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L J Deftos

Publications and source records attributed to L J Deftos.

At least 109 records · Page 6Linked to original sources
PubMed1990

The rate of bone mineral loss in normal men and the effects of calcium and cholecalciferol supplementation.

OBJECTIVE: To determine the rate of bone loss in normal men, and to examine the effects of dietary calcium and cholecalciferol supplementation on bone loss in men. DESIGN: Double-blinded, placebo-controlled 3-year trial of supplementation with calcium (1000 mg/d) and cholecalciferol (25 micrograms/d). SETTING: Clinical research center at a university medical facility. SUBJECTS: Normal men 30 to 87 years old, recruited from the Portland community. MEASUREMENTS AND MAIN RESULTS: Radial bone mineral content (assessed by single-photon absorptiometry) fell by 1.0%/y (95% CI, -1.3% to 0.7%) at a proximal radial site and 1.0%/y (95% CI, -1.4% to -0.6%) at a distal radial site. Vertebral bone mineral content (assessed by dual-energy quantitative computed tomography) declined by 2.3%/y (95% CI, -2.8% to -1.8%). In these healthy men with a high basal dietary calcium intake (1159 mg/d), calcium and cholecalciferol supplementation did not affect bone loss at any site. CONCLUSIONS: Normal men experience a substantial bone loss at both axial and appendicular sites that is not prevented by calcium and vitamin D supplementation in a well-nourished population.

Adult↗
PubMed1990

Serum osteocalcin (BGP) levels in normal men: a longitudinal evaluation reveals an age-associated increase.

Serum levels of bone gla protein (BGP) have been reported to increase with aging and hence to reflect an age-related increase in bone remodeling activity. To evaluate the relationship between aging and serum BGP levels in a study of longitudinal design, we measured BGP concentrations in 77 normal men at 6 month intervals over a 3 year period. Mean BGP levels at the onset (4.95 +/- 1.5 ng/ml) increased significantly during the study (p = 0.004), and the mean of individual BGP slopes was positive (0.38 +/- 0.6 ng/ml per year, p = 0.0001). The rate of change in BGP was not related to serum creatinine levels or dietary calcium intake.

Adult↗
PubMed1990

A chromogranin A-derived peptide differentially regulates the secretion of calcitonin gene products.

We studied the regulation of the secretion of CT and CGRP by chromogranin A (CgA)-derived peptides in a human lung tumor cell line. The amino-terminal peptide of CgA, CgA1-40, stimulated the secretion of CGRP and inhibited the secretion of CT; both effects occurred in a dose-dependent manner. These studies demonstrate a differential effect of a CgA-derived peptide on two products of the CT gene, CT itself and CGRP. CgA may be processed at its multiple dibasic sites to peptides that specifically regulate the secretion of its coresident hormones, in this case two calcitonin gene products that are present in the same secretory vesicle. This novel mechanism represents a new pathway for the control of calcium regulating hormones.

Calcitonin↗
PubMed1990

Intraperitoneal free fatty acids induce severe hypocalcemia in rats: a model for the hypocalcemia of pancreatitis.

Indirect evidence suggests a causative role for intraperitoneal free fatty acids (FFA) in hypocalcemia associated with pancreatitis. We examined the effects of intraperitoneal injection of four naturally occurring FFAs on serum calcium in rats. Two saturated FFAs, stearate and palmitate, induced little or no hypocalcemia. Two unsaturated FFAs, oleate and linoleate, caused dramatic hypocalcemia in treated versus control rats (6.3 +/- 1.4 and 5.3 +/- 0.7 mg/dl, respectively, versus 10.1 +/- 0.6). Dose-response studies demonstrated that minute quantities of oleate (100 microliters per 250 g rat) caused marked hypocalcemia (7.2 +/- 0.3 mg/dl). Treated versus control rats also revealed a decrease in ionized calcium (3.15 +/- 0.2 versus 5.6 +/- 0.05 mg/dl) and magnesium (1.4 +/- 0.15 versus 2.0 +/- 0.10), an appropriate increase in PTH levels (1670 +/- 451 versus 396 +/- 235 pg/ml), and a fall in calcitonin levels (70.4 +/- 21.3 versus 47.5 +/- 16.4 pg/ml) but no change in albumin or phosphate levels. In vitro, the Ksp of calcium dioleate was shown to be 5.3 x 10(-8) m3/liter3; thus under physiologic conditions 100 microliters oleate binds 7.2 mg calcium, or approximately twice the total ECF ionized calcium in the rat. The amounts of intraperitoneal FFA that can easily be achieved in pancreatitis complex pathophysiologically significant amounts of calcium and may lead to severe hypocalcemia.

