Osteomalacia secondary to osteosarcoma. A case report.
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Bone Neoplasms↗
Biomedical subjects
R S Mason
Publications and source records attributed to R S Mason.
Extracellular matrix modulates the function of human melanocytes but not melanoma cells.
Normal human epidermal melanocytes are attached to a basement membrane, a specialized form of extracellular matrix (ECM), located between the epithelium and underlying dermal tissues. To determine whether ECM influences pigmented cell behavior in vitro, human epidermal melanocytes and melanoma cells were cultured on uncoated or ECM-coated plastic culture surfaces, and a comparison was made between growth and function in the presence or absence of ECM. Melanocytes cultured on ECM-coated surfaces developed flatter and larger cell bodies and produced more melanin than melanocytes cultured on uncoated surfaces. In the presence of phorbol-myristate-acetate and cholera toxin, the rate of melanocyte replication was increased by ECM. In the absence of these mitogens, ECM significantly enhanced the adhesiveness of nonproliferating melanocytes. ECM had little or no effect on these parameters (morphology, tyrosinase activity, replication) in a pigmented human malignant melanoma cell line. These findings indicate that normal human epidermal pigment cells have the ability to recognize and respond to matrix signals, whereas this capacity appears to be absent in melanoma cells.
Cell Division↗
Human melanoma cells: functional modulation by calciotropic hormones.
Four human melanoma cell lines were examined for their responsiveness to the hormones 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), calcitonin, and parathyroid hormone (1-34). Cells from each of the 4 lines contained high affinity binding sites for 1,25(OH)2D3. At high cell densities, binding of 1,25(OH)2D3 was diminished due to a decrease in receptor number with no apparent change in affinity. Preincubation with 1,25(OH)2D3 (10(-10) to 10(-8) M) increased tyrosinase activity 1.3- to 3.2-fold and 25-hydroxyvitamin D3-24-hydroxylase activity 1.4- to 10-fold. Human calcitonin (0.82 to 82.5 ng/well) raised the intracellular concentration of cyclic adenosine monophosphate 1.4- to 9.4-fold. Tyrosinase activity increased in response to calcitonin in 2 of the cell lines, decreased in the third, and showed no change in the fourth. Human parathyroid hormone (1-34) in concentrations of 1 to 10 ng/ml produced no significant changes in cyclic adenosine monophosphate accumulation, cell numbers, or tyrosinase activity in any of the cell lines. This study indicates that the phenotype of human melanoma cells can be modulated by the calciotropic hormones 1,25(OH)2D3 and calcitonin.
Calcitonin↗
Human melanocytes as a target tissue for hormones: in vitro studies with 1 alpha-25, dihydroxyvitamin D3, alpha-melanocyte stimulating hormone, and beta-estradiol.
Clinical evidence exists which suggests that normal pigment cell (melanocyte) function is subject to hormonal influences, but the nature of these interactions at a cellular level is poorly understood. We have investigated the effects of the vitamin D-derived secosteroid hormone 1 alpha-25, dihydroxyvitamin D3 (1,25(OH)2D3), the pituitary-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH), and the sex steroid beta-estradiol on melanocytes cultured from normal human foreskin. Human melanocytes specifically internalized 1,25(OH)2D3 with high affinity (Kd 0.5-0.8 nM). Incubation with 1,25(OH)2D3 (10(-9) M) for 48 h resulted in a 100% increase in 25-hydroxyvitamin D3-24-hydroxylase activity and a 50% increase in tyrosinase activity. There was no significant effect of 1,25(OH)2D3 on intracellular cyclic adenosine monophosphate (cAMP). In contrast to 1,25(OH)2D3, alpha-MSH at a concentration of 5 X 10(-7) M caused a sevenfold increase in intracellular cAMP after 12 min but only a modest increase (less than 20%) in melanocyte tyrosinase activity after 48 h. Incubation with beta-estradiol for 24 h caused a dose-dependent increase in tyrosinase activity. The maximal response varied from 145%-213% of basal activity depending on the donor source. These results indicate that melanocytes from normal human foreskin in culture have the capacity to respond directly to several hormones. They also suggest that these cells form a useful model to study the effect of various hormones on pigment cell function.
