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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All presently available replication-competent proviral clones of human immunodeficiency virus type 1 (HIV-1) are derived from cell culture-amplified virus. Since tissue culture is highly selective for viral strains with an in vitro growth advantage, such clones may not be representative of the biologically relevant virus present in vivo. In this study, we report the molecular cloning and genotypic characterization of 10 HIV-1 genomes directly from uncultured brain tissue of a patient with AIDS dementia complex. Targeting unintegrated circular HIV-1 molecules for recombinant lambda phage cloning, we obtained four full-length genomes with one or two long terminal repeats (LTRs), three defective genomes with internal deletions, two rearranged genomes with inverted LTR sequences, and one integrated proviral half with flanking cellular sequences. Nucleotide sequence analysis of these clones demonstrated chromosomal integration, circle formation, genomic inversion, and LTR-mediated autointegration of HIV-1 genomes in vivo. Comparison of a 510-bp hypervariable envelope region among 8 lambda phage-derived and 12 polymerase chain reaction-derived clones from the same brain specimen identified a predominant viral form as well as genetically divergent variants. Variability among 19 of 20 clones ranged between 0.2 and 1.2%. One clone exhibited 8.2% nucleotide sequence differences consisting almost exclusively of G-to-A changes. Transfection of the four full-length HIV-1 genomes identified one clone (YU-2) as replication competent and exhibiting growth characteristics similar to those of tissue culture-derived macrophage tropic strains of HIV-1. These results demonstrate, for the first time, that replication-competent HIV-1 genomes, complex mixtures of defective viral forms, and chromosomally integrated provirus persist in vivo. In addition, the brain-derived viral clones are expected to prove valuable for future studies of macrophage and neurotropism as well as for the analysis of other viral properties that are subject to in vitro selection pressures.
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PMID:Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes. 183 Jan 10

Sixty-seven patients with different stages of human immunodeficiency virus (HIV) infection (47 CDC group IV, 20 CDC groups II or III) were followed prospectively for a median of 18 months with neurological examination, magnetic resonance imaging (MRI), and computerized tomography (CT) to evaluate the incidence of the AIDS dementia complex (CDC definition) and other neurological complications. Ten patients developed CNS opportunistic infection or malignancy. Among the remaining 57 patients, 12 of 37 (32%) belonging to CDC group IV, and 1 of 20 (5%) belonging to CDC groups II/III developed the AIDS dementia complex (p = 0.03). MRI white matter lesions occurred in 32% of CDC group IV patients and 5% of CDC groups II/III patients (p = 0.03). The corresponding figures for brain atrophy at CT were 71% and 30% (p less than 0.01) and for neurologic signs 49% and 20% (p = 0.06). The development of the AIDS dementia complex was significantly associated with the occurrence of MRI white matter lesions and a CD4 cell count of less than 200 x 10(6)/l, whereas it was not statistical significantly associated with brain atrophy at baseline. It is concluded that the AIDS dementia complex is a common feature of late stage HIV infection. Brain atrophy occurs in a large percentage of HIV infected patients, but the clinical significance of this atrophy is not clear.
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PMID:Central nervous system involvement in human immunodeficiency virus disease. A prospective study including neurological examination, computerized tomography, and magnetic resonance imaging. 191 36

Infection with the human immunodeficiency virus (HIV-1) often produces a set of neuropsychiatric dysfunctions which have been termed the AIDS dementia complex. This complex appears due to the infection of brain cells by HIV-1. If so, brain cells might be expected to contain a binding site for the same viral envelope glycoprotein that enables HIV-1 to bind to other cells (e.g. CD4+ T-cells), gp120. The present study shows that the cells of the brain-derived U-138MG, U-373MG, SK-N-MC and SK-N-SH cell lines bind gp120 in an inhibitable fashion. Binding of gp120 to these cells is inhibited by the dyes Aurintricarboxylic acid (ATA) and Evans blue (EB), which are known to inhibit specific gp120 and HIV-1 binding, and block HIV-1 infection, in CD4-expressing cells. Binding is not inhibited by Aurin, a dye related to ATA but lacking its anti-HIV effects. As expected, anti-CD4 antibodies are ineffective in blocking gp120 binding to brain-derived cells. These results suggest that human brain-derived cells possess a specific binding site for gp120 that is not the CD4 antigen.
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PMID:Brain-derived cells contain a specific binding site for Gp120 which is not the CD4 antigen. 193 87

Human immunodeficiency virus (HIV) infection is frequently complicated by a variety of disease processes affecting the central nervous system (CNS). One of them is AIDS dementia complex (ADC), which, in the absence of opportunistic infection, is believed to be caused by HIV itself. ADC is characterized by a constellation of cognitive, motor, and behavioral symptoms that progressively get worse. This study was coined to recruit AIDS patients without any opportunistic CNS infection but with signs of CNS abnormality as evidenced by behavioral and subtle motor changes, then to categorize them into five stages, and finally to perform the cerebral blood flow scan using Ceretec. The aim of this study was to correlate the abnormalities of the brain scan with the different stages of ADC. Five patients were analyzed, with dementias ranging from mild to severe according to Price's classification. After confirming the absence of CNS opportunistic infections and AIDS associated malignancies by CT of the brain, the patients underwent psychiatric evaluation and brain scans. The SPECT scans were very sensitive in showing uptake defects in the brain, even in the early stages of ADC. The blood flow defects were more pronounced in the later stages, while the CT scans remained negative except in patients with the most severe dementia.
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PMID:Cerebral blood flow SPECT with Tc-99m exametazine correlates in AIDS dementia complex stages. A preliminary report. 193 27

Sustained increases in CSF concentrations of the excitotoxin quinolinic acid (QUIN) occur in patients with AIDS and have been implicated in the pathogenesis of the AIDS dementia complex. Macaques in captivity may also develop immunodeficiency syndromes caused by retrovirus infection, including simian retrovirus type-D. In the present study, CSF QUIN concentrations were moderately increased in retrovirus type-D-positive/antibody-negative macaques (163.8 +/- 35.1 nmol/l; P less than 0.0001, n = 21) but not virus-negative/antibody-positive macaques (27.4 +/- 9.4 nmol/l, n = 8) compared to uninfected control macaques (23.0 +/- 1.6 nmol/l; n = 22). CSF QUIN concentrations in virus-positive/antibody-negative macaques tended to remain elevated over a 4-20 month period. Post-mortem studies of 9 virus-positive/antibody-negative macaques and 6 virus-negative/antibody-positive macaques revealed inflammatory responses in the brains of 6 of 9 virus-positive/antibody negative macaques, including lymphocytic infiltrates of the choroid plexus in 3 macaques, glial nodules in 3 macaques and perivascular infiltrates in 1 macaque. These lesions were not extensive and no evidence of brain atrophy was observed. No lesions were observed in the 6 antibody-positive/virus-negative macaques. Small increases in plasma L-kynurenine in virus-positive/antibody-negative macaques are consistent with activation of indoleamine-2,3-dioxygenase, the first enzyme in the kynurenine pathway. We conclude that sustained moderate increases in CSF QUIN occur in viremic simian retrovirus type-D macaques. The increases in CSF QUIN may reflect inflammatory responses within the brain or synthesis of QUIN precursors in systemic tissues, their entry into brain and subsequent conversion to QUIN. The neuropathologic significance of these increases in CSF QUIN remains to be determined.
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PMID:Sustained increases in cerebrospinal fluid quinolinic acid concentrations in rhesus macaques (Macaca mulatta) naturally infected with simian retrovirus type-D. 196 97

The encephalopathy resulting from direct infection of the brain by human immunodeficiency virus (HIV), which correlates clinically with the AIDS dementia complex, has been reported as being localized to the white matter where it induces myelin loss, gliosis and perivascular infiltration by mononuclear macrophages and multinucleated giant cells. Damage to the cortical grey matter in HIV encephalopathy was investigated in nine randomly selected HIV-positive cases with or without clinical or morphological evidence of encephalopathy and in five age-matched controls, using routine histology and immunohistochemical methods [glial fibrillary acidic protein (GFAP), microglia and HIV antibodies]. Increased numbers of GFAP-expressing astrocytes and Ricinus communis agglutinin 1-120-expressing microglial cells were found in all the HIV-positive cases (including asymptomatic) and their severity could be correlated with the severity of the encephalopathy in the white matter; the increase in number of cells expressing GFAP was diffuse and the intensity of the staining higher than that of microglial cells. The subpial region was the most severely involved. It is suggested that involvement of the cortical grey matter is more common in HIV infection than previously suspected and that clinical evidence of a dementing process in AIDS is not necessarily due only to white matter lesions.
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PMID:The involvement of the cerebral cortex in human immunodeficiency virus encephalopathy: a morphological and immunohistochemical study. 208 94

We have measured levels of soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) in serum and cerebrospinal fluid (CSF) of 127 human immunodeficiency virus (HIV)-seropositive and 51 HIV-seronegative individuals. Serum levels of sIL-2R and sCD8 were higher in HIV+ than in HIV- individuals. HIV+ individuals were grouped by neurological status: asymptomatic, abnormal on neuropsychological screening, HIV-related meningitis, inflammatory demyelinating polyneuropathy, opportunistic central nervous system (CNS) infections and HIV-related dementia, myelopathy or sensory neuropathy. Serum levels of sIL-2R and sCD8 were higher in all HIV+ categories compared to HIV- individuals. Patients with HIV-related meningitis had higher levels of sIL-2R and sCD8 than asymptomatic HIV+ individuals, and inflammatory polyneuropathy patients had higher levels of sCD8. CSF levels of sCD8 were higher in all categories of HIV+ than in HIV- individuals. Patients with HIV-related meningitis, inflammatory neuropathy and opportunistic infections had higher levels than asymptomatic individuals. Examination of the time course showed that serum and CSF levels of sIL-2R and sCD8 increased to very high levels during acute HIV infections. Serum levels then declined over several months to relatively stable elevated levels. By 1-2 years after HIV infection sIL-2R was relatively low in CSF, while sCD8 remained elevated with a gradual decrease over the subsequent years of follow-up.
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PMID:Soluble interleukin-2 receptor and soluble CD8 in serum and cerebrospinal fluid during human immunodeficiency virus-associated neurologic disease. 211 34

