研究者詳細 - 松川　昭博

妊娠中に発症し高度のネフローゼを呈した急性糸球体腎炎の生検例

伏見聡一郎, 桑本聡史, 野坂加苗, 徳安祐輔, 中本周, 上浦望, 尾田高志, 城謙輔, 松川昭博

診断病理 30 ( 1 ) 66 - 70 2013年1月

記述言語：日本語出版者・発行元：(一社)日本病理学会

症例は妊娠中の20代女性。高度のネフローゼ症候群を呈し、腎生検が行われた。組織学的に糸球体の腫大と管内への炎症細胞浸潤を認めた。免疫染色では有意な所見は得られなかったが、組織化学的に糸球体でplasmin活性が認められ、溶連菌感染後急性糸球体腎炎と考えられた。本例の鑑別診断においてplasmin活性の酵素組織化学的所見が意義あると考えられた。文献的考察も加えて報告する。(著者抄録)

Occult Compression Fracture of Metacarpal Head without Evidence of Avascular Necrosis. 査読

Keiichiro Nishida, Hiroyuki Hashizume, Akihiro Matsukawa, Kenzo Hashizume, Yasunori Shimamura, Yasuyuki Torigoe, Toshifumi Ozaki

Acta medica Okayama 67 ( 5 ) 311 - 7 2013年

記述言語：英語掲載種別：研究論文（学術雑誌）

We report a case of 4th metacarpal head collapse of a 19-year-old healthy man. MRI revealed T1 low and T2 high regions in the collapsed 4th metacarpal head, as well as in the right 3rd and left 4th metacarpal head. Our initial diagnosis was occult compression fracture due to avascular necrosis, known as Dieterich's disease. However, pathological findings of surgically resected right 4th metacarpal head were compatible with transient osteoporosis and metacarpal head fracture followed by active tissue repair. The autologous osteochondral transplants from costchondral junction survived and maintained their size and shape even at 10-year follow-up.

マウスインフルエンザ肺炎におけるレドックス制御蛋白チオレドキシン(TRX-1)の治療的効果

八代将登, 塚原宏一, 松川昭博, 山田睦子, 藤井洋輔, 長岡義晴, 津下充, 山下信子, 伊藤利洋, 山田雅夫, 増谷弘, 淀井淳司, 森島恒雄

岡山医学会雑誌 125 ( 2 ) 109-112 (J-STAGE) - 112 2013年

Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells. 査読国際誌

Yoshimura T, Howard OM, Ito T, Kuwabara M, Matsukawa A, Chen K, Liu Y, Liu M, Oppenheim JJ, Wang JM

PloS one 8 ( 3 ) e58791 2013年

The linkage of innate and adaptive immune response during granulomatous development. 査読国際誌

Ito T, Connett JM, Kunkel SL, Matsukawa A

Frontiers in immunology 4 10 - 10 2013年

Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4. 査読国際誌

Yasuyuki Shiozaki, Takashi Kitajima, Tetsuro Mazaki, Aki Yoshida, Masato Tanaka, Akihiro Umezawa, Mariko Nakamura, Yasuhiro Yoshida, Yoshihiro Ito, Toshifumi Ozaki, Akihiro Matsukawa

International journal of nanomedicine 8 1349 - 60 2013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）

PURPOSE: Bone defects and nonunions are major clinical skeletal problems. Growth factors are commonly used to promote bone regeneration; however, the clinical impact is limited because the factors do not last long at a given site. The introduction of tissue engineering aimed to deter the diffusion of these factors is a promising therapeutic strategy. The purpose of the present study was to evaluate the in vivo osteogenic capability of an engineered bone morphogenetic protein-4 (BMP4) fusion protein. METHODS: BMP4 was fused with a nanosized carrier, collagen-binding domain (CBD), derived from fibronectin. The stability of the CBD-BMP4 fusion protein was examined in vitro and in vivo. Osteogenic effects of CBD-BMP4 were evaluated by computer tomography after intramedullary injection without a collagen-sponge scaffold. Recombinant BMP-4, CBD, or vehicle were used as controls. Expressions of bone-related genes and growth factors were compared among the groups. Osteogenesis induced by CBD-BMP4, BMP4, and CBD was also assessed in a bone-defect model. RESULTS: In vitro, CBD-BMP4 was retained in a collagen gel for at least 7 days while BMP4 alone was released within 3 hours. In vivo, CBD-BMP4 remained at the given site for at least 2 weeks, both with or without a collagen-sponge scaffold, while BMP4 disappeared from the site within 3 days after injection. CBD-BMP4 induced better bone formation than BMP4 did alone, CBD alone, and vehicle after the intramedullary injection into the mouse femur. Bone-related genes and growth factors were expressed at higher levels in CBD-BMP4-treated mice than in all other groups, including BMP4-treated mice. Finally, CBD-BMP4 potentiated more bone formation than did controls, including BMP4 alone, when applied to cranial bone defects without a collagen scaffold. CONCLUSION: Altogether, nanocarrier-CBD enhanced the retention of BMP4 in the bone, thereby promoting augmented osteogenic responses in the absence of a scaffold. These results suggest that CBD-BMP4 may be clinically useful in facilitating bone formation.

