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)

Parathyroid hormone-related protein (PTHrP), which is responsible for producing hypercalcemia in patients with humoral hypercalcemia of malignancy, has recently been identified in several normal tissues. Because PTHrP, like parathyroid hormone (PTH), is known to exhibit vasodilatory properties, we investigated the expression and regulation of PTHrP mRNA in cultured rat aortic smooth muscle cells (SMC). We report here that PTHrP mRNA is expressed in SMC and is markedly induced by serum in a time- and concentration-dependent fashion. Addition of 10% fetal calf serum to serum-deprived, confluent cells, resulted in a marked induction of PTHrP mRNA by 2 h with a peak at 4-6 h. PTHrP was detected in SMC by immunocytochemistry and radioimmunoassay of conditioned medium, and was shown to be up-regulated within 24 h after the addition of serum. The serum induction of PTHrP mRNA was blocked by actinomycin D and by cycloheximide indicating the need for protein synthesis to evoke the serum effect on PTHrP gene transcription. In addition, treatment with dexamethasone, which has been previously shown to reduce the constitutive expression of PTHrP in human cancer cells, also blunted the serum induction of PTHrP mRNA in SMC. Treatment of quiescent cells with the serum mitogens platelet-derived growth factor or insulin-like growth factor-I had no effect on PTHrP, whereas the vasoactive peptides endothelin, norepinephrine and thrombin stimulated PTHrP expression. Exogenous addition of recombinant PTHrP-(1-141) had no significant effect on SMC DNA synthesis as measured by [3H]thymidine incorporation. In summary, the abundance of PTHrP mRNA and the characteristics of its regulation in SMC suggest a major role for PTHrP as a local modulator in vascular smooth muscle.
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PMID:Abundant expression of parathyroid hormone-related protein in primary rat aortic smooth muscle cells accompanies serum-induced proliferation. 175 45

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism. However, to our best knowledge, at least 163 cases of functioning parathyroid carcinoma appeared in the English literature from 1981 to 1989. We summarize the available information obtained from the reports of those patients and compare it with previous descriptions of the disease. The etiology of parathyroid carcinoma is usually obscure, but the possibility of a radiation-induced malignant change in the parathyroid gland became evident in a few patients. Clinical manifestations, including age, sex, symptoms, and biochemical findings in this review were comparable to those in previous reviews. Noninvasive localization studies such as ultrasonography may offer a diagnostic clue to parathyroid carcinoma. Measurement of DNA content is a useful adjunct for making the histologic diagnosis of parathyroid carcinoma and prediction of the clinical outcome. Since the initial operation offers the best chance for cure, pre-operative suspicion and intra-operative recognition of the parathyroid cancer are essential. The initial operation should be en bloc resection of the tumor, avoiding rupture of the tumor capsule and spillage of tumor cells. As parathyroid carcinoma is a slow-growing but tenacious malignancy, repeated resection of local recurrent tumors or even distant metastases is effective for palliation of recurrent hypercalcemia and occasional cure. When hypercalcemia is refractory to surgical therapy or no recurrent tumor can be identified, other modalities of therapy must be considered. New drugs to control hypercalcemia by inhibiting bone resorption may hold promise in patients with recurrent parathyroid carcinoma.
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PMID:Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. 176 40

A patient with chronic T-cell leukemia characterized by a suppressor phenotype is reported. A 71-year-old woman presented with symptoms and signs of hypercalcemia. Peripheral blood specimen showed abnormal lymphoid cells with an oval to cleaved nucleus, rather condensed chromatin, occasional prominent nucleolus, and basophilic cytoplasms with vacuoles which seems to be a T-cell counterpart of B-cell chronic lymphocytic leukemia with mixed cell types. The phenotype of these cells was CD4-, CD8+, CD5+, CD6+ with poor expression of CD3, CD7, and CD25. Southern blot analysis of T-cell receptor beta-chain gene revealed one allele rearranged band. The serum antibodies were positive against human T-cell leukemia virus, type I-associated antigens, but monoclonal integration of proviral DNA was not detected in the leukemic cells suggesting that she was just a carrier of this virus. Interestingly, serum PTH-related peptide (PRP) was elevated. The combination therapy with vincristine and prednisolone for leukemia decreased not only the number of leukemic cells but also the serum PRP levels. The clinical course was aggressive. She only responded transiently to treatments, and died of renal failure due to uncontrollable hypercalcemia six weeks after admission.
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PMID:A patient of CD4-/CD8+ chronic T-cell leukemia associated with hypercalcemia. 182 9

