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 SL/Ni strain of mice spontaneously develops a necrotizing polyarteritis (NPA) that is histologically quite similar to human polyarteritis nodosa. This NPA most frequently affected parametrial tissues and/or ovaries of females and small arterioles of the major salivary glands. Electron microscopic studies of early arterial lesions revealed massive budding of C-type particles from arterial smooth muscle cells just before or at the onset of arteritis. In addition, binding of mouse IgG and C3 to the plasma membrane of virus-producing smooth muscle cells was shown by immunoelectron microscopy. Antibody-bound muscle cells showed disintegration of their plasma membrane, but degeneration and necrosis of muscle cells were not associated with dense infiltration of neutrophils. SL/Ni mice had natural antibodies that bound specifically to a fibroblast cell line infected with an endogenous ecotropic murine leukemia virus (MuLV) recovered from a SL/Ni mouse. Most of the natural antibodies were cytotoxic in the presence of murine complement. Western blot immunoassays revealed that among 14 SL/Ni female mice tested, all of the 9 mice that were affected by arteritis had anti-gp70 antibodies, while the 3 anti-gp70- mice were not affected. The presence of anti-p30 or anti-p15 (anti-p12) antibodies, which were also detected in some SL/Ni mice, did not correlate with the development of arteritis. These results strongly support the hypothesis that NPA in SL/Ni mice is mediated by the lysis of arterial smooth muscle cells due to the deposition of cytotoxic natural antibodies directed to cell membrane-bound gp70 molecules of an endogenous ecotropic MuLV.
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PMID:Pathogenesis of arteritis of SL/Ni mice. Possible lytic effect of anti-gp70 antibodies on vascular smooth muscle cells. 288 32

The vast majority (71 of 77) of human tumor cells derived from various tissue origins were found to express specific membrane receptors for gamma-interferon (IFN-gamma). Six receptor-negative tumors were found among leukemic cells of lymphoid origin. Scatchard analysis with 125I-labeled human recombinant IFN-gamma revealed a similar binding affinity with a mean dissociation constant (Kd) of around 2 X 10(-11) M not only for various established cell lines, but also for leukemic and carcinoma cells derived from biopsy material. In contrast to similar KdS, large differences in the number of expressed IFN-gamma membrane receptors were found on distinct tumor cells of the same cell type ranging from a few hundred up to 2 X 10(4) for both carcinoma cells and leukemic cells. For comparison, the IFN-gamma receptor number on normal lymphocytes (mean, approximately 300/cell) and normal bone marrow cells (mean, approximately 1000/cell) was consistently found to be low. Cross-linking of membrane-bound 125I-IFN-gamma with disuccinimidyl suberate and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed, in both leukemia and carcinoma cells, three distinct complexes with molecular weights of approximately 70,000, 92,000, and 160,000, suggesting the existence of IFN-gamma receptor subunits. A dimeric structure of the functional IFN-gamma receptor with an estimated molecular weight of about 128,000 +/- 10,000 is proposed. Together with the Scatchard analysis, these data suggest the existence of a single class of high affinity IFN-gamma receptors in tumor cells of distinct tissue origin.
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PMID:Quantitation and characterization of gamma-interferon receptors on human tumor cells. 294 78

