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)

Four analogues of vitamin D3 with an oxygen atom in the side chain skeleton were synthesized to determine whether their differentiation-inducing activity could be separated structurally from their activity to induce hypercalcemia. The order of the in vitro potency to reduce nitroblue tetrazolium in human myeloid leukemia cells (HL-60) was 22-oxa-1 alpha, 25-(OH)2D3 greater than 1 alpha, 25-(OH)2D3 greater than 20-oxa-1 alpha, 25-(OH)2D3 not equal to 22-oxa-1 alpha-(OH)D3 greater than 1 alpha-(OH)D3 greater than 20-oxa-1 alpha-(OH)D3. 22-Oxa-1 alpha, 25-(OH)2D3 was also about 10-times more potent than 1 alpha, 25-(OH)2D3 in suppressing proliferation and inducing differentiation of mouse myelomonocytic leukemia cells (WEHI-3), but the former was much weaker than the latter in inducing the release of 45Ca from prelabeled fetal mouse calvaria. These results suggest that the differentiation-inducing activity of vitamin D compounds can be separated structurally from their activity to induce hypercalcemia.
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PMID:Synthetic analogues of vitamin D3 with an oxygen atom in the side chain skeleton. A trial of the development of vitamin D compounds which exhibit potent differentiation-inducing activity without inducing hypercalcemia. 282 55

Sixteen Italian patients with chronic T-cell lymphocytic leukaemia (T-CLL) and leukaemic T-helper phenotype lymphocytes (Thp-CLL) were investigated for serum antibodies against human T-cell leukaemia virus I (HTLV-I) or its integrated DNA sequences. Common features of this series of patients were an aggressive clinical course with poor response to treatment, high white blood-cell count, bone-marrow infiltration, splenomegaly, and chromosome abnormalities. Three patients had skin infiltration and one had hypercalcaemia. Immunological analysis showed a Thp (OKT4+) in all cases, and a heterogeneity, within the OKT4 population, of phenotypes and functional activities. Three patients had either HTLV-I integrated DNA sequences or anti-HTLV-I serum antibodies, or both. These patients had not received any blood transfusions, denied intimate contact with foreigners, and had always lived in small towns of central or southern Italy. Clinical and immunological findings in this series of patients suggest that both HTLV-I related and unrelated cases of Thp-CLL should be regarded as one disease arising from the same subpopulation of mature T-lymphocytes.
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PMID:T-helper phenotype chronic lymphocytic leukaemia and "adult T-cell leukaemia" in Italy. Endemic HTLV-I-related T-cell leukaemias in southern Europe. 286 33

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

Adult T-cell leukemia (ATL) has a range of clinical characteristics. Phenotypically the leukemic cells usually express the helper/inducer associated antigen OKT4 with lack of OKT8. We have observed three patients with acute ATL cytologically indistinguishable from OKT4+/OKT8- ATL but whose neoplastic cells had the unusual phenotype, OKT3+, OKT4+, OKT6-, OKT8+ OKT9+/-, OKT11+, Tac+/-, TdT-. All patients had abnormal karyotypes and antibodies against anti-ATL associated antigens as well as proviral DNA of human T-cell leukemia virus in the leukemic cells. The clinical course was complicated by skin eruptions, hypercalcemia, pulmonary infection and disseminated intravascular coagulopathy. All died of complications shortly after diagnosis. The clinical features of these patients were similar to those of OKT4+/OKT8- ATL. However, their acute course suggests that co-expression surface antigens OKT4 and OKT8 may be a sign of aggressive nature of the disease with poor prognosis.
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PMID:Clinical features of OKT4+/OKT8+ adult T-cell leukemia. 286 55

Thirteen patients with hematological neoplasms were treated with Bestrabucil (100 mg/day po, total dose 700-9,900 mg), which is the benzoate of an estradiol-chlorambucil conjugate. The diseases from which they suffered consisted of T-cell leukemia (3), lymphoma (3), myeloma (5) and essential thrombocytosis (2). Although this drug was less effective against myeloma, the other diseases were more or less relieved with this medication. That is, Bestrabucil was effective in all three patients with T-cell leukemia, both with essential thrombocytosis and two of the three with lymphoma. It is most interesting that adult T-cell leukemia (ATL) cells decreased remarkably with Bestrabucil, along with the disappearance of several symptoms (bone pain, hypercalcemia etc.). The main side effects during this medication were mammary pain (eight of 13 patients, 62%), anorexia (five of 13 patients, 39%) and loss of libido (three of 13 patients, 23%), but neither severe myelosuppression nor hepatorenal dysfunction was induced.
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PMID:[Clinical trial of bestrabucil (KM 2210) in hematopoietic malignancies]. 287 6

