Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four young milk-fed calves were fitted with catheters chronically implanted in the mesenteric, portal and hepatic veins and in the hepatic artery. Electromagnetic blood flow probes in the portal vein and hepatic artery allowed continuous measurement of hepatic IGF-1 production. In accordance with a latin square design these calves received iv mesenteric infusion (for 60 min) of calcium (Ca, 0.125 mmol.kg body wt-1), the synthetic human parathyroid hormone-related protein (1-34) fragment (PTHrP, 1 nmol.kg body wt-1), the synthetic analogue [tyr]34-bovine PTH-(7-34) NH2 (2 nmol.kg body wt-1) and PTHrP (1 nmol.kg body wt-1) or solvent alone (1.2 ml.kg body wt-1). Hypercalcaemia observed following Ca infusion had no significant effect on hepatic IGF-1 production. PTHrP induced a slight but significant increase in plasma Ca and IGF-1 concentrations measured in the hepatic vein, without changing blood flows measured in the hepatic artery and portal vein. Thus PTHrP increased hepatic IGF-1 production (15.1 +/- 2.7 nmol.6 h-1.kg body wt-1 vs 4 +/- 1.3 nmol.6 h-1.kg body wt-1 in controls; p less than 0.05). These effects induced by PTHrP were inhibited by the synthetic analogue [tyr]34-bPTH-(7-34) NH2.
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PMID:The influence of parathyroid hormone-related protein on hepatic IGF-1 production. 130 83

The mechanisms by which tumor cells metastasize to bone are not well understood. We have investigated the role of the basement membrane glycoprotein, laminin, in bone metastasis, since antagonists to laminin have been shown to inhibit the formation of lung metastases. We studied the formation of osteolytic metastases caused by a human tumor which is known to cause osteolysis and hypercalcemia in nude mice. We found that tumor-bearing nude mice developed hypercalcemia, cachexia, and characteristic osteolytic lesions throughout the skeleton after injection of this human melanoma cell line (A375) into the left ventricle. When we gave injections to nude mice with A375 cells which had been exposed to C(YIGSR)3-NH2, a laminin-derived synthetic peptide containing three linear sequences of YIGSR with an amino-terminal cysteine which competes with laminin for its receptor, we found a decrease in the formation of detectable osteolytic bone metastases. The tumor cells were incubated with the antagonist and then inoculated into nude mice which were administered the antagonist i.p. Hypercalcemia and cachexia were also decreased in tumor-bearing mice treated with the laminin antagonist. In contrast, laminin itself increased the number of osteolytic bone metastases, as has been shown for other tumor cells. These data suggest that laminin plays a role in the formation of osteolytic bone metastases in this model and that laminin antagonists may be useful in the prevention of bone metastases in some human tumors.
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PMID:A synthetic antagonist to laminin inhibits the formation of osteolytic metastases by human melanoma cells in nude mice. 139 44

The effect of synthetic human parathyroid hormone-related peptide fragment 1-34 (hPTHrP) on plasma concentration and urinary excretion of inorganic phosphorus (P) was compared to that of synthetic bovine PTH fragment 1-34 (bPTH) in four 120- to 130-day-old fetal lambs chronically catheterized in utero. They received by I.V. infusion according to a Latin square design either bPTH (6 nmol per fetus) or hPTHrp (6 nmol per fetus) alone, or after the synthetic analogue [Tyr34]bPTH(7-34)NH2 (12 nmol per fetus). Control fetuses received the same volume of solvent alone. Both bPTH and hPTHrP stimulated diuresis. They induced hypercalcaemia, hyperphosphaturia and hypophosphataemia. The effects of hPTHrP were inhibited by [Tyr34]bPTH(7-34)NH2, indicating that PTHrP might work through the PTH receptor.
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PMID:Parathyroid hormone-related peptide increases urinary phosphate excretion in fetal lambs. 158 Oct 66

The biological properties of a new synthetic analog of parathyroid hormone-related protein [PTHrP-(7-34)NH2] were examined in vivo using a well characterized thyroparathyroidectomized (TPTX) rat model. The phosphaturic and urine cyclic AMP response induced by infusion of PTHrP-(1-34)NH2 (0.16 nmol/h) was inhibited by 70% (P less than 0.01, n = 6) by co-infusion of PTHrP-(7-34)NH2 at a 10-fold molar excess (1.6 nmol/h). The 7-34 PTHrP analog also antagonized the PTHrP-(1-34)NH2-induced hypercalcemia and rises in blood 1,25-dihydroxyvitamin D concentrations. However, when infused alone at a higher dose rate (8 nmol/h), PTHrP-(7-34)NH2 displayed significant PTH agonist activity. This profile contrasts to that of [Tyr-34]bPTH-(7-34)NH2 which is comparatively less potent (10-20-fold) with respect to its antagonist activity but has no appreciable agonist activity in vivo.
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PMID:A 7-34 analog of the parathyroid hormone-related protein has potent antagonist and partial agonist activity in vivo. 185 Jun 33

Many factors, such as interleukin 1, TGF alpha, TNF alpha, and beta and prostaglandins, have been implicated in aetiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the NH2-terminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support for this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have a similar intron/exon organization as the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have enabled detailed structure-function studies that have identified NH2-terminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP has added to our understanding of the mechanisms of hypercalcemia, and may contribute to the understanding of other metabolic bone diseases such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in fetal calcium metabolism and in normal cell physiology.
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PMID:A novel parathyroid hormone-related protein: role in pathology and physiology. 218 38

Parathyroid hormone related peptide (PTHrP) has been implicated in the cause of the hypercalcemia associated with a number of malignant tumours. The data presented here suggests that PTHrP (in addition to its known role of mediating hypercalcemia) may be involved in the autocrine regulation of growth of some tumours. Polyclonal PTHrP antiserum almost totally inhibited the growth of a human renal cell carcinoma cell line, known to secrete PTHrP, in vitro and growth was significantly inhibited by the competitive PTH antagonist PTH (3-34)NH2.
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PMID:Parathyroid hormone related peptide can function as an autocrine growth factor in human renal cell carcinoma. 232 62

In fresh-water rainbow trout, Oncorhynchus mykiss (formerly called Salmo gairdneri), experimentally induced mild hypercalcemia results in release of immunoreactive stanniocalcin from the corpuscles of Stannius (CS) and stimulated synthetic and releasing activities of the glands as measured in vitro. Pulse-chase experiments showed that stanniocalcin (STC) is a 56-kDa glycoprotein, processed from a 64-kDa precursor, prostanniocalcin (PSTC). PSTC and STC are homodimeric molecules that are readily split into monomers in the presence of reducing agents such as 2-mercaptoethanol. The monomeric form of PSTC and STC contains an approximately 5- to 6-kDa glycomoiety. Neither this sugar residue nor the NH2-terminal amino acid sequences of PSTC or STC proved to contain antigenic sites for the antiserum used in this study. Two-dimensional gel electrophoresis indicated the presence of several isoforms of PSTC and STC molecules that may reflect different stages of maturation of the (pro)hormone.
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PMID:Rainbow trout corpuscles of Stannius: stanniocalcin synthesis in vitro. 233 96

Four analogues of parathyroid hormone-related protein (PTHrP), PTHrP(7-34)NH2, (10-34)NH2, (15-34)NH2 and (20-34)NH2, were synthesized and their antagonistic activity against PTHrP(1-34) was examined in vitro and in vivo. In vitro studies revealed that all four analogues antagonized PTHrP-stimulated cyclic AMP production in rat osteosarcoma cells (ROS 17/2.8), and that PTHrP(7-34)NH2 and PTHrP(10-34)NH2 had potent antagonistic activity. In vivo experiments in nude mice also revealed that PTHrP(7-34)NH2 completely inhibited hypercalcemia induced by PTHrP(1-34), indicating that these analogues antagonize the effects of PTHrP(1-34) in vitro and in vivo.
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PMID:In vitro and in vivo antagonists against parathyroid hormone-related protein. 253 30

Many factors, such as interleukin 1, TGF alpha, tumor necrosis factor alpha and beta, and PGs, have been implicated in etiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and were found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the NH2 terminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have a similar intron--exon organization as the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have enabled detailed structure-function studies that have identified NH 2-terminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP have added to our understanding of the mechanisms of hypercalcemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology.
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PMID:Parathyroid hormone-related protein: isolation, molecular cloning, and mechanism of action. 268 46

Aluminium-containing phosphate binders were replaced by a calcium and magnesium carbonate-containing antacid in 20 patients on long-term haemodialysis, over a three-month period in all of them, for 12 months in ten. After two months the serum aluminium level fell (mean +/- SD) from 3.0 +/- 1.6 to 1.4 +/- 0.5 mumol/l (P less than 0.001). After three months the serum phosphate level had fallen from 1.8 +/- 0.4 to 1.5 +/- 0.4 mumol/l (P less than 0.05), while during the same period parathormone (PTH-NH2) fell from 1.4 +/- 1.4 to 0.8 +/- 0.7 ng/ml (P less than 0.05). Serum total calcium concentration rose after two months from 2.2 +/- 0.2 to 2.4 +/- 0.2 mmol/l (P less than 0.001). In a third of patients the uraemic acidosis was corrected, standard bicarbonate rising from 18 +/- 2 to 21 +/- 3 mmol/l (P less than 0.05). Serum pH, potassium, sodium, magnesium and alkaline phosphatase did not change significantly. Hypercalcaemia was an expected disadvantage: repeated symptom-free episodes of hypercalcaemia occurred in six of 20 patients during the first three months and in a further two up to 12 months. These episodes were successfully controlled by a reduction of CaCO3/MgCO3 dosage and readministration of Al(OH)3. Extraosseous calcifications were not observed.
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PMID:[Replacement of aluminum-containing phosphate binders by calcium and magnesium carbonates in long-term hemodialysis]. 270 34


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