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  • 1
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vinzolidine, a semisynthetic vinca alkaloid, was studied as oral therapy in 30 patients with Kaposi's sarcoma, non-small cell lung cancer, colorectal cancer, and breast cancer. Substantial variations in morbidity were observed among the patients, some patients receiving doses up to 45 mg/m2 without toxicity while others had severe hematologic toxicity at doses as low as 25 mg/m2. Nausea/vomiting and diarrhea also occurred. Responses were seen in two of 11 patients with Kaposi's sarcoma but not in other patients. Unpredictable severe hematologic toxicity led to early closure of this study. The heterogeneity of patient tolerance may relate to variable oral drug biovailability, and it is conceivable that vinzolidine could be administered more safely by the IV route.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-2592
    Keywords: Acquired immunodeficiency syndrome (AIDS) ; antibody-dependent cellular cytotoxicity (ADCC) ; CD4+ T lymphocytes ; human immunodeficiency virus (HIV)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The acquired immunodeficiency syndrome (AIDS) is defined in clinical terms by the development of Kaposi's sarcoma and/or severe opportunistic infections in persons without predisposing conditions. A hallmark of the syndrome has been a decrease in the number of CD4+ T helper cells. The reduction in the frequency of the CD4+ lymphocytes has been postulated to be primarily the result of human immunodeficiency virus (HIV) tropism and cytophathogenicity for the T-cell subset. Yet only a small percentage of cells is actually infected with HIV. Recently, we provided evidence indicating that AIDS patients' natural killer cells can mediate normal levels of antibody-dependent cellular cytotoxicity (ADCC) despite exhibiting a defect in natural killer (NK) effector function (J Immunol 139:55, 1987). This finding prompted us to investigate whether AIDS patients' effector cells could mediate ADCC against circulating CD4+ T cells infected with or expressing HIV antigen. The findings reported herein demonstrate that AIDS effector cells can mediate lysis of CEM (CD4+ T-cell line) coated with HIV protein in the presence of HIV-specific antibody. Lysis was specific, as non-HIV-coated CEM or the addition of HIV-negative serum resulted in no lysis. We then examined HIV-coated peripheral blood-derived CD4+ T lymphocytes as targets in ADCC. We demonstrate that in the presence of HIV-specific antibody, HIV-coated CD4+ T lymphocytes serve as targets for ADCC by AIDS effector cells. The lytic activity obtained with AIDS effector cells was comparable to that obtained with normal effector cells. These results demonstrate that AIDS effector cells can mediate ADCC against HIV-coated CD4+ T lymphocytes and suggest that ADCC may play a rolein vivo in the pathogenesis of AIDS.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-2592
    Keywords: Acquired immune deficiency syndrome ; natural killer cells ; cell phenotype ; viral infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Testing of cytotoxic function using a panel of natural killer (NK)-sensitive target cells, including a unique herpes simplex virus-infected Raji-cell target, was performed in conjunction with phenotypic cell analysis by dual-color flow cytometry to characterize the NK system. Subjects included in the study were at risk for or infected with the etiologic agent of the acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV). A generalized defect in NK function was temporally correlated with disease manifestations, as evidenced by deficient NK lytic function in patients with AIDS and AIDS-related complex (ARC). Healthy at-risk subjects, including those seropositive for HIV, exhibited robust NK-cell function. Phenotypic analysis revealed that normal proportions of the NK-associated CD16+ (Leu11) Leu7− and CD16+(Leu11)Leu7+ lymphocyte subsets were maintained throughout the clinical progression of HIV infection. However, the proportion and numbers of cells of the CD8+(Leu2)Leu7+ subset were increased in AIDS, ARC, and healthy at-risk subjects, including those seronegative for HIV. These results are consistent with a qualitative defect in the NK system in AIDS, perhaps secondary to CD4-cell depletion and a concomitant lack of essential accessory factors. The elevation in CD8+(Leu2)/Leu7+ cells is not solely the result of HIV infection and may be a general response to viruses and/or other antigenic stimulation.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Biotherapy 2 (1990), S. 173-181 
    ISSN: 1573-8280
    Keywords: G-CSF ; GM-CSF ; erythropoietin ; HIV infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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