Researcher Database

Norimasa Iwasaki
Faculty of Medicine Specialized Medicine Reconstructive Surgery and Rehabilitation Medicine
Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Medicine Specialized Medicine Reconstructive Surgery and Rehabilitation Medicine

Job Title

  • Professor

Degree

  • medical doctor

J-Global ID

Research Interests

  • 整形外科学   

Research Areas

  • Life sciences / Immunology
  • Life sciences / Biomaterials
  • Life sciences / Biomedical engineering
  • Life sciences / Orthopedics

Education

  •        - 1998  北海道大学大学院
  •        - 1998  Hokkaido University  Graduate School, Division of Medicine
  •        - 1988  Asahikawa Medical University  School of Medicine  Medical Course
  •        - 1988  Asahikawa Medical College  Faculty of Medicine

Association Memberships

  • 北海道整形災害外科学会   日本臨床バイオメカニクス学会   日本マイクロサージャリー学会   日本手の外科学会   日本整形外科学会   

Research Activities

Published Papers

  • Shigeto Hiratsuka, Masahiko Takahata, Yoshihiro Hojo, Tomomichi Kajino, Yuichiro Hisada, Akira Iwata, Katsuhisa Yamada, Norimasa Iwasaki
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 24 (1) 14 - 18 0949-2658 2019/01 [Refereed][Not invited]
     
    BACKGROUND: Lumbar decompression surgery is a commonly used treatment for degenerative lumbar spinal stenosis; however, some patients develop symptomatic spinal instability following decompression surgery. The objective of this study was to reveal risk factors for delayed instability following decompression surgery for lumbar spinal stenosis. METHODS: One hundred ten patients who underwent single-level lumbar decompression between 2008 and 2014 were retrospectively reviewed. Surgical indication for decompression surgery was symptomatic lumbar canal stenosis without spondylolisthesis or with minimum spondylolisthesis (less than 4 mm translation). Patients with gross segmental motion (>10° in disc angle, >2 mm translation) on flexion-extension lumbar radiographs were excluded. Age, sex, body mass index, smoking history, diabetes mellitus, autoimmune connective tissue diseases including rheumatoid arthritis, and the use of glucocorticoids were investigated. Radiographic measurements included disc angle, disc height, slippage, facet angle, segmental motion (flexion-extension), lumbar alignment, facet effusion, and disc degeneration. Data were analyzed using multivariate forward selection stepwise logistic regression, chi-square tests, and Student t-test. RESULTS: Six of 110 patients (5.5%) developed symptomatic spinal instability at the operative level and underwent spinal fusion surgery at an average of 2.1 years postoperatively. Autoimmune connective tissue disorders and chronic use of glucocorticoids were associated with the occurrence of symptomatic spinal instability requiring spine fusion surgery, while there was no significant difference in radiographic parameters and demographic factors excluding autoimmune connective tissue diseases between reoperation and non-reoperation groups. CONCLUSIONS: Patients with autoimmune connective tissue disorders receiving chronic glucocorticoid therapy are more likely to develop symptomatic spinal instability following decompression surgery for lumbar canal stenosis without or with minimal spondylolisthesis.
  • Hiroyuki Nakamura, Sanae Shimamura, Shinsuke Yasuda, Michihito Kono, Michihiro Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Tomohiro Shimizu, Norimasa Iwasaki, Tatsuya Atsumi
    Annals of the rheumatic diseases 77 (12) 1765 - 1772 0003-4967 2018/12 [Refereed][Not invited]
     
    OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune polyarthritis, in which fibroblast-like synoviocytes (FLS) play a key role in cartilage and bone destruction through tumour-like proliferation and invasiveness. Considering still unsatisfactory remission rate in RA even under treatment with biological disease-modifying antirheumatic drugs, novel therapeutic strategy for treatment-resistant RA is still awaited. In this study, we analysed the expression and function of Ras guanine nucleotide-releasing proteins (RASGRPs), guanine exchange factors for small GTPase Ras, in FLS as a potential therapeutic target for RA. METHODS: The expression of RASGRPs mRNA was quantified by a real-time PCR assay in FLS isolated from synovial tissue samples. RASGRP2 protein was also evaluated immunohistochemically. Then, we transiently transfected FLS with RASGRP2 expression vector and assessed their proliferation, adhesion, migration and invasion by cellular functional assays and downstream signalling activation using immunoblot. Finally, the therapeutic effect of RASGRP2 silencing was evaluated in type-II collagen-induced arthritis rats. RESULTS: RASGRP2 was abundantly expressed in FLS from RA synovium, whereas scarcely found in those from osteoarthritis. Expression of RASGRP2 in RA-FLS was enhanced by transforming growth factor-beta. RASGRP2 activated RAP-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. RASGRP2-overexpressed FLS had increased abilities of adhesion, migration and interleukin (IL)-6 production. Silencing of RASGRP2 using the intra-articular injection of Rasgrp2-specific siRNAs dampened experimental arthritis in rats by inhibiting pannus formation. CONCLUSIONS: RASGRP2 was identified to be involved in the pathogenesis of RA by promoting adhesion, migration and IL-6 production from FLS, proposed as a potential novel non-immunosuppressive therapeutic target for RA.
  • Masahiko Takahata, Katsuhisa Yamada, Iwata Akira, Tsutomu Endo, Hideki Sudo, Hidetoki Yokoyama, Norimasa Iwasaki
    European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 27 (11) 2754 - 2762 0940-6719 2018/11 [Refereed][Not invited]
     
    PURPOSE: The cervical pedicle screw (CPS) requires careful and accurate placement because of the critical risk for neurovascular injury. This study aimed to introduce and evaluate the safety and efficacy of a new CPS placement technique using intraoperative C-arm cone-beam CT (CBCT) and a pilot screw without navigation system. METHODS: This was a case-control study to compare the accuracy and safety of intraoperative C-arm CBCT-guided CPS placement with freehand CPS placement under lateral fluoroscopy using control data from a previous multicenter study. A total of 166 CPSs were inserted under intraoperative C-arm CBCT guidance in 48 consecutive patients (20 rheumatoid arthritis, 16 degenerative spinal disorders, 6 spinal tumor, 2 congenital deformity, 2 ossification of posterior longitudinal ligament, and 2 fracture dislocation). Accuracy and safety of CPS placement were assessed. RESULTS: The overall malposition rate was 2.4% (4 screws in grade 1: malposition by less than half-screw diameter, 0 in grade 2: malposition by more than half-screw diameter), which was significantly lower than the reported malposition rate of 14.8% in lateral fluoroscopy-guided freehand placement. There were no complications directly related to CPS insertion. The average estimated effective radiation dose per surgery was 14.7 mSv. CONCLUSIONS: The novel technique enables intraoperative adjustment of the trajectory of the CPS as well as confirmation of the CPS path before penetrating the isthmus of the pedicle, resulting in accurate and safe CPS placement, which outweighs the demerits of radiation exposure. These slides can be retrieved under Electronic Supplementary Material.
  • Sato D, Takahata M, Ota M, Fukuda C, Tsuda E, Shimizu T, Okada A, Hiruma Y, Hamano H, Hiratsuka S, Fujita R, Amizuka N, Hasegawa T, Iwasaki N
    Bone 116 172 - 180 8756-3282 2018/11 [Refereed][Not invited]
  • Tsukuda Y, Kawamura D, Matsui Y, Iwasaki N
    The Journal of hand surgery, European volume 1753193418803522  1753-1934 2018/10 [Refereed][Not invited]
  • Sudo H, Abe Y, Kokabu T, Kuroki K, Iwata A, Iwasaki N
    Spine 43 (19) E1135 - E1142 0362-2436 2018/10 [Refereed][Not invited]
  • Takahata M, Iwasaki N
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 23 (5) 842 - 844 0949-2658 2018/09 [Refereed][Not invited]
  • Yamada K, Sudo H, Kaneda K, Shono Y, Abe Y, Iwasaki N
    Journal of neurosurgery. Pediatrics 1 - 7 1933-0707 2018/09 [Refereed][Not invited]
  • Motomiya M, Funakoshi T, Ishizaka K, Nishida M, Matsui Y, Iwasaki N
    Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 37 (7) 1597 - 1604 0278-4297 2018/07 [Refereed][Not invited]
  • Kokabu T, Kanai S, Abe Y, Iwasaki N, Sudo H
    Journal of orthopaedic research : official publication of the Orthopaedic Research Society 0736-0266 2018/07 [Refereed][Not invited]
  • Tohru Irie, Daisuke Takahashi, Tsuyoshi Asano, Ryuta Arai, Muhammad Alaa Terkawi, Yoichi M Ito, Norimasa Iwasaki
    Clinical orthopaedics and related research 476 (7) 1455 - 1465 0009-921X 2018/07 [Refereed][Not invited]
     
    BACKGROUND: The definitive treatment of borderline-to-mild dysplasia remains controversial. A more comprehensive understanding of the etiology of osteoarthritis (OA) and clarification of any possible association between borderline-to-mild dysplasia and the pathogenesis of OA are essential. QUESTIONS/PURPOSES: (1) Does the distribution of acetabular subchondral bone density increase according to dysplasia severity? (2) Is there an association between borderline-to-mild dysplasia and OA pathogenesis? METHODS: We evaluated bilateral hips of patients with developmental dysplasia of the hip who underwent eccentric rotational acetabular osteotomy (ERAO) for inclusion in the dysplasia group and contralateral hips of patients with unilateral idiopathic osteonecrosis of the femoral head (ONFH) who underwent curved intertrochanteric varus osteotomy (CVO) for the control group. ERAO was performed in 46 patients and CVO was performed in 32 patients between January 2013 and August 2016 at our institution. All patients underwent bilateral hip CT. The study included 55 hips categorized according to dysplasia severity: (1) borderline-mild, 19 hips (15° ≤ lateral center-edge angle [LCEA] < 25°); (2) moderate, 20 hips (5° ≤ LCEA < 15°); (3) severe, 16 hips (LCEA < 5°); and (4) control, 15 hips. Thirty-seven dysplastic hips (age < 15 or > 50 years old, prior hip surgery, subluxation, aspherical femoral head, cam deformity, and radiographic OA) and 17 control hips (age < 15 or > 50 years old, bilateral ONFH, LCEA < 25° or ≥ 35°, cam deformity, and radiographic OA) were excluded. CT-osteoabsorptiometry (OAM) predicts physiologic biomechanical conditions in joints by evaluating subchondral bone density. We evaluated the distribution of subchondral bone densities in the acetabulum with CT-OAM, dividing the stress distribution map into six segments: anteromedial, anterolateral, centromedial, centrolateral, posteromedial, and posterolateral. We calculated the percentage of high-density area, which was defined as the upper 30% of Hounsfield units values in each region and compared least square means difference estimated by the random intercept model among the four groups. RESULTS: In all regions, the percentage of high-density area did not differ between the borderline-mild group and the control (eg, anterolateral, 16.2 ± 5.6 [95% CI, 13.4 to 18.9] versus 15.5 ± 5.7 [95% CI, 12.4 to 18.5, p = 0.984]; centrolateral, 39.1 ± 5.7 [95% CI, 36.4 to 41.8] versus 39.5 ± 4.7 [95% CI, 36.6 to 42.5, p = 0.995]; posterolateral, 10.9 ± 5.2 [95% CI, 8.0 to 13.8] versus 15.1 ± 6.8 [95% CI, 11.7 to 18.5, p = 0.389]). In the anterolateral region, a smaller percentage of high-density area was observed in the borderline-mild group than in both the moderate group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 28.2 ± 5.1 [95% CI, 25.5-30.9], p < 0.001) and the severe group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 22.2 ± 6.8 [95% CI, 19.2-25.2, p = 0.026). CONCLUSIONS: Our results suggest that the cumulative hip stress distribution in borderline-to-mild dysplasia was not concentrated on the lateral side of the acetabulum, unlike severe dysplasia. CLINICAL RELEVANCE: Based on the stress distribution pattern, our results may suggest that there is no association between borderline-to-mild dysplasia and the pathogenesis of OA. Further studies are needed to evaluate the association between borderline-to-mild dysplasia and instability of the hip.
  • Funakoshi T, Momma D, Matsui Y, Kamishima T, Matsui Y, Kawamura D, Nagano Y, Iwasaki N
    The American journal of sports medicine 46 (8) 1943 - 1951 0363-5465 2018/07 [Refereed][Not invited]
  • Rikiya Baba, Tomohiro Onodera, Masatake Matsuoka, Kazutoshi Hontani, Zenta Joutoku, Shinji Matsubara, Kentaro Homan, Norimasa Iwasaki
    The American journal of sports medicine 46 (8) 1970 - 1979 0363-5465 2018/07 [Refereed][Not invited]
     
    BACKGROUND: The optimal treatment for a medium- or large-sized cartilage lesion is still controversial. Since an ultrapurified alginate (UPAL) gel enhances cartilage repair in animal models, this material is expected to improve the efficacy of the current treatment strategies for cartilage lesions. HYPOTHESIS: The bone marrow stimulation technique (BMST) augmented by UPAL gel can induce hyaline-like cartilage repair. STUDY DESIGN: Controlled laboratory study. METHODS: Two cylindrical osteochondral defects were created in the patellar groove of 27 beagle dogs. A total of 108 defects were divided into 3 groups: defects without intervention (control group), defects with the BMST (microfracture group), and defects with the BMST augmented by implantation of UPAL gel (combined group). At 27 weeks postoperatively, macroscopic and histological evaluations, micro-computed tomography assessment, and mechanical testing were performed for each reparative tissue. RESULTS: The defects in the combined group were almost fully covered with translucent reparative tissues, which consisted of hyaline-like cartilage with well-organized collagen structures. The macroscopic score was significantly better in the combined group than in the control group ( P < .05). The histological scores in the combined group were significantly better than those in the control group ( P < .01) and microfracture group ( P < .05). Although the repaired subchondral bone volumes were not influenced by UPAL gel augmentation, the mechanical properties of the combined group were significantly better than those of the microfracture group ( P < .05). CONCLUSION: The BMST augmented by UPAL gel elicited hyaline-like cartilage repair that had characteristics of rich glycosaminoglycan and matrix immunostained by type II collagen antibody in a canine osteochondral defect model. The present results suggest that the current technique has the potential to be one of the autologous matrix-induced chondrogenesis techniques of the future and to expand the operative indications for the BMST without loss of its technical simplicity. CLINICAL RELEVANCE: The data support the clinical reality of 1-step minimally invasive cartilage-reparative medicine with UPAL gel without harvesting donor cells.
  • Momma D, Nimura A, Muro S, Fujishiro H, Miyamoto T, Funakoshi T, Mochizuki T, Iwasaki N, Akita K
    Journal of experimental orthopaedics 5 (1) 16  2018/06 [Refereed][Not invited]
  • Yusuke Nishio, Eiji Kondo, Jun Onodera, Tomohiro Onodera, Tomonori Yagi, Norimasa Iwasaki, Kazunori Yasuda
    Orthopaedic Journal of Sports Medicine 6 (5) 2325967118773685  2325-9671 2018/05/21 [Refereed][Not invited]
     
    Background: Several recent studies have reported that favorable clinical results and a high level of patient satisfaction can generally be obtained with no increased risk of complications after single-bundle anterior cruciate ligament (ACL) reconstruction performed in patients > 40 years of age. However, no studies have yet clarified the age-based differences in clinical outcomes after double-bundle reconstruction. Purpose: To compare clinical outcomes after double-bundle ACL reconstruction using hamstring tendon hybrid grafts between patients in 2 different age groups: ≥40 years and < 40 years. Study Design: Cohort study Level of evidence, 3. Methods: A retrospective study was conducted using 96 patients (48 men, 48 women mean age, 37 years) who underwent unilateral ACL reconstruction between 2008 and 2011. These patients were divided into 2 groups: group M included patients ≥40 years of age (n = 40 patients), and group Y included patients < 40 years of age (n = 56 patients). All patients underwent the same anatomic double-bundle ACL reconstruction procedure. Clinical outcomes were evaluated at 2 years after surgery. Tunnel enlargement was also evaluated by computed digital radiography at 1 week and 2 years after surgery. Results: Mean postoperative side-to-side differences in anterior laxity were 0.5 ± 1.9 mm and 1.2 ± 1.5 mm in groups M and Y, respectively there was a significant difference between the 2 groups (P =.039). There were no significant differences between the groups in Lysholm knee scores, International Knee Documentation Committee (IKDC) scores, or peak muscle torque of the hamstring. On the other hand, peak muscle torque of the quadriceps was significantly lower in group M (81%) than in group Y (89%) (P =.025). With respect to femoral tunnel enlargement, the posterolateral tunnel in group M was significantly larger than that in group Y on anteroposterior and lateral radiographs (P =.015 and P =.002, respectively). Conclusion: Equivalent clinical outcomes were seen between the 2 age groups after double-bundle ACL reconstruction. Postoperative anterior laxity was significantly less in older patients than in younger patients, however, older patients had significantly less quadriceps muscle strength than younger patients. Surgeons should be aware of residual muscle weakness and tunnel enlargement when performing double-bundle ACL reconstruction in older patients.
  • Yuki Matsui, Tadanao Funakoshi, Daisuke Momma, Azusa Miyamoto, Kaori Endo, Kozo Furushima, Kazuhiro Fujisaki, Norimasa Iwasaki
    Journal of Shoulder and Elbow Surgery 27 (5) 923 - 930 1532-6500 2018/05/01 [Refereed][Not invited]
     
    Background: Predictive factors for the development of osteoarthritis in adolescent osteochondritis dissecans (OCD) of the humeral capitellum remain unclear. The objectives of this study were to assess subchondral bone density in the radial head fovea of patients with OCD and to evaluate stress distribution in the radiocapitellar joint. The relationship between radiologic classification and stress distribution, according to multivariate ordinal regression analysis, was also investigated. Methods: Computed tomography (CT) imaging data from 54 male patients with OCD (mean age, 13.1 years) were collected. Stress in the radial head fovea was measured using CT osteoabsorptiometry. A stress map was constructed and divided into 4 sections, and percentages of high-density regions in each section were quantitatively analyzed. Multivariate ordinal regression analyses were performed of bone density, incorporating the stage, location, and size of the OCD lesion and the presence of medial elbow disturbance in the radiographic images. Results: The percentage of high-density area in the anteromedial, posteromedial, and the anterolateral sections of the radial head fovea were significantly increased compared with the posterolateral section. Multivariate ordinal regression analysis revealed that the location and size of the lesion and a history of excessive valgus stress were associated with imbalances in the radial head fovea. Conclusions: When the OCD lesion is large and located laterally and a medial epicondyle disturbance is apparent on radiographs, the risk for developing advanced radiocapitellar osteoarthritis should be considered. These findings can be useful in the decision-making process for treating OCD.
  • Ota M, Takahata M, Shimizu T, Momma D, Hamano H, Hiratsuka S, Amizuka N, Hasegawa T, Iwasaki N
    Journal of bone and mineral metabolism 0914-8779 2018/05 [Refereed][Not invited]
  • Asano T, Shimizu T, Takahashi D, Ota M, Sato D, Hamano H, Hiratsuka S, Takahata M, Iwasaki N
    Journal of bone and mineral metabolism 0914-8779 2018/05 [Refereed][Not invited]
  • Tomoyo Irie, Makoto Motomiya, Norimasa Iwasaki
    BMC Research Notes 11 (1) 240  1756-0500 2018/04/11 [Refereed][Not invited]
     
    Background: Volar locking plate fixation of distal radius fractures is commonly performed because of its good clinical outcomes. The flexor carpi radialis (FCR) approach is one of the most popular approaches to dissecting the volar side of the distal radius because of its simplicity and safety. We describe an extremely rare case of an absent FCR identified during a volar approach for fixation of a distal radius fracture. Case presentation: A 59-year-old woman with distal radius fracture underwent surgery using the usual FCR approach and volar locking plate. We could not identify the absence of the FCR tendon preoperatively because of severe swelling of the distal forearm. At first, we wrongly identified the palmaris longus tendon as the FCR because it was the tendinous structure at the most radial location of the volar distal forearm. When we found the median nerve just radial to the palmaris longus tendon, we were then able to identify the anatomical abnormality in this case. To avoid iatrogenic neurovascular injuries, we changed the approach to the classic Henry's approach. Conclusions: Although the FCR approach is commonly used for fixation of distal radius fractures because of its simplicity and safety, this is the first report of complete absence of the FCR during the commonly performed volar approach for fixation of a distal radius fracture, to our knowledge. Because the FCR is designated as a favorable landmark because of its superficially palpable location, strong and thick structure, and rare anatomical variations, there is the possibility of iatrogenic complications in cases of the absence of the FCR. We suggest that surgeons should have a detailed knowledge of the range of possible anomalies to complete the fixation of a distal radius fracture safely.
  • Shigeto Hiratsuka, Masahiko Takahata, Tomohiro Shimizu, Hiroki Hamano, Masahiro Ota, Dai Sato, Norimasa Iwasaki
    Journal of Orthopaedic Research 36 (4) 1256 - 1261 1554-527X 2018/04/01 [Refereed][Not invited]
     
    The lack of an effective drug therapy against ossification of spinal ligament (OSL) warrants investigation into the therapeutic target of this disease. An endogenous inhibitor of biomineralization, pyrophosphate (PPi) is a potential therapy for ectopic ossification however, exogenous PPi is rapidly hydrolyzed by tissue non-specific alkaline phosphatase (TNAP) present in body fluids. In this study, we examined whether a drug therapy targeting PPi is efficacious for the treatment of OSL using the Enpp1ttw/ttw (twy) mouse model. Twenty male twy mice were randomized into four groups: (i) vehicle (Control) (ii) alkaline phosphatase inhibitor levamisole (5 mg/kg/day sc continuously) (iii) levamisole + exogenous PPi (160 µmol/kg/day sc continuously) and (iv) nuclear retinoic acid receptor-γ (RARγ) agonist (6 µg/kg sc daily). The RARγ agonist, which is a proven inhibitor of ectopic endochondral ossification, was used as a positive control. Treatments commenced when the mice were 5 weeks of age and continued for 4 weeks. Longitudinal micro-computed tomography and postmortem histological analysis were performed. Administration of levamisole alone and in combination with PPi increased serum PPi concentration by 17% and 52%, respectively, compared to that in vehicle-treated mice. The development of OSL in twy mice was suppressed by levamisole + PPi and RARγ agonist treatments, but not by levamisole alone. The levamisole + PPi therapy did not cause osteoporosis, whereas RARγ agonist-treated mice developed osteoporosis. Treatment of twy mice with levamisole in combination with exogenous PPi increased serum PPi level, which slowed the progression of OSL without producing adverse effect on bone. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1256–1261, 2018.
  • Yuichiro Matsui, Daisuke Kawamura, Hiroaki Kida, Kanako C. Hatanaka, Norimasa Iwasaki
    BMC Musculoskeletal Disorders 19 (1) 90  1471-2474 2018/03/27 [Refereed][Not invited]
     
    Background: Trigger wrist is a rare condition first described by Marti in 1960, and various causes have been reported. The condition mostly occurs with finger flexion and extension, and rarely with flexion and extension of the wrist itself. Avascular necrosis of the capitate is also a rare condition, first described by Jönsson in 1942. While some reports of this condition have been published, little is known about its etiology. Therefore, no established treatment exists. We report a case of trigger wrist caused by avascular necrosis of the capitate. Case presentation: A 16-year-old right-handed male who was a high school handball player was referred to our department from a nearby hospital 5 months after the onset of pain in the dorsal aspect of the right wrist, with an unknown cause. At the previous hospital, imaging findings led to a diagnosis of avascular necrosis of the capitate, and conservative treatment with a wrist brace did not improve the pain. At the initial visit to our department, the patient was noted to have a painful trigger wrist that was brought on by wrist flexion and extension. Preoperative imaging findings led to a diagnosis of trigger wrist caused by capitolunate instability secondary to avascular necrosis of the capitate. We performed a partial excision of the proximal capitate with tendon ball interposition. Two years after surgery, the patient's clinical outcome was favorable, with no recurrence of wrist pain or triggering. Conclusions: Both trigger wrist and avascular necrosis of the capitate are rare disorders. When a patient presents with painful triggering at the wrist, surgeons must bear in mind that avascular necrosis of the capitate may result in this phenomenon. We recommend partial excision of the proximal capitate with tendon ball interposition for the treatment of this lesion.
  • Matsumae G, Motomiya M, Iwasaki N
    The journal of hand surgery Asian-Pacific volume 23 (1) 132 - 136 2424-8355 2018/03 [Refereed][Not invited]
  • Hiromi Kimura-Suda, Masahiko Takahata, Teppei Ito, Tomohiro Shimizu, Kyosuke Kanazawa, Masahiro Ota, Norimasa Iwasaki
    PLoS ONE 13 (2) e0189650  1932-6203 2018/02/01 [Refereed][Not invited]
     
    Fourier transform infrared (FTIR) imaging is a powerful tool for the assessment of bone quality however, it requires the preparation of thin bone sections. Conventional poly(methyl methacrylate) (PMMA) embedding for the preparation of sections takes more than two weeks and causes denaturation of the bone. Development of a quick and easy sample preparation technique without denaturation is needed for accurate clinical evaluation of fresh calcified bone using FTIR imaging. Frozen sectioning allows the quick and easy preparation of thin sections without denaturation, but it requires a substrate with good chemical resistance and improved heat shock resistance. Polypropylene (PP) film afforded both good chemical resistance and greater heat shock resistance, and the 4-μm-thick PP film coated with glue was thin enough for the IR beam to pass through it, while the optical anisotropy of infrared bands overlapping with PO4 3- band was negligible. The bone quality of femoral thin sections prepared by the conventional PMMA embedding and sectioning procedure (RESIN-S) or the newly developed frozen sectioning procedure (FROZEN-S) was evaluated by FTIR imaging. The mineral-to-matrix ratio and crystallinity in the RESIN-S sections were higher than those in the FROZEN-S sections, whereas the carbonate-to-phosphate ratio in the RESIN-S sections was lower than that in the FROZEN-S sections. In RESIN-S, the increased mineral-to-matrix ratio could be caused by dehydration, and the increased crystallinity and decreased carbonate-to-phosphate ratio might be consequence of dissolution of bone mineral during PMMA embedding. Therefore, the combined use of PP film coated with glue and the frozen sectioning procedure without denaturation appears well suited to the assessment of the bone quality of fresh calcified bone using FTIR imaging.
  • Takashi Ohnishi, Hideki Sudo, Takeru Tsujimoto, Norimasa Iwasaki
    Journal of Orthopaedic Research 36 (1) 224 - 232 1554-527X 2018/01/01 [Refereed][Not invited]
     
    The pathogenesis of intervertebral disc degeneration is unclear, but it is a major cause of several spinal diseases. Animal models have historically provided an appropriate benchmark for understanding the human spine. However, there is little information about when intervertebral disc degeneration begins in the mouse or regarding the relationship between magnetic resonance imaging and histological findings. The aim for this study was to obtain information about age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine using magnetic resonance imaging and a histological score regarding when the intervertebral disc degeneration started and how rapidly it progressed, as well as how our histological score detected the degeneration. The magnetic resonance imaging index yielded a moderate correlation with our Age-related model score. The Pfirrmann grade and magnetic resonance imaging index had moderate correlations with age. However, our Age-related model score had a high correlation with age. Intervertebral disc level was not a significant variable for the severity of disc degeneration. Both Pfirrmann grade and the Age-related model score were higher in the ≥14-month-old group than in the 6-month-old group. The present results indicated that mild but significant intervertebral disc degeneration occurred in 14-month-old mice, and the degree of degeneration progressed slowly, reaching a moderate to severe condition for 22-month-old mice. At least a 14-month follow-up is mandatory for evaluating spontaneous age-related mouse intervertebral disc degeneration. The histological classification score can precisely detect the gradual progression of age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine, and is appropriate for evaluating it. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:224–232, 2018.
  • Mohamad Alaa Terkawi, Masanari Hamasaki, Daisuke Takahashi, Masahiro Ota, Ken Kadoya, Tomoyo Yutani, Keita Uetsuki, Tsuyoshi Asano, Tohru Irie, Ryuta Arai, Tomohiro Onodera, Masahiko Takahata, Norimasa Iwasaki
    Acta Biomaterialia 65 417 - 425 1878-7568 2018/01/01 [Refereed][Not invited]
     
    Osteolysis is a serious postoperative complication of total joint arthroplasty that leads to aseptic loosening and surgical revision. Osteolysis is a chronic destructive process that occurs when host macrophages recognize implant particles and release inflammatory mediators that increase bone-resorbing osteoclastic activity and attenuate bone-formation osteoblastic activity. Although much progress has been made in understanding the molecular responses of macrophages to implant particles, the pathways/signals that initiate osteolysis remain poorly characterized. Transcriptomics and gene-expression profiling of these macrophages may unravel key mechanisms in the pathogenesis of osteolysis and aid the identification of molecular candidates for therapeutic intervention. To this end, we analyzed the transcriptional profiling of macrophages exposed to ultra-high molecular weight polyethylene (UHMWPE) particles, the most common components used in bearing materials of orthopedic implants. Regulated genes in stimulated macrophages were involved in cytokine, chemokine, growth factor and receptor activities. Gene enrichment analysis suggested that stimulated macrophages elicited common gene expression signatures for inflammation and rheumatoid arthritis. Among the regulated genes, tumor necrosis factor superfamily member 15 (TNFSF15) and chemokine ligand 20 (CCL20) were further characterized as molecular targets involved in the pathogenesis of osteolysis. Treatment of monocyte cultures with TNFSF15 and CCL20 resulted in an increase in osteoclastogenesis and bone-resorbing osteoclastic activity, suggesting their potential contribution to loosening between implants and bone tissues. Statement of Significance Implant loosening due to osteolysis is the most common mode of arthroplasty failure and represents a great challenge to orthopedic surgeons and a significant economic burden for patients and healthcare services worldwide. Bone loss secondary to a local inflammatory response initiated by particulate debris from implants is considered the principal feature of the pathogenesis of osteolysis. In the present study, we analyzed the transcriptional profiling of human macrophages exposed to UHMWPE particles and identified a large number of inflammatory genes that were not identified previously in macrophage responses to wear particles. Our data provide a new insight into the molecular pathogenesis of osteolysis and highlights a number of molecular targets with prognostic and therapeutic implications.
  • Haraya K, Yamada K, Kokabu T, Iwata A, Endo T, Sudo H, Iwasaki N, Takahata M
    Spinal cord series and cases 4 81  2018 [Refereed][Not invited]
  • Konomi T, Suda K, Matsumoto S, Komatsu M, Takahata M, Iwasaki N, Minami A
    Spinal cord series and cases 4 18  2018 [Refereed][Not invited]
  • Konomi T, Suda K, Matsumoto S, Komatsu M, Takahata M, Iwasaki N, Minami A
    Spinal cord series and cases 4 20  2018 [Refereed][Not invited]
  • Naoki Seito, Tomohiro Onodera, Yasuhiko Kasahara, Eiji Kondo, Norimasa Iwasaki, Tokifumi Majima
    The Knee 24 (6) 1462 - 1468 0968-0160 2017/12 [Refereed][Not invited]
  • Akira Iwata, Masahiko Takahata, Ken Kadoya, Hideaki Sudo, Terufumi Kokabu, Katsuhisa Yamada, Norimasa Iwasaki
    SPINE 42 (18) 1362 - 1366 0362-2436 2017/09 [Refereed][Not invited]
     
    Study Design. Basic science. Objective. This study aimed to compare the techniques of surgical repair of dural tear using bioabsorbable material and fibrin glue. Summary of Background Data. Cerebrospinal fluid (CSF) leakage caused by dural tear can often be difficult to manage even after repair when the same materials are used in a similar manner. Methods. Burst pressure was measured for repaired porcine dura with holes of different diameters using spray of combined fibrinogen and thrombin solution (fibrin spray) alone as a control and the 5-mm hole following different methods using fibrinogen and thrombin solutions plus polyglactin 910 sheet (PGS). For group 1, fibrinogen was applied on the dura followed by PGS and thrombin. For group 2, thrombin was followed by PGS and fibrinogen. For group 3, fibrinogen was followed by PGS and fibrin spray. For group 4, thrombin was followed by PGS and fibrin spray. Microscopic observation was conducted for each specimen. Results. Repair using fibrin spray alone was successful for the 0.3-mm diameter pinhole (breakdown pressure: 27.8 +/- 8.6 mmHg), but was not able to cover the 2.7-and 5-mm holes. For a 5-mm diameter hole, the breakdown pressure was 54.4 +/- 38.8 mmHg in group 1, 26.3 +/- 19.4 mmHg in group 2, 147.7 +/- 65.0 mmHg in group 3, and 35.5 +/- 23.4 mmHg in group 4 (P< 0.001). There was little fibrin glue in the burst layer between the dural surface and PGS with thrombin on the dural surface (group 2 and group 4). Conclusion. Suppression of excessive CSF leakage could be successful by performing several cycles of the group 1 method (fibrinogen was applied on the dura followed by PGS and thrombin), followed by the group 3 method (fibrinogen was applied on the dura followed by PGS and fibrin spray), with thrombin solution wash each time.
  • Gen Matsumae, Makoto Motomiya, Naoya Watanabe, Norimasa Iwasaki
    MICROSURGERY 37 (6) 689 - 693 0738-1085 2017/09 [Refereed][Not invited]
     
    Treatment of a nonunion of the proximal humerus remains a challenge because of the small proximal fragment and poor central cancellous bone stock of the humeral head. In this report, we describe our experience using a half-folded pedicled scapular bone flap with an anatomical locking plate to treat an atrophic nonunion of the proximal humerus in a 64-year-old right-handed woman. The patient had fallen and experienced a common humeral neck fracture 2.5 years previously. During the operation, we elevated the pedicled scapular bone flap, which measured 8.0 cm long and 1.5 cm wide, with a vascular pedicle about 10 cm long. We modified the bone flap to the half-folded type to fill the massive bone cavity in the humeral head. The proximal tip of the flap was divided into two segments while keeping the ventral soft tissue intact. The grafted bone bridging between the head and shaft of the humerus was rigidly fixed with a plate and screw. The operated shoulder was fixed with a sling and a chest belt for 3 weeks, after which the patient began active motion exercises of the shoulder joint. The flap survived without serious donor site morbidity, and good bone healing was obtained about 3.5 months after surgery. The patient was able to use the shoulder comfortably in daily activity without any serious donor site morbidity at 16 months after the surgery. This procedure may be effective in treating nonunion of the proximal humerus with a massive bone cavity in the humeral head.
  • Terufumi Kokabu, Masahiko Takahata, Nobuhisa Ishiguro, Norimasa Iwasaki
    JOURNAL OF ORTHOPAEDIC SCIENCE 22 (5) 822 - 827 0949-2658 2017/09 [Refereed][Not invited]
     
    Background: Hematogenous vertebral osteomyelitis (HVO) has a generally favorable prognosis if appropriate treatment is initiated in its early phase; however, some intractable cases with HVO can develop neurological impairment as well as spinal deformity during the course of treatment and these sequelae may lead to impaired quality of life (QOL). In this study, we aimed to evaluate the long-term relapse rate, mortality, and QOL of patients with HVO. Methods: In this retrospective case series study, medical records of 60 patients with HVO with a mean follow-up period of 8 years (5-23 years) were reviewed to assess demographic data, details of infection, and clinical course. Mortality rate was assessed using a Kaplan-Meier plot. QOL was measured using the EuroQol 5 Dimension (EQ-5D) questionnaire and residual pain using a numeric rating scale (NRS). Results: HVO relapsed in 4 of 60 patients (7%). Overall 5-year survival rate in 60 patients with HVO was 85%. The factors associated with increased mortality were malignant tumor, diabetes mellitus, chronic use of glucocorticoids, and drug-resistant strains of staphylococcus. Female-to-male ratio, NRS, prevalence of neurological impairment were significantly higher in patients with low EQ-5D score (poor health) compared to those with high EQ-5D score (good health). Conclusions: Patients with HVO have shorter life expectancy if they have malignancy, diabetes mellitus, chronic use of glucocorticoids, and a history of drug-resistant strains of staphylococcus infection. Female gender, residual neurological defects and persistent back pain are associated with impaired QOL in patients with HVO. (C) 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
  • Yasushi Sato, Hisashi Mera, Daisuke Takahashi, Tokifumi Majima, Norimasa Iwasaki, Shigeyuki Wakitani, Mutsumi Takagi
    CYTOTECHNOLOGY 69 (3) 405 - 416 0920-9069 2017/06 [Refereed][Not invited]
     
    Aiming to increase the content of type 2 collagen in scaffold-free cartilage-like cell sheets prepared using human bone marrow mesenchymal stem cells, the effect of several kinds of additives in a chondrogenic medium was investigated. Addition of ascorbic acid 2 phosphate (VCP) at a high concentration (250 A mu g/ml) and type 1 atelocollagen (5 A mu g/ml) increased the accumulation of type 2 collagen by fourfold and twofold, respectively. On the other hand, an antioxidant, glutathione showed no such effect. The synergistic effect of VCP and type 1 atelocollagen resulted in an eightfold increase in the accumulation level of type 2 collagen. Furthermore, the gene expression level of type 2 collagen increased and that of matrix metalloproteinase-13 (MMP-13) decreased to approximately one-third of the control. The increase in type 2 collagen accumulation in the scaffold-free cartilage-like cell sheet might be due to not only the enhancement of the synthesis but also the suppression of the degradation of type 2 collagen by MMP-13.
  • Akira Iwata, Masahiro Kanayama, Fumihiro Oha, Tomoyuki Hashimoto, Norimasa Iwasaki
    BMC MUSCULOSKELETAL DISORDERS 18 (1) 148  1471-2474 2017/04 [Refereed][Not invited]
     
    Background: Teriparatide (recombinant human parathyroid hormone 1-34) is increasingly used for the treatment of severe osteoporosis because it stimulates bone formation and may potentially enhance fracture healing. The objective of this study was to investigate the effects of teriparatide versus a bisphosphonate on radiographic outcomes in the treatment of osteoporotic vertebral compression fractures (OVCF). Methods: A total of 98 patients undergoing non-operative treatment for recent single-level OVCF were reviewed retrospectively. Thirty-eight patients were treated by a once-daily subcutaneous injection of 20 micrograms of teriparatide (TPD group), whereas 60 patients received 35 mg of alendronate weekly (BP group). Except for these medications, the same treatment protocol was applied to both groups. The radiographic assessments included union status, vertebral kyphosis, and mid-vertebral body height. The rates of fracture site surgical intervention were also compared between the two groups. The mean follow-up period was 27 months (median 22.5, range 2 - 75 months). Results: Cox regression analysis showed that TPD reduced the time-to-union (adjusted relative hazard ratio: 1.86, 95% C.I.: 1.21 - 2.83). The union rate at six months after treatment was 89% in the TPD group and 68% in the BP group; the surgical intervention rate was significantly higher in the TPD group (p = 0.026, adjusted odds ratio: 8.15, 95% C.I.: 2.02 - 43.33). The change in local kyphosis was 4.6 degrees in the TPD group and 3.8 degrees in the BP group (p = 0.495, paired t-test). The change of mid-vertebral body height was 4.4 mm in the TPD group and 3.4 mm in the BP group (p = 0.228, paired t-test). Fracture site surgical interventions were not required in the TPD group; however, two patients in the BP group eventually underwent surgical treatment for symptomatic non-union or vertebral collapse. Conclusions: This retrospective study suggests that teriparatide may enhance fracture healing and improve the union rate in OVCF.
  • Masatake Matsuoka, Tomohiro Onodera, Kentaro Homan, Fumio Sasazawa, Jun-ichi Furukawa, Daisuke Momma, Rikiya Baba, Kazutoshi Hontani, Zenta Joutoku, Shinji Matsubara, Tadashi Yamashita, Norimasa Iwasaki
    SCIENTIFIC REPORTS 7 43729  2045-2322 2017/03 [Refereed][Not invited]
     
    Elucidation of the healing mechanisms in damaged tissues is a critical step for establishing breakthroughs in tissue engineering. Articular cartilage is clinically one of the most successful tissues to be repaired with regenerative medicine because of its homogeneous extracellular matrix and few cell types. However, we only poorly understand cartilage repair mechanisms, and hence, regenerated cartilage remains inferior to the native tissues. Here, we show that glycosylation is an important process for hypertrophic differentiation during articular cartilage repair. GM3, which is a precursor molecule for most gangliosides, was transiently expressed in surrounding damaged tissue, and depletion of GM3 synthase enhanced cartilage repair. Gangliosides also regulated chondrocyte hypertrophy via the Indian hedgehog pathway. These results identify a novel mechanism of cartilage healing through chondrocyte hypertrophy that is regulated by glycosylation. Manipulation of gangliosides and their synthases may have beneficial effects on articular cartilage repair.
  • Yusuke Kameda, Tadanao Funakoshi, Shunsuke Takeuchi, Katsura Sugawara, Norimasa Iwasaki
    ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY 33 (2) 291 - U550 0749-8063 2017/02 [Refereed][Not invited]
     
    Purpose: To assess the histological properties of cells from displaced fragments obtained from patients with advanced osteochondritis dissecans (OCD) of the elbow and to examine whether these displaced fragments could be used as cell sources for autologous chondrocyte implantation. Methods: We harvested 6 displaced fragments from 6 patients who underwent osteochondral mosaicplasty for OCD of the elbow. The displaced fragments were examined histologically and digested to obtain chondrocytes. The cells obtained from young patients and skeletally matured cadaveric donors were examined using quantitative reverse transcription polymerase chain reaction analysis to quantify the expression of chondrocyte marker genes. The cells were cultured in atelocollagen, and the properties of 3-dimensional cultured cartilage were examined. Results: All 6 displaced fragments contained hyaline cartilage tissue. Chondrocyte marker genes were examined using cells from only 4 patients, because we obtained enough cells in only 4 patients. The relative expression levels of aggrecan, type II, Sox 9 were 2.61, 4.03, and 1.71, respectively. Three-dimensional cultured cartilage from all 6 displaced fragments contained 62.0 pg/cell (range, 22.8-91.3 pg/cell) of glycosaminoglycan and expressed type II collagen in the superficial and middle layer. Conclusions: The chondrocytes obtained from the displaced fragments remained viable and exhibited chondrogenic features. These cells may potentially be a cell source of autologous chondrocytes implantation. Clinical Relevance: We have shown that displaced fragments from OCD of the elbow have potential for a cell source for generating 3-dimensional cultured cartilage.
  • Ryuta Arai, Tomohiro Onodera, Mohamad Alaa Terkawi, Tomoko Mitsuhashi, Eiji Kondo, Norimasa Iwasaki
    BMC MUSCULOSKELETAL DISORDERS 18 (1) 79  1471-2474 2017/02 [Refereed][Not invited]
     
    Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, reduction of 1,25-dihydroxyl vitamin D, and bone calcification disorders. Tumors associated with TIO are typically phosphaturic mesenchymal tumors that are bone and soft tissue origin and often present as a solitary tumor. The high production of fibroblast growth factor 23 (FGF23) by the tumor is believed to be the causative factor responsible for the impaired renal tubular phosphate reabsorption, hypophosphatemia and osteomalacia. Complete removal of the tumors by surgery is the most effective procedure for treatment. Identification of the tumors by advanced imaging techniques is difficult because TIO is small and exist within bone and soft tissue. However, systemic venous sampling has been frequently reported to be useful for diagnosing TIO patients. Case presentation: We experienced a case of 39-year-old male with diffuse bone pain and multiple fragility fractures caused by multiple FGF23-secreting tumors found in the hallux. Laboratory testing showed hypophosphatemia due to renal phosphate wasting and high levels of serum FGF23. Contrast-enhanced MRI showed three soft tissue tumors and an intraosseous tumor located in the right hallux. Systemic venous sampling of FGF23 revealed an elevation in the right common iliac vein and external iliac vein, which suggested that the tumors in the right hallux were responsible for overproduction of FGF23. Thereafter, these tumors were surgically removed and subjected to histopathological examinations. The three soft tissue tumors were diagnosed as phosphaturic mesenchymal tumors, which are known to be responsible for TIO. The fourth tumor had no tumor structure and was consisting of hyaline cartilage and bone tissue. Immediately after surgery, we noted a sharply decrease in serum level of FGF23, associated with an improved hypophosphatemia and a gradual relief of systematic pain that disappeared within two months of surgery. Conclusion: The authors reported an unusual case of osteomalacia induced by multiple phosphaturic mesenchymal tumors located in the hallux. Definition of tumors localization by systemic venous sampling led to successful treatment and cure this patient. The presence of osteochondral tissues in the intraosseous tumor might be developed from undifferentiated mesenchymal cells due to high level of FGF23 produced by phosphaturic mesenchymal tumors.
  • Masahiko Takahata, Kuniyoshi Abumi, Hideki Sudo, Ken Nagahama, Norimasa Iwasaki
    MODERN RHEUMATOLOGY 27 (5) 901 - 904 1439-7595 2017 [Refereed][Not invited]
     
    To highlight the risk of cervical myelopathy due to occult, atraumatic odontoid fracture in patients with rheumatoid arthritis, we retrospectively reviewed radiographic findings and clinical observations for 7 patients with this disorder. This fracture tends to occur in patients with long-lasting rheumatoid arthritis and to be misdiagnosed as simple atlantoaxial dislocation. Since this fracture causes multidirectional instability between C1 and C2 and is expected to have poor healing potential due to bone erosion and inadequate blood supply, posterior spinal arthrodesis surgery is indicated upon identification of the fracture to prevent myelopathy.
  • Atsushi Urita, Tadanao Funakoshi, Tatsunori Horie, Mutsumi Nishida, Norimasa Iwasaki
    JOURNAL OF SHOULDER AND ELBOW SURGERY 26 (1) 149 - 156 1058-2746 2017/01 [Refereed][Not invited]
     
    Background: Vascularity is the important factor of biologic healing of the repaired tissue. The purpose of this study was to clarify sequential vascular patterns of repaired rotator cuff by suture techniques. Methods: We randomized 21 shoulders in 20 patients undergoing arthroscopic rotator cuff repair into 2 groups: transosseous-equivalent repair (TOE group, n = 10) and transosseous repair (TO group, n = 11). Blood flow in 4 regions inside the cuff (lateral articular, lateral bursal, medial articular, and medial bursal), in the knotless suture anchor in the TOE group, and in the bone tunnel in the TO group was measured using contrast-enhanced ultrasound at 1 month, 2 months, 3 months, and 6 months postoperatively. Results: The sequential vascular pattern inside the repaired rotator cuff was different between groups. The blood flow in the lateral articular area at 1 month, 2 months, and 3 months (P = .002, .005, and .025) and that in the lateral bursal area at 2 months (P = .031) in the TO group were significantly greater than those in the TOE group postoperatively. Blood flow was significantly greater for the bone tunnels in the TO group than for the knotless suture anchor in the TOE group at 1 month and 2 months postoperatively (P = .041 and .009). Conclusion: This study clarified that the sequential vascular pattern inside the repaired rotator cuff depends on the suture technique used. Bone tunnels through the footprint may contribute to biologic healing by increasing blood flow in the repaired rotator cuff. (C) 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.
  • Akira Iwata, Masahiro Kanayama, Fumihiro Oha, Tomoyuki Hashimoto, Norimasa Iwasaki
    European Journal of Orthopaedic Surgery and Traumatology 27 (1) 87 - 92 1432-1068 2017/01/01 [Refereed][Not invited]
     
    Purpose: In the healing of osteoporotic vertebral fracture, global spinal mal-alignment might increase the load sharing at the fracture site and deteriorate the fracture healing. This study aimed to evaluate the effect of spinopelvic alignment on the union status of thoracolumbar osteoporosis-related vertebral compression fracture (OVCF). Methods: Consecutive 48 patients with a single-level thoracolumbar fresh OVCF were treated non-operatively. Union was judged by three independent observers at 6 months, and patients were divided into union group and non-union group. Spinopelvic alignment was measured using upright whole spine radiograph before treatment as follows: pelvic incidence (PI), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), sagittal vertical axis (SVA), and DSVA, defined as the distance from a plumb line dropped from the center of the C7 body to the center of fractured vertebral body. Result: Global spinal alignment was different in union group and non-union group: SVA (4.7 ± 0.7 cm in union group vs. 8.9 ± 1.3 cm in non-union group, P = 0.007), DSVA (4.2 ± 0.6 cm in union group vs. 9.5 ± 1.0 cm in non-union group, P <  0.001), and PI–LL (18.9° ± 2.2° in union group vs. 30.3° ± 3.9° in non-union group, P = 0.014). Over 5 cm of DSVA [P = 0.022, adjusted odds 7.9 (95 % CI 1.3–77.0)] and/or over 30° of PI–LL [P = 0.026, adjusted odds 6.6 (95 % CI 1.5–44.2)] showed the significant risk factors for non-union using multivariate logistic regression analysis in the other background status. Conclusions: Global spinal mal-alignment, showing over 5 cm of DSVA and/or over 30° of PI–LL, affected the union status of OVCF.
  • Tohru Irie, Daisuke Takahashi, Tsuyoshi Asano, Ryuta Arai, Takuya Konno, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
    HIP INTERNATIONAL 27 (1) 49 - 54 1120-7000 2017/01 [Refereed][Not invited]
     
    Purpose: Eccentric rotational acetabular osteotomy (ERAO) is a modification of rotational acetabular osteotomy (RAO); it has been reported that ERAO allows the femoral head to translate medially and distally. However, no study has compared femoral head translation following RAO or ERAO. The purpose of this study was to compare immediate postoperative translation of the femoral head after RAO and ERAO in comparison with the preoperative position by radiological methods. Methods: Patients treated by RAO or ERAO between 2006 and 2014 were retrospectively evaluated. 19 hips (17 patients) were treated with RAO, and 25 hips (22 patients) were treated with ERAO. The acetabular roof angle and the location of the femoral head were measured on anteroposterior pelvic radiographs. Results: The mean preoperative acetabular roof angle was 20.9 degrees in the RAO group and 22.0 degrees in the ERAO group, showing no significant difference. The mean acetabular roof angle immediately postoperatively was -0.5 degrees in the RAO group and -0.4 degrees in the ERAO group, again showing no significant difference. The mean femoral head translation immediately postoperatively was 3.1 mm (95% confidence interval (CI), 1.5-4.7 mm) laterally and 3.0 mm (95% CI, 1.3-4.7 mm) proximally in the RAO group and 0.8 mm (95% CI, -0.7-2.3 mm) medially and 2.8 mm (95% CI, 1.5-4.1 mm) distally in the ERAO group; this difference was very highly significant (p<0.001). Conclusions: In contrast with RAO, ERAO resulted in significant femoral head translation both medially and distally immediately postoperatively.
  • Ryuta Arai, Daisuke Takahashi, Masahiro Inoue, Tohru Irie, Tsuyoshi Asano, Takuya Konno, Mohamad Alaa Terkawi, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
    BMC MUSCULOSKELETAL DISORDERS 18 (1) 24  1471-2474 2017/01 [Refereed][Not invited]
     
    Background: Collapse of the femoral head associated with nontraumatic osteonecrosis (NOFH) is one of the most common causes of disability in young adult patients. Excessive bone resorption by osteoclast coincident with the suppression of osteogenesis are believed to be responsible for collapse progression. Alendronate that inhibits bone resorption by inducing osteoclast apoptosis has been traditionally used for treating NOFH; however, several reports documented serious complications by the use of this drug. On the other hand, teriparatide activates osteoblasts leading to an overall increase in bone volume, and is expected to reduce the progression of femoral head collapse in NOFH. Therefore, the present study was undertaken to examine pharmacological effects of teriparatide on collapse progression of NOFH and to compare these effects with alendronate. Methods: We conducted a retrospective study in our facility for comparing the pharmacological effects of teriparatide and alendronate on 32 NOFH patients diagnosed with osteoporosis. Between 2007 and 2013, patients were treated with daily administration of 20 mu g teriparatide (15 patients: 18 hips), or with 35 mg of alendronate once a week (17 patients: 22 hips). The mean period of follow-up was 18.7 months. The progression of collapse was evaluated prior to the administration and later every three months by anteroposterior radiographs. Collapse progression with > 1 mm was defined as advanced collapse, while with < 1 mm was defined as stable radiologic disease. Student's t-test and the chi-square test was used to do compare the pharmacological effects of the two groups. Results: Treatment with terparatide had a tendency to reduce the rate of advanced collapse as compared to that with alendronate (p = 0.105). Kaplan-Meier curves related to stable radiologic disease showed that teriparatide-treated patients had better stable states than these treated with alendronate (p = 0.08, log-rank test). Moreover, treatment with teriparatide resulted in a significant reduction in collapse progression as compared to that with alendronate, noted at the end of follow-up period (p = 0.049). Conclusion: The present study suggests that teriparatide has greater pharmacological effects than alendronate for treating NOFH and preventing the collapse of femoral head.
  • Ushiku C, Suda K, Matsumoto S, Komatsu M, Takahata M, Iwasaki N, Minami A
    Spinal cord series and cases 3 16040  2017 [Refereed][Not invited]
  • Koji Iwasaki, Hideki Sudo, Yasuhiko Kasahara, Katsuhisa Yamada, Takashi Ohnishi, Takeru Tsujimoto, Norimasa Iwasaki
    ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY 32 (10) 2026 - 2036 0749-8063 2016/10 [Refereed][Not invited]
     
    Purpose: To determine the in vivo effects of multiple local anesthetic injections of 0.5% bupivacaine on normal and osteoarthritic articular cartilage. Methods: Rats with normal knee joints received an intra-articular injection of 0.9% saline solution or 0.5% bupivacaine in their right knees joint once a week for 5 consecutive weeks, starting 4 weeks after the beginning of the experiment. Rats were humanely killed at 8, 16, and 24 weeks. In a parallel experiment, rats underwent anterior cruciate ligament transection to induce osteoarthritic changes. These rats were subjected to the same protocol as those with normal knee joints, starting 4 weeks after the procedure. Static weight-bearing tests were performed on both hind limbs to evaluate changes in weight-bearing ability throughout the experiments. Rats were humanely killed at 8 and 16 weeks. Cell viability was assessed with confocal microscopy, using samples from the distal femur. Histologic assessment of osteoarthritis was performed using samples from the tibial plateau based on the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment system (i.e., OARSI score). Results: Static weight-bearing tests showed no significant changes after intra-articular injection of saline solution or bupivacaine, and bupivacaine injection did not increase weight bearing compared with saline solution injection, regardless of whether there were osteoarthritic changes. There were also no significant differences in cell viability, cell density, or OARSI scores between the saline solution and bupivacaine groups at each time point, regardless of whether osteoarthritic changes were induced. Conclusions: This study suggested that single or intermittent intra-articular bupivacaine injections might not have deleterious effects on either osteoarthritic or normal joints.
  • Noriaki Mori, Shoichi Kimura, Tomohiro Onodera, Norimasa Iwasaki, Izumi Nakagawa, Takeshi Masuda
    KNEE 23 (5) 887 - 889 0968-0160 2016/10 [Refereed][Not invited]
     
    Background: There has been controversy regarding the incidence of deep vein thrombosis (DVT) after total knee arthroplasty (TKA) with or without the use of a tourniquet. The aim of this randomized, prospective study was to clarify the effects of tourniquet use on DVT in TKA. Methods: The subjects were 109 patients scheduled to undergo TKA from April 2008 to March 2009 before the establishment of the American Association of Orthopedic Surgeons (AAOS) practice guidelines. They were randomized into two groups: 51 patients in the tourniquet group (group T) and 52 patients in the control group without a tourniquet (group C). We investigated the thrombotic presence using ultrasonography one week after surgery and compared both groups. Results: There was no difference in the rate of proximal DVTs (P = 0.63). However, the risk of distal DVT was significantly higher in group T than in group C (52.9% vs. 23.1%; P = 0.002). Conclusions: Use of the tourniquet in TKA increased the risk of distal DVT. (C) 2016 Elsevier B.V. All rights reserved.
  • Takeru Tsujimoto, Masahiko Takahata, Terufumi Kokabu, Megumi Matsuhashi, Norimasa Iwasaki
    JOURNAL OF ORTHOPAEDIC SCIENCE 21 (5) 694 - 697 0949-2658 2016/09 [Refereed][Not invited]
  • Hideki Sudo, Yuichiro Abe, Terufumi Kokabu, Manabu Ito, Kuniyoshi Abumi, Yoichi M. Ito, Norimasa Iwasaki
    SPINE JOURNAL 16 (9) 1049 - 1054 1529-9430 2016/09 [Refereed][Not invited]
     
    BACKGROUND CONTEXT: Controversy exists regarding the effects of multilevel facetectomy and screw density on deformity correction, especially thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery. PURPOSE: This study aimed to evaluate the effects of multilevel facetectomy and screw density on sagittal plane correction in patients with main thoracic (MT) AIS curve. STUDY DESIGN: A retrospective correlation and comparative analysis of prospectively collected, consecutive, non-randomized series of patients at a single institution was undertaken. PATIENT SAMPLE: Sixty-four consecutive patients with Lenke type 1 AIS treated with posterior correction and fusion surgery using simultaneous double-rod rotation technique were included. OUTCOME MEASURES: Patient demographics and preoperative and 2-year postoperative radiographic measurements were the outcome measures for this study. METHODS: Multiple stepwise linear regression analysis was conducted between change in TK (T5-T12) and the following factors: age at surgery, Risser sign, number of facetectomy level, screw density, preoperative main thoracic curve, flexibility in main thoracic curve, coronal correction rate, preoperative TK, and preoperative lumbar lordosis. Patients were classified into two groups: TK< 15 degrees group defined by preoperative TK below the mean degree of TK for the entire cohort (< 15 degrees) and the TK >= 15 degrees group, defined by preoperative TK above the mean degree of kyphosis (>= 15 degrees). Independent sample t tests were used to compare demographic data as well as radiographic outcomes between the two groups. There were no study-specific biases related to conflicts of interest. RESULTS: The average preoperative TK was 14.0 degrees, which improved significantly to 23.1 degrees (p<.0001) at the 2-year final follow-up. Greater change in TK was predicted by a low preoperative TK (p<.0001). The TK < 15 degrees group showed significant correlation between change in TK and number of facetectomy level (r=0.492, p=.002). Similarly, significant correlation was found between change in TK and screw density (r=0.333, p=.047). Conversely, in the TK >= 15 degrees group, correlation was found neither between change in TK and number of facetectomy level (r=0.047, p=.812), nor with screw density (r= 0.030, p=.880). Furthermore, in patients with preoperative TK< 15 degrees, change in TK was significantly correlated with screw density at the concave side (r=0.351, p=.036) but not at the convex side (r=0.144, p=.402). CONCLUSIONS: In patients with hypokyphotic thoracic spine, significant positive correlation was found between change in TK and multilevel facetectomy or screw density at the concave side. This indicates that in patients with AIS who have thoracic hypokyphosis as part of their deformity, the abovementioned factors must be considered in preoperative planning to correct hypokyphosis. (C) 2016 Elsevier Inc. All rights reserved.
  • Takashi Ohnishi, Hideki Sudo, Koji Iwasaki, Takeru Tsujimoto, Yoichi M. Ito, Norimasa Iwasaki
    PLOS ONE 11 (8) e0160486  1932-6203 2016/08 [Refereed][Not invited]
     
    Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region.
  • Terufumi Kokabu, Hideki Sudo, Yuichiro Abe, Manabu Ito, Yoichi M. Ito, Norimasa Iwasaki
    PLOS ONE 11 (8) e0161906  1932-6203 2016/08 [Refereed][Not invited]
     
    Flattening of the preimplantation rod contour in the sagittal plane influences thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery. The effects of multilevel facetectomy and screw density on postoperative changes in spinal rod contour have not been documented. This study aimed to evaluate the effects of multilevel facetectomy and screw density on changes in spinal rod contour from before implantation to after surgical correction of thoracic curves in patients with AIS prospectively. The concave and convex rod shapes from patients with thoracic AIS (n = 49) were traced prior to insertion. Postoperative sagittal rod shape was determined by computed tomography. The angle of intersection of the tangents to the rod end points was measured. Multiple stepwise linear regression analysis was used to identify variables independently predictive of change in rod contour (Delta theta). Average Delta theta at the concave and convex side were 13.6 degrees +/- 7.5 degrees and 4.3 degrees +/- 4.8 degrees, respectively. The Delta theta at the concave side was significantly greater than that of the convex side (P < 0.0001) and significantly correlated with Risser sign (P = 0.032), the preoperative main thoracic Cobb angle (P = 0.031), the preoperative TK angle (P = 0.012), and the number of facetectomy levels (P = 0.007). Furthermore, a Delta theta at the concave side +/- 14 degrees significantly correlated with the postoperative TK angle (P = 0.003), the number of facetectomy levels (P = 0.021), and screw density at the concave side (P = 0.008). Rod deformation at the concave side suggests that corrective forces acting on that side are greater than on the convex side. Multilevel facetectomy and/or screw density at the concave side have positive effects on reducing the rod deformation that can lead to a loss of TK angle postoperatively.
  • Tsukuda Y, Funakoshi T, Nasuhara Y, Nagano Y, Shimizu C, Iwasaki N
    Journal of patient safety 1549-8417 2016/06 [Refereed][Not invited]
  • Tadanao Funakoshi, Kozo Furushima, Daisuke Momma, Kaori Endo, Yuichiro Abe, Yoshiyasu Itoh, Kazuhiro Fujisaki, Shigeru Tadano, Norimasa Iwasaki
    AMERICAN JOURNAL OF SPORTS MEDICINE 44 (4) 989 - 994 0363-5465 2016/04 [Refereed][Not invited]
     
    Background: Repetitive valgus stress applied during a throwing motion can lead to various elbow disturbances, including ulnar collateral ligament (UCL) injury. Subchondral bone density reportedly reflects the cumulative force on a joint surface under actual loading conditions. Purpose: (1) To evaluate the distribution of subchondral bone density across the elbow joint in asymptomatic baseball pitchers and symptomatic valgus instability pitchers and (2) to clarify the alterations in stress distribution pattern associated with symptomatic UCL insufficiency pitching activities. Study Design: Controlled laboratory study. Methods: Computed tomography (CT) imaging data were collected from the dominant-side elbow of 7 nonathletic volunteers (controls), 12 asymptomatic pitchers (asymptomatic group), and 12 symptomatic valgus instability pitchers with UCL insufficiency (symptomatic group). Bone mineral density across the elbow joint was measured with CT osteoabsorptiometry. A 2-dimensional mapping model was divided into 4 areas of the distal end of the humerus and 5 areas of the ulna with the radial head. The locations and percentages of high-density areas on the articular surface were quantitatively analyzed. Results: High-density areas in the asymptomatic and symptomatic groups were found in the anterolateral and posteromedial parts of the humerus and in the radial head, posteromedial to the ulna. The high-density areas in the anterior and posteromedial of the humerus, the radial head, and the posteromedial part of the ulna in the controls were smaller than those in the baseball group. In the symptomatic group, the percentages of high-density areas in the anterolateral part of the humerus (mean, 36.3%; 95% CI, 31.9%-40.7%) and the anterolateral part of the ulna (mean, 31.7%; 95% CI, 24.3%-39.1) were significantly greater than those in the asymptomatic group (P = .047 and P < .0001, respectively). Conclusion: Symptomatic UCL insufficiency was associated with characteristic high-stress distribution patterns on the anterolateral part of the capitellum and the anterolateral part of the ulna. The current results indicate that symptomatic UCL insufficiency produces excessive and cumulative stress in the elbow joint. Clinical Relevance: The information obtained from the CT images can useful for early detection of overstress conditions of the elbow joint.
  • Hideki Sudo, Kiyoshi Kaneda, Yasuhiro Shono, Norimasa Iwasaki
    SPINE JOURNAL 16 (3) 281 - 287 1529-9430 2016/03 [Refereed][Not invited]
     
    BACKGROUND CONTEXT: Consensus regarding the optimal upper vertebra to be instrumented during surgical treatment of Lenke 5C thoracolumbar and lumbar adolescent idiopathic scoliosis (AIS) remains limited. PURPOSE: This study aimed to assess whether a short fusion strategy is appropriate for correction of a Lenke 5C AIS curve by anterior correction and fusion surgery using dual-rod instrumentation. STUDY DESIGN: This study design used retrospective comparative analysis of a prospectively collected, consecutive, non-randomized series of patients at a single institution. PATIENT SAMPLE: Thirty consecutive patients with Lenke 5C AIS treated with anterior correction and fusion surgery using dual-rod instrumentation were included. OUTCOME MEASURES: Patient demographics, radiographic measurements, and Scoliosis Research Society-22 questionnaire (SRS-22) scores were the outcome measures for this study. METHODS: Thirty patients were treated surgically for AIS with a Lenke 5C curve (mean age, 14.4 years [11-19 years)]) and followed up for a mean period of 17.2 years (12-23 years). Radiographical parameters and clinical outcomes were compared between patients treatment with the end vertebra (EV) instrumented (n=14) and those treated by short fusion (S group) with instrumentation starting at the vertebra one level caudal to the EV (n=16 patients). There were no study-specific biases related to conflicts of interest. RESULTS: In the EV group, a mean preoperative Cobb angle of 56 degrees was corrected to 5 degrees after surgery and to 8 degrees at the final follow-up. In the S group, a mean preoperative Cobb angle of 55 degrees was corrected to 10 degrees after surgery and 14 degrees at the final follow-up. The mean correction rate at the final follow-up was significantly lower in the S group (74%) than in the EV group (86%; p=.020). The coronal and sagittal balance, thoracic kyphosis, lumbar lordosis, and clinical outcomes evaluated using SRS-22 did not differ between the two groups. CONCLUSIONS: The short fusion strategy, which involves instrumentation of the vertebra one level caudal to the upper EV, can be considered as an alternative to the conventional strategy, which includes instrumentation of the upper EV, for treating Lenke 5C curves via anterior spinal fusion. (C) 2016 Elsevier Inc. All rights reserved.
  • Atsushi Urita, Tadanao Funakoshi, Toraji Amano, Yuichiro Matsui, Daisuke Kawamura, Yusuke Kameda, Norimasa Iwasaki
    JOURNAL OF SHOULDER AND ELBOW SURGERY 25 (3) 384 - 389 1058-2746 2016/03 [Refereed][Not invited]
     
    Background: Disorders of the long head of the biceps (LHB) tendon contribute to anterior shoulder pain. Although LHB tendon disorders are associated with rotator cuff disease, distinguishing between biceps and rotator cuff pathology is difficult. The objective was to identify the predictors of LHB tendon disorders associated with a supraspinatus tear. Methods: In 55 patients (average age, 65 years) undergoing arthroscopic rotator cuff repair, bicipital groove morphology were assessed using computed tomography, and subscapularis tear and bicipital groove effusion were assessed using magnetic resonance imaging, retrospectively. The LHB tendon was evaluated arthroscopically according to the Lafosse classification. Univariate and multivariate ordinal logistic regression analyses were conducted for injury grade with all covariates. Results: The arthroscopic evaluation of the LHB tendon showed that there were 23 shoulders classified as grade 0, 15 as grade 1, and 17 as grade 2. Univariate logistic regression analysis showed that the width and depth, a medial spur of the bicipital groove, and a subscapularis tear were significantly associated with LHB tendon disorders. Multivariate ordinal logistic regression analysis identified a medial spur and subscapularis tear as significant predictors of LHB tendon disorders. Conclusions: The preoperative computed tomography and magnetic resonance images, notably the presence of a spur on the bicipital groove or a subscapularis tear, were useful for identifying LHB tendon disorders. When these are found in preoperative images, the clinician should evaluate the patient for the presence of an LHB tendon disorder as a pain generator. (C) 2016 Journal of Shoulder and Elbow Surgery Board of Trustees
  • Yuichiro Matsui, Tadanao Funakoshi, Hideyuki Kobayashi, Tomoko Mitsuhashi, Tamotsu Kamishima, Norimasa Iwasaki
    BMC MUSCULOSKELETAL DISORDERS 17 130  1471-2474 2016/03 [Refereed][Not invited]
     
    Background: Bizarre parosteal osteochondromatous proliferation (BPOP), first described by Nora et al. in 1983 and therefore termed "Nora's lesion", is a rare lesion that occurs in the short bones of the hands and feet and eventually presents as a parosteal mass. Reports of BPOP in the long bones are very rare. A benign disease, BPOP does not become malignant, although a high rate of recurrence following surgical resection is reported. Because of its atypical imaging findings and histopathological appearance, a BPOP might be misdiagnosed as a malignant tumor such as an osteochondroma with malignant transformation, a parosteal osteosarcoma, or a periosteal osteosarcoma. Case presentation: A 58-year-old woman complained of left ulnar wrist pain at the time of her initial presentation. Plain x-rays showed ectopic calcifications in and around the distal radioulnar joint, which supported the diagnosis of subacute arthritis with hydroxyapatite crystal deposition. She was initially given a wrist brace and directed to follow-up, but her persistent pain required the administration of corticosteroid injections into the distal radioulnar joint. Increasing ulnar wrist joint pain and limited forearm pronation and wrist flexion necessitated computed tomography and contrast-enhanced magnetic resonance imaging. BPOP was diagnosed based on the preoperative imaging studies, and a resection of the lesion was performed along with the decortication of the underlying the cortical bone to reduce recurrence rates. The diagnosis of BPOP was confirmed by pathologic examination. Two years after surgery, the patient has no subsequent pain complaints and an improved range of motion. Conclusions: BPOP affecting the distal end of the ulna is exceedingly rare. Because BPOP was diagnosed primarily based upon preoperative imaging findings in our patient, decortication of the underlying cortical bone was performed to reduce recurrence rates. Further careful follow-up in these patients is essential, despite the non-recurrence of the lesion.
  • Hideki Sudo, Yuichiro Abe, Kuniyoshi Abumi, Norimasa Iwasaki, Manabu Ito
    EUROPEAN SPINE JOURNAL 25 (2) 569 - 577 0940-6719 2016/02 [Refereed][Not invited]
     
    There is limited consensus on the optimal surgical strategy for double thoracic adolescent idiopathic scoliosis (AIS). Recent studies have reported that pedicle screw constructs to maximize scoliosis correction cause further thoracic spine lordosis. The objective of this study was to apply a new surgical technique for double thoracic AIS with rigid proximal thoracic (PT) curves and assess its clinical outcomes. Twenty one consecutive patients with Lenke 2 AIS and a rigid PT curve (Cobb angle a parts per thousand yen30A(0) on side-bending radiographs, flexibility a parts per thousand currency sign30 %) treated with the simultaneous double-rod rotation technique (SDRRT) were included. In this technique, a temporary rod is placed at the concave side of the PT curve. Then, distraction force is applied to correct the PT curve, which reforms a sigmoid double thoracic curve into an approximate single thoracic curve. As a result, the PT curve is typically converted from an apex left to an apex right curve before applying the correction rod for PT and main thoracic curve. All patients were followed for at least 2 years (average 2.7 years). The average main thoracic and PT Cobb angle correction rate at the final follow-up was 74.7 and 58.0 %, respectively. The average preoperative T5-T12 thoracic kyphosis was 9.3A degrees, which improved significantly to 19.0A degrees (p < 0.0001) at the final follow-up. Although 71 % patients had preoperative level shoulders or a positive radiographic shoulder height, all patients had mildly imbalanced or balanced shoulders at the final follow-up. The average preoperative main thoracic apical vertebral rotation angle of 20.7A degrees improved significantly after surgery to 16.4A degrees (p = 0.0046), while the average preoperative total SRS questionnaire score of 3.7 improved significantly to 4.4 (p = 0.0012) at the final follow-up. Radiographic findings and patient outcomes were satisfactory. Thoracic kyphosis can be maintained or improved, while coronal and axial deformities can be corrected using SDRRT for Lenke 2 AIS with a rigid PT curve.
  • Hiroki Hamano, Masahiko Takahata, Masahiro Ota, Shigeto Hiratsuka, Tomohiro Shimizu, Yusuke Kameda, Norimasa Iwasaki
    CALCIFIED TISSUE INTERNATIONAL 98 (2) 140 - 148 0171-967X 2016/02 [Refereed][Not invited]
     
    Diffuse idiopathic skeletal hyperostosis (DISH) is a common skeletal disorder in the elderly, which can develop into periosteal hyperostosis and paradoxically into immobilization-associated trabecular osteoporosis. The bone anabolic agent, teriparatide (TPD), seems to be a rational treatment for the immobilization-associated osteoporosis. However, it can lead to development of hyperostosis lesions in DISH patients. Here, we demonstrate TPD effectively treats trabecular osteoporosis while simultaneously promoting ankylosis of the spine in DISH model tiptoe-walking Yoshimura (twy) mice, compared with the ICR mice. Eighteen male twy mice were divided into three groups, and ICR mice were used as a normal control. Subcutaneous injections of TPD or phosphate-buffered saline (PBS) were performed according to three dosing regimens; 40 A mu g/kg once daily (TPD x 1 group), 40 A mu g/kg three times daily (TPD x 3 group), and PBS (control; Ctl group). Treatment was commenced at the age of 7 weeks and continued for 5 weeks. Micro-computed tomography (A mu CT) and histological analysis were performed. Longitudinal A mu CT study revealed that trabecular bone volume in both the vertebral body and distal femur decreased with time in the Ctl group, but increased dramatically in the TPD x 3 group. The twy mice developed ankylosis of the spine, the progression of which was accelerated with TPD therapy. We also confirmed that TPD therapy promoted ossification of spinal ligaments. Histomorphometrical study revealed that TPD treatment increased bone formation at the vertebrae enthesis region and in the trabecular bone. TPD therapy effectively treats trabecular osteoporosis, but potentially promotes ankylosis of the spine in patients with DISH.
  • Eiji Kondo, Kazunori Yasuda, Nobuto Kitamura, Jun Onodera, Masashi Yokota, Tomonori Yagi, Norimasa Iwasaki
    BMC MUSCULOSKELETAL DISORDERS 17 65  1471-2474 2016/02 [Refereed][Not invited]
     
    Background: In anatomic double-bundle anterior cruciate ligament (ACL) reconstruction, there are great controversies concerning the ideal graft tension protocols. The purpose of this study was to clarify differences in the effect of two graft tension protocols on the clinical outcome after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction by comparing the minimum 2-year clinical results. Methods: Ninety-seven patients with unilateral anatomic double-bundle ACL reconstruction were divided into two groups. In the first 44 patients (Group I), a 40-N tension was applied to each of the two hamstring autografts at 30 degrees of knee flexion, and simultaneously fixed onto the tibia. In the remaining 53 patients (Group II), a 30-N tension was applied to each graft at 10 degrees of knee flexion, and simultaneously fixed onto the tibia. Each patient was examined 2 years after surgery. Results: There wasn't a significant difference in the background of the two groups. There was no significant difference in the postoperative anterior laxity between the two groups. The average was 1.1 mm and 0.9 mm in Groups I and II, respectively. There wasn't any differences between the two groups in Lysholm knee score, International Knee Documentation Committee (IKDC) evaluation and muscle strength. Four patients had loss of knee extension in a range of 5 degrees and 10 degrees in Group I and none of the patients in Group II exhibited any loss in knee extension; which was statistically significant (p = 0.025). Conclusion: The two initial graft tension protocols did not result in any significant differences in the Lysholm knee score and IKDC grade. However, it was noted that the 40-N tension applied to each graft at 30 degrees of knee flexion more significantly induced loss of knee extension in comparison to the 30-N tension applied to each graft at 10 degrees. From a clinical viewpoint, the loss of knee extension is one of the pathological conditions that should be absolutely avoided after ACL reconstruction. Therefore, the 30-N tension applied to each graft at 10 degrees is preferable to the other graft tension protocol.
  • Kaori Endo, Satoshi Yamada, Masahiro Todoh, Masahiko Takahata, Norimasa Iwasaki, Shigeru Tadano
    PEERJ 4 e1562  2167-8359 2016/01 [Refereed][Not invited]
     
    The incidence of osteoporotic fractures was estimated as nine million worldwide in 2000, with particular occurrence at the proximity of joints rich in cancellous bone. Although most of these fractures spontaneously heal, some fractures progressively collapse during the early post-fracture period. Prediction of bone fragility during progressive collapse following initial fracture is clinically important. However, the mechanism of collapse, especially the gradual loss of the height in the cancellous bone region, is not clearly proved. The strength of cancellous bone after yield stress is difficult to predict since structural and mechanical strength cannot be determined a priori. The purpose of this study was to identify whether the baseline structure and volume of cancellous bone contributed to the change in cancellous bone strength under cyclic loading. A total of fifteen cubic cancellous bone specimens were obtained from two 2-year-old bovines and divided into three groups by collection regions: ferrioral head, neck, and proximal metaphysic. Structural indices of each 5-mm cubic specimen were determined using micro-computed tomography. Specimens were then subjected to five cycles of uniaxial compressive loading at 0.05 mm/min with initial 20 N loading, 0.3 min displacement, and then unloading to 0.2 mm with 0.1 mm displacement for five successive cycles. Elastic modulus and yield stress of cancellous bone decreased exponentially during five loading cycles. The decrease ratio of yield stress from baseline to fifth cycle was strongly correlated with bone volume fraction (BV/TV, r = 0.96, p < 0.01) and structural model index (SMI, r = 0.81, p < 0.01). The f decrease ratio of elastic modulus from baseline to cycle was also correlated with BV/TV (r = 0.80, p < 0.01) and SMI (r-= 0.78, p < 0.01). These data indicate that structural deterioration of cancellous bone is associated with bone strength after yield stress. This study suggests that baseline cancellous bone structure estimated from adjacent non-fractured bone contributes to the cancellous bone strength during collapse.
  • Miki Komatsu, Kota Suda, Masahiko Takahata, Satoko Matsumoto, Chikara Ushiku, Katsuhisa Yamada, Junichi Yamane, Tsutomu Endo, Norimasa Iwasaki, Akio Minami
    Spinal cord series and cases 2 16031 - 16031 2016 [Refereed][Not invited]
     
    INTRODUCTION: There are considerable risks for the secondary spinal cord injury and the initial and/or delayed vertebral artery occlusion in cases of cervical fracture dislocation. CASE PRESENTATION: An 86-year-old man was injured in a car accident and was diagnosed with no fracture or dislocation of the cervical spine by the emergency physician. However, he was transferred to our hospital 3 days later because he had motor weakness that was evaluated to be 32 points (out of 50 points) on the upper limb American Spinal Injury Association (ASIA) motor score and was diagnosed with spontaneously reduced fracture dislocation at C5/6. Magnetic resonance images revealed that the bilateral vertebral arteries were occluded, and there were some microinfarction lesions in the brain. On the first visit to his previous doctor, he was found to have a flow void in the right vertebral artery. This indicated that it was occluded during the waiting period at his previous doctor. On the day of his arrival at our hospital, the patient underwent a C5/6 posterior spinal fusion. Three months after surgery, he recovered to 46 points on the upper extremity ASIA motor score, and blood flow in the left vertebral artery was resumed. DISCUSSION: Early reduction and stabilization are necessary for cervical spine fracture dislocation; however, it is important not only for the prevention of the secondary injury but also for the reduction of the risk of vertebral artery occlusion.
  • Yukio Nakamura, Shingo Kikugawa, Shoji Seki, Masahiko Takahata, Norimasa Iwasaki, Hidetomi Terai, Mitsuhiro Matsubara, Fumio Fujioka, Hidehito Inagaki, Tatsuya Kobayashi, Tomoatsu Kimura, Hiroki Kurahashi, Hiroyuki Kato
    BMC Research Notes 8 (1) 228  1756-0500 2015/12/14 [Refereed][Not invited]
     
    Background: The VACTERL association is a typically sporadic, non-random collection of congenital anomalies that includes vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, renal anomalies, and limb abnormalities. Although several chromosomal aberrations and gene muta tions have been reported as disease-causative, these findings have been sparsely replicated to date. Case presentation: In the present study, whole exome sequencing of a case with the VACTERL association uncovered a novel frameshift mutation in the PCSK5 gene, which has been reported as one of the causative genes for the VACTERL association. Although this mutation appears potentially pathogenic in its functional aspects, it was also carried by the healthy father. Furthermore, a database survey revealed several other deleterious variants in the PCSK5 gene in the general population. Conclusions: Further studies are necessary to clarify the etiological role of the PCSK5 mutation in the VACTERL association.
  • Rikiya Baba, Tomohiro Onodera, Daisuke Momma, Masatake Matsuoka, Kazutoshi Hontani, Sameh Elmorsy, Kaori Endo, Masahiro Todoh, Shigeru Tadano, Norimasa Iwasaki
    TISSUE ENGINEERING PART C-METHODS 21 (12) 1263 - 1273 1937-3384 2015/12 [Refereed][Not invited]
     
    Cartilage injuries are a common health problem resulting in the loss of daily activities. Bone marrow stimulation technique, one of the surgical techniques for the cartilage injuries, is characterized by technical simplicity and less invasiveness. However, it has been shown to result in fibrous or fibrocartilaginous repair with inferior long-term results. This study focused on using ultrapurified alginate gel (UPAL gel) as an adjuvant scaffold in combination with a bone marrow stimulation technique. The objective of this study was to assess the efficacy of a bone marrow stimulation technique augmented by UPAL gel in a rabbit osteochondral defect model. To achieve this goal, three experimental groups were prepared as follows: defects without intervention, defects treated with a bone marrow stimulation technique, and defects treated with a bone marrow stimulation technique augmented by UPAL gel. The macroscopic and histological findings of the defects augmented by UPAL gel improved significantly more than those of the others at 16 weeks postoperatively. The combination technique elicited hyaline-like cartilage repair, unlike bone marrow stimulation technique alone. This combination procedure has the potential of improving clinical outcomes after use of a bone marrow stimulation technique for articular cartilage injuries.
  • Yukinori Tsukuda, Tomohiro Onodera, Masayuki Ito, Yasuharu Izumisawa, Yasuhiko Kasahara, Tatsuya Igarashi, Nobuo Ohzawa, Masahiro Todoh, Shigeru Tadano, Norimasa Iwasaki
    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 103 (11) 3441 - 3448 1549-3296 2015/11 [Refereed][Not invited]
     
    Objective: This study aimed to elucidate the therapeutic effects of intra-articular administration of ultra-purified low endotoxin alginate (UPLE-alginate) on osteoarthritis (OA) using a canine anterior cruciate ligament transection (ACLT) model. Design: We used 20 beagle dogs. ACLT was performed on the left knee of each dog and a sham operation was performed on the right knee as a control. All animals were randomly divided into the control (saline) and therapeutic (UPLE-alginate) groups. Animals in the control and therapeutic groups received weekly injections with 0.7 mL normal saline or 0.7 mL 0.5% UPLE-alginate, respectively, from 0 to 3 weeks after ACLT or sham operation. At 9 weeks after ACLT, the knee joints of all animals were observed using arthroscopy. All animals were euthanized at 14 weeks after ACLT and evaluated using morphologic assessment, histologic assessment, and biomechanical testing. Results: Arthroscopic findings showed intact cartilage surface in both groups. Morphologic findings in the therapeutic group showed milder degeneration compared with those of the control group, but there were no significant differences between groups. Histologic scores of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) were better in the therapeutic group than the control group (MFC: p=0.009, LFC: p=0.009). Joint lubrication did not differ significantly between groups. Conclusion: Intra-articular administration of UPLE-alginate in the early stage of OA slowed disease progression in canines. UPLE-alginate may have potential as a therapeutic agent for OA patients and reduce the number of patients who need to undergo total joint arthroplasty. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3441-3448, 2015.
  • Katsuhisa Yamada, Manabu Ito, Toshiyuki Akazawa, Masaru Murata, Toru Yamamoto, Norimasa Iwasaki
    EUROPEAN SPINE JOURNAL 24 (11) 2530 - 2537 0940-6719 2015/11 [Refereed][Not invited]
     
    To evaluate the osteoconductivity and the bonding strength of the newly developed interbody cage covered with the porous titanium sheet (porous Ti cage) to vertebral bodies in a sheep model. Twelve sheep underwent anterior lumbar interbody fusion at L2-3 and L4-5 using either the new porous Ti cages (Group-P) or conventional Ti cages with autogenous iliac bone (Group-C). The animals were euthanized at 2 or 4 months postoperatively and subjected to radiological, biomechanical, and histological examinations. Computed tomography analyses showed that the ratio of bone contact area in Group-P was significantly increased at 4 months compared with that at 2 months (p = 0.01). Although the ratio of bone contact area in Group-C was significantly higher than Group-P at 2 months (p < 0.001), there was no statistically significant difference between the two groups at 4 months. Biomechanical test showed that there was no significant difference in bonding strength between the two groups at either 2 or 4 months. Histological analyses revealed that the bone apposition ratio increased significantly with time in Group-P (p < 0.001). Although Group-C showed significantly higher bone apposition ratio than Group-P at 2 months (p = 0.001), there was no statistical difference between the two groups at 4 months. There was bone ingrowth into the porous Ti sheet, and bonding capacity of the porous Ti cage to the host bone increased with time. However, the speed of union to the bone with a porous Ti cage was marginally lower than a conventional cage along with an autogenous bone graft. Although it needs further experiment with a larger sample size, the results of the current study suggested that this material could achieve interbody fusion without the need for bone grafts.
  • Tomohiro Shimizu, Masahiko Takahata, Yusuke Kameda, Tsutomu Endo, Hiroki Hamann, Shigeto Hiratsuka, Masahiro Ota, Norimasa Iwasaki
    BONE 79 65 - 70 8756-3282 2015/10 [Refereed][Not invited]
     
    Osteoclastogenesis requires immunoreceptor tyrosine-based activation motif signaling. Multiple immuno-receptors associated with immunoreceptor tyrosine-based activation motif adaptor proteins, including DNAX-activating protein 12 kDa (DAP12) and Fc receptor common gamma (FcR gamma), have been identified in osteoclast lineage cells, and some are involved in arthritis-induced bone destruction. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption in association with DAP12. Whether Siglec-15 is involved in arthritis-induced bone lesions, however, remains unknown. Here we used a murine antigen-induced arthritis model to examine the role of Siglec-15 in the development of bone lesions induced by joint inflammation. Arthritis was unilaterally induced in the knee joints of 8-week-old female wild-type (WT) and Siglec-15(-/-) mice, and the contralateral knees were used as a control. The degree of joint inflammation, and cartilage and subchondral bone destruction in Siglec-15(-/-) mice was comparable to that in WT mice, indicating that Siglec-15 is not involved in the development of arthritis and concomitant cartilage and subchondral bone destruction. On the other hand, the degree of periarticular bone loss in the proximal tibia of the arthritic knee was significantly lower in Sig1ec-15(-/-) mice compared to WT mice. Although osteoclast formation in the metaphysis was enhanced in both WT and Siglec-15(-/-) mice after arthritis induction, mature multinucleated osteoclast formation was impaired in Siglec-15(-/-) mice, indicating impaired osteoclast bone resorptive function in the periarticular regions of the arthritic joint in Siglec-15(-/-) mice. Confirming this result, Siglec-15(-/-) primary unfractionated bone marrow cells harvested from arthritic femurs and tibiae failed to develop into mature multinuclear osteoclasts. Our findings suggest that Siglec-15 is a therapeutic target for periarticular bone loss, but not for joint destruction, in inflammatory arthritis, such as rheumatoid arthritis. (C) 2015 Elsevier Inc. All rights reserved.
  • Tsutomu Endo, Koyu Ito, Junko Morimoto, Masashi Kanayama, Daichi Ota, Masahiro Ikesue, Shigeyuki Kon, Daisuke Takahashi, Tomohiro Onodera, Norimasa Iwasaki, Toshimitsu Uede
    Arthritis & rheumatology (Hoboken, N.J.) 67 (9) 2512 - 22 2326-5191 2015/09 [Refereed][Not invited]
     
    OBJECTIVE: Syndecan 4 has been implicated as a critical mediator of inflammatory responses because of its functions as a coreceptor and reservoir for growth factors and chemokines. Although syndecan 4 is known to be expressed on B cells, its role in immune responses remains unclear. The purpose of this study was to investigate the contribution of syndecan 4 to the development of immune arthritis in murine models. METHODS: The clinical severity of 3 immunopathologically distinct models, collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and collagen antibody-induced arthritis (CAIA), was evaluated in wild-type (WT) mice and in syndecan 4-deficient (Sdc4(-/-) ) mice. Germinal center (GC) formation, B cell profiles, humoral immune responses, and B cell migration were analyzed during the course of CIA. RESULTS: Sdc4(-/-) mice were resistant to the induction of CIA, which is T cell and B cell dependent, but AIA and CAIA, which are T cell dependent and T cell independent, respectively, occurred with equal frequency in WT mice and Sdc4(-/-) mice. Furthermore, Sdc4(-/-) mice had reduced numbers of B cells and deficient GC formation in draining lymph nodes (DLNs) during the course of CIA, resulting in reduced production of collagen-specific autoantibodies. Compared with B cells from WT mice, B cells from Sdc4(-/-) mice showed reduced chemotactic migration toward stromal cell-derived factor 1 (SDF-1) and reduced SDF-1-mediated Akt phosphorylation. Consistent with these findings, in vivo transfer experiments showed that fewer Sdc4(-/-) B cells than WT B cells were found in and around the follicles in the DLNs. CONCLUSION: Our findings suggest that syndecan 4 contributes to the development of CIA by promoting GC formation and autoantibody production through its regulation of SDF-1-mediated B cell migration.
  • Reiji Yamamoto, Makoto Motomiya, Keisuke Sakurai, Hirotake Sekiguchi, Tadanao Funakoshi, Norimasa Iwasaki
    MICROSURGERY 35 (6) 489 - 493 0738-1085 2015/09 [Refereed][Not invited]
     
    Because of its anatomical location, the superficial radial nerve is vulnerable to trauma as well as injury during various surgical procedures. Once the nerve adheres to surrounding scar tissue, radiating pain often occurs due to nerve traction caused by loss of smooth gliding. Since it has been reported that the success rate with neurolysis only is lower, additional preventive procedures for recurrent neural readhesion are recommended. In the current report, we describe our experience performing neurolysis followed by nerve coverage using a free temporoparietal fascial flap for recurrent neural adhesion of the superficial radial nerve. A 45-year-old male complained of motion pain of the left wrist and thumb joints caused by recurrent neural adhesion of the superficial radial nerve after a chain saw trauma and following multiple reconstructive procedures. The radiating pain completely disappeared after neurolysis performed by a previous surgeon; however, it recurred 4 weeks later. Four months after the previous neurolysis the patient underwent external neurolysis and covering of the nerve with a free temporoparietal fascial flap to prevent neural readhesion because local soft tissue could not be used due to the massive scar tissues on the forearm. One year after the secondary neurolysis, the symptoms of radiating pain during wrist and thumb motion were drastically improved. A free adipofascial flap such as a temporoparietal flap may be an option for prevention of neural readhesion after neurolysis of the superficial radial nerve in cases where a local flap cannot be used on the forearm. (C) 2015 Wiley Periodicals, Inc.
  • Masatake Matsuoka, Tomohiro Onodera, Fumio Sasazawa, Daisuke Momma, Rikiya Baba, Kazutoshi Hontani, Norimasa Iwasaki
    TISSUE ENGINEERING PART C-METHODS 21 (8) 767 - 772 1937-3384 2015/08 [Refereed][Not invited]
     
    To analyze the genetic and biomolecular mechanisms underlying cartilage repair, an optimized mouse model of osteochondral repair is required. Although several models of articular cartilage injury in mice have recently been established, the articular surface in adult C57Bl/6 mice heals poorly. Since C57Bl/6 mice are the most popular strain of genetically manipulated mice, an articular cartilage repair model using C57Bl/6 mice would be helpful for analysis of the mechanisms of cartilage repair. The purpose of this study was to establish a cartilage repair model in C57Bl/6 mice using immature animals. To achieve this goal, full-thickness injuries were generated in 3-week-old (young), 4-week-old (juvenile), and 8-week-old (adult) C57Bl/6 mice. To investigate the reproducibility and consistency of full-thickness injuries, mice were sacrificed immediately after operation, and cartilage thickness at the patellar groove, depth of the cartilage injury, cross-sectional width, and cross-sectional area were compared among the three age groups. The depth of cartilage injury/cartilage thickness ratio (%depth) and the coefficient of variation (CV) for each parameter were also calculated. At 8 weeks postoperatively, articular cartilage repair was assessed using a histological scoring system. With respect to the reproducibility and consistency of full-thickness injuries, cartilage thickness, depth of cartilage injury, and cross-sectional area were significantly larger in young and juvenile mice than in adult mice, whereas cross-sectional width and %depth were almost equal among the three age groups. CVs of %depths were less than 10% in all groups. With respect to articular cartilage repair, young and juvenile mice showed superior results. In conclusion, we established a novel cartilage repair model in C57Bl/6 mice. This model will be valuable in achieving mechanistic insights into the healing process of the joint surface, as it will facilitate the use of genetically modified mice, which are most commonly developed on a C57Bl/6 background.
  • Masayuki Nakahara, Manabu Ito, Naoya Hattori, Keiichi Magota, Masahiko Takahata, Ken Nagahama, Hideki Sudo, Tamotsu Kamishima, Nagara Tamaki, Norimasa Iwasaki
    ACTA RADIOLOGICA 56 (7) 829 - 836 0284-1851 2015/07 [Refereed][Not invited]
     
    Background: Surgical debridement is often required to treat spinal infections. Successful surgery requires accurate localization of the active infections, however, current imaging technique still requires surgeons' experience to narrow the surgical fields to achieve less invasive procedures. Purpose: To investigate the use of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for successful surgical planning. Material and Methods: Nine patients with suspected spinal infection underwent magnetic resonance imaging (MRI) and FDG-PET/CT before surgery to locate active foci of infections. The spinal structures were divided into seven compartments at each intervertebral disc level for a total of 315 compartments investigated. The same classification system was used to design operating fields for histological correlation. Results: FDG-PET/CT diagnosed fewer compartments as active infection (34 compartments, 10.8%) than MRI (62 compartments, 19.7%, P = 0.002). Surgical exploration was performed in 49 compartments, and demonstrated active infection in 25 compartments. The sensitivity / specificity of FDG-PET/CT was 100% / 79%, respectively, which was superior to those of MRI, 76% / 42%. Foci of active infection showed hypermetabolic activity with a SUVmax of 7.1 +/- 2.6 (range, 3.0-12.7). Receiver operating characteristic (ROC) analysis indicated an optimal threshold for active spinal infection at a SUVmax of 4.2, corresponding to a sensitivity of 90.3% and specificity of 91.2%. Conclusion: FDG-PET/CT demonstrated limited areas of abnormality allowing accurate delineation, and is thus useful to narrow the surgical fields. Since overall diagnostic accuracy of FDG-PET/CT was superior to that of MRI, FDG-PET/CT is a useful technique to narrow the surgical field for successful less invasive surgery.
  • Tomohiro Onodera, Yasuhiko Kasahara, Toshiyuki Kasemura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki
    FOOT & ANKLE INTERNATIONAL 36 (7) 774 - 779 1071-1007 2015/07 [Refereed][Not invited]
     
    Background: Ultrasonography is among the valid methods to assess articular cartilage in the foot. This study aimed to evaluate the validity of ultrasonographic grading to assess metatarsal head articular cartilage for rheumatoid forefoot deformity in vivo and to compare the findings with in vitro ultrasonographic and histologic gradings. Methods: Participants were 15 patients scheduled to undergo resection arthroplasty of the metatarsal heads of the lesser toes because of rheumatoid arthritis of the metatarsophalangeal joints. Ultrasonographic examination was performed in vivo the day before surgery. Specimens of the second to fifth metatarsal heads taken intraoperatively were graded from in vitro ultrasonographic and histologic evaluations. Correlations among in vivo ultrasonographic, in vitro ultrasonographic, and histologic gradings were analyzed. Results: In 46 metatarsal heads, the distribution of grading ranged from grade 1 to 6 for in vivo ultrasonographic examinations and from grade 1 to 4 for histologic examinations. In vivo ultrasonographic grading showed significant correlation to both in vitro ultrasonographic grading (P < .001, R = 0.74) and histologic grading (P < .001, R = 0.67). Conclusions: The significant correlations between in vivo ultrasonographic and histologic gradings suggest that a semiquantitative in vivo ultrasonographic assessment of forefoot deformity in rheumatoid arthritis may be possible. Ultrasonographic grading may prove useful for pre- and postoperative evaluation of remaining joint function in rheumatoid forefoot deformity. An ultrasonographic grading system for remaining joint surfaces might be helpful in selecting surgical procedures such as joint-sparing osteotomy and metatarsal head resection. Level of Evidence: Level IV, case series.
  • Kei Kuroki, Hideki Sudo, Norimasa Iwasaki
    SPINE JOURNAL 15 (5) 1154 - 1155 1529-9430 2015/05 [Refereed][Not invited]
  • Hirotake Sekiguchi, Makoto Motomiya, Keisuke Sakurai, Dai Matsumoto, Tadanao Funakoshi, Norimasa Iwasaki
    MICROSURGERY 35 (2) 158 - 162 0738-1085 2015/02 [Refereed][Not invited]
     
    It is difficult for most plastic and orthopaedic surgeons to treat nerve dysfunction related to neural adhesion because the pathophysiology and suitable treatment have not been clarified. In the current report, we describe our experience of surgical treatment for adhesive ulnar neuropathy. A 58-year-old male complained of pain radiating to the ulnar nerve-innervated area during elbow and wrist motion caused by adhesive ulnar neuropathy after complex open trauma of the elbow joint. The patient obtained a good clinical outcome by surgical neurolysis of the ulnar nerve combined with a brachial artery perforator-based propeller flap to cover the soft tissue defect after resection of the scar tissue and to prevent readhesion of the ulnar nerve. This flap may be a useful option for ulnar nerve coverage after neurolysis without microvascular anastomosis in specific cases. (c) 2014 Wiley Periodicals, Inc. Microsurgery 35:158-162, 2015.
  • Yusuke Kameda, Masahiko Takahata, Shintaro Mikuni, Tomohiro Shimizu, Hiroki Hamano, Takashi Angata, Shigetsugu Hatakeyama, Masataka Kinjo, Norimasa Iwasaki
    BONE 71 217 - 226 8756-3282 2015/02 [Refereed][Not invited]
     
    Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption in association with an immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein, DNAX-activating protein 12 kDa (DAP12). Although Siglec-15 has an important role in physiologic bone remodeling by modulating RANKL signaling, it is unclear whether it is involved in pathologic bone loss in which multiple osteoclastogenic factors participate in excessive osteoclastogenesis. Here we demonstrated that Siglec-15 is involved in estrogen deficiency-induced bone loss. WT and Siglec-15(-/-) mice were ovariectomized (Ovx) or sham-operated at 14 wk of age and their skeletal phenotype was evaluated at 18 and 22 wk of age. Siglec-15(-/-) mice showed resistance to estrogen deficiency-induced bone loss compared to WT mice. Although the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts increased after ovariectomy in both WT and Siglec-15(-/-) mice, the increase was lower in Siglec-15(-/-) mice than in WT mice. Importantly, osteoclasts in Siglec-15(-/-) mice were small and failed to spread on the bone surface, indicating impaired osteoclast differentiation. Because upregulated production of TNF-alpha as well as RANKL is mainly responsible for estrogen deficiency-induced development of osteoclasts, we examined whether Siglec-15 deficiency affects TNF-alpha-induced osteoclastogenesis in vitro. The TNF-alpha mediated induction of TRAP-positive multinucleated cells was impaired in Siglec-15(-/-) cells, suggesting that Siglec-15 is involved in TNF-alpha induced osteoclastogenesis. We also confirmed that signaling through osteoclast-associated receptor/Fc receptor common gamma chain, which is an alternative ITAM adaptor to DAP12, rescues multinucleation but not cytoskeletal organization of TNF-alpha and RANKL-induced Siglec-15(-/-) osteoclasts, indicating that the Siglec-15/DAP12 pathway is especially important for cytoskeletal organization of osteoclasts in both RANKL and TNF-alpha induced osteoclastogenesis. The present findings indicate that Siglec-15 is involved in estrogen deficiency-induced differentiation of osteoclasts and is thus a potential therapeutic target for postmenopausal osteoporosis. (C) 2014 Elsevier Inc. All rights reserved.
  • Motomiya M, Tazaki Y, Iwasaki N
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 20 (2) 325 - 329 0218-8104 2015 [Refereed][Not invited]
  • Takuya Konno, Tomohiro Onodera, Yusuke Nishio, Yasuhiko Kasahara, Norimasa Iwasaki, Tokifumi Majima
    JOURNAL OF ARTHROPLASTY 29 (12) 2305 - 2308 0883-5403 2014/12 [Refereed][Not invited]
     
    The aim of this study is to evaluate the relationship between patellofemoral contact stress and intraoperative knee kinematic patterns after mobile bearing total knee arthroplasty (TKA). Medial osteoarthritic knees of forty-six posterior-stabilized total knee prostheses were evaluated using a computed tomography-guided navigation system. Subjects were divided into two groups based on intraoperative knee kinematic patterns: the medial pivot group (n = 19) and the non-medial pivot group (n = 27). Mean intraoperative patellofemoral contact stress was significantly lower in the medial pivot group than in the non-medial pivot group (1.7 MPa vs. 3.2 MPa, P < 0.05). An intraoperative medial pivot pattern results in reduced patello-femoral contact stress. (C) 2014 Elsevier Inc. All rights reserved.
  • Daisuke Kawamura, Tadanao Funakoshi, Shuji Mizumoto, Kazuyuki Sugahara, Norimasa Iwasaki
    JOURNAL OF ORTHOPAEDIC SCIENCE 19 (6) 1028 - 1035 0949-2658 2014/11 [Refereed][Not invited]
     
    Background Chondroitin sulfate (CS) has been used in cartilage tissue engineering techniques as a positive modulator of scaffolds. CS is a linear polysaccharide consisting of variously sulfated repeating disaccharides. The sulfation patterns of CS are closely related to their biological functions, but only monosulfated CS has been applied to scaffolds. In this study, we investigated the effects of various sulfation patterns of CS on chondrogenic differentiation using ATDC5 chondroprogenitor cells. Methods Disaccharide composition analysis of CS produced by ATDC5 cells at various differentiation steps was performed using high-performance liquid chromatography. ATDC5 cells were cultured with exogenously added, variously sulfated CS. Cell proliferation was analyzed by the 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt (WST-8) assay. Extracellular matrix production was evaluated by Alcian blue staining. Alkaline phosphatase (ALP) activity was evaluated using an ALP assay kit. Expression of chondrogenic markers was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) or an enzyme-linked immunosorbent assay (ELISA) using a Type II Collagen Detection kit. Results The major components of CS produced by ATDC5 cells were 4-O-monosulfated disaccharides throughout chondrogenic differentiation. Low proportions of 4,6-O-disulfated disaccharides were also detected. Compared to the control group, which did not contain GAGs, the WST-8 assay indicated fewer viable cells when treated with CS-E, which are rich in 4,6-O-disulfated disaccharides. CS-E significantly enhanced Alcian blue staining in a dose-dependent manner and decreased ALP activity after 21 days of culture. Real-time RT-PCR showed that CS-E significantly enhanced all chondrogenic markers, col2a1, aggrecan, and sox9, either at day 4 or day 14 of culture. The results of ELISA analysis confirmed that CS-E significantly enhanced the production of type II collagen. Conclusions ATDC5 cells produced four different monosulfated or disulfated disaccharides in their extracellular matrices. The sulfation patterns of exogenously added CS affected chondrogenic differentiation of ATDC5 cells. In particular, CS-E rich in disulfated disaccharides significantly promoted chondrogenic differentiation of ATDC5 cells. Thus, CS containing this disulfated structure may be a useful scaffold component for enhancing chondrogenesis in cartilage tissue engineering.
  • Michiyo Terashima, Maho Amano, Tomohiro Onodera, Shin-Ichiro Nishimura, Norimasa Iwasaki
    STEM CELL RESEARCH 13 (3) 454 - 464 1873-5061 2014/11 [Refereed][Not invited]
     
    Alterations in the structure of cell surface glycoforms occurring during the stages of stem cell differentiation remain unclear. We describe a rapid glycoblotting-based cellular glycomics method for quantitatively evaluating changes in glycoform expression and structure during neuronal differentiation of murine induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs). Our results show that changes in the expression of cellular N-glycans are comparable during the differentiation of iPSCs and ESCs. The expression of bisect-type N-glycans was significantly up-regulated in neurons that differentiated from both iPSCs and ESCs. From a glycobiological standpoint, iPSCs are an alternative neural cell source in addition to ESCs. (C) 2014 The Authors. Published by Elsevier B.V.
  • Kinya Ishizaka, Mutsumi Nishida, Makoto Motomiya, Megumi Satoh, Mamiko Inoue, Yusuke Kudoh, Satomi Omotehara, Tatsunori Horie, Tadanao Funakoshi, Norimasa Iwasaki
    JOURNAL OF MEDICAL ULTRASONICS 41 (4) 481 - 486 1346-4523 2014/10 [Refereed][Not invited]
     
    Purpose The purpose of the study was to validate the reliability of quantitative intraneural enhancement patterns by using contrast-enhanced ultrasonography (CEUS). Methods Nine asymptomatic wrists underwent a total of three CEUS examinations each conducted at 1-month intervals. The CEUS enhancement pattern of median nerves was quantitatively evaluated. The area under the time-intensity curve was calculated by placing the regions of interest at the proximal, center, and distal regions of the median nerve. An intra-class correlation coefficient for intra-observer, inter-observer, and inter-examination reproducibility was calculated. Results The intra- and inter-observer reproducibility was almost perfect. Inter-examination reproducibility of the proximal, center, and distal regions was 0.891, 0.614, and 0.535, respectively. In this study, we found that the reproducibility of the distal and center regions of the median nerve in the carpal tunnel was lower than that of the proximal region. Conclusion High intra-observer, inter-observer, and inter-examination reproducibility of CEUS was obtained in the evaluation of the intraneural enhancement pattern when the region of interest was placed in the proximal region of the median nerve.
  • Koji Iwasaki, Hideki Sudo, Katsuhisa Yamada, Hideaki Higashi, Takashi Ohnishi, Takeru Tsujimoto, Norimasa Iwasaki
    PLOS ONE 9 (10) e109851  1932-6203 2014/10 [Refereed][Not invited]
     
    Background: Analgesic discography (discoblock) can be used to diagnose or treat discogenic low back pain by injecting a small amount of local anesthetics. However, recent in vitro studies have revealed cytotoxic effects of local anesthetics on intervertebral disc (IVD) cells. Here we aimed to investigate the deteriorative effects of lidocaine and bupivacaine on rabbit IVDs using an organotypic culture model and an in vivo long-term follow-up model. Methods: For the organotypic culture model, rabbit IVDs were harvested and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine or 0.5% bupivacaine). Nucleus pulposus (NP) cell death was measured using confocal microscopy. Histological and TUNEL assays were performed. For in vivo study, each local anesthetic was injected into rabbit lumbar IVDs under a fluoroscope. Six or 12 months after the injection, each IVD was prepared for magnetic resonance imaging (MRI) and histological analysis. Results: In the organotypic culture model, both anesthetic agents induced time-dependent NP cell death; when compared with injected saline solution, significant effects were detected within 7 days. Compared with the saline group, TUNEL-positive NP cells were significantly increased in the bupivacaine group. In the in vivo study, MRI analysis did not show any significant difference. Histological analysis revealed that IVD degeneration occurred to a significantly level in the saline-and local anesthetics-injected groups compared with the untreated control or puncture-only groups. However, there was no significant difference between the saline and anesthetic agents groups. Conclusions/Significance: In the in vivo model using healthy IVDs, there was no strong evidence to suggest that discoblock with local anesthetics has the potential of inducing IVD degeneration other than the initial mechanical damage of the pressurized injection. Further studies should be performed to investigate the deteriorative effects of the local injection of analgesic agents on degenerated IVDs.
  • Yusuke Minami, Shinji Kohsaka, Masumi Tsuda, Kazuhiro Yachi, Nobuaki Hatori, Mishie Tanino, Taichi Kimura, Hiroshi Nishihara, Akio Minami, Norimasa Iwasaki, Shinya Tanaka
    CANCER SCIENCE 105 (9) 1152 - 1159 1347-9032 2014/09 [Refereed][Not invited]
     
    MicroRNA (miRNA) can function as tumor suppressors or oncogenes, and also as potential specific cancer biomarkers; however, there are few published studies on miRNA in synovial sarcomas, and their function remains unclear. We transfected the OncomiR miRNA Precursor Virus Library into synovial sarcoma Fuji cells followed by a colony formation assay to identify miRNAs to confer an aggressive tumorigenicity, and identified miR-17-5p from the large colonies. MiR-17 was found to be induced by a chimeric oncoprotein SS18-SSX specific for synovial sarcoma, and all examined cases of human synovial sarcoma expressed miR-17, even at high levels in several cases. Overexpression of miR-17 in synovial sarcoma cells, Fuji and HS-SYII, increased colony forming ability in addition to cell growth, but not cell motility and invasion. Tumor volume formed in mice in vivo was significantly increased by miR-17 overexpression with a marked increase of MIB-1 index. According to PicTar and Miranda algorithms, which predicted CDKN1A (p21) as a putative target of miR-17, a luciferase assay was performed and revealed that miR-17 directly targets the 3-UTR of p21 mRNA. Indeed, p21 protein level was remarkably decreased by miR-17 overexpression in a p53-independent manner. It is noteworthy that miR-17 succeeded in suppressing doxorubicin-evoked higher expression of p21 and conferred the drug resistance. Meanwhile, introduction of anti-miR-17 in Fuji and HS-SYII cells significantly decreased cell growth, consistent with rescued expression of p21. Taken together, miR-17 promotes the tumor growth of synovial sarcomas by post-transcriptional suppression of p21, which may be amenable to innovative therapeutic targeting in synovial sarcoma.
  • Norimasa Iwasaki
    JOURNAL OF ORTHOPAEDIC SCIENCE 19 (5) 699 - 706 0949-2658 2014/09 [Refereed][Not invited]
  • Tomohiro Shimizu, Masahiko Takahata, Yusuke Kameda, Hiroki Hamano, Teppei Ito, Hiromi Kimura-Suda, Masahiro Todoh, Shigeru Tadano, Norimasa Iwasaki
    BONE 64 95 - 101 8756-3282 2014/07 [Refereed][Not invited]
     
    Teriparatide (PTH1-34) promotes skeletal repair and increases bone mass. Vitamin K is involved in bone mineralization as a coenzyme of gamma-carboxylase for Gla proteins, and therefore vitamin K insufficiency caused by malnutrition or therapeutic intake of the vitamin K antagonist warfarin could affect the efficacy of PTH1-34 therapy for bone repair. In the present study, we investigated whether vitamin K influences the efficacy of PTH1-34 therapy for bone repair in a rat osteotomy model. Female 12-week-old Sprague-Dawley rats were subjected to a closed midshaft osteotomy of the femur and randomized into four groups (n = 10 per group): vehicle, PTH1-34 (daily 30 mu g/kg/day subcutaneous injection) + solvent (orally, three times a week), PTh1-34 + warfarin (0.4 mg/kg/day orally, three times a week), and PTH1-34 + vitamin K-2 (menatetrenone, 30 mg/kg/day orally, three times a week). Serum gamma-carboxylated and uncarboxylated osteocalcin (Gla-OC and Glu-OC) levels and radiographic healing were monitored every 2 weeks. Skeletal repair was assessed by micro-computed tomography, mechanical testing, and histology at 8 weeks after surgery. PTH1-34 amplified the osteotomy-induced increase in Gla-OC and improved the mechanical properties as well as the volumetric bone mineral tissue density of the fracture callus. Concurrent use of warfarin decreased the response to PTH1-34 therapy in terms of mechanical recovery, probably by impairing mineralization due to the lack of Gla-OC. Although the effects of combination therapy with PTH1-34 and vitamin K-2 on bone repair did not significantly exceed those of PTH1-34 monotherapy in rats fed sufficient dietary vitamin K, postoperative Gla-OC levels were correlated with the mechanical properties of the osteotomized femur in PTH1-34-treated rats regardless of the use of warfarin or vitamin K-2. These findings suggest the importance of vitamin K dependent gamma-carboxylation of DC for realizing the full effects of PTH1-34 on skeletal repair. (C) 2014 Elsevier Inc. All rights reserved.
  • Hideki Sudo, Manabu Ito, Yuichiro Abe, Kuniyoshi Abumi, Masahiko Takahata, Ken Nagahama, Shigeto Hiratsuka, Kei Kuroki, Norimasa Iwasaki
    SPINE 39 (14) 1163 - 1169 0362-2436 2014/06 [Refereed][Not invited]
     
    Study Design. Retrospective analysis of a prospectively collected, consecutive, nonrandomized series of patients. Objective. To assess the surgical outcomes of the simultaneous double-rod rotation technique for treating Lenke 1 thoracic adolescent idiopathic scoliosis (AIS). Summary of Background Data. With the increasing popularity of segmental pedicle screw spinal reconstruction for treating AIS, concerns regarding the limited ability to correct hypokyphosis have also increased. Methods. A consecutive series of 32 patients with Lenke 1 main thoracic AIS treated with the simultaneous double-rod rotation technique at our institution was included. Outcome measures included patient demographics, radiographical measurements, and Scoliosis Research Society questionnaire scores. Results. All 32 patients were followed up for a minimum of 2 years (average, 3.6 yr). The average main thoracic Cobb angle correction rate and the correction loss at the final follow-up were 67.8% and 3.3 degrees, respectively. The average preoperative thoracic kyphosis (T5-T12) was 11.9, which improved significantly to 20.5 degrees (P < 0.0001) at the final follow-up. An increase in thoracic kyphosis was significantly correlated with an increase in lumbar lordosis at the final follow-up (r = 0.42). The average preoperative vertebral rotation angle was 19.7 degrees, which improved significantly after surgery to 14.9 degrees (P = 0.0001). There was no correlation between change in thoracic kyphosis and change in apical vertebral rotation (r = - 0.123). The average preoperative total Scoliosis Research Society questionnaire score was 3.0, which significantly improved to 4.4 (P < 0.0001) at the final follow-up. Throughout surgery and even after, there were no instrumentation failures, pseudarthrosis, infection of the surgical site, or clinically relevant neurovascular complications. Conclusion. The simultaneous double-rod rotation technique for treating Lenke 1 AIS provides significant sagittal correction of the main thoracic curve while maintaining sagittal profiles and correcting coronal and axial deformities.
  • Yusuke Nishio, Tomohiro Onodera, Yasuhiko Kasahara, Daisuke Takahashi, Norimasa Iwasaki, Tokifumi Majima
    JOURNAL OF ARTHROPLASTY 29 (4) 702 - 706 0883-5403 2014/04 [Refereed][Not invited]
     
    The aim of this study was to evaluate the relationship between clinical results including patient-reported outcomes and intraoperative knee kinematic patterns after total knee arthroplasty (TKA). A cross-sectional survey of forty consecutive medial osteoarthritis patients who had a primary TKA using a CT-based navigation system was conducted. Subjects were divided into two groups based on intraoperative kinematic patterns: a medial pivot group (n = 20) and a non-medial pivot group (n = 20). Subjective outcomes with the new Knee Society Score and clinical outcomes were evaluated. The functional activities, patient satisfaction and the knee flexion angle of the medial pivot group were significantly better than those of the non-medial pivot group. An intraoperative medial pivot pattern positively influences deep knee flexion and patient-reported outcomes. (C) 2014 Elsevier Inc. All rights reserved.
  • Yuichiro Matsui, Tadanao Funakoshi, Makoto Motomiya, Atsushi Urita, Michio Minami, Norimasa Iwasaki
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 39 (4) 679 - 685 0363-5023 2014/04 [Refereed][Not invited]
     
    Purpose To clarify long-term clinical and radiological results more than 10 years after radial shortening osteotomy for Kienbock disease. Methods Eleven wrists of 10 patients that had been classified as Lichtman stages 3A (2 wrists), 3B (8 wrists), and 4 (1 wrist) underwent radial shortening for Kienbock disease. The mean follow-up period was 14.3 years (range, 10-21 y). Clinical outcomes were quantified using the Japanese version of the Disabilities of the Arm, Shoulder, and Hand questionnaire and the modified Mayo wrist score. Radiographic and magnetic resonance imaging studies were performed for 9 of the 10 patients preoperatively, and all 10 patients at follow-up. Results At follow-up, 6 wrists were asymptomatic and the remaining 5 had mild occasional pain. The mean range of extension and grip strength significantly improved. The mean modified Mayo wrist score and Disabilities of the Ann, Shoulder, and Hand scores were 92 (range, 80-100) and 5 (range, 0-18), respectively. At follow-up, no progression of the Lichtman stage was found in any patient. There was no significant progressive Innate collapse in any patient. The magnetic resonance imaging in 7 wrists showed increased signal intensity of the lunate; the remaining 3 wrists had no alteration in signal intensity of the bone. Conclusions Our study demonstrated satisfactory clinical results after 10 or more years in patients who underwent radial shortening for Kienbock disease. Although we found no improvement in signal intensity of the lunate in 3 wrists, unloading of the diseased lunate after radial shortening gives long-lasting symptom relief and may prevent lunate collapse. (Copyright (C) 2014 by the American Society for Surgery of the Hand. All rights reserved.)
  • Tsuyoshi Asano, Norimasa Iwasaki, Shigeyuki Kon, Masashi Kanayama, Junko Morimoto, Akio Minami, Toshimitsu Uede
    RHEUMATOLOGY 53 (3) 415 - 424 1462-0324 2014/03 [Refereed][Not invited]
     
    Objective. The role of the joint tissue microenvironment in the pathogenesis of human RA has recently attracted much attention. The present study investigated the roles of alpha 9 beta 1 integrin and its ligands in synovial specimens of human RA patients in generating the unique human arthritic tissue microenvironment. Methods. Synovial fibroblasts and macrophages were isolated from the synovial tissue of patients with RA or OA. The expression of alpha 9 beta 1 integrin was analysed using FACS with multicolour staining. The production of MMPs and proinflammatory cytokines was analysed in cultures of synovial fibroblasts and macrophages with alpha 9 beta 1 integrin ligands. Results. Synovial fibroblasts and macrophages derived from arthritic joints spontaneously secreted tenascin-C and osteopontin. Synovial fibroblasts and macrophages obtained from patients with RA expressed alpha 9 beta 1 integrins, a common receptor for osteopontin and tenascin-C. In the synovial fibroblasts of RA, the amount of tenascin-C protein produced was much greater than that of osteopontin in synovial fibroblasts of RA. Importantly, autocrine and paracrine interactions of alpha 9 beta 1 integrin and tenascin-C induced the expression of MMPs and IL-6 in synovial fibroblasts, as well as TNF-alpha and IL-1 beta in synovial macrophages. Conclusion. These findings indicate that autocrine and paracrine interaction of alpha 9 beta 1integrin and tenascin-C in the joint tissue microenvironment contributes to the pathogenesis of RA. Therefore alpha 9 beta 1 integrin may become a potential therapeutic target for RA.
  • Katsuhisa Yamada, Hideki Sudo, Koji Iwasaki, Naoki Sasaki, Hideaki Higashi, Yusuke Kameda, Manabu Ito, Masahiko Takahata, Kuniyoshi Abumi, Akio Minami, Norimasa Iwasaki
    AMERICAN JOURNAL OF PATHOLOGY 184 (3) 753 - 764 0002-9440 2014/03 [Refereed][Not invited]
     
    Intervertebral disk (IVD) degeneration causes debilitating low back pain in much of the worldwide population. No efficient treatment exists because of an unclear pathogenesis. One characteristic event early in such degeneration is the apoptosis of nucleus pulposus (NP) cells embedded in IVDs. Excessive biomechanical loading may also be a major etiology of IVD degeneration. The present study used in vitro and in vivo models of compressive loading to elucidate the underlying mechanism of IVD degeneration. In addition, we investigated whether the inhibition of apoptosis is a potential clinical therapeutic strategy for the treatment of IVD degeneration induced by biomechanicaL stress. A TUNEL assay showed that NP cell agarose three-dimensional composite cultures subjected to uniaxiaL, unconfined, static, compressive loading exhibited a time-dependent increase in apoptosis. Western blot analysis revealed the upregulation of several extracellular matrix-degrading enzymes and down-regulation of tissue inhibitor of metaLloproteinase 1. These responses to compressive loading were all significantly inhibited by caspase 3 siRNA. In the in vivo model of compressive Loading-induced IVD degeneration, a single Localinjection of caspase 3 siRNA significantly inhibited IVD degeneration by magnetic resonance imaging, histological findings, IHC, and TUNEL assay. The present study suggests that caspase 3 siRNA attenuates overload-induced IVD degeneration by inhibiting NP cell apoptosis and the expression of matrix-degrading enzymes.
  • Koji Iwasaki, Hideki Sudo, Katsuhisa Yamada, Manabu Ito, Norimasa Iwasaki
    PLOS ONE 9 (3) e92442  1932-6203 2014/03 [Refereed][Not invited]
     
    Background: Discography and discoblock are imaging procedures used to diagnose discogenic low back pain. Although needle puncture of the intervertebral disc (IVD) itself induces disc degeneration, the agents used in these procedures may also have harmful effects on IVD cells. The purpose of this study was to analyze whether radiocontrast agents and local anesthetic agents have detrimental effects on human nucleus pulposus (NP) cells. Methods: Healthy human NP cells were cultured for 7 days in three-dimensional (3D) cell-alginate bead composites, and were then exposed to clinically relevant doses of a radiocontrast agent (iotrolan) or local anesthetic (lidocaine or bupivacaine). Cell viability and apoptosis were measured by confocal microscopy and flow cytometry. On the basis of caspase expression profiles, the apoptotic pathways activated by the agents were identified by Western blot analysis. Results: The radiocontrast agent iotrolan did not affect NP cell viability or induce apoptosis. In contrast, both the anesthetic agents significantly decreased cell viability and increased the apoptotic cell number in a time-and dose-dependent manner. After 120 min, 2% lidocaine and 0.5% bupivacaine decreased percent live cells to 13% and 10%, respectively (p<0.05). The number of apoptotic cells was doubled by increasing lidocaine dosage from 1% to 2% (23% and 42%) and bupivacaine from 0.25% to 0.50% (25% and 48%) (p<0.05). Western blot analysis revealed that both anesthetic agents upregulated cleaved caspase-3 and caspase-8, whereas only bupivacaine upregulated cleaved caspase-9. Conclusions/Significance: The present study demonstrates that iotrolan does not affect the viability of healthy human NP cells. In contrast, the two anesthetic agents commonly used in discography or discoblock may cause extensive damage to IVDs by inducing apoptotic cell death.
  • Takuji Miyazaki, Hideki Sudo, Shigeto Hiratsuka, Norimasa Iwasaki
    SPINE JOURNAL 14 (2) 381 - 382 1529-9430 2014/02 [Refereed][Not invited]
  • Ishihara T, Kakiya K, Takahashi K, Miwa H, Rokushima M, Yoshinaga T, Tanaka Y, Ito T, Togame H, Takemoto H, Amano M, Iwasaki N, Minami A, Nishimura S
    Biochimica et biophysica acta 1840 (1) 645 - 655 0006-3002 2014/01 [Refereed][Not invited]
  • Matsubara S, Motomiya M, Iwasaki N
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 19 (1) 119 - 122 0218-8104 2014 [Refereed][Not invited]
  • Yusuke Kameda, Masahiko Takahata, Miki Komatsu, Shintaro Mikuni, Shigetsugu Hatakeyama, Tomohiro Shimizu, Takashi Angata, Masataka Kinjo, Akio Minami, Norimasa Iwasaki
    JOURNAL OF BONE AND MINERAL RESEARCH 28 (12) 2463 - 2475 0884-0431 2013/12 [Refereed][Not invited]
     
    Siglecs are a family of sialic acid-binding immunoglobulin-like lectins that regulate the functions of cells in the innate and adaptive immune systems through glycan recognition. Here we show that Siglec-15 regulates osteoclast development and bone resorption by modulating receptor activator of nuclear factor B ligand (RANKL) signaling in association with DNAX-activating protein 12kDa (DAP12), an adaptor protein bearing an immunoreceptor tyrosine-based activation motif (ITAM). Among the known Siglecs expressed in myeloid lineage cells, only Siglec-15 was upregulated by RANKL in mouse primary bone marrow macrophages. Siglec-15-deficient mice exhibit mild osteopetrosis resulting from impaired osteoclast development. Consistently, cells lacking Siglec-15 exhibit defective osteoclast development and resorptive activity in vitro. RANKL-induced activation of phosphatidylinositol 3-kinase (PI3K)/Akt and Erk pathways were impaired in Siglec-15-deficient cells. Retroviral transduction of Siglec-15-null osteoclast precursors with wild-type Siglec-15 or mutant Siglec-15 revealed that the association of Siglec-15 with DAP12 is involved in the downstream signal transduction of RANK. Furthermore, we found that the ability of osteoclast formation is preserved in the region adjacent to the growth plate in Siglec-15-deficient mice, indicating that there is a compensatory mechanism for Siglec-15-mediated osteoclastogenesis in the primary spongiosa. To clarify the mechanism of this compensation, we examined whether osteoclast-associated receptor (OSCAR)/Fc receptor common (FcR) signaling, an alternative ITAM-mediated signaling pathway to DAP12, rescues impaired osteoclastogenesis in Siglec-15-deficient cells. The ligands in type II collagen activate OSCAR and rescue impaired osteoclastogenesis in Siglec-15-deficient cells when cultured on bone slices, indicating that Siglec-15-mediated signaling can be compensated for by signaling activated by type II collagen and other bone matrix components in the primary spongiosa. Our findings indicate that Siglec-15 plays an important role in physiologic bone remodeling by modulating RANKL signaling, especially in the secondary spongiosa. (c) 2013 American Society for Bone and Mineral Research.
  • Hideki Sudo, Manabu Ito, Kiyoshi Kaneda, Kuniyoshi Abumi, Yoshihisa Kotani, Ken Nagahama, Akio Minami, Norimasa Iwasaki
    Spine Journal 13 (12) 1726 - 1732 1529-9430 2013/12/01 [Refereed][Not invited]
     
