研究者詳細 - 尾﨑　敏文

論文 - 尾﨑　敏文

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Multiple Regression Analysis for Grading and Prognosis of Cubital Tunnel Syndrome: Assessment of Akahori's Classification 査読

Masutaka Watanabe, Seizaburo Arita, Hiroyuki Hashizume, Mitsugi Honda, Keiichiro Nishida, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 67 ( 1 ) 35 - 44 2013年2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：OKAYAMA UNIV MED SCHOOL

The purpose of this study was to quantitatively evaluate Akahori's preoperative classification of cubital tunnel syndrome. We analyzed the results for 57 elbows that were treated by a simple decompression procedure from 1997 to 2004. The relationship between each item of Akahori's preoperative classification and clinical stage was investigated based on the parameter distribution. We evaluated Akahori's classification system using multiple regression analysis, and investigated the association between the stage and treatment results. The usefulness of the regression equation was evaluated by analysis of variance of the expected and observed scores. In the parameter distribution, each item of Akahori's classification was mostly associated with the stage, but it was difficult to judge the severity of palsy. In the mathematical evaluation, the most effective item in determining the stage was sensory conduction velocity. It was demonstrated that the established regression equation was highly reliable (R = 0.922). Akahori's preoperative classification can also be used in postoperative classification, and this classification was correlated with postoperative prognosis. Our results indicate that Akahori's preoperative classification is a suitable system. It is reliable, reproducible and well-correlated with the postoperative prognosis. In addition, the established prediction formula is useful to reduce the diagnostic complexity of Akahori's classification.

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Comparison between normal and loose fragment chondrocytes in proliferation and redifferentiation potential 査読

Kenichiro Sakata, Takayuki Furumatsu, Shinichi Miyazawa, Yukimasa Okada, Masataka Fujii, Toshifumi Ozaki

INTERNATIONAL ORTHOPAEDICS 37 ( 1 ) 159 - 165 2013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

Loose fragments in osteochondritis dissecans (OCD) of the knee require internal fixation. On the other hand, loose fragments derived from spontaneous osteonecrosis of the knee (SONK) are usually removed. However, the difference in healing potential between OCD- and SONK-related loose fragments has not been elucidated. In this study, we investigated proliferative activity and redifferentiation potential of normal cartilage-derived and loose fragment-derived chondrocytes.
Cells were prepared from normal articular cartilages and loose fragment cartilages derived from knee OCD and SONK. Cellular proliferation was compared. Redifferentiation ability of pellet-cultured chondrocytes was assessed by real-time PCR analyses. Mesenchymal differentiation potential was investigated by histological analyses. Positive ratio of a stem cell marker CD166 was evaluated in each cartilaginous tissue.
Normal and OCD chondrocytes showed a higher proliferative activity than SONK chondrocytes. Chondrogenic pellets derived from normal and OCD chondrocytes produced a larger amount of safranin O-stained proteoglycans compared with SONK-derived pellets. Expression of chondrogenic marker genes was inferior in SONK pellets. The CD166-positive ratio was higher in normal cartilages and OCD loose fragments than in SONK loose fragments.
The OCD chondrocytes maintained higher proliferative activity and redifferentiation potential compared with SONK chondrocytes. Our results suggest that chondrogenic properties of loose fragment-derived cells and the amount of CD166-positive cells may affect the repair process of osteochondral defects.

DOI： 10.1007/s00264-012-1728-x

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Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes

Saito T., Nishida K., Furumatsu T., Yoshida A., Ozawa M., Ozaki T.

