95 research outputs found

    The Role of STAT3 Activation in Glomerulonephritis

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    岡崎における第三者敬語の位置づけ : 「第三者尊敬表現」,「第三者謙譲表現」各場面のデータを中心に

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    神戸学院大学東京外国語大学 名誉教授国立国語研究所 時空間変異研究系 非常勤研究員Kobe Gakuin UniversityEmeritus Professor, Tokyo University of Foreign StudiesAdjunct Researcher, Department of Language Change and Variation, NINJAL本稿は,2008年に実施された第3次岡崎敬語調査から新たに加えられた第三者尊敬表現と第三者謙譲表現に関する設問に対する回答のデータに焦点をあて,岡崎市における第三者敬語の位置づけについて分析・検討したものである。その結果以下のようなことが明らかになった。岡崎市における敬語体系自体がどの段階にあるか,という観点から見ると以下のようである。(1)目上の人物である先生を話題にして,対友人場面で尊敬語を使わず,対先生場面で尊敬語を使うという回答が多数を占めた。世代別に見ると,若い世代にかけてこの傾向が強まる。男性の方が女性よりこの傾向が強く,女性に一歩先んじてこのような運用となっている。この結果から,見かけ時間の変化ではあるが,尊敬語の対者敬語的使用(敬語体系全体の丁寧語化)への変化が進んでいると言える。ただし,話し相手と話題ともに上位者を設定した場面では,回答が分かれ,話題と話し相手との関係も考慮した回答が一定数認められた。これは相対敬語的用法と言える。(2)「第三者謙譲表現」場面のデータには,他人を話し相手として身内の父親に言及する際,尊敬語使用はごく少数しか認められなかった。この結果から身内尊敬用法がほとんど行われていないことがわかった。第1 次調査の別の項目の結果からは身内尊敬用法がかなり行われていることが認められるので,この点でも変化が認められることになる。岡崎市の敬語の地理的位置づけ,という観点から見ると以下のようである。(3)敬語の運用上の特徴は,西日本的とされる,身内尊敬用法のような,絶対敬語的運用を残す運用や,くだけた場面でも素材敬語が高頻度で用いられるという運用は衰退し,東日本的な敬語体系全体の丁寧語化のような運用に変わりつつある。また,尊敬語伝統形の衰退のような語形の変化よりも,丁寧語化のような運用の変化が遅れていることもわかった。This paper aims to examine the positioning of third-person honorifics in Okazaki, focusing on data obtained from responses related to third-person honorific expressions that were newly added from the third Okazaki Survey on Honorifics conducted in 2008. The results of this study answered the following question.What kinds of gradations exist within the honorific language system in the city of Okazaki? The following gradations were found in this study: First, the results of the analysis indicated that an evolution of respectful honorifics toward polite (addressee) honorific usage is ongoing, although there is a change in apparent time. However, in a setting wherein both one\u27s conversation partner and the person who is the topic of conversation are established as being high-ranking people, certain extent of answers can be regarded as relative honorific usage.Second, for the data on scenarios involving "third-person humiliative expressions," the usage of only a few respectful honorifics was observed when referring to a speaker\u27s father with another person as the conversation partner. This result clarified that a change toward relative honorific usage from absolute honorific usage has been identified in this regard.From the perspective of the geographical positioning of honorific language in Okazaki, the usages, characteristic in western Japan, which remain absolute honorifics, and broad respectful honorifics that are used in reference to third parties, still in casual settings, have indicated a decline. Instead, the usage trend is shifting toward an honorific system entirely comprising addressee honorifics, a characteristic of eastern Japan

    Development of NIR Bioimaging Systems

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    Abstract. Fluorescence bioimaging is one of the most important technologies in the biomedical field. The most serious issue concerning current fluorescence bioimaging systems is the use of short wavelength light, UV or VIS, for the excitation of phosphors such as fluorescent proteins or quantum dots. The authors propose a fluorescence bioimaging system excited by near infrared light using rare-earth doped ceramic nanophosphors. The requirements for the nanophosphors are a designed emission scheme under the near infrared excitation, a controlled size between 10 and 200 nm and surface modification of the particles with a biofunctional polymer, which prevents particle agglomeration and non-specific interaction to nontargeting substances and gives them a specific interaction for the targeted objects. The preparation of the bioimaging probe and demonstrative imaging work are reported

    Point mutation of tyrosine 759 of the IL-6 family cytokine receptor, gp130, augments collagen-induced arthritis in DBA/1J mice

