Characteristics of Suppressor Macrophages Induced by Mycobacterial and Protozoal Infections in relation to Alternatively Activated M2 Macrophages

In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of certain types of suppressor macrophage populations. During the course of Mycobacterium tuberculosis (MTB) and Mycobacterium avium-intracellulare complex (MAC) infections, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This paper describes the immunological properties of M1- and M2-type macrophages generated in tumor-bearing animals and those generated in hosts with certain microbial infections. In addition, this paper highlights the immunological and molecular biological characteristics of suppressor macrophages generated in hosts with mycobacterial infections, especially MAC infection

Neural responses to syllable-induced P1m and social impairment in children with autism spectrum disorder and typically developing Peers

In previous magnetoencephalography (MEG) studies, children with autism spectrum disorder (ASD) have been shown to respond differently to speech stimuli than typically developing (TD) children. Quantitative evaluation of this difference in responsiveness may support early diagnosis and intervention for ASD. The objective of this research is to investigate the relationship between syllable-induced P1m and social impairment in children with ASD and TD children. We analyzed 49 children with ASD aged 40–92 months and age-matched 26 TD children. We evaluated their social impairment by means of the Social Responsiveness Scale (SRS) and their intelligence ability using the Kaufman Assessment Battery for Children (K-ABC). Multiple regression analysis with SRS score as the dependent variable and syllable-induced P1m latency or intensity and intelligence ability as explanatory variables revealed that SRS score was associated with syllable-induced P1m latency in the left hemisphere only in the TD group and not in the ASD group. A second finding was that increased leftward-lateralization of intensity was correlated with higher SRS scores only in the ASD group. These results provide valuable insights but also highlight the intricate nature of neural mechanisms and their relationship with autistic traits

Genetic analysis of TP53 in childhood myelodysplastic syndrome and juvenile myelomonocytic leukemia

信州大学博士（医学）・学位論文・平成23年3月31日授与（甲第886号)・齋藤章治ArticleLEUKEMIA RESEARCH. 35(12):1578-1584 (2011)journal articl

COPD 急性増悪後1 年間における再入院に関連する入院中の因子

研究論文Original Articles【目的】本研究の目的は，COPD 急性増悪患者を対象に，退院後1 年間の再入院に関連する因子を明らかにすることであった．【方法】対象は2014 年4 月から2016 年9 月にCOPD 急性増悪の診断で入院し，退院後1 年間の追跡が可能な46 例（平均年齢78.0 ± 8.0 歳）であった．退院後1 年間の再入院の有無で2 群に分け，入院時のデータを電子カルテより収集し，分析を行った．【結果】再入院群は15 例，非再入院群は31 例であった．2 群間の比較では過去の増悪歴（60% vs 29%,p=0.04）に有意差があり，理学療法開始までの日数（5.0 ± 3.0 日vs 3.4 ± 1.7 日，p=0.07）は有意差がなかった．多重ロジスティック回帰分析の結果，過去の増悪歴（OR：4.45，95%CI：1.09-18.2）と理学療法開始までの日数（OR：1.41，95%CI：1.03-1.93）が退院後1 年間の再入院と関連していた．【結論】本研究の結果，急性増悪後の理学療法介入開始の遅延は，退院後1 年間の再入院リスクを増加させる可能性が示唆された．急性増悪後早期の理学療法介入は，再入院の予防に有効である可能性がある．Purpose　The purpose of this study was to clarify the factors related to readmission for one year after discharge in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease（ COPD）.Method　Among patients who were admitted with a diagnosis of acute exacerbation of COPD between April 2014 and September 2016, 46 patients （mean age 78.0 ± 8.0 years old） who could be followed-up for one year after discharge were evaluated. The subjects were divided into two groups based on whether or not they were re-hospitalized within one year after being discharged, and data from the time of the first admission was collected from their electronic medical records and analyzed.Result　15 patients were included in the readmission group and 31 patients in the non-readmission group. There was a significant difference in previous history of exacerbations （60% vs. 29%, p = 0.04） between the two groups, and a borderline difference in the number of days to commencement of physical therapy （5.0 ± 3.0 days vs. 3.4 ± 1.7, p = 0.07）. Multiple logistic regression analysis revealed that previous history of exacerbations（ OR: 4.45, 95% CI: 1.09 - 18.2） and the number of days to commencing physical therapy （OR: 1.41, 95% CI: 1.03 - 1.93） were related to readmission rate.Conclusion　The findings of this study suggest that a delay in the start of physical therapy after acute exacerbation of COPD might increase the risk of readmission for one year after discharge of the patient from the hospital. Early physical therapy intervention after acute exacerbation of COPD might be effective in preventing readmission due to further exacerbations

