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

The AIDS-associated lymphomas represent a heterogeneous set of disease processes. The largest histologic subset of lymphomas is the large-cell lymphomas, which represent a spectrum of disease processes ranging from monomorphic monoclonal B-cell proliferations to very polymorphic and polyclonal mixtures of B cells, T cells and macrophages. The next most frequent class of systemic lymphoma are the small non-cleaved cell or Burkitt's-like lymphomas. These are relatively monomorphic, monoclonal malignant B-cell proliferations. The final subset of lymphomas, which are likely to become more common as the AIDS epidemic progresses, are the primary CNS lymphomas, which are expansions of EBV-immortalized B cells. The high incidence of tumor-associated EBV in the CNS lymphomas makes these lesions somewhat analogous to an opportunistic EBV infection. In HIV disease there is a long lag after infection before the appearance of clinical manifestations of impaired T-cell immunity. During this period, both appropriate B-cell proliferation in response to antigen (including the ubiquitous HIV) and abnormal B-cell proliferation (autoimmune, dysregulated) occur as the follicular architecture is disrupted by the virus and potential APC are exposed and/or infected with HIV. The destruction of FDC or the involution of their processes could interfere with the elimination by apoptosis of low-avidity B-cell clones. Antigen-competent B cells with pre-existing chromosomal translocations such as the t(8;14) (c-myc, IgH) would have a selective growth advantage in this setting. Figure 9 shows a schematic representation of prelymphomatous and lymphomagenic events as they are projected to occur. A similar pathogenetic scheme has been postulated for follicular B-cell lymphomas: PCR studies have demonstrated that a pool of t(14;18) (IgH;bcl-2) B-cells are present in lymph nodes featuring follicular hyperplasia. In response to antigen (the evidence favoring antigen drive is extensive hypersomatic mutation in sequences related to binding sites), B cells with the t(14;18) translocation have a selective advantage because the bcl-2 oncogene confers a resistance to apoptosis. Burkitt's lymphomas, particularly sporadic or HIV variants, fulfill at least the key criteria for antigen competence, mainly the presence of surface Ig. The c-myc-associated chromosomal translocational events are likely to occur early during the enzymatic machinations of gene rearrangement. Such B cells would be in the dysregulated cytokine and antigen milieu of HIV disease and ultimately could have a selective advantage. EBV infection of B cells probably requires activation and expression of the CD21 receptor. Furthermore, CD5+ B cells of CLL are refractory to EBV infection.(ABSTRACT TRUNCATED AT 400 WORDS)
AIDS 1994 Aug
PMID:Pathogenesis of AIDS lymphomas. 798 99

Organ transplant recipients and other immunodeficient individuals are at risk for the development of Epstein-Barr virus-related B-cell lymphomas. The incidence of lymphoma after cardiac transplantation ranges from 2 to 11%. To determine whether the clinical presentation, histological subtype, or clinical outcome correlated with DNA content, 17 patients with postcardiac transplant lymphoma were studied by flow and image cytometry. Their mean age was 52 yr (range: 33 to 67 yr) with a mean interval of 10 mo (range: 0.5 to 50 mo) between the time of transplantation and the diagnosis of lymphoma. Of the 17 specimens analyzed by flow cytometry, 14 (82%) were diploid and 3 (18%) aneuploid. By image cytometry, 15 (88%) were diploid and 2 (12%) aneuploid. Agreement between flow cytometry and image cytometry was 94%. No statistically significant correlation between DNA content (ploidy and % S-phase fraction) and the interval since transplantation, histological subtype, or clinical outcome could be determined. A rate of DNA aneuploidy was seen that was lower than previously reported for lymphomas with the same histological grade and cell proliferation rate occurring in immunocompetent individuals. These findings are similar to those reported for AIDS-related lymphomas.
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PMID:Flow and image cytometric DNA analysis of postcardiac transplant lymphomas. 805 5

