摘要:

SummaryNeurologic dysfunction and neuropathology are common findings in patients infected with HIV and in cats infected with feline immunodeficiency virus(FIV). The pathogenesis of lentivirus-associated alterations in the central nervous system(CNS) is multifactorial. Because seizures, alterations in memory, and behavioral changes are clinical manifestations in adults and children infected with HIV, we explored the possibility that changes in neuronal structure may occur in the hippocampus. To do this, we examined the dentate gyrus of FIV-infected cats, an animal model of HIV infection. Neuropathologic findings included gliosis within the hilus of the dentate gyrus and granule cell axonal sprouting. Using the Timm's method, which labels axons of dentate gyrus granule cells, abnormally high amounts of staining were observed in the inner one third of the molecular layer in 45% of FIV-infected cats (n= 11) and in none of the controls (n= 19). Prominent axonal sprouting was seen in three FIV-infected cats that were infected as kittens, suggesting that younger cats may be more susceptible. Axon reorganization of the dentate granule cells has been hypothesized to underlie complex partial seizure activity in human temporal lobe epilepsy. These results suggest that FIV infection causes granule cell axon reorganization in the hippocampus of cats. A similar neuropathogenetic mechanism may contribute to neurologic dysfunction in HIV-infected patients.

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The HIV Tat protein, primarily characterized as a transcriptional activator of the viral long terminal repeat (LTR), is also a potent repressor of major histocompatibility complex (MHC) class I transcription. In the present study, we demonstrate that these two functional activities are distinct and mediated by discrete, but overlapping, structural domains of Tat. Tat repressor activity depends on C-terminal sequences, whereas transactivation depends on N-terminal sequences; both functions require core sequences. The repressor activity requires a domain encompassing the region encoded by the second exon of the Tat gene, beginning at amino acid 73, with a C-terminal limit between amino acids 80 and 83. Tat repressor function also depends on the presence of a lysine at position 41, located within the core of the protein. Tat repressor activity is independent of two N-terminal domains essential for transactivation: the acidic segment and the cysteine-rich region. Conversely, Tat transactivation is independent of the second exon-encoded region of Tat. As further support for this novel model of separable Tat functions, we show that in murine fibroblasts, Tat represses class I promoter activity, but does not transactivate the HIV LTR. We propose that distinct structural domains mediate the two functionally distinct activities associated with the Tat protein.

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Phase I studies using monoclonal antibodies (mAbs) that bind to the Ig-CDR3-like loop in domain 1 of CD4 (e.g., 13B8-2 mAb) have already been documented for HIV-1-infected patients. In vitro, such mAbs do not inhibit virus to cell fusion but are able to inhibit virus envelope-mediated syncytia formation. Moreover, these mAbs inhibit Tat-induced activation of HIV-1 promoter and HIV-1 transcription in infected CD4+cells. Here, we report the selection of escaped mutant virus or viruses derived from HIV-1Laicapable of replicating in vitro in the presence of concentrations of 13B8-2 mAb, that usually inhibit HIV-1Laiparticle production. The escaped mutant virus or viruses, termed HIV-1Lai 13 EM, kept the major enzymatic restriction sites found in HIV-1Laiand remained sensitive to anti-CD4 mAb-, soluble CD4-, and recombinant gp 120-mediated inhibition of syncytia formation. Possible genetic changes affecting thetatgene or the 5' long terminal repeat (LTR) were investigated. Partial sequence analysis of HIV-1Lai13EMand a control HIV-1Laigrown for 85 days in CEM cells, demonstrated that the first tat exon of these two viruses encoded identical proteins. Although a point mutation G>A was frequently encountered (6 of 13 sequences) in the LTRs of HIV-1Lai13EMat position -188 within the negative regulatory element (NRE), this mutation did not confer the escape mutant phenotype. Our study indicates that the mutant phenotype probably requires genetic changes in a region or regions outside the LTRs.

