Immunohistochemical findings in the pancreatic islets of a patient with transfusional iron overload and diabetes : case report

Excessive iron storage sometimes causes diabetes in patients with hemochromatosis, a disease caused by iron overloading. We performed an immunohistochemical analysis to study an autopsy case of aplastic anemia and diabetic hemochromatosis caused by frequent blood transfusions, and extensive hemosiderin deposition was observed in the liver and pancreas. The pancreatic islets of the patient and a control subject were stained to detect glucagon, insulin, and proinsulin. Significantly lower levels of immunoreactivity with both insulin antibodies and proinsulin antibodies, but not with glucagon antibodies, was observed in the islet cells in the patient’s tissue than in the islet cells of the control. Hemosiderin deposition in the islets is known to be exclusively distributed in the β-cells, thus, selective iron-induced damage to the β-cells may have affected insulin synthesis and secretion and led to glucose intolerance in the patient

Pneumonia Caused by Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza Virus: A Multicenter Comparative Study

Background: Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. Methods: A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. Results: Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. Conclusions: Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings

長島未来プロジェクト／〜 環境デザインによる地域再生の実践的研究 〜

　地方都市を対象として、地域の調査や分析などによる課題の抽出を行い、環境デザイン、建築、まちづくりなどからの解決策の実践的な提案を行ない、少子高齢化社会や持続可能型社会に向けた地方都市の創生（地域再生）のあり方を提言するデザイン手法論を研究することを目的とする。岡山県瀬戸内市長島の国立ハンセン病療養所の保存と再生をテーマとし、地域の現地調査・分析、現地WS などを踏まえて、長島全体の将来計画を提案する。また、瀬戸内海沿岸地帯・島嶼部の視点から、長島を拠点とした裳掛地区全体のまちづくり構想も提案する総合的な地域再生デザインである。長島未来プロジェクト（本研究）は、両園の将来構想を基調に「長島全体の将来構想」に係る環境デザインからの構想計画を提案すること及びその実現に向けた活動に取り組むこと、並びに今後、長島の将来構想を計画へと具体化する段階で関係者の議論に供することにより、構想の実現に資することを目的とする。更に、長島を拠点として瀬戸内沿岸地域・島嶼部一帯が連携した地域再生の取組みを進めることにより、“長島入所者の想い”を未来につなぎ、瀬戸内沿岸・島嶼部一帯の活性化に寄与することに本プロジェクトの意義がある。The aim of the research is to, at first, based on the surveysand analysis of the study area, detect the challenges, which will be followed by practical proposal of the solutionstrategy that encompasses environmental design,architecture as well as community development. The practical proposal of our research is a design methodology which tackles with phenomena of regional city revitalization in the context of low birth rate, aging society and sustainable society. Under the topic of preservation and regeneration of the National Hansen\u27s Disease Sanatorium in Nagashima (Setouchi City, Okayama Prefecture) and based on regional field survey, analysis, workshops etc. we will propose future plan of Nagashima Island as a whole. Furthermore, from the point of view of the Seto Inland Sea coastal zone and the islands, and with Nagashima Island as a base, the entire district of Mokakechiku will be included in the comprehensive community development plan within the regional city revitalization design concept.The research of Nagashima Mirai Project encompasses several main objectives. First is the proposal of the environmental design conceptual plan based on the theme of “Future vision of Nagashima as a whole“, followed by the implementation activities and the inclusion of the stakeholders by sharing the findings of the research during the realization of the plan phases, and lastly by advancing and promoting the regional revitalization of Seto Inland Sea coastal zone and the islands, our research project is to bring forth the “Nagashima residents’ spirit” and tie it to Nagashima’s future.Main research project and its objectives are devised to make a significant contribution to revitalization of Seto Inland Sea coastal zone and the islands zone as whole

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

Cell Proliferation PET Imaging with 4DST PET/CT in Colorectal Adenocarcinoma and Adenoma

An age of 70-year-old man was incidentally found two focal high 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake in the descending colon and in the sigmoid colon. We observed the feature of these two areas in the preplanned 4′-[methyl-11C]-thiothymidine (4DST) positron emission tomography (PET)/computed Tomography (CT)providing cell proliferation imaging. A mass forming high 4DST uptake in the descending colon and focal moderate 4DST uptake in the sigmoid colon was confirmed, and that were proven pathologically as adenocarcinoma and moderate to severe type tubular adenoma, respectively. This is the first report to present that colorectal adenoma can be visualized by proliferation PET imaging and the degree of uptake may enable discrimination of colorectal adenoma from adenocarcinoma, based on pathological considerations

Preventive Effect of Lactobacillus helveticus SBT2171 on Collagen-Induced Arthritis in Mice

We recently reported that the intraperitoneal inoculation of Lactobacillus helveticus SBT2171 inhibited the development of collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA). In the present study, we evaluated the effect of the oral administration of L. helveticus SBT2171 on CIA development and on the regulation of antigen-specific antibody production and inflammatory immune cells, which have been implicated in the development of RA. Both oral administration and intraperitoneal inoculation of L. helveticus SBT2171 reduced joint swelling, body weight loss, and the serum level of bovine type II collagen (CII)-specific antibodies in the CIA mouse model. The intraperitoneal inoculation also decreased the arthritis incidence, joint damage, and serum level of interleukin (IL)-6. In addition, the numbers of total immune cells, total B cells, germinal center B cells, and CD4+ T cells in the draining lymph nodes were decreased following intraperitoneal inoculation of L. helveticus SBT2171. These findings demonstrate the ability of L. helveticus SBT2171 to downregulate the abundance of immune cells and the subsequent production of CII-specific antibodies and IL-6, thereby suppressing the CIA symptoms, indicating its potential for use in the prevention of RA