Affinity-based screening of MDM2/MDMX-p53 interaction inhibitors by chemical array: Identification of novel peptidic inhibitors.

MDM2 and MDMX are oncoproteins that negatively regulate the activity and stability of the tumor suppressor protein p53. The inhibitors of protein-protein interactions (PPIs) of MDM2-p53 and MDMX-p53 represent potential anticancer agents. In this study, a novel approach for identifying MDM2-p53 and MDMX-p53 PPI inhibitor candidates by affinity-based screening using a chemical array has been established. A number of compounds from an in-house compound library, which were immobilized onto a chemical array, were screened for interaction with fluorescence-labeled MDM2 and MDMX proteins. The subsequent fluorescent polarization assay identified several compounds that inhibited MDM2-p53 and MDMX-p53 interactions

A Practical Study on School Volunteer Promotion Supports in cooperation with Student Staffs

　2013年10月よりスクールボランティアビューローに「学生スタッフ制度」を新たに設け，活動開始後2年が経過した。その間，学生スタッフと大学教職員が協働し，スクールボランティアフェアの開催，スクールボランティア活動事例集の作成・編集・発行と各教育委員会等への配布，スクールボランティアツアーの実施等様々な学生目線のスクールボランティア推進支援事業に取り組んできた。それぞれの事業では，学生スタッフが学生らしい工夫を随所に凝らしており，企画・準備から実施・反省に至るまで多大な尽力・努力をした。これらの活動を通して，スクールボランティア活動に参加しようと思っている学生やなかなか一歩が踏み出せない学生に対する啓発活動として大変効果的な事業であったことは成果と言えるが，学生の参加減少や学生への周知の難しさ，また，学生スタッフのなり手不足や大学教職員からの学生への働きかけの重要性など課題も残っている

A New Support Program to Urge University Students to Participate in School Volunteer Activities

　教員養成における学校現場での実践的・体験的活動が昨今一層求められている。教育再生実行会議での提言 や中央教育審議会での報告でも，採用前の学生の学校現場でのボランティア活動を推奨している。こうした中， 2013 年度の岡山大学におけるスクールボランティア活動の登録者数が大幅に減少した。要因としては学校現場 でのインターンシップ活動が必修化された点が大きいが，インターンシップとボランティアの長短を学生は理解 し参加していく必要がある。こうした社会的要請や大学における課題などを踏まえ，スクールボランティアビュー ローに新たに「学生スタッフ制度」を設けた。学生の立場から，スクールボランティア活動を多面的に支援し， 関連事業の企画・参画・連携を学生と教職員が協働して実施するものである。最初の取り組みとして，2014 年4 月には「スクールボランティアフェア2014」を開催した

Interstitial pneumonia associated with MPO-ANCA: Clinicopathological features of nine patients

SummaryMyeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) is a well known marker for small vessel vasculitis. Recent reports have demonstrated that interstitial pneumonia (IP) may rarely be associated with serum MPO-ANCA. Yet, little is known about the histological features.We reviewed surgical lung biopsy from nine patients with IP of uncertain etiology with serum MPO-ANCA.There was a male predominance (6:3) with a median age of 62.1. Histologically, eight patients presented with a usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis, frequently accompanied by areas of nonspecific interstitial pneumonia (NSIP) pattern. One patient showed diffuse alveolar damage (DAD), and two patients showed mixture of UIP and DAD reflecting acute exacerbation of UIP. Microscopic honeycomb cysts were common, but fibroblastic foci were inconspicuous. The most frequent additional findings were small airway disease (9/9), and lymphoid follicles (7/9). Neither capillaritis nor vasculitis was seen in any of our cases. Three patients had microscopic hematuria, but none progressed to microscopic polyangiitis during the follow up. Mortality rate was 44% (median follow up 39.1 months).IP associated with MPO-ANCA showed characteristic histology dominated by UIP pattern. Vasculitis was not identified in our cohort, but small airways disease and lymphoid follicles were present in most cases. IP associated with MPO-ANCA may be a histologically distinctive disease from idiopathic pulmonary fibrosis. Mortality was relatively high and life threatening acute exacerbation may occur

Probable Noonan syndrome in a boy without PTPN11 mutation, manifesting unusual complications.

The definitive version is available at www.blackwell-synergy.co

The clinical significance of 5% change in vital capacity in patients with idiopathic pulmonary fibrosis: extended analysis of the pirfenidone trial

<p>Abstract</p> <p>Background</p> <p>Our phase III clinical trial of pirfenidone for patients with idiopathic pulmonary fibrosis (IPF) revealed the efficacy in reducing the decline of vital capacity (VC) and increasing the progression-free survival (PFS) time by pirfenidone. Recently, marginal decline in forced VC (FVC) has been reported to be associated with poor outcome in IPF. We sought to evaluate the efficacy of pirfenidone from the aspects of 5% change in VC.</p> <p>Methods</p> <p>Improvement ratings based on 5% change in absolute VC, i.e., "improved (VC ≥ 5% increase)", "stable (VC < 5% change)", and "worsened (VC ≥ 5% decrease)" at month 3, 6, 9 and 12 were compared between high-dose pirfenidone (1800 mg/day; n = 108) and placebo (n = 104) groups, and (high-dose and low-dose (1200 mg/day; n = 55)) pirfenidone (n = 163) and placebo groups. PFS times with defining the disease progression as death or a ≥ 5% decline in VC were also compared between high-dose pirfenidone and placebo groups, and low-dose pirfenidone and placebo groups. Furthermore, considering "worsened" and "non-worsened (improved and stable)" of the ratings at months 3 and 12 as "positive" and "negative", respectively, and the positive and negative predictive values of the ratings were calculated in each group.</p> <p>Results</p> <p>In the comparison of the improvement ratings, the statistically significant differences were clearly revealed at months 3, 6, 9, and 12 between pirfenidone and placebo groups. Risk reductions by pirfenidone to placebo were approximately 35% over the study period. In the comparison of the PFS times, statistically significant difference was also observed between pirfenidone and placebo groups. The positive/negative predictive values in placebo and pirfenidone groups were 86.1%/50.8% and 87.1%/71.7%, respectively. Further, the baseline characteristics of patients worsened at month 3 had generally severe impairment, and their clinical outcomes including mortality were also significantly worsened after 1 year.</p> <p>Conclusions</p> <p>The efficacy of pirfenidone in Japanese phase III trial was supported by the rating of 5% decline in VC, and the VC changes at month 3 may be used as a prognostic factor of IPF.</p> <p>Trial Registration</p> <p>This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13^th, 2005 (Registration Number: JAPICCTI-050121).</p

The relationship between physical signs of aging and social functioning in persons with Down syndrome in Japan

Background: In Japan, there have been no substantial studies of social function and physical aging in adults with Down syndrome. The aim of the present study was to examine social functions (movement, conversation, and daily living skills) and physical signs of aging in adults with Down syndrome in Japan, and to analyze the relationship between changes in social function and age.Methods: A cross-sectional survey of persons with Down syndrome who were 15 years of age or older (15-65 years old) was conducted. The survey was conducted in patients associations, institutes, group homes, and workplaces from July to December 2009. Primary caregivers, such as family members and institute staff, were asked to complete a questionnaire on the subjects’ living situation, movement ability, conversational skills, daily living skills, and 10 characteristics of physical aging at the time of the survey.Results: The total number of subjects was 315. Subjects’ movement ability, conversational ability, and daily living skills declined as a function of age. Canities (40.6%) were the most prevalent physical sign of aging, followed by missing teeth, hump back, and skin wrinkling. Further, physical aging was related to a decline in social functions (p < 0.001).Conclusion: The present study showed that adults with Down syndrome exhibit signs of physical aging earlier than do the general population, and that physical aging is associated with social functioning. Thus, the appearance of physical aging might indicate a decline in social functioning

Adenovirus vector-mediated assay system for hepatitis C virus replication

The efficient delivery of the hepatitis C virus (HCV) RNA subgenomic replicon into cells is useful for basic and pharmaceutical studies. The adenovirus (Ad) vector is a convenient and efficient tool for the transduction of foreign genes into cells in vitro and in vivo. However, an Ad vector expressing the HCV replicon has never been developed. In the present study, we developed Ad vector containing an RNA polymerase (pol) I-dependent expression cassette and a tetracycline-controllable RNA pol I-dependent expression system. We prepared a hybrid promoter from the tetracycline-responsive element and the RNA pol I promoter. Ad vector particles coding the hybrid promoter-driven HCV replicon could be amplified, and interferon, an inhibitor of HCV replication, reduced HCV replication in cells transduced with the Ad vector coding HCV replicon. This is the first report of the development of an Ad vector-mediated HCV replicon system