Indispensable roles of OX40L-derived signal and epistatic genetic effect in immune-mediated pathogenesis of spontaneous pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Pulmonary hypertension (PH) refers to a spectrum of diseases with elevated pulmonary artery pressure. Pulmonary arterial hypertension (PAH) is a disease category that clinically presents with severe PH and that is histopathologically characterized by the occlusion of pulmonary arterioles, medial muscular hypertrophy, and/or intimal fibrosis. PAH occurs with a secondary as well as a primary onset. Secondary PAH is known to be complicated with immunological disorders. The aim of the present study is to histopathologically and genetically characterize a new animal model of PAH and clarify the role of OX40 ligand in the pathogenesis of PAH.</p> <p>Results</p> <p>Spontaneous onset of PAH was stably identified in mice with immune abnormality because of overexpression of the tumor necrosis factor (TNF) family molecule OX40 ligand (OX40L). Histopathological and physical examinations revealed the onset of PAH-like disorders in the C57BL/6 (B6) strain of OX40L transgenic mice (B6.TgL). Comparative analysis performed using different strains of transgenic mice showed that this onset depends on the presence of OX40L in the B6 genetic background. Genetic analyses demonstrated a susceptibility locus of a B6 allele to this onset on chromosome 5. Immunological analyses revealed that the excessive OX40 signals in TgL mice attenuates expansion of regulatory T cells the B6 genetic background, suggesting an impact of the B6 genetic background on the differentiation of regulatory T cells.</p> <p>Conclusion</p> <p>Present findings suggest a role for the OX40L-derived immune response and epistatic genetic effect in immune-mediated pathogenesis of PAH.</p

Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E–deficient mice

Cyclophilin A promotes atherosclerosis in part by inducing reactive oxygen species and promoting endothelial cell apoptosis and macrophage recruitment into lesions

Evaluation of Tomographic Technique of Temporomandibular Joint using COMMCAT IS-2000^<TM> Imaging System

COMMCAT IS-2000^は顎顔面領域専用の断層エックス線撮影装置で,顎関節の矢状断および冠状断撮影の機能を有する。本装置の顎関節撮影における有用性をエックス線不透過性の鋼鉄製マーカーを付けた4個のヒト乾燥頭蓋骨を用いて検討した。スライス位置の正確性を調べるため下顎頭の表面中央にマーカーを固定し,マーカー直上,それより近心,遠心にそれぞれ1mm,2mm離れた計5点に対して矢状断撮影を行ったところ,スライス位置の誤差は±1mmの範囲内であった。写真の寸法精度を調べるため,下顎頭の実測値と断層写真上での寸法をデジタルキャリパーを用いて比較した。両者の差は前後径では平均0.43mm,近遠心径では平均0.52mmであった。断層軌道および断層厚さの違いが写真画質におよぼす影響を調べた。同一撮影条件下ではhypocycloidal軌道で1mmの断層厚さで撮影した場合,ぶれや周囲の構造物の写り込みが少ないため,最も写真画質が良好であることがわかった。以上の結果よりCOMMCAT IS-2000^はTMJの骨構造を画像化する上で有用な診断装置であることが示唆された。The COMMCAT IS-2000^ (Imaging Sciences International, Hatfield, PA, USA) is a tomographic machine for scanning the dentomaxillofacial region and is capable of imaging the sagittal and coronal sections of the temporomandibular joint (TMJ). The feasibility and accuracy of tomography for the TMJ were examined by use of the COMMCAT IS-2000^ and four dried human skulls with radiopaque steel markers. To assess the setting accuracy of the slice position, a steel marker was fixed at the center of the superior surface of the condyle, and images of five sagittal sections were taken, i.e., directly above the marker and 1 mm and 2 mm distance from it in both the medial and distal planes. The deviation of the slice position was found to be within ± 1 mm for all test subjects. To evaluate the dimensional accuracy of this method, the difference between the actual value and the graphically observed value with respect to the tomographic image of the condyle was examined using a digital caliper. The difference between values for the anteroposterior distance was 0.43 mm and that for the mediolateral distance was 0.52 mm. The effect of the difference in tomographic motion and slice thickness on the image quality was then evaluated. Under identical exposure conditions, hypocycloidal tube motion and the slice thickness of 1 mm produced the best image quality because blurring of the image and the degree of superimposition of the surrounding structures were minimal. These results suggest that the COMMCAT IS-2000^ is a high-quality diagnostic tool for visualizing the bone structure of the TMJ

コドモ ノ マナザシ ニ タツ ショウガイジ ホイク ノ アリヨウ ニツイテ

本稿では、障碍のある子どもに対し、一人ひとり人間としての尊厳や主体性が最大限尊重され、自己肯定感を醸成しうるかかわりや「支援」について、子どものまなざしに立つことから考えてみる。障碍は個人に内在するのではなく、社会（大人）との関係のなかで生起する。保育学者である津守や障碍当事者である東田の言葉、保育実践者である和仁や筆者のエピソード記録を紐解くことで、子どもと出会い、ともに動くなかで生起する関係性やかかわりのなかで子どもの内面を理解していくことの大切さについてその価値を新たにした。わからなさを抱えながらもわかろうと関わるなかで、互いにわかち合っていく保育の営みこそが、障碍のある子どものまなざしに立つ保育と言えるのではないだろうか。また、障碍のある子どもの保育・幼児教育において、インクルーシブな保育・幼児教育を実現していくために大切なのは、一人ひとりの違いを認め合うことであり、差異を学びの時とすることである