Alterations in genes that function in normal growth and development have been linked to malignant cell transformation. The mononuclear phagocyte colony-stimulating factor (CSF-1 or M-CSF) is a polypeptide growth factor synthesized by mesenchymal cells, which stimulates the survival, proliferation, and differentiation of haematopoietic cells of the monocyte-macrophage series. Multiple forms of soluble CSF-1 are produced by proteolytic cleavage of membrane-bound precursors, some of which are stably expressed at the cell surface. The c-fms proto-oncogene encodes the CSF-1 receptor, which is composed of an extracellular ligand-binding domain linked by a single membrane-spanning segment to a cytoplasmic tyrosine-specific protein kinase domain. Whereas the tyrosine kinase activity of the normal receptor is stimulated by CSF-1, mutations in the c-fms gene can constitutively activate the kinase to provide growth-stimulatory signals in the absence of the ligand. Oncogenic activation of the c-fms gene product appears to involve removal of a negative regulatory tyrosine residue near the carboxyl terminus of the receptor and one or more additional mutations that may simulate a conformational change induced by CSF-1 binding. Expression of the human c-fms gene in mouse NIH-3T3 cells confers a CSF-1 stimulated growth phenotype, indicating that receptor transduction is sufficient for fibroblasts to respond to a haematopoietic growth factor. In contrast, the v-fms oncogene induces factor-independent growth and tumorigenicity in factor-dependent myeloid cell lines, and contributes to the development of proliferative disorders of multiple haematopoietic lineages when introduced into murine bone marrow progenitors. Aberrant expression of an endogenous c-fms gene secondary to proviral insertion and transcriptional activation has also been implicated in virus-induced myeloblastic leukaemia in mice. The c-fms and CSF-1 genes have been mapped on the long arm of human chromosome 5, a region that frequently undergoes interstitial deletions in certain haematopoietic disorders including acute myelogenous leukaemia. The study of CSF-1 and its receptor should provide information concerning the role of tyrosine kinases in regulating the normal growth and differentiation of haematopoietic cells and in contributing to their malignant transformation.
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PMID:The colony-stimulating factor 1 (CSF-1) receptor (c-fms proto-oncogene product) and its ligand. 297 16

Anticalmodulin and calcium channel blockers have been shown to reverse Adriamycin resistance by reducing the drug efflux from resistant cells. Since cellular calcium and calmodulin levels are probably related to these effects, we have measured the total, membrane-bound, and intracellular calcium levels in Adriamycin-resistant (P388/R) and -sensitive (P388/S) leukemia cells. In P388/R cells, total calcium was approximately 1.4-fold higher than that of P388/S cells. Membrane-bound and intracellular calcium levels were also higher in P388/R cells. No major difference was observed in the calmodulin content of these cells. The P388/R cells had a higher (approximately 1.4-fold) protein content. When calculated on the basis of per unit protein, P388/S and P388/R cells had similar total calcium but a higher intracellular free calcium and calmodulin content in P388/S cells. Thus our studies suggested that the lower drug efflux and increased drug retention in P388/R cells may not be related to calcium and calmodulin levels but may be due to some other membrane-related factors.
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PMID:Calcium, calmodulin, and protein content of adriamycin-resistant and -sensitive murine leukemic cells. 394 Jan 93

The indirect membrane immunofluorescence test and the absorption analysis of rabbit anti-FeLV, rabbit anti-FeLVp 30, and rabbit anti-MuLVp 30 antisera yielded the following conclusions. An antigen shared by mammalian (murine and feline) C-type RNA leukemia and sarcoma viruses was detected on the surface of cells infected or transformed by C-type viruses. The antigen was characterized as membrane-bound gs antigen bearing two determinants, membrane-bound gs-1, intraspecies-specific antigenic determinant, and membrane-bound gs-3, interspecies-specific antigenic determinant. Membrane-bound gs antigen was located on the cell surface, frequently near the site of virus budding but not on the envelope of murine C-type RNA virus.
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PMID:Common cell surface antigen associated with mammalian C-type RNA viruses. Cell membrane-bound gs antigen. 413 13

We present evidence that virus-specific RNA is present in polyribosomes of transformed cells replicating the murine sarcoma-leukemia virus complex and that it serves as messenger RNA for the synthesis of viral-coded proteins. Both virus-specific RNA (detected by hybridization with the [(3)H]DNA product of the viral RNA-directed DNA polymerase) and nascent viral polypeptides (measured by precipitation with antiserum to purified virus) were found in membrane-bound and free polyribosomes. Membrane-bound polyribosomes contained a higher content of both virus-specific RNA and nascent viral polypeptides. From 60 to 70% of viral RNA sequences were released from polyribosomes with EDTA, consistent with a function as messenger RNA. Maximum amounts of both virus-specific RNA and nascent viral polypeptides were found in the polyribosome region sedimenting at about 350 S.
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PMID:Virus-specific messenger RNA and nascent polypeptides in polyribosomes of cells replicating murine sarcoma-leukemia viruses. 435 69

