Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progressive multifocal leukoencephalopathy (PML) is a lytic infection of oligodendrocytes by the human papovavirus JC. Patients with defects in cell-mediated immunity are at risk for active disease: a usually lethal demyelination of the brain. PML develops in at least 4% of patients with the acquired immunodeficiency syndrome (AIDS). Definitive diagnosis currently requires brain biopsy. Previous attempts to detect JC virus DNA by polymerase chain reaction in cerebrospinal fluid of PML patients, particularly those with human immunodeficiency virus type 1 (HIV-1) infection, have been of low sensitivity. In the present study, cerebrospinal fluid was assayed by polymerase chain reaction from 26 HIV-1-positive patients with PML, 114 HIV-1-positive control subjects, and 16 control subjects who were HIV-1 negative or were without risk factors for HIV disease. Polymerase chain reaction conditions were optimized to detect a single copy of viral DNA in 50 microliters of cerebrospinal fluid. Specificity of the polymerase chain reaction product was confirmed by size on gel electrophoresis and Southern blot hybridization. JC virus DNA was detected in 24 of 26 samples from patients with PML: 8 of 8 with tissue diagnosis and 16 of 18 with strong clinical and magnetic resonance imaging evidence of PML. Among control subjects, 11 of 130 samples were positive for JC virus: 10 of 114 samples from HIV-infected patients and one from an HIV-negative patient with risk factors for PML and an unexplained hemiparesis. Overall sensitivity was 92% (24/26); specificity was, at minimum, 92% (119/130). Treatments for PML are now in clinical trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:JC virus DNA in cerebrospinal fluid of human immunodeficiency virus-infected patients: predictive value for progressive multifocal leukoencephalopathy. 769 39

We examined the ability of human immunodeficiency virus (HIV) type 1 (HIV-1) to infect in vitro, primary brain-derived human microvascular endothelial cells (HMEC) that constitute the blood-brain barrier (BBB). Immunofluorescence (IFA) and antigen capture assays failed to demonstrate p24 antigen from HIV inoculated endothelial cells and supernatants did not contain detectable levels of reverse transcriptase (RT). HIV could be rescued by cocultivation of infected HMEC with a susceptible T-lymphocyte line (CEM-SS), which were then shown to form syncytia and produce RT activity and p24 Ag (IFA, antigen captive assay). Polymerase chain reaction (PCR) was successfully used to amplify HIV-specific gag and env gene sequences from HMEC. CD4 expression was not identified on these cells by IFA. These results suggest that HIV infection of BBB endothelium occurs, but that viral replication is minimal. Infection of the BBB by HIV may give the virus a foothold in the CNS and suggests that the brain might be infected directly and may not be limited to just the passage of infected mononuclear cells.
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PMID:HIV-1 infection of human brain-derived microvascular endothelial cells in vitro. 769 39

Multiple genetic subtypes of human immunodeficiency virus type 1 (HIV-1) have been identified among internationally collected isolates. The HIV-1 epidemic in Thailand is largely due to B and E subtypes of virus. Dual infection with distinct HIV-1 subtypes would suggest that antiviral immunity evoked by one subtype can be incompletely protective against a second. Polymerase chain reaction typing and serologic typing were used to screen a panel of specimens from HIV-1-infected subjects in Thailand. Two persons simultaneously harbored HIV-1 of env subtypes B and E, and this was confirmed by colony hybridization with subtype-specific probes and nucleotide sequence analysis of a 630-bp fragment of gp120 from multiple molecular clones. In addition, both subtypes were identified in cocultured peripheral blood mononuclear cells from 1 individual. These data provide the first evidence of dual HIV-1 infection in humans and reinforce the need for polyvalent vaccines.
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PMID:Dual infection with human immunodeficiency virus type 1 of distinct envelope subtypes in humans. 770 6

Polymerase chain reaction based assays, which amplify a region of the gag gene, have been developed for the direct detection of simian immunodeficiency virus (SIV) DNA sequences in the blood of experimentally infected cynomolgus macaques. In macaques infected with a characterised virus pool (11/88 pool SIVmac 32H), an assay employing a single round of amplification was found to be highly sensitive and specific. However, in animals infected with the SIV molecular clones J5 and C8 (Rud et al., J. Gen. Virol. 75, 529-543), it was necessary to use two rounds of amplification and nested primer pairs in order to achieve sensitivity > 90%. In order to differentiate macaques infected with either of the two genetically distinct SIV clones, J5 or C8, a third PCR based assay has been developed, which amplifies a 492 bp region of the nef gene. Sequence differences between the nef genes of the two molecular clones enabled the PCR product amplified from each virus to be distinguished by restriction analysis. These sensitive and specific assays complement virological detection of SIV and enable superinfection studies to be evaluated; a prerequisite for the testing of live attenuated immunodeficiency virus vaccines.
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PMID:The development of PCR based assays for the detection and differentiation of simian immunodeficiency virus in vivo. 773 43

