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

In this immunoradiometric assay (IRMA) of parathyrin (PTH) a polyclonal anti-amino-PTH(1-34) is the capture antibody and a radiolabeled monoclonal anti-hPTH(44-68) is the second antibody. Gel filtration of serum from a hyperparathyroid patient yielded only a single peak of PTH, corresponding to the elution position of synthetic PTH(1-84). Healthy elderly individuals (ages 78 +/- 5 y, mean +/- SD, n = 45) had PTH concentrations (21 +/- 13 ng/L) not significantly higher than those from healthy younger (38 +/- 11 y) adults (20 +/- 8 ng/L, n = 94). Assay results agreed well with those obtained with a carboxyl-terminal PTH assay both in normal subjects (r = 0.63, P less than 0.001) and in patients with primary hyperparathyroidism (r = 0.59, P less than 0.001). Both assays equally discriminated patients with surgically confirmed primary hyperparathyroidism from normal individuals, but the PTH(1-84) IRMA also allowed a nearly absolute discrimination between normal subjects and patients with primary hypoparathyroidism (undetectable serum PTH in 18 of 21 cases) and secondary hypoparathyroidism (caused by hypercalcemia that was caused by a malignant tumor, PTH 1.3 +/- 1.3 ng/L, n = 32). Moreover, the PTH(1-84) IRMA is more sensitive (detection limit in serum, 0.8 ng/L) and easier and quicker to perform than the carboxyl-terminal assay.
 ...
PMID:Immunoradiometric assay of parathyrin with polyclonal and monoclonal region-specific antibodies. 168 22

This study examined the pathophysiological role of parathyroid hormone-related protein (PTHrP) in humoral hypercalcaemia of malignancy (HHM). Seven human tumour xenografts were analysed in nude mice; five tumours (KEsC-2, oesophageal carcinoma; FA-6, pancreatic carcinoma; SEKI, melanoma; Lu-65A and Lu-61, lung carcinomas) were associated with hypercalcaemia and two tumours (MIA PaCa-2, pancreatic carcinoma; PLC/PRF/5, hepatocellular carcinoma) with normocalcaemia. Northern blot analyses, radioimmunoassay and bioassay confirmed the synthesis of PTHrP-like peptides by all five tumours associated with hypercalcaemia, but not by the two associated with normocalcaemia. These observations indicated a very close relationship between the production of PTHrP and the development of HHM. Gel filtration studies of three tumour tissue extracts revealed at least two different molecules with both PTHrP-like immunological and biological activities. One peak eluted at a position between PTHrP (1-141) and cytochrome C and the other at a position identical to cytochrome C. These results suggest that PTHrP molecules with a molecular size equal to or greater than cytochrome C participate as causative agents of HHM. All five tumour xenografts caused hypercalcaemia when grown to a size of 1.5 g in nude mice. Under cell culture conditions, four original cell lines, KEsC-2, FA-6, SEKI and Lu-65A secreted 450.0, 45.0, 3.6 and 3.0 pmol of immunoreactive PTHrP/1.5 x 10(9) cells (approximately equivalent to 1.5 g wet weight) 24 h-1 into their respective culture media. Since a subcutaneous infusion of 100 pmol 24 h-1 of PTHrP (1-34) into nude mice was sufficient to induce significant hypercalcaemia, we speculate that PTHrP alone released from tumour cells could induce hypercalcaemia at least in the case of KEsC-2, and possibly in FA-6. With regard to other tumours associated with hypercalcaemia, further examination of PTHrP and other compounds with bone-resorbing activity in these transplantable tumours is required to obtain a better understanding of this morbidity.
 ...
PMID:Production of parathyroid hormone-related protein in tumour xenografts in nude mice presenting with hypercalcaemia. 199 2

We assessed the relationship between the parathyroid hormone-related protein (PTHrP) and the development of humoral hypercalcemia of malignancy (i.e., hypercalcemia due to the production by solid tumors of hypercalcemic factors) by assaying tumor extracts from hypercalcemic and normocalcemic patients with cancer for immunoreactive PTHrP contents. Immunoreactive PTHrP was demonstrated in extracts of 21 of 22 tumor tissues obtained from 22 patients with humoral hypercalcemia of malignancy. Immunoreactive PTHrP was rarely seen in tumor tissue extracts obtained from 34 normocalcemic patients with cancer and two hypercalcemic patients with cancer with severe bone metastases. Gel filtration studies of tumor extracts revealed a molecular-size heterogeneity of immunoreactive PTHrP. These radioimmunoassay data indicate a close relationship between detection of PTHrP in tumor tissues and the development of humoral hypercalcemia of malignancy.
 ...
PMID:Parathyroid hormone-related protein in tumor tissues obtained from patients with humoral hypercalcemia of malignancy. 229 55

We have examined circulating concentrations of a parathyroid hormone-like peptide (PLP) in patients with malignancies and in patients with hyperparathyroidism. The radioimmunoassay employed reacts with synthetic amino-terminal fragments of PLP but not with parathyroid hormone. Elevated plasma PLP concentrations were observed in 50% of patients with malignancy and hypercalcemia and in 15% of normocalcemic cancer patients, mean values being higher in the former group. Detectable plasma PLP concentrations were found in 2 of 39 control subjects. In 2 patients with breast cancer plasma PLP declined concomitantly with a reduction in tumor burden. Adenocarcinoma of the breast and squamous cell carcinomas were most frequently associated with high plasma PLP levels although a variety of histologic types were represented. The presence of metastases on bone scans did not correlate with either the severity of hypercalcemia or the extent of PLP elevation. Increased concentrations of plasma PLP were also observed in 4 of 20 patients with primary hyperparathyroidism and in 5 of 16 patients with chronic renal failure and secondary hyperparathyroidism. Gel filtration analysis of immunoreactive PLP in plasma from 2 hypercalcemic breast cancer patients revealed heterogeneity, with, in each case, both large (greater than 15 kD) and small (6-7 kD) molecular weight amino-terminal moieties. The results document the presence of PLP in the circulation of patients with cancer and are consistent with a pathogenetic role for PLP in the hypercalcemia of malignancy irrespective of whether skeletal metastases have occurred. PLP may also contribute to the skeletal and/or renal manifestations of hyperparathyroid states.
 ...
PMID:Circulating concentrations of parathyroid hormone-like peptide in malignancy and in hyperparathyroidism. 231 98

A 54-yr-old man with a left adrenal pheochromocytoma showed mild hypercalcemia and elevated nephrogenous cAMP. Serum levels of PTH and 1,25-dihydroxyvitamin D3 were not elevated. Postoperatively, serum calcium and nephrogenous cAMP declined to normal ranges. Pathologically, the tumor was a benign pheochromocytoma. The clinical findings resembled those of humoral hypercalcemia of malignancy (HHM), and PTH-related protein (PTHrP) immunoreactivity was detected in the tumor extract at a concentration of 80.7 pmol/g wet wt, which is high compared to levels in malignant tumors causing HHM. Production of PTHrP was further confirmed by the demonstration of PTHrP mRNA with Northern blot hybridization analysis. Gel filtration of the extract revealed the presence of at least two different molecules with both immunological and biological activities. One of the peaks appeared close to PTHrP-(1-34), and the other between cytochrome-c and BSA. The latter showed a higher bioactivity to immunoreactivity ratio. These data indicate the multiplicity of PTHrP molecules in pheochromocytoma and support the idea that PTHrP produced by pheochromocytoma causes hypercalcemia in a similar fashion as HHM.
 ...
PMID:A case of pheochromocytoma producing parathyroid hormone-related protein and presenting with hypercalcemia. 234 92

Extract of exocrine pancreatic cancer associated with humoral hypercalcemia of malignancy was examined for biological activities of PTH-like factor and transforming growth factor (TGFA and TGFB), both of which are possible causes of hypercalcemia. The crude extract had both PTH-like and TGF activities. On Bio Gel P-60 column chromatography, PTH-like and TGFA activities were eluted at around 10 kD, whereas TGFB activity was eluted at around void fractions, 10 kD and 6 kD. Liver extract, used as a control material, exhibited only TGFB activity at around 6 kD. CM-cellulose column chromatography of 10 kD fractions resulted in a subtle distinction between PTH-like activity and TGF activities. Further fractionation of the peak with PTH-like activity on reverse-phase high performance liquid chromatography separated PTH-like activity distinctly from TGFB activity. TGFA activity was lost through the procedure. It was concluded that the exocrine pancreatic cancer associated with hypercalcemia produced not only PTH-like activity but also TGFA and TGFB activities. Several chromatographic analyses suggested that PTH-like activity and at least TGFB activity stem from distinct molecules and that the PTH-like factor has no significant TGFB activity intrinsically.
 ...
PMID:On the activities of parathyroid hormone-like factor and transforming growth factors in extract of pancreatic cancer associated with humoral hypercalcemia of malignancy. 316 57

In order to elucidate the pathogenesis of humoral hypercalcemia and leukocytosis in a 71-year-old patient with squamous cell carcinoma of the thyroid, bone-resorbing activity (BRA) and colony-stimulating activity in the conditioned medium of T3M-5 cells, a clonal cell line established from the tumor, were studied. Gel chromatography of the concentrated conditioned medium revealed respective single peaks of colony-stimulating activity (Mr approximately 27,000) and BRA (Mr 15,000-20,000). BRA did not elicit parathyroid-hormone-like activity but greatly enhanced phytohemagglutinin-induced thymocyte proliferation. This interleukin 1 (IL-1)-like activity exactly coeluted with BRA upon gel chromatography, DEAE-Sepharose ion-exchange chromatography, and isoelectric focusing (pI, 4.7-5.2). BRA was partially inhibited by indomethacin and hydrocortisone, and completely inhibited by anti-IL-1 alpha antiserum, whereas anti-IL-1 beta antiserum had no effect. Furthermore, transplantation of T3M-5 cells into nude mice caused marked hypercalcemia as well as leukocytosis. These findings suggested that excessive production of colony-stimulating factor and IL-1 alpha-like factor by the squamous cell carcinoma was responsible for leukocytosis and hypercalcemia, respectively, in the tumor-bearing nude mice and in the patient. Since several similar cases have been reported in Japan, the syndrome of leukocytosis and hypercalcemia associated with certain solid tumors may constitute a new paraneoplastic syndrome.
 ...
PMID:Production of interleukin 1 alpha-like factor and colony-stimulating factor by a squamous cell carcinoma of the thyroid (T3M-5) derived from a patient with hypercalcemia and leukocytosis. 349 74

The immunoreactive forms of parathyroid hormone (iPTH) in the plasma of six patients with primary, adenomatous hyperparathyroidism and six patients with ectopic hyperparathyroidism due to non-parathyroid cancer were compared by using gel filtration on columns of Bio-Gel P-150 and radioimmunoassay of iPTH in eluted fractions after concentration. We found much less (p<0.001) small (mol wt<9,500) COOH-terminal fragments of iPTH in plasma samples from ectopic hyperparathyroid patients (0.52+/-0.13 ng eq/ml) than in samples from primary hyperparathyroid patients (3.70+/-1.15 ng eq/ml). The quantity of iPTH eluting with or before native bovine PTH [1-84] was the same in both syndromes (ectopic hyperparathyroidism, 0.82+/-0.22 ng eq/ml; primary hyperparathyroidism, 0.73+/-0.09 ng eq/ml), and these values correlated positively with plasma calcium concentration (ectopic hyperparathyroidism, r=0.908; primary hyperparathyroidism, r=0.919). In both syndromes, plasma samples had an iPTH component that eluted well before PTH [1-84] (mol wt 9,500), but this component was present in much larger quantities in three patients with ectopic hyperparathyroidism. We conclude that (a) the decreased quantity of biologically inactive COOH-terminal fragments of iPTH circulating in ectopic hyperparathyroidism accounts for the previously reported relatively lower total serum iPTH values in this syndrome as compared with primary hyperparathyroidism (Riggs et al. 1971. J. Clin. Invest. 50: 2079); (b) there appears to be sufficient iPTH with presumed biologic activity to account for the hypercalcemia in both syndromes; (c) a large PTH component, not previously recognized in plasma, is present in both ectopic and primary hyperparathyroidism and may exist as the predominant immunoreactive form of the hormone in some patients with ectopic hyperparathyroidism.
 ...
PMID:Immunoreactive forms of circulating parathyroid hormone in primary and ectopic hyperparathyroidism. 483 87

