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Biomedical subjects

M Berelowitz

Publications and source records attributed to M Berelowitz.

At least 91 records · Page 5Linked to original sources
PubMed1980

Vitamin D metabolism during recovery from severe osteitis fibrosa cystica of primary hyperparathyroidism.

Serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D] and immunoreactive parathyroid hormone were measured before and for 7 months after the removal of a 15-g parathyroid adenoma from a 44-yr-old woman with primary hyperparathyroidism and severe osteitis fibrosa cystica. Despite the fall in parathyroid hormone levels from preoperative levels of 20 to 1--2 ng/ml after surgery (normal, up to 1.2 ng/ml), serum 1,25-(OH)2D concentrations remained markedly elevated (156 pg/ml) preoperatively; 124 pg/ml 17 weeks postoperative), approaching the normal range (18--56 pg/ml) only after 5 months (65 pg/ml). Hypocalcemia and hypophosphatemia persisted despite oral 1,25-(OH)2D3 (1 and 2 micrograms/day) and large doses of (oral and iv) calcium gluconate (up to 30 g/day). Healing of the skeletal lesions, reversal of the myopathy, and return of 1,25-(OH)2D circulating levels to normal corresponded to the time when serum phosphate became normal. The stimulus for the persistently elevated serum 1,25-(OH)2D levels may have been hypocalcemia per se, low serum phosphate, or an unidentified signal that paralleled serum phosphate, as serum PTH levels remained in the upper normal range throughout the recovery period.

Adenoma↗
PubMed1980

Ectopic production of somatostatin-like immuno- and bioactivity by cultured human pulmonary small cell carcinoma.

Eleven continuous cultures of human pulmonary small cell carcinoma cells were examined, and eight were shown to secrete quantities of somatostatin-like immunoreactivity (SRIF-LI) ranging from 0.07-27 ng/ml culture medium/4 days, SRIF-LI was also found in a 2-N acetic acid extract of one of three human pulmonary small cell carcinomas obtained at autopsy as well as in the extract of a solid tumor resulting from inoculation of nude, athymic mice with SRIF-LI-producing, cultured small cell carcinoma cells. The SRIF-LI produced by one continuous cell line, DMS 53, was characterized in terms of its immunological, chromatographic, and biological properties. SRIF-LI from DMS 53 culture media and lysed cells was heat stable and exhibited parallel displacement to synthetic SRIF standard in a double antibody RIA. DMS 53 SRIF-LI was quantitatively retained on an immunoaffinity column of sheep anti-SRIF-Sepharose 4B under neutral conditions and could be eluted with 2 N acetic acid. Gel filtration chromatography of immunoaffinity-purified SRIF-LI revealed multiple molecular weight forms, the largest of which had an apparent molecular weight of 10,000-12,000 daltons and may represent a precursor form. This high molecular weight SRIF-LI form was resistant to exposure to denaturing conditions (8 M urea or 4 M urea plus 0.5% mercaptoethanol), suggesting the absence of noncovalent and/or disulfide linkages. A low molecular weight form coeluted with synthetic SRIF. Additional evidence for the identity of this form with the tetradecapeptide was provided by highly specific reverse phase high performance liquid chromatography. The rate of degradation of high molecular weight SRIF-LI by the cultures was markedly reduced in comparison to that of the SRIF monomer, resulting in a preferential accumulation of high molecular weight SRIF-LI in 4-day culture medium. Bioactivity of DMS 53 SRIF-LI was assessed in 4-day primary monolayer cultures of rat adenohypophyseal cells where 10(-10)-10(-9) M synthetic SRIF elicited a linear log-dose suppression of 5 X 10(-4) M synthetic SRIF elicited a linear log-dose suppression of 5 X 10(-4) M dibutyryl cAMP-stimulated rat GH release. Immunoaffinity-purified SRIF-LI from DMS 53 lysed cells and 1-h serum-free incubation medium, which consisted predominantly of monomeric SRIF, was equipotent to synthetic SRIF, SRIF-LI from 4-day culture medium consisted mostly of the high molecular weight form and exhibited a reduced bioassay potency ratio relative to synthetic SRIF of 0.73 (95% confidence limits, 0.99-0.53). Chromatographically purified high molecular weight SRIF-LI had significant bioactivity with a bioassay to immunoassay ratio of 0.19 (95% confidence limits, 0.33-0.09). The demonstration of ectopic SRIF, production by human pulmonary small cell carcinoma is consistent with the proposed derivation of this tumor from a cell type in the amine precursor uptake and decarboxylation cell series.

Animals↗
PubMed1980

Pentagastrin and glucagon stimulate serum somatostatin-like immunoreactivity in man.