DOI： 10.2147/IJN.S44124

Elevated Levels of Monocyte Chemoattractant Protein-1 in the Aqueous Humor after Phacoemulsification 査読国際誌

Motofumi Kawai, Toshihiro Inoue, Masaru Inatani, Naoko Tsuboi, Kohei Shobayashi, Akihiro Matsukawa, Akitoshi Yoshida, Hidenobu Tanihara

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 53 ( 13 ) 7951 - 7960 2012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：ASSOC RESEARCH VISION OPHTHALMOLOGY INC

PURPOSE. To elucidate the impact of phacoemulsification on aqueous monocyte chemoattractant protein-1 (MCP-1) levels, and identify its cell origin.
METHODS. For clinical study, aqueous humor samples were collected before and after surgery (17.0 +/- 4.0 months postoperatively) from 21 cataract cases that underwent phacoemulsification and intraocular lens (IOL) implantation. Aqueous MCP-1 levels were determined using a multiplex immunoassay. For animal experiments, rabbits underwent phacoemulsification (+/- IOL). Aqueous humor samples were collected from nonoperated eyes and operated eyes, and immunoassays were performed. Eyes were analyzed by reverse transcription-polymerase chain reaction and immunohistochemical studies.
RESULTS. In the clinical study, mean (+/- SD) aqueous MCP-1 levels were higher postoperatively (1773.5 +/- 321.2 pg/mL) than preoperatively (796.9 +/- 211.3 pg/mL; P < 0.0001). In animal experiments, mean aqueous MCP-1 levels (pg/mL) were higher in postoperative eyes on day 30 (207.1 +/- 62.9) than in nonoperated eyes (31.2 +/- 12.5; P = 0.018). IOL implantation did not affect the changes in MCP-1 levels. After phacoemulsification, MCP-1 mRNA expression was increased in the cornea, iris, ciliary body, and capsular bag. Expression of MCP-1 mRNA in the capsular bag, but not the other tissues, increased from day 30 to 90. Immunohistochemical studies showed positive immunoreactivity for MCP-1 in cells of the posterior capsule after phacoemulsification.
CONCLUSIONS. Aqueous MCP-1 levels were elevated in both human and animal eyes after phacoemulsification. Proliferated lens epithelial cells on the capsule might be the major cell origin for prolonged MCP-1 production after phacoemulsification. (http://www.umin.ac.jp/number, UMIN000005788.) (Invest Ophthalmol Vis Sci. 2012;53:7951-7960) DOI: 10.1167/iovs.12-10231

DOI： 10.1167/iovs.12-10231

炎症の発現・制御におけるサイトカインシグナル伝達

松川昭博

小児感染免疫 24 ( 3 ) 303 - 307 2012年10月

Spred-2 deficiency exacerbates acetaminophen–induced hepatotoxicity in mice. 査読国際誌

Wakabayashi H, Ito T, Fushimi S, Nakashima Y, Itakura J, Qiuying L, Min Min Win, Cuiming S, Chen C, Sato M, Mino M, Ogino T, Makino H, Yoshimura A, Matsukawa A

