一般住民における耐糖能異常の有病率の疫学調査 : 久山町研究

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Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance.

[Introduction]B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play a crucial role in B cell development, survival, and antibody production. Here we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with an immunoglobulin (Ig) G4-related disease (IgG4-RD). [Methods]We measured serum levels of BAFF and APRIL in patients with IgG4-RD, primary Sjögren's syndrome (pSS), and healthy individuals. Serum BAFF and APRIL levels in IgG4-RD were assessed for correlations with serological parameters, including Ig, particularly IgG4, and the number of affected organs. Serum BAFF and APRIL levels in IgG4-RD were monitored during glucocorticoid (GC) therapy. [Results]Serum BAFF and APRIL levels in patients with IgG4-RD were significantly higher (P < 0.01) than in healthy individuals. The BAFF levels of patients with IgG4-RD were comparable to those of patients with pSS. Although clinical parameters, such as serum IgG4 and the number of affected organs, were not correlated with the levels of BAFF, serum APRIL levels were inversely correlated with serum IgG4 levels (r = -0.626, P < 0.05). While serum BAFF levels decreased following GC therapy, serum APRIL levels increased during follow-up. [Conclusion]These results indicate that BAFF and APRIL might be useful markers for predicting disease activity in IgG4-RD. Further studies are needed to elucidate the role of BAFF and APRIL in the pathogenesis of IgG4-RD

V-I Curve Based Condition Monitoring System for Power Devices

According to gaining importance of power electronics systems in the society, reliability issues of power semiconductor devices are the constrains on availability of the system operations. Regular interval based maintenance for higher availability, on the other hand, increases operation cost since the lifetime of power devices have a large deviation with production lots or conditions which they are used. Condition based maintenance (CBM) of power semiconductor devices will be a promising solution for both the availability and cost of power electronics system maintenance. In this study, a high signal resolution condition monitoring system board has been demonstrated. The system monitors real time V-I curve for both switching device and diode with case temperature and the data is stored on board memory and can be monitored on-line. The board was mounted on the gate driver board being supplied power from the gate driver board and demonstrated on a commercial 60kVA inverter.32nd International Symposium on Power Semiconductor Devices and ICs (ISPSD 2020), 13-18 September, 2020, Vienna, Austria （新型コロナ感染拡大に伴い、現地開催中止

Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury

Peripheral nerve injury induces substantial molecular changes in the somatosensory system that leads to maladaptive plasticity and cause neuropathic pain. Understanding the molecular pathways responsible for the development of neuropathic pain is essential to the development of novel rationally designed therapeutics. Although lipids make up to half of the dry weight of the spinal cord, their relation with the development of neuropathic pain is poorly understood. We aimed to elucidate the regulation of spinal lipids in response to neuropathic peripheral nerve injury in mice by utilizing matrix-assisted laser desorption/ionization imaging mass spectrometry, which allows visualization of lipid distribution within the cord. We found that arachidonic acid (AA) containing [PC(diacyl-16:0/20:4)+K]+ was increased temporarily at superficial ipsilateral dorsal horn seven days after spared nerve injury (SNI). The spatiotemporal changes in lipid concentration resembled microglia activation as defined by ionized calcium binding adaptor molecule 1 (Iba1) immunohistochemistry. Suppression of microglial function through minocycline administration resulted in attenuation of hypersensitivity and reduces [PC(diacyl-16:0/20:4)+K]+ elevation in the spinal dorsal horn. These data suggested that AA containing [PC(diacyl-16:0/20:4)+K]+ is related to hypersensitivity evoked by SNI and implicate microglial cell activation in this lipid production

チカク サレタ ソーシャル サポート ノ ブンセキテキ ケンキュウ

個々の内的特性の一つである充足感,満足感,達成感といった実存性も,ソーシャル・サポートの媒介要因の一つとして個人の精神的健康に作用する。このような考えに基づいて,本研究では,知覚されたソーシャル・サポートと精神的健康の因果影響関係について,実存的意識を媒介要因として検討することを目的とした。そして,個人を取り巻く対人関係の構造の分析,それから知覚されたソーシャル・サポートと実存的意識の分析をより詳細に行うために行った多変量解析の結果から,実存的視点でのサポートの認識は,どの対人関係においても同一のものではなく,サポートが知覚される対人関係にそれぞれ存在する固有のサポート内容の中から,有効なサポートを選択的に知覚し,実存的意識の増進にそのサポートを利用していると考えた。また,内的特性である実存的意識が,自覚される精神的健康に直接的に関係していることが検討された。つまり,個人を取り巻く対人関係から知覚されたソーシャル・サポートが,直接的に実存的意識の認識へ,また間接的に精神的健康に影響力を及ぼしている状況が示されたのではないかと考えられる。This study examined the influence of perceived social support on mental health, through the concept of purpose in life which leads to the existential aspect. University students (N=250) completed a social support questionnaire, GHQ and PIL as measures of mental health and purpose in life. Correlation analysis between scores of GHQ and PIL showed positive results. As the existential aspect was stronger, mental health also improved. Factor analyses were conducted on responses to 12 social support scales by 10 support sources, and produced 2 or 3 factors. Results of regression analysis indicated that social support factors from families and friends were related to the existential aspect. These results suggest that social sup port from particular persons can improve the existential aspect, and conse-quently it can also improve mental health

Phenotypic drug screen uncovers the metabolic GCH1/BH4 pathway as key regulator of EGFR/KRAS-mediated neuropathic pain and lung cancer

Increased tetrahydrobiopterin (BH4) generated in injured sensory neurons contributes to increased pain sensitivity and its persistence. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the de novo BH4 synthetic pathway, and human single-nucleotide polymorphism studies, together with mouse genetic modeling, have demonstrated that decreased GCH1 leads to both reduced BH4 and pain. However, little is known about the regulation of Gch1 expression upon nerve injury and whether this could be modulated as an analgesic therapeutic intervention. We performed a phenotypic screen using about 1000 bioactive compounds, many of which are target-annotated FDA-approved drugs, for their effect on regulating Gch1 expression in rodent injured dorsal root ganglion neurons. From this approach, we uncovered relevant pathways that regulate Gch1 expression in sensory neurons. We report that EGFR/KRAS signaling triggers increased Gch1 expression and contributes to neuropathic pain; conversely, inhibiting EGFR suppressed GCH1 and BH4 and exerted analgesic effects, suggesting a molecular link between EGFR/KRAS and pain perception. We also show that GCH1/BH4 acts downstream of KRAS to drive lung cancer, identifying a potentially druggable pathway. Our screen shows that pharmacologic modulation of GCH1 expression and BH4 could be used to develop pharmacological treatments to alleviate pain and identified a critical role for EGFR-regulated GCH1/BH4 expression in neuropathic pain and cancer in rodents

Social entrepreneurship: problems and ways of their solution

For modern constantly developing societies, it is normal to create categories in the process of the activity of the participants of socio-economic processes themselves. Practice is theoretical, and theory is pragmatic, because it creates those concepts in which «practice» exists and develops. Such a category is "social entrepreneurship", which is "umbrella" for a number of socio-economic phenomena. The general term for social entrepreneurship includes those types of entrepreneurial activity that contradict the traditional notion of entrepreneurship as an activity of independent economic entities aimed at maximizing their profits. The development of social entrepreneurship is an indicator of the quality of the business climate in the region and requires a set of measures to ensure the mechanism and access of non-governmental organizations to the provision of services in the social sphere, the provision of state support to socially-oriented non-profit organizations, and the promotion of the development of PPP practices in the social sphere

Anti-inflammatory effects of a novel non-antibiotic macrolide, EM900, on mucus secretion of airway epithelium.

Objective:Low-dose, long-term use of 14-membered macrolides is effective for treatment of patients with chronic airway inflammation such as diffuse panbronchiolitis or chronic rhinosinusitis. However, long-term use of macrolides can promote the growth of drug-resistant bacteria, and the development of anti-inflammatory macrolides that lack antibiotic effects is desirable. Previously, we developed EM900, a novel 12-membered erythromycin A derivative, which has potent anti-inflammatory and immunomodulatory activities and lacks any antibacterial activity. We examined the anti-inflammatory effects of EM900 on mucus secretion from airway epithelial cells.Methods:To examine the in vivo effects of EM900 on airway inflammation, we induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium via intranasal instillation of lipopolysaccharides. In vitro effects of EM900 on airway epithelial cells were examined using cultured human airway epithelial (NCI-H292) cells. Mucus secretion was evaluated via enzyme-linked immunosorbent assays with an anti-MUC5AC monoclonal antibody.Results:Oral administration of EM900 or clarithromycin (CAM) significantly inhibited LPS-induced mucus production from rat nasal epithelium. EM900, CAM, or erythromycin significantly inhibited MUC5AC secretion induced by tumor necrosis factor-α from NCI-H292 cells. MUC5AC mRNA expression was also significantly lower in EM900-treated cells.Conclusion:These results indicated that a novel non-antibiotic macrolide, EM900 exerted direct inhibitory effects on mucus secretion from airway epithelial cells, and that it may have the potential to become a new anti-inflammatory drug for the treatment of chronic rhinosinusitis