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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a series of 33 cynomolgus monkeys (Macaca fascicularis) experimentally infected with Simian Immunodeficiency virus (SIV), strain smm3, 13 animals developed malignant Non-Hodgkin lymphomas. These lymphomas presented with unusual primary manifestations like in the orbita, testes, and brain. The morphological features and immunophenotyping identified the tumors as high malignant B-cell lymphomas. In all tumors as well as in tumor-derived cell lines a cynomolgus B-lymphotropic herpes virus (CBLV) with structural homogeneity to the Epstein-Barr virus (EBV) could be demonstrated by Southern blotting with EBV-specific probes. The lymphoma cells also expressed CBLV-associated nuclear antigens involved in B-cell transformation crossreacting with EBNA-specific human sera and monoclonal antibodies. Ig-gene rearrangement studies revealed clonal populations, however, no translocations of the c-myc oncogene could be detected. The lymphomas developing with high frequency in SIV-induced immunodeficiency resemble a major subtype of human EBV-associated AIDS lymphomas. This animal model can therefore be used to further elucidate interactions of HIV and EBV in AIDS-related lymphomagenesis.
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PMID:[Opportunistic malignant lymphomas in SIV infected primates--a model for Epstein-Barr virus associated lymphomas in AIDS]. 128 56

Epstein-Barr virus (EBV) is associated with B-cell malignancy in immunosuppressed humans and SCID mice receiving human peripheral blood leukocyte grafts (hu-PBL-SCID). We have further characterized the process of lymphoma development in hu-PBL-SCID mice. We report that EBV-seropositive donors differ markedly in the capacity of their PBL to give rise to immunoblastic lymphomas in SCID mice; some donors (high incidence) generated tumors rapidly in all hu-PBL-SCID mice, other donors (intermediate-low incidence) gave rise to sporadic tumors after a longer latent period (greater than 10 weeks), and some donors failed to produce tumors. B-cell lymphomas arising from high incidence donors were multiclonal in origin, and EBV replication was detected in all tumors. Tumors derived from intermediate-low incidence donors were monoclonal or oligoclonal and often had no evidence of viral replication. All tumors, regardless of the donor, resembled EBV-transformed lymphoblastoid cell lines in surface phenotype but differed from lymphoblastoid cell lines by having less Epstein-Barr nuclear antigen 2 and CD23 expression. The variable patterns of lymphomagenesis seen among different EBV-sero-positive donors may be explained by lower levels of specific immunity to EBV in high incidence donors, permitting activation of EBV replication and potential transformation of secondary B-cell targets. In addition, there may be differences in the transforming potential of EBV infecting different donors. The use of the hu-PBL-SCID model may help predict patients at high risk for posttransplant or acquired immunodeficiency syndrome-associated lymphomas.
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PMID:Heterogeneity among Epstein-Barr virus-seropositive donors in the generation of immunoblastic B-cell lymphomas in SCID mice receiving human peripheral blood leukocyte grafts. 131 93

We have established a line of malignantly transformed human B cells by infecting purified primary B lymphocytes with human immunodeficiency virus type 1 (HIV-1). This line, termed B-HIV1, may serve as a model system for a subset of AIDS-related B-cell lymphomas in which the transformed phenotype may be initiated and/or maintained through an HIV-1 gene product. The B-HIV1 line contains both Epstein-Barr virus (EBV) and HIV-1 genomes. In addition, the c-myc gene is expressed at levels 10 to 20 times those in normal B cells. Similarly, EBV sequences, including those for the latent membrane protein (LMP), are expressed at greatly enhanced levels relative to expression in normal, EBV-immortalized B cells. The upregulation of c-myc and of EBV gene expression can both be produced by infection of susceptible B cells (not already harboring HIV) with exogenous HIV-1. The B-HIV1 line exhibits properties of malignantly transformed cells, in that it grows logarithmically in 1% serum, clones in soft agar, and produces invasive, malignant B-cell lymphomas in severe combined immunodeficient (SCID) mice. We have shown that HIV-1 has the ability to infect primary human B cells and to activate expression of EBV and c-myc. HIV activation of EBV has been documented previously in certain cell lines, here we note that such activation can occur in primary B cells and, under certain conditions, can result in outgrowth of immortalized cell lines. This phenomenon may contribute to the clinical manifestation of lymphadenopathy early after infection with HIV. In addition, we have demonstrated that HIV infection of primary B cells in vitro can result in appearance of a fully malignant phenotype. This phenotype is likely to be due, at least in part, to the activation of c-myc by HIV. Preliminary experiments indicate that Tat, the gene product of the transactivator of viral gene transcription tat, can upregulate c-myc transcription after addition to the culture media of certain B-cell lines. This raises the possibility that Tat can bind to target sequences in cellular RNA and enhance transcription as it does for HIV.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human immunodeficiency virus activates c-myc and Epstein-Barr virus in human B lymphocytes. 131 11

A recent addition to the lymphokine network is human IL-10 (hIL-10). This novel lymphokine has striking homology to BCRF1 protein, the product of a previously uncharacterized open-reading frame in the Epstein-Barr virus (EBV) genome. To date, IL-10 expression has been described in several T clones induced with anti-CD3 and phorbol myristate acetate (PMA), in monocytes stimulated with lipopolysaccharide (LPS), and in murine B-cell lymphomas. We sought to determine whether human B cells express hIL-10 and, if so, its relationship to EBV and to other B-cell lymphokines. We studied 21 EBV-positive B-cell lines derived from patients with acquired immunodeficiency syndrome (AIDS) and Burkitt's lymphoma (n = 6), American Burkitt's (n = 3), African Burkitt's (n = 5), and normal lymphoblastoid cell lines (n = 7), in comparison with seven EBV-negative cell lines. All cell lines were activated with the tumor promoters PMA and teleocidin and were studied by Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunoadsorbent assay (ELISA). We demonstrated that EBV-positive cell lines derived from patients with American Burkitt's lymphoma, and especially those from patients with AIDS, constitutively express large quantities of hIL-10 by Northern blot analysis and ELISA (range, 3,101 to 25,915 pg/mL), and that both teleocidin and PMA induce hIL-10 in these cell lines. In contrast, six of seven EBV-negative cell lines did not express hIL-10 even by RT-PCR, and hIL-10 was not triggered by PMA or teleocidin. To assure that the 350 bp amplified by PCR was hIL-10 and not BCRF1, we used PCR primers, which do not amplify a fragment from plasmid templates containing BCRF1. Cloning and sequencing of the 350 bp product also demonstrated that B-cell IL-10 is identical to hIL-10 from the T-cell clone B21. Correlation of hIL-10 with other B-cell lymphokines secreted by these B-cell lines demonstrated that hIL-10 secretor cell lines also constitutively secrete or can be induced to secrete IL-6, although to a much lesser amount. Since both lymphokines influence B-cell growth and differentiation, we suggest that hIL-10 may contribute to the polyclonal B-cell activation and hyperglobulinemia seen in AIDS patients. Finally, several reports support the hypothesis that EBV is an important cofactor in the development of human immunodeficiency virus type 1 (HIV-1)-related B-cell lymphomas. Detection of large quantities of hIL-10 in B-cell lines derived from AIDS patients, the close association between EBV and hIL-10 shown in this report, and the ability of BCRF1 to capture hIL-10 activities, make hIL-10/BCRF1 an attractive candidate as a factor causing B-cell growth and immortalization in patients with AIDS and B-cell lymphomas.
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PMID:Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10. 842 93

Patients infected with the human immunodeficiency virus are at increased risk for developing intermediate-grade and high-grade B-cell lymphomas that in many instances contain Epstein-Barr viral (EBV) DNA. Because interleukin-5 (IL-5), a potent stimulator of eosinophil growth and differentiation, has been detected recently in EBV-infected B-cells, we hypothesized that some acquired immunodeficiency syndrome-related lymphomas with EBV DNA also might contain eosinophilia and IL-5. After reviewing files entered into our archives during the past 3 years, we identified four cases of human immunodeficiency virus-associated, high-grade, B-cell lymphomas that also contained extensive infiltration by eosinophils. Cryopreserved DNA from two of these four cases was available for amplification by the polymerase chain reaction, and both cases yielded an easily identifiable, EBV-specific amplification product. From one of these cases we also were able to extract mRNA and perform messenger amplification phenotyping (MAPPING) for the detection of mRNA coding for IL-5. After reverse transcription of mRNA from this case to cDNA and amplification by the polymerase chain reaction, we identified an amplification product that co-migrated with IL-5-positive controls in an agarose gel. We conclude that some AIDS-related lymphomas are associated with eosinophilia and that the eosinophilia may be related to EBV infection and transcriptional activation of the IL-5 gene.
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PMID:Epstein-Barr virus and interleukin-5 mRNA in acquired immunodeficiency syndrome-related lymphomas with eosinophilia. 133 44

We have characterized cells from an AIDS-associated non-Hodgkin's lymphoma (NHL). We found a malignant CD5+ B cell (approximately three-fourths of cells), with the balance of cells comprised of T cells having an activated phenotype. The lymphoma was unusual, in that all cells bear "T-lineage" markers, CD3 and CD5, and "B-lineage" markers, CD19 and CD20. Thus, conventional immunohistologic techniques were insufficient to type this mixture of cells; single-cell analysis was required. These "mixed-phenotype" lymphomas may occur frequently in AIDS-associated NHL. Our results show striking similarity to those obtained in the analysis of certain murine CD5+ B-cell lymphomas, suggesting that the study of lymphomagenesis in the mouse may aid in the understanding of AIDS-associated NHL.
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PMID:Large-cell "mixed-phenotype" lymphoma in AIDS. Identification of a CD5-expressing subset of B-cell non-Hodgkin's lymphoma. 137 58

