乳腺腺様嚢胞癌においてサイトケラチン5/6の腺腔形成細胞の染色性は類似病変との鑑別に有用である

Adenoid cystic carcinoma (AdCC) of the breast is an uncommon but distinct neoplasm composed of a dual cell population polarized around true glandular (luminal) spaces and pseudolumina. The aim of this study was to clarify whether various immunohistochemical markers (CK7, EMA, CD117, p63, calponin, CD10, S100, CK5/6, CK14, vimentin, and type IV collagen) can distinguish between the two cell types in classical AdCC (n = 14) and in collagenous spherulosis (n = 5). The sensitivity and specificity of these 11 markers to distinguish luminal from abluminal cells were evaluated using a curve created by plotting the true-positive rate (sensitivity) against the false-positive rate (1 - specificity) at threshold settings of 0, 10, 50, and 70 %. The most sensitive and specific markers for luminal cells in AdCC were CK7 and EMA; those for abluminal cells were type IV collagen, p63, and vimentin. CD10 and S100 did not act as abluminal markers in AdCC. CK5/6, one of the basal/myoepithelial markers, was expressed more frequently in luminal than in abluminal cells of AdCC. Thus, CK5/6 immunostaining resulted in a reverse expression pattern, analogous to what we recently documented in clear cells in mammary adenomyoepithelioma. In conclusion, compared with myoepithelial/abluminal cells of normal breast or collagenous spherulosis, the neoplastic abluminal cells of classical AdCC are characterized by enhanced vimentin and attenuated CD10 and S100. Furthermore, the luminal cells of AdCC show a unique aberrant staining pattern for CK5/6 that may aid in the differential diagnosis.博士（医学）・乙第1389号・平成28年11月24日© Springer-Verlag Berlin Heidelberg 2016The final publication is available at Springer via http://dx.doi.org/10.1007/s00428-016-1963-

Marmoset Serotonin 5-HT 1A Receptor Mapping with a Biased Agonist PET Probe 18 F-F13714: Comparison with an Antagonist Tracer 18 F-MPPF in Awake and Anesthetized States

International audienceBackgroundIn vivo mapping by positron emission tomography of the serotonin 1A receptors has been hindered by the lack of suitable agonist positron emission tomography probes. 18 F-labeled F13714 is a recently developed biased agonist positron emission tomography probe that preferentially targets subpopulations of serotonin 1A receptors in their " active state, " but its brain labeling pattern in nonhuman primate has not been described. In addition, a potential confound in the translatability of PET data between nonhuman animal and human arise from the use of anesthetics that may modify the binding profiles of target receptors. MethodsPositron emission tomography scans were conducted in a cohort of common marmosets (n = 4) using the serotonin 1A receptor biased agonist radiotracer, 18 F-F13714, compared with a well-characterized 18 F-labeled antagonist radiotracer, 18 F-MPPF. Experiments on each animal were performed under both consciousness and isoflurane-anesthesia conditions. Results18 F-F13714 binding distribution in marmosets by positron emission tomography differs markedly from that of the of the18F-MPPF. Whereas 18F-MPPF showed highest binding in hippocampus and amygdala, 18F-F13714 showed highest labeling in other regions, including insular and cingulate cortex, thalamus, raphe, caudate nucleus, and putamen. The binding potentialvalues of 18F-F13714 were about one-third of those observed with 18F-MPPF, with marked individual- and region-specificdifferences under isoflurane-anesthetized vs conscious conditions.ConclusionsThese findings highlight the importance of investigating the brain imaging of serotonin 1A receptors using agonist probes such as 18F-F13714, which may preferentially target subpopulations of serotonin 1A receptors in specific brain regions of nonhuman primate as a biased agonist

The trial of animal assisted education in kindergarten

本研究は, 動物介在療法の流れを汲む「動物介在教育」を通して「いのち」の大切さ, 他者への思いやり, 自然環境への配慮を教えることで, 肉体的にも精神的にも健康な子どもたちを育てることを目的とする。具体的には, 様々な分野の専門家が研究分担者・研究協力者として参加する「CoP-AAE: 動物介在教育のための実践コミュニティ」の構築を通して, 幼稚園で実践可能な「子どもたちのための心を育む動物介在教育プログラム」の開発に取り組む。 昨年度(平成21年度)は, 「動物介在教育実践コミュニティ」を立ち上げ, 「子どもに対する4つの動物介在教育の実践手法」に関する予備研究を, 広島大学大学院生物圏科学研究科の谷田研究室, 広島大学附属三原幼稚園, 広島大学附属幼稚園, 広島アニマルケア専門学校, 福山平成大学と共同で行った。本年度は, 昨年度と同様にCoP-AAEのメンバーと, 「自然体験を通した教育の実践と効果の検証」「動物の訪問による命の教育」「動物飼育・世話体験を通した共感教育」について共同研究を行ったのでその内容について簡潔に紹介する

A basic study on the development of young children's musical ability (1) :Focusing on young children's singing voice in unison singing.

本研究の目的は, 幼児が一斉歌唱活動を行う際に伴奏の有無, およびイヤホンで自分の声をモニターしながら歌うか否か, という異なる条件下で幼児個々の歌声がどのように変化するのかを明らかにすることである。その結果, 以下のことが明らかとなった。第1に, 正確な音高での歌唱は, イヤホンで自分の声をモニターすること, および伴奏による音高の補助があることの2つの要素によって導かれる。第2に, 正確な音高での歌唱に密接に関わるのは, 年少では自分の声をモニターする要素であり, 年中および年長では伴奏の要素である。第3に, G4以上の高い音域よりもG4未満の低い音域の方が正確な音高で歌唱できる。第4に, どなり声の生起は一斉歌唱時に自分の声が聞こえにくい状況においてその生起率は高くなる。しかし, 年長になると伴奏の有無やイヤホンの有無といった条件への依存度が低くなり, どのような条件下でも比較的一定して歌声に近いものとなる

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting