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Biomedical subjects

L J Deftos

Publications and source records attributed to L J Deftos.

At least 163 records · Page 9Linked to original sources
PubMed1985

Imparied calcitonin secretion in patients with Williams syndrome.

Williams syndrome is associated with neonatal hypercalcemia of unclear pathogenesis. To learn more about the hormonal control of calcium metabolism in patients with Williams syndrome, we studied five such children, with intravenous calcium and parathyroid hormone infusions as provocative stimuli. These patients were found to have significantly higher mean baseline calcium concentrations, delayed clearance of calcium after intravenous calcium loading, and blunted calcitonin responses after calcium infusion, compared with a group of seven normal children. No abnormalities of vitamin D metabolite concentrations were found, either before or after parathyroid hormone stimulation. Our studies demonstrate that patients with Williams syndrome have a defect in the synthesis or release of immunoreactive calcitonin. A deficiency of calcitonin may explain the abnormalities of calcium metabolism seen in these patients and can serve as an important endocrine marker for Williams syndrome.

Calcitonin↗
PubMed1985

Salmon calcitonin-like immunoactivity in extracts of Tetrahymena pyriformis.

Acid extracts of Tetrahymena pyriformis, a ciliated protozoan grown in defined medium revealed the presence of materials with salmon-type calcitonin immunoactivity. These findings add support to earlier reports of the presence of materials closely resembling vertebrate peptide hormones in unicellular microbes.

Animals↗
PubMed1985

Serum bone Gla protein and other biochemical estimates of bone turnover in early postmenopausal women during prophylactic treatment for osteoporosis.

Serum bone Gla protein (BGP) and conventional biochemical indices of bone metabolism were determined in 66 early postmenopausal women during a double-blind therapeutic trial performed to investigate the effect of oestrogen, calcium and 1,25 (OH)2D3 on postmenopausal osteoporosis. The biochemical variables were determined before, during and after withdrawal of therapy. We found a very high correlation between serum BGP and serum alkaline phosphatase--a measure of bone formation, less high correlation between serum BGP and the remaining parameters--indices of bone resorption. It is concluded that serum BGP probably reflects bone formation and may prove to be a useful new biochemical marker.

1-Carboxyglutamic Acid↗
PubMed1985

Calcitonin produces hypercalcemia in leopard sharks.

Calcitonin was detected by RIA in sera from four marine species, leopard sharks (Triakis semifasciata), horn sharks (Heterodontus francisci), thornback rays (Platyrhinoides triseriata), and kelp bass (Paralabrax clathratus). These animals have levels of calcitonin and calcium higher than freshwater and terrestrial species have. The administration of salmon calcitonin to bass (4 micrograms/kg BW) produced hypocalcemia and hypophosphatemia as has been reported for other bony vertebrates. In marked contrast, calcitonin produced a prompt hypercalcemia in sharks; the average was 9.8% increase in serum calcium in nine animals with no attendant change in phosphorus. These findings demonstrate that calcitonin can increase serum calcium in sharks. Because shark skeleton is composed of cartilage, this hypercalcemic effect of calcitonin does not require a bony skeleton.

Animals↗
PubMed1985

Hypercalcemia in rats bearing growth hormone- and prolactin-secreting transplantable pituitary tumors.

We evaluated the effects of chronic massive elevations of serum GH and PRL on calcium metabolism in rats bearing the MStT/W15 and 7315a transplantable pituitary tumors. MStT/W15 tumor rats manifest elevated serum GH and PRL levels, hypercalcemia, hypercalciuria, and elevated serum levels of PTH and 1,25-dihydroxyvitamin D. The hypercalcemia was not reversed by dexamethasone or propranolol treatment, but was ameliorated by starvation. Parathyroidectomy produced hypocalcemia in the MStT/W15 tumor rats, confirming the parathyroid dependence of the hypercalcemia. The 7315a tumor produced a milder degree of hypercalcemia, along with elevated serum levels of PRL, ACTH, and corticosterone; serum GH was normal. In high concentrations, PRL and/or GH may stimulate the secretion of PTH as well as enhance dietary calcium absorption, in part through the mediation of 1,25-dihydroxyvitamin D.

Animals↗
PubMed1985

Metabolism of calcium and phosphorus during pregnancy and lactation in white-tailed deer.

