ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The polymerase chain reaction (PCR) was used to detect HIV-1 sequences (gag,pol, andenv) in the cerebrospinal fluid (CSF) and serum samples from 53 HIV-1-positive patients and the results correlated with clinical evidence of neurological disease. Twenty-three out of 24 patients with neurological disease had HIV-1-specific sequences in CSF compared with four out of 20 asymptomatic patients who had no evidence of neurological involvement. The detection of HIV RNA sequences by PCR in the CSF of HIV-positive patients may provide early, rapid and direct evidence of neurological involvement in asymptomatic subjects.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To characterize CD8 T-cell activation during HIV-1 infection we measured serum soluble CD8 (sCD8) levels longitudinally in seroconverters and in individuals with established HIV infection who were in different stages of illness. CD8 T-cell activation occurs very early in HIV infection. Serum sCD8 levels were elevated in 91.5% of the first seropositive samples in seroconverters. Furthermore, CD8 T-cell activation persists throughout HIV infection. sCD8 predicted the occurrence of AIDS in HIV-seropositive individuals and so the addition of serum sCD8 levels to CD4 T-cell measurements increased the power in predicting the onset of AIDS. The serum level of sCD8 was particularly relevant to the prediction of subsequent CD4 T-cell fall relatively early in infection, for example, in the 3 years after seroconversion. However, later in HIV infection, for example within 2 years prior to development of AIDS, sCD8 levels were less predictive. sCD8 correlated with levels of β2-microglobulin and neopterin, which reflect activation of cell types other than CD8. Thus, serum sCD8 level can be a useful marker of specific CD8 T-cell activation, and is an independent predictor of prognosis in HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

High levels of the soluble form of the CD8 molecule (sCD8) are detectable in the serum of HIV-1-infected patients. To investigate the mechanisms accountable for the release of this molecule we evaluated the presence of sCD8 in the supernatants obtained fromin vitrocultures of highly purified CD8 cells isolated from 20 HIV-1-infected patients. At resting conditions cultured CD8 cells from HIV-1-infected patients released low amounts of sCD8; no statistically significant differences were observed between unstimulated cultures from HIV-1-seropositive patients and from HIV-1-seronegative subjects at risk for HIV-1 infection or normal healthy controls. Followingin vitroactivation of highly purified CD8 cells with a series of stimulatory agents, including phorbol myristate acetate, phytohemagglutinin (PHA) and recombinant interleukin-2, CD8 cells of HIV-1-infected patients significantly increased the shedding of sCD8. By expressing the results of activation-related release index (ARRI = sCD8 levels detected in the cultures with stimulatory agent/sCD8 levels detected in the unstimulated cultures), significantly higher values were observed upon PHA stimulation in HIV-1-infected patients than in control subjects. In order to identify the cell subset responsible for the enhanced release of sCD8 by PHA-stimulated cultures, we correlated the amounts of sCD8 detected in the supernatants with the phenotypic profile of CD8+ cells recovered from the cultures. A significant relationship was demonstrated between the percentage of CD8 + /HLA-DR+ lymphocytes and sCD8 levels. The relationship between the expression of HLA-DR determinants by CD8 cells and the release of sCD8 was also supported by the finding that serum sCD8 levels strongly paralleled the absolute number of circulating CD8 +/HLA-DR + cells. Our data suggest that CD8 cells coexpressing the activation marker HLA-DR might represent the main cell source of sCD8 molecules during HIV-1 infection and provide further evidence of the immune activation state of the CD8 cellular compartment in AIDS and AIDS-related disorders.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Spontaneousin vitroproduction of HIV-1-specific antibodies, a hallmark of infected subjects, is often down-regulated by the addition of pokeweed mitogen. We observed that a decrease in such ongoing anti-HIV-1 antibody synthesis could also be induced in cultures from most patients by addition of phytohemagglutinin and Concanavalin A, but not by Epstein-Barr virus, a selective B-cell mitogen. In most cases, this down-regulatory effect of mitogens was evident within the first 24 h of culture. The observed mitogen-associated decrease in spontaneous antibody synthesis was prevented by treating peripheral blood mononuclear cells with agents inhibiting non-major histocompatibility complex-restricted cytotoxic activity or by adding third-party cells to the cultures. In most cases, the mitogen-induced effect was also counteracted by removal of T lymphocytes or CD8+ T-cell sub-population. These findings recall a similar phenomenon observed in normal subjects following intentional immunization, and indicate that mitogen-induced down-regulation of spontaneousin vitroanti-HIV-1-antibody production most probably occurs through a lectin-dependent cytotoxic effect on activated B cells.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Eighteen monoclonal antibodies (MAb) to simian immunodeficiency virus (SIV) envelope have been characterized. AH MAb were shown to bind to viral antigens on the surface of unfixed SIV-infected cells and to precipitate surface glycoproteins of SIVmac251. In Western blot 11 MAb bound to gp160 and gp120, five bound to gp160 and the transmembrane protein gp41 and two MAb did not react with denatured antigen. Preliminary competition assays identified the existence of six competition groups; two groups were within gp41 and four were within gp120. Of the latter four groups, three contained MAb with neutralizing activity. Two of the neutralizing MAb (KK5 and KK9) did not react with denatured antigen in Western blot suggesting that they may recognize conformational epitopes. Enzyme-linked immunosorbent-assay titres of MAb against SIVmac251 ranged from 102.4to 105.6and although similar titres were obtained with some MAb against other SIV and HIV antigens, the presence of isolate specific and shared group epitopes was demonstrated.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Six men were selected from a large cohort of homosexual men participating in a study on HIV infection that was followed from seroconversion to AIDS. The patients were studied retrospectively for immunological functions of T cells, T-cell subset distribution and biological phenotype of HIV. A severe decrease in anti-CD3 monoclonal antibody (MAb)-induced T-cell proliferation at seroconversion was observed in two out of six men. After this acute phase, CD4+ T-cell numbers were in the normal range in the early asymptomatic period; the proliferative response was subnormal, whereas the capacity to generate cytotoxic T cells (CTL) was normal. From seroconversion on, CD4 + CD29 + memory T-cell numbers were decreased to approximately 50% of normal values, which may contribute to loss of T-cell reactivity. In the asymptomatic phase only slow-replicating non-syncytium-inducing HIV variants were observed. The T-cell proliferative response further declined with the depletion of naive CD4 + CD45RA + T cells and CD4 + T -cell numbers started to decline. This second decrease in T-cell function coincided with the emergence of more rapidly replicating, often (four out of six) syncytium-inducing variants. At diagnosis of AIDS, T-cell proliferation and CD4+ T-cell numbers were extremely low in five out of six patients and CTL function had declined in three out of five individuals tested. Circulating CD8+ cells had gradually shifted to an immature CD38 + CD28− phenotype. Our findings support the theory that HIV-induced immune dysfunction allows for the emergence of virulent HIV variants associated with CD4+ cell loss and disease.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

