インターロイキン-1β暴露下のラットの血管におけるエタノールによる誘導型一酸化窒素合成酵素抑制を介した弛緩反応の抑制

Nitric oxide produced by inducible nitric oxide synthase (iNOS) regulates sepsis-induced hypotension. During septic shock, interleukin (IL)-1β is synthesized in endothelial cells and smooth muscle cells by endotoxin. Ethanol (EtOH) suppresses endotoxin-induced hypotension. The present study aimed to elucidate the effect of EtOH on gradual relaxation and iNOS expression induced by IL-1β in isolated rat superior mesenteric arteries (SMAs). Exposure to IL-1β–induced contraction in SMA rings, followed by a gradual relaxation of phenylephrine precontracted tone. Contraction was abolished by indomethacin (IM), cycloheximide (Chx), and endothelium denudation. In contrast, the gradual relaxation was abolished by NOS inhibitors, Chx, endothelium denudation, and inhibited by EtOH (50 and 100 mM). However, IM had no effect on relaxation. Western blot analysis demonstrated that iNOS expression was induced by IL-1β and was inhibited by EtOH and endothelium denudation. Furthermore, messenger RNA expression of iNOS, but not endothelial NOS, was inhibited by EtOH. These data suggest that IL-1β–induced contraction is mediated by thromboxane A2, whereas IL-1β–induced relaxation occurs via NO derived from iNOS. The endothelium plays an important role in vasorelaxation. Taken together, EtOH inhibits IL-1β–mediated vasorelaxation by suppressing endothelium iNOS expression. This study provides the first evidence of EtOH -induced inhibition of IL-1β–mediated vasorelaxation.博士（医学）・甲第647号・平成28年3月15日© The Author(s)Copyright © 2016 by SAGE PublicationsThe definitive version is available at " http://dx.doi.org/10.1177/0960327115611944

Multiplex PCRを用いた簡便で感度の高い溺死診断法の開発

For diagnosing death due to drowning, the method of acid digestion of diatoms is widely used to detect plankton in the organs of the corpse. However, the method is limited by its　being complex, hazardous, time-consuming, and insufficiently sensitive. We therefore, developed a novel simple method to diagnose death due to drowning, and determined the location of drowning by detecting genes of representative bacteria in the environment. To procure all the information in one step, the multiplex PCR method was designed. For the diagnosis of drowning, the genes of upper respiratory indigenous bacteria, Streptococcus salivarius and Streptococcus sanguinis were used as indicators. For detection of the location of drowning, Aeromonas hydrophila and Microcystis aeruginosa were used as indicators of freshwater, and Vibrio harveyi as an indicator of seawater. A set of primers was designed for multiplex PCR. to amplify all the bacterial genes simultaneously. Using this method, 47 cases of drowning were examined, and the causes and locations of death were diagnosed.博士（医学）・乙第1428号・平成31年3月15

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

Objectives: 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.本文は発行元が定める公開猶予期間終了後に公開

The dilemma of nurses in the field of lifesaving：Literature review

The purpose of this study was to clarify the dilemmas that nurses have in the field of lifesaving through a literature review in Japan. As a result of analysis and discussion, it was found that there are four aspects to the dilemma that nurses have: “dilemma of giving priority to lifesaving,” “dilemma of performing the role as a nurse in a team,” “dilemma of the difficulty of practicing nursing under severe conditions,” and “dilemma of confronting oneself. It was inferred that these four aspects were related to each other. In addition, these dilemmas have two characteristics: social conflicts felt in the organization and intra-individual conflicts felt in oneself. Dilemmas are not necessarily harmful, even moderate dilemmas have positive aspects of functioning. By examining and managing dilemmas embraced by nurses, it is suggested that dilemmas can lead to their technical and spiritual growth, their improvement in the quality of nursing, and ultimately their organizational development

Male mice, caged in the International Space Station for 35 days, sire healthy offspring

Matsumura, T., Noda, T., Muratani, M. et al. Male mice, caged in the International Space Station for 35 days, sire healthy offspring. Sci Rep 9, 13733 (2019). https://doi.org/10.1038/s41598-019-50128-

口腔内所見を用いた新たな年齢推定法

In forensic science, age estimation is an important step in identifying unidentified cadavers. As teeth are resistant to environmental degradation for long periods of time, they are often used to estimate age. Although there have been many reports of age estimation based on dental morphology, these methods tend to be subjective and cannot be used i n the case of edentulous jaws. In the present study, we developed a new method of age estimation from dental parameters (number of upper teeth [UT], lower teeth [LT], and prostheses [NP]; tooth attrition [TA]; and occlusal area [OA]) and the mandibular angle (MA) measured at proposed an equation for calculating the age. The results show that the mean error of this method is similar to that of previous methods, and even demonstrated improved accuracy in subjects aged >60 years. We also proposed an equation for age estimation from only the MA, and showed that we can perform age estimation even in edentulous cases using this equation. Because our method is superior in its simplicity, objectivity, and applicability when compared with previous methods, we believe our method wll prove useful for age estimation in a wide variety of cases.博士（医学）・甲611号・平成26年3月17

Bivalent Human Papillomavirus Vaccine Effectiveness in a Japanese Population : High Vaccine-Type-Specific Effectiveness and Evidence of Cross-Protection

Acknowledgments.  We thank Dr Tomomi Egawa-Takata, Dr Akiko Morimoto, Dr Yusuke Tanaka, Ms Asami Yagi, Ms Yuka Watanabe, Ms Sachiko Ono, Ms Anna Ishida, and the administrators of Niigata, Nagaoka, Shibata, Sanjo, Joetsu, and Mitsuke cities for their support in conducting the survey. Financial support. This work was supported by the Health and Labor Sciences Research Grant (26272001) and the Japanese Agency for Medical Research and Development (AMED) under grant number JP15ck0106103 and JP17ck0106369.Peer reviewedPublisher PD

Risk factors for HPV infection and high-grade cervical disease in sexually active Japanese women

Funding Information: This work was supported by the Health and Labor Sciences Research Grant [26272001] and the Japanese Agency for Medical Research and Development [JP15ck0106103].Peer reviewedPublisher PD

Suspension of proactive recommendations for HPV vaccination has led to a significant increase in HPV infection rates in young Japanese women : real-world data

Funding Information: We would like to thank Ms. Yuka Watanabe, Ms. Sachiko Ono, Ms. Anna Ishida, and administrator of Niigata city for their support in conducting the survey. This work was supported by the Japanese Agency for Medical Research and Development (JP15ck0106103).Peer reviewedPublisher PD

Epidemiologic profile of type-specific human papillomavirus infection after initiation of HPV vaccination

Funding Information: This work was supported by the Health and Labor Sciences Research Grant [26272001] and the Japanese Agency for Medical Research and Development [JP15ck0106103]. Acknowledgments: We would like to thank Yuka Watanabe, Sachiko Ono, Anna Ishida, Yoko Motoki and the administrator of Niigata city for their support in conducting the surveyPeer reviewedPublisher PD