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Biomedical subjects

L J Deftos

Publications and source records attributed to L J Deftos.

At least 145 records · Page 8Linked to original sources
PubMed1987

Effects of dietary calcium and age on parathyroid hormone, calcitonin and serum and milk minerals in the periparturient dairy cow.

Ten pregnant heifers and 10 pregnant cows (three or more pregnancies) were assigned to groups of five and fed either the recommended (low) amount of calcium or excess (high) calcium in their diet for 4 wk before parturition to determine the influence of prepartum calcium intake and age on hormonal control of peripartum calcium homeostasis. After parturition all groups received a diet with calcium adequate for lactation. Jugular blood samples from 21, 14, 7, 6, 5, 4, 3, 2, and 1 d prepartum through 0, 1, 2, 3, 5, 7, 14 and 21 d postpartum were assayed for concentration of parathyroid hormone, calcitonin, calcium, magnesium and phosphorus. Heifers and cows receiving high calcium diets had higher calcium and lower parathyroid hormone in blood serum before parturition than animals receiving the low calcium diets. Cows, but not heifers, fed high calcium diets exhibited severe hypocalcemia at parturition, remained hypocalcemic for 3 d and had low serum calcitonin. Regardless of dietary group, concentrations of parathyroid hormone and magnesium in serum increased after the first week of lactation. Feed intake during lactation, corrected for metabolic body weight, was similar for both dietary treatments and ages. Milk production per kilogram metabolic body weight was highest during the first week of lactation for cows fed low calcium diets before parturition. There was no correlation between hypocalcemia and loss of calcium in colostrum or milk. Feeding low dietary calcium to cows in the prepartum period was effective in the prevention of severe hypocalcemia at parturition. In contrast, dietary treatment of heifers had no effect on serum calcium concentration at parturition.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

A cloned chromogranin A (CgA) cDNA detects a 2.3Kb mRNA in diverse neuroendocrine tissues.

CgA is a 72Kd protein of unknown function that is present in many neuroendocrine tissues and co-secreted with their resident hormones. We prepared a cDNA library to the mRNA from CgA-producing human medullary thyroid carcinoma (MTC) cells in the expression vector lambda gt11. The library was screened with a panel of one polyclonal and two monoclonal antibodies to CgA. The specificity of the antibodies for CgA was demonstrated by immunoassay, immunohistology, and immunoprecipitation of the in vitro translation products of mRNA from CgA-producing tissues. A chromogenic second antibody identified five immunoreactive clones. Their cDNA inserts were isolated after EcoRI digestion and agarose gel electrophoresis. These cDNAs were 32P-labelled and used as probes in Northern hybridization studies. An mRNA of approximately 2.3Kb was detected with the cDNA probes in human cell lines from MTC and lung cancers that were shown to produce CgA and in human pheochromocytoma and bovine adrenal medulla tissue. To confirm its identity, one of the putative CgA cDNAs was subcloned into a plasmid and was used to hybridization-arrest the in vitro translation of CgA mRNA. These studies demonstrate the cloning of cDNAs which hybridize with CgA mRNA from diverse neuroendocrine tissues.

Adrenal Medulla↗
PubMed1986

Secretion of chromogranin A by peptide-producing endocrine neoplasms.

Chromogranin A, the protein that is co-stored and co-released with catecholamines from the adrenal medulla, has recently been identified in a variety of human endocrine tissues, both normal and neoplastic. We investigated the secretion of chromogranin A by peptide hormone-producing human tumors in studies of patients with the following neoplastic disorders: pheochromocytoma, parathyroid adenoma, primary parathyroid hyperplasia, medullary thyroid carcinoma, thyroidal C-cell hyperplasia, carcinoid tumor, oat-cell lung carcinoma, pancreatic islet-cell tumor, and aortic-body tumor. All these patient groups had elevated concentrations of plasma chromogranin A. We distinguished different forms of immunoreactive plasma chromogranin A by size with the use of gel filtration. Plasma chromogranin A levels were not elevated in patients with diverse "control" conditions--both benign and malignant and both endocrine and nonendocrine--in which peptide hormones are not produced. The sensitivity and specificity of plasma chromogranin A elevations in the diagnosis of peptide-producing endocrine neoplasms were 81 and 100 percent, respectively. The elevation of plasma chromogranin A in our subjects suggests that their neoplasms co-release chromogranin A along with the usual resident hormone of the tumor, that these neoplasms could be characterized as "chromograninomas," and that measurement of plasma chromogranin A may be a useful diagnostic procedure in subjects with endocrine tumors, especially multiple endocrine neoplasia.

