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 enzyme carbonic anhydrase has been suggested as a critical participant in osteoclast-mediated bone resorption. In humoral hypercalcemia of malignancy (HHM) intense osteoclastic bone resorption is principally responsible for the observed hypercalcemia. We therefore undertook to examine the effect of the carbonic anhydrase inhibitor acetazolamide on the hypercalcemia induced by the H500 Leydig cell tumor in Fisher rats, a well-described model of HHM. Acetazolamide treatment for 10 h at 10 mg/h resulted in a significant fall in serum calcium in the five drug-treated animals (14.2 +/- 0.9 to 11.5 +/- 0.1 mg/dl, p less than 0.05). Conversely, the six animals infused with vehicle alone showed a significant rise in serum calcium (12.5 +/- 0.5 to 13.8 +/- 0.1 mg/dl, p less than 0.05). At the end of the infusion, the acetazolamide-treated animals had a significantly lower mean serum calcium than those receiving vehicle alone (11.5 +/- 0.1 versus 13.8 +/- 0.1, p less than 0.05). There was no significant change in serum phosphorus, urine calcium, urine phosphorus, or nephrogenous cyclic AMP excretion between the two groups. Acetazaolamide and HTS 5-(3-hydroxybenzoyl)-2-thiophenesulfonamide, another carbonic anhydrase inhibitor, both significantly inhibited in vitro bone resorption induced by 5 X 10(-9) M 36Tyr(1-36)-PTHrP-amide (PTHrP, parathyroid hormone-related protein). Acetazolamide also inhibited the resorption induced by 10(-8) M (1-141)-PTHrP and 2.5 X 10(-9) M (1-74)-PTHrP. We conclude that acetazolamide is effective in lowering the serum calcium in animals with humoral hypercalcemia of malignancy. The data are consistent with the hypothesis that the mechanism of action for this effect is direct inhibition of osteoclast-mediated bone resorption.
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PMID:Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase. 196 58

With a newly developed monoclonal anti-PTHrP antibody, 4B3, the immunohistochemical localization of the parathyroid hormone-related protein (PTHrP) was studied on the formalin-fixed and paraffin-embedded sections of normal human tissues and various subtypes of lung cancer. Among normal epithelial tissues, keratinocytes in squamous epithelia, transitional and bronchial epithelia with squamous metaplasia, meningoepithelial cells, and mammary ductal cells with lactating changes showed positive immunoreactivity. Also, among endocrine tissues, cells in the parathyroid gland, pancreatic islets, adrenal cortex, pituitary gland, and testis were sporadically positive for PTHrP. These distribution patterns suggested that in a physiologic condition, PTHrP was closely related to keratinization and local secretion and/or the metabolism of calcium in specifically differentiated tissues. In lung cancer, however, PTHrP was detected in all cases of well-differentiated and moderately differentiated squamous cell carcinoma and in most cases of small cell carcinoma, irrespective of the patients' serum calcium level. However, PTHrP was not detected in two of five cases of poorly differentiated squamous cell carcinoma and in all cases of adenocarcinoma. Consequently, it was found that PTHrP was commonly produced by squamous cell carcinomas of the differentiated type, and that humoral hypercalcemia of malignancy could be induced when the PTHrP transgressed the homeostatic mechanisms.
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PMID:Immunohistologic evaluation of parathyroid hormone-related protein in human lung cancer and normal tissue with newly developed monoclonal antibody. 199 Dec 68

Parathyroid hormone-related protein (PTHrP) has been shown to be present in milk of various mammals. We have assayed PTHrP in milk of various species by radioimmunoassay and estimated the molecular weights by Western blot analysis. PTHrP concentrations in bovine, ovine and human milk were 59.2 +/- 18.5, 74.1 +/- 35.0 and 36.6 +/- 20.7 micrograms/l (mean +/- S.D.) respectively, in pooled samples collected at various stages of lactation. PTHrP in mammalian milk was found to exist in two forms with molecular weights of 17.5 kDa and 21.5 kDa approximating those of PTHrP(1-108) and (1-141) respectively. In comparison, marsupial milk PTHrP appeared as a single low molecular weight form of 14.4 kDa which approximated to that of PTHrP(1-84). We performed a longitudinal study measuring the concentration of PTHrP in milk throughout lactation in cows, and found it to increase with the duration of lactation (r = 0.669, n = 91). We further examined the relationship between the concentration of PTHrP and total calcium in bovine milk, and the differences between these constituents in milk from Friesian and Jersey cows. PTHrP concentrations correlated positively with total milk calcium (r = 0.346, n = 105). The mean milk concentration of PTHrP of the Jerseys was significantly higher than that of the Friesians (52.6 +/- 5.4 micrograms/l compared with 41.0 +/- 4.8 micrograms/l, P less than 0.01), as was the mean milk calcium concentration (30.5 +/- 3.0 mmol/l compared with 26.7 +/- 2.7 mmol/l, P less than 0.01). We therefore postulate that production of PTHrP by the mammary gland may be associated with calcium transport from blood to milk. Also PTHrP may play a role in the development of milk fever in Jerseys which are predisposed to this condition.
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PMID:Parathyroid hormone-related protein in milk and its correlation with bovine milk calcium. 199 73

Previous associations of primary hyperparathyroidism-induced hypercalcemia and medullary sponge kidney (MSK) have been reported. In this report, we describe a lactating woman MSK noted to be hypercalcemic throughout lactation, without evidence of hyperparathyroidism. After the baby was weaned, the serum calcium returned to normal. A bone biopsy performed while the patient was hypercalcemic was consistent with hyperparathyroidism, suggesting the presence of a parathyroid-like protein produced during lactation.
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PMID:Postpartum hypercalcemia in a patient with medullary sponge kidneys. 202 62

46-year-old male patient was born in Niigata Prefecture and thereafter lived in Tokyo. In late January 1985, he noticed swelling of the bilateral inguinal lymph-nodes followed by fever and lumbago. In February, he consulted a local doctor and hepatosplenomegaly, marked leukocytosis and renal dysfunction were pointed out and he was referred to our hospital on February 22nd. The clinical laboratory data on admission were as follows; WBC 23,200/microliter, serum-Ca 18.4 mg/dl, BUN 85.3 mg/dl, creatinine 5.4 mg/dl, antibody to ATLV x160. ATL was diagnosed by biopsy of lymph nodes and examinations of peripheral blood and bone marrow hemogram. Remission was achieved in March by the treatment with adriacin. Renal failure and hypercalcemia also improved. However his respiratory dysfunction gradually worsened. The chest radiographies++ showed pulmonary edema, although there was no clinical evidence of heart failure. When his condition became stable, TBLB was performed and revealed extensive deposition of calcium along alveolar septae, suggesting that pulmonary edema was induced by the metastatic calcification of the lung. After the second treatment for ATL, he died of pneumonia. The autopsy showed calcium deposition not only in the lung but in pyramids of the kidney and in sub-serous layer of the small intestine. There was no tumor cell invasion into the bone or parathyroid gland. High urinary c-AMP together with normal levels of PTH suggested that the hypercalcemia in this case was induced by PTH-related protein. It was concluded that careful treatment for hypercalcemia is important as regards the occurrence of pulmonary edema.
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PMID:[An autopsy case of adult T-cell leukemia complicated with metastatic calcification of the lung]. 204 Dec 50

Parathyroid hormone related protein (PTHrP) is the main factor of humoral hypercalcemia of malignancy (HHM). Using anti-PTHrP monoclonal antibody 4B3, we investigated the immunohistochemical localization of PTHrP in human normal renal tissues and renal cell carcinomas. Among normal renal tissues, distal tubules and collecting ducts showed positive immunostaining. Among 36 cases of renal cell carcinoma, PTHrP was detected in 30 cases (83%), and there was no significant correlation between the degree of the immunostaining and the serum calcium levels of the patients. As for the histopathological types of the renal cell carcinomas, granular cell subtypes tended to be more strongly positive than clear cell ones. In conclusion, it was not uncommon that PTHrP was commonly presented by renal cell carcinoma, and HHM occurred when the PTHrP transgressed the homeostatic mechanisms.
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PMID:[Immunohistochemical study of parathyroid hormone related protein (PTHrP) in renal cell carcinoma]. 205 95

PTH and calcitonin are the two major hormones controlling calcium metabolism. Recently two new substances related to these hormones have been isolated: calcitonin gene related peptide (CGRP) and PTH-related protein (PTHrP). CGRP is a potent vasodilator and stimulant of intestinal secretion while PTHrP is probably the agent responsible for humoral hypercalcaemia of malignancy. We report here a patient with a prostatic tumour presenting with vasodilation, diarrhoea and hypercalcaemia. Our investigations revealed that the primary prostatic and liver secondary tumour contained CGRP, calcitonin and PTHrP. Most of the immunoreactive CGRP in the tumour and plasma co-eluted with the biologically active form of CGRP. The circulating levels of CGRP correlated with the presence of the diarrhoea. PTHrP concentration in the tumours was one of the highest reported for any tumour although previous studies may have utilized less than optimal extraction procedures. The somatostatin analogue, octreotide (SMS 201-995), did not reduce the plasma CGRP or the diarrhoea, a finding similar to that seen in patients with medullary thyroid carcinoma and high plasma CGRP. The hypercalcaemia was also unaffected by octreotide administration. This is the first report of a prostatic tumour associated with over-production of calcitonin, PTHrP and CGRP. The major life-threatening effects of this unusual case of prostatic carcinoma were diarrhoea and hypercalcaemia. Both these effects could be tentatively ascribed to newly discovered substances, CGRP and PTHrP. With the greater availability of assays to measure CGRP and PTHrP in plasma, a detailed examination of the incidence of over-production of these substances in various cancers will be possible.
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PMID:Production of calcitonin gene related peptide, calcitonin and PTH-related protein by a prostatic adenocarcinoma. 206 Jan 48

