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)

Dichloromethylene diphosphonate (Cl2MDP) antagonized the action of vitamin D on bone in thyroparathyroidectomized rats by reducing the metabolic activity of osteoblasts and osteocytes and decreasing the number of osteoclasts. Ultrastructurally, osteoblasts in Cl2MDP-treated rats were interpreted to be less active in bone matrix synthesis. Osteocytes in Cl2MDP-treated rats were interpreted ultrastructurally to be inactive; there was no evidence of bone resorption when compared to osteocytes in rats given vitamin D alone. Abnormal osmiophilic densities in the pericellular bone matrix of rats given vitamin D alone were not present in rats given vitamin D and Cl2MDP. The ultrastructure of osteoclasts was unaltered by Cl2MDT. These cellular changes were associated with a decrease in serum calcium and increase in bone ash and magnesium concentration in rats given high levels (10 mg/kg) of Cl2MDP. Bone adenosine triphosphatase and alkaline phosphatase activities were not affected by Cl2MDP. These results suggest that Cl2MDP may limit the hypercalcemia of hypervitaminosis D by directly inhibiting bone cells in addition to its physicochemical action.
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PMID:Interaction of dichloromethylene diphosphonate and vitamin D on bone of thyroparathyroidectomized rats. 14 91

Despite extensive study since the first report of familial benign hypercalcemia (FBH, or hypocalciuric hypercalcemia) in 1972, there is no evidence of the specific abnormal gene product. FBH is highly suitable for either a candidate gene or a reverse genetics approach to localizing the genetic abnormality, because it is inherited in an autosomal dominant pattern, is highly penetrant, does not affect survival, and can be diagnosed in families with readily available measurements. Importantly, several candidate genes have been cloned and mapped. Therefore, we collected blood samples and extracted leukocyte DNA from 94 members of 4 families with well documented FBH (44 affected, 45 unaffected, and 5 unclassifiable). We digested the DNA samples with various restriction endonucleases, conducted standard Southern blotting, and searched for restriction fragment length polymorphisms for the following candidate genes (probe names in parentheses): multiple endocrine neoplasia (MEN) type 1 (pMCMP.1, pHBI59, p3C7, and pTHH26), MEN 2a (MCK2 and cTB14.34), basic fibroblast growth factor (pHFL1-7), (Ca2+,Mg2+)ATPase isoform 4 (hPMCA4), membrane Na/Ca exchanger (cNC28 M-A), PTH (pPTH-LF), and calbindin-D28K (pSKCalb). In addition, we used the anonymous variable number tandem repeat marker pYNH24 to verify pedigree structures by excluding misinheritances. Data were analyzed using the Linkage program. For none of the genes was there significant linkage with the FBH trait; logarithm of odds scores ranged from -1.3 to -26.0 at a recombination fraction of 0.001, and from 0.6 to -5.6 at a recombination fraction of 0.10. We conclude that FBH is unrelated to the MEN syndromes and is not caused by mutations in any of the calcium-regulating or -binding proteins or growth factors studied thus far.
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PMID:Genetic linkage analysis in familial benign hypercalcemia using a candidate gene strategy. I. Studies in four families. 151 76

In the lymphocytes infected in vitro with BLV (bovine leukemia virus) the contents of Ca2+ and Mg2+ were determined using roentgen microanalyser JXA-5 A Joel-form (Japan). In the smears prepared from these cells the activity of enzyme markers of cell membranes i.e. alkaline phosphatase (AP - EC 3.1.3.1), 5'-nucleotidase (5'-NT - EC 3.1.3.5) and adenosine-triphosphatases - Ca2+ and Mg2+ dependent (ATP-ase - EC 3.6.1.3) was determined. The decrease in AP and ATP-assess activity and increase in 5'-NT in the membranes of leukemic lymphocytes were observed. During these changes the increase in Ca2+ and decrease in Mg2+ ions occurred. These processes lead to clear disturbances in the metabolism of cells transformed by the neoplasm. The effect of this phenomenon is probably the opening of calcium canals with the following cytoplasmatic hypercalcemia. It's very destructive for the change in permeability of the membrane of lymphocytes.
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PMID:[The content of Ca2+ and Mg2+ ions and membrane enzyme activity (AP, 5'-NT, ATPases) in the lymphocytes infected in vitro with bovine leukemia virus]. 166 9

