Cases reported "AIDS-Related Complex"

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1/12. One-year follow-up of vaccine therapy in HIV-infected immune-deficient individuals: a new strategy.

    immunization of AIDS/ARC patients with autologous cells expressing hiv antigens, although providing clinical and biological benefits, fails to restore cellular immunity. The latter result is due partly to the antiproliferative effect of hiv-1 on activated T-cells (immune suppression), which leads to blockade of specific immune reactions. To overcome immune suppression, a new vaccine strategy was designed consisting of an immunization against hiv-1 combined with components of the T-cell-suppressive (antiproliferative) network. This new vaccine treatment proved to be innocuous in mice, monkeys, and two non-HIV-infected humans. A Phase I clinical trial was performed in six patients previously under cellular immunotherapy and still presenting a cellular immune defect. Preliminary results confirmed, after a 1-year follow-up of the patients, the safety of the new vaccine, which also partially restored the cellular immune response, including anti-HIV HLA-restricted cell-mediated cytotoxicity, delayed hypersensitivity to recall antigens, and proliferation of T-cells specifically activated by recall antigens.
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2/12. Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection.

    Antibodies against cytoplasmic antigens of neutrophils, producing perinuclear (p-ANCA) as well as cytoplasmic staining with central accentuation (c-ANCA), have been described in non-HIV-infected patients with specific pathology such as glomerulonephritis and vasculitis. Here, we report on a patient with a vasculitis-like syndrome and a positive ANCA-test who appeared to be infected by HIV. Further analysis revealed that ANCA, p-ANCA as well as c-ANCA without central accentuation can be demonstrated in the serum of HIV individuals. In a cross-sectional study on individuals in different stages of HIV infection, we found that the occurrence of ANCA was limited to the symptomatic stages of HIV infection: p-ANCA was found in one out of 10 ARC patients and in two out of 11 AIDS patients with malignancies (AIDS-MAL), but not in AIDS patients with opportunistic infections (AIDS-OI). c-ANCA was found in four of the ARC patients, in two of the 14 AIDS-OI patients and in two AIDS-MAL patients. The presence of ANCA was not related to the degree of hypergammaglobulinaemia nor to specific symptomatology. ANCA containing sera from HIV individuals did not react with HEp2 cells nor with cytoplasmic antigens of lymphocytes, natural killer (NK) cells or eosinophils. Five out of the 11 (two p-ANCA and three c-ANCA) sera reacted weakly with cytoplasmic antigens of monocytes. All sera reacted with karyoplasts but not with cytoplasts prepared from neutrophils. These results suggest that HIV-ANCA might be directed against myeloid cell-specific granule constituents. However, sandwich-ELISAs with MoAbs against granule antigens that are frequently the target antigens of ANCA in HIV- individuals were negative. Also immunoprecipitation and immunoblotting, using lysates of neutrophil granules, did not allow further identification of the target antigens of HIV-ANCA.
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3/12. Low yield of screening for cryptococcal antigen by latex agglutination assay on serum and cerebrospinal fluid from Danish patients with AIDS or ARC.

    From July 1, 1989 to September 5, 1990, 530 serum specimens and 50 cerebrospinal fluid (CSF) specimens from 334 hiv-1 infected patients, most of whom had AIDS or ARC, were analysed in a cryptococcal antigen latex agglutination assay, and all were negative. Three cases of meningitis due to cryptococcus neoformans diagnosed by microscopy and culture in 3 hiv-1 infected patients are presented. Stored specimens of serum and CSF from these patients were assayed for cryptococcal antigen, and in all 3 the onset of meningitis was preceded by the presence of cryptococcal antigen in serum. It is concluded that the low occurrence of cryptococcosis in our patient population does not justify a routine serum screening for cryptococcal antigen.
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4/12. cytomegalovirus encephalopathy in an infant with congenital acquired immuno-deficiency syndrome.

    A female infant born pre-term to a HIV seropositive mother presented at birth with seropositivity for HIV and CMV viruria. At five months of age she developed an aids-related complex. Six months later she died from rapidly progressive diffuse encephalopathy. Post mortem examination revealed generalized CMV infection. Neuropathological examination showed a nodular encephalitis with occasional cytomegalic cells containing characteristic CMV inclusion bodies. There was no evidence of HIV encephalitis; immunostaining for HIV antigen (gp 41) was negative. opportunistic infections in infants with congenital AIDS are the exception. To our knowledge, only one case of CMV encephalitis in an infant with congenital AIDS has been reported previously. In that case, as in the present one, a reactivation of a congenital CMV infection is likely.
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5/12. Dual infection of retina with human immunodeficiency virus type 1 and cytomegalovirus.

    We examined retinal tissue from eight human immunodeficiency virus type 1 (hiv-1) seropositive patients with acquired immunodeficiency syndrome (AIDS) or aids-related complex for evidence of dual infection with hiv-1 and cytomegalovirus. culture demonstrated simultaneous infection with hiv-1 and cytomegalovirus in two of 13 retinal specimens. This was confirmed by both immunofluorescence and immunohistochemical staining. Moreover, coinfection of individual cells with cytomegalovirus and hiv-1 was observed by immunohistochemical staining. Infection of retina with cytomegalovirus or hiv-1 alone occurred in one and six of the 13 retinal specimens, respectively. hiv-1 antigens were present on scattered cells in all layers of the retina and on retinal vascular endothelium. hiv-1 was isolated from retinal tissue derived from eyes both with and without gross ocular lesions. cytomegalovirus antigens were found in all layers of the retina, but not on vascular endothelial cells. The atypically rapid clinical progression of retinitis in one of the patients with dual hiv-1 and cytomegalovirus infection suggests the possibility that interactions between these two viruses may influence retinal disease in patients with AIDS.
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6/12. Epithelioid angiomatosis: a distinct vascular disorder in patients with the acquired immunodeficiency syndrome or aids-related complex.