Parathyroid hormone-related protein (PTHrP) has significant homology with parathyroid hormone (PTH) especially in the amino-terminal sequence. We compared some effects of human synthetic analogue of amino terminal PTHrP [hPTHrP (1-34)] with those of human synthetic analogue of amino terminal PTH [hPTH (1-34)]. Intravenous administration of hPTHrP (1-34) in parathyroidectomized rats caused hypercalcemic, hypophosphatemic and phosphaturic effects in the same degree of hPTH (1-34). In the kinetic study, apparent Km and Vmax of phosphate transport in renal brush border membrane vesicles were identical in both peptides (hPTHrP(1-34) Km = 27.6 +/- 0.8 mumol, Vmax = 3.78 +/- 0.04 nmol/mg.protein; hPTH(1-34) Km = 29.6 +/- 0.9 mumol, Vmax = 3.04 +/- 0.9 nmol/mg.protein). hPTHrP(1-34) and hPTH(1-34) were equipotent in eliciting a 9-fold increase of adenosine 3',5'-monophosphate (cAMP) production. These results demonstrate that the effect of hPTHrP (1-34) is similar to hPTH(1-34) on serum calcium, phosphorus and nephrogenous cAMP in vivo, and Na(+)-dependent phosphate transport in brush border membrane vesicles.
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PMID:[Effect of parathyroid hormone-related protein on Na(+)-dependent phosphate transport in renal brush border membrane vesicles in rats]. 206 12

Humoral hypercalcemia in malignant disease results from the production of humoral factors that act on bone to demineralize the skeleton, with subsequent release of calcium. It is characteristic of certain tumours without bony metastases. A recently discovered parathyroid hormone-related protein (PTHrP) has been implicated as a causative hypercalcemic agent. PTHrP exerts its calcium-mobilizing effects by interaction with parathyroid hormone (PTH) receptors in bone and kidney through its amino-terminal sequence, which is homologous with that of PTH. The human PTHrP gene could encode multiple isoforms of the protein due to alternative exon usage. Apart from its involvement in humoral hypercalcemia of malignancy, PTHrP has also been identified in normal tissues, such as keratinocytes and placenta, and is present in high concentration in milk. PTHrP may modulate the calcium homeostasis in some normal physiological conditions, probably acting in a paracrine fashion.
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PMID:[Malignant humoral hypercalcemia and the parathyroid hormone related protein]. 206 84

The syndrome of humoral hypercalcemia of malignancy (HHM) is thought to be mainly a result of the production of parathyroid hormone-related protein (PTHRP) by malignant tumors. Serum 1,25-dihydroxyvitamin D (1,25-DHD) concentrations are generally low in such patients, which contrasts with the findings in animal studies. A patient is reported with HHM from a clear cell ovarian carcinoma and elevated serum immunoreactive PTHRP (about five times the upper limit of normal) in whom serum 1,25-DHD concentrations were abnormally high (200 pmol/l) and associated with increased intestinal calcium absorption. Treatment with two different nitrogen-containing bisphosphonates (pamidronate and [3-dimethyl-amino-1-hydroxypropylidene]-1,1-bisphosphonate) did not normalize serum and urinary calcium despite effective inhibition of bone resorption. These observations suggested an additional intestinal contribution to the maintenance of hypercalcemia. Tumor removal was followed by decreases in serum immunoreactive PTHRP and 1,25-DHD concentrations to their respective normal ranges and normocalcemia. Separating HHM into Types I and II, according to the prevailing serum 1,25-DHD concentrations, can provide a basis for a better understanding of the pathogenesis of hypercalcemia, and it also may have practical use in the successful management of these patients.
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PMID:The role of 1,25-dihydroxyvitamin D in the maintenance of hypercalcemia in a patient with an ovarian carcinoma producing parathyroid hormone-related protein. 206 86


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