2,017 research outputs found
HIV-1 infection in the lymphoid organs
No full textAIM: To develop a model of HIV disease progression. METHOD: Comparative analysis of viral burden and replication between peripheral blood and lymphoid organs and of the changes in viral distribution in the lymphoid tissue. RESULTS: In early-stage disease HIV-1-infected cells were sequestered in the lymphoid tissue, and the viral particles were concentrated and trapped in the germinal centers. The dichotomy in viral burden and viral replication between peripheral blood and lymphoid tissue was related to the histopathologic abnormalities associated with different stages of disease. CONCLUSIONS: These histopathologic abnormalities may not only explain the changes in viral distribution observed in the lymphoid tissue in different stages of the disease, but may also reflect different functional states of the immune system during the progression of HIV-1 infection from early- to late-stage disease
Effect of anti-V3 antibodies on cell-free and cell-to-cell human immunodeficiency virus transmission.
No full textThe present study was undertaken to compare the effects of a type-specific (HIV-1 MN) anti-V3 antibody on in vitro human immunodeficiency virus (HIV) infection of peripheral blood mononuclear cells in systems of cell-free versus cell-to-cell transmission of virus. Anti-V3 antibody completely prevented HIV-1 infection when cell-free virus was the sole mechanism of infection. A significant reduction of the neutralizing activity of the anti-V3 antibody was observed when infectivity was dependent on both cell-free and cell-to-cell mechanisms of infection. Furthermore, when cell-to-cell transfer of virions was the primary mechanism of HIV-1 infection, inhibition of HIV-1 infection was not observed. Therefore, a potent neutralizing antibody with a single epitope specificity failed to effectively control dissemination of a persistent HIV-1 infection in a system characterized predominantly by cell-to-cell transfer of virus
Expression of a wide T cell receptor V beta repertoire in human T lymphocytes derived in vitro from embryonic liver cell precursors.
No full textAnalysis of the T-cell receptor beta-chain variable-region (V beta) repertoire in monozygotic twins discordant for human immunodeficiency virus: evidence for perturbations of specific V beta segments in CD4+ T cells of the virus-positive twins.
No full textWe analyzed the T-cell receptor (TCR) V beta repertoire in human immunodeficiency virus type 1 (HIV-1)-infected individuals at different stages of disease. To circumvent the effect of HLA and other loci on the expressed TCR repertoire, we compared the TCR repertoire in nine pairs of monozygotic twins who were discordant for HIV infection. A semiquantitative polymerase chain reaction (PCR) assay and flow cytometry enabled us to show distinct differences in the V beta repertoire in the HIV-positive twin compared with the HIV-negative twin. By combining PCR and cytofluorometry, these differences were restricted to a specific set of TCR V beta segments, with members of the V beta 13 family perturbed in six out of seven cases and those of the V beta 21 family perturbed in four out of seven cases studied. Most of the other V beta families remained unchanged. Our results provide direct evidence for a skewed TCR repertoire in HIV infection.We analyzed the T-cell receptor (TCR) Vβ repertoire in human immunodeficiency virus type 1 (HIV-1)-infected individuals at different stages of disease. To circumvent the effect of HLA and other loci on the expressed TCR repertoire, we compared the TCR repertoire in nine pairs of monozygotic twins who were discordant for HIV infection. A semiquantitative polymerase chain reaction (PCR) assay and flow cytometry enabled us to show distinct differences in the Vβ repertoire in the HIV-positive twin compared with the HIV-negative twin. By combining PCR and cytofluorometry, these differences were restricted to a specific set of TCR Vβ segments, with members of the Vβ13 family perturbed in six out of seven cases and those of the Vβ21 family perturbed in four out of seven cases studied. Most of the other Vβ21 families remained unchanged. Our results provide direct evidence for a skewed TCR repertoire in HIV infection
Role of Lymphoid Organs in the Pathogenesis of Human Immunodeficiency Virus (HIV) Infection
