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)

1 alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to be a hormonally active form of vitamin D3 in the regulation of intracellular and extracellular calcium levels and of differentiation of myeloid cells and epidermal keratinocytes. We found that 1 alpha,24(R)-dihydroxyvitamin D3 (1,24(OH)2D3), a novel synthetic derivative of vitamin D3, is also active in regulating the differentiation of epidermal keratinocytes. 1,24(OH)2D3 had the same affinity as 1,25(OH)2D3 for a receptor isolated from the epidermis of newborn mice. The incubation of mouse epidermal keratinocytes with 1,24(OH)2D3 induced their differentiation in a time- and dose-dependent manner, as determined by the formation of a cornified envelope and an increase in the activity of transglutaminase. 1,24(OH)2D3 inhibited DNA synthesis of epidermal keratinocytes and also increased their cytosolic calcium level. These effects of 1,24(OH)2D3 were similar to, or rather more than, those of physiologically active 1,25(OH)2D3. However, 1,24(OH)2D3 was found to cause less hypercalcemia than 1,25(OH)2D3 when administrated intravenously to rats, suggesting its possible therapeutic value in psoriasis.
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PMID:1,24(R)-dihydroxyvitamin D3, a novel active form of vitamin D3 with high activity for inducing epidermal differentiation but decreased hypercalcemic activity. 216 63

Parathyroid hormone-related peptide (PTHrp), a polypeptide synthesized by tumors associated with hypercalcemia and known to cause bone resorption, was examined for its effects on bone formation in cultures of 21-day fetal rat calvariae. Continuous treatment with PTHrp for 24-72 h stimulated DNA synthesis, but inhibited [3H] proline incorporation into collagen by about 50%. In contrast, transient exposure to PTHrp at 0.1-1.0 nM for 24 h followed by removal of the factor for 48 h caused an increase in [3H]proline incorporation into collagen and noncollagen protein by 2- and 1.6-fold, respectively. The stimulatory effect was seen in the periosteum-free bone, and was decreased, but not prevented by hydroxyurea. PTHrp at 1-10 nM for 24 h increased medium insulin-like growth factor (IGF) I levels by 2.5-4.4-fold, and the effect was sustained 48 h after the removal of the agent. An IGF I neutralizing antibody prevented the stimulatory effect of PTHrp on bone collagen synthesis. PTH had the same stimulatory effects as those of PTHrp on bone collagen synthesis and IGF I concentrations, although slightly lower doses were needed to observe the enhancement of [3H]proline incorporation into collagen. It is concluded that continuous treatment with PTHrp inhibits, whereas transient treatment stimulates, collagen synthesis; the stimulatory effect appears mediated by an enhancement in the local production of IGF I.
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PMID:Differential effects of continuous and transient treatment with parathyroid hormone related peptide (PTHrp) on bone collagen synthesis. 231 43

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

We analyzed human T cell lymphotrophic virus type I (HTLV-I)-infected T cells for the presence of mRNA coding for parathyroid hormone-related protein (PTHrP) by Northern blotting using synthetic DNA probes. We report here that PTHrP mRNAs were detected in a HTLV-I-infected T cell line, MT-2, but not in uninfected T cell or B cell lines, and that PTH-like bioactivity was detected only in the conditioned medium of MT-2 cells. Our study suggests that the pathophysiology of hypercalcemia in patients with adult T cell leukemia/lymphoma may resemble that which occurs with solid tumors.
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PMID:Expression of parathyroid hormone-related protein in a human T cell lymphotrophic virus type I-infected T cell line. 245 68

