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/lymphoma is a disseminated malignancy of T lymphocytes infected by the human T-lymphotrophic virus type I. It is endemic in southern Japan, the Caribbean basin, the southeastern United States, and central Africa. The virus is transmitted through intimate contact or exposure to blood products; only a small proportion of those infected develop adult T-cell leukemia/lymphoma. The malignant cells are activated T-helper cells that have suppressor function and multiple cytogenetic abnormalities. The disease occurs in mid to late life, years after exposure to the human T-lymphotrophic virus type I, with hypercalcemia, skin involvement, lymphadenopathy, hepatospenomegaly, lytic bone lesions, and leukemia. Although the disease usually has a rapidly progressive clinical course, there is a spectrum of clinical and pathologic features with smoldering and subacute forms. Our knowledge of this malignancy has grown rapidly and is leading to greater understanding of the relationships between human retroviruses and oncogenes.
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PMID:Pathology and immunology of adult T-cell leukemia/lymphoma. 204 93

The clinical, pathologic, and immunologic features of 78 cases of peripheral/post-thymic T-cell lymphomas are described. These neoplasms were extremely heterogeneous and were classified as small lymphocytic, mixed small and large cell, large cell, lymphoepithelioid cell, angiocentric, and adult T-cell leukemia/lymphoma type. Some cases revealed angioimmunoblastic or Hodgkin's-like features. These neoplasms mainly affected older adults (mean age, 57 years; median age, 60 years). Lymphadenopathy represented the most frequent clinical presentation, although most patients demonstrated both nodal (87%) and extranodal involvement (77%) during the course of disease. Sites of extranodal disease included skin/soft tissue, spleen, lung, liver, bone, gastrointestinal tract, central nervous system, peripheral blood, nasopharynx, and retrovaginal tissue. Splenomegaly at presentation was most frequently observed in lymphoepithelioid cell lymphomas. Angiocentric lymphomas involved lung. A mediastinal presentation was typically observed in young adults and associated with a poor prognosis. Patients with gastrointestinal lymphomas presented with bleeding and/or malabsorption. B symptoms were present in most cases (65%). Hypercalcemia occurred in four patients. Phenotypic studies of T-cell antigens demonstrated the loss of one or more pan-T-cell markers in eight of 47 cases evaluated. Assessment of T-cell subsets revealed a helper/inducer phenotype for nearly all immunoreactive cases. For the overall series, 32 patients died of disease (median survival time, 11.5 mo). There was a statistical difference between the combined groups of small lymphocytic and lymphoepithelioid cell types as compared with mixed and large cell types, with a poorer survival for the latter group. Angiocentric and adult T-cell leukemia/lymphoma were associated with poor survival. This series of T-cell lymphomas further documents the marked heterogeneity of this group of neoplasms as well as the poor prognosis observed for certain histologic types.
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PMID:Peripheral/post-thymic T-cell lymphomas: a spectrum of disease. Clinical, pathologic, and immunologic features of 78 cases. 229 66

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

A 60-year-old man with adult T cell leukemia had been suffering from intractable hypercalcemia resistant to saline hydration, intravenous administration of furosemide, elcatonin, prednisolone and phosphate, and also hemodialysis. Since there was one report suggesting that bleomycin could act as an anticalcemic agent, peplomycin, a new derivative of blerivative of bleomycin, was given at a dose of 10 mg/day by continuous intravenous infusion for 3 days and rapid normalization of serum calcium and creatinine levels resulted. The mechanism of this antihypercalcemic effect is not clear, but peplomycin directly inhibit bone resorption.
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PMID:[Peplomycin for hypercalcemia in a patient with adult T cell leukemia]. 242 35

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

HTLV-I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and HTLV-I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL-1 alpha, IL-1 beta and IL-3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL-1 expression and clinical manifestations. IL-2, IL-4 and GM-CSF mRNA expression was not detected. HTLV-I viral RNA expression was detected only in one case in which IL-3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL-2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV-I expression in peripheral blood fresh leukemic cells except in one unusual case.
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PMID:Expression of cytokine mRNA in leukemic cells from adult T cell leukemia patients. 250 74

