エンドセリン-1 によるエールリッヒ腹水癌細胞からのリポタンパク質リパーゼの分泌(発表論文抄録(2010))

Since the role of endothelin (ET)-1 in lipoprotein metabolism in tumor cells is unclear, we investigated the effect of ET-1 on the secretion of lipoprotein lipase (LPL) from mouse Ehrlich ascites tumor cells. ET-1 increased the secretion of LPL from these cells in a time-dependent manner. Two antagonists of ET-receptor type A (ET-A), namely, BQ123 and FR139317, inhibited the stimulatory effect of ET-1 on the secretion of LPL. However, an antagonist of ET-receptor type B (ET-B), BQ788, did not have any effect. Neomycin, a phospholipase C (PLC) inhibitor, and H-7, a protein kinase C (PKC) inhibitor, also suppressed the ET-1-stimulated secretion of LPL. ET-1 also increased PKC activity in tumor cells in a dose-dependent manner. These results imply that ET-1 stimulates secretion of LPL from tumor cells by stimulating the PLC-PKC signaling pathway through the ET-A receptor rather than the ET-B receptor.Since the role of endothelin (ET)-1 in lipoprotein metabolism in tumor cells is unclear, we investigated the effect of ET-1 on the secretion of lipoprotein lipase (LPL) from mouse Ehrlich ascites tumor cells. ET-1 increased the secretion of LPL from these cells in a time-dependent manner. Two antagonists of ET-receptor type A (ET-A), namely, BQ123 and FR139317, inhibited the stimulatory effect of ET-1 on the secretion of LPL. However, an antagonist of ET-receptor type B (ET-B), BQ788, did not have any effect. Neomycin, a phospholipase C (PLC) inhibitor, and H-7, a protein kinase C (PKC) inhibitor, also suppressed the ET-1-stimulated secretion of LPL. ET-1 also increased PKC activity in tumor cells in a dose-dependent manner. These results imply that ET-1 stimulates secretion of LPL from tumor cells by stimulating the PLC-PKC signaling pathway through the ET-A receptor rather than the ET-B receptor

プラゾシンによる初代培養ラット肝細胞からの肝性リパーゼの分泌促進(発表論文抄録(2010))

Prazosin is an alpha 1 adrenoceptor antagonist, and it is used as an antihypertensive agent. The effects of prazosin on the activity of hepatic triacylglycerole lipase (HTGL) are not fully understood. In this study, we demonstrated that prazosin stimulates the release of HTGL activity from primary cultures of rat hepatocytes in a time- and dose-dependent manner. U-73122, a phopholipase C (PLC) inhibitor, suppresses prazosin\u27s stimulation of the release of HTGL activity. Moreover, prazosin stimulated the increase of PLC activity in the hepatocytes in a time- and dose-dependent manner. In addition, the prazosin-stimulated release of HTGL activity was reduced by Quin2/AM (an intracellular Ca2+-chelator), W-7 (a Calmodulin inhibitor), and KN-93 [an inhibitor of Ca2+/Calmodulin dependent protein kinase (CaMK)-II]. These results suggest that the prazosin-stimulated release of HTGL activity is partly due to the activation of CaMK-II that is associated with the elevation of PLC activity in the hepatocytes.Prazosin is an alpha 1 adrenoceptor antagonist, and it is used as an antihypertensive agent. The effects of prazosin on the activity of hepatic triacylglycerole lipase (HTGL) are not fully understood. In this study, we demonstrated that prazosin stimulates the release of HTGL activity from primary cultures of rat hepatocytes in a time- and dose-dependent manner. U-73122, a phopholipase C (PLC) inhibitor, suppresses prazosin\u27s stimulation of the release of HTGL activity. Moreover, prazosin stimulated the increase of PLC activity in the hepatocytes in a time- and dose-dependent manner. In addition, the prazosin-stimulated release of HTGL activity was reduced by Quin2/AM (an intracellular Ca2+-chelator), W-7 (a Calmodulin inhibitor), and KN-93 [an inhibitor of Ca2+/Calmodulin dependent protein kinase (CaMK)-II]. These results suggest that the prazosin-stimulated release of HTGL activity is partly due to the activation of CaMK-II that is associated with the elevation of PLC activity in the hepatocytes

Beneficial effects of nasal high flow oxygen therapy after weaning from non-invasive ventilation: A prospective observational study

It remains unknown whether application of nasal high flow (NHF) is effective after liberation from non-invasive ventilation (NIV). This study was aimed at investigating the effect of NHF in patients ready for weaning from NIV. With institutional ethic committee approval, patients receiving NIV due to hypoxemic respiratory failure for more than 24 hours were enrolled. After passing the weaning criteria with continuous positive airway pressure (CPAP) mode [fraction of inspiratory oxygen (FIO2) ≦0.5, positive end expiratory pressure (PEEP) 4 cmH2O], patients received NHF (Flow 50 L/min, FIO2 ≦0.5) immediately after liberation from NIV. Before the initiation of the study, eight sequential patients who received oxygen via face mask after NIV treatment, served as the historical control. Respiratory parameters [partial pressure of arterial oxygen (PaO2) to FIO2 ratio (P/F ratio), respiratory rate (RR)] 1 hour after liberation from NIV were evaluated with those during NIV as the primary outcome. The frequency of rescue NIV therapy, intubation, and respiratory failure were also recorded. Nine eligible patients received NHF therapy after liberation from NIV. P/F ratio and RR did not change significantly compared with those during NIV (231 ± 43.6 versus 250.7 ± 34.2 mmHg, 20.8 ± 2.3 versus 21 ± 1.6 /min), while P/F ratio decreased significantly in the historical control group (194.3 ± 20.1 versus 255.9 ± 58.1 mmHg, p=0.013). Rescue NIV therapy, intubation, and respiratory failure never occurred in the NFH group, although two patients received NIV rescue therapy, of whom one was intubated in the historical control. NHF after liberation from NIV might be effective in patients recovering from hypoxemic respiratory failure

Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome

Flavonoids are a subclass of polyphenols which are attractive, due to possessing various physiological activities, including a radioprotective effect. Tumor suppressor p53 is a primary regulator in the radiation response and is involved in the pathogenesis of radiation injuries. In this study, we revealed that isorhamnetin inhibited radiation cell death, and investigated its action mechanism focusing on DNA damage response. Although isorhamnetin moderated p53 activity, it promoted phosphorylation of ataxia telangiectasia mutated (ATM) and enhanced 53BP1 recruitment in irradiated cells. The radioprotective effect of isorhamnetin was not observed in the presence of ATM inhibitor, indicating that its protective effect was dependent on ATM. Furthermore, isorhamnetin-treated mice survived gastrointestinal death caused by a lethal dose of abdominal irradiation. These findings suggested that isorhamnetin enhances the ATM-dependent DNA repair process, which is presumably associated with the suppressive effect against GI syndrome

A study on the development of technical skills in nursing education : through the skill evaluation using simulated patients

本研究の目的は，模擬患者を導入した看護技術試験の効果の検討であった． 研究実施にあたっては，Ｂ大学倫理審査委員会の承認を得た後，被験者と模擬患者に口頭と文書による説明を行い，同意を得た． 調査は，Ａ短期大学の看護学科２年次生３０名を対象に，筆者らが作成した７段階評価の２３項目の質問紙を用いて行われた．手順としては，まず２００４年９月に質問紙を用いた看護技術試験前の調査を行った．１０月に看護技術試験のために「吸引」についての事例およびチェックリストを配布し，デモンストレーションを実施した．１１月に学生が患者役となる形式の技術試験を行った．１２月に模擬患者を導入した技術試験を実施し，その後に９月と同様の質問紙の調査を行った． 肯定的表現に７点，否定的表現に１点を配した質問紙の各項目を看護技術試験前後で比較・検討した結果，技術試験前の高得点は，「緊張感がある－緊張感がない」，「効果的－効果的でない」であり，技術試験後は「よい－よくない」，「有用な－有用でない」および「継続してほしい－継続してほしくない」であった．技術試験前の低得点は，「易しい－難しい」，「明確な－混乱した」であり，技術試験後は「易しい－難しい」，「明確な－混乱した」であった．技術試験前後で得点が上昇したのは，「易しい－難しい」，「有益－有益でない」であり，得点が低下したのは，「やる気がでる－やる気がでない」，「達成感がある－達成感がない」であった．得点が変化しなかったのは，「刺激的な－刺激のない」および「実力を発揮できる－実力を発揮できない」であった． 学生の看護技術の習得レベルを評価し看護実践力を向上させるために，模擬患者を導入した看護技術試験は効果的な方法であることが示唆されたが，学生に過度の緊張を与えず，コミュニケーションスキルが身につくような配慮の工夫が必要であると思われた．The purpose of this study was to investigate the effectiveness of a test of technical nursing skills using simulated patients. Prior to the study, we obtained the permission of the ethics committee of University B, and explained the research to the subjects and simulated patients in order to obtain their informed consent. A survey was carried out using a questionnaire constructed by the researchers comprising ２３ items with a７‐point Likert scale. The subjects were ３０ senior nursing students at Junior College A. In September ２００４, we conducted an initial survey using the questionnaire, and in October gave the subjects a paper patient and the lists for checking their nursing techniques, and a suction demonstration. In November, we gave an ordinary skills test, and in December, using the same questionnaire as before, we conducted a second survey after a test of technical nursing skills using simulated patients. Pre - and post - test analysis of the questionnaire responses（the most positive answer being awarded７ points and the most negative answer being awarded１point）, showed that pre - test high scores were obtained on the “nervous- not nervous” and “effective-not effective” items ; post-test，“good test-not a good test”, “useful-not useful” and “like to continue-not like to continue”. The pre-test low scores were “easy-difficult” and “clear-unclear” ; and post-test，“easy-difficult” and “clear-unclear”. The increased scores between pre- and post-test were “easy-difficult”, “beneficial-not beneficial” and the decreased scores were “motivation-no motivation” and “sense of achievement-no sense of achievement”. The items which were unchanged were “stimulating-not stimulating”，“developed practical ability-did not develop practical ability”. These results show that the test using simulated patients was an effective method of developing students’ nursing techniques. However, teachers need to pay attention to developing students’ communication skills and not create excessive tension for them when they have skills tests

Impact of shear wave dispersion slope analysis for assessing the severity of myocarditis

This study aimed to elucidate the utility of a novel ultrasound-based technique, shear wave dispersion slope (SWDS) analysis, which estimates tissue viscosity, for evaluating the severity of myocardial inflammation. Experimental autoimmune myocarditis (EAM) at different disease phases [3-week (acute phase): n = 10, 5-week (subacute phase): n = 9, and 7-week (late phase): n = 11] were developed in male Lewis rats. SWDS was measured in the right and the left ventricular free walls (RVFW and LVFW) under a retrograde perfusion condition. Histological myocardial inflammation was evaluated by CD68 staining. The accumulation of CD68-positive cells was severe in the myocardium of the EAM 3-week group. The median (interquartile range) SWDS of RVFW was significantly higher in the EAM 3-week group [9.9 (6.5-11.0) m/s/kHz] than in the control group [5.4 (4.5-6.8) m/s/kHz] (P = 0.034). The median SWDS of LVFW was also significantly higher in the EAM 3-week group [8.1 (6.4-11.0) m/s/kHz] than in the control group [4.4 (4.2-4.8) m/s/kHz] (P = 0.003). SWDS and the percentage of CD68-positive area showed a significant correlation in RVFW (R-2 = 0.64, P < 0.001) and LVFW (R-2 = 0.73, P < 0.001). This study showed that SWDS was elevated in ventricular walls with acute inflammation and also significantly correlated with the degree of myocardial inflammation. These results suggest the potential of SWDS in estimating the histological severity of acute myocarditis

Effects of image lag on real-time target tracking in radiotherapy

There is a concern that image lag may reduce accuracy of real-time target tracking in radiotherapy. This study was performed to investigate influence of image lag on the accuracy of target tracking in radiotherapy. Fluoroscopic image: were obtained using a direct type of dynamic flat-panel detector (FPD) system under conditions of target tracking during radiotherapy. The images continued to be read out after X-irradiations and cutoff, and image lag properties in the system were then determined. Subsequently, a tungsten materials plate with a precision edge was mounted on to a motor control device, which provided a constant velocity. The plate was moved into the center of the detector at movement rate of 1 and 20 mm/s, covering lung tumor movement of normal breathing, and MTF and profile curves were measured on the edges covering and uncovering the detector. A lung tumor with blurred edge due to image lag was simulated using the results and then superimposed on breathing chest radiographs of a patient. The moving target with and without image lag was traced using a template-matching technique. In the results, the target could be traced within a margin for error ii external radiotherapy. The results indicated that there was no effect of image lag on target tracking in usual breathing speed in a radiotherapy situation. Further studies are required to investigate influence by the other factors, such a: exposure dose, target size and shape, imaging rate, and thickness of a patient\u27s body. © 2010 SPIE

Susceptibility of Influenza Viruses to the Novel Cap-Dependent Endonuclease Inhibitor Baloxavir Marboxil

The novel cap-dependent endonuclease inhibitor baloxavir marboxil was approved for the treatment of influenza A and B virus infections in February 2018 in Japan. Because of the need to monitor influenza viruses for reduced susceptibility to this drug, we used two cell-based screening systems – a conventional plaque reduction assay and a focus reduction assay – to evaluate the susceptibility of influenza viruses to baloxavir. First, we generated a reference virus possessing an I38T substitution in the polymerase acidic subunit (PA), which is known to be associated with reduced susceptibility to baloxavir, and demonstrated the validity of our systems using this reference virus. We then determined the susceptibility of a panel of neuraminidase (NA) inhibitor-resistant viruses and their sensitive counterparts to baloxavir. No significant differences in baloxavir susceptibilities were found between the NA inhibitor-resistant and -sensitive viruses. We also examined seasonal influenza viruses isolated during the 2017–2018 influenza season in Japan and found that no currently circulating A(H1N1)pdm09, A(H3N2), or B viruses had significantly reduced susceptibility to baloxavir and none of the viruses possessed an amino acid substitution at PA residue 38. Use of a combination of methods to analyze antiviral susceptibility and detect amino acid substitutions is valuable for monitoring the emergence of baloxavir-resistant viruses