12 research outputs found

    Development of Novel Therapeutic Strategies to Prevent the Development of Kidney Disease

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    Inhibition of influenza A virus infection by Galectin-9

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    Galectin-9 (Gal-9) inhibited the infection of H1N1, H3N2 and H5N1 influenza A viruses in vitro and in vivo. Fifty percent effective doses (ED50) of Gal-9 were 0.1-0.5 M depending on virus strains in the plaque reduction assay. Gal-9 but not Gal-1 bound to the virus particles of A/Puerto Rico/8/34 (H1N1) (PR/8), resulting in inhibition of virus attachment to the host cells. Lactose but not sucrose inhibited the binding of Gal-9 to the viruses. Endogenous Gal-9 expression was detected and increased with the course of infection with influenza A viruses in mice. Fifty percent of Gal-9-transgenic mice survived after the challenge with PR/8, while all of the wild-type mice died. Gal-9 treatment of mice affected diminishing influenza virus replication in the lungs, body weight loss and the expression level of inflammatory cytokines. Combined administration of Gal-9 and oseltamivir was more effective than the use of single compound in mouse model. The present results indicate that Gal-9 is a candidate compound for influenza A virus infection therapy

    Developing a Framework for a Program of Life-Career Education - From an Analysis of Home Economics Textbooks in Japan and the USA -

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    本研究では、今後のライフキャリア教育の実践をめざし、具体的な教材である日米家庭科教科書を分析し、その結果をもとに授業プログラムの枠組みを構築することを目的とする。具体的には、日米の中等教育家庭科教科書を、ライフキャリアに関する能力領域(河﨑, 2011)「自己理解」「人間関係」「意思決定」「職業開発」「生活実践」「キャリア統 合」の6つの領域より分析した。日本の家庭科教科書は「自己理解」「人間関係」「生活実践」に重点が置かれ、前半では「自己理解」「人間関係」、後半では「生活実践」を学ぶようになっていた。米国の家庭科は、日本で重点が置かれていた内容に加えて「意思決定」「就業開発」「キャリア統合」の能力領域も含められており、総合的にライフキャリアに関する能力育成を目指しているという特徴が認められた。得られた知見を基にライフキャリア教育における授業プログラムの枠組み(案)を提示した

    Aggregability of the SQSTM1/p62-based aggresome-like induced structures determines the sensitivity to parthanatos

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    Abstract Overactivation of poly (ADP-ribose) polymerase-1 (PARP-1) triggers a noncanonical form of programmed cell death (PCD) called parthanatos, yet the mechanisms of its induction are not fully understood. We have recently demonstrated that the aggresome-like induced structures (ALIS) composed of the autophagy receptor SQSTM1/p62 and K48-linked polyubiquitinated proteins (p62-based ALIS) mediate parthanatos. In this study, we identified the D1 dopamine receptor agonist YM435 as a unique parthanatos inhibitor that acts as the disaggregating agent for the p62-based ALIS. We found that YM435 structurally reduces aggregability of the ALIS, and then increases its hydrophilicity and liquidity, which prevents parthanatos. Moreover, dopamine and L-DOPA, a dopamine precursor, also prevented parthanatos by reducing the aggregability of the ALIS. Together, these observations suggest that aggregability of the p62-based ALIS determines the sensitivity to parthanatos, and the pharmacological properties of YM435 that reduces the aggregability may be suitable for therapeutic drugs for parthanatos-related diseases such as neurodegenerative diseases

    Epidemiological and clinical features of invasive pneumococcal disease caused by serotype 12F in adults, Japan.

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    Enhanced surveillance of invasive pneumococcal disease (IPD) in adults was conducted during April 2013-March 2018 in 10 of 47 prefectures in Japan, and a total of 1277 IPD patients were enrolled. An emergence of IPD caused by serotype 12F was identified during May 2015-March 2018 through this surveillance. 12F isolates were composed of four related sequence types. In total, 120 patients with 12F IPD were reported during this period. To characterize the clinical features of 12F IPD, the disease characteristics of these patients were compared with those of 1157 patients with non-12F IPD. Compared with the non-12F IPD patients, a significantly lower proportion of 12F IPD patients was aged 65 years or older (55% vs. 70%), vaccinated with 23-valent pneumococcal polysaccharide (4% vs. 14%), had comorbid illness (65% vs. 77%), or were immunocompromised (19% vs. 30%; all P < 0.05). No significant difference in the proportion of case fatalities was found between the two groups. The proportions of those aged 65 years or older (53% vs. 69%) and with bacteremic pneumonia (35% vs. 69%) were significantly lower in 17 patients who died from 12F IPD than in 205 patients who died from non-12F IPD (all P < 0.05). Differences in clinical features were similarly found between 12F IPD patients and patients in low- or intermediate-level invasive potential serogroups. Our data demonstrated that serotype 12F was associated with IPD in younger adults and a lower proportion of comorbid illness, including immunocompromised conditions, in adult IPD, suggesting the high invasive potential of the serotype 12F. In addition, patients who died from 12F IPD were younger and had proportionately more bacteremia without focus. These findings may provide new insight into the pathogenesis of IPD in adults caused by 12F serotype with a high invasive potential
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