and radioimmunoassay (RIA) measurements of growth hormone (hGH) in acromegalic patients. Due to limitations in RRA sensitivity, such comparisons could not be made in normal subjects. RRA methodology has now been adapted to allow detection of hGH at normal circulating levels. Since variations in Na+, K+, Ca++, and Mg++, incubation at 37 C and 4 C, and delayed tracer addition failed to improve assay sensitivity, specimen size was increased to 300 mul and incubation volume to 1.5 ml, while holding the quantity of added receptor constant. Best assay sensitivity, in room temperature incubations in 25 mM Tris for 16 h at pH 7.6 and 10 mM Ca++, was 0.66 +/- 0.30 ng hGH per ml serum. Under these conditions, 200 mug hepatic receptor protein bount 15.8 +/- 0.83% of added 125I-hGH, and 8.72 +/- 0.85% of bound tracer was displaced by 0.25 ng added unlabeled hGH. Nonspecific depression of binding by serum did not impair assay sensitivity with most receptor preparations. The basal hGH measured by RIA (antiserum 68-416) in a group of normal short children was 1.97 ng/ml, similar to the RRA result, 1.89 ng/ml (P = NS). Comparative measurements were also made in selected samples of sufficient volume during the 1 1/2 h following administration of hGH secretagogues (insulin, arginine, L-dopa). In these samples, the RIA value was 9.34 +/- 0.68 and the RRA value 6.29 +/- 0.62 ng/ml (P less than 0.01); the RIA/RRA was 1.77 +/- 0.18. Thus, no significant measurement discrepancy was found in basal samples from normal subjects, in contrast to previous findings in acromegalics. The appearance of such a discrepancy within 90 min after stimulation of hGH might be due to RIA/RRA discordance in secreted molecular subspecies, or might arise from peripheral hGH metabolism.

Acromegaly↗