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)

Using a sandwich enzyme-linked immunosorbent assay (ELISA) we were able to detect a soluble form of the CD30 antigen (CD30s) in the supernatant of cell lines expressing membrane-bound CD30 and in T and B cells after transformation with human T-cell leukemia virus (HTLV-I) and Epstein-Barr-Virus (EBV). While CD30s was not found in 250 healthy controls, it was detected in the sera of patients with Hodgkin's disease (23/100), anaplastic large-cell (6/9), angioimmunoblastic (2/2) and one unclassified high-grade non-Hodgkin's lymphoma (NHL), as well as in 18/20 patients with acute adult T-cell leukemia (ATL, HTLV-I-positive). It was absent in a large number of patients with other high-grade NHL, all low-grade NHLs, acute or chronic leukemias and solid tumors. The only non-malignant disease with detectable levels of CD30s was infectious mononucleosis (9/10). The membrane-bound form of CD30 has a molecular weight of 120 kDa. Western blot analysis revealed that CD30s in the serum of patients has a molecular weight of 88 kDa, identical to the antigen released by cell lines in vitro. CD30s disappeared in all originally positive cases after successful treatment and reappeared in relapsing patients. Thus, CD30s may be useful as a specific marker for disease activity of certain types of lymphoma and ATL.
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PMID:Detection of a soluble form of the CD30 antigen in sera of patients with lymphoma, adult T-cell leukemia and infectious mononucleosis. 215 38

A lymphoma cell line (MCC) was derived from an abdominal mass from a 13-yr-old castrated male cat. The cells resemble natural killer precursor cells, have membrane-bound granules, and are positive for chloroacetate esterase, alpha-naphthyl butyrate esterase, and tartrate-resistant acid phosphatase activities. The MCC cells are negative for rearranged feline T-cell receptor genes, negative for feline T-cytotoxic antigen, Ia, and surface mu, tau, and lambda chains and do not form E-rosettes. The MCC cell line is negative for the feline leukemia virus (FeLV); e.g., negative for exogenous FeLV (exU3) sequences, negative for cytoplasmic and surface FeLV major core protein of 27,000 daltons (p27) by indirect immunofluorescence assay, negative for helper FeLV by clone 81 assay, and negative for release of soluble FeLV p27 by enzyme-linked immunosorbent assay. Electron microscopy reveals budding type C retrovirus particles and MCC cells react with anti-RD-114 (anti-endogenous feline retrovirus) reference serum. After in vitro infection, MCC replicate FeLV readily, but replication is noncytopathic.
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PMID:A feline large granular lymphoma and its derived cell line. 216 27

Merocyanine 540 (MC 540) is a photosensitizing dye that is used clinically for the purging of autologous bone marrow grafts and preclinically for the inactivation of enveloped viruses in blood products. Its mechanism of action is not yet well understood. This paper investigates the sites of MC 540-mediated photodamages in L1210 leukemia cells by examining the effects of MC 540-sensitized photoirradiation on several soluble and membrane-bound marker enzymes. When exposed to MC 540 and white light under a standard set of conditions, the activities of Na+/K(+)-ATPase, Mg2(+)-ATPase, and 5'-nucleotidase (three plasma membrane-bound enzymes) were reduced by 54, 49, and 55%, respectively. None of the intracellular enzymes included in this survey was affected by MC 540-sensitized photoirradiation as long as the plasma membrane remained intact. The two soluble enzymes, lactate dehydrogenase and malate dehydrogenase, remained refractory to MC 540-sensitized photoirradiation even after the plasma membrane had been disrupted. By contrast, the activities of the membrane-bound enzymes, NADPH-cytochrome c reductase and succinate dehydrogenase, were reduced in cell lysates by 55 and 81%, respectively. Purified NADPH-cytochrome c reductase was about 3 times less sensitive than the microsomal enzyme, suggesting that the membrane environment facilitated photoinactivation. The MC 540-sensitized photoinactivation of enzymes was accelerated in the presence of deuterium oxide and inhibited if oxygen in the medium was displaced by nitrogen or azide was added to the medium. Taken together, these data support the view that the plasma membrane is a major target of MC 540-mediated photodamages, that the inactivation of membrane-bound enzymes is an oxidative process, and that at least some photodynamic damages are mediated by type II chemistry.
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PMID:Merocyanine 540-sensitized photoinactivation of soluble and membrane-bound enzymes in L1210 leukemia cells. 217 31

Cyclo-oxygenase (COX) production in human promyelocytic leukaemia (HL-60) cells was studied during monocytic differentiation induced by 1 alpha, 25-dihydroxyvitamin D3 (24 nM; 3 days) or phorbol 12-myristate 13-acetate (100 nM; 1 day), or during granulocytic differentiation induced by retinoic acid (1 microns; 4 days). Undifferentiated or differentiated HL-60 cells were labelled with [35S]methionine, and membrane-bound COX was solubilized and quantified by SDS/PAGE. Immunoprecipitated 35S-labelled COX from cells induced to differentiate into monocytic or granulocytic lineage were clearly detected on the autoradiograms as a protein of approx. 70 kDa molecular size, whereas only a very faint COX band was detected in untreated HL-60 cells. During both monocytic and granulocytic differentiation, COX activity (measured by the conversion of exogenous arachidonic acid into prostaglandin E2) was dramatically increased. In addition, thromboxane synthesis was preferentially enhanced during monocytic differentiation. HL-60 cells, induced to differentiate into the monocytic or granulocytic lineage, provide a useful tool to investigate the cellular mechanisms involved in regulation of the synthesis of individual prostanoid-metabolizing enzymes.
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PMID:Induction of cyclo-oxygenase synthesis in human promyelocytic leukaemia (HL-60) cells during monocytic or granulocytic differentiation. 217 83

For simultaneous demonstration of cellular ultrastructure, myeloperoxidase activity, and presence of a membrane-bound antigen in a given blood cell, we examined three different fixatives: periodate-lysine-paraformaldehyde (PLP) and paraformaldehyde and glutaraldehyde for their applicability to preembedding electron microscopic immunocytochemistry using monoclonal antibodies and the avidin-biotin-peroxidase complex (ABC) technique. This procedure was examined in samples from 3 normal volunteers and 29 patients with acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), lymphosarcoma cell leukemia (LSCL), blastic phase of chronic myelogenous leukemia (CML-BC), or other unclassified leukemias. PLP fixation preserved the immunoreactivity of surface glycoproteins as well as immunoglobulins to the most satisfactory extent. Leukemic cells fixed with PLP maintained their fine structural details, so that we could identify their cytoplasmic organelles, although glutaraldehyde produced the best preservation of cellular ultrastructure. In three patients with ALL, our method revealed that a significant portion of blasts possessed both lymphoid surface antigens and peroxidase-positive cytoplasmic granules. Our method was also useful in identifying the lineage of peroxidase-negative leukemic cells, including monoblastic leukemia and megakaryoblastic leukemia cells. Ultraimmunocytochemistry using PLP fixation and the ABC technique may be a promising strategy for determining the nature of blastic cells that remain unclear after a conventional work-up, for characterizing leukemic cells in patients with a relatively low blast cell count in the bone marrow or peripheral blood, and for estimating the presence and frequency of leukemia with multilineage expression.
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PMID:Application of the avidin-biotin-peroxidase complex technique for ultraimmunocytochemical characterization of leukemic cells. 218 36

Studies on cell-membrane-bound proteins in the human hematopoetic system revealed that the expression of certain peptides is restricted to the differentiation lineage. We applied discontinuous polyacrylamide gel electrophoresis of triton X-114 lysates to identify such proteins for a new diagnostic approach in human leukemia. A polypeptide with an apparent molecular mass range of 24 kd (p24) was found predominantly in cells of chronic granulocytic leukemia (CGL), myeloic type of blast crisis, and normal granulocytes. The data presented here suggest a role of this protein in the biology of malignant cells in chronic granulocytic leukemia throughout the course of the disease.
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PMID:Heterogeneity in protein patterns of CGL blast crisis cells: discrimination between lymphatic and myeloic lineages. 232 63

