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)

Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cis-platin in Sprague-Dawley rats. The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride. Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat. Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin-induced nephrotoxicity. The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat. With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds. With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin. Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur-containing compounds currently in clinical use may have equivalent or superior properties in this respect.
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PMID:Control of the nephrotoxicity of cisplatin by clinically used sulfur-containing compounds. 160 Dec 18

The knowledge about the differentiation of basophilic leukocytes is fragmentary. This report discusses a detailed phenotypic characterization of molecular markers for hematopoietic differentiation in a basophilic leukemia cell line, KU812. The expression of markers for lymphoid, erythroid, neutrophil, eosinophil, monocytic, megakaryocytic, mast cell and basophil differentiation was analyzed at the mRNA level by Northern blots in the KU812 cells, and for reference, in a panel of human cell lines representative of the different hematopoietic differentiation lineages. KU812 was found to express a number of mast cell and basophil-related proteins, i.e. mast cell tryptase, mast cell carboxypeptidase A, high-affinity immunoglobulin (IgE) receptor alpha and gamma chains and the core protein for heparin and chondroitin sulphate synthesis. We found no expression of a number of monocyte/-macrophage or neutrophil leukocyte markers except for lysozyme. From earlier studies, it has been shown that lysozyme is not expressed in murine mucosal mast cell lines. This finding, together with the expression of the mast cell carboxypeptidase in KU812 might distinguish the phenotype of this cell line from that typical of mucosal mast cell lines in rodents. We found a low level of expression of the eosinophil and basophil marker, major basic protein, which might indicate a relationship between basophils and eosinophils. No expression is, however, detected with the eosinophil-specific markers eosinophil cationic protein, eosinophil-derived neurotoxin or eosinophil peroxidase. We also report an extensive screening for inducers of basophilic differentiation of the KU812 cells. The most efficient protocol of induction included serum starvation which led to a dramatic increase in a number of markers specific for mast cells and basophils such as tryptase, carboxypeptidase A and the heparin core protein. Finally, diisopropylfluorophosphate analysis of total protein extracts from KU812 show four labeled protein bands with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that this cell line expresses at least three previously undescribed serine proteases of which one or more could be a potential basophil-specific marker(s).
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PMID:Phenotypic characterization of KU812, a cell line identified as an immature human basophilic leukocyte. 163 3

The first high performance liquid chromatographic method for determination of the plasma concentration of 2-chloro-2'-deoxyadenosine (CdA) in patients, which is significantly more sensitive than the previously used RIA method, is presented. CdA is a purine analogue with useful clinical activity against lymphoproliferative disorders and it has recently been found to be the single most active agent in the treatment of hairy cell leukaemia. Guaneran (6-nitroimidazol-6-thioguanine) was added to 1 mL plasma as the internal standard and CdA was extracted using ethyl acetate. A Perkin-Elmer C18, 3 mu, 8 cm column was used for the separation of CdA and the internal standard from endogenous compounds in the sample with a mixture of sodium phosphate buffer 10 mM, methanol and acetonitrile (85:10:5, pH = 3.0) as the mobile phase. The sensitivity of the method (1 nM) allows the determination of CdA in plasma 24 h after the administration of 0.14 mg/kg as a 2 h infusion.
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PMID:Determination of 2-chloro-2'-deoxyadenosine in human plasma. 168 27

