Kiminori Yukata, Takeshi Nikawa, Mitsuhiko Takahashi and Natsuo Yasui : Overexpressed osteoactivin reduced osteoclastic callus resorption during distraction osteogenesis in mice, Journal of Pediatric Orthopaedics. Part B, Vol.30, No.5, 500-506, 2021.
(Summary)
Distraction osteogenesis is a widely used surgical technique to treat bone deformity and shortening. Several biological treatments have been studied to enhance bone formation during distraction osteogenesis in animals. However, role of osteoactivin in the osseous tissues during distraction osteogenesis remains poorly understood. In this animal experimental study, we investigated the spatiotemporal expression of osteoactivin by immunohistochemistry and real-time PCR using a mouse model for tibial lengthening. Furthermore, to address the role of osteoactivin in bone lengthening, we subjected the osteoactivin-transgenic mice to distraction osteogenesis model. During the lag phase, the fibroblast-like cells (possible progenitors of the osteoblasts or chondrocytes), which mainly express osteoactivin, were infiltrated into the osteotomy site. Osteoactivin was ubiquitously expressed in the lengthened segment during the distraction and consolidation phases. Consistent with the immunohistochemical analysis, the levels of the osteoactivin transcripts in the tibias were significantly increased throughout the distraction osteogenesis process. The bone mineral content in the osteoactivin-transgenic mice calculated using peripheral quantitative computed tomography was also significantly increased at the remodeling zone. The histomorphometric analysis revealed that newly formed callus resorption in the remodeling zone was significantly reduced but bone formation was not altered in the osteoactivin-transgenic mice. We conclude that osteoactivin functions as an inhibitor of callus resorption during the consolidation phase of distraction osteogenesis.
(Keyword)
Animals / Bone Resorption / Bone and Bones / Eye Proteins / Membrane Glycoproteins / Mice / Mice, Transgenic / Osteogenesis, Distraction / Osteotomy / Tibia
Ravi Savarirayan, Louise Tofts, Melita Irving, William Wilcox, A Carlos Bacino, Julie Hoover-Fong, Rosendo Font Ullot, Paul Harmatz, Frank Rutsch, B Michael Bober, E Lynda Polgreen, Ignacio Ginebreda, Klaus Mohnike, Joel Charrow, Daniel Hoernschemeyer, Keiichi Ozono, Yasemin Alanay, Paul Arundel, Shoji Kagami, Natsuo Yasui, K Klane White, M Howard Saal, Antonio Leiva-Gea, Felipe Luna-González, Hiroshi Mochizuki, Donald Basel, M Dania Porco, Kala Jayaram, Elena Fisheleva, Alice Huntsman-Labed and Jonathan Day : Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial., The Lancet, Vol.396, No.10252, 684-692, 2020.
(Summary)
BioMarin Pharmaceutical.
(Keyword)
Absorptiometry, Photon / Achondroplasia / Adolescent / Biomarkers / Body Height / Bone Density / Child / Child, Preschool / Collagen Type X / Double-Blind Method / Female / Humans / Injection Site Reaction / Injections, Subcutaneous / Male / Natriuretic Peptide, C-Type / Osteogenesis
Shun-ichi Toki, Kousaku Higashino, Hiroaki Manabe, Masatoshi Morimoto, Kosuke Sugiura, Fumitake Tezuka, Kazuta Yamashita, Yoichiro Takata, Toru Maeda, Toshinori Sakai, Natsuo Yasui and Koichi Sairyo : Morphometric Analysis of Subaxial Cervical Spine with Myelopathy: A Comparison with the Normal Population., Spine Surgery and Related Research, Vol.5, No.1, 34-40, 2020.
(Summary)
The morphometry of the sagittal diameter of the spinal canal, sagittal-transverse ratio, and canal-body ratio on axial reconstructive CT images appears useful for distinguishing cervical spinal canal stenosis involving myelopathy.
Nori Sato, Takako Taniguchi, Yuichiro Goda, Hirofumi Kosaka, Kosaku Higashino, Toshinori Sakai, Shinsuke Katoh, Natsuo Yasui, Koichi Sairyo and Hisaaki Taniguchi : Proteomic Analysis of Human Tendon and Ligament: Solubilization and Analysis of Insoluble Extracellular Matrix in Connective Tissues., Journal of Proteome Research, Vol.15, No.12, 4709-4721, 2016.
(Summary)
Connective tissues such as tendon, ligament and cartilage are mostly composed of extracellular matrix (ECM). These tissues are insoluble, mainly due to the highly cross-linked ECM proteins such as collagens. Difficulties obtaining suitable samples for mass spectrometric analysis render the application of modern proteomic technologies difficult. Complete solubilization of them would not only elucidate protein composition of normal tissues but also reveal pathophysiology of pathological tissues. Here we report complete solubilization of human Achilles tendon and yellow ligament, which is achieved by chemical digestion combined with successive protease treatment including elastase. The digestion mixture was subjected to liquid chromatography-mass spectrometry. The low specificity of elastase was overcome by accurate mass analysis achieved using FT-ICR-MS. In addition to the detailed proteome of both tissues, we also quantitatively determine the major protein composition of samples, by measuring peak area of some characteristic peptides detected in tissue samples and in purified proteins. As a result, differences between human Achilles tendon and yellow ligament were elucidated at molecular level.
Ichiro Tonogai, Mitsuhiko Takahashi, Kiminori Yukata, Ryosuke Sato, Takeshi Nikawa, Natsuo Yasui and Koichi Sairyo : Osteoactivin attenuates skeletal muscle fibrosis after distraction osteogenesis by promoting extracellular matrix degradation/remodeling., Journal of Pediatric Orthopaedics. Part B, Vol.24, No.2, 162-169, 2015.
(Summary)
The aim of this study was to determine whether osteoactivin attenuated skeletal muscle fibrosis caused by distraction osteogenesis. Tibial osteotomies were performed on wild-type and osteoactivin-transgenic (OA-Tg) mice, and tibiae were distracted for 2 weeks. Ankle plantar flexion torque and the gastrocnemius muscles were analyzed. The amount and area of collagenous tissue and the passive torque were reduced in the OA-Tg group at 8 weeks after osteotomy. Transcript levels of matrix metalloprotease (mmp)-3 and MMP-9 were upregulated, and MMP-3 and MMP-9 proteins were increased in the OA-Tg group. Osteoactivin-mediated increase in MMPs may attenuate skeletal muscle fibrosis.
Mitsuhiko Takahashi, Natsuo Yasui, Tetsuya Enishi, Nori Sato, Takatoshi Mizobuchi, Yukako Homma and Koichi Sairyo : Diverse muscle architecture adaptations in a rabbit tibial lengthening model., Muscles, Ligaments and Tendons Journal, Vol.4, No.4, 433-437, 2015.
(Summary)
this study demonstrated that muscle belly length largely adapted to the lengthening. The increase in sarcomere number did not match the increase in muscle belly length. We estimated that elongation of the intramuscular aponeuroses is another mechanism of the adaptation in addition to the increase in sarcomere number.
S Kimura, Yuka Ueda, Takayuki Ise, Shusuke Yagi, Takashi Iwase, K Nishikawa, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Shinsuke Katoh, Masashi Akaike, Natsuo Yasui and Masataka Sata : Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease., International Heart Journal, Vol.56, No.1, 105-109, 2015.
(Summary)
Urinary albumin excretion is a predictor of cardiovascular death. Cardiac rehabilitation (CR) with exercise training (ET) has been shown to improve exercise capacity and prognosis in patients with cardiovascular disease (CVD). However, it remains unclear whether CR reduces urinary albumin excretion in CVD patients. We performed a retrospective, observational study using data obtained from 98 male CVD patients without macroalbuminuria and estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m(2) who participated in CR with ET during hospitalization. Twenty-three patients continued supervised ET for 6 months (supervised group) and 75 patients quit supervised ET (non-supervised group). The supervised ET program consisted of 60 minutes of supervised sessions 1-3 times a week and 30-60 minutes of home exercise at least twice a week. Urinary albumin/creatinine ratio (ACR) was significantly decreased in the supervised group at 6 months after enrollment (43 ± 71 mg/g to 17 ± 20 mg/g creatinine, P < 0.05) but not in the non-supervised group. eGFR was unchanged in the supervised group but was significantly decreased in the non-supervised group (72 ± 18 mL/minute/1.73 m(2) to 67 ± 17 mL/minute/1.73 m(2), P < 0.001). The results of multiple regression analysis showed that only supervised ET was an independent contributor to ACR. CR with supervised ET decreased urinary albumin excretion without deterioration of renal function. These findings suggest that continuation of a supervised ET program is associated with reduction in the development of CVD and reduction in cardiovascular morbidity and mortality in CVD patients.
(Keyword)
Cardiac rehabilitation / Renal function / Cardiovascular disease
Toshihiko Nishisho, Naoyoshi Hanaoka, Ryo Miyagi, Toshinori Sakai, Shunichi Toki, Mitsuhiko Takahashi, Kenji Endo, Natsuo Yasui and Koichi Sairyo : Local administration of zoledronic Acid for giant cell tumor of bone., Orthopedics, Vol.38, No.1, e25-30, 2015.
(Summary)
Giant cell tumor of bone is a locally aggressive tumor with a high local recurrence rate. Several adjuvant therapies have been employed to reduce the recurrence rate, but their effectiveness remains controversial. The authors attempted local administration of zoledronic acid, a nitrogen-containing bisphosphonate that strongly inhibits bone resorption, as an adjuvant treatment for histologically proven giant cell tumor of bone in 5 patients at their institution. After biopsy, 4 patients were treated with local administration of zoledronic acid with artificial bone and 1 was treated with zoledronic acid without artificial bone. Histologic response to the treatment was evaluated with surgically resected specimens. The 4 patients treated with artificial bone showed local control, with histologic tumor necrosis rates of 90%, 90%, 50%, and 10%. Magnetic resonance imaging showed poor gadolinium enhancement, and histologic examination after local zoledronic acid treatment showed tumor necrosis. One patient without artificial bone showed no histologic tumor necrosis and had local recurrence in soft tissue 18 months after tumor resection. A 3-week waiting period between biopsy and zoledronic acid treatment appears reasonable from the histological study. Complication of this therapy was delayed wound healing and it occurred in 2 cases. Taken together, this case series suggests that local administration of zoledronic acid with artificial bone is a potential adjuvant therapy for giant cell tumor of bone. On the other hand, effective local administration of zoledronic acid requires some bone matrix, including artificial bone. Campanacci's grading is important for predicting the effect of local administration of zoledronic acid. [Orthopedics. 2015; 38(1):e25-e30.].
Rie Hashimoto, Atsuko Sakai, Masumi Murayama, Arisa Ochi, Tomoki Abe, Katsuya Hirasaka, Ayako Ohno, Shigetada Teshima-Kondo, Hiroaki Yanagawa, Natsuo Yasui, Mikiko Inatsugi, Daisuke Doi, Masanori Takeda, Rie Mukai, Junji Terao and Takeshi Nikawa : Effects of dietary soy protein on skeletal muscle volume and strength in humans with various physical activities, The Journal of Medical Investigation : JMI, Vol.62, No.3, 177-183, 2015.
(Summary)
Background: In recent years, the number of bedridden people is rapidly increasing due to aging or lack of exercise in Japan. This problem is becoming more serious, since there is no countermeasure against it. In the present study, we designed to investigate whether dietary proteins, especially soy, had beneficial effects on skeletal muscle in 59 volunteers with various physical activities. Methods: We subjected 59 volunteers with various physical activities to meal intervention examination. Persons with low and high physical activities were divided into two dietary groups, the casein diet group and the soy diet group. They ate daily meals supplemented with 7.8 g of powdered casein or soy protein isolate every day for 30 days. Bedridden patients in hospitals were further divided into three dietary groups: the no supplementation diet group, the casein diet group and the soy diet group. They were also subjected to a blood test, a urinalysis, magnetic resonance imaging analysis and muscle strength test of the knee before and after the meal intervention study. Results: Thirty-day soy protein supplementation significantly increased skeletal muscle volume in participants with low physical activity, compared with 30-day casein protein supplementation. Both casein and soy protein supplementation increased the volume of quadriceps femoris muscle in bedridden patients. Consistently, soy protein significantly increased their extension power of the knee, compared with casein protein. Although casein protein increased skeletal muscle volume more than soy protein in bedridden patients, their muscle strength changes by soy protein supplementation were bigger than those by casein protein supplementation. Conclusions: The supplementation of soy protein would be one of the effective foods which prevent the skeletal muscle atrophy caused by immobilization or unloading. J. Med. Invest. 62: 177-183, August, 2015
Ichiro Tonogai, Mitsuhiko Takahashi, Takahiko Tsutsui, Tomohiro Goto, Daisuke Hamada, Naoto Suzue, Tetsuya Matsuura, Natsuo Yasui and Koichi Sairyo : Forearm lengthening by distraction osteogenesis: A report on 5 limbs in 3 cases., The Journal of Medical Investigation : JMI, Vol.62, No.3-4, 219-222, 2015.
(Summary)
Radioulnar length discrepancy causes pain and decreases function of the wrist, forearm, and elbow. Limb lengthening, which has been used in the treatment of various deformities of the forearm, is necessary to restore balance between the ulna and radius. We treated 5 limbs in 3 patients (2 boys, 1 girl; mean age 9.3 years old) with radioulnar length discrepancy by distraction osteogenesis of either the ulna or radius using external fixators. We dissected the interosseous membrane between the ulna and radius in 3 limbs in 2 cases and did not do so in 2 limbs of 1 case. These cases include 2 cases with hereditary multiple exostoses, and 1 case with multiple epiphyseal dysplasia. The results were investigated and evaluated in this study, using appropriate clinical and radiographic parameters, noting the state of the interosseous membrane, which has an important role in forearm stability. The mean fixation period was 113 days. The mean distraction distance was 22.8 mm. The mean follow-up period was 637.7 days. The mean ulnar shortening and radial articular angle respectively improved from 7.4 mm and 30.2° preoperatively to -0.1 mm and 34.8° postoperatively. Balance between the ulna and radius was restored, and the results showed significant improvements in range of motion of the joints. However, 2 unintended radial head subluxations occurred in 2 limbs without dissection of the interosseous membrane. In addition, a keloid remained in 1 limb due to pin site infection. Forearm lengthening by distraction osteogenesis was useful in our cases. It is important to recognize the function of the interosseous membrane when lengthening is performed by osteotomy of the proximal ulna by gradual distraction with an external fixator. J. Med. Invest. 62: 219-222, August, 2015.
Fumitake Tezuka, Toshinori Sakai, Ryo Miyagi, Yoichiro Takata, Kousaku Higashino, Shinsuke Katoh, Koichi Sairyo and Natsuo Yasui : Complete resolution of a case of calcific tendinitis of the longus colli with conservative treatment., Asian Spine Journal, Vol.8, No.5, 675-679, 2014.
(Summary)
Acute calcific tendinitis of the longuscolli is a self-limiting inflammatory condition caused by calcium hydroxyapatite deposition in the longuscolli tendon. Although several case reports have described its radiological presentation, few reports provide detailed chronological accounts through symptomatic and radiologic resolution. A 59-year-old woman presented with severe neck pain and stiffness of a few days duration as well as moderate discomfort when swallowing. Lateral radiographs revealed a large calcium deposit anterior to the C1.C2 joint and swelling of the prevertebral soft tissue from C1 to C5. CT and magnetic resonance imaging showed fluid in the retropharyngeal gap.A soft collar and non-steroidal anti-inflammatory drug were prescribed, without antibiotics. At 4 months after presentation, the calcium deposit and all symptoms had resolved completely. Although this disease is comparatively rare, physicians should keep it in mind when a patient presents with acute severe neck pain.
Tetsuya Enishi, Kiminori Yukata, Mitsuhiko Takahashi, Ryosuke Sato, Koichi Sairyo and Natsuo Yasui : Hypertrophic chondrocytes in the rabbit growth plate can proliferate and differentiate into osteogenic cells when capillary invasion is interposed by a membrane filter., PLoS ONE, Vol.9, No.8, e104638, 2014.
(Summary)
The fate of hypertrophic chondrocytes during endochondral ossification remains controversial. It has long been thought that the calcified cartilage is invaded by blood vessels and that new bone is deposited on the surface of the eroded cartilage by newly arrived cells. The present study was designed to determine whether hypertrophic chondrocytes were destined to die or could survive to participate in new bone formation. In a rabbit experiment, a membrane filter with a pore size of 1 µm was inserted in the middle of the hypertrophic zone of the distal growth plate of ulna. In 33 of 37 animals, vascular invasion was successfully interposed by the membrane filter. During 8 days, the cartilage growth plate was enlarged, making the thickness 3-fold greater than that of the nonoperated control side. Histological examination demonstrated that the hypertrophic zone was exclusively elongated. At the terminal end of the growth plate, hypertrophic chondrocytes extruded from their territorial matrix into the open cavity on the surface of the membrane filter. The progenies of hypertrophic chondrocytes (PHCs) were PCNA positive and caspase-3 negative. In situ hybridization studies demonstrated that PHCs did not express cartilage matrix proteins anymore but expressed bone matrix proteins. Immunohistochemical studies also demonstrated that the new matrix produced by PHCs contained type I collagen, osteonectin, and osteocalcin. Based on these results, we concluded that hypertrophic chondrocytes switched into bone-forming cells after vascular invasion was interposed in the normal growth plate.
Mitsuhiko Takahashi, Toshinori Sakai, Koichi Sairyo, Shoichiro Takao, S Mima and Natsuo Yasui : Magnetic resonance imaging in adolescent symptomatic navicular tuberosity., The Journal of Medical Investigation : JMI, Vol.61, No.1-2, 22-27, 2014.
(Summary)
The accessory navicular bone is one of the most common accessory ossicles, which sometimes become symptomatic. Abnormalities in magnetic resonance (MR) image, e. g. edema-like bone marrow pattern, have been reported for symptomatic accessory navicular. However, it has not been completely understood the edema-like bone marrow pattern correlates to the symptom of navicular tuberosity. We investigated the edema-like bone marrow pattern in correlation with alleviation of the symptom and the presence of accessory navicular bone. Ten adolescents with pain localized to the navicular tuberosity were recruited and seven cases were further examined with consecutive MR images. Edema-like bone marrow pattern was found in all symptomatic navicular but not in asymptomatic navicular. Intensity of the pattern diminished with alleviation of the symptom. Moreover, this correlation was recognized even in the patients who had no accessory navicular bones. MR images could be used not only for diagnosis but for monitor of healing in adolescent symptomatic navicular. There may be different pathologic mechanism for adolescent symptomatic navicular tuberosity, such as an osteitis, in adolescents.
(Keyword)
accessory navicular / magnetic resonance image / edema-like bone marrow pattern / adolescents
J Hopkins, Toshinori Sakai, Koichi Sairyo, J Mefford, NN Bhatia, Ichiro Tonogai, Akira Dezawa and Natsuo Yasui : Endoscope Assisted Excision of a Juxtafacet Cyst in an Adolescent Athlete: A Case Report., Journal of Neurological Surgery. Part A, Central European Neurosurgery, Vol.74, No.Suppl 1, e66-e69, 2013.
(Summary)
Juxtafacet cysts (JFCs) are a cause of back and radicular pain that can be treated conservatively and operatively. Such strategies include lumbosacral brace, epidural injection, open surgery, and minimally invasive surgery; although surgical treatment is usually reserved for unsuccessful conservative treatment. The role of minimally invasive surgery in athletic youth with JFCs has yet to be determined. The patient is a 16-year-old basketball player with a JFC. We performed endoscope-assisted cystectomy. Endoscope-assisted JFC excision immediately and completely resolved the patient's lower back and leg pain with no recurrence of symptoms 4 years after surgery. We suggest that JFCs of the lumbar spine be a part of the differential diagnosis in young patients with back and radicular pain. Furthermore, we recommend that endoscope-assisted surgery be employed in the treatment of JFCs in young athletes.
(Keyword)
Adolescent / Basketball / Cystectomy / Cysts / Endoscopy / Humans / Low Back Pain / Magnetic Resonance Imaging / Male / Pain / Recovery of Function / Surgical Procedures, Minimally Invasive / Treatment Outcome / Zygapophyseal Joint
AR Rahimnia, A Abbaspour, Y Rezaei, A Khodadadi, AM Alizadeh, MA Mohagheghi, H Semeyari, AA Fooladi Imani, M Izadi, P Keshavarz and Natsuo Yasui : Antibiotic-coated pins for prevention of pin-tract infection: a rabbit study., Journal of Orthopaedic Surgery (Hong Kong), Vol.21, No.2, 213-215, 2013.
(Summary)
PURPOSE. To evaluate the efficacy of antibiotic-coated pins for prevention of pin tract infection in a rabbit model. METHODS. 10 rabbits were divided into 2 groups. A unilateral external fixator was applied to the tibia with 4 self-taping 1.8-mm pins. In the test group, pins were coated with hydroxyapatite and antibiotic. In the control group, pins were not coated. All pins were then placed in Staphylococcus aureus- containing media. At postoperative day 5, all 40 pin sites were subcutaneously inoculated with S aureus. The sites were clinically examined for signs of pin tract infection. Nine days later, a piece of soft tissue around the pin site was harvested for microbiologic examination. RESULTS. In the test group, all except one pin sites appeared clean and without clinical infection, and the culture media remained clear. In the control group, all pin sites showed evidence of clinical infection and yielded positive cultures, and the culture media became dark indicating growth of S aureus. CONCLUSION. Antibiotic-coated pins were effective in preventing pin tract infection.
Kousaku Higashino, Tetsuya Matsuura, Katsuyoshi Suganuma, Kiminori Yukata, Toshihiko Nishisho and Natsuo Yasui : Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats., Journal of Neuroengineering and Rehabilitation, Vol.10, No.1, 46, 2013.
(Summary)
BACKGROUND: Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-gamma coactivatior-1alpha (PGC-1alpha) expression brought about by spinal cord transection and by peripheral nerve transection. METHODS: Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. RESULTS: Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1alpha protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1alpha protein in the soleus muscle. The results of the expression of PGC-1alpha were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. CONCLUSION: In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1alpha protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1alpha protein in the soleus muscle.
Ichiro Tonogai, Mitsuhiko Takahashi, Hiroaki Manabe, Toshihiko Nishisho and Natsuo Yasui : A massive chondroblastoma in the proximal humerus simulating malignant bone tumors, Case Reports in Orthopedics, Vol.2013, 673576, 2013.
(Summary)
Chondroblastoma is a mostly benign bone neoplasm that typically affects the second decade of life and exhibits a lytic lesion in the epiphysis of long bones. We report an extreme case of massive, destructive chondroblastoma of the proximal humerus in a 9-year-old girl. It was difficult to differentiate using imaging information the lesion from malignant bone tumors such as osteosarcoma. Histopathological examination from biopsy proved chondroblastoma. The tumor was resected after preoperative transcatheter embolization. Reconstructive procedure for the proximal humerus was not performed due to the local destruction. The present case demonstrates clinical and radiological differentiations of the massive chondroblastoma from the other lesions and histopathological understandings for this lesion.
Mitsuhiko Takahashi, Tetsuya Enishi, Nori Sato, Kousaku Higashino, Shinjiro Takata, Shinsuke Katoh and Natsuo Yasui : Diverse Muscular Adaptation between Aged and Young Groups in a Rabbit Model of Tibial Lengthening, The Japanese Journal of Rehabilitation Medicine, Vol.50, No.1, 43-47, 2013.
(Summary)
Skeletal muscles are overstretched following limb lengthening procedures. Muscles can adapt to this lengthening by adding new sarcomeres in series. Recent developments in limb lengthening provide adult patients more opportunities to undergo limb lengthening procedures. The purpose of this study was to clarify the difference in muscle adaptation between adult and young groups using a rabbit model of limb lengthening. Five mature (10-43 month old) and 6 immature (3-4 month old) white rabbits underwent tibial osteotomy. After a 1-week lag phase, tibial lengthening was applied at a rate of 1.4 mm/day for 2 weeks. Animals were euthanized after the completion of lengthening. Both hindlimbs were immersed in buffered formalin with the ankle and knee at a right angle. Muscle belly length, muscle fiber bundle length and sarcomere length were measured, and sarcomere number and internal tendon length were calculated in five representative muscles around the lengthened segment. Muscle belly length increased in all the lengthened muscles compared with the corresponding contralateral muscles regardless the group. Aponeurosis length increased significantly in one muscle for the adult group and three muscles for the young group. Sarcomere length tended to be longer or was significantly longer in the lengthened muscles. Serial sarcomere number significantly increased in 3 lengthened muscles in the adult group with a more conspicuous increase in the amount, while this occurred in 2 muscles in the young group with only a tiny increase. The predominant processes of skeletal muscle adaptation to the limb lengthening are sarcomere number addition in muscle fibers for the adult group and elongation of internal tendon for the young group.
(Keyword)
bone lengthening / sarcomere / intramuscular tendon
岩目 敏幸, Naoto Suzue, 立石 智彦, 武田 芳嗣, 加藤 憲治 and Natsuo Yasui : プロサッカー選手に生じた大腿直筋近位腱断裂に対する手術治療の経験, Japanese Journal of Orthopaedic Sports Medicine, Vol.33, No.2, 207-211, 2013.
23.
Inui Ami, Shunji Nakano, Yoshioka Shinji, Tomohiro Goto, Daisuke Hamada, Yoshiteru Kawasaki, Hiroshi Egawa and Natsuo Yasui : Subchondral cysts in dysplastic osteoarthritic hips communicate with the joint space: analysis using three-dimensional computed tomography, European Journal of Orthopaedic Surgery & Traumatology, Vol.23, No.7, 791-795, 2012.
(Summary)
INTRODUCTION: Bone cyst formation in hips increases as osteoarthritis worsens. Although bone cysts in hips have been described in many studies, their etiology remains unclear and under debate. The purpose of this study was to investigate the communication between a bone cyst and the joint space, as well as the relationship between the severity of osteoarthritis and the formation of subchondral bone cysts in dysplastic hips. METHOD: We studied bone cysts from 150 dysplastic hips in 97 patients by computed tomography (CT) and plain radiography. We investigated the distribution of the bone cysts and the presence or absence of a communication path between the cysts and the joint space by three-dimensional (3D) CT. RESULT: Of the 150 hips, 94 acetabula and 55 femoral heads were found to contain cysts. Of the 94 hips containing acetabular cysts, 89 and 5 hips showed black lines and gray lines connecting the cyst and the joint space, respectively, on 3D-CT. The rate of cyst presentation in the hip increased as the joint space became narrower. The number of hips that possessed cysts in the anterior and/or middle portion was significantly higher than that in the posterior portions. CONCLUSION: Bone cysts in dysplastic osteoarthritic hips were found to communicate with the joint space in all cases. This suggests that the formation and enlargement of the cysts in dysplastic hips may be greatly influenced by the joint fluid. Cyst formation was initially observed in the anterior acetabulum, gradually progressing to involve the entire joint, including the posterior acetabulum and the femoral head, with worsening of the osteoarthritis.
(Keyword)
Acetabulum / Adolescent / Adult / Aged / Bone Cysts / female / Femur Head / Hip Dislocation / Humans / Imaging, Three-Dimensional / male / Middle Aged / Osteoarthritis, Hip / Tomography, X-Ray Computed / Young Adult
Ryou Miyagi, Koichi Sairyo, Toshinori Sakai, H Yoshioka and Natsuo Yasui : Two types of laminolysis in adolescent athletes., Journal of Orthopaedics and Traumatology, Vol.13, No.4, 225-228, 2012.
(Summary)
Bony defects in the spine are divided into three main types: spondylolysis, pediculolysis, and laminolysis. Lumbar spondylolysis is a well-known stress fracture that occurs frequently in adolescent athletes. Pediculolysis means stress fracture of the pedicle, which sometimes occurs subsequent to unilateral spondylolysis. Laminolysis is a rarely reported stress fracture similar to spondylolysis and pediculolysis that sometimes causes low back pain (LBP). However, its pathomechanism has not been elucidated. Recently, we encountered four adolescent athletes with symptomatic laminolysis. Mean age was 15.8 (range 15-17) years. All subjects reported severe LBP exacerbated by extension of the lumbar spine, and radiology revealed two types of laminolysis: hemilaminar type and intralaminar type. To elucidate the mechanisms of each type, we reviewed a biomechanical study, and found that the hemilaminar type was thought to be subsequent to contralateral spondylolysis, while the intralaminar type might be a result of a stress fracture due to repetitive extension loading.
Yoshiteru Kawasaki, Hiroshi Egawa, Daisuke Hamada, Shoichiro Takao, Shunji Nakano and Natsuo Yasui : Location of intrapelvic vessels around the acetabulum assessed by three-dimensional computed tomographic angiography: prevention of vascular-related complications in total hip arthroplasty., Journal of Orthopaedic Science, Vol.17, No.4, 397-406, 2012.
(Summary)
During total hip arthroplasty (THA), the external iliac, femoral, and obturator vessels are at risk of vascular injury when penetrating the inner cortex of the pelvis. The purpose of this study was to clarify the location of these vessels using three-dimensional computed tomographic angiography (3DCT-A). We enrolled 100 subjects (200 hips) without hip disease and performed examinations on the following. (1) External iliac-femoral vessels: we measured the shortest distance from these vessels to the pelvis on axial CT images and investigated the factors affecting distance. The anatomical course of the iliac artery was classified as straight, curved, or tortuous, and the correlation between course and age was established. (2) Obturator vessels: we measured the shortest distance from the obturator vessels to the quadrilateral surface on axial CT images. (3) Visualization of pelvic vessels was through the pelvis by dual-phase 3DCT-A. (1) The external iliac vein was located significantly closer to the pelvis than the artery, especially on the left side and in aged and female subjects. The single-curved and tortuous double-curved vessel types were found in aged subjects, and external iliac vessels of these types were closer to the pelvis than vessels of the straight type. In 36 subjects, the external iliac veins lay directly on the osseous surface of the pelvis (right 16, left 36). Of these 36 subjects, only one had straight-type vessels. (2) Obturator vessels were located just behind the acetabulum near the obturator foramen. (3) Reconstructed 3DCT images enabled us to visualize the pelvic vessels and demonstrated the danger area for penetrating the inner cortex of the pelvis. Understanding the anatomical orientation of the pelvic vessels around the acetabulum using 3DCT-A could be helpful for preventing vascular injury during THA.
Kousaku Higashino, Koichi Sairyo, Shinsuke Katoh, Shoichiro Takao, Hirofumi Kosaka and Natsuo Yasui : Long-term outcomes of lumbar posterior apophyseal end-plate lesions in children and adolescents., The Journal of Bone and Joint Surgery. American Volume, Vol.94, No.11, e74(1)-(7), 2012.
(Summary)
A lesion of the lumbar posterior apophyseal end plate in children and adolescents causes symptoms similar to those associated with a herniated disc. However, the end-plate lesion and the herniated disc differ in terms of pathology. The purpose of this study was to clarify the long-term clinical and radiographic outcomes in children and adolescents who were treated either surgically or conservatively for a lumbar posterior apophyseal end-plate lesion. We identified twenty-four consecutive patients who had been treated in the sports clinic of our hospital. The mean age at the first medical examination was 14.5 years. The mean follow-up time was 13.8 years. The mean age at the time of final follow-up was 28.4 years. All twenty-four patients had symptomatic low back pain with sciatica. All but two were active in sports. Sixteen patients were treated conservatively, and eight patients underwent surgical intervention. Skeletal maturity was evaluated on the basis of the appearance of the secondary ossification center of L3. The apophyseal stage ("A" stage), which was assigned when the secondary ossification center of the vertebral body was visible on radiographs, was seen most frequently. Both the surgically treated group and the conservatively treated group demonstrated progressive disc degeneration at the involved level. The average Roland-Morris Disability Questionnaire (RDQ) score was 1.3 for the patients treated conservatively and 1.8 for those treated surgically, a nonsignificant difference. One patient developed spinal stenosis after twelve years of conservative treatment. One patient treated surgically demonstrated severe lumbar instability. There were no significant associations between the magnetic resonance imaging (MRI) findings and RDQ scores. Histological examination of surgical specimens showed irregular alignment of the anulus fibrosus, with degenerative matrix and chondrocytes without a nucleus. The long-term outcome for patients with a posterior end-plate lesion is favorable, regardless of whether it is treated surgically or nonsurgically.
(Keyword)
Adolescent / Adult / Age Factors / Cohort Studies / Disease Progression / female / Follow-Up Studies / Growth Plate / Humans / Intervertebral Disc / Low Back Pain / Lumbar Vertebrae / magnetic resonance imaging / male / Manipulation, Orthopedic / Orthopedic Procedures / Pain Measurement / Recovery of Function / Risk Assessment / Severity of Illness Index / Sex Factors / Spinal Diseases / Spinal Stenosis / Statistics, Nonparametric / Time Factors / Tomography, X-Ray Computed / Treatment Outcome / Young Adult
Koichi Sairyo, Toshinori Sakai, Natsuo Yasui and Dezawa Akira : Conservative treatment for pediatric lumbar spondylolysis to achieve bone healing using a hard brace: what type and how long?, Journal of Neurosurgery. Spine, Vol.16, No.6, 610-614, 2012.
(Summary)
Various kinds of trunk braces have been used to achieve bone healing in cases of pediatric lumbar spondylolysis. However, the optimal brace for achieving bone healing is unclear. The purpose of the present study was to determine in what types of spondylolysis bone healing can be achieved and how long it takes. In this prospective study, 63 pars interarticularis defects (spondylolysis) among 37 patients who were younger than 18 years (mean 13.5 ± 2.7 years) were treated using a hard brace. The youngest patient was 8 years old. Based on the results of CT scanning, the lyses were classified into 3 categories: early, progressive, and terminal defects. Progressive defects were further divided into 2 types according to STIR MRI findings: those with high signal intensity at the adjacent pedicle and those with low signal intensity (that is, a normal appearance). A hard brace, such as a molded plastic thoracolumbosacral orthosis, was used to immobilize the trunk. Approximately every 3 months, CT scanning was performed to evaluate bone healing until approximately 6 months. The union rates were 94%, 64%, 27%, and 0% for the early, progressive with high signal intensity, progressive with low signal intensity, and terminal defects, respectively. It was noted that no terminal defect was healed using conservative treatment. The mean time to healing among the defects that showed bone healing was 3.2, 5.4, and 5.7 months for the early, progressive with high signal intensity, and progressive with low signal intensity groups, respectively. Patients with early-stage defects are the best candidates for conservative treatment with a hard brace because more than 90% of such cases can be healed in 3 months.
Tetsuya Matsuura, Naoto Suzue, Shinji Kashiwaguchi, 岩瀬 毅信, Kokichi Arisawa and Natsuo Yasui : 少年野球選手の肘関節痛発症に関する前向き調査━危険因子の検討とガイドラインの検証━, Japanese Journal of Orthopaedic Sports Medicine, Vol.32, No.3, 38-43, 2012.
31.
Seiji Iwamoto, Shoichiro Takao, Hayato Nose, Yoichi Otomi, Mitsuhiko Takahashi, Toshihiko Nishisho, Junji Ueno, Natsuo Yasui and Masafumi Harada : Usefulness of transcatheter arterial embolization prior to excision of hypervascular musculoskeletal tumors., The Journal of Medical Investigation : JMI, Vol.59, No.3-4, 284-288, 2012.
(Summary)
The objective of this study was to evaluate the usefulness of transcatheter arterial embolization prior to surgical excision of musculoskeletal tumors. We reviewed the records of nine patients (3 females and 6 males) who received arterial embolization prior to excision of musculoskeletal tumors in our hospital from December 2009 to April 2010. We evaluated tumor region, size, histopathology, feeding artery, embolic material, and blood loss during surgery. We compared the actual amount of intraoperative bleeding with arterial embolization to estimated amounts of bleeding without embolization predicted by three orthopedic surgeons. Arterial embolization was performed on the same day or within 5 days before surgery. Operations were performed as planned in all patients without serious complications. The amount of intraoperative bleeding was 35-4200 mL and there was significantly less bleeding with arterial embolization compared with the estimated amounts (p<0.01). Our results show that arterial embolization prior to resection of hypervascular musculoskeletal tumors reduces the amount of bleeding during surgery and contributes to patient safety.
Masatoshi Morimoto, Mitsuhiko Takahashi, Nori Sato, Toshihiko Nishisho, Seiko Kagawa, Eiji Kudo, Shoichiro Takao and Natsuo Yasui : Expansively Hemorrhagic Foreign Body Granuloma at the Pelvis Caused by Microscopic Materials., Open Journal of Orthopedics, Vol.2, No.1, 1-5, 2012.
Toshinori Sakai, Koichi Sairyo, Bhatia N. Nitin, Miyagi Ryo, Tamura Tatsuya, Shinsuke Katoh and Natsuo Yasui : MRI Changes of the Spinal Subdural Space after Lumbar Spine Surgeries: Report of Two Cases., Asian Spine Journal, Vol.5, No.4, 262-266, 2011.
(Summary)
Although magnetic resonance imaging (MRI) is frequently used to assess the lumbar spine, there are few reports in the medical literature that have evaluated using MRI immediately following spinal surgery. Furthermore, descriptions of the subdural changes after lumbar spine surgery are also infrequent. In this paper, we present two cases with subdural change seen on MRI immediately after lumbar surgery. Both the patients had mild symptoms that resolved spontaneously, and the follow-up MRI scans showed resolution of the subdural changes. Subdural changes should be considered as one of the possible causes of unexpected symptoms in patients following lumbar spinal surgery.
Kouji Komatsu, Shigetaka Nakao, 増田 有紀, 岡久 哲也, 近藤 心, 西川 幸治, Toshifumi Ohsawa, Shinjiro Takata and Natsuo Yasui : Effect of Hallux Valgus during Gait, Rigakuryoho Kagaku, Vol.26, No.5, 717-722, 2011.
(Summary)
[Purpose] The purpose of this study was to investigate the characteristics of gait in patients with hallux valgus and the effects on the joints of the lower extremities (hip, knee and ankle). [Subjects] The patient was a 69-year-old female diagnosed with rheumatoid arthritis (RA) including hallux valgus. The patient had a chief complaint of pain on the medial side of the right hallux in gait. [Methods] Gait analyses, using the VICON-MX systems were performed preoperatively and postoperatively at 6 months. [Results] The postoperative valgus of knee moments decreased, and valgus of ankle moments had increased on the operated side. The varus of knee moments on the non-operated side was higher than on the operated side. [Conclusion] The results revealed instability in the lateral direction of the lower extremity with deformity of the foot. Hallux valgus associated with valgus knee deformity on the operated and varus on the non-operated side is a potential cause of osteoarthritis of the knee. We should be careful not only to prevent the recurrence of hallux valgus on the operated side but also osteoarthritis of the knee on the opposite side. These results are useful indicators for rehabilitation management of hallux valgus.<br>
(Keyword)
three-dimensional motion analysis / hallux valgus / Oxford foot model
Yoshinori TAKAHASHI, Mitsuhiko Takahashi, Shinsuke Katoh and Natsuo Yasui : One case of malunion after colles fracture treated by intramedullary nail ; A case report, 中部日本整形外科災害外科学会雑誌. 中部日本整形外科災害外科学会抄録, Vol.54, No.5, 945-946, 2011.
Risa Utsunomiya, Toshinori Sakai, Keizo Wada, Koichi Sairyo, Hirofumi Kosaka, Shinsuke Katoh and Natsuo Yasui : Hemorrhagic Facet Cyst in the Lumbar Spine Causing Contralateral Leg Symptoms: A Case Report, Asian Spine Journal, Vol.5, No.3, 196-200, 2011.
(Summary)
Here we present a case of hemorrhagic lumbar facet cyst presenting with progressive radiculopathy only on the contralateral side. If a patient has previous back pain or neuropathy for several months and then suddenly deteriorates, hemorrhagic facet cyst of the lumbar spine should be part of the differential diagnosis. However, as in the present case, we should be aware that there is a possibility of a contralateral lesion.
Shinjiro Takata, Hiroshi Yonezu, Akira Sibata, Tetsuya Enishi, Nori Sato, Mitsuhiko Takahashi, Shigetaka Nakao, Kouji Komatsu and Natsuo Yasui : Mineral to matrix ratio determines biomaterial and biomechanical properties of rat femur -application of Fourier transform infrared spectroscopy., The Journal of Medical Investigation : JMI, Vol.58, No.3-4, 197-202, 2011.
(Summary)
We studied the changes of biomaterial and biomechanical properties of the rat femur during development. Thirty male Wistar rats were allocated to 6 groups: aged 6 weeks (n=5), 9 weeks (n=5), 12 weeks (n=5), 15 weeks (n=5), 24 weeks (n=5), and 36 weeks (n=5). The mineral to matrix ratio (M/M ratio) of rat femur by Fourier transform infrared spectroscopy was 0.97 ± 0.10 at the age of 6 weeks, and reached the maximum of 1.52 ± 0.17 at the age of 36 weeks. Total bone mineral density (BMD) by peripheral quantitative computed tomography of the femoral shaft aged 6 weeks was 479.1 ± 58.7 mg/cm(3), and reached the maximum of 1022.2 ± 42.3 mg/cm(3) at the age of 36 weeks. The ultimate load to failure of the femur of the rat aged 6 weeks by the three-point bending test was 29.6 ± 6.1 N. At the age of 36 weeks, the ultimate load to failure of the rat femur increased to the maximum of 283.5 ± 14.7 N. The results showed that the M/M ratio increased with development as total BMD and bone strength increased. The results suggest that the M/M ratio is one of the determinants of the biomaterial and biomechanical properties of bone.
(Keyword)
Animals / Biocompatible Materials / biomechanics / Body Weight / Bone Density / Bone Matrix / Femur / Male / Rats / Rats, Wistar / Spectroscopy, Fourier Transform Infrared
Michiharu Kashihara, Shigetaka Nakao, Jun Kawasaki, Shinjiro Takata, Shinji Nagahiro, Ryuji Kaji and Natsuo Yasui : Long-term outcome of severe stroke patients: Is the ADL status at discharge from a stroke center indicative of the long-term outcome?, The Journal of Medical Investigation : JMI, Vol.58, No.3-4, 227-234, 2011.
(Summary)
The objective of this study was to examine the possibility of predicting the long-term outcome of severe stroke patients from the ADL status at discharge. The design is a retrospective observational study in the stroke center at Tokushima University Hospital. Severe stroke patients at discharge with Barthel Index (BI) scores 40 (N=51) were divided into two subgroups retrospectively, improved and unimproved. The Functional Independence Measure (FIM) and BI were analyzed at discharge, 3 and 6 months after onset. Correlation analysis between BI and FIM showed good correlation, especially between BI and motor FIM (mFIM). In conclusion, the ADL status at discharge from a stroke center is not definitely indicative of the long-term outcome, although good recovery of severe stroke cases was observed in males and younger patients, and in patients with motor FIM score>25. This result shows that the first 3 months after the attack should be regarded as an important time window for intensive rehabilitation.
(Keyword)
Activities of Daily Living / Aged / Female / Humans / Male / Middle Aged / Patient Discharge / Retrospective Studies / Stroke
Shigetaka Nakao, Shinjiro Takata, Kouji Komatsu, Toshio Tanaka, Eiji Tamura, Michiharu Kashihara, Toshifumi Osawa, Yuki Masuda, Koji Nishikawa, Megumi Yamada, Yoshimi Ogata, Yuka Nakamura and Natsuo Yasui : Three dimensional motion analyses for rehabilitation version of Awa Odori exercise and the expectancy of physical effects., The Journal of Medical Investigation : JMI, Vol.58, No.3-4, 259-263, 2011.
(Summary)
'Awa Odori Exercise--Rehabilitation version--was developed in 2006 for the new trial of physical exercise for the aging and the impaired person with lower balance performance in Tokushima prefecture, Japan. Public relations of this exercise had been spreading over Tokushima since then. The characteristics of the exercise were highly familiar with most of people in Tokushima because of popularity in original 'Awa Odori'. This study proposed the efficacies of Awa Odori Exercise as a rehabilitation exercise. This exercise expected the flexible balance reinforcements and the substitution for walking training with prevention of fall, bedridden and participating restriction for the old people, also promoting the health in Tokushima.
Shigetaka Nakao, Kouji Komatsu, Waka Sakai, Michiharu Kashihara, Yuki Masuda, Koji Nishikawa, Tetsuya Okahisa, Shin Kondo, Toshifumi Osawa, Ryuji Kaji, Satoshi Goto, Shinji Nagahiro, Shinjiro Takata and Natsuo Yasui : Gait and posture assessments of a patient treated with deep brain stimulation in dystonia using three-dimensional motion analysis systems., The Journal of Medical Investigation : JMI, Vol.58, No.3-4, 264-272, 2011.
(Summary)
Kinesiologic analysis of gait disorders, postural instabilities and abnormal movements is quite difficult to assess objectively by clinical observation, such as by specific scale and video recordings. In this study, we reported one of the aspects of the usefulness of three-dimensional motion analysis (Vicon Systems, Oxford, United Kingdom), which can measure inclusive data of movement disorders and substitute for conventional assessments. A 49-year-old man who had various dystonic symptoms, mainly on his left side of the body, responded well to deep brain stimulation (DBS). The examination quantified how the involuntary movements or other symptoms with dystonia changed before and after treatments.
(Keyword)
Deep Brain Stimulation / Dystonia / Gait / Humans / Male / Middle Aged / Motion / Posture
Mitsuhiko Takahashi, 溝渕 貴俊, 本間 友佳子, Tetsuya Enishi, 菅沼 勝義 and Natsuo Yasui : Effect of muscle properties on muscle adaptation to limb lengthening, The Journal of the Japanese Orthopaedic Association, Vol.85, No.7, 437-441, 2011.
(Keyword)
Limb lengthening / Muscle-tendon unit / Sarcomere / Adaptation
Toshihiko Nishisho, Naoyoshi Hanaoka, Kenji Endo, Mitsuhiko Takahashi and Natsuo Yasui : Locally administered zoledronic Acid therapy for giant cell tumor of bone., Orthopedics, Vol.34, No.7, e312-e315, 2011.
(Summary)
Giant cell tumor of bone is locally aggressive and occurs in the meta-epiphyseal region of long bones. Because of its high recurrence rate, local adjuvant therapies such as phenol or liquid nitrogen have been recommended. In the present study, zoledronic acid, a nitrogen-containing bisphosphonate, was administered locally as an adjuvant during a biopsy. An otherwise healthy 43-year-old man presented with pain and swelling in the right knee. Plain radiographs showed an osteolytic lesion of the right proximal tibia. An open biopsy was performed and the intraoperative pathologic diagnosis was giant cell tumor of bone. Following biopsy, the defect was filled with betatricalcium phosphate, and 4 mg of zoledronic acid was locally administered into the tumor lesion. Two months after the biopsy, curettage and bone grafting were performed. Sections were obtained during the curettage for histology to evaluate the response to bisphosphonate treatment. Histologic examination revealed massive tumor cell death in the lesion in which both stromal cells and osteoclast-like giant cells were necrotic. Curettage was performed and the defect was filled with a commercial preshaped hydroxyapatitetricalcium phosphate bone substitute. Eighteen months after curettage, the patient had regained full range of motion and good function of the knee, and radiographs at 18 months after curettage revealed no recurrence of giant cell tumor of bone.
(Keyword)
Adult / Antineoplastic Agents / Bone Density Conservation Agents / Bone Neoplasms / Bone Substitutes / Bone Transplantation / Curettage / Diphosphonates / Giant Cell Tumor of Bone / Humans / Hydroxyapatites / Imidazoles / Knee Joint / Male / Necrosis / Osteoclasts / Osteolysis / Prostheses and Implants / Range of Motion, Articular / Remission Induction / Tibia
Toshihiko Nishisyo, Kenji Hata, Masako Nakanishi, Yoshihiko Morita, Ge-Hong Wada Sun, Yoh Wada, Natsuo Yasui and Toshiyuki Yoneda : The a3 isoform vacuolar type H-ATPase promotes distant metastasis in the mouse B16 melanoma cells., Molecular Cancer Research : MCR, Vol.9, No.7, 845-855, 2011.
(Summary)
Accumulating evidence indicates that the acidic microenvironments critically influence malignant behaviors of cancer including invasiveness, metastasis, and chemoresistance. Because the vacuolar-type H(+)-ATPase (V-ATPase) has been shown to cause extracellular acidification by pumping protons, we studied the role of V-ATPase in distant metastasis. Real-time PCR analysis revealed that the high-metastatic B16-F10 melanoma cells strongly expressed the a3 isoform V-ATPase compared to the low-metastatic B16 parental cells. Consistent with this, B16-F10 cells created acidic environments in lung metastases by acridine orange staining and strong a3 V-ATPase expression in bone metastases by immunohistochemistry. Immunocytochemical analysis showed B16-F10 cells expressed a3 V-ATPase not only in cytoplasm but also plasma membrane, whereas B16 parental cells exhibited its expression only in cytoplasm. Of note, knockdown of a3 V-ATPase suppressed invasiveness and migration with reduced MMP-2 and MMP-9 expression in B16-F10 cells and significantly decreased lung and bone metastases, despite that tumor growth was not altered. Importantly, administration of a specific V-ATPase a3 inhibitor FR167356 reduced bone metastasis of B16-F10 cells. These results suggest that a3 V-ATPase promotes distant metastasis of B16-F10 cells by creating acidic environments via proton secretion. Our results also suggest that inhibition of the development of cancer-associated acidic environments by suppressing a3 V-ATPase could be a novel therapeutic approach for the treatment of cancer metastasis.
Jason Mefford, Koichi Sairyo, Toshinori Sakai, Justin Hopkins, Madoka Inoue, Rui Amari, Nitin N Bhatia, Akira Dezawa and Natsuo Yasui : Modic Type 1 Change in Lumbar Spine in Golfers., Skeletal Radiology, Vol.40, No.4, 467-473, 2011.
(Summary)
Low back pain (LBP) is the most prevalent musculoskeletal complaint among professional and amateur golfers; however, associated radiological changes in golf-related LBP have not been examined in the literature. We suspect that Modic Type 1 changes in the lumbar spine are linked to golf-related LBP. In this retrospective case series, four middle-aged golfers (one professional and three high-level amateurs) presented to our clinic with LBP. Inflammation of the right side of endplates in the lumbar spine was suspected based on Modic Type 1 changes detected by magnetic resonance imaging (MRI) in each patient. All four cases were diagnosed with right-sided endplate inflammation and administered intradiscal steroid injections with a non-steroidal anti-inflammatory drug (NSAID). Treatment swiftly alleviated LBP and diminished Modic Type 1 changes on follow-up MRI 3-6 months later in all four patients. We suggest that Modic Type 1 changes play a significant role in the diagnosis and treatment of golf-related LBP.
(Keyword)
Golf / Humans / Low Back Pain / Lumbar Vertebrae / Magnetic Resonance Imaging / Male / Middle Aged
Mitsuhiko Takahashi, Shinjiro Takata, Natsuo Yasui, R Samuel WARD and L Richard LIEBER : Tendon Transfer Increases Passive Tension of the Entire Muscle, Fiber Bundle and Single Fiber, The Japanese Journal of Rehabilitation Medicine, Vol.48, No.2, 129-133, 2011.
(Summary)
Skