Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta 2-Microglobulin is a low molecular weight protein that is found in most biological fluids. It was originally isolated from urine of cadmium-poisoned patients. Its amino acid sequence was established and shown to be structurally related to immunoglobulin constant domains. With the aid of antibodies specific against beta 2-microglobulin, the protein was detected on the membranes of all nucleated cells, normal and neoplastic. Measuring the quantity of beta 2-microglobulin showed that high levels are present in patients with renal tubular deficiencies and several other pathological conditions including neoplastic diseases. Extremely high levels were detected in seminal fluid and colostrum. Despite the structural relationship to immunoglobulins, no immunological relationship was demonstrated with these proteins using antibodies specific for beta 2-microglobulin. However, such antibodies are cytotoxic to all cells carrying beta 2-microglobulin on their surfaces. The discovery that beta 2-microglobulin is an integral part of the histocompatibility antigens of human and murine origin stimulated further research and interest in this molecule. Several groups of investigators have shown that beta 2-microglobulin is the low molecular weight chain and is noncovalently bound to a high molecular weight chain which carries the histocompatibility antigens. The structure of the histocompatibility antigens of lymphocytes (HLA) was shown by immunochemical as well as biological methods, and it is now well accepted. The antibodies against beta 2-microglobulin are extremely useful in the isolation of the histocompatibility antigens for sequence studies. Furthermore, the antibody to beta 2-microglobulin revealed that other structures may be bound to beta 2-microglobulin such as phytohemoagglutimin (PHA) receptors, mixed lymphocyte culture (MLC) antigens, etc. Murine thymus leukemia (TL) antigen also contains beta 2-microglobulin as an integral part of its structure; other tumor antigens may have a similar structure. Through all these studies, beta 2-microglobulin emerged as the best known membrane protein that can serve as a model for study of the arrangement and the function of the cell membrane.
 ...
PMID:beta 2-Microglobulin: methods and clinical applications. 8 22

Moloney leukemia virus activated both the classical and alternative pathways of human complement. About 500,000 virions were required to detect activation of the classical pathway whereas 5,000 times as many virions were necessary to initiate the alternative pathway, indicating that in this system only the former is of biological significance. Disruption of the virus with Triton X-100 destroyed its ability to initiate the alternative pathway without affecting its ability to activate the classical pathway. After ultracentrifugation of disrupted virus the active component could be recovered in the supernate and was isolated by isoelectric focusing in granulated gels. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic and analysis and cyanogen bromide digestion studies revealed that the activity resided in a methionine-containing protein having a pI of 7.5 and a molecular weight of approximately equal to 15,000 daltons. The purified protein interacts strongly with Clq and efficiently activates Cl. RNase and lipolytic enzymes had no effect on the isolated protein but incubation with trypsin resulted in loss of activity. Enzymatic digestion studies of surface-labeled virus indicate that the active protein is a viral membrane protein. On the basis of these results it is concluded that the complement receptor of Moloney leukemia virus is the surface protein p15E.
 ...
PMID:Lysis of oncornaviruses by human serum. Isolation of the viral complement (C1) receptor and identification as p15E. 63 50

Lymphocytes isolated from the peripheral blood of patients with nonmalignant and malignant disorders were studied for fluidity of membrane lipids and lateral mobility of concanavalin A (Con A) receptors. The degree of fluidity of the surface membrane lipid core was monitored quantitatively by fluorescence polarization analysis using the probe 1,6-diphenyl-1,3,5-hexatriene embedded in lipid regions of the surface membrane of intact cells. Mobility of Con A surface receptors was determined by the cap-forming ability after binding of fluorescent Con A. The present studies were performed on lymphocytes from 28 patients with malignant lymphomas, 22 patients with leukemia, 28 individuals who either were healthy or had nonmalignant disorders, and 5 patients with carcinoma. The results showed that lymphocytes and mononuclear cells from patients with malignant lymphomas and leukemias have a more fluid lipid layer in their surface membrane than do lymphocytes obtained from healthy individuals or from patients with other malignant and nonmalignant disorders. This increase in membrane fluidity was less pronounced in lymphocytes isolated from leukemic patients in clinical remission and from leukemic patients receiving treatment with steroids. The results also show a marked difference in the cap-forming ability of lymphocytes from patients with malignant lymphomas or leukemia as compared with lymphocytes from patients with non-malignant disorders or carcinoma. Lymphocytes isolated from lymphoma and chronic lymphatic leukemia patients during remission stages of the disease exhibited a higher cap-forming ability. The cap-forming ability of cells from patients with chronic lymphocytic leukemia was unaffected by treatment with steroids. The present results, which are in line with previous observations, have shown that normal lymphocytes can be characterized by a low degree of lipid fluidity but a high degree of mobility of Con A receptors, whereas leukemic lymphocytes are characterized by a high degree of lipid fluidity but a low degree of mobility of Con A receptors. These results confirmed our general hypothesis on the dynamic interrelation between membrane lipids and membrane protein receptors, and they indicate that the widely accepted term "membrane fluidity" requires better consideration for different membrane components.
 ...
PMID:Fluidity of membrane lipids and lateral mobility of concanavalin A receptors in the cell surface of normal lymphocytes and lymphocytes from patients with malignant lymphomas and leukemias. 85 60

Red cell membrane protein behaviour was studied in patients with polycythaemia vera, polyglobulia secondary to cardiorespiratory disorders, chronic myeloid leukaemia and acute granuloblastic leukaemia. Electrophoretic pictures were examined after solubilisation in urea or SDS and on various supports. Chromatographic analysis was also made of acid, neutral and basic amino acids obtained by hot-acid hydrolysis of the stromas. Protein electrophoretic changes in polycythaemia differed from those observed in granuloblastic leukaemia and chronic cor pulmonale. Different stromal protein amino acid percents were also noted, with marked variations between each disease.
 ...
PMID:[Changes in the proteins of erythrocyte membrane in polycythemia vera]. 106 56

YT cells, originally reported as a natural-killer-like (NK-like) lymphoid cell line, were investigated for Epstein-Barr virus (EBV) genome, gene rearrangement for T-cell receptor (TCR), phenotype and function. The YT cells of the original batch (YT-0) and two subclones (YT2C2 and YTC3) expressed EBV-associated nuclear antigen, and the BamHI-digested DNA showed the 3.4 kb hybridizing band with the BamHIW probe of EBV DNA in Southern blot analysis. When tested with latent-infection membrane protein probe, an identical hybridizing band was shared, indicating that all three sources of YT cells were of monoclonal derivation in terms of the terminal repeat junctional structure of EBV DNA, and that the original YT cells had been infected with EBV before the isolation of the two subclones. The cell-surface antigen analysis revealed the expression of CD7, CD28, CD30, CD45R0, TLiSA and S6F1 antigen besides the originally recorded CD25, CD56 and HLA-DR antigen. Gene rearrangement analysis showed the germ-line genotype, including TCR gamma and delta as well as beta chain. The Northern blot study using the CD3 epsilon and CD3 delta chain gene probes revealed CD3 epsilon, but not CD3 delta RNA. The YT-0 cells exhibited NK and antibody-dependent cellular cytotoxicity activity, but the YT2C2 and YTC3 cells did not. It was not resolved whether the fresh neoplastic NK-like cells of the YT-cell donor carry EBV genome, but YT cells, the first lymphoid cell line found to have EBV genome and non-B lymphoid properties, are valuable for investigating the relationship between EBV and human non-B lymphoid hematopoietic cells.
Leukemia 1992 Feb
PMID:Detection of Epstein-Barr virus genome in natural-killer-like cell line, YT. 131 26

This study analyzes the association of Epstein-Barr virus (EBV) with non-Hodgkin's lymphoma (NHL) arising in patients without pre-existing overt immunodeficiency. The authors examined 201 lymphomas (105 high-grade B-cell, 82 peripheral T-cell, 7 high-grade non-B-cell, non-T-cell, and 7 hairy-cell leukemia) for EBV gene expression by immunohistologic procedures using monoclonal antibodies to EBV latent, immediate early, and replicative infection antigens. Transformation-associated EBV latent membrane protein 1 (LMP 1) was detected in 13 (6%) NHL, comprising 4 (4%) high-grade B-cell, 8 (10%) peripheral T-cell, and 1 non-B-cell, non-T-cell lymphomas. Anaplastic large-cell lymphoma of T-cell type was consistently LMP 1-negative. EBV nuclear antigen 2 was demonstrated in only three (1%) cases. Induction of replication as defined by expression of the immediate early BamHI Z leftward reading frame 1 (BZLF1) protein was detected in five cases, but early (EA) and late (VCA and MA) lytic cycle antigens were only found in two cases and in one case, respectively. The presence of EBV was confirmed by in situ DNA hybridization in 9 of 11 EBV antigen-positive lymphomas. This study shows the surprisingly frequent presence of EBV in peripheral T-cell NHL in European patients without pre-existing overt immunodeficiency. Interestingly, most sporadic B-cell NHL are not associated with the virus. Furthermore, the usefulness of selected monoclonal antibodies for the routine immunohistological diagnosis of EBV infection was confirmed.
 ...
PMID:A survey of Epstein-Barr virus gene expression in sporadic non-Hodgkin's lymphomas. Detection of Epstein-Barr virus in a subset of peripheral T-cell lymphomas. 131 39

A variant line (CEM-7A) "overproducing" the reduced folate/MTX carrier system was isolated from human CCRF-CEM leukemia cells grown under selective conditions in medium containing 0.25 nM 5-formyl-THF as the sole folate source. This line exhibits a 95-fold increased Vmax for [3H]-MTX influx as compared to parental cells. The values for [3H]-MTX influx Km, efflux t1/2 and structural specificity for other (anti)folate compounds were unchanged. The amount of carrier protein, estimated by NHS-[3H]-MTX affinity labeling, was approximately 30-fold higher in CEM-7A cells than in parental cells. Influx of [3H]-MTX in CEM-7A cells was found to be down-regulated 6-7-fold after preincubation of cells with adenosine, 5-formyl-THF or 5-methyl-THF, but could be prevented exclusively by inhibitors of dihydrofolate reductase. The underlying mechanism(s) of these effects have not as yet been elucidated. A radioiodinated photoaffinity analog of MTX was used to prove the molecular events in carrier-mediated MTX uptake in parental CCRF-CEM cells, CEM-7A cells, and a line exhibiting a MTX-transport defect (CEM-MTX). Specific labeling of an 80-85 kDa membrane protein was observed in parental cells, but not in CEM/MTX cells. Uptake of photoprobe and levels of the 80-85 kDa membrane protein were significantly increased in CEM-7A cells. Due to extensive glycosylation the MW of the carrier protein in human cells seems to be substantially higher than that of its counterpart in murine L1210 leukemia cells (46-48 kDa). Pulse-labeling experiments at 37 degrees C demonstrated that in CEM-7A cells photoprobe uptake proceeds via a specific pathway. The 80-85 kDa membrane protein is involved in the initial binding and translocation of photoprobe, after which a 38 kDa cytosolic protein is responsible for further intracellular distribution. At this time, the combination of photoaffinity labeling techniques and the availability of variant cell lines overexpressing the reduced folate/MTX carrier protein has provided new insights into the MTX transport process in human leukemia cell lines. In the near future this approach should also allow a further elucidation of the regulatory aspects of carrier function.
 ...
PMID:Molecular events in the membrane transport of methotrexate in human CCRF-CEM leukemia cell lines. 132 3

