Comparison of clinical course of polymyositis and dermatomyositis : a follow-up study in Tokushima University Hospital

Polymyositis (PM) and dermatomyositis (DM) are systemic inflammatory disorders affecting skeletal muscles and other organs, and are associated with high morbidity and mortality rates. In this study, we studied the prevalence, clinical features and its comparative outcome of PM/DM, comparing PM and DM. Twenty-three PM/DM patients (9 PM and 14 DM) were included in this study. The complication of interstitial pneumonia (IP) was found in 17 patients (74%). HRCT showed that non-specific interstitial pneumonia pattern was the most common in patterns of lung involvement. Twenty-one patients (91%) with PM/DM received high dose of prednisolone therapy. The percentage of patients who received methylprednisolone (mPSL) pulse and cyclosporin A was higher in DM patients than in PM patients. The percentage of patients who received mPSL pulse and cyclosporin A was higher in later (after Apr 2004) patients than in former (before Mar 2004) patients. Malignant diseases appeared in 3 patients with DM which consisted of breast cancer, epipharyngeal cancer and gastric cancer. We observed 2 deaths in DM patients during the course of therapy ; one was due to IP, and the other due to miliary tuberculosis. This study showed that a poorer prognosis was observed in patients with DM when compared with those with PM, and immunosuppressive medications may be implicated at least partially in increased risk of infections and malignancies in PM/DM patients especially DM patients, indicating that patients with PM/DM may require careful monitoring during the clinical course

Treatment responses and their predictors in patients with rheumatoid arthritis treated with biological agents

Biological agents represent an important advancement in for the treatment of rheumatoid arthritis (RA), but there is a subset of patients who do not improve despite therapy. This study aimed to determine the efficacy of biological agents for RA and to identify clinical factors that are associated with their response. We studied 98 patients with RA who started an initiating biological agent which was selected from infliximab, etanercept, adalimumab and tociliximab at 4 medical institutions. Etanercept was the most frequently used biological agent followed by infliximab although there was a difference in the selection of the biological agents among medical institutions. We found that etanercept achieved the highest treatment response, remission rate and drug survival rate. A high disease activity in the baseline disease activity score-c-reactive protein (CRP) was shown to be a negative predictor of the treatment response, and high patient global assessment was significantly less likely to achieve a good response. At week 4, decreases in 28 swollen joint counts and CRP were useful as predictors for sustaining the efficacy up to week 48. These data demonstrate that assessments of the disease activity at baseline and the early treatment response may be useful in predicting the efficacy and drug survival rate of biological agents

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

Design and Evaluation of Broad-Band High Pass Filter of Metal Perforated Sheets for Microwave Diagnostics

This paper reports characteristic evaluations of perforated metal sheet type high pass filters for milli- or microwave by numerical analysis and the guiding principle of designing broad-band high pass filters. The broad-band filters will be used for the microwave plasma diagnostics such as ECE, interferometer and reflectometer. We used 3D-modeling electromagnetic field calculation code to take complex interferences into account. The validity of the numerical analysis is guaranteed by a good agreement between calculated results and measured results. It is found that the frequency characteristic over the cut-off frequency depends on the filter thickness and that a thin filter is desirable for the ideal broad-band frequency filter