Calcitriol↗
Interactions between 1,25-dihydroxyvitamin D3 and vitamin D2: effects of pharmacologic doses in normal individuals.
To determine whether the administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) affects the conversion of a pharmacologic dose of vitamin D2 to 25-hydroxyvitamin D (25OHD), 20 normal subjects received two separate doses of vitamin D2--one with and the other without the concomitant administration of 1,25(OH)2D3. Serum 1,25(OH)2D rose in response to 1,25(OH)2D3 administration and fell when vitamin D2 was given alone. Serum osteocalcin rose in response to 1,25(OH)2D3 administration. Serum 25OHD rose in response to vitamin D2 administration regardless of whether the subjects also received 1,25(OH)2D3. The data from this study in humans support the suggestion that the effects of 1,25(OH)2D3 on serum 25OHD concentrations are mediated through mechanisms other than impairment of production.
25-Hydroxyvitamin D 2↗
Clinical and laboratory studies of 1,25-dihydroxycholecalciferol in myelofibrosis.
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Aged↗
Humoral hypercalcaemia of malignancy: report of two further patients with biochemical studies on tumour extracts.
Tumour extracts from two patients with humoral hypercalcaemia of malignancy contained material which stimulated adenylate cyclase in chick renal membranes and in rat osteosarcoma cells. Adenylate cyclase-stimulating activity in each system was inhibited by a specific parathyroid hormone (PTH) antagonist. Studies in two HPLC systems suggested that the adenylate cyclase-stimulating factors extracted from these tumours differed from each other and from synthetic human parathyroid hormone 1-34. The presence of similar PTH-like adenylate cyclase stimulating material(s) in oncogenic osteomalacia suggests that adenylate cyclase stimulating factor(s) may not be the direct or the sole cause of hypercalcaemia.
Adenylyl Cyclases↗
Clinching the diagnosis: an approach to the investigation of hypercalcemia.
Hypercalcemia is a common biochemical abnormality. It is usually possible to make a presumptive diagnosis of its cause by relatively simple means. In a large majority of cases this involves differentiating between primary hyperparathyroidism and malignancy-associated hypercalcemia. Clinical evaluation and parathyroid hormone assay are particularly useful. Since the management of hypercalcemia in the short term generally involves non-specific measures such as rehydration, the inability to make an immediate accurate diagnosis presents less of a problem than might otherwise be the case. The definitive diagnosis of hyperparathyroidism, malignancy and sarcoidosis requires histological confirmation.
Adrenal Cortex Hormones↗
The effect of metabolic acidosis on vitamin D metabolites and bone histology in uremic rats.
Biochemical data and skeletal histomorphometric measurements are presented for normal rats and for two groups of rats rendered uremic by partial nephrectomy. In one of these groups chronic acidosis was induced by the oral administration of hydrochloric acid. Uremic animals had higher urine calcium excretion rates and lower serum concentrations of vitamin D metabolites than normal rats. Chronic acid loading of uremic rats resulted in hypercalcemia, elevated serum parathyroid hormone concentrations, and a significant loss of trabecular bone in addition to the above changes. greater osteoclast densities and higher resorption surfaces wee seen in the uremic acidotic animals than in the other two groups. The acidotic uremic state induced more potent changes in calcium metabolism and bone structure than uremia alone.
Acidosis↗
Some problems associated with adenylate cyclase bioassays for parathyroid hormone.
A renal adenylate cyclase system was assessed for its suitability in the performance of parathyroid hormone (PTH) bioassays. Membrane preparations from 1 week old chicks were found to be more sensitive to PTH than material from humans, dogs or rats. Because of the presence of non-specific inhibitors and stimulators of adenylate cyclase in human serum, each serum sample was assayed in the presence and in the absence of a specific PTH inhibitor and the difference was used to calculate PTH activity. Calcium, an inhibitor of adenylate cyclase, was either removed from serum samples by pretreatment with Chelex resin or chelated during assay by means of EGTA. Human and bovine PTH (1-34) stimulated adenylate cyclase in this system to the same extent. The lower limit of detectability was 19.5 pg/ml (final concentration). The intra-assay coefficient of variation at a final concentration of 45 pg/ml was 18%. The index of precision was 0.08 +/- 0.04 (n = 7). When synthetic human PTH (1-34) was infused into three normal volunteers, the mean biological half-life of this material was found to be 3.2 min. PTH-like bioactivity could be routinely detected in sera from normal rats, while such activity was significantly decreased in rats subjected to thyroparathyroidectomy.
Adenylyl Cyclases↗
An adenylate cyclase bioassay for parathyroid hormone: some clinical experiences.
An adenylate cyclase bioassay for parathyroid hormone (PTH) was evaluated in peripheral sera of ten normal subjects, 15 patients with various types of hypoparathyroidism, nine patients with malignancy-associated hypercalcaemia and 60 patients with primary or secondary hyperparathyroidism. The lower limit of detectability was 150 pg/ml in terms of synthetic human PTH (1-34). PTH-like bioactivity was not detected in normal subjects, in patients with surgical hypoparathyroidism, in patients with idiopathic hypoparathyroidism or in patients with malignancy-associated hypercalcaemia. Serum from one untreated pseudohypoparathyroid patient consistently contained PTH-like bioactivity. Bioactivity was detected in sera from 50% of patients with primary or secondary hyperparathyroidism. In two patients with secondary hyperparathyroidism calcium infusions suppressed this activity within 5 min. Both in primary and in secondary hyperparathyroidism there was a significant positive correlation between levels of PTH-like bioactivity, PTH immunoreactivity and the histological severity of the disease.
Adenylyl Cyclases↗
Parathyroid hormone-like bioactivity in tumours from patients with oncogenic osteomalacia.
Extracts from the tumours of three patients with oncogenic osteomalacia stimulated renal adenylate cyclase in a parathyroid hormone (PTH) responsive system. The stimulation was suppressed by a specific PTH antagonist. These observations suggest that osteomalacia-producing tumours exert some of their effects through PTH-like material acting on PTH receptors.
Adenylyl Cyclases↗
Bioactive parathyroid hormone in the rat: effects of calcium and calcitriol.
Bioactive PTH was measured in Wistar rats under a variety of experimental conditions. The mean activity in normal rat sera was 0.17 +/- 0.12 ng/ml (expressed in terms of bovine PTH 1-34). Sera from animals reared on a vitamin D deficient diet showed a mean value of 0.46 +/- 0.24 ng/ml (P less than 0.01), whereas sera from animals with 1,25-dihydroxyvitamin D (1,25(OH)2D) deficiency had a mean activity of 0.62 +/- 0.23 ng/ml (P less than 0.01). Dietary calcium deficiency also resulted in high serum PTH levels (0.71 +/- 0.34 ng/ml, P less than 0.01) in spite of marked elevations of serum 1,25(OH)2D concentrations in these animals. A significant negative correlation was noted between serum calcium and bioactive PTH. Calcium infusions into hypocalcemic, vitamin D-deficient rats caused a fall in serum bioactive PTH concentrations to a mean of 13% of control values within 10 min. Intraperitoneal administration of 1,25(OH)2D3 to hypocalcemic, 1,25(OH)2D-deficient rats did not suppress serum bioactive PTH concentrations after 30 or 60 min even though serum 1,25(OH)2D concentrations were greater than 900 pmol/liter in each animal at these time points. To our knowledge, this is the first study using PTH bioassays for physiological experiments in rats.
Adenylyl Cyclases↗
International training in quality assurance.
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Education, Continuing↗
Vitamin D conversion by sarcoid lymph node homogenate.
Recent studies suggest that hypercalcemia of sarcoidosis is due to high blood concentrations of calcitriol and that this compound may be synthesized at an extra-renal site. We report that sarcoid lymph node homogenate metabolized calcifediol to a substance indistinguishable from calcitriol, whereas six nonsarcoid lymph nodes failed to produce this compound.
Calcifediol↗
Vitamin D metabolism in nephrotic rats.
Vitamin D metabolites were measured in sera of normal, vitamin D deficient and nonazotemic nephrotic rats. The concentrations of all metabolites were reduced in nephrotic and vitamin D deficient animals although 1,25-dihydroxyvitamin D values remained relatively normal in the nephrotic group. Twenty-four hours after the intravenous injection of tritiated 25-hydroxycholecalciferol, approximately 34% of the injected radioactivity appeared in the urine of the nephrotic animals compared with 0.4% in the controls. In extracts from nephrotic sera subjected to high performance liquid chromatography, the percentage of radioactive counts comigrating with 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol was significantly increased. The various metabolites were present in urine in approximately the same ratios as in serum. Dynamic histomorphometry of tibial metaphyses showed no abnormality. Urinary losses of vitamin D metabolites constitute the major cause for low serum values in nephrotic rats. The apparent synthetic rates are not impaired.
24,25-Dihydroxyvitamin D 3↗
The synthesis of vitamin D metabolites by human melanoma cells.
Two melanin-producing human melanoma cell lines originally established from fresh surgical specimens were incubated with 25 hydroxyvitamin D3 (25 OHD3). Both cell lines produced material comigrating with 1,25 dihydroxy-vitamin D3 (1,25(OH)2D3) and 24,25 dihydroxyvitamin D3 (24,25(OH)2D3) in straight and reverse phase high performance liquid chromatography systems and displacing the relevant labeled ligands in competitive binding assays. The material designated 1,25(OH)2D3 was found almost entirely within the cells, whereas 24,25(OH)2D3 was evenly distributed between cells and medium. The synthesis of dihydroxylated materials was time dependent and was not observed if the cells were boiled before incubation with 25 OHD3. Preincubation with 1,25(OH)2D3 caused an increase in the synthesis of 24,25(OH)2D3 and a decrease in the synthesis of 1,25(OH)2D3. Michaelis-Menten constant (Km) values were 1.4 X 10(-9) mol/liter 25 OHD3 for the 1-alpha-hydroxylase enzyme and 72 X 10(-9) mol/liter for 24-hydroxylase. These studies constitute further evidence for the extrarenal synthesis of 1,25(OH)2D3. The suppressibility of 1 alpha-hydroxylase by preincubation with 1,25(OH)2D3 suggests a regulatory function for this system in the skin.
24,25-Dihydroxyvitamin D 3↗
Vitamin D metabolism in hypophosphatemic rickets.
Vitamin D metabolites were measured in 21 patients with hypophosphatemic osteomalacia of juvenile onset. In eight patients who had not received any antirachitic treatment, serum 25-hydroxyvitamin D(25-OH-D) and 1,25-dihydroxyvitamin D (1,25-[OH]2D) values were normal, whereas serum 24,25-dihydroxyvitamin D (24,25-[OH]2D) values were lower than in normal subjects. In 13 patients who were receiving ergocalciferol and oral elemental phosphorus, serum 25-OH-D and 24,25-(OH)2D concentrations were elevated and serum 1,25-(OH)2D values were low. The findings in untreated patients supported the hypothesis that vitamin D metabolism is abnormal in hypophosphatemic rickets/osteomalacia. The reduction of serum 1,25-(OH)2D levels with ergocalciferol and phosphate therapy gives further support to a therapeutic role for 1,25-(OH)2D in this disorder.
24,25-Dihydroxyvitamin D 3↗