    Background context With the increase of the elderly population, osteoporotic vertebral fractures have been frequently reported. Surgical intervention is usually recommended in osteoporotic vertebral collapse with neurologic deficits. However, very few reports on surgical interventions exist. Purpose To compare surgical results of anterior and posterior procedures for treating osteoporotic thoracolumbar vertebral collapse with sustained neurologic deficits. Study design Retrospective comparative study. Patient sample Fifty patients who sustained osteoporotic thoracolumbar vertebral collapse with neurologic deficits were treated either by anterior decompression and strut graft (n=32) or by posterior decompression and pedicle screw fixation with vertebroplasty (n=18). Outcome measures Incidence of complications, sagittal Cobb angle, spinal canal encroachment, and Japanese Orthopedic Association score. Methods The authors retrospectively reviewed the results of a consecutive series of patients undergoing anterior decompression and strut graft or posterior decompression and pedicle screw fixation with vertebroplasty for osteoporotic thoracolumbar vertebral collapse with neurologic deficits. Operative notes, clinical charts, and radiographs were analyzed. Results Operative time was similar between the groups, but intraoperative blood loss was significantly lower in the posterior group. All patients showed neurologic recovery. No significant difference was observed in the neurologic improvement, kyphosis correction angle, and loss of correction. Perioperative respiratory complications were found in 11 patients (34%) in the anterior group. In the anterior group, early posterior reinforcement was required in patients with very low bone density below 0.60 g/cm2 and/or in those with three segments of instrumentation for two vertebral collapses. Posterior group patients did not undergo additional surgery. Conclusions Anterior reconstruction for osteoporotic vertebral collapse is significant because anterior elements, particularly those at the thoracolumbar junction, play a major role in load bearing. However, difficulties arise when anterior reconstruction is performed in cases with very low bone density and in those with multiple vertebral collapse.
  • Makoto Motomiya, Norimasa Iwasaki, Akio Minami, Yuichiro Matsui, Atsushi Urita, Tadanao Funakoshi
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 38A (8) 1484 - 1491 0363-5023 2013/08 [Refereed][Not invited]
     
    Purpose To evaluate the clinical and radiological results of radiolunate (RL) arthrodesis for rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs and/or biologicals with an average of 7 years of follow-up. In addition, we compared the results in advanced stages with those in less advanced stages in patients with comparatively low disease activity of RA. Methods This study included RL arthrodesis for 22 wrists in 19 patients with comparatively low disease activity of RA. The mean follow-up period was 7 years (range, 2-16 y). Fourteen wrists with Larsen classification grade III and 8 wrists with grade IV were included in this study. The range of motion was calculated, and clinical scores were graded using the Mayo wrist score and the Stanley classification. The carpal height ratio (CHR) and ulnar translation (UT) were determined from the radiographs. Results All wrists achieved radiographic fusion. Clinical scores were markedly improved, although there was a decrease in flexion. The Larsen grade did not deteriorate during follow-up. CHR and UT improved immediately after operation and remained good through the final follow-up. Although the flexion/extension range of motion of the grade IV wrists was smaller than that of the grade In wrists at follow-up, both groups obtained good clinical results. Conclusions Our results for RL arthrodesis were clinically and radiologically better than those of previous reports. Control of the disease activity of RA could theoretically be a factor in obtaining good long-term clinical and radiographic outcomes. RL arthrodesis is our recommended procedure for the RA wrist even in the advanced stage. (Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.)
  • Atsushi Urita, Norimasa Iwasaki, Makoto Kondo, Yasuhiko Nishio, Tamotsu Kamishima, Akio Minami
    Journal of Hand Surgery 38 (3) 498 - 503 0363-5023 2013/03 [Refereed][Not invited]
     
    Purpose: To test the hypothesis that low-intensity pulsed ultrasound (LIPUS) may accelerate healing at osteotomy sites after forearm bone shortening osteotomies. Methods: In this prospective study, we enrolled 27 patients who underwent ulnar shortening osteotomy for ulnar impaction syndrome or radial shortening osteotomy for Kienböck disease. We randomized limbs to be treated with LIPUS (14 osteotomies, LIPUS group) or without LIPUS (13 osteotomies, control group). At 1 week postoperatively, patients in the LIPUS group received once-daily 20-minute LIPUS treatments that continued until at least 12 weeks postoperatively. At 2, 4, 6, 8, 12, 16, and 24 weeks postoperatively, we assessed union of the osteotomy site to determine the time to union using 4 projections of x-rays. Results: In this study, all osteotomies achieved complete union. The mean times to complete cortical union were 57 days in the LIPUS group and 76 days in the control group. Regarding endosteal union, the mean times were 121 days in the LIPUS group and 148 days in the control group. The LIPUS group had significantly reduced times for both types of union. Conclusions: Application of LIPUS shortened the time to cortical union by 27%, and to endosteal union by 18%. Our results indicate that LIPUS accelerated bone healing after we performed forearm bone shortening osteotomies. This may provide earlier return to activity and work for patients undergoing forearm osteotomies. Type of study/level of evidence: Therapeutic I. © 2013 American Society for Surgery of the Hand.
  • Katsuhisa Yamada, Naoki Suenaga, Norimasa Iwasaki, Naomi Oizumi, Akio Minami, Tadanao Funakoshi
    JOURNAL OF PEDIATRIC ORTHOPAEDICS 33 (2) 205 - 211 0271-6798 2013/03 [Refereed][Not invited]
     
    Background: The clinical results of surgical procedures for severe Sprengel deformity have been uncertain. To obtain improved elevation, we consider that it is necessary to realign the lateral border of the scapula for upward rotation. The purposes of the current study were to evaluate the clinical results and range of motion of the scapula after such realignment. Methods: Seven cases of Sprengel deformity of Cavendish grade 3 or 4 were treated surgically and then clinically evaluated and examined using 3-dimensional computed tomography (3D CT). (Two boys and 5 girls aged 50.9 +/- 15.4mo, mean +/- SD at the time of operation.) The mean follow-up was 53.1 months (range, 12 to 92mo). After the omovertebral bone and the superomedial side of the scapula were removed, the levator scapulae and rhomboids were reattached to wrap around the scapula at maximum upward rotation to assist in maintaining this position. Cavendish and Rigault grades were used for evaluation of postoperative appearance. The superior displacement and rotation of the scapula were measured on the trunk posterior view using 3D CT. The relationship between improvement in the range of motion and radiologic change were analyzed statistically. Results: The postoperative flexion (97.9 +/- 12.9 to 160 +/- 11.5 degrees) and abduction (99.3 +/- 13.0 to 161.4 +/- 15.7 degrees) were significantly improved compared with the mean preoperative values (P<0.0001). 3D CT revealed that in all patients the malrotation of the scapula was improved postoperatively. The current study shows that successful realignment of the scapula led to these improved clinical results. Conclusions: Our procedure has advantages not only for recovery of the range of motion but also for reducing the characteristic lump in the web of the neck. However, our procedure has an inherent limitation related to asymmetric shoulder level and width. 3D CT may be useful for preoperative planning and postoperative evaluation.
  • Hideki Sudo, Katsuhisa Yamada, Koji Iwasaki, Hideaki Higashi, Manabu Ito, Akio Minami, Norimasa Iwasaki
    PLOS ONE 8 (3) e58806  1932-6203 2013/03 [Refereed][Not invited]
     
    Background: Intervertebral disc degeneration is a significant cause of degenerative spinal diseases. Nucleus pulposus (NP) cells reportedly fail to survive in large degenerated discs with limited nutrient availability. Therefore, understanding the regulatory mechanism of the molecular response of NP cells to nutrient deprivation may reveal a new strategy to treat disc degeneration. This study aimed to identify genes related to nutrient deprivation in NP cells on a global scale in an experimental nutrient deprivation model. Methodology/Principal Findings: Rat NP cells were subjected to serum starvation. Global gene expression was profiled by microarray analysis. Confirmation of the selected genes was obtained by real-time polymerase chain reaction array analysis. Western blotting was used to confirm the expression of selected genes. Functional interactions between p21(Cip1) and caspase 3 were examined. Finally, flow cytometric analyses of NP cells were performed. Microarray analysis revealed 2922 differentially expressed probe sets with >= 1.5-fold changes in expression. Serum starvation of NP cells significantly affected the expression of several genes involved in DNA damage checkpoints of the cell cycle, including Atm, Brca1, Cdc25, Gadd45, Hus1, Ppm1D, Rad 9, Tp53, and Cyclin D1. Both p27(Kip1) and p53 protein expression was upregulated in serum-starved cells. p21(Cip1) expression remained in NP cells transfected with short interfering RNA targeting caspase 3 (caspase 3 siRNA). Both G1 arrest and apoptosis induced by serum starvation were inhibited in cells transfected with caspase 3 siRNA. Conclusions/Significance: Nutrient deprivation in NP cells results in the activation of a signaling response including DNA damage checkpoint genes regulating the cell cycle. These results provide novel possibilities to improve the success of intervertebral disc regenerative techniques.
  • Motomiya M, Iwasaki N, Kawamura D
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 18 (1) 85 - 87 0218-8104 2013 [Refereed][Not invited]
  • Minami A, Suda K, Iwasaki N, Motomiya M
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 18 (1) 99 - 102 0218-8104 2013 [Refereed][Not invited]
  • Tomoya Matsuhashi, Naoki Suenaga, Naomi Oizumi, Tadanao Funakoshi, Norimasa Iwasaki, Akio Minami
    JOURNAL OF ORTHOPAEDIC SCIENCE 17 (5) 538 - 544 0949-2658 2012/09 [Refereed][Not invited]
     
    The objectives of this study are to evaluate the clinical and radiographic mid- to long-term outcomes of patients treated by teres minor with bone pedicle transfer for irreparable massive rotator cuff tear and to investigate the limitations of this procedure. Clinical outcomes were assessed by quantifying: the range of shoulder motion; a visual analog pain scale; the University of California, Los Angeles Shoulder Score (UCLA score); and the Disability of the Arm, Shoulder, and Hand (DASH) score. Radiographs were assessed for deterioration of the glenohumeral joint and upper migration of the humeral head. Eighteen patients with mean age of 66.9 years and mean follow-up of 74.4 months were included. The technique resulted in significant decrease in shoulder pain. The mean UCLA score improved from 10.3 points initially to 24.1 points at time of final follow-up. However, the postoperative results were classified as poor in 11 shoulders. The mean postoperative DASH score was 27.6 points. The mean active forward elevation significantly improved from 75.9A degrees initially to 121.6A degrees at time of final follow-up. In radiographic assessment, osteoarthritis of the glenohumeral joint progressed in 15 shoulders, and the upper migration of humeral head progressed in 14 shoulders. Aggravation of the glenohumeral joint and upper migration of the humeral head both progressed postoperatively at a high rate. Therefore, we conclude that this procedure should no longer be performed despite its relative simplicity.
  • Tomohiro Onodera, Tokifumi Majima, Norimasa Iwasaki, Tamotsu Kamishima, Yasuhiko Kasahara, Akio Minami
    INTERNATIONAL ORTHOPAEDICS 36 (9) 1871 - 1876 0341-2695 2012/09 [Refereed][Not invited]
     
    The stress distribution of an ankle under various physiological conditions is important for long-term survival of total ankle arthroplasty. The aim of this study was to measure subchondral bone density across the distal tibial joint surface in patients with malalignment/instability of the lower limb. We evaluated subchondral bone density across the distal tibial joint in patients with malalignment/instability of the knee by computed tomography (CT) osteoabsorptiometry from ten ankles as controls and from 27 ankles with varus deformity/instability of the knee. The quantitative analysis focused on the location of the high-density area at the articular surface, to determine the resultant long-term stress on the ankle joint. The area of maximum density of subchondral bone was located in the medial part in all subjects. The pattern of maximum density in the anterolateral area showed stepwise increases with the development of varus deformity/instability of the knee. Our results should prove helpful for designing new prostheses and determining clinical indications for total ankle arthroplasty.
  • Naoki Seito, Tadashi Yamashita, Yukinori Tsukuda, Yuichiro Matsui, Atsushi Urita, Tomohiro Onodera, Takeomi Mizutani, Hisashi Haga, Naoki Fujitani, Yasuro Shinohara, Akio Minami, Norimasa Iwasaki
    ARTHRITIS AND RHEUMATISM 64 (8) 2579 - 2588 0004-3591 2012/08 [Refereed][Not invited]
     
    Objective Glycosphingolipids (GSLs) are ubiquitous membrane components that modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix interactions. GSL expression is decreased in the articular cartilage of humans with osteoarthritis (OA). This study was undertaken to determine the functional role of GSLs in cartilage metabolism related to OA pathogenesis in mice. Methods We generated mice with knockout of the chondrocyte-specific Ugcg gene, which encodes an initial enzyme of major GSL synthesis, using the Cre/loxP system (Col2-Ugcg-/- mice). In vivo OA and in vitro cartilage degradation models were used to evaluate the effect of GSLs on the cartilage degradation process. Results Although Col2-Ugcg-/- mice developed and grew normally, OA changes in these mice were dramatically enhanced with aging, through the overexpression of matrix metalloproteinase 13 and chondrocyte apoptosis, compared to their wild-type (WT) littermates. Col2-Ugcg-/- mice showed more severe instability-induced pathologic OA in vivo and interleukin-1a (IL-1a)induced cartilage degradation in vitro. IL-1a stimulation of chondrocytes from WT mice significantly increased Ugcg messenger RNA expression and up-regulated GSL metabolism. Conclusion Our results indicate that GSL deficiency in mouse chondrocytes enhances the development of OA. However, this deficiency does not affect the development and organization of cartilage tissue in mice at a young age. These findings indicate that GSLs maintain cartilage molecular metabolism and prevent disease progression, although GSLs are not essential for chondrogenesis of progenitor and stem cells and cartilage development in young mice. GSL metabolism in the cartilage is a potential target for developing a novel treatment for OA.
  • Tomohiro Shimizu, Norimasa Iwasaki, Kinya Nishida, Akio Minami, Tadanao Funakoshi
    CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 470 (6) 1534 - 1539 0009-921X 2012/06 [Refereed][Not invited]
     
    It is important to understand the loading conditions when considering the pathology of shoulder disorders in overhead athletes. However, because throwing is a complicated motion and methods to directly determine stress distribution are complex, direct measurement of the stress distribution across the glenohumeral joint has not been attempted. Subchondral bone density reportedly reflects the cumulative stress acting on a joint surface under actual loading conditions. To assess alterations in stress distribution across the glenoid cavity caused by pitching, we investigated the distribution of subchondral bone density in nonathletic volunteers and asymptomatic baseball players, including fielders and pitchers. We collected CT imaging data from the dominant-side shoulder of 10 nonathletic volunteers (controls), 10 fielders, and 10 pitchers in a competitive college baseball league (all men aged 19-24 years, mean 20.7 years). We measured the distribution of subchondral bone density of the glenoid cavity using CT osteoabsorptiometry. The obtained stress distribution map was divided into four segments: anterosuperior, anteroinferior, posteroinferior, and posterosuperior regions. We quantitatively analyzed the location and percentages of high-density regions on the articular surface. The percentages of high-density regions, including the anteroinferior and posterior segments, were greater in pitchers and fielders than in controls. The percentages of high-density regions did not differ between pitchers and fielders. The bicentric density patterns indicated that the cumulative force of pitching activity affected the long-term stress distribution across the glenoid cavity. Our data should be useful for analyzing pitching activity and clarifying the pathology of shoulder disorders associated with throwing.
  • Ritsu Shiozawa, Shigeharu Uchiyama, Yoshihiro Sugimoto, Shota Ikegami, Norimasa Iwasaki, Hiroyuki Kato
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 37A (6) 1211 - 1216 0363-5023 2012/06 [Refereed][Not invited]
     
    Purpose Because pediatric trigger finger is much less common than pediatric trigger thumb, there is no consensus on the efficacy of splinting, owing to both the rarity of the condition and a lack of natural history and comparative therapeutic data. We performed the present retrospective study on 47 fingers to compare pediatric trigger finger treatment by splinting and nonsplinting. Methods We included 24 children with a total of 47 trigger fingers. Affected fingers included 4 index, 28 middle, 11 ring, and 4 little fingers. Patient age at initial examination ranged from 1 month to 9 years (mean, 2 y). We observed 24 fingers treated with a static splint and 23 fingers treated without it. The time from initial examination to follow-up ranged from 2 to 18 years. Results In the splinting group, 16 fingers (67%) resolved, 4 fingers (17%) improved, and 4 fingers (17%) remained unchanged. Seven fingers (29%) ultimately required surgery. In the nonsplinting group, 7 fingers (30%) resolved spontaneously, 1 (4%) improved, and 15 (65%) remained unchanged. Fifteen fingers (65%) later underwent surgical release. The rate of resolution in the splinting group was significantly higher than that in the nonsplinting group. The proportion of fingers needing surgical treatment in the splinting group was significantly lower than that in the nonsplinting group. Conclusions For treatment of pediatric trigger finger, it is advisable to fit a static splint at the first visit. (J Hand Surg 2012;37A:1211-1216. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.)
  • Yukinori Tsukuda, Norimasa Iwasaki, Naoki Seito, Masashi Kanayama, Naoki Fujitani, Yasuro Shinohara, Yasuhiko Kasahara, Tomohiro Onodera, Koji Suzuki, Tsuyoshi Asano, Akio Minami, Tadashi Yamashita
    PLOS ONE 7 (6) e40136  1932-6203 2012/06 [Refereed][Not invited]
     
    Rheumatoid arthritis (RA), a chronic systemic inflammatory disorder that principally attacks synovial joints, afflicts over 2 million people in the United States. Interleukin (IL)-17 is considered to be a master cytokine in chronic, destructive arthritis. Levels of the ganglioside GM3, one of the most primitive glycosphingolipids containing a sialic acid in the structure, are remarkably decreased in the synovium of patients with RA. Based on the increased cytokine secretions observed in in vitro experiments, GM3 might have an immunologic role. Here, to clarify the association between RA and GM3, we established a collagen-induced arthritis mouse model using the null mutation of the ganglioside GM3 synthase gene. GM3 deficiency exacerbated inflammatory arthritis in the mouse model of RA. In addition, disrupting GM3 induced T cell activation in vivo and promoted overproduction of the cytokines involved in RA. In contrast, the amount of the GM3 synthase gene transcript in the synovium was higher in patients with RA than in those with osteoarthritis. These findings indicate a crucial role for GM3 in the pathogenesis and progression of RA. Control of glycosphingolipids such as GM3 might therefore provide a novel therapeutic strategy for RA.
  • Atsushi Sukegawa, Norimasa Iwasaki, Yasuhiko Kasahara, Tomohiro Onodera, Tatsuya Igarashi, Akio Minami
    TISSUE ENGINEERING PART A 18 (9-10) 934 - 945 1937-3341 2012/05 [Refereed][Not invited]
     
    The objective of this study was to determine whether the local administration of stromal cell-derived factor-1 (SDF-1) using ultrapurified alginate gel (UPAL gel) could improve reparative tissues of osteochondral defects compared with those without treatment. For the investigation, a full-thickness osteochondral defect 4.5mm in diameter and 3mm in depth was created in the patella groove of the distal femur in rabbits. Local expression of SDF-1 protein was temporarily upregulated at 1 week after creating the osteochondral defect. The local administration of SDF-1 enhanced the migration of host cells, mainly bone marrow stromal cells (BMSCs), to the site of the osteochondral defect. In vitro cell migration assay supported this result. In the SDF-1 (UPAL gel containing SDF-1) treatment group, the histological scores and the compressive modulus of reparative tissues were significantly improved compared with the no-treatment and vehicle (UPAL gel without SDF-1) groups. On the other hand, SDF-1 did not influence the cellular proliferation and chondrogenesis of BMSCs. Based on the results obtained here, we speculate that SDF-1 enhances the reparative process of osteochondral injuries not through direct effects on the behavior of host cells, but through increased migration of host cells to the injured site. UPAL gel, as a vehicle material, may play an important role in chondrogenesis of recruited cells, mainly BMSCs. The cell-free approach with local administration of SDF-1 may be an effective strategy for developing a minimally invasive technique for cartilage tissue regeneration.
  • Daisuke Momma, Norimasa Iwasaki, Naomi Oizumi, Kazuhiro Fujisaki, Tadanao Funakoshi, Yuichiro Abe, Tamotsu Kamishima, Shigeru Tadano, Akio Minami
    JOURNAL OF ORTHOPAEDIC SCIENCE 17 (3) 253 - 260 0949-2658 2012/05 [Refereed][Not invited]
     
    The distribution of subchondral bone density well reflects long-term resultant stress acting on an articular surface in living joints. Consequently, a measurement of the distribution pattern can determine the stress distribution across the elbow joint surface under long-term loading conditions of baseball pitching. Our purpose was to elucidate the characteristic alterations in the distribution pattern of subchondral bone density across the forearm bones of the elbow with pitching activities. The hypothesis is that pitching activities would change the stress distribution in living subjects. The analysis was performed using computed tomography (CT) images obtained from the dominant elbow of ten nonthrowing athletes (control group), ten college baseball fielders (fielder group), and ten college baseball pitchers (pitcher group). The distribution pattern of subchondral bone density through the articular surface of the proximal radius and ulna bones was assessed using CT osteoabsorptiometry. The maximum density area was located in the posterior part of the trochlea notch in all study participants. This maximum density area was significantly increased in the baseball groups compared with that in the control group. The pitcher group also showed a significant distribution of the maximum density area in the anterior part of the radial head. Our analysis indicates that pitching activities increase actual stress on the articular surface not only in the posterior part of the trochlea notch but also in the anterior part of the radial head. The stress across the elbow may be expanded from the ulnohumeral to the radiohumeral joint by repetitive pitching activities in living subjects.
  • Kinya Nishida, Norimasa Iwasaki, Kazuhiro Fujisaki, Tadanao Funakoshi, Tamotsu Kamishima, Shigeru Tadano, Akio Minami
    AMERICAN JOURNAL OF SPORTS MEDICINE 40 (4) 909 - 914 0363-5465 2012/04 [Refereed][Not invited]
     
    Background: To theoretically minimize complications of osteochondral graft harvest from the knee, grafts should be obtained from the site of lowest stress distribution across the joint. Hypothesis: Long-term stress distribution over the patellofemoral (PF) joint surface is not equal in athletes. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Measurement of subchondral bone density can determine long-term resultant stress acting on an articular surface in living joints. Our analysis was performed using computed tomography (CT) image data obtained from bilateral knees of 10 college baseball fielders (fielder group) and 10 college baseball pitchers (pitcher group) and 2 control groups, including 10 college soccer players (soccer group) and 10 nonathletes (nonathlete group). The distribution pattern of subchondral bone density throughout the articular surface of the PF joint was assessed using the CT osteoabsorptiometry method. The quantitative analysis focused on the location of the low-density area at the articular surface to assess potential osteochondral donor sites. Results: All participants in the pitcher and fielder groups demonstrated a low-density area widely distributed in the proximal part of the lateral trochlea. On the other hand, a high-density area was located in the distal part of the lateral notch, of the medial notch, and of the medial trochlea. No apparent differences in the distribution pattern were found between the baseball groups and the control groups. Conclusion: Our analysis, based on CT osteoabsorptiometry, indicates that the proximal lateral trochlea of the distal femur has the highest percentage area of low bone density at the PF joint level in donor knees of baseball players, soccer players, and nonathlete controls. Clinical Relevance: From a biomechanical viewpoint, the proximal lateral trochlea is the optimal site for harvesting osteochondral grafts in performing mosaicplasty for baseball players. This selection for the donor site may minimize postoperative PF joint symptoms.
  • Norimasa Iwasaki, Tamotsu Kamishima, Hiroyuki Kato, Tadanao Funakoshi, Akio Minami
    AMERICAN JOURNAL OF SPORTS MEDICINE 40 (3) 624 - 630 0363-5465 2012/03 [Refereed][Not invited]
     
    Background: Magnetic resonance imaging (MRI) has been widely used to characterize osteochondritis dissecans (OCD) lesions. However, the usefulness of MRI for predicting fragment stability in OCD of the humeral capitellum (capitellar OCD) remains unclear. Hypothesis: Preoperative MRI cannot accurately diagnose fragment instability of capitellar OCD in overhead athletes. Study Design: Cohort study (diagnosis); Level of evidence, 1. Methods: Twenty-seven male overhead athletes who had undergone surgery for capitellar OCD were included in the study. A single senior musculoskeletal radiologist blindly reviewed preoperative MRI of these OCD lesions. The radiologist reported the presence or absence of each of the 4 MRI signs indicating fragment instability as described by De Smet et al. The lesions were also classified according to the MRI staging system of Dipaola et al for characterizing the lesions. Intraoperative assessment of fragment stability was used as the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for fragment instability as assessed by MRI. Results: According to the MRI criteria by De Smet et al and the Dipaola et al staging system, 21 (78%) and 20 (74%) lesions were defined as unstable, respectively. The obtained results yielded a sensitivity of 89% and a specificity of 44% for diagnosing fragment instability using the De Smet et al MRI criteria and a sensitivity of 83% and a specificity of 44% using the Dipaola et al MRI staging system. The PPV and NPV for fragment instability were 76% and 67% using the De Smet et al criteria and 75% and 57% according to the Dipaola et al staging system, respectively. The overall correlation rate of Dipaola et al MRI and intraoperative stages was 41%. Conclusion: Preoperative MRI cannot precisely diagnose fragment instability of capitellar OCD that requires operative treatments in overhead athletes. Especially, MRI indicating stable lesions is considered not to be useful in predicting intraoperative instability of capitellar OCD in this study population.
  • Tatsuya Igarashi, Norimasa Iwasaki, Daisuke Kawamura, Yasuhiko Kasahara, Yukinori Tsukuda, Nobuo Ohzawa, Masayuki Ito, Yasuharu Izumisawa, Akio Minami
    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 100A (1) 180 - 187 1549-3296 2012/01 [Refereed][Not invited]
     
    We developed an ultra-purified in situ forming gel as an injectable delivery vehicle of bone marrow stromal cells (BMSCs). Our objective was to assess reparative tissues treated with autologous BMSCs implanted using the injectable implantation system into osteochondral defects in a canine model. Forty-eight osteochondral defects in the patella groove of the knee joint were created in 12 adult beagle dogs (two defects in each knee). The defects were divided into a defect group (n = 16), an acellular novel material implantation (material) group (n = 16), and a BMSCs implantation using the current vehicle system (material with BMSCs) group (n = 16). The reparative tissues at 16 weeks postoperatively were assessed through gross, histological, and mechanical analyses. The reparative tissues of the material with BMSCs group were substituted with firm and smooth hyaline-like cartilage tissue that was perfectly integrated into the host tissues. This treatment group obviously enhanced the subchondral bone reconstruction. The compressive modulus of the reparative tissues was significantly higher in the material with BMSCs group than the other groups. This study demonstrated that the implantation of BMSCs using our novel in situ forming material induced a mature hyaline-like cartilage repair of osteochondral defects in a canine model. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 180-187, 2012.
  • Tatsuya Igarashi, Norimasa Iwasaki, Daisuke Kawamura, Yukinori Tsukuda, Yasuhiko Kasahara, Masahiro Todoh, Shigeru Tadano, Akio Minami
    CARTILAGE 3 (1) 70 - 78 1947-6035 2012/01 [Refereed][Not invited]
     
    Objective: We have developed an ultrapurified low endotoxin alginate (UPLE alginate), which can drastically reduce endotoxin levels. Our purposes were to examine the effects of UPLE alginate administration on osteoarthritis (OA) progression and to determine the adequate molecular weight of the UPLE alginate for therapeutic effects. Design: To induce knee OA, 35 Japanese White rabbits underwent anterior cruciate ligament transection. Intra-articular injections of 0.3 mL solution of each material were started at 4 weeks postoperatively for a total of 5 weekly injections. Seventy knees were divided into the following groups: AL430 (430 kDa molecular weight UPLE alginate), AL1000 (1,000 kDa), AL1700 (1,700 kDa), HA (hyaluronan), and NS (normal saline). At 9 weeks postoperatively, all knees were assessed macroscopically, histologically, and mechanically. Results: Macroscopically, the UPLE alginate groups exhibited milder cartilage degradation compared to that of the NS and HA groups. Histological findings of the UPLE alginate groups showed an obvious reduction in the severity of OA. The histological scores of Kikuchi et al. were superior in the alginate treatment groups compared to the NS group. The friction coefficient of the AL1000 group was significantly lower than that of the NS and HA groups. Conclusion: This study indicates that our UPLE alginates, especially AL1000, have promising potential as an effective agent in preventing OA progression.
  • Nishida K, Iwasaki N, Funakoshi T, Motomiya M, Minami A
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 17 (1) 25 - 31 0218-8104 2012 [Refereed][Not invited]
  • Motomiya M, Iwasaki N, Minami A
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 17 (1) 85 - 87 0218-8104 2012 [Refereed][Not invited]
  • Tadanao Funakoshi, Norimasa Iwasaki, Tamotsu Kamishima, Mutsumi Nishida, Yoichi Ito, Kinya Nishida, Makoto Motomiya, Naoki Suenaga, Akio Minami
    AMERICAN JOURNAL OF SPORTS MEDICINE 39 (12) 2640 - 2646 0363-5465 2011/12 [Refereed][Not invited]
     
    Background: The alterations in blood flow after rotator cuff repair remain unclear. Visualization of vascular patterns could clarify basic and clinical investigations. Purpose: To assess longitudinal blood flow inside the repaired cuff and the surrounding tissue after rotator cuff repair, using contrast-enhanced ultrasonography. Study Design: Descriptive laboratory study. Methods: Fifteen patients (7 men and 8 women; mean age, 65.0 +/- 9.8 years) consented to participate. The patients underwent an ultrasound scan before and 1, 2, and 3 months after surgery. Enhanced ultrasound images were recorded for 1 minute after intravenous injection of contrast reagent. Four regions of interest inside the cuff and 2 regions in the anchor hole and subacromial bursa were superimposed on the obtained images. Calculated areas under the time-intensity curves were expressed in acoustic units (AU). Results: We found area-dependent differences in patterns of alteration and magnitude of blood flow inside the repaired cuff and peritendinous tissues. Vascularity in the articular distal and bursal distal region of the repaired cuff at 1 month postoperatively increased significantly compared with that at the preoperative baseline (76 vs 5 AU, P = .0037; 92 vs 7 AU, P = .043). The vascularity peaked at 1 month after surgery in the bursal area within the cuff but at 2 months in the articular area. The vascularity in the articular proximal region of the repaired cuff was significantly lower than that in the bursal proximal (P = .0046), bursal distal (P = .0183), and articular distal regions (P = .0163) 1 month after surgery. Conclusion: Enhancement patterns in intratendinous tissue increased at 1 or 2 months postoperatively and decreased at 3 months. We found area-dependent differences in enhancement patterns inside the repaired cuff and peritendinous tissue. Clinical Relevance: Visualization of vascularization using contrast-enhanced ultrasound could help in deciding on an appropriate repair technique or on the form of postoperative rehabilitation after rotator cuff repair.
  • Atsushi Urita, Tomoya Matsuhashi, Tomohiro Onodera, Hiroaki Nakagawa, Megumi Hato, Maho Amano, Naoki Seito, Akio Minami, Shin-Ichiro Nishimura, Norimasa Iwasaki
    ARTHRITIS AND RHEUMATISM 63 (11) 3428 - 3438 0004-3591 2011/11 [Refereed][Not invited]
     
