The Results of a New Distal Protection Method in Intervention for Chronic Total Occlusion of the Superficial Femoral Artery

Aims. To determine the efficacy of a new distal protection method in SFA CTO interventions. Methods and Results. From June 2003 to February 2009, ninety-two consecutive, chronic total occlusions of superficial femoral arteries were treated with catheter-based intervention using a bidirectional approach. Nine of these cases were managed with our original, distal protection method, based on symptoms, angiographic images, wire resistance, and intravascular ultrasound images. The average age was 73 years; eight patients were male. The mean occlusion length was 17.1 cm. A distal protection balloon was inserted from the retrograde sheath in the popliteal artery and placed distal to the occluded lesion after successful wire crossing. Lesion dilatation with a balloon was performed antegradely and debris was removed by 6Fr. guiding catheter. Debris was retrieved from all lesions, consisting mainly of thrombus. Where we decided not to use the distal protection method, there was no distal thromboembolism. Conclusion. In SFA-CTO intervention, the risk of distal embolization is 10%, which can be anticipated and eliminated by the distal protection method

Przezskórna ablacja opornego na farmakologiczne leczenie ustawicznego migotania komór w przebiegu ostrego incydentu wieńcowego

Mężczyznę w wieku 77 lat przyjęto do szpitala z powodu ostrego incydentu wieńcowego, ciężkiej niewydolności serca oraz nawracających epizodów migotania komór. Pojedyncze przedwczesne skurcze komorowe wywoływały częstoskurcz komorowy, który powtarzalnie przechodził w migotanie komór. W wyniku zastosowania ablacji tylno-przegrodowej części lewej komory, gdzie poprzednio rejestrowano podwójne potencjały pochodzące z włókien Purkinjego, wyeliminowano dodatkowe przedwczesne skurcze komorowe. Po zabiegu ustąpiły objawy „burzy elektrycznej” serca, a podczas wykonywanej po ablacji programowanej stymulacji komór nie wywołano żadnej tachyarytmii. Dodatkowe przedwczesne skurcze komorowe stały się mechanizmem wyzwalającym, a zarazem również substratem dla powstania częstoskurczu komorowego oraz migotania komór w przebiegu ostrego incydentu wieńcowego współistniejącego z niewydolnością serca. (Folia Cardiologica Excerpta 2006; 1: 492-496

Whole-exome sequencing analysis of supernumerary teeth occurrence in Japanese individuals

A common disorder of human dentition is the existence of supernumerary teeth. Impacted supernumerary teeth occur most frequently in the maxillary incisor area and are termed mesiodens. We conducted whole-exome sequencing of non-syndromic Japanese individuals possessing supernumerary teeth to identify genes and/or loci involved in the pathogenesis of the condition

SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression

臓器チップ技術を用いて新型コロナウイルスが血管へ侵入するメカニズムを解明 --Claudin-5発現抑制による呼吸器の血管内皮バリア破壊--. 京都大学プレスリリース. 2022-09-22.A study using an organ-on-a-chip reveals a mechanism of SARS-CoV-2 invasion into blood vessels --Disruption of vascular endothelial barrier in respiratory organs by decreasing Claudin-5 expression--. 京都大学プレスリリース. 2022-09-27.In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin–mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2–induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2–induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19

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