One of the strains of the Walker 256 carcinosarcoma induces in the rat a humoral hypercalcaemia of malignancy (HHM) syndrome which is similar to that reported in human patients. We have isolated from this tumour a chromatographic fraction which displays an adenylate cyclase stimulating activity in dog kidney cortical membranes, similar to that of a parathormone (PTH) related protein isolated from various HHM related tumours. In addition, this fraction stimulated initial calcium (Ca) uptake in confluent Madin-Darby canine kidney (MDCK) cell monolayers in a dose-dependent manner. Maximal stimulation of Ca uptake was associated with an enhanced Ca efflux from MDCK cells preloaded with the cation, and with an increased DNA synthesis in these cells. These activities might be involved in development of increased tubular calcium reabsorption in Walker 256 tumour-bearing rats.
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PMID:Co-purification of calcium transport-stimulating and DNA synthesis-stimulating agents with parathormone-like activity isolated from the hypercalcaemic strain of the Walker 256 tumour. 183 87

We have investigated the possibility of mutations in the calcitonin/calcitonin gene related peptide (CGRP) gene in children with Williams syndrome. Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. To test the hypothesis that mutations in the calcitonin/CGRP gene might be responsible for the reduced calcitonin levels, we examined the calcitonin/CGRP gene structure in Williams syndrome children. Analysis of white blood cell DNA by Southern blot hybridizations in 5 individuals did not show any detectable large deletions or rearrangements in the calcitonin/CGRP gene locus. The possibility of small deletions or point mutations within the exon encoding the mature calcitonin hormone is unlikely based on ribonuclease protection assays with patient DNA amplified by the polymerase chain reaction (PCR) technique. These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion.
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PMID:Characterization of the calcitonin/CGRP gene in Williams syndrome. 186 60

The nuclear DNA content of paraffin-embedded parathyroid tumors from 49 patients with proven primary hyperparathyroidism was determined by flow cytometric analysis. The lesions included 14 primary and 11 locally recurrent or metastatic lesions from 16 carcinoma patients, 28 single adenomas from 28 patients, and 15 hyperplastic glands from five patients with familial multiple endocrine neoplasia type 1. No abnormal DNA stemline was found in any of the hyperplastic glands. One (3.6%) of the adenomas was aneuploid. There was no difference in ploidy patterns between the primary and recurrent lesions of the carcinomas and five (31%) of the carcinomas expressed aneuploidy. Four of the five patients with aneuploid carcinoma had recurrences including pulmonary metastases. One of them died of this disease 12 years after the initial operation, and all except one of the others are hypercalcemic even after removal of the successive recurrent or metastatic tumors. Of the 11 patients with diploid carcinoma, four had either local recurrence or pulmonary metastasis. Two of them are living with normocalcemia 3 and 6 years, respectively, after removal of the recurrent tumors and the others are alive with mild hypercalcemia. The remaining seven patients with diploid carcinoma, however, have no recurrence 2 to 5 years after the initial operation. Thus aneuploid parathyroid carcinomas are likely to show more malignant behavior than those with a diploid DNA pattern. All of the patients with adenoma and hyperplasia have been normocalcemic after a mean follow-up interval of 37 months. This study indicates that flow cytometric analysis of nuclear DNA content is a valuable adjunct to histologic examination in the diagnosis of parathyroid carcinoma and the prediction of the clinical outcome.
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PMID:Flow cytometric DNA analysis of parathyroid tumors with special reference to its diagnostic and prognostic value in parathyroid carcinoma. 196 27

In a series of fourteen patients with adult T-cell lymphoma-leukaemia (ATLL) in Brazil the main features were lymphadenopathy, hepatosplenomegaly, hypercalcaemia, and high leucocyte counts, with abnormal lymphoid cells which had irregular nuclei. The series included the youngest patient with ATLL so far (18 months). Analysis with monoclonal antibodies showed a mature T-cell phenotype (CD4+, CD8-). Antibodies to HTLV-I and/or integration of HTLV-I proviral DNA were found in eleven patients. In the other three HTLV-I DNA could not be demonstrated even by means of the polymerase chain reaction; they therefore had HTLV-I-negative ATLL. This report of ATLL in Brazil corroborates serological reports that HTLV-I may be endemic in some parts of that country. Follow-up studies are required to identify precisely the main route of transmission of HTLV-I in South America and the risk factors for the development of ATLL in carriers.
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PMID:Adult T-cell leukaemia/lymphoma in Brazil and its relation to HTLV-I. 167 Nov 54