The development of AIDS-related lymphomas (ARL) has been on the rise in recent years. During an analysis of ARL from AIDS patients, one individual developed atypical syncytial variants of high-grade Burkitt's-type B-cell lymphomas, which prompted further study. However, the search for a HIV-1 retrovirus, which we hypothesized was infecting these cells, led to the subsequent discovery of a type D retrovirus in two early-passage lymphoma cell lines derived from this patient. Nucleotide and amino acid sequence analysis, as well as immunologic reactivity, indicated that the virus was closely related to Mason-Pfizer monkey virus (MPMV) or simian retrovirus type 1 (SRV-1). MPMV and SRV-1 are immunosuppressive type D retroviruses that cause an AIDS-like syndrome in rhesus macaques. Amplification of DNA from the patient's diagnostic bone marrow biopsy specimen by the polymerase chain reaction generated MPMV-specific fragments indicative of infection by a retrovirus similar to MPMV. Additionally, the patient's serum contained antibodies that recognized type D retroviral env proteins (gp20 and gp70) and gag proteins (p27 and p14) as assayed by immunoblot and radioimmunoprecipitation techniques. Although there have been reports of human cell lines infected with type D retroviruses and of type D reactive human sera, this is the first report of a type D retrovirus infection in a human confirmed by virus isolation, serum immunoreactivity, and viral DNA identification in tumor tissue.
AIDS Res Hum Retroviruses 1992 May
PMID:Studies on a type D retrovirus isolated from an AIDS patient lymphoma. 138 Dec 7

The neuropathologic findings in the spinal cord were reviewed in 138 consecutive autopsies of patients with the acquired immunodeficiency syndrome. In all cases both the brain and spinal cord were examined by conventional histologic techniques, and in 63 cases immunohistochemistry was used to detect human immunodeficiency virus (HIV), Toxoplasma gondii, cytomegalovirus, and JC papovavirus antigens. The most common observation was a normal spinal cord (60%). Vacuolar myelopathy (VM) was observed in 23 (17%) cases. Human immunodeficiency virus myelitis was evident in 8% of cases. Human immunodeficiency virus myelitis was associated with HIV encephalitis in 65% of the cases. Opportunistic infections of the spinal cord were uncommon, consisting of cryptococcosis (five cases), cytomegalovirus (four cases), toxoplasmosis (one case), and progressive multifocal leukoencephalopathy (one case), and almost always were seen with cerebral and/or systemic infection by these agents. Malignant lymphoma rarely involved the spinal cord (four cases); all were B-cell lymphomas and were associated with cerebral and/or systemic lymphoma. Other abnormalities rarely observed were Wallerian degeneration of the corticospinal tracts or posterior columns (6%) and focal microinfarcts. Most cases of VM (78%) were not associated with HIV myelitis, and in the five patients with both VM and HIV myelitis, HIV-infected cells were not found in the regions affected by VM. In contrast, 65% of cases with VM were associated with HIV encephalitis. The pathogenesis of VM remains unknown; it is probably not due to direct infection by HIV.
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PMID:Neuropathology of the spinal cord in the acquired immunodeficiency syndrome. 139 40

Tissues containing Hodgkin's disease (HD) are frequently infiltrated by large numbers of eosinophils. Because eosinophils as well as Reed-Sternberg (RS) cells express membrane receptors (CD23) for IgE, this study was performed to determine if IgE is present in tissue sections of HD and to correlate the results, when possible, with serum IgE levels and the presence of interleukin-5 (IL-5) messenger RNA (mRNA) in RS cells. Paraffin-embedded, B-5-fixed slices of 13 cases of HD, one case of acquired immunodeficiency syndrome (AIDS)-related HD, seven cases of benign lymphoid hyperplasia (including two cases from HD patients), and five cases of B-cell lymphomas were analyzed by a sensitive immunoperoxidase staining technique that used a murine monoclonal antibody specific for human IgE. In the benign hyperplastic lymph nodes and non-Hodgkin's lymphomas, IgE was generally detectable only in rare plasma cells and in follicular dendritic cells. In 11 of the 14 cases of HD, including one case of AIDS-related HD, IgE was readily detectable within RS cells and variants and on the surrounding cells and connective tissue. These cases also had significant numbers of eosinophils, and IL-5 mRNA was detectable in three of the cases that were tested. Serum IgE was moderately elevated in the two serum specimens from HD patients that were available for analysis. The results of this study, therefore, indicate that some cases of HD contain abundant deposits of IgE, which may account for the extensive infiltration by eosinophils seen in this neoplasm.
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PMID:IgE in Reed-Sternberg cells of Hodgkin's disease with eosinophilia. 153 40

LP-BM5 retrovirus complex-infected C57BL/6 mice develop immunodeficiency, somewhat analogous to AIDS, termed murine AIDS (MAIDS). After secondary stimulation with syngeneic B-cell lymphomas from LP-BM5-infected mice, C57BL/6 mice produced vigorous CD8+ cytotoxic T lymphocytes specific for MAIDS-associated tumors. An anti-LP-BM5 specificity was suggested because spleen and lymph node cells from LP-BM5-infected mice served as target cells in competition assays, and cells from LP-BM5, but not ecotropic, virus-infected mice functioned as secondary in vitro stimulators to generate cytotoxic T lymphocytes to MAIDS tumors.
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PMID:Cytolytic T lymphocytes specific for tumors and infected cells from mice with a retrovirus-induced immunodeficiency syndrome. 156 May 46


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