Association of clinical findings in Yusho patients with serum concentrations of polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8-pentachlorodibenzofuran more than 30 years after the poisoning event

<p>Abstract</p> <p>Background</p> <p>The Yusho poisoning incident, which was caused by rice bran oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) generated by heat denaturation of PCB, occurred in 1968 in western Japan. Annual physical, dermatological, dental, ophthalmological and laboratory examinations were conducted for Yusho patients after the incident. From 2001, blood levels of individual PCDF congeners were also measured. The blood levels of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF), PCBs and PCQs in Yusho patients were found to be significantly higher than those of the general population. We investigated the relationships between blood concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in Yusho patients and the items measured in the annual medical examination.</p> <p>Methods</p> <p>Medical and laboratory examination data from 501 Yusho patients enrolled in the study from 2001 to 2004 were analyzed. The relationships between blood 2,3,4,7,8-PeCDF, PCB and PCQ concentrations and medical/laboratory examination data were investigated using principal components and logistic regression analyses.</p> <p>Results</p> <p>Serum Concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in blood tended to correlate with either acneform eruptions, black comedones, cutaneous and mucosal pigmentation, and hypersecretion of meibomian glands as well as general fatigue, headaches, cough/sputum, abdominal pain, arthralgia, increased blood sugar, increased serum γ-GTP and decreased total bilirubin. The majority of these signs and symptoms are included in the diagnostic criteria for Yusho.</p> <p>Conclusion</p> <p>After Yusho patients had suffered chronic exposure to these chlorinated compounds for more than 35 years, the serum concentration of 2,3,4,7,8-PeCDF in blood was significantly related to arthralgia and decreased albumin/globulin (A/G) ratio; the serum concentration of PCBs was significantly related to ophthalmologic symptoms; and the serum concentration of PCQ to increased total cholesterol. These findings suggest that the co-contaminants may affect other functions than those originally associated with Yusho.</p

Cutaneous symptoms such as acneform eruption and pigmentation are closely associated with blood levels of 2,3,4,7,8-penta-chlorodibenzofurans in Yusho patients, using data mining analysis

<p>Abstract</p> <p>Background</p> <p>Yusho an intoxication caused by oral dioxins and polychlorinated biphenyls occurred in 1968. Patients suffered from various systemic symptoms, including general fatigue, nausea, muscular and articular pain, acneform eruptions, black comedones, cutaneous and oral pigmentation, and increased eye discharge. The major causative factor was the contamination of rice oil with 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF). Recent technical advances have allowed us to measure blood levels of PeCDF. However, there is little information on which symptoms and laboratory data are directly associated with PeCDF levels.</p> <p>Methods</p> <p>Yusho patients underwent annual medical check-ups from 2001 to 2003. Blood PeCDF levels were correlated with the presence or absence of symptoms in medical, hematological, dermatological, dental and ophthalmological examinations. This study analyzed all combinations by using the association analysis. This is the most suitable method to evaluate all combinations of the data comprehensively. This method was used to determine the rate of patients with high PeCDF level in the population with each symptom, and to extract combinations of three symptoms which were strongly associated with high PeCDF level.</p> <p>Results and Conclusion</p> <p>The rate of the patients with high PeCDF level was high in populations with high uric acid, black comedones (face), second highest quartile of age, or high urea nitrogen. The combination of three symptoms associated with the highest rate of patients with high PeCDF level was "high uric acid, female sexuality, and history of acneform eruptions", followed by "history of Yusho in and after 1968, high cholesterol level, and subjective symptoms." This analysis newly suggested that PeCDF concentration may be associated with history of dermatological symptoms, high uric acid, and elevated erythrocyte sedimentation rate.</p

E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis

Chronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno) in liver fibrosis.The expression and localization of synoviolin in the liver were analyzed in CCl(4)-induced hepatic injury models and human cirrhosis tissues. The degree of liver fibrosis and the number of activated hepatic stellate cells (HSCs) was compared between wild type (wt) and Syno(+/-) mice in the chronic hepatic injury model. We compared the ratio of apoptosis in activated HSCs between wt and Syno(+/-) mice. We also analyzed the effect of synoviolin on collagen synthesis in the cell line from HSCs (LX-2) using siRNA-synoviolin and a mutant synoviolin in which E3 ligase activity was abolished. Furthermore, we compared collagen synthesis between wt and Syno(-/-) mice embryonic fibroblasts (MEF) using quantitative RT-PCR, western blotting, and collagen assay; then, we immunohistochemically analyzed the localization of collagen in Syno(-/-) MEF cells.In the hepatic injury model as well as in cirrhosis, synoviolin was upregulated in the activated HSCs, while Syno(+/-) mice developed significantly less liver fibrosis than in wt mice. The number of activated HSCs was decreased in Syno(+/-) mice, and some of these cells showed apoptosis. Furthermore, collagen expression in LX-2 cells was upregulated by synoviolin overexpression, while synoviolin knockdown led to reduced collagen expression. Moreover, in Syno(-/-) MEF cells, the amounts of intracellular and secreted mature collagen were significantly decreased, and procollagen was abnormally accumulated in the endoplasmic reticulum.Our findings demonstrate the importance of the E3 ubiquitin ligase synoviolin in liver fibrosis