Osteoarthritis and Cartilage 21 ( 1 ) 165 - 174 2013年1月

記述言語：英語出版者・発行元：Elsevier Ltd

Objective: To investigate the inhibitory effects and the regulatory mechanisms of histone deacetylase (HDAC) inhibitors on mechanical stress-induced gene expression of runt-related transcription factor (RUNX)-2 and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 in human chondrocytes. Methods: Human chondrocytes were seeded in stretch chambers at a concentration of 5 x 10(4) cells/chamber. Cells were pre-incubated with or without HDAC inhibitors (MS-275 or trichostatin A; TSA) for 12 h, followed by uniaxial cyclic tensile strain (CTS) (0.5 Hz, 10% elongation), which was applied for 30 min using the ST-140-10 system (STREX, Osaka, Japan). Total RNA was extracted and the expression of RUNX-2, ADAMTS-5, matrix metalloproteinase (MMP)-3, and MMP-13 at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The activation of diverse mitogen-activated protein kinase (MAPK) pathways with or without HDAC inhibitors during CTS was examined by western blotting. Results: HDAC inhibitors (TSA: 10 nM, MS-275: 100 nM) suppressed CTS-induced expression of RUNX-2, ADAMTS-5, and MMP-3 at both the mRNA and protein levels within 1 h. CTS-induced activation of p38 MAPK (p38), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (INK) MAPKs was downregulated by both HDAC inhibitors. Conclusion: The CTS-induced expression of RUNX-2 and ADAMTS-5 was suppressed by HDAC inhibitors via the inhibition of the MAPK pathway activation in human chondrocytes. The results of the current study suggested a novel therapeutic role for HDAC inhibitors against degenerative joint disease such as osteoarthritis.

DOI： 10.1016/j.joca.2012.09.003

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若年性特発性関節炎による股関節強直に対し人工股関節全置換術を行った1例

原田遼三, 藤原一夫, 三澤治夫, 三宅由晃, 岡田芳樹, 尾﨑敏文, 遠藤裕介

中国・四国整形外科学会雑誌 25 ( 1 ) 13 - 17 2013年

記述言語：日本語出版者・発行元：中国・四国整形外科学会

In patients with variable changes in pelvic inclination, total hip arthroplasty (THA) is required for accurate cup installation to prevent dislocation. Here we reported the use of THA for hip ankylosis due to juvenile idiopathic arthritis (JIA) and variable pelvic inclination with changes in posture. The patient was a 55-year-old woman, who had received medical treatment for JIA until the age of 14 year. She had been examined two years previously for bilateral leg pain and gait disturbance. Clinically, the lumbar spine had degenerative changes and the left hip joint was ankylosed at a 50-degree -flexed position, causing severe lordosis of the pelvis and lumbar spine and more severe lordosis during changes in posture. We treated the lumbar spine by laminectomy, and then THA was performed under a navigation system. Postoperatively, the patient was relieved of her symptoms and her ambulatory ability was improved. Anteversion of the pelvis with changes in posture remains, but the large femoral head has ensured that no dislocation has occurred up to the present. In cases of variable pelvic inclination due to changes in posture, use of a navigation system is useful intraoperatively for accurate cup installation, and a large femoral head matches any postoperative changes in pelvic inclination.

DOI： 10.11360/jcsoa.25.13

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その他リンク： http://search.jamas.or.jp/link/ui/2013299772

ACL再建術後の3D-CTによる骨孔位置評価と臨床成績

藤井政孝, 古松毅之, 宮澤慎一, 岡田幸正, 尾﨑敏文, 阿部信寛

中国・四国整形外科学会雑誌 25 ( 1 ) 73 - 77 2013年

記述言語：日本語出版者・発行元：中国・四国整形外科学会

The present study was conducted to evaluate the femoral and tibial tunnel positions created by the transtibial and outside-in techniques, and to assess the difference in clinical outcome between the two techniques after anterior cruciate ligament (ACL) reconstruction. The study included 45 patients who underwent ACL reconstruction using either the transtibial (n=15) or outside-in (n=30) technique. Computed tomography scans of the treated knees were performed two weeks after surgery, and three-dimensional surface models were then produced. The positions of the femoral tunnels were measured by the quadrant method. Tibial tunnel aperture centers were measured in the anterior-to-posterior and medial-to-lateral directions on the tibial plateau. The clinical outcomes were measured in terms of range of motion, the Lachman test, pivot shift test, KT-2000 arthrometry, and Lysholm score at 6 months after surgery. On the femoral side, outside-in technique can create tunnels more accurately at the anatomic ACL footprint center than the transtibial technique. On the tibial side, the bone tunnel positions for the transtibial and outside-in techniques were both significantly closer to the tunnel position that was indicated by data from previous studies. There were no significant differences between the two groups in any of the physical parameters determined, or the Lysholm score. The outside-in technique showed more accurate positioning of the femoral tunnels than the transtibial technique. It was difficult to create two femoral tunnels using the transtibial technique because the positions of the femoral tunnels are defined by the direction of the tibial tunnel. The present findings suggest that the outside-in technique is useful because it can create accurate positioning of the femoral tunnels independently.

DOI： 10.11360/jcsoa.25.73

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その他リンク： http://search.jamas.or.jp/link/ui/2013299783

A new navigation system for minimally invasive total knee arthroplasty. 査読

Yokoyama Y, Abe N, Fujiwara K, Suzuki M, Nakajima Y, Sugita N, Mitsuishi M, Nakashima Y, Ozaki T

Acta medica Okayama 67 ( 6 ) 351 - 358 2013年

Management of lumbar artery injury related to pedicle screw insertion. 査読

Sugimoto Y, Tanaka M, Gobara H, Misawa H, Kunisada T, Ozaki T

Acta medica Okayama 67 ( 2 ) 113 - 116 2013年

外科的摘出および定位放射線治療が有用であった転移性滑膜肉腫の1例

大谷理浩, 市川智継, 黒住和彦, 柳井広之, 国定俊之, 尾崎敏文, 伊達勲

Neurological Surgery 41 ( 3 ) 255 - 262 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

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

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The clinical manifestations of lumbar disease are correlated with self-rating depression scale scores 査読

Tomoko Tetsunaga, Haruo Misawa, Masato Tanaka, Yoshihisa Sugimoto, Tomonori Tetsunaga, Tomoyuki Takigawa, Toshifumi Ozaki

Journal of Orthopaedic Science 18 ( 3 ) 374 - 379 2013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：Springer Tokyo

Background: Depression can exacerbate symptoms of chronic pain and worsen disability. The symptoms of lumbar disease may be particularly sensitive to psychological state, but statistical associations between low back pain (LBP) severity and mental health status have not been established. Methods: Of the 151 patients with LBP, 122 completed questionnaires probing depressive symptoms, LBP severity, and degree of disability. In addition to completing self-report questionnaires, patients provided demographic and clinical information. A self-rating depression scale (SDS) was used to screen for depression. Pain and disability were assessed by the visual analog scale (VAS) and the Roland-Morris disability questionnaire (RDQ), respectively. Overall clinical severity was assessed using the Japanese Orthopaedic Association (JOA) score. Kendall's tau correlation coefficients were calculated to examine the relationships among these variables. Results: Ninety-four patients (77 %) were in a depressive state as indicated by SDS score ≥40, including mild depression group (47 patients, SDS score from 40 to 49) and depression group (47 patients, SDS score ≥50). There were only 28 patients in the no depression group (SDS score ≤39). There was no significant difference in both age and pain duration among the three groups. The mean VAS score in the depression group (70 ± 19 mm) was higher than both no depression (41 ± 24 mm) and mild depression groups (52 ± 21 mm). The mean JOA score in the no depression group (14 ± 5.0 points) was higher than both mild depression (12 ± 4.0 points) and depression groups (10 ± 6.0 points). The mean RDQ in the depression group (15.1 ± 6.0 points) was higher than both no depression (6.4 ± 5.0 points) and mild depression groups (10.9 ± 5.4 points). Factors significantly correlated with SDS score included VAS, JOA score, and RDQ score. In contrast, SDS did not correlate with patient age or pain duration. Conclusions: The majority of chronic LBP patients examined were in a depressed state and the severity of depression correlated with pain severity, degree of self-rated disability, and clinical severity. © 2013 The Japanese Orthopaedic Association.

