IgA腎症における扁桃腺摘出+ステロイドパルス療法が腎予後に与える影響：多施設コホート研究

筑波大学 (University of Tsukuba)201

A Case of Rapidly Progressive Diabetic Nephropathy Induced by Osimertinib

The number of patients with diabetic nephropathy is increasing worldwide and it is important to understand the underlying pathological mechanisms of the disease. In early stage diabetic nephropathy, the hyperglycemic environment leads to vascular endothelial cell damage, resulting in overexpression of vascular endothelial growth factor (VEGF) in podocytes and renal pathology of glomerular hypertrophy, glomerular basement membrane thickening, and mesangial hyperplasia. In diabetic nephropathy, renal thrombotic microangiopathy (TMA) develops and the nephropathy progressively worsens in some cases of severe glomerular podocyte damage. Further, receptor tyrosine kinase inhibitors (RTKIs) may suppress VEGF secretion via VEGF receptor-2 tyrosine kinase inhibition in podocytes, which results in renal TMA and rapid deterioration of diabetic nephropathy. Osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR)-TKI, is approved as a first-line treatment agent for metastatic or locally advanced EGFR mutation-positive non-small cell lung cancer. We encountered a case of a patient with diabetic nephropathy with lung adenocarcinoma treated with osimertinib, whose condition deteriorated from early nephropathy to end-stage renal disease in approximately 4 months. The patient had early diabetic nephropathy, but the use of a RTKI suppressed VEGF expression in podocytes, resulting in the induction of renal TMA and the development of rapidly progressive diabetic nephropathy

大学教育の総合評価 : その4 在学生・卒業生・教職員による学生生活の評価の比較研究

Purpose In concluding a series of evaluative study of the student life at ICU, the present study compared responses to a questionnaire obtained from 3 groups: undergraduate students, almnus members, and faculty members and staffs. Specific aims of the study were as follows: (1) to find both common and different value orientations among the groups, (2) to analyze their conflicts produced from the gaps between their goals and their assessments of student life, (3) to diagnose psychological tensions among the groups and within the individuals, and (4) to explore the possibility of improving our educational activities. Method A questionnaire consisted of 121 items in 8 areas of student life (general impression, academic programs, extracurricular activities, university events, unique characteristics of ICU, facilities and equipments, cultural environment, and daily living) was distributed, and 197 undergraduate students, 133 alumni and 27 faculty members and staffs voluntarily responded. Responses for those items were obtained on 5 point scales, separately indicating how much they were important and how much they were fulfilled. Results and discussion General trends observed hereby were as follows: 1. Three groups showed very similar response patterns in all areas. 2. The sense of satisfaction fell short of the sense of importance in all areas by all groups; thus great degrees of dissatisfaction were manifested. 3. While the evaluation of importance were in the order of the faculty members and staffs, the alumni and the students, much higher satisfaction than others was shown by the alumni. Therefore, the faculty members and staffs manifested the most and the alumni the least dissatisfaction. 4. Assessments of the alumni were significantly lower than the other groups on those items representing the utility of higher education in general, but the faculty members and staffs evaluated the unique characteristics of ICU significantly higher than the others. Therefore, though the students appreciated secular values of higher education, they tended to ignore the goals and the uniqueness of ICU. The facts hitherto described imply enormous psychological dissents both between those who are in the campus at present and who have left, and between those who are teaching now and who are studing or have studied in the same campus. From the present study, we are able not only to reveal various problems involved in our student life, but also to gain some insights for the directions which we should pursuit our educational goals. Some of those inevitable questions we are confronted are mentioned as follows: 1. Methods to clarify our common value orientations. 2. Methods to practice the actualization of own values on campus. 3. Methods to perticipate in decision making. 4. Methods to enhance our communication. 5. Methods to deepen our understanding of group dynamism. 6. Methods to promote our community mental health. 7. Methods to establish longterm comprehensive evaluation programs

Value of adding the renal pathological score to the kidney failure risk equation in advanced diabetic nephropathy

金沢大学医薬保健研究域医学系Background There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD) is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD. Methods We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3–5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters) and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR) of incident ESRD were reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83). Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0–0.8%). Conclusions We found that the predict values of the KFRE and the D-score were not as good as reported, and combining the D-score with the KFRE did not significantly improve prediction of the risk of ESRD in advanced diabetic nephropathy. To improve prediction of renal prognosis for advanced diabetic nephropathy may require different approaches with combining clinical and pathological parameters that were not measured in the KFRE and the RPS DN Classification. © 2018 Yamanouchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

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

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target