    Objective. The process of N-glycosylation is involved in the pathogenesis of various diseases. However, little is known about the contribution of changes in N-glycans in osteoarthritis (OA). The aim of this study was to identify the alterations in N-glycans in human OA cartilage, to characterize the messenger RNA (mRNA) expression of N-glycan biosynthesis enzyme genes (N-glycogenes) in mouse articular chondrocytes during cartilage degradation, and to analyze the relationship between altered N-glycan patterns and mechanisms of cartilage degradation. Methods. Alterations in N-glycans were analyzed in human OA cartilage and degraded mouse cartilage by high-performance liquid chromatography and mass spectrometry. N-glycogene mRNA expression in mouse chondrocytes was measured using reverse transcription-polymerase chain reaction. To assess the relationship between the altered N-glycans and degradation of mouse cartilage, experiments involving either knockdown or overexpression of N-glycogenes were performed in mouse articular chondrocytes. Results. Alterations in high-mannose type N-glycans were observed in both human OA cartilage and degraded mouse cartilage. The expression of beta 1,2N-acetylglucosaminyltransferase I (GlcNAc-TI) mRNA, which converts high-mannose type N-glycans, was significantly increased in degraded mouse cartilage. Mouse chondrocytes with suppressed GlcNAc-TI expression had reduced levels of matrix metalloproteinase 13 (MMP-13) and ADAMTS-5 (aggrecanase 2) mRNA following stimulation with interleukin-1 alpha (IL-1 alpha). In contrast, mouse chondrocytes overexpressing GlcNAc-TI had increased levels of MMP-13 and ADAMTS-5 mRNA following stimulation with IL-1 alpha. Conclusion. These findings indicate that alterations in high-mannose type N-glycans and N-glycogenes in chondrocytes correlate with the release of MMP-13 and ADAMTS-5 during cartilage degradation. These findings suggest that N-glycans play a crucial role in the initiation and progression of OA.
  • Hiroyuki Matsuki, Junichi Ishikawa, Norimasa Iwasaki, Shigeharu Uchiyama, Akio Minami, Hiroyuki Kato
    JOURNAL OF ORTHOPAEDIC SCIENCE 16 (6) 749 - 755 0949-2658 2011/11 [Refereed][Not invited]
     
    Since proximal pole fractures of the scaphoid are frequently overlooked, the poor vascularity in the proximal pole fragment often leads to nonunion. Vascularized bone grafts have been recently tested in cases with scaphoid proximal pole nonunion, but the indication for this treatment has not been well established. Alternatively, we have been treating such patients with a non-vascularized iliac bone graft and Herbert-type screw fixation with considerable success. The purpose of this investigation is to evaluate these cases retrospectively and clarify the surgical efficacy of our procedure. Between 1996 and 2009, 11 consecutive patients with proximal pole scaphoid nonunion were treated with a non-vascularized corticocancellous iliac bone graft and Herbert-type screw fixation. They were all male aged from 12 to 26 years. In two patients, avascular changes were recognized in the proximal pole in preoperative radiographs or MRI. Follow-up ranged from 12 to 76 months. Bone union was radiographically confirmed in all patients, who returned to their former activities without any complications. The period from operation to union ranged from 12 to 24 weeks. The mean Mayo modified wrist score was 76.4 points preoperatively and 91.4 points postoperatively, and was improved in all cases. A non-vascularized iliac bone graft with Herbert-type screw fixation obtained satisfactory clinical and radiographic results in cases with scaphoid proximal pole nonunion, regardless of the vascularity in the proximal fragment.
  • Norimasa Iwasaki, Kinya Nishida, Makoto Motomiya, Tadanao Funakoshi, Akio Minami
    ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY 27 (10) 1371 - 1378 0749-8063 2011/10 [Refereed][Not invited]
     
    Purpose: The objective of this study was to conduct a follow-up evaluation of an arthroscopic reattachment technique using an avulsed deep component of the triangular fibrocartilage complex (dc-TFCC) from the fovea of the distal ulna (ulnar fovea). Methods: A retrospective study was performed on a consecutive cohort of 12 patients who underwent arthroscopic reattachment of the avulsed dc-TFCC into the ulnar fovea over a 24-month period. The mean age was 31 years (range, 20 to 50 years). There were 6 men and 6 women. This technique anchors the avulsed portion of the dc-TFCC to the ulnar fovea by means of a repair suture passed through the created osseous tunnel from the ulnar neck to the foveal surface. Postoperative clinical and functional outcomes were quantitatively evaluated with the Modified Mayo Wrist Score. The Disabilities of the Arm, Shoulder and Hand questionnaire served to assess each patient's subjective outcome. A questionnaire regarding each patient's return to his or her previous job was also completed. Radiographic evaluation was based on computed tomography and magnetic resonance imaging examinations. Results: At the mean follow-up of 30 months, all patients had significant reduction of wrist pain. The mean Modified Mayo Wrist Score was 92.5 +/- 7.5, and all patients were rated as having excellent or good clinical results. The Disabilities of the Arm, Shoulder and Hand score significantly improved from 59.5 +/- 18.5 to 7.7 +/- 11.9 postoperatively (P < .0001). Of the 9 working patients, 7 returned to their previous work. Two patients had occasional extensor carpi ulnaris tendinitis after surgery. Magnetic resonance images at 12 weeks postoperatively showed findings indicating attachment of the triangular fibrocartilage complex (TFCC) to the fovea. Conclusions: Arthroscopic reattachment of the avulsed TFCC to the ulnar fovea by the described technique is a valid alternative for treating avulsion of the foveal TFCC insertion. Level of Evidence: Level IV, therapeutic case series.
  • Hikaru Makabe, Norimasa Iwasaki, Tamotsu Kamishima, Naomi Oizumi, Shigeru Tadano, Akio Minami
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 36A (7) 1158 - 1164 0363-5023 2011/07 [Refereed][Not invited]
     
    Purpose The distribution pattern of subchondral bone density is considered to closely reflect the stress distribution across a joint under physiological loading conditions. Our purpose was to determine alterations in the distribution pattern of subchondral bone density across the distal articular surfaces of the radius and the ulna in patients with Kienbock disease after radial shortening. Methods We collected preoperative and postoperative computed tomography (CT) image data from 7 wrists of 7 patients who had undergone radial shortening for Kienbock disease. We measured the distribution of subchondral bone density through the distal articular surface of the radius and the ulna using a CT osteoabsorptiometry method. The obtained data were quantitatively assessed by calculating the high-density area ratio of the entire radiocarpal joint surface, scaphoid fossa, lunate fossa, and distal ulnar surface. Results At the mean postoperative period of 27 months, the mean high-density area ratio in the entire distal articular surface of the radius significantly decreased from 0.413 preoperatively to 0.141 postoperatively. The postoperative value in each fossa demonstrated a significant reduction from 0.253 to 0.096 in the scaphoid fossa and from 0.160 to 0.045 in the lunate fossa. No significant alteration in the value was found in the distal ulna at follow-up. Conclusions Our CT osteoabsorptiometry analysis suggests that the distribution of subchondral bone density in both scaphoid and lunate fossae notably decreases after radial shortening. This indicates that radial shortening unloads the lunate by reducing the actual stress across the distal articular surface of the radius in subjects with Kienbock disease. (J Hand Surg 2011;36A:1158-1164. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.)
  • Hiroshi Yamazaki, Hiroyuki Kato, Shigeharu Uchiyama, Norimasa Iwasaki, Hisamitsu Ishikura, Akio Minami
    JOURNAL OF HAND SURGERY-EUROPEAN VOLUME 36E (4) 303 - 307 1753-1934 2011/05 [Refereed][Not invited]
     
    We retrospectively reviewed the long-term clinical outcomes of one-stage flexor tendon grafting for seven paediatric patients with isolated flexor digitorum profundus (FDP) tendon injuries in Zones 1 or 2. Free tendon grafts (one palmaris longus tendons and six plantaris tendons) were used for reconstruction by Pulvertaft's procedure. The ages of the patients at reconstruction ranged from 7 to 15 (mean 11) years. The time from injury to surgery ranged from three to 78 (mean 25) months. These patients were followed up from 2.5 to 21 years after surgery (mean 8.5 years). All cases were started on early active extension and passive flexion according to the modified Kleinert mobilization for postoperative rehabilitation. The mean active motion after surgery was 49 degrees (range 20-80 degrees) for the DIP joints and 106 degrees (range 95-110 degrees) for the PIP joints. The total active range of motion was on average 237 degrees (range 195-275 degrees). Excellent results were achieved in five patients, good in one, and fair in one. Growth arrest of the distal phalanx was seen in one patient. One-stage flexor tendon grafting in paediatric patients combined with early controlled mobilization can be used to reconstruct neglected isolated ruptures of the FDP tendon with satisfactory results.
  • Xianjun Ding, Masahiko Takahata, Toshiyuki Akazawa, Norimasa Iwasaki, Yuichiro Abe, Miki Komatsu, Masaru Murata, Manabu Ito, Kuniyoshi Abumi, Akio Minami
    JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE 22 (5) 1247 - 1255 0957-4530 2011/05 [Refereed][Not invited]
     
    Even though synthetic hydroxyapatite (HAp) has a chemical composition similar to the mineral phase of bone, it is minimally absorbed and replaced by bone tissue. This could be because HAp is composed of compactly arranged apatite crystals with homogenously large grains. In this study, the surface and non-stoichiometry of the synthetic HAp crystals was modified by partial dissolution and precipitation (PDP) to improve bioabsorbability of HAp. In vitro cell culture demonstrated that more osteoclasts were activated on PDP-HAp compared with HAp. In vivo implantation using a rabbit bone defect model revealed that PDP-HAp was gradually degraded and was replaced by bone tissue. Consistent with the in vitro results, more osteoclasts were activated in PDP-HAp than in HAp, indicating that the former was absorbed through the stimulation of osteoclastic activity. These results suggest that the PDP technique may have clinical utility for modifying synthetic HAp for use as superior bone graft substitutes.
  • Daisuke Mommma, Norimasa Iwasaki, Naomi Oizumi, Hiroki Nakatsuchi, Tadanao Funakoshi, Tamotsu Kamishima, Shigeru Tadano, Akio Minami
    AMERICAN JOURNAL OF SPORTS MEDICINE 39 (2) 336 - 341 0363-5465 2011/02 [Refereed][Not invited]
     
    Background: The distribution pattern of subchondral bone density is considered to highly reflect the stress distribution across a joint under long-term physiologic loading conditions. Therefore, the biomechanical characteristics over the elbow joint surface under long-term loading conditions of baseball pitching can be determined by a measurement of the distribution pattern. Hypothesis: Stress distribution over the elbow joint surface alters with long-term pitching activities. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Computed tomography (CT) imaging data from the dominant elbow of 10 nonthrowing athletes, 10 college baseball fielders, and 10 college baseball pitchers were collected for the current analysis. The distribution of subchondral bone density through the distal articular surface of the humerus was measured using a CT osteoabsorptiometry method. The quantitative analysis of the obtained data focused on location and size of the maximum density area at the articular surface. Results: The maximum density area of subchondral bone across the articular surface of the distal humerus was located in the posterior part of the trochlea in all subjects. This maximum density area was significantly increased in the pitcher group, compared with that in other groups. Additionally, the pitcher group demonstrated a significant distribution of the maximum density area in the anterior part of the capitellum. Conclusion: The results indicate that actual stress across the elbow is concentrated in the posterior part of the trochlea in humans. Baseball pitching may produce excessive or repetitive stress against not only this part, but also the anterior part of the capitellum. The majority of osteochondritis dissecans lesions affecting the elbow are found in the anterior part of the capitellum in throwing athletes. The results may support an important role of mechanical conditions in the cause of elbow osteochondritis dissecans.
  • Katsuhisa Yamada, Tatsuya Masuko, Norimasa Iwasaki
    JOURNAL OF HAND SURGERY-EUROPEAN VOLUME 36E (1) 77 - 78 1753-1934 2011/01 [Refereed][Not invited]
  • Makoto Motomiya, Norimasa Iwasaki, Yasushi Tazaki, Kinya Nishida, Tadanao Funakoshi, Akio Minami
    MICROSURGERY 31 (2) 155 - 158 0738-1085 2011 [Refereed][Not invited]
     
    It is important to preserve the length, appropriate durable skin, and sensation of the stump when performing below-knee amputation to achieve functional ambulation with a prosthesis. There are many reports of reconstruction procedures using microvascular surgery to preserve the optimum length of the amputation stump for prosthesis; however, free tissue reconstruction is necessary to accompany with the donor site morbidity. In this report, we describe our experience with a below-knee amputation and stump covering using the pedicled dorsalis pedis flap from the no longer usable foot in the case of a severe osteomyelitis of a lower extremity after highly contaminated Gustilo type IIIB fracture. We achieved a well-healed amputated stump with enough length for a prosthesis and for protective sensation. The pedicled dorsalis pedis flap is easily elevated without microvascular anastomosis and is one useful option for the reconstruction of the below-knee amputated stump in the specific case. (C) 2010 Wiley-Liss, Inc. Microsurgery 31:155-158, 2011.
  • Matsuhashi T, Iwasaki N, Kato H, Minami M, Minami A
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 16 (3) 277 - 282 0218-8104 2011 [Refereed][Not invited]
  • Miki Komatsu, Masahiko Takahata, Mitsuru Sugawara, Yoh Takekuma, Takashi Kato, Manabu Ito, Yuichiro Abe, Tohru Irie, Norimasa Iwasaki, Akio Minami
    EUROPEAN SPINE JOURNAL 19 (12) 2149 - 2155 0940-6719 2010/12 [Refereed][Not invited]
     
    Linezolid belongs to a new class of synthetic antimicrobial agent that is effective for a variety of methicillin-resistant Staphylococcus aureus (MRSA) infections including bone and joint MRSA infections, but the effectiveness of linezolid for the treatment of MRSA spine infection remains controversial. In this study, we investigated the diffusion of linezolid or vancomycin into normal rabbit spinal tissues to determine the adequacy of linezolid for the treatment of spinal infection. The penetration efficacy of linezolid into the annulus fibrosus, nucleus pulposus, and vertebral bone (10, 8, and 10%, respectively) was lower than that of vancomycin (27, 11, and 14%, respectively). The penetration efficacy of linezolid into the bone marrow and iliopsoas muscle (88 and 84%, respectively), however, was higher than that of vancomycin (67 and 9%, respectively). These results suggest that linezolid is inadequate for the treatment of spine infection limited to the intervertebral disc, but may be effective for the treatment of infection extending into the muscle and bone marrow, such as in vertebral osteomyelitis, iliopsoas abscess, and postsurgical infection.
  • Tadanao Funakoshi, Norimasa Iwasaki, Tamotsu Kamishima, Mutsumi Nishida, Yoichi Ito, Makoto Kondo, Akio Minami
    AMERICAN JOURNAL OF SPORTS MEDICINE 38 (12) 2464 - 2471 0363-5465 2010/12 [Refereed][Not invited]
     
    Background: Hypoxia and decreased blood supply have been proposed as risks for tendon rupture. Visualization of the vascularity of intact and torn rotator cuffs would be useful for improving treatments for rotator cuff tear. Purpose: To assess vascularity inside a tendon or an adjacent rotator cuff insertion point in patients differing in age and extent of damage to the tendon. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Ten volunteers (all men) and 15 patients (10 men, 5 women) consented to participate in the study. Contrast agent for enhanced ultrasound was injected intravenously. Enhanced ultrasound images of the torn cuff and the contralateral shoulder were recorded for 1 minute. Four small regions of interest, the articular and bursal sides of the tendon and the medial and lateral sides of the bursa, were studied in all shoulders. Results: There was a significant decrease in blood flow in the intratendinous region in elderly subjects compared with young subjects, but age had no effect on blood flow in bursal tissue. Blood flow in ruptured rotator cuffs did not differ from that in intact rotator cuffs. The intraclass correlation coefficient for intraobserver reproducibility was 0.82 (95% confidence interval: 0.77-0.86). Conclusions: The findings of this investigation were the hypovascular pattern in intratendinous tissue compared with the subacromial bursa, the age-related decrease in intratendinous vascularity, and the hypovascular pattern in the tendon, regardless of rupture of the tendon. Clarification of vascular patterns inside or around the torn ends of a rotator cuff will assist in the development of successful treatments for torn rotator cuffs.
  • Norimasa Iwasaki, Shintarou Yamane, Kinya Nishida, Tatsuya Masuko, Tadanao Funakoshi, Tamotsu Kamishima, Akio Minami
    JOURNAL OF SHOULDER AND ELBOW SURGERY 19 (8) E1 - E6 1058-2746 2010/12 [Refereed][Not invited]
  • Tatsuya Igarashi, Norimasa Iwasaki, Yasuhiko Kasahara, Akio Minami
    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 94A (3) 844 - 855 1549-3296 2010/09 [Refereed][Not invited]
     
    We developed a novel cellular implantation system using an in situ forming ultra-purified alginate gel with quite low endotoxity. The aims of this study were to determine the superiority of chondrogenic potential of bone marrow stromal cells (BMSCs) cultured in the purified alginate gel compared with a commercial grade gel, and to assess reparative tissues treated with BMSCs implanted using the developed system into cartilage defects in rabbit knees. The effects of each alginate gel on cellular proliferation and chondrogenesis of rabbit BMSCs were determined by in vitro assessments. Using our purified alginate gel, a novel vehicle system for injecting BMSCs into osteochondral defects without periosteal patch was successfully established in this animal models. The in vitro analyses demonstrated that the purification of alginate significantly enhanced the cellular proliferation and chondrogenic differentiation of BMSCs. The in vivo assessments suggested that the implantation of BMSCs with the developed system using the purified alginate gel histologically and mechanically improved the reparative tissue of osteochondral defects. This system using the purified alginate gel shows the clinical potential for arthroscopically injectable implantation of BMSCs for the treatment of cartilaginous lesions. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 94A: 844-855, 2010
  • Norimasa Iwasaki, Takashi Terashima, Akio Minami, Hiroyuki Kato
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 35A (9) 1502 - 1505 0363-5023 2010/09 [Refereed][Not invited]
     
    A deformity of the distal phalanx of the little finger with a curvature in the dorsal direction, referred to as a reverse Kirner's deformity, is extremely rare. We present a case of such a deformity found in a 6-year-old girl. A successful result was obtained after double corrective osteotomy of the distal phalanx at 12 years of age. (J Hand Surg 2010;35A:1502-1505. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)
  • Norimasa Iwasaki, Hiroyuki Kato, Jyunichi Ishikawa, Tatsuya Masuko, Tadanao Funakoshi, Akio Minami
    JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME 92A 208 - 216 0021-9355 2010/09 [Refereed][Not invited]
     
    BACKGROUND: Although autologous osteochondral mosaicplasty is widely used as a procedure for osteochondritis dissecans lesions, the effectiveness of this procedure in elbow lesions remains unclear. Our aim was to clarify the surgical efficacy of mosaicplasty for teenage athletes with advanced lesions of capitellar osteochondritis dissecans. METHODS: From 2001 to 2006, nineteen teenage male patients who were competitive athletes and had advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. The mean age of the patients was 14.2 years. The surgical technique involved obtaining small-sized cylindrical osteochondral grafts with a mean diameter of 3.5 mm from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting the grafts (mean, 3.3 grafts) to prepared osteochondral defects. The patients were evaluated clinically and radiographically at a mean of forty-five months after surgery. RESULTS: Eighteen patients were free from elbow pain, and one had mild pain occasionally. The mean total arc of elbow motion and standard deviation increased significantly from 112 degrees +/- 17 degrees preoperatively to 128 degrees +/- 12 degrees postoperatively (p < 0.005). The mean clinical score described by Timmerman and Andrews (with a maximum of 200 points) improved significantly from 131 +/- 23 points preoperatively to 191 +/- 15 points postoperatively (p < 0.0001). All patients except one had an excellent or good clinical result. All donor knees were graded as excellent on the basis of the Lysholm knee scoring system. All patients except two returned to a competitive level of the sport they had previously played. Neither loose-body formation nor secondary osteoarthritic changes were found in any patient. CONCLUSIONS: The current midterm results indicate that mosaicplasty can provide satisfactory clinical outcomes for teenage athletes with advanced capitellar osteochondritis dissecans lesions. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. ORIGINAL ABSTRACT CITATION: "Autologous Osteochondral Mosaicplasty for Osteochondritis Dissecans of the Elbow in Teenage Athletes" (2009;91:2359-66).
  • Toru Irie, Masahiko Takahata, Tokifumi Majima, Yuichiro Abe, Miki Komatsu, Norimasa Iwasaki, Akio Minami
    CONNECTIVE TISSUE RESEARCH 51 (3) 179 - 187 0300-8207 2010/06 [Refereed][Not invited]
     
    The selective estrogen receptor modulator raloxifene is therapeutically beneficial for postmenopausal connective tissue degradation, such as osteoporosis, vascular sclerosis, and dermal degradation; however, the effects of raloxifene on postmenopausal tendon metabolism have not been clarified. In this study, we investigated the effects of raloxifene analogue (LY117018) on cell proliferation and collagen metabolism using cultured rat Achilles tendon fibroblasts. 17 beta-Estradiol (E(2); 10<SU-11</SU-10<SU-9</SU M) and LY117018 (10<SU-9</SU-10<SU-7</SU M) had no significant effects on tendon fibroblast proliferation, based on a BrdU (5-bromo-2'-deoxyuridine) incorporation assay (24 hr) and a WST-8 colorimetric assay (2 or 6 days). Neither E(2) nor LY117018 significantly altered the expression of type I collagen, which is a main component of the tendon extracellular matrix (ECM), whereas both E(2) and LY117018 significantly increased the expression of matrix metalloproteinase (MMP)-13, which is responsible for tendon collagen degradation in rat. Also, both E(2) and LY117018 increased the expression of type III collagen and elastin, which are minor components of tendon ECM, but are considered to govern the elastic properties of tendons. These changes in collagen and MMP induced by either E(2) or LY117018 were attenuated by the estrogen receptor alpha blocker ICI 182,780. The results of this study suggest that postmenopausal estrogen deficiency might downregulate tendon collagen turnover and decrease tendon elasticity. Further, raloxifene treatment might restore these changes to premenopausal levels.</.
  • Michiyo Terashima, Miwako Kobayashi, Makoto Motomiya, Nobuo Inoue, Tetsu Yoshida, Hideyuki Okano, Norimasa Iwasaki, Akio Minami, Ichiro Matsuoka
    JOURNAL OF NEUROSCIENCE RESEARCH 88 (7) 1387 - 1393 0360-4012 2010/05 [Refereed][Not invited]
     
    We previously identified a novel family of genes, BRINP1, 2, and 3, that are predominantly and widely expressed in both the central nervous system (CNS) and peripheral nervous system (PNS). In the present study, we analyzed the expression pattern of three BRINP genes during differentiation of mouse embryonic stem (ES) cell-derived neural stem cells (NSCs) and their effects on the cell-cycle regulation of NSCs. While there was no significant expression of any BRINP-mRNA expressed in mouse ES cells, BRINP 1 and 2-mRNAs was expressed at high levels in the ES cell-derived neural stem cells. Upon differentiation into neuronal cells in the presence of retinoic acid and BDNF, all three types of BRINP-mRNA were induced with a similar time course peaking at day three of treatment. Upon differentiation into astroglial cells in the presence of serum, BRINP1-mRNA was slightly up-regulated, while BRINP2- and BRINP3-mRNAs were almost abolished in the astrocytes. While 69.2, 26.1, and 7.7% of cells in a population of NSCs in the exponentially growing phase were in the G1, S and G2 phases, respectively, over-expression of any one of the three BRINP genes completely abolished cells in the G2 phase and significantly reduced the cells in S phase to 11.8-13.8%. Based on these results, the physiological roles of induced BRINP genes in the cell-cycle suppression of terminally differentiated post-mitotic neurons are discussed. (C) 2009 Wiley-Liss, Inc.
  • Maho Amano, Misa Yamaguchi, Yasuhiro Takegawa, Tadashi Yamashita, Michiyo Terashima, Jun-ichi Furukawa, Yoshiaki Miura, Yasuro Shinohara, Norimasa Iwasaki, Akio Minami, Shin-ichiro Nishimura
    MOLECULAR & CELLULAR PROTEOMICS 9 (3) 523 - 537 1535-9476 2010/03 [Refereed][Not invited]
     
    Although various glycoforms appear to participate independently in multiple molecular interactions in cellular adhesion that contribute to embryogenesis and organogenesis, a full portrait of the glycome diversity and the effect of the structural variations of cellular glycoforms on individual cell stages in proliferation and differentiation remain unclear. Here we describe a novel concept for the characterization of dynamic glycoform alteration during cell differentiation by means of "glycoblotting-based cellular glycomics," the only method allowing for rapid and quantitative glycan analysis. We demonstrated that processes of dynamic cellular differentiation of mouse embryonic carcinoma cells, P19CL6 and P19C6, and mouse embryonic stem cells into cardiomyocytes or neural cells can be monitored and characterized quantitatively by profiling entire N-glycan structures of total cell glycoproteins. Whole N-glycans enriched and identified by the glycoblotting method (67 glycans for P19CL6, 75 glycans for P19C6, and 72 glycans for embryonic stem cells) were profiled and bar-coded quantitatively with respect to the ratio of subgroups composed of characteristic glycoforms, namely glycotypes. Molecular & Cellular Proteomics 9: 523-537, 2010.
  • Norimasa Iwasaki, Akio Minami
    JOURNAL OF HAND SURGERY-EUROPEAN VOLUME 35E (1) 71 - 72 1753-1934 2010/01 [Refereed][Not invited]
  • Iwasaki N, Masuko T, Funakoshi T, Minami A
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 15 (1) 47 - 51 0218-8104 2010 [Refereed][Not invited]
  • Matsuhashi T, Iwasaki N, Nishida K, Motomiya M, Minami A
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 15 (1) 53 - 55 0218-8104 2010 [Refereed][Not invited]
  • Akio Minami, Norimasa Iwasaki, Kinya Nishida, Makoto Motomiya, Katsuhisa Yamada, Daisuke Momma
    Case Reports in Medicine 2010 871278  1687-9635 2010 [Refereed][Not invited]
     
    Giant-cell tumor of bone occurred in the distal end of the ulna is extremely uncommon. A 23-year-old male had a giant-cell tumor occurred in the distal end of the ulna. After wide resection of the distal segment of the ulna including giant-cell tumor, ulnar components of the wrist joint were reconstructed with modified Sauvé-Kapandji procedure using the iliac bone graft, preserving the triangular fibrocartilage complex and ulnar collateral ligament in order to maintain ulnar support of the wrist, and the proximal stump of the resected ulna was stabilized by tenodesis using the extensor carpi ulnaris tendon. One year after operation, the patient's wrist was pain-free and had a full range of motion. Postoperative X-rays showed no abnormal findings including recurrence of the giant-cell tumor and ulnar translation of the entire carpus. The stability of the proximal stump of the distal ulna was also maintained. Copyright © 2010 Akio Minami et al.
  • Norimasa Iwasaki, Hiroyuki Kato, Tamotsu Kamishima, Akio Minami
    AMERICAN JOURNAL OF SPORTS MEDICINE 37 (12) 2349 - 2354 0363-5465 2009/12 [Refereed][Not invited]
     
    Background: The goal of osteochondral mosaicplasty (mosaicplasty) against osteochondritis dissecans of the humeral capitellum (capitellar OCD) is to allow patients to return to their sports activities without functional disturbance of the affected elbow. Consequently, the rehabilitation protocol and the interval before returning to sports activities must be established. Although surgeons need this type of data for establishing sequential alterations of grafts in the elbow, no such data have been published. Hypothesis: The findings of magnetic resonance imaging (MRI) improve with increasing time after mosaicplasty for capitellar OCD. Study Design: Case series; Level of evidence, 4. Methods: Ten young male athletes with advanced lesions of capitellar OCD, treated with mosaicplasties, underwent MRI scans at 3, 6, and 12 months, postoperatively. The surgical technique involved obtaining small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting them to the capitellar lesion. The MRI findings were semiquantitatively assessed according to the scoring system of Henderson et al (4, normal; 16, no repair). Results: At 12 months, all patients returned to their competitive level of sports without any disturbances of the operated elbow. Fluid surrounding the graft was found in all patients at 3 months and 4 patients at 6 months. The grafts were all well seated within the recipient sites, with no MRI evidence of graft loosening at 12 months. The overall MRI scores significantly improved from 3 to 12 months. Conclusion: The MRI findings indicate that the graft incorporation to the surrounding tissues occurs around or after 6 months, postoperatively. This finding suggests that rehabilitation precautions be taken for up to 6 months after mosaicplasty for young athletes with capitellar OCD.
  • Norimasa Iwasaki, Hiroyuki Kato, Jyunichi Ishikawa, Tatsuya Masuko, Tadanao Funakoshi, Akio Minami
    JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME 91A (10) 2359 - 2366 0021-9355 2009/10 [Refereed][Not invited]
     
    Background: Although autologous osteochondral mosaicplasty is widely used as a procedure for osteochondritis dissecans lesions, the effectiveness of this procedure in elbow lesions remains unclear. Our aim was to clarify the surgical efficacy of mosaicplasty for teenage athletes with advanced lesions of capitellar osteochondritis dissecans. Methods: From 2001 to 2006, nineteen teenage male patients who were competitive athletes and had advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. The mean age of the patients was 14.2 years. The surgical technique involved obtaining small-sized cylindrical osteochondral grafts with a mean diameter of 3.5 mm from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting the grafts (mean, 3.3 grafts) to prepared osteochondral defects. The patients were evaluated clinically and radiographically at a mean of forty-five months after surgery. Results: Eighteen patients were free from elbow pain, and one had mild pain occasionally. The mean total arc of elbow motion and standard deviation increased significantly from 112 degrees +/- 17 degrees preoperatively to 128 degrees +/- 12 degrees postoperatively (p < 0.005). The mean clinical score described by Timmerman and Andrews (with a maximum of 200 points) improved significantly from 131 +/- 23 points preoperatively to 191 +/- 15 points postoperatively (p < 0.0001). All patients except one had an excellent or good clinical result. All donor knees were graded as excellent on the basis of the Lysholm knee scoring system. All patients except two returned to a competitive level of the sport they had previously played. Neither loose-body formation nor secondary osteoarthritic changes were found in any patient. Conclusions: The current midterm results indicate that mosaicplasty can provide satisfactory clinical outcomes for teenage athletes with advanced capitellar osteochondritis dissecans lesions.
  • Tamotsu Kamishima, Akiko Hasegawa, Kanako C. Kubota, Naomi Oizumi, Norimasa Iwasaki, Akio Minami, Satoru Sasaki, Yuhei Yamamoto, Tokuhiko Omatsu, Yuya Onodera, Satoshi Terae, Hiroki Shirato
    JAPANESE JOURNAL OF RADIOLOGY 27 (8) 328 - 332 1867-1071 2009/10 [Refereed][Not invited]
     
