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)

Treatment of leukotriene A4 (LTA4) methyl ester with sodium hydroxide in aqueous methanol at 4 degrees C afforded LTA4, the presence of which was inferred from the UV spectrum of the compound, its rate of reaction with water, and the identity of the hydration products obtained. The half-life of LTA4 in water (pH 7.4, room temperature) was increased from 14 to 500 s by 1 mg/ml of bovine serum albumin. This stabilized (chiral) LTA4 was converted to LTB4 by an epoxide hydrolase activity in the 100,000 x g supernatant fraction from sonified rat basophilic leukemia cells. Neither the ester of LTA4 nor the biologically incorrect enantiomer of LTA4 was metabolized to LTB4 under these conditions.
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PMID:Leukotriene A4: preparation and enzymatic conversion in a cell-free system to leukotriene B4. 629 15

The histopathological changes in the lungs of 32 patients who died after bone marrow transplantation for leukaemia have been studied and compared with those found in 21 patients treated by conventional chemotherapy. The transplanted patients exhibited a higher incidence of interstitial pneumonitis, vascular lesions and viral infections, particularly cytomegalovirus (CMV), although bacterial and fungal diseases were commoner in the non-grafted subjects. The pathogenesis of interstitial pneumonitis is discussed with specific reference to the possible roles of irradiation, chemotherapy, viruses and the immunosuppressive drug cyclosporin A. Ten patients died of a syndrome characterised clinically by fever, skin rash, fluid retention, uraemia, low serum albumin concentrations, low central venous pressure and acute pulmonary oedema. These patients exhibited intra-alveolar haemorrhagic fibrinous exudation with or without interstitial changes. The aetiology of this syndrome is not known but it occurs more frequently in recipients of mismatched grafts and evidence is presented suggesting that viruses may play a significant causative role. No lesion was identified that could be directly attributed to Graft-versus-Host disease.
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PMID:Histopathology of the lung after bone marrow transplantation. 634 14

Using terminal position, hydrophilicity, predicted reverse turns and type specificity as criteria, five oligopeptides were selected for synthesis from the amino acid sequence of the envelope glycopolypeptide gp70 of Friend murine leukaemia virus. These peptides corresponded to the amino acids 6-12 (pep1), 124-131 (pep2), 256-262 (pep3), 283-290 (pep4) and 434-441 (pep5). After coupling to carriers, bovine serum albumin or keyhole limpet hemocyanin, antisera were prepared in rabbits. All of the five oligopeptides were immunogenic and pep1, pep2, pep4 and pep5 were able to elicit antibodies to the native glycopolypeptide. These sequence-specific antisera distinguished between glycoproteins of different leukaemia viruses. At least three of the selected peptides, the type-specific oligopeptides pep3, pep4 and pep5, were found to be natural epitopes of gp70.
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PMID:Structural and immunological characterization of Friend murine leukaemia virus glycopolypeptide using synthetic oligopeptides. 647 53

Human peripheral blood monocytes isolated from normal donors and patients with acute myelomonocytic leukemia (AMML) were separated on a discontinuous density gradient of bovine serum albumin (BSA) into five fractions. Cells from each fraction were assayed for cell surface markers, prostaglandin E2 (PGE2) production, ability to affect proliferation in response to antigen by autologous peripheral blood lymphocytes previously depleted of monocytes, and ability to regulate immunoglobulin (Ig) synthesis by allogeneic B-lymphocytes. Fractions 1-5 from normal donors contained 11, 10, 23, 34, and 22%, respectively, of the total number of monocytes. In contrast, in 6 patients with AMML fraction 3 was considerably larger (52%) than any other fraction, in 1 patient comprising 87% of her monocytes. Cells from each fraction differed markedly in accessory function. In general, cells from fraction 3 were poorer as helper cells than cells from other fractions. They also produced after stimulation larger amounts of PGE2 than did cells from other fractions of the gradient. These data show that PBL contain a subpopulation of monocytes, which either helps poorly or suppresses in vitro immunologic function of T-cells (proliferation) and B-cells (lg synthesis), and that this subpopulation is increased in the blood of patients with AMML.
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PMID:Altered heterogeneity of monocytes in acute myelomonocytic leukemia. 660 26

Rauscher leukaemia virus (RLV), extensively purified by rate and density gradient centrifugation procedures, exhibited aminopeptidase (AP) activity. The amount of virion activity was about 0.005 times the specific activity of purified hog kidney aminopeptidase M (EC 3.4.11.2). The activity was also found in purified Moloney and Gross leukaemia viruses, but not in comparable gradient fractions of uninfected JLSV-9 cells. Furthermore replacement of serum by bovine serum albumin in the growth medium of virus producing cells did not affect the AP activity. These results indicate that murine leukaemia viruses (MuLV) possess a tightly bound AP activity which is present as a minor component of the virion preparation and is probably not due to host cell membrane or serum contamination. Characterization of the pH optimum and substrate specificity show the MuLV aminopeptidase activity is similar to but different from both hog kidney, leucine aminopeptidase (EC 3.4.11.1) and aminopeptidase M (EC 3.4.11.2).
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PMID:Aminopeptidase activity associated with purified murine leukaemia viruses. 677 35

The membrane protein component in basophils, responsible for the specific, Ca2+-dependent, binding of the anti-allergic drug cromolyn [disodium cromoglycate, DSCG; the disodium salt of 1,2 bis(2- carboxychromon -5- yloxy )-2-hydroxy propane] was isolated by two procedures based on affinity for the drug. In the first procedure, involving immunoprecipitation, rat basophilic leukemia cells (RBL-2H3), surface labeled by 125I were reacted with a polyvalent conjugate of DSCG and bovine serum albumin and then subjected to solubilization by the non-ionic detergent Nonidet P-40 (NP-40). From these lysates, precipitation was specifically attained by subsequent addition of rabbit anti-DSCG antibodies. In an SDS-polyacrylamide gel electrophoresis (SDS-PAGE), a single radioactive band was observed, having an apparent mol. wt. of 60 000 daltons. Competitive inhibition of the immunoprecipitation in the presence of free drug or excess of EDTA demonstrated the specificity of the isolation. Furthermore, this particular membrane component could not be isolated from several other cell types examined. The second isolation from several other cell types examined. The second isolation procedure employed affinity chromatography on DSCG immobilized on polyacryl- hydrazido agarose beads. The DSCG-binding protein was eluted from the affinity column with either DSCG or with EDTA and also migrated on SDS-PAGE as a single band of 60 000 mol. wt., similar to that obtained by the immunoprecipitation procedure. These and other results suggest that this newly isolated protein is the one responsible for the Ca2+-dependent binding of the drug to the basophil membrane.
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PMID:Isolation of a basophilic membrane protein binding the anti-allergic drug cromolyn. 682 55

A difference in the mechanism of transmembrane transport was demonstrated for methotrexate (MTX) and MTX bound to the high molecular weight carrier bovine serum albumin (MTX-BSA) when the drug dose needed to reduce growth of cells to 50% of that of untreated cells (ID50) was compared in the sensitive L1210 leukemia and 3 L1210 sublines resistant to MTX by virtue of either deficient MTX transport or high levels of dihydrofolate dehydrogenase (DHFD). The loss of transport increased the ID50 for inhibition of growth rate by free MTX tenfold to twentyfold, whereas the elevation of DHFD levels increased the ID50 by tenfold. In contrast, deficiency of transport resulted in only a twofold increase in the ID50 for MTX-BSA, and elevation of DHFD caused a tenfold increase similar to that for free MTX. This difference was confirmed in studies of inhibition of DHFD activity by free and BSA-bound MTX. MTX-BSA but not MTX had antitumor activity against the transport-deficient L1210 line in (C57BL/6 x DBA/2)F1. These studies confirm a separate mode of cell entry for MTX-BSA and suggest a role for these complexes in overcoming resistance.
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PMID:Activity of free and carrier-bound methotrexate against transport-deficient and high dihydrofolate dehydrogenase-containing methotrexate-resistant L1210 cells. 693 52

Daunorubicin (DNR) has been conjugated to succinylated serum albumin by an amide bond joining the amino group of the drug and a carboxyl side chain of the protein either directly or with the intercalation of a peptide spacer arm varying from one to four amino acids. During in vitro incubation with lysosomal hydrolases, intact DNR could be released extensively only from conjugates prepared with a tri- or tetrapeptide spacer arm. These latter conjugates remained very stable in the presence of serum. When tested in vivo against the intraperitoneal form of L1210 leukemia, the conjugates in which DNR was linked to serum albumin directly or via one amino acid were completely inactive but the conjugate with a dipeptide spacer arm was not more active than free DNR. In parallel with the in vitro studies, the best therapeutic results were obtained with the conjugates formed with tri- and tetrapeptidic spacer arms; they were much more active than DNR, inducing a high percentage of long-term survivors. Thus, use of a tri- or tetrapeptide spacer arm is essential to obtain DNR-protein conjugates that remain stable in serum and from which DNR can be released through the action of lysosomal hydrolases. The in vivo results suggest, moreover, that these conjugates are endocytosed by L1210 cells and that DNR is released intracellularly after digestion by lysosomal enzymes. This conjugation method can be applied to other drugs possessing a free amino group and to various potential carriers, such as antibodies, polypeptide hormones, and glycoproteins, that have amino or carboxyl side chains.
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PMID:A covalent linkage between daunorubicin and proteins that is stable in serum and reversible by lysosomal hydrolases, as required for a lysosomotropic drug-carrier conjugate: in vitro and in vivo studies. 695 14

Separation of preleukemic cells (having the potential to develop further into overt T-cell leukemias) from bone marrow cell populations was attempted. Donor mice of preleukemic bone marrow included C57BL/6 mice inoculated intrathymically with D-RadLV or AKR/J mice carrying spontaneous preleukemic cells among their bone marrow cells. Fractionation of bone marrow cells suspended in bovine serum albumin (BSA) by equilibrium density centrifugation or by velocity sedimentation at 1 g unit gravity using discontinuous density gradient of Ficoll was applied. The leukemogenic potential of the separated bone marrow fractions was tested by evaluating leukemia development following their transfer into appropriate recipients. No enrichment of D-RadLV-induced preleukemic cells was found in any of the four bone marrow fractions obtained following separation on BSA gradient. Separation of D-RadLV-induced preleukemic cells was afforded by using the Ficoll gradients. Preleukemic cells were located mainly among four out of 21 fractions tested, consisting mostly of 10 to 14 micrometers size cells. In contrast, preleukemic cells from AKR donors were distributed among most of the separated fractions. It is suggested that these variable results may reflect homogeneity or heterogeneity of progenitor target cells undergoing transformation.
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PMID:Distribution of preleukemic cells in fractionated bone marrow of mice. 714 27

The influence of human serum albumin (HA) on the biological effects of 13 chemotherapeutic agents was studied in vitro in the human leukaemia cell line MOLT-3. On the basis of changes in biological activity influenced by HA, these drugs may be divided into three types. Type I agents include cis-diamminedichloroplatinum (II), 4'-(9-acridinylamino)methanesulphon-m-anisidide, neocarzinostatin, nitrogen mustard, adriamycin, daunorubicin and mitomycin C--drugs whose biological activities are reduced in the presence of HA. The biological activities of Type II drugs (cytosine arabinoside, fluorouracil and actinomycin D) are not influenced by HA. The biological activities of Type III drugs (bleomycin, vincristine and vinblastine) are increased in the presence of HA. These results indicate that serum HA interferes in vitro with certain anticancer agents in terms of biological activity and, probably, clinical effectiveness. HA-drug interaction may be a major factor governing the pharmacology of Type I anticancer agents in man.
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PMID:Interaction of human serum albumin with anticancer agents in vitro. 719 20


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