    Unusual cutaneous vascular neoplasms distinct from Kaposi's sarcoma were observed in five patients with the acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 infection. The cutaneous lesions were solitary or multiple papules and nodules. In some patients the lesions also affected internal organs. Histologically the neoplasms were composed of proliferating blood vessels and cells with epithelioid features. Immunoperoxidase studies of one lesion showed that the cells expressed both factor viii antigen, a maker for endothelial cells, and alpha 1-anti-chymotrypsin, a marker for histiocytes. In some patients the lesions gradually disappeared but in two they were the cause of death, in one case from disseminated intravascular coagulation and in the other from laryngeal obstruction by the tumour.
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7/12. Abnormal antibody responses in patients with persistent generalized lymphadenopathy.

    Persistent, generalized lymphadenopathy (PGL) is a recognized component of human immunodeficiency virus (HIV) infection. We conducted longitudinal studies of B and T cell function in seven homosexual men with HIV infection and PGL. All seven had abnormal antibody-mediated immunity as studied by sequential assessment of in vivo antibody responses after immunization with the T-dependent neoantigens bacteriophage phi x 174 and keyhole limpet hemocyanin (KLH), the T-independent tetradecavalent pneumococcal polysaccharide vaccine, and the recall antigens diphtheria and tetanus toxoid. Compared to HIV-negative heterosexual controls, PGL patients responded with lower antibody titers and, following immunization with phage, failed to develop immunologic memory and to switch from IgM- to IgG-isotype antibody. in vitro antigen-induced antibody production was markedly diminished; and some patients showed depressed mitogen responses. There was a correlation between the degree of compromised immunity and the clinical condition; those with the most severe symptoms showed the most extensive immune deficiency. Yet despite obvious immunologic impairment five of the seven men have remained clinically stable over a 3-year follow-up period.
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8/12. High titer anti-HIV antibody reactivity associated with a paraprotein spike in a homosexual male with AIDS related complex.

    We observed a human immunodeficiency virus (HIV)-infected homosexual male with AIDS related complex (ARC) who had a serum globulin level of 80 g/L. serum protein electrophoresis revealed a gamma globulin fraction of 40 g/L, of which 50% (20 g/L) was contained within a paraprotein spike, comprised predominantly of IgG kappa. This patient also had high titer anti-hiv antibodies in his serum, which were Western blot reactive at a final dilution of 1:500,000, and recognized gp120env, p66pol, p55gag, p53pol, p41gag, and p24gag. Because paraproteins in the past have been shown to be directed against specific antigens, we purified this patient's paraprotein using a modified high performance liquid chromatography (HPLC)-hydroxylapatite procedure and tested the purified paraprotein for anti-HIV antibody activity. The purified paraprotein retained anti-HIV antibody activity to a final dilution of 1:100,000, and recognized p66pol, p55gag, p53pol, p41gag, and p24gag. The recognition of both "gag" and "pol" gene products suggested that the purified paraprotein might not be monoclonal in origin. sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the purified paraprotein contained at least two immunoglobulin light chain species (Mol wt 30 to 33 Kd). Affinity chromatography of the purified paraprotein using a p24-sepharose 4B matrix separated the "gag" and "pol" antibody activities. Immunoglobulin gene rearrangement analysis of a bone marrow aspirate (which contained 15% plasma cells) failed to reveal a clonal population of immunoglobulin producing cells. We conclude that this patient's paraprotein accounted for most of the anti-HIV activity present in whole serum, and that this paraprotein was not monoclonal in origin.
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9/12. Study of AIDS-related lymphadenopathy in the intraparotid and perisubmaxillary gland lymph nodes.

    Salivary gland lymph node involvement is rare in patients at risk for AIDS. Intraparotid and perisubmaxillary gland lymph node biopsies from 2 intravenous drug abusers serologically positive for human immunodeficiency virus (HIV) affected by persistent generalized lymphadenopathy (PGL) were also analyzed immunohistologically. We found hypervascular reactive lymphoid hyperplasia with prevalence of suppressor T-cells within follicular centers often lacking surface IgD-positive mantle zone cells and showing disruption of the network of dendritic reticulum cells revealed with DRC-1 and anti-S-100 protein antibodies. Within the nodes there were numerous cysts lined by metaplastic squamous epithelium/positive for epithelial membrane antigen and containing numerous lymphocytes positive for leukocyte common antigen, macrophages positive for alpha 1 -antichymotrypsin, and langerhans cells positive for OKT6. Salivary gland lymph nodes are immunohistologically similar to those of other sites in PGL and their increased epithelial metaplastic component containing cells involved in the immune response might represent an exuberant reaction to HIV infection.
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10/12. Immunologic studies of lymph node lymphocytes in the generalized lymphadenopathy syndrome.

    A generalized lymphadenopathy syndrome (GLS) occurs in persons at high risk for development of acquired immunodeficiency syndrome (AIDS). The natural history and immunologic status of patients with GLS are not fully known, although in some persons GLS may progress to full AIDS. We present the clinical and immunologic findings in two children with severe hemophilia a with nonprogressive GLS for 18-24 months. The functional activity in vitro of lymphocytes from both peripheral blood and biopsied lymph nodes were compared. The peripheral blood lymphocytes responded normally to both mitogens and antigens; lymph node lymphocytes failed to respond to antigens, but did respond to mitogens. The implications of these abnormalities for understanding the pathogenesis of GLS are discussed.
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