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

SummaryBased on the earliest intracellular synthesis of nascent HIV-1 long terminal repeat (LTR) fragments, we have established a heminested polymerase chain reaction(HNPCR) amplification of the 5' LTR sequences (LTR-HNPCR) for molecular assay of virus-neutralizing antibodies (VNAb). We incubated HIV antibodies with virus isolates for an hour, followed by addition of lymphoid cells (H9or peripheral blood mononuclear cells [PBMC]) and further incubation for an hour. After washing the cells three times for thorough removal of free virions and antibodies, LTR-HNPCR consistently revealed HIV DNA in H9cells after 15 minutes, in PBMC after 4 hours, and corresponding virion expression after 7 days in culture. Replication-competent HIV detected by LTR-HNPCR following overnight culture of infected PBMC for 16 to 18 hours was comparable with tissue culture infectivity measured by p24 antigen expression at 7 days. After establishing a molecular assay for in vitro HIV neutralization by HIV Ig, a panel of five HIV isolates tested with 6 monoclonal antibodies and HIV Ig revealed that LTR-HNPCR was comparable with other VNAb assays. These preliminary data indicate that the molecular assay for HIV neutralization has a clear-cut end point, is specific, reliable, and more rapid than other VNAb assays. Therefore, it offers potential utility in evaluating immune response to candidate vaccines.

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Repeated emergency department (ED) visits by HIV-infected persons may signify poor access to care or treatment from inexperienced ambulatory providers. We examined features of 157 clinics following 6820 HIV-infected patients and associations with repeated (≥2) ED visits by these patients in the year before their first AIDS diagnosis. Patient clinical and health care data came from 1987-1992 New York State(NYS) Medicaid files and clinic data came from interviews of clinic directors. The HIV/AIDS experience of each study patient's clinic was measured as the annual number of Medicaid enrollees newly diagnosed with AIDS who were comtemporaneously followed by the patient's clinic. Repeated ED use was observed for 24%. The adjusted odds ratio (AOR) of repeated ED visits was reduced for patients in clinics with a physician on-call (0.77; 95% confidence interval [CI]= 0.65, 0.92), evening or weekend clinic hours (0.77; 95% CI = 0.64, 0.93), or >50 AIDS patients/year in 1987-1988 (0.56; 95% CI = 0.44, 0.71) versus fewer patients in those years. Patients in clinics with more than one feature promoting accessibility or HIV expertise had a greater reduction in their AOR of repeated ED use. HIV-infected patients in clinics with greater accessibility and HIV expertise rely less on the ED for care.

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

SummaryOnly one fifth or fewer of the female sexual partners of HIV-1-infected men with hemophilia become infected. The risk factors associated with heterosexual transmission of HIV-1 are not well understood. To investigate the hypothesis that HIV-1 viral load may be related to heterosexual HIV-1 transmission, we measured HIV-1 RNA by polymerase chain reaction (PCR) in frozen samples from 39 men with hemophilia and HIV-1 infection obtained between 20 and 62 months after HIV-1 seroconversion, during at least a 6-month relationship with a female sexual partner. The median time from the hemophilic viral load determination to the estimated date of transmission to the female partner was 9 months (range, 4-41 months). The proportion of HIV-positive hemophilic men with >100,000 HIV RNA copies/ml was significantly higher in transmitters (TR) (3 of 5 [60%]), than in nontransmitters(NTR) (3 of 34[9%];p= 0.027). There were no differences between TR and NTR in age at seroconversion(32.4 years each), in time from seroconversion to AIDS (67 versus 79 months), in mean CD4 number (245/µl versus 260/µl); nor in the proportion who developed AIDS (4 of 5 [80%] versus 24 of 34 [71%]). These findings appear to suggest that high HIV viral load in HIV-infected hemophilic men increases the risk of HIV transmission to heterosexual partners. Viral load determinations may be helpful in counseling hemophilic couples regarding transmission to female partners.