Prophylactic zidovudine (ZDV) therapy in feline immunodeficiency virus (FIV) inoculated cats was evaluated for 12 months postinfection (pi) and 11 months post drug treatment. Plasma FIV antigenemia was prevented in six of six ZDV-treated and none of six untreated cats during the initial phase of infection. The present study is a continuation of that earlier work. CD4 lymphocyte numbers from ZDV-treated cats were higher than in the untreated cats. CD8 lymphocytes numbers were maintained within control limits in the ZDV-treated cats, while they declined in the untreated cats. Anti-FIV antibody titers were comparable between the ZDV-treated and the untreated cats. Histologically, lymphoid tissues for the untreated and ZDV-treated cats were unremarkable and similar to those of the uninfected control cats. Low-level FIV antigen was detected by enzyme-linked immunosorbent assay in thymus or lymph node homogenates from 3 of 11 cats tested. Polymerase chain reaction analysis showed FIV DNA in blood, lymph node, bone marrow, spleen, thymus, and brain from FIV-inoculated cats irrespective of ZDV treatment. Therefore, while prophylactic ZDV treatment prevented detectable plasma antigenemia and FIV-induced CD8 lymphocyte decline, it did not slow infection of tissues and blood cells of FIV-inoculated cats.
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PMID:Early suppression of viremia by ZDV does not alter the spread of feline immunodeficiency virus infection in cats. 774 86

This recently recognised member of the genus Chlamydia is one of the most widespread pathogens of man, though up to 90% of infected people have few or no symptoms. Several studies have estimated the population prevalence of antibodies to C. pneumoniae at 40-55% in the northern hemisphere, and over 60% in under-developed countries. The incidence of infections follows a cyclical pattern, with peaks at regular intervals of 2-10 years, but no apparent seasonal periodicity. Nosocomial transmission may be mediated by environmental surfaces as well as aerosols, and immunosuppression, for example by the human immunodeficiency virus, predisposes to infection. Chlamydia pneumoniae causes predominantly atypical pneumonia, often severe in adults, especially the elderly; including 5-10% of community-acquired pneumonia in Scandinavian countries. Serological evidence indicates associations with asthma, bronchitis, exacerbations of chronic airflow obstruction, otitis media and bronchiolitis. Several studies, using both serological and morbid anatomical techniques, also indicate associations with vascular atheroma and ischaemic heart disease, and with acute myocardial infarction. Chronic, latent and recurrent infections have been documented, and it is postulated that, like chronic or recurrent C. trachomatis infections, these may produce disease as a consequence of the host's immunological hypersensitivity. Several techniques are available for serological diagnosis: the technique of choice is micro-immunofluorescence, using fixed whole elementary or reticulate bodies as antigen, but antibody responses are highly variable. Traditional alternatives, antigen detection (by direct immunofluorescence or enzyme immunoassay) and cell culture, have major disadvantages. Polymerase chain reactions have not yet been widely applied to the clinical setting. tetracycline antibiotics, erythromycin and quinolones are not very efficacious in the treatment of C. pneumoniae infection. The azalide antibiotic, azithromycin, and the macrolide, clarithromycin, are active in vitro against C. pneumoniae, and may become treatments of choice. The development of anti-chlamydial vaccines remains an important research goal.
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PMID:Clinical aspects of Chlamydia pneumoniae infection. 789 84

The pigtail macaque (Macaca nemestrina) has a marked sensitivity to infection by simian immunodeficiency virus and human immunodeficiency virus type 2 (HIV-2). On this basis, we previously studied this species' susceptibility to HIV-1 and demonstrated infection in six macaques inoculated with either cell-associated HIV-1 or cell-free virus alone. This report expands upon our initial in vitro and in vivo findings. Five laboratory-adapted and one primary clinical strain of HIV-1 replicated in vitro in human and M. nemestrina peripheral blood mononuclear cells (PBMCs). Replication was enhanced when CD4+ purified PBMCs were infected and inhibited when PBMC cultures were treated with zidovudine. All six macaques demonstrated HIV-1 infection of PBMCs from 2 to 8 weeks after inoculation but nearly all PBMC cultures were negative from weeks 10 to 40. Polymerase chain reaction showed HIV-1 gag DNA in the PBMCs of all infected macaques, including times when the macaques were culture negative. All macaques developed and maintained antibodies to gag and envelope HIV-1 proteins from week 4 after inoculation through the period of observation. Five macaques showed neutralizing antibody. These findings suggest that M. nemestrina can be infected by cell-free and cell-associated HIV-1. This model of acute HIV-1 infection may help in evaluating the pathogenesis of HIV-1 replication and candidate vaccines and therapies.
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PMID:Acute infection of Macaca nemestrina by human immunodeficiency virus type 1. 810 73

