Autologous fibrin-coated small-caliber vascular prostheses improve antithrombogenicity by reducing immunologic response

ObjectiveWe have recently developed a thrombin-free fibrin-coated vascular prosthesis that has a high performance rate in producing graft antithrombogenicity. We hypothesized that autologous, compared with xenologous, fibrin coatings could improve the antithrombogenicity of grafts by reducing immunologic response.MethodsAutologous fibrin-coated vascular prostheses and/or xenologous fibrin-coated vascular prostheses (internal diameter, 2 mm; length, 2.5 cm) were implanted in the bilateral carotid arteries of 50 Japanese white rabbits. They were classified into 2 groups by the selection of grafts in the individual: group I (autologous fibrin-coated vascular prosthesis and xenologous fibrin-coated vascular prosthesis); and group II (group IIa: both autologous fibrin-coated vascular prostheses, or group IIx: both xenologous fibrin-coated vascular prostheses). During a maximum of 180 days after implantation, we evaluated the thrombotic, inflammatory, and immunologic responses associated with both types of graft.ResultsAll grafts were patent at each end point. In group I, both platelet deposition and anti-graft antibodies in autologous fibrin-coated vascular prostheses were significantly less than those in xenologous fibrin-coated vascular prostheses until postoperative day 30. At postoperative day 10, there were significantly fewer CD45-positive infiltrating cells in autologous fibrin-coated vascular prostheses, and intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and nuclear factor-kappa B expression in autologous fibrin-coated vascular prostheses were less than those in xenologous fibrin-coated vascular prostheses. The neointimal hyperplasia in autologous fibrin-coated vascular prostheses was significantly decreased at postoperative day 180. In group II, serial changes of serum levels of immunoglobulin M, immunoglobulin G, interleukin-1β, and tissue-type plasminogen activator/plasminogen activator inhibitor-1 ratio in autologous fibrin-coated vascular prostheses were significantly less than those in xenologous fibrin-coated vascular prostheses. In both grafts, platelet deposition significantly correlated with serum immunoglobulin G level and tissue-type plasminogen activator/plasminogen activator inhibitor-1 ratio.ConclusionThese findings suggest that autologous fibrin coating in thrombin-free fibrin-coated vascular prostheses improve antithrombogenicity by reducing immunologic response and have a potential for clinical use in hybrid small-caliber vascular grafts

浸潤および血管新生を通しての人肝細胞癌の進行におけるケラチン19分子の役割

BACKGROUND: Keratin (K) 19-positive hepatocellular carcinoma (HCC) is well known to have a higher malignant potential than K19-negative HCC: However, the molecular mechanisms involved in K19-mediated progression of HCC remain unclear. We attempted to clarify whether K19 directly affects cell survival and invasiveness in association with cellular senescence or epithelial-mesenchymal transition (EMT) in K19-positive HCC. METHODS: K19 expression was analysed in 136 HCC surgical specimens. The relationship of K19 with clinicopathological factors and survival was analysed. Further, the effect of K19 on cell proliferation, invasion, and angiogenesis was examined by silencing K19 in the human HCC cell lines, HepG2, HuH-7, and PLC/PRF/5. Finally, we investigated HCC invasion, proliferation, and angiogenesis using K19-positive HCC specimens. RESULTS: Analysis of HCC surgical specimens revealed that K19-positive HCC exhibited higher invasiveness, metastatic potential, and poorer prognosis. In vitro experiments using the human HCC cell lines revealed that K19 silencing suppressed cell growth by inducting apoptosis or upregulating p16 and p27, resulting in cellular senescence. In addition, transfection with K19 siRNA upregulated E-cadherin gene expression, significantly inhibited the invasive capacity of the cells, downregulated angiogenesis-related molecules such as vasohibin-1 (VASH1) and fibroblast growth factor 1 (FGFR1), and upregulated vasohibin-2 (VASH2). K19-positive HCC specimens exhibited a high MIB-1 labelling index, decreased E-cadherin expression, and high microvessel density around cancer foci. CONCLUSION: K19 directly promotes cancer cell survival, invasion, and angiogenesis, resulting in HCC progression and poor clinical outcome. K19 may therefore be a novel drug target for the treatment of K19-positive HCC.博士（医学）・乙第1399号・平成29年3月15日© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Elderly infection in the community due to ST5/SCCmecII methicillin-resistant Staphylococcus aureus (the New York/Japan clone) in Japan: Panton–Valentine leukocidin-negative necrotizing pneumonia

An 89-year-old man suffered from and died of necrotizing pneumonia with rapid progression and cavity formation due to methicillin-resistant Staphylococcus aureus (MRSA). He was at no risk for hospital-acquired MRSA infection. His MRSA exhibited genotype ST5/spa2(t002)/agr2/SCCmecII/coagulaseII and was negative for Panton–Valentine leukocidin, indicating the New York/Japan clone (the predominant epidemic hospital-acquired MRSA clone in Japan). However, this strain expressed the cytolytic peptide (phenol-soluble modulin or δ-hemolysin) genes at high level, similar to USA300 (the most common community-acquired MRSA in the United States), indicating a variant of the New York/Japan clone with an important feature of community-acquired MRSA

〔研究ノート〕都市のオープンスペースの空間構成について（その1）2018年度広場・オープンスペース研究会活動報告

Based on knowledge obtained from research into open spaces for the past 30 years conducted both in Japan and overseas, the author (Kaneko) organized a research group consisting of students to further pursue this field of research. This study note reviews 37 domestic open spaces visited in academic year 2018 and introduces five samples in more detail including pictures and plans

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

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