ミスマッチ修復遺伝子発現欠損を伴う子宮体癌のMRI所見と臨床像

Purpose: The purpose of this study was to identify the magnetic resonance imaging (MRI) features of uterine endometrial carcinoma (EC) with DNA mismatch repair (MMR) deficiency. Materials and methods: This was a retrospective study approved by our institutional review board. The study included 118 patients pathologically diagnosed as having EC in our institution from April 2014 to December 2016. Of 118 patients, 8 were excluded because of insufficient data. Immunohistochemical analysis of MMR was performed retrospectively to observe the expressions of MLH1, MSH2, MSH6, and PMS2. A tumor with MMR deficiency was detected in 17 of 110 cases (15%). Clinical background characteristics and MRI findings were reviewed. These findings were compared between MMR deficiency group and the other group as a control group. Statistical significance was determined using the Fisher's exact test and the Mann-Whitney U test, as appropriate. Results: The clinical background characteristics of patients with EC with MMR deficiency were not significantly different from those of other patients. On MRI, the tumor was significantly more often located in the lower uterine site (MMR(-) vs. MMR(+): 29.4 vs. 8.9% [p = 0.0366]). Conclusion: EC with MMR deficiency tends to be located lower in the uterus, though most other findings were not significantly different from those of EC without MMR deficiency.博士（医学）・甲第749号・令和2年6月30日© Japan Radiological Society 2018© 2018 Springer Nature Switzerland AG. Part of Springer Nature.This is a post-peer-review, pre-copyedit version of an article published in Japanese journal of radiology. The final authenticated version is available online at: http://doi.org/10.1007/s11604-018-0741-4

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

Relationship between suicidal ideation and family problems among young callers to the Japanese crisis hotline.

Previous studies have reported an association between family relationships and suicidal behavior, and found that people with high suicidal ideation are not likely to consult with others about their distress. An effective consulting service is therefore necessary for such individuals. Crisis hotlines are effective for reducing suicide risk, but their associated suicide ideation rate and odds ratio of family problems children remain unclear. The present study investigated the suicidal ideation rate and odds ratio of callers under 20 years of age (N = 24,333) with family problems to the Japanese crisis hotline in 2012. There were 5,242 (21.5%), 18,061 (74.2%), and 1,030 (4.2%) calls related to family problems, other problems, and both, respectively. The suicidal ideation rate and odds ratio of callers with family problems were 2.2% and 0.426, respectively. This result suggested that callers with family problems have a significantly lower rate and odds ratio for suicidal ideation compared with others. However, some associations with a high suicide ideation rate were found for individual items among callers with family problems such as abuse (20.4%), family breakdown (16.1%), and domestic violence (10.6%). Further studies are needed to understand the suicidal ideation of callers with family problems and develop more effective preventive strategies

Relationship between suicidal ideation and family problems among young callers to the Japanese crisis hotline.

Previous studies have reported an association between family relationships and suicidal behavior, and found that people with high suicidal ideation are not likely to consult with others about their distress. An effective consulting service is therefore necessary for such individuals. Crisis hotlines are effective for reducing suicide risk, but their associated suicide ideation rate and odds ratio of family problems children remain unclear. The present study investigated the suicidal ideation rate and odds ratio of callers under 20 years of age (N = 24,333) with family problems to the Japanese crisis hotline in 2012. There were 5,242 (21.5%), 18,061 (74.2%), and 1,030 (4.2%) calls related to family problems, other problems, and both, respectively. The suicidal ideation rate and odds ratio of callers with family problems were 2.2% and 0.426, respectively. This result suggested that callers with family problems have a significantly lower rate and odds ratio for suicidal ideation compared with others. However, some associations with a high suicide ideation rate were found for individual items among callers with family problems such as abuse (20.4%), family breakdown (16.1%), and domestic violence (10.6%). Further studies are needed to understand the suicidal ideation of callers with family problems and develop more effective preventive strategies