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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alteration in calcium metabolism in rats ingested with saline was investigated. Rats were freely given saline as drinking water for 2 and 7 days. Calcium concentration in the serum was significantly elevated by saline ingestion for 2 and 7 days, while serum inorganic phosphorus concentration was not altered. Serum urea nitrogen concentration was significantly increased by saline ingestion for 7 days. Calcium content in the femoral-diaphyseal and metaphyseal tissues was not altered by saline ingestion for 7 days. Calcium content in the kidney cortex was significantly elevated by saline ingestion for 7 days. Ca2+-ATPase activity in the basolsateral membranes of kidney cortex was clearly increased by saline ingestion for 2 and 7 days. The enzyme activity was not altered by the addition of sodium chloride (10(-3) and 10(-2) M), parathyroid hormone (10(-7) and 10(-6) M), and calcitonin (3 x 10(-8) and 3 x 10(-7) M) in the enzyme reaction mixture. A calcium-binding protein regucalcin mRNA expression in the kidney cortex was markedly suppressed by saline ingestion for 7 days, although such a suppression was not seen for 2 days. These results suggest that saline ingestion causes the disturbance of calcium transport system in the kidney cortex of rats, and that the renal disorder may induce hypercalcemia.
Mol Cell Biochem 1997 May
PMID:Alterations in Ca2+-ATPase activity and calcium-binding protein regucalcin mRNA expression in the kidney cortex of rats with saline ingestion. 914 14

Cachexia consists of a constellation of metabolic changes that occur in cancer patients, including the reduction of muscle and fat tissue, asthenia, anorexia, hypoglycemia and hypercalcemia. These syndromes complicate therapeutic intervention and decrease the quality of life of the patient. This review discusses the involvement of cytokines in cancer cachexia and describes the contribution of IL-6 and other cytokines to the wasting of C-26-bearing mice. The neutralization of IL-6 by antibody, or IL-6 receptor antagonism by suramin, significantly reduce the severity of key parameters of cachexia. The participation of several other factors (PGE2, IL-1, IL-10 and TNF-alpha) in the cellular communication between the C-26 tumor cell and tumor-infiltrating macrophages is also described.
Cytokines Mol Ther 1995 Jun
PMID:Inhibition of experimental cancer cachexia by anti-cytokine and anti-cytokine-receptor therapy. 938 67

1. The exact role of the parathyroid hormone-related peptide (PTHrP) is not fully understood. We used immunohistochemistry to localize the PTHrP and its receptor in the brain of the red stingray, particularly in the saccus vasculosus (SV) and choroid plexus. 2. Immunoreactive PTHrP and its receptor were detected in the epithelial cells of the SV and the choroid plexus. In addition, the neuronal perikarya in the nucleus of the SV located in the hypothalamus is positive for the PTHrP. 3. No PTHrP-containing neurons were detected in the choroid plexus. Extracts of SV and choroid plexus showed positive reactions against the PTHrP and its receptor antibody in Western blot analysis. 4. High levels of immunoreactive PTHrP were detected in the plasma equivalent to those present in human humoral malignant hypercalcemia. In contrast, the immunoreactive PTHrP concentration in the cerebrospinal fluid was below detectable levels. 5. Our results suggest that the regulation of the PTHrP in the SV differs from that in the choroid plexus in the red stingray.
Cell Mol Neurobiol 1998 Jun
PMID:Distribution of the parathyroid hormone-related peptide and its receptor in the saccus vasculosus and choroid plexus in the red stingray (Dasyatis akajei: Elasmobranch). 959 May 65

