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Pharmacology & Pharmacy 2012年第3期3卷 316-321页

作者： Yuta Takahashi Shizuyo Horiyama Yoko Kimoto Noriko Yoshikawa Masaru Kunitomo Satomi Kagota kazumasa shinozuka Kazuki Nakamura Analytical Center School of Pharmacy and Pharmaceutical Sciences Mukogawa Women’s University Nishinomiya Japan Department of Pharmacology School of Pharmacy and Pharmaceutical Sciences Mukogawa Women’s University Nishinomiya Japan Institute for Biosciences Mukogawa Women’s University Nishinomiya Japan

We investigated the effect of a nicotine-and tar-free cigarette smoke extract (CSE) using an experimental metastasis mouse model which was intravenously injected with B16-BL6 mouse melanoma cells. Three-hour pretreatment of cells with various concentrations of CSE (0, 0.1, 0.3, and 1%) dose-dependently reduced the number of lung metastatic nodules 14 days after tumor injection. To elucidate the mechanism of this anti-metastatic effect of CSE, we examined the invasion and migration activities of B16-BL6 cells pretreated with CSE for three hours in vitro. CSE significantly reduced the invasion of cells at 1% and the migration at 0.3% and 1%. Under the same pretreatment conditions, CSE had no effect on the proliferation of cells. These findings suggest that CSE contains some ingredients that suppress hematogenic lung metastasis via inhibition of the invasion and migration activities of mouse melanoma cells.

关键词： Cigarette Smoke Extract (CSE) Anti-Metastasis B16-BL6 Mouse Melanoma Cells Invasion Migration

<i>Cordyceps sinensis</i>Acts As an Adenosine A<sub>3</sub>Receptor Agonist on Mouse Melanoma and Lung Carcinoma Cells, and Human Fibrosarcoma and Colon Carcinoma Cells

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Pharmacology & Pharmacy 2011年第4期2卷 266-270页

作者： Noriko Yoshikawa Arisa Nishiuchi Erika Kubo Yu Yamaguchi Masaru Kunitomo Satomi Kagota kazumasa shinozuka Kazuki Nakamura 不详

Cordyceps sinensis, a parasitic fungus on the larva of Lapidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells and mouse Lewis lung carcinoma (LLC) cells was inhibited by cordycepin (3’-deoxyadenosine), an ingredient of Cordyceps sinensis, and its effect was antagonized by MRS1191, a selective adenosine A3 receptor (A3-R) antagonist although adenosine (up to 100 μM) had no effect on the growth of B16-BL6 and LLC cells. In this study, we investigated whether water extracts of Cordyceps sinensis (WECS) inhibit the growth of B16-BL6 cells, LLC cells, HT1080 human fibrosarcoma (HT1080) cells and CW-2 human colon carcinoma (CW-2) cells via their A3-R. As a result, the growth of all cell lines were potently inhibited by WECS (10 μg/mL) and the inhibitory effect of WECS was significantly antagonized by MRS1191 (1 μM). Furthermore, WECS included 2.34% w/w cordycepin and 0.12% w/w adenosine as components according to the HPLC- ECD system. In conclusion, WECS inhibited the proliferation of four cancer cell lines by stimulation of A3-R and the main component in WECS with anticancer action might be cordycepin instead of adenosine.

关键词： Cordyceps Sinensis Adenosine A3 Receptor Cordycepin HPLC-ECD

Experimental verification of bridge seismic damage states quantified by calibrating analytical models with empirical field data

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Earthquake Engineering and Engineering Vibration 2008年第4期7卷 383-393页

作者： Swagata Banerjee Masanobu shinozuka Department of Civil and Environmental Engineering University of California

Bridges are one of the most vulnerable components of a highway transportation network system subjected to earthquake ground motions. Prediction of resilience and sustainability of bridge performance in a probabilistic manner provides valuable information for pre-event system upgrading and post-event functional recovery of the network. The current study integrates bridge seismic damageability information obtained through empirical, analytical and experimental procedures and quantifies threshold limits of bridge damage states consistent with the physical damage description given in HAZUS. Experimental data from a large-scale shaking table test are utilized for this purpose. This experiment was conducted at the University of Nevada, Reno, where a research team from the University of California, Irvine, participated. Observed experimental damage data are processed to identify and quantify bridge damage states in terms of rotational ductility at bridge column ends. In parallel, a mechanistic model for fragility curves is developed in such a way that the model can be calibrated against empirical fragility curves that have been constructed from damage data obtained during the 1994 Northridge earthquake. This calibration quantifies threshold values of bridge damage states and makes the analytical study consistent with damage data observed in past earthquakes. The mechanistic model is transportable and applicable to most types and sizes of bridges. Finally, calibrated damage state definitions are compared with that obtained using experimental findings. Comparison shows excellent consistency among results from analytical, empirical and experimental observations.