DOI： 10.1007/s00776-013-0363-8

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Histological analysis of failed cartilage repair after marrow stimulation for the treatment of large cartilage defect in medial compartmental osteoarthritis of the knee 査読

Kenichiro Sakata, Takayuki Furumatsu, Nobuhiro Abe, Shinichi Miyazawa, Yoshimasa Sakoma, Toshifumi Ozaki

Acta Medica Okayama 67 ( 1 ) 65 - 74 2013年

記述言語：英語掲載種別：研究論文（学術雑誌）

Bone marrow-stimulating techniques such as microfracture and subchondral drilling are valuable treatments for full-thickness cartilage defects. However, marrow stimulation-derived reparative tissues are not histologically well-documented in human osteoarthritis. We retrospectively investigated cartilage repairs after marrow stimulation for the treatment of large cartilage defects in osteoar-thritic knees. Tissues were obtained from patients who underwent total knee arthroplasty (TKA) after arthroscopic marrow stimulation in medial compartmental osteoarthritis. Clinical findings and cartilage repair were assessed. Sections of medial femoral condyles were histologically investigated by safranin 0 staining and anti-type II collagen antibody. Marrow stimulation decreased the knee pain in the short term. However, varus leg alignment gradually progressed, and TKA conversions were required. The grade of cartilage repair was not improved. Marrow stimulations resulted in insufficient cartilage regeneration on medial femoral condyles. Safranin O-stained proteoglycans and type II collagen were observed in the deep zone of marrow-stimulated holes. This study demonstrated that marrow stimulation resulted in failed cartilage repair for the treatment of large cartilage defects in osteoarthritic knees. Our results suggest that arthroscopic marrow stimulation might not improve clinical symptoms for the long term in patients suffering large osteoarthritic cartilage defects. © 2013 by Okayama University Medical School.

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Development of dysphagia and trismus developed after c1-2 posterior fusion in extended position 査読

Haruo Misawa, Masato Tanaka, Yoshihisa Sugimoto, Kouichiro Koshimune, Toshifumi Ozaki

Acta Medica Okayama 67 ( 3 ) 185 - 190 2013年

記述言語：英語掲載種別：研究論文（学術雑誌）

Cervical misalignment after upper cervical fusion including the occipital bone may cause trismus or dysphagia, because the occipito-atlanto joint is associated with most of the flex and extended motion of the cervical spine. There are no reports of dysphagia and trismus after Cl-2 fusion. The purpose of this paper is to demonstrate the potential risk of dysphagia and trismus even after upper cervical short fusion without the occipital bone. The patient was a 69-year-old man with myelopathy caused by os odontoideum and Klippel-Feil syndrome, who developed dysphagia and trismus immediately after Cl-2 fusion and C3-6 laminoplasty. Radiographs and CT revealed that his neck posture was extended, but his symptoms still existed a week after surgery. The fixation angle was hyperextended 12 days after the first surgery. His symptoms disappeared immediately after revision surgery. The fixation in the neck-flexed position is thought to be the main cause of the patient's post-operative dysphagia and tris-mus. Dysphagia and trismus may occur even after short upper cervical fusion without the occipital bone or cervical fusion in the neck-extended position. The pre-operative cervical alignment and range of motion of each segment should be thoroughly evaluated.

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Novel chondrogenic and chondroprotective effects of the natural compound harmine 査読

Hara, Emilio Satoshi, Ono, Mitsuaki, Kubota, Satoshi, Sonoyama, Wataru, Oida, Yasutaka, Hattori, Takako, Nishida, Takashi, Furumatsu, Takayuki, Ozaki, Toshifumi, Takigawa, Masaharu, Kuboki, Takuo

Biochimie 95 ( 2 ) 374 - 381 2013年

脱臼性股関節症に対するTHAの工夫

遠藤裕介, 三谷茂, 藤原一夫, 岡田芳樹, 尾崎敏文

中部日本整形外科災害外科学会雑誌 56 ( 1 ) 25 - 26 2013年

Recovery of Motor Function in Patients with Subaxial Cervical Spine Injury Relevant to the Fracture Pattern 査読

Yasuyuki Shiozaki, Yasuo Ito, Yoshihisa Sugimoto, Masao Tomioka, Tetsuya Shimokawa, Tetsuro Mazaki, Koichiro Koshimune, Masato Tanaka, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 66 ( 6 ) 469 - 473 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：OKAYAMA UNIV MED SCHOOL

In this study, we studied the relationship between fracture patterns and motor function recovery in 70 consecutive patients with cervical spinal cord injury. Fractures were categorized into 6 fracture types and subdivided into stages according to the Allen-Ferguson classification system: compressive flexion (CF), distractive flexion (DF), compressive extension (CE), distractive extension (DE), vertical compression (VC) and lateral flexion (LF). Paralysis was evaluated using the American Spinal Injury Association (ASIA) impairment scale at the time of injury and 3 months afterwards. The residual rate of complete motor palsy (ASIA grade A or B) at the final examination was higher in those patients with DE fractures than those with CF, DF or CE. The final outcomes were as follows. Of the 14 patients who were classified with CF fractures, residual palsy was frequently seen in patients who had stage 5 injury. Of the 27 patients with DF fractures, residual palsy occurred in about half of the patients who had stage 4 or 5 injury. Of the 18 patients with CE fractures, residual palsy occurred in half of the patients with stage 3 injury or higher. Finally, of the 7 patients with DE fractures, the rate of residual palsy was high even for the stage 1 and 2 cases; indeed, all DE patients who had complete motor palsy at the first examination had residual palsy at the final examination. Accordingly, we conclude that motor recovery may be related to fracture pattern.

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Surgical Treatment for Congenital Kyphosis Correction Using Both Spinal Navigation and a 3-dimensional Model 査読

Yoshihisa Sugimoto, Masato Tanaka, Ryuichi Nakahara, Haruo Misawa, Toshiyuki Kunisada, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 66 ( 6 ) 499 - 502 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：OKAYAMA UNIV MED SCHOOL

An 11 year-old girl had 66 degrees of kyphosis in the thoracolumbar junction. For the purpose of planning for kyphosis correction, we created a 3-D, full-scale model of the spine and consulted spinal navigation. Three-dimensional models are generally used as tactile guides to verify the surgical approach and portray the anatomic relations specific to a given patient. We performed posterior fusion from Th10 to L3, and vertebral column resection of Th12 and L1. Screw entry points, directions, lengths and diameters were determined by reference to navigation. Both tools were useful in the bone resection. We could easily detect the posterior element to be resected using the 3D model. During the anterior bony resection, navigation helped us to check the disc level and anterior wall of the vertebrae, which were otherwise difficult to detect due to their depth in the surgical field. Thus, the combination of navigation and 3D models helped us to safely perform surgery for a patient with complex spinal deformity.

DOI： 10.18926/AMO/49047

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クラウドを利用した遠隔カスタムメイドインプラント作成システム

井上円加, 中原龍一, 島村安則, 野田知之, 国定俊之, 尾崎敏文

骨折 34 ( 4 ) 959 - 963 2012年12月

記述言語：日本語出版者・発行元：(一社)日本骨折治療学会

【目的】当科では鎖骨骨幹部骨折に対し、CT画像を元にプレベンディングしたプレートを用いたMIPO法を行い、良好な結果を得ている。遠隔地の小規模施設でも同様の手術を行うため、クラウドサーバー経由でのCTの編集画像を転送し、作成したプレートを当該施設に輸送して手術を行うシステムを構築した。【方法】健側鎖骨のCT画像からプレベンディング用の画像データを作成する。手術を行う施設で画像処理を行い、クラウドサーバーに匿名化した編集画像を転送する。データを元に当院でプレートをプレベンディングし、当該施設に輸送し、手術を行った。【結果】当該施設でのデータ編集は30分で可能であった。編集後の画像データ量は大幅に削減でき、ネットワーク上での転送に支障はなかった。【結論】当科と手術を行う病院でクラウドサーバーを構築し、低コストでカスタムメイドインプラント作成ネットワークを作り、大学病院の手術方法を他院で実現できた。(著者抄録)