Adenoma↗
PubMed1986

1 alpha,25-Dihydroxyvitamin D3-binding macromolecules in human B lymphocytes: effects on immunoglobulin production.

Previous studies have indicated that upon in vitro activation with mitogenic lectins, human peripheral blood T lymphocytes express receptors for the steroid hormone 1 alpha, 25-dihydroxyvitamin D3(1,25(OH)2D3). Furthermore, the hormone can inhibit interleukin 2 production by the activated cells. In this investigation, we report that human peripheral B lymphocytes activated in vitro with the B lymphotropic Epstein-Barr virus (EBV) also express 1,25(OH)2D3 receptor-like macromolecules. These receptors are localized in the cell nucleus and exhibit properties similar to those found in classical target tissues for 1,25(OH)2D3. They sediment on sucrose gradients at 3.3 S, display a dissociation constant (Kd) of 4 X 10(-10) M, and can bind to DNA. In addition to the 1,25(OH)2D3 receptors, however, EBV-activated lymphocytes express a second class of 1,25(OH)2D3-binding proteins that appear to occur mainly in the cell cytosol and exhibit distinct biochemical properties from the receptor, including higher sedimentation coefficients (3.7 S to 4 S) and the lack of ability to bind to DNA. The addition of 1,25(OH)2D3 to cultures of EBV-infected cells inhibited the production of IgM and IgG by the B cells. The vitamin D3 analog 24,25(OH)2D3 did not inhibit Ig production, thus suggesting that the effect is probably mediated through the high affinity receptor macromolecule localized in the nucleus. Because the EBV-induced Ig production is independent of T cell participation, the data also suggest that the effects of 1,25(OH)2D3 are exerted directly on the B cell. The present results add to the evidence of the importance of 1,25(OH)2D3 as an immunoregulatory hormone.

B-Lymphocytes↗
PubMed1986

1,25-Dihydroxyvitamin D3 promotes in vitro morphologic and enzymatic changes in normal human monocytes consistent with their differentiation into macrophages.

1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been shown to promote the in vitro differentiation of established human monocytic cell lines and normal human bone marrow progenitor cells toward the macrophage phenotype. The possibility that 1,25(OH)2D3 exerts a similar effect on the differentiation of peripheral monocytes from normal individuals, has been examined in the present study. Monocytes were isolated by density gradient sedimentation on Ficoll-Paque followed by adherence to plastic. Cells were subsequently maintained in culture in 10% autologous serum for 4 weeks either with or without 1,25(OH)2D3 (10(-8) M). In five experiments using monocytes from different donors we found that cells grown in the absence of the hormone underwent morphologic changes toward the macrophage phenotype as well as a gradual increase in the activities of lysosomal enzymes (beta-acetyl-glucosaminidase and beta-galactosidase). In the presence of the hormone the morphologic changes appeared at earlier stages of the culture, and the increase in enzymatic activities occurred earlier and was one- to twofold greater than the activity of the control cells. In addition, 1,25(OH)2D3 enhanced the adherence of the cultured cells.

Acetylglucosaminidase↗
PubMed1986

Osteoclasts can be induced in fish having an acellular bony skeleton.

