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 Pr65gag proteolytic factor obtained from Moloney (MoLV) or Rauscher (RLV) leukaemia virus has been characterized. We found that it was present in small amounts in virions and was extremely unstable. Although it eluted at the trailing edge of p12 on Sephadex G-75 columns, it could clearly be separated from p12 on DEAE-Sephadex A-50M columns, making it unlikely that the factor is p12 or any other major murine leukaemia virus (MuLV) protein. This fact also distinguishes the murine factor from the avian tumour viruses and is stable to column purification methods (von der Helm, 1977; Dittmar & Moelling, 1978). We further observed that: (i) the murine proteolytic factor had an estimated mol. wt. of 20,000 to 22,000, relative to MuLV p12, which eluted as a dimer on Sephadex G-75 columns in the presence of 0.1% NP-40; and (ii) in vitro cleavage of an iodinated Pr65gag-rich, p30-deficient substrate yielded a clear increase in both p30 and p12, which suggests that the in vitro cleavage of Pr65gag is similar to its processing in vivo.
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PMID:Physicochemical characterization and specificity of the murine leukaemia virus Pr65gag proteolytic factor. 699 61

Tumor-specific transplantation antigens unique to each of MM2, MM46 and Ehrlich mouse ascites tumor cells (cell line-specific antigens) were released from the cells into the medium during incubation in 0.12M saline at 37 degrees for 30 min. The released antigens were purified by identical procedures which consisted of ultracentrifugation, affinity chromatography using Sepharose 4B conjugated with Ricinus communis lectin, and DEAE-cellulose column chromatography. The recovery was about 700 micrograms (protein) from 100 g (wet weight) cells. The recovered materials induced specific immunity in C3H/He mice against transplantation of the corresponding tumor cells only when they were administered after treatment with the corresponding tumor-regressor C3H/He mouse serum. Single injection into the peritoneal cavity of 10 mcrograms of each of the pretreated materials inhibited transplantation of 5 x 10(3) corresponding tumor cells. Spleen cells from mice immunized by repeated injections of the pretreated antigen neutralized transplantability of the tumor cells. Specific humoral antibody was also detected. The specific antigens obtained from these cells were similar to each other with respect to sedimentation coefficient (16S), electrophoretic characteristics and xenogeneic antigenicity, and were free of beta-2 microglobulin, murine leukemia virus major structural proteins such as gp70 or p30 and murine mammary tumor virus proteins such as gp55 and p28.
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PMID:Purification of cell line-specific transplantation antigens from mouse ascites tumor cells. 711 55

Two isoenzyme of beta-glucuronidase from a rat basophil leukaemia tumour were co-purified 4067-fold by (NH4)2SO4 precipitation and sequential chromatography on concanavalin A--Sepharose, Sephadex G-200, DEAE-cellulose, CM-cellulose and phosphocellulose. The purity of the mixture was established by the coincidence of the peaks of enzyme activity and protein at a molecular weight of 300 000 on Bio-Gel P-300, the presence of only two protein bands, both of them enzymically active, in polyacrylamide gels after electrophoresis under non-denaturing conditions, and the presence of a single subunit species, of mol.wt. 75 000, after electrophoresis in polyacrylamide gels under a denaturing conditioning. The major isoenzyme co-migrated with the L form from rat liver during electrophoresis in alkaline polyacrylamide gels, whereas the minor isoenzyme migrated more rapidly than either the lysosomal form or the rat liver microsomal form and was designated the tumour (T) isoenzyme. A mixture of the purified isoenzymes from two preparations had an average specific activity of 1389 units/mg for phenolphthalein beta-D-glycopyranosiduronic acid. The L and T isoenzymes, which had pI5.9 and 5.7 respectively, could be obtained free of cross-contamination by isoelectric focusing and had similar specific activities. Although the T isoenzyme could be a catabolic product of the M or the L form, it could also be a unique tumour product, because it was not detected in extracts of normal rat tissues.
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PMID:Purification and characterization of a lysosomal form and a variant form of beta-glucuronidase from the rat basophil leukaemia tumour. 730 55

A solid leukemia sarcoma has been successfully developed after subcutaneous inoculation of the cultured human promyelocytic leukemia cells (HL-60 cells) into nude mice. The solid leukemia sarcoma is a more plentiful source than the cultured cells for enzymatic study and its growing environment is closer to that of the human body than the cultured cells. We established an efficient procedure of purifying HL-60 cells DNA methylase which includes: disruption of HL-60 cells by homogenization and sonication, removing the cell fragments and cellular particles by centrifuge and ultracentrifuge (105,000 g); removing endogenous DNA by streptomycin sulfate, salting out by (NH4)2SO4, ion exchange chromatography on DEAE-cellulose (DE-52), gel filtration over Sephadex G-100 column. The DNA methylase from HL-60 cells has been purified 204 fold by this procedure. The purified enzyme shows a single-band on PG-PAGE. A 479-kD molecular weight of this enzyme is measured by PG-PAGE. The enzyme properties of HL-60 DNA methylase are also studied.
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PMID:Purification and characterization of DNA methylase from HL-60 cells. 806 96