Animals↗
PubMed1990

Factors influencing the enhanced hypocalcemic action of liposome-entrapped calcitonin.

The mechanism whereby liposomal entrapment enhances the hypocalcemic effect of calcitonin (CT) was evaluated in the rat. Phosphatidylcholine (PC) and PC plus cholesterol (PCC) preparations of large multilammelar vesicles (MLV) and small unilammelar vesicles (SUV) were used to entrap human calcitonin (hCT). The effect of each of these preparations was assessed by measuring plasma calcium after their parenteral administration. Changes in calcium were compared with plasma concentrations of liposomal hCT (L-hCT) and free hCT (F-CT). The plasma form of hCT was also evaluated by gel filtration chromatography. Most of the liposomal preparations had a greater hypocalcemic effect than unencapsulated hCT. Following I.V. administration, the MLV-hCT preparations had the greatest hypocalcemic effect. Thus, to enhance the hypocalcemic effect of hCT, large vesicular size is important for I.V. administration and the absence of cholesterol in the liposome is important for I.M. administration. In general, the greatest hypocalcemic effect was achieved by those liposomal preparations that resulted in the most sustained increase of L-hCT and F-hCT in plasma. Thus, liposomal entrapment enhances the hypocalcemic effect of hCT by prolonging the presence of the peptide in the peripheral circulation.

Animals↗
PubMed1990

Serum markers of bone formation in parenteral nutrition patients.

Bone gamma-carboxyglutamic acid containing protein (BGP) has been utilized effectively as a serum marker of bone turnover in healthy normals and in individuals with a variety of metabolic bone disorders including postmenopausal osteoporosis and Paget's disease. The utility of this serum marker in other bone disorders, including that associated with the maintenance of patients on long-term parenteral nutrition, still requires definition. Because of our interest in this clinical syndrome and the availability of serum and of bone formation rates (BFR) measured directly from double tetracycline labeling in 11 long-term parenteral nutrition patients, we measured BGP levels in these patients and attempted to correlate this measure with BFR. Serum vitamin D metabolites, immunoreactive parathyroid hormone (PTH), and alkaline phosphatase (alk phos) were also measured. Serum BGP was only weakly and not significantly correlated (r = 0.24, p = NS) with bone formation rate for the group as a whole. However, in a subgroup of 10 patients without hyperparathyroidism, there was strong and significant correlation (r = 0.81, P less than 0.01) between BGP and BFR. There was also a strong correlation between bone formation rate and serum 1,25 dihydroxyvitamin D [1,25(OH)2D] levels (r = 0.89, P less than 0.01, n = 11). The mechanism of this association could not be established. A correlation of borderline significance was observed between bone formation rate and serum alk phos (r = 0.60, P = 0.05, n = 11). The current data suggest that additional studies may help to more fully define the utility of serum measurements in quantifying bone dynamics in parenteral nutrition patients, and that measures of vitamin D metabolites, BGP, and alk phos may prove useful.

1-Carboxyglutamic Acid↗
PubMed1990

Distinct patterns of chromogranin A-related species can be demonstrated in endocrine cells.

We have studied the pattern of chromogranin A (CgA)-related species in different human endocrine cells that produce CgA and also express the calcitonin gene. Antibodies against CgA peptides that span its linear sequence were used in Western analysis of cell lines derived from medullary thyroid carcinoma (MTC), small cell lung cancers (SCLC), epidermoid cell lung cancer (ECLC) and a pulmonary carcinoid tumor (CRND). Each of the cell lines demonstrated a distinct pattern of CgA-related species. Gel filtration studies also revealed multiple and different forms of immunoreactive CgA in the cell lines. Although proteolysis may contribute to our results, these observations suggest that native CgA is processed to smaller species in a tissue-specific pattern by different endocrine cells. More conclusive studies, however, are necessary to establish that cell processing leads to the specific CgA moieties that we have observed.

Blotting, Western↗
PubMed1990

Heat shock proteins bind calcitonin.

We have demonstrated two heat shock proteins (HSP's) in the human placenta that specifically bind calcitonin. Binding specificity was shown by ligand-affinity chromatography and by competitive binding studies. The HSP's were identified by Western analysis and by amino acid sequence. Our observations are consistent with the hypothesis that HSP's may function by binding and interacting with cellular proteins and peptides during their biogenesis. This interaction may both depend upon and produce conformational changes in these ligands during their intracellular processing. Additionally, HSP-peptide hormone interactions may confound studies designed to investigate classical receptor-hormone interactions.

Amino Acid Sequence↗
PubMed1989

Rapid, simple identification of individual osteoblastic cells and their specific products by cell blotting assay.

Biochemical and molecular biological studies of osteoblastic cell function and hormonal regulation are frequently confounded by the inherent cellular heterogeneity and phenotypic instability of existing in vitro and in vivo model systems. A new technique (derived from Western blotting or antibody-based detection of protein molecules bound to nitrocellulose paper) is described for identification of individual cells which synthesize osteoblast-specific gene products (bone Gla-protein, type I collagen, and alkaline phosphatase) or produce cAMP in response to parathyroid hormone (PTH) or isoproterenol. Dispersed primary neonatal rat calvariae or osteogenic sarcoma cells were "plated" on Immobilon-P (a hydrophobic transfer membrane with very high protein-binding capacity) for 30 minutes to several hours, followed by agonist treatment, formalin fixation, hematoxylin staining, and immunostaining with a battery of antibodies specific for osteoblastic products. Individual cells and their secretory zones were visualized by light microscopy and counted. Treatment with PTH with or without isoproterenol resulted in increases in the percentages of osteoblastic cells elaborating cAMP, as well as the intensity of immunostaining, but had no effects on MCF-7 cells, a nonosteoblastic breast carcinoma control line. The percentage of cells within each primary osteoblastic cell population isolated or rat osteogenic sarcoma cell clone (G2 or C12) that elaborated bone-specific proteins or that generated cAMP in response to PTH varied with time and the individual cellular preparation, reconfirming the cellular heterogeneity of these systems. This method, in conjunction with techniques such as in vitro hybridization, should prove useful in characterizing discrete osteoblastic bone cell subpopulations and in clarifying mechanisms of hormonal regulation by local and systemic agents.

Alkaline Phosphatase↗
PubMed1989

Rapid changes of light microscopic indices of osteoclast-bone relationships correlated with electron microscopy.

The relationships of tibial endosteal osteoclasts to bone surfaces were quantitatively evaluated during initiation of calcium repletion in calcium-deficient rats. To do this, indices of osteoclast-bone relationships obtained by light microscopy were devised and evaluated by comparing with those obtained by electron microscopy (EM). These indices are the percent of the osteoclast width that (1) exhibits markers indicative of a ruffled border, (2) is in close contact with bone, (3) is isolated from bone by other cell types, and (4) is separated from bone by intercellular material. The indices obtained by light microscopy were strongly correlated with similar indices obtained by EM and were equally sensitive but considerably easier to obtain. The ruffled border and contact index were significantly decreased by 3 hours after beginning the meal whereas cells of other types became interposed between the osteoclasts and the bone.

Animals↗
PubMed1989

Absence of hyperparathyroidism in severe liver disease.