During the latter half of 1989, HIV prevalence in South Australian prisoners was 1.4%. The prevalence of HIV infection across the prison system did not change significantly during 1989 but there was clustering of HIV-infected prisoners in some prisons. Almost half the prisoners from all of the South Australian prisons agreed to participate in our studies, from which we estimate that about 42% of prisoners engage in risk behaviours at least once while incarcerated. Prisoners estimated that 36% of all prisoners inject drugs intravenously at some stage during their stay and that 12% engage in anal intercourse at least once. Interviews with former prisoners who had a history of intravenous drug use revealed that about half had injected themselves while in prison, 60% shared needles and most did not clean shared needles adequately. Most of these prisoners injected themselves once a month or less frequently. The conditions for spread of HIV within the prison system exist but at the current prevalence of infection, transmission can be expected to be infrequent. The opportunity exists now to improve and expand preventive measures.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

In this study we evaluated the survival of 515 AIDS patients diagnosed in Amsterdam between 1982 and 1988 and followed-up until April 1990. Non-resident patients survived for a shorter period than resident patients (median survival time 10 versus 16 months). Residents had a 1-, 2− and 3-year survival of 56.1, 33.0 and 17.2%, respectively. Heterosexual intravenous drug users tended to have a better survival than homosexual men, although this was not significant. The survival time was longer for AIDS patients < 30 years of age at diagnosis and varied for the different clinical manifestations leading to AIDS diagnosis. We calculated the 1− and 2-year survival probability by year of diagnosis for patients initially presenting with aPneumocystis cariniipneumonia (PCP). The 1-year survival improved greatly in 1986 and continued to rise in the following years. The 2-year survival was similar in 1986 and 1987 (26.8 versus 28.2%) but increased in 1988 (38.9%). We conclude that besides better clinical experience and diagnostic methods, this improvement in prognosis could be explained by the start of secondary prophylaxis for PCP in 1985 and the introduction of zidovudine therapy in 1987.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To examine cross-reactivity of antibodies to heterologous antigens, on HIV-1 and HIV-2 Western blots, we tested sera from 1362 consecutive tuberculosis (TB) patients and 2127 consecutive blood donors. Specimens positive on enzyme-linked immunosorbent assay (ELISA) for HIV-1 or HIV-2 were further characterized by synthetic peptide-based tests, and tested by HIV-1− and HIV-2-specific Western blots. Dual serologic reactivity on synthetic peptide tests was proportionately more frequent in HIV-positive TB patients than in blood donors, and HIV-2 reactivity less frequent. Positive HIV-1 Western blots were seen in 73–83% of specimens specifically characterized as positive for HIV-2 on synthetic peptide tests. Cross-reactivity to HIV-2 Western blots by HIV-1-positive specimens was significantly more frequent in TB patients (35%) than in asymptomatic donors (9%;P< 0.001). Using recently recommended criteria for HIV-2 Western blot interpretation (presence of two env bands) reduced the overall proportion of HIV-1-positive specimens having a positive HIV-2 Western blot from 27.5 to 16.4%, suggesting minimal effect on sensitivity in the diagnosis of HIV-2 reactivity on specimens positive on synthetic peptide tests.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID