研究者詳細 - 松川　昭博

Increased CCL2 Expression and Macrophage/Monocyte Migration During Microbicide-Induced Vaginal Irritation 査読国際誌

Carsten Alt, Travis Harrison, Linda Dousman, Nahoko Fujita, Ken Shew, Thanh-Thuy Tran, Sara Shayesteh, Akihiro Matsukawa, Jon Mirsalis, Annalisa D&apos, Andrea

CURRENT HIV RESEARCH 7 ( 6 ) 639 - 649 2009年11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：BENTHAM SCIENCE PUBL LTD

Despite availability of successful prevention strategies, HIV continues to spread at alarming rates, especially among women in developing countries. Vaginal microbicides offer a promising approach for blocking transmission of HIV when condom use cannot be negotiated with male partners. A major problem in the development of vaginal microbicides is chemically induced vaginal irritation, which can enhance the risk of HIV transmission. Evaluation of vaginal irritation prior to clinical trials typically uses an expensive and animal-intensive rabbit vaginal irritation model, which could be supplemented by measuring additional inflammatory biomarkers. We studied several immunological parameters as potential biomarkers of vaginal irritation, using the spermicides nonoxynol-9 and benzalkonium chloride as test microbicides. We measured amounts of cytokines, as well as inflammatory cells, in vaginal tissue lysates and on the vaginal surface. We observed that treatment with the selected microbicides increases quantities of the inflammatory cytokines interleukin-1, CXCL8, and CCL2 in the vaginal tissue parenchyma, and of CCL2 on the vaginal surface. This observation was correlated with increases in macrophages in the vaginal parenchyma. We suggest that measurements of CCL2 and macrophages can serve as new inflammatory biomarkers to evaluate the safety of promising novel microbicides for prevention of HIV.

DOI： 10.2174/157016209789973682

Successful steroid pulse therapy for brain lesion caused by Shiga toxin 2 in rabbits (vol 46, pg 179, 2009) 査読

Jun Fujii, Yoshimasa Kinoshita, Akihiro Matsukawa, Sharon Y. A. M. Villanueva, Takashi Yutsudo, Shin-ichi Yoshida

MICROBIAL PATHOGENESIS 46 ( 6 ) 345 - 345 2009年6月

Galectin-9 accelerates transforming growth factor beta 3-induced differentiation of human mesenchymal stem cells to chondrocytes 査読国際誌

Tomohiro Arikawa, Akihiro Matsukawa, Kota Watanabe, Ken-mei Sakata, Masako Seki, Megumi Nagayama, Keisuke Takeshita, Kanako Ito, Toshiro Niki, Souichi Oomizu, Rika Shinonaga, Naoki Saita, Mitsuomi Hirashima

BONE 44 ( 5 ) 849 - 857 2009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：ELSEVIER SCIENCE INC

Galectin-9 (Gal-9), a beta-galactoside binding lectin, plays a crucial role in innate and adaptive immunity. in the rat collagen-induced arthritis model, administration of Gal-9 induced repair of existing cartilage injury even when joints were already swollen with cartilage destruction. We thus attempted to explore the role of Gal-9 in chondrocyte differentiation utilizing human mesenchymal stem cell (MSC) pellet Cultures. During chondrogenesis induced by transforming growth factor beta 3 (TGF beta 3), MSCs strongly expressed endogenous Gal-9. Expression of Gal-9 peaked on day 14 and the neutralization of endogenous Gal-9 resulted in the reduced chondrogenesis, indicating possible involvement of Gal-9 in TGF beta-mediated chondrogenesis. In pellets, addition of Gal-9 significantly enhanced TGF beta 3-induced chondrogenesis. as evidenced by increasing proteoglycan content, but not cell proliferation. In the absence of Gal-9, collagen expression by MSCs switched from type I to type II on 28 days after stimulation with TGR beta 3. When MSCs were co-stimulated with Gal-9, the class switch occurred on day 21. In addition, Gal-9 synergistically enhanced TGF beta 3-induced phosphorylation of Smad2, though Gal-9 did not itself induce detectable Smad2 phosphorylation. These results Suggest that Gal-9 has a beneficial effect on cartilage repair in injured joints by induction of differentiation of MSCs into chondrocytes. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bone.2009.01.365