Soluble sonic extracts of several strains were examined for their ability to alter proliferation of a cell line derived from acute lymphoblastic leukaemia (BALL-1). Extracts of all strains tested caused dose-dependent suppression of proliferation when assessed by DNA (tritiated thymidine incorporation), RNA (tritiated uridine incorporation) and protein (tritiated leucine incorporation) synthesis. There was no effect on the viability of BALL-1 as measured by either trypan-blue exclusion or extracellular release of the cytoplasmic enzyme lactate dehydrogenase. The suppressive factor(s) was separated in a well-defined peak by high-pressure liquid DEAE ion-exchange chromatography, which revealed a single active peak with a molecular mass of 48 kDa. Characterization of the peak indicated that the suppressive factor(s) was heat labile (activity destroyed at 80 degrees C) and sensitive to the proteolytic enzyme pronase P. The soluble suppressive factor(s) from Campylobacter rectus thus has protein-like properties and no cytotoxicity to a human B-cell leukaemic cell line.
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PMID:Suppression of proliferation of a human B-cell leukaemic cell line derived from acute lymphoblastic leukaemia by soluble factor(s) from Campylobacter rectus. 834 67

We looked for chemotaxin/interleukin 8 (CT/IL-8) activity in the culture fluids of 97 human leukemia cell lines and found it in two of the T cell lines, six of the myeloid cell lines, and one of the normal B-cell lines. It was particularly strong in the culture fluids of two cell lines. These cell lines secreted a chemotactic protein into the culture fluids under certain conditions of stimulation with phorbol-12-myristate 13-acetate (PMA), lipopolysaccharide, or hemagglutinin-P. A myeloid leukemia cell line, ML-1, secreted an inducible chemotaxin when stimulated with PMA (1 ng/ml) for 24 h. We purified the chemotaxin from ML-1 cell culture fluid using an improved procedure: concentration with DEAE-Sepharose CL-6B and CM-Sepharose CL-6B, CM-Sepharose column chromatography, and reverse-phase 5TMS-300 column on HPLC with the retention time coinciding with that of LUCT/IL-8 [Suzuki et al., 1989, J. Exp. Med. 169, 1895]. The yield was 200 micrograms protein from 6 liters of the culture fluid. The N terminus of CT/IL-8 was AVLPR-SAKELRXQXIKTYSK- - -, the same as that of LUCT/IL-8, which is constitutively secreted from lung giant cell carcinoma LU65C cells. The optimal concentration in the chemotactic activity of CT/IL-8, equivalent to that of bacterial chemotactic peptide fMet-Leu-Phe (10 nM), was found to be 5 nM. The results show that this chemotaxin is identical to LUCT/IL-8.
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PMID:Isolation and amino acid sequence of a chemotactic protein, LECT/interleukin 8, from a human myeloid leukemia cell line, ML-1. 834 17

Intradermal injection of a cloned bovine leukemia virus (BLV) provirus (pV344) into sheep allowed direct evaluation of intrastrain variability. A sheep was injected with pV344 DNA mixed with DEAE-dextran and became persistently infected with BLV strain 344. After 18 months, DNA was extracted from peripheral blood leukocytes from a single 0.5-ml blood sample. The long terminal repeat (LTR) and the env gene were amplified by using the polymerase chain reaction, cloned, and sequenced. Nineteen independent LTR clones (0.6-kb inserts) and 16 env clones (1-kb inserts) were analyzed. The in vivo rate of nucleotide change was 0.009%/year (two mutations out of 14,464 bp in 1.5 years), corresponding to only one amino acid change in the env gene. Five point mutations (all transitions), corresponding to a modification rate of 0.034%/year (five mutations out of 9,709 bp in 1.5 years), were identified in the LTR. As a control for Taq DNA polymerase errors, the same procedure using pV344 plasmid DNA was carried out. Out of 9,944 bp sequenced, three point mutations were found (i.e., one misincorporation in 3,315 nucleotides). These data demonstrate the extremely low level (or absence) of intrastrain variability of BLV in vivo. Consequently, BLV persistence in the infected host does not seem to result from an escape mutant strategy, in sharp contrast with the high mutation rates observed in the lentivirus family. The lack of genetic variation supports the possibility of successful vaccine against BLV and probably against the related human T-cell leukemia viruses.
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PMID:Bovine leukemia virus, an animal model for the study of intrastrain variability. 838 Apr 55

Deoxycytidine kinase is a key anabolic enzyme for the activation of ara-C and other antitumor drugs, as well as normal purine and pyrimidine deoxynucleotides. Previously, two forms of the kinase have been identified; deoxycytidine kinase I (70 kDa) and deoxycytidine kinase II (70 kDa). Deoxycytidine kinase I utilized dCyd and ara-C as substrates, while deoxycytidine kinase II used dCyd and dThd as substrates. Deoxycytidine kinase kinase II had very low activity on ara-C as a substrate. We report a procedure for the purification of a novel deoxycytidine kinase (52 kDa) from isolated human peripheral blood leukemia cell mitochondria. This enzyme has activity similar to deoxycytidine kinase II. The enzyme was extracted from the mitochondria with digitonin (1 mg/8 mg protein) and 0.3 M NaCl, and the extract was purified by DEAE-cellulose chromatography and thymidine-Sepharose affinity chromatography. This procedure produced a near homogeneous enzyme preparation with a yield of 70%. The mitochondrial deoxycytidine kinase was localized to the outer mitochondrial membrane. The enzyme phosphorylated dCyd (Km = 17 microM), however, ara-C was not a good substrate for the mitochondrial deoxycytidine kinase. ATP was the best phosphate donor, whereas dCTP and dTTP were potent inhibitors of mitochondrial deoxycytidine kinase. In contrast, phosphorylation of ara-C by deoxycytidine kinase I utilized GTP, dGTP, or ATP as a phosphate donor.
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PMID:Purification and characterization of deoxycytidine kinase from acute myeloid leukemia cell mitochondria. 839 94

Transferrin-neocarzinostatin (NCS) conjugates with differing molar ratios of drug to protein were synthesized and their intracellular metabolism was investigated. The conjugate mixtures of transferrin-NCS were separated by DEAE-Sephacel column chromatography. The separated molecular species were examined with respect to binding affinity to transferrin receptor, cytotoxicity and intracellular metabolism using the human leukemia cell line, K562. Transferrin-NCS conjugate is capable of binding to transferrin receptors specifically and its reactivity became weaker as the ratio of bound NCS to transferrin was increased. Transferrin-6NCS did not bind measurably to the receptor. On the other hand, the cytotoxicity was augmented when the number of NCS molecules bound per molecule of transferrin was increased to 4NCS/transferrin, while transferrin-5NCS and transferrin-6NCS species exhibited low activity. Examination of the kinetics of metabolism by pulse chase study using 125I-labeled ligand indicated that unconjugated transferrin and transferrin-NCS conjugates were internalized in similar ways, although the degradation of internalized conjugate was more marked in the case of transferrin-4NCS than transferrin-1NCS. Thus, the molar ratio of transferrin-drug conjugate could be optimized with respect to both the binding activity to receptor and the intracellular metabolic pathway.
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PMID:Intracellular metabolism and cytotoxicity of transferrin-neocarzinostatin conjugates of differing molar ratios. 846 35

The protein tau was degraded to distinct products by a DNA-stimulated protease isolated from human leukemia HL-60 cell extracts. The enzyme partially purified by sequential chromatography on GTP-agarose, DEAE-cellulose, and TSK 3000 (0.6 X 60 mm) columns eluted as a 300-450 kDa protein which appeared as 60-90 kDa polypeptides on SDS-PAGE. Protease activity was stimulated by synthetic and natural DNAs and was most active at pH 8.5. Human recombinant tau3 was degraded by the DEAE-cellulose-eluted protease to a 26-kDa and several 14- to 16-kDa peptides. Degradation of tau was partially blocked by preincubation with tubulin, suggesting that the DNA-stimulated cleavage of tau occurred at the carboxyl-terminus, at or near the "tubulin-interactive" domains. The 26-kDa fragment was shown by amino acid sequencing to correspond to the N-terminus of tau whereas sequencing of the 16-kDa fragment yielded YKPVDLSKVT. These results show the existence of a DNA-stimulated protease capable of cleaving tau3 between valine-220 and tyrosine-221 (equivalent to valine 309 and tyrosine-310 of tau4).
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PMID:Specific cleavage of recombinant protein tau3 between valine-220 and tyrosine-221 (val-309 and tyr-310 of tau4) by a double-stranded DNA-stimulated protease. 861 41


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