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)

Carrier-immobilized mono- or disaccharides and other carbohydrate structures, derived by custom-made chemical synthesis, have already proven to be valuable ligands for localizing carbohydrate-binding proteins in tissue sections. Defined purified glycopeptides, as components of neoglycoproteins, offer the possibility of increasing their structural complexity and, thereby, their receptor selectivity. To test the feasibility of this approach, the glycopeptide man6-glcNAc2-asparagine derived from ovalbumin was purified after pronase digestion. It was coupled to bovine serum albumin as carrier protein with the homobifunctional linking agent bis-(sulphosuccinimidyl)suberate to yield the diglycosylated concanavalin A-reactive product. Following biotinylation, it was used to detect mannose-specific binding sites in fixed cells of seven human leukemia or lymphoma lines and in fixed, paraffin-embedded sections of human breast cancer. In comparison to chemically mannosylated bovine serum albumin with ten sites of glycosylation or to ovalbumin, this derivative produced a similar pattern of reaction with a quantitatively lower extent of staining in most cases. Remarkably, the presence of potential endogenous ligands for the detected receptor sites was ascertained using the plant lectin concanavalin A. Thus, the conjugation of a purified, deliberately selected glycopeptide to a suitable carrier produces a histochemical tool for detecting glycopeptide-specific binding sites.
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PMID:Glycopeptide-albumin derivative: it preparation and histochemical ligand properties. 172 27

A number of lactose-binding lectins have recently been identified in the rat and mouse intestine, one of which corresponds to the C-terminal domain of IgE-binding proteins, originally identified in rat basophilic leukemia (RBL) cells and mouse 3T3 fibroblasts. In the present report, we describe the affinity purification of a rat intestinal lactose-specific lectin which binds murine IgE antibodies. This binding most likely occurs via the immunoglobulin carbohydrate chains, as it is inhibited by lactose. This intestinal lectin molecule is also immunologically related to the previously described IgE-binding protein (epsilon BP) isolated from RBL cells, since it is recognized by antibodies raised against recombinant epsilon BP. This intestinal form of epsilon BP has a molecular mass of 17.5 kDa, which is much lower than that of its RBL cell analogue (31 kDa). The attachment of IgE to the mouse intestinal epithelium was demonstrated by immunohistochemistry, along with the presence of a corresponding mouse intestinal epsilon BP. The carbohydrate-dependent nature of this attachment was established by demonstrating that IgE binding to mouse epithelium was specifically abolished by lactose (4 mM) and by a blood-group-A-active tetrasaccharide (0.2 mM), but not by mannose (10 mM). Finally, the association of IgE with the mouse intestinal epithelium was prevented by competition with the purified IgE-binding lectin isolated from rat intestine. Although the physiological function of this intestinal protein is still unknown, the finding that IgE binds to a lectin in the intestinal epithelium pinpoints a possible novel mechanism for the regulation of IgE-mediated disorders, such as food allergy.
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PMID:An intestinal galactose-specific lectin mediates the binding of murine IgE to mouse intestinal epithelial cells. 173 27

DNA topoisomerase inhibitors, camptothecin and 4'-demethylepipodophyllotoxin ethylidene-beta-D-glucoside (VP16) had strong differentiation-inducing activity for all five kinds of leukemia cells examined (human HL60, U937, ML1, and K562 cells and mouse M1 cells) as judged from measurements of various differentiation markers. The characteristics that appeared as a result of differentiation induced by these inhibitors were essentially similar in every cell line. Exposure to VP16 for 2 h induced both differentiation and DNA-strand breaks in K562 cells, whereas podophyllotoxin, which lacks topoisomerase II inhibitory activity, induced neither differentiation nor DNA-strand breaks in these cells. These results suggest a parallelism between the induction of differentiation and that of DNA-strand breaks. The combination of VP16 and recombinant tumor necrosis factor alpha (rTNF alpha) synergistically induced differentiation of human U937, ML1, and M1 cells and had an additive effect on HL60 cells. Simultaneous treatment with rTNF alpha plus camptothecin or VP16, or pretreatment with camptothecin or VP16, followed by rTNF alpha induced marked differentiation of M1 cells. These results indicate that inhibition of topoisomerase (either topoisomerase I or II) followed by the action of rTNF alpha was effective in inducing differentiation of leukemia cells.
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PMID:Topoisomerase inhibitors have potent differentiation-inducing activity for human and mouse myeloid leukemia cells. 184 45

