Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various compounds active in promoting in vitro differentiation of certain murine leukemia cell lines (Friend erythroleukemia cells and mouse myeloid leukemia cells) were tested for their capacity to induce differentiation of HL-60 cells, a human promyelocytic leukemia cell line capable of terminally differentiating in vitro to functionally mature granulocytes. Polar planar compounds including hexamethylene bisacetamide (HMBA), certain purines (particularly hypoxanthine), and actinomycin-D induced morphological and functional (as assessed by the capacity to reduce NBT dye) differentiation of HL-60. In contrast, hemin, ouabain, prostaglandin E1, X-irradiation, dexamethasone and some other anti-leukemic chemotherapeutic agents induced little if any significant differentiation of HL-60 cells. These results, together with previous observations with murine leukemia cells, suggest that the human HL-60 cells share common cellular target sites for the inducing action of polar planar compounds, hypoxanthine and actinomycin-D with some murine leukemic cells. In contrast, hemin, ouabain and prostaglandin E1 may be specific for mouse erythroleukemia cells, while X-irradiation and chemotherapeutic agents induce differentiation of both types (erythroid and myeloid) of mouse leukemic cells, but have little effect on HL-60 cells.
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PMID:Induction of morphological and functional differentiation of human promyelocytic leukemia cells (HL-60) by componuds which induce differentiation of murine leukemia cells. 615 28

Down's Syndrome patients are known to be of short stature, prone to infections, autoimmune disease, hypothyroidism, leukaemia, heart defects and later Alzheimer's disease. They tend to have older mothers, like Alzheimer's disease patients. The latter tend to have sibs with either Down's Syndrome or lymphoma/leukaemia. Evidence, looking at 28 Down's Syndrome patients, suggests that multiple food allergies, gluten-gliadin sensitivity or intolerance are causing a coeliac disease-like picture with a malabsorption state for essential vitamins, minerals and severe autoimmune disease. It is hoped that missed gluten-gliadin sensitivity or intolerance with or without coeliac disease will be considered as a cause of abnormal oogenesis and spermatogenesis resulting in trisomy 21 and other aneuploidies. The mechanism most likely is low B1 interfering with sufficient release of cAMP for normal meiosis. Alternatively exorphins and peptides from foods may suppress prostaglandin E1 synthesis, or food sensitivities may alter toxic metal absorption mechanisms, which are thought to play a role in the development of Alzheimer's disease. Adequate vitamin/mineral supplementation, especially B1, prior to conception and in the first trimester is recommended for mothers at risk for DS, especially older mothers and a gluten free diet for those with coeliac disease or gluten-gliadin sensitivity/intolerance. Hopefully this will prevent conception of a DS child, or prevent heart defects/stigmata if one is conceived. DS children should be investigated for the above and commence a food allergy free diet with relevant supplements to meet their needs as early as maximum development.
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PMID:Down's syndrome: nutritional intervention. 624 80

The effects of cyclic nucleotides and PGE1 upon the proliferation of normal granulocyte/macrophage progenitors were examined in in vitro systems and contrasted to the effects of these compounds on (1) granulocyte/macrophage progenitors from the peripheral blood of patients with myeolofibrosis/myeloid metaplasia (MF) and chronic myelogeneous leukemia (CML); and (2) blast progenitors from the peripheral blood of patients with acute myelogenous leukemia (AML) and acute monocytic leukemia (AMoL). Cyclic AMP was found to be a concentration dependent inhibitor of colony proliferation in all systems tested. Cyclic GMP was an inconsistent enhancer of colony proliferation in all systems in a manner which was not clearly concentration dependent. The effect of PGE1 in normal systems was highly variable depending on the culture conditions, but it was generally found to be an inhibitor of colony proliferation. Cyclic AMP, cyclic GMP and PGE1 altered the release of colony stimulating activity from adherent bone marrow cells in a manner opposite to the direct effects of these compounds on progenitor cell proliferation. Abnormalities in response to PGE1 were found in progenitors from patients with CML (deficient inhibition), AMoL (stimulation of proliferation in certain concentration ranges), and MF (enhanced proliferation). Studies on one of the patients with MF indicated that a normally responding population could be defined by density-gradient separation. These data confirm the capacity of these compounds to modulate in vitro proliferation of myeloid progenitors, and suggest that aberrations of response to PGE1 may occur in subpopulations of cells from several myeloproliferative disorders.
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PMID:Modulation of normal and abnormal myeloid progenitor proliferation by cyclic nucleotides and PGE1. 625 72

The adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), at low concentrations (less than 10 microM), enhances the inhibitory activity of adenosine against lymphocyte-mediated cytolysis (LMC) without itself being inhibitory. At higher concentrations, EHNA alone is inhibitory to LMC with an IC50 of 160 microM. This inhibition is reversible upon washout, appears to affect an early stage of the lytic process, and does not appear to involve changes in basal levels of cyclic AMP (cAMP), ribonucleoside 5'-triphosphate pool sizes, S-adenosylhomocysteine levels, or protein carboxymethylation. EHNA does enhance the cAMP response of cytolytic lymphocytes (CL) to activators of adenylate cyclase such as prostaglandin E1. EHNA inhibits lymphocyte high-affinity cAMP phosphodiesterase at immunosuppressive levels, exhibiting hyperbolic mixed-type inhibition (Ki = 83 microM, alpha = 0.47, beta = 0.18). Whereas inhibition of intralymphocytic ADA is complete at low concentrations (less than 25 microM) of EHNA, inhibition of LMC and intralymphocytic cAMP phosphodiesterase increases linearly with EHNA concentration to at least 200 microM. The presence of 200 microM EHNA during the centrifugation of mixtures of CL and EL4 leukemia target cells leads to increased CL cAMP levels. 2'-Deoxycoformycin, a more potent ADA inhibitor than EHNA, is not inhibitory to LMC and shows none of these cAMP-related effects. These results suggest that CL-target cell contact stimulates adenylate cyclase in the CL and that EHNA inhibits LMC due to its enhancement of this target cell-stimulated elevation of cAMP.
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PMID:Inhibition of lymphocyte-mediated cytolysis and cyclic AMP phosphodiesterase by erythro-9-(2-hydroxy-3-nonyl)adenine. 629 34

An identical class of high-affinity binding sites for the 125I-labelled beta-adrenergic antagonist hydroxybenzylpindolol, was identified on intact human normal and leukaemic peripheral blood leukocytes. On normal unfractionated lymphocytes, polymorphonuclear leukocytes, and monocytes, receptor density did not differ significantly (1200-1400 receptors per cell; P greater than 0.3), but it was higher on B- than on T-lymphocytes (P less than 0.05). In leukaemia, monocytic blast cells expressed highest receptor numbers, whereas very low receptor density was seen on the pathologic B-cells from chronic lymphocytic leukaemia. Among normal leukocytes, adenylate cyclase activation by hormones (isoproterenol, prostaglandin E1, histamine) and sodium fluoride was strongest in plasma membranes from monocytes, but very weak in polymorphonuclear leukocytes either due to uncoupling of hormone receptors from adenylate cyclase or to low catalytic activity. In T-cells, enzyme activity was significantly lower than in B-cells. Loss of adenylate cyclase sensitivity to hormones and fluoride occurred in leukaemic cells from chronic and acute lymphocytic leukaemia.
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PMID:Differences in beta-adrenergic receptor density and adenylate cyclase activity between normal and leukaemic leukocytes. 631 63

The effects of prostaglandin E1 (PGE1) on leukemia colony formation were investigated in seven cases of acute nonlymphocytic leukemia. In contrast to the almost constant results observed for normal myeloid colony formation, in patients there were apparent individual variations. Strong inhibition of colony formation by PGE1 was observed in three cases. In one case, enhancement rather than inhibition was observed. These in vitro inhibitory or stimulatory effects of PGE1 were not related to the degree of the in vivo proliferation of leukemia cells. Morphologic analysis of colonies revealed that preferential inhibition of monocytic colony formation by PGE1, characteristic of normal bone marrow cultures, was not always observed in leukemia cell cultures. These abnormal responses to PGE1 suggest that the proliferation and differentiation of leukemic progenitor cells are regulated in a different way from normal hemopoiesis.
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PMID:Effects of prostaglandin E on the proliferation and differentiation of leukemic progenitor cells in acute nonlymphocytic leukemia. 658 1

AKR mice develop spontaneous lymphoid leukemia late (8 to 12 months) in life, although persistent murine leukemia virus production occurs throughout their life. This suggests that age-related changes are involved in development of leukemia. Prostaglandin biosynthesis was therefore studied in 24-hr cultures in vitro at 37 degrees of peritoneal macrophages, splenocytes, thymocytes, bone marrow, and lymph node cells. AKR mice of 2, 6, and 8 to 12 months of age were studied. Prostaglandin E1, prostaglandin E2, prostaglandin F2 alpha, 6-ketoprostaglandin F1 alpha, and thromboxane B2 were measured. In cultures of peritoneal macrophages and cells from spleen, thymus, and lymph nodes, the biosynthesis of all five prostaglandin moieties was higher in those cultures prepared from 8- to 12-month-old spontaneously leukemic mice in comparison with those from 2-month-old nonleukemic AKR mice. However, when leukemia was transplanted in 3-month-old AKR mice, synthesis of all five compounds was reduced significantly in cultures of peritoneal macrophages and splenocytes prepared from these 3-month-old leukemic mice. The present data demonstrate abnormalities in prostaglandin synthesis by various cells of the immune system in leukemic mice. However, the nature of these changes was different in cultures of cells from spontaneously leukemic mice from those with transplanted leukemia. Age-related increases in prostaglandin synthesis by various lymphoid cells from spontaneously leukemic AKR mice (8 to 12 months old) occurred at a much earlier age than in BALB/c mice and may be related to the leukemic condition.
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PMID:Prostaglandins in cells of the lymphoid system in AKR leukemia. 669 54

The behaviour of phagocytosis and that of PGE1 and PGE2 in the circulating granulocytes of normal and leukaemic subjects was investigated by the comparison of latex particles and the PAP (peroxidase-antiperoxidase) immuno-enzymatic method respectively. Generally speaking, it was found that chronic myeloid leukaemia and acute myeloblastic leukaemia were accompanied by a marked reduction in phagocyting capacity, whereas this is apparently normal in CLL and ALL. PCE values, on the other hand, were well down in lymphatic leukaemia, AML and AMML, but not in CML, where high PGE (especially PGE2) was noted both basally and after phagocytosis. That the PGE take part in phagocytosis is shown by their redistribution in phagocyting cells, with elective accumulation in the membrane and around the engulfed material.
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PMID:[Behavior of PGE1 and PGE2 in the granulocytes of normal and leukemic subjects during phagocytosis in vitro]. 695 84

A functional cDNA for the human prostacyclin receptor was isolated from a cDNA library of CMK cells, a human megakaryocytic leukaemia cell line. The cDNA encodes a protein consisting of 386 amino acid residues with seven putative transmembrane domains and a deduced molecular weight of 40,956. [3H]Iloprost specifically bound to the membrane of CHO cells stably expressing the cDNA with a Kd of 3.3 nM. This binding was displaced by unlabelled prostanoids in the order of iloprost = cicaprost >> carbacyclin > prostaglandin E1 (PGE1) > STA2. PGE2, PGD2 and PGF 2 alpha did not inhibit it. Iloprost in a concentration-dependent manner increased the cAMP level and generated inositol trisphosphate in these cells, indicating that this human receptor can couple to multiple signal transduction pathways.
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PMID:Cloning and expression of a cDNA for the human prostacyclin receptor. 751 39

We performed retrospective analysis of hepatic veno-occlusive disease (VOD) in 57 cases with leukemia after allogeneic bone marrow transplantation (BMT). Prostaglandin E1 (PGE1) was used to prevent VOD in 8 cases at a dose of 0.3 micrograms/kg/hr from day -8 to day 30. No VOD was noted in the PGE1 group, while the incidence of VOD was 8/49 (16.3%) in the non PGE1 group. In twelve patients with pretransplant liver dysfunction, VOD was noted in 0/3 in the PGE1 group and 4/9 (44.4%) in the non PGE1 group, respectively. However, prophylactic effects of PGE1 on VOD is not significant in this study, so further studies are needed to determine the efficacy of PGE1. One of 8 patients with PGE1 prophylaxis had edema and erythema on extremities, however, severe toxicity was not experienced.
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PMID:[A trial use of prostaglandin E1 for prevention of hepatic veno-occlusive disease after allogeneic bone marrow transplantation]. 796 53


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