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)

Adult T cell leukemia (ATL) is associated with human T cell leukemia virus type 1 (HTLV-1) infection, and almost all ATL patients have the complication of hypercalcemia. To understand the mechanism of the high incidence of hypercalcemia in ATL, we studied the expression of a parathyroid hormone-related protein (PTHrP) gene that has been proposed as a causative factor of hypercalcemia in some solid tumors. The polymerase chain reaction coupled with reverse transcription of mRNA was applied to RNA from peripheral blood mononuclear cells. Cells from all 13 ATL patients examined showed abundant expression of the PTHrP gene, while cells from uninfected normal subjects did not. Significant expression of PTHrP gene was also detected in HTLV-1 carriers without any symptoms and in patients with HTLV-1-associated myelopathy or tropical spastic paraparesis. PTHrP mRNA levels correlated with the number of infected cells that were estimated by the integrated HTLV-1 DNA. These results suggest that HTLV-1-infected cells are expressing the PTHrP gene. This concept was further supported by the finding that the HTLV-1 trans-activator, the tax gene product, caused trans-activation of the PTHrP gene promoter linked to the CAT gene. These observations might explain the general expression of the PTHrP gene in ATL patients and the high incidence of hypercalcemia in ATL.
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PMID:Constitutive expression of parathyroid hormone-related protein gene in human T cell leukemia virus type 1 (HTLV-1) carriers and adult T cell leukemia patients that can be trans-activated by HTLV-1 tax gene. 238 34

Despite the increasing awareness of gastrinoma and its lethal peptic ulcer sequelae, the diagnosis is often initially missed or made as a terminal event. The authors screened all patients with peptic ulcer symptoms serious enough to warrant hospital admission or those associated with diarrhea, nephrolithiasis, hypercalcemia, or pituitary abnormality. In a one-year period (1979-1980) nine (of 14 suspected) new gastrinoma patients were identified using a sensitive and specific gastrin radioimmunoassay in combination with provocative tests including IV secretin, calcium, and food. Conventional upper GI series, CAT scan, arteriography, and endoscopy provided no additional information other than to confirm the presence of ulcer disease. Basal plasma gastrin levels were more than 200 pmol L-1 in only three of the nine (normal fasting plasma gastrin levels are less than 25 pmol L-1). Three patients presented with acute ulcer perforation, and the diagnosis of gastrinoma was suspected because of multiple ulcers and pancreatic masses. In three other patients, previous duodenal ulcer surgery had failed. One patient with dyspepsia, high basal plasma gastrin, negative secretin and calcium infusion studies, and a positive meal test was diagnosed as having G-cell hyperplasia; this was confirmed by biopsy and antral gastrin extraction. Antrectomy alone resulted in cure. In all patients tested, a positive calcium infusion or secretin bolus (greater than 100% rise over basal) strongly suggested the diagnosis of gastrinoma, which was confirmed at surgery. In the acute perforations, initial management with omental patch and cimetidine therapy allowed survival of two patients, while emergency total gastrectomy in the third resulted in death due to esophagojejunal leak. Elective patients were treated with cimetidine initially for at least two weeks before total gastrectomy. In this group there were no operative mortalities, and postoperative morbidity was minimal. This series illustrates three important points: (1) careful screening of an ulcer population using gastrin radioimmunoassay and provocative tests has enabled a high yield of gastrinomas while conventional investigations are of minimal values; (2) a high index of suspicion in appropriate cases is necessary; and (3) total gastrectomy performed under elective circumstances is safe and allows the patients to resume a normal and healthy life without the sequelae of aggressive peptic ulceration or daily drug administration.
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PMID:The early diagnosis of gastrinoma. 712 38

The clinical and laboratory data, and histologic, electron microscopic and immunocytochemical findings of a carcinoid tumor of the lung associated with parathyroid hyperplasia and persistent hypercalcemia are described. The carcinoid tumor consists of uniform cuboidal cells with regular round vesicular nuclei and eosinophilic granular cytoplasm. The tumor cells were chromogranin and neuron-specific enolase positive. The CAT scan of the abdomen revealed an adrenal mass, 3 cm in diameter, and an enlarged body in the pancreas. Our patient is still suffering from hypercalcemia and renal colic, despite repeated parathyroid gland removal, and enucleation of the lung mass. Recent parathyroid scintigraphy with Tc revealed an enlarged parathyroid gland. The thoracic CAT scan is normal. We believe that our patient is suffering from multiple endocrine neoplasia type-1 with persistent hypercalcemia due to hyperparathyroidism.
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PMID:Carcinoid tumor of the lung and type-1 multiple endocrine neoplasia associated with persistent hypercalcemia: a case report. 781 97

