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)

We investigated the expression of fos oncogene proteins in lymphoproliferative disorders, using a monoclonal antibody (FO-120) that was prepared against a synthetic oligopeptide of fos protein (amino acid sequence from 127 to 152). Although peripheral blood leukocytes were rarely positive for FO-120, they were transiently stained after lectin (PHA) stimulation. After culture with IL-2 for 1 or 2 weeks, less than 40% of the lymphocytes weakly reacted with FO-120, whereas strongly positive cells were detected in more than 70% of cells in half the T-cell lines established from preleukemic state of adult T-cell leukemia (pre-ATL) and all of ATL derived T-cell lines. All in vivo specimens of non-Hodgkin's malignant lymphomas, except for one case of T-cell lymphoma were also strongly positive. In addition, the extent of the antibody reactivity correlated with the histopathological grade of malignancy in B-cell lymphoma. The reactivity to most AILD-IBL lesions overlapped with that to T-lymphomas, and could be distinguished from that to reactive lesions. FO-120 appears to be a useful tool for detecting early neoplastic changes in lymphoproliferative disorders.
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PMID:Detection of fos oncogene products by monoclonal antibody FO-120 in lymphoproliferative disorders. 251 20

Two types of activation Ag, low affinity FcR for IgE (Fc epsilon R2)/CD23 and IL-2R (Tac/p55), were expressed and differently regulated on human eosinophilic leukemia cell lines (EoL-1 and EoL-3). Because the binding of IgE on EoL-3 cells was completely inhibited by H107 (anti-Fc epsilon R2/CD23 mAb) but not by irrelevant mAb, essentially all the low affinity Fc epsilon R2 on EoL-3 seemed to be the Fc epsilon R2/CD23 molecules. Both IL-4 and IFN-gamma enhanced the surface expression of Fc epsilon R2, whereas IL-1, IL-2, and IL-5 showed no effects, as determined by surface staining with anti-Fc epsilon R2 antibody (H107). In contrast to Fc epsilon R2 up-regulation, IL-4 and IFN-gamma showed a differential effect on the regulation of IL-2R (Tac/p55). Whereas IFN-gamma up-regulated the receptor expression of IL-2R/Tac, IL-4 did not. The result suggests that these lymphokines are involved in the different aspects of the activation pathway of the eosinophils. The possible role of Fc epsilon R2 and IL-2R on the function of eosinophils in allergic reaction is discussed.
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PMID:Differential regulation of the low affinity Fc receptor for IgE (Fc epsilon R2/CD23) and the IL-2 receptor (Tac/p55) on eosinophilic leukemia cell line (EoL-1 and EoL-3). 252 45

Cells from six cases of adult T cell leukaemia were studied with respect to phenotypical and functional features. All cells were reactive with anti-CD4 and anti-CDw29 monoclonal antibodies (antibody against helper inducer T cells) but were unreactive with anti-CD45R monoclonal antibody (antibody against suppressor inducer T cells). Functionally, these cells secreted a B cell differentiation factor detected by SKW6-CL4 cell differentiation to IgM-producing cells, this secretion being enhanced by culture with recombinant IL-2. Though these results indicate that adult T cell leukaemia cells are of mature helper inducer T cell origin, these cells strongly suppressed PWM-induced B cell differentiation in the absence of CD8+ suppressor effector T cells.
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PMID:Adult T cell leukaemia cells are of CD4+ CDw29+ T cell origin and secrete a B cell differentiation factor. 252 51