Passive immunization with somatostatin (SRIF) antiserum suggests that gastrin, glucagon, and calcitonin secretion may be exerted either locally by contiguity of SRIF-like immunoreactivity (SRIF-LI)-containing D cells and G (gastrin) and A (glucagon) cells (paracrine) or by an endocrine effect. To determine whether a reciprocal relationship exists in man between these peptides and SRIF-LI, the effects of pentagastrin (0.5 microgram/kg BW), glucagon (1 mg), and calcium (15 mg/kg BW) on serum SRIF-LI were examined. The coexistence of SRIF-LI and calcitonin in normal thyroid parafollicular C cells and medullary carcinoma of the thyroid prompted a study of the effects of the known secretagogues of calcitonin, calcium (15 mg/kg BW), and pentagastrin (0.5 microgram/kg BW) on serum SRIF-LI. Sixteen normal subjects, two patients with metastatic medullary carcinoma of the thyroid, and one patient who had undergone thyroparathyroidectomy were evaluated. We demonstrated that whereas both pentagastrin and glucagon significantly elevated serum SRIF-LI, calcium infusion had no effect. Basal and stimulated SRIF-LI levels in the normal controls, patients with medullary carcinoma of the thyroid, and the patient with thyroparathyroidectomy were similar. These results suggest that SRIF-LI secretion is related to stimulation by peptides produced in closely juxtaposed cells, that SRIF-LI, unlike calcitonin, may not be a serum marker for medullary carcinoma of the thyroid in man, and that little, if any, serum SRIF-LI originates in the thyroid.

Calcitonin↗
PubMed1980

Temporal relationship of tissue somatostatin-like immunoreactivity to metabolic changes in genetically obese and diabetic mice.

Somatostatin-like immunoreactivity (SRIF-LI) content in 2 N acetic acid extracts of hypothalamus, gastric antrum, and pancreas was measured in genetically obese (C57BL/6J ob/ob and db/db) and diabetic (C57BL/KsJ db/db and ob/ob) mice and normal littermate controls from 5 to 24 wk to determine the relationship of previously reported changes to the development of metabolic abnormalities. Hypothalamic SRIF-L concentration was similar in control, diabetic, and obese mice at all ages and increased progressively with age in all groups. Gastric antrum SRIF-LI was similar in all groups of mice at all ages. Obese mice gained weight progressively and showed moderate hyperglycemia and marked hyperinsulinemia from 5 wk of age. Pancreatic SRIF-LI content in obese (C57BL/6J) animals was similar to that in lean littermate controls, but pancreatic SRIF-LI concentration (expressed by weight or protein content) was decreased until 8 (6J ob/ob) and 10 (6J db/db) wk. Diabetic (C57BL/KsJ) mice showed a similar metabolic pattern until 10 wk with no change in pancreatic SRIF-LI content or concentration. Thereafter a progressive fall in serum insulin and a marked rise in serum glucose was associated with increasing pancreatic SRIF-LI content and concentration. These studies suggest that the genetically hyperphagic syndromes are unassociated with any change in hypothalamic or gastric SRIF-LI; that pancreatic SRIF-LI increases occur in response to, rather than as the cause of, relative hypoinsulinemia; and that the genetic background of the mice (KsJ or 6J) rather than the mutant gene (db or ob) determines the defect in carbohydrate metabolism and the pancreatic SRIF-LI response.

Animals↗
PubMed1979

Kinetics of somatostatin inhibition of pentagastrin-stimualted gastric acid secretion.

Dogs with gastric fistulae and denervated gastric pouches received graded doses of pentagastrin with and without a background infusion of somatostatin (1 microgram kg-1 h-1). Similarly, graded doses of somatostatin (0.25, 0.5, 1, 2 and 4 microgram kg-1 h-1) were infused after a steady state gastric secretion had been achieved with pentagastrin (1.5 microgram kg-1 h-1), about twice the dose required to produce half maximal (D50) response. Somatostatin inhibited pentagastrin-stimulated gastric acid secretion with competitive inhibition kinetics, but its precise site of action remains uncertain. The minimum effective dose of somatostatin on a twice D50 dose of pentagastrin was 0.25 microgram kg-1 h-1.

Animals↗
PubMed1979

Growth hormone release inhibitory hormone-like immunoreactivity in pancreas and gut in streptozotocin diabetes in the rat and response to insulin administration.

In streptozotocin diabetes in the rat, growth hormone release-inhibitory hormone-like immunoreactivity (GHRIH-LI) content of pancreas, gastric antrum and colon was increased. Insulin therapy significantly lowered the increased pancreatic GHRIH-LI content but did not affect that of the gastric antrum and colon at the dosage used. The relevance of these findings in relation to pancreatic and gastrointestinal function in diabetes awaits clarification.

