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  • 1
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    Transformation and plasmacytoid differentiation of EBV-infected human B lymphoblasts by ras oncogenes (1989)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1989-02-03
    Description: The biological effects of ras oncogene activation in B cells were studied by using amphotropic retroviral vectors to introduce H- or N-ras oncogenes into human B lymphoblasts immortalized by Epstein-Barr virus. Expression of both H- and N-ras oncogenes led to malignant transformation of these cells, as shown by clonogenicity in semisolid media and tumorigenicity in immunodeficient mice. In addition, terminal differentiation into plasma cells was detectable as specific changes in morphology, immunoglobulin secretion, and cell surface antigen expression. This combined effect, promoting growth and differentiation in human lymphoblasts, represents a novel biological action of ras oncogenes and has implications for the pathogenesis of terminally differentiated B-lymphoid malignancies such as multiple myeloma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seremetis, S -- Inghirami, G -- Ferrero, D -- Newcomb, E W -- Knowles, D M -- Dotto, G P -- Dalla-Favera, R -- CA-37165/CA/NCI NIH HHS/ -- CA49236/CA/NCI NIH HHS/ -- EY 06337/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1989 Feb 3;243(4891):660-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, New York University, NY 10016.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2536954" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism/*pathology ; Cell Differentiation ; *Cell Transformation, Neoplastic ; *Cell Transformation, Viral ; DNA Replication ; Flow Cytometry ; Fluorescent Antibody Technique ; Gene Expression Regulation ; *Genes, ras ; *Herpesvirus 4, Human ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental/etiology ; Phenotype ; Plasma Cells/*pathology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Growth- and tumor-promoting effects of deregulated BCL2 in human B-lymphoblastoid cells. (1989)
    National Academy of Sciences
    Details
    Publication Date: 1989-06-01
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    TdT-positive acute leukemia with monocytoid characteristics: clinical, cytochemical, cytogenetic, and immunologic findings (1984)
    American Society of Hematology
    Details
    Publication Date: 1984-07-01
    Description: Thirteen patients with acute leukemias that were difficult to classify by the use of cytochemical staining and terminal deoxyribonucleotidyl transferase (TdT) activity are reported. The phenotype of the leukemic cells was characterized by the presence of mature or early monocyte lineage antigens and intense Ia antigen expression detected by monoclonal antibodies, terminal deoxytransferase activity, and cytochemical features, including both Sudan black B and periodic acid- Schiff activity. The mean age of this group of patients was 60 years. Five patients had leukemia occurring after chemotherapy or radiotherapy of a prior malignant disease, and two patients had a refractory anemia prior to development of acute leukemia. These patients had a low response rate to chemotherapy. This series of leukemia appears to form a distinct nosologic entity, representing a leukemic transformation among early cells of the monocyte lineage, resulting in a predominant neoplastic cell that is less mature than either the French-American- British M4 acute myelomonocytic leukemia or M5 acute monoblastic leukemia. The presence of terminal deoxytransferase activity was interpreted as indicating the primitive state of the cells in the differentiation sequence, rather than as implying any significance with respect to lineage.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 4
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    Internalization of human immunodeficiency virus type I and other retroviruses by megakaryocytes and platelets (1990)
    American Society of Hematology
    Details
    Publication Date: 1990-05-15
    Description: Direct infection of megakaryocytes and platelets by human immunodeficiency virus type I (HIV-I) or other retroviruses has not been demonstrated. To determine whether this could occur, murine bone marrow was co-cultivated with the amphotropic retrovirus-producing cell line PA317-N2, and freshly isolated normal human bone marrow and platelets were co-cultivated with HIV-infected H9 cells. In each case, ultrastructural analyses showed viruses within megakaryocytes and platelets. In murine specimens, the uptake of retrovirus was avid at all stages of differentiation. In human specimens, viral uptake was less frequent. These results suggest that direct infection of megakaryocytes could play a role in the pathophysiology of HIV- associated disease. In addition, these observations suggest that cells of the megakaryocyte lineage could serve as target cells in gene transfer experiments using retroviral-based vectors.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 5
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    TdT-positive acute leukemia with monocytoid characteristics: clinical, cytochemical, cytogenetic, and immunologic findings (1984)
    American Society of Hematology
    Details
    Publication Date: 1984-07-01
    Description: Thirteen patients with acute leukemias that were difficult to classify by the use of cytochemical staining and terminal deoxyribonucleotidyl transferase (TdT) activity are reported. The phenotype of the leukemic cells was characterized by the presence of mature or early monocyte lineage antigens and intense Ia antigen expression detected by monoclonal antibodies, terminal deoxytransferase activity, and cytochemical features, including both Sudan black B and periodic acid- Schiff activity. The mean age of this group of patients was 60 years. Five patients had leukemia occurring after chemotherapy or radiotherapy of a prior malignant disease, and two patients had a refractory anemia prior to development of acute leukemia. These patients had a low response rate to chemotherapy. This series of leukemia appears to form a distinct nosologic entity, representing a leukemic transformation among early cells of the monocyte lineage, resulting in a predominant neoplastic cell that is less mature than either the French-American- British M4 acute myelomonocytic leukemia or M5 acute monoblastic leukemia. The presence of terminal deoxytransferase activity was interpreted as indicating the primitive state of the cells in the differentiation sequence, rather than as implying any significance with respect to lineage.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 6
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    Monoclonal antibodies to the human CSF-1 receptor (c-fms proto-oncogene product) detect epitopes on normal mononuclear phagocytes and on human myeloid leukemic blast cells (1989)
    American Society of Hematology
    Details
    Publication Date: 1989-02-15
    Description: The first monoclonal antibodies (MoAbs) to epitopes in the extracellular domain of the human c-fms proto-oncogene product (receptor for the macrophage colony stimulating factor, CSF-1) were used with flow cytometric techniques to study receptor expression on normal human peripheral blood monocytes, bone marrow cells, and leukemic blasts. On normal cells CSF-1 receptors were restricted in their expression to cells of the mononuclear phagocyte lineage. CSF-1 receptors were detected on leukemic blasts from 15 (30%) of 50 children with acute myeloid leukemia, compared with four (15%) of 26 adults. By contrast, detectable CSF-1 receptors were uniformly absent on blasts from 19 children with acute lymphoblastic leukemia. CSF-1 receptors on normal monocytes and myeloid leukemia cells could be induced to downmodulate by incubation with either human recombinant CSF-1 or phorbol esters, confirming that the receptors had functional ligand- binding sites and responded to transmodulation by inducers of protein kinase C. The numbers of receptors per cell and the percentage of positive cases were highest for leukemic blasts with cytochemical and morphological features of monocytes. However, CSF-1 receptors were also detected on a subset of leukemic blast cells with features of granulocytic differentiation (FAB subtypes M1 through M3). Southern blotting analyses of DNA from 47 cases of acute myeloid leukemia demonstrated no rearrangements within the 32 kb of genomic sequences that contain CSF-1 receptor coding exons or in the 50 kb upstream of the first coding exon. Analysis of the upstream region of the c-fms locus revealed that sequences representing the terminal 112 untranslated nucleotides of c-fms mRNA map 26 kb 5′ to the first coding exon, suggesting that at least one c-fms promoter is separated from the receptor coding sequences by a very long intron. Whereas expression of the CSF-1 receptor in myeloid leukemic blasts is not restricted to cells with monocytic characteristics, the apparently aberrant pattern of receptor synthesis in a subset of cases with granulocytic features appears not to be due to chromosomal rearrangements within 50 kb upstream of sequences encoding the receptor.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 7
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    Diversity in inhibitory effects of IFN-gamma and IFN-alpha A on the induced DNA synthesis of a hairy cell leukemia B lymphocyte clone reflects the nature of the activating ligand (1988)
    American Society of Hematology
    Details
    Publication Date: 1988-11-01
    Description: A hairy cell leukemia population was used as a clonal model for studying the direct immunomodulatory effects of recombinant interferon- alpha A (rIFN-alpha A) and rIFN-gamma on human B-cell proliferation. The leukemic cell population KON was notably quiescent when incubated in medium alone but was induced to significant in vitro DNA synthesis when cultured with any of four activators of human B cells: anti-IgM antibody, Staphylococcus aureus cells (SAC), phorbol myristate acetate (PMA), or B-cell growth factor (BCGF). While both rIFN-gamma and rIFN- alpha A exhibited suppressive effects on these responses, their inhibitory patterns were distinct and reciprocal. Thus, rIFN-gamma exclusively suppressed anti-IgM-and SAC-induced leukemic DNA synthesis, and rIFN-alpha A significantly suppressed only PMA- and BCGF-induced DNA synthesis. The effects of the rIFN preparations were ablated in the presence of IFN type-specific monoclonal antibodies. Kinetic analyses and pulsing studies revealed that inhibition was most notable when cells were exposed concomitantly to IFN and the activating ligand. That the diverse effects of IFN-gamma and IFN-alpha A are manifested on a single B-cell clone was confirmed by Southern blot analysis of restriction enzyme-digested KON cell DNA with a JH-specific probe. These studies suggest that the therapeutic potential of the two types of IFN may be influenced by the nature of the extracellular ligands in the leukemic mileau that promote leukemic clonal expansion.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 8
