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Biomedical subjects

C W Cooper

Publications and source records attributed to C W Cooper.

At least 127 records · Page 7Linked to original sources
PubMed1975

Hypercalcemic effect of catecholamines and its prevention by thyrocalcitonin.

Earlier work by others has shown that the catecholamines, epinephrine and isoproterenol, can raise blood calcium levels in parathyroidectomized but not intact rats, and can restrict the hypocalcemic effect of injected thyrocalcitonin (TCT). The present findings support this earlier work, further showing that such catecholamines can produce hypercalcemia in rats after removal of the thyroid gland by acute thyroparathyroidectomy (TPTX) and indicating that these drugs may raise blood calcium by mobilizing calcium from bone. Rats were fasted overnight, subjected to TPTX and concurrently injected with adrenergic agonist or antagonist drugs alone or in combination. Epinephrine, isoproterenol, and the beta-2 adrenergic agonist, salbutamol, in doses greater than or equal to 1 mg/kg raised blood calcium from low normal levels (approximately 9-10 mg/100 ml) by 1.5 to 2 mg/100 ml (p less than 0.01). Hypercalcemia was apparent by 1 hour after injection and lasted for 1-4 hours. The extent of Ca elevation was dose-related. Pretreatment of rats with the alpha-adrenergic antagonist, phenoxybenzamine, enhanced the effect of epinephrine while pretreatment with the beta-antagonist, propranolol, reduced the effect of isoproterenol. The more selective beta-2 antagonist, butoxamine, but not the beta-1 antagonist, practolol, also reduced the hypercalcemic effect of isoproterenol in TPTX rats. These results suggest that catecholamine-induced hypercalcemia in TPTX rats is mediated by beta-2 adrenergic receptors. Related studies using rats prelabeled with 45Ca further suggest that the catecholamines, like parathyroid hormone, may act to raise blood calcium by mobilizing calcium from bone. The fact that these catecholamines could induce marked hypercalcemia in acutely TPTX rats but not in intact rats indicated that endogenous TCT protects the thyroid intact rat against hypercalcemia. The present findings support this idea in showing that isoproterenol and salbutamol raised levels of immunoreactive rat TCT in both thyroid venous and peripheral blood. Catecholamines apparently can promote TCT secretion, either directly or by a small transient increase in blood calcium. This, in turem, acts to combat hypercalcemia in thhroid-intact rats.

Albuterol↗
PubMed1975

Stimulation of thyrocalcitonin secretion by ethanol in patients with medullary thyroid carcinoma--an effect apparently not mediated by gastrin.

We have compared the effects of oral and intravenous ethanol on the secretion of both thyrocalcitonin and gastrin in five patients with medullary carcinoma of the thyroid. Ethanol caused a moderate rise in plasma thyrocalcitonin to 316% +/- 343% of baseline when given intravenously and to 197% +/- 106% of baseline when given orally. Only oral ethanol caused a measurable rise in serum gastrin levels. Serum calcium did not change significantly from baseline during either oral or intravenous administration. The results suggest that stimulation of thyrocalcitonin secretion by ethanol is not secondary to increased secretion of gastrin nor to the induction of hypercalcemia. Neither oral nor intravenous ethanol appears to be as effective as intravenous pentagastrin in testing for the presence of medullary carcinoma.

Administration, Oral↗
PubMed1975

The early diagnosis of medullary carcinoma of the thyroid gland in patients with multiple endocrine neoplasia type II.

Pentagastrin is a potent stimulator of thyrocalcitonin secretion from "C" cells. Since medulllary carcinoma of the thyroid gland (MCT) is a tumor composed of "C" cells, pentagastrin was used to screen a large kindred with multiple endocrine neoplasia type II (MCT, pheochromocytoma (s), and parathyroid hyperplasia). Four children with no thyroid abnormalities evident on physical examination, with negative thyroid scans, and with normal levels of plasma thyrocalcitonin both before and after calcium infusion, were found to have elevated peripheral levels of this hormone following pentagastrin injection. All four children were found to have very small foci of MCT, in both thyroid lobes at the time of total thyroidectomy. Pentagastrin stimulation used conjointly with selective catheterization of the inferior thyroid vein provided even greater diagnostic accuracy in detecting elevations in thyrocalcitonin secretion. This test has great diagnostic utility, especially in screening patients with multiple endocrine neoplasia type II.

Adult↗
PubMed1975

Purification, characterization and radioimmunoassay of thyrocalcitonin from rat thyroid glands.