Adult T-cell leukemia (ATL) is a disease found endemic in Southern Japan and the Caribbean basin. The human T-cell leukemia virus I (HTLV-I) has been implicated epidemiologically as the causative agent in this disease. This paper describes the identification of this disease in Hawaii in a second generation immigrant from Southern Japan. The disease was initially indolent, then clinically explosive, characterized by cutaneous lesions, leukemic lymphocytes with convoluted nuclei of T-cell phenotype, hypercalcemia, and a terminal infection.
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PMID:HTLV-I-associated T-cell leukemia in Hawaii. 287 81

Adult T cell leukaemia/lymphoma was first identified by Japanese investigators in the mid 1970s. Distinctive characteristics include hypercalcaemia, metabolic bone disease, opportunistic infections and evidence of multiorgan involvement. The malignant cell has the surface phenotype of a T helper lymphocyte but functions as a T suppressor cell, and in leukaemic patients this cell usually has a unique multilobed appearance, which may aid in recognizing the disease. The overwhelming majority of patients with ATLL originate from the south-west Japanese archipelago, as well as the Caribbean basin and south-east USA. The geographic localization of this disease is the result of the endemic distribution of the human retrovirus (HTLV-I) which has been established as the cause of ATLL. Infection with this virus may result in no disease (asymptomatic carriers) or ATLL. While ATLL usually pursues an acute or subacute (prototypic) course, patients are also seen with 'chronic' or 'smouldering' disease. Over time, these more indolent variations may progress to the prototypic form. When aggressive, ATLL must be treated with intense combinations of cytotoxic drugs similar to those used to treat the more common B cell lymphoproliferative disorders. Even though half of the patients treated achieve a remission, the duration is usually brief and the overall actuarial median survival is only 11 months. In addition to recurrent disease, these patients frequently succumb to opportunistic infections.
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PMID:Adult T cell leukaemia/lymphoma. 287 62

Two young adults presenting with acute lymphoblastic leukaemia (ALL) associated with hypercalcaemia and osteolytic lesions were both found to have T cell ALL. Hypercalcaemia is a rare feature of ALL and has not previously been related to T cell disease. Both cases, in some respects, resembled (age between 10 and 20 years and low white cell count) the few other previously reported cases. In one of our cases increased concentrations of vitamin D3 seemed to have a role in the pathogenesis of the hypercalcaemia.
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PMID:Hypercalcaemia in T cell acute lymphoblastic leukaemia: report of two cases. 287 13

Of 95 patients consecutively diagnosed with non-Hodgkin lymphoma, 52 (55%) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positivity was strongly associated with skin involvement, leukemia, and hypercalcemia (p less than 0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 9 patients had indolent courses and a median survival of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinant of adult T-cell leukemia-lymphoma.
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PMID:Non-Hodgkin lymphoma in Jamaica and its relation to adult T-cell leukemia-lymphoma. 288 May 36

Eighteen autopsy cases of adult T-cell leukemia (ATL) were investigated clinicopathologically. Thirteen of the patients had hypercalcemia during their clinical course. Nine of the thirteen had a high level of serum calcium at the terminal stage, even after extensive chemotherapy. Microscopic examination of the bone revealed proliferation of osteoclasts and bone resorption in eight patients. No osteoclast proliferation or bone resorption was found in the other nine normocalcemic patients. The infiltration of ATL cells was observed in only two patients--one was hypercalcemic and the other, normocalcemic. The factors affecting the serum calcium level were examined in two hypercalcemic patients. Hypercalcemia could not be accounted for by parathyroid hormone or prostaglandins E levels, which were in the normal range, or by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, which were low. Our findings are consistent with the mechanism proposed by several investigators, that the malignant T-lymphocytes produced an osteoclast-activating-factor-like substance that caused osteoclast proliferation and hypercalcemia.
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PMID:Hypercalcemia and osteoclast proliferation in adult T-cell leukemia. 288 Jun 56


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