Classical multidrug resistance is characterized by overexpression of a membrane protein, P-glycoprotein, which acts like a drug-extruding pump, reducing accumulation of cytotoxic drugs inside malignant cells. We have developed a simple method for detecting an intracellular epitope of P-glycoprotein in normal and leukemic cells by the monoclonal antibody JSB-1 and fluorescence-activated flow cytometry. Permeabilization of blood and bone marrow cells in unprocessed samples is achieved by a commercially available red blood cell lysing solution which excellently preserves the light scatter properties of leukocytes. The method is suitable for analyzing samples in clinical routine. Lower than 1% reactivity was seen in the lymphoid gate of normal peripheral blood and bone marrow samples as compared with over 60% of reacting cells in some leukemic samples. Twelve patients with acute de novo leukemia were studied at presentation, 13 patients at a refractory stage, and 28 in remission. There was a positive correlation between the P-glycoprotein and the CD34 expression in acute myelogenous leukemia and an association between the P-glycoprotein expression and the blast count in both acute myelogenous and lymphatic leukemias.
 ...
PMID:Flow cytometric analysis of P-glycoprotein in normal and leukemic cells. 135 49

When aggregated, cell surface proteins become resistant to solubilization by detergents, presumably because of aggregation-induced or -stabilized interactions between the membrane protein and the cytoskeleton or plasma membrane skeleton. We genetically engineered variants of the tetrameric high-affinity receptor for IgE (Fc epsilon RI) to identify a site on its alpha, beta, or gamma chains that mediates such putative interactions. Using flow cytofluorometry, we studied rat basophilic leukemia cells, transiently transfected COS cells, and stably transfected P815 cells bearing wild-type and mutated receptors. We observed that (i) solubilization was markedly dependent on the degree of aggregation, the extent varying somewhat with the cell type and, particularly at lower levels of aggregation, with the time after addition of detergent; (ii) truncation of no single cytoplasmic domain of the alpha, beta, or gamma chains ablated the insolubilization effect; and (iii) incomplete receptors were also efficiently insolubilized by aggregation. Thus receptors consisting only of alpha and gamma chains, a "receptor" consisting of only the ectodomain of the alpha chain attached to the plasma membrane by a glycosyl-phosphatidyl inositol anchor, and "receptors" consisting only of minimally modified gamma chains were resistant to solubilization after aggregation. We conclude that no unique subunit or domain of Fc epsilon RI mediates the insolubilization phenomenon. Our results support a model in which the bridging of membrane proteins leads to their becoming nonspecifically enmeshed in a network of membrane skeletal proteins on either the outside and/or the inside of the membrane so that dissolution of the lipid bilayer becomes irrelevant.
 ...
PMID:Interaction of aggregated native and mutant IgE receptors with the cellular skeleton. 153 Aug 86

The ability of variations of membrane protein concentrations to modulate the lateral diffusion rate of an exemplary membrane protein has been studied in healthy and osmotically shocked cultured cells of the rat basophilic leukemia cell line, 2H3 subclone. Cell surface protein was redistributed by the method of in situ electrophoresis; exposure to electric fields of 1.25-5 V/cm results in cathodal migration of the majority of the surface proteins on this cell type (Ryan, T. A., J. Myers, D. Holowka, B. Baird, and W. W. Webb. Science [Wash. DC]. 239:61-64). Even in these small fields, the steady-state distribution becomes "crowded" with more than an 80% protein occupancy of accessible membrane area at the cathodal end of these spheroidal cells, and the anodal end becomes significantly depleted. We have employed fringe pattern fluorescence photobleaching with CCD imaging detection to measure lateral diffusion coefficients of the liganded IgE receptor on both crowded and uncrowded regions of individual rat basophilic leukemia cells. We find no significant difference in lateral diffusion rates in these regions. Cells swollen by hypoosmotic stress exhibit faster diffusion overall, with the uncrowded regions having a significantly greater increase in diffusion coefficient than the crowded regions. These results are consistent with the partial or total release of cytoskeletal constraints to membrane protein diffusion induced by osmotic stress.
 ...
PMID:Effects of protein concentration on IgE receptor mobility in rat basophilic leukemia cell plasma membranes. 153 97


1 2 3 4 5 6 7 8 9 10 Next >>