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)

Parathyroid hormone (PTH) release and cytoplasmic calcium concentrations were investigated at ambient calcium concentrations of 0.5-3.0 mmol/l in dispersed parathyroid cells from 44 hypercalcaemic patients with primary or uraemic hyperparathyroidism (HPT). In comparison with parathyroid cells from adult cattle, release of PTH by human preparations was reduced and values of the ambient calcium concentration causing half-maximal inhibition of PTH release (median effective dose, ED50) were significantly increased. Half-maximal inhibition of PTH release was obtained with concentrations of cytoplasmic calcium almost identical to the concentrations of ionized calcium in the plasma of the individual patients. Cytoplasmic concentrations of calcium in the parathyroid cells were inversely related to release of PTH. Concentrations of cytoplasmic calcium were significantly lower in human than in bovine cells and the ED50 for ambient calcium increase on cytoplasmic calcium was raised to the same extent as the ED50 for ambient calcium inhibition of PTH release in human compared with bovine cells. The magnitude of the increased ED50 for ambient calcium inhibition of PTH release and increase of cytoplasmic calcium concentration was similar in adenomas and sporadic as well as hereditary primary hyperplasias, but the secretion was the least aberrant in uraemic hyperplasias, although they had by far the largest glandular mass. Serum concentrations of total calcium before surgery correlated with the ED50 for ambient calcium effects of PTH release and cytoplasmic calcium, but not with glandular weight. These findings demonstrate a universally abnormal regulation of cytoplasmic calcium in HPT and its importance for PTH release, and that disturbance of cytoplasmic calcium rather than the increased glandular mass contributes to the hypercalcaemia in adenomatous and hyperplastic HPT.
 ...
PMID:Relationship between external and cytoplasmic calcium concentrations, parathyroid hormone release and weight of parathyroid glands in human hyperparathyroidism. 335 32

Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation.
 ...
PMID:Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy. 337 58

Eight patients with childhood acute lymphoblastic leukemia (ALL) and hypercalcemia, osteopenia, or vertebral compression fractures seen at our institution during the last 12 years were evaluated for biochemical evidence of bone disease. Five patients were hypercalcemic, three had abnormal phosphorous levels, and four had elevated alkaline phosphatase values. Parathyroid hormone (PTH) was measured by a polyvalent radioimmunoassay in five patients and these levels were abnormally high in three patients. Four of these five patients also had PTH measured by a midregion-specific radioimmunoassay. One patient had a high PTH value. Two patients had low levels and one patient had a normal PTH level. Although these studies suggest diverse biochemical mechanisms may be contributing to the bone changes and hypercalcemia seen in childhood ALL, ectopic PTH production as well as ectopically produced fragments of PTH may have a role in mediating bone resorption and hypercalcemia.
 ...
PMID:The spectrum of metabolic bone disease in lymphoblastic leukemia. 346 23

An asymptomatic 11-year-old boy was found to have primary hyperparathyroid secondary to an isolated parathyroid adenoma. This rare disorder of childhood can have asymptomatic hypercalcemia as its only manifestation. Parathyroid hormone assays and studies of urinary calcium excretion, especially the calcium-creatinine clearance ratio, distinguish parathyroid hormone excess from hypocalciuric forms of hypercalcemia. Real-time ultrasonography and dual-isotope subtraction scanning provide accurate, noninvasive, preoperative localization of abnormal parathyroid tissue. The prognosis of untreated, asymptomatic primary hyperparathyroidism in children is not known, and the indications for surgery are unclear. Diagnostic certainty is, therefore, especially important prior to surgical exploration.
 ...
PMID:Asymptomatic primary hyperparathyroidism in children. Newer methods of preoperative diagnosis. 352 97

The records of 100 patients operated on for primary hyperparathyroidism, from Jan 21, 1982 to June 11, 1984, were reviewed. In each patient, hypercalcemia had been documented on at least two separate occasions. A history, physical examination, chest roentgenogram, complete blood cell count with differential, 18-factor automated blood chemistry analysis, and urinalysis were used to screen for other causes of hypercalcemia. Of the 100 patients who had surgery, 88 had a preoperative parathyroid hormone level determination. Preoperative parathyroid hormone levels were normal in 41% of patients with parathyroid disease demonstrated at surgery. Parathyroid hormone assays produce variable results even from the best laboratories. A serum calcium determination remains the best test for diagnosing primary hyperparathyroidism.
 ...
PMID:Parathyroid hormone assay. Unreliable and overused. 371 18

The performance and clinical utility of a 'C-terminal' parathyroid hormone (PTH) radioimmunoassay (Dac-Cel, Wellcome Diagnostics) is described. Parathyroid hormone, as measured by the Dac-Cel method, is stable in whole blood samples for at least 24 h. 84% of patients with hypercalcaemia due to primary hyperparathyroidism have values above the upper limit seen in normocalcaemic subjects (0.5 micrograms/L), with detectable serum PTH demonstrable in the remaining 16%. In patients with hypocalcaemia due to hypoparathyroidism serum PTH was undetectable in 73% and 'inappropriately' low in the remainder. In 50% of patients with malignancy-associated hypercalcaemia serum PTH was undetectable, but was above 0.5 micrograms/L in 13%. Increased PTH concentrations were invariably found in patients with renal failure. The Dac-Cel method is a reliable and robust technique for measurement of PTH and in conjunction with determination of calcium facilitates the diagnosis of primary parathyroid disorders. Caution is required in the interpretation of PTH measurements in patients with renal failure; the significance of detectable PTH in some patients with malignancy-associated hypercalcaemia is not clear.
 ...
PMID:Performance and clinical utility of a commercially available 'C-terminal' PTH assay. 376 72

A patient on maintenance hemodialysis had widely disseminated tuberculosis, hypercalcemia, and elevated levels of calcitriol (1,25-dihydroxycholecalciferol). Hypercalcemia was not observed until the eighth month of hemodialysis, when persistent fevers began. At the end of a calcium-free dialysis, the plasma calcium concentration decreased to 6.6 mg/dL (1.65 mmol/L). The baseline calcitriol level was 56 pg/mL (normal, 19 to 50 pg/mL) and increased to 147 pg/mL at the end of hemodialysis. Parathyroid hormone levels by three separate assays did not appreciably increase during the hypocalcemia induced by the calcium-free hemodialysis. The serum phosphate concentration decreased from 7.3 to 4.5 mg/dL (2.36 to 1.45 mmol/L). Extrarenal production of calcitriol may occur in disseminated tuberculosis and may be stimulated by hypocalcemia and reduced serum phosphate. The expected parathyroid hormone response to hypocalcemia may have been inhibited by persistently elevated calcitriol levels or preexisting hypercalcemia.
 ...
PMID:Hypercalcemia and elevated calcitriol in a maintenance dialysis patient with tuberculosis. 376 40

We studied mineral metabolism in 15 thyrotoxic patients and 15 controls matched for sex, age, and weight. Thyrotoxic subjects showed significantly higher serum calcium, phosphate, alkaline phosphatase, and globulin and lower serum creatinine, magnesium, and albumin. Parathyroid hormone immunoreactivity (iPTH) was measured with three different antisera. Thyrotoxic patients showed markedly reduced iPTH values in the most sensitive assay, a midregion-specific assay based on homologous antiserum BG-6. Antiserum 211/32 gave slightly reduced iPTH values, but antiserum NG-1 gave values that were increased by 65%. The limited sensitivity of these later two antisera, like that of others used earlier for such studies, may have blunted the apparent fall in iPTH (antiserum 211/32) or predisposed the assay to a systematic artifact (antiserum NG-1). These results show that for use in the evaluation of hypercalcemia in thyrotoxic patients, a PTH assay must first be characterized as to the expected result in uncomplicated thyrotoxicosis. Twelve of the thyrotoxic subjects entered a random order cross-over study in which propranolol and placebo were given in double-masked fashion for 6 consecutive days each. Overall, the drug did not alter calcium, phosphate, or magnesium metabolism. It lowered serum calcium only in two overtly hypercalcemic subjects, whose urinary calcium excretion did not decline. These results confirm that propranolol may reduce elevated serum calcium levels in thyrotoxicosis and suggest that in this setting the drug may have a direct or indirect effect on renal calcium metabolism.
 ...
PMID:A controlled study of the effects of thyrotoxicosis and propranolol treatment on mineral metabolism and parathyroid hormone immunoreactivity. 384 May 65

Adult T-cell leukemia (ATL) is known to be frequently accompanied by hypercalcemia, but the mechanisms responsible for hypercalcemia in this disorder are not fully understood. We have recently experienced two male patients (25 and 36 yr old) with ATL diagnosed from typical leukemic cells with grooved and folded nucleus, surface marker, anti-ATLA antibody etc. Serum calcium levels of these patients were 16.4 and 21.4 mg/dl, respectively, with no radiological evidence of bone destruction. Peripheral blood leukemic lymphocytes from these patients were purified by the Ficoll-Hypaque method and cultured at a concentration of 1.5 X 10(6) cells/ml for 3 days on F-10 medium supplemented with 10% fetal calf serum. The supernatant fluids from the cell cultures were bioassayed for bone resorption-stimulating activity (BRSA) by an assay based on the release of 45Ca from prelabeled fetal mouse forearm bones in organ culture according to Raisz's method. The supernatant fluid of cultures from both patients which showed marked BRSA was nondialyzable through a dialysis membrane with a molecular weight cutoff of 3500. Parathyroid hormone and prostaglandins were not detectable in the supernatant fluids of the leukemic cell cultures. In one patient, BRSA was measured twice and found to be decreased to a normal level when the patient was in hematological remission with a normal calcium level (8.3 mg/dl). These results suggest that the hypercalcemia observed in patients with ATL is due, in part, to a bone resorption-stimulating factor which is produced by leukemic T-cell lymphocytes.
 ...
PMID:Evidence of bone resorption-stimulating factor in adult T-cell leukemia. 387 74

Urinary excretion of cyclic adenosine 3',5'-monophosphate (3',5'-AMP) was tested in normal subjects and patients with pseudohypoparathyroidism, idiopathic hypoparathyroidism, surgical hypoparathyroidism, and pseudopseudohypoparathyroidism under basal conditions and after a 15 min infusion of purified parathyroid hormone. Basal excretion of the nucleotide was less than normal in the patients with hypocalcemic disorders and greater than normal in pseudopseudohypoparathyroidism. Parathyroid hormone caused a marked increase in excretion of 3',5'-AMP in all subjects except those with pseudohypoparathyroidism; nine patients with this disorder did not respond to the hormone and four showed a markedly deficient response. Radioimmunoassay showed that parathyroid hormone circulated in increased amounts in plasma from patients with pseudohypoparathyroidism and became undetectable when serum calcium was increased above 12 mg/100 ml. Suppression of parathyroid hormone secretion by induction of hypercalcemia did not alter the deficient response to exogenous hormone. The results indicate that: (a) parathyroid hormone circulates in abnormally high concentrations in pseudohypoparathyroidism and secretion of the hormone responds normally to physiological control by calcium; (b) testing urinary excretion of 3',5'-AMP in response to infusion of purified parathyroid hormone appears to be an accurate and sensitive index for establishing the diagnosis of pseudohypoparathyroidism; and (c) the metabolic defect of the disorder can be accounted for by a lack of or defective form of parathyroid hormone-sensitive adenyl cyclase in bone and kidney.
 ...
PMID:Pseudohypoparathyroidism: defective excretion of 3',5'-AMP in response to parathyroid hormone. 430 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>