研究者詳細 - 川部　勤

SHIP recruitment attenuates FcγRIIB-induced B cell apoptosis 査読有り

Pearse R., Kawabe T., Bolland S., Guinamard R., Kurosaki T., Ravetch J.

Immunity 10 巻 ( 6 ) 頁： 753 - 760 1999年6月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Immunity

FcγRIIB is an inhibitory receptor that terminates activation signals initiated by antigen cross-linking of the BCR through the recruitment of SHIP. FcγRIIB can also signal independently of BCR coligation to directly mediate an apoptotic response, requiring only an intact transmembrane domain. Failure to recruit SHIP, either by deletion of SHIP or mutation of FcγRIIB, results in enhanced FcγRIIB-triggered apoptosis. Thus, in the germinal center, where ICs are retained by FDCs, FcγRIIB may be an active determinant in the negative selection of B cells whose BCRs have reduced affinity for antigen as a result of somatic hypermutation. Selection of B cells may represent the sum of opposing signals generated by the interaction of ICs with the BCR and FcγRIIB through pathways modulated by SHIP.

DOI： 10.1016/S1074-7613(00)80074-6

Immunosuppressive activity induced by nitric oxide in culture supernatant of activated rat alveolar macrophages 査読有り

Kawabe T, Isobe K, Hasegawa Y, Nakashima I, Shimokata K

Immunology 76 巻 ( 1 ) 頁： 72-78 1992年4月

T Cell Development in Mice Lacking All T Cell Receptor ζ Family Members (ζ, η, and FcεRIγ) 査読有り

Shores EW, Ono M, Kawabe T, Sommers CL, Tran T, Lui K, Udey MC, Ravetch J, Love PE

J Exp Med 187 巻 ( 7 ) 頁： 1093-1101 1998年4月

Investigation of Calibration Methodology Using Mouth Airflow for Wearable Sensor Toward Quantitative Respiration Monitoring 招待有り査読有り

Kenta Horie, Muhammad Salman Al Farisi, Yoshihiro Hasegawa, Miyoko Matsushima, Tsutomu Kawabe, Mitsuhiro Shikida

IEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING 19 巻 ( 5 ) 2024年3月

Pitot Tube Sensor Probe System for Simultaneous Airflow and Pressure Measurement of Expiration Inside Pulmonary Airway 査読有り

Aoi Miyawaki, Muhammad Salman Al Farisi, Yoshihiro Hasegawa, Miyoko Matsushima, Tsutomu Kawabe, Mitsuhiro Shikida

IEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING 19 巻 ( 5 ) 2024年2月

Facile In-Tube-Center Packaging of Flexible Airflow Rate Microsensor for Simultaneous Respiration and Heartbeat Measurement 査読有り

Muhammad Salman Al Farisi, Yang Wang, Yoshihiro Hasegawa, Miyoko Matsushima, Tsutomu Kawabe, Mitsuhiro Shikida

IEEE SENSORS JOURNAL 23 巻頁： 12626 - 12633 2023年6月

Decrease in cholesterol in the cell membrane is essential for Nrf2 activation by quercetin. 査読有り国際誌

The Journal of nutritional biochemistry 頁： 109329 2023年3月

Neonatal lethality of mouse A/J-7SM consomic strain is caused by an insertion mutation in the Dchs1 gene. 査読有り

Miyasaka Y, Kobayashi T, Gotoh N, Kuga M, Kobayashi M, Horio F, Hashimoto K, Kawabe T, Ohno T.

Mamm Genome 34 巻 ( 1 ) 頁： 32 - 43 2023年3月

The fruits of CD40 research in basic and clinical medicine will soon be harvested. 100th Anniversary of Nagoya J Med Sci: Comments to the Highly Cited Articles. 招待有り査読有り

Tsutomu Kawabe

Nagoya Journal of Medical Science 85 巻頁： 21 - 22 2023年2月

Analysis of Airstream Inside the Slip Joint of Tracheal Intubation Tube for Breathing Measurement. 査読有り

Tsukada, T., Hasegawa, Y., Al Farisi, M.S, Matsushima, M., Kawabe, T., Shikida, M.

IEEJ Transactions on Sensors and Micromachines 143 巻 ( 1 ) 頁： 6 - 12 2023年1月

Development of MEMS Flow and Pressure Sensor Device for Detection of Extravasation at an Early Stage. 査読有り

Hasegawa, Y., Shimohira, C., Matsushima, M., Sugiyama, T., Kawabe, T., Shikida, M.

IEEJ Transactions on Sensors and Micromachines 18 巻 ( 1 ) 頁： 139 - 146 2023年1月

Correlation of theophylline levels in rat exhaled breath and lung tissue after its intravenous injection 査読有り国際誌

Matsushima Miyoko, Tanihata Souma, Kusakabe Junpei, Okahira Momoha, Ito Hiroshi, Yamamoto Atsushi, Yamamoto Masanori, Yamamoto Ryohei, Kawabe Tsutomu

JOURNAL OF BREATH RESEARCH 16 巻 ( 3 ) 2022年7月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Breath Research

It is important to know the drug level in the target tissue to determine its dose. Some methods rely on blood levels of a drug to estimate its concentration in the tissues, which can be inaccurate. We thought that drug levels in exhaled breath aerosol (EBA) to give a more accurate value of the level of a test drug in the lung. Rats were intravenously injected with the bronchodilator theophylline and exhaled breath was collected up to 10-20 min after administration. Immediately after breath collection, lung, liver, kidney, and blood were collected and the pharmacokinetics were examined using these samples. Awake free-moving rats were used to efficiently collect exhaled breath from rats with low tidal volume. The amount of exhaled breath of rats was estimated by the amount of exhaled water vapor, and the drug concentration in exhaled breath sample was expressed by the amount of water vapor as the denominator. By using the active sampling method in which the adsorbent is sucked by a pump, theophylline in rat exhaled breath could be measured accurately. When the correlation of theophylline concentration in each sample was examined, a high correlation (r 2 = 0.74) was found only in exhaled breath and lung tissue. EBA was considered better than blood in pharmacokinetic analysis of lung tissue.

DOI： 10.1088/1752-7163/ac6b4b

Resistance to mutant KRASV12-induced senescence in an hTERT/Cdk4-immortalized normal human bronchial epithelial cell line. 査読有り国際共著国際誌

Muraki N, Yamada M, Doki H, Nakai R, Komeda K, Goto D, Kawabe N, Matsuoka K, Matsushima M, Kawabe T, Tanaka I, Morise M, Shay JW, Minna JD, Sato M

Experimental cell research 414 巻 ( 1 ) 頁： 113053 2022年5月

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

Mutant KRAS, the most frequently occurring (∼30%) driver oncogene in lung adenocarcinoma, induces normal epithelial cells to undergo senescence. This phenomenon, called “oncogene-induced senescence (OIS)”, prevents mutant KRAS-induced malignant transformation. We have previously reported that mutant KRASV12 induces OIS in a subset of normal human bronchial epithelial cell line immortalized with hTERT and Cdk4. Understanding the mechanism and efficacy of this important cancer prevention mechanism is a key knowledge gap. Therefore, this study investigates mutant KRASV12-induced OIS in upregulated telomerase combined with the p16/RB pathway inactivation in normal bronchial epithelial cells. The normal (non-transformed and non-tumorigenic) human bronchial epithelial cell line HBEC3 (also called “HBEC3KT”), immortalized with hTERT (“T”) and Cdk4 (“K”), was used in this study. HBEC3 that expressed mutant KRASV12 in a doxycycline-regulated manner was established (designated as HBEC3-RIN2). Controlled induction of mutant KRASV12 expression induced partial epithelial-to-mesenchymal transition in HBEC3-RIN2 cells, which was associated with upregulated expression of ZEB1 and SNAIL. Mutant KRASV12 caused the majority of HBEC3-RIN2 to undergo morphological changes; suggestive of senescence, which was associated with enhanced autophagic flux. Upon mutant KRASV12 expression, only a small HBEC3-RIN2 cell subset underwent senescence, as assessed by a senescence-associated β-galactosidase staining (SA-βG) method. Furthermore, mutant KRASV12 enhanced cell growth, evaluated by colorimetric proliferation assay, and liquid and soft agar colony formation assays, partially through increased phosphorylated AKT and ERK expression but did not affect cell division, or cell cycle status. Intriguingly, mutant KRASV12 reduced p53 protein expression but increased p21 protein expression by prolonging its half-life. These results indicate that an hTERT/Cdk4 -immortalized normal bronchial epithelial cell line is partially resistant to mutant KRASV12-induced senescence. This suggests that OIS does not efficiently suppress KRASV12-induced transformation in the context of the simultaneous occurrence of telomerase upregulation and inactivation of the p16/Rb pathway.

DOI： 10.1016/j.yexcr.2022.113053

Miniaturization of Respiratory Measurement System in Artificial Ventilator for Small Animal Experiments to Reduce Dead Space and Its Application to Lung Elasticity Evaluation 査読有り

Wireless Stent Flow Sensor System for the Evaluation of Breathing Airflow in the Airway of Experimental Animals 査読有り

Hasegawa Yoshihiro, Noma Hayato, Matsushima Miyoko, Hasegawa Shin, Kawabe Tsutomu, Shikida Mitsuhiro

IEEJ Transactions on Sensors and Micromachines 142 巻 ( 1 ) 頁： 2 - 7 2022年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：The Institute of Electrical Engineers of Japan

A wireless stent flow sensor system was developed to evaluate the changes in breathing characteristics in the airways of experimental animals caused due to drug administration under free movement conditions for drug development. The system was composed of a stent flow sensor, a signal conditioning module, and a PC module. To develop the stent flow sensor, a tube flow sensor and a stent structure were separately fabricated, and they were interlocked at the connection area formed on both elements. The analog sensor outputs were converted into digital outputs with a sampling frequency of 1.0 kHz in a signal conditioning module and transmitted to a PC module through Bluetooth Low Energy 5.0 operated at 2.4 GHz, as the wireless communication. The stent flow sensor and the signal conditioning module were operated using a 165-mAh battery. A simulation experiment was conducted using a plush doll after obtaining calibration curves. A transparent tube was used as the airway and it was placed inside the doll, and an artificial ventilator designed for a small experimental animal was connected to the tube. The stent flow sensor fixed inside the tube was connected to the airway tube, and the signal conditioning module was placed on the back of the neck of the doll. The stent flow sensor output was successfully transmitted to the PC module through Bluetooth. It was demonstrated that the system developed in this study can measure the breathing airflow with a tidal volume accuracy of less than 3.7%.

DOI： 10.1541/ieejsmas.142.2

CiNii Research

Advancements in MEMS technology for medical applications: Microneedles and miniaturized sensors 査読有り国際誌

Shikida M., Hasegawa Y., Farisi M.S.A., Matsushima M., Kawabe T.

Japanese Journal of Applied Physics 61 巻 ( SA ) 2022年1月

Yoshida Homare, Hasegawa Yoshihiro, Matsushima Miyoko, Sugiyama Tomoshi, Kawabe Tsutomu, Shikida Mitsuhiro

SENSORS 21 巻 ( 15 ) 2021年8月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Sensors

A respiratory measurement system composed of pressure and airflow sensors was introduced to precisely control the respiratory condition during animal experiments. The flow sensor was a hot‐wire thermal airflow meter with a directional detection and airflow temperature change compensation function based on MEMS technology, and the pressure sensor was a commercially available one also produced by MEMS. The artificial dead space in the system was minimized to the value of 0.11 mL by integrating the two sensors on the same plate (26.0 mm × 15.0 mm). A balloon made of a silicone resin with a hardness of A30 was utilized as the simulated lung system and applied to the elasticity evaluation of the respiratory system in a living rat. The inside of the respiratory system was normally pressurized without damage, and we confirmed that the devel-oped system was able to evaluate the elasticity of the lung tissue in the rat by using the pressure value obtained at the quasi‐static conditions in the case of the ventilation in the animal experiments.

DOI： 10.3390/s21155123

Fibroblasts positive for meflin have anti-fibrotic property in pulmonary fibrosis. 査読有り

Nakahara Y, Hashimoto N, Sakamoto K, Enomoto A, Adams TS, Yokoi T, Omote N, Poli S, Ando A, Wakahara K, Suzuki A, Inoue M, Hara A, Mizutani Y, Imaizumi K, Kawabe T, Rosas IO, Takahashi M, Kaminski N, Hasegawa Y

The European respiratory journal 2021年5月

Micro-machined stent flow sensor for detecting breathing and heartbeat from airflow in airway of rat 査読有り

Noma H., Hasegawa Y., Matsushima M., Kawabe T., Shikida M.

Journal of Micromechanics and Microengineering 31 巻 ( 2 ) 2021年2月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Micromechanics and Microengineering

We developed a stent flow sensor using micro-electromechanical systems (MEMS) technology in order to measure airflow in the airways of laboratory animals. An airflow waveform contains a respiration signal produced by lung motion and heartbeats as these functions are physically connected. This enables both respiration and heart functions to be evaluated under unrestrained and unanesthetized conditions during drug development. Using MEMS technology, we fabricated a tube flow sensor based on a thermal principle, and the stent structure was produced by photolithography and wet etching. The fabricated flow sensor and stent were integrated via a connection area on both elements. In the proof-of-concept trial, we verified that the flow sensor was placed in the center of the tube by expanding the stent. We evaluated the flow detection characteristics, sensor output vs flow rate and sensor response and used the developed stent flow sensor to measure the airflow in the airway of a rat. The respiration and heartbeat signals were successfully identified from the airflow waveform by applying Fourier transform analysis.

DOI： 10.1088/1361-6439/abd07a

Development of sensor-probe system with function of measuring flow and pressure for evaluating breathing property at airway in lungs 査読有り

Fibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis 査読有り国際共著

European Respiratory Journal 58 巻 ( 6 ) 頁： 2003397 2021年

KAWAMOTO Yuji, MAEDA Yoshihumi, HASEGAWA Yoshihiro, MATSUSHIMA Miyoko, KAWABE Tsutomu, SHIKIDA Mitsuhiro

Microsystem Technologies 2021年

Catheter sensor system for in-situ breathing and optical imaging measurements at airway in inside of lung 査読有り

MAEDA Yoshihumi, HASEGAWA Yoshihiro, TANIGUCHI Kazuhiro, MATSUSHIMA Miyoko, SUGIYAMA Tomoshi, KAWABE Tsutomu, SHIKIDA Mitsuhiro

Microsystem Technologies 26 巻 ( 12 ) 頁： 3705 - 3713 2020年12月

Involvement of heme oxygenase-1 in suppression of T cell activation by quercetin 査読有り

Sugiyama Tomoshi, Matsushima Miyoko, Ohdachi Tomoko, Hashimoto Naozumi, Hasegawa Yoshinori, Yokoi Kohei, Kawabe Tsutomu

Immunopharmacology and immunotoxicology 42 巻 ( 4 ) 頁： 295 - 305 2020年8月

Micro-machined respiratory monitoring system development for artificial ventilator in animal experiment 査読有り

Yoshida Homare, Hasegawa Yoshihiro, Matsushima Miyoko, Sugiyama Tomoshi, Kawabe Tsutomu, Shikida Mitsuhiro

Microsystem Technologies 26 巻 ( 12 ) 頁： 3715 - 3724 2020年4月

Development of micromachined flow sensor for drip infusion system 査読有り

Shimohira Chihiro, Hasegawa Yoshihiro, Taniguchi Kazuhiro, Matsushima Miyoko, Kawabe Tsutomu, Shikida Mitsuhiro

Microsystem Technologies 26 巻 ( 12 ) 頁： 3677 - 3683 2020年4月

UHRF1, a Regulator of Methylation, as a Diagnostic and Prognostic Marker for Lung Cancer 査読有り

Goto Daiki, Komeda Kazuki, Uwatoko Natsuki, Nakashima Moeka, Koike Mayu, Kawai Kaho, Kodama Yuta, Miyazawa Ayako, Tanaka Ichidai, Hase Tetsunari, Morise Masahiro, Hasegawa Yoshinori, Kawabe Tsutomu, Sato Mitsuo

Cancer investigation 38 巻 ( 4 ) 頁： 240 - 249 2020年4月

Energy-less respiration monitoring device using thermo-sensitive film 査読有り

Maeda Yoshihumi, Hasegawa Yoshihiro, Taniguchi Kazuhiro, Matsushima Miyoko, Kawabe Tsutomu, Shikida Mitsuhiro

Microsystem Technologies 26 巻 ( 2 ) 頁： 489 - 497 2020年2月

Body temperature measurement based on breathing airflow for continuous monitoring of patient body condition during large scale disasters

Fujinori Tomohiro, Hasegawa Yoshihiro, Matsushima Miyoko, Kawabe Tsutomu, Shikida Mitsuhiro

25 巻 ( 11 ) 頁： 4313 - 4321 2019年11月

Mouse NC/Jic strain provides novel insights into host genetic factors for malaria research. 査読有り

Ohno T, Miyasaka Y, Kuga M, Ushida K, Matsushima M, Kawabe T, Kikkawa Y, Mizuno M, Takahashi M

Experimental animals 68 巻 ( 3 ) 頁： 243-255 2019年8月

A micro-machined flow sensor formed on copper on a polyimide substrate and its application to respiration measurement 査読有り

Kato Ayami, Hasegawa Yoshihiro, Taniguchi Kazuhiro, Matsushima Miyoko, Kawabe Tsutomu, Shikida Mitsuhiro

JAPANESE JOURNAL OF APPLIED PHYSICS 58 巻 ( SD ) 2019年6月

Repressive role of stabilized hypoxia inducible factor 1 α expression on transforming growth factor beta-induced extracellular matrix production in lung cancer cells 査読有り

Ando Akira, Hashimoto Naozumi, Sakamoto Koji, Omote Norihito, Miyazaki Shinichi, Nakahara Yoshio, Imaizumi Kazuyoshi, Kawabe Tsutomu, Hasegawa Yoshinori

CANCER SCIENCE 110 巻 ( 6 ) 頁： 1959-1973 2019年6月

Wavelength Dependence of Ultrahigh-Resolution Optical Coherence Tomography Using Supercontinuum for Biomedical Imaging 招待有り査読有り

Nishizawa Norihiko, Kawagoe Hiroyuki, Yamanaka Masahito, Matsushima Miyoko, Mori Kensaku, Kawabe Tsutomu

IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS 25 巻 ( 1 ) 2019年

呼気への不揮発性化合物の排泄機構とその非侵襲的薬物モニタリングへの応用招待有り査読有り

山本　敦、山本良平、川部　勤

ぶんせき 2018 巻 ( 12 ) 頁： 534 - 539 2018年12月

Analysis of measurement conditions for detecting change in vital signs with catheter flow sensor 査読有り

Hasegawa Y., Mitsunari Y., Kawaoka H., Matsushima M., Kawabe T., Shikida M.

JOURNAL OF MICROMECHANICS AND MICROENGINEERING 28 巻 ( 10 ) 2018年10月

Catheter type thermal flow sensor with small footprint for measuring breathing function 査読有り

Y. Hasegawa, H. Kawaoka, Y. Mitsunari, M. Matsushima, T. Kawabe, M. Shikida

Microsystem Technologies 24 巻 ( 8 ) 頁： 3455 - 3465 2018年8月

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

We preivously developed a catheter type flow sensor for measuring breathing and heartbeat information from breathing at the mouth [Hasegawa et al. J Micromech Microeng 27(12): 125016, (2017)
Kawaoka et al. Tech. Dig. IEEE Micro Electro Mechanical Systems Conference 2016, pp 359–362]. In this study, we redesigned and developed the new sensor configuraiton for the catheter flow sensor to downsize and improve the sensor characteristics. The previous flow sensor consists of two pairs of a heater and a temperature compensation sensor for flow rate detection. The two heaters also functioned not only for flow rate detection but also for flow direction detection. The two temperature compensation sensors had a large footprint and corresponded to each heater. Therefore, the sensor occupied a large area, and it was necessary to match the heater characteristics for flow rate detection. The newly designed sensor is composed of a set of a heater and a temperature compensation sensor and two flow direction sensors. By providing the new flow direction sensors, the number of temperature compensation sensors with a large footprint was reduced to one. Thus, the area of the new sensor design was 15.0 mm2, which was reduced to 54.5% of the 27.0 mm2 of the previous sensor area by providing the flow direction sensors. Then, the new catheter type flow sensor was fabricated, and the flow characteristics for measuring breathing funciton were evaluated. Finally, we applied the catheter type flow sensor to an animal experiment using a rat, and it could evaluate the flow rate characteristics of the rat’s breathing as a reciprocating flow including flow direction. Moreover, the obtained breathing characteristics were within the range of the physiological values of rats.

DOI： 10.1007/s00542-018-3748-y

Development of tube flow sensor by using film transfer technology and its application to in situ breathing and surface image evaluation in airways

24 巻 ( 8 ) 頁： 3417 - 3424 2018年8月

Obstetric factors associated with salivary cortisol levels of healthy full-term infants immediately after birth

Takahashi Y., Matsushima M., Nishida T., Tanabe K., Kawabe T., Tamakoshi K.

CLINICAL AND EXPERIMENTAL OBSTETRICS & GYNECOLOGY 45 巻 ( 6 ) 頁： 828-832 2018年

Characterization of basket-forceps-type micro-flow-sensor for breathing measurements in small airway 査読有り

Naoaki Harada, Yoshihiro Hasegawa, Ryota Ono, Miyoko Matsushima, Tsutomu Kawabe, Mitsuhiro Shikida

Microsystem Technologies 23 巻 ( 12 ) 頁： 5397 - 5406 2017年12月

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

We previously proposed a basket-forceps-type flow sensor, in which a flexible thermal flow sensor is mounted onto basket forceps to fix the flow sensor onto the inside surface of the airway. The basket-forceps-type flow sensor has an asymmetrical structure to prevent reciprocating airflow; thus, we investigated the characteristics of the basket-forceps-type flow sensor under both expired- and inspired-airflow conditions in this study. The thermal flow sensor was fabricated on a flexible polyimide film and mounted onto a guide tube of a basket-forceps. Two heaters and their electrical wiring patterns were designed to produce symmetric heat distribution over the heaters. The effects of the basket structure and guide tube on flow-rate measurement were experimentally evaluated, and it was confirmed that they did not affect sensor output. Conversely, sensor output decreased with the increase in tube diameter due to the reduction in the average flow velocity with the diameter increase. Thus, we carried out a procedure to construct a calibration curve under an arbitrary tube diameter. Finally, we applied the basket-forceps-type flow sensor in an animal experiment in which it successfully detected the breathing properties in the airway of a rat.

DOI： 10.1007/s00542-016-3265-9

Heartbeat Signal Detection From Analysis of Airflow in Rat Airway Under Different Depths of Anaesthesia Conditions 査読有り

Hidetaka Kawaoka, Takayuki Yamada, Miyoko Matsushima, Tsutomu Kawabe, Yoshihiro Hasegawa, Mitsuhiro Shikida

IEEE SENSORS JOURNAL 17 巻 ( 14 ) 頁： 4369 - 4377 2017年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC

We inserted a tubular flow sensor incorporating micro-electro-mechanical systems technologies directly into the rat airway and analyzed the airflow waveforms obtained under different depths of anaesthesia conditions by using discrete Fourier transformation (DFT) to evaluate the heartbeat frequency. The electrocardiogram (ECG) signal was used as the reference heartbeat frequency. The calibration curve of the flow sensor used to measure the oscillating airflow in the rat airway was determined on the basis of King's law. The airflow waveform at the rat airway caused by only the heartbeat was measured by applying deep anaesthesia; the waveform frequency coincided with the simultaneously measured ECG signal frequency. DFT analysis of the airflow signals measured under deep and shallow anaesthesia conditions verified the fundamental heartbeat frequency values. The airflow components related to heartbeat motion were successfully extracted by using the heartbeat frequency spectrum. The respiration and heartbeat signals were thus successfully detected.

DOI： 10.1109/JSEN.2017.2707594

Development of implantable catheter flow sensor into inside of bronchi for laboratory animal 査読有り

Mitsuhiro Shikida, Takuya Matsuyama, Takayuki Yamada, Miyoko Matsushima, Tsutomu Kawabe

Microsystem Technologies 23 巻 ( 1 ) 頁： 175 - 185 2017年1月

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

An implantable catheter flow sensor with legs for measuring the breathing characteristics of disease-model animals was developed. The unique feature of this sensor is the use of legs to fix the sensor to the inside wall surface of the air passage without preventing ciliary motion. Differently shaped legs were fabricated by application of a heat shrinkable tube. Prototype sensors was inserted into tubes with inner diameters ranging from 2.4 to 2.7 mm and successfully anchored to the inside surface by the legs. An evaluation of the relationship between the sensor output and the flow rate demonstrated that the sensor output against the flow rate obeyed King's law. The sensor output variation with different inner tube diameters was suppressed to less than 3 %. The developed catheter flow sensor was applied to the breathing measurements in the rat and the rabbit. The breathing waveform obtained from the flow sensor in the rat coincidented to the mechanism of breathing. The sensor was implated into the rabbit bronchus by using a fiberscope, and the breathing characteristics in the bronchus 3 days after implant were successfully measured.

DOI： 10.1007/s00542-015-2663-8

Exogenous induction of unphosphorylated PTEN reduces TGF β-induced extracellular matrix expressions in lung fibroblasts 査読有り

Modulation of immunological activity on macrophages induced by diazinon 査読有り

OGASAWARA Nanako, MATSUSHIMA Miyoko, KAWAMURA Nami, ATSUMI Kazuko, YAMAGUCHI Takehiro, OCHI Haruka, KUSATSUGU Yuto, OYABU Sayaka, HASHIMOTO Naozumi, HASEGAWA Yoshinori, UEYAMA Jun, KAWABE Tsutomu

Toxicology 379 巻頁： 22-30 2017年

Respiration and heartbeat signal detection from airflow at airway in rat by catheter flow sensor with tmeparature compensation function 査読有り

HASEGAWA Yoshihiro, KAWAOKA Hidenori, YAMADA Takayuki, MATSUSHIMA Miyoko, KAWABE Tsutomu, SHIKIDA Mitsuhiro

Journal of Micromechanics and Microengineering 27 巻 2017年

Motohiro Kimura, Naozumi Hashimoto, Masaaki Kusunose, Daisuke Aoyama, Koji Sakamoto, Shinichi Miyazaki, Akira Ando, Norihiro Omote, Kazuyoshi Imaizumi, Tsutomu Kawabe, Yoshinori Hasegawa

WOUND REPAIR AND REGENERATION 25 巻 ( 1 ) 頁： 86 - 97 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Transforming growth factor beta (TGF beta) plays an important role in regulating aberrant extracellular matrix (ECM) production from alveolar/epithelial cells (AECs) and fibroblasts in pulmonary fibrosis. Although the tumor suppressor gene phosphatase and tensin homologue deleted from chromosome 10 (PTEN) can negatively control many TGF beta-activated signaling pathways via the phosphatase activity, hyperactivation of the TGF beta-related signaling pathways is often observed in fibrosis. Loss of PTEN expression might cause TGF beta-induced ECM production. In addition, TGF beta was recently shown to induce loss of PTEN enzymatic activity by phosphorylating the PTEN C-terminus. Therefore, we hypothesized that exogenous transfer of unphosphorylated PTEN (PTEN4A) might lead to reduce TGF beta-induced ECM expression in not only epithelial cells but also fibroblasts. Adenovirus-based exogenous PTEN4A induction successfully reduced TGF beta-induced fibronectin expression and retained beta-catenin at the cell membrane in human epithelial cells. Exogenous unphosphorylated PTEN also attenuated TGF beta-induced ECM production and inhibited TGF beta-induced b-catenin translocation in a human fibroblast cell line and in mouse primary isolated lung fibroblasts. Conversely, TGF beta-induced a-smooth muscle actin expression did not seem to be inhibited in these fibroblasts. Our data suggest that exogenous administration of unphosphorylated PTEN might be a promising strategy to restore TGF beta-induced loss of PTEN activity and reduce aberrant TGF beta-induced ECM production from epithelial cells and fibroblasts in lung fibrosis as compared with wild-type PTEN induction.

DOI： 10.1111/wrr.12506

MEMS技術の医用応用査読有り

式田光宏, 長谷川義大, 川部勤, 松島充代子

表面技術 68 巻 ( 7 ) 頁： 367 - 372 2017年

Hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers 査読有り

Takashi Kohnoh, Naozumi Hashimoto, Akira Ando, Koji Sakamoto, Shinichi Miyazaki, Daisuke Aoyama, Masaaki Kusunose, Motohiro Kimura, Norihito Omote, Kazuyoshi Imaizumi, Tsutomu Kawabe, Yoshinori Hasegawa

CANCER CELL INTERNATIONAL 16 巻 ( 1 ) 頁： 33 2016年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BIOMED CENTRAL LTD

Background: Persistent hypoxia stimulation, one of the most critical microenvironmental factors, accelerates the acquisition of epithelial-mesenchymal transition (EMT) phenotypes in lung cancer cells. Loss of phosphatase and tensin homologue deleted from chromosome 10 (PTEN) expression might accelerate the development of lung cancer in vivo. Recent studies suggest that tumor microenvironmental factors might modulate the PTEN activity though a decrease in total PTEN expression and an increase in phosphorylation of the PTEN C-terminus (p-PTEN), resulting in the acquisition of the EMT phenotypes. Nevertheless, it is not known whether persistent hypoxia can modulate PTEN phosphatase activity or whether hypoxia-induced EMT phenotypes are negatively regulated by the PTEN phosphatase activity. We aimed to investigate hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers.
Methods: Western blotting was performed in five lung cancer cell lines to evaluate total PTEN expression levels and the PTEN activation. In a xenograft model of lung cancer cells with endogenous PTEN expression, the PTEN expression was evaluated by immunohistochemistry. To examine the effect of hypoxia on phenotypic alterations in lung cancer cells in vitro, the cells were cultured under hypoxia. The effect of unphosphorylated PTEN (PTEN4A) induction on hypoxia-induced EMT phenotypes was evaluated, by using a Dox-dependent gene expression system.
Results: Lung cancer cells involving the EMT phenotypes showed a decrease in total PTEN expression and an increase in p-PTEN. In a xenograft model, loss of PTEN expression was observed in the tumor lesions showing tissue hypoxia. Persistent hypoxia yielded an approximately eight-fold increase in the p-PTEN/PTEN ratio in vitro. PTEN4A did not affect stabilization of hypoxia-inducible factor 1 alpha. PTEN4A blunted hypoxia-induced EMT via inhibition of beta-catenin translocation into the cytoplasm and nucleus.
Conclusion: Our study strengthens the therapeutic possibility that compensatory induction of unphosphorylated PTEN may inhibit the acquisition of EMT phenotypes in lung cancer cells under persistent hypoxia.

DOI： 10.1186/s12935-016-0308-3

Predictors of surgery-induced muscle proteolysis in patients undergoing cardiac surgery 査読有り

IIDA Yuki, YAMAZAKI Takenori, ARIMA Hajime, KAWABE Tsutomu, YAMADA Sumio

J Cardiol. 68 巻頁： 536 2016年

Direct regulation of TGF β-induced EMT by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells. 査読有り

KUSUNOSE Masaaki, HASHIMOTO Naozumi, KIMURA Motohiro, OGATA Ryo, AOYAMA Daisuke, SAKAMOTO Koji, MIYAZAKI Shinichi, ANDO Akira, OMOTE Norihiro, IMAIZUMI Kazuyoshi, KAWABE Tsutomu, HASEGAWA Yoshinori

Cancer Sci. 106 巻 ( 12 ) 頁： 1693 - 1704 2015年12月

Ppm level methane detection using micro-thermoelectric gas sensors with Pd/Al2O3 combustion catalyst films 査読有り

Nagai Daisuke, Nishibori Maiko, Itoh Toshio, Kawabe Tsutomu, Sato Kazuo, Shin Woosuck

SENSORS AND ACTUATORS B-CHEMICAL 206 巻頁： 488 - 494 2015年1月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Sensors and Actuators, B: Chemical

The CH4 combustion performance of a micro-thermoelectric gas sensor (TGS) with Pd-Al2O3 catalysts prepared using two different methods, impregnation and colloid mixing, has been investigated. Three crystal phases of Al2O3, α, θ, and γ, were used for the catalyst support; the Pd/θ-Al2O3 catalyst showed the best combustion performance. The Pd/θ-Al2O3 catalyst exhibited the best dispersion of Pd nanoparticles as analyzed by both a pulse adsorption technique and transmission electron microscopy. The effect of the catalyst thickness on the H2 and CH4 detection performance of the TGS using this Pd/θ-Al2O3 catalyst prepared using a colloid mixing method was investigated. It was found that the response voltage, ΔV, of the TGS to CH4 increased with increasing film thickness, but the ΔV to H2 decreased. The TGS with the Pd/θ-Al2O3 catalyst whose thickness was 35 μm could detect as low as 1 ppm of CH4 in air by the thermoelectric conversion of the combustor heat to an electrical voltage.

DOI： 10.1016/j.snb.2014.09.059

Design and development of a suitable adsorbent to capture theophylline for non-invasive therapeutic drug monitoring with exhaled breath 査読有り

A. Yamamoto, S. Hioki, C. Tanada, T. Miwa, Y. Inoue, R. Yamamoto, M. Matsushima, T. Kawabe

ANALYTICAL METHODS 7 巻 ( 2 ) 頁： 423 - 427 2015年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ROYAL SOC CHEMISTRY

The possibility of using exhaled breath as a substitute for blood/plasma in areas of therapeutic drug monitoring was investigated. Theophylline was used as a model chemical of non-volatile drugs and the adsorbents suitable for drug capture from exhaled breath were studied. Two macro-porous adsorbents with different monomer compositions were prepared by suspension copolymerization. The capture properties of the synthesized adsorbents and two conventional gas adsorbents packed in a cartridge were evaluated by both aerosol generation and rat expiration. The efficiency of drug capture did not improve by decreasing the pore size and by increasing the specific surface area. A hydrophilic region was found to be necessary for holding the aerosol particles on the adsorbent surface, but a hydrophobic region is also necessary for the adsorption of theophylline. The materials were applied to the intravenous bolus experiment of rats. The amount of theophylline collected from exhaled breath was in the range of 0-0.02 ng min(-1), and it varied similarly to the concentration in blood, which was in the range of 0-37 mu g mL(-1).

DOI： 10.1039/c4ay02243b

The suppressive effect of quercetin on Toll-like receptor 7-mediated activation in alveolar macrophages. 査読有り

YASUI Masahiro, MATSUSHIMA Miyoko, OMURA Aya, MORI Kanae, OGASAWARA Nanako, KODERA Yuka, SHIGA Marika, ITO Komei, KOJIMA Seiji, KAWABE Tsutomu

Pharmacology 96 巻 ( 5-6 ) 頁： 201-209 2015年

Protective effects of intratracheally administered quercetin on lipopolysaccharide-induced acute lung injury. 査読有り

TAKASHIMA Koji, MATSUSHIMA Miyoko, HASHIMOTO Katsunori, NOSE Haruka, SATO Mitsuo, HASHIMOTO Naozumi, HASEGAWA Yoshinori, KAWABE Tsutomu.

Respir Res. 15 巻 ( 1 ) 頁： 150 2014年11月

Catheter flow sensor with temperature compensation for tracheal intubation tube system 査読有り

Mitsuhiro Shikida, Kazuhiro Yoshikawa, Takuya Matsuyama, Yudai Yamazaki, Miyoko Matsushima, Tsutomu Kawabe

SENSORS AND ACTUATORS A-PHYSICAL 215 巻頁： 155 - 160 2014年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE SA

A micro-electro-mechanical systems catheter flow sensor was integrated into the tracheal intubation tube system to prevent the insertion of the tube into the esophagus. A temperature sensing mechanism was integrated into the catheter flow sensor to compensate for the temperature change in air during flow-rate measurement, and the sensor was placed on the inside the slip joint by using an adapter produced using a molding process. The relationship between the sensor output and flow rate was evaluated, and closely matched sensor outputs for both the forward and backward flows were obtained. The tracheal tube in the modified system was inserted into the air passage of a rabbit, and the air flow passing through the tube was directly measured using the integrated catheter flow sensor in real time. By adding the temperature compensation mechanism, the volumes of the expired- and inspired-air almost matched. We believe that a doctor will easily be able to evaluate whether the tube is inserted into the bronchi or the esophagus when using the modified system. (C) 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.sna.2013.08.004

呼吸器内科医を対象とした喘息治療ステップダウンの実態調査

2. 武田直也、伊藤　理、指尾豊和、平松哲夫、木村智樹、大林浩幸、馬場研二、若原恵子、若山尚士、今泉和良、川部　勤、長谷川好規

アレルギー・免疫 21 巻 ( 4 ) 頁： 106-114 2014年3月

Postoperative muscle proteolysis affects systemic muscle weakness in patients undergoing cardiac surgery 査読有り

Iida Y, Yamazaki T, Kawabe T, Usui A, Yamada S

Int J Cardiol 172 巻 ( 3 ) 頁： 595-597 2014年1月

呼気吸気計測を目的とした自己温度補償型カテーテル流量センサの開発査読有り

松山拓矢, 山﨑雄大, 松島充代子, 川部勤, 式田光宏

電気学会論文誌E（センサ・マイクロマシン部門誌） 134 巻 ( 6 ) 頁： 126-131 - 131 2014年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：IEEJ Transactions on Sensors and Micromachines

We introduced groove structures in between the flow- and temperature-sensors to avoid the heat flow to the temperature sensor from the heater used as the flow sensing. The grooves were produced by oxygen plasma etching, and thermal isolation effect by those was confirmed by an infrared thermography. The relationships between the flow rate and the flow sensor output with and without temperature compensation were evaluated. We finally confirmed that the variations of the flow sensor output by the change of the fluid temperature were successfully compensated by the temperature sensor.

DOI： 10.1541/ieejsmas.134.126

Involvement of TGF β-Induced Phosphorylation of the PTEN C-Terminus on TGF β-Induced Acquisition of Malignant Phenotypes in Lung Cancer Cells 査読有り

Aoyama Daisuke, Hashimoto Naozumi, Sakamoto Koji, Kohnoh Takashi, Kusunose Masaaki, Kimura Motohiro, Ogata Ryo, Imaizumi Kazuyoshi, Kawabe Tsutomu, Hasegawa Yoshinori

PLOS ONE 8 巻 ( 11 ) 頁： e81133 2013年11月

[Immunoreaction and blood transfusion--chairmen's introductory remarks]. 査読有り

Kawabe T, Matsushita T

Rinsho byori. The Japanese journal of clinical pathology 61 巻 ( 5 ) 頁： 397 - 8 2013年5月

An aqueous fraction of Sauropus androgynus might be responsible for bronchiolitis obliterans 査読有り

Hashimoto I, Imaizumi K, Hashimoto N, Furukawa H, Noda Y, Kawabe T, Honda T, Ogawa T, Matsuo M, Imai N, Ito S, Sato M, Kondo M, Shimokata K, Hasegawa Y

Respirology 18 巻 ( 2 ) 頁： 340-347 2013年2月

Detection of loci for allergic asthma using SMXA recombinant inbred strains of mice. 査読有り

Ohno T, Okamoto M, Hara T, Hashimoto N, Imaizumi K, Matsushima M, Nishimura M, Shimokata K, Hasegawa Y, Kawabe T.

Immunogenetics 65 巻 ( 1 ) 頁： 17-24 2013年1月

Micromachined catheter flow sensor and its applications in breathing measurements in animal experiments. 査読有り

Shikida M, Shikano T, Matsuyama T, Yamazaki Y, Matsushima M, Kawabe T.

Microsyst Technol. 20 巻 ( 3 ) 頁： 505-513 2013年1月

Respiratory Volume Estimation by a Stretchable Textile Sensor 査読有り

Enokibori Yu, Ito Yoshu, Ikeda Koji, Suzuki Akihisa, Shimakami Yuuki, Kawabe Tsutomu, Mase Kenji

SMART AND INTERACTIVE TEXTILES 80 巻頁： 136 - + 2013年

THE RELATIONSHIP BETWEEN MUSCLE WEAKNESS AND POSTOPERATIVE CATABOLISM AFTER CORONARY ARTERY BYPASS GRAFT SURGERY 査読有り

Iida Y., Iwatsu K., Kawabe T., Tsubouchi H., Usui A., Yamada S.

INTENSIVE CARE MEDICINE 38 巻頁： S90 - S91 2012年10月

Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury 査読有り

Sakamoto K, Hashimoto N, Kondoh Y, Imaizumi K, Aoyama D, Kohnoh T, Kusunose M, Kimura M, Kawabe T, Taniguchi H, Hasegawa Y

Am J Physiol Lung Cell Mol Physiol 303 巻 ( 1 ) 頁： L43-53 2012年7月

Involvement of the transcription factor twist in phenotype alteration through epithelial-mesenchymal transition in lung cancer cells 査読有り

Nakashima H, Hashimoto N, Aoyama D, Kohnoh T, Sakamoto K, Kusunose M, Imaizumi K, Takeyama Y, Sato M, Kawabe T, Hasegawa Y.

Mol Carcinog. 51 巻 ( 5 ) 頁： 400-410 2012年7月

Inspiratory capacity as a preoperative assessment of patients undergoing thoracic surgery 査読有り

Matsuo M, Hashimoto N, Usami N, Imaizumi K, Wakai K, Kawabe T, Yokoi K, Hasegawa Y.

Interact Cardiovasc Thorac Surg. 14 巻 ( 5 ) 頁： 560-564 2012年5月

Observation of Fine Lung Structure by Ultrahigh-Resolution Optical Coherence Tomography Using 800, 1060, and 1300nm Supercontinua 査読有り

Ishida S, Nishizawa N, Kitatsuji M, Ohshima H, Hasegawa Y, Matsushima M, Kawabe T.

Jpn. J. Appl. Phys 51 巻頁： 047001 2012年3月

Quercetin protects against pulmonary oxidant stress via heme oxygenase-1 induction in lung epithelial cells 査読有り

Hayashi Y, Matsushima M, Nakamura T, Shibasaki M, Hashimoto N, Imaizumi K, Shimokata K, Hasegawa Y, Kawabe T.

Biochem Biophys Res Commun 417 巻 ( 1 ) 頁： 169-174 2012年1月

The usefulness of casein-specific IgE and IgG4 antibodies in cow's milk allergic children. 査読有り

Ito K, Futamura M, Moverare R, Tanaka A, Kawabe T, Sakamoto T, Borres MP

Clin Mol Allergy 10 巻 ( 1 ) 頁： 1-7 2012年1月

ミルクタンパク質全網羅ペプチドアレイを用いたIgG結合ペプチドの探索査読有り

片山　真、杉田智哉、加藤竜司、大河内美奈、松島充代子、川部　勤、高瀬智和、吉田安子、川瀬三雄、本多裕之

化学工学論文集 37 巻 ( 6 ) 頁： 546-550 2011年9月

CD40/CD40 ligand interactions in immune responses and pulmonary immunity 査読有り

Kawabe T, Matsushima M, Hashimoto N, Imaizumi K, Hasegawa Y.

Nagoya J Med Sci 73 巻 ( 3-4 ) 頁： 69-78 2011年8月

Attenuation of Transforming Growth Factor-β-Stimulated Collagen Production in Fibroblasts by Quercetin-Induced Heme Oxygenase-1 査読有り

Nakamura T, Matsushima M, Hayashi Y, Shibasaki M, Imaizumi K, Hashimoto N, Shimokata K, Hasegawa Y, Kawabe T.

Am J Respir Cell Mol Biol 44 巻 ( 5 ) 頁： 614-620 2011年5月

Comparison of salivary cortisol, heart rate, and oxygen saturation between early skin-to-skin contact with different initiation and duration times in healthy, full-term infants 査読有り

Yuki Takahashi, Koji Tamakoshi, Miyoko Matsushima, Tsutomu Kawabe

EARLY HUMAN DEVELOPMENT 87 巻 ( 3 ) 頁： 151 - 157 2011年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER IRELAND LTD

Background: There are few studies that compare the physiological and biological efficacies between different early skin-to-skin contacts (SSC) post birth.
Aim: To investigate physiologically and biochemically how early SSC with different initiation and duration time influence the stress post birth for full-term infants.
Study design: Non-experimental study.
Subjects: Study I; Thirty-two infants who began SSC 5 min or less [birth SSC, mean initiation time (standard deviation): 1.6 (1.1) min] after birth and 36 infants who did so more than 5 min [very early SSC, 26.3 (5.0) min] in heart rate (HR) and oxygen saturation (SpO(2)) analysis. Study II; Eighteen infants who underwent SSC for 60 min or less [mean initiation time: 7.5 (12.2) min] and 61 infants who did so for more than 60 min [15.3 (12.5) min] in salivary cortisol analysis.
Outcome measures: HR and SpO(2) measured for 30 min post birth. Salivary cortisol concentration measured at 1 min, 60 min, and 120 min post birth.
Results: Birth SSC group reached HR stability of 120-160 bpm significantly faster than very early SSC group by Kaplan-Meier analysis (P=0.001 by log-rank test). As for SpO(2) stability of 92% and 96%, no significantly between-group difference was found. Salivary cortisol levels were significantly lower between 60 and 120 min after birth in SSC group, continuing for more than 60 min compared with SSC group for 60 min or less after adjustment for salivary cortisol level at 1 min besides the infant stress factors (P=0.046).
Conclusions: Earlier SSC beginning within 5 min post birth and longer SSC continuing for more than 60 min within 120 min post birth are beneficial for stability of cardiopulmonary dynamics and the reduction of infant stress during the early period post birth. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.earlhumdev.2010.11.012

Ex-vivo ultra-high-resolution optical coherence tomography imaging of fine lung structure by use of a high-power Gaussian-like supercontinuum at 0.8-um wavelength. 査読有り

Nishizawa N., Ishida S., Ohta T., Itoh K., Kitatsuji M., Ohshima H., Hasegawa Y., Matsushima M., Kawabe T.

ENDOSCOPIC MICROSCOPY VI 7893 巻 2011年

The Role Of Interleukin-17/Th17 In Human Interstitial Pneumonia 査読有り

Ogawa T., Imaizumi K., Hashimoto N., Hashimoto I., Imai N., Tomita Y., Kounou T., Sakamoto K., Aoyama D., Kusunose M., Ito S., Sato M., Kondo M., Kawabe T., Hasegawa Y.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 183 巻 2011年

Characteristics of an optimized catheter-type thermal flow sensor for measuring reciprocating airflows in bronchial pathways 査読有り

M. Shikida, T. Yokota, T. Kawabe, T. Funaki, M. Matsushima, S. Iwai, N. Matsunaga, K. Sato

JOURNAL OF MICROMECHANICS AND MICROENGINEERING 20 巻 ( 12 ) 頁： 1-11 2010年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：IOP PUBLISHING LTD

We optimized a catheter-type thermal flow sensor to measure the reciprocating airflows in bronchial pathways. The electrical wiring in the outer tube was extracted to keep the symmetry of the temperature distribution on the heaters. First, a flexible sensor was fabricated on polyimide film with photolithography, and then the enameled wires were bonded to the contact pads on the film with anisotropic conductive film. The film sensor was finally assembled with a catheter configuration that had a diameter of 1.8 mm by applying a heat shrinkable tube. We experimentally confirmed that the sensor outputs under both forward and reverse flow conditions had the same output characteristics when a design with symmetrical heating elements was applied. The sensor outputs we obtained at a reciprocating flow frequency ranging from 1 to 3 Hz almost coincided, and they also fit that obtained under unidirectional airflow conditions. Finally, the aspirated-and inspired-air characteristics in the air passages of small laboratory animals (rats and mice) were measured. Due to our development of a flexible method of electrical wiring, we could try a new approach to intubation measurements in which the sensor was inserted into the air passage from the mouth with a fiberscope, and we confirmed that the sensor we developed was able to directly measure the breathing characteristics in air passages. Implanted measurements were also attempted in this study.

DOI： 10.1088/0960-1317/20/12/125030

Ghrelin and obestatin promote the allergic action in rat peritoneal mast cells as basic secretagogues. 査読有り

Hirayama T, Kawabe T, Matsushima M, Nishimura Y, Kobe Y, Ota Y, Baba K, Takagi K.

Peptides 31 巻 ( 11 ) 頁： 2109-13 2010年11月

Endothelial-Mesenchymal Transition in Bleomycin-Induced Pulmonary Fibrosis 査読有り

Naozumi Hashimoto, Sem H. Phan, Kazuyoshi Imaizumi, Masaki Matsuo, Harunori Nakashima, Tsutomu Kawabe, Kaoru Shimokata, Yoshinori Hasegawa

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 43 巻 ( 2 ) 頁： 161 - 172 2010年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER THORACIC SOC

The pathological hallmark lesions in idiopathic pulmonary fibrosis are the fibroblastic foci, in which fibroblasts are thought to be involved in the tissue remodeling, matrix deposition, and cross-talk with alveolar epithelium. Recent evidence indicates that some fibroblasts in fibrosis may be derived from bone marrow progenitors as well as from epithelial cells through epithelial-mesenchymal transition. To evaluate whether endothelial cells could represent an additional source for fibroblasts, bleomycin-induced lung fibrosis was established in Tie2-Cre/CAG-CAT-LacZ double-transgenic mice, in which LacZ was stably expressed in pan-endothelial cells. Combined X-gal staining and immunocytochemical staining for type I collagen and alpha-smooth muscle actin revealed the presence of X-gal-positive cells in lung fibroblast cultures from bleomycin-treated mice. To explore the underlying mechanisms, by which loss of endothelial-specific markers and gain of mesenchymal phenotypes could be involved in microvascular endothelial cells, the effects of activated Ras and TGF-beta on the microvascular endothelial cell line MS1 were analyzed. Combined treatment with activated Ras and TGF-beta caused a significant loss of endothelial-specific markers, while inducing de nova mesenchymal phenotypes. The altered expression of these markers in MS1 cells with activated Ras persisted after withdrawal of TGF-beta in vitro and in vivo. These findings are the first to show that lung capillary endothelial cells could give rise to significant numbers of fibroblasts through an endothelial-mesenchymal transition in bleomycin-induced lung fibrosis model.

DOI： 10.1165/rcmb.2009-0031OC

Differential Th1/Th2 chemokine expression in interstitial pneumonia. 査読有り

Honda T, Imaizumi K, Yokoi T, Hashimoto N, Hashimoto I, Kawabe T, Matsuo M, Iwano S, Shimokata K, Hasegawa Y.

Am J Med Sci 339 巻 ( 1 ) 頁： 41-8 2010年1月

Heme oxygenase-1 mediates the anti-allergic actions of quercetin in rodent mast cells. 査読有り

Matsushima M, Takagi K, Ogawa M, Hirose E, Ota Y, Abe F, Baba K, Hasegawa T, Hasegawa Y, Kawabe T.

Inflammation Research 58 巻 ( 10 ) 頁： 705-715 2009年10月

A catheter-type flow sensor for measurement of aspirated- and inspired-air characteristics in the bronchial region. 査読有り

Shikida M, Naito J, Yokota T, Kawabe T, Hayashi Y and K Sato.

J Micromech Microeng 19 巻 ( 10 ) 頁： 1-9 2009年10月

Peptide array-based analysis of the specific IgE and IgG4 in cow's milk allergens and its use in allergy evaluation. 査読有り

Matsumoto N, Okochi M, Matsushima M, Kato R, Takase T, Yoshida Y, Kawase M, Isobe K, Kawabe T, Honda H.

Peptides 30 巻 ( 10 ) 頁： 1840-1847 2009年10月

Erythromycin-induced CXCR4 expression on microvascular endothelial cells. 査読有り

Takagi Y, Hashimoto N, Phan SH, Imaizumi K, Matsuo M, Nakashima H, Hashimoto I, Hayashi Y, Kawabe T, Shimokata K, Hasegawa Y.

Am J Physiol (Lung Cell Mol Physiol) 297 巻 ( 3 ) 頁： L420-431 2009年9月

An influence of Interferon-gamma gene polymorphisms on treatment response to tuberculosis in Japanese population. 査読有り

Shibasaki M, Yagi T, Yatsuya H, Okamoto M, Nishikawa M, Baba H, Hashimoto N, Senda K, Kawabe T, Nakashima K, Imaizumi K, Shimokata K, Hasegawa Y.

Journal of Infection 58 巻 ( 6 ) 頁： 467-469 2009年6月

Up-regulation of surfactant protein production in a mouse model of secondary pulmonary alveolar proteinosis. 査読有り

Shibasaki M, Hashimoto K, Okamoto M, Hayashi Y, Imaizumi K, Hashimoto N, Ozaki N, Yokoi T, Takagi K, Hasegawa Y, Shimokata K, Kawabe T.

Am J Respir Cell Mol Biol 40 巻 ( 5 ) 頁： 536-542 2009年5月

Involvement of heme oxygenase-1 in kaempferol-induced anti-allergic actions in RBL-2H3 cells. 査読有り

Hirose E, Matsushima M, Takagi K, Ota Y, Ishigami K, Hirayama T, Hayashi Y, Nakamura T, Hashimoto N, Imaizumi K, Baba K, Hasegawa Y, Kawabe T.

Inflammation 32 巻 ( 2 ) 頁： 99-108 2009年4月

Inhibition of Degranulation by Myricetin-induced Heme Oxygenase-1 in Mast Cells 査読有り

Ota Y, Matsushima M, Ogawa M, Hirose E, Hirayama T, Yuasa E, Yabuta K, Baba K, Hasegawa Y, Takagi K, Kawabe T.

Occupational and Environmental Allergy 16 巻 ( 2 ) 頁： 61-73 2009年4月

Development of peptide arrays for detection of IgE-binding epitopes in cow's milk allergens. 査読有り

Matsumoto N, Okochi M, Matsushima M, Ogawa A, Takase T, Yoshida Y, Kawase M, Isobe K, Kawabe T, Honda H.

J Biosci Bioeng 107 巻 ( 3 ) 頁： 324-30 2009年3月

Milk Allergen-Specific IgE And IgG4 Antibodies In Patients With Milk Allergy 査読有り

Ito K., Futamura M., Hirayama M., Otsuji K., Kawabe T., Sakamoto T., Tanaka A.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 123 巻 ( 2 ) 頁： S181 - S181 2009年2月

Cytoprotective Effect of Geranylgeranylacetone in Bleomycin-Induced Lung Injury/Fibrosis. 査読有り

Hashimoto N., Fujibayashi T., Nakashima H., Matsuo M., Imaizumi K., Kawabe T., Hasegawa Y.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 179 巻 2009年

Involvement of Transcription Factor Twist into Phenotype Change in Lung Cancer Cells through Epithelial-Mesenchymal Transition. 査読有り

Nakashima H., Hashimoto N., Imaizumi K., Matsuo M., Hashimoto I., Nakamura T., Hayashi Y., Kawabe T., Hasegawa Y.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 179 巻 2009年

Th1/Th2 immune response in lung fibroblasts in interstitial lung disease 査読有り

Sumida Atsushi, Hasegawa Yoshinori, Okamoto Masakazu, Hashimoto Naozumi, Imaizumia Kazuyoshi, Yatsuya Hiroshi, Yokoi Toyoharu, Takagi Kenzo, Shimokata Kaoru, Kawabe Tsutomu

ARCHIVES OF MEDICAL RESEARCH 39 巻 ( 5 ) 頁： 503 - 510 2008年7月

担当区分：最終著者,　責任著者記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Archives of Medical Research

Background: Inflammatory response in pulmonary fibrosis closely resembles a T-helper (Th) 2 immune response. For recruitment to an inflammatory lesion, the majority of Th1 cells express CXC chemokine receptor 3, recognizing monokine induced by interferon-gamma (Mig), interferon γ-inducible protein of 10 kD (IP-10), and interferon-inducible T-cell α chemoattractant (I-TAC). Th2 cells express CC chemokine receptor 4, recognizing thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). We investigated the Th1/Th2 chemokine production patterns by lung fibroblasts and their evaluation in bronchoalveolar lavage (BAL) fluid of interstitial lung disease. Methods: The production pattern of Th1/Th2 chemokines by lung fibroblasts was examined in ELISA and quantitative reverse transcriptase polymerase chain reactions. Th1/Th2 chemokine levels in BAL fluid of idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP) were examined to evaluate the clinical relevance of Th1/Th2 chemokines. Results: The lung fibroblasts were polarized to produce Th1-type chemokines by the pro-inflammatory cytokine, tumor necrosis factor (TNF)-α and the anti-fibrotic cytokine, interferon (IFN)-γ. However, the induction patterns of chemokines by these two cytokines were different, i.e., involving predominant induction of IP-10 and I-TAC by TNF-α and induction of Mig by IFN-γ. Although Mig, IP-10, and I-TAC were produced within the BAL fluid of patients, TARC and MDC were at significantly low levels. Conclusions: Our results suggest that lung fibroblasts tend to induce a Th1-type immune response under normal conditions, and that a Th2-type immune response does not play a significant role in smoldering inflammation around the established lesions in IPF and NSIP. © 2008 IMSS.

DOI： 10.1016/j.arcmed.2008.02.005

Diazotization of kynurenine by acidified nitrite secreted from indoleamine 2,3-dioxygenase-expressing myeloid dendritic cells. 査読有り

Hara T, Yamakura F, Takikawa O, Hiramatsu R, Kawabe T, Isobe KI, Nagase F.

J Immunol Methods 332 巻 ( 1-2 ) 頁： 162-169 2008年3月

High-affinity uptake of kynurenine and nitric oxide-mediated inhibition of indoleamine 2,3-dioxygenase in bone marrow-derived myeloid dendritic cells. 査読有り

Hara T, Ogasawara N, Akimoto H, Takikawa O, Hiramatsu R, Kawabe T, Isobe K, Nagase F.

Immunol Letters 116 巻 ( 1 ) 頁： 95-102 2008年2月

Cinnabarinic acid generated from 3-hydroxyanthranilic acid strongly induces apoptosis in thymocytes through the generation of reactive oxygen species and the induction of caspase. 査読有り

Hiramatsu R, Hara T, Akimoto H, Takikawa O, Kawabe T, Isobe K, Nagase F.

J Cell Biochem 103 巻 ( 1 ) 頁： 42-53 2008年1月

Xenin and xenopsin induce histamine release from rat peritoneal mast cells. 査読有り

Matsushima M, Kitaichi K, Kawabe T, Suzuki R, Baba K, Hasegawa T, Takagi K

14 巻 ( 2 ) 頁： 60-67 2007年9月

Macrophage-derived chemokine in malignant and tuberculous pleurisy 査読有り

Okamoto M, Imaizumi K, Hasegawa Y, Hashimoto N, Sumida A, Shibazaki M, Takagi K, Shimokata K, Kawabe T,

Respirology 12 巻頁： 581–584 2007年7月

Macrophage-derived chemokine in malignant and tuberculous pleural effusions 査読有り

Okamoto Masakazu, Imaizumi Kazuyoshi, Hasegawa Yoshinori, Hashimoto Naozumi, Sumida Atsushi, Shibazaki Masataka, Takagi Kenzo, Shimokata Kaoru, Kawabe Tsutomu

RESPIROLOGY 12 巻 ( 4 ) 頁： 581 - 584 2007年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Respirology

Background and objectives: Macrophage-derived chemokine (MDC/CCL22) is recognized as a T-helper (Th) 2-type chemokine. Both malignant and tuberculous pleural effusions are typically lymphocytic pleural effusions. Tuberculous pleural effusions have a more polarized Th1 reaction than malignant effusions, which are predominantly Th2 in nature. The aim of this study was to compare the levels of MDC in malignant pleural effusions with those in tuberculous pleural effusions to help delineate the role of MDC in Th2 versus Th1 effusions. Methods: Forty-three patients with pleural effusions (32 malignant, 11 tuberculous) were studied. The concentration of MDC in the pleural effusion was measured by ELISA. Results: The median concentration of MDC was lower in malignant pleural effusions than in tuberculous pleural effusions (P < 0.005). Conclusions: MDC has been reported to both promote and suppress antitumour immunity. The low concentration of MDC in malignant effusions is likely to minimise its antitumour activity but the precise role of MDC in malignant and tuberculous effusions needs to be investigated further. © 2007 The Authors.

DOI： 10.1111/j.1440-1843.2007.01059.x

Expression of macrophage-derived chemokine (MDC)/CCL22 in human lung cancer. 査読有り

Nakanishi T, Imaizumi K, Hasegawa Y, Kawabe T, Hashimoto N, Okamoto M, Shimokata K,

Cancer Immunol Immunother 55 巻 ( 11 ) 頁： 1320-1329 2006年11月

Successful re-treatment with gefitinib for carcinomatous meningitis as disease recurrence of non-small-cell lung cancer 査読有り

Hashimoto N, Imaizumi K, Honda T, Kawabe T, Nagasaka T, Shimokata K, T, Hasegawa Y,

Lung cancer 53 巻 ( 3 ) 頁： 387-390 2006年9月

総説：マウス喘息モデルを用いた疾患感受性遺伝子の検索招待有り査読有り

川部　勤

日本職業・環境アレルギー学会誌 13 巻 ( 2 ) 頁： 1-10 2006年5月

Pulmonary infectious complications associated with anti-TNF alpha therapy (infliximab) for rheumatoid arthritis 査読有り

Imaizumi Kazuyoshi, Sugishita Mihoko, Usui Miho, Kawabe Tsutomu, Hashimoto Naozumi, Hasegawa Yoshinori

INTERNAL MEDICINE 45 巻 ( 10 ) 頁： 685 - 688 2006年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Internal Medicine

Two patients with rheumatoid arthritis (RA) that developed serious infectious complications following anti-TNFα therapy (infliximab) are reported. Patient 1 developed tuberculosis with high fever, refractory diarrhea and mediastinal lymphadenopathy. Trans-bronchial needle biopsy was useful to confirm the diagnosis. Patient 2 showed sudden onset of dyspnea with diffuse bilateral lung infiltration caused by pneumocystis jiroveci pneumonia and the diagnosis was confirmed by broncho-alveolar lavage. Physicians should be alerted to infectious complications with atypical presentation and rapid progression in infliximab-treated patients. Invasive diagnostic procedures including fiber-optic bronchoscopy may be necessary early in the course for such cases. © 2006 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.45.1623

T-Helper Type 1/T-Helper Type 2 Balance in Malignant Pleural Effusions Compared to Tuberculous Pleural Effusions 査読有り

Chest 128 巻頁： p4030-4035 2005年12月

Interstitial lung disease associated with gefitinib. 査読有り

Kataoka K, Taniguchi H, Hasegawa Y, Kondoh Y, Kimura T, Nishiyama O, Imaizumi K, Kawabe T, Kume H, Shimokata K,

Respiratory Medicine 100 巻 ( 4 ) 頁： 698-704 2005年4月

Evaluation of interferon-gamma, interferon-gamma-inducing cytokines, and interferon-gamma-inducible chemokines in tuberculous pleural effusions 査読有り

Okamoto M, Kawabe T, Iwasaki Y, Hara T, Hashimoto N, Imaizumi K, Hasegawa Y, Shimokata K

J Lab Clin Med 145 巻 ( 2 ) 頁： 88-93 2005年2月

Krüppel-like factor 6 is frequently down-regulated and induces apoptosis in non-small cell lung cancer cells. 査読有り

Ito G, Uchiyama M, Kondo M, Mori S, Usami N, Maeda O, Kawabe T, Hasegawa Y, Shimokata K, Sekido Y

Cancer research 64 巻 ( 11 ) 頁： 3838 - 43 2004年6月

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

Krüppel-like factor 6 (KLF6) is a ubiquitously expressed zinc finger transcriptional factor, which has been suggested to be a candidate tumor suppressor gene in prostate cancer and astrocytic glioma. Because KLF6 is located at chromosome 10p15, where non-small cell lung cancers (NSCLCs) also exhibit frequent allelic loss, we hypothesized that the inactivation of KLF6 is also involved in the development of NSCLC. To determine this, we performed mutational analysis for 105 NSCLCs, including 9 cell lines and 96 primary tumors, and Northern blot analysis for 74 NSCLCs, including the 9 cell lines and 65 primary tumors. Although somatic mutations were not detected in the coding sequence of KLF6, expression of KLF6 mRNA was down-regulated in the 9 cell lines and in 55 (85%) of the 65 primary tumors compared with normal lung tissue. Treatment of two cell lines expressing KLF6 at low levels with 5-azacytidine did not induce KLF6 expression, suggesting that KLF6 down-regulation is not due to promoter hypermethylation. We also performed loss of heterozygosity (LOH) analysis using the laser capture microdissection technique, and found that 21 of 62 (34%) informative samples had LOH in the KLF6 gene locus. Comparing the LOH status with mRNA expression of KLF6, we found that 14 of the 14 (100%) samples with LOH showed KLF6 down-regulation, and that even 23 of 31 (74%) samples without LOH also showed this down-regulation. We also studied the expression of the WAF1 gene, a possible downstream gene of KLF6, and detected simultaneous down-regulation of WAF1 and KLF6 mRNA in 6 of 9 (67%) cell lines and 48 of the 55 (87%) primary tumors, although there was not a significant association between loss of KLF6 and WAF1 expression. Furthermore, colony formation assay of two NSCLC cell lines (NCI-H1299 and NCI-H2009) induced a markedly reduced colony formation by KLF6 transfection, and Annexin V staining and terminal deoxynucleotidyl transferase-mediated nick end labeling assays revealed that KLF6 induced apoptosis. Our present studies demonstrated that KLF6 is frequently down-regulated in NSCLC and suppresses tumor growth via induction of apoptosis in NSCLC, which may suggest that KLF6 is a tumor suppressor for NSCLC.

DOI： 10.1158/0008-5472.CAN-04-0185

DR1-like element in human topoisomerase II alpha gene involved in enhancement of etoposide-induced apoptosis by PPAR gamma ligand 査読有り

CD40 plays a crucial role in lipopolysaccharide-induced acute lung injury 査読有り

Hashimoto N, Kawabe T, Imaizumi K, Hara T, Okamoto M, Kojima K, Shimokata K, Hasegawa Y

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 30 巻 ( 6 ) 頁： 808 - 815 2004年6月

Kanbe E, Abe A, Towatari M, Kawabe T, Saito H, Emi N

EXPERIMENTAL HEMATOLOGY 31 巻 ( 4 ) 頁： 300 - 308 2003年4月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Experimental Hematology

Objective. The nuclear peroxisome proliferator-activated receptor γ (PPARγ) ligands may enhance the etoposide-induced apoptosis by modulating the topoisomerase (Topo) IIα expression through binding to direct repeat 1 (DR1)-like element. Methods. To investigate the effect of etoposide-induced apoptosis by PPARγ ligands, leukemia cell lines were treated with troglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) in the presence of etoposide and studied about various biological responses. Results. We found the enhancement of etoposide-induced apoptosis by PPARγ ligands in several leukemia cell lines, which was dependent on the expression of PPARγ and specific for TopoIIα inhibitor. We also observed the increased expression of TopoIIα protein by 15d-PGJ2 in Jurkat and HUVEC cells, which might lead to the increased sensitivity to etoposide. Furthermore, we demonstrated that 15d-PGJ2 enhanced the promoter activity of human TopoIIα promoter construct with a DR1-like site by sevenfold when expressed with PPARγ and RXRα. The mutation of DR1-like site decreased the promoter activity, although the direct binding between DR1-like site and PPARγ/RXRα heterodimer was not demonstrated. Conclusions. We conclude that the induction of TopoIIα expression by PPARγ ligands via DR1-like site is an important mechanism for the enhancement of etoposide-induced apoptosis and a DR1-like site in TopoIIα promoter is involved in transcriptional regulation dependent on PPARγ ligands and PPARγ/RXRα heterodimer. © 2003 International Society for Experimental Hematology. Published by Elsevier Science Inc.

DOI： 10.1016/S0301-472X(03)00003-1

Perfusion and ventilation isotope lung scans in constrictive bronchiolitis obliterans. A series of three cases 査読有り

Hasegawa Y, Imaizumi K, Sekido Y, Iinuma Y, Kawabe T, Hashimoto N, Shimokata K

Respiration 69 巻 ( 6 ) 頁： 550-555 2002年4月

Critical involvement of CD40 in protection against herpes simplex virus infection in a murine model of genital herpes 査読有り

Inagaki-Ohara K, Kawabe T, Hasegawa Y, Hashimoto N, Nishiyama Y.

Arch Virol 147 巻 ( 1 ) 頁： 187-194 2002年4月

Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-γ gene into lung cancer 査読有り

Noguchi M., Imaizumi K., Kawabe T., Wakayama H., Horio Y., Sekido Y., Hara T., Hashimoto N., Takahashi M., Shimokata K., Hasegawa Y.

Cancer Gene Therapy 8 巻 ( 6 ) 頁： 421 - 429 2001年8月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Cancer Gene Therapy

CD40-CD40 ligand (CD40L) interaction is an important costimulatory signaling pathway in the crosstalk between T cells and antigen-presenting cells. This receptor-ligand system is known to be essential in eliciting strong cellular immunity. Here we demonstrate that murine lung cancer cells (3LLSA) transduced with the CD40L gene (3LLSA-CD40L) were rejected in syngeneic C57BL/6 mice, but grew in CD40-deficient mice to the same extent as control tumor cells. Immunohistochemical study showed that inflammatory cells, including CD4+, CD8+ T cells and NK cells, infiltrated into the inoculated 3LLSA-CD40L tumor tissue. Inoculation of 3LLSA-CD40L cells into mice resulted in the induction of 3LLSA-specific cytotoxic T-cell immunity, and the growth of parental 3LLSA tumors was inhibited when 3LLSA cells were inoculated into C57BL/6 mice mixed with 3LLSA-CD40L cells or when they were rechallenged 4 weeks after 3LLSA-CD40L cells were rejected. Furthermore, co-inoculation of interferon (IFN)-γ-transduced cells (3LLSA-IFNγ) with 3LLSA-CD40L cells enhanced the antitumor immunity efficiently in vivo. These results indicate that the in vivo priming with CD40L- and IFN-γ gene-transduced lung cancer cells is a promising strategy for inducing antitumor immunity in the treatment of lung cancer.

DOI： 10.1038/sj.cgt.7700320

DOI： https://doi.org/10.1002/(SICI)1521-4141(200004)30:4<1182::AID-IMMU1182>3.0.CO;2-H

Effect of erythromycin on matrix metalloproteinase-9 and cell migration 査読有り

Hashimoto N, Kawabe T, Hara T, Imaizumi K, Wakayama H, Saito H, Shimokata K, Hasegawa Y.

J Lab Clin Med 137 巻 ( 3 ) 頁： 176-183 2001年4月

Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcRγ-deficient mice 査読有り

Wakayama H., Hasegawa Y., Kawabe T., Hara T., Matsuo S., Mizuno M., Takai T., Kikutani H., Shimokata K.

European Journal of Immunology 30 巻 ( 4 ) 頁： 1182 - 1190 2000年5月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：European Journal of Immunology

Several recent studies have demonstrated the central role of Fc receptors (FcR) rather than the complement system in triggering hypersensitivity reactions. We investigated the role of FcR for IgG (FcγR) using a murine model of accelerated anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis as a representative of type II hypersensitivity diseases. Intravenous injection of rabbit anti-GBM antibody after preimmunization with normal rabbit IgG induced proteinuria and azotemia in wild-type C57BL/6 and CD40(+/-) mice but not in FcR γ chain (FcRγ)(-/-) mice or CD40(-/-) mice. Light microscopic findings revealed marked tissue damage in the glomeruli of wild-type C57BL/6 and CD40(+/-) mice. However, no tissue damage except polymorphonuclear cell infiltration was observed in the glomeruli of FcRγ(-/-) mice. The glomeruli of CD40(-/-) mice were almost normal. Immunohistochemistry revealed the binding of rabbit IgG to the GBM in all mice injected with anti-GBM antibody. However, depositions of mouse IgG and complement to the glomeruli were not observed in CD40(-/-) mice, and deposition of fibrin was not observed in FcRγ(-/-) or CD40(-/-) mice. These findings suggest that FcγR may initiate anti-GBM antibody-mediated renal disease. We conclude that FcγR rather than the complement system is critically involved in the development of type II hypersensitivity diseases.

Enhancement of tumoricidal activity of alveolar macrophages via CD40- CD40 ligand interaction 査読有り

Imaizumi K., Kawabe T., Ichiyama S., Kikutani H., Yagita H., Shimokata K., Hasegawa Y.

American Journal of Physiology - Lung Cellular and Molecular Physiology 277 巻 ( 1 21-1 ) 1999年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Physiology - Lung Cellular and Molecular Physiology

CD40-CD40 ligand (CD40L) interaction was originally defined as important molecules for the development of humoral immunity. Thereafter, some investigations have focused on its essential roles for the induction of cell- mediated immunity in host defenses. Here we investigated the antitumor activity of murine alveolar macrophages through CD40-CD40L interaction. The CD40L gene was transfected into murine lung cancer cells (3LLSA), and CD40L- expressing clones (3LLSA-CD40L) were established. Stimulation of CD40 molecules on the surface of alveolar macrophages with 3LLSA-CD40L cells induced the production of nitric oxide, tumor necrosis factor-α, and interleukin-12 and the tumoricidal activity of alveolar macrophages in the presence of interferon-γ, which increased the surface expression of CD40 molecules on alveolar macrophages. These findings were not observed when alveolar macrophages were obtained from CD40-deficient mice. On the other hand, interleukin-6 production by alveolar macrophages did not depend on CD40-CD40L interaction. We also established a murine melanoma cell line expressing CD40L (B16 4A5-CD40L) that could induce tumoricidal activity of alveolar macrophages. Furthermore, when spleen cells were cocultivated with 3LLSA-CD40L cells, specific cytotoxic T lymphocytes for wild-type 3LLSA cells could be induced. These results suggest that CD40L gene transfer into tumor cells may induce antitumor immunity in a tumor-bearing host and may offer a new strategy for cancer gene therapy.

DOI： 10.1152/ajplung.1999.277.1.l49