Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:7440-70-2 (calcium)
 333,191 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ultrastructure of parathyroid chief cells was examined from four groups of nude mice (NIH:Swiss) with different serum calcium concentrations. The groups consisted of eight male mice with hypercalcemia induced by transplantable canine adenocarcinoma (CAC-8), eight female mice with hypercalcemia induced by infusion of parathyroid hormone-related protein, ten male control mice, and six male mice fed a low calcium (0.01%) diet. Hypercalcemia induced by malignancy or parathyroid hormone-related protein infusion was associated with low serum phosphorus concentration, a decrease in the number of secretory and prosecretory granules in the parathyroid chief cells, and an increase in the cytoplasmic area of chief cells. Prominent myelinlike membranous whorls were present in the cytoplasm of chief cells of tumor-bearing and parathyroid hormone-related protein-infused hypercalcemic mice. Mice fed a low calcium diet had decreases in the number of secretory granules and cell area but increases in the number of prosecretory granules compared with control mice. The number of mitochondria and the nuclear area of chief cells were similar in all four groups. The prominent membranous whorls and increased cytoplasmic area of chief cells from these hypercalcemic mice mark these cells as distinctly different from the parathyroid chief cells of other species with hypercalcemia.
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PMID:Effects of humoral hypercalcemia of malignancy on the parathyroid gland in nude mice. 151 21

Parathyroid hormone-related protein (PTHRP) has been quantified by sensitive specific immunoassays in mammary venous blood and milk from 7 days before to 7 days after parturition in the goat. A significant venous-arterial concentration gradient in plasma PTHRP 1-86 concentrations was demonstrated across the mammary gland, indicating that PTHRP enters the maternal circulation and may have a role in calcium homoeostasis during lactation. Significant and sustained increases in mammary venous and milk PTHRP 1-86 concentrations were found from 1 day before parturition to 7 days afterwards, with peak concentrations of 1.57 +/- 0.58 pmol/l (plasma) and 8.69 +/- 2.95 nmol/l (milk) (mean +/- S.E.M.) occurring on day -1 and the day of parturition respectively. Estimates of the mammary output of PTHRP into plasma in four goats averaged 9% (range 1-25%) of that secreted into milk. Suppression of maternal prolactin concentrations by bromocriptine significantly reduced milk yield and the mammary venous PTHRP concentration, without affecting the concentration of PTHRP in milk. In conclusion, parturition in the goat is associated with a sustained increase in secretion of PTHRP into both plasma and milk; the former may be involved in maternal calcium homoeostasis, whereas the latter may have a role in the neonate.
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PMID:Production of parathyroid hormone-related protein by the mammary gland of the goat. 151 11

In animal models, parathyroid hormone-related protein (PTHrP) increases placental calcium transport and inhibits contraction of uterine smooth muscle. The present studies were undertaken to characterize the expression of PTHrP in human uteroplacental tissues. PTHrP mRNA was identified by Northern analysis as a single species (approximately 1.8 kilobases) in human amnion, chorion, placenta, decidua, and myometrium. The most abundant signal was seen in amnion, where it was 10-400 times that in the other uteroplacental tissues. PTHrP mRNA abundance was decreased in amnion (but not in the other tissues) following the onset of labor (P less than 0.001). PTHrP mRNA in amnion appeared to be translated to a bioactive peptide, as PTHrP bioactivity and immunoreactive PTHrP in amnion correlated closely with PTHrP mRNA content (r = 0.86 and 0.95, respectively; P less than 0.05 and P less than 0.01). Amniotic fluid contained PTHrP, 21 +/- 6 pmol/liter (n = 10) at 16 weeks and 41 +/- 9 pmol/liter (n = 7) at 38 weeks (P = 0.05). These concentrations equaled or exceeded those found in plasma of patients with hypercalcemia secondary to PTHrP. After rupture of the fetal membranes, PTHrP mRNA in amnion was decreased by 78% (P less than 0.0001). This decrease appeared to be specific for PTHrP mRNA, as glyceraldehyde-3-phosphate dehydrogenase mRNA was unchanged following rupture of membranes. Like PTHrP mRNA, PTHrP bioactivity and immunoreactive PTHrP in amnion decreased significantly following rupture of membranes (P less than 0.03 and P less than 0.01, respectively). Since PTHrP is a potent antagonist of uterine muscle contraction, the decrease of PTHrP following rupture of the fetal membranes may play a key role in the onset of labor.
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PMID:Abundant expression of parathyroid hormone-related protein in human amnion and its association with labor. 151 72