The effects of pregnancy and early lactation on blood parameters were studied in 4 white-tailed does in 1981-82 and 8 in 1982-83. No year or fecundity effects (P less than 0.05) were found on plasma calcium (Ca), inorganic phosphorus (P), calcitonin (CT), parathyroid hormone (PTH), or oestradiol -17 beta (E2). An increase (P less than 0.05) in dry matter and metabolic feed intake occurred during pregnancy and lactation. Plasma Ca tended to increase during pregnancy and peaked 5-7 weeks pre-partum, while hypocalcaemia was observed 1-2 weeks pre-partum. Elevated concentrations of plasma Ca and P were found during lactation. During the last trimester of pregnancy, plasma concentrations of alkaline phosphatase (AP), PTH, and E2 but not of CT were higher (P less than 0.05) than in the other trimesters. The results indicate a physiological hyperparathyroidism in pregnant deer. Plasma concentrations of CT were higher (P less than 0.05) during lactation and post-weaning than during pregnancy. Increased AP and PTH during late pregnancy may be responsible for Ca absorption and mobilization, whereas elevated plasma concentrations of E2 may function to block excessive bone resorption. After parturition, lowered E2 may allow bone resorption to proceed, relatively high PTH may enhance Ca absorption and mobilization, and elevated CT may protect the skeleton against excessive bone resorption.

Animals↗
PubMed1985

Activation of the 1,25-dihydroxyvitamin D3 receptor in cultured rat osteogenic sarcoma cells.

Activation of the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] receptor-hormone complex was studied in-vitro using cytosolic preparations of rat osteogenic sarcoma cell ROS 17/2-8 and a DNA-cellulose assay. We found that salt was required for extraction of the unoccupied receptor indicating its possible nuclear localization. The 1,25(OH)2D3 receptor underwent an activation process similar to other steroid hormones which could be stimulated by heat and salt. At physiological ionic strength 100% of the complexes were, however, activated at 2 degrees C, indicating that the activation process is not absolutely temperature dependent. In contrast to other steroid hormones, 30-50% of the complexes were in an activated state in the absence of heat and salt moreover, alkaline phosphatase and ammonium sulphate had no effect on activation. Activation was also stimulated by ATP and ATP plus 8BrcAMP indicating the possible role of phosphorylation in the activation process; however, further work is required to clarify this point.

Adenine Nucleotides↗
PubMed1985

Exercise-induced hypercalcemia and the calciotropic hormones.

Sixteen healthy male volunteers exercised on a bicycle ergometer starting at 40% Vo2max and progressing at 5-minute intervals up to 75% Vo2max over a 20-minute period. Blood was drawn from an indwelling venous catheter at baseline, at 5 minutes through 20 minutes, and at 10 and 20 minutes after the exercise was ended. Significant increases (which returned toward baseline in the rest period) were observed during the exercise period in total calcium and calcium ion activity, phosphate, potassium, magnesium, albumin, and lactic acid levels. Plasma volume (based on hematocrit value) decreased during the exercise period. Serum parathyroid hormone levels decreased and calcitonin levels increased at the early period of the short-term exercise. Although hemoconcentration was of sufficient magnitude to explain the change in calcium ion activity, the increase in potassium and phosphate were caused in part by additional factors.

Adult↗
PubMed1984

1,25-Dihydroxyvitamin D3 receptors in a subset of mitotically active lymphocytes from rat thymus.

Lymphocytes from the rat thymus gland were separated on Percoll gradient in two subsets. The first subset was enriched in large mitotically active cells and the second in small mitotically inert cells. The former cell preparation possessed a 3.3 S macromolecule with high affinity for 1,25-Dihydroxyvitamin D3 (Kd = 3.3 X 10(-10)M) which bound to DNA cellulose and was eluted from this resin with 0.26 M KCl. In contrast, the small-cell-enriched subset of thymic cells was negative for 1,25-Dihydroxyvitamin D3 specific binding. These findings support evidence from studies in human lymphocytes that there exists an association between mitotic activity and 1,25-Dihydroxyvitamin D3 receptor expression in this class of leukocytes.

Animals↗
PubMed1984

Glucocorticoids increase the 1,25(OH)2D3 receptor concentration in rat osteogenic sarcoma cells.