A highly purified preparation of rat thyrocalcitonin (TCT) has been obtained from lyophilized thyroid glands by gel chromatography following acid-acetone extraction. Biological activity of Sephadex G-50 eluates appeared in two peaks. The TCT in the major peak was concentrated, and applied to a Bio-Gel P-6 column, and a major protein peak was eluted which coincided with TCT activity. Potency, estimated by bioassay in rats, increase approximately 3500-fold from 0.075 MRC U/mg lyophilized glands to 250-400 MRC U/mg in the final product. The overall yield of TCT activity was about 36%. The purified product was characterized by chemical procedures and evaluated for its antigenic properties and use for radioimmunoassay. The purified rat TCT was used both labeled with 125I and as unlabeled standard. The following results were obtained: 1) Guinea pig antisera to either human or rat TCT were capable of binding 125I-rat TCT or 125I-human TCT; 2) Using either 125I-human or 125I-rat TCT and antisera to either TCT, pg amounts of rat and human TCT reacted in the assay while ng to mug amounts of salmon calcitonin or porcine TCT failed to react; 3) Using 125I-rat TCT and antisera to human or rat TCT, synthetic C-terminal (10-32 or 22-32) fragments of human TCT reacted well, while N-terminal (1-18) or desamide (1-32) derivatives reacted poorly or not at all; 4) Rat TCT was easily detected in normal thyroid venous plasma (5-10 ng/ml) and thyroid gland extracts (similar to 1 mug/gland) but not in peripheral blood; 5) Bioassay and radioimmunoassay of rat thyroid extracts (N equals 18) showed good agreement (r equals 0.86, p less than 0.001). The results support the idea that rat TCT is closely related to human TCT, indicate that major antigenic determinants reside in the C-terminal portion of the molecule, and show that antisera to either human or rat TCT can be used to measure rat TCT.

Amino Acids↗
PubMed1975

Identification of C-cells in normal and goitrous rat thyroid tissues using antiserum to rat thyrocalcitonin and the immunoperoxidase bridge technique.

Application of the immunoperoxidase bridge technique to the light microscopic localization of C-cells in rat thyroid tissue is described. Guinea pig antisera to rat thyrocalcitonin (TCT) were produced by the injection of highly purified rat TCT (100-300 MRC U/mg) emulsified in complete Freund's adjuvant. A 1:1000 dilution of the antiserum used in this study gave a strong positive reaction with rat C-cells, and 1 ml of undiluted antiserum provided sufficient material for staining approximately 5000 slides. The substitution of nonimmune guinea pig serum for the anti-rat TCT serum or the prior absorption of anti-rat TCT serum with increasing amounts of highly purified rat TCT both eliminated the staining of thyroid C-cells. Likewise, no staining was observed in tissue sections from rat parathyroid, ovary, pituitary gland, and skeletal muscle. Antiserum to synthetic human TCT also could be used to identify rat thyroid C-cells. The method revealed abundant C-cells in goiters from rats fed a low-iodine diet for more than 1 year. This finding was supported by electron microscopic evaluation of goitrous tissue and by the detection, by radioimmunoassay, of TCT in thyroid tissue and in peripheral blood from goitrous rats.

Animals↗
PubMed1975

Ability of several cations to promote secretion of thyrocalcitonin in the pig-1-2 (38559).

Various ions were tested to see whether or not at pharmacological plasma levels they affected TCT secretion from the pig thyroid gland in vivo. Test solutions were infused either systemically (femoral vein) or directly into the thyroid artery for brief (10-12 min) periods. Infusions of large doses of magnesium, potassium, strontium and barium, as well as calcium, produced increases in TCT in thyroid venous plasma ranging from two- to tenfold. Blood analyses reveled that levels of these stimulatory cations produced in plasma during the infusions indeed were high. In contrast, infusions of sodium and phosphate suggested that neither hypernatermia nor hyperhosphatemia directly altered TCT secretion. The findings are in accord with previous suggstions that although cations other than calcium are capable of increasing TCT secretion, probably only calcium plays an important role in the physical regulation of TCT secretion. Neverthless, other effective agents, such as those reported here, may consitute useful pharmacological tools for studying the mechanisms involved in secretion of TCT.

Animals↗
PubMed1975

Relationship of blood concentrations of calcium, phosphate, gastrin and calcitonin to the onset of feeding in the rat.

Daily fluctuations in plasma calcium concentrations in rats trained to a closely regulated feeding pattern have been compared to corresponding plasma gastrin and calcitonin concentrations. The time period studied was that extending from 4 hr prior to the start of the feeding. Both plasma calcium and phosphate levels fedd prior to the start of the feeding period and remained low at least for the first 2 hr of feeding. This pattern was also observed in rats in which food was withheld for 2 hr past the regular feeding time. Plasma 45Ca and 32P concentrations (radionuclide injected at least one week prior to sampling) did not follow the pattern of their stable counterparts. Instead, these values rose or remained constant until after feeding had commenced, after which they fell precipitously. Both plasma calcitonin and gastrin levels rose rapidly after the start of the feeding period. The primary point of emphasis is that calcitonin secretion was produced in these rats by an intestinal related stimulus and not by a rise in plasma calcium concentration.

Animals↗