Yukihide Iwamoto

Kyushu University, Hukuoka, Fukuoka, Japan

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Publications (731)1819.87 Total impact

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    ABSTRACT: CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that is activated in the synovium in rheumatoid arthritis (RA) and promotes expression of various matrix metalloproteinases. In this study, we examined whether C/EBPβ mediates the expression of receptor activator of nuclear factor-kappa-B ligand (RANKL) and drives osteoclast formation in primary fibroblast-like synoviocytes (FLS) from RA patients. The cooperation of C/EBPβ and activation transcription factor-4 (ATF4) in the regulation of the RANKL promoter was also investigated. Immunofluorescence staining was performed for C/EBPβ, RANKL, and ATF4 in synovium from RA patients. Adenovirus expression vectors for two major isoforms, C/EBPβ-liver-enriched activator protein (LAP) and - liver-enriched inhibitory protein (LIP), or small interfering RNA for C/EBPβ, were used to manipulate C/EBPβ expression in RA-FLS. RA-FLS over-expressing C/EBPβ were co-cultured with peripheral blood mononuclear cells (PBMCs) to test osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. A promoter assay for RANKL, a chromatin immunoprecipitation (ChIP) assay and an immunoprecipitation (IP) assay were also performed. Immunofluorescence staining showed colocalization of C/EBPβ, ATF4 and RANKL in RA synovium. Western blotting revealed the expression of C/EBPβ-LAP and -LIP in RA-FLS. Over-expression of either C/EBPβ-LAP or -LIP significantly increased the expression of RANKL mRNA, while C/EBPβ-LIP down-regulated osteoprotegerin (OPG) mRNA. The RANKL/OPG mRNA ratio was significantly increased by C/EBPβ-LIP over-expression. Knockdown of C/EBPβ with siRNA decreased the expression of RANKL mRNA. The number of TRAP-positive multinucleated cells was increased in co-cultures of PBMCs and FLS over-expressing either C/EBPβ-LAP or -LIP, but was more significant with LIP. C/EBPβ-LIP does not have a transactivation domain. However, promoter assays showed that C/EBPβ-LIP and ATF4 synergistically transactivate the RANKL promoter. ChIP and IP assays revealed the cooperative binding of C/EBPβ and ATF4 on the RANKL promoter. We demonstrated that C/EBPβ, especially C/EBPβ-LIP in cooperation with ATF4, is involved in osteoclast formation by regulating RANKL expression in RA-FLS. These findings suggest that C/EBPβ plays a crucial role in bone destruction in RA joints.
    Arthritis Research & Therapy 12/2015; 17(1). DOI:10.1186/s13075-015-0532-6 · 4.12 Impact Factor
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    ABSTRACT: In patients with degenerative meniscal tears, subclinical cartilage degeneration may be present even if gross morphological changes are not evident. The aim of this study was to detect occult cartilage degeneration using T1ρ MRI mapping in patients with meniscal tears without obvious radiographic osteoarthritis (OA). A total of 22 subjects with degenerative meniscal tears in the early stages of osteoarthritis [Kellgren-Lawrence (KL) grade of 0-2] and 19 healthy subjects as the control group were examined. The femoral condyle was divided into four 30° wedges (-30°-0° anteriorly, 0°-30°, 30°-60° and 60°-90° posteriorly), and each area of cartilage was further divided into superficial and deep layers of equal thickness. The tibial side was divided into anterior and posterior areas with superficial and deep layers in each. The mean T1ρ values (ms) in each area were calculated. On the femoral side, T1ρ values of the superficial and deep regions (-30°-0°, 0°-30° and 30°-60°) in the meniscal tear group were significantly higher than those in the control group [superficial (-30°-0°): 49.0 ± 4.0 (meniscal tear group) vs 45.1 ± 2.1 (control group), deep (-30°-0°): 45.2 ± 3.3 vs 39.5 ± 5.0, superficial (0°-30°): 54.5 ± 5.3 vs 47.4 ± 5.7, deep (0°-30°): 46.8 ± 4.0 vs 40.7 ± 6.3, superficial (30°-60°): 50.5 ± 3.1 vs 47.1 ± 5.7]. On the tibial side, the meniscal tear group had significantly higher T1ρ values superficially in both anterior and posterior regions compared with the control group [superficial (anterior): 52.0 ± 4.3 vs 46.7 ± 5.4, superficial (posterior): 53.1 ± 5.1 vs 46.0 ± 4.9]. Moreover, these significant differences were observed when comparing patients in the meniscal tear group with KL grades of 0 or 1 and the control group. Our study suggested that early biochemical changes in cartilage associated with degenerative meniscal tears occur first in the superficial zones in areas of contact during slight flexion. Characterising the early relationship between cartilage degeneration and degenerative meniscal tears using T1ρ MRI mapping may be of clinical benefit and provide further evidence linking meniscal injury to OA.
    BMC Musculoskeletal Disorders 12/2015; 16(1). DOI:10.1186/s12891-015-0487-4 · 1.90 Impact Factor
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    ABSTRACT: Fracture of the femoral stem in total hip arthroplasty (THA) is a rare complication. We have encountered 2 cases of neck fractures of the femoral stem occurring 9 and 12 years after THA. Morphological and biomechanical analysis were performed to investigate the mechanism of these fractures. A titanium alloy femoral stem having a slot with sharp corners (R = 0.2 mm) at the neck had been implanted in both cases. Fracture surfaces were examined by use of scanning electron microscopy (SEM). Stress concentration was simulated by using a finite element method (FEM) to compare slots with sharp (R = 0.2 mm) and smooth (R = 2 mm) corners. Study of the retrieved stems revealed that neck fractures had occurred at the distal end of the slot in both cases. SEM revealed numerous fine fissures extending from the anterolateral edge, striations on the middle of the fracture surface, and dimples on the posteromedial surface, suggesting that the fractures had occurred from the anterolateral aspect toward the posteromedial aspect because of metallic fatigue. FEM analysis showed that mechanical stress was concentrated at the distal and anterolateral corners of the slot. Under 3500-N loading force, the stress at the sharp corner was 556 MPa, which was approximately twofold that at the smooth corner and exceeded the fatigue strength of titanium alloy. These findings showed that the sharp corner of slot increased stress concentrations at the anterolateral aspect and led to the neck fractures.
    Journal of Orthopaedic Science 07/2015; DOI:10.1007/s00776-015-0745-1 · 1.01 Impact Factor
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    ABSTRACT: This study examined the outcomes of applying transtrochanteric rotational osteotomy (TRO) for posttraumatic osteonecrosis of the femoral head (ON). We retrospectively reviewed 28 hips in 28 patients (male, n = 17; female n = 11) with a mean age of 34.8 years (12-61 years) at the time of TRO. Transtrochanteric anterior rotational osteotomy (ARO) was used when the lesion was localized on the anterior aspect of the femoral head, and transtrochanteric posterior rotational osteotomy (PRO) was indicated in patients with lesions limited to the posterior aspect of the femoral head. The mean follow-up period was 12.3 years (5.0-21.3 years). We investigated the patients' clinical and radiological factors, including age, sex, body mass index, preoperative Harris Hip Score (HHS), type of antecedent trauma, preoperative stage, and postoperative intact ratio (the ratio of the intact articular surface of the femoral head to the weight-bearing surface of the acetabulum). We divided the patients into a hip-survival group and a conversion-to-total hip arthroplasty (THA) group and then compared these factors between the two groups. At the final follow-up, 22 hips had survived with a mean HHS of 85.8. The remaining six hips underwent THA at a mean of 10.2 years after TRO. The preoperative stage was correlated with hip survival. Furthermore, the postoperative intact ratio was significantly lower in the conversion-to-THA group. Based on the receiver operating characteristic curve, a ratio of less than 33.6 % was found to be associated with the need to convert to THA. TRO to correct posttraumatic ON resulted in favorable midterm results. The possible risk factors for conversion to THA were an advanced preoperative stage and a postoperative intact ratio of less than 33.6 %.