Elevated serum levels of intact parathyroid hormone (PTH) have been reported in severe versus mild biliary cirrhosis. The aim of this study was to determine whether hyperparathyroidism was present in severe liver disease on the basis of the inability of the liver to catabolize the hormone. Because biologic activity resides in the amino terminal, and amino terminal PTH determinations have not been routinely made in liver disease, it is possible that hyperparathyroidism was previously missed in these patients. Accordingly, we obtained fasting blood from 11 patients with severe liver disease and 8 age-matched controls. We measured intact, amino terminal, and mid-region PTH, vitamin D metabolites, bone gamma carboxyglutamic acid protein (BGP), ionized calcium, phosphorus, magnesium, and liver function tests. Serum levels of PTH were normal with all assays and 1,25(OH)2D levels were not elevated. These findings argue against the possibility that hyperparathyroidism plays a role in the pathogenesis of hepatic osteodystrophy.

Adult↗
PubMed1989

Changes in plasma vitellogenin, sex steroids, calcitonin, and thyroid hormones related to sexual maturation in female brown trout (Salmo trutta).

Female brown trout (Salmo trutta) from a wild strain (Baltic sea trout) and a cultured strain were sampled individually for blood plasma at regular intervals during the period around final sexual maturation. The plasma samples were analyzed for vitellogenin (VTG), estradiol-17 beta, testosterone, 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P), calcitonin, tri-iodothyronine (T3), thyroxine (T4), and total and free plasma calcium. In the wild fish, VTG, estradiol-17 beta, and testosterone peaked 30 days before ovulation, while 17,20 beta-P had a sharp peak at ovulation. Both T3 and T4 declined at the beginning of the sampling period, reached minimal levels 30 days before ovulation, and rose sharply at the time of ovulation. Calcitonin levels were elevated during final maturation. Total plasma calcium correlated with plasma VTG levels. In the cultured strain, sampling was started 2 weeks before ovulation. The levels of VTG, estradiol-17 beta, and testosterone decreased throughout the sampling period. 17,20 beta-P and calcitonin concentrations were high during the period close to ovulation. Plasma thyroxine remained at basal levels in cultured trout. The discrepancies observed between wild and cultured females may be due to differences in stress susceptibility, environmental conditions, life cycles, or to genetic divergence between the strains.

Animals↗
PubMed1989

A high-fat diet increases calcitonin secretion in the rat.

We have studied the effects of diet-induced obesity on thyroidal calcitonin, plasma calcitonin, calcium and phosphorus in rats. Twelve 9-week-old female rats were randomly divided into two groups. One group was fed a low-fat diet while the other was fed a high-fat diet. Both diets had 0.76% Ca, 0.56% P and 2.2 U/g vitamin D; however, the high-fat diet had hydrogenated vegetable oil added at 405 g/kg. All rats were pair-fed and consumed 11 g/day per rat for 27 weeks at which time the rats were fasted overnight and exsanguinated. The rats on the high-fat diet weighted 406 +/- 21 g (mean +/- SEM) versus 292 +/- 13 g for controls and had higher levels of serum calcitonin (104 +/- 12 versus 57 +/- 9 pg/ml). The obese rats also had increased thyroidal calcitonin by radioimmunoassay and increased thyroidal C-cells by immunohistology. The increased calcitonin levels occurred without a concomitant increase in calcium levels. These data indicate that a high-fat diet in rats stimulates C-cell growth and calcitonin secretion.

Animals↗
PubMed1989

Smoltification and seawater adaptation in coho salmon (Oncorhynchus kisutch): plasma calcium regulation, osmoregulation, and calcitonin.