Because many patients with adult T-cell leukemia/lymphoma (ATLL) develop hypercalcemia with similar characteristics to those of humoral hypercalcemia of malignancy (HHM) (Arch. Intern. Med., 148: 921-925, 1988), we investigated if ATLL cells produce parathyroid hormone (PTH)-like activity. Conditioned media from cultures of human T-cell lymphotropic virus type I-infected cell line (MT-2) as well as peripheral lymphocytes from a hypercalcemic ATLL patient stimulated cyclic AMP production in osteoblast-like rat osteogenic sarcoma cells (UMR 106) and bone resportion in organ cultures of fetal mouse calvaria. Furthermore, the stimulation of cyclic AMP production by conditioned medium of MT-2 cells was inhibited by human PTH(3-34), indicating that MT-2 cells secrete PTH-like activity. The PTH-like activity from MT-2 cells was chromatographically indistinguishable from the one extracted from a solid tumor causing HHM. The present results along with our previous observation that MT-2 cells constitutively express mRNA for PTH-related protein (Biochem. Biophys. Res. Commun., 154: 1182-1188, 1988) demonstrate that a PTH-like activity is synthesized and secreted by these cells, and are consistent with the hypothesis that elaboration of PTH-like activity by ATLL cells may be the mechanism by which hypercalcemia develops in ATLL patients as well as in solid cancer patients with HHM. However, these results do not rule out the possibility that other factors such as interleukin 1 are also involved and may act in concert with PTH-like activity in the development of hypercalcemia in ATLL.
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PMID:Secretion of parathyroid hormone-like activity from human T-cell lymphotropic virus type I-infected lymphocytes. 254 61

Adult T-cell leukemia-lymphoma, an aggressive T-cell leukemia, is characterized by the presence in the peripheral blood of malignant T cells that have highly indented or lobulated nuclei. Phenotypically the cells are usually helper T cells, but functionally they behave as suppressor cells. Patients have skin and lung involvement, hepatosplenomegaly, moderate lymphadenopathy sparing the mediastinum, and various metabolic abnormalities such as hypercalcemia. The clinical course may be chronic or acute, usually followed by a rapidly progressive terminal course. Adult T-cell leukemia-lymphoma is now known to be caused by human T-cell lymphotropic virus type I, which has been identified in the cells of patients with the disease.
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PMID:Adult T-cell leukemia-lymphoma. 266 14

As part of epidemiologic studies of human T-lymphotropic virus (HTLV)-I-associated malignancies in Jamaica, the authors evaluated 26 patients with non-Hodgkin's lymphoma for the presence of integrated HTLV-I provirus in their malignant cells. Fifteen of 26 patients had integrated provirus. All 15 also were HTLV-I antibody positive. Eleven patients did not have integrated provirus, and all 11 were antibody negative. All of the antibody-positive cases had onset of their disease in adulthood (age range, 21-57 years) as opposed to the broad age range of negative cases (4-66 years). Clinical features which were more common in provirus positive than negative patients included leukemic phase, skin involvement, and hypercalcemia, which are all features frequently seen in HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The presence of skin involvement, circulating malignant cells, abnormal liver function tests, or the presence of two or more of these four features were statistically significantly different between virus-positive and virus-negative cases. Although the survival of positive cases (6 months) was shorter than that of negative cases (9 months), this was not statistically significant. The only significant determinant of survival was hypercalcemia, with those who developed hypercalcemia at some point in their disease course, independent of their HTLV-I status, surviving a mean of 5 months as compared to a mean of 17.5 months in those who never became hypercalcemic. The six HTLV-I-positive lymphomas that underwent cell typing were all primarily OKT4 positive, whereas two HTLV-I antibody-negative cases that were typed were B-cell lymphomas.
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PMID:Molecular epidemiology of HTLV-I-associated non-Hodgkin's lymphomas in Jamaica. 283 Sep 60

The retrovirus-associated adult T-cell leukemia/lymphoma (ATL) has not been previously documented in Taiwan. Five cases identified recently by the authors are reported. Three of the patients were women, and their ages ranged from 36 to 60 years. The most important diagnostic clue was the observation of polylobated lymphoid cells in the peripheral blood. Other variably observed significant features included hypercalcemia, cutaneous eruptions, osteolytic bone lesion, hepatomegaly, and lymphadenopathy. Surface marker studies revealed that the leukemic or lymphoma cells were T-helper cells. Histopathologic examination revealed one case of pleomorphic type and three cases of medium-sized cell type. No tissue was available for study in one case. The diagnosis of ATL was confirmed by the indirect immunofluorescence test on MT-1 cell for antibodies to adult T-cell leukemia virus-associated antigen (ATLA). Three patients were dead within 6 months, and two patients had been in clinical remission for 7 and 10 months, respectively. These two latter cases were similar to the so-called smoldering type of ATL. Two descendents among nine relatives of the patients were also positive for anti-ATLA (22%). Two husbands were negative. Four of the five patients lived in the same county in northeastern coastal Taiwan, which suggested a possible clustering of ATL in that region.
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PMID:Adult T-cell leukemia/lymphoma in Taiwan. A clinicopathologic observation. 286 99


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