Fas and Fas ligand are not involved in the suppression of HIV replication by CD8 cells.
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Antibodies, Monoclonal↗
Biomedical subjects
J A Levy
Publications and source records attributed to J A Levy.
Induction of human herpesvirus-8 gene expression by recombinant interferon gamma.
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Gene Expression Regulation, Viral↗
Acetylcholine affects the spatial scale of attention: evidence from Alzheimer's disease.
Location precues were used to manipulate the spatial scale of attention in visual search for a target in an array of letters in patients with dementia of the Alzheimer type (DAT) and in age-matched older controls. Cue size varied in the amount of spatial precision conferred. Scopolamine, a muscarinic antagonist, decreased overall arousal and broadened spatial attention after a precise precue (small and valid) to target location for DAT patients but not for controls, suggesting a selective effect for attentional impairment induced by cholinergic blockade. In contrast, physostigmine, a cholinesterase inhibitor, did not alter the distribution of spatial attention relative to no-drug baseline testing for patients. Results support a differential role for cholinergic mechanisms in the modulation of the spatial scale of visual attention.
Acetylcholine↗
CD8(+) cell noncytotoxic anti-human immunodeficiency virus response inhibits expression of viral RNA but not reverse transcription or provirus integration.
CD8(+) T cells from human immunodeficiency virus (HIV)-infected individuals can suppress HIV replication in CD4(+) cells by a noncytotoxic mechanism that inhibits the expression of viral RNA. The present study examined whether other step(s) in the virus replicative cycle could be affected by the CD8(+) cells. Culturing HIV-infected CD4(+) T cells with antiviral CD8(+) T cells did not significantly reduce the amounts of (i) early HIV DNA reverse transcripts (detected by LTR-U3/R), (ii) total nuclear HIV gag DNA, or (iii) integrated proviral DNA. However, exposure to the CD8(+) T cells did cause a reduction in the amount of multiply spliced tat and full-length gag mRNA expressed by the infected CD4(+) T cells, confirming previous observations. The levels of glyceraldehyde-3-phosphate dehydrogenase and interleukin-2 receptor-alpha mRNA were not affected. The results support the conclusion that the noncytotoxic anti-HIV response of CD8(+) T cells, demonstrable in vitro, does not affect any of the virus replication steps leading to the integration of proviral HIV, but specifically interrupts the expression of viral RNA.
CD4-Positive T-Lymphocytes↗
Emery-Dreifuss muscular dystrophy: anatomical-clinical correlation (case report).
We report on a man that had weakness of humeroperoneal distribution associated with limited range of motion of the cervical spine and elbows since he was 5 years old. At age 26 he developed tachycardia episodes. A complex arrhythmia was discovered, and a nodal ablation was done with a cardiac pacemaker implanted. The patient had an arrhythmia and sudden death followed this. Emery-Dreifuss muscular dystrophy is a rare recessive X-linked muscular disorder where mixed patterns in electromyography and muscle histology (neurogenic and/or myopathic) have caused nosological confusion. The autopsy findings are here described and correlated to the clinical features in an attempt to better understand the ambiguous findings concerning the process etiology.
Adult↗
Antibody and cellular immune responses in breakthrough infection subjects after HIV type 1 glycoprotein 120 vaccination.
HIV-specific antibodies and CD8+ T cell antiviral responses were evaluated in three human immunodeficiency virus 1 (HIV-1) gp120 vaccine recipients who later became infected with HIV-1. Titers of neutralizing antibody to the HIV-1(SF2) vaccine isolate were boosted, but titers of antibody to the autologous infecting viruses were never high and required at least 6 months after HIV infection to develop. Similarly, a marginal noncytotoxic CD8+ T cell antiviral response was observed only in one of the three vaccinees 3 months after HIV-1 infection. The infecting virus isolates had several amino acid substitutions in the HIV-1 envelope V3 region but were similar to other regional HIV-1 clade B isolates. Viral loads were similar to those of other HIV-1-infected individuals who had not been vaccinated and transient CD4+ T cell declines were observed in each person, suggesting that the vaccine was not effective at controlling these prognostic markers early in infection.
AIDS Vaccines↗
Lack of differences in nef alleles among HIV-infected asymptomatic long-term survivors and those who progressed to disease.