We report two women presenting with parathyroid cysts. A 20 years old woman presented with goiter and a cystic lesion in the left thyroid lobe was identified on ultrasound examination and CAT scan. The patient had hypercalcemia and elevated PTH levels. The content of the cyst, obtained by needle aspiration, had an extremely high PTH concentration. The patient was operated, removing the cyst and a remaining thymus. Pathological study confirmed the diagnosis of a parathyroid cyst. An 11 years old girl presented with a mass in the left thyroid lobe. An ultrasound examination disclosed the presence of a cystic nodule. The patient was otherwise asymptomatic and laboratory work up was normal. The patient was operated and pathological examination of the surgical piece revealed a parathyroid cyst.
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PMID:[Functioning and non-functioning parathyroid cysts: entities with different origin and clinical characteristics in 2 cases]. 959 97

Prostate cancer cells contain specific receptors (VDR) for la,25-dihydroxyvitamin D (1alpha,25(OH)2D), which is known to inhibit the proliferation and invasiveness of these cells. These findings support the use of 1alph,25(OH)2D for prostate cancer therapy. However, because 1alpha,25(OH)2D can cause hypercalcemia, analogs of 1alpha,25(OH)2D that are less calcemic but which exhibit potent antiproliferative activity would be attractive as therapeutic agents. We studied four vitamin D compounds: 25-hydroxyvitaminD3 [25(OH)D3], which is converted to 1alpha,25(OH)2D3 in prostate cells, and three analogs of 1alpha,25(OH)2D3: EB1089, 19-nor-1alpha,25(OH)2D2 and hexafluoro-1alpha,25(OH)2D3 (F6-1alpha,25(OH)2D3). 19-nor-1alpha,25(OH)2D2 has been shown to be less calcemic than 1alpha,25(OH)2D3 in clinical trials. F6-1alpha,25(OH)2D3 has been shown to be 100-fold more active than 1alpha,25(OH)2D3 and to be longer-lasting in inhibiting keratinocyte proliferation in vitro. EB1089 has been shown to be less calcemic than 1alpha,25(OH)2D3 in rats implanted with Leydig cell tumors. For 25(OH)D3, 19-nor-1alpha,25(OH)2D2 and F6-1alpha,25(OH)2D3, we studied the in vitro effects and compared their activity to 1alpha,25(OH)2D3 on cellular proliferation by 3H-thymidine incorporation assay. In addition, we studied transactivation of the VDR in the presence of 25(OH)D3 and 19-nor-1alpha,25(OH)2D2 in prostate cells. For EB1089, we compared its inhibition of prostate cancer metastasis to that induced by 1alpha,25(OH)2D3 in vivo in the rat Dunning MAT LyLu prostate cancer model. We found that 1alpha,25(OH)2D3 and 19-nor-1alpha,25(OH)2D2 caused similar dose-dependent inhibition in 3H-thymidine incorporation into DNA in prostate cells and behaved similarly in the CAT reporter gene transactivation assay in PC-3/VDR cells. F6-1alpha,25(OH)2D3 is 10- to 50-fold more active than 1alpha,25(OH)2D3 in 3H-thymidine incorporation into DNA in the primary cultured prostate cells. Likewise, 25(OH)D3 had comparable antiproliferative activity to la,25(OH)2D3. In the rat model, tumor volumes and the number of metastases in the lungs were significantly reduced by both 1alpha,25(OH)2D3 (10.4 +/- 2.81 tumor foci) and EB1089 (7.7+/-1.29 tumor foci) compared to controls (22.7 +/- 1.98 tumor foci). Although serum calcium levels were significantly elevated in both 1alph,25(OH)2D3- and EB1089-treated rats, EB1089 was significantly less calcemic than 1alpha,25(OH)2D3 (12.59+/-0.21 mg/dl versus 14.47+/-.46 mg/dL; 1 microg/kg; p < 0.001). In conclusion, our data indicate that 25(OH)D3 and the three 1alpha,25(OH)2D analogs represent two different solutions to the problem of hypercalcemia associated with vitamin D-based prostate cancer therapies: 25(OH)D3 requires the presence of 25-hydroxyvitaminD-1alpha-hydroxylase, whereas 19-nor-1alpha,25(OH)2D2, F6-1alpha,25(OH)2D3 and EB1089 do not. These compounds may be good candidates for human clinical trials in prostate cancer.
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PMID:Evaluation of vitamin D analogs as therapeutic agents for prostate cancer. 1289 29