Persistence of Cryoglobulinemia in Patients with Chronic Hepatitis C after Successful Treatment with Direct-acting Antivirals

Hepatitis C virus（HCV）infection can cause chronic liver disease; it has also been associated with lymphoproliferative disorders（LPDs）, such as cryoglobulinemia and B-cell non-Hodgkin’s lymphoma. Our previous studies suggested that cryoglobulinemia, high titer of rheumatoid factor（RF）, and hypocomplementemia are immunological markers of LPDs. In addition, recent therapies with direct-acting antivirals（DAAs）have achieved high rates of sustained virological response（SVR）in patients with chronic hepatitis C（CH-C）. This study analyzed the efficacy of DAA therapy in CH-C patients with cryoglobulinemia, and the association of biochemical and other immune markers for LPDs with persistence of cryoglobulinemia in patients after DAA therapy. Of 226 patients tested, 31（13.7％）had cryoglobulinemia prior to receiving DAAs, and these individuals showed lower complement 4 levels, decreased complement hemolytic activity, and higher IgM than patients without cryoglobulinemia. Of the 24 cryoglobulinemia-positive patients（83％）who could be followed for 24 weeks, 20 became cryoglobulinemia negative after the therapy. The remaining four patients retained the abnormal LPD markers, indicating the possibility of long-term LPD persistence even following successful eradication of HCV in CH-C patients. Thus, long-term follow-up is recommended to avoid exacerbation of extrahepatic manifestations as well as new events

パブリックスペースに関するフィールドワーク報告 : 居場所をつくるサイトリノベーション

This paper reports on various field works of Sugiura\u27s laboratory on renovation of public spaces. Our laboratory has carried out architectural studies and field works for joining together human beings and space. We transformed dead spaces into living spaces with "Installation" which is a sort of contemporary art. We show separate various projects comprehensively and explore our future potential possibilities for the renovation of public spaces

パブリックスペースに関するフィールドワーク報告 : 二子玉川におけるサイト・リノベーション

This paper reports on collaborative field works of Sugiura\u27s laboratory on renovation of public spaces in 2004. Our laboratory has carried out architectural studies and field works for joining human beings and space together. We aim at transforming dead spaces into living spaces with \u27installations\u27 which is a sort of contemporary art. We show how, in a puplic wood of Futakotamagawa, we built frames and covered them with boughs and leaves to make a tunnel so that people could pass through it or just relax sitting alongside the path when out rambling. During 16 days of this tentative installation, 1,954 people visited it. The restoration of the site brought the wood back to life for a while

パブリックスペースに関するフィールドワーク報告 : 新潟県十日町市におけるサイト・リノベーション

This series reports on collaborative field works of Sugiura\u27s laboratory on renovation of public spaces. The laboratory has carried out architectural studies and field works for joining human beings and space together. We aim at transforming dead spaces into living spaces with \u27installations\u27 which is a sort of contemporary art. This shows our artwork exhibited in \u27Echigo-Tsumari Art Triennial 2006\u27, held from July 23 through September 10 in Niigata prefecture. We used the very same site where we installed pieces of white netting at the prior festival in 2003. It was a creation of passages where eaves of some neighboring houses were connected with the white netting creating a cocoon for communication. But the site was damaged by the earthquake in 2004. Some houses were destroyed and an elderly resident killed. Naturally our work in 2006 had a consolatory meaning to both the dead and bereft people. The crochet work of 10,000 white motifs sewn together turned into white see-through walls in the air around which many people got together and renewed their souls

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