高不安者におけるワーキングメモリ注意制御機構の調節異常

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 丹野 義彦, 東京大学教授 石垣 琢麿, 東京大学教授 中澤 公孝, 東京大学准教授 本吉 勇, 東京大学准教授 四本 裕子University of Tokyo(東京大学

Subpial Lipoma at the Conus Medullaris Level

We report a rare case of adult subpial spinal lipoma at the conus medullaris level. A 61-year-old man presented with lower back pain, numbness in his legs, difficulty walking and a sensation of residual urine. T1- and T2-weighted magnetic resonance imaging showed a well-demarcated hyperintense intradural tumor level with the lower part of the T12 vertebra. Laminectomy at the T12 level and partial removal of the tumor using ultrasonic aspiration were performed. Pathologically, the excised mass was composed of mature adipose tissue with no evidence of inflammatory cell invasion or malignancy. Symptoms other than numbness and hypoesthesia in the left leg were relieved postoperatively. This case report indicated that partial tumor removal and ultrasonic aspiration are useful methods for removing tumors with significant adhesion to the spinal cord

Impact of laparoscopic surgery on short‐term and long‐term outcomes in elderly obese patients with colon cancer

[Background] Laparoscopic surgery is reported to be useful in obese or elderly patients with colon cancer, who are at increased risk of postoperative complications because of comorbidities and physical decline. However, its usefulness is less clear in patients who are both elderly and obese and may be at high risk of complications. [Methods] Data for obese patients (body mass index ≥25) who underwent laparoscopic or open surgery for stage II or III colon cancer between January 2009 and December 2013 were collected by the Japan Society of Laparoscopic Colorectal Surgery. Surgical outcomes, postoperative complications, and relapse-free survival (RFS) were compared between patients who underwent open surgery and those who underwent laparoscopic surgery according to whether they were elderly (≥70 y) or nonelderly (<70 y). [Results] Data of 1549 patients (elderly, n = 598; nonelderly, n = 951) satisfied the selection criteria for analysis. Length of stay was shorter and surgical wound infection was less common in elderly obese patients who underwent laparoscopic surgery than in those underwent open surgery. There were no significant between-group differences in overall complications, anastomotic leakage, ileus/small bowel obstruction, or RFS. There were also no significant differences in RFS after laparoscopic surgery according to patient age. [Conclusion] Laparoscopic surgery is safe in elderly obese patients with colon cancer and does not worsen their prognosis. There was no significant difference in the effectiveness of laparoscopic surgery between obese patients who were elderly and those who were nonelderly

Surgical Outcomes of Posterior Short Segment Fixation for Thoracolumbar Burst Fractures: A Study of Patients Treated without Vertebroplasty

There is no widespread agreement regarding the treatment of thoracolumbar burst fractures. While performing posterior short segment fixation of thoracolumbar burst fractures, we evaluated therapeutic outcomes in patients treated with screw insertion into fractured vertebral bodies without vertebroplasty. We also investigated the limitations associated with the treatment of burst fractures when vertebroplasty is not performed. Twenty-one of 51 patients with thoracolumbar burst fractures who were treated surgically in Ohta Nishinouchi Hospital were evaluated in the present study. These patients underwent posterior short segment fixation with screw insertion into the fractured vertebral bodies (only pedicle screws were inserted one level above and one level below the fractured vertebral bodies) without vertebroplasty. Vertebral angles were measured before surgery, immediately after surgery, and at the final follow-up examination. Changes in vertebral angles were compared and analyzed. The mean vertebral angles before and after surgery and at the final follow-up examination were 15.4°, 6.6°, and 9.1°, respectively. The mean postoperative correction loss was 2.5°. The therapeutic outcomes of posterior short segment fixation with screw insertion into fractured vertebral bodies without vertebroplasty were generally favorable

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

European Ethnopharmaceuticals for Self-Medication in Japan: Review Experience of Vitis vinifera L., Folium Extract and Vitex agnus-castus L., Fructus Extract as OTC Drugs

Since the publication of “Application Guideline for Western Traditional Herbal Medicines as OTC Drugs” in 2007, only two European ethnopharmaceuticals, Vitis vinifera L., folium extract (Antistax) and Vitex agnus-castus L., fructus extract (Prefemin), have been approved as OTC drugs in Japan. In this review, we describe the current regulation of Western ethnopharmaceuticals in Japan, summarize our regulatory experiences and discuss the scientific and regulatory issues involved

The Effectiveness and Applicability of Compensatory Cognitive Training for Japanese Patients with Schizophrenia: A Pilot Study

Although cognitive remediation or training for schizophrenia has been developed, few studies on the subject have focused on Japanese patients. The aim of the present study was to examine the effectiveness and applicability of compensatory cognitive training (CCT) in Japanese patients with schizophrenia. Twenty-six participants diagnosed with schizophrenia were assigned to either the CCT plus treatment as usual group (n=13) or the treatment as usual alone group (n=13). CCT is a 12-session, manualized, group-based training that coaches compensatory strategies in four cognitive domains (prospective memory, attention, verbal memory, and executive functions). Cognitive, functional, and clinical symptom measures were implemented at baseline, after treatment, and at 3-month follow-up. Mixed design analyses of variance with group and time for each measure demonstrated that effects of CCT on verbal memory, processing speed, and social functioning at postintervention were significant, and the effects on processing speed were maintained at follow-up. Our study suggests that CCT has beneficial effects on cognitive performance, improving functional outcomes in Japanese patients with schizophrenia. Additionally, the high degrees of attendance rates and level of satisfaction rated by the CCT participants ensure the applicability of this methodology to this population