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コンバラトキシンによる凝固亢進における単球由来組織因子陽性細胞外小胞の関与
Get PDFObjectives:
Convallatoxin (CNT) is a natural cardiac glycoside extracted from lily of the valley (Convallaria majalis). Although it is empirically known to cause blood coagulation disorders, the underlying mechanism remains unclear. CNT exerts cytotoxicity and increases tissue factor (TF) expression in endothelial cells. However, the direct action of CNT on blood coagulation remains unclear. Therefore, herein, we investigated the effects of CNT on whole blood coagulation system and TF expression in monocytes.
Methods:
Blood samples were collected from healthy volunteers to measure plasma thrombin–antithrombin complex (TAT) concentration using ELISA and to perform rotational thromboelastometry (ROTEM) and whole-blood extracellular vesicle (EV)-associated TF (EV-TF) analysis. The effects of CNT were also investigated using the monocytic human cell line THP-1. Quantitative real-time PCR and western blotting were performed, and PD98059, a mitogen-activated protein kinase (MAPK) inhibitor, was used to elucidate the action mechanism of CNT-mediated TF production.
Results:
CNT treatment increased EV-TF activity, shortened the whole blood clotting time in rotational thromboelastometry analysis, and increased TAT levels, which is an index of thrombin generation. Furthermore, CNT increased TF mRNA expression in THP-1 cells and EV-TF activity in the cell culture supernatant. Therefore, CNT may induce a hypercoagulable state with thrombin generation, in which elevated EV-TF activity derived from monocytes might be involved. These procoagulant effects of CNT were reversed by PD98059, suggesting that CNT-induced TF production in monocytes might be mediated by the MAPK pathway.
Conclusions:
The findings of the present study have further clarified the procoagulant properties of CNT.権利情報：© 2023 Wolters Kluwer Health, Inc. All rights reserved. This is a non-final version of an article published in final form in [Morimoto, Mami et al. Involvement of monocyte-derived extracellular vesicle-associated tissue factor activity in convallatoxin-induced hypercoagulability. Blood Coagulation & Fibrinolysis. April 2023 - Volume 34 - Issue 3 - p 184-190, doi: http://dx.doi.org/10.1097/MBC.0000000000001211]
ラット肝腫瘍モデルにおける化学療法の早期効果判定に有用なダイナミック造影超音波のパラメータについて
Get PDFObjectives: The objective of the study is to determine a parameter on the time-intensity curve (TIC) of dynamic
contrast-enhanced ultrasonography (DCE-US) that best correlates with tumor growth and to evaluate whether
the parameter could correlate with the early response to irinotecan in a rat liver tumor model.
Material and Methods: Twenty rats with tumors were evaluated (control: Saline, n = 6; treatment: Irinotecan,
n = 14) regarding four parameters from TIC: Peak intensity (PI), k value, slope (PI × k), and time to peak (TTP).
Relative changes in maximum tumor diameter between day 0 and 10, and parameters in the first 3 days were
evaluated. The Mann-Whitney U-test was used to compare differences in tumor size and other parameters.
Pearson’s correlation coefficients (r) between tumor size and parameters in the control group were calculated.
In the treatment group, relative changes of parameters in the first 3 days were compared between responder and
non-responder (<20% and ≥20% increase in size on day 10, respectively).
Results: PI, k value, PI × k, and TTP significantly correlated with tumor growth (r = 0.513, 0.911, 0.665, and 0.741,
respectively). The mean RC in k value among responders (n = 6) was significantly lower than non-responders
(n = 8) (mean k value, 4.96 vs. 72.5; P = 0.003).