Regulatory effects on myelopoiesis and myelogenous leukaemia cell proliferation mediated by a human T cell clone (TCC) carrying a gamma/delta receptor have been studied. MHC-unrestricted cytotoxicity could be induced in this clone by culture with IL-2 but not IL-4. Increasing concentrations of IL-2 resulted in increased lysis of natural killer (NK)-susceptible target cells but lysis of NK-resistant targets could not be induced. Moreover, cytotoxicity on fresh chronic myeloid leukaemia cells was not measurable even after culture with 1000 U/ml IL-2. However, NK-resistant targets could be lysed when anti-receptor antibodies (OKT3 or TCR-delta 1) were added to the assay. Clone 290-2 cells secreted lymphokines potentially inhibitory for myelopoiesis (TNF-alpha, IFN-gamma), and their supernatants could inhibit optimally stimulated granulocyte/macrophage colony formation by normal bone marrow. Moreover, 290-2 cells prevented the consistently observed IL-3-stimulated enhancement of proliferation of CML cells, although even IL-3-pretreated leukaemic cells were still resistant to lysis by this clone. Thus, cells of this type, even when not directly cytolytic, could have a role in the regulation of myeloid cell growth.
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PMID:Regulation of normal myelopoiesis and chronic myelogenous leukaemia cell proliferation through a non-cytotoxic mechanism by a gamma/delta T cell clone. 253 Jan 64

We have developed a series of human intrathyroidal T-T cell hybridomas and evaluated their phenotypic characteristics and lymphokine secretions in order to further understand the role of the T cell in Graves' disease. Mitogen-stimulated T cell blasts were generated from intrathyroidal lymphocyte preparations and fused with a hypoxanthine-, aminopterin-, and thymidine-sensitive variant of the Molt 4 human leukemia T cell line. The resulting intrathyroidal T-T cell hybridomas and T-T cell hybridomas obtained from normal peripheral blood mitogen-stimulated T cell blasts were expanded and tested for their biological function. None of the generated T cell hybridomas exhibited antigen-specific IL-2 secretion when stimulated with autologous thyrocytes, although 60% of the hybridomas expressed CD3 antigen and the T cell receptor alpha/beta heterodimer. However, 9 intrathyroidal and 11 peripheral blood T cell hybridomas secreted a factor(s) that significantly enhanced immunoglobulin G secretion in vitro (P less than 0.005, by Student-Newman-Keuls test; mean +/- SEM, 338 +/- 60% increase). In summary, we have successfully used a technique that allows the construction of T-T cell hybridomas derived from intrathyroidal T cell cultures. The data demonstrated that a predominance of helper factor-secreting T cells were available for fusion within the Graves' thyroid gland. Such observations are further evidence for intact T cell help within the thyroid gland of patients with Graves' disease.
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PMID:Successful production of intrathyroidal human T cell hybridomas: evidence for intact helper T cell function in Graves' disease. 253 Nov 54

A 34-year-old male patient developed an isolated pericardial relapse of an acute myelogenous leukemia (M3) 11 months after marrow grafting from his HLA-identical brother. Alloenzyme pattern analysis revealed recipient type of the myeloblasts obtained from the pericardial effusion. Recurrence of the original leukemia was preceded by a reactivation of latent cytomegalovirus (CMV) infection which, in spite of a systemic humoral immune response to the virus, persisted in the pericardium as shown by dot-blot hybridization using CMV-specific DNA fragments. Activated T cells propagated with IL-2 from the pericardial effusion did not reveal any cytotoxic or restimulation capacity on the original or relapse myeloblasts, nor on other donor, recipient or NK target cells. Local coincidence of virus persistence and leukemic relapse suggested CMV-mediated modulation of the immune response in the pericardium with consequent induction of a proliferation of the original malignant cell clone. After local chemotherapy and one course of systemic treatment the patient is still in complete remission--longer than after the marrow grafting.
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PMID:Isolated pericardial relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia. 254 72