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

六甲山系の自然と地域特性を活かした高大連携授業に関する研究/総合学習の時間を利用したデザインカリキュラム

本研究は、文部科学省における「高等学校と大学との接続における一人一人の能力を伸ばすための連携（高大連携）の在り方について」の指針に基づいて、本校の位置する六甲山系の自然と地域の特性を活かした高大連携授業の在り方について、実践的活動を通して実地検証していくことを目的とした。　総合学習に於いて実施した科目は以下の通りである。講座①：神戸鈴蘭台高校を「計測」する（長濱・宮本）講座②：使いやすい減災グッズ制作（見寺・野口・ばんば）講座③：自然素材を用いた雑貨制作（大田・相澤・佐野・田頭）講座④：テクノ工作（相良・古賀・逸身・向井・見明）講座⑤：高大連携授業のドキュメンテーションと情報発信（曽和）。　本研究の結果、以下の成果を得た。①高等学校における総合学習に組み入れることにより、年間を通じたプロジェクトを推進するカリキュラムを作成することができた。②文部科学省における「高校生に対して、大学レベルの教育研究に触れる機会の促進」をデザイン教育の視点から取り組むことができた。③地域の特性を活用することで、高大連携を主軸とした、地域のデザイン教育活動の活性化を図ることが可能となった。This research had the purpose of verifying integrated study in high school by making use of regional and natural assets of Mt.Rokko through the activities with high school, based on “Cooperation in order to extend the person\u27s ability in connection with the high school and university” by Ministry of education.The subject of integrated study was;(1)“Measurement” of Kobe Suzurandai High School: NAGAHAMA and MIYAMOTO.(2)Making of useful disaster mitigation goods: MITERA, NOGUCHI and BAMBA.(3)Production of living goods used by natural material: OOTA, AIZAWA, SANO and TAGASHIRA.(4)Craft and Computer Programming: SAGARA, KOGA, ITSUMI, MUKAI and MIAKE.We had the results as follows; (1) We could make the curriculum for a year by based on including the integrated study. (2) We could provide the design subject based on the guideline of Ministry of Education. (3) We could activate the design education using by the character of region

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

Bedside Teaching in Rural Family Medicine Education in Japan

Bedside teaching is essential in family medicine education so that residents may learn about various clinical conditions and develop professional skills. In particular, bedside teaching is useful in a rural context because rural family medicine deals with a broad scope of biopsychosocial problems among older patients. Accordingly, based on an inductive thematic analysis, we propose a framework for bedside teaching in rural family medicine education, which consists of four themes: accommodation of different learners, near-peer learning, the change in engagement of medical teachers in bedside teaching, and driving interpersonal collaboration. Bedside teaching can promote interactions between different medical learners. Near-peer learning in bedside teaching compensates for the limited availability of educators and improves learners’ motivation for self-directed learning. Through bedside teaching, medical learners can observe each other and provide constructive feedback, thereby improving their relationships and learning. For effective bedside teaching, medical educators should facilitate learners and collaborate with other medical professionals. Additionally, bedside teaching should accommodate a variety of learners, facilitate near-peer and self-directed learning, educators’ involvement based on cognitive apprenticeship, along with interprofessional collaboration with nurses. Interprofessional collaboration between rural family medicine teachers, learners, and nurses may improve the quality of patient care due to the increased understanding between patients and other medical staff in hospitals

Associations between Perception of Help-Seeking Behaviors and Quality of Life among Older People in Rural Communities: A Cross-Sectional Study

Older people’s help-seeking behaviors (HSBs) may be limited because of various factors and are essential in improving healthcare in aging societies. This cross-sectional study investigated the association between perception of HSBs, concrete HSBs, quality of life (QOL), and other variables among people over 65 in rural Japan using standardized questionnaires. Participants were divided into high or low health status index score groups based on a median split. Logistic regression was used to assess the association between perception of HSBs and high QOL while controlling for age, sex, living conditions, annual health checks, having chronic diseases, regular clinic visits, smoking, habitual alcohol consumption, education, living conditions, social support, social capital, socioeconomic status (SES), and health literacy. Participants in the high QOL group were younger (p < 0.001), and had fewer chronic diseases and regular clinic visits than those in the low QOL group (p < 0.001). The multivariate logistic regression model revealed that age, chronic diseases, tobacco usage, family consultation, and consulting primary care physicians negatively predicted QOL. High SES, social capital and support, and HSB intention positively predicted QOL. Self-efficacy and intention regarding HSBs should be investigated to improve health among older rural people