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    <p>Abstract</p> <p>Background</p> <p>Knock-in mice (gp130F759) with a Y759F point mutation in gp130, a signal transducing receptor subunit shared by members of the IL-6 cytokine family, show sustained activation of STAT3, enhanced acute-phase or immune responses, and autoimmune arthritis. We conducted a detailed analysis of collagen-induced arthritis (CIA) in gp130F759 with a DBA/1J background (D/J.gp130F759).</p> <p>Methods</p> <p>We backcrossed gp130F759 to C57BL/6 and DBA/1J, and compared the pathologic changes, including occurrence of arthritis, in the two distinct genetic backgrounds. We analyzed CIA in D/J.gp130F759 and investigated the effects of methotrexate (MTX) on CIA.</p> <p>Results</p> <p>C57BL/6 background gp130F759 mice, but not D/J.gp130F759, spontaneously developed polyarthritis and glomerulonephritis. On the other hand, keratitis of the eyes only developed in D/J.gp130F759, indicating the influence of genetic background on disease development in gp130F759 mice. Resistance of the DBA/1J background against spontaneous arthritis urged us to examine CIA in D/J.gp130F759. CIA in D/J.gp130F759 was more severe, with greater bone destruction, than the control mice. After collagen immunization, splenomegaly and serum levels of rheumatoid factor and anti-DNA antibody were augmented in D/J.gp130F759. Bio-Plex analysis of serum cytokines revealed increased IL-12p40 and PDGF-BB before immunization, and increased levels of IFN-γ, IL-17, TNF-α, IL-9, and MIP-1β 8 days after the booster dose. IL-6 and PDGF-BB in D/J.gp130F759 showed distinct kinetics from the other cytokines; higher levels were observed after arthritis development. MTX partially attenuated the development of arthritis and inhibited bone destruction in D/J.gp130F759, with reduction of anti-type II collagen antibody levels, suggesting that MTX mainly affects antigen-specific immune responses in CIA.</p> <p>Conclusion</p> <p>The Tyr-759 point mutation of the IL-6 family cytokine receptor subunit, gp130, caused autoimmune disease, and this was also influenced by the genetic background. CIA in D/J.gp130F759 is useful for evaluating drugs in a relatively short period because sustained activation of STAT3 may enhance the disease symptoms.</p

    Association between shift work and the risk of death from biliary tract cancer in Japanese men

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    Background: There is increasing evidence suggesting that shift work involving night work may increase cancer risk. Methods: We examined the association between working rotating shifts and the risk of death from biliary tract cancer among Japanese men who participated in the Japan Collaborative Cohort Study. Of the 46, 395 men recruited, 22, 224 men aged 40-65 at baseline (1988-1990) who reported working full-time or were self-employed were included in the present analysis. The study subjects were followed through December 31, 2009. Information regarding occupation and lifestyle factors was collected using a self-administered questionnaire. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for the risk of death from biliary tract cancer in relation to shift work. Results: During a mean 17-year follow-up, we observed 94 biliary tract cancer deaths, including 23 deaths from gallbladder cancer and 71 deaths from extrahepatic bile duct cancer. Overall, shift work was associated with a statistically non-significant increase in the risk of biliary tract cancer, with an HR of 1.50 (95 % CI: 0.81-2.77), among rotating shift workers. When the analysis was limited to extrahepatic bile duct cancer, a significant association appeared, with a multivariable-adjusted HR of 1.93 (95 % CI: 1.00-3.72) for rotating shift workers. Conclusion: Our data indicate that shift work may be associated with increased risk of death from extrahepatic bile duct cancer in this cohort of Japanese men. The association with gallbladder cancer remains unclear because of the small number of deaths

    Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in the human RAD6A–RAD18 ternary complex

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    RAD18, a RING-type ubiquitin ligase (E3) that plays an essential role in post-replication repair, possesses distinct domains named RING, UBZ, SAP and the RAD6-binding domain (R6BD) and forms a dimer. RAD6, an ubiquitin-conjugating enzyme (E2), stably associates with R6BD in the C-terminal portion. In this study, we established a method to distinguish between the two subunits of RAD18 by introduction of different tags, and analyzed mutant complexes. Our results, surprisingly, demonstrate that RAD6A and RAD18 form a ternary complex, RAD6A–(RAD18)2 and the presence of only one R6BD in the two RAD18 subunits is sufficient for ternary complex formation and the ligase activity. Interestingly, ligase activity of a mutant dimer lacking both R6BDs is not restored even with large amounts of RAD6A added in solution, suggesting a requirement for precise juxtaposition via interaction with R6BD. We further show that mutations in both subunits of either RING or SAP, but not UBZ, strongly reduce ligase activity, although inactivation in only one of two subunits is without effect. These results suggest an asymmetric nature of the two RAD18 subunits in the complex
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