Mutations of the p53 tumor suppressor gene are among the most common genetic alterations found in many different human malignancies, including those of the colon, lung, and breast. Alterations in wild-type p53 lead to loss of the suppressor function and thus contribute to tumorigenesis. The potential role of p53 mutations in a sampling of B-cell lymphomas, the majority of which were associated with Epstein-Barr virus (EBV), was investigated. Twenty-six biopsy specimens from immunocompromised patients, including allograft recipients and patients with AIDS, Wiscott-Aldrich syndrome, and human T-cell leukemia virus type 1 infection, in comparison with three Burkitt lymphomas and four Burkitt lymphoma cell lines were analyzed. Mutation in p53 was detected in all four Burkitt lymphoma cell lines as well as the three Burkitt lymphoma biopsy specimens. In patients with AIDS, 5 of 10 lymphomas were EBV positive, and 1 had a mutation in p53. Mutation in p53 was not detected in 14 EBV-positive lymphomas which arose in transplant recipients. These data indicate that with the exception of Burkitt lymphomas, p53 mutations are not involved in the majority EBV-positive B-cell lymphomas which develop in immunocompromised patients.
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PMID:Alterations of the p53 gene in Epstein-Barr virus-associated immunodeficiency-related lymphomas. 810 96

Research progress in the understanding of HIV and its effects on the human immune system continues at a rapid pace. Such research is yielding new ideas for chemotherapeutic agents, immunologic stimulators and modifiers, and potential vaccines. Clinical trials to test these approaches are under way. Despite the accomplishments, the epidemic progresses unchecked, resulting in continued suffering and death and enormous demands on the health care system of many nations. Clinicians have had to deal with new and difficult opportunistic infections. Yet advances in the treatment and prevention of these illnesses have benefited many AIDS victims. In the United States, the AIDS epidemic is now concentrating in the inner cities, involving injection drug users, minorities, heterosexuals, women and their offspring. In the developing world, AIDS continues to be predominantly a heterosexually transmitted disease, where more than one third of prostitutes in central African cities are infected. The major burden of the AIDS epidemic in the remainder of this and the next century will be in India and Southeast Asia, again predominantly via heterosexual spread. A great deal is now understood concerning the life cycle of HIV. More light has been shed on the interaction of HIV and CD4+ T cells, the cellular and viral factors involved in viral expression vs. latency, the function of the viral regulatory and structural proteins and the role of cytokines in regulation of HIV expression. Our understanding of the precise mechanisms whereby HIV causes a loss of CD4+ T cells remains incomplete. The direct infection and cell killing of CD4+ T cells is important and is supported by recent evidence demonstrating a high viral burden in these cells in the lymphoid tissue of patients. Over the last 1 to 2 years, there has been new evidence for indirect mechanisms of CD4+ T-cell depletion and/or dysfunction including: autoimmune reactions, perturbations of specific V beta T-cell receptor populations, infection of T-cell precursors in bone marrow and thymus, immunosuppression and dysregulation by viral proteins, possible super-antigen effects, and antigen-induced apoptosis or programmed cell death. New information has come forth in our understanding of B-cell abnormalities in HIV pathogenesis, including the putative role of IL-6 in B-cell activation and the identification of EBV in B-cell lymphomas in the CNS of patients with AIDS. It is expected that these and future discoveries concerning immunopathogenesis of HIV infection will help steer the therapeutic effort. Major strides continue to be made in the therapeutic arena for HIV infection and its complications.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human immunodeficiency virus and acquired immunodeficiency syndrome: an update. 814 Sep 58

We have established a cell line (DS-1) of B-cell lineage in long-term culture. It was derived from an immunodeficient patient with intestinal lymphangiectasia and lymphoma by culturing malignant pleural effusion cells with IL-6 in vitro. The cell surface phenotype was; PCA-1, HLA Class II(+); CD25, CD19, CD20, CD30, CD38(-). Cell proliferation was poor in medium and exhibited an eight-fold, dose-dependent increase of proliferation in response to rIL-6 of human but not murine origin. The secretion of IgG into culture supernatants by DS-1 was not enhanced by rIL-6. While constitutive production of IL-6 was not detected by bioassay using murine B9 hybridoma cells or by ELISA, the presence of IL-6 message was detected in polyA+ selected mRNA by Northern analysis. Spontaneous proliferation of DS-1 cells was inhibited by neutralizing polyclonal antibodies to IL-6 (37%) and mAb to IL-6 (54%) and IL-6R (53%). DS-1 expressed both high and low affinity IL-6 receptors (Kd 1.2 x 10(-11) and 6.7 x 10(-10), respectively) by radiolabelled binding and Scatchard analysis. Thus, DS-1 represents an autocrine IL-6-producing cell line of B-cell lineage which resembles lymphoid malignancies arising in patients with AIDS and other immunodeficiency diseases. Despite constitutive IL-6 production, the in vitro growth of DS-1 is dependent upon exogenous IL-6. DS-1 may thus be useful as a model of IL-6 dependency. This cell line may also facilitate development of strategies for diagnosis and treatment of B-cell lymphomas in immunocompromised patients.
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PMID:Characterization of a new IL-6-dependent human B-lymphoma cell line in long term culture. 814 4

