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)

Addition of nicotine causes a dose- and time-dependent inhibition of cell growth in the human promyelocytic HL-60 leukemia cells, with 4 mM nicotine resulting in a 50% inhibition of cellular proliferation after 48-50 h. Accompanying the anticellular effect of nicotine is a significant change in the cell cycle distribution of HL-60 cells. For example, treatment with 4 mM nicotine for 20 h causes an increase in the proportion of G1-phase cells (from 49% to 57%) and a significant decrease in the proportion of S-phase cells (from 41% to 32%). These results suggest that nicotine causes partial cell arrest in the G1-phase which may in part account for its effects on cell growth. To determine whether nicotine changes the cellular uptake/transport to macromolecular precursors, HL-60 cells were treated with 2-6 mM nicotine for 30 h, at the end of which time cells were labeled with [3H]-thymidine, [3H]uridine, [14C]lysine and [35S]methionine, the trichloroacetic acid soluble and insoluble radioactivities from each of the labeling conditions were determined. These studies show that nicotine mainly affects the de novo synthesis of proteins.
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PMID:Effects of nicotine on cellular proliferation, cell cycle phase distribution, and macromolecular synthesis in human promyelocytic HL-60 leukemia cells. 346 51

Peripheral blood lymphocytes (PBL) isolated from BALB/c mice bearing a B-cell leukemia (BCL1) showed a marked proliferative response upon two days culturing with poly(L-lysine) (PLL) of various molecular weights. An inverse relationship was noted between the molecular weight of the PLL and the dose required for optimal proliferative response. PLL showed no proliferative activity when cultured with normal PBL or with lymphocytes isolated from the spleen or other lymphoid organs of BCL1-bearing mice. Double exposure to PLL and lipopolysaccharide (LPS) had a marked synergistic effect on BCL1 PBL stimulation but not on PBL isolated from normal mice. The data suggest that PLL, in contrast to LPS, may cause a selective proliferation of a subpopulation(s) of B-tumor cells at a particular stage(s) of differentiation.
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PMID:Proliferative response of murine B-cell leukemia (BCL1) to poly(L-lysine). 387 70

Polyriboinosinic-polycytidylic acid with poly-L-lysine stabilized with carboxymethylcellulose [poly(I,C)-LC] augmented, in a dose- and time-dependent manner, secretion of colony-stimulating factor (CSF) by peritoneal macrophages (M phi) and bone marrow cells (BMC). Optimal effects were found after 2 days of in vitro culture of the cells with 50 micrograms/ml of poly(I,C)-LC or 14 h to 3 days after a single intraperitoneal injection of 1-2 mg/kg of poly(I,C)-LC into normal mice. The increase in CSF secretion by M phi and BMC was paralleled in vivo by an increase in serum CSF levels, followed by a rise in committed granulocyte and M phi progenitor cells (GM-CFU-C), nucleated BMC, and blood leukocytes of myelomonocytic origin. Poly(I,C)-LC at doses greater than 4 mg/kg, however, were strongly myelosuppressive. In vitro treatment of undifferentiated myelomonocytic leukemia cells from the WEHI-3B cell line with 10-1,000 micrograms/ml of poly(I,C)-LC resulted in a significant increase in CSF secretion by the leukemic cells and a concomitant inhibition of their proliferation. Incubation of cells from the WEHI-3B D+ subline, which differentiate in response to GM-CSF or G-CSF, with 50-100 micrograms/ml poly(I,C)-LC in agar cultures induced in approximately 45% of the leukemic colonies a differentiation into granulocytes and/or M phi. Poly(I,C)-LC, however, had no effect on differentiation of cells from the CSF unresponsive WEHI-3B D- subline. The CSF-inducing biological response modifier poly(I,C)-LC thus has the potential to stimulate growth and differentiation of normal, as well as differentiation of malignant myelopoietic progenitor cells.
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PMID:Effects of poly(I,C)-LC on growth and differentiation of normal and malignant myelopoietic progenitor cells. 387 62

Regiospecific syntheses of gamma- and alpha-conjugates of methotrexate and poly(L-lysine) are described. The alpha- and gamma-t-butyl esters, respectively, of methotrexate were coupled to poly(L-lysine) with diphenylphosphoryl azide in N,N-dimethylformamide, the ester-protecting group was cleaved with 15% hydrogen bromide in acetic acid, and small molecules were removed by dialysis. Poly(L-lysine) of Mr = 1,500-8,000 and 8,000-30,000 was used to prepare six different conjugates, which were characterized by ultraviolet absorbance measurement and quantitative amino acid analysis. The degree of substitution varied from one methotrexate per 4.7 lysines to one methotrexate per 10.2 lysines. Dihydrofolate reductase inhibition in a cell-free assay was observed with alpha- and gamma-conjugates, but the latter had the greater affinity (only 3-fold less than that of methotrexate itself). The binding of the conjugates exhibited a slight pH dependence, with affinity being greater at pH 7.2 than at pH 8.5 for both alpha- and gamma-conjugates. Toxicity to cultured rat hepatoma cells (H35) was also greater for the gamma-conjugates, and showed some dependence on the chain-length and degree of substitution of the poly(L-lysine) carrier. Cells resistant to methotrexate by virtue of a transport defect (H35R0.3 line) retained their sensitivity to the gamma-conjugate, but less so to the alpha-conjugate. There was also some retention of sensitivity in a more highly resistant cell line (H35R10) with impaired methotrexate transport and a concomitant increase in dihydrofolate reductase activity. gamma-Conjugation was likewise more favorable in cytotoxicity assays against L1210 murine leukemia cells, and there was partial retention of activity against highly methotrexate-resistant lines (L1210/R71 and L1210/R81) with a transport defect and/or an elevation of dihydrofolate reductase content. In antitumor assays against intraperitoneal L1210 leukemia in mice, a gamma-conjugate with Mr = 8,000-30,000 and one methotrexate per 5.5 lysines produced a 35-75% increase in lifespan when administered intraperitoneally at single doses equivalent to 10-20 mg/kg of methotrexate. A similar increase in lifespan with methotrexate alone on the single-dose regimen required 50-150 mg/kg. An alpha-conjugate of similar Mr and degree of substitution was inactive at nontoxic doses, as were other gamma-conjugates of lower Mr and/or degree of substitution.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regiospecific gamma-conjugation of methotrexate to poly(L-lysine). Chemical and biological studies. 396 26

Resonance energy-transfer methods have been used to investigate the structure of immunoglobulin E (IgE) bound to its high-affinity receptor on plasma membrane vesicles derived from rat basophilic leukemia cells. The structural mapping of receptor-bound IgE was initiated in an earlier study [Holowka, D., & Baird, B. (1983) Biochemistry 22, 3475], and it is based on measuring the minimal distance from IgE sites that are selectively labeled with donor probes to a plane of amphipathic acceptors at the membrane surface. This paper describes the use of monoclonal IgE specific for 5-(dimethylamino)naphthalene-1-sulfonyl (DNS) to place a donor probe, DNS-L-Lys, in the antibody combining sites. The distance from these sites to the membrane surface was determined to be greater than 100 A with two different amphipathic acceptor probes. Another site in the Fab segments of monoclonal IgE (anti-dinitrophenyl) could be labeled selectively with N-[4-[7-(diethylamino)-4-methylcoumarin-3-yl]phenyl]maleimide (CPM) in the absence of reducing agents [CPM(-)], and the reaction could not be blocked by prereaction with N-ethylmaleimide. The pattern of CPM(-)-labeled proteolytic fragments and the lack of fluorescence quenching by (trinitrophenyl)lysine in the antibody combining sites suggested the CPM(-)-labeled site to be in the C epsilon 1 domain of IgE. The distance between this site on receptor-bound IgE and the membrane surface was determined to be 75-87 A with two different amphipathic acceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structural mapping of Fc receptor bound immunoglobulin E: proximity to the membrane surface of the antibody combining site and another site in the Fab segments. 408 17

It has been previously shown that alloantisera prepared by reciprocal immunization of strain 2 and strain 13 guinea pigs specifically block the activation of T lymphocytes from immune guinea pigs by antigens, the response to which is controlled by Ir genes. In this report we have examined the effect of absorption of the 13 anti-2 serum with different populations of lymphoid cells. It is unlikely that the inhibitory activity of the anti-2 serum on the proliferation of (2 x 13)F(1) lymphocytes to a DNP derivative of a copolymer of L-glutamic and L-lysine (DNP-GL) is due to the presence of antibodies specific for the unique antigenic determinants (idiotypes) of clonally distributed T-lymphocyte receptors. Thus, cells obtained from a normal animal and a DNP-GL immune animal were equivalent in their absorptive capacity. Populations of T lymphocytes were ineffective in absorbing either the cytotoxic or inhibitory activity of the anti-2 serum, while L(2)C leukemia cells, a malignant B-cell population, were most efficient in absorbing both activities. Thus, the antigen(s) against which the cytotoxic and inhibitory activities are directed are present to a greater extent on B lymphocytes than on T lymphocytes. However, these results do not allow us to definitively determine whether the inhibitory activity of the alloantisera is due to antibodies specific for Ir gene products or antibodies specific for linked antigens in the MHC. We also examined the effect of a number of anti-immunoglobulin reagents which had specificity for the heavy and/or light chains of guinea pig immunoglobulin on the in vitro lymphocyte proliferative response to antigen. Under conditions in which we were able to completely and specifically suppress the response of (2 x 13)F(1) lymphocytes to DNP-GL with anti-2 serum, the anti-immunoglobulin reagents were devoid of inhibitory effect on the response of these same F(1) cells to DNP-GL, a copolymer of L-glutamic and L-tyrosine (GT), or purified protein derivative of tuberculin (PPD). These results strongly suggest that conventional serum-type immunoglobulin is not important in antigen recognition by the T cells involved in the DNA synthetic response.
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PMID:Alloantiserum-induced inhibition of immune response gene product function. I. Cellular distribution of target antigens. 459 Nov 74

The effect of lysine/arginine antagonism on the survival of mice with virally - produced leukemia was investigated by feeding AKR mice diets low in arginine with varying amounts of lysine. Over a period of one year, a diet containing 5.6% lysine and no arginine resulted in a significantly lower mortality than one with lower levels of lysine, plus arginine.
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PMID:Effect of lysine on survival of AKR leukemic mice. 609 57

Monoclonal DNP-specific IgG (lambda 2 epsilon 2), IgM (kappa 2 mu2) and IgG [kappa 2 (gamma 1)2] were isolated fom the culture supernatant of hybridomas by affinity chromatography with 2,4-dinitrophenol bovine serum albumin (DNP-BSA) sepharose and characterized by biochemical and biological methods. The molecular weights were 84,200 for the epsilon chain, 55,400 for the gamma chain and 77,500 for the mu chain as determined by sodium dodecylsulphate polyacrylamide del electrophoresis (SDS-PAGE). The association constants for [3H]-DNP-lysine determined by equilibrium dialysis were 0 . 87 X 10(7) l/mol for IgE and 1 . 91 X 10(8) 1/mol for IgG1. The isoelectric focusing of the purified monoclonal antibodies revealed for IgG1 seven bands at a pH range of 6 . 3 - 7 . 2 and for IgE sixteen bands at a pH range of 4 . 5 to 6 . 8. the binding of 125I-anti-IgE to rat basophilic leukaemia (RBL) and rat mast cells which had been preincubated with various amounts of monoclonal IgE was studied. At saturation conditions of IgE, about 2 . 14 X 10(5) molecules of anti-IgE were bound per rat mast cell. Rat mast cells coated with monoclonal anti-DNP IgE were triggered for the release of histamine in the presence of either the antigen or guinea-pig anti-mouse IgE. A mutual inhibition of the passive cutaneous anaphylaxis (PCA) reaction in the rat by either mixing mouse reaginic serum directed against ovalbumin or rat reaginic serum directed against Nippostrongylus brasiliensis with monoclonal mouse anti-DNP IgE was demonstrated.
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PMID:Generation of monoclonal murine anti-DNP-IgE, IgM and IgG1 antibodies: biochemical and biological characterization. 618 Sep 75

The gag-related proteins found in cells transformed by avian erythroblastosis virus (AEV) and the avian myelocytomatosis viruses MC29 and CMII have been compared by tryptic peptide fingerprinting. A comparison of the methionine-containing tryptic peptides of the AEV 75-kilodalton protein, the CMII 90-kilodalton protein, and the MC29 110-kilodalton protein with the gag gene product Pr76 of their naturally occurring helper leukemia viruses enabled us to distinguish those peptides related to the gag gene from the non-gag-related peptides. The 12 non-gag peptides found in the AEV 75-kilodalton protein were unique to this protein and not found in the MC29 110-kilodalton or CMII 90-kilodalton proteins. In contrast, the MC29 110-kilodalton protein shared two methionine-containing non-gag tryptic peptides with the CMII 90-kilodalton protein. When these experiments were repeated with [14C]lysine and [14C]arginine as the labeled amino acids, the MC29 110-kilodalton protein and the CMII 90-kilodalton protein were found to share 30 out of approximately 40 non-gag-related peptides. These results demonstrate that viruses with a similar transformation spectrum synthesize related proteins and suggest that the gag-related proteins represent the transforming proteins of the replication-defective avian leukemia viruses.
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PMID:Comparative tryptic peptide mapping studies suggest a role in cell transformation for the gag-related protein of avian erythroblastosis virus and avian myelocytomatosis virus strains CMII and MC29. 624 97

Mink cells nonproductively-infected with the weakly-transforming T-8 isolate of murine leukemia virus (MuLV) express a 110,000 mol wt polyprotein designated T-8 P110. By immunoprecipitation analysis, T-8 P110 is shown to contain AKR-MuLV amino terminal gag gene-specific components (p15, p12) but to lack p30, p10, gp70, and p15(E) antigenic determinants. These observations are further substantiated by tryptic peptide analysis indicating T-8 P110 to share approximately six lysine-containing tryptic peptides with AKR-MuLV Pr65gag, and none with AKr-MuLV Pr82env. Furthermore, of seven methionine-containing T-8 P110 tryptic peptides, at least four can be conclusively shown not to be present in either AKr-MuLV Pr180gag/pol or Pr82env. A clonal mink cell line nonproductively infected by T-8, and expressing high levels of P110, although not morphologically transformed, is shown to lack elevated levels of tyrosine-specific protein kinase activity and reduction of epidermal growth factor binding sites characteristic of cells transformed by many other RNA-transforming viruses. These findings argue either that the T-8 viral genome contains acquired cellular sequences encoding a portion of P110, or that T-8 P110 represents an inphase deletion of AKR-MuLV Pr180gag/pol with extensive posttranlational modification and that an as yet unidentified protein is responsible for T-8 associated transformation.
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PMID:Identification of tryptic peptides unique to a 110,000-molecular weight polyprotein encoded by the T-8 isolate of murine leukemia virus. 625 65


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