    Archives of Orthopaedic and Trauma Surgery 07/2015; DOI:10.1007/s00402-015-2282-y · 1.36 Impact Factor
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    ABSTRACT: Neural stem/progenitor cell (NSPC) transplantation is a promising therapeutic strategy for spinal cord injury (SCI). However, the efficacy of NSPC transplantation on severe SCI is poorly understood. We herein show that NSPC transplantation promotes functional recovery after mild and moderate SCI, but not after severe SCI. In severe SCI mice, there were few remaining host neurons within the range of NSPC engraftment; thus, we examined whether the co-distribution of transplant and host is a contributory factor for functional improvement. A cellular selective analysis using laser microdissection revealed that drug-induced host neuronal ablation considerably decreased the synaptogenic potential of the engrafted NSPCs. Furthermore, following host neuronal ablation, neuronal retrograde tracing showed less propriospinal relay connections bridging the lesion after NSPC transplantation. Our findings suggest that the interactive synaptic reorganization between engrafted NSPCs and spared host neurons is crucial for functional recovery, providing significant insight for establishing therapeutic strategies for severe SCI. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Stem Cell Reports 07/2015; DOI:10.1016/j.stemcr.2015.06.004
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    ABSTRACT: Subchondral insufficiency fracture of the femoral head may be confused with osteonecrosis, mainly because of radiological overlap. SPECT/CT with Tc-99 m hydroxymethylene diphosphonate images in 7 patients with subchondral insufficiency fracture were retrospectively reviewed and compared with those from 11 patients with symptomatic early osteonecrosis. In all of the hips with subchondral insufficiency fracture, SPECT/CT showed increased uptake at the subchondral lesions of the femoral head. On the other hand, in all of the hips with osteonecrosis, absence of uptake was confirmed at the subchondral lesions. SPECT/CT may assist in differentiating subchondral insufficiency fracture from osteonecrosis.
    Clinical nuclear medicine 07/2015; DOI:10.1097/RLU.0000000000000886 · 2.86 Impact Factor
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    ABSTRACT: The purpose of our study was to evaluate the accuracy of the tibial bone cut in total knee arthroplasty using the anterior tibial border as a guide compared to using bony and soft tissue landmarks of the ankle joint. The extramedullary alignment guide was set parallel to a line connecting the proximal and distal one-thirds of the anterior border of the tibia while the rotational direction of the distal end of the guide was adjusted to the anteroposterior axis of the proximal tibia. Significant differences were detected in the ideal coronal tibial component angles with improvements from 87.2% to 95.9%. In conclusion, the anterior tibial border was a reliable landmark in total knee arthroplasty in clinical practice, as shown by our previous computer simulation.
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    ABSTRACT: Deep venous thrombosis (DVT) in spinal cord injury (SCI) patients is a life-threatening comorbidity. Despite its seriousness, prophylaxis and screening for DVT in SCI patients is still not sophisticated. This study aimed to (i) define the epidemiology and incidence of DVT in acute traumatic cervical SCI in a Japanese population; (ii) determine the best timing for DVT screening; and (iii) determine the optimal D-dimer threshold level for use as an easy and minimally invasive screening tool. A prospective clinical study. Acute traumatic cervical SCI patients who were admitted to our facility within two weeks after injury. Multivariate logistic regression was performed for outcome measure. We enrolled 268 patients (223 men and 45 women), between April 2007 and December 2012. After excluding early drop-out patients, 211 patients remained. Assessment for neurological status and blood chemistry, especially blood coagulation levels (prothrombin time, prothrombin time-international normalized ratio, activated partial thromboplastin time, and serum D-dimer) was performed every week until one month after injury. Ultrasonography was performed for DVT detection every two weeks. This study was funded by The General Insurance Association of Japan, The Japan Labour Health and Welfare Organization, and The Japan Orthopedics and Traumatology Foundation, and there was no conflict of interest. DVTs were detected in 22 patients (10.4% of patients studied). All DVT-positive patients demonstrated severe paralysis classified as C or greater on the ASIA Impairment Scale. Multivariate logistic regression of clinical and laboratory parameters revealed that only the D-dimer level at two weeks after injury was an accurate predictor of DVT formation. The optimal threshold of D-dimer for prediction was determined to be 16 μg/dL. The sensitivity and specificity for detecting DVT were 77.3% and 69.2%, respectively. D-dimer levels may be used to predict the likelihood of DVT development in patients with acute cervical SCI. Furthermore, the optimal timing for screening test by D-dimer is two weeks after injury and optimal threshold level for D-dimer for diagnosing DVT is 16 μg/dL. Such a screening test would be cost-efficient and simple to administer, and could then be followed with additional investigations, such as ultrasonography or venography. Copyright © 2015 Elsevier Inc. All rights reserved.
    The spine journal: official journal of the North American Spine Society 06/2015; DOI:10.1016/j.spinee.2015.06.060 · 2.80 Impact Factor
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    ABSTRACT: Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associated with bone metastases in prostate and breast cancer patients, and is known to occur in ES. Here we investigated the effects of Cad-11 on bone metastases of ES. Human ES cell lines RD-ES, SK-ES-1, SK-N-MC, and TC-71 cells were transduced with lentivirus containing Cad-11 shRNA or control shRNA (ES/Cad-11 and ES/Ctr). RD-ES and TC-71 were infected with a lentivirus luciferase vector. Adhesion assays were performed using these cells and recombinant Cad-11-Fc chimera or mouse osteoblast cell line MC3T3-E1. Cell motility was investigated via wound-healing assay. Intracardiac injection of RD-ES/Cad-11 and RD-ES/Ctr was used to create a mouse model of experimental bone metastasis. The association between Cad-11 expression and bone metastases and clinical prognosis in ES patients was analyzed by immunohistochemistry. We found knockdown of Cad-11 in ES cells resulted in reduced attachment ability and cell motility. In a mouse model of metastasis, RD-ES/Cad-11 cells caused fewer metastases than RD-ES/Ctr cells. The expression of Cad-11 in ES patients was significantly related to bone metastases (P < 0.05, logistic regression) and poorer overall survival (P < 0.05, log-rank test). These findings may explain that Cad-11 in ES cells may be essential for cell adhesion and motility, and is a promising molecular target for patients with ES.
    Clinical and Experimental Metastasis 06/2015; DOI:10.1007/s10585-015-9729-y · 3.73 Impact Factor
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    ABSTRACT: A 37-year-old female had been treated with corticosteroids for systemic lupus erythematosus clinically diagnosed at age 10. She suddenly had right hip pain without any antecedent trauma. Four months after the onset of pain, she visited her primary care physician. On magnetic resonance imaging, joint space narrowing at the weight-bearing area was already seen with bone marrow edematous lesions in both the femoral head and acetabulum. She was treated non-operatively; however, her pain continued to worsen in severity. Thirteen months after the onset of pain, she was referred to our hospital. A plain radiograph showed subluxation of the collapsed femoral head accompanied by destruction of the acetabular rim. Because of her severe intractable pain, she underwent total hip arthroplasty 1 month after her first visit. Histological examination of the resected femoral head revealed pseudogranulomatous lesions along with prominent callus formation, suggesting rapid destruction of the femoral head.
    Rheumatology International 06/2015; DOI:10.1007/s00296-015-3304-3 · 1.63 Impact Factor
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    ABSTRACT: Background Combined anteversion is the sum of femoral and acetabular anteversion and represents their morphological relationship in the axial plane. Few studies have investigated the native combined anteversion in patients with symptomatic dysplastic hips. Questions/purposes We hypothesized the following: (1) dysplastic hips have two distinct populations, which differ from each other and from normal hips in their combined anteversion; and (2) these populations differ clinically in terms of correlation between age of onset of symptoms and amount of anteversion. Methods We measured radiographic parameters by CT of 100 dysplastic hips in 76 patients who were symptomatic enough to undergo periacetabular osteotomy and of 50 normal hips in 44 patients who had CT scans as part of preparation for computer-navigated TKAs; these patients had no visible hip arthritis or dysplasia and no hip symptoms. Dysplastic hips were divided into the anteversion (83 hips) and retroversion groups (17 hips) based on acetabular version. Age at pain onset was determined from their medical charts. Results Combined anteversion in the anteversion group was greater than that in the retroversion and control groups: 47° ± 12°, 30° ± 16°, and 36° ± 9°, respectively. In the anteversion group, combined anteversion (r = −0.49; 95% confidence interval [CI], −0.66 to −0.27; p Conclusions These results suggest that not only lateral coverage of the femoral head, but also axial joint morphology is important for the development of pain in the anteversion group. Optimal combined anteversion should be considered during periacetabular osteotomy. Level of Evidence Level IV, prognostic study.
    Clinical Orthopaedics and Related Research 05/2015; DOI:10.1007/s11999-015-4373-z · 2.88 Impact Factor
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    ABSTRACT: Amyloid deposits are prevalent in osteoarthritis (OA)-affected joints. This study defined the dominant precursor and determined if the deposits affect chondrocyte functions. Amyloid deposition in normal and OA human knee cartilage was determined by Congo red staining. Transthyretin (TTR) in cartilage and synovial fluid was analyzed by immunohistochemistry and western blotting. The effects of recombinant amyloidogenic and non-amyloidogenic TTR variants were tested in human chondrocyte cultures. Normal cartilage from young donors did not contain detectable amyloid deposits but 58% (7/12) of aged normal cartilage and 100% (12/12) of OA cartilage samples showed Congo red staining with green birefringence under polarized light. TTR, located predominantly at the cartilage surfaces, was detected in all OA and a majority of aged, but not young normal cartilage. Chondrocytes and synoviocytes did not contain significant amounts of TTR mRNA. Synovial fluid TTR levels were similar in normal and OA knees. In cultured chondrocytes, only an amyloidogenic TTR variant induced cell death, the expression of proinflammatory cytokines, and extracellular matrix degrading enzymes. The effects of amyloidogenic TTR on gene expression were mediated by in part by Toll-like receptor-4, Receptor for advanced glycation endproducts and p38 MAP kinase. TTR-induced cytotoxicity was inhibited by resveratrol, a plant polyphenol that stabilizes the native tetrameric structure of TTR. The findings are the first to suggest that TTR amyloid deposition contributes to cell and extracellular matrix damage in articular cartilage in human OA and that therapies designed to reduce TTR amyloid formation might be useful. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    05/2015; DOI:10.1002/art.39178
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    ABSTRACT: Background: Patients with anterior cruciate ligament (ACL)-injured knees are at an increased risk of posttraumatic osteoarthritis (OA). OA changes secondary to ACL injuries have many variations, and when and where early cartilage degenerative change begins has not yet been established.
    05/2015; 3(5). DOI:10.1177/2325967115585092
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    ABSTRACT: Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)‑6, and IL‑17. Effective treatments, including pathogenesis‑based biological agents against psoriasis, are currently under development. Although the role of reactive oxygen species (ROS) in the pathogenesis of psoriasis has been investigated, it remains to be fully elucidated; ROS‑targeted therapeutic strategies are also lacking at present. Therefore, the objective of the present study was to assess whether H2, a ROS scavenger, has a therapeutic effect on psoriasis‑associated inflammation by reducing hydroxyl radicals or peroxynitrite in the immunogenic psoriasis cascade. Three methods were used to administer H2: Drop infusion of saline containing 1 ppm H2 (H2‑saline), inhalation of 3% H2 gas, and drinking of water containing a high concentration (5‑7‑ppm) of H2 (high‑H2 water). Treatment efficacy was estimated using the disease activity score 28 (DAS28) system, based on C‑reactive protein levels, and the psoriasis area and severity index (PASI) score, determined at baseline and following each H2 treatment. Furthermore, levels of TNFα, IL‑6, and IL‑17 were analyzed. The DAS28 and PASI score of the three patients decreased during H2 treatment, regardless of the administration method. The psoriatic skin lesions almost disappeared at the end of the treatment. IL‑6 levels decreased during H2 treatment in Case 1 and 2. IL‑17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. In conclusion, H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis‑associated skin lesions and arthritis.
    Molecular Medicine Reports 04/2015; DOI:10.3892/mmr.2015.3707 · 1.48 Impact Factor
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    ABSTRACT: The configuration of the distal surface of the femur would be more important in terms of the patellofemoral (PF) joint contact because the patella generally contacts with the distal surface of the femur in knee flexion. Some total knee arthroplasty (TKA) designs configurate medially prominent asymmetric femoral condyles. This difference in the design of distal femoral condyle may affect the PF joint congruity in knee flexion. Furthermore, some surgeons advocate a concept aligning the symmetric components parallel to the native joint inclination, not perpendicular to the mechanical axis. This concept would also make a difference on the PF joint congruity at the distal femur in knee flexion. However, no fundamental study has been reported on the PF congruity at the distal femur to discuss the theoretical priority of these concepts. The current study investigated the angular relationship between the tibial attachment of the patellar tendon and the distal surface of the femur at 90° of flexion in normal knees. The open magnetic resonance images of 45 normal knees at 90° of flexion were used to measure the angles between the tibial attachment of the patellar tendon, the equatorial line of the patella, and the distal surface of femoral condyles. The distal surface of femoral condyles was internally rotated relative to the tibial attachment of the patellar tendon and the equatorial line of the patella in all the knees (8.2° ± 3.5° and 5.8° ± 2.5°, respectively), not parallel. Distal femoral condyle is internally rotated to the patellar tendon at 90° of flexion in normal knees. When the symmetric femoral component is aligned perpendicular to the femoral mechanical axis, the patellar tendon would be possibly more twisted than the condition in normal knees, and the deviation of the PF contact force on the patellar component might be caused. The configuration and alignment of the distal condyle of the femoral component can affect the PF joint congruity in knee flexion. In this respect, our results provide important information in considering designs and alignment in the distal femur of TKA and the PF joint congruity in knee flexion.
    Journal of Orthopaedic Surgery and Research 04/2015; 10(1):54. DOI:10.1186/s13018-015-0197-5 · 1.58 Impact Factor
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    ABSTRACT: Nontraumatic osteonecrosis of the femoral head (ONFH) is a rare disorder caused by ischemic necrosis of unknown etiology. A few studies have demonstrated trends in the number of patients with ONFH. However, there are no data on temporal trends in characteristics such as age, gender, and causative factors. To investigate this, we examined data from a multicenter hospital-based sentinel monitoring system in Japan. A total of 3041 newly-diagnosed ONFH patients from 34 participating hospitals who were reported to the system from 1997-2011 were analyzed. We examined age at diagnosis, potential causative factors, and underlying diseases for which patients received systemic steroid administration. Their temporal trends were assessed according to date of diagnosis in 5-year intervals (1997-2001, 2002-2006, and 2007-2011). The gender ratio and distribution of potential causative factors did not change. Regarding underlying diseases requiring steroid administration, the proportion of patients with systemic lupus erythematosus decreased in males (10% to 6.4%) and in females (37% to 29%). Proportion of patients with renal transplantation fell consistently across the study period in both males (3.8% to 1.2%) and females (3.2% to 0.8%). In contrast, the proportion of patients receiving steroids for pulmonary disease (except asthma) significantly increased in both males (0.5% to 5.5%) and females (0.5% to 3.6%). This large descriptive study is the first to investigate temporal trends in the characteristics of ONFH, which provide useful information for future studies.
    Journal of Epidemiology 04/2015; 25(6). DOI:10.2188/jea.JE20140162 · 2.86 Impact Factor
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    ABSTRACT: The efficacy of perioperative chemotherapy for soft tissue sarcomas is controversial and only a few prospective studies of pre-operative chemotherapy for soft tissue sarcomas in the extremities have been reported. We therefore carried out Phase II study of perioperative chemotherapy for patients with soft tissue sarcomas in the extremities. Patients with Stage III non-round cell soft tissue sarcomas in the extremities were eligible. The patients were treated with pre-operative chemotherapy consisted of doxorubicin 60 mg/m(2) and ifosfamide 10 g/m(2) for three courses. After the tumor resection, additional two courses of the same regimen were carried out. A total of 72 patients were enrolled and 70 patients were eligible. The median age of the patients was 49 years. The major pathological subtypes were synovial sarcoma in 20 and undifferentiated pleomorphic sarcoma in 17 patients. The protocol treatments were completed in 74% of the eligible cases. The 2-year and 5-year progression-free survival rates were 75.7% (95%CI, 63.9-84.1%) and 63.8% (95%CI, 51.3-73.9%), respectively. The 5-year overall survival was 82.6% (95%CI, 71.3-89.7%). There was no treatment-related death. Grade 3 or 4 hematological toxicities (leucopenia and neutropenia) were observed in most of the patients. Although the toxicities of the regimen were significant, pre-operative chemotherapy followed by post-operative chemotherapy using doxorubicin and high-dose ifosfamide was feasible. The outcome of the trial for the patients with high-grade soft tissue sarcomas in the extremities was favorable, and this regimen is promising for further investigation. This trial was registered at the UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/) as C000000096. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Japanese Journal of Clinical Oncology 04/2015; DOI:10.1093/jjco/hyv042 · 1.75 Impact Factor
  • Osteoarthritis and Cartilage 04/2015; 23:A195. DOI:10.1016/j.joca.2015.02.985 · 4.66 Impact Factor
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    ABSTRACT: To investigate the prevalence of and to identify independent predictors associated with scoliosis in patients with multiple hereditary exostoses (MHE). Fifty patients with MHE were clinically examined, and the diagnosis of scoliosis was made based on radiographs. To classify disease severity, three classes based on the presence of deformities and functional limitations were defined. Significant independent predictors of scoliosis in MHE were statistically analyzed. Scoliosis was present in 36 patients (MHE-scoliosis) (72 %). In the MHE-scoliosis group, the mean primary curve was 15.3° ± 5.7° (range 10°-34°) and the mean minor curve was 10.6° ± 7° (range 6°-32°). Left curve was predominant (72 %), and the apex was located in the thoracolumbar or lumbar spine in 64 % of patients. Univariable and multivariable analyses confirmed that MHE severity was a significant predictor of moderate scoliosis (≥20°). Our study confirmed that scoliosis is a common feature of MHE and disease severity is a predictor of moderate scoliosis (≥20°).
    European Spine Journal 03/2015; DOI:10.1007/s00586-015-3883-4 · 2.47 Impact Factor
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    ABSTRACT: We used a musculoskeletal model validated with in vivo data to evaluate the effect of tibial posterior slope on knee kinematics, quadriceps force, and patellofemoral contact force after posterior-stabilized total knee arthroplasty. The maximum quadriceps force and patellofemoral contact force decreased with increasing posterior slope. Anterior sliding of the tibial component and anterior impingement of the anterior aspect of the tibial post were observed with tibial posterior slopes of at least 5° and 10°, respectively. Increased tibial posterior slope contributes to improved exercise efficiency during knee extension, however excessive tibial posterior slope should be avoided to prevent knee instability. Based on our computer simulation we recommend tibial posterior slopes of less than 5° in posterior-stabilized total knee arthroplasty. Copyright © 2015. Published by Elsevier Inc.
    The Journal of arthroplasty 03/2015; DOI:10.1016/j.arth.2015.02.042 · 2.37 Impact Factor

Publication Stats

10k Citations
1,819.87 Total Impact Points


  • 1992–2015
    • Kyushu University
      • Department of Orthopaedic Surgery
      Hukuoka, Fukuoka, Japan
  • 2014
    • Saga University
      • Department of Advanced Technology Fusion
      Сага Япония, Saga Prefecture, Japan
  • 2013
    • Osaka City University
      Ōsaka, Ōsaka, Japan
    • The Scripps Research Institute
      • Department of Molecular and Experimental Medicine
      La Jolla, California, United States
  • 2011
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
  • 2002–2009
    • Kyushu Sangyo University
      Hukuoka, Fukuoka, Japan
    • National Institutes of Health
      Maryland, United States
  • 2007–2008
    • Hospital for Special Surgery
      • Department of Radiology and Imaging
      New York, New York, United States
  • 2001–2007
    • Fukuoka University
      • Department of Orthopaedic Surgery
      Hukuoka, Fukuoka, Japan
    • Matsuyama Red Cross Hospital
      Matuyama, Ehime, Japan
  • 2006
    • Keio University
      • Department of Orthopedic Surgery
      Edo, Tōkyō, Japan
    • National Institute of Allergy and Infectious Diseases
      Maryland, United States
    • Okayama University
      • Department of Orthopaedic Surgery
      Okayama, Okayama, Japan
  • 2004
    • National Cancer Center, Japan
      Edo, Tōkyō, Japan
    • Kitakyushu University
      • Faculty of Environmental Engineering
      Kitakyūshū, Fukuoka-ken, Japan
  • 2003
    • Kitasato University
      • Department of Orthopedic Surgery
      Edo, Tōkyō, Japan
    • Bryn Mawr College
      Bryn Mawr, Pennsylvania, United States
  • 2001–2003
    • Kyushu Rosai Hospital
      Kitakyūshū, Fukuoka, Japan