Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1

Prostaglandin E2 (PGE2) exerts its actions via four subtypes of the PGE receptor, EP1–4. We show that mice deficient in EP1 exhibited significantly attenuated Th1 response in contact hypersensitivity induced by dinitrofluorobenzene (DNFB). This phenotype was recapitulated in wild-type mice by administration of an EP1-selective antagonist during the sensitization phase, and by adoptive transfer of T cells from sensitized EP1−/− mice. Conversely, an EP1-selective agonist facilitated Th1 differentiation of naive T cells in vitro. Finally, CD11c+ cells containing the inducible form of PGE synthase increased in number in the draining lymph nodes after DNFB application. These results suggest that PGE2 produced by dendritic cells in the lymph nodes acts on EP1 in naive T cells to promote Th1 differentiation

Pharmacodynamic analysis of eribulin safety in breast cancer patients using real-world postmarketing surveillance data

Postmarketing surveillance is useful to collect safety data in real-world clinical settings. In this study, we applied postmarketing real-world data on a mechanistic model analysis for neutropenic profiles of eribulin in patients with recurrent or metastatic breast cancer. Demographic and safety data were collected using an active surveillance method from eribulin-treated recurrent or metastatic breast cancer patients. Changes in neutrophil counts over time were analyzed using a mechanistic pharmacodynamic model. Pathophysiological factors that might affect the severity of neutropenia were investigated, and neutropenic patterns were simulated for different treatment schedules. Clinical and laboratory data were collected from 401 patients (5199 neutrophil count measurements) who had not received granulocyte colony-stimulating factor and were eligible for pharmacodynamic analysis. The estimated mean parameters were as follows: mean transit time =\ua0104.5\ua0h, neutrophil proliferation rate constant =\ua00.0377\ua0h−1, neutrophil elimination rate constant =\ua00.0295\ua0h−1, and linear coefficient of drug effect =\ua00.0413\ua0mL/ng. Low serum albumin levels and low baseline neutrophil counts were associated with severe neutropenia. The probability of grade ≥3 neutropenia was predicted to be 69%, 27%, and 27% for patients on standard, biweekly, and triweekly treatment scenarios, respectively, based on virtual simulations using the developed pharmacodynamic model. In conclusion, this is the first application of postmarketing surveillance data to a model-based safety analysis. This analysis of safety data reflecting authentic clinical settings will provide useful information on the safe use and potential risk factors of eribulin

Sputum YKL-40 Levels and Pathophysiology of Asthma and Chronic Obstructive Pulmonary Disease.

Background: Recent evidence suggests that YKL-40, also called chitinase-3-like-1 protein, is involved in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Details of sputum YKL-40 in asthma and COPD, however, remain unknown. Objectives: To clarify associations of sputum YKL-40 levels with clinical indices in asthma and COPD. Methods: Thirty-nine patients with asthma, 14 age-matched never-smokers as controls, 45 patients with COPD, and 7 age-matched smokers as controls were recuited for this study. Sputum YKL-40 levels were measured and YKL-40 expression in sputum cells was evaluated by immunocytochemistry. Results: Sputum YKL-40 levels were higher in patients with COPD (346 ± 325 ng/ml) than in their smoker controls (125 ± 122 ng/ml; p < 0.05), but were not significantly different between patients with asthma (117 ± 170 ng/ml) and their controls (94 ± 44 ng/ml; p = 0.15). In patients with asthma only, sputum YKL-40 levels were positively correlated with disease severity (r = 0.34, p = 0.034) and negatively correlated with pre- and postbronchodilator %FEV(1) (r = -0.47 and -0.42, respectively; p < 0.01) and forced mid-expiratory flow (r = -0.48 and -0.46, respectively, p < 0.01). Sputum YKL-40 levels were positively correlated with sputum neutrophil counts in asthma (r = 0.55, p < 0.001) and with neutrophil and macrophage counts in COPD (r = 0.45 and 0.65, respectively, p < 0.01). YKL-40 was expressed in the cytoplasm of sputum neutrophils and macrophages in all groups. Conclusions: Elevated sputum YKL-40 reflects airflow obstruction in asthma whereas the roles of YKL-40 in the proximal airways in COPD remain to be elucidated

エンカク ニヨル ニホンゴ ジュギョウ カンサツ ト キョウドウ ガクシュウ ヲ トオシタ ニホンゴ キョウシ ヨウセイ ノ ココロミ

新型コロナウイルス感染症の流行により、教育現場ではオンライン対応が進んでいる。このような状況であっても学びの質を高めるべく、大阪大学日本語日本文化教育センター（CJLC）の遠隔オンライン授業見学システムを用い、CJLC、愛知県立大学、京都産業大学の合同による日本語授業観察と協働学習を実施した。本実践は、①観察課題設定、②遠隔オンライン授業見学、③オンライン合同ディスカッションの順で行った。そして、この実践をふまえ、①～③の各段階における学生の記述を分析し、彼らの気づきと学びの変化を考察した。③の記述では、複数の大学の協働学習を通して、異なる学習段階にある学生と日本語学習者が話し合い、複数の日本語教師の考えを聞くことで、学生は自身の捉え方にさまざまな視点を交差させ理解を深めていた。異なる学習段階にある、異なる視点を持つ学生との協働学習がオンライン授業見学という手段により可能となり、本実践の方法は日本語教育の多様性の理解を促す日本語教師養成の一手法として有効であると考えられる