Faculty Profiles - OZAKI Toshifumi

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久慈怜, 高畑智宏, 松川昭博, 古松毅之, 野田知之, 尾崎敏文

日本整形外科学会雑誌 82 ( 8 ) S1260 - S1260 2008.8

マウス抗II型コラーゲン抗体関節炎におけるTh1/2反応とSOCS3・SOCS5による制御

高畑智宏, 松川昭博, 西田圭一郎, 尾崎敏文

日本整形外科学会雑誌 82 ( 8 ) S1244 - S1244 2008.8

Intra-articular injection of interleukin-4 decreases nitric oxide production by chondrocytes and ameliorates subsequent destruction of cartilage in instability-induced osteoarthritis in rat knee joints

M. Yorimitsu, K. Nishida, A. Shimizu, H. Doi, S. Miyazawa, T. Komiyama, Y. Nasu, A. Yoshida, S. Watanabe, T. Ozaki

OSTEOARTHRITIS AND CARTILAGE 16 ( 7 ) 764 - 771 2008.7

Language：English Publisher：ELSEVIER SCI LTD

Objective: To investigate the in vitro and in vivo effects of interleukin (IL)-4 on mechanical stress-induced nitric oxide (NO) expression by chondrocytes, and destruction of cartilage and NO production in an instability-induced osteoarthritis (OA) model in rat knee joints, respectively.
Materials and methods: Cyclic tensile stress (CTS; 0.5 Hz and 7% elongation) was applied to cultured normal rat chondrocytes with or without pre-incubation with recombinant rat IL-4 (rrIL-4). Inducible NO synthase (iNOS) mRNA expression and NO production were examined with real-time polymerase chain reaction and the Griess reaction, respectively. OA was induced in rat knee joints by transection of the anterior cruciate and medial collateral ligaments and resection of the medial meniscus. rrIL-4 (10, 50, and 100 ng/joint/day) was injected intra-articularly, and knee joint samples were collected 2, 4, and 6 weeks after surgery. Cartilage destruction was evaluated by the modified Mankin score and Osteoarthritis Research Society International scoring system on paraffin-embedded sections stained with safranin O. Cleavage of aggrecan and NO production were examined by immunohistochemistry for aggrecan neoepitope (NITEGE) and of nitrotyrosine (NT), respectively.
Results: rrIL-4 down-regulated CTS-induced iNOS mRNA expression and NO production by chondrocytes. The intra-articular injection of rrIL-4 gave rise to a limited, but significant amelioration of cartilage destruction, prevention of loss of aggrecan, and decrease in the number of NT-positive chondrocytes, an effect that was not dose-dependent.
Conclusion: The present study suggests that IL-4 may exert chondroprotective properties against mechanical stress-induced cartilage destruction, at least in part, by inhibiting NO production by chondrocytes. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.joca.2007.11.006

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Photodynamic therapy with ATX-S10 center dot Na(II) inhibits synovial sarcoma cell growth

Ken Takeda, Toshiyuki Kunisada, Shinichi Miyazawa, Yoshinori Nakae, Toshifumi Ozaki

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 466 ( 7 ) 1726 - 1733 2008.7

Language：English Publisher：SPRINGER

Photodynamic therapy (PDT) is an effective cancer treatment modality that allows selective destruction of malignant tumor cells. We asked whether PDT could inhibit in vivo and in vitro growth of synovial sarcoma cells. We analyzed PDT using ATX-S10 center dot Na(II) and a diode laser for a synovial sarcoma cell line (SYO-1). Photodynamic therapy with ATX-S10 center dot Na(II) showed an in vitro cytotoxic effect on the cultured SYO-1 cells. The in vitro effect of PDT depended on the treatment concentration of ATX-S10 center dot Na(II) and the laser dose of irradiation. ATX-S10 center dot Na(II) was detected in the tumor tissue specimens that were excised from nude mice bearing SYO-1 within 6 hours after intravenous injection, but it was eliminated from the tumor 12 hours after injection. Photodynamic therapy suppressed the tumor growth of nude mice bearing SYO-1, and high-dose irradiation induced no viable tumor cells in histologic specimens. Photodynamic therapy performed after marginal resection of the tumor of nude mice bearing SYO-1 reduced the rate of local recurrence of the tumor. Our results suggest PDT using ATX-S10 center dot Na(II) and laser irradiation may be a potentially useful treatment for synovial sarcoma, especially to reduce the surgical margin and preserve critical anatomic structures adjacent to the tumor.

DOI： 10.1007/s11999-008-0284-6

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1A1-C12 A tool system to protect soft tissues for robot-assisted orthopedic surgery

Osa Takayuki, SUGITA Naohiko, NAKAJIMA Yoshikazu, FUJIWARA Kazuo, ABE Nobuhiro, OZAKI Toshifumi, SUZUKI Masahiko, MITSUISHI Mamoru

2008 "1A1 - C12(1)"-"1A1-C12(2)" 2008.6

Language：Japanese Publisher：The Japan Society of Mechanical Engineers

In robot-assisted orthopedic surgery system, rotational tools are often used because traditional industrial CAM can be applied to these systems. On the other hand, in case that a rotational cutting tool is used, non-working part of the cutting edge is likely to collide and damage soft tissue such as skin, tendon and patella. We developed a cutting tool equipped with a tool cover to cover a non-working part of the cutting edge to protect soft tissue in minimally invasive orthopedic surgery. In order to evaluate the cutting tool system, we performed a total knee arthroplasty with a cadaver. The experiment showed that the cutting tool system decreased the damage of soft tissue and the cutting tool system was effective.

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Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel

Takeshi Kikuchi, Satoshi Kubota, Koji Asaumi, Harumi Kawaki, Takashi Nishida, Kazumi Kawata, Shigeru Mitani, Yasuhiko Tabata, Toshifumi Ozaki, Masaharu Takigawa

TISSUE ENGINEERING PART A 14 ( 6 ) 1089 - 1098 2008.6

Language：English Publisher：MARY ANN LIEBERT, INC

CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a unique molecule that promotes the entire endochondral ossification process and regeneration of damaged articular cartilage. Also, CCN2 has been shown to enhance the adhesion and migration of bone marrow stromal cells as well as the growth and differentiation of osteoblasts; hence, its utility in bone regeneration has been suggested. Here, we evaluated the effect of CCN2 on the regeneration of an intractable bone defect in a rat model. First, we prepared two recombinant CCN2s of different origins, and the one showing the stronger effect on osteoblasts in vitro was selected for further evaluation, based on the result of an in vitro bioassay. Next, to obtain a sustained effect, the recombinant CCN2 was incorporated into gelatin hydrogel that enabled the gradual release of the factor. Evaluation in vivo indicated that CCN2 continued to be released at least for up to 14 days after its incorporation. Application of the gelatin hydrogel-CCN2 complex, together with a collagen scaffold to the bone defect prepared in a rat femur resulted in remarkable induction of osteoblastic mineralization markers within 2 weeks. Finally, distinct enhancement of bone regeneration was observed 3 weeks after the application of the complex. These results confirm the utility of CCN2 in the regeneration of intractable bone defects in vivo when the factor is incorporated into gelatin hydrogel.

DOI： 10.1089/ten.tea.2007.0167

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Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen anti body-induced arthritis mouse model

Y. Nasu, K. Nishida, S. Miyazawa, T. Komiyama, Y. Kadota, N. Abe, A. Yoshida, S. Hirohata, A. Ohtsuka, T. Ozaki

OSTEOARTHRITIS AND CARTILAGE 16 ( 6 ) 723 - 732 2008.6

Language：English Publisher：ELSEVIER SCI LTD

Objective: To investigate the effect of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on joint inflammation and cartilage degeneration in a collagen antibody-induced arthritis (CAIA) mouse model.
Methods: CAIA mice were given daily subcutaneous injections of various concentrations of TSA (0, 0.5, 1.0, and 2.0 mg/kg) and various parameters were monitored for 14 days. On Day 15, the hind paws were examined histologically. To investigate the effects of TSA on the expressions of matrix metal lop roteinase (MMP)-3, MMP-13, tissue inhibitor of MMP-1 (TIMP-1), and acetyl-H4 by chondrocytes, another group of mice was sacrificed on Day 6. In vitro direct effect of TSA was examined by real-time PCR for mRNA of type II collagen, aggrecan, MMP-3, and MMP-13 in murine chondrogenic ATDC5 cells after pro-inflammatory cytokine stimulation.
Results: In the TSA-treated group, clinical arthritis was significantly ameliorated in a dose-dependent manner. The severity of synovial inflammation and the cartilage destruction score were significantly lower in the TSA 2.0 mg/kg group compared to the other TSA-treated groups. On immunohistochemistry, the number of MMP-3 and MMP-13-positive chondrocytes was significantly lower in the TSA 2.0 mg/kg group than in the control group. In contrast, the number of TIMP-II-positive cells and acetyl-histone H4-positive cells was significantly higher in the TSA 2.0 mg/kg group than in the control group. TSA suppressed interleukin 1-beta and tumor necrosis factor-a-stimulated up-regulation of MMP-3, but not MMP-13 mRNA expression by ATDC5.
Conclusion: The systemic administration of TSA ameliorated synovial inflammation in CAIA mice. Subsequently cartilage destruction was also suppressed by TSA, at least in part, by modulating chondrocyte gene expression. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.joca.2007.10.014