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

The functional and phenotypic characteristics of Ly-4(CD4)+ and Ly-2(CD8)+ T cells were studied after induction of murine AIDS with LP-BM5 murine leukemia virus. Assays of spleen cells for their ability to generate in vitro CTL responses to TNP-modified autologous cells (self + x CTL) and to alloantigens (allo CTL) showed that self + x CTL responses were greatly impaired at 3 to 4 wk postinfection and were undetectable thereafter. Allo CTL responses were normal at 3 to 4 wk, but were reduced at 8 to 9 wk and absent at 14 wk postinfection. This sequential loss of self + x and allo CTL responses was related to a selective defect in Ly-4(CD4)+ Th cell function associated with impaired production of IL-2 and deficient proliferative responses to Con A or to soluble Ag. Changes in the functional characteristics of Ly-4(CD4)+ T cells were unrelated to changes in their frequency in spleen, but did correlate with marked alterations in their distribution among four subsets defined by mAb SM3C11 and SM6C10. Assays of CTL responses generated by mixtures of spleen cells from normal and infected mice suggested that active suppression of Ly-4(CD4)+ Th function may contribute to this defect. Studies of Ly-2(CD8)+ T cells showed that infection with LP-BM5 murine leukemia virus also induced a major phenotypic shift in subpopulations defined by their reactivity with mAb 6C10. However, this phenotypic change did not appear to correlate with major functional defects.
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PMID:Functional and phenotypic alterations in T cell subsets during the course of MAIDS, a murine retrovirus-induced immunodeficiency syndrome. 254 79

Essential fatty acids, from which PG derive, can participate in development and regulation of immune responses and have been shown to suppress inflammation and tissue injury in animal models. In this report, we investigate the effects of the immediate (DGLA, precursor to PGE1), arachidonic acid (AA, PGE precursors, dihomogamma linolenic acid (DGLA, precursor to PGE1), arachidonic acid (AA, precursor to PGE2), and eicosapentaenoic acid (EPA, precursor to PGE3) on IL-2 production by PHA-stimulated human PBMC. DGLA and AA inhibited IL-2 production in a dose-dependent manner: half-maximal inhibition was obtained by using the fatty acids at the dose of 10 micrograms/ml without significant effects on cell viability. EPA inhibited IL-2 production by PBMC of only some donors. Incubation of cells in the presence of oleic, stearic, and palmitic acids, which are not PG precursors, did not affect mitogen-induced IL-2 production. A progressive increase in incorporation of DGLA into cellular lipids was observed over a 48-h incubation period. IL-2 production was reduced also when PBMC were pretreated overnight with DGLA or AA and washed before exposure to PHA. Whereas addition of the cyclo-oxygenase inhibitor, indomethacin, at the time of mitogenic stimulation led to increased IL-2 production and prevented mitogen- and fatty acid-induced increases in PGE release, it had no significant effect on the capacity of the fatty acids to suppress IL-2 production. Time course experiments showed that DGLA and AA inhibited IL-2 production even at times of minimal or no PGE release by the treated cultures. Moreover, DGLA and AA inhibited IL-2 production by the human leukemia T cell line Jurkat which, when appropriately induced, is able to release high levels of IL-2 in the absence of accessory cells and measurable PGE production. Taken together, these data indicate that essential fatty acids inhibit IL-2 production directly without conversion into their cyclo-oxygenase pathway products, and suggest that human lymphocyte function may be altered profoundly by small changes in their fatty acid profile.
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PMID:Prostaglandin E precursor fatty acids inhibit human IL-2 production by a prostaglandin E-independent mechanism. 254 87

We have previously described a monoclonal antibody (MoAb), H2, which recognized a tumour-unique antigen on a human T-cell chronic lymphatic leukaemia (T-CLL, CD3,4+). However, further characterization of H2 has revealed a reactivity with the majority of T lymphocytes and a minority of B lymphocytes, some malignant T cells and a few cell lines of leukaemia or of hematopoietic tumour origin. The molecular weight of the antigen (80,000) precipitated by the MoAb H2 from the cell lines NALM-6 and Reh corresponded to that previously found. When PBL were stimulated with PHA, IL-2, or Con A a reduced reactivity of H2 could be seen. The MoAb H2 was submitted to the Fourth International Conference on Human Leucocyte Differentiation Antigens, Vienna, 1989. H2 did not cluster in any of the 78 clusters of differentiation (CD 1-78) discussed at the conference, indicating its unique reactivity. This suggests that we have defined a new antigen on lymphocytes with a possible role along the resting-proliferating axis.
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PMID:A monoclonal antibody, H2, defines a new surface antigen expressed on human lymphocytes. 258 34


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