骨系統疾患の出生前診断を目的とするMDCTの逐次近似画像再構成法を用いた被曝低減 : 正常胎児標本を使用した予備的研究

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

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

Phenylpropanoid, Sapnol A, Lignan and Neolignan Sophorosides, Saposides A and B, Isolated from Canadian Sugar Maple Sap

One new phenolic compound, sapnol A (1), and two new aromatic sophorosides, named saposides A (2) and B (3) were isolated from sugar maple sap. In addition, seven known phenolic compounds 4–10 were isolated. These structures were determined on the basis of NMR experiments as well as chemical evidence. Furthermore, all the isolated compounds 1–10 were tested for antioxidative activity by the superoxide dismutase (SOD)-like assay

Pituitary Volumes and Functions in Children with Growth Hormone Deficiency: Volumetric Magnetic Resonance Findings

Purpose: The purpose of the study was to compare pituitary volumes calculated from magnetic resonance imaging (MRI) in patients with idiopathic growth hormone deficiency (GHD) without structural abnormalities in the pituitary gland with clinical and biochemical features.Methods: This study was designed as a retrospective review and the need for informed consent was waived. MRI of the head was performed for 39 male and 17 female patients ranging in age from 10 to 14 years. Pituitary volumes were calculated from sectional area and ellipsoid formula. Pituitary volumes were compared between boys and girls. Pituitary volumes were also compared with measurements of pituitary function, age, and standard deviation scores (SDS) for height.Results: Whole pituitary volumes in patients were 405.1 ± 150.6 mm3 for the male group and 348.6 ± 161.1 mm3 for the female group. No significant difference was identified between mean pituitary volumes of the female and male groups. A weak correlation was found between pituitary volume and height SDS for boys (Ï = 0.34, p = .03). For girls, a moderate correlation was identified between pituitary volume and FSH level (Ï = 0.67, p < .01).Conclusion: Pituitary volumes of GHD patients correlated with height SDS in boys and FSH levels in girls. Brain MRI can be used not only to rule out anatomical abnormalities of the pituitary gland in GHD patients, but also to assess pituitary functions in clinical settings

Health survey of numbness/pain and its associated factors in Kotohira, Japan.

We conducted a survey of adults in Kotohira, a town of about 10,000 people located in the Nakatado District of Kagawa Prefecture, Japan. The survey was distributed to 8184 individuals, and effective responses were received from 3863 persons (response rate, 47.2%) during the survey period. Results regarding numbness and pain showed numbness alone in 7.7%, pain alone in 7.2%, both numbness and pain in 6.0%, and neither numbness nor pain in 79.6%. Spine and spinal cord damage was reported present by 5.4%, and absent by 94.6%. Analysis using the Short-Form Health Survey questionnaire, with comparison between subjects reporting both numbness and pain in the extremities and subjects with either numbness or pain alone, showed lower scores for in Short-Form Health Survey subscales (physical functioning, role [physical, emotional], bodily pain, vitality, and mental health). Subjects with numbness alone generally reported no disability in daily life. In a secondary survey, analysis of neurological findings by specialists identified 6 cases of "pain following spinal cord damage" in which spinal cord-related pain developed in the hands or feet. This represented 0.15% of the survey population starting from the primary survey

Portal-Systemic Shunt between the Inferior Mesenteric Vein and Inferior Vena Cava in a Patient with Hepatic Encephalopathy : Successful Occlusion by Balloon-Occluded Retrograde Transvenous Obliteration

A large shunt between the inferior mesenteric vein (IMV) and the inferior vena cava (IVC) is a rare type of portosystemic shunt in patients with hepatic encephalopathy. We report a patient with hepatic encephalopathy due to a large IMV-IVC shunt who was successfully treated by balloon-occluded retrograde transvenous obliteration. The procedure involved a combination of 11 metallic coils and 5 ml of 5% ethanolamine oleate with iopamidol as the sclerosing agent. After complete obliteration of the shunt, his symptoms disappeared. At 2-years follow-up he was free of clinical symptoms, the size of his liver had slightly increased, and his liver function was preserved