Clin Immunol. 144 ( 3 ) 272 - 282 2012年9月

Notch system in the linkage of innate and adaptive immunity. 査読国際誌

Ito T, Connett JM, Kunkel SL, Matsukawa A

Journal of leukocyte biology 92 ( 1 ) 59 - 65 2012年7月

Effects of Pharyngeal Cooling on Brain Temperature in Primates and Humans A Study for Proof of Principle 査読国際誌

Yoshimasa Takeda, Hiroshi Hashimoto, Koji Fumoto, Tetsuya Danura, Hiromichi Naito, Naoki Morimoto, Hiroshi Katayama, Soichiro Fushimi, Akihiro Matsukawa, Aiji Ohtsuka, Kiyoshi Morita

ANESTHESIOLOGY 117 ( 1 ) 117 - 125 2012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：LIPPINCOTT WILLIAMS & WILKINS

Background: Pharyngeal cooling decreases brain temperature by cooling carotid arteries. This study was designed to evaluate the principle of pharyngeal cooling in monkeys and humans.
Methods: Monkeys (n = 10) were resuscitated following 12 min of cardiac arrest. Pharyngeal cooling (n = 5), in which cold saline (5 degrees C) was perfused into the cuff at the rate of 500 ml/min, was initiated simultaneously with the onset of resuscitation for 30 min. Patients (n = 3) who were in an intensive care unit were subjected to 30 min of pharyngeal cooling under propofol anesthesia.
Results: In the animal study, core brain temperature was significantly decreased compared with that in the control group by 1.9 degrees C (SD = 0.8, P < 0.001) and 3.1 degrees C (SD = 1.0, P < 0.001) at 10 ruin and 30 min after the onset of cooling, respectively. The cooling effect was more evident in an animal with low postresuscitation blood pressure. Total dose of epinephrine, number of direct current shocks, and recovery of blood pressure were not different between the two groups. The pharyngeal epithelium was microscopically intact on day 5. In the clinical study, insertion of the cuff and start of perfusion did not affect heart rate or blood pressure. Tympanic temperature was decreased by 0.6 +/- 0.1 degrees C/30 min without affecting bladder temperature. The pharynx was macroscopically intact for 3 days.
Conclusions: Pharyngeal cooling rapidly and selectively decreased brain temperature in primates and tympanic temperature in humans and did not have adverse effects on return of spontaneous circulation, even when initiated during cardiac arrest in primates.

DOI： 10.1097/ALN.0b013e3182580536

Spred-2 negatively regulates influenza A virus (H1N1)-induced pneumonia 査読

Toshihiro Ito, Akihiko Yoshimura, Akihiro Matsukawa

JOURNAL OF IMMUNOLOGY 188 2012年5月

Egr1: a novel target for ameliorating acute allograft rejection in an experimental lung transplant model 査読国際誌

Naohisa Waki, Masaomi Yamane, Sumiharu Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Akihiro Matsukawa, Takahiro Oto, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 41 ( 3 ) 669 - 675 2012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：OXFORD UNIV PRESS INC

Acute allograft rejection is one of the significant complications occurring in lung transplant recipients. Early growth response-1 (Egr-1), zinc-finger-type transcription factor, is known as a master switch regulator of diverse chemical mediators. We used an orthotopic mouse model of left lung transplant to elucidate the function of Egr-1 in acute pulmonary rejection.
Left lung grafts retrieved from C57BL/6 wild mice or C57BL/6 Egr-1-null mice were orthotopically transplanted into BALB/c mice; the lungs were harvested at day 1, 3, 5 or 7 after lung transplantation. The grade of acute rejection was histopathologically evaluated. The intragraft gene expression levels of Egr-1 and downstream target mediators were quantitatively measured by real-time polymerase chain reaction. Immunohistochemical analysis was used to determine the location and distribution of the Egr-1 protein in the pulmonary graft.
Severe acute rejection was observed in allografts from wild-type mice at 5 days after transplantation. Only minimal rejection was seen in the lung graft from Egr-1-null donor mice at 5 days after transplantation. Strong upregulation of Egr-1 mRNA transcripts was observed at day 1, which then decreased during the next 5 days. The mRNA of Egr-1 target mediators [interleukin-1-beta (IL-1 beta), monocyte chemotactic protein-1 (MCP-1) and plasminogen activator inhibitor-1] reached maximal levels at day 5. Egr-1-null allografts exhibited significantly lower expressions of IL-1 beta and MCP-1 mRNA (P < 0.05).
Our study showed that deletion of Egr-1 in lung allografts ameliorates severe acute rejection with the reduction of expression levels of chemical mediators, implying a new possible strategy for treating acute pulmonary allograft rejection.

DOI： 10.1093/ejcts/ezr030

Local effects of intra-articular injection of anti-rabbit tumor necrosis factor alpha monoclonal antibody in antigen-induced arthritis of the rabbit temporomandibular joint 査読国際誌

Taishi Ohtani, Manabu Habu, Amit Khanal, Izumi Yoshioka, Akihiro Matsukawa, Kazuhiro Tominaga

JOURNAL OF ORAL PATHOLOGY & MEDICINE 41 ( 1 ) 96 - 105 2012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：WILEY-BLACKWELL

BACKGROUND: Local effects of intra-articular (IA) injection of anti-rabbit tumor necrosis factor alpha monoclonal antibody (anti-TNF alpha mAb) for antigen-induced mono-arthritis (AIA) of the rabbit temporomandibular joint (TMJ) and its systemic influences were evaluated.
METHODS: Biochemical analysis of synovial fluid (SF), clinical and histopathological analyses of TMJ, and serum analysis were performed after inducing AIA in bilateral TMJs of 40 New Zealand White rabbits. IA injection of anti-TNF alpha mAb in unilateral TMJ (TNF blockade side; n = 12) and IgG (n = 12) was performed while saline injected on the contralateral side. TNF alpha and IL-1 beta in SF was analyzed at Days 1, 3, 7, and 21. Joint swelling and head withdrawal reflex threshold (WRT) over TMJs were evaluated in TNF blockade side (n = 12) with histopathological analysis at Days 3, 7, and 21. In remaining four animals with TNF blockade, TNF alpha and anti- TNF alpha mAb in serum were analyzed.
RESULTS: Tumor necrosis factor alpha in SF was significantly lower in TNF blockade side on all days but IL-1 beta was lower only on Day 3. WRT was significantly higher at all times in the blockade side. Less inflammatory reactions and degenerative changes of cartilage were observed on Days 7 and 21 in the blockade side. TNF alpha and anti- TNF alpha mAb were under detection level in serum at all times.
CONCLUSIONS: Intra-articular injection of anti- rabbit TNF alpha mAb in mono-arthritis model was effective to control local inflammation and degenerative joint changes. Further, low-dose IA injection of antibody may not have systemic side effects. J Oral Pathol Med (2012) 41: 96105

DOI： 10.1111/j.1600-0714.2011.01056.x

Prostatic stromal tumor of uncertain malignant potential (STUMP) with unrecognized growth pattern 査読国際誌

Soichiro Fushimi, Tetsuya Ogino, Ken Aoki, Junya Itakura, Toshihiro Ito, Tadashi Oeda, Hiroyuki Yanai, Akihiro Matsukawa

PATHOLOGY INTERNATIONAL 62 ( 1 ) 69 - 71 2012年1月

Correlation of neutrophil and monocyte derived interleukin-1 receptor antagonist and interleukin-8 with colitis severity in the rabbit 査読国際誌

Kenta Kaneda, Fumio Saitoh, Hirom Shibusawa, Hidetaka Maegawa, Abbi R. Saniabadi, Nobuhito Kashiwagi, Akihiro Matsukawa

CYTOKINE 56 ( 2 ) 508 - 514 2011年11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：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD

Activated neutrophils and monocytes produce interleukin (IL)-8, a pro-inflammatory chemokine, but also IL-1 receptor antagonist (IL-1ra), which is an anti-inflammatory cytokine. We were interested to see the profiles of IL-8 and IL-1ra in the colonic tissue and in the peripheral blood leukocytes (PBL) during the development of immune complex induced colitis in rabbits. IL-1ra and IL-8 in PBL were measured in 26 rabbits at time 0 h, 24 h, and 48 h after induction of colitis. The colons were removed at 48 h for measuring myeloperoxidase (MPO), ulcer area, IL-1ra and IL-8. Epithelial damage, crypt abscess formation and leukocyte infiltration of the colonic tissue were major features of this colitis model. During the development of colitis, there was an increase in circulating neutrophils and monocytes (P < 0.0001), but not lymphocytes. Likewise, elevated amounts of IL-Ira (P = 0.0001) and IL-8 (P = 0.0219) production by PBL were observed following induction of colitis. Flow cytometry revealed major source of IL-1ra was monocytes, while the main sources of IL-8 were neutrophils and monocytes. There was correlation between MPO and ulcer area (R(s) = 0.6327, P < 0.0001). At 24 h, PBL from MPO(High) group (n = 11) showed increased IL-1ra (P = 0.027) and IL-8 (P = 0.0128) levels vs MPO(Low) group (n = 15). IL-8 production by PBL showed correlation with tissue MPO (R(s) = 0.4273, P = 0.0295). The colitis in this model was associated with an increase in circulating monocytes and neutrophils, which released increased amounts of IL-8 and IL-1ra. Further, IL-8 and IL-1ra showed correlation with the severity of colitis. These observations should significantly further understandings on the role of neutrophils and monocytes in the immunopathogenesis of ulcerative colitis. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.cyto.2011.07.008

The Critical Role of Notch Ligand Delta-like 1 in the Pathogenesis of Influenza A Virus (H1N1) Infection 査読国際誌

Toshihiro Ito, Ronald M. Allen, William F. Carson, Matthew Schaller, Karen A. Cavassani, Cory M. Hogaboam, Nicholas W. Lukacs, Akihiro Matsukawa, Steven L. Kunkel

PLOS PATHOGENS 7 ( 11 ) e1002341 2011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：PUBLIC LIBRARY SCIENCE

Influenza A viral infections have been identified as the etiologic agents for historic pandemics, and contribute to the annual mortality associated with acute viral pneumonia. While both innate and acquired immunity are important in combating influenza virus infection, the mechanism connecting these arms of the immune system remains unknown. Recent data have indicated that the Notch system is an important bridge between antigen-presenting cells (APCs) and T cell communication circuits and plays a central role in driving the immune system to overcome disease. In the present study, we examine the role of Notch signaling during influenza H1N1 virus infection, focusing on APCs. We demonstrate here that macrophages, but not dendritic cells (DCs), increased Notch ligand Delta-like 1 (Dll1) expression following influenza virus challenge. Dll1 expression on macrophages was dependent on retinoic acid-inducible gene-I (RIG-I) induced type-I IFN pathway, and not on the TLR3-TRIF pathway. We also found that IFN alpha-Receptor knockout mice failed to induce Dll1 expression on lung macrophages and had enhanced mortality during influenza virus infection. Our results further showed that specific neutralization of Dll1 during influenza virus challenge induced higher mortality, impaired viral clearance, and decreased levels of IFN-gamma. In addition, we blocked Notch signaling by using gamma-secretase inhibitor (GSI), a Notch signaling inhibitor. Intranasal administration of GSI during influenza infection also led to higher mortality, and higher virus load with excessive inflammation and an impaired production of IFN-gamma in lungs. Moreover, Dll1 expression on macrophages specifically regulates IFN-gamma levels from CD4(+) and CD8(+) T cells, which are important for anti-viral immunity. Together, the results of this study show that Dll1 positively influences the development of anti-viral immunity, and may provide mechanistic approaches for modifying and controlling the immune response against influenza H1N1 virus infection.

DOI： 10.1371/journal.ppat.1002341

黒色真菌Exophiala. jeanselmeiによる左手背皮下膿瘍を呈したフェオヒフォミコーシスの１例

森三郎, 平谷恵子, 井上さおり, 川上直明, 藤野寿幸, 松川昭博

尾道市立病院医学雑誌 27 ( 1 ) 55 - 58 2011年

記述言語：日本語出版者・発行元：尾道市立市民病院

84歳女性。左手指示中手指関節背側の腫脹および発赤、圧痛、左手背部の軽度熱感を主訴に近医を受診後、著者らの施設へ紹介受診となった。左手指示中手指関節背側に対し皮化膿瘍部の穿刺吸引、排膿、ならびに患部切開排膿が施行された。その結果、、微生物的検査では糸状菌が、また培養検査では黒色真菌が検出された。更に加えて生育温度テストではExophiala jeanselmeiが同定された。尚、施行後は抗真菌薬の服用により左手背腫脹は軽減し、疼痛も消失した。