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)

An attempt has been made to prepare antibodies against leukaemia-specific surface antigens by immunizing (C57 B1/6 X C3H/He)F1 mice with formaldehyde-stabilized AKR leukaemic cells. The presence of antibodies was examined by indirect immunofluorescence microscopy (IFM) and the indirect antiglobulin rosetting reaction (IARR). Galactose oxidase treatment destroyed the ability of leukaemic cells to react with antibodies prepared in the hybrid mice, an effect that was reversed by treating the enzyme-modified cells with borohydride. Analysis by immunoprecipitation and polyacrylamide gel electrophoresis of leukaemic cells, labelled by the galactose oxidase/[3H]-NaBH4 technique, indicated that a group of glycoproteins of apparent molecular weight greater than 70 000 was involved. Antibodies could be raised in AKR mice to the same group of glycoproteins by immunization with irradiated leukaemic cells or irradiated neuraminidase-treated leukaemic cells. The level of antibody raised in AKR mice had no effect on the growth of leukaemic lymphoblasts introduced subcutaneously into the host. Antibodies prepared in hybrid mice against leukaemic cells also were absorbed by lymphoid cells of pre-leukaemic 6-month-old AKR mice, indicating that contrary to previous claims in the literature antigens detected by such antisera are not related to malignancy. Hybrid mouse serum cross-reacted with antigens from purified RNA virus isolated from Abelson lymphoma, as demonstrated by the immunoelectrophoretic blotting technique. The pattern of reactivity was not appreciably altered following the absorption of antibodies directed against leukaemic cells. It is concluded that the glycoproteins detected by us may not be viral antigens but normal high molecular weight lymphoid glycoproteins with altered glycosylation patterns that are induced when the viral genomes are expressed.
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PMID:Glycoproteins of the AKR leukaemia cell surface and their relevance to leukaemia-specific surface antigens. 636 29

The relative mutagenic activities of chloroethyl-nitrosourea and methylnitrosourea antitumor agents in active clinical use were determined with the use of the Ames Salmonella typhimurium assay. The results indicated that the drugs induced base substitutions. 2-Deoxy-2-[[(methylnitrosoamino)carbonyl]amino]-D-glucopyranose (also called streptozotocin), a glucose-containing methylnitrosourea, was the most mutagenic of all compounds tested and showed at least a 250-fold increase in activity when compared to that of its chloroethyl analog, 2-[[[(2-chloroethyl) nitrosoamino]carbonyl]-amino]-2-deoxy-D-glucose (also called chlorozotocin). All nitrosoureas, with the exception of N'-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-N-(2-chloroethyl)-N-nitrosourea monohydrochloride, a pyrimidine chloroethyl analog, demonstrated an increase in mutagenicity after incubation with induced Sprague-Dawley rat liver microsomes. No correlation between in vitro chemical alkylating activity and mutagenic potential was observed. Mutagenic activity was not observed to be of predictive value for antitumor activity in the L1210 leukemia model system.
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PMID:Mutagenic activity of nitrosourea antitumor agents. 644 11

Cell surface receptors for immunoglobulin E were isolated by repetitive affinity chromatography from rat basophilic leukemia cells biosynthetically labeled with L-[35S]methionine and D-[3H]mannose. Native immunoglobulin E receptor appeared as a very broad band in the 45,000 to 62,000 Mr region in sodium dodecyl sulfate polyacrylamide gels. However, from cells cultured in the presence of tunicamycin, a relatively narrow band with an apparent Mr of 38,000 was isolated. The 38,000 Mr band rebound to immunoglobulin E-Sepharose, was immunoprecipitated with antibodies to immunoglobulin E receptor, shared tryptic peptides with native receptor, and was labeled with L-[35S]methionine but not D-[3H]mannose, and thus appears to be immunoglobulin E receptor lacking N-linked oligosaccharides. It is demonstrated that N-linked oligosaccharides account for much of the apparent heterogeneity of native receptor in sodium dodecyl sulfate polyacrylamide gels and in two-dimensional gel electrophoresis. A receptor-associated protein with apparent Mr = 30,000, prominently labeled with L-[35S]methionine but not with D-[3H]mannose, did not have altered molecular properties when isolated from tunicamycin-cultured cells, and did not share tryptic peptides with receptor.
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PMID:The cell surface receptor for immunoglobulin E. Effect of tunicamycin on molecular properties of receptor from rat basophilic leukemia cells. 645 41

Conjugates of the monoclonal antibody anti-Thy 1:1 (OX7) and ricin have been constructed, using a thioether bond, such that the ricin no longer can bind Sepharose or asialofetuin. These conjugates were found to be very toxic to Thy 1:1 expressing AKR-A cells whereas they showed little toxicity to Thy 1:2 expressing EL4 cells. By comparison, OX7-ricin conjugates which retained galactose-binding capability were still highly toxic to EL4 cells and this toxicity was antagonized by lactose. A second conjugate made from the W3/25 monoclonal antibody was constructed. The W3/25-ricin conjugate which had lost Sepharose-binding capacity was toxic to W3/25 antigen-expressing rat T-leukaemia cells. This is in sharp contrast to the disulphide linked W3/25-ricin A-chain conjugate which is totally inactive, suggesting that the role of the B-chain in membrane transport of the A-chain into the cytosol is independent of galactose recognition.
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PMID:Antibody-ricin conjugates: a method of linkage which blocks the galactose binding site of ricin. 647 50

Normal human monocytes and macrophages, as well as in vitro human leukaemic promyelocytic cell line (HL-60) transformed into macrophage-like cells by 12-0-tetradecanoylphorbol-13-acetate (TPA) generate potent procoagulant activity (PCA) similar to tissue thromboplastin. In the present study, only mild PCA was detected in primary cultures of cells from the peripheral blood of patients with acute lymphatic leukaemia (ALL), acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). After exposure to TPA, AML and CML cells assumed characteristics specific to monocytes and macrophages. Differentiation was associated with the generation of PCA. PCA was not found in ALL cells exposed to TPA. The PCA of TPA-induced macrophages derived from AML and CML cells resembled tissue thromboplastin and normal monocyte and macrophage PCA in several aspects: (a) accelerated clotting via the extrinsic coagulation pathway, (b) inhibition by concanavalin A and protection against lectin inhibition by methyl-alpha-D-mannopyranoside, (c) localization in the cell membrane. The capacity for PCA generation is additional evidence for the similarity between TPA-induced macrophages derived from AML and CML cells and normal human monocytes and macrophages.
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PMID:Generation of procoagulant activity (PCA) by macrophage-like cells derived from acute and chronic myeloid leukaemia cells in response to phorbol esters. 657 80

The effects of monosaccharides on the cytotoxic activity of cytotoxic T lymphocytes (CTL) and three cloned long-term cytotoxic T-lymphocyte lines (CTLL) are compared. Uncultured CTL and clones CTLL-A2 and CTLL-A11 were derived from the peritoneal cavity of C57BL/6 mice immunized against the H-2Dd determinants on the BALB/c sarcoma Meth A. Clone CTLL-R5 was derived from spleen of (BALB/c X C57BL)F1 mice immunized against a unique determinant on the BALB/c radiation-induced leukemia RL male 1. The cell-surface phenotype of the clones is Lyt-1+,2+,3+. Cytotoxic activity of CTLL-A2 and CTLL-R5 as determined by a 4-hr 51Cr-release assay was inhibited over 50% by 1 mM 2-deoxy-D-glucose. CTLL-A11 and the uncultured cytotoxic T cells were more resistant to inhibition by 2DG (40% at 20 mM). Surprisingly, it was found that the addition of D-mannose, D-galactose, D-glucose, L-fucose, alpha-methyl-D-mannose, and N-acetyl-D-glucosamine also inhibited, in a dose-related manner, the cytotoxicity of CTLL-A2 and CTLL-A11. CTLL-R5 showed a more restricted inhibition pattern: only D-mannose and D-galactose were inhibitory. The mechanism of inhibition remains to be clarified.
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PMID:Characterization of IL-2-dependent cytotoxic T-cell clones. III. Inhibition of killing activity by monosaccharides. 660 19

The carbohydrate composition of a purified plasma membrane fraction derived from the peripheral blood lymphocytes of a patient with a pro-lymphocytic leukaemia has been investigated and compared to the expression of lectin receptors at the membrane surface of the intact cell. The presence of galactose, mannose, fucose, glucose, sialic acid, N-acetylgalactosamine, N-acetylglucosamine and sialic acid substituted O-glycosidic linked beta-D-galactopyranosyl (1 leads to 3) N-acetyl-D-galactosamine was confirmed on membrane glycoconjugates by gas chromatography. A lectin induced agglutinin assay using intact leukaemia cells demonstrated the accessibility of different lectin receptors at the native membrane surface, while the peanut agglutinin and the Helix pomatia receptor was only accessible after neuraminidase treatment.
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PMID:Plasma membrane carbohydrate composition and lectin receptors of lymphocytes from pro-lymphocytic leukaemia. 660 72

A method is described for preparing specific cytotoxic agents by linking intact ricin to antibodies in a manner that produces obstruction of the galactose-binding sites on the B chain of the toxin and so diminishes the capacity of the conjugate to bind non-specifically to cells. The conjugates were synthesised by reacting iodoacetylated ricin with thiolated immunoglobulin and the components of conjugate with reduced galactose-binding capacity were separated by affinity chromatography on Sepharose (a beta-galactosyl matrix) and asialofetuin-Sepharose. Fluorescence-activated cell sorter (FACS) analyses revealed that the fraction of a monoclonal anti-Thy1.1-ricin conjugate that passed through a Sepharose column had markedly diminished capacity to bind non-specifically to Thy1.2-expressing CBA thymocytes and EL4 lymphoma cells. The fraction of conjugate that passed through an asialofetuin-Sepharose column displayed no detectable non-specific binding. Both fractions of conjugate were potent cytotoxic agents for Thy1.1-expressing AKR-A lymphoma cells in tissue culture. They reduced the [3H]leucine incorporation of the cells by 50% at a concentration of 2-5 pM. Comparable inhibition of EL4 cells was only achieved with 3000-7500-fold greater concentrations of conjugate. By contrast, the fraction of anti-Thy1.1-ricin that retained Sepharose-binding capacity showed marked non-specific binding and toxicity to EL4 cells. A conjugate with diminished galactose-binding capacity was also prepared from the W3/25 monoclonal antibody which recognises an antigen upon helper T-lymphocytes in the rat. It elicited powerful and specific toxic effects upon W3/25 antigen-expressing rat T-leukaemia cells. This finding is of particular importance because isolated ricin A-chain disulphide-linked to W3/25 antibody is not cytotoxic. The property of the B-chain in intact ricin conjugates that facilitates delivery of the A-chain to the cytosol thus appears to be independent of galactose recognition. It is concluded that the 'blocked' ricin conjugates combine the advantages of high potency, which is often lacking in antibody-A-chain conjugates, with high specificity, which previously was lacking in intact ricin conjugates.
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PMID:Blockade of the galactose-binding sites of ricin by its linkage to antibody. Specific cytotoxic effects of the conjugates. 660 47

A mouse monoclonal antibody (IgM) was obtained by cell hybridization between X63-Ag8.653 myeloma cells and spleen cells from a BALB mouse that was immunized with GRSL leukemia cells of the GR strain. This antibody identified a unique fetal antigen, which is expressed exclusively on embryonic thymocytes of all strains tested. Therefore, the antigen defined was named fetal thymus antigen-1, FT-1. The proportion of FT-1+ fetal thymocytes detected by immunofluorescence assay sharply decreases as gestation time increases, and finally they disappear from the thymus. On the other hand, Thy-1+ cells increase in inverse proportion. The immunofluorescence studies and absorption tests showed that FT-1 antigen is not detectable on brain, liver, kidney, or lymphoid tissue cells of adult mice. However, it is expressed on some leukemia cells of various mouse strains, which demonstrated that this is the first example of an oncofetal antigen of a mouse leukemia. The molecular weight of FT-1 antigen on leukemia cells was estimated to be 130,000 by means of biosynthetic labeling with [3H]galactose and [35S]methionine. The two-dimensional gel electrophoresis pattern of FT-1 antigen shows a family of glycoproteins with extensive charge heterogeneity. It was also shown that the FT-1 antigen molecule carries the receptor for DBA lectin.
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PMID:A new differentiation antigen (FT-1) shared with fetal thymocytes and leukemic cells in the mouse. 660 76

Qualitative variations in the glycoconjugates which make up the lectin receptor sites on the membranes of leukemic lymphocytes, compared with those of normal cells, have been studied by the use of three tritiated lectins: Robinia pseudoacacia lectin, Concanavalin A and Ricinus communis (var. Sanquineus) agglutinin (RCA 120). The binding specificity of these lectins has been demonstrated using specific determinants: alpha-methylmannoside and galactose for Concanavalin A and Ricinus communis agglutinin respectively. For the Robinia lectin this specificity was determined by saturation of the receptor sites with the unlabeled Robinia lectin before the addition of isotopically labeled Robinia lectin. The results show a decrease in the number of receptor sites on the leukemia cells, especially in chronic lymphoid leukemia, relative to that on normal cells. The apparent affinity constants of leukemic cells in all cases remain higher than those of normal cells.
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PMID:Decrease in human lymphocyte surface glycoconjugates in leukemia as demonstrated by lectin binding. 661 30


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