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)

A 23-year-old female with extreme hypercalcaemia was treated with calcitonin, mitramycin and parathyroidectomy and normocalcaemia was achieved after 4 weeks. Nevertheless, the patient later died of cutaneous necrosis, impaired circulation and multiple organ failure. Serum immunoreactive parathyroid hormone was in the normal range and parathyroid tissue normal. Mixed connective tissue disease was diagnosed on the basis of high titers of antibody to extractable nuclear antigen, moderately elevated levels of antibody to nuclear antigen and only marginal elevation of anti-double standed DNA. The role of Cl. difficile toxin in the blood and an acinic cell tumour is unclear.
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PMID:Excessive hypercalcaemia and mixed connective tissue disease. 377 2

In an attempt to better define hyperplasia from adenoma and for more accurate discernment of grossly normal but histologically abnormal presumed hyperfunctioning gland, parathyroid tissue obtained at operation was subjected to flow cytometric analysis producing DNA histogram. Seventeen abnormal specimens and seven normal specimens obtained from parathyroidectomy cases were placed in RPMI 1640 culture medium, treated to produce a monodispersed cell suspension, and stained with propidium iodide fluorescent dye to provide a measure of DNA content that could be graphically demonstrated. All cell cycles for affected cell populations could be demonstrated on DNA histogram in the G0G1, S, and G2M phases. Proliferative index was arbitrarily derived by combining percentages of G2M plus S phases. It was apparent that the value so derived showed a tendency for higher value for the abnormal parathyroid tissue but the overlap was sufficient so that no specific discriminating value could be placed on DNA histogram. While flow cytometry may not be of significant use in intraoperative identification of abnormal parathyroid tissue, the values obtained may indicate that a spectrum of activity occurs in hyperparathyroidism that cannot be fully appreciated at the present time and that may in the light of incomplete knowledge manifest itself in the clinical state of hyperparathyroidism and hypercalcemia. The findings of our flow cytometry study may indeed lend credence to the view that all hyperparathyroidism represents a four-gland hyperfunction although this does not support as a consequence routine subtotal parathyroidectomy but should stimulate further inquiry into the pathogenesis of primary hyperparathyroidism.
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PMID:DNA histogram of parathyroid tissue in determining extent of parathyroidectomy. 407 81

We used a sensitive and specific hybridization assay that detects evidence of parathyroid hormone synthesis in tumors to investigate whether this hormone mediates the hypercalcemia of malignant disease. The assay uses radiolabeled, cloned parathyroid hormone DNA to hybridize selectively with parathyroid hormone messenger RNA. We assayed 13 human and 3 animal tumors of diverse cell origins that are frequently associated with the hypercalcemia of cancer. Five of the human tumors were obtained from patients known to be hypercalcemic at the time of tumor excision, two were from normocalcemic patients, and six were from patients with breast cancer whose serum calcium levels were unknown. Messenger RNA was prepared from cultured cell lines or tumors; active RNA fractions were hybridized with either human or bovine cloned parathyroid hormone DNA that had been labeled to a high specific activity with [32P]nucleotide. We were unable to detect parathyroid hormone RNA transcripts in any of the tumors. Our results indicate that parathyroid hormone rarely, if ever, causes hypercalcemia in malignant disease.
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PMID:Absence of parathyroid hormone messenger RNA in nonparathyroid tumors associated with hypercalcemia. 686 67

Inactivating mutations of the parathyroid cell calcium receptor (CaR) gene cause one form of familial benign/hypocalciuric hypercalcemia, and in homozygous form, cause neonatal severe primary hyperparathyroidism with parathyroid hyperplasia. Thus, we postulated that partial or total loss of CaR function might contribute to calcium insensitivity or even stimulate cell proliferation in sporadic parathyroid adenomas (PAds). To examine this possibility, we sought loss of heterozygosity (LOH) for markers flanking the CaR locus (3cen-3q21) in 35 PAds. We used 16 highly-polymorphic PCR-based markers in paired normal and tumor DNA, extracted from slices of archived surgical specimens. Nineteen to 24 of the DNA pairs were informative with at least one marker. In two informative pairs, we found LOH for markers D3S1303, D3S1267, or D3S1269, which are tightly-linked with and flank the CaR locus. In one tumor, deletion mapping confined the lost area between D3S1271 and D3S1238 (41.7 centimorgans, cM). In the other tumor, LOH spanned most of chromosome 3, ranging at least from D3S1307 to D3S1311 (271.4 cM). LOH was confirmed by repetition of the experiments and quantified by phosphorimaging. Thus, we found LOH encompassing the CaR locus in approximately 10% of sporadic PAds. These data are consistent with the hypothesis that loss of CaR function may occur in PAds, with functional consequences for calcium sensitivity and cell proliferation.
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PMID:Genetic abnormalities in sporadic parathyroid adenomas: loss of heterozygosity for chromosome 3q markers flanking the calcium receptor locus. 759 8