Sequences of the human immunodeficiency virus (HIV) nef gene in virus isolates from 12 long-term survivors (LTSs) and 7 progressors were compared to determine if any association existed between the sequences and the corresponding clinical status. The sequences of at least five clones were determined for each subject. Conceptual translations of the open reading frames (ORFs) were examined with respect to a consensus with a prototypic nef sequence (HIV-1SF2) and for conservation of functionally described motifs. Premature stops were observed at equivalent, yet low, frequencies among the different clinical groups: 2 of 60 (3.33%) and 1 of 45 (2.22%) respectively. No remarkable differences in protein motifs implicated in several activities ascribed to Nef were noted. An association between nef sequence characteristics and the clinical state was not found.
Alleles↗
The role of CD80 and CD86 in enhancing CD8(+) cell suppression of HIV replication.
CD8(+) cells activated in the presence of autologous macrophages (Mphi) have an increased ability to suppress HIV replication compared to the same cells stimulated in the absence of Mphi. Blocking the B7 molecules decreases the ability of Mphi to increase CD8(+) cell antiviral activity. In the present study CD8(+) cells exposed to purified forms of both the CD80 and the CD86 molecules during stimulation with anti-CD3 antibodies (Ab) had a greater ability to suppress HIV replication than CD8(+) cells exposed to anti-CD3 Ab alone. The addition of anti-CD86 blocking Ab, but not anti-CD80 blocking Ab, to Mphi decreased their ability to enhance CD8(+) cell suppression of HIV replication. Moreover, anti-CD86 Ab and not anti-CD80 Ab blocked the production of IL-2 by CD8(+) cells stimulated in the presence of Mphi. The incapacity of anti-CD80 Ab to block the enhanced antiviral activity and IL-2 production of CD8(+) cells stimulated in the presence of Mphi was not due to the inability of this Ab to function since anti-CD80 Ab are able to block proliferation of CD8(+) cells cultured in the presence of Mphi. Thus, while both B7 molecules can deliver a costimulatory signal sufficient to increase CD8(+) cell antiviral activity, CD86 appears to be the molecule that serves as the costimulatory molecule on Mphi to enhance CD8(+) cell suppression of HIV replication. The difference in use of CD86 over CD80 molecules on Mphi by CD8(+) cells mediating the antiviral suppressing activity most likely results from a higher number of Mphi expressing the CD86 molecule compared with the CD80 molecule. This information offers a possible therapeutic approach to increase CD8(+) cell anti-HIV response.
Antibodies, Monoclonal↗
Reconstruction after multilevel corpectomy in the cervical spine. A sagittal plane biomechanical study.
STUDY DESIGN: An in vitro biomechanical study of reconstruction techniques used after multilevel cervical corpectomy. OBJECTIVES: To determine the biomechanical behavior of the cervical spine after a multilevel corpectomy and reconstruction with a strut graft and supplementation of the graft with anterior and posterior plates. SUMMARY OF BACKGROUND DATA: Reconstruction of the spine after multilevel corpectomy represents a significant challenge, with nonunion or graft dislodgment being relatively common. Anterior and posterior plate fixation have increased the possibilities for supplemental stabilization. Although some clinical studies have been performed to examine multilevel corpectomies reconstructed with plates, biomechanical studies are few and are limited to single-segment models. METHODS: Flexibility testing was performed on 11 intact cervical spine preparations. Flexibility testing was also conducted on the spine preparations after reconstruction with a strut graft, after supplementation of the graft with an anterior plate, and after supplementation of the graft with lateral mass plates. Physiologic moments were applied dynamically, and the three-dimensional motion of the specimen was recorded with stereophoto-grammetry. Failure testing was performed on the plated specimens in compression. Load displacement curves and failure modes were analyzed. RESULTS: The range of motion after reconstruction compared with the control was decreased 24% after strut grafting, 43% after application of an anterior plate, and 62% after application of posterior plates. Similarly, flexibility coefficients showed that the posterior plate technique was the least flexible, followed by the anterior plate technique, with the graft alone being the most flexible reconstruction construct. Load to initial failure tended to be higher in posterior than in anterior plate specimens, and screw pullout was the predominant failure mode. CONCLUSIONS: The application of plates to the cervical spine as an adjunct to bone graft may improve the surgeon's ability to stabilize the spine after multilevel corpectomy. Understanding the biomechanics of these devices and the potential mode of failure is important in their use.
Adult↗
Lack of infection in HIV-exposed individuals is associated with a strong CD8(+) cell noncytotoxic anti-HIV response.
Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely to have either natural or acquired resistance to the virus. We have studied four such exposed uninfected cohorts, representing 60 individuals, for evidence of protective immunity. This population included participants exposed to HIV through anal or vaginal receptive intercourse on multiple occasions over many years. We observed CD8(+)-cell noncytotoxic inhibition of HIV replication in acutely infected CD4(+) cells in the vast majority of individuals most recently exposed to the virus (within 1 year). The levels of this CD8(+)-cell response were sufficient to inhibit the in vitro infection of the exposed subjects' peripheral blood mononuclear cells. We found no evidence of a significant role for CCR5 Delta32 mutation in this population, nor did CD4(+) cell susceptibility to infection or HIV-specific cytotoxic T-lymphocytes correlate with resistance to infection in the individuals tested. Therefore, the observed strong noncytotoxic CD8(+)-cell anti-HIV responses may be an antiviral immune activity contributing to the apparent protection from infection in these exposed uninfected individuals.
Adult↗
Xenotropism: the elusive viral receptor finally uncovered.
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Animals↗
Suppression of human immunodeficiency virus type 1 replication by a soluble factor produced by CD8+ lymphocytes from HIV-2-infected baboons.
Human immunodeficiency virus type 2 (HIV-2)-infected baboons (Papio cynocephalus) provide a valuable animal model for the study of acquired immunodefidency syndrome (AIDS) pathogenesis since many features of disease progression resemble HIV-1-infection of humans. In some HIV-2-infected baboons that are clinically healthy, a CD8+ cell antiviral response, that is partly mediated by a soluble factor, controls viral replication in vitro. In the present study, we demonstrate that CD8+ cells derived from HIV-2-infected baboon peripheral blood, lymph nodes, adenoids and tonsils had antiviral activity in co-cultures of CD8+ and CD4+ cells that inversely correlates with viral load. A soluble factor was found to be active against the chemokine-resistant, syncytium-inducing HIV-1SF2 and HIV-1SF33 isolates and was relatively heat stable at 100 degrees C for 10 min. Moreover, inhibition of the transcription from the long terminal repeat of HIV-1 was observed in 1G5 cells after activation with phorbol 12-myristate 13-acetate. Therefore, the soluble suppressing activity of CD8+ cells in HIV-2-infected baboons may be analogous to the CD8+ cell antiviral factor described in human HIV-infected asymptomatic people.
Acquired Immunodeficiency Syndrome↗
Merosin-positive congenital muscular dystrophy in two siblings with cataract and slight mental retardation.
We report on two siblings that have been followed for 14 years, with merosin-positive congenital muscular dystrophy (CMD), cataract, retinitis pigmentosa, dysversion of the optic disc, but no cerebral anomalies, except for microcephaly and slight mental retardation (MR). The younger child had three generalized seizures easily controlled by anticonvulsant therapy. Both children presented hypotonia from birth, delayed psychomotor development, generalized muscular weakness, and atrophy and joint contractures of knees and ankles. The course of the disease, apparently static during the first 10 years of life, became progressive during the second decade with loss of deambulation by the age of 13. Creatine kinase was increased in both children. Bilateral cataract was diagnosed at 6-months of age. In spite of the occurrence of microcephaly, MR was slight and the siblings acquired reading and writing skills after the aged 10. Head magnetic resonance imaging showed normal results in both siblings. The classification of these cases within the broad spectrum of CMD is difficult since most of the known muscle-eye-brain syndromes generally show severe MR and brain anomalies. We consider these cases as corresponding to the rarer syndromes of merosin-positive CMD with associated features such as cataract and MR that were particularly emphasized during the 50th ENMC International Workshop on CMD [Dubowitz V. Workshop report: 50th ENMC International workshop on congenital muscular dystrophy. Neuromusc Disord 1997;7:539-547]. Further genetic, pathological, neuroradiological, and immunocytochemical studies will be necessary for better elucidation of the classification and pathogenesis of CMD.
Adolescent↗
Increased human herpesvirus 8 seroprevalence in young homosexual men who have multiple sex contacts with different partners.
The objective of this study was to evaluate the behavioral risks that are associated with human herpesvirus 8 (HHV-8) infection in a cohort of young homosexual men. Seventy-nine subjects (ages 22-33 years) who completed a questionnaire about their sexual and drug use behavior over the preceding year were recruited from the San Francisco Young Men's Health Study. Plasma samples were tested for anti-HHV-8 antibodies using an indirect IFA. Thirty-eight subjects (48.1%) were infected with HHV-8. HHV-8 infection was significantly linked to an increasing number of male sex partners (P=.025, Mantel-Haenszel chi2 test for trend), suggesting a strong association between HHV-8 infection and multiple homosexual contacts.
Adult↗
Differential effects of human immunodeficiency virus isolates on beta-chemokine and gamma interferon production and on cell proliferation.
All human immunodeficiency virus (HIV) isolates can grow readily in primary CD4(+) T cells, but they can be distinguished by their ability to replicate in macrophages and established T-cell lines. The macrophage-tropic viruses are generally non-syncytium inducing (NSI), whereas the T-cell-line-tropic viruses are syncytium inducing (SI) in cultured cells. We now demonstrate that infection of CD4(+) T cells by NSI and SI viruses shows a differential effect on production of beta-chemokines and gamma interferon. Infection by NSI viruses increased production of MIP-1alpha, MIP-1beta, and gamma interferon, whereas infection by SI viruses had no effect or decreased production of these cytokines. Production of RANTES was slightly increased during infection by both virus phenotypes. This differential effect of NSI and SI viruses was observed at the level of beta-chemokine mRNA as well as at the level of protein expression. Infection by NSI viruses also increased CD4(+) cell proliferation. These results may have relevance for a differential role of HIV strains in AIDS pathogenesis.
CD4-Positive T-Lymphocytes↗
Differential effects of CD28 costimulation on HIV production by CD4+ cells.
We have observed that CD28 costimulation of CD4+ cells can have differential effects on HIV replication. Triggering the CD28 molecule on peripheral blood CD4+ cells during stimulation with anti-CD3 Abs enhances virus production following acute infection with HIV. Endogenous virus production in CD4+ cells from HIV-infected individuals is also increased by this procedure. The enhanced virus production occurs equally when anti-CD28 Abs and soluble forms of the natural ligands for CD28, CD80Ig, and CD86Ig are used to trigger CD28 on CD4+ cells during stimulation. This increased virus replication is observed only when the source of CD28 costimulation is removed immediately after stimulation and before infection. Continual exposure of CD4+ cells to anti-CD3 and CD28 Ab beads following acute infection prevents virus production. These findings may have relevance to therapeutic approaches aimed at inhibiting HIV replication by CD28 costimulation.
Antibodies, Monoclonal↗
Differences in HIV replication in CD4+ lymphocytes are not related to beta-chemokine production.
CD4+ T lymphocytes from different donors vary in their ability to replicate different isolates of HIV. Beta-chemokines have been shown to reduce the rate of HIV replication in cultured cells. We now demonstrate, using CD4+ cells from 19 different donors, that the variations in viral replication observed in CD4+ lymphocytes are not due to endogenous production of beta-chemokines by the cells. Instead of finding a correlation of high-level beta-chemokine production with low-level replication of virus, we found either no consistent relationship between these two parameters or a correlation between high-level beta-chemokine production and high-level virus replication. This observation was made with both chemokine-sensitive and chemokine-resistant HIV isolates. Thus, other mechanisms appear to be involved in the variability in HIV replication in cultured CD4+ cells.
CD4-Positive T-Lymphocytes↗
Virological and immunological features of long-term human immunodeficiency virus-infected individuals who have remained asymptomatic compared with those who have progressed to acquired immunodeficiency syndrome.
Infection with the human immunodeficiency virus (HIV) leads to a decrease in CD4(+) T cells and disease progression within a decade of seroconversion. However, a small group of infected people, despite being infected by HIV for 10 or more years, remain clinically asymptomatic and have stable CD4(+) cell counts without taking antiretroviral medication. To determine why these individuals, known as long-term survivors (LTS), remain healthy, the hematological profiles, viral load and properties, HIV coreceptor genotype, and anti-HIV immune responses of these people were compared with those of individuals who have progressed to disease (Progressors) over the same time period. Unlike Progressors, LTS have a low circulating viral load and a low number of HIV-infected cells. These differences in the levels of the viral load were not associated with a dominant biologic viral phenotype, varying growth kinetics of the virus, mutation in the cellular CCR5 gene, or the presence of neutralizing antibodies. Importantly, the difference in viral load could be explained by the enhanced ability of CD8(+) cells from LTS to suppress HIV replication.
Acquired Immunodeficiency Syndrome↗