看護師の類似薬剤名に対する識別の正確性 : 薬剤名への指差呼称の影響

首都大学東京, 2018-03-25, 博士（学術）, 甲第823号首都大学東

Involvement of RNA-binding protein Hfq in the osmotic-response regulation of invE gene expression in Shigella sonnei

<p>Abstract</p> <p>Background</p> <p>The expression of Type III secretion system (TTSS) in <it>Shigella </it>is regulated in response to changes in environmental osmolarity and temperature. Temperature-dependent regulation of <it>virF</it>, the master regulator of TTSS synthesis, is believed to occur at the transcriptional level. We recently demonstrated, however, that TTSS synthesis also involves post-transcriptional regulation of the synthesis of InvE, a target of <it>virF </it>and key regulator of TTSS synthesis. The mRNA levels of <it>invE </it>(<it>virB</it>) are stable at 37°C, but mRNA stability markedly decreases at low temperatures where the TTSS synthesis is tightly repressed. Deletion of <it>hfq</it>, which encodes an RNA chaperone in Gram-negative bacteria, results in the restoration of expression of <it>invE </it>and other TTSS genes at low temperature due to an increase in the stability of <it>invE </it>mRNA. To date, the molecular details of the regulation of TTSS expression in response to osmotic pressure are not known. In the current study, we investigated the mechanism of regulation of TTSS by osmotic pressure.</p> <p>Results</p> <p>Transcription of <it>virF</it>, which encodes the master regulator of TTSS expression, was partially repressed under low osmotic conditions. Several lines of evidence indicated that osmolarity-dependent changes in TTSS synthesis are controlled at the post-transcriptional level, through the regulation of InvE synthesis. First, the expression InvE protein was tightly repressed under low osmotic growth conditions, even though <it>invE </it>mRNA transcripts were readily detectable. Second, under low osmotic conditions, <it>invE </it>mRNA was rapidly degraded, whereas deletion of <it>hfq</it>, which encodes an RNA chaperone, resulted in increased <it>invE </it>mRNA stability and the production of InvE protein. Third, the binding of purified Hfq <it>in vitro </it>to <it>invE </it>RNA was stronger in low-salt buffer, as assessed by gel-shift analysis and surface plasmon resonance (Biacore analysis).</p> <p>Conclusion</p> <p>Osmolarity-dependent changes in TTSS synthesis in <it>Shigella </it>involve the post-transcriptional regulation of InvE expression, in addition to partial transcriptional activation by <it>virF</it>. The stability of <it>invE </it>mRNA is reduced under low osmotic conditions, similar to the effect of temperature. Deletion of an RNA chaperone gene (<it>hfq</it>) abolished the repression of TTSS synthesis at low osmolarity through a mechanism that involved increased stability of <it>invE </it>mRNA. We propose that the expression of <it>Shigella </it>virulence genes in response to both osmolarity and temperature involves the post-transcriptional regulation of expression of InvE, a critical regulator of TTSS synthesis.</p

Impact of the 2011 tsunami on the littoral system around offshore breakwaters on Sendai Coast

After the 2011 Great East Japan Earthquake Tsunami, littoral system on Sendai Coast have been changing due to tsunami-induced highly non-equilibrium condition along the coast. In order to clarify the modification of littoral environment and its subsequent recovery on Sendai Coast, analysis of shoreline change has been carried out. In this study, the shoreline was extracted from frequently captured aerial photographs from 2009 until now, and analysis using an empirical orthogonal function (EOF) method was conducted. It is seen that the shoreline retreated greatly due to tsunami event. In particular, tombolo which existed behind the offshore breakwater completely disappeared due to the tsunami. Total of contribution of the 1st and 2nd EOF components is more than 70%. It is concluded that the 1st component originated from cross-shore sediment movement, while the 2nd component represents longshore sediment transport. Although the 1st component shows only slight modification after the tsunami, the 2nd component resulting from a longshore sediment transport shows distinct change after the tsunami around the offshore breakwaters

Memet Fuat, Piraye ve Nazım

Taha Toros Arşivi, Dosya Adı: Nazım Hikmetİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

An experimental study on the difficulty of error detection during drug identification: Differences in characters of drug names and doses

