受精鶏卵を用いたヒト骨軟部悪性腫瘍の転移巣に対する抗がん剤感受性試験

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1094号, 学位授与年月日：平成5年6月30日,学位授与年：199

A novel technique of percutaneous intraluminal cracking using a puncture needle for severe calcified lesions of below-the-knee and below-the-ankle arteries

PURPOSEEndovascular therapy has recently become acceptable for the reconstruction of below-the-knee (BTK) and below-the-ankle (BTA) arterial lesions. However, we have sometimes experienced BTK or BTA lesions with calcifications that are too severe for balloon catheters to cross or expand despite successful guidewire passage. In this study, we assessed the feasibility and safety of the novel inner PIERCE technique for breaking down the calcium burden of BTK and BTA arterial lesions.METHODSWe retrospectively reviewed the records of patients who had undergone endovascular therapy between August 2018 and December 2019. The inner PIERCE technique was performed in those cases where low-profile balloon catheters were unable to pass through the target lesions or balloon indentation did not disappear beyond the rated burst pressure. An externalized guidewire system was established in 8 cases via bidirectional approaches, and a 20-gauge needle was directly inserted through the guidewires from the distal puncture site. In 10 cases of successful antegrade wiring, the tibial or pedal arteries distal to the lesion site were punctured for a retrograde guidewire approach to the lesion. The needle was slowly rotated and advanced across the lesion.RESULTSWe found that all lesions were severely calcified and 83.3% had chronic total occlusion. The inner PIERCE procedure allowed successful passage of the needle and subsequent low-profile balloon catheters in all cases. Optimal balloon dilatation was achieved in 94.4% of the cases using this technique. No procedure-related adverse events were observed.CONCLUSIONThe novel inner PIERCE technique is a safe and feasible method for disrupting calcified BTK and BTA lesions

チカク サレタ ソーシャル サポート ノ ブンセキテキ ケンキュウ

個々の内的特性の一つである充足感,満足感,達成感といった実存性も,ソーシャル・サポートの媒介要因の一つとして個人の精神的健康に作用する。このような考えに基づいて,本研究では,知覚されたソーシャル・サポートと精神的健康の因果影響関係について,実存的意識を媒介要因として検討することを目的とした。そして,個人を取り巻く対人関係の構造の分析,それから知覚されたソーシャル・サポートと実存的意識の分析をより詳細に行うために行った多変量解析の結果から,実存的視点でのサポートの認識は,どの対人関係においても同一のものではなく,サポートが知覚される対人関係にそれぞれ存在する固有のサポート内容の中から,有効なサポートを選択的に知覚し,実存的意識の増進にそのサポートを利用していると考えた。また,内的特性である実存的意識が,自覚される精神的健康に直接的に関係していることが検討された。つまり,個人を取り巻く対人関係から知覚されたソーシャル・サポートが,直接的に実存的意識の認識へ,また間接的に精神的健康に影響力を及ぼしている状況が示されたのではないかと考えられる。This study examined the influence of perceived social support on mental health, through the concept of purpose in life which leads to the existential aspect. University students (N=250) completed a social support questionnaire, GHQ and PIL as measures of mental health and purpose in life. Correlation analysis between scores of GHQ and PIL showed positive results. As the existential aspect was stronger, mental health also improved. Factor analyses were conducted on responses to 12 social support scales by 10 support sources, and produced 2 or 3 factors. Results of regression analysis indicated that social support factors from families and friends were related to the existential aspect. These results suggest that social sup port from particular persons can improve the existential aspect, and conse-quently it can also improve mental health

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

Voxel based analysis of surgical revascularization for moyamoya disease: Pre- and postoperative SPECT studies

Moyamoya disease (MMD) is a chronic, progressive, cerebrovascular occlusive disease that causes abnormal enlargement of collateral pathways (moyamoya vessels) in the region of the basal ganglia and thalamus. Cerebral revascularization procedures remain the preferred treatment for patients with MMD, improving the compromised cerebral blood flow (CBF). However, voxel based analysis (VBA) of revascularization surgery for MMD based on data from pre- and postoperative data has not been established. The latest algorithm called as Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) has been introduced for VBA as the function of statistical parametric mapping (SPM8), and improved registration has been achieved by SPM8 with DARTEL. In this study, VBA was conducted to evaluate pre- and postoperative single photon emission computed tomography (SPECT) images for MMD by SPM8 with DARTEL algorithm, and the results were compared with those from SPM8 without DARTEL (a conventional method). Thirtytwo patients with MMD who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery as the first surgery were included and all patients underwent pre- and postoperative 3D T1-weighted imaging and SPECT. Pre- and postoperative SPECT images were registered to 3D T1-weighted images, then VBA was conducted. Postoperative SPECT showed more statistically increased CBF areas in the bypassed side cerebral hemisphere by using SPM8 with DARTEL (58, 989 voxels; P<0.001), and increased ratio of CBF after operation was less than 15%. Meanwhile, postoperative SPECT showed less CBF increased areas by SPM8 without DARTEL. In conclusion, VBA was conducted for patients with MMD, and SPM8 with DARTEL revealed that postoperative SPECT showed statistically significant CBF increases over a relatively large area and with at most 15% increase ratio