Interleukin 2 (IL-2) is a secreted glycoprotein which acts as an activation and proliferative signal for lymphocytes expressing membrane-bound glycoprotein IL-2 receptors. We have recently established that swainsonine (SW), an inhibitor of mannosidase II during N-linked glycoprotein processing, augmented mitogen-induced mononuclear leukocyte IL-2 receptor expression and IL-2-induced proliferation. The objective of the present investigation was to examine the effect of SW on lymphokine-activated killer (LAK) cell induction. Human mononuclear leukocytes were treated with various concentrations of SW (0.1-10 micrograms/ml) and IL-2 (1-100 units/ml) for up to 72 h. SW augmented IL-2-induced LAK activity directed against human lung carcinoma, melanoma, and leukemia cells 2-3-fold. LAK activity generated in the presence of SW at suboptimal doses of IL-2 (10 units/ml) was similar to that observed with higher concentrations of IL-2 (100 units/ml) alone. SW treatment alone or in combination with IL-2 increased the percentage of IL-2 receptor-positive cells. Furthermore, pretreatment with SW subsequently enhanced IL-2-induced lymphocyte proliferation. SW-treated mononuclear leukocytes exhibited an increase in high-mannose type glycoproteins based upon [3H]mannose labeling, susceptibility to alpha-mannosidase, and binding to concanavalin A-Sepharose. These results indicate that modulators of glycoprotein processing may be useful in lowering the concentrations of IL-2 required for LAK induction and maintenance.
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PMID:Potentiation of human lymphokine-activated killer cell activity by swainsonine, an inhibitor of glycoprotein processing. 250 Oct 20

Large granular lymphocytes (LGL) have been characterized phenotypically and functionally as cytotoxic T lymphocytes, NK cells or lymphokine-activated killer cells. The most prominent morphologic feature of LGL is large cytoplasmic granules that are thought to contain the molecules responsible for cell lysis. In this study, we describe the morphologic and functional characteristics of IL-2-dependent cytotoxic lymphocytes derived from feline PBL. Stimulation of feline PBL with Con A followed by culturing in 50 U of gibbon monkey IL-2 human rIL-2 induced long term lymphocyte cultures. These lymphocytes are cytotoxic for the feline leukemia virus-induced T cell lymphoma (FL74), in a 4-h 51Cr release assay. All cell lines are either constitutively cytotoxic for FL74 cells, or cytotoxic in a lectin-dependent cell cytotoxic assay, the latter being a characteristic of low passage cultures. In contrast, no cell lines express self lysis or lysis for other lines. [3H]TdR uptake showed that 1 U of human rIL-2 produces a 50% maximal proliferative response by feline lymphocytes suggesting a high degree of homology between the ligand binding sites of feline and human IL-2R. Feline cytotoxic lymphocytes possess abundant cytoplasm containing large azurophilic granules characteristic of LGL. These granules are bound by a bilipid membrane and contain numerous smaller membrane-bound vesicles 50 to 60 nm in diameter. A model is proposed, whereby subsequent to binding of LGL to target cell the large granules fuse to the LGL plasma membrane and release the small vesicles into the binding pocket. The vesicles then transport the lytic molecules directly and selectively to the target cell membrane.
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PMID:Feline cytotoxic large granular lymphocytes induced by recombinant human IL-2. 254 49