Bleomycin (BLM) has been successfully used to treat a number of human neoplasms. The main toxicity associated with BLM therapy is an acute pulmonary inflammation that can culminate in diffuse chronic fibrosis. The effect of BLM-induced pulmonary inflammation on the cytostatic activity of alveolar macrophages (AM) was investigated using AM obtained from rats that had been previously treated with BLM. Bronchoalveolar lavage fluid was collected at selected time intervals following a single fibrogenic dose of intratracheally administered BLM (3.6 mg/kg). AM obtained 12 to 72 h following intratracheal BLM (BLM-AM) caused cytostasis of murine leukemia L1210 cells in co-culture, whereas AM obtained from saline-treated controls were not cytostatic. These results indicate that the growth-inhibitory activity of the AM was related to the pulmonary inflammation. Cytostatic activity in control AM could be induced by in vitro exposure to lipopolysaccharide (5 micrograms). When RBC were added to the AM-L1210 co-culture, the cytostatic activity of the BLM-AM was abrogated. The fact that chemical treatment of the RBC with sodium nitrite and potassium cyanide or N-ethylmaleimide did not alter the ability of the RBC to abrogate AM cytostatic activity suggests that the RBC is not acting as a scavenger of oxygen radicals. In contrast, the addition of FeSO4 to the AM-L1210 co-culture mimicked the effect of RBC addition. Aconitase, an iron-sulfur-containing enzyme necessary for mitochondrial respiration, is decreased in L1210 cells that have been co-cultured with BLM-AM but not when the co-cultures also contain RBC. These results suggest that (a) pulmonary inflammation induces cytostatic activity in AM, (b) the alteration of iron homeostasis plays an important role in this cytostatic process, and (c) RBC can prevent this cytostatic activity.
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PMID:Effect of erythrocytes on alveolar macrophage cytostatic activity induced by bleomycin lung damage in rats. 169 May 96

The presence of 10 microM dipyridamole in incubation media of L1210/C2 cells decreased initial rates of zero-trans influx of formycin B (FB, 50 microM), a poorly metabolized inosine analogue, from 4.84 pmol/microliters cell water/s to 0.87 pmol/microliter cell water/s. However, after a 5-min interval of uptake, free FB levels in dipyridamole-treated cells were 165 pmol/microliters cell water, 2.3-fold greater than in dipyridamole-free cultures. This indicated the presence of a concentrative, dipyridamole-insensitive nucleoside transport (NT) system in L1210 cells, in addition to the equilibrative NT systems known to be expressed in these cells. The concentrative system was demonstrable only in the presence of NT inhibitors and required extracellular Na+. The presence of 8 microM 6-[(4-nitrobenzyl)thio]-9-beta-D- ribofuranosylpurine or 15 microM dilazep also induced an accumulation of free FB above steady-state levels, although of a lesser magnitude than that observed with dipyridamole. It appears that NT inhibitors induced nucleoside accumulation by inhibiting bidirectional nucleoside movements mediated by the equilibrative component of nucleoside transport in L1210/C2 cells without interfering with inward FB fluxes mediated by the Na(+)-dependent transporter. The presence of NT inhibitors also enhanced the cellular accumulation and retention of arabinosyladenine and its 5'-triphosphate in these cells. The increased cellular accumulation of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosyladenine triphosphate by dipyridamole was associated with enhanced antiproliferative activity of 9-beta-D-arabinofuranosyladenine towards the leukemia cells.
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PMID:Sodium-dependent and equilibrative nucleoside transport systems in L1210 mouse leukemia cells: effect of inhibitors of equilibrative systems on the content and retention of nucleosides. 169 38

The effect of nedocromil sodium on the generation of neutrophil-derived histamine-releasing activity (HRA-N) from human peripheral blood neutrophils and on the secretory effects of HRA-N and anti-IgE on rat basophil leukemia (RBL) cells was studied. Nedocromil sodium caused dose-related inhibition of HRA-N generation by human neutrophils (10(-7) to 10(-4) mol/L; inhibitory concentration of 50%, 1.5 x 10(-8) mol/L). In contrast, the presence of nedocromil sodium had no effect on HRA-N-mediated serotonin release from RBL cells. In five experiments, with one crude and four partially purified HRA-N preparations, serotonin release from RBL cells exposed to native HRA-N or HRA-N in the presence of nedocromil sodium (10(-4) mol/L) was 28% +/- 6% and 26% +/- 5%, respectively. Similar results were found with all concentrations of nedocromil sodium studied. Preincubation of RBL cells with nedocromil sodium (10(-4) mol/L) for 0 to 60 minutes also did not affect HRA-N-mediated serotonin release. Likewise, nedocromil sodium (10(-7) to 10(-4) mol/L) had no effect on anti-IgE-induced serotonin release from RBL cells. In 10 experiments, anti-IgE alone or in the presence of nedocromil sodium (10(-4) mol/L) induced 32% +/- 6% and 32% +/- 5% serotonin release, respectively. Preincubation of RBL cells with nedocromil sodium before anti-IgE exposure had no further effect. This is the first study of pharmacologic manipulation of the generation of a histamine-releasing factor. It is hypothesized that one possible mechanism whereby nedocromil sodium protects against asthma and allergic rhinitis is through inhibition of HRA-N generation.
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PMID:Neutrophils and mast cells: nedocromil sodium inhibits the generation of neutrophil-derived histamine-releasing activity (HRA-N). 170 28

