Web of Science

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cold Spring Harbor Laboratory  

Therapeutic drug monitoring (TDM) is a routine clinical practice used to individualize drug dosing and thereby maintain drug efficacy and minimize the consequences of overexposure. TDM is applied to many drug classes, including immunosuppressants, anticoagulants, antineoplastic agents, and antibiotics. Considerable efforts have been made to establish routine TDM practice for each drug. However, because TDM has been developed within the context of specific drugs, there is insufficient understanding of historical trends in TDM research itself. In this study, we employed text mining approaches to explore trends in the TDM research field. We first performed a PubMed search to determine which drugs and drug classes have been extensively studied in the context of TDM. This investigation revealed that the most commonly studied drugs were warfarin and cyclosporine, followed by tacrolimus, heparin, and vancomycin. In terms of drug classes, most publications focused on antineoplastic agents, anticoagulants, immunosuppressants, and antibiotics. We next used a newly developed python-based module to obtain PubMed records of publications relevant to TDM, and then subjected them to text mining. Our analyses revealed how TDM research has evolved over the years.

DOI： 10.1101/2023.06.22.23291733

担当区分：最終著者,　責任著者   出版者・発行元：Cold Spring Harbor Laboratory  

Abstract

The budding yeastSaccharomyces cerevisiaeis commonly used as an expression platform to produce valuable compounds. Yeast-based genetics research can uniquely utilize use auxotrophy in transformant selection: auxotrophic complementation by an auxotrophic marker gene on exogenous DNA (such as plasmids). However, the number of auxotrophic nutrients required restricts the number of plasmids maintained by the cells. We therefore developed novel Δ10 strains that are auxotrophic for 10 different nutrients, and new plasmids with two multicloning sites and auxotrophic markers for use in Δ10 strains. We confirmed that Δ10 strains could maintain 10 types of these plasmids. Because each plasmid can express two different genes, this Δ10 strain-based expression system has the potential to co-express a maximum of 20 different proteins.

DOI： 10.1101/2023.05.01.538886

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pharmacological Research  

Copy-number variations in the ARHGAP10 gene encoding Rho GTPase–activating protein 10 are associated with schizophrenia. Model mice (Arhgap10 S490P/NHEJ mice) that carry “double-hit” mutations in the Arhgap10 gene mimic the schizophrenia in a Japanese patient, exhibiting altered spine density, methamphetamine-induced cognitive dysfunction, and activation of RhoA/Rho-kinase signaling. However, it remains unclear whether the activation of RhoA/Rho-kinase signaling due to schizophrenia-associated Arhgap10 mutations causes the phenotypes of these model mice. Here, we investigated the effects of fasudil, a brain permeable Rho-kinase inhibitor, on altered spine density in the medial prefrontal cortex (mPFC) and on methamphetamine-induced cognitive impairment in a touchscreen‑based visual discrimination task in Arhgap10 S490P/NHEJ mice. Fasudil (20 mg/kg, intraperitoneal) suppressed the increased phosphorylation of myosin phosphatase–targeting subunit 1, a substrate of Rho-kinase, in the striatum and mPFC of Arhgap10 S490P/NHEJ mice. In addition, daily oral administration of fasudil (20 mg/kg/day) for 7 days ameliorated the reduced spine density of layer 2/3 pyramidal neurons in the mPFC. Moreover, fasudil (3–20 mg/kg, intraperitoneal) rescued the methamphetamine (0.3 mg/kg)-induced cognitive impairment of visual discrimination in Arhgap10 S490P/NHEJ mice. Our results suggest that Rho-kinase plays significant roles in the neuropathological changes in spine morphology and in the vulnerability of cognition to methamphetamine in mice with schizophrenia-associated Arhgap10 mutations.

DOI： 10.1016/j.phrs.2022.106589

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

開催年月日： 2023年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年5月

記述言語：英語   会議種別：ポスター発表  

開催年月日： 2023年5月

記述言語：英語   会議種別：ポスター発表  

開催年月日： 2022年11月 - 2022年12月

会議種別：口頭発表（招待・特別）  

開催年月日： 2022年11月

会議種別：口頭発表（招待・特別）