The development of high-grade, malignant B-cell lymphoma is a well-recognized complication of human immunodeficiency virus (HIV) infection. Plasma cell neoplasms, however, have been rarely encountered in HIV-infected people. This study presents the morphologic and immunologic features of an unusual plasma cell tumor occurring in a 31-year-old HIV-antibody-positive male. The malignancy was characterized by widespread dissemination and hypercalcemia at presentation and a clinically aggressive course. Immunoperoxidase staining of tumor tissue obtained from biopsy and at autopsy had positive results for IgM and lambda. In the patient's serum, only an IgG kappa paraprotein was detected, indicating that the tumor was nonsecretory. DNA analysis of autopsy-derived tumor tissues demonstrated clonal rearrangements of the immunoglobulin (Ig) heavy chain gene locus and rearrangements in both kappa and lambda light chain gene loci. Furthermore, DNA hybridization studies revealed the presence of Epstein-Barr virus (EBV) genomes in tumor tissue but not in nontumor tissue from this patient.
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PMID:Plasma cell malignancy in the acquired immune deficiency syndrome. Association with Epstein-Barr virus. 254 9

A 60-year-old man born in Okinawa was admitted to our hospital because of epigastralgia. Physical examination revealed general lymphadenopathy, mild hepatomegaly and skin eruption. The peripheral blood leukocyte count was 168,600/microliters, with 93% abnormal lymphocytes showing convoluted or lobulated nuclei. Anti HTLV-1 antibody was positive with titer of 1: 1280 (PA). Leukemic cells had typical ATL cells' surface markers (OKT3; 97.2%, T4; 93.3%, T8; 2.8%, OKIA1; 39.6%, IL-2R; 41.8%) and complete monoclonal HTLV-1 provirus DNA. Endoscopic examination with biopsy revealed massive involvement of ATL cells into gastric mucosa. In the course of the treatment, he had extremely massive melena, and was saved by emergency operation. Multiple ulcers were found in the resected colon. Histological examination showed the marked infiltration of the ATL cells into the mucous or submucous membrane. Thereafter, he was treated well with ALG (Anti Lymphocyte Globulin), until hypercalcemia occurred. He died of acute renal failure after hypercalcemia.
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PMID:[Adult T-cell leukemia with massive melena due to marked gastrointestinal involvement]. 259 52

It has been generally believed that reverse triiodothyronine (reverse T3, rT3) is biologically inactive. Nevertheless the serum rT3 level is very high in fetal life, when the serum calcium level is higher than in the maternal. For this hypercalcemia in fetal life, there is no convincing evidence that any major calcium regulating hormone is responsible. And the assumption that rT3 may be concerned in active transport of calcium at placenta could be suggested. In this study nuclear protein was isolated from human placenta by extraction with 0.4M KCl buffer and binding studies utilizing radioactive rT3 were carried out. Scatchard analysis presented a curvilinear pattern, suggesting two classes of receptors: One with a association constant (Ka) of 1.14 X 10(8) M-1 and a limited capacity (Bmax) of 32.0 X 10(-15) mol/100 micrograms DNA and the other with Ka = 4.34 X 10(6) and Bmax = 454 X 10(-15). Its relative affinities for several thyroid hormone analogues were calculated. If the affinity for rT3 was assigned l, that for triiodothyronine would be 1/40, thyroxine: 1/63, Triiodothyroacetic acid: 1/18. Sulfhydryl agents affecting these binding characteristics were also studied. The Ka was not substantially changed but the Bmax was notably decreased by dithiothreitol (43%) and 2-mercaptoethanol (26%). In liver nuclei, the binding characteristics of rT3 receptor were analyzed for comparison. In this case only a single class of low affinity-high capacity rT3 binding site with a Ka of 6.69 X 10(6) was detected, a finding which was apparently different from those in placenta.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nuclear binding sites for reverse triiodothyronine in human placenta. 262 41

We investigated the growth of hyperplastic parathyroid glands removed at operation from 16 patients with chronic renal failure complicated by hypercalcemia, by incubating fresh tissue with tritiated thymidine. In each gland the proportion of cells synthesizing DNA was determined directly by counting labeled nuclei after autoradiography and indirectly from incorporation of label into DNA, and the mean diameter of chief cell nuclei was measured. Both DNA synthesis and mean nuclear diameter were positively correlated with plasma calcium level. Assuming the mean duration of S phase to be 12 hours, the birthrate of new cells (mean +/- SD) was 18.5% +/- 23.6% per year, significantly (p less than 0.05) greater than the 11.5% +/- 7.4% per year found in 63 parathyroid adenomas previously studied. On the basis of estimated disease duration, the minimum birthrate needed to grow glands of the observed weight was 23.4% +/- 16.5% per year. The similarity between observed and needed birthrates indicates that the glands were growing almost as fast as when renal failure began, and that parathyroid growth was no longer regulated in accordance with normal plasma calcium homeostasis. To account for this, we propose that the disordered growth is a consequence of an increase in secretory set point, which in turn is a consequence of calcitriol deficiency. Because the effectiveness of parathyroid hormone is impaired in renal failure, a large increase in total hormone secretion is needed to raise the plasma calcium level to the new set point, and the necessary increase in gland size can be achieved only by a sustained increase in the rate of cell division.
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PMID:The parathyroid glands in chronic renal failure: a study of their growth and other properties made on the basis of findings in patients with hypercalcemia. 267 97

Proteins with biochemical function and sequence similarity to PTH are produced by many tumors associated with hypercalcemia and may have a role in pathological bone remodeling. Synthetic polypeptides comprising the amino-terminus of human PTH-related protein (PTH-rp) were examined for effects in intact fetal rat calvariae, and in osteoblast-enriched (ob) cultures isolated from fetal rat parietal bone. In cultured calvariae, 0.5-5 nM PTH-rp stimulated [3H]thymidine incorporation into DNA by 25-70% after 24 h of treatment and decreased relative [3H]proline incorporation into collagen by 50%; the inhibitory effect on collagen production was not altered by hydroxyurea, which decreased DNA synthesis by 85%. PTH-rp also increased [3H]hydroxyproline levels by 100% in culture medium from bones prelabeled with [3H]proline, indicating accelerated matrix turnover. In contrast to results in intact calvariae, PTH-rp had little effect on basal DNA and collagen synthesis in serum-deprived ob cultures. However, when ob cultures were treated with transforming growth factor type beta at concentrations similar to those found in calvarial culture medium, 0.02-2 nM PTH-rp enhanced DNA synthesis and decreased collagen production. Furthermore, equimolar PTH-rp and PTH concentrations similarly displaced 125I-PTH-rp binding and enhanced cAMP synthesis in ob cultures. These studies suggest that PTH-rp regulates osteoblastic cell activity primarily through PTH-related pathways and may act in part by modulating the effects of locally produced transforming growth factor-beta in bone.
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PMID:Parathyroid hormone-related protein modulates the effect of transforming growth factor-beta on deoxyribonucleic acid and collagen synthesis in fetal rat bone cells. 273 43

A rat Leydig cell tumor cDNA library was screened with a 32P-labeled genomic restriction fragment encoding human PTH-like peptide (hPLP), and three cDNA clones were isolated. The largest cDNA insert contained 1146 nucleotides. The cloned cDNA encodes a 177-amino acid protein consisting of a predicted 36-amino acid leader sequence and a 141-amino acid mature peptide in which 9 of 13 amino-terminal residues are identical to rat PTH (rPTH). Comparison of rPLP with hPLP reveals marked conservation of both the nucleotide and amino acid sequences through the prepro, amino-terminal, and midregion portions of the molecules. There is also striking conservation of the 3' noncoding regions of rPLP and hPLP mRNAs, both of which contain AU-rich repeated sequences that may affect mRNA stability. A single species of mRNA of approximately 1.4-kilobases was identified in the rat Leydig cell tumor and in normal rat stomach. Southern blot analysis is consistent with the presence of a single copy of the rPLP gene per haploid genome, and there is no major rearrangement or amplification of the rPLP gene in DNA isolated from the tumor per se. The results demonstrate the presence of a single gene transcript in a rat model of malignancy associated with hypercalcemia which encodes a peptide homologous to hPLP, document the marked interspecies sequence conservation that exists in major functional domains of the mRNAs and peptides, and show the expression of mRNA encoding rPLP in normal stomach as well as in neoplastic rat tissue.
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PMID:Rat parathyroid hormone-like peptide: comparison with the human homologue and expression in malignant and normal tissue. 274 58


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