    Intravenous pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that usually occurs in the veins of the neck and upper extremities. We report two cases of intravenous pyogenic granuloma localized in the finger, giving details of the magnetic resonance imaging (MRI) findings. These two cases had similar locations in fingers and identical MRI findings. The differential diagnoses of this rare entity are also discussed.
  • Norimasa Iwasaki, Akio Minami
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 34A (7) 1323 - 1326 0363-5023 2009/09 [Refereed][Not invited]
     
    Triangular fibrocartilage complex (TFCC) insertion into the fovea of the distal ulna plays a crucial role in stabilizing the distal radioulnar joint. Consequently, surgical reattachment against avulsion of the foveal TFCC insertion is required to stabilize the distal radioulnar joint. However, because of technical difficulties, no arthroscopic procedure for such a lesion has currently been established. We present a new technique for arthroscopic reattachment of the avulsed TFCC into the fovea. An osseous tunnel 2.9 mm in diameter is created from the ulnar neck to the foveal surface. Under arthroscopic guidance, a nonabsorbable suture passed into a 21-gauge needle is placed into the TFCC through the osseous tunnel. The avulsed portion of the TFCC is anchored to the fovea by means of a repair suture passed through the TFCC. To achieve normal tension of the TFCC, the suture is tied onto the periosteum around the proximal entrance of the osseous tunnel. Our arthroscopic technique is relatively simple and has great advantages for progressive healing at the attachment site between the TFCC and the fovea. (J Hand Surg 2009;34A:1323-1326. Copyright (C) 2009 by the American Society for Surgery of the Hand. All rights reserved.)
  • Tomoya Matsuhashi, Norimasa Iwasaki, Naomi Oizumi, Hiroyuki Kato, Michio Minami, Akio Minami
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 34A (7) 1242 - 1247 0363-5023 2009/09 [Refereed][Not invited]
     
    Purpose We hypothesized that radial shortening osteotomy (radial shortening) for skeletally immature patients with Kienbock's disease would induce overgrowth of the radius. The purpose of this study was to determine the effect of radial shortening on radial growth in skeletally immature patients with Kienbock's disease and to clarify the relationship between the postoperative growth alterations and the clinical results. Methods Eight wrists of 8 skeletally immature patients with Kienbock's disease were treated with radial shortening. There were 3 boys and 5 girls, ranging in age from 11 to 18 (mean, 14) years old. All patients presented with open physis and negative ulnar variance. The length of the radial shortening equaled the amount of negative ulnar variance. Clinical assessment was based on the modified Nakamura scoring system. Radiographic assessment, including Lichtman's stages, ulnar variance, carpal height ratio, radial inclination, and volar tilt, was performed before surgery, immediately after surgery, and at follow-up. A difference in ulnar variance of more than 2 mm between these 3 measurements was considered to be overgrowth. Statistical comparisons were performed using paired t-tests. Results At a mean follow-up period of 69 months, the mean clinical score was 19.7 of 21. maximum points, with all wrists rated as excellent. Radiographically, no progression of Lichtman stage was found in any patient. At follow-up, the x-ray and magnetic resonance imaging findings indicated lunate revascularization in all patients. Four of the 8 had overgrowth in the operated radius. On the other hand, other radiographic parameters showed no significant changes at follow-up. The occurrence of postoperative radial overgrowth did not notably affect the clinical scores. Conclusions The current results suggest the probability of overgrowth of the radius in skeletally immature patients with Kienbock's disease treated with radial shortening. The postoperative radial overgrowth after this osteotomy had no effect on clinical and other radiographic outcomes. (J Hand Surg 2009;34A:1242-1247. (C) 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)
  • Kazumi Shimode, Norimasa Iwasaki, Tokifumi Majima, Tadanao Funakoshi, Naohiro Sawaguchi, Tomohiro Onodera, Akio Minami
    TISSUE ENGINEERING PART A 15 (8) 2277 - 2284 1937-3341 2009/08 [Refereed][Not invited]
     
    In the present study the local expression of stromal cell-derived factor-1 (SDF-1) after ligament injury and correlated change in the homing rate of systemically induced bone marrow stromal cells (BMSCs) to the injured site were clarified using a rat medial collateral ligament (MCL) injury model. SDF-1 was temporarily upregulated peaking at 2 weeks after injury. Correlated with the alteration in SDF-1 expression, the homing rate of systemically induced BMSCs was temporarily upregulated peaking at 2-4 weeks after injury. The SDF-1 expression in the MCL seems to play a crucial role in cell homing. In addition, SDF-1 did not influence the BMSCs behavior in vitro in terms of the proliferation, adhesivity, and expression of ligament fibroblast markers. The cell-based therapy for ligament and tendon injury with reference to local expression of SDF-1 may be one of the available applications.
  • Daisuke Takahashi, Norimasa Iwasaki, Shigeyuki Kon, Yuichiro Matsui, Tokifumi Majima, Akio Minami, Toshimitsu Uede
    ARTHRITIS AND RHEUMATISM 60 (8) 2372 - 2380 0004-3591 2009/08 [Refereed][Not invited]
     
    Objective. The hypothesis of this study was that synovial factors playing a pivotal role in the pathogenesis of osteoarthritis (OA) and thus gene expression in the synovium would be altered at the initial stage of OA. The aims of this study were to identify the candidate genes in synovium related to OA initiation, to evaluate cartilage degeneration after knockdown of the gene using small interfering RNA (siRNA) gene silencing in the knee joints at the initial stage of OA, and to determine the potential role of the knocked-down gene in OA initiation. Methods. Genes overexpressed in synovium at the initial stage of disease in a rabbit model of anterior cruciate ligament transection (ACLT)-induced OA were identified using the suppression subtractive hybridization technique and differential screening. Candidate gene expression in the synovium of the knees of rabbits with OA was manipulated with electroporation-assisted siRNA transduction 4 times before and after operation. Four weeks after surgery, histologic analysis was performed. Results. Cathepsin K gene and protein expression was significantly up-regulated in synovium at the initial stage of OA in rabbits. Down-regulation of cathepsin K in synovium at the initial stage of OA significantly accelerated cartilage degeneration. Conclusion. These results indicate that cathepsin K plays a protective role in cartilage degeneration at the initial stage of OA. We believe that the current results obtained from models of the early phase of OA will provide useful information for developing a novel strategy to prevent disease progression.
  • Yuichiro Matsui, Norimasa Iwasaki, Shigeyuki Kon, Daisuke Takahashi, Junko Morimoto, Yutaka Matsui, David T. Denhardt, Susan Rittling, Akio Minami, Toshimitsu Uede
    ARTHRITIS AND RHEUMATISM 60 (8) 2362 - 2371 0004-3591 2009/08 [Refereed][Not invited]
     
    Objective. To investigate the role of osteopontin (OPN) in the development of osteoarthritis (OA) under in vivo and in vitro conditions. Methods. Both instability-induced and aging-associated OA models were generated using OPN-deficient (OPN(-/-)) and control wild-type (WT) mice. An in vitro cartilage degradation model was also used, to evaluate the effect of OPN on proteoglycan loss from joint cartilage. Results. OPN deficiency exacerbated both aging-associated and instability-induced OA. Both structural changes and an increased loss of proteoglycan from cartilage tissue were augmented in the absence of OPN. OPN deficiency also led to the induction of matrix metalloproteinase 13 (MMP-13), which degrades a major component of the cartilage matrix protein type II collagen. Both the loss of proteoglycan and the induction of the collagen-degrading enzyme MMP-13 facilitated the development of OA. Conclusion. OPN plays a pivotal role in the progression of both instability-induced and aging-associated spontaneous OA. OPN is a critical intrinsic regulator of cartilage degradation via its effects on MMP-13 expression and proteoglycan loss.
  • Kinya Nishida, Norimasa Iwasaki, Akio Minami
    JOURNAL OF HAND SURGERY-EUROPEAN VOLUME 34E (4) 538 - 539 1753-1934 2009/08 [Refereed][Not invited]
  • Masashi Kanayama, Daisuke Kurotaki, Junko Morimoto, Tsuyoshi Asano, Yutaka Matsui, Yosuke Nakayama, Yoshinari Saito, Koyu Ito, Chiemi Kimura, Norimasa Iwasaki, Koji Suzuki, Tanenobu Harada, Hong Mei Li, Jun Uehara, Tadaaki Miyazaki, Akio Minami, Shigeyuki Kon, Toshimitsu Uede
    Journal of immunology (Baltimore, Md. : 1950) 182 (12) 8015 - 25 0022-1767 2009/06/15 [Refereed][Not invited]
     
    Osteopontin is critically involved in rheumatoid arthritis; however, the molecular cross-talk between osteopontin and joint cell components that leads to the inflammatory joint destruction is largely unknown. We found that not only osteopontin but also tenascin-C and their common receptor, alpha(9) integrin, are expressed at arthritic joints. The local production of osteopontin and tenascin-C is mainly due to synovial fibroblasts and, to a lesser extent, synovial macrophages. Synovial fibroblasts and macrophages express alpha(9) integrin, and autocrine and paracrine interactions of alpha(9) integrin on synovial fibroblasts and macrophages and its ligands contribute differently to the production of proinflammatory cytokines and chemokines. alpha(9) integrin is also involved in the recruitment and accumulation of inflammatory cells. Inhibition of alpha(9) integrin function with an anti-alpha(9) integrin Ab significantly reduces the production of arthrogenic cytokines and chemokines and ameliorates ongoing arthritis. Thus, we identified alpha(9) integrin as a critical intrinsic regulator that controls the development of autoimmune arthritis.
  • Masuko T, Iwasaki N, Ishikawa J, Kato H, Minami A
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 14 (1) 15 - 21 0218-8104 2009 [Refereed][Not invited]
  • Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system
    Hisamitsu Ishikura, Hiroaki Ikeda, Hiroyuki Abe, Takayuki Ohkuri, Hiroaki Hiraga, Kazuo Isu, Tomohide Tsukahara, Noriyuki Sato, Hidemitsu Kitamura, Norimasa Iwasaki, Naoki Takeda, Akio Minami, Takashi Nishimura
    INTERNATIONAL JOURNAL OF ONCOLOGY 30 (2) 461 - 467 1019-6439 2007/02 [Refereed][Not invited]
     
    Since the prognosis of human osteosarcoma in advanced stage remains poor, the development of new and effective therapies including immunotherapy is required. To identify tumor-associated antigens of osteosarcoma applicable to the immunotherapy of this malignancy, we employed the serological analysis of recombinant cDNA expression library (SEREX) technique that defines tumor antigens recognized by the humoral immune system. Screening a cDNA library derived from an osteosarcoma cell line MG63 with sera from osteosarcoma patients identified 43 positive clones, representing 14 distinct antigens. Among them, CLUAP1 (clusterin-associated protein 1) was highly expressed in osteosarcoma tissue samples and cell lines. Overexpression of CLUAP1 was observed in other malignancies including ovarian, colon, and lung cancers. Our results suggest that CLUAP1 may be useful as a prognostic/diagnostic marker and/or for a target of immunotherapy of osteosarcoma.
  • Kazumi Shimode, Norimasa Iwasaki, Tokifumi Majima, Tadanao Funakoshi, Naohiro Sawaguchi, Tomohiro Onodera, Akio Minami
    TISSUE ENGINEERING 13 (2) 333 - 341 1076-3279 2007/02 [Refereed][Not invited]
     
    Feeder effects of bone marrow stromal cells (BMSCs) on tendon fibroblasts were investigated using a coculture method for the application of ligament or tendon tissue engineering and cell therapy. BMSCs had significant effects on enhancing cell proliferation, the ability of cells to migrate, and cell adhesivity but little effect on the extracellular matrix (ECM) synthesis of tendon fibroblasts without cell-cell contact. Furthermore, the conditioned medium from BMSCs, despite the existence of fibroblasts, significantly increased the number of fibroblasts. Based on these results, the mechanism of the feeder effects is considered to be a certain signal of soluble factors from BMSCs to the fibroblasts. Comparative proteome analysis of the conditioned medium from co-culture of fibroblasts and BMSCs revealed less expression of plasminogen, which showed inhibitory effects on fibroblast proliferation. With regard to the relationships between plasminogen and BMSCs in the co-culture system, we speculate that BMSCs allow resolution of plasminogen or its cleavage activity in the medium via some mechanism.
  • Tomohiro Onodera, Kenichi Niikura, Norimasa Iwasaki, Noriko Nagahori, Hideyuki Shimaoka, Ryusuke Kamitani, Tokifumi Majima, Akio Minami, Shin-Ichiro Nishimura
    BIOMACROMOLECULES 7 (11) 2949 - 2955 1525-7797 2006/11 [Refereed][Not invited]
     
    We synthesized an aminooxyl polymer that is reactive with the reduced end of carbohydrates using our sugar-displaying approach. The carbohydrates were easily immobilized on the polymer film (glycoblotting film) by simple immersion in a in sugar solution through stable oxime bond. The in vitro behaviors of human fibroblasts on the carbohydrate-coated surface were investigated. The adhesion of human fibroblasts on the cellobiose- and cellotriose-coated surfaces was much greater than on the other coated surfaces and the noncoated surface. This result indicated that simple structural differences in carbohydrates induced biological changes in human cells, especially cell adhesion. Our approach provides a high-throughput assay system for carbohydrate-related cell adhesion and proliferation.
  • Norimasa Iwasaki, Hiroyuki Kato, Jyunichi Ishikawa, Satoru Saitoh, Akio Minami
    AMERICAN JOURNAL OF SPORTS MEDICINE 34 (8) 1233 - 1239 0363-5465 2006/08 [Refereed][Not invited]
     
    Background: Autologous osteochondral mosaiciplasty is a new technique to provide hyaline repair for articular defects. Although recent studies have reported the successful treatment of articular defects in the knee and ankle joints with this surgical procedure, little attention has been given to the surgical efficacy of mosaicplasty in the treatment of osteochondritis dissecans of the humeral capitellum. Purpose: To clarify the clinical outcomes of mosaiciplasty for teenaged patients with advanced lesions of capitellar osteochondritis dissecans. Study Design: Case series; Level of evidence, 4. Methods: Eight teenaged patients with advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. All patients were baseball players who were affected on the right side, which was also their throwing side. The surgical technique involves obtaining small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyles and transplanting them to prepared osteochondral defects. At a mean follow-up of 24 months, all patients were evaluated clinically and radiographically. Results: Seven of the 8 patients were free from elbow pain, and the remaining patient had mild pain occasionally. The mean clinical score described by Timmerman and Andrews (a maximum of 200 points) significantly improved from 140 points to 183 points postoperatively. All patients except one had excellent or good clinical results. Radiographically, the graft incorporation and a normal contour of the subchondral cortex were found in all patients. Magnetic resonance imaging showed that the preoperative heterogeneity of the lesion had disappeared and the signal intensity returned to normal. Six of the 8 patients, including all 3 pitchers, returned to competitive-level baseball. Conclusion: Mosaicplasty for advanced lesions of capitellar osteochondritis dissecans in teenaged baseball players can provide satisfactory clinical and radiographic results.
  • N Oizumi, S Tadano, Y Narita, N Suenaga, N Iwasaki, A Minami
    JOURNAL OF SHOULDER AND ELBOW SURGERY 15 (3) 331 - 338 1058-2746 2006/05 [Refereed][Not invited]
     
    Because some shoulder muscles originate from a wide area, the modeling of such muscles has been a significant problem in a computer simulation. We demonstrated a new method of determining a vector for each of the muscles originating from a wide area. A 3-dimensional musculoskeletal model of a human shoulder was constructed from computed tomography data of a normal volunteer. Numerical analysis of I I muscle forces and the joint reaction force during shoulder abduction from 10 degrees to 150 degrees was performed from the static equilibrium equations. An optimal origin point for the vector of the muscle with a wide origin area was determined in every analyzed position. Electromyography was carried out to validate the results of the simulation, and a significant correlation with the analyzed force was obtained in each muscle. The anatomic biomechanical model with the new muscle modeling method led to the results reflecting the actual muscle activities in a living body.
  • A Minami, N Iwasaki, J Ishikawa, N Suenaga, H Kato
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 31A (3) 440 - 444 0363-5023 2006/03 [Refereed][Not invited]
     
    Purpose: The Sauve-Kapandji procedure is considered a useful treatment option for distal radioulnar disorders. Postoperative instability of the proximal ulnar stump and radioulnar convergence, however, may be symptomatic. We modified the Sauve-Kapandji procedure by stabilizing the proximal ulnar stump with a half-slip of the extensor carpi ulnaris tendon. We previously reported on 13 patients with this procedure at an average follow-up period of 35 months; the patients had satisfactory clinical results and improved stability of the proximal ulnar stump as shown by x-ray examination. In this article we address the question of whether those clinical and radiographic results noted at an average follow-up period of 35 months after surgery were maintained at later follow-up examinations. Methods: We re-examined 12 of the 13 original patients and compared their initial follow-up results with their current results after an average follow-up period of 95 months. Results: The results of this series after 95 months of follow-up evaluation were similar to the results at 35 months. Conclusions: The results presented in this article suggest that the clinical radiographic results at the 35-month follow-up examination were maintained in the long-term 95-month follow-up evaluation despite the finding that the hole in the proximal ulnar stump had broken in 3 wrists at follow-up examination.
  • T Funakoshi, T Majima, N Suenaga, N Iwasaki, S Yamane, A Minami
    JOURNAL OF SHOULDER AND ELBOW SURGERY 15 (1) 112 - 118 1058-2746 2006/01 [Refereed][Not invited]
     
    Twenty-one rabbits were used to investigate the feasibility of using nonwoven chitin fabric as an acellular matrix for rotator cuff regeneration. Infraspinatus tendons were cut bilaterally to create 10 x 10-mm defects. The defect in the right shoulder was covered with chitin fabric. The contralateral defect was left free as a control. The specimens were evaluated histologically and immunohistochemically at 2, 4, 8, and 12 weeks and biomechanically at 12 weeks after surgery. The acellular matrix increased cell numbers and improved collagen fiber alignment. The regenerated tissues were composed of type III collagen. The structural properties of the grafted shoulder were significantly greater than those of the control. This study revealed that using chitin fabric as an acellular matrix has advantages in enhancing both biologic and mechanical regeneration of rotator cuff tendons.
  • J Ishikawa, N Iwasaki, A Minami
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 30A (6) 1178 - 1184 0363-5023 2005/11 [Refereed][Not invited]
     
    Purpose: To analyze the influence of subluxation of the distal radioulnar joint (DRUJ) on restricted forearm rotation after distal radius fracture. Methods: Twenty-two cases of healed unilateral distal radial fracture with restricted forearm rotation were included in the study. The subluxation of the DRUJ was evaluated using helical computed tomography scan at neutral, maximum pronation, and maximum supination and presented as the percent displacement of the ulnar head in both the injured and uninjured sides. The radiographic parameters of palmar tilt, radial inclination, dorsal shift, radial shift, and ulnar variance were measured on plain x-ray films and the rotational deformity of the distal radius was evaluated from the computed tomography scan. The differences of each radiographic parameter from the uninjured side were calculated. The relationships between the restricted forearm rotation and the percent displacement of the ulnar head and each of the radiographic parameters were analyzed statistically. Results: When forearm pronation was restricted the ulnar head was located palmarly at neutral, maximum supination, and maximum pronation with severe dorsal tilt of the distal radius. When supination was restricted the u1nar head was located dorsally at maximum supination with severe ulnar-positive variance. Conclusions: The subluxation of the DRUJ was related to restricted forearm rotation. The radiographic parameters of palmar tilt and ulnar variance showed an adverse influence on the position of the ulnar head at the DRUJ, which might lead to restricted forearm rotation after distal radial fracture.
  • N Iwasaki, A Minami, J Ishikawa, H Kato, M Minami
    CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 439 (439) 116 - 122 0009-921X 2005/10 [Refereed][Not invited]
     
    Age seems to affect the efficacy of radial osteotomies for Kienbock disease. We questioned whether an osteotomy would produce acceptable results in teenagers. We retrospectively identified II patients (six males and five females) between 11-19 years of age who were treated with radial osteotomies for Kienbock disease. Preoperatively, three patients had Lichtman Stage II disease, two patients had Stage IIIA disease, and six patients had Stage IIIB disease. Two patients with zero or positive ulnar variance had lateral closing wedge osteotomies, and nine patients with negative ulnar variance had radial shortenings. All patients were evaluated clinically and radiographically. At a mean followup of 50 months, 10 of 11 patients were free from pain, and the remaining one patient had moderate wrist pain during strenuous activity. All patients except one, who had Stage IIIB disease, had an excellent clinical outcome. Radiographic improvement, indicating lunate revascularization, was seen for eight patients. Despite Stage IIIB disease, radial osteotomies produced excellent clinical results in five of six teenage patients. The current results indicate that radial osteotomies are effective in improving not only short-term clinical outcomes, but also radiographic findings in teenage patients with Kienbock disease.
  • T Masuko, N Iwasaki, S Yamane, T Funakoshi, T Majima, A Minami, N Ohsuga, T Ohta, SI Nishimura
    BIOMATERIALS 26 (26) 5339 - 5347 0142-9612 2005/09 [Refereed][Not invited]
     
    In the present study, we have developed a novel and versatile method for the preparation of chitosan-peptide complex based on the selective reaction of chitosan with 2-iminothiolane. The new type of SH-chitosan derivative showed an excellent solubility to aqueous solution even in the alkaline conditions. This characteristic greatly facilitated further modification study of chifosan with a variety of bioactive substances. A synthetic peptide, RGDSGGC containing RGDS moiety that is known as one of the most important cell adhesive peptides, was readily coupled by disulfide bonds formation with sulfhydryl groups of SH-chitosan in the presence of dimethyl sulfoxide. Next, the effect of the introduction of RGDSGGC moiety to chitosan on cell adhesion and proliferation activity of chondrocytes and fibroblasts were evaluated. As a result, it was suggested that this polysaccharide-peptide conjugate exhibited excellent capacities for both cell adhesion and cell proliferation of chondrocytes and fibroblasts. Considering the growing importance of the biocompatible scaffolds in the recent tailored tissue engineering technique, these results indicate that the present strategy of 2-iminothiolane-based conjugation of polysaccharides with biologically active peptides will become a key and potential technology to develop desirable scaffold materials for the tissue regenerations. (c) 2005 Elsevier Ltd. All rights reserved.
  • T Funakoshi, T Majima, N Iwasaki, S Yamane, T Masuko, A Minami, K Harada, H Tamura, S Tokura, SI Nishimura
    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 74A (3) 338 - 346 1549-3296 2005/09 [Refereed][Not invited]
     
    To clarify the feasibility of using novel chitosan-based hyaluronan hybrid polymer fibers as a scaffold in ligament tissue engineering, their mechanical properties and ability to promote cellular adhesion, proliferation, and extracellular matrix production were studied in vitro. Chitosan fibers and chitosan-based 0.05% and 0.1% hyaluronan hybrid fibers were developed by the wet spinning method. Hyaluronan coating significantly increased mechanical properties, compared to the chitosan fibers. Rabbit fibroblasts adhesion onto hybrid fibers was significantly greater than for the control and chitosan fibers. For analysis of cell proliferation and extracellular matrix production, a three-dimensional scaffold was created by simply piling up each fiber. At I day after cultivation, the DNA content in the hybrid scaffolds was higher than that in the chitosan scaffold. Scanning electron microscopy showed that the fibroblasts had produced collagen fibers after 14 days of culture. Immunostaining for type I collagen was clearly predominant in the hybrid scaffolds, and the mRNA level of type I collagen in the hybrid scaffolds were significantly greater than that in the chitosan scaffold. The present study revealed that hyaluronan hybridization with chitosan fibers enhanced fiber mechanical properties and in vitro biological effects on the cultured fibroblasts. (c) 2005 Wiley Periodicals, Inc.
  • T Funakoshi, T Majima, N Iwasaki, N Suenaga, N Sawaguchi, K Shimode, A Minami, K Harada, S Nishimura
    AMERICAN JOURNAL OF SPORTS MEDICINE 33 (8) 1193 - 1201 0363-5465 2005/08 [Refereed][Not invited]
     
    Background: The current surgical procedures for irreparable rotator cuff tears have considerable limitations. Tissue engineering techniques using novel scaffold materials offer potential alternatives for managing these conditions. Hypothesis: A chitosan-based hyaluronan hybrid scaffold could enhance type I collagen products with seeded fibroblasts and thereby increase the mechanical strength of regenerated tendon in vivo. Study Design: Controlled laboratory study. Methods: The scaffolds were created from chitosan-based hyaluronan hybrid polymer fibers. Forty-eight rabbit infraspinatus tendons and their humeral insertions were removed to create defects. Each defect was covered with a fibroblast-seeded scaffold (n = 16) or a non-fibroblast-seeded scaffold (n = 16). In the other 16 shoulders, the rotator cuff defect was left free as the control. At 4 and 12 weeks after surgery, the engineered tendons were assessed by histological, immunohistochemical (n = 2), and biomechanical (n = 6) analyses. Results: Type I collagen was only seen in the fibroblast-seeded scaffold and increased in the regenerated tissue. The tensile strength and tangent modulus in the fibroblast-seeded scaffold were significantly improved from 4 to 12 weeks postoperatively. The fibroblast-seeded scaffold had a significantly greater tangent modulus than did the non-fibroblast-seeded scaffold and the control at 12 weeks. Conclusion: This scaffold material enhanced the production of type I collagen and led to improved mechanical strength in the regenerated tissues of the rotator cuff in vivo. Clinical Relevance: Rotator cuff regeneration is feasible using this tissue engineering technique.
  • Minami A, Iwasaki N, Kutsumi K, Suenaga N, Yasuda K
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 10 (1) 77 - 82 0218-8104 2005/07 [Refereed][Not invited]
  • T Majima, T Funakosi, N Iwasaki, ST Yamane, K Harada, S Nonaka, A Minami, SI Nishimura
    JOURNAL OF ORTHOPAEDIC SCIENCE 10 (3) 302 - 307 0949-2658 2005/05 [Refereed][Not invited]
     
    Selecting the material for a scaffold is critically important for the success of tissue engineering. To simplify complicated biosynthetic matrices and achieve a novel class of potential materials, a model of polyion complex fibers was prepared from alginate and chitosan. In the current in vitro study, we thought that alginate-based chitosan hybrid biomaterials could provide excellent supports for fibroblast adhesion. In the current study, alginate polymer fiber (alginate group) and alginate-based chitosan hybrid polymer fibers (alginate with 0.05% chitosan, alginate-chitosan 0.05% group; alginate with 0.1% chitosan, alginate-chitosan 0.1% group) were originally prepared. We investigated the adhesion behavior of rabbit tendon fibroblast onto alginate polymer fibers versus the adhesion of the fibroblast onto alginate-based chitosan hybrid polymer fibers. Furthermore, mechanical properties and synthesis of the extracellular matrix were investigated. Mechanically, the novel fiber has considerable tensile strength of more than 200MPa. We demonstrated that the alginate-based chitosan hybrid polymer fibers showed much improved adhesion capacity with fibroblast compared with alginate polymer fiber. Additionally, morphologic studies revealed the dense fiber of the type I collagen produced by the fibroblast in the hybrid polymer fibers. We concluded that an alginate-based chitosan hybrid polymer fiber has considerable potential as a desirable biomaterial scaffold for tendon and ligament tissue engineering.
  • T Masuko, A Minami, N Iwasaki, T Majima, SI Nishimura, YC Lee
    ANALYTICAL BIOCHEMISTRY 339 (1) 69 - 72 0003-2697 2005/04 [Refereed][Not invited]
     
    Among many colorimetric methods for carbohydrate analysis, the phenol-sulfuric acid method is the easiest and most reliable method. It has been used for measuring neutral sugars in oligosaccharides, proteoglycans, glycoproteins, and glycolipids. This method is used widely because of its sensitivity and simplicity. In its original form, it required 50-450 nmol of monosaccharides or equivalent for analysis and thus is inadequate for precious samples. A scaled-down version requiring only 10-80 nmol of sugars was reported previously. We have now modified and optimized this method to use 96-well microplates for high throughput, to gain greater sensitivity, and to economize the reagents. This modified and optimized method allows longer linear range (1-150 nmol for Man) and excellent sensitivity. Moreover, our method is more convenient, requiring neither shaking nor covering, and takes less than 15 min to complete. The speed and simplicity of this method would make it most suitable for analyses of large numbers of samples such as chromatographic fractions. (c) 2004 Elsevier Inc. All rights reserved.
  • T Masuko, A Minami, N Iwasaki, T Majima, SI Nishimura, YC Lee
    BIOMACROMOLECULES 6 (2) 880 - 884 1525-7797 2005/03 [Refereed][Not invited]
     
    Chitosan has a variety of biological functions through conjugating of other compounds to their amino and hydroxyl groups. To further expand applicability of chitosan, we have modified the amino group of chitosan with 2-iminothiolane to bestow thiol groups and obtained about 20% yield, which is equivalent to 913 mu equiv SH/g chitosan or 457 nequiv SH/nmol chitosan. Bovine serum albumin (BSA) was reacted with N-(c-maleimidocaproyloxy)sulfosuccinimide ester (sulfo-EMCS), and maleimide-modified BSA (MaINBSA) was obtained. The yield of sulfo-EMCS addition was 12.8-36.8 mol MaIN/mol BSA. When the chitosan-SH was reacted with MalN-BSA via thioether, 97.8% of the maleimide group was reacted, and 37.2% of the SH group was consumed. The remaining SH group was quenched by bromoacetamide. This is the first report of covalent conjugation of a protein to chitosan. Our method should find many applications in developing new chitosan-based biomedical materials containing other components such as growth factors and cell adhesion molecules, known to be crucial to cells. Our thiolated chitosan will facilitate conjugation of such biomedical components to provide new types of materials for tissue engineering.
  • S Yamane, N Iwasaki, T Majima, T Funakoshi, T Masuko, K Harada, A Minami, K Monde, S Nishimura
    BIOMATERIALS 26 (6) 611 - 619 0142-9612 2005/02 [Refereed][Not invited]
     
    In this study, we hypothesized that hyaluronic acid could provide superior biological effects on the chondrocytes in a three-dimensional culture system. To test this hypothesis, we investigated the in vitro behavior of rabbit chondrocytes oil a novel chitosan-based hyaluronic acid hybrid polymer fiber. The goal of the current study was to show the Superiority of this novel fiber as a scaffold biomaterial for cartilage tissue engineering. Chitosan polymer fibers (chitosan group) and chitosan-based hyaluronic acid hybrid polymer fibers (HA 0.04% and HA 0.07% groups, chitosan coated with hyaluronic acid 0.04% and 0.07%, respectively) were originally developed by the wetspinning method. Articular chondrocytes were isolated from Japanese white rabbits and cultured in the sheets consisting of each polymer fiber. The effects of each polymer fiber oil cell adhesivity, proliferation, morphological changes. and synthesis of the extracellular matrix were analyzed by quantitative a cell attachment test, DNA quantification, light and scanning electron microscopy, semi-quantitative RT-PCR, and immunohistochemical analysis. Cell adhesivity, proliferation and the synthesis of agrecan were significantly higher in the hybrid fiber (HA 0.04% and 0.07%) groups than in the chitosan group. On the cultured hybrid polymer materials, scanning electron microscopic observation showed that chondrocytes proliferated while maintaining their morphological phenotype and with a rich extracellular matrix synthesis around the cells. Immunohistochemical staining with an anti-type II collagen antibody demonstrated rich production of the type II collagen in the pericellular matrix from the chondrocytes. The chitosan-based hyaluronic acid hybrid polymer fibers show great potential as a desirable biomaterial for cartilaginous tissue scaffolds. (C) 2004 Elsevier Ltd. All rights reserved.
  • Minami A, Iwasaki N, Ishikawa J, Suenaga N, Yasuda K, Kato H
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 10 (2-3) 243 - 248 0218-8104 2005 [Refereed][Not invited]
  • N Iwasaki, ST Yamane, T Majima, Y Kasahara, A Minami, K Harada, S Nonaka, N Maekawa, H Tamura, S Tokura, M Shiono, K Monde, SI Nishimura
    BIOMACROMOLECULES 5 (3) 828 - 833 1525-7797 2004/05 [Refereed][Not invited]
     