关键词： highway bridges nonlinear time history analysis fragility curves threshold damage limits mechanisticmodel calibration

Screening Method for 23 Alkaloids in Human Serum Using LC/MS/MS with a Pentafluorophenyl Column in Dynamic Multiple Reaction Monitoring Mode

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American Journal of Analytical Chemistry 2022年第11期13卷 399-414页

作者： Chizuko Sasaki Tatsuo shinozuka Fumiko Satoh Department of Legal Medicine Kitasato University School of Medicine Sagamihara Japan Department of Pathophysiology Yokohama University of Pharmacy Yokohama Japan

Alkaloids are nitrogen-containing organic compounds, generally basic, and found in plants, fungi, and bacteria. Some alkaloids are used in medicine, but some compounds are highly toxic. Accidental ingestion, homicide, and suicide have occurred due to plants containing alkaloids. The identification of toxic components in biological samples is important for the diagnosis and/or treatment of poisoning cases in forensic and emergency medicine. Alkaloids have a wide variety of structures, such as isoquinoline alkaloid, indole alkaloid, tropane alkaloid, and diterpene alkaloid;therefore, there are few reports of simultaneous analysis methods. We have established a method for the simultaneous analysis of 23 alkaloids in human serum with a liquid chromatograph-tandem mass spectrometer (LC/MS/MS). A liquid-liquid extraction which was modified from the first step of the QuEChERS AOAC method was used for serum pretreatment. The separation of the compounds was performed using a pentafluorophenyl (PFP) column, CAPCELL CORE PFP (2.1 mm I.D. × 100 mm, 2.7 μm) in gradient mode. Mobile phase A consisted of 10 mM ammonium formate and 0.1% formic acid in ultrapure water, and mobile phase B was 10 mM ammonium formate and 0.1% formic acid in methanol. Simultaneous analysis was performed in dynamic multiple reaction monitoring mode. The separation of 23 alkaloids was satisfactory, as PFP columns exhibited different retention behaviors than alkyl phase columns. The PFP column effectively retained polar aromatic compounds;therefore, it was suitable for alkaloid analysis. The validated method was applied to a forensic case of aconite poisoning. The present method was useful in LC/MS/MS screening for 23 alkaloids in human serum.

关键词： Alkaloid Pentafluorophenyl Column LC/MS/MS QuEChERS Simultaneous Analysis

Effect of seismic retrofit of bridges on transportation networks

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Earthquake Engineering and Engineering Vibration 2003年第2期2卷 169-179页

作者： Masanobu shinozuka Yuko Murachi Michal J.Orlikowski Department of Civil and Environmental Engineering University of CaliforniaIrvineUSA Distinguished Professor and Chair Department of Civil and Environmental Engineering University of CaliforniaIrvineUSA Research Associate Department of Civil and Environmental Engineering Princeton UniversityUSA Undergraduate Student.

The objective of this research is to determine the effect earthquakes have on the performance of transportation network *** do this,bridge fragility curves,expressed as a function of peak ground acceleration(PGA)and peak ground velocity(PGV),were *** damage was evaluated under the 1994 Northridge earthquake and scenario earthquakes.A probabilistic model was developed to determine the effect of repair of bridge damage on the improvement of the network performance as days passed after the *** an example,the system performance degradation measured in terms of an index,'Drivers Delay,'is calculated for the Los Angeles area transportation system,and losses due to Drivers Delay with and without retrofit were estimated.

关键词： fragility curves seismic retrofit probabilistic model bridges transportation networks drivers delay performance index Northridge earthquake.

LC-MS/MS Analysis of Lycorine and Galantamine in Human Serum Using Pentafluorophenyl Column

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American Journal of Analytical Chemistry 2022年第9期13卷 300-313页

作者： Chizuko Sasaki Tatsuo shinozuka Kuniko Yoshimura Takaaki Maruhashi Yasushi Asari Fumiko Satoh Department of Legal Medicine School of Medicine Kitasato University Sagamihara Japan Department of Pathophysiology Yokohama University of Pharmacy Yokohama Japan Department of Emergency and Critical Care Medicine School of Medicine Kitasato University Sagamihara Japan

Lycorine and galantamine are natural alkaloids found in Amaryllidaceae plants, such as narcissus. Narcissus leaves and roots are sometimes accidentally ingested because they resemble vegetables. Lycorine and galantamine are toxic and cause such effects as nausea, vomiting, and abdominal pain, when accidentally ingested. In a case of narcissus poisoning, the detection of lycorine and galantamine in biological samples is vital to determine whether they have been ingested. This study establishes a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to measure the lycorine and galantamine content of human serum, which can be used for mild to fatal poisoning cases. A serum pretreatment procedure was performed using acetonitrile and QuEChERS AOAC powder. The separation of the compounds was conducted using a pentafluorophenyl column, CAPCELL CORE PFP (2.1 mm I.D. × 100 mm, 2.7 μm). Lycorine, galantamine, and galantamine-d6 (internal standard) were identified by the transitions of m/z 288 → 147, m/z 288 → 213, and m/z 294 → 216, respectively. The calibration curves were linear in the ranges of 0.05 to 5 ng/mL and 5 to 100 ng/mL, with R2 > 0.999. The precision and accuracy were within the permissible range. The matrix effects of lycorine and galantamine were 94.3% - 98.4% and 87.8% - 91.1%, respectively. The extraction recovery rates of lycorine and galantamine were 101.9% - 112.7% and 95.6% - 107.1%, respectively. The present method detected lycorine and galantamine in the sera of three patients with mild poisoning that had accidentally ingested. This method is applicable in cases of lycorine and galantamine poisoning.

关键词： Lycorine Galantamine Narcissus Pentafluorophenyl Column LC/MS/MS

Angiosarcoma of the scalp diagnosed by the presence of neck inflammation:a case report

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International Journal of Oral Science 2012年第3期4卷 166-169页

作者： Rei Karube Hiroyoshi Sasaki Keiji shinozuka Yasuhiro Fujisawa Toru Yanagawa Kenji Yamagata Kojiro Onizawa Fujio Otsuka Hiroki Bukawa Department of Oral and Maxillofacial Surgery Faculty of MedicineUniversity of Tsukuba Department of Dermatology Faculty of MedicineUniversity of Tsukuba

Angiosarcoma is an uncommon malignancy, which spread out from the endothelial cells of vessels. Scalp angiosarcoma with cervical lymph node metastasis is particularly rare. This article describes a rare case of angiosarcoma of the scalp, presenting as neck inflammation. Imaging procedures such as computed tomography （CT）, magnetic resonance image （MRI） and ultrasonography （US） were not sufficient to diagnose this case. A needle biopsy provided an effective and accurate diagnosis of cervical lymph node metastasis. Additional observation and physical examination was required to diagnose the origin of the primary cancerous lesion. Once the angiosarcoma diagnosis was confirmed histologically, sequential weekly and monthly docetaxel （DTX） treatment was effective in preventing reoccurrence. Nonetheless, the optimization of angiosarcoma treatment remains a future goal. Although patients generally describe pain and swelling at the primary lesion site, this patient complained only of painful neck inflammation, without any indication of pain or swelling of the scalp. A revised diagnostic protocol should note that cervical lymph node metastasis of unknown primary origin may result from angiosarcoma of the scalp.

关键词： angiosarcoma docetaxel neck inflammation needle biopsy scalp

Effectiveness of Radiofrequency Ablation of Initial Recurrent Hepatocellular Carcinoma after Hepatectomy: Long-Term Results and Prognostic Factors

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Open Journal of Radiology 2017年第3期7卷 177-189页

作者： Ken shinozuka Toshiya Shibata Rinpei Imamine Masako Kataoka Kaori Togashi Department of Radiology Kyoto University Graduate School of Medicine Kyoto Japan Department of Radiology Kyoto College of Medical Science Kyoto Japan

Background: Intrahepatic recurrence of hepatocellular carcinoma (HCC) is frequently noted in patients after hepatectomy of HCC. Recurrence HCC is usually diagnosed as small nodule ≤ 2 cm in diameter due to the frequent postoperative check up with US, dynamic CT, or dynamic EOB-MRI. Radiofrequency ablation (RFA) is recommended for these small HCCs, because RFA is minimally invasive, effective, and repeatedly performed. Purpose: To investigate the long-term outcome and prognostic factors of RFA in recurrent HCC after heaptectomy. Material and Methods: Between February 2002 and October 2011, 75 patients with initial intrahepatic recurrence of HCC after hepatectomy underwent RFA. The 57 patients were men and 18 women, whose age ranged from 44 years to 83 years (median, 69 years). Sixty-nine patients had a single nodule and 6 patients had two nodules. The size of the 81 nodules ranged 5 - 30 mm (median, 15 mm). Regular follow-up after RFA was performed to evaluate rates of local tumor progression, overall survival rates, and disease-free survival rates. Prognostic factors related to overall survivals and disease-free survivals were evaluated, too. Results: During follow-up periods after RFA (3 to 151 months, median, 55 months), local recurrence was noted in 10 nodules of 10 patients (10/81 nodules = 12.3%). The rates of local recurrence of 1-yr, 3-yr, 5-yr, and 8-yr were 7.6%, 12.0%, 12.0%, and 12.0%, respectively. During the follow-up periods, 36 patients were alive and 39 died. The cumulative overall survival rates of 1-yr, 3-yr, 5-yr, and 10-yr were 97.3%, 79.1%, 56.6%, and 32.2%, respectively. The cumulative disease-free survival rates of 1-yr, 3-yr, and 5-yr were 42.7%, 18.8%, and 12.6%, respectively. Child-Pugh Class (A or B) before RFA for a recurrent HCC was a significant prognostic predictor of overall survival rates (p = 0.007), and Child-Pugh class (A or B) before hepatectomy was that of disease-free survival rates (p = 0.004). Conclusion: RFA was an effective

关键词： Hepatocellular Carcinoma (HCC) Recurrent HCC Radiofrequency Ablation (RFA)

Screening Method for 23 Alkaloids in Human Serum Using LC/MS/MS with a Pentafluorophenyl Column in Dynamic Multiple Reaction Monitoring Mode

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Sensitive Liquid Chromatography/Tandem Mass Spectrometry Method for the Simultaneous Determination of Risperidone, Olanzapine, Quetiapine, Clozapine, Ziprasidone, Perospirone, Aripiprazole and Blonanserin in Human Serum

American Journal of Analytical Chemistry 2022年第11期

作者： chizuko sasaki tatsuo shinozuka fumiko satoh

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American Journal of Analytical Chemistry 2018年第2期9卷 88-97页

作者： Keiko Tonooka Lynn Yoshida Koji Tomobe Yoko Kunisue Masaru Terada Tatsuo shinozuka Department of Pathophysiology Yokohama University of Pharmacy Kanagawa Japan Foundation for Promotion of Material Science and Technology of Japan Tokyo Japan

The sensitive method for the simultaneous determination of eight atypical antipsychotic drugs (risperidone, olanzapine, quetiapine, clozapine, ziprasidone, perospirone, aripiprazole and blonanserin) in human serum has been developed based on a high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) with electrospray ionization (ESI). The chromatographic separation was performed on a Mightysil-RP-18 MS column (2.0 mm × 150 mm, particle size 3 μm). The mobile phase consisted of 10 mM formic ammonium buffer (pH 6.0) and acetonitrile and was delivered at a flow rate of 0.20 mL/min. The triple quadrupole mass spectrometer was operated in positive ion mode, and multiple reaction monitoring was used for drug quantification. Solid-phase extraction of the eight antipsychotic drugs added to the human serum was performed with an Oasis®HLB extraction cartridges column. The method was linear for the investigated drugs over the concentration range of 20 - 100 ng/mL. The recoveries of these drugs were in the range of 81.3% - 140%. The intraday and inter day standard deviation (SD) values for all analytes were <0.10. Therefore, the selectivity, accuracy and precision of this method are sufficient for clinical and forensic studies. This simultaneous screening method will be also applicable to analyze other atypical antipsychotic drugs.

关键词： LC/MS/MS Atypical Antipsychotic Drugs Analysis Solid Phase Extraction