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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 41 (1995), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The ganglioside GD3 has a variety of biological functions. These include stimulatory effects is on proliferation, natural killer activity and cytokine production by freshly isolated peripheral T cells. In this study we have characterized anti-GD3 antibody (MoAb Z21) mediated effects on T cell clones. Our data indicate that α/β TCR CD4+ and CD8+ as well as γ/δ TCR positive T cells can be stimulated resulting in proliferation and cytokine production. This effect could be blocked by cyclosporin A and did not involve the LFA-3 or CD4 molecule. Apart from IFN-γ and IL-2 production by T helper I and T helper 0 cells we have observed production of IL-4 and IL-10 by T helper 2 cells indicating that the GD3 molecule is not a marker for a certain functional T cell subset. In contrast to anti-CD3 mediated activation, the responsiveness of T cells to stimulation via GD3 was dependent on the cell surface expression of the molecule and could be enhanced by costimulation via CD2, CD3, CD26 or CD28. In addition, anti-GD3 antibodies delivered a potent costimulatory signal for antigen-induced proliferation of CD4+ T lymphocytes. In summary, our experiments illuminate the mechanisms of anti-GD3 antibody induced T cell activation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Human immunodeficiency virus ; Hepatitis B virus ; Interferon-α ; Corticosteroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 48-year-old male patient was admitted with acquired immunodeficiency syndrome (stage III, Centers for Disease Control 1993) and viremic hepatitis B. Blood CD4 count was 15/μl. Discontinuation of prednisolone, previously prescribed by the patient's family practitioner because of elevated liver enzymes, resulted in severe hepatitis (alanine aminotransferase 〉 300U/1). Administration of interferon-α, (9 × 106U s.c. 3 × weekly) was initiated. Serum markers of viral replication disappeared, and aminotransferase levels returned to normal within a few weeks. The patient's serum was found negative for HBsAg after 3 months. Immunohistochemical analysis of liver biopsies before and during interferon therapy showed disappearance of all hepatitis B virus antigens and a marked reduction in inflammatory activity. Hepatitis B virus seroconversion remained stable until the patient died from the syndrome 2 years later. This case shows that in spite of severe HIV-associated immune deficiency with CD4 counts constantly below 100/μl, interferon-α can lead to sustained serological and histological improvement of viremic hepatitis B. Previous administration and discontinuation of cortisone may have helped to reach this effect.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2307
    Keywords: Stomach neoplasms ; Pancreatic neoplasms ; Cell differentiation ; Histocompatibility antigens ; Interferon gamma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two new cell lines from stomach cancers and one from a pancreatic carcinoma are presented. MZ-GC-1 was established from a hepatic metastasis of a well differentiated gastric adenocarcinoma. MZ-GC-2 was derived from ascites induced by a poorly differentiated gastric adenocarcinoma. MZ-PC-1 originated from the pleural effusion of a moderately well differentiated pancreatic ductal adenocarcinoma. MZ-GC-1 cells were adherent and partially polarized, connected tightly via desmosomes. In contrast MZ-GC-2 cells consisted of slightly adherent or floating subpopulations and displayed no desmosomes. MZ-PC-1 cells were adherent and showed polarized growth, connected by apical junctional complexes. Cell doubling times were 7 days for MZ-GC-1 and 45 h for MZ-GC-2 and MZ-PC-1 cells. MZ-GC-2 and MZ-PC-1 gave rise to nude mouse tumours, resembling the original lesions. Chromosome analysis of the cell lines revealed a high range of numerical abnormalities. Each cell line had cytokeratin patterns fitting well to typical in vivo patterns. Furthermore the cell lines expressed a panel of antigens typical for gastrointestinal epithelia. Unique for MZ-PC-1 were high amounts of secreted Ca19-9. γ-Interferon enhanced HLA-class I antigens up to twofold and induced ICAM-1 expression on each cell line. HLA-class II antigens were differentially enhanced by γ-interferon. Due to their distinct characteristics the three tumour cell lines may be useful models in the investigation of the cell biology and immunogenicity of gastrointestinal tumours.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-069X
    Keywords: Antigenic modulation ; Monoclonal antibodies ; Melanoma ; Radioimmunoelectron microscopy ; Radioantibody binding assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary There is a wealth of information about monoclonal antibody (MAb) specificity and function on fixed tissues, yet little is known about formation and release of antigen-antibody complexes and their functional behavior in vivo. We analyzed the pathway of radiolabeled MAbs directed against melanoma-associated antigens by radioimmunoelectron microscopy (RIEM) on metabolically active cells of the melanoma cell lines SK-MEL-28, MeWo and Colo 38 at different time intervals. In parallel, binding and release of MAbs were investigated by the radioantibody binding assay (RBA). Both procedures gave essentially concordant results. Preferentially stable binding of immune complexes (ICs) to the cell surface after 30 and 120 min was shown for the MAb L10. Internalization was demonstrated for the MAb M.2.9.4. At the ultrastructural level, direct evidence of this phenomenon was obtained by visualization of radioactivity within the cytoplasm after 120 min. In the RBA this process was indicated by resistance of bound MAbs to acid buffer desorption. RIEM pointed to different transport mechanisms: constitutive internalization by endocytotic vesicles, or receptor-mediated endocytosis by coated vesicles. Shedding was indicated for the MAb R24 by release of the ICs from the cell membrane. It was demonstrated that stable fixation of ICs on the cell surface or modulation by internalization led to high accumulation rates, while shedding of antigen-antibody complexes resulted in a low accumulation of the MAb in tumor cells. Assuming that the potential of MAbs for clinical application is determined by the biological behavior of antigen-antibody complexes, these methods are suitable for demonstration of antigenic modulation by MAbs and eventually enable us to predict the localization, penetration and distribution pattern of individual MAbs in the melanoma patient.
    Type of Medium: Electronic Resource
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