Employing a cytochemical assay initially developed for measuring parathyroid hormone (PTH), bioactivity was assessed in 33 patients with malignancies. Initial studies in vitro were consistent with a role for cAMP as a second messenger in the bioassay. Cytochemical bioactivity was increased in the peripheral plasma of 10 of 16 hypercalcemic patients with elevated nephrogenous cAMP excretion, and mean levels were 10-fold higher in these patients than in 17 normocalcemic or hypercalcemic patients with normal or suppressed nephrogenous cAmP excretion, respectively. Plasma bioactivity, serum calcium, and nephrogenous cAMP excretion all fell to normal in 1 patient after tumor resection, and cytochemical bioactivity was demonstrable in the tissue culture medium in which the neoplasm was maintained. Gel chromatographic analysis revealed that a major component of plasma bioactivity eluted before rather than with PTH-(1-84) in patients with malignancy in contrast with that in patients with primary hyperparathyroidism. The studies, therefore, demonstrate the capacity of the cytochemical bioassay to measure increased activity in patients with malignancy, hypercalcemia, and elevated nephrogenous cAMP excretion; suggest that the material responsible for the activity differs from PTH-(1-84); and provide a sensitive detector system for further analysis of this material and its role in the pathogenesis of this disease.
 ...
PMID:Malignancy-associated hypercalcemia: evaluation with a cytochemical bioassay for parathyroid hormone. 627 Jan 84

Ascites sarcoma 180 (S180A) is a transplantable tumor which causes hypercalcemia in tumor-bearing mice, and stimulates bone resorption without parathyroid hormone-like activity. In the present study, parathyroid hormone-related protein (PTHrP) mRNA could not be detected in total RNA from S180A cells. Bone-resorbing activity (BRA) derived from serum-free conditioned medium of S180A cells (S180A-CM) was coeluted with either transforming growth factor alpha (TGF alpha) activity (peak A, approximate M(r), 29 kDa) or lymphocyte-activating factor (LAF) activity (peak B, M(r), 20.1-24 kDa) in Bio-Gel P-100 column chromatography. Fractions in peak A and B contained IL-6 but not tumor necrosis factor alpha (TNF alpha). Subsequent separation of peak A by reverse-phase high performance liquid chromatography produced a single fraction which contained both BRA and TGF alpha activity. Recombinant human TGF alpha-induced bone resorption was completely inhibited by indomethacin. The BRA in peak A was partially inhibited by indomethacin and almost completely inhibited by simultaneous treatment of indomethacin and anti-IL-6 antibody. The BRA in peak B was partially inhibited by neutralization with anti-IL-1 alpha antibody and was completely inhibited by simultaneous treatment with anti-IL-1 alpha and anti-IL-6 antibody in the absence of indomethacin. Bone resorption induced by S180A-CM was associated with an increased production of prostaglandin E2 (PGE2) by calvaria. The BRA in S180A-CM, however, was not completely abolished by the simultaneous addition of indomethacin and anti-IL-1 alpha, anti-IL-1 beta and anti-IL-6 antibodies. Our findings indicate that (1) BRA derived from S180A cells includes TGF alpha, IL-1 alpha, IL-6 and some other unknown factor(s), distinct from PTHrP, IL-1 beta and TNF alpha, and (2) these unknown factors resorb bone in part via a PGE2-independent pathway.
 ...
PMID:Ascites sarcoma 180, a tumor associated with hypercalcemia, secretes potent bone-resorbing factors including transforming growth factor alpha, interleukin-1 alpha and interleukin-6. 769 88


1 2 Next >>