Human immunodeficiency virus 1 (HIV-1) infection is associated with a vigorous cellular immune response that allows detection of cytotoxic T lymphocyte (CTL) activity using freshly isolated peripheral blood mononuclear cells (PBMC). Although restricting class I antigens and epitopes recognized by HIV-1-specific CTL have been defined, the effector cells mediating this vigorous response have been characterized less well. Specifically, no studies have addressed the breadth and duration of response to a defined epitope. In the present study, a longitudinal analysis of T cell receptor (TCR) gene usage by CTL clones was performed in a seropositive person using TCR gene sequences as a means of tracking responses to a well-defined epitope in the glycoprotein 41 transmembrane protein. 10 CTL clones specific for this human histocompatibility leukocyte antigen-B14-restricted epitope were isolated at multiple time points over a 31-mo period. All clones were derived from a single asymptomatic HIV-1-infected individual with a vigorous response to this epitope that was detectable using unstimulated PBMC. Polymerase chain reaction amplification using V alpha and V beta family-specific primers was performed on each clone, followed by DNA sequencing of the V-D-J regions. All 10 clones utilized V alpha 14 and V beta 4 genes. Sequence analysis of the TCR revealed the first nine clones isolated to also be identical at the nucleotide level. The TCR-alpha junctional region sequence of the tenth clone was identical to the junctional region sequences of the other nine, but this clone utilized distinct D beta and J beta gene segments. This study provides evidence that the observed high degree of HIV-1-specific CTL activity may be due to monoclonal or oligoclonal expansion of specific effector cells, and that progeny of a particular CTL clone may persist for prolonged periods in vivo in the presence of a chronic productive viral infection. The observed limited TCR diversity against an immunodominant epitope may limit recognition of virus variants with mutations in regions interacting with the TCR, thereby facilitating immune escape.
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PMID:Longitudinal analysis of T cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire. 814 43

In asymptomatic human immunodeficiency virus (HIV) infection in humans, disturbed T cell functions such as anergy and programmed cell death, thought to result from inappropriate signaling by antigen-presenting cells due to HIV infection, precede increase in virus load, decline in CD4+ T cell numbers, and subsequent disease progression. Here, in 3 long-term HIV-1-infected asymptomatic chimpanzees, antigen-presenting cell function was intact and T cells had normal proliferative capacity with no evidence of HIV-1-associated programmed cell death. Polymerase chain reaction analysis demonstrated low frequencies of cells harboring proviral DNA. Primary virus isolation from the infected animals demonstrated the absence of monocytotropic HIV-1 variants, in concordance with complete insusceptibility of chimpanzee monocytes for HIV-1 infection. Possibly, because of the incapacity of HIV-1 to infect monocytes, systemic immune dysfunction will not occur, contributing to controlled viral replication and maintenance of the asymptomatic state in HIV-infected chimpanzees.
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PMID:Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants. 819 28

Prophylactic zidovudine (ZDV) therapy was evaluated in the feline immunodeficiency virus (FIV)-inoculated cat model for HIV-1 infection in humans. ZDV treatment (30 mg/kg/day via continuous subcutaneous infusion) was initiated 48 h prior to virus inoculation and continued for 28 days. Transient plasma antigenemia evident in six of six untreated cats at week 2 post-inoculation (pi) was absent in the ZDV-treated cats although at 10 and 14 weeks pi (6 and 10 weeks after drug treatment), one of the ZDV-treated cats had low-level antigenemia. Both CD4 and CD8 lymphocyte numbers were consistently higher in the ZDV-treated cats when compared to both the FIV-inoculated untreated cats and the virus-naive, age-matched controls. CD4:CD8 ratios were lower for the ZDV-treated cats than either the FIV-inoculated untreated or virus-naive, control cats. The decreased CD4:CD8 ratios were the result of an increase in CD8 lymphocytes in the ZDV-treated cats while decreased ratios in the FIV-inoculated untreated cats were due to cell loss. Both ZDV-treated and untreated cats showed nearly identical FIV-specific antibody responses beginning 2 weeks pi. Polymerase chain reaction (PCR) results from blood lymphocytes showed that six of six ZDV-treated and six of six untreated cats were positive for FIV-specific gag sequences. Although primary infection was not prevented, these results suggest that prophylactic ZDV therapy deterred early systemic spread of infection mediated by viremia and delayed absolute CD4 and CD8 lymphocyte decline.
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PMID:Prophylactic ZDV therapy prevents early viremia and lymphocyte decline but not primary infection in feline immunodeficiency virus-inoculated cats. 838 67


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