29 research outputs found

    Abnormally High Levels of Virus-Infected IFN-γ+CCR4+CD4+CD25+ T Cells in a Retrovirus-Associated Neuroinflammatory Disorder

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    BACKGROUND:Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL). The pathogenesis of HAM/TSP is known to be as follows: HTLV-1-infected T cells trigger a hyperimmune response leading to neuroinflammation. However, the HTLV-1-infected T cell subset that plays a major role in the accelerated immune response has not yet been identified. PRINCIPAL FINDINGS:Here, we demonstrate that CD4(+)CD25(+)CCR4(+) T cells are the predominant viral reservoir, and their levels are increased in HAM/TSP patients. While CCR4 is known to be selectively expressed on T helper type 2 (Th2), Th17, and regulatory T (Treg) cells in healthy individuals, we demonstrate that IFN-gamma production is extraordinarily increased and IL-4, IL-10, IL-17, and Foxp3 expression is decreased in the CD4(+)CD25(+)CCR4(+) T cells of HAM/TSP patients as compared to those in healthy individuals, and the alteration in function is specific to this cell subtype. Notably, the frequency of IFN-gamma-producing CD4(+)CD25(+)CCR4(+)Foxp3(-) T cells is dramatically increased in HAM/TSP patients, and this was found to be correlated with disease activity and severity. CONCLUSIONS:We have defined a unique T cell subset--IFN-gamma(+)CCR4(+)CD4(+)CD25(+) T cells--that is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system

    Global Norms, Local Activism, and Social Movement Outcomes: Global Human Rights and Resident Koreans in Japan

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    The authors integrate social movement outcomes research and the world society approach to build a theoretical model to examine the impact of global and local factors on movement outcomes. Challenging the current research on policy change, which rarely examines the effects of global norms and local activism in one analysis, they argue (1) that global regimes empower and embolden local social movements and increase pressure on target governments from below, and (2) that local activists appeal to international forums with help from international activists to pressure the governments from above. When the pressures from the top and the bottom converge, social movements are more likely to succeed. Furthermore, these pressures are stronger in countries integrated into global society and on issues with strong global norms. The empirical analysis of social movements by resident Koreans in Japan advocating for four types of human rights—civil, political, social/economic, and cultural—demonstrates that the movements produced more successes as Japan\u27s involvement in the international human rights regime expanded since the late 1970s, and that activism on issues with strong global norms achieved greater successes. The analysis also shows that lack of cohesive domestic activism can undercut the chances of social movements\u27 success even with strong global norms on the issue

    Accelerating Instant Question Search with Database Techniques

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    Distributed question answering services, like Yahoo Answer 1 and Aardvark 2, are known to be useful for end users and have also opened up numerous topics ranging in many research fields. In this paper, we propose a user-support tool for composing questions in such services. Our system incrementally recommends similar questions while users are typing their question in a sentence, which gives the users opportunities to know that there are similar questions that have already been solved. A question database is semantically analyzed and searched in the semantic space by boosting the performance of similarity searches with database techniques such as server/client caching and LSH (Locality Sensitive Hashing). The more text the user enters, the more similar the recommendations will become to the ultimately desired question. This unconscious editing-as-a-sequence-of-searches approach helps users to form their question incrementally through interactive supplementary information. Not only askers nor repliers, but also service providers have advantages such as that the knowledge of the service will be autonomously refined by avoiding for novice users to repeat questions which have been already solved

    A Case of Inflammatory Generalized Type of Peeling Skin Syndrome Possibly Caused by a Homozygous Missense Mutation of CDSN

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    A 54-year-old Japanese woman had repetitive superficial skin peeling and ensuing erythematous changes in the sites since infancy. Her parents had a consanguineous marriage, and she was the only individual affected in her family tree. The erythematous changes seemed to worsen in the summer. Histologically, hyperkeratosis and splitting of the epidermis within the stratum corneum was noted, and electron microscopy revealed shedding of corneal cells in the horny layer and normal-looking corneodesmosomes. Gene analysis revealed a homozygous missense mutation at c.1358G>A in CDSN. Electron microscopic examination of the length and number of corneodesmosomes revealed statistically significant shortness and sparsity in the affected individual (mean ± SD 386.2 ± 149.5 nm) compared with that of an age- and site-matched control (406.6 ± 182.3 nm). We speculate that this size shrinkage of corneodesmosomes might be the result of a missense mutation of CDSN and that this could be one of the factors contributing to the pathological process of skin peeling
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