The purpose of this study was to characterize the surface receptor for toxin A, the enterotoxin from Clostridium difficile, on rabbit intestinal brush borders (BB) and on rat basophilic leukemia (RBL) cells. Purified toxin A was radiolabeled using a modified Bolton-Hunter method to sp act 2 microCi/micrograms, with retention of full biologic activity. 3H-Toxin A bound specifically to a single class of receptors on rabbit BB and on RBL cells with dissociation constants of 5.4 x 10(-8) and 3.5 x 10(-8) M, respectively. RBL cells were highly sensitive to toxin A (cell rounding) and had 180,000 specific binding sites per cell, whereas IMR-90 fibroblasts were far less sensitive to toxin A and lacked detectable specific binding sites. Exposure of BB to trypsin or chymotrypsin significantly reduced 3H-toxin A specific binding. Preincubation of BB with Bandeirea simplicifolia (BS-1) lectin also reduced specific binding, and CHAPS-solubilized receptors could be immobilized with WGA-agarose. The addition of 100 nM toxin A accelerated the association of 35S-GTP gamma S with rabbit ileal BB, and preincubation of BB with the GTP analogues GTP gamma S or Gpp(NH)p, significantly reduced 3H-toxin A specific binding. Our data indicate that the membrane receptor for toxin A is a galactose and N-acetyl-glucosamine-containing glycoprotein which appears to be coupled to a G protein.
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PMID:Characterization of rabbit ileal receptors for Clostridium difficile toxin A. Evidence for a receptor-coupled G protein. 190 25

An ecotropic virus was chemically modified in order to determine whether its target cell specificity could be altered. We hypothesized that chemical coupling of galactose residues to a virus might permit specific infection of hepatocytes mediated by asialoglycoprotein receptors unique to these cells. To test this hypothesis, we took advantage of the fact that: 1) artificial asialoglycoproteins can be created by chemical coupling of lactose to proteins; and 2) viruses that are ecotropic have a narrow species specificity. An ecotropic, rodent-specific, replication-defective murine leukemia virus containing the gene for beta-galactosidase was chemically modified with lactose to contain 5.9 mumol of lactose per mg of viral RNA. Modified and unmodified viruses were incubated for 5 days with HepG2, a human hepatoma line that possesses asialoglycoprotein receptors, and SK Hep1, a human cell line that does not. As expected from the ecotropism, unmodified virus did not produce beta-galactosidase activity in either cell type. Modified virus did not produce beta-galactosidase activity in SK Hep1 cells. However, modified virus did produce beta-galactosidase activity, 71.2 units/mg of cell protein, in the human receptor (+) HepG2 cells. Interestingly, modification of the virus also resulted in decreased enzyme activity in previously susceptible host rodent cells. Competition with modified virus by an excess of an asialoglycoprotein completely prevented development of enzymatic activity in HepG2 cells. Histochemical treatment of cells with 5-bromo-4-chloro-3-indoyl beta-D-galactoside to detect in situ beta-galactosidase activity demonstrated that only HepG2 cells treated with modified virus were positive and that 36% of these cells were stained after 5 days. These data indicate that chemical modification of a virus can result in a redirection of the infectivity of the virus toward hepatocyte-derived cells mediated by the presence of asialoglycoprotein receptors.
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PMID:Chemical modification of an ecotropic murine leukemia virus results in redirection of its target cell specificity. 190 69

We assayed in the yeast S. cerevisiae the transcriptional transactivation activity of the c-myb products encoded by a normal thymus cDNA and of an aminoterminally truncated version of it (minus 58 amino acids) corresponding to the cDNAs isolated from lymphoma and leukemia cells from different origins. Both proto-oncogene products were expressed under the control of the galactose inducible GAL10 promoter. The reporter system used to monitor the transactivation potential of the myb products consisted of a CYCl-lacZ gene fusion in which the UASCYC signals were replaced by one or multiple copies of the myb recognition element (mRE). As shown by Northern blot analyses and by primer extension experiments both c-myb products increase the level of beta-galactosidase transcription. Interestingly, the c-myb product corresponding to lymphoma cDNAs stimulates transcription four to five times more efficiently than does the normal thymic c-myb product.
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PMID:Two c-myb proteins differing by their aminotermini exhibit different transcriptional transactivation activities (yeast/reporter-effector system). 199 38

We have studied the biosynthesis of altered O-glycan structures on leukocytes from patients with chronic myelogenous leukemia and with acute myeloblastic leukemia (AML). It has been shown previously that the activity of CMP-NeuAc:Gal beta 1-3GalNAc alpha-R (sialic acid to galactose) alpha(2-3)-sialytransferase (EC 2.4.99.4) is increased in leukocytes from patients with chronic myelogenous leukemia (M. A. Baker, A. Kanani, I. Brockhausen, H. Schachter, A. Hindenburg, and R. N. Taub, Cancer Res., 47: 2763-2766, 1987) and with AML (A. Kanani, D. R. Sutherland, E. Fibach, K. L. Matta, A. Hindenburg, I. Brockhausen, W. Kuhns, R. N. Taub, D. van den Eijnden and M. A. Baker, Cancer Res., 50: 5003-5007, 1990). This increased activity may in part be responsible for the hypersialylation observed in leukemic leukocytes; however, hypersialylation may also be due to changes in underlying O-glycan structures. To test this hypothesis, we have assayed in normal human granulocytes and leukemic leukocytes several glycosyltransferases involved in the synthesis and elongation of the four common O-glycan cores. UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta(1-6)-GlcNAc transferase (EC 2.4.1.102), which synthesizes O-glycan core 2 (GlcNAc beta 1-6[Gal beta 1-3]GalNAc alpha), is significantly elevated in chronic myelogenous leukemia (4-fold) and AML (18-fold) leukocytes relative to normal human granulocytes. Neither normal nor leukemic cells show detectable activities of GlcNAc transferases which synthesize O-glycan core 3 (GlcNAc beta 1-3GalNAc-R) and core 4 (GlcNAc beta 1-6[GlcNAc beta 1-3] GalNAc-R) or the blood group I structure. The beta 3-GlcNAc transferase which elongates core 1 and core 2 was found at low levels in normal granulocytes but was not detectable in leukemic cells. The beta 3-GlcNAc transferase and beta 4-Gal transferase involved in poly-N-acetyllactosamine synthesis, as well as the beta 3-Gal transferase synthesizing core 1 (Gal beta 3 GalNAc), were present in all samples but were significantly increased in patients with AML. The observed changes are consistent with hypersialylation in leukemia.
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PMID:Biosynthesis of O-glycans in leukocytes from normal donors and from patients with leukemia: increase in O-glycan core 2 UDP-GlcNAc:Gal beta 3 GalNAc alpha-R (GlcNAc to GalNAc) beta(1-6)-N-acetylglucosaminyltransferase in leukemic cells. 199 66

The effect of adriamycin, daunomycin, N,N-dimethyladriamycin, N,N-dimethyldaunomycin, pyrromycin, marcellomycin, and aclacinomycin A on erythroid differentiation and glycoprotein synthesis in Friend erythroleukemia cells, clone F4-6 was investigated. Whereas N-dimethylated natural anthracyclines, pyrromycin, marcellomycin, and aclacinomycin A stimulated erythroid differentiation (induction of hemoglobin synthesis), this was not seen with adriamycin, daunomycin and their N-dimethylated derivatives. The incorporation of 3H-mannose in glycoprotein was inhibited by the N-alkylated natural anthracyclines at a concentration at which they induced erythroid differentiation. N,N-Dimethyladriamycin and N,N-dimethyldaunomycin only inhibited 3H-mannose incorporation into glycoprotein at cytotoxic concentrations. However, adriamycin and daunomycin did not inhibit glycoprotein synthesis, even at high cytotoxic concentrations. Aclacinomycin A decreased the incorporation of 3H-mannose into proteins earlier than the incorporation into dolichol-linked oligosaccharide intermediates. Tunicamycin, a specific inhibitor of glycoprotein synthesis, failed to stimulate differentiation in Friend erythroleukemia cells. These results indicate a structure-specific induction of the differentiation and inhibition of glycoprotein synthesis in Friend cells by N-alkylated anthracyclines. The inhibition of glycoprotein synthesis may be involved in the induction of differentiation by N-alkylated anthracyclines, but it cannot be the only target for the differentiation-inducing effect of these substances.
Leukemia 1991 Feb
PMID:Structure-activity relationship between anthracycline-induced differentiation and inhibition of glycoprotein synthesis in Friend erythroleukemia cells. 202 Feb