Hypercalcemia may occur as a complication of haematological malignancies, in association with solid tumors with bone metastases, and with solid tumors in the absence of bone metastases. The latter syndrome, known as the humoral hypercalcemia of malignancy (HHM) shares many features with primary hyperparathyroidism. A parathyroid hormone-related protein (PTHrP) has been identified, isolated and cloned, which is most likely responsible for the calcium disturbances in HHM, PTHrP is a previously unrecognized hormone which has limited amino-terminal sequence homology with PTH and is the product of a separate gene. Tissue localization studies have identified PTHrP in squamous cell carcinomata, renal cortical carcinomata, in a proportion of breast cancers and in adult T-cell leukemia/lymphoma. In normal tissues, PTHrP has been immunohistochemically localized in keratinocytes, placenta and fetal parathyroid glands. In addition to its role in mediating hypercalcemia in cancer, PTHrP is likely to have an important endocrine role in the fetus, and perhaps a paracrine function in several organs.
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PMID:Hypercalcemia in cancer. 152 53

Mithramycin (0.1 mg/kg) was administered intravenously to eight Beagle dogs on days 0 and 7 to determine its effects on calcium and phosphorus metabolism, serum parathyroid hormone concentration, osteoclastic bone resorption, and serum biochemical and hematologic parameters. Ionized calcium concentration was paradoxically increased on day 1 and decreased on day 8 in association with an increased serum parathyroid hormone concentration. Serum phosphorus concentration was decreased on days 1 and 2. Osteoclastic bone resorption in iliac cancellous bone was significantly decreased on day 8. There were mild increases in serum alkaline phosphatase (days 1, 2, 4, 8, 9), aspartate aminotransferase (day 9), and gammaglutamyl transpeptidase (days 7, 9) activities. Platelet numbers were increased on days 7 through 13, and packed red blood cell volumes were mildly decreased. This investigation demonstrates that two doses of mithramycin can be administered safely to dogs and may inhibit bone resorption in diseases associated with increased osteoclastic bone resorption, such as humoral hypercalcemia of malignancy.
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PMID:Effects of mithramycin on calcium metabolism and bone in dogs. 153 47

We investigated the immunohistochemical localization of parathyroid hormone-related protein (PTHrP), a major factor responsible for the humoral hypercalcemia of malignancy, in uterine cervical lesions. Formalin-fixed paraffin-embedded specimens from 16 cases of normal and reactive conditions, 45 cases of cervical intra-epithelial neoplasm (CIN) and 63 cases of invasive cancer were studied immunohistochemically by the avidine-biotin-peroxidase method, using an anti-PTHrP monoclonal antibody (MAb), 4B3. In normal and reactive conditions, PTHrP was positive in parabasal cells, squamous metaplasia, and hyperplastic reserve cells. In neoplastic conditions, 96% (43/45) of invasive squamous-cell carcinomas were positive for PTHrP, regardless of the patients' serum calcium levels. Two cases with hypercalcemia were strongly positive for PTHrP and showed prominent stromal interaction of the scirrhous type. In CIN, including koilocytic atypia, 76% (32/42) of cases were positive for PTHrP. In contrast, 91% (10/11) of adenocarcinomas were negative for PTHrP. In conclusion, we found, first, that in non-neoplastic conditions, the presence of PTHrP was correlated with the transformation of progenitor cells into squamous epithelia and with the maturation of keratinocytes and, second, that in squamous-cell carcinoma, the degree of keratinization and stromal interaction was higher in direct proportion to the apparent incidence of detectable PTHrP.
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PMID:Immunohistochemical evaluation of parathyroid hormone-related protein (PTHrP) in the uterine cervix. 154 6

We purified a serum calcium-decreasing factor, which showed chymotrypsin-like protease activity, from porcine pancreas to homogeneity. The factor administered to mice intravenously at a dose of 20 micrograms/kg b.w. decreased serum calcium by 15%. Treatment of the factor with the serine protease inhibitor, PMSF, caused a leftward shift in the dose-response curve, showing strengthened activity. It also caused a decrease in serum calcium and hydroxyproline levels in rats. At a dose of 10 ng/ml, the factor inhibited 45Ca release from cultured fetal long bone stimulated by parathyroid hormone (PTH) and PTH-related protein, but not by interleukin-1 alpha, prostaglandin E1 and 1,25-dihydroxy vitamin D3. No other well-known pancreatic proteases had these effects. In view of the results of experiments using protease inhibitor and pancreatic proteases, and in view of the specificity of this factor in vitro, we propose that the factor exerts its serum calcium-decreasing activity most probably not through proteolytic degradation of PTH, but through an inhibition of PTH action on bones by a yet undefined mechanism.
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PMID:Serum calcium-decreasing factor (caldecrin) from porcine pancreas has proteolytic activity which has no clear connection with the calcium decrease. 157 66