We have used cultured osteoblastlike rat osteogenic sarcoma cells (ROS 17/2) which have receptors for 1,25(OH)2D3 and for glucocorticoids, and have examined the modulation of the 1,25(OH)2D3 receptor by the potent glucocorticoid triamcinolone acetonide. We report that triamcinolone acetonide caused an increase of the 1,25(OH)2D3 receptor concentration in these cells but it did not affect the affinity of the receptor to 1,25(OH)2D3; this phenomenon occurred in a dose-dependent fashion for triamcinolone (10(-9) to 10(-7) M) with a maximum increase of 1,25(OH)2D3 receptor concentration of approximately equal to twofold. During the culture period, the 1,25(OH)2D3 receptor concentration was altered both in untreated as well as in triamcinolone-treated cells, being highest at the early logarithmic phase and diminished progressively as cells approached confluence. However, throughout the culture period, the 1,25(OH)2D3 receptor concentration was higher in the triamcinolone-treated cells.

Animals↗
PubMed1984

Serum bone Gla protein variations during estrogen and calcium prophylaxis of postmenopausal women.

We have evaluated serum bone Gla protein (BGP) changes in a double-blind study of early postmenopausal women during treatment with estrogen and calcium. To substantiate the changes in bone turnover, serum alkaline phosphatase, 24-hour urinary calcium, and bone mineral content (BMC) have also been measured. Our results indicate that serum BGP is a valuable measurement of bone metabolism.

Alkaline Phosphatase↗
PubMed1984

Calcitonin levels in sera of infants and children: relations to age and periods of bone growth.

Serum calcitonin levels have been reported to be elevated in premature and newborn infants, a period of maximal rate of bone growth. To determine whether calcitonin remains elevated during the first year of life, a time of rapid extrauterine bone growth, fasting serum calcitonin levels were determined in 31 hospitalized infants and children ages 24 weeks gestation to 6 years. Calcitonin levels were significantly higher in the premature and newborn infants than in the first year of life. However, calcitonin levels in the first year of life were still significantly higher than during the second to sixth years. This fall in serum calcitonin levels parallels the age-related decline in rate of bone growth. One can speculate that the changes in serum calcitonin levels during the first year of life may indicate that it plays a role in bone growth or mineralization. However, the possibility that the changes in calcitonin levels are unrelated to changes in bone growth or mineralization has not been ruled out.

Age Factors↗
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

Liposome entrapment enhances the hypocalcemic action of parenterally administered calcitonin.

The hypocalcemic effect of liposomal-entrapped calcitonin (CT) was evaluated in rats. Salmon CT and human CT were entrapped in liposomes composed of egg phosphatidylcholine with or without an equimolar amount of cholesterol. The liposomes were separated by Sepharose 4B chromatography into fractions consisting of large multilamellar vesicles and small unilamellar vesicles. The incorporation of CT was monitored by counting [125I]CT and by specific RIA. Liposomal entrapment enhanced the hypocalcemic potency of parenterally administered salmon CT and human CT. After iv administration, the large multilamellar vesicles were more potent than small unilamellar vesicles in their hypocalcemic effect; cholesterol inclusion in the MLV liposome preparation prolonged the hypocalcemia. However, with im administration, the cholesterol-free liposomes were more potent than their cholesterol-containing counterparts regardless of size. These studies demonstrate that liposomal entrapment can be used to enhance the hypocalcemic potency of CT. It appears that both the size and composition of the liposome preparation are important in this effect, as is the route of administration. It may be possible to produce liposome-CT preparations with advantageous pharmacological characteristics.

Animals↗
PubMed1984

Seasonal levels of serum parathyroid hormone, calcitonin and alkaline phosphatase in relation to antler cycles in white-tailed deer.

Seasonal levels of serum parathyroid hormone (PTH), calcitonin (CT), and alkaline phosphatase (AP) were studied in relation to antler growth cycles in 8 male (2.5-6 years old) white-tailed deer. Feed consumption was recorded weekly, whereas body weight was recorded biweekly. Antler length was measured from the pedicle to the tip after velvet growth was initiated. Serum samples were obtained biweekly while animals were tranquilized with xylazine hydrochloride. Serum Ca was significantly (P less than 0.05) elevated during the summer. Serum P was significantly (P less than 0.05) elevated only during early fall. There was an increase in serum PTH during velvet initiation in April-May, but not thereafter. CT increased during the rapid antler growth period. Serum PTH levels were significantly (P less than 0.05) elevated (0.628 vs 0.884 ng/ml) during post-velvet shedding and decreased (0.602 vs 0.346 ng/ml, P less than 0.05) during post-antler casting. Serum AP activity was highest during rapid velvet antler growth. Feed intake was lowest in early winter, but a compensatory increase was found in late winter. Feed intake peaked in May, then gradually decreased. Body weight was maximum in November and minimum in March. It is concluded that increased PTH during velvet initiation is responsible for Ca absorption and/or mobilization. Increasing PTH levels are related to final mineralization of antlers post-velvet shedding. Higher levels of serum Ca in June-July inhibit continued increase in PTH. Increased CT during rapid antler growth may have prevented excessive bone resorption.

Alkaline Phosphatase↗
PubMed1984

Effects of xylazine immobilization on biochemical and endocrine values in white-tailed deer.

The effect of xylazine hydrochloride on biochemical and endocrine parameters in plasma was examined in adult white-tailed deer (Odocoileus virginianus (Zimmermann]. In the first experiment, seven animals were injected intramuscularly via a blowgun dart with 0.65 mg/kg xylazine (100 mg/ml) and were bled 10, 20, 30, and 60 min post-injection. In the second experiment, eight animals were manually restrained for the first blood sampling and then injected manually and bled as before. Plasma calcium (Ca), inorganic phosphorus (P), and alkaline phosphatase (AP) were measured spectrophotometrically. Plasma parathyroid hormone (PTH), calcitonin (CT), thyroxine (T4), triiodothyronine (T3), and cortisol were measured by radioimmunoassay. Plasma PTH, CT, T4, T3, and AP activity did not differ (P greater than 0.05) during the 1 hr period studied in either experiment. Plasma Ca and P decreased significantly (P less than 0.05) in the second experiment, whereas cortisol levels increased significantly (P less than 0.05) 10 min post-injection in both experiments. The results may have been due to a drug effect or a combined drug and stress effect. It is suggested that xylazine may be safely used as an anesthetic in measuring PTH, CT, T4 and T3, and plasma AP up to 60 min post-injection in deer. Caution should be taken in using xylazine as an anesthetic to study adrenocortical function.

Animals↗
PubMed1984

Potential role of parathyroid hormone as an inhibitor of erythropoiesis in the anemia of renal failure.

Patients with varying degrees of renal insufficiency and patients with end-stage renal disease receiving continuous ambulatory peritoneal dialysis or regular hemodialysis therapy were studied to assess the independent relationship between serum parathyroid hormone concentration, and both severity of anemia and degree of serum inhibition of erythropoiesis. In patients with renal insufficiency not receiving dialysis, a significant curvilinear relationship between serum parathyroid hormone and creatinine concentrations was present (r = 65, p less than 0.001). Serum parathyroid hormone (by radioimmunoassay) also correlated with hematocrit level (r = -0.54, p less than 0.001) and degree of serum inhibition of in vitro erythroid progenitor cell growth in fetal mouse liver cultures (r = -0.45, p less than 0.001). However, multiple linear regression analysis revealed that after controlling for the effect of creatinine, m-parathyroid hormone is no longer a significant predictor of hematocrit level or erythroid progenitor cell growth. On the other hand, when a restricted population of patients with creatinine values between 1 and 4 mg/dl was analyzed separately, controlling for the effect of creatinine, there was still a significant correlation between hematocrit level and m-parathyroid hormone, but no such relationship was seen when participants with parathyroid hormone levels of less than or equal to 1000 pg/ml were analyzed. No significant correlation was seen between hematocrit level or inhibition of erythroid colony growth and serum parathyroid hormone concentrations in patients receiving either regular hemodialysis or continuous ambulatory peritoneal dialysis. In 13 patients given regular hemodialysis studied before and after parathyroidectomy, there was no significant change in serum erythropoietin (by radioimmunoassay) or serum inhibition of erythropoiesis, although hematocrit levels increased in six of the 13 patients. The 1-34 human parathyroid hormone, 1-84 bovine parathyroid hormone, and 1,25-dihydroxycholecalciferol had no effect on in vitro erythroid burst-forming unit growth. Parathyroid hormone (8 mu/ml) inhibited and 1,25-dihydroxycholecalciferol (4.0 ng/ml) stimulated erythroid colony-forming unit growth only in the absence of exogenous erythropoietin in culture. In summary, it was not possible to demonstrate a significant relationship between serum parathyroid hormone levels and anemia or inhibition of erythropoiesis in patients with uremia either before starting dialysis or after receiving long-term dialysis treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