Transcriptional Regulation of ATP2C1 Gene by Sp1 and YY1 and Reduced Function of its Promoter in Hailey–Hailey Disease Keratinocytes

Hailey–Hailey disease (HHD) is a blistering skin disease caused by malfunction of the Ca2+-dependent ATPase, ATP2C1. In this study, key regulatory regions necessary for the expression of the gene encoding human ATP2C1 were investigated. The transient reporter assay demonstrated that region +21/+57 was necessary for activation of the ATP2C1 promoter, and the electrophoretic mobility shift assay demonstrated that the region was recognized by the transcription factors, Sp1 and YY1. In accordance with this result, when Sp1 or YY1 was overexpressed in keratinocytes, an obvious increase in ATP2C1 promoter activity was observed, which was in contrast with the case where a mutant promoter lacking the binding sites for Sp1 and YY1 was used as the reporter. Ca2+-stimulation signal increased nuclear Sp1 proteins and ATP2C1 mRNA levels in normal keratinocytes. In contrast, both these increases were suppressed in keratinocytes from HHD patients. These results indicate that Sp1 and YY1 transactivate the human ATP2C1 promoter via cis-enhancing elements and that incomplete upregulation of ATP2C1 transcription contributes to the keratinocyte-specific pathogenesis of HHD. This is a report describing the regulation of the expression of ATP2C1

Nursing Education for a Gender-equal Society* - The Situation of Male Student Nurses -

題目:男女共同参画社会における看護教育―男子看護学生の動向について― 1975年の国際婦人年以来,カイロ宣言でのリプロダクテイブヘルス/ライツ,北京宣言等次々に男女差別の撤回と女性の自立をめざした運動が推進されてきた｡この女性のエンパワーメント運動の中で,我が国は労働基準法,男女雇用機会均等法,育児休業法等の制定および改正を経て,1999年6月｢男女共同参画社会基本法｣の施行に至った｡以来,国を挙げて男女共同参画社会の構築に取組んでいる｡看護界にあっては昭和23年に制定された保健婦助産婦看護婦法における看護職者は女子とされ,男子には国家免許を得る正式な資格が無かった｡やがて,法の改正とともに男性看護職者の進出が可能となってきた｡しかし,半世紀を経て,なお男性看護職者の占める割合は低く,看護界における男女共同参画の現状は進んでいるとはいい難い｡男性看護職者養成の沿革と現状を概観し,その問題点と課題を検討することとした｡Until quite recently, Japanese women had very few opportunities to become financially independent. However, women's rights and independence have been gradually promoted since 1975, the International Women's Year. The 1994 Cairo Conference on Population emphasized women's reproductive rights. Such international movements resulted in the enactment of the 1985 Equal Employment Opportunity Law and the 1999 Law for a Gender-Equal Society in Japan. On the other hand, nursing education had been offered for women only until it became possible for men to become nurses in 1968, when the 1948 law on nursing profession was amended. Almost half a century has passed, but the percentage of male nurses is still limited. There is still much to be done for achieving equality between male nurses and female nurses. We will overview the history of nursing education and discuss the problems that male nurses face. *Low No.78 of 1999 was established to promote genuine eguality between woman and me

チイキ ホウカツ イリョウ ジッシュウ ノ ジュコウセイ ノ トクセイ ト ソノ キョウイク コウカ ニ カンスル ケンキュウ

全国的に地域枠入学者による医学部定員増加が行われている.それに伴い医学部では,より良い地域医療教育の導入が求められている.そこで本研究は,地域医療を目指す学生の特性を知るとともに地域医療教育の効果を学生の自己評価点とSOC (Sense of Coherence) 得点の地域教育導入前後比較により検討することを目的とした.調査対象は,獨協医科大学医学部第1学年おける地域包括医療実習受講生の16名( 男子9名,女子7名:平均年齢18.9±1.0歳) と非受講生の1年生98名( 男子66名,女子32名:平均年齢19.9±1.7歳) である.平成22 年7 月15 日に対象者全員に対して研究の説明を行い,文書による研究参加への同意を得た後,行動規範26項目の自己評価 (7 点満点) とSense of Coherence (SOC) 29 項目及び生活習慣に関する質問12 項目に回答する自記式アンケート調査を行った.さらに,平成22 年12 月11 日に,受講生のみを対象に7 月15 日に施行したものと同一のアンケート調査を行った.地域包括医療実習I 受講生は,非受講生に比較して,家族と同居しているもの,現在運動をしていないものが多かった.また,学習態度の自己評価点とSOC 処理可能感の得点が有意に高かった.地域包括医療実習I の実習前後の変化を検討したところ,生活態度の自己評価が終了時には有意に上昇していた.しかしSOC 把握可能感の得点が有意に低下していた.地域医療教育導入前後でほとんどの項目で大きな変化はなかったが,生活態度の行動変容に良い効果が得られた.また,把握可能感が低下していたため,面接などで適切な支援が必要である.The quotas of students who wish to be involved in communitymedicine have increased in medical schools in Japan.Accordingly, programs focused on community medicineare required in medical education. In this study weaimed to identify the characteristics of medical studentswho pursue community medicine. We also aimed to evaluatethe effects of the local community medical educationcourse for medical students by examining changes in thescores of self-evaluation of standards of conduct and in thescores of sense of coherence (SOC) before and after thecourse.Participants were 16 first-year students (9 men, 7 women;mean age, 18.9±1.0 years) at Dokkyo Medical Universitywho took the comprehensive community medicinepractice course( community medicine course students) and98 students (66 men, 32 women;mean age, 19.9±1.7years) who did not take the course( non-community medicinecourse students).Information on the study was provided on July 15, 2010,and written informed consent was obtained from all participants.A self-evaluation questionnaire comprising 26 itemsregarding standards of conduct, each to be rated on a seven-point scale, and a questionnaire comprising 29 items ofSOC and 12 items of lifestyle were used. Both questionnaireswere completed by all participants on July 15, 2010and by the community medicine course students on DecemberThe percentage of students who lived with their familiesand the percentage of students who did not regularly exerciseat the time of the questionnaire survey were higher inthe community medicine course students than in the noncommunitymedicine course students. In addition, the selfevaluationscore for attitude toward leaning and the SOCscore for sense of manageability were significantly higher inthe community medicine course students than in the noncommunitymedicine course students. In the communitymedicine course students, the self-evaluation score for attitudetoward life was significantly increased, while the SOCscore for sense of comprehensibility significantly decreasedby the end of the course.The comprehensive community medicine practice coursehad a positive effect on student attitude toward life, andpreferable behavioral modifications were observed, althoughscores for most items remained unchanged by the end ofthe course. Our findings revealed a decrease in sense ofcomprehensibility, indicating that appropriate student support,such as consultation, is necessary

PU.1 Suppresses Th2 Cytokine Expression via Silencing of GATA3 Transcription in Dendritic Cells.

The transcription factor PU.1 is predominantly expressed in dendritic cells (DCs) and is essential for DC differentiation. Although there are several reports that PU.1 positively regulates the expression of DC-specific genes, whether PU.1 also has a suppressive effect on DCs is largely unknown. Here we demonstrate that PU.1 suppresses the expression of Th2 cytokines including IL-13 and IL-5 in bone marrow-derived DCs (BMDCs), through repression of the expression of GATA3, which is a master regulator of Th2 differentiations. When PU.1 siRNA was introduced into BMDCs, LPS-induced expression of IL-13 and IL-5 was increased along with upregulation of the constitutive expression of GATA2 and GATA3. The additional introduction of GATA3 siRNA but not of GATA2 siRNA abrogated PU.1 siRNA-mediated upregulation of IL-13 and IL-5. A chromatin immunoprecipitation assay showed that PU.1 bound to Gata3 proximal promoter region, which is more dominant than the distal promoter in driving GATA3 transcription in DCs. The degree of histone acetylation at the Gata3 promoter was decreased in PU.1 siRNA-introduced DCs, suggesting the involvement of PU.1 in chromatin modification of the Gata3 promoter. Treatment with a histone deacetylase (HDAC) inhibitor, trichostatin A, increased the degree of histone H3 acetylation at the Gata3 promoter and induced the subsequent expression of GATA3. Experiments using HDAC inhibitors and siRNAs showed that HDAC3 suppressed GATA3 expression. The recruitment of HDAC3 to the Gata3 promoter was decreased by PU.1 knockdown. LPS-induced IL-13 expression was dramatically reduced in BMDCs generated from mice lacking the conserved GATA3 response element, termed CGRE, which is an essential site for the binding of GATA3 on the Il-13 promoter. The degree of H3K4me3 at CGRE was significantly increased in PU.1 siRNA-transfected stimulated DCs. Our results indicate that PU.1 plays pivotal roles in DC development and function, serving not only as a transcriptional activator but also as a repressor