The glycoproteins on the surface of HL-60/S wild-type, drug-sensitive human leukemia cells and HL-60/AR anthracycline-resistant cells which do not overexpress the P-glycoprotein, were characterized by labeling with [35S]-methionine, NaB[3H4], phosphorus 32, or sodium iodide I 125. HL-60/S and HL-60/AR cell lysates and membrane fractions tagged with [35S]-methionine or phosphorus 32 showed no significant differences in their protein patterns as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and by autoradiography. HL-60/S cells labeled with NaB[3H4] yielded glycoproteins that were smeared predominantly in the molecular-weight range of 210,000 and 160,000 Da, with pI values ranging between pH 4 and pH 4.4. In contrast, NaB[3H4]-labeled HL-60/AR cells showed 7-8 discrete glycoproteins within a molecular-weight range of 170,000 and 140,000 Da, with pI values also ranging between pH 4 and pH 4.4. In addition, [3H]-glucosamine incorporation into HL-60/S and HL-60/AR cells revealed that the latter showed lower uptake of [3H]-glucosamine than did the former. Following treatment with tunicamycin, [3H]-glucosamine uptake in HL-60/S cells decreased, whereas that in HL-60/AR cells remained unchanged. Surface-membrane radioiodination of HL-60/S and HL-60/AR cells showed two distinct protein electrophoretic patterns, with differences being observed in both the high-(220-95 kDa) and low-molecular-weight ranges (21 kDa). Flow cytometric analysis of HL-60/S and HL-60/AR cells using myeloid and lymphoid antigen-specific antibodies demonstrated no antigenic differences between HL-60/S and HL-60/AR cells. HL-60/S cells incubated in the presence of tunicamycin, an inhibitor of N-linked glycosylation, or the protein kinase C agonist phorbol 12-myristate 13-acetate (PMA) developed a glycoprotein pattern similar to that observed in HL-60/AR cells. In addition, tunicamycin treatment of HL-60/S cells decreased daunorubicin (DNR) retention and altered its intracellular distribution as compared with that in HL-60/AR cells. These data indicate that HL-60/AR cells do not possess either de novo or amplified high-molecular-weight surface-membrane proteins; instead, existing proteins are hypoglycosylated. These results also show that HL-60/AR cells exhibit the multidrug-resistant phenotype in association with altered membrane glycoproteins of both high (220-95 kDa) and low molecular weight (21 kDa), but without overexpression of the P-glycoprotein. Furthermore, in HL-60/S cells, the multidrug-resistant phenotype is partially inducible by inhibition of N-linked glycosylation of cell-surface proteins.
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PMID:Membrane glycoprotein changes associated with anthracycline resistance in HL-60 cells. 171 35

Tyrosine protein kinase activity was examined during the induction of granulocytic differentiation of WEHI-3B murine monomyelocytic leukemia cells by retinoic acid and aclacinomycin A. Tyrosine kinase activity was found to increase throughout the period of induced maturation. The specificity of this increase in enzymatic activity for the differentiated state was demonstrated by the findings that (a) it was independent of the inducer used, and (b) the treatment of a differentiation-resistant subline of this murine leukemia with an inducer did not produce a significant elevation of tyrosine kinase activity. To determine whether tyrosine protein kinase activity was involved in the differentiation process itself or whether it was a product of the mature state, a series of experimental approaches was employed. Kinetic analyses showed that tyrosine protein kinase activity continued to increase beyond the peak in the level of differentiation. In addition, the total cellular protein phosphotyrosine content, measured by immunoblotting and flow cytometric analysis with anti-phosphotyrosine antibodies, did not increase in accord with the elevation of tyrosine kinase activity. Increases in protein phosphotyrosine content, which were dependent upon the length of exposure to the inducing agent, were observed when cultured cells were treated with the phosphotyrosine phosphatase inhibitor, sodium orthovanadate. Thus, the effect of the increasing tyrosine kinase activity in maturing cells appeared to be negated by competing protein phosphotyrosine phosphatase activity. Finally, the inhibitors of tyrosine kinase activity, genistein and PKI-23, did not interfere with the induction of differentiation by retinoic acid. These findings support the concept that myeloid differentiation associated tyrosine protein kinase activity may not be involved in the initiation of the differentiation process itself. This conclusion deviates from previous assumptions, based on earlier work in this laboratory as well as in that of others, that the differentiation associated kinase activity has an essential role in the initiation of the maturation process. An attractive alternative speculation is that this activity may have a functional role in the mature myeloid cell.
Leukemia 1991 Oct
PMID:Myeloid differentiation associated tyrosine protein kinase activity in WEHI-3B murine monomyelocytic leukemia cells. 172 Apr 91

We have previously shown that transferrin receptor (TfR) recycles from the cell surface through the Golgi complex in K562 human leukemia cells. However, little is known about the transport pathway that carries these receptors to the Golgi complex. To learn more about this transport, we studied the effects of treatments that block specific types of vesicular traffic. K562 cells were cultured in test media and the transport of surface TfR to the Golgi complex was assessed by measuring the entry of asialo-TfR into the sialyltransferase compartment of the Golgi complex. Depletion of cellular potassium, which blocks formation of coated vesicles at the cell surface, stimulated asialo-TfR resialylation by 60% over controls, suggesting that coated vesicle formation is not the rate-limiting step in cell surface-to-Golgi transport. Similarly, culture in sodium-free medium, which blocks transport from endosomes to lysosomes, increased asialo-TfR resialylation by 40%, arguing that lysosomes do not lie on the transport pathway. In contrast, incubation of cells in hypertonic medium, which blocks many vesicular transport steps, inhibited TfR resialylation by 40%, confirming the importance of vesicular traffic in transport of asialo-TfR from the cell surface to the Golgi complex. These results are consistent with two possible pathways for cell surface-to-Golgi transport. Receptor could be transported via an endosomal intermediate, with the rate-limiting step occurring at a post-endosomal site. Alternatively, receptor could be transported directly to the Golgi via a pathway that does not involve endosomes.
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PMID:Role of vesicular traffic in the transport of surface transferrin receptor to the Golgi complex in cultured human cells. 172 35

Human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) were purified by sucrose density gradient centrifugation in the presence of 1 mM EDTA. Pelleted gradient fractions were analyzed for total protein, total Gag capsid protein, and total zinc. Zinc was found to copurify and concentrate with the virus particles. Through successive cycles of resuspending in buffer containing EDTA and repelleting, the zinc content remained constant at about 1.7 mol of zinc per mol of Gag protein. Proteins from purified virus (HIV-1 and HTLV-I) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted to polyvinylidene fluoride paper, and probed with 65ZnCl2. Viral nucleocapsid (NC) proteins (HIV-1 p7NC and HTLV-I p15NC) bound 65Zn2+. Other retroviruses, including simian immunodeficiency virus, equine infectious anemia virus, bovine leukemia virus, Moloney murine leukemia virus, mouse mammary tumor virus, and Mason-Pfizer monkey virus, were found to contain amounts of zinc per milligram of total protein similar to those found in HIV-1 and HTLV-I. Collectively, these data support the hypothesis that retroviral NC proteins function as zinc finger proteins in mature viruses.
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PMID:Tightly bound zinc in human immunodeficiency virus type 1, human T-cell leukemia virus type I, and other retroviruses. 173 Nov 11


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