Successful steroid pulse therapy for brain lesion caused by Shiga toxin 2 in rabbits 査読国際誌

Jun Fujii, Yoshirnasa Kinoshita, Akihiro Matsukawa, Sharon Y. A. M. Villanueva, Takashi Yutsudo, Shin-ichi Yoshida

MICROBIAL PATHOGENESIS 46 ( 4 ) 179 - 184 2009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：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD

Betamethasone sodium phosphate (BSP) is usually used as a steroid therapy for human brain edema. High doses of BSP (36 mg/kg) twice a day for two days statistically reduced the mortality rate and improved the survival period of Stx2 (1.4 mu g/kg: 1.6LD(50))-toxemic rabbits. We made evaluations on three kinds of magnetic resonance images (MRI) including T1-weighted, T2-weighted, and enhanced MRI using gadopentetate dimeglumine (Gd-DTPA) to detect brain lesion induced by an intravenous injection of Stx2 in rabbits. Enhanced T1-weighted MRI was the most sensitive tool to find leakage of Gd-DTPA suggesting impairment of the blood brain barrier caused by Stx2. Enhanced MRI revealed that BSP treatment inhibited the leakage of Gd-DTPA, as directly evidenced by the protective effect of BSP against brain edema induced by intravenous injection of Stx2. Interleukin 1 beta was not induced after Stx2 treatment in brain primary mixed cell culture. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.micpath.2009.01.005

Activation of c-Jun N-terminal kinase is essential for oxidative stress-induced Jurkat cell apoptosis by monochloramine 査読国際誌

Tetsuya Ogino, Michitaka Ozaki, Mutsumi Hosako, Masako Omori, Shigeru Okada, Akihiro Matsukawa

LEUKEMIA RESEARCH 33 ( 1 ) 151 - 158 2009年1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：PERGAMON-ELSEVIER SCIENCE LTD

Leukemic cell apoptosis may be enhanced by appropriate oxidative stress. We report here the mechanism of Jurkat cell apoptosis by monochloramine (NH(2)Cl), a neutrophil-derived oxidant. NH(2)Cl induced caspase-dependent apoptosis, which was preceded by cytochrome c and Smac/Diablo release from mitochondfia. Within 10 min of NH(2)Cl treatment, c-Jun N-terminal kinase (JNK) activation and elevation of cytosolic Ca(2+) were observed. JNK inhibitors (SP600125 or JNK inhibitor VIII) significantly suppressed the apoptosis as well as caspase cleavage and cytochrome c release. In contrast, Ca(2+) chelation by EGTA + acetoxymethyl-EGTA had no effects on apoptosis. Our results indicated that JNK activation contributed most importantly to the NH(2)Cl-induced apoptosis. (C) 2008 Elsevier Ltd. All fights reserved.

DOI： 10.1016/j.leukres.2008.07.009

Pathophysiology of sepsis and recent patents on the diagnosis, treatment and prophylaxis for sepsis 招待査読国際誌

Yasumasa Okazaki, Akihiro Matsukawa

Recent Patents on Inflammation and Allergy Drug Discovery 3 ( 1 ) 26 - 32 2009年

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Despite advances in the development of powerful antibiotics and intensive care unit, sepsis is still life threatening and the mortality rate remains unchanged for the past three decades. Recent prospective trials with biological response modifiers have shown a modest clinical benefit. The pathological basis of sepsis is initially an excessive inflammatory response against invading pathogens, leading to systemic inflammatory response syndrome (SIRS). Evidence reveals that a variety of inflammatory mediators orchestrate the intense inflammation through complicated cellular interactions. More recent data indicate that most septic patients survive this stage and then subjected to an immunoparalysis phase, termed compensatory anti-inflammatory response syndrome (CARS), which is more fatal than the initial phase. Sepsis is a complicated clinical syndrome with multiple physiologic and immunologic abnormalities. In this review, we summarize the recent understandings of the pathophysiology of sepsis, and introduce recent patents on diagnosis, treatment and prophylaxis for sepsis. © 2009 Bentham Science Publishers Ltd.

DOI： 10.2174/187221309787158416

Scopus

Invasion of atheromatous plaques into tunica media causes coronary outward remodeling in WHHLMI rabbits 査読国際誌

Masashi Shiomi, Satoshi Yamada, Akihiro Matsukawa, Hiroyuki Itabe, Takashi Ito

ATHEROSCLEROSIS 198 ( 2 ) 287 - 293 2008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：ELSEVIER IRELAND LTD

To clarify the mechanism of coronary outward remodeling, we examined atherosclerotic coronary arteries morphologically using WHHLMI rabbits that develop coronary atherosclerosis spontaneously. Perfusion-fixed coronary segments of WHHLMI rabbits were prepared at 500 mu m intervals. After immunohistochemical staining and histopathological staining, the areas and lengths of the arterial wall and the lesions were measured. Obvious outward remodeling was observed in coronary sections with greater than 40% cross-sectional narrowing. In coronary sections with greater than 40% cross-sectional narrowing, the tunica media was thick at the shoulder of atheromatous plaque and was thin beneath the atheromatous plaques. Macrophages infiltrated those attenuated tunica media expressed matrix metalloproteinases and oxidized LDL was accumulated in those areas. In those areas, collagen fibers and the internal elastic lamina had disappeared partly and apoptotic smooth muscle cells were observed. Proliferation of smooth muscle cells was observed at the attenuated tunica media and adjacent adventitia. The present results suggest that invasion of atheromatous plaques into the tunica media causes coronary outward remodeling. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2008.02.010

Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis 査読国際誌

Masako Seki, Souichi Oomizu, Ken-mei Sakata, Atsuko Sakata, Tomohiro Arikawa, Kota Watanabe, Kanako Ito, Keisuke Takeshita, Toshiro Niki, Naoki Saita, Nozomu Nishi, Akira Yamauchi, Shigeki Katoh, Akihiro Matsukawa, Vijay Kuchroo, Mitsuomi Hirashima

CLINICAL IMMUNOLOGY 127 ( 1 ) 78 - 88 2008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：ACADEMIC PRESS INC ELSEVIER SCIENCE

The effects of galectin-9 on a mouse collagen-induced arthritis (CIA) model were assessed to clarify whether galectin-9 suppresses CIA by regulating T cell. immune responses. Galectin-9 suppressed CIA in a dose-dependent manner, and such suppression was observed even when treatment was started on 7 days after the booster, indicating its preventive and therapeutic effects. Galectin-9 induced the decreased levels of pro-inflammatory cytokines, IL-17, IL-12, and IFN gamma in the joint. Gatectin-9 induced the decreased number of CD4(+) TIM-3(+) T cells in peripheral blood. Galectin-9-deficient mice became susceptible to CIA may be by increased number of CD4(+) TIM-3(+) T cells and decreased number of Treg cells. We further found that galectin-9 induces differentiation of naive T cells to Treg cells, and it suppresses differentiation to Th17 cells in vitro. The present results suggested that galectin-9 ameliorates CIA by suppressing the generation of Th17, promoting the induction of regulatory T cells. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.clim.2008.01.006

悪性中皮腫の１剖検例

尾関孝二, 三輪栄子, 筑田絵理, 原田美由紀, 松川昭博

日本臨床細胞学会岡山支部会誌 26 37 - 38 2008年

乳腺血管肉腫の１例.

松岡博美, 井上博文, 今井みどり, 藤田勝, 森下由美子, 大森昌子, 市村浩一, 柳井広之, 大原信哉, 松川昭博

日本臨床細胞学会岡山支部会誌 27 34 - 35 2008年

記述言語：日本語出版者・発行元：岡山県臨床細胞学会

32歳女。主訴は左乳房のしこりであった。腫瘤は20cm大で、針生検にて血管系腫瘍が疑われた。右乳房にも超音波・MRIで左腫瘍と類似した腫瘤影があり、左皮下乳腺全摘+右乳腺部分切除術を施行した。摘出材料は出血を伴った充実性腫瘤で、HE標本ではクロマチン増量と核異型を有する短紡錘形細胞が毛細血管類似の管腔を形成し、浸潤性増殖していた。捺印細胞標本では赤血球を背景に単在〜集塊状に類円形細胞と紡錘形細胞が混在する腫瘍細胞を認め、いずれも切れ込みを有する核や核の抱きこみ像を多数認めた。細胞質内にはhaloを伴う赤血球様物質を容れた腫瘍細胞やベルリン青陽性ヘモジデリン顆粒を貪食した細胞を認め、免疫染色ではCD31・CD34が類円形細胞・紡錘形細胞ともに陽性で、MIB1陽性率は40%であり、血管肉腫と診断した。

悪性転化を示したnuclear palisadingを伴う隆起性皮膚線維肉腫の一例.

大森昌子, 柳井広之, 荻野哲也, 松川昭博, 吉野正

診断病理 25 ( 2 ) 72 - 76 2008年

記述言語：日本語出版者・発行元：(一社)日本病理学会

症例は59歳女性。左膝窩部の皮膚から皮下組織におよぶ8×6cm大の腫瘍が存在し、腫瘍切除術が施行された。組織学的には、通常型の隆起性皮膚線維肉腫(dermatofibrosarcoma protuberans;DFSP)の領域から移行して明瞭なnuclear palisadingを示す部分が散在性に認められた。いずれの領域もCD34はびまん性に強陽性を示した。また線維肉腫に相当する高悪性度肉腫の領域が存在し、その部分ではCD34が減弱〜陰性化していた。Nuclear palisadingを示すDFSPから発生した稀なfibrosarcomaの1例を報告する。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J03623&link_issn=&doc_id=20080515230004&doc_link_id=%2Fcd9jjodp%2F2008%2F002502%2F004%2F0072-0076%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcd9jjodp%2F2008%2F002502%2F004%2F0072-0076%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

HEART's Original [症例] 生前診断が困難であった非細菌性血栓性心内膜炎の1例

橘元見, 久保元基, 高村俊行, 小林博夫, 松本佳則, 松川昭博

心臓 40 ( 10 ) 875 - 880 2008年

記述言語：日本語

症例は55歳,女性.2006年11月感冒症状にて近医通院中,見当識障害が出現し当院紹介入院となる.入院時血液検査で炎症反応の上昇を認め,頭部CTで多発性脳梗塞,心エコーで僧帽弁に疣贅が認められたため.感染性心内膜炎に伴う脳塞栓症と判断し抗生物質を投与したが疣贅の縮小はみられなかった.治療期間中施行した血液培養はすて陰性だった.疣贅は抗菌薬抵抗性で可動性も大きく脳梗塞の再発が危惧された.腹部骨盤CTにて偶然卵巣癌が発見されたが,まず心内膜炎治療が優先されると考え手術目的で転院したが,手術目前で再度脳梗塞をきたし手術適応外となり当院に再入院となった.その後も抗菌薬治療を継続したが疣贅の縮小はなく,2007年4月卵巣癌の進行により永眠された.剖検では疣贅はフィブリン塊,粗な結合組織から成り,その組織内に炎症所見,細菌像はなく培養も陰性であり非細菌性血栓性心内膜炎と考えられた.

DOI： 10.11281/shinzo1969.40.10_875

CiNii Article

第34回医学教育者のためのワークショップ (富士研ワークショップ) の記録

齋藤宣彦, 伴信太郎, 堀内三郎, 平出敦, 木下牧子, 中島宏昭, 吉岡俊正, 船橋俊一, 小林直人, 日野原重明, 竹内弘高, 水流聡子, 本田麻由美, 三浦公嗣, 栗山雅秀, 菅野典子, 海老根潤, 久保田久里, 伊藤達朗, 今中啓之, 川前金幸, 酒井賢一郎, 清水俊明, 冨田泰彦, 松本哲哉, 和佐勝史, 青木昭子, 和泉俊一郎, 犬塚裕樹, 及川公生, 大槻眞嗣, 大野浩司, 栂博久, 奈良正之, 伊坪真理子, 井廻道夫, 内ヶ崎西作, 岡見豊一, 高水間亮治, 錦見尚道, 濱田久之, 稲葉宗通, 入江徹美, 内田伸恵, 首藤太一, 永山和宜, 廣川慎一郎, 増田友之, 吉村明修, 樫田光夫, 金子一成, 田中克之, 谷憲治, 福沢嘉孝, 俣木志朗, 松川昭博, 守屋利佳

医学教育 39 ( 3 ) 205 - 220 2008年

腹水中に腫瘍細胞を認めた乳腺小葉癌の１例.

藤田勝, 松岡博美, 井上博文, 今井みどり, 森下由美子, 大森昌子, 市村浩一, 柳井広之, 大原信哉, 松川昭博

日本臨床細胞学会岡山支部会誌 27 36 - 37 2008年

記述言語：日本語出版者・発行元：岡山県臨床細胞学会

70歳女。5年前に右乳癌にて乳房切除を施行され化学療法を続けてきたが、CEAの上昇とともに結腸の多発通過障害が出現したため開腹手術を行った。腹膜・大網に播種結節を認め、貯留腹水の細胞診では核異型が軽度で散在性ないし小集塊状の腫瘍細胞が散見された。一部の腫瘍細胞では細胞質の突出像や相互封入像を認め、PAS反応は細胞質にびまん性陽性を認めた。大網生検組織でも均一な小型の異型細胞が疎な結合を示して浸潤性に増殖し、原発巣に類似する組織所見を認めた。PAS反応では腫瘍細胞の胞体にびまん性陽性を認め、免疫染色ではエストロゲン受容体陽性、プロゲステロン受容体・HER2・Eカドヘリン陰性であり、乳癌invasive lobular carcinoma転移と診断した。

STAT proteins in innate immunity during sepsis: Lessons from gene knockout mice 招待査読

Akihiro Matsukawa

ACTA MEDICA OKAYAMA 61 ( 5 ) 239 - 245 2007年10月

担当区分：筆頭著者,　最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

The innate immune system provides immediate defense against infection and serves as the first line of host defense during infection. In innate immunity, leukocytes such as neutrophils; and macrophages recognize and respond to pathogens in a non-specific manner. Therefore, the recruitment and activation of leukocytes are essential in innate immunity, and are governed by a variety of chemical mediators including cytokines. Cytokines are generally divided into 2 types, termed type-1 and type-2 cytokines. Type-1 cytokines are important in local host defense, while type-2 cytokines play a protective role when inflammatory response spreads to the body. These cytokines exert their biological functions through the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1/3/4/6 are transcription factors that mediate IFN gamma/IL-10/IL-12/IL-13 cytokine signaling, respectively. Evidence indicates that STAT proteins have a significant impact on innate immunity during sepsis. This review focuses on recent understandings in the regulation of innate immunity by STAT proteins during sepsis and septic shock. The suppressor of cytokine signaling (SOCS) proteins are a family of SH2 domain-containing cytoplasmic proteins that complete a negative feedback loop to attenuate signal transduction from cytokines that act through the JAK/STAT pathway. The participation of SOCS proteins in sepsis is also discussed.

DOI： 10.18926/AMO/32897