The Ca2+-sensing receptor (CaR) is a member of the seven-transmembrane domain, G-protein-coupled receptor superfamily. It is expressed in parathyroid, kidney, and other tissues. In parathyroid, activation of the CaR by extracellular Ca2+ negatively regulates the secretion of parathyroid hormone. In the the thick ascending limb of Henle's loop, receptor activation decreases renal reabsorption of Ca2+. Heterozygous inactivating mutations of the CaR cause familial benign hypocalciuric hypercalcemia while homozygous inactivating mutations cause neonatal severe hyperparathyroidism. Conversely, activating mutations of the CaR cause autosomal dominant and sporadic hypoparathyroidism. Affected individuals have hypocalcemia which ranges from mild and asymptomatic to life-threatening. They also show a greater tendency to hypercalciuria than do other patients with hypoparathyroidism. Most, but not all, of the reported activating mutations occur in the amino-terminal, extracellular domain of the receptor. When expressed in cultured cells, mutant receptors can show both increased receptor sensitivity to Ca2+ and increased maximal signal transduction capacity.
Mol Genet Metab 1998 Jul
PMID:Activating mutations of the Ca2+-sensing receptor. 971 29

We report the histological and biological behavior characteristics of a lung tumor (P07) that arose spontaneously in a Balb/c mouse. P07 is a moderately to poorly differentiated adenocarcinoma that secretes granulocyte-macrophage colony stimulating factor (GM-CSF) in culture supernatants. This tumor presents some paraneoplastic syndromes, such as leukocytosis, hypercalcemia and cachexia. taken together with the peripheral blood leukocyte (PBL) counts and serum calcium levels during s.c. tumor growth and after surgery, this study suggests that P07 may be a useful experimental model to study the biology of lung cancer and paraneoplastic syndromes.
Int J Mol Med 1998 Jul
PMID:Spontaneous murine lung adenocarcinoma (P07): A new experimental model to study paraneoplastic syndromes of lung cancer. 985 41

The extracellular calcium-sensing receptor (CaR) originally cloned from bovine parathyroid gland is a G protein-coupled receptor. The physiological relevance of the cloned CaR for sensing and regulating the extracellular calcium concentration has been established by identifying hyper- and hypocalcemic disorders resulting from inactivating and activating mutations, respectively, in the CaR. The cloned CaR has been stably or transiently expressed in human embryonic kidney cells and significant progress has been made in elucidating its biochemical and functional features using physiological, biochemical and molecular biological methods. A large collection of naturally occurring CaR mutations offers a valuable resource for studies aimed at understanding the structure-function relationships of the receptor, including receptor-receptor interactions. In turn, characterization of these naturally occurring mutations has clarified the pathogenesis of clinical conditions involving abnormalities in the CaR, such as familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, and the physiology of certain cell types, such as keratinocytes.
Int J Mol Med 1999 Aug
PMID:Structure and function of the extracellular calcium-sensing receptor (Review). 1040 76

Anaplastic carcinoma of thyroid is uncommon and is associated with a poor prognosis. an effective treatment of this carcinoma has not been found. We have examined the inhibition of promotion by 1, 25(OH)2D3 and its analogue without hypercalcemia, 22-oxacalcitriol (OCT) in the thyroid anaplastic carcinoma cell line. TTA-1, thyroid anaplastic carcinoma cell line, and TAC-1, thyroid anaplastic carcinoma cells. TPC-1,2,3,4, which are all papillary carcinoma of thyroid were used as control. Tumor growth was measured by MTT assay. 1,25(OH)2D3 additive cell growth was observed in diphasic pattern in 3/4 papillary carcinoma cell lines. OCT was more effective, showing dose-dependent inhibition of cell growth in anaplastic carcinoma cell lines, than that in papillary carcinoma cells. Conclusively, OCT might be useful for the inhibition of growth in anaplastic thyroid cancer.
Int J Mol Med 1999 Dec
PMID:Antineoplastic activity of 1,25(OH)2D3 and its analogue 22-oxacalcitriol against human anaplastic thyroid carcinoma cell lines in vitro. 1056 71

