福島県の女子高校生を対象としたキャリアメンタリングプログラムの実践 : 『ヤングアメリカンズワークショップ』を用いて

本研究の目的は，福島県の女子高校生を対象としたキャリアメンタリングプログラムの効果を検討することであった。プログラムは，ステップ1「ヤングアメリカンズ」，ステップ2「外国人留学生とのセッション」，ステップ3「社会人女性とのセッション」，ステップ4「キャリアプログラムの企画・実施」という4つのステップから構成されていた。4段階で実施したアンケートの得点を用いて， 一元配置分散分析を実施したところ， 「自信」「自己表現」「チームワーク」で有意差がみられ，いずれも得点が上昇していることが示された。また，各ステップ終了後の自由記述の回答のまとめから，各ステップの肯定的な効果及び各ステップのキャリアメンタリングの効果の違いについて示唆が得られた。現場への提言が述べられている。The purpose of the present study was to conduct a career mentoring program to high school student girls in Fukushima and explore the effect of its program. The program was consisted of 4 steps: (l) The Young Americans Workshop. (2) Session with students from abroad. (3) Session with working women, (4) Planning and conducting career program for their juniors. Using the date conducted at the end of each session. we conducted one-way ANOVA and found out that the scores of "confidence", "expression". "teamwork" significantly increased. Written feedback of the participants revealed the positive effects of each session and the difference effect of each session. The implication of this result was briefly discussed

Allogeneic stem cell transplantation for X-linked agammaglobulinemia using reduced intensity conditioning as a model of the reconstitution of humoral immunity

Abstract Background We herein report the first case of X-linked agammaglobulinemia (XLA) that underwent allogeneic stem cell transplantation using reduced intensity conditioning (RIC). We chronologically observed the reconstitution of humoral immunity in this case. Case presentation The patient was a 28-year-old Japanese male with XLA who previously had life-threatening infectious episodes and was referred for the possible indication of allogeneic stem cell transplantation. After a thorough discussion within specialists from different backgrounds, we decided to perform allogeneic peripheral stem cell transplantation from his HLA-identical elder brother. Due to the non-malignant nature of XLA, we selected RIC consisting of fludarabine, cyclophosphamide, anti-thymocyte globulin, and 3 Gy of total body irradiation. Neutrophil engraftment was achieved on day 11 with complete donor chimerism. No major complications, except for stage 1 skin graft-versus-host disease, were observed. The patient was discharged on day 75 and has been followed as an outpatient without any infectious episodes for more than 500 days. Conclusions Regarding immune reconstitution, CD19+ cells, IgA, and IgM, which were undetectable before allogeneic stem cell transplantation (allo-SCT), started to increase in number 10 days after allo-SCT and continued to increase for more than 1 year. Anti-B antibodies appeared as early as day 10. Total IgG levels decreased after the discontinuation of IgG replacement and spontaneously recovered after day 350. However, most anti-viral IgG titers, except EB virus-virus capsid antigen IgG, disappeared after the discontinuation of IgG replacement. A seasonal vaccination to influenza was performed on day 148, with neither anti-influenza type A nor type B being positive after the vaccination. The transient transfer of allergic immunity to orchard grass was observed. Similar Bruton’s tyrosine kinase (BTK) expression levels in monocytes and B-cells were observed between the patient and healthy control. B-cells in the peripheral blood (PB) of the patient on day 279 showed sufficient proliferation after a CD40L and IL-21 or CD40L and CpG stimulation. Effective immunoglobulin production and class switching were also observed after a CD40L and IL-21 or CpG stimulation. Signal joint kappa-deleting recombination excision circles (sjKRECs) became positive 16 days post-SCT, increased to 6300 copies/μg DNA at 42 days, and were maintained at a high level thereafter. The recovery of T-cell receptor excision circles (TRECs) was slow, but became detectable 1 year post-hematopoietic stem cell transplantation (HSCT)

Discovery of Potent Mcl-1/Bcl-xL Dual Inhibitors by Using a Hybridization Strategy Based on Structural Analysis of Target Proteins

Mcl-1 and Bcl-xL are crucial regulators of apoptosis, therefore dual inhibitors of both proteins could serve as promising new anticancer drugs. To design Mcl-1/Bcl-xL dual inhibitors, we performed structure-guided analyses of the corresponding selective Mcl-1 and Bcl-xL inhibitors. A cocrystal structure of a pyrazolo­[1,5-<i>a</i>]­pyridine derivative with Mcl-1 protein was successfully determined and revealed the protein–ligand binding mode. The key structure for Bcl-xL inhibition was further confirmed through the substructural analysis of ABT-263, a representative Bcl-xL/Bcl-2/Bcl-w inhibitor developed by Abbott Laboratories. On the basis of the structural data from this analysis, we designed hybrid compounds by tethering the Mcl-1 and Bcl-xL inhibitors together. The results of X-ray crystallographic analysis of hybrid compound <b>10</b> in complexes with both Mcl-1 and Bcl-xL demonstrated its binding mode with each protein. Following further optimization, compound <b>11</b> showed potent Mcl-1/Bcl-xL dual inhibitory activity (Mcl-1, IC₅₀ = 0.088 μM; and Bcl-xL, IC₅₀ = 0.0037 μM)