聖隷クリストファー大学看護基礎教育におけるシミュレーション教育の実践

紀要委員会企画Special Articles　本報告では、聖隷クリストファー大学看護基礎教育におけるシミュレーション教育の実践環境の構築、各領域における実践、教育力向上の取り組み、そして課題も含め今後の展望を報告する。本学は米国サミュエルメリット大学と2013 年に大学間交流協定を締結して以来、学生や教員が毎年、研修に赴きシミュレーション教育について学んできた。2016年に看護学部の教員有志によるワーキンググループが結成し、2017 年度より看護学部諮問委員会としてシミュレーション教育委員会が発足した。本学では、看護学部を中心にアクティブラーニングを実践するひとつの手法としてシミュレーション教育を検討し環境構築、研修会など学習の機会の提供、シミュレーションルームの機材および備品管理、シミュレーション教育実施の支援、広報活動など推進してきた。今後、シミュレーション教育を遂行する上で、以下の課題と展望がある。1．教育環境のさらなる充実、2．人員の確保、3．地域の拠点としてのシミュレーション教育の推進、4．活動のための運営資金の獲得である

聖隷クリストファー大学看護基礎教育における2020年度シミュレーション教育の実践報告

紀要委員会企画Special Articles　本報告では、聖隷クリストファー大学看護基礎教育における2020 年度のシミュレーション教育委員会の活動報告および各領域における実践について、以下の内容をふまえ報告する。　①シミュレーション教育の実践環境の構築および学内研修、②コロナ禍における通信設備・運用のテクニカルサポート、③シミュレーション教育の実践（看護学部各領域におけるシミュレーション教育の実践内容）、④看護学部シミュレーション教育ホームページ、⑤本学看護学部のシミュレーション教育に関する国内外の学会発表の実績　今後もシミュレーション教育を推進するための本学の課題である、教育環境のさらなる充実、人員の確保、地域の拠点としてのシミュレーション教育の推進、活動のための運営資金の獲得を目指すべく、近隣施設との連携、研究推進とともに、教員の理解と同意を得ながらさらなる教育環境の整備や教育力の向上のため邁進していく

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

High-resolution seismic reflection profiling across the Shiraiwa fault, eastern margin of the Yokote basin fault zone, northeast Japan : data acquisition and processing

The eastern margin of the Yokote basin fault zone extends about 56km at the western foot of the Ou Backbone Range, northeast Japan. The Rikuu earthquake (M=7.2) occurred in the Ou Backbone Range (Mahiru Range) on 31st August, 1896. Associated with this earthquake, four thrust faults-Obonai, Shiraiwa, Ota, and Senya fault3 appeared on the surface of the western foot of the Mahiru Range. These faults were highly sinuous with numerous gaps and en echelon steps. We conducted a high-resolution seismic reflection profiling survey across the Shiraiwa fault. The obtained seismic reflection data were processed by conventional common mid-point methods, post-stack migration, and depth conversion. The subsurface structure across the Shraiwa fault is characterized by branched low-angle reverse faults and conjugate back-thrust. The emergent thrust associated with the 1896 earthquake is regarded to be a subsidiary reverse fault

Effects of soil compaction on the seedlings growth and ectomycorrhizal fungal community in hybrid larch

Soil physical composition is one of the fundamental factors regulating plant growth as well as soil microbes. For the rising expectation to optimize techniques of forestry machinery for sustainable forest managements in Japan, it is essential to assess the effects of soil compaction caused by machinery running on seedlings of afforestation tree species. Since most afforestation tree species interact with soil microbes, such as the symbiosis with ectomycorrhizal fungi, the effects of soil compaction would extend to the relationship between these microbes and planted seedlings. We evaluated the effects of soil compaction on growth and ectomycorrhizal fungi in hybrid larch seedlings. The experimental site was established with no compacted and compacted plots in the Sapporo experimental forest site of Hokkaido University, where two-year-old seedlings were planted. At compacted plots, the surface hardness was 25 kg cm-2 and the bulk density was 1.1 g cm-3. Height growth of seedlings was significantly suppressed, and the dry weight was decreased 50% at compacted plots than that of seedlings grown at uncompacted plots. The dominant group of associated ectomycorrhizal fungi was changed by soil compaction. Our data showed that the effect of soil compaction can suppress growth of seedlings and shape the specific ectomycorrhizal fungal community