Animals↗
PubMed1979

Metabolic clearance and plasma half-disappearance time of exogenous somatostatin in man.

The MCR and half-disappearance time of exogenously administered somatostatin have been measured during and after cessation of a constant infusion. Studies were performed on normal volunteers and patients with chronic liver disease and failure. Immunoreactive somatostatin was measured by a sensitive and specific RIA using an antiserum directed against the core of the molecule. Normal subjects had a mean MCR of 1949 +/- 250 ml/min (28.4 +/- 4.2 ml/min . kg BW) (mean +/- SEM), similar to values found in five patients with chronic liver disease. However, patients with chronic renal failure showed a highly significant (P less than 0.001) lowering of the MCR (501 +/- 32.7 ml/min or 7.8 +/- 0.6 ml/min . kg). The rate of disappearance of somatostatin after infusion was linear for 7-10 min, after which a much slower component was observed. In normal subjects, the t 1/2 of the first component varied from 1.1-3.0 min, in patients with liver disease it varied from 1.2-4.8 min, and in patients with chronic renal failure it varied from 2.6-4.9 min. Exogenously administered somatostatin is rapidly cleared in normal subjects and patients with chronic liver disease, but the MCR in end stage chronic renal failure is markedly lowered. The kidney may have a role in the metabolic clearance of exogenously administered somatostatin, or uremia may impair catabolism nonspecifically.

Adult↗
PubMed1979

Tissue and serum somatostatin-like immunoreactivity in fed, 15-h-fasted, and 72-h-fasted rats.

Somatostatin-like immunoreactivity (SLI) was measured in extracts of gastric antrum, colon, pancreas, and central nervous system, as well as in unextracted portal and inferior vena caval serum from fed, 15-h-fasted, and 72-h-fasted rats. No differences were found in SLI in the central nervous system of the three groups. However, striking variations were found in the gastrointestinal tract and pancreas; the antrum, colon, and pancreas of 15-h-fasted rats contained the least SLI, the content being significantly elevated in these three areas after feeding and after a 72-h fast. Portal serum levels were highest after feeding but lowest in 72-h-fasted rats, in spite of high intestinal and pancreatic SLI content in both. These tissue and serum differences suggest a physiologic role for SLI in nutrient homeostasis not only at tissue level, but also putatively as a hormone in the portal system.

Animals↗
PubMed1978

Circulating antibodies in diabetics treated with conventional and purified insulins.

Conventional insulins contain impurities which are immunogenic; these include pancreatic polypeptide (PP), glucagon and somatostatin and intermediates of insulin synthesis co-extracted during purification. Monocomponent (MC) insulins are free of these contaminants. In 49 insulin-treated diabetic patients, antibodies were found to insulin (94%), pro-insulin (68%) and PP (68%). Antibodies to glucagon and somatostatin were not detected. There was a significantly lower mean maximum binding and titre of insulin and PP antibodies and total circulating insulin (i.e. antibody bound and free) in patients receiving MC insulin. In patients treated with MC insulins for longer than 2 years there was a significant fall in the mean maximum binding of insulin and total serum insulin, but no consistent change in diabetes control and daily insulin dose. It seems that except in the special instances of fat atrophy, insulin allergy and certain cases of insulin resistance, there is no need to resort to MC insulin.

Adolescent↗
PubMed1978

Somatostatin--paracrine and neuromodulator peptide in gut and nervous system.

Somatostatin, a tetradecapeptide widely distributed in nervous tissue and gut, has inhibitory effects on secretion and neuromuscular activity. The actions of this peptide probably embrace three types of transmitter-receptor interaction, namely that of a neurotransmitter in the nervous system, that of a hormone in the hypophyseal portal circulation and that of a local (paracrine) effector in gut and pancreas.

Animals↗
PubMed1978

Tissue growth hormone release inhibiting hormone-like immunoreactivity in experimental hypothyroidism and hypopituitarism.

Hypothyroidism in rats was associated with an increase in immuno-reactive GH-RIH in brain, pancreas and gut, although release from the latter may be diminished as portal GH-RIH-like immunoreactivity was lower than control values. Hypophysectomy resulted in a depletion of immunoreactive GH-RIH in the septum and preoptic area of the brain and gastric antrum, but an increase in pancreas; portal venous GH-RIH-like immunoreactivity was not different from control concentrations, possibly reflecting both elevated and lowered immunol-reactive GH-RIH in different regions of tissue subserved by the portal vein. Inferior vena caval GH-RIH-like immunoreactivity was always lower than in the portal vein and was not influenced by tissue pertubations in hypothyroidism and hypopituitarism which made regional blood sampling of great important in evaluating tissue changes.

Animals↗