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Midterm results of prostaglandin E-1 treatment in patients with lumbar spinal canal stenosis accompanied by intermittent claudication

Kazuo Nakanishi, Masato Tanaka, Haruo Misawa, Tomoyuki Takigawa, Toshifumi Ozaki

SPINE 33 ( 13 ) 1465 - 1469 2008.6

Language：English Publisher：LIPPINCOTT WILLIAMS & WILKINS

Study Design. The midterm results of prostaglandin E-1 (PGE(1)) treatment in patients with lumbar spinal canal stenosis, and discuss the factors influencing the improvement rate by using multivariable analysis.
Objective. We report the clinical results of PGE(1) treatments in patients with lumbar spinal canal stenosis.
Summary of Background Data. Neurogenic intermittent claudication, a prominent symptom of lumbar spinal canal stenosis, poses a substantial impairment of quality of life in patients. A variety of approaches to treatment for lumbar spinal canal stenosis have been reported. However, general systemic complications make it difficult for many elderly people to undergo surgical treatment. Sometimes the only reasonable option is to receive conservative treatment.
Methods. The subjects were 63 patients with lumbar spinal canal stenosis. After admission, patients were given an intravenous infusion of PGE(1) (60 mu g/d) for approximately 2 weeks. To obtain the spinal canal stenosis rate, the area of the dural canal observed on magnetic resonance imaging and CT myelography was measured by using image analysis software (NIH image). The correlation of improvement rates to ages, JOA scores, claudication distances, and stenosis rate obtained through magnetic resonance imaging was evaluated using multivariable analysis.
Results. Regardless of stenosis type, JOA scores significantly improved after PGE(1) administration (the mixed type: P < 0.0001, the nerve root type: P < 0.01, and the cauda equina type: P < 0.01), and claudication distance was significantly improved. Multivariable analysis showed that JOA scores before PGE(1) administration significantly contributed to the improvement rates.
Conclusion. Our midterm results showed that PGE(1) was useful for treating intermittent claudication in patients with lumbar spinal canal stenosis. The effect of PGE(1) was not related to the degree of stenosis obtained with images, age, or claudication distance, but was correlated with baseline disease severity (JOA scores before administration).

DOI： 10.1097/BRS.0b013e3181753c1e

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Novel magnetic resonance imaging evaluation for valgus instability of the knee caused by medial collateral ligament injury

Hisanori Ikuma, Nobuhiro Abe, Youichiro Uchida, Takayuki Furumatsu, Kazuo Fujiwara, Keiichiro Nishida, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 62 ( 3 ) 185 - 191 2008.6

Language：English Publisher：OKAYAMA UNIV MED SCHOOL

Instability of the knee after the medial collateral ligament (MCL) injury is usually assessed with the manual valgus stress test, even though, in recent years, it has become possible to apply magnetic resonance imaging (MRI) to the assessment of the damage of the ligament. The valgus instability of 24 patients (12 isolated injuries and 12 multiple ligament injuries) who suffered MCL injury between 1993 and 1998 was evaluated with the Hughston and Eilers classification, which involves radiographic assessment under manual valgus stress to the injured knees. We developed a novel system for classifying the degree of injury to the MCL by calculating the percentage of injured area based on MRI and investigated the relationship between this novel MRI classification and the magnitude of valgus instability by the Hughston and Eilers classification. There was a significant correlation between the 2 classifications (p = 0.0006). On the other hand, the results using other MRI based classification systems, such as the Mink and Deutsch classificaiton and the Petermann classification, were not correlated with the findings by the Hughston and Eilers classification in these cases (p > 0.05). Since MRI is capable of assessing the injured ligament in clinical practice, this novel classification system would be useful for evaluating the stability of the knee and choosing an appropriate treatment following MCL injury.

DOI： 10.18926/AMO/30974

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2-4-15 SF36を用いたTHA術後の経時的QOL評価(骨関節(股・大腿骨(4)),口演,一般演題,リハビリテーション医学の進歩"評価から治療介入へ",第45回日本リハビリテーション医学会学術集会)

遠藤裕介, 堅山佳美, 三谷茂, 千田益生, 藤原一夫, 皆川寛, 鉄永智紀, 尾崎敏文

リハビリテーション医学 : 日本リハビリテーション医学会誌 45 S260 2008.5

2-7-6 変形性股関節症に対する全人工股関節置換術前の移動能力と術後D-dimer値の関連(骨関節(股・転倒),口演,一般演題,リハビリテーション医学の進歩"評価から治療介入へ",第45回日本リハビリテーション医学会学術集会)

千田益生, 大石豪彦, 安光正治, 越智信夫, 野田知之, 中西一夫, 尾崎敏文

リハビリテーション医学 : 日本リハビリテーション医学会誌 45 S297 2008.5

3-7-25 ADL動作自立のために必要な手指の力 : 人工筋肉を応用した手指動作支援装置開発にあたって(運動学,口演,一般演題,リハビリテーション医学の進歩"評価から治療介入へ",第45回日本リハビリテーション医学会学術集会)

那須巧, 千田益生, 堅山佳美, 秋山明三, 安光正治, 尾崎敏文

リハビリテーション医学 : 日本リハビリテーション医学会誌 45 S408 2008.5

Interleukin-4 downregulates the cyclic tensile stress-induced matrix metalloproteinases-13 and cathepsin B expression by rat normal chondrocytes

Hideyuki Doi, Keiichiro Nishida, Masanori Yorimitsu, Takamitsu Komiyama, Yasutaka Kadota, Tomonori Tetsunaga, Aki Yoshida, Satoshi Kubota, Masaharu Takigawa, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 62 ( 2 ) 119 - 126 2008.4

Language：English Publisher：OKAYAMA UNIV MED SCHOOL

Mechanical stress plays a key role in the pathogenesis of cartilage destruction seen in osteoarthritis (OA). We investigated the effect of cyclic tensile stress (CTS) on the anabolic and catabolic gene expression of rat cultured normal chondrocytes using the Flexercell strain unit. The effects of interleukin (IL)-4, a chondroprotective cytokine, on the changes in gene expression induced by CTS were also investigated. CTS (7% elongation at 0.5 Hz) for 24 h did not affect the expression of aggrecan and type 11 collagen, whereas CTS significantly upregulated matrix metalloproteinase (MMP)-13 and cathepsin B mRNA expression by chondrocytes. IL-1 beta expression was also significantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1 beta. Furthermore, pre-treatment with IL-4 (10 ng/ml) suppressed both MMP-13 and cathepsin B induction by mechanical stress, as well as CTS-induced IL-1 beta expression. Our results suggest that IL-4 might have a therapeutic value in the treatment of OA by downregulation of mechanical stress-induced MMP-13 and cathepsin B expression by chondrocytes.

DOI： 10.18926/AMO/30956

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マウス抗II型コラーゲン抗体関節炎におけるTh1/2/17反応とSOCS3・SOCS5による制御

高畑智宏, 松川昭博, 西田圭一郎, 尾崎敏文

日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 52回・17回 385 - 385 2008.4

Comparison of two MIS lumbar interbody fusion procedures for degenerative spondylolisthesis

MISAWA H.

19 ( 2 ) 213 - 213 2008.3

The subaxial alignment change after atlantoaxial fusion

TANAKA M.

19 ( 1 ) 51 - 51 2008.3

Surgical Treatment of Neuromuscular Scoliosis

TANAKA M.

19 ( 2 ) 455 - 455 2008.3

Application of laminar screws to posterior fusion of cervical spine

Kazuo Nakanishi, Masato Tanaka, Yoshihisa Sugimoto, Haruo Misawa, Tomoyuki Takigawa, Kazuo Fujiwara, Keiichiro Nishida, Toshifumi Ozaki

SPINE 33 ( 6 ) 620 - 623 2008.3

Language：English Publisher：LIPPINCOTT WILLIAMS & WILKINS

Study Design. Morphometric analysis.
Objective. For safe and solid fixation, it is necessary to measure the diameter of the vertebral arch to ascertain whether or not screws can be used and if so, the appropriate size of screws to be used.
Summary of Background Data. Cervical pedicle screws are the most biomechanically stable screws. However, their use carries a high risk of neurovascular complications during screw insertion. In 2004, a new method to avoid such vertebral artery injuries was reported by insertion of screws with crosswise to the lamina of C2. For safe and solid fixation, it is necessary to measure the diameter of the vertebral arch to ascertain whether or not screws can be used and if so, the appropriate size of screws to be used. There is no report of the diameter of the vertebral arch by a navigation system.
Methods. Morphometric analysis was performed on 42 patients who had undergone a CT scan of the cervical spine for either surgery or diagnostic purposes. To examine the possibilities to insert laminar screws, the diameter of the vertebral arch was measured using a navigation system.
Results. The diameter of the vertebral arch in C2 was the largest in the cervical spine, individual differences ranging between 0.8 and 8.4 mm. In C2, insertion of screws with a diameter of 3 mm was possible in 80% of males and 63% of females. As for screws with a diameter of 4 mm, insertion was possible in 50% of the males and 24% of the females in C2. In C2, gender had a significant effect, but left-right differences and height did not.
Conclusion. Laminar screws are useful as they can prevent vascular injuries, but a preoperative evaluation is necessary.

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2.特発性側弯症におけるCobb角の進行と重心動揺(第20回日本リハビリテーション医学会中国・四国地方会)

迫間巧将, 千田益生, 堅山佳美, 田中雅人, 中西一夫, 三澤治夫, 尾崎敏文

リハビリテーション医学 : 日本リハビリテーション医学会誌 45 ( 2 ) 129 - 129 2008.2

Prognostic implication of SYT-SSX fusion type in synovial sarcoma: A multi-institutional retrospective analysis in Japan

Satoshi Takenaka, Takafumi Ueda, Norifumi Naka, Nobuhito Araki, Nobuyuki Hashimoto, Akira Myoui, Toshifumi Ozaki, Tomitaka Nakayama, Junya Toguchida, Kazuhiro Tanaka, Yukihide Iwamoto, Akihiko Matsumine, Atsumasa Uchida, Makoto Ieguchi, Mitsunori Kaya, Takuro Wada, Ichiro Baba, Ikuo Kudawara, Yasuaki Aoki, Hideki Yoshikawa

ONCOLOGY REPORTS 19 ( 2 ) 467 - 476 2008.2

Language：English Publisher：PROFESSOR D A SPANDIDOS

The prognostic implication of SYT-SSX fusion type in synovial sarcomas is still controversial. The aim of this study is to clarify the prognostic impact of fusion type, in association with other clinical factors, in patients with synovial sarcoma in Japan. Data on 108 SYT-SSX fusion transcript-positive patients with synovial sarcoma, treated in I I tertiary referral cancer centers in Japan, were retrospectively analyzed. The following parameters were examined for their potential prognostic impact: SYT-SSX fusion type, patient age at presentation, sex, primary tumor location, tumor size, histological subtype, histological grade, treatment modalities and disease stage at presentation. Among the patients with localized disease at presentation, 5-year overall survival (OS) for SYT-SSX1 and -2 subgroups were 84.4 and 74.9%, respectively (P=0.244). Five-year metastasis-free survival (MFS) rates were 67.8% for SYT-SSX1 and 68.5% for SYT-SSX2 (P=0.949). Univariate survival analyses for 91 patients with localized disease at presentation showed that tumor size was the only significant prognostic factor for OS (P=0.0033) and MFS (P=0.0029) and the histological grade was marginally significant for MFS (P=0.0785), whereas the SYT-SSX fusion type and other variables were not. Multivariate survival analyses further indicated that tumor size was the most significant independent prognostic factor for OS and MFS and the histological grade was also significant for MFS. In conclusion, the SYT-SSX fusion type is not a significant prognostic factor unlike tumor size, followed by histological grade for patients with localized synovial sarcoma in Japan.

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