    The ideal cell-carrier material for cartilage regeneration should be one that closely mimics the natural environment in a living articular cartilage matrix. In the current study, we considered that alginate-based chitosan hybrid biomaterials could provide excellent supports for chondrocyte adhesion. To test this hypothesis, we investigated the adhesion behavior of rabbit chondrocytes onto an alginate polymer versus the adhesion of the chondrocytes onto some alginate-based chitosan hybrid polymer fibers in vitro. We demonstrated that the alginate-based chitosan hybrid polymer fibers showed much improved adhesion capacity with chondrocytes in comparison with alginate polymer fiber. Additionally, morphologic studies revealed maintenance of the characteristic round morphology of the chondrocyte and the dense fiber of the type II collagen produced by the chondrocytes in the hybrid polymer. On the basis of these results, we conclude that an alginate-based chitosan hybrid polymer fiber has considerable potential as a desirable biomaterial for cartilage tissue scaffolds.
  • T Funakoshi, H Kato, A Minami, N Suenaga, N Iwasaki
    JOURNAL OF SHOULDER AND ELBOW SURGERY 13 (2) 230 - 234 1058-2746 2004/03 [Refereed][Not invited]
  • N Iwasaki, A Minami, N Oizumi, S Yamane, N Suenaga, H Kato
    CLINICAL ORTHOPAEDICS AND RELATED RESEARCH (415) 157 - 162 0009-921X 2003/10 [Refereed][Not invited]
     
    The factors affecting the clinical results after radial osteotomies for Kienbock's disease are unknown. In the current study, we reviewed the data of 41 patients treated with radial osteotomies for Kienbock's disease and analyzed which preoperative factors significantly affected the clinical results of these procedures. Lateral closing wedge osteotomies of the radius were done for 22 patients (six patients with Lichtman Stage II disease, three patients with Lichtman Stage IIIA disease, 12 patients with Lichtman Stage IIIB disease, and one patient with Lichtman Stage IV disease) with zero or positive ulnar variance, and radial shortenings were done for 19 patients (four patients with Stage II disease, two patients with Stage IIIA disease, 12 patients with Stage IIIB disease, and one patient with Stage IV disease) with negative ulnar variance. The mean age of the patients at surgery was 36 years and the average followup was 38 months. To statistically assess the prognostic factors, multiple regression analysis focused on the postoperative clinical score as a dependent variable and preoperative patient data as independent variables. In the current analysis, patient age was the preoperative factor most clearly predictive of clinical results after radial osteotomies for Kienbock's disease. We think that the lower effectiveness of radial osteotomies must be considered in doing these procedures for elderly patients.
  • Treatment of scapholunate dissociation: ligamentous repair associated with modified dorsal capsulodesis.
    Minami A, Kato H, Iwasaki N
    Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 8 (1) 1 - 6 0218-8104 2003/07 [Refereed][Not invited]
  • N Oizumi, N Suenaga, A Minami, N Iwasaki, T Miyazawa
    JOURNAL OF ORTHOPAEDIC RESEARCH 21 (3) 393 - 398 0736-0266 2003/05 [Refereed][Not invited]
     
    When a rotator cuff tear occurs, forces compressing the humeral head toward the glenoid are disturbed, and the kinematics of the glenohumeral joint change. Therefore, stress distributions at the coracoacromial arch in cuff tear shoulders should differ from those in normal shoulders. To investigate this hypothesis, we studied stress distribution patterns at the coracoacromial arch in normal and cuff tear shoulders using a computed tomography (CT) osteoabsorptiometry method, in which bone density correlates directly with long-term physiologic loading. Eight normal subjects and 11 patients with cuff tear were examined. The stress distributions at the undersurface of the acromion and the posterolateral surface of the coracoid process differed markedly between normal and cuff tear shoulders. In cuff tear shoulders, a high-density area was located at the anterior or the anterolateral part of the undersurface of the acromion, while it was located at the posterior part in all but one normal shoulder. Additionally, a high-density area was located at the superior or the lateral part of the coracoid process in most of the cuff tear shoulders; on the other hand, it was located at the base in all but one normal shoulder. We believe that the differences in stress distribution patterns are due to impingement at the coracoacromial arch in cuff tear shoulders. CT osteoabsorptiometry can provide useful information in performing coracoacromial arch decompression for cuff tear shoulders. (C) 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
  • T Gohda, N Iwasaki, C Yoshioka, A Minani
    PLASTIC AND RECONSTRUCTIVE SURGERY 111 (5) 1653 - 1658 0032-1052 2003/04 [Refereed][Not invited]
     
    Although a number of experimental studies have demonstrated that high-dose administration of FK-506 induces the success of limb allogeneic transplantation in rats, some of them have reported occurrences of lethal side effects. Therefore, a more effective regimen with lower-dose administration of this agent must be developed. The objective of this study was to determine an optimal timing of a single-dose administration of FK-506 in rat limb allografts. In the current study, orthotopic hindlimb transplantations were performed using major histocompatibility mismatched pairs of inbred rats. The rats were classified into five groups on the basis of the different time schedules of FK-506 administration as follows: syngeneic group, Lewis-to-Lewis transplantation; control group, ACI-to-Lewis without any immunotherapy; day 0 group, recipients treated with a single-dose administration of FK-506 (5 mg/kg of body weight, intramuscular injection) at day 0 postoperatively; day 1 group, with a single-dose administration of FK-506 at day 1 postoperatively; and day 2 group, with a single-dose administration of FK-506 at day 2 postoperatively. The median graft survival time in each group (n = 5) was 9 days in the control group, 19 days in the day 0 group, 49 days in the day 1 group, and 42 days in the day 2 group. The values in the day 1 and the day 2 groups significantly increased compared with those in other groups. For prolonged survival of a grafted limb, a single-dose administration of FK-506 is more effective at 24 to 48 hours after transplantation.
  • H Kato, N Iwasaki, A Minami, T Kamishima
    JOURNAL OF HAND SURGERY-AMERICAN VOLUME 28A (1) 44 - 47 0363-5023 2003/01 [Refereed][Not invited]
     
    A rare case of acute posterior interosseous nerve palsy caused by septic elbow arthritis is reported. The nerve was compressed beneath the arcade of Frohse by hypertrophied synovium and joint fluid at the anterior aspect of the radial neck. Decompression of the nerve, synovectomy, and irrigation of the elbow joint were done. effective. Six months after the surgery the nerve palsy had recovered completely. Two years after surgery there was no recurrence of the infection or nerve palsy.
  • Minami A, Kato H, Suenaga N, Iwasaki N
    Journal of reconstructive microsurgery 19 (1) 11 - 16 0743-684X 2003/01 [Refereed][Not invited]
  • Akio Minami, Hiroyuki Kato, Naoki Suenaga, Norimasa Iwasaki
    Journal of Orthopaedic Science 8 (3) 319 - 322 0949-2658 2003 [Refereed][Not invited]
     
    The long-term effectiveness of scaphotrapeziotrapezoid (STT) fusion is still controversial. We evaluated our clinical and radiological results of 30 STT fusions in 30 patients (average age 41 years 23 males, 7 females). The follow-up period averaged 84 months. The indications were Kienböck's disease (n = 23), isolated STT arthrosis (n = 6), and dislocation of the trapezium (n = 1). A total of 26 simultaneous associated procedures were performed. Excisional arthroplasty of the lunate was done in all 23 patients with Kienböck's disease. Of the 30 total patients, 5 had post-operative pain ranging from mild to severe 4 patients were dissatisfied with the results. Postoperative ranges of motion of the wrist were 84% of extension and 91% of flexion compared with preoperative motion. The postoperative grip strength improved to 27 kgf from the preoperative value of 18 kgf. Altogether, 26 patients returned to their previous activities. All patients obtained uneventful STT fusion in an average of 11.2 weeks. Eight patients (27%) experienced postoperative complications seven had radioscaphoid arthroses, five had trapeziometacarpal arthrodeses, and one had a flexor pollicis longus tendon rupture. Although radioscaphoid arthrosis occurred in 23% of this series after STT fusion, the results suggest that it is an effective procedure for Kienböck's disease and isolated STT arthrosis.
  • Kato H, Minami A, Suenaga N, Iwasaki N, Kimura T
    Journal of pediatric orthopedics 22 (6) 732 - 735 0271-6798 2002/11 [Refereed][Not invited]
  • Cubital tunnel syndrome associated with medial elbow Ganglia and osteoarthritis of the elbow.
    Kato H, Hirayama T, Minami A, Iwasaki N, Hirachi K
    The Journal of bone and joint surgery. American volume 84-A (8) 1413 - 1419 0021-9355 2002/08 [Refereed][Not invited]
  • Vascularized fibular graft after excision of giant-cell tumor of the distal radius: Wrist arthroplasty versus partial wrist arthrodesis
    A Minami, H Kato, N Iwasaki
    PLASTIC AND RECONSTRUCTIVE SURGERY 110 (1) 112 - 117 0032-1052 2002/07 [Refereed][Not invited]
     
    Several reconstructive procedures have been described for the complete defect of the distal radius that is created after a wide excision of a giant-cell tumor of bone, including hemiarthroplasty using the vascularized fibular head and partial wrist arthrodesis between a vascularized fibula and the scapholunate portion of the proximal carpal row. The objectives of this study are to compare clinical and radiographic results between the partial wrist arthrodesis and the wrist arthroplasty, and to discuss which procedure is superior. Four patients with giant-cell tumors involving the distal end of the radius were treated with en bloc resection and reconstruction with a free vascularized fibular graft. The wrists in two patients were reconstructed with an articular fibular head graft and the remaining two patients underwent partial wrist arthrodesis using a fibular shaft transfer. There was radiographic evidence of bone union at the host-graft junctions in all cases. In the newly reconstructed wrist joint, there was palmar subluxation of the carpal bones and degenerative changes in both patients. Local recurrence was seen in one patient. According to the functional results described by Enneking et al., the mean functional score was 67 percent. The functional scores including wrist/forearm range of motion in the cases with partial wrist arthrodesis were superior to those with wrist arthroplasty. A partial wrist arthrodesis using a vascularized fibular shaft graft appears a more useful and reliable procedure for reconstruction of the wrist after excision of the giant-cell tumor of the distal end of the radius than a wrist arthroplasty using the vascularized fibular head, although our study includes only a small number of patients.
  • Feasibility of immunosuppression in composite tissue allografts by systemic administration of CTLA4Ig
    N Iwasaki, T Gohda, C Yoshioka, A Murakami, M Inobe, A Minami, T Uede
    TRANSPLANTATION 73 (3) 334 - 340 0041-1337 2002/02 [Refereed][Not invited]
     
    Background. Although recent experimental studies have demonstrated CTLA4Ig to be a potent immunosuppressant in vascularized solid organ allografts, little attention has been given to the effect of this soluble recombinant fusion protein on immunosuppression in composite tissue allografts (CTAs). Using a rat hind limb allograft model, we examined the efficacy of CTLA4Ig against the allograft rejection of composite tissue. Methods. The hind limbs of ACI rats (RT1(a)) were heterotopically transplanted to Lewis rats (RT1(1)). Controls received no immunotherapy. Experimental recipients were treated with a single i.p. injection of either human immunoglobulin (Ig)G (0.5 mg/body) or CTLA4Ig (0.5 mg/body) according to different time schedules. Graft survival time and histopathological changes for each experimental group were evaluated and statistically compared. Results. Graft survival times were prolonged significantly in rats treated with CTLA4Ig on day 1 and day 2 after transplantation, compared with survival times of controls. In particular, the most significant prolongation was found in rats treated on day 2. At 7 days after transplantation, moderate-to-severe histological rejection occurred in all tissues in control rats. On the other hand, in rats treated with CTLA4Ig, all tissues showed significantly better preservation. Among these treated rats, the rats treated on day 2 showed excellent histopathological conditions in each tissue. Conclusions. This study supports the feasibility of using CTLA4Ig for preventing acute rejection in CTA. On the basis of the current results, the administration of CTLA4Ig for CTA is more effective at 24-48 hr after transplantation, after the initial immune response has been allowed to begin.

MISC

  • T. Matsuhashi, N. Iwasaki, H. Nakagawa, M. Hato, M. Kurogochi, T. Majima, A. Minami, S. I. Nishimura  OSTEOARTHRITIS AND CARTILAGE  16-  (7)  772  -778  2008/07  [Not refereed][Not invited]
     
    Objective: Osteoarthritis (OA) is the most common of all joint diseases, but the molecular basis of its onset and progression is controversial. Several studies have shown that modifications of N-glycans contribute to pathogenesis. However, little attention has been paid to N-glycan modifications seen in articular cartilage. The goal of this study was to identify disease specific N-glycan expression profiles in degenerated cartilage in a rabbit OA model induced by anterior cruciate ligament transection (ACLT). Methods: Cartilage samples were harvested at 7, 10, 14, and 28 days after ACLT and assessed for cartilage degeneration and alteration in N-glycans. N-Glycans from cartilage were analyzed by high performance liquid chromatography and mass spectrometry. Results: Histological analysis showed that osteoarthritic changes in cartilage occurred 10 days after ACLT. Apparent alterations in the N-glycan peak pattern in cartilage samples were observed 7 days after ACLT, and overall N-glycan changes in CA reflected alterations in both sialylation and fucosylation. These changes apparently preceded histological changes in cartilage. Conclusion: These results indicate that changes in the expression of N-glycans are correlated with OA in an animal model. Understanding mechanisms underlying changes in N-glycans seen in CA may be of therapeutic value in treating cartilage deterioration. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
  • Kinya Nishida, Masataka Horiuchi, Nobuo N. Noda, Kiyohiro Takahasi, Norimasa Iwasaki, Akio Minami, Fuyuhiko Inagaki  ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS  63-  (63)  1061  -1063  2007/12  [Not refereed][Not invited]
     
    The Tob/BTG family is a group of antiproliferative proteins that contain two highly homologous regions named Box A and Box B. These proteins all associate with CCR4-associated factor 1 (Caf1), which belongs to the ribonuclease D family of deadenylases. The antiproliferative region of human Tob (residues 1-138) and intact hCaf1 were co-expressed in Escherichia coli, purified and successfully cocrystallized. The crystal belongs to the tetragonal space group I422, with unit-cell parameters a = b = 150.9, c = 113.9 angstrom, and is estimated to contain one heterodimer per asymmetric unit. The crystal diffracted to around 2.6 angstrom resolution.
  • Norimasa Iwasaki, Hiroyuki Kato, Tamotsu Kamishima, Naoki Suenaga, Akio Minami  AMERICAN JOURNAL OF SPORTS MEDICINE  35-  (12)  2096  -2100  2007/12  [Not refereed][Not invited]
     
    Background: One significant disadvantage of autologous osteochondral mosaicplasty (mosaicplasty) is the harvesting of osteochondral grafts from the normal articular area of the knee joint. However, the effect of harvesting grafts on knee function remains unclear. Purpose: To clarify the functional effects on the donor knee of harvesting osteochondral grafts and to perform magnetic resonance imaging evaluation of donor site repair after mosaicplasty for capitellar osteochondritis dissecans in young athletes. Study Design: Case series; Level of evidence, 4. Methods: Eleven, male competitive athletes with advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. The surgical technique involves obtaining small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting them to osteochondral defects in the capitellum. Assessment at a mean follow-up of 26 months included local findings of the donor knees, a Lysholm knee scoring scale, International Knee Documentation Committee standard evaluation form, and magnetic resonance imaging evaluation. Results: All patients returned to a competitive level of their previous sports without any donor site disturbances. Based on the Lysholm knee score and International Knee Documentation Committee evaluation form, all knees were graded as excellent and normal, respectively. The magnetic resonance imaging showed 50% to 100% defect fill in 6 of 9 patients and normal or nearly normal signals in 4 patients at the donor sites. Conclusion: No adverse effects of osteochondral graft harvest on donor knee function were found after mosaicplasty for capitellar osteochondritis dissecans in young athletes. However, magnetic resonance imaging indicates that the donor site is resurfaced with fibrous tissue.
  • T. Majima, T. Irie, N. Sawaguchi, T. Funakoshi, N. Iwasaki, K. Harada, A. Minami, S-I Nishimura  PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE  221-  (H5)  537  -546  2007/07  [Not refereed][Not invited]
     
    To establish medical use of tissue engineering technology for ligament and tendon injuries, a scaffold was developed which has sufficient ability for cell growth, cell differentiation, and mechanical properties. The scaffold made from chitosan and 0.1 per cent hyaluronic acid has adequate biodegradability and biocompatibility. An animal experiment showed that the scaffold has less toxicity and less inflammation induction. Furthermore, in-vivo animal experiments showed that the mechanical properties of the engineered ligament or tendon had the possibility to stabilize the joint. It was shown that newly developed hybrid-polymer fibre scaffold has feasibility for joint tissue engineering.
  • Masahiko Takahata, Norimasa Iwasaki, Hiroaki Nakagawa, Yuichiro Abe, Takuya Watanabe, Manabu Ito, Tokifumi Majima, Akio Minami  BONE  41-  (1)  77  -86  2007/07  [Not refereed][Not invited]
     
    Sialic acid. which is located at the end of the carbohydrate moiety of cell surface glycoconjugates, is involved in many biologic responses, such as intercellular reactions and virus-cell fusion, especially in hematopoietic cells. Here we provide experimental evidence that the sialic acid of cell surface glycoconjugates has a role in osteoclast differentiation. Lectin histochemical study demonstrated the existence of both alpha (2,3)-linked-sialic acid and alpha (2,6)-linked-sialic acid in mouse bone marrow-derived macrophages and in the RAW264.7 macrophage cell line, which are osteoclast precursors. Flow cytometric analysis of surface lectin staining revealed the kinetics of these sialic acids during osteoclastogenesis: alpha (2,3)-linked-sialic acid was abundantly expressed throughout osteoclastogenesis, whereas alpha (2,6)-linked-sialic acid levels declined at the terminal stage of osteoclast differentiation. To investigate the role of sialic acid in osteoclast differentiation, we performed an osteoclastogenesis assay with or without exogenous sialidase treatment. Desialylated cells formed TRAP-positive mononuclear cells, but did not become multinuclear cells despite the normal expression of osteoclast markers such as cathepsin K, integrin 3, and nuclear factor-ATc1. Flow cytometric analysis also demonstrated that exogenous sialidase effectively removed alpha (2,6)-linked-sialic acid, but only slightly changed the alpha (2,3)-linked-sialic acid content, suggesting that alpha (2,6)-linked-sialic acid might be involved in osteoclast differentiation. Findings from knockdown analysis using small interfering RNA oligonucleotides against alpha 2,6-sialyttransferase support this idea: alpha (2,6)-linked-sialic acid-deficient cells markedly inhibit the formation of multinuclear osteoclasts. Our findings suggest that alpha (2,6)- linked-sialic acid of cell surface glycoconjugates has a role in osteoclast differentiation, possibly via its role in the cell-cell fusion process. (c) 2007 Elsevier Inc. All rights reserved.
  • Hiroaki Nakagawa, Megumi Hato, Yasuhiro Takegawa, Kisaburo Deguchi, Hiroki Ito, Masahiko Takahata, Norimasa Iwasaki, Akio Minami, Shin-Ichiro Nishimura  JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES  853-  (1-2)  133  -137  2007/06  [Not refereed][Not invited]
     
    Altered N-glycosylation occurs in many diseases. In rheumatoid arthritis (RA), for example, reduction in galactose residues in IgG and an increase in fucose residues in alpha 1-acid glycoprotein have been observed. To further analyse N-glycans in disease, we show N-glycan profiling from whole serum employing reversed phase high performance liquid chromatography/negative-ion mode by sonic spray ionization ion trap mass spectrometry with pyridylamination. Profiles from female 15 RA patients and 18 aged-matched healthy women were compared. The most significant change seen in RA was decreased levels of mono-galactosyl bi-antennary N-glycans, in agreement with the previous reports regarding IgG. We also show previously unreported differences between isomers and increased tri-antennary oligosaccharides. These results indicate that LC-MS analysis of whole serum N-glycans can identify N-glycan alterations in RA and that this is a promising method both for studies of RA mechanisms and diagnosis. (c) 2007 Elsevier B.V. All rights reserved.
  • 舟状骨近位部偽関節に対する手術治療―腸骨移植による骨接合術の成績を中心にー(共著)
    東日本整災会誌  19-  419  -422  2007  [Not refereed][Not invited]
  • Trigger wrist caused by tendon adhesion between the flexor pollicis longus and flexor digitorum superficialis tendons: A case report.(共著)
    J Hand Surg Eur  32-  472  -473  2007  [Not refereed][Not invited]
  • Clin Orthop Relat Res  465-  215  -219  2007  [Not refereed][Not invited]
  • J Biomed. Mater. Res. A,  2007  [Not refereed][Not invited]
  • J Bone Joint Surg Am  89-  1238  -1247  2007  [Not refereed][Not invited]
  • Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system.(共著)
    Int J Oncol  30-  461  -467  2007  [Not refereed][Not invited]
  • Makoto Motomiya, Miwako Kobayashi, Norimasa Iwasaki, Akio Minami, Ichiro Matsuoka  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS  352-  (3)  623  -629  2007/01  [Not refereed][Not invited]
     
    We previously identified a family of novel developmentally regulated genes: BRINP1, 2, and 3, which are predominantly and widely expressed in the CNS from earlier developmental stages to adulthood. In the present study, we investigated the activity-dependent regulation of BRINP expression in the CNS. Among the three BRINP genes, BRINP1-mRNA was specifically up-regulated in the dentate gyrus of mouse hippocampus by kainic acid treatment. In cultured hippocampal neurons, the induction of BRINP1-mRNA was also observed by the activation of glutamate receptors. Although BDNF-mRNA is up-regulated in a similar activity-dependent manner, BDNF itself did not induce BRINP1-mRNA. From these results, the physiological roles of the activity-dependent induction of BRINP1-mRNA are discussed. (c) 2006 Elsevier Inc. All rights reserved.
  • Noriaki Mori, Tokifumi Majima, Norimasa Iwasaki, Shigeyuki Kon, Kiyoshi Miyakawa, Chiemi Kimura, Kunio Tanaka, David T. Denhardt, Susan Rittling, Akio Minami, Toshimitsu Uede  MATRIX BIOLOGY  26-  (1)  42  -53  2007/01  [Not refereed][Not invited]
     
    It has been shown that musculoskeletal tissues undergo dynamic tissue remodeling by a process that is quite sensitive to the mechanical environment. However, the detailed molecular mechanism underlying this process remains unclear. We demonstrate here that after denervation-induced mechanical stress deprivation, tendons undergo dynamic tissue remodeling as evidenced by a significant reduction of the collagen fibril diameter. Importantly, the transient up-regulation of osteopontin (OPN) expression was characteristic during the early phase of tendon tissue remodeling. Following this dynamic change of OPN expression, matrix metalloproteinase (MMP)-13 expression was induced, which presumably accounts for the morphological changes of tendon by degrading tendon collagen fibrils. The modulation of MMP-13 expression by OPN was specific, since the expression of MMP-2, which is also known to be involved in tissue remodeling, did not alter in the tendons under the absence or presence of OPN. We also demonstrate that the modulation of MMP-13 expression by OPN is due to the signaling through cell surface receptors for OPN. Thus, we conclude that OPN plays a crucial role in conveying the effect of denervation-induced mechanical stress deprivation to the tendon fibroblasts to degrade the extracellular matrices by regulating MMP-13 expression in tendon fibroblasts. (c) 2006 Elsevier B.V./International Society of Matrix Biology. All rights reserved.
  • N Iwasaki, T Gohda, H Itoga, A Minami, K Kaneda  JOURNAL OF HAND SURGERY-AMERICAN VOLUME  26A-  (3)  540  -545  2001/05  [Not refereed][Not invited]
     
    Differences in the major histocompatibility complex (MHC) between recipients and donors present a problem because of immunologic responses in graft rejection. The purpose of this study is to clarify the efficacy of MHC matching against acute graft rejection of allogeneic limb transplants in rats. Right hindlimb transplantations were performed using various MHC-mismatched pairs of inbred rats. The rats were classified into 5 groups according to the differences in subregions of the RT1 (rat MHC) between the recipient and the donor: group 1, RT1-A,B,D barrier (the differences of RT1-A,B,D subregions); group 2, RT1-A barrier; group 3, RT1-B,D barrier; group 4, RT1-B barrier; and group 5, RT1- D barrier. The mean survival time significantly decreased in group 1 and increased in group 4. The results suggest that MHC matching clearly improves survival of transplanted limbs. Specifically, both RT1-A and D matching is the most effective compatibility in prolonging survival time of allogeneic limb transplants in rats. Copyright (C) 2001 by the American Society for Surgery of the Hand.
  • 遺伝子導入による免疫抑制(共著)
    医学のあゆみ  196-  895  -899  2001  [Not refereed][Not invited]
  • Feasibility of immunosuppression in limb allografts by blocking the CD28/B7 T cell costimularory pathway. (共著)
    47th Annual Meeting Orthopaedic Research Society  2001  [Not refereed][Not invited]
  • 血管柄付き関節移植の実験的研究(共著)
    骨・関節 靭帯  13-  1013  -1017  2000  [Not refereed][Not invited]
  • 部分的手関節固定術のバイオメカニクス(共著)
    13-  (2)  19  -23  2000  [Not refereed][Not invited]
  • Experimental study of vascularized Joint allograft
    13-  1013  -1017  2000  [Not refereed][Not invited]
  • Long-term survival of allogeneic limb grufts induced by CTLA4Ig(共著)
    55th American Society for Surgery of the Hand, Adrian F. Flatt Resident and Fellow Conference  2000  [Not refereed][Not invited]
  • Biomechanics of Limited Intercarpal Fusions
    Monthly Book Orthopaedics  13-  (2)  19  -23  2000  [Not refereed][Not invited]
  • 肘屈曲機能再建術(Steinaler法)の筋力数値解析(共著)
    日本臨床バイオメカニクス学会誌  20-  493  -496  1999  [Not refereed][Not invited]
  • Muscle Force Analysis of Steindler Flexorplasty
    20-  493  -496  1999  [Not refereed][Not invited]
  • Shapping of Triceps Tendon After Anterior Nerve Transposition for Recurrent Subluxation of the Ulhar Nerve(共著)
    Hand Surgery  4-  (2)  193  -196  1999  [Not refereed][Not invited]
  • (]G0319[)骨遠位関節面の生理的荷重条件下における応力分布-CT osteoabsorptimetry法を用いて-(共著)
    日本臨床バイオメカニクス学会誌  19-  237  -240  1998  [Not refereed][Not invited]
  • 正常手関節における3次元力学的解析-剛体バネモデルを用いた理論的解析-
    北海道整形災害外科学会雑誌  40-  (2)  34  -41  1998  [Not refereed][Not invited]
  • In vivo Stress analysis of the joint surface of the distal radius : Using a CT osteoabsorptiometry
    19-  237  -240  1998  [Not refereed][Not invited]
  • Three-dimensional Biomechanical Analysis of Normal Wrist Joint : Theoretical Analysis Using a Rigid Body Spring Model
    40-  (2)  34  -41  1998  [Not refereed][Not invited]
  • Force Trunsmission Through the Wrist Joint in Kienb(]E88D8[)ck's Disease : A Two-Dimensional Theoretical Study(共著)
    Journal of Hand Surgery  (234)  415  -424  1998  [Not refereed][Not invited]
  • 剛体バネモデルを用いたkienbock病における理論的応力解析(共著)
    日本手の外科学会雑誌  13-  (6)  1024  -1027  1997  [Not refereed][Not invited]
  • kienbock病に対する部分的手関節固定術の力学的評価-3次元剛体バネモデルを用いて-(共著)
    日本手の外科学会雑誌  13-  (5)  67  -70  1997  [Not refereed][Not invited]
  • Theoretical Analysis of Force Transmission Through the Wrist Joint in Keinb(]E88D8[)ck's Disease-Using A Two-Dimensional Rigid Body Spring Model-
    13-  (6)  1024  -1027  1997  [Not refereed][Not invited]
  • Biomechanical Analysis of Limited Intercarpal Fusion of Treating Kienb(]E88D8[)ck's Disease : Using a Three-Dimensional Rigid Body Spring Model
    13-  (5)  67  -70  1997  [Not refereed][Not invited]

Research Grants & Projects

  • 組織工学的手法を用いた軟骨再生
  • 同種肢移植に関する実験的研究
  • 上肢におけるバイオメカニクス
  • Cartilage Regeneration Using Tissue Engineering Technique
  • Experimental Study on Allogeneic Limb Transplantation
  • Biomechanics of Upper Extremity

Educational Activities

Teaching Experience

  • 研究発表技法Ⅰ
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
  • Advanced Social and behavioral Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 健康増進科学、健康増進活動、栄養、食生活、運動、身体活動
  • 研究発表技法Ⅱ
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
  • Master's Thesis Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 整形外科学的研究,筋骨格系研究,脊髄末梢神経研究
  • 研究発表技法Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Basic Principles of Medicine
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 運動器,形態学,骨軟骨代謝学,免疫学,運動学,生体力学
  • 研究発表技法Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Basic Principles of Medicine
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 脊椎再建医学、組織工学、分子生物学
  • 基盤医学研究Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Soft Matter Medical Engineering
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 生命科学院
    キーワード : 再生医学、臨床医学、入門
  • 基盤医学研究Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Principles of Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 脊椎再建医学、組織工学、骨代謝、分子生物学
  • 臨床医学研究Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Dissertation Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 運動器,形態学、骨軟骨代謝学,免疫学、運動学、生体材料工学、生体力学,再生工学
  • 臨床医学研究Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Principles of Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 運動器,形態学、骨・軟骨代謝学,免疫学、運動学、生体力学,生体工学,生体材料
  • 医学総論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Dissertation Research in Clinical Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 運動器,病態,治療法,臨床研究
  • 研究発表技法Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
  • 研究発表技法Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
  • 整形外科学・スポーツ医学
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部
  • 選択実習Ⅰ
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部
  • 選択実習Ⅱ
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部
  • 全科臨床実習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部
  • 診療参加型選択科臨床実習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部

Campus Position History

  • 2019年4月1日 
    2021年3月31日 
    教育研究評議会評議員
  • 2019年4月1日 
    2021年3月31日 
    大学院医学院副学院長
  • 2019年4月1日 
    2021年3月31日 
    大学院医学研究院副研究院長

Position History

  • 2019年4月1日 
    2021年3月31日 
    教育研究評議会評議員
  • 2019年4月1日 
    2021年3月31日 
    大学院医学院副学院長
  • 2019年4月1日 
    2021年3月31日 
    大学院医学研究院副研究院長


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