Serum calcium is under tight physiological control, but it is also a quantitative trait with substantial genetic regulation. Mutations of the CASR gene cause familial hypocalciuric hypercalcemia or autosomal dominant hypoparathyroidism, depending on whether they decrease or increase, respectively, ligand binding to the receptor protein. We described an association between ionized calcium and a common polymorphism (A986S) found in the cytoplasmic tail of this G protein-coupled receptor. We report here on an independent study of 387 healthy young women. Genotyping was performed by allele-specific amplification and serum chemistries were measured by automated clinical assay. Frequencies of SS, AS, and AA genotypes were 6, 107, and 274, respectively, yielding a 986S allele frequency of 15.4%. Mean total serum calcium (Ca(T)) was significantly higher in the SS (9.88 +/- 0.29 mg/dL, P = 0.015) and AS groups (9.45 +/- 0.05 mg/dL, P = 0.002), than in the AA group (9.23 +/- 0.04 mg/dL). In multiple regression modeling, the A986S genotype remained an independently significant predictor of Ca(T) (P < 0.0001) when serum albumin, globulin, inorganic phosphate, and creatinine covariates were included. These data are the first to show significant association between a common polymorphism and concentrations of a serum electrolyte. The A986S polymorphism is also a potential predisposing factor in disorders of bone and mineral metabolism.
Mol Genet Metab 2001 Feb
PMID:Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene. 1116 43

Vitamin D, parathyroid hormone (PTH), and parathyroid hormone-related peptide (PTHrP) are major regulators of calcium metabolism and vitamin D can also reduce the growth of normal cells and tumor cells. PTHrP and PTH act via a common membrane receptor (PTHR). The mouse PTHR is regulated by a kidney-selective upstream promoter P(1) and ubiquitous downstream promoter P(2). In vitro and in vivo 1,25(OH)(2)D can inhibit PTHR expression in bone but not cartilage by downregulating transcription via P(2). Gene transcription of PTHrP per se can also be downregulated by 1,25(OH)(2)D and by low calcemic vitamin D analogs. This inhibitory effect may reduce the hypercalcemia caused by overproduction of PTHrP by tumor cells. In a malignant keratinoctye cell line, phosphorylation of the retinoid X receptor alpha occurs through the activated Ras-MAP kinase pathway and results in attenuated trans-activation by the vitamin D receptor, its heterodimeric partner. This decreases the growth-inhibitory efficacy of 1,25(OH)(2)D. Studies of the capacity of vitamin D to alter PTHrP production and action and of its anti-proliferative effects can, therefore, shed important light on basic mechanisms controlling these events, and may also have major implications for clinical medicine and therapeutics.
J Steroid Biochem Mol Biol
PMID:Studies of the effects of 1,25-dihydroxyvitamin D on skeletal and calcium homeostasis and on inhibition of tumor cell growth. 1138 62

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disease characterized by mild hypercalcemia, an inappropriately high parathyroid hormone level, and absence of hypercalciuria. Heterozygous inactivating mutations of calcium-sensing receptor (CaSR) are found in about two thirds of patients with FHH. Histologic examination of parathyroid glands in FHH is reported to show normal histology or chief cell hyperplasia. Thus, histologic features of the parathyroid glands in FHH vary, and there is no clear histologic criterion that indicates FHH. The authors have encountered three hypercalcemic patients with characteristic histologic features of enlarged parathyroid glands. Clusters of parenchymal cells were mixed with fat cells, and the area of fat cells was 33% to 49% of the total area. These features are similar to those described as parathyroid lipohyperplasia. Postoperative evaluation showed that fractional excretion of calcium was low in these patients. Direct sequencing of the polymerase chain reaction product showed that the first patient was heterozygous for an already reported inactivating mutation of CaSR (P55L). The second patient was also heterozygous for a novel inactivating mutation (R220W). The third was homozygous for an inactivating mutation (Q27R). These results indicate that histologic features of parathyroid lipohyperplasia suggest the presence of inactivating mutations of CaSR.
Diagn Mol Pathol 2001 Dec
PMID:Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia. 1176 15


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