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メカニカルストレスによる軟骨基質分解酵素発現に対するヒストン脱アセチル化酵素阻害剤の抑制効果

斎藤太一, 西田圭一郎, 古松毅之, 小澤正嗣, 金澤智子, 原田遼三, 尾崎敏文

移植 47 ( 6 ) 499 - 499 2012年12月

THA再置換遠位横止め式セメントレスロングステムによる人工股関節再置換術の1例

中道亮, 藤原一夫, 遠藤裕介, 三宅由晃, 岡田芳樹, 尾崎敏文

日本人工関節学会誌 42 579 - 580 2012年12月

記述言語：日本語出版者・発行元：(一社)日本人工関節学会

66歳男。16年前に人工股関節全置換術(THA)を施行したが、術後3年で感染が生じたためインプラントを抜去して、抗菌剤含有セメントスペーサーを設置した。感染が沈静化した1年後に、セメントロングステムでの再度THAを施行した。その後状態は安定していたが、術後15年頃から左大腿部痛が出現した。X線でステム周囲の広範な空洞化を認め、ステム遠位から大腿骨は内反、前彎変形していた。CTでは、再置換術を行った際のステム遠位端の開窓部と一致して前方皮質の欠損を確認し、AAOS分類でtype IVと診断した。感染の可能性は否定的であった。大腿骨の広範な骨欠損に加え、ステム遠位での大腿骨の角状変形を有していたことから、ステムに前彎をつけた遠位横止め式セメントレスロングステムを用いて再置換術を施行した。術後9ヵ月の現在、1本杖歩行が可能な状態となり、左股関節のJOAスコアは術前31点から71点に改善した。

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Mechanical stretch increases Smad3-dependent CCN2 expression in inner meniscus cells 査読

Takayuki Furumatsu, Tomoko Kanazawa, Yoshiaki Miyake, Satoshi Kubota, Masaharu Takigawa, Toshifumi Ozaki

JOURNAL OF ORTHOPAEDIC RESEARCH 30 ( 11 ) 1738 - 1745 2012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：WILEY-BLACKWELL

The intrinsic zone-specific properties of the menisci are determined by biomechanical environments. In this study, we examined mechanical stretch-dependent expression of multifunctional growth factor CYR61/CTGF/NOV (CCN) 2, and investigated the role of CCN2 in meniscus cells. Uni-axial cyclic tensile strain (CTS) was applied using a STB-140 system. CTS-induced expression of CCN2 and a1(I) collagen (COL1A1) was assessed by quantitative real-time PCR analysis. The distribution of CCN2 and Smad2/3 in stretched cells was investigated by immunohistochemical analysis. Smad2/3-dependent CCN2 transactivation was measured by luciferase reporter assay. The relationship between Smad2/3 and CTS-induced CCN2 transcription was investigated by chromatin immunoprecipitation. CTS stimulated gene expression of CCN2 and COL1A1 in inner meniscus cells, but not in outer meniscus cells. Recombinant CCN2 increased COL1A1 expression only in inner meniscus cells. CCN2 synthesis and nuclear translocalization of phosphorylated Smad2/3 in inner meniscus cells were stimulated by CTS. The CCN2 promoter activity was synergistically enhanced by overexpressed Smad3 in stretched inner meniscus cells, but was not by Smad2. Chromatin immunoprecipitation revealed that CTS increased the association between Smad3 and the Smad-binding element on the CCN2 proximal promoter in inner meniscus cells. Our results suggest that stretch-induced CCN2 may have a crucial role in regulating COL1A1 expression in the inner meniscus. (c) 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:17381745, 2012

DOI： 10.1002/jor.22142

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