We have explored a potential autocrine role for parathyroid hormone-related protein (PTHRP) in malignant squamous carcinoma cells (SqCC) and their nonmalignant counterpart, human epidermal keratinocytes (HK). Specific binding of Tyr36 human PTHRP-(1-36)NH2 (125I-[Tyr36]hPTHRP-(1-36)NH2) was identified in 75% of unselected SqCC lines. In contrast, no binding was detected on the mouse keratinocyte line BALB-MK or on five different HK lines. Although each SqCC and keratinocyte line secreted immunoreactive PTHRP into its medium, there was no correlation between PTHRP concentration and number of binding sites. Inhibition of binding by [Tyr36]hPTHRP-(1-36)NH2 yielded half-maximal inhibitory concentration values of approximately 100 nM in all SqCC lines. Affinity cross-linking of SqCC cells revealed 98- and 70-kDa binding proteins with similar affinity (approximately 100 nM). Exposure of fura-2-loaded SqCC cells to PTHRP and PTH resulted in equivalent, dose-dependent transient increases in intracellular calcium [half-maximal effective concentration (EC50) = 0.08 nM]. PTHRP also increased intracellular calcium in HK (EC50 = 0.05 nM). No adenosine 3',5'-cyclic monophosphate (cAMP) response to PTHRP or PTH was elicited in either SqCC or HK, despite brisk isoproterenol responses in both. We conclude that high-capacity low-affinity binding sites for PTHRP are detectable in the majority of SqCC lines but not in HK. These low-affinity binding sites are unlikely to represent receptors. The sensitive intracellular calcium response suggests the additional presence of high-affinity receptors on SqCC as well as on HK. However, the failure of PTHRP or PTH to stimulate cAMP production in otherwise cyclase-competent cells suggests that these are not classical PTH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of PTHRP binding and signal transduction mechanisms in benign and malignant squamous cells. 159 Mar 71

The effect of lowering ionized calcium on circulating parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) was assessed in twenty patients with hypercalcemia of malignancy following treatment with Pamidronate Disodium. Ionized calcium levels fell rapidly in all treated patients. PTH concentrations were initially suppressed below normal in 18 patients, but rose from 0.48 +/- 0.42 pmol/L to 3.63 +/- 3.13 pmol/L (p less than 0.01) after treatment, reaching higher than normal values in some patients even in the presence of persistent hypercalcemia. PTHrP concentrations did not change significantly after treatment. These findings are consistent with an increased sensitivity of parathyroid tissue to changes in ionized calcium following prolonged exposure to hypercalcemia. Regulation of tumor secretion of PTHrP by calcium was not apparent within the range of calcium concentrations in this study.
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PMID:Circulating PTH and PTHrP levels before and after treatment of tumor induced hypercalcemia with Pamidronate Disodium (APD). 159 95

Primary hyperparathyroidism and malignancy are responsible for the majority of reported cases of hypercalcemia. Suspected hypercalcemia should be documented on more than one occasion, preferably with the measurement of ionized calcium. Determination of intact parathyroid hormone with a modern two-site immunoassay is the single most important laboratory analysis in the differential diagnosis of hypercalcemia. Intact parathyroid hormone is increased or inappropriately high in primary hyperparathyroidism and suppressed or low normal in hypercalcemia of malignancy. Midregion and carboxylterminal radioimmunoassays are less effective in separating parathyroid and nonparathyroid hypercalcemia. In malignancy, hypercalcemia may result from local osteolysis or humoral factors. Although ectopic parathyroid hormone is produced rarely and certain lymphomas secrete 1,25-dihydroxyvitamin D, parathyroid hormone-related protein is elevated in the majority of patients with humoral hypercalcemia of malignancy. Recent developments in the measurement of parathyroid hormone-related protein should help to define the physiologic function of parathyroid hormone-related protein and its role in the differential diagnosis and therapy of hypercalcemia.
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PMID:Hypercalcemia and parathyroid disorders. 159 19


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