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)

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

An antigen histochemically localized in the nuclei and cytoplasmic granules of normal and leukemic human myeloid cells has been identified as myeloperoxidase (MPO; EC 1.11.1.7). The localization and amount of the enzyme was determined by using a murine monoclonal antibody designated H-43-5 raised against nuclear proteins derived from human promyelocytic HL-60 leukemia cells. The highest amount of nuclear MPO (3.5 micrograms per 10(6) nuclei) was found in granulocytes; less than half of this amount was detected in nuclei from HL-60 cells. Still lower levels were found in nuclei from monocytes and a series of human monomyelocytic leukemia cells. MPO from HL-60 cells was purified by immunoaffinity chromatography and fractionated into three components (forms I, II, and III) by CM-cellulose chromatography. Chromatography of these MPO forms on DNA-Sepharose columns confirmed that all three forms of MPO were tightly bound to DNA with apparent relative affinities in the order of form III greater than form II greater than form I. The affinity of MPO form III for DNA was sufficient to enable the formation and elution of DNA-MPO complexes during size-exclusion chromatography at high ionic strength and neutral pH. This form of MPO was also able to shield DNA from strand scission induced by active oxygen species generated by xanthine oxidase acting aerobically on xanthine. These data suggest that intranuclear MPO may help to protect DNA against damage resulting from oxygen radicals produced during myeloid cell maturation and function.
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PMID:Myeloperoxidase: a myeloid cell nuclear antigen with DNA-binding properties. 282 20

Cerebral blood flow (CBF) was measured by the non-invasive xenon-133 technique in patients with increased blood viscosity as a result of paraproteinaemia or leukaemia. A highly significant inverse relation was found between CBF and arterial oxygen content in 59 paraproteinaemic patients. There was no significant correlation between CBF and whole blood viscosity, and no significant difference between CBF in paraproteinaemic patients and a matched group of anaemic patients. 7 leukaemic patients with up to threefold increases in whole blood viscosity were also found to have CBF appropriate to their degree of anaemia. The effects of treatment to reduce blood viscosity were studied in 7 paraproteinaemic and 5 leukaemic patients; changes in CBF were significantly related to changes in arterial oxygen content but not to changes in blood viscosity. These studies confirm the importance of arterial oxygen content in the determination of CBF, and demonstrate that regulatory mechanisms can maintain normal cerebral oxygen transport despite increased plasma and whole blood viscosity.
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PMID:Regulation of cerebral blood flow in response to changes in blood viscosity. 285 47

Three patients with gas gangrene of the lower limbs are presented. In 2 of the 3 patients gas gangrene developed after lower-limb amputation, indications for amputation being atherosclerotic and diabetic gangrene. In the third patient associated leukaemia was diagnosed. All 3 patients presented with the typical clinical manifestations of gas gangrene. Clostridium perfringens was isolated from the affected leg in each patient. The current application of surgery and hyperbaric oxygen therapy in the treatment of gas gangrene is discussed.
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PMID:[Gas gangrene: A discussion of 3 cases and review of the literature]. 286 25

Selective in vitro photodestruction of HPB-ALL human T-cell leukemia cells was accomplished using the photosensitizer chlorin e6 coupled through dextran molecules to an anti-T-cell monoclonal antibody (mAb), anti-Leu-1. Conjugates with mAb/chlorin molar ratios as high as 1:36 retained mAb binding activity, and the absorption spectrum and quantum efficiency for singlet oxygen production of bound chlorin (0.7 +/- 0.2) were unchanged from that of the free photosensitizer. Phototoxicity, as measured by a clonogenic assay and by uptake of ethidium bromide, was dependent on the doses of both mAb-chlorin and 630- to 670-nm light, was enhanced by 2H2O, and was observed only in target populations that bound the mAb. Similarly, free chlorin e6 in solution had no photodynamic effect in amounts 100 times more than that carried by the mAb. For this antibody-targeted system, approximately 10(10) molecules of singlet oxygen were necessary to kill a cell.
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PMID:Antibody-targeted photolysis: selective photodestruction of human T-cell leukemia cells using monoclonal antibody-chlorin e6 conjugates. 287 61