No full textThe pathogenic mechanisms of HIV disease are multifactorial and multi-phasic. The common denominator of the disease is the profound immunosuppression that occurs in the vast majority of infected patients. Studies in lymphoid tissues in HIV disease have provided considerable insight into the pathogenic processes involved from the earliest phases of infection through the advanced stages. Following primary infection, virus is disseminated throughout the body and seeds the lymphoid tissue where its replication is only incompletely suppressed and where a reservoir of virus is established. Extracellular virus is trapped within the FDC of the lymph node germinal centers and serves as a source of infection for cells which reside in or migrate through the lymph node throughout the course of infection even during the early and often prolonged asymptomatic period. Eventually, the architecture of the lymphoid tissue is destroyed, compounding the immune dysfunction that results from the depletion of CD4+ T cells. In this regard, the lymphoid tissue of LTNPs is relatively intact and viral burden and replication is considerably lower in the peripheral blood and lymph node mono-nuclear cells of LTNPs than in individuals whose disease progresses. Cytokines probably play a major role in the modulation of HIV expression in the milieu of the lymphoid tissue. Further understanding of the pathogenic mechanisms operative in the lymphoid tissues of HIV-infected individuals will have important implications in the design of therapeutic strategies involving both antiretroviral and immunomodulatory approaches
Kinetics of cytokine expression during primary human immunodeficiency virus type 1 infection
No full textIn the present study, we have determined the kinetics of constitutive expression of a panel of cytokines [interleukin (IL) 2, IL-4, IL-6, IL-10, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha)] in sequential peripheral blood mononuclear cell samples from nine individuals with primary human immunodeficiency virus infection. Expression of IL-2 and IL-4 was barely detected in peripheral blood mononuclear cells. However, substantial levels of IL-2 expression were found in mononuclear cells isolated from lymph node. Expression of IL-6 was detected in only three of nine patients, and IL-6 expression was observed when transition from the acute to the chronic phase had already occurred. Expression of IL-10 and TNF-alpha was consistently observed in all patients tested, and levels of both cytokines were either stable or progressively increased over time. Similar to IL-10 and TNF-alpha, IFN-gamma expression was detected in all patients; however, in five of nine patients, IFN-gamma expression peaked very early during primary infection. The early peak in IFN-gamma expression coincided with oligoclonal expansions of CD8+ T cells in five of six patients, and CD8+ T cells mostly accounted for the expression of this cytokine. These results indicate that high levels of expression of proinflammatory cytokines are associated with primary infection and that the cytokine response during this phase of infection is strongly influenced by oligoclonal expansions of CD8+ T cells
Studies in subjects with long-term nonprogressive human immunodeficiency virus infection.
No full textBACKGROUND: In a small percentage of persons infected with human immunodeficiency virus type 1 (HIV-1), there is no progression of disease and CD4+ T-cell counts remain stable for many years. Studies of the histopathological, virologic, and immunologic characteristics of these persons may provide insight into the pathogenic mechanisms that lead to HIV disease and the protective mechanisms that prevent progression to overt disease. METHODS AND RESULTS: We studied 15 subjects with long-term nonprogressive HIV infection and 18 subjects with progressive HIV disease. Nonprogressive infection was defined as seven or more years of documented HIV infection, with more than 600 CD4+ T cells per cubic millimeter, no antiretroviral therapy, and no HIV-related disease. Lymph nodes from the subjects with nonprogressive infection had significantly fewer of the hyperplastic features, and none of the involuted features, characteristic of nodes from subjects with progressive disease. Plasma levels of HIV-1 RNA and the viral burden in peripheral-blood mononuclear cells were both significantly lower in the subjects with nonprogressive infection than in those with progressive disease (P = 0.003 and P = 0.015, respectively). HIV could not be isolated from the plasma of the former, who also had significantly higher titers of neutralizing antibodies than the latter. There was viral replication, however, in the subjects with nonprogressive infection, and virus was consistently cultured from mononuclear cells from the lymph nodes. In the lymph nodes virus "trapping" varied with the degree of formation of germinal centers, and few cells expressing virus were found by in situ hybridization. HIV-specific cytotoxic activity was detected in all seven subjects with nonprogressive infection who were tested. CONCLUSIONS: In persons who remain free of disease for many years despite HIV infection the viral load is low, but viral replication persists. Lymph-node architecture and immune function appear to remain intact
Business Model Innovation of JF Logistics Company
No full text摘要 随着全球化经济的发展，市场竞争变得越来越复杂。信息时代使得物流供应链管理已上升到企业的战略管理高度。在这样的背景下，本文应用翁君奕老师的介观商务模式创新观点，对JF物流公司所处行业现状进行剖析，重新审视了外部客户市场以及内部自身情况，找出了JF物流公司自身的优势，并结合外部市场客户的需求，提出了“为客户提供个性化的集物流、资金流、信息流于一体的供应链物流服务”这一价值主张，并在此基础上，重新定位客户市场，创新服务产品，理顺内部管理架构和业务流程以支撑和保持这一价值主张。文中同时以例证来说明依据新价值主张所创新的服务产品给JF物流公司所带来的变化，以此说明通过商务模式创新来实行自身的战略...Abstract With the development of the global economy, the competition in market becomes more complicated. In the era of information, logistics and supply chain management is regarded as important as part of the company strategy. Under such background , the author of this essay uses the concept of “JieGuan Business Model Innovation” proposed by Professor Weng Junyi of Xiamen University, and analy...学位：管理学硕士院系专业：管理学院高级经理教育中心（EMBA项目）_管理经济学学号：X200615614
Temporal and spatial variability in speakers with Parkinson's Disease and Friedreich's Ataxia
No full textSpeech variability in groups of speakers with Parkinson's disease (PD) and with Friedreich's ataxia was compared with healthy controls. Speakers repeated the same phrase 20 times at one of two rates (fast or habitual). A non-linear analysis of variability was performed which used some of the principles behind the spatio-temporal index (STI). The STI usually employs variation in lip displacement over repetitions of the same utterance and a linear analysis of such signals is conducted to represent the combined variation in spatial and temporal control. When working with patients, audio measures (here we used speech energy) are preferred over kinematics ones as they are minimally disruptive to speech. Non-linear methods allow spatial variability to be estimated separately from temporal variability. The results are tentatively interpreted as showing that PD speakers were distinguished from healthy control speakers in spatial variability and ataxic speakers were distinguished from controls in temporal variability. These findings are consistent with the speech symptoms reported for these disorders. We conclude that the non-linear analysis using the speech energy measure is worth investigating further as it is potentially revealing of the differences underlying these two pathologies
Accumulation of human immunodeficiency virus-specific cytotoxic T lymphocytes away from the predominant site of virus replication during primary infection
No full textDown-regulation of the initial burst of viremia during primary human immunodeficiency virus (HIV) infection is thought to be mediated predominantly by HIV-specific CD8+ cytotoxic T lymphocytes (CTL). This response is associated with major perturbations in the T cell receptor (TCR) repertoire. To investigate the failure of the cellular immune response to adequately control viral spread and replication and to prevent establishment of HIV infection, changes in the TCR repertoire and in the distribution of virus-specific CTL between blood and lymph node were analyzed in three patients with primary infection. By the combined use of clonotype-specific polymerase chain reaction and analysis of the frequency of in vivo activated HIV-specific CTL, it was shown that HIV-specific CTL clones preferentially accumulated in blood as opposed to lymph node. Accumulation of HIV-specific CTL in blood occurred prior to effective down-regulation of virus replication in both blood and lymph node. These findings should provide new insights into how HIV, and possibly other viruses, elude the immune response of the host during primary infection
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