In order to examine the dynamics of ion regulation, osmoregulation, and plasma calcitonin during the parr-smolt transformation (smoltification), blood and gill tissue were collected from yearling coho salmon, Oncorhynchus kisutch, from February to October. Fish were kept in fresh water (FW) throughout this period. In addition, fish were exposed to seawater (SW) at the peak of smoltification in mid-April, and samples from these fish were collected until July. Plasma osmolality, gill Na+,K+-ATPase activity, plasma levels of calcitonin, and free and total calcium and magnesium were measured. SW adaptability of FW fish was assessed throughout the study by measurements of plasma osmolality following a 24-hr exposure to seawater. The greatest hypoosmoregulatory ability occurred in April-May, although SW-adapted fish had higher plasma osmolality than FW-adapted fish at all times. Gill Na+,K+-ATPase activity in FW-adapted fish increased from April to June and increased rapidly following exposure of fish to SW, and remained elevated in SW-adapted fish. Free plasma calcium and magnesium levels increased following SW exposure, but returned to prior levels within 1 week. Netting and confinement stress during sampling caused an increase in plasma osmolality and free calcium and magnesium levels in both FW- and SW-adapted fish. Changes in hypoosmoregulatory ability during smoltification and SW adaptation were correlated with changes in gill Na+,K+-ATPase activity. A sharp transitory peak in plasma calcitonin levels occurred early in smoltification (March) and in SW-adapted fish in June. Plasma calcitonin levels gradually increased in FW-adapted fish during the period of desmoltification. However, no change in plasma calcitonin levels occurred during SW-induced hypercalcemia, suggesting that the hormone does not play a major role in short-term plasma calcium regulation in coho salmon.

Acclimatization↗
PubMed1989

PTHrP secretion is stimulated by CT and inhibited by CgA peptides.

We studied the regulation of the secretion in vitro of the parathyroid hormone-related protein (PTHrP) associated with the hypercalcemia of malignancy by Chromogranin A (CgA)-derived peptides and by human calcitonin (CT) in the BEN human lung tumor cell line. The amino terminal peptide of CgA, CgA1-40, inhibited the secretion of PTHrP, whereas other peptides had no such effect. Human CT stimulated the secretion of PTHrP, whereas other hormones had no such effect. Both effects occurred in a dose-dependent manner. These studies reveal novel regulatory pathways among peptides and proteins that are commonly associated with each other and can have paracrine interactions. CgA may be processed at its multiple dibasic sites to peptides that regulate the secretion of its co-resident hormones, in this case PTHrP. In addition to a paracrine effect, CT may be clinically useful as a provocative agent for PTHrP secretion. Complex interactions are present among the calcium-regulating hormones and their associated proteins.

Calcitonin↗
PubMed1989

17 beta-estradiol increases plasma calcitonin levels in salmonid fish.

The functional role of calcitonin in teleost fish is in question. Data on the role of calcitonin in calcium regulation are inconsistent, and while a participation in some aspects of sexual maturation has been strongly indicated, the exact function is not known. To establish if there exists a functional relationship between 17 beta-estradiol (E2) and calcitonin in salmonid species, rainbow trout (Oncorhynchus mykiss), Atlantic salmon (Salmo salar), and coho salmon (Oncorhynchus kisutch) were injected ip with a single or repeated doses of E2. It is concluded that E2 treatment increases plasma calcitonin levels directly or indirectly, and that it is possible that E2 is responsible for the rise in calcitonin levels during late sexual maturation of female salmonids. In accord with earlier studies, no correlation was found between changes in calcitonin levels and free plasma calcium levels. It seems clear that changes in free plasma calcium levels are not the primary cause of the plasma calcitonin changes in teleost fish. It is possible that calcitonin is involved in mobilizing calcium or directing its mobilization by protection of certain calcium pools during vitellogenesis. However, the increase in calcitonin occurs so close to ovulation that a reproductive role other than a calcium regulatory one is likely. The possibility of transfer of calcitonin itself to the developing oocytes and a subsequent role in embryonic development must also be considered.

Animals↗
PubMed1989

Human pituitary tumors secrete chromogranin-A.

Chromogranin-A (CgA) has emerged as a serum and tissue marker for a number of endocrine tumors. We studied 15 patients with pituitary tumors to evaluate the clinical value of CgA as a serum and tissue marker for such tumors. One third of the patients had elevated serum CgA levels; 2 of these patients had nonsecreting pituitary tumors, and the other 3 had corticotroph adenomas. CgA-positive cells were detected in 9 of the 11 anterior pituitary tumors that were immunostained; in these 9 tumors at least half of the cells were CgA positive. We conclude that CgA production is common in pituitary tumors and that immunohistochemical studies for CgA may aid in their classification. In addition, serum CgA measurements may help to identify patients with pituitary tumors, especially those that do not secrete a known pituitary peptide.

Biomarkers, Tumor↗