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    Human leukemic B cell activation: functional consequence of membrane IgM interaction with anti-IgM ligand is an alterable cell characteristic (1987)
    American Society of Hematology
    Details
    Publication Date: 1987-10-01
    Description: A functional study of several human malignant B cell populations has indicated that occasional leukemic clones are extraordinarily sensitive to signal transduction through membrane IgM. One isolated hairy cell leukemia (HCL) with low background DNA synthesis was stimulated to significant levels of DNA synthesis when cultured with high (100 micrograms/mL) concentrations of soluble anti-IgM ligands. In contrast to the activation of normal peripheral blood polyclonal B cells, this DNA synthesis was completely independent of accessory T cell factors. Although the HCL clone could also be induced to enter S phase by incubation in media supplemented with only activated T cell supernatant, culture of the clone with activated T cell supernatant plus anti-IgM Ab resulted in DNA synthesis that was significantly less than that induced by either activator alone. Factor(s) in T cell supernatant appear to modulate the leukemic clone so that the binding of ligand to membrane IgM is perceived as an inhibitory rather than a stimulatory signal for DNA synthesis. In terms of Ig Fc independence and low ligand dose requirements, anti-IgM-mediated inhibitory signal transduction in the T cell supernatant-activated HCL clone was found to mimic anti-IgM mediated suppression of the spontaneous DNA synthesis of an alternative HCL clone. The functional results suggest that the type of signal transduced anti-Ig ligands may reflect differences in the activation state of receptive leukemic B cells.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 9
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    Diversity in inhibitory effects of IFN-gamma and IFN-alpha A on the induced DNA synthesis of a hairy cell leukemia B lymphocyte clone reflects the nature of the activating ligand (1988)
    American Society of Hematology
    Details
    Publication Date: 1988-11-01
    Description: A hairy cell leukemia population was used as a clonal model for studying the direct immunomodulatory effects of recombinant interferon- alpha A (rIFN-alpha A) and rIFN-gamma on human B-cell proliferation. The leukemic cell population KON was notably quiescent when incubated in medium alone but was induced to significant in vitro DNA synthesis when cultured with any of four activators of human B cells: anti-IgM antibody, Staphylococcus aureus cells (SAC), phorbol myristate acetate (PMA), or B-cell growth factor (BCGF). While both rIFN-gamma and rIFN- alpha A exhibited suppressive effects on these responses, their inhibitory patterns were distinct and reciprocal. Thus, rIFN-gamma exclusively suppressed anti-IgM-and SAC-induced leukemic DNA synthesis, and rIFN-alpha A significantly suppressed only PMA- and BCGF-induced DNA synthesis. The effects of the rIFN preparations were ablated in the presence of IFN type-specific monoclonal antibodies. Kinetic analyses and pulsing studies revealed that inhibition was most notable when cells were exposed concomitantly to IFN and the activating ligand. That the diverse effects of IFN-gamma and IFN-alpha A are manifested on a single B-cell clone was confirmed by Southern blot analysis of restriction enzyme-digested KON cell DNA with a JH-specific probe. These studies suggest that the therapeutic potential of the two types of IFN may be influenced by the nature of the extracellular ligands in the leukemic mileau that promote leukemic clonal expansion.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 10
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    Human leukemic B cell activation: functional consequence of membrane IgM interaction with anti-IgM ligand is an alterable cell characteristic (1987)
    American Society of Hematology
    Details
    Publication Date: 1987-10-01
    Description: A functional study of several human malignant B cell populations has indicated that occasional leukemic clones are extraordinarily sensitive to signal transduction through membrane IgM. One isolated hairy cell leukemia (HCL) with low background DNA synthesis was stimulated to significant levels of DNA synthesis when cultured with high (100 micrograms/mL) concentrations of soluble anti-IgM ligands. In contrast to the activation of normal peripheral blood polyclonal B cells, this DNA synthesis was completely independent of accessory T cell factors. Although the HCL clone could also be induced to enter S phase by incubation in media supplemented with only activated T cell supernatant, culture of the clone with activated T cell supernatant plus anti-IgM Ab resulted in DNA synthesis that was significantly less than that induced by either activator alone. Factor(s) in T cell supernatant appear to modulate the leukemic clone so that the binding of ligand to membrane IgM is perceived as an inhibitory rather than a stimulatory signal for DNA synthesis. In terms of Ig Fc independence and low ligand dose requirements, anti-IgM-mediated inhibitory signal transduction in the T cell supernatant-activated HCL clone was found to mimic anti-IgM mediated suppression of the spontaneous DNA synthesis of an alternative HCL clone. The functional results suggest that the type of signal transduced anti-Ig ligands may reflect differences in the activation state of receptive leukemic B cells.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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