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We determined the frequency and clinical nature of severe hyperglycemia in a university clinic for HIV-1-infected patients. The medical records of 1392 adult HIV-infected patients were reviewed for cases of severe hyperglycemia, defined as two or more serum glucose values > 250 mg/dl or diabetes treatment during clinic care. Demographic information, family histories of diabetes mellitus, body weights, CD4+lymphocyte counts, and use of corticosteroids, megestrol acetate, pentamidine, or didanosine were recorded for subjects meeting the case definition. Comparisons were made between preexisting diabetic (group 1) and incident hyperglycemic cases(group 2). Less than 2% of the total clinic population experienced severe hyperglycemia: 12 in group 1 and 13 in group 2. Group 2 had lower body weights (mean, 70.6 kg versus 90.0 kg;p< 0.05) and more advanced HIV disease (mean CD4 count, 79/mm3versus 550/mm3;p< 0.05) than group 1. Group 2 cases had evidence of drug-associated hyperglycemia; four cases demonstrated hyperglycemia coinciding with large fluctuations in weight during megestrol therapy. Among megestrol recipients, cases did not differ from noncases in demographics, weight, or CD4 count. Severe hyperglycemia is uncommon in adult HIV-infected patients. Approximately one half of these patients have preexisting diabetic conditions; many of the remainder may have drug-induced hyperglycemia, especially as a result of corticosteroids or megestrol acetate.

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Low serum total cholesterol (TC) is associated with a variety of nonatherosclerotic diseases, but the association of TC with infectious disease has been little studied. In this study, we examined the relationship between serum TC and HIV infection in members of a large health maintenance organization in Northern California. The cohort consisted of 2446 unmarried young men 15 to 49 years of age at high risk of HIV infection, defined as self-reported history of sexually transmitted disease or liver disease. Baseline measurements were taken between 1979 and 1985, and subjects were passively followed for HIV infection until the end of 1993(average length of follow-up, 7.7 years). From a multivariate-adjusted Cox regression, the rate ratio (RR) of HIV infection was 1.66 (95% CI = 1.07, 2.56) for men with serum TC levels <160 mg/dl compared with those with TC levels between 160 and 199 mg/dl. Similar excess risk of AIDS and AIDS-related death was observed. These findings suggest that low serum TC levels should be considered a marker of increased risk of HIV infection in men already at heightened risk of HIV infection.

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

To study the genetic variation of the HIV-1 strains prevalent in South Korea, we analyzed thenefsequences derived from 46 HIV-1-positive individuals living in various geographic regions in Korea. Phylogenetic analysis revealed four subtypes of HIV-1: A (3 patients), B (41 patients), D (1 patient), and a type that could not be clearly classified to any known subtype (1 patient). Thirty-five of the 41 Korean subtype B isolates formed a distinct monophyletic clade that is not related to any of the international sequences from the Los Alamos Database or GenBank as of June 1997. Indeed, the presence of unique conserved sequences was identified among the Korean isolates in this Korean subtype B group. The variations in the nucleotide sequences of a majority (32 of 35) subtype B samples within the Korean clade were 1.9% to 8.8%, and amino acid sequences varied from 3.9% to 15.5%. These results suggest that HIV-1 strains currently present in South Korea might have originated from a few sources or might be developing through a certain selective pressure. This is the first report on the molecular nature of the HIV-1 infection present in South Korea.

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Polymerase chain reaction (PCR) methodology was used to detect Epstein-Barr virus (EBV) DNA in peripheral blood mononuclear cells (PBMCs) from children and adults whose HIV status (i.e., infected or uninfected) is known. Initial EBV infections especially occurred in children between the ages of 7 and 24 months. EBV-positive children with vertically acquired HIV infection tended to have a detectable blood level of EBV DNA for a period of years, and their EBV DNA blood levels often exceeded 10,000 copies/0.1 ml of blood-hundreds of times higher than levels typically found in EBV-positive, HIV-uninfected children of the same age. EBV DNA was found in PBMCs in 26% of 49 HIV-infected mothers who were sampled during their pregnancy, but the median EBV DNA level in their EBV-positive samples was low-only 50 copies/0.1 ml blood. In limited tests with specimens from children infected with both HIV and EBV, high blood levels of EBV DNA unexpectedly appeared to be associated with decreased blood levels of HIV DNA (p= .063).

ISSN:1077-9450    

出版商:OVID    

年代:1998

数据来源: OVID