To our knowledge, familial occurrence of small-cell carcinoma of the ovary in first-degree relatives has not been described before. We studied two separate cases of small-cell carcinoma in a 21-year-old patient and in her 40-year-old mother, both of whom died of disseminated disease. Both tumors were studied with immunohistochemistry, using a variety of antibodies, and with flow cytometry. Microscopically, the tumor in the daughter was of the usual small-cell type, while that of her mother belonged to a large-cell variety. Immunohistochemically, both tumors showed some degree of epithelial differentiation but also expressed reactivity to some other antigens, most notably to smooth-muscle actin and muscle-specific actin. Both tumors showed a diploid DNA pattern and low S-phase fraction with flow cytometry. Neither of the cases expressed hypercalcemia. Small-cell carcinoma of the ovary may appear as a small-cell or large-cell variety in a familial setting. A diploid DNA pattern appears to be characteristic. Because this tumor was first reported relatively recently, the frequency of its familial occurrence is not known.
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PMID:Familial occurrence of small-cell carcinoma of the ovary. 760 68

Familial hypocalciuric hypercalcemia (FHH) is generally characterized by lifelong hypercalcemia without hypercalciuria and is inherited in an autosomal dominant manner. Affected individuals show abnormal parathyroid and renal responses to changes in the extracellular calcium concentration. A Japanese FHH family was screened for mutations in the Ca(2+)-sensing receptor gene by the polymerase chain reaction and single strand conformation polymorphism. The proband with hypercalcemia showed an abnormal pattern in exon 1 of the gene, whereas her two sisters with normocalcemia showed a normal pattern. The consanguineous parents with borderline serum calcium concentrations showed both patterns. Nucleotide sequence analysis identified a G-->C point mutation at nucleotide 118 that resulted in the conversion of the normal codon for proline into a codon for alanine at amino acid 40 (numbered according to the bovine complementary DNA). The proband was homozygous for the mutation, and the parents were heterozygous. These results imply that this mutation in the human Ca(2+)-sensing receptor gene causes FHH and that the dosage of the gene defect determines disease phenotype.
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PMID:Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene. 767

Parathyroid hormone-related protein (PTHRP) is expressed in a large number of tumors and is the mediator of parathyroid hormone-like effects seen in humoral hypercalcemia of malignancy. The gene coding for PTHRP has been localised to the short arm of chromosome 12. This is at the same region as the oncogene KRAS2, and amplification of KRAS2 has previously been found in human lung cancer. The BEN cell line which is known to express PTHRP was established from a patient who had squamous cell carcinoma of the lung with hypercalcemia. Cytogenetic analysis of the BEN cell line revealed a very complex karyotype with many marker chromosomes. Chromosomal in situ hybridization with biotinylated DNA probes visualized by a biotin-streptavidin-polyalkaline-phosphatase complex was used to analyse two dicentric marker chromosomes containing homogeneously staining regions (hsr) in BEN. The hsr were found to contain amplified PTHRP and KRAS2 at levels of 30-fold and 14-fold per cell, respectively. The higher level of amplification of the PTHRP gene would suggest that PTHRP is the target gene of amplification in the amplicon. This is the first report of gene amplification of PTHRP and in addition its co-amplification with KRAS2.
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PMID:Co-amplification of the gene for parathyroid hormone-related protein (PTHRP) and KRAS2 in a human lung cancer cell line. 769 47

Small cell carcinoma of the ovary is a rare and often lethal tumor, occurring primarily in young women. In as many as two-thirds of reported cases there is an associated paraneoplastic hypercalcemia, the symptoms of which are often what bring the patient to medical attention. This phenomenon also provides a convenient biochemical marker useful for follow-up. The origin of these tumors is unknown. Recent studies using flow cytometry would appear to distinguish these tumors from other ovarian tumors based on their DNA diploid histograms. These tumors have a very poor prognosis, and a proven regimen of adjuvant chemotherapy is yet to be defined. A case of a young woman with small cell carcinoma of the ovary with hypercalcemia, alive, with no evidence of recurrence 5 years after surgery followed by chemotherapy is reported.
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PMID:Small cell carcinoma of the ovary with hypercalcemia: report of a case of survival without recurrence 5 years after surgery and chemotherapy. 770 85

The authors studied DNA content in a case of small cell carcinoma with hypercalcemia. This tumor exhibited typical clinical, histological, immuno-histochemical, ultrastructural and biological patterns. DNA content was measured both by flow and image cytometry performed on unfixed tumoral samples. The proliferation index was 10%. These results are similar to those of the literature obtained retrospectively from 10% formalin fixed tissues. The DNA content is a clue to distinguish this entity from other small cell carcinomas of the ovary because immunohistochemical findings are not always informative. The diagnosis of small cell carcinoma of hypercalcemic type should be questioned if DNA content is abnormal.
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PMID:[Ploidy analysis in a case of ovarian small cell carcinoma with hypercalcemia]. 775 3

Neoplastic angioendotheliosis (NAE) is a rare neoplastic disease, and its pre-mortem diagnosis is extremely difficult. A 49-year-old male developed vertigo, hearing and visual disturbance, transverse myelopathy below Th 5 and hypercalcemia. These symptoms were markedly improved by VEPA chemotherapy. Thirty-four months after onset, diffuse reticular shadows were noted on chest X-ray. The biopsy specimen of the lung revealed intravascular lymphoid cells differentially stained with L26 and LCA. Southern blot analysis of the DNA from the tissue showed rearranged bands for the immunoglobulin gene (JH). A diagnosis of NAE of B-cell nature was established.
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PMID:[Neoplastic angioendotheliosis diagnosed by open lung biopsy]. 778 26


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