Cytolytic T lymphocytes (CTL) can be raised against C57BL/6 B-cell lymphomas from mice with LP-BM5 murine leukemia virus-induced AIDS (MAIDS). Adoptive transfer of polyclonal anti-MAIDS tumor CTL or two CTL clones specific for the B6-1710 MAIDS lymphoma caused preservation of major histocompatibility complex-restricted and allogeneic CTL responses, which may be interpreted as indices of protection from LP-BM5 murine leukemia virus-induced immunodeficiency.
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PMID:Adoptive transfer of polyclonal and cloned cytolytic T lymphocytes (CTL) specific for mouse AIDS-associated tumors is effective in preserving CTL responses: a measure of protection against LP-BM5 retrovirus-induced immunodeficiency. 820 44

The human immunodeficiency virus tat protein, a transactivator of viral and cellular genes, is suspected to be involved in the pathogenesis of acquired immunodeficiency syndrome-associated tumors. We report that transgenic mice carrying a recombinant DNA containing BK virus early region and the human immunodeficiency virus tat gene develop skin leiomyosarcomas, squamous cell papillomas and carcinomas, adenocarcinomas of skin adnexa, glands, and B-cell lymphomas. Although the incidence of hepatocellular carcinoma is low, most animals show a liver cell dysplasia of variable degree. These mice are also affected by skin lesions resembling the early stages of Kaposi's sarcoma. The transgene was detected intact in all the organs of transgenic mice, generally as multiple tandemly integrated copies. BK virus early region and tat were expressed in essentially all tissues and organs of BK virus/tat transgenic mice. This transgenic mouse model is representative of the systemic involvement of tat in human immunodeficiency virus natural infection and may be applied to investigate the role of tat in malignancies associated to acquired immunodeficiency syndrome, to study Kaposi's sarcoma pathogenesis and cell of origin, to characterize preneoplastic conditions established by tat in the skin and liver, and to assess in vivo the efficacy of antiangiogenic and anti-tat-specific drugs.
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PMID:Systemic expression of HIV-1 tat gene in transgenic mice induces endothelial proliferation and tumors of different histotypes. 822 99

Marrow regeneration is known to be associated with an increase in immature B cells, including CD10+ cells. A similar phenotype has been seen in some children with unusual cytopenias. This article describes 21 adult patients not recovering from chemotherapy, who had increased CD10+ cells in their marrows. These cells had the relatively uniform scatter properties of small lymphocytes by flow cytometry, and by multiparameter analysis were found to have a distinct phenotype in that they were CD19+, lacked surface immunoglobulin, and heterogeneity expressed CD20. In two of three patients tested, some but not all of these early B cells were TdT+. CD10+ cells accounted for 10-76% of total mononuclear cells. All 21 patients had some systemic illness. Thirteen patients had a diagnosis of lymphoma (three Hodgkin's, ten non-Hodgkin's); all ten of the latter were extranodal and seven of seven phenotyped cases were B-cell lymphomas. Seven patients had autoimmune disease (one also had lymphoma) and one had the acquired immunodeficiency syndrome with mycobacterial infection of the marrow. One patient with a history of a "viral illness" had a lymph node showing atypical lymphoid hyperplasia with progressive transformation of germinal centers. Examination of marrow core biopsies in these patients showed a proliferation of small lymphocytes ranging from a barely perceptible diffuse increase to numerous lymphoid aggregates. The extensive lymphocytosis seen in two marrows suggested a diagnosis of lymphoma on morphologic grounds alone, but neither these patients nor any others had B-cell clonal excess. The presence of this phenotype suggests nonspecific stimulation of marrow B-cell precursors associated with systemic B-cell activation in either an immunologic or neoplastic disorder. Presence of this unusual phenotype does not imply involvement of marrow by B-cell neoplasia.
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PMID:Marrow B-cell precursors are increased in lymphomas or systemic diseases associated with B-cell dysfunction. 834 38