The major nucleoside transporter of the human T leukemia cell line CEM has been identified by photoaffinity labeling with the transport inhibitor nitrobenzylmercaptopurine riboside (NBMPR). The photolabeled protein migrates on SDS-PAGE gels as a broad band with a mean apparent molecular weight (75,000 +/- 3000) significantly higher than that reported for the nucleoside transporter in human erythrocytes (55,000) (Young et al. (1983) J. Biol. Chem. 258, 2202-2208). However, after treatment with endoglycosidase F to remove carbohydrate, the NBMPR-binding protein in CEM cells migrates as a sharp peak with an apparent molecular weight (47,000 +/- 3000) identical to that reported for the deglycosylated protein in human erythrocytes (Kwong et al. (1986) Biochem. J. 240, 349-356). It therefore appears that the difference in the apparent molecular weight of the NBMPR-sensitive nucleoside transporter between the CEM cell line and human erythrocytes is a result of differences in glycosylation. The NBMPR-binding protein from CEM cells has been solubilized with 1% octyl glucoside and reconstituted into phospholipid vesicles by a freeze-thaw sonication technique. Optimal reconstitution of uridine transport activity was achieved using a sonication interval of 5 to 10 s and lipid to protein ratios of 60:1 or greater. Under these conditions transport activity in the reconstituted vesicles was proportional to the protein concentration and was inhibited by NBMPR. Omission of lipid or protein, or substitution of a protein extract prepared from a nucleoside transport deficient mutant of the CEM cell line resulted in vesicles with no uridine transport activity. The initial rate of uridine transport, in the vesicles prepared with CEM protein, was saturable with a Km of 103 +/- 11 microM and was inhibited by adenosine, thymidine and cytidine. The Km for uridine and the potency of the other nucleosides as inhibitors of uridine transport (adenosine greater than thymidine greater than cytidine) were similar to intact cells. Thus, although the nucleoside transporter of CEM cells has a higher molecular weight than the human erythrocyte transporter, it exhibits typical NBMPR-sensitive nucleoside transport activity both in the intact cell and when reconstituted into phospholipid vesicles.
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PMID:Identification and reconstitution of the nucleoside transporter of CEM human leukemia cells. 211 49

FeLV-FAIDS, an immunodeficiency-inducing isolate of feline leukemia virus, is composed of a pathogenic but replication-defective genome (molecular clone 61C) and a replication-competent but non-immunodeficiency-inducing variant genome (molecular clone 61E). The chimeric virus EECC, composed of the 5' gag-pol of 61E fused to the env-3' LTR of 61C, also induces immunodeficiency. The 61C (or EECC) gp80 can be distinguished from that of 61E on the basis of antigenic recognition, size, and rate of posttranslational processing. We found that the nascent precursor polypeptides of the two viruses were the same size; however, the 61E gp80 rapidly shifted to a smaller size and was subsequently cleaved to gp70, whereas EECC gp80 maintained its nascent size and was cleaved to gp70 only after a prolonged time. Endo-beta-N-acetyl glucosaminidase H and N-glycanase digestions of newly formed glycoproteins resulted in a similar banding pattern for both viruses, indicating that both contained the same number of oligosaccharide side chains and that all of these were high mannose sugars. The metabolic inhibitors of glycosylation, castanospermine or N-methyldeoxynojirimycin, prevented both the rapid trimming of 61E gp80 and its cleavage to gp70. Treatment with mannosidase inhibitors, however, did not affect 61E gp80 processing or size, suggesting that retention of glucose residues on EECC was responsible for these distinguishing properties of the glycoprotein. The pathological consequence of aberrant viral glycoprotein processing was evaluated in feline 3201 T lymphocytes, which are infectable by both 61E and EECC but are killed only by EECC. As in fibroblasts, the EECC glycoprotein produced in lymphocytes was larger, antigenically distinct, and processed more slowly than was the glycoprotein of 61E. Castanospermine treatment of 61E-infected 3201 T cells, however, not only abrogated the antigenic differences between the 61E and EECC glycoproteins but also resulted in a cytopathic effect. Our results suggest that (i) intracellular accumulation of EECC envelope glycoprotein may occur consequent to retention of glucose residues on carbohydrate side chains and (ii) a strong correlation exists between delayed glycoprotein processing and cytopathicity in FeLV-FAIDS-infected T lymphocytes.
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PMID:Characterization and significance of delayed processing of the feline leukemia virus FeLV-FAIDS envelope glycoprotein. 216 20


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