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)

The present work is based on the results of in vivo experiments on rats, which had shown that hypercalcemia had led to morphological and biochemical hyperfunction of thyroid follicular cells. The regulation of the activity of follicular cells should directly, or indirectly via paracrine action of serotonin secreted from parafollicular cells, depend on the presence of calcium ions. The effect of calcium was studied on a cell line of rat follicular cells FRTL-5 (Fischer Rat Thyroid cells in Low serum) using three methods: measuring the quantity of produced cAMP (cyclic adenosine 3',5'-monophosphate), measuring [3H]thymidine incorporation into cell DNA and transmission electron microscopy. Results show that calcium has no effect on cAMP production. Calcium at 1.3 mM, 3 mM, 10 mM, 20 mM and 30 mM concentrations increases [3H]thymidine incorporation into cell DNA when compared with controls without calcium. Calcium at the concentration of 30 mM has no effect on FRTL-5 cell morphology. TSH (thyrotropin) stimulates follicular cells; at higher extracellular concentrations (3 mM, 10 mM, 20 mM, 30 mM), calcium diminishes its effect, presumably by activation of a cAMP phosphodiesterase which disintegrates cAMP and/or by inhibition of adenyl cyclase.
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PMID:The influence of calcium on thyroid follicular cells FRTL-5 in vitro. 1073 Aug 56

Adult T-cell leukemia/lymphoma(ATL) was first discovered and reported in Japan, where it has a high incidence in the southwestern region of the country. The retrovirus human T-cell leukemia virus type I(HTLV-I) is considered to be related to its etiology. ATL shows divers clinical features. It can be divided into four types of smoldering, chronic, acute, and lymphoma. ATL cells originate from the CD4-positive subset of peripheral T cells showing a characteristic notch in the nucleus and a tendency for lobulation. A definit diagnosis of ATL is made by documenting the presence of HTLV-I proviral DNA in the DNA of leukemic or lymphoma cells. Crinico-Pathological aspects of ATL are more complexed than other types of lymphoma because of the verity of the disease type, state of immunodeficiency, hypercalcemia, cytokine activation, and so on.
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PMID:[Clinico-pathological aspects of adult T-cell leukemia/lymphoma(ATL)]. 1074 Nov 41

Breast cancer has a prodigious capacity to metastasize to bone. In women with advanced breast cancer and bone metastases, bisphosphonates reduce the incidence of hypercalcaemia and skeletal morbidity. Recent clinical findings suggest that some bisphosphonates reduce the tumour burden in bone with a consequent increase in survival, raising the possibility that bisphosphonates may have a direct effect on breast cancer cells. We have investigated the in vitro effects of bisphosphonates zoledronate, pamidronate, clodronate and EB 1053 on growth, viability and induction of apoptosis in three human breast cancer cell lines (MDA-MB-231, Hs 578T and MCF-7). Cell growth was monitored by crystal violet dye assay, and cell viability was quantitated by MTS dye reduction. Induction of apoptosis was determined by identification of morphological features of apoptosis using time-lapse videomicroscopy, identifying morphological changes in nucleis using Hoechst staining, quantitation of DNA fragmentation, level of expression of bcl-2 and bax proteins and identification of the proteolytic cleavage of Poly (ADP)-ribose polymerase (PARP). All four bisphosphonates significantly reduced cell viability in all three cell lines. Zoledronate was the most potent bisphosphonate with IC50 values of 15, 20 and 3 microM respectively in MDA-MB-231, MCF-7 and Hs 578T cells. Corresponding values for pamidronate were 40, 35 and 25 microM, whereas clodronate and EB 1053 were more than two orders of magnitude less potent. An increase in the proportion of cells having morphological features characteristic of apoptosis, characteristic apoptotic changes in the nucleus, time-dependent increase in the percentage of fragmented chromosomal DNA, down-regulation in bcl-2 protein and proteolytic cleavage of PARP, all indicate that bisphosphonates have direct anti-tumour effects on human breast cancer cells.
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PMID:Bisphosphonates induce apoptosis in human breast cancer cell lines. 1078 May 27

We experienced a case of adult T cell leukemia/lymphoma (ATLL) in a 48-year-old Korean female, who has never been abroad since birth and no history of blood transfusion. The patient had hypercalcemia and multiple lymphadenopathy. Histopathologic study of left cervical lymph node (LN) and bone marrow (BM) revealed that infiltrates of malignant lymphoid cells were composed of small, medium and large cells with pleomorphic nuclei. Smears of peripheral blood (PB) showed lymphopenia (16%) with the appearance of a few atypical lymphoid cells (less than 2%), but not the typical clover leaf cells seen in ATLL. Immunophenotypic study of LN and BM revealed T cell phenotype. PB showed increased CD4+ T cell (T(H), CD3/CD4+, 57%) and decreased CD8+ T cell counts (T(S), CD3/CD8+, 6.7%). The sera of the patient and her family were reactive for HTLV-I antibody. The specific sequences of pol, env, and tax of HTLV-I DNA were detected in the lymphoma cells and peripheral blood mononuclear cells (PBMC) using polymerase chain reaction. Ultrastructural examination of PBMC confirmed numerous type c virus particles in extracellular space. This case was an acute type of ATLL without overt leukemic features in PB. Despite chemotherapy and intensive conservative treatment, she died 3 months after admission.
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PMID:Adult T cell leukemia/lymphoma with lymphopenia in a Korean. 1080 4

We screened three unrelated Danish families with familial hypocalciuric hypercalcemia (FHH) for mutations in the Ca2+-sensing receptor (CASR) gene by polymerase chain reaction amplification and DNA sequencing of exons 2-7, which include the entire coding region of the gene. In one family the affected individuals have a T-->C mutation that changes the normal arginine at codon 220 to a tryptophan. In the other two FHH families, affected individuals have the same A-->G mutation, leading to conversion of the normal glycine at codon 552 to an arginine. These results confirm that FHH can be caused by non-conservative missense mutations in the CASR gene leading to abnormal calcium homeostasis. Both mutations are located in the amino-terminal extracellular domain of the receptor, which contains the binding site for extracellular Ca2+, the CASR's principal physiological agonist.
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PMID:Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism associated with mutations in the human Ca2+-sensing receptor gene in three Danish families. 1088 94

A complementary DNA (cDNA) encoding the rat homologue of receptor activator of NF-kappaB ligand/osteoprotegerin ligand/osteoclast differentiation factor/tumor necrosis factor (TNF)-related activation-induced cytokine (RANKL/OPGL/ODF/TRANCE) was cloned and sequenced from tibias of ovariectomized (OVX) rats. The predicted amino acid sequence of rat RANKL (rRANKL) has 84% and 96% identity to that of human and mouse RANKL, respectively, and 35% and 37% similarity to that of human and mouse TNF-related apoptosis-inducing ligand (TRAIL), respectively. RANKL transcripts were expressed abundantly in the thymus and bone tissues of OVX rats. rRANKL has a single hydrophobic region between residues 53 and 69, which is most likely to serve as a transmembrane domain. The long C-terminal region containing beta-sheet-forming sequences of the TNF-like core is considered the extracellular region. Three truncated domains within the TNF-like core region were expressed as glutathione S-transferase (GST) fusion proteins and investigated for their ability to induce osteoclastogenesis. The results showed that GST-rRANKL (aa160-318) containing the full TNF-like core region had the highest capability to induce the formation of osteoclast-like cells from RAW264.7 cells. GST-rRANKL (aa239-318 and aa160-268) had lesser degrees of osteoclast inductivity. Furthermore, the GST-rRANKL (aa160-318) is capable of (1) inducing osteoclast formation from rat spleen cells in the presence of macrophage colony-stimulating factor (M-CSF), (2) stimulating mature rat osteoclast polarization and bone resorption ex vivo, and (3) inducing systemic hypercalcemia in vivo; thus the full TNF-like core region of rRANKL is an important regulator of calcium homeostasis and osteoclastic function.
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PMID:Cloning, sequencing, and functional characterization of the rat homologue of receptor activator of NF-kappaB ligand. 1109 98

A 44-year-old female with familial hypocalciuric hypercalcemia (FHH) due to a homozygous missense mutation (Pro40Ala) in calcium sensing receptor (CaSR) gene has type 2 diabetes mellitus. The identical heterozygous mutation of CaSR gene was observed in consanguineous parents and all other family members examined except her two sisters. Many subjects with abnormal glucose tolerance were observed in this family, which is compatible with maternal inheritance. Mitochondrial function of complex I (NADH-coenzyme Q reductase) activity in cybrid cells between mitochondrial DNA (mtDNA)-deleted (rho(0)) HeLa cells and mtDNA from the proband was decreased by 35%. The proband has eight substitutions and among these 4833 A/G is a missense substitution in NADH dehydrogenase 2 gene and may probably be a major pathogenic mutation of impaired complex I activity. These results suggest that coexistence of nuclear gene and mtDNA mutations may have caused or modified the development of abnormal glucose tolerance in this family.
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PMID:A patient with type 2 diabetes mellitus associated with mutations in calcium sensing receptor gene and mitochondrial DNA. 1109 89

Hypercalcemia is associated with numerous chronic granulomatous processes and chronic infections. Increased production of calcitriol by activated macrophages has been shown to be the cause in most cases. In this article, we describe three cases of hypercalcemia associated with inappropriately elevated calcitriol levels and suppressed PTH in hemodialysis. In addition to conventional techniques for tuberculosis diagnosis we used Ligase Chain Reaction (LCR) to detect mycobacterial DNA in pleural effusion with acid-fast stain and culture negativity. Antituberculous therapy was associated with a decrease in the levels of calcium, as well as in serum calcitriol concentrations, and a substantial increase in the levels of iPTH. The serum levels of 25(OH)D3 remained unchanged. These findings suggested ectopic production of calcitriol. The discussion reviews the previously reported cases of hypercalcemia and tuberculosis that occurred during hemodialysis, and concludes that ectopic production of calcitriol by tuberculous granulomas is extremely unusual and its demonstration requires a high index of suspicion. Molecular techniques are a potentially useful approach for early and rapid diagnosis of tuberculous infection in dialysis patients.
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PMID:[Association of hypercalcemia, elevated levels of calcitriol and tuberculosis in patients on hemodialysis]. 1110 Jun 67

Primary hyperparathyroidism is the third most frequent endocrine disorder. The condition required for diagnosis is inappropriately elevated secretion of parathyroid hormone (PTH) with respect to calcemia. Most often, the disease is due to a parathyroid adenoma, i.e. a monoclonal benign parathyroid tumor, less often to a parathyroid hyperplasia. The main tumorogenic mechanisms currently proposed are a DNA rearrangement in the PTH locus (transposition of the PTH promoter upstream to Cyclin D1/PRAD 1 gene) and a mutation of the gene responsible for multiple endocrine neoplasia type I. The clinical presentation has strikingly evolved towards a milder, asymptomatic form, frequently diagnosed on systematic screenings. Though the mechanism of hypercalcemia is better understood, several hypothesis are still being considered about the regulation of tumoral PTH secretion: the role of the expression of calcium-receptor in parathyroid gland cells, vitamin D receptor and estrogen receptor polymorphisms, etc. Surgery is still advised for symptomatic forms of the disease, either because of a bone involvement, or because of an evolutive nephrolithiasis. In the near future, the new calcium-receptor agonists could be a relevant therapeutic approach.
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PMID:[Primary hyperparathyroidism]. 1111 7

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder characterized by high penetrance of relatively benign, lifelong persistent hypercalcemia and hypocalciuria. By contrast, neonatal severe hyperparathyroidism represents a life-threatening form of hypercalcemia that can cause the early newborn mortality if immediate intervention is not undertaken. Both disorders are due to inactivation mutation of the human calcium-sensing receptor (CaSR) gene on chromosome 3q21-24. Up to now, more than 30 mutations in the CaSR gene associated with FHH have been described. In this study, we analyzed one 79-yr-old male with hypocalciuric hypercalcemia without siblings or children to compare with an additional group of 50 normal Chinese subjects in Taiwan. DNA sequence analysis of the CaSR gene was performed. The result showed that the proband had a heterozygous nonsense mutation in exon 7 of the CaSR gene at codon 648 (CGA-->TGA/Arg-->Ter). This mutation, located in the COOH-terminal of the first intracellular loop of the CaSR, predicts a markedly truncated protein. We have identified a novel R648X mutation in the CaSR gene in one patient with FHH in Taiwan
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PMID:A novel mutation in the calcium-sensing receptor gene in a Chinese subject with persistent hypercalcemia and hypocalciuria. 1123 70


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