Two peaks of phosphoinositide-specific phospholipase C (PI-PLC) activity were resolved when guinea pig uterus cytosolic proteins were chromatographed on a DEAE-Sepharose column. The first peak of enzyme activity eluting from the DEAE-Sepharose column (PI-PLC I) was further purified to homogeneity, whereas the second peak of enzyme activity was enriched 300-fold. PI-PLC I migrated as a 62-kDa protein on sodium dodecyl sulfate-polyacrylamide gels. Antibodies prepared against PI-PLC I failed to react with PI-PLC II. PI-PLC I hydrolyzed all three phosphoinositides, exhibiting a greater Vmax for phosphatidylinositol 4,5-bisphosphate greater than phosphatidylinositol 4-phosphate greater than phosphatidylinositol. Hydrolysis of phosphatidylinositol was calcium-dependent, whereas significant hydrolysis of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate occurred in the presence of 2.5 mM EGTA. At physiological concentrations of calcium, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate were the preferred substrates. Antibodies specific for PI-PLC I reacted with a 62-kDa protein in both the cytosol and membrane fractions from guinea pig uterus. Quantitation of the immunoblots revealed that 25% of the 62-kDa protein was membrane-associated, whereas only 5% of the total enzyme activity was membrane-associated. Approximately 20% of the membrane-bound phospholipase C activity and immunoreactive material were loosely bound, whereas the remainder required detergent extraction for complete solubilization. The 62-kDa protein associated with the membrane fractions did not bind lectin affinity columns, suggesting that it was not glycosylated. PI-PLC I was identified as a phosphoprotein in [32P]orthophosphate-labeled rat basophilic leukemia (RBL-1) cells by two-dimensional gel electrophoresis followed by immunoblotting. In untreated cells, 32P-labeled PI-PLC I was found in the cytosolic fraction. Treatment of RBL-1 cells with those phorbol esters which are known to activate the Ca2+/phospholipid-dependent enzyme protein kinase C, resulted in a time-dependent increase in the phosphorylation of both membrane-bound and cytosolic PI-PLC I. Thus, in RBL-1 cells, protein kinase C may play an important role in the regulation of phospholipase C through protein phosphorylation.
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PMID:Purification and characterization of a phosphoinositide-specific phospholipase C from guinea pig uterus. Phosphorylation by protein kinase C in vivo. 282 Sep 80

Cell lysates of mouse peritoneal macrophages, in the presence of reduced glutathione, converted leukotriene LTA4 to LTC4, and neither LTD4 nor LTE4 was detected. Therefore, like cultured rat basophilic leukemia cells (RBL cells), the peritoneal macrophage contains LTC4 synthetase and appears to contain little, if any, gamma-glutamyl transpeptidase. When LTA4 was added to subcellular fractions of mouse macrophage lysate, the highest specific activity of LTC4 synthetase (nmol LTC4/mg protein per 10 min) was associated with the particulate or membrane fractions (i.e., 10(4) and 10(5) X g pellets). The 10(5) X g supernatant contains approx. 1% of the specific activity and 6% of the total LTC4 synthetase activity compared with that of the 10(5) X g pellet. Conversely, the 10(5) X g supernatant had four-times more specific activity and 19-times more total GSH S-transferase activity than did the 10(5) X g pellet when evaluated using 1-chloro-2,4-dinitrobenzene (DNCB) as the substrate. LTA4 was converted to LTC4 by the membrane enzyme LTC4 synthetase in a dose-dependent manner at low LTA4 concentrations (3-50 microM) and reached a plateau of approx. 30 microM LTA4 using the macrophage 10(5) X g pellet as an enzyme source. The apparent Km value of LTC4 synthetase for LTA4 was estimated to be 5 microM based on Lineweaver-Burk plots. Enzyme in the 10(5) X g supernatant produced negligible quantities of LTC4 (1% or less of the particulate fractions) over a wide range of LTA4 concentrations. However, an enzyme in the 10(5) X g supernatant fraction presumed to be GSH S-transferase effectively catalyzes the conjugation of glutathione (GSH) with the aromatic compound DNCB. The apparent Km value of GSH S-transferase for DNCB was estimated to be 1.0-1.5 mM. On the other hand, enzyme from the membrane fraction (i.e., 10(5) X g pellet) catalyzed this reaction at a negligible rate over a wide range of DNCB concentrations. The apparent Km value of LTC4 synthetase for GSH was estimated to be 0.36 mM and the corresponding Km value estimated for the glutathione S-transferase was 0.25-0.76 mM. These values indicate similar kinetics for GSH utilization by both enzymes. These Km values are also significantly lower than the intracellular GSH levels of 2 to 5 mM. Therefore, it is suggested that the substrate limiting LTC4 synthetase activity is LTA4 and not GSH. Our results indicate that LTC4 synthetase from mouse peritoneal macrophages is a particulate or membrane-bound enzyme, as was reported by Bach et al.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characterization of leukotriene C4 synthetase in mouse peritoneal exudate cells. 283 15


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