Cells infected by Rauscher leukemia virus synthesize virus-specific RNA which can be detected by hybridization to the single-stranded DNA copy of the viral RNA. Evidence is provided that virus-specific RNA is present in free and membrane-bound polyribosomes of these cells. The relative content of virus-specific RNA, as measured by hybridization, is 6-10 times less on free polyribosomes than on membrane-bound polyribosomes. The messenger RNA associated with both classes of polyribosomes was characterized by density gradient centrifugation. In addition to a major RNA species identified as 36S RNA, at least 2 minor components in the 14S and 21S region have also been found. There is a striking difference in the distribution of these RNA species between free and membrane-bound polyribosomes.
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PMID:Virus-specific messenger RNA on free and membrane-bound polyribosomes from cells infected with Rauscher leukemia virus. 452 17

In order to investigate the properties of the membrane-bound IgE-receptor complex, a simple procedure has been adapted for preparing large plasma membrane vesicles from rat basophilic leukemia cells. These vesicles pinch off from the adherent cells after treatment with 2 mM N-ethylmaleimide or 50 mM formaldehyde and 1 mM dithiothreitol, and they are isolated from the supernatant after two centrifugation steps with yields of 20-25% of the initial cell-bound 125I-IgE. With phase and fluorescence microscopy, micron-size vesicles are seen which are unilamellar and spherically shaped and devoid of intracellular organelles. On dextran gradients at least 70% of the 125I-IgE is bound to membranes which band at low density, indicating large, intact vesicles that are impermeable to macromolecules. Between 60 and 75% of the bound 125I-IgE is accessible to the external medium, showing the vesicles to be predominantly right side out. This preparation was found to be suitable for resonance energy-transfer measurements. We have determined that amphipathic, fluorescent donor and acceptor probes partition into the vesicle bilayer in a randomly distributed, noninteracting manner. The densities of the probes can be ascertained directly from the amount of energy transfer that is observed as a function of acceptor concentration. This experimental system will allow energy-transfer measurements to determine distances between sites on receptor-bound IgE and the membrane surface.
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PMID:Structural studies on the membrane-bound immunoglobulin E-receptor complex. 1. Characterization of large plasma membrane vesicles from rat basophilic leukemia cells and insertion of amphipathic fluorescent probes. 622 55

The immunoperoxidase technique was employed to localize, at the ultrastructural level, protein Pr76 (a precursor of the 'gag' gene protein of avian leukemia and sarcoma viruses) in chick embryo cells infected with RSV-RAV-2 virus. The protein was confined to free and membrane-bound ribosomes. This was often particularly conspicuous in the perinuclear region. No staining was found in the ergastoplasmic cisternae, in the Golgi apparatus, or in the nucleus. This pattern of localization is compatible with previous studies where the protein was searched for in various cell subfractions.
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PMID:Immunoelectron microscopic localization of Rous sarcoma virus structural protein p27 in infected chicken embryo fibroblasts. 626 99

During the last nine years, two important methodologies have been used to characterize the cell surfaces of normal lymphocytes and malignant lymphoblasts. Normal mature T-cells have a receptor for sheep erythrocyte (E+) while mature B-cells bear membrane-bound immunoglobulin molecules (sIg+). These two findings can be used to divide acute lymphoblastic leukemia of childhood into three major groups; B-cell leukemia (sIg+ E-), which is rare (approximately 2 percent) and has the poorest prognosis, T-cell leukemia (sIg-, E+) which is more common (10 percent) but also has a poor prognosis and null cell leukemia (sIg-, E-) which is the most common (85 percent) and has the best prognosis. By the use of additional immunological methods, subgroups within T-cell leukemia and null cell leukemia have also been proposed. One of the most valuable of these additional methods is the detection of surface antigens. Three of the more commonly detected antigens currently being evaluated are (1) common leukemia antigen (cALL), (2) a normal B Lymphocyte antigen the Ia antigen (Ia) which is not generally expressed on most T lymphocytes and (3) a normal T lymphocyte antigen (T) not expressed on B lymphocytes. Within null cell leukemia, the most commonly identified and probably the largest subgroup if Ia+, cALL+, T-, E-, sIg-. In another but smaller subgroup within null cell leukemia, the lymphoblasts contain cytoplasmic immunoglobulin but do not express surface immunoglobulins or E receptors. This subgroup is designated pre B-cell leukemia. Subgroups with T-cell leukemia have also been suggested. These include T+ E-, T+ E+, in which the rosettes are thermolabile and T+ E+, in which the rosettes are thermostable. Whether or not there are any prognostic differences in these three subgroups remains to be determined.
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PMID:Cell surface markers in acute lymphoblastic leukemia. 696 78


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