The brains of 65 individuals with antibodies to human immunodeficiency virus type 1 (HIV-1), 20 HIV-1 seronegative homosexual men, and 75 heterosexual controls were examined by a quantitative magnetic resonance imaging technique. A white matter aberration was detected most frequently in patients with AIDS-related complex (ARC) or AIDS, but also in asymptomatic HIV-1 seropositive persons and in HIV-1 seronegative homosexual men, of whom two of three tested were reactive for HIV-1 DNA by polymerase chain reaction. The aberration was not found in the control group. Brain atrophy was mainly confined to patients with ARC or AIDS. The brain lesions correlated with the presence of HIV-1 in cerebrospinal fluid and with elevated levels of beta 2-microglobulin and neopterin. The most pronounced brain aberrations were in patients with AIDS-dementia complex. These findings indicate that brain aberrations may occur in persons in the early stages of HIV-1 infection, although to no greater extent than in HIV-1 seronegative homosexual men. The occurrence of pronounced brain lesions seems to be associated with the presence of an advanced immunodeficiency.
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PMID:Quantitative detection of brain aberrations in human immunodeficiency virus type 1-infected individuals by magnetic resonance imaging. 223 Feb 57

The AIDS dementia complex (ADC) is one of the most common and important causes of morbidity associated with infection by human immunodeficiency virus type 1 (HIV-1). The evaluation of ADC in clinical trials is significant not only because of the clinical impact of this syndrome, but also because of the value of measuring its cardinal features as an index of drug efficacy and because of its emerging role as a major clinical end point. The objectives of therapy include both prevention of ADC in the presymptomatic patient and alleviation of established disease. At present, the pathogenesis of ADC is incompletely understood in several critical aspects, particularly the processes underlying the clinical manifestations of central nervous system (CNS) HIV-1 infection and, further, how such processes are related to systemic disease. Consequently, it is not yet clear to what extent, or in which patients, it is necessary to achieve "therapeutic" drug levels within the CNS. Nevertheless, the assessment of ADC prevention and treatment relies principally on the complementary approach of neurological examination for diagnosis and neuropsychological testing for quantitative serial measurement of treatment effects. Additionally, surrogate markers in cerebrospinal fluid (CSF) may hold promise for objective, rapid assessment of treatment response and dose adjustment. Other measurements, including more routine CSF analysis, neuroimaging, and neurophysiological assessments, are used principally for differential diagnosis rather than for monitoring ADC status. Accumulating experience with available antiviral agents suggests that ADC can be effectively prevented and treated, at least for some period of time, and that assessment of this condition is indeed a valuable approach for measuring antiviral therapy.
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PMID:Evaluation of the AIDS dementia complex in clinical trials. 223 3

Human immunodeficiency virus (HIV) infections are accompanied by many different types of neurological complications. Opportunistic infections and neoplasms, particularly lymphoma, are often an underlying cause for these complications in patients with acquired immunodeficiency syndrome (AIDS). Frequently, these can be detected by cerebrospinal fluid (CSF) examination, double-dose contrast transmission computed tomography (CT), and/or magnetic resonance imaging (MRI). It has become apparent that the HIV itself is responsible for a significant percentage of neurological disease in the HIV-seropositive individual. The onset may be subtle and may occur before the onset of frank immunosuppression. Diagnosis of HIV encephalitis or AIDS dementia complex (ADC) is complicated by the frequent coexistence of opportunistic infections. Structural neuroimaging (CT or MRI) shows atrophy and in some case white matter abnormalities, but imaging-pathological correlation suggests that these modalities are relatively insensitive to the presence of HIV brain infection. Functional neuroimaging, both 18fluorodeoxyglucose positron emission tomography (PET) for evaluation of glucose metabolism and 123I iodoamphetamine or 99mTc-HMPAO single-photon emission computed tomography (SPECT) for evaluation of cerebral perfusion, can demonstrate abnormalities in the subcortical gray matter structures and the cerebral cortex in patients with ADC. These abnormalities may be observed early in the course of ADC even when MRI is negative and the patient is relatively asymptomatic. Also, PET and SPECT may be useful to follow progression of the dementia or response to therapy.
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PMID:Brain imaging in acquired immunodeficiency syndrome dementia complex. 223 53


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