The Japanese classification of computed tomography for pneumoconioses with standard films: comparison with the ILO international classification of radiographs for pneumoconioses

Computed tomography (CT) has recently come to be used for personal diagnosis of pneumoconioses and preliminarily for epidemiological purposes. This study aimed to compare the diagnosis of pneumoconioses b y t h e J a p a n e s e C l a s s i f i c a t i o n o f C T f o r Pneumoconioses (Hosoda-Shida Classification) with that by the ILO International Classification of Radiographs of Pneumoconioses (ILO 1980 standard). The Hosoda-Shida Classification is also described in this article. Subjects and Methods: CT and chest posterior-anterior X-ray (CXR) were performed in 21 subjects with an occupational history of mining, and 6 subject without exposure to any risk of pneumoconiosis. Three radiologists independently described the findings of CT and CXR according to both the Hosoda-Shida Classification and the ILO 1980 standard, respectively. Results: At least two of the three readers agreed in determining both the profusion and the type of small rounded opacities in 96% (26/27) of the CT films. The inter-reader agreement of profusion was satisfactory Received May 25, 2000; Accepted Oct 3, 2000 Correspondence to: N. Suganuma, Department of Environmental Health, Fukui Medical University School of Medicine, Fukui 910-1193 with the Cohen's weighted kappa value of 0.57 to 0.71. The weighted kappa for CXR and CT in describing the profusion and the type of small rounded opacities were 0.70 and 0.77, respectively. Conclusion: The HosodaShida Classification for pneumoconioses is shown to be reliable and compatible with the ILO 1980 standard in describing the profusion and the type of small opacities. (J Occup Health 2001; 43: 24-31

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

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

Strong cytoplasmic expression of NF-κB/p65 correlates with a good prognosis in patients with triple-negative breast cancer

Purpose: Recent studies have indicated that constitutive NF-κB activity could be involved in the proliferation of triple-negative breast cancer. Methods: NF-κB/p65 expression and the effects of the NF-κB inhibitor, (-)-DHMEQ were examined in triple-negative MDA-MB-231 breast cancer cells. Women with triple-negative breast cancer treated with neoadjuvant chemotherapy between 2002 and 2012 were retrospectively analyzed. Expression of NF-κB/p65, Bcl2 and Ki67 was examined by immunohistochemistry in pre- and post-treatment specimens, and predictive factors for neoadjuvant chemotherapy and prognosis were analyzed. Results: NF-κB/p65 was dominantly expressed in the cytoplasm in MDA-MB-231 cells. Of 34 triple-negative breast cancer patients, positive staining for NF-κB/p65 expression was detected in the nuclei of a few cells in 7 tumors before neoadjuvant chemotherapy, although expression of NF-κB/p65 in the cytoplasm was detected in almost all tumor cells of 33 tumors. Expression levels of NF-κB/p65 were not associated with response to neoaduvant chemotherapy, although expression levels of cytoplasmic NF-κB/p65 intensity were significantly decreased in post-treatment tumor samples compared with those in pretreatment samples. All patients whose tumors showed strong cytoplasmic NF-κB/p65 expression before neoadjuvant chemotherapy are currently disease-free. Conclusion: Our results suggest that strong cytoplasmic NF-κB/p65 expression could be a prognostic marker in triple-negative breast cancer

Characterization of the multimeric structure of poly(A)-binding protein on a poly(A) tail

Abstract Eukaryotic mature mRNAs possess a poly adenylate tail (poly(A)), to which multiple molecules of poly(A)-binding protein C1 (PABPC1) bind. PABPC1 regulates translation and mRNA metabolism by binding to regulatory proteins. To understand functional mechanism of the regulatory proteins, it is necessary to reveal how multiple molecules of PABPC1 exist on poly(A). Here, we characterize the structure of the multiple molecules of PABPC1 on poly(A), by using transmission electron microscopy (TEM), chemical cross-linking, and NMR spectroscopy. The TEM images and chemical cross-linking results indicate that multiple PABPC1 molecules form a wormlike structure in the PABPC1-poly(A) complex, in which the PABPC1 molecules are linearly arrayed. NMR and cross-linking analyses indicate that PABPC1 forms a multimer by binding to the neighbouring PABPC1 molecules via interactions between the RNA recognition motif (RRM) 2 in one molecule and the middle portion of the linker region of another molecule. A PABPC1 mutant lacking the interaction site in the linker, which possesses an impaired ability to form the multimer, reduced the in vitro translation activity, suggesting the importance of PABPC1 multimer formation in the translation process. We therefore propose a model of the PABPC1 multimer that provides clues to comprehensively understand the regulation mechanism of mRNA translation