Cardiac Na+,K(+)-ATPase, the receptor molecule for digitalis glycosides, have isoforms with different intrinsic affinities for the glycosides. Expression of these isoforms are under developmental and hormonal regulation. Switching in isoforms to those with lower intrinsic affinity may decrease digitalis sensitivity of the heart. In addition to the intrinsic affinity of the cardiac Na+,K(+)-ATPase for the glycoside, increases in the rate of Na+ influx and decreases in extracellular K+ concentrations increase glycoside sensitivity of the heart and also reduces the margin of safety by reducing reserve capacity of the sodium pump. Reserve capacity of the sodium pump is also reduced by pathological conditions or aging, resulting in reduced margin of safety for the glycoside. Events that follow sodium pump inhibition also affect sensitivity of the heart to digitalis toxicity. These are hypercalcemia and magnesium depletion. It is now feasible to predict digitalis sensitivity of the heart, not empirically but based on the understanding of the mechanisms responsible for the positive inotropic and toxic actions of the glycoside.
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PMID:Digitalis sensitivity of Na+,K(+)-ATPase, myocytes and the heart. 184 28

The pathogenesis of familial benign hypercalcemia (FBH) is unknown. Possible explanations for the disorder include a set-point error in parathyroid gland regulation and intrinsic renal hyperreabsorption of calcium. Thus, FBH may involve an alteration in cellular calcium transport, especially in renal and parathyroid cells. A primary mediator of cellular calcium transport is (Ca2+,Mg2+)ATPase. Therefore, we examined in detail the kinetics of (Ca2+,Mg2+)ATPase activity in erythrocyte plasma membranes from 11 patients with FBH from 7 families, 5 patients with untreated primary hyperparathyroidism, and equal numbers of age- and sex-matched normal subjects. (Ca2+,Mg2+)ATPase activity was measured in isolated membranes as a function of free calcium (0.05-300 mumol/L) in the presence or absence of calmodulin (600 nmol/L) and as a function of calmodulin (0-1800 nmol/L). We found no significant differences in calcium- or calmodulin-dependent (Ca2+,Mg2+)ATPase kinetics between patients with FBH or primary hyperparathyroidism and their age- and sex-matched normal subjects. None of the kinetic parameters was correlated with serum calcium or serum PTH values. We postulate that a mechanism other than a global defect in (Ca2+,Mg2+)ATPase activity is responsible for the hypercalcemia in patients with FBH.
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PMID:Kinetics of erythrocyte plasma membrane (Ca2+, Mg2+)ATPase in familial benign hypercalcemia. 252 97

A major unanswered question in central nervous system physiology concerns the mechanism by which cerebrospinal fluid (CSF) Ca2+ homeostasis is maintained in the face of hypo- or hypercalcemia. To address this question, we sought and found a protein of Mr approximately 140,000 in choroid plexus plasma membranes that forms a phosphorylated intermediate with characteristics of a plasma membrane Ca2+-pump. A choroid plexus plasma membrane protein of this molecular weight also bound to a monoclonal antibody prepared against the human erythrocyte plasma membrane Ca2+-Mg2+ ATPase Ca2+-pump. When this monoclonal antibody was used for immunohistochemical localization, the plasma membrane Ca2+-pump was found primarily in the CSF-facing membranes of choroid plexus cells from rats, cats, and man. The localization of a plasma membrane Ca2+-pump in the CSF-facing membranes of the choroid plexus suggests that the choroid plexus, by mechanisms including this pump, may regulate CSF Ca2+ concentrations.
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PMID:Cerebrospinal fluid calcium homeostasis: evidence for a plasma membrane Ca2+-pump in mammalian choroid plexus. 252 46

In freshwater-acclimated American eels (Anguilla rostrata LeSueur), ovine prolactin and grafts of the part of the pituitary gland containing the prolactin cells induced hypercalcemia. The hypercalcemia was associated with increased uptake of calcium from the water (resulting from increased influx and decreased efflux) and with enhanced high-affinity Ca2+-adenosinetriphosphatase (ATPase) activity in the gills, the putative biochemical correlate of the branchial Ca2+ pump. Kinetic analyses of ATPase-mediated Ca2+ transport in plasma membrane vesicles of branchial epithelium provided evidence that prolactin enhanced the maximum velocity of the Ca2+ pump. Prolactin treatments raised plasma cortisol levels slightly but significantly in eels. However, cortisol per se was not hypercalcemic in eels and did not stimulate the branchial Ca2+ pump. We conclude that the hypercalcemic potency of prolactin in fish relates to its stimulatory action on active Ca2+ transport in the gills.
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PMID:Calcitropic actions of prolactin in freshwater North American eel (Anguilla rostrata LeSueur). 252 94

In order to examine the dynamics of ion regulation, osmoregulation, and plasma calcitonin during the parr-smolt transformation (smoltification), blood and gill tissue were collected from yearling coho salmon, Oncorhynchus kisutch, from February to October. Fish were kept in fresh water (FW) throughout this period. In addition, fish were exposed to seawater (SW) at the peak of smoltification in mid-April, and samples from these fish were collected until July. Plasma osmolality, gill Na+,K+-ATPase activity, plasma levels of calcitonin, and free and total calcium and magnesium were measured. SW adaptability of FW fish was assessed throughout the study by measurements of plasma osmolality following a 24-hr exposure to seawater. The greatest hypoosmoregulatory ability occurred in April-May, although SW-adapted fish had higher plasma osmolality than FW-adapted fish at all times. Gill Na+,K+-ATPase activity in FW-adapted fish increased from April to June and increased rapidly following exposure of fish to SW, and remained elevated in SW-adapted fish. Free plasma calcium and magnesium levels increased following SW exposure, but returned to prior levels within 1 week. Netting and confinement stress during sampling caused an increase in plasma osmolality and free calcium and magnesium levels in both FW- and SW-adapted fish. Changes in hypoosmoregulatory ability during smoltification and SW adaptation were correlated with changes in gill Na+,K+-ATPase activity. A sharp transitory peak in plasma calcitonin levels occurred early in smoltification (March) and in SW-adapted fish in June. Plasma calcitonin levels gradually increased in FW-adapted fish during the period of desmoltification. However, no change in plasma calcitonin levels occurred during SW-induced hypercalcemia, suggesting that the hormone does not play a major role in short-term plasma calcium regulation in coho salmon.
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PMID:Smoltification and seawater adaptation in coho salmon (Oncorhynchus kisutch): plasma calcium regulation, osmoregulation, and calcitonin. 254 13

It has been suggested that the parathyroid glands and the kidneys are insensitive to the high extracellular calcium levels found in familial benign hypercalcaemia (FBH) (familial hypocalciuric hypercalcaemia) and that there may be a general disorder of the plasma membrane 'calcium pump'. We have found that the activity of the calcium-stimulated, magnesium-dependent ATPase of erythrocyte ghost membranes from patients with FBH was significantly higher (p less than 0.01) than that from normal subjects. Values in FBH, as a group, were higher than those in primary hyperparathyroidism, but the difference was not significant. We suggest that the membrane abnormality in FBH could be a disorder of the regulation of the calcium pump.
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PMID:Calcium-ATPase activity in erythrocyte ghosts from patients with familial benign hypercalcaemia. 316 Jan 2

Increases in intracellular and mitochondrial calcium content that accompany ischemic and toxic acute renal failure have been suggested to mediate renal tubular cell injury and dysfunction, but the mechanism(s) are unknown. We studied the effects of in vivo vitamin D-induced chronic hypercalcemia on rat renal cortical brush-border and basolateral membranes and mitochondria. In the brush-border membrane, hypercalcemia caused significant decreases in alkaline phosphatase-specific activity, total phospholipid molar content, and phosphatidylserine percent molar composition and increases in the cholesterol-to-total phospholipid molar ratio and phosphatidylinositol percent molar composition. In the basolateral membrane, hypercalcemia caused significant decreases in Na+-K+-ATPase-specific activity and total phospholipid molar content and increases in the cholesterol-to-total phospholipid molar ratio and phosphatidylinositol 4,5-bisphosphate percent molar composition. In the mitochondria, hypercalcemia caused a mild increase in the mitochondrial calcium content, but no alterations in succinic dehydrogenase-specific activity, succinate-, ADP-, or uncoupler-induced respiration. Thus hypercalcemia caused alterations in brush-border and basolateral membrane enzyme activity and lipid composition, but no functional changes were detected in mitochondria. These hypercalcemia-induced plasma membrane biochemical alterations may be markers of early cell injury and suggest a role for calcium in causing or predisposing to renal tubular cell injury.
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PMID:Effects of vitamin D-induced chronic hypercalcemia on rat renal cortical plasma membranes and mitochondria. 381 41


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