We report here 10 cases of adult T-cell leukemia/lymphoma (ATL) seen in South Florida between February 1988 and July 1989. All were seropositive for human T-lymphotropic virus type I (HTLV-I) and seronegative for human immunodeficiency virus type 1 (HIV-1). DNA extracted from tumor biopsies/peripheral blood lymphocytes of nine patients was shown by the polymerase chain reaction (PCR) to contain HTLV-I proviral DNA. Blot hybridization of DNA extracted from seven patients with an HTLV-I cDNA probe revealed a monoclonal pattern of proviral integration consistent with a diagnosis of ATL. Eight of the 10 patients were women. Six patients were from Haiti, three from Jamaica, and one from the Bahamas. All patients had very aggressive non-Hodgkin's lymphoma. Two patients presented with sinus and retro-orbital involvement; another had gastric lymphoma that perforated. Nine patients developed hypercalcemia. Eight patients died within 1 year of diagnosis. Two were lost to follow-up. During the course of this study, 66 new cases of non-Hodgkin's lymphoma were diagnosed at this hospital. Ten of these cases were ATL. The prevalence of HTLV-I-related lymphoma in this sample was 15%. Since tissue from all patients was not available for HTLV-I screening, however, it is possible that other cases of ATL went undetected. We conclude from this initial survey that a retroviral etiology should be considered in patients from populations known to be at risk for HTLV-I infection who present with non-Hodgkin's lymphoma.
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PMID:HTLV-I-associated leukemia/lymphoma in south Florida. 199 5

To clarify the mechanism of secondary hyperparathyroidism in chronic renal failure at the parathyroid hormone (PTH) synthesis level, we measured PTH messenger RNA (mRNA) levels in parathyroid glands in a rat model of chronic renal failure. Four weeks after 7/8 nephrectomy, hyperplasia of parathyroid glands was evident and serum PTH levels were elevated. Serum concentration of calcium, inorganic phosphate, and 1,25-dihydroxyvitamin D (1,25(OH)2D) of rats with chronic renal failure were not detectably different from those of sham-operated rats. In chronic renal failure rats, PTH mRNA levels were elevated both per RNA and per DNA of parathyroid cells, suggesting increased PTH mRNA levels per cell. The elevated levels of PTH mRNA were returned to normal levels by achieving supraphysiological concentrations of 1,25(OH)2D3 given i.p. twice at 24 and 48 hours before sacrifice, although this was attended by slight hypercalcemia. A synthetic analogue of vitamin D, 22-oxa-1,25(OH)2D3, also suppressed PTH mRNA to normal levels, but without hypercalcemia. These data suggest that secondary hyperparathyroidism in early chronic renal failure may be due in part to the resistance of parathyroid cells to the physiological concentration of 1,25(OH)2D in circulation on PTH synthesis and that 22-oxa-1,25(OH)2D3 may be useful in the management of secondary hyperparathyroidism of chronic renal failure.
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PMID:Regulation of parathyroid hormone synthesis in chronic renal failure in rats. 206 3

A large previously reported family with hyperparathyroidism has been reinvestigated recently because of the occurrence of multiple ossifying jaw fibromas in two affected members of the third generation similar to the jaw tumors of four of five affected members of the first generation. These maxillary and mandibular tumors can be differentiated from the "brown tumors" of hyperparathyroidism because they can appear and enlarge even though the hypercalcemia is surgically corrected. These tumors are histologically distinct fibroosseous lesions without the giant cells seen in "brown tumors." The parathyroid enlargement was mostly uniglandular, with multiple tumors found occasionally. Studies in DNA linkage were performed within this large family and a similar family in Houston to determine if the gene for this syndrome, termed HRPT2, is linked to DNA markers on chromosome 11, to which the gene for multiple endocrine neoplasia (MEN) type 1 has been linked. (This linkage is supported by our findings in one family with MEN 1 reported here.) Linkage studies were also performed with markers on chromosome 10, to which the genes for MEN 2A and MEN 2B have been linked. Evidence against close linkage with chromosome 10 and chromosome 11 markers suggests that this clinically distinct syndrome is also genetically distinct.
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PMID:Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome. 212 61


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