Fe(III) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric and spectroscopic measurements, we have shown that adriamycin and daunorubicin form two well-defined species with Fe(III), which can be formulated as respectively Fe(HAd)3 and Fe(HDr)3. In these formulas, HAd and HDr stand for adriamycin and daunorubicin in which the 1,4-dihydroxy-anthraquinone moiety is half-deprotonated. Both complexes are six-membered chelates. The stability constant is beta = (2.5 +/- 0.5) X 10(28) for both complexes. Interaction with DNA has been studied showing that, despite strong coordination to Fe(III), anthracyclines are able to intercalate between DNA bases pairs, releasing the metal. These complexes display antitumor activity against P 388 leukemia that compares with that of the free drug. Fe(HAd)3, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase. Moreover, it is shown that the triferric adriamycin compound so called "quelamycin" is in fact a mixture of Fe(HAd)3 and polymeric ferric hydroxide.
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PMID:Iron(III)-adriamycin and Iron(III)-daunorubicin complexes: physicochemical characteristics, interaction with DNA, and antitumor activity. 298 53

Fe(III) complex of an antitumoral antibiotic carminomycin has been studied. Using potentiometric and spectroscopic measurements we have shown that carminomycin forms with Fe(III) a well-defined species in which three molecules of drug are chelated to one Fe(III) ion. This occurs with the release of one proton per molecule of drug. Magnetic susceptibility measurements suggest that six oxygen atoms are bound to iron. The stability constant is 3 X 10(34). The in vitro inhibition of P 388 leukemia cell growth by this complex compares with that of the free drug. This complex, unlike the free drug, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase.
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PMID:Physicochemical studies of the iron(III)-carminomycin complex and evidence of the lack of stimulated superoxide production by NADH dehydrogenase. 298 12

A human cell line, ZC, derived from the blood of a patient with acute myelomonocytic leukemia, was established and cloned. One of the clones, ZC-1.6, was subsequently characterized. As for its morphology and cytochemistry, ZC-1.6 clone shares a number of features with immature cells of the monocytic or myelocytic lineages. Surface marker analysis shows positivity for 4F2 (100% of the cells), and OKM1 (38%) monoclonal antibodies, and presence of surface HLA-D/DR antigens (100%) and Fc (11%) and complement (C3b) receptors (100%). Functional capabilities of ZC-1.6 cells include adherence, spreading, and phagocytosis of latex and opsonized zymosan particles. Despite its morphological immaturity, the ZC-1.6 clone produces relevant amounts of O2- in the presence of different stimuli (phorbol myristate acetate, opsonized zymosan, or latex particles). The production of O2- by ZC-1.6 cells is the first evidence that reactive oxygen intermediate production may represent an early feature of cells of the myelomonocytic lineage.
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PMID:Establishment and characterization of a new human cloned myelomonocytic cell line (ZC-1.6). 299 3

Following induction of differentiation by incubation with 1.25% dimethylsulfoxide (DMSO), cells of the HL60 promyelocytic leukaemia cell line acquire certain characteristics of the mature polymorphonuclear leucocyte (PMN) including the ability to produce oxygen radicals and to phagocytose opsonized bacteria. However, these cells are unable to fix 125I during phagocytosis and are only able to kill phagocytosed microorganisms (C. albicans and S. aureus) to a small degree compared to mature PMN. Further, release of myeloperoxidase (MPO) from cytoplasmic granules occurs to approximately 20% of control levels after 6 days culture with DMSO, and drops to negligible levels by 7 days. These data suggest an immature or inactive MPO/peroxide/halide killing system. Insensitivity to the cyclooxygenase pathway inhibitor indomethacin suggests that there may also be a defect in this pathway.
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PMID:Differentiated HL60 promyelocytic leukaemia cells have a deficient myeloperoxidase/halide killing system. 300 85

The photochemistry of merocyanine 540 (MC 540), a sensitizing dye that binds preferentially to leukemia and electrically excitable cells, has been investigated. MC 540-mediated photooxidation of histidine, arachidonate, and unsaturated phospholipid vesicles was assessed by spin label oximetry and shown to involve type II (singlet oxygen) chemistry. The dye was also shown to be a potent sensitizer of lipid peroxidation in a natural cell membrane, the erythrocyte ghost. Inhibition by azide, stimulation by 2H2O, and identification of the cholesterol product 5 alpha-cholest-6-ene-3 beta,5-diol in this system, all were consistent with singlet oxygen intermediacy. Finally, MC 540 was found to be considerably more phototoxic to K-562 leukemia cells in 2H2O than in H2O. We conclude that singlet oxygen plays a major role in the phototherapeutic effects of this dye.
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PMID:Photodynamic action of merocyanine 540 on artificial and natural cell membranes: involvement of singlet molecular oxygen. 303 73


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