Murine AIDS (MAIDS) is induced by a replication-defective virus (BM5d). In susceptible mice (C57BL/6J), inoculation with LP-BM5 murine leukemia virus, which consists of the BM5d virus and replication-competent B-tropic ecotropic (BM5e) and milk cell focus-inducing (BM5-MCF) helper viruses results in the polyclonal proliferation of T and B cells, immunodeficiency, and the expansion of B cells containing the BM5d provirus followed by the development of B-cell lymphomas. Several strains of mice that are resistant to LP-BM5-induced murine AIDS have been identified, and major histocompatibility complex genes as well as non-major histocompatibility complex genes were shown to play a role in this resistance. In the present study, we have examined and compared the replication of the BM5d and BM5e viruses after inoculation of LP-BM5 into sensitive (C57BL/6J) and resistant (C57BL/KSJ) mice. Using a specific polymerase chain reaction, we could detect the BM5d and BM5e proviruses as early as 1 week postinfection in the sensitive mice, and the levels of both viruses increased significantly with the progression of the disease. In contrast, in the resistant C57BL/KSJ mice, replication of BM5d and BM5e was restricted and no BM5d and only very low levels of the BM5e provirus could be detected either at early or late times postinoculation with the LP-BM5 virus mixture. Inoculation with LP-BM5 did not lead to the production of antibodies that could recognize the BM5d-encoded Pr60gag in either the sensitive or resistant mice; however, production of antibodies recognizing the env-related proteins of the helper virus was detected in the resistant but not in the sensitive mice at late times postinfection. Interestingly, inoculation with LP-BM5 increased polyclonal stimulation of spleen cells and decreased mitogen stimulation in both strains of mice. This stimulation of splenocytes persisted in the sensitive mice but decreased after a few weeks in the resistant mice. These results show an early block in BM5d and BM5e replication in the resistant C57BL/KSJ mice and indicate that resistance is a consequence of the inhibition of an onset of the BM5d virus infection and its expansion. However, initial responses to virus infection such as proliferation of spleen cells and response to mitogen are similar in both strains of mice and are therefore not necessarily related to the development of the disease.
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PMID:Dissociation between lymphoproliferative responses and virus replication in mice with different sensitivities to retrovirus-induced immunodeficiency. 838 Apr 73

Although immunophenotypic abnormalities have been reported in B-cell non-Hodgkin's lymphomas (NHLs) occurring in the general population, there are no extensive studies on such abnormalities in AIDS-related B-cell NHLs. Reactivity of CD45RO/UCHL1 and expression of other T-cell associated antigens (CD43, OPD4, CD3, CD5, EMA) were examined by immunohistochemistry in 66 diffuse aggressive AIDS-related B-cell NHLs and in 296 AIDS-unrelated B-cell NHLs of similar morphology analyzed in the same institution. EBER in situ hybridization studies were also carried out in 57 of the 66 AIDS-related B-cell NHLs investigated. CD45RO/UCHL1 was expressed in 27% of AIDS-related B-cell NHLs, but only in 8% of diffuse aggressive AIDS-unrelated B-cell NHLs. The difference was highly significant (P < .001) overall and, within the Working Formulation subtypes, especially marked among small noncleaved cell (SNCC) lymphomas. Conversely, the reactivity of other T-cell associated antigens seemed to be very similar in AIDS-related and AIDS-unrelated NHLs. However, for CD43, a significantly lower number of positive cases was found in AIDS-related NHLs among SNCC lymphomas. Among AIDS-related B-cell NHLs, the highest frequency of CD45RO/UCHL1 expression was found in the immunoblastic subset with plasmacytoid differentiation. In the latter CD45RO/UCHL1 preferentially associated with EMA expression and EBV infection of the tumor clone, but not with CD45RA. The present finding of an excess of CD45RO/UCHL1 expression in AIDS-related B-cell lymphomas may reflect the preferential expansion of CD45RO expressing B-cell clones with putative autoreactive potential, as suggested by the expansion of CD45RO expressing B-cells in autoimmune disorders.
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PMID:High frequency of CD45RO expression in AIDS-related B-cell non-Hodgkin's lymphomas. 852 13


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