Conclusion: Parameters of DCE-US could be a useful parameter for identifying early response to irinotecan.博士（医学）・甲第879号・令和5年3月15日©2021 Published by Scientific Scholar on behalf of Journal of Clinical Imaging Science
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms
大規模言語モデルを使用した現病歴からの精神疾患の診断
Get PDFAim: Recent advances in natural language processing models are expected to provide diagnostic assistance in psychiatry from the history of present illness (HPI). However, existing studies have been limited, with the target diseases including only major diseases, small sample sizes, or no comparison with diagnoses made by psychiatrists to ensure accuracy. Therefore, we formulated an accurate diagnostic model that covers all psychiatric disorders. Methods: HPIs and diagnoses were extracted from discharge summaries of 2,642 cases at the Nara Medical University Hospital, Japan, from 21 May 2007, to 31 May 31 2021. The diagnoses were classified into 11 classes according to the code from ICD-10 Chapter V. Using UTH-BERT pre-trained on the electronic medical records of the University of Tokyo Hospital, Japan, we predicted the main diagnoses at discharge based on HPIs and compared the concordance rate with the results of psychiatrists. The psychiatrists were divided into two groups: semi-Designated with 3–4 years of experience and Residents with only 2 months of experience. Results: The model’s match rate was 74.3%, compared to 71.5% for the semi-Designated psychiatrists and 69.4% for the Residents. If the cases were limited to those correctly answered by the semi-Designated group, the model and the Residents performed at 84.9% and 83.3%, respectively. Conclusion: We demonstrated that the model matched the diagnosis predicted from the HPI with a high probability to the principal diagnosis at discharge. Hence, the model can provide diagnostic suggestions in actual clinical practice.権利情報：© 2023 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made
単音節の有効持続時間と感音難聴者の語音明瞭度との関係
Get PDFAmong the temporal elements in the autocorrelation function, the effective duration (τe) is a useful indicator of speech recognition for patients with sensorineural hearing impairment. We assessed the influence of speech recognition performance on the relationship between the percentage of accurately perceived articulation and the median τe (τe-med) and the relationship between monosyllabic confusion and the τe-med. Significant correlations were observed between the articulation percentage and the average τe-med in groups with high, middle, and low speech recognition scores (SRSs). Two-factor mixed analysis of variance revealed significant main effects for the condition (presentation/response). There was no significant main effect for group (high-, middle-, or low-SRS) scores and no significant interaction between the groups. The average τe-med of the response was significantly longer than that of the presentation in all three groups. Monosyllables with short τe-med values tended to be misheard as monosyllables with a long τe-med when confusion occurred. The τe-med was useful for estimating monosyllables that patients with sensorineural hearing impairment find easy to listen to, independent of speech recognition performance.権利情報：© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
RNAウイルスに対する迅速な全ゲノム決定法の構築
Get PDFRNA viruses are the etiological agents of many infectious diseases. Since RNA
viruses are error-prone during genome replication, rapid, accurate and economical
whole RNA viral genome sequence determination is highly demanded. Next generation sequencing (NGS) techniques perform whole viral genome sequencing
due to their high-throughput sequencing capacity. However, the NGS techniques
involve a significant burden for sample preparation. Since to generate complete
viral genome coverage, genomic nucleic acid enrichment is required by reverse
transcription PCR using virus-specific primers or by viral particle concentration.
Furthermore, conventional NGS techniques cannot determine the 5′ and 3′
terminal sequences of the RNA viral genome. Therefore, the terminal sequences
are determined one by one using rapid amplification of cDNA ends (RACE).
However, since some RNA viruses have segmented genomes, the burden of the
determination using RACE is proportional to the number of segments. To date,
there is only one study attempting whole genome sequencing of multiple RNA
viruses without using above mentioned methods, but the generated sequences’
accuracy compared to the reference sequences was up to 97% and did not reach
100% due to the low read depth. Hence, we established novel methods, named
PCR-NGS and RCA-NGS, that were optimized for an NGS machine, MinION.
These methods do not require nucleic acid amplification with virus-specific PCR
primers, physical viral particle enrichment, and RACE. These methods enable
whole RNA viral genome sequencing by combining the following techniques: (1)
removal of unwanted DNA and RNA other than the RNA viral genome by nuclease
treatment; (2) the terminal of viral genome sequence determination by barcoded
linkers ligation; (3) amplification of the viral genomic cDNA using ligated linker
sequences-specific PCR or an isothermal DNA amplification technique, such as
rolling circle amplification (RCA). The established method was evaluated using
isolated RNA viruses with single-stranded, double-stranded, positive-stranded,
negative-stranded, non-segmented or multi-segmented genomes. As a result, all
the viral genome sequences could be determined with 100% accuracy, and these
mean read depths were greater than 2,500×, at least using either of the methods.
This method should allow for easy and economical determination of accurate
RNA viral genomes.権利情報：© 2023 Misu, Yoshikawa, Sugimoto, Takamatsu, Kurosu, Ouji, Yoshikawa, Shimojima, Ebihara and Saijo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