Kelp bass (Paralabrax clathratus) and leopard sharks (Triakis semifasciata) are characterized by an acellular (anosteocytic) bony skeleton and a focally calcified cartilaginous endoskeleton, respectively. These skeletal forms are not considered to function as mineral reservoirs. Previous studies showed that implanted bone particles are resorbed in rats by large multinucleated cells with ultrastructural features (ruffled borders) characteristic of osteoclasts. We tested the ability of fish to resorb bone matrix and to adapt to reduced salinity conditions. Bone particles were implanted in sharks and bass maintained in seawater (34 ppt, 40.5 mg of calcium per dl) or in diluted seawater (26 ppt, 28.5 mg of calcium per dl). Sera and elicited tissues were harvested 4 weeks later. In sharks, bone particles were not resorbed, and multinucleated cells were not evident under either normal or hyposalinity conditions. Shark sera were isoosmolar with the seawater or diluted seawater, with serum chemistries of the hyposalinity group reflecting the 23% reduction in environmental minerals and electrolytes, compared to sharks in normal seawater. In marked contrast, bass adapted to diluted seawater resorbed bone particles and maintained normal serum chemistries. Electron microcopy showed that the bone particles were surrounded by large, foamy multinucleated cells, many with membrane specializations typical of osteoclasts from higher vertebrates, i.e., extensive clear zones apposed to intact bone matrix and active ruffled borders overlying areas of matrix undergoing dissolution. Although osteoclasts had not been described in these fish, this study shows that bass have stem cells that can be stimulated to differentiate into bone-resorbing osteoclasts.

Journal Article↗
PubMed1986

Calcium-regulating hormones across the menstrual cycle.

Midcycle elevations of serum PTH, calcitonin (CT), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] in women have been reported. To examine the effects of cyclic changes in ovarian steroid secretion on calcitropic hormone concentrations, we used a cytoreceptor assay for 1,25-(OH)2D and homologous RIAs for PTH and CT to measure these hormones in daily blood samples obtained from six women throughout the menstrual cycle. Significant changes in serum PTH, CT, 1,25-(OH)2D, calcium, and phosphorus concentrations during the cycle were not found; transverse means (+/- SE) were 101 +/- 3.5 pg/ml for PTH, 30.8 +/- 1.8 pg/ml for CT, and 40.1 +/- 1.7 pg/ml for 1,25-(OH)2D. In addition, CT reserve was assessed by calcium infusion (3 mg/kg, iv, in 10 min) during the early and late follicular and midluteal phases of the cycle. Although serum CT increased significantly (P less than 0.01) after calcium infusion, the mean (+/- SE) increment (23.2 +/- 2.2 pg/ml) did not significantly differ in the three phases of the cycle (early follicular, 23.8 +/- 4.0; late follicular, 23.3 +/- 3.4; midluteal, 22.5 +/- 4.1). Our data do not support previous reports of midcycle elevations in serum PTH, CT, and 1,25-(OH)2D concentrations, and we conclude that serum concentrations of the calcitropic hormones do not significantly vary during the menstrual cycle.

Adult↗
PubMed1986

The antiproliferative effect of calcitriol on human peripheral blood mononuclear cells.

Activation of lymphocytes leads to the expression of receptors for the calcitropic hormone calcitriol [1,25(OH)2D3], and calcitriol is a potent inhibitor of interleukin-2 (IL-2) and of lymphocyte proliferation. We used peripheral blood mononuclear cells (PBM) activated in vitro with phytohemagglutinin to study 1) the relationship between 1,25(OH)2D3 receptor expression, IL-2 production, and 1,25(OH)2D3-induced inhibition of PBM proliferation in connection with the cell cycle; 2) the effect of 1,25(OH)2D3 on PBM activation and on the expression of activation-related molecules including the IL-2 receptor, and 3) the role of calcium in the antiproliferative effect of the hormone. 1,25(OH)2D3 receptor expression occurred when PBM entered the G1a phase of the cell cycle. The concentration of the receptor protein reached a peak at G1b and declined during the S phase. 1,25(OH)2D3 inhibited cell proliferation by blocking PBM at the G1a-G1b border. The antiproliferative effect of calcitriol was not caused by hormonal interference with the calcium-dependent activation process nor with the expression of activation-related molecules including the IL-2 receptor. Moreover, this effect was not influenced by extracellular calcium, suggesting that the hormonal action cannot be due to calcium translocation. These findings support the contention that 1,25(OH)2D3-induced inhibition of PBM proliferation is mediated through selective inhibition of IL-2 production.

Antigens, Surface↗
PubMed1986

The involvement of calcitonin in the reproductive physiology of the rainbow trout.

Plasma from rainbow trout (Salmo gairdneri) of both sexes was sampled every month throughout an annual reproductive cycle in order to elucidate possible relationships between plasma calcitonin and free and protein-bound calcium and magnesium. This was then studied in greater detail around the time of ovulation in the female fish. The plasma levels of the parameters studied were stable in males during the whole annual cycle and were similar to the levels found in females during at least 6 months of the cycle. Plasma levels of protein-bound calcium and magnesium as well as calcitonin were raised in the females for 6, 4 and 3 months respectively. These increases occurred concomitantly during the months before and after ovulation, but no correlations between the protein-bound ion and calcitonin levels were found during this period. With the exception of a decrease observed in December, the free plasma levels of calcium and magnesium were stable in both males and females throughout the cycle. This decrease was attributed to the high production rate of the yolk-protein precursor vitellogenin, which binds both calcium and magnesium. In the detailed study on the ovulating females, plasma calcitonin levels were high 4 weeks before, and continued to increase until the time of ovulation, when a sharp decrease towards normal was noted. The free plasma calcium and magnesium levels were not affected, while the protein-bound levels of calcium and magnesium were found to decline towards normal for the duration of the experiment, without any obvious correlation with the time of ovulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Elevated serum chromogranin A concentrations in small-cell lung carcinoma.

Serum chromogranin A concentrations measured by radioimmunoassay in patients with small-cell lung carcinoma were compared with values from healthy adults and patients with non-small-cell lung carcinoma or chronic obstructive pulmonary disease. The mean (+/- SE) level was significantly higher (p less than or equal to 0.02) in patients with small-cell lung carcinoma (815 +/- 290 ng/mL, n = 46) than in normal controls (123 +/- 6 ng/mL, n = 20) or patients with chronic obstructive pulmonary disease (169 +/- 18 ng/mL, n = 39), lung adenocarcinoma (180 +/- 22, ng/mL, n = 62), large-cell lung carcinoma (183 +/- 23 ng/mL, n = 18), or lung epidermoid carcinoma (203 +/- 37 ng/mL, n = 78). The mean concentration in extensive-stage small-cell lung carcinoma (1155 +/- 449 ng/mL, n = 29) was significantly greater (p = 0.026) than in limited disease (234 +/- 56 ng/mL, n = 17). Elevated serum chromogranin A values were seen in 53% of patients with limited and 72% with extensive disease. Four patients originally classified as having non-small-cell lung carcinomas with raised chromogranin A levels were subsequently found to have mixed small-cell and non-small-cell tumors. Serum chromogranin A concentrations may be a useful marker of small-cell lung carcinoma disease activity.

Adult↗
PubMed1986

Biochemical markers of bone turnover in rheumatoid arthritis. Relation to anti-inflammatory treatment, sex, and menopause.

Bone turnover was determined in 125 patients with rheumatoid arthritis (RA). Bone Gla protein (BGP) and alkaline phosphatase (AP) were used as markers of bone formation. Fasting urinary calcium relative to creatinine (FU Ca/Cr) and fasting urinary hydroxyproline relative to creatinine (FU Hpr/Cr) were used as markers of bone resorption. These variables were compared to the values of two groups of normal controls in order to elucidate the pathophysiology of the osteopenia occurring in patients with RA. When the patients were divided into groups according to treatment (gold salts, penicillamine, or glucocorticoids), serum AP was highly significantly increased in all three groups, whereas serum BGP was below the normal mean. FU Ca/Cr and FU Hpr/Cr were moderately decreased in the groups treated with gold salts or penicillamine, but increased in the glucocorticoid-treated group. When divided according to sex and menopausal state and glucocorticoid treatment versus non-glucocorticoid treatment, there was a balance between bone formation and bone resorption parameters in all groups, except glucocorticoid-treated men and premenopausal women who had increased values of bone resorption parameters.

Adult↗
PubMed1986

Measures of bone loss in rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) are prone to develop osteoporosis, especially women receiving steroid hormone therapy. Inhibition of bone formation and/or excessive bone resorption may be responsible. Bone gamma-carboxyglutamic acid-containing protein (BGP), the major noncollagen protein of bone and a plasma marker of bone formation, was measured in 81 consecutive RA patients and 79 age- and sex-matched control subjects, in addition to the hormone regulators of bone metabolism, calcitonin, parathyroid hormone, and 1,25-dihydroxyvitamin D. Mean (+/- SE) BGP levels (picomoles per milliliter) were lower for RA men (1.46 +/- 0.14) and women (1.52 +/- 0.2) compared with their respective controls (2.05 +/- 0.17 for men, 2.47 +/- 0.22 for women). Women taking steroids had the lowest levels (1.13 +/- 0.22) and, in contrast to men, this value was lower than the nonsteroid-treated group. Steroid treatment appears to be a major determinant of low BGP levels; the effect of RA itself is suspected but not proved in this study. Calcitonin levels were lower in RA men as well as in all women. Diminution of BGP in these subjects supports the view that "low-dose" corticosteroid treatment may suppress bone formation, especially in women. Prevention or remediation of osteopenia may be monitored by BGP, if further studies validate this hypothesis with other measures of skeletal mass.

1-Carboxyglutamic Acid↗
PubMed1985

Bone turnover in male puberty: a longitudinal study.

In a longitudinal study of male puberty, 18 boys were examined every 3 months for at least 2 years. Serum bone Gla protein (BGP), a biochemical marker of bone formation, was determined and related to changes in serum testosterone (T), serum alkaline phosphatase (AP), serum calcitonin, and bone mineral content (BMC). The data demonstrate a steep increase in serum T during puberty (P less than 0.001), with an almost concomitant increase in serum BGP (P less than 0.001) and serum AP (P less than 0.001). Ten months after the maximal increase in serum T, the increase in BMC reached its maximum, whereas there was no significant change in the serum calcitonin. The data demonstrate that the steep increase in serum T during puberty, directly or indirectly, produces acute stimulation of bone formation (estimated from BGP and AP) followed by a highly significant increase in the integrated measurement of bone apposition (BMC).

Alkaline Phosphatase↗
PubMed1985

Plasma calcium and calcitonin in the marine teleost, Gadus morhua.

Total, free and ionic plasma levels of calcium as well as total plasma magnesium and inorganic phosphate levels were studied in the Atlantic cod, Gadus morhua, in relation to salmon calcitonin injections. Plasma ion levels and endogenous levels of calcitonin were studied during environmentally induced hypercalcemia. It is concluded that no apparent relationship between calcitonin and calcium levels was found, and it is implied that calcitonin in fish may have a physiological function not related to blood calcium regulation.

Animals↗
PubMed1985

Effect of bromocriptine on serum PTH, calcium and phosphate levels in azotemic rats.

The dopamine agonist, bromocriptine, was studied with respect to its effects on PTH secretion and calcium homeostasis in Sprague-Dawley rats made azotemic by either total or subtotal nephrectomy. The oral or intraperitoneal administration of 0.25 mg of bromocriptine resulted in a significant increase in the serum calcium concentration when compared to animals given placebo. Bromocriptine produced no significant change in the BUN or the serum concentrations of creatinine, inorganic phosphate or PTH. The mechanism of the hypercalcemic effect of bromocriptine in azotemic rats is unknown. The hypercalcemia may, however, be due to stimulation of PTH secretion, since PTH levels in the serum were inappropriately high for the corresponding levels of calcium.

Animals↗