8 research outputs found

    ホクオウテキ ヘイワ キンコウ : フンソウ コウゾウ ノ ヘンカン ノタメノ アプローチ 、 カイケツ シュホウ ト ソノ ゲンリ

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    PDF/A formatsAccess: via World Wide Web東京外国語大学大学院総合国際学研究科博士 (学術) 論文 (2017年1月)Author's thesis (Ph.D)--Tokyo University of Foreign Studies, 2017博甲第222号Bibliography: p. 208-231Summary in English and Japanese東京外国語大学 (Tokyo University of Foreign Studies)博士 (学術

    北欧的平和均衡 : 紛争構造の変換のためのアプローチ、解決手法とその原理

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    Global Conventions and Regional Cooperation: The Multifaceted Dynamics of Arctic Governance

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    The Arctic is a globally embedded space. This is as true for the impact of global climate change on the Arctic and the consequences of Arctic climate change for the rest of the world as it is for governance for and in the Arctic. This chapter analyzes the dynamics that structure and result from the coexistence of global and regional governance mechanisms in four issue areas: the governance of marine and maritime spaces, Indigenous Peoples, climate governance, and environmental protection and conservation. It assesses how global conventions impacted regional governance and, in turn, how regional cooperation influenced governance on the global level. In order to do this, we distinguish four ways in which the nexus between global governance and regional cooperation can be established: as harmonious, cooperative, conflictive, and indifferent. For each way, an outside-in (from the global to the regional level) and an inside-out (from the regional to the global level) perspective can be considered. This yields a typology of eight different kinds of links between regional cooperation and global conventions. Much of the previous research has focused on harmonious and cooperative links. By contrast, we intend to show that as global interest in the Arctic grows, along with the need for regulatory governance in the region, the nexus might increasingly become conflictive. In order to retain control over the region and its governance, Arctic states’ cooperation seeks to limit both their own global commitments and the influence of exogenous actors or institutions

    Critical comparative analyses of anti-alpha-actinin and glomerulus-bound antibodies in human and murine lupus nephritis

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    Objective. Although anti-double-stranded DNA (anti-dsDNA) antibodies are important in lupus nephritis, the question regarding which glomerular structures (a-actinin, nucleosomes, or others) are recognized by nephritogenic anti-dsDNA antibodies is still controversial. In this study, we determined which glomerular structures are recognized by monoclonal and in vivo-bound nephritogenic antibodies. Methods. Western blotting was used to analyze the ability of nephritogenic anti-dsDNA antibodies to recognize glomerular and nucleosomal structures. Sera from patients with lupus nephritis, sera from random antinuclear antibody-positive patients, and paired antibodies from sera and kidney eluates from nephritic (NZB X NZW)F-1 mice were analyzed for activity against proteins identified by monoclonal nephritogenic antibodies, and against a-actinin, dsDNA, nucleosomes, histone H1, heparan sulfate, DNase I, and type IV collagen. Immunoelectron microscopy was used to determine the glomerular localization of a-actinin and in vivo-bound autoantibodies in nephritic (NZB X NZW)F-1 mouse kidneys. Results. Anti-alpha-actinin antibodies were observed in human and murine lupus nephritis sera and in sera from patients without systemic lupus erythematosus and were not detected in kidney eluates from nephritic mice. Antibodies to dsDNA and histone H1 were detected in all eluates. Western blot analyses revealed that nephritogenic anti-dsDNA antibodies recognized a 32-kd band, identified as histone H1. Competitive enzyme-linked immunosorbent assay demonstrated that nephritogenic monoclonal antibodies, and dominant antibodies eluted from nephritic kidneys, cross-reacted with dsDNA and H1. This cross-reactive anti-H1 specificity was largely absent in sera from those mice. Immunoelectron microscopic analysis of nephritic (NZB X NZW)F-1 mouse kidneys revealed that antibodies eluted from kidneys, but not anti-alpha-actinin antibodies, bound to distinct nephritis-associated electron-dense structures linked to glomerular basement membranes. Conclusion. Cross-reactive anti-dsDNA/anti-histone H1 antibodies, but not anti-alpha-actinin antibodies, are central among those deposited in nephritic glomeruli

    Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.

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    A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis

    Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis

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    Antibodies to double-stranded (dsDNA) are associated with systemic lupus erythematosus (SLE) and directly involved in human lupus nephritis. Information about their glomerular target antigens is inconsistent, and whether availability of target antigens, antibody specificity or avidity are nephritogenic parameters, is not determined. In this study, we analyzed renal tissue from anti-dsDNA antibody-positive lupus patients with nephritis by morphological and immunological assays, including immune electron microscopy (IEM) and colocalization IEM, an EM-based confocal microscopy assay. IEM demonstrated that antibody deposits were confined to electron dense structures (EDS) in glomerular membranes. These autoantibodies colocalized with nucleosome-binding anti-dsDNA/-histone/-transcription factor antibodies. To confirm the colocalization IEM-data, we developed a colocalization terminal deoxynucleotidyltransferase (TdT) biotin-dUTP nicked end-labeled (TUNEL) IEM assay where extracellular DNA was traced by TdT-mediated introduction of biotinylated nucleotides and autoantibodies by IEM. Results consistently demonstrated that DNA colocalized with autoantibodies in glomerular membrane-associated EDS. The colocalization IEM and colocalization TUNEL IEM assays thus demonstrate that intra-glomerular membrane-associated nucleosomes are targeted by anti-dsDNA autoantibodies in human lupus nephritis. The data provide a new approach to understand basic molecular and immunological processes accounting for antibody-mediated nephritis in human SLE

    Low diagnostic and predictive value of anti-dsDNA antibodies in unselected patients with recent onset of rheumatic symptoms: results from a long-term follow-up Scandinavian multicentre study.

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    Objectives: To verify the diagnostic accuracy of anti-double-stranded DNA (anti-dsDNA) antibodies detected by the Crithidia luciliae immunofluorescence test (CLIFT) in a cohort of unselected patients, referred to a rheumatologist due to recent onset of rheumatic symptoms. Method: A total of 1073 consecutive patients were screened for anti-nuclear antibodies (ANAs). Serum samples from 292 ANA-positive and 292 matching ANA-negative patients were tested three times for anti-dsDNA antibodies, using two different CLIFT kits (ImmunoConcepts(®) and Euroimmun(®)). An initial clinical diagnosis was made by rheumatologists unaware of the results. The diagnoses were updated after a median follow-up of 4.8 years. Results: CLIFT was positive at least once in 60 patients but only 23 patients were CLIFT positive in all of the assays. Diagnosis of systemic lupus erythematosus (SLE) was made initially in 65 patients, of whom 24 (37%) were CLIFT positive. Many other diagnoses were observed among the CLIFT-positive patients. Overall, 16 (5.5%) ANA-negative patients were CLIFT positive. After approximately 5 years, the diagnosis of SLE remained unchanged in 63 patients (23 CLIFT positive) and altered in only two (one CLIFT positive). Among the 36 CLIFT-positive patients who were not diagnosed with SLE at study entry, only one developed SLE during the follow-up period. Conclusions: CLIFT was not reliable as a diagnostic tool in unselected patients with rheumatic symptoms. ANAs were of little value as a screening test before the CLIFT analysis. CLIFT had surprisingly low positive predictive value (PPV) for the diagnosis of SLE despite its high specificity. For non-SLE patients, being CLIFT positive poses little risk of developing SLE within 5 years
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