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)

The FL-74 cell, a feline lymphoblastoid cell line derived from a tumor induced by leukemia virus, grows equally well in static suspension culture (plastic T-flask or silicone treated glass bottles) or in spinner culture. No growth was observed in unsiliconized glass bottles. Although feline leukemia virus production was nearly the same in FL-74 grown in each of the above types of vessel, the expression of the feline oncornavirus membrane associated antigen (FOCMA), as determined by membrane immunofluorescence, was more intense and more complete on cells grown in static suspension. Moreover, higher fluorescent antibody titer endpoints were observed with cells from static suspension cultures than with cells from spinner cultures, FL-74 cells grown in spinner culture, when subjected to partial synchrony by cold block or by deprivation of essential amino acids (arginine and/or isoleucine) for 12 hr, achieved a membrane fluorescent pattern for FOCMA similar to cells grown in static suspension. It is proposed that the expression of FOCMA on the cell membrane surface is cell-cycle dependent, and that the rate at which a cell passes through the cell cycle determines the pattern and intensity of the fluorescence of the cell membrane.
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PMID:Influence of culture conditions of growth of FL-74 cells and feline oncornavirus cell membrane associated antigen production. 17 37

The toxicity of lectins from castor bean (Ricinus communis L.), ricin-D, ricin-E, and castor bean hemagglutinin, was investigated on five cultured cell lines. The differential effect of their constituent polypeptide chains was also investigated using these cell lines. Ricin-D, ricin-E, and castor bean hemagglutinin (CBH) possessed cytoagglutinating activity and cytotoxic activity to all five cell lines. These lectins showed the strongest toxicity to L5178Y cells, which are leukemic cells. The toxic activity of ricin-D was stronger than that of CBH in all cell lines. The constituent polypebtide chains of ricin-D and CBH were separated by DEAE-cellulose chromatography and designated as isoleucine chain and alanine chain denoted by their N-terminal amino acids. Only alanine chain of ricin-D was toxic to cells grown in vitro, whereas isoleucine chain of ricin-D and alanine chain of CBH were not toxic to the cells. Moreover, it was found that both lectins caused syncytium formation in NIH3T3 cells infected with Moloney leukemia virus and this cell fusion activity was shown to be exclusively associated with the alanine chain. Cytotoxic, cell agglutinating, and syncytium forming effect of the lectins is due to binding of the alanine chain of ricin-D to galactose-like residues of the membrane constituents of these cells.
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PMID:Cytotoxic, cell agglutinating, and syncytium forming effect of purified lectins from Ricinus communis on cultured cells. 52 Jul 50

Avian c-erbB is activated to a leukemia oncogene following truncation of its amino-terminal, ligand-binding domain by retroviral insertion. The insertionally activated transcripts encode protein products that have constitutive tyrosine kinase activity and that can induce erythro-leukemia but not sarcomas. We have found that a single point mutation within the ATP-binding pocket of the tyrosine kinase domain in this truncated molecule can increase the ability of this oncogene to induce anchorage-independent growth of fibroblasts in vitro and fibrosarcoma formation in vivo. Associated with this increased transforming potential is a corresponding increase in the kinase activity of the mutant erbB protein product. The mutation, which converts a valine to isoleucine at position 157 of the insertionally activated c-erbB product, is at a residue that is highly conserved within the protein kinase family. To our knowledge, this is the first demonstration of a point mutation in the ATP-binding pocket that activates a tyrosine kinase.
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PMID:Tissue-specific transformation by epidermal growth factor receptor: a single point mutation within the ATP-binding pocket of the erbB product increases its intrinsic kinase activity and activates its sarcomagenic potential. 197 68

Friend murine leukemia virus is a replication-competent retrovirus that contains no oncogene and that exerts lytic and leukemogenic properties. Thus, newborn mice inoculated with Friend murine leukemia virus develop severe early hemolytic anemia before appearance of erythroleukemia. To identify the retroviral determinants regulating these effects, we used chimeric infectious constructions and site-directed point mutations between a virulent Friend murine leukemia virus strain and a naturally occurring variant attenuated in lytic and leukemogenic effects. We found that severe hemolytic anemia was always associated with higher numbers of blood reticulocytes with budding retroviral particles. Furthermore, a remarkably conservative leucine to isoleucine change in the extracellular SU component of the retroviral envelope was sufficient to attenuate this lytic effect. Also, this leucine at position 348 of the envelope precursor protein was located within the only stretch of five amino acids that is conserved in the extracellular SU component of all murine, feline, and primate type C and type D retroviral envelopes. This observation suggested an important structural function for this yet undescribed conserved sequence of the envelope. Lastly, we observed that lytic and leukemogenic effects were attenuated by a deletion of a second repeat in the transcriptional enhancer region of the viral long terminal repeats of the variant strain.
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PMID:Substitution of leucine for isoleucine in a sequence highly conserved among retroviral envelope surface glycoproteins attenuates the lytic effect of the Friend murine leukemia virus. 206 71

Acivicin is an investigational amino acid antitumor antibiotic currently being evaluated in Phase II clinical trials. In humans acivicin causes reversible, dose-limiting central nervous system (CNS) effects including somnolence, ataxia, personality changes, and hallucinations. We have observed and reported previously that acivicin-treated cats exhibit symptoms (ataxia, sedation, somnolence) resembling CNS toxicity reported in humans. We hypothesized that if acivicin uptake into brain were mediated by a saturable transport system common to endogenous amino acids, drug uptake and CNS toxicity might be blocked by elevation of normal amino acid concentrations in circulating plasma. To test this hypothesis, cats received constant-rate i.v. infusions of either saline or Aminosyn, 10% (a commercially available mixture of 16 amino acids not containing glutamine, glutamate, aspartate, or cysteine) for 4 h prior to and 18 h subsequent to administration of acivicin at a dose producing marked behavioral changes in control cats. Presence or absence of ataxia and sedation were noted at intervals after acivicin treatment. Results showed that Aminosyn infusion prevented CNS symptoms in six of eight cats. Subsequent experiments showed that acivicin levels in brain tissue of Aminosyn-treated cats were 13% of the drug levels in saline-infused cats. Acivicin levels in most peripheral tissues were also decreased significantly by Aminosyn infusion but not to the extent observed in brain. Decreased brain uptake was shown to be due to a combination of amino acid blockade of drug transport into that organ and of increased total body clearance of drug. Concomitant Aminosyn treatment did not alter the efficacy of acivicin in mice bearing L1210 leukemia or MX-1 human mammary carcinoma. Further studies demonstrated that a solution containing only four large neutral amino acids (leucine, isoleucine, phenylalanine, and valine) could also protect cats from acivicin-induced CNS toxicity, apparently without increasing acivicin total body clearance. However, a mixture of several other amino acids contained in Aminosyn (alanine, arginine, tyrosine, histidine, proline, serine, and glycine) failed to prevent CNS toxicity. We conclude that cotreatment with Aminosyn or a mixture of large neutral amino acids could protect cancer patients from acivicin-induced CNS toxicity without ablating antitumor efficacy.
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PMID:Prevention of central nervous system toxicity of the antitumor antibiotic acivicin by concomitant infusion of an amino acid mixture. 238 52

The replication of Moloney murine leukemia virus (MMuLV) in chronically infected mouse cells arrested at the G0/G1 phase of the cell cycle by different procedures was investigated. MMuLV production was inhibited in glutamine- and isoleucine (Gln-Ile)-deprived G0/G1 cells. In contrast, butyric acid treatment, which efficiently arrested the cells at the G0/G1 phase of the cell cycle, did not inhibit MMuLV production. Furthermore, the inhibition of MMuLV production caused by either Gln-Ile deprivation or by interferon (IFN) treatment was overcome by butyric acid treatment. Thus, the replication of MMuLV could be dissociated from cell proliferation. The inhibition of MMuLV production in Gln-Ile-deprived cell cultures was compared to the inhibitory effect of IFN, which is known to affect budding and release of the virus. Rates of MMuLV protein synthesis were not affected in both the IFN-treated and Gln-Ile-deprived cells. However, processing of the viral polyprotein Pre65gag into p30 was blocked in the Gln-Ile-deprived cells. Furthermore, whereas in IFN-treated cells, MMuLV accumulated on the cell surface and could be released upon treatment with trypsin, in Gln-Ile-deprived cells, no virions were released by such treatment. These results indicate that in cells arrested by Gln-Ile deprivation, MMuLV is inhibited at a posttranslation step. This step appears to precede the anti-MMuLV block induced by IFN.
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PMID:Regulation of Moloney murine leukemia virus replication in chronically infected cells arrested at the G0/G1 phase. 258 48

A large scale production of human recombinant IL-5 (hIL-5) was performed by way of recombinant DNA technology. In this study, we transfected Chinese hamster ovary cells with pdKCR-hIL-5gene-dhfr plasmid and selected a cell line, with the use of methotrexate, producing large amounts of hIL-5. The recombinant hIL-5 thus obtained induced IgM production of murine B cell leukemia BCL1, and its activity was inhibited by TB13 anti-mouse IL-5 monoclonal antibody. hIL-5 could be purified from the cell-free supernatants of the transfectants with high recoveries by using anti-mouse IL-5 antibody-coupled immunoaffinity column in combination with a gel permeation column chromatography. N terminal amino acid sequence analysis of purified hIL-5 revealed that a single amino-terminal amino acid (isoleucine) is detected and hIL-5 consists of 115 amino acid residues.
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PMID:Rapid methods for purification of human recombinant interleukin-5 (IL-5) using the anti-murine IL-5 antibody-coupled immunoaffinity column. 260 55

The envelope glycoproteins of the human immunodeficiency virus (HIV) type 1 are synthesized as a precursor molecule, gp160, which is cleaved to generate the two mature envelope glycoproteins, gp120 and gp41. The cleavage reaction, which is mediated by a host protease, occurs at a sequence highly conserved in retroviral envelope glycoprotein precursors. We have investigated the sequence requirements for this cleavage reaction by introducing four single-amino-acid changes into the glutamic acid-lysine-arginine sequence immediately amino terminal to the site of cleavage. We have also examined the effects of these mutations on the syncytium formation induced by HIV envelope glycoproteins. Our results indicate that a glutamic acid to glycine change at gp120 amino acid 516, a lysine to isoleucine change at amino acid 517, and an arginine to lysine change at amino acid 518 affect neither gp160 cleavage nor syncytium formation. The results obtained with the arginine to lysine change at amino acid 518 differ significantly from the results obtained with the same mutation at the envelope precursor cleavage site of a murine leukemia virus (E. O. Freed, and R. Risser, J. Virol. 61:2852-2856, 1987). An arginine to threonine mutation at gp120 amino acid 518, the terminal residue of gp120, abolishes both gp160 cleavage and syncytium formation. These findings demonstrate that despite its highly conserved nature, the basic pair of amino acids at the site of gp160 cleavage is not absolutely required for proper envelope glycoprotein processing. This report also supports the idea that cleavage of gp160 is required for activation of the HIV envelope fusion function.
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PMID:Mutational analysis of the cleavage sequence of the human immunodeficiency virus type 1 envelope glycoprotein precursor gp160. 267

The production of Moloney murine leukaemia virus from chronically infected cells was inhibited after starvation of glutamine. While the rate of synthesis of the precursor of the core proteins, Pr65gag, was not affected in the starved cells, its proteolytic processing was blocked. Pulse-chase experiments indicated that glutamine was required during the synthesis of Pr65gag to facilitate its subsequent processing. In addition, the synthesis of Pr200gag-pol, the precursor of the protease, reverse transcriptase and endonuclease, was inhibited in the glutamine-starved cells. Starvation for other essential amino acids such as tyrosine and isoleucine affected neither the synthesis nor the processing of the virus proteins. These results suggest that the readthrough mechanism which enables synthesis of the Pr200gag-pol polyprotein is modulated in the chronically infected cells by glutamine levels. Since the viral protease is part of the pol gene, its synthesis may be inhibited in the glutamine-starved cells and Pr65gag is therefore not processed.
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PMID:Glutamine starvation of murine leukaemia virus-infected cells inhibits the readthrough of the gag-pol genes and proteolytic processing of the gag polyprotein. 348 14

Previously, in vitro recombinant DNA studies demonstrated that genetic determinants of N-tropism and B-tropism, or Fv-1-related host range properties of murine leukemia viruses, were located in a BamHI-HindIII DNA segment derived from the 5' portion of the cloned viral genome. We sequenced this segment and its immediate 5' region from cloned DNA of two BALB/c mouse C-type viruses (WN1802N and WN1802B) and found base differences at 12 positions out of the otherwise identical 1,390-base-pair sequences. Analysis of the most likely reading frame showed that 6 of the 12 base differences would result in four encoded amino acid changes, three of which occur at positions 109 (glutamine in WN1802N versus threonine in WN1802B), 110 (arginine in WN1802N versus glutamic acid in WN1802B), and 159 (glutamic acid in WN1802N versus glycine in WN1802B) of the p30 protein. The remaining one is located at position 36 (threonine in WN1802N versus isoleucine in WN1802B) of the viral polymerase protein. Significant conformational alteration of the p30 protein could be predicted from these amino acid changes.
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PMID:Nucleotide sequences of gag-pol regions that determine the Fv-1 host range property of BALB/c N-tropic and B-tropic murine leukemia viruses. 631 71


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