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 human leukemia cell line K562 is erythroid and expresses the major red cell sialoglycoprotein, glycophorin A. With this cell line we have studied the biosynthesis of glycophorin A after pulse-chase labeling with [35S] methionine. Using lectin-Sepharose affinity chromatography and immune precipitation with specific anti-glycophorin A antiserum followed by polyacrylamide slab gel electrophoresis a precursor of glycophorin A was visualized. This had an apparent molecular weight of 37000 and contained an incompleted N-glycosidic oligosaccharide and unfinished O-glycosidic oligosaccharides. After chase for 10 min, the completed glycophorin A with an apparent molecular weight of 39000 was seen and it appeared at the cell surface in about 30 min. Using tunicamycin N-glycosylation was inhibited but not O-glycosylation. The absence of the N-glycosidic oligosaccharide did not affect the migration of the protein to the cell surface but the yield of glycophorin A was diminished. Translation of glycophorin A messenger-RNA was achieved in a rabbit reticulocyte cell-free system. This yielded a non-glycosylated protein with an apparent molecular weight of 19500, which exceeded that of the glycophorin A apoprotein with about 5000. This indicates the presence of a "signal sequence" in the preprotein. When the translation was performed in the presence of microsomal membranes from dog pancreas the glycophorin A apoprotein aws both N-and O-glycosylated and the apparent molecular weight (37000) of the synthesized protein was identical to that of the precursor obtained from cells.
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PMID:Biosynthesis of the major human red cell sialoglycoprotein, glycophorin A. A review. 701 5

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

Hydrogenolysis of 3-(benzyloxy)cyclophosphamide (10) using Pd/C catalyst and ethyl acetate as solvent leads to the formation of 3-hydroxycyclophosphamide (3, approximately 20%) and cyclophosphamide (1, approximately 10%), accompanied by regioselective hydrogen-exchange reactions at the C-4 and C-5 positions in 3 and 1. A variety of oxidizing reagents and liver microsomal incubation failed to provide evidence (31P NMR) for conversion of 1 into 3, whereas identical incubation of 3 led to its reduction to 1. Compound 3 is stable at pH 6.5-8.2, 37 degrees C, and exhibits anticancer activity comparable to 1 when tested against L1210 leukemia in mice. Data are discussed with regard to a previously reported suggestion that metabolism of 1 may involved oxidation to give 3 followed by rearrangement of 3 to 2.
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PMID:Synthesis of 3-hydroxycyclophosphamide and studies related to its possible role in the metabolism of cyclophosphamide. 731 Aug 17

It has been shown that the major cyclooxygenase product in rat basophilic leukemia (RBL-1) cells and in normal rat mast cells is prostaglandin D2. In RBL-1 cells, prostaglandin D2 is isomerase activity was found in the 150 000 X g microsomal pellet as well as the supernatant fraction. Incubation of RBL-1 microsomes with arachidonic acid without cofactors yielded 17.5 +/- 2% prostaglandin E2 and 9.1 +/- 1.4% prostaglandin D2. The cyclooxygenase activity was enhanced (25%) by epinephrine and the addition of reduced glutathione led to a marked increase in prostaglandin D2 synthesis (3-fold). Incubations with arachidonic acid, glutathione and epinephrine gave the maximum conversion to prostaglandin D2, yielding 7 +/- 0.4% prostaglandin E2 and 35.6 +/- 3.5% prostaglandin D2. Incubations with [14C]prostaglandin H2 to bypass cyclooxygenase confirmed the presence and glutathione dependence of the prostaglandin D2 isomerase in the microsomal fraction and also revealed the presence of the same enzyme in the 150 000 X g supernant. In contrast to RBL-1 cells, incubations of microsomes and supernatant from normal rat mast cells with [14C]-arachidonic acid and [14C]prostaglandin H2 localized the prostaglandin D2 isomerase activity in the soluble fraction. Similar to the enzyme in the RBL-1 cells, the mast cell enzyme was glutathione dependent.
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PMID:Enzymatic formation of prostaglandin D2 by rat basophilic leukemia cells and normal rat mast cells. 737 31

The function of a 58-kDa liver microsomal protein (P58) is controversial. To help clarify the physiological function of this protein, particularly in humans, a full-length human liver cDNA clone was isolated, sequenced, and expressed in milligram quantities with the use of a baculovirus expression system. The deduced amino acid sequence of the mature protein contained two thioredoxin-like active site motifs (CGHC) and in its C-terminus a nuclear localization motif (KPKKKKK), and an ER-retention/retrieval motif (QEDL). The mature form of human P58 shared 95% amino acid sequence identity with the deduced amino acid sequences of a bovine liver cDNA, 93% with a murine B lymphocyte cDNA, and 91% with a rat basophilic leukemia cell cDNA. In contrast to reports on the activities of nonhuman forms of P58, the purified expressed human P58 showed no carnitine acyltransferase or protease activities. However, it did have protein disulfide isomerase activity, indicating that the physiological activity of human liver P58 may be attributed, at least in part, to this activity.
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PMID:cDNA cloning and baculovirus expression of the human liver endoplasmic reticulum P58: characterization as a protein disulfide isomerase isoform, but not as a protease or a carnitine acyltransferase. 748 4

Human T-lymphotropic virus type I (HTLV-I) is a causative retrovirus of adult T-cell leukemia lymphoma and HTLV-I associated myelopathy/tropical spastic paraparesis. HTLV-I is also associated with some forms of pulmonary alveolitis, chronic arthropathy, polymyositis, and uveitis. In this study, the possible role of HTLV-I infection in the pathogenesis of autoimmune thyroid diseases with positive antithyroid antibody (ATA) to microsomal antigen or thyroglobulin was evaluated. In Fukuoka Prefecture or the northern part of Kyushu Island located in the southwestern part of Japan, the prevalence of patients with HTLV-I antibody was screened using the particle agglutination test and then was further confirmed either by the indirect immunofluorescence method or the western blot method. The observed prevalence in patients with thyroid disorders and the estimated prevalence calculated considering the sex- and age-specific prevalence among healthy blood donors (n = 16,008) were as follows: 19 (7.4%) vs 7.8 (3.0%) (p < 0.001) for ATA-positive chronic thyroiditis (n = 257), 21 (7.0%) vs 6.6 (2.2%) (p < 0.001) for ATA-positive Graves' disease (n = 298), 4 (4.3%) vs 2.1 (2.2%) (ns) for ATA-negative Graves' disease (n = 94), 1 (2.9%) vs 1.1 (3.1%) (ns) in ATA-negative hypothyroidism (n = 35), and 3 (1.8%) vs 5.0 (2.9%) (ns) for ATA-negative nodular goiter (n = 170). These findings thus suggest that HTLV-I infection may have some relationship to ATA-positive thyroid disorders.
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PMID:A high prevalence of human T-lymphotropic virus type I carriers in patients with antithyroid antibodies. 771 4

Overnight (10-16 h) incubation of retinoic acid (RA), a derivative of vitamin A, specifically induced LTC4 synthase activity (5 to 10-fold), but not LTA4 hydrolase activity in the lysate of rat basophilic leukemia-1 (RBL-1) cells. A time course study revealed that the increase of LTC4 synthase activity was time dependent and that the peak value was obtained after a 24-hour incubation with RA. The induction of enzyme activity was specifically localized to the microsomal fraction. Glutathione (GSH) S-transferase activity measured by using the same cell lysate as an enzyme source and 1-chloro-2,4-dinitrobenzene (DNCB) as a substrate was not influenced by RA treatment, indicating that the induction by RA is specific for membrane-bound LTC4 synthase. The induction of LTC4 synthase may be an important regulatory mechanism of peptide-LT synthesis in allergy and inflammatory diseases.
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PMID:Specific induction of LTC4 synthase by retinoic acid in rat basophilic leukemia-1 cells. 811 Dec 44

The compound 4-(diethylamino)benzaldehyde (DEAB) is a potent inhibitor of cytosolic (class 1) aldehyde dehydrogenase (ALDH) in vitro and can overcome cyclophosphamide resistance in murine leukemia cells characterized by their high content of ALDH. In this study, we examined the in vivo effect of DEAB in mice on ethanol metabolism and on antipyrine clearance as a measure of the microsomal mixed function oxidase activity. DEAB administered in doses of 50 and 100 mg/kg increased the blood acetaldehyde concentration and decreased the plasma acetate concentration in mice treated with ethanol. A pharmacokinetic approach demonstrated that DEAB in doses of 50 and 100 mg/kg inhibited the fraction of ethanol converted to acetate by 32.5 and 67.5%, respectively. This inhibition was comparable with that produced by disulfiram. DEAB produced optimal inhibition of ALDH 10-15 min after administration. DEAB did not change the half-life or the total clearance of antipyrine. We conclude that DEAB is a potent inhibitor of ALDH in vivo and has no effect on the mixed function oxidase activity as determined by antipyrine clearance.
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PMID:Effect of 4-(diethylamino)benzaldehyde on ethanol metabolism in mice. 811 35

We investigated the mechanism of resistance in murine L1210 leukaemia cells selected after treatment with FCE 23762 methoxymorpholinyl doxorubicin: (MMRDX), a methoxymorpholinyl derivative of doxorubicin active in vitro and in vivo on multidrug-resistant (mdr) cells, currently undergoing phase I clinical trials. The resistant subline obtained after repeated in vitro treatments, L1210/MMRDX, is resistant in vitro and in vivo to all tested methoxymorpholinyl derivatives and to cyanomorpholinyl doxorubicin, but shows resistance to morpholinyl derivatives only in vivo or following their activation with rat S9-liver fractions in vitro. L1210/MMRDX cells are sensitive to classic mdr- and altered topoisomerase (AT)-mdr-associated drugs. These cells do not appear to overexpress the mdr1 gene, nor do they exhibit impaired intracellular drug accumulation and efflux or altered levels of glutathione and glutathione S-transferase. The extent of DNA single-strand break formation and, after microsomal activation, of DNA interstrand cross-links after treatment with MMRDX was similar in the parent and the resistant subline. The mechanism of resistance in L1210/MMRDX cells remains to be identified but may prove a novel one, highly specific for this class of mdr-active anthracyclines.
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PMID:L1210 cells selected for resistance to methoxymorpholinyl doxorubicin appear specifically resistant to this class of morpholinyl derivatives. 829 27

The expression of angiotensin-I converting enzyme (ACE; EC 3.4.15.1) in human circulating mononuclear cells was studied. T-lymphocytes contained the highest level of enzyme, approx. 28 times more per cell than monocytes. No activity was detected in B-lymphocytes. ACE was present mainly in the microsomal fraction, where it was found to be the major membrane-bound bradykinin-inactivating enzyme. An mRNA for ACE was detected and characterized after reverse transcription and amplification by PCR in T-lymphocytes and several T-cell leukaemia cell lines. We have previously observed that the interindividual variability in the levels of ACE in plasma is, in part, genetically determined and influenced by an insertion/deletion polymorphism of the ACE gene. To investigate the mechanisms involved in the regulation of ACE biosynthesis, the ACE levels of T-lymphocytes from 35 healthy subjects having different ACE genotypes were studied. These levels varied widely between individuals but were highly reproducible and influenced by the polymorphism of the ACE gene. T-lymphocyte levels of ACE were significantly higher in subjects who were homozygote for the deletion than in the other subjects. These results show that ACE is expressed in T-lymphocytes and indicate that the level of ACE expression in cells synthesizing the enzyme is genetically determined.
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PMID:Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. 838 80


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