薬剤を患者へ投与する際には，医師や薬剤師，看護師は，患者名や薬剤名，薬剤量と いった情報を確認する．薬剤名も薬剤量も文字情報であり，処方箋や薬剤ラベルにはセット で表記されることが多い．しかし，薬剤名はカタカナ文字，薬剤量は数字と単位で構成され ており，文字のタイプが異なる．先行研究から，数字は文字と比較して差異の検出が容易で あるとされるが，薬剤名が一致している場合や，類似している場合には，それに続く薬剤量 が違っていても差異が検出されず，過剰投与や過少投与，類似する薬剤の誤薬の原因となる． そこで本研究では，薬剤名と薬剤量を個々に単独呈示した場合の識別エラーを検討する事を 目的として実験的検討を行った．実験は，パソコンの画面上に薬剤名または数字と単位で構 成される薬剤量の文字列を呈示し，それに先行して呈示される文字列が，一致しているか否 かを判断する正誤判断課題であった．実験の結果，薬剤量条件は薬剤名条件よりもエラーが 少なかった．単独呈示の場合には，薬剤量は薬剤名よりも識別が容易で，エラーを検出しや すいことが示唆された．また，薬剤名，薬剤量ともに連続して呈示される文字列が不一致の 場合に，一致している場合よりエラーが多く，反応時間も延長した．このことから，薬剤の 照合では，一致していることの確認は容易であるが，不一致の場合には検出が困難で，見逃 されやすいことが示唆された．When administering drugs to patients, doctors, pharmacists, and nurses typically confirm information such as the patient’s name, drug name, and doses. Drug names are written as letter strings with Katakana, while doses are written as numbers and units – both of which consist of characters. Previous studies have suggested that people accurately discriminate differences for number strings compared to letter strings. However, if the drug names are identical or similar, it can be determined that they are the same drugs even if the following doses are different. These will lead to administration errors such as the wrong medicine or dosage. In this study, a same-different matching task was used to investigate the identification accuracy for drug names and doses. The preceding stimuli and target stimuli were drug names that were 5-6 Katakana characters long, and doses that were 4-5 numbers long and included units（ g，mg，㎍，ng，ml，%）. Results showed that error rates were lower for doses than for drug names. Moreover, in the inconsistent trials where preceding stimuli and target stimuli did not match, there were more errors and longer reaction times in comparison to the consistent trials where the drug name and dose matched. These results suggest that doses are easier to discriminate than drug names, and that it is difficult to detect mistakes in the drug names or doses.departmental bulletin pape

Current Immunotherapeutic Approaches in Pancreatic Cancer

Pancreatic cancer is a highly aggressive and notoriously difficult to treat. As the vast majority of patients are diagnosed at advanced stage of the disease, only a small population is curative by surgical resection. Although gemcitabine-based chemotherapy is typically offered as standard of care, most patients do not survive longer than 6 months. Thus, new therapeutic approaches are needed. Pancreatic cancer cells that develop gemcitabine resistance would still be suitable targets for immunotherapy. Therefore, one promising treatment approach may be immunotherapy that is designed to target pancreatic-cancer-associated antigens. In this paper, we detail recent work in immunotherapy and the advances in concept of combination therapy of immunotherapy and chemotherapy. We offer our perspective on how to increase the clinical efficacy of immunotherapies for pancreatic cancer

Klotho and Aminopeptidases as Early Biomarkers of Renal Injury in Zucker Obese Rats

The aim of this study was to investigate if urinary glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), Klotho and hydroxyproline can be considered as potential biomarkers of renal injury and fibrosis in an experimental model of obesity. Male Zucker lean (ZL) and obese (ZO) rats were studied from 2 to 8 months old. Kidneys from ZO rats at the end of the study (8 months old) developed mild focal and segmental glomerulosclerosis as well as moderate tubulointerstitial injury. Urinary excretion of Klotho was higher in ZO rats at 2, 5, and 8 months of study, plasma Klotho levels were reduced and protein abundance of Klotho in renal tissue was similar in ZL and ZO rats. GluAp and AlaAp urinary activities were also increased in ZO rats throughout the time-course study. ZO rats showed an augmentation of hydroxyproline content in renal tissue and a significant increase of tubulointerstitial fibrosis. Correlation studies demonstrated that GluAp, AlaAp, and Klotho are early diagnostic markers of renal lesions in Zucker obese rats. Proteinuria and hydroxyproline can be considered delayed diagnostic markers because their contribution to diagnosis starts later. Another relevant result is that GluAp, AlaAp, and Klotho are related not only with diagnosis but also with prognosis of renal lesions in Zucker obese rats.This study was supported by the grants PI13/02743 and PI13/02384 from the Carlos III Health Institute of Spain, and the Red de Investigación Renal REDinREN RD16/0009/0033 “FEDER una manera de hacer Europa

Neurophysiological modeling of bladder afferent activity in the rat overactive bladder model

The overactive bladder (OAB) is a syndrome-based urinary dysfunction characterized by “urgency, with or without urge incontinence, usually with frequency and nocturia”. Earlier we developed a mathematical model of bladder nerve activity during voiding in anesthetized rats and found that the nerve activity in the relaxation phase of voiding contractions was all afferent. In the present study, we applied this mathematical model to an acetic acid (AA) rat model of bladder overactivity to study the sensitivity of afferent fibers in intact nerves to bladder pressure and volume changes. The afferent activity in the filling phase and the slope, i.e., the sensitivity of the afferent fibers to pressure changes in the post-void relaxation phase, were found to be significantly higher in AA than in saline measurements, while the offset (nerve activity at pressure ~0) and maximum pressure were comparable. We have thus shown, for the first time, that the sensitivity of afferent fibers in the OAB can be studied without cutting nerves or preparation of single fibers. We conclude that bladder overactivity induced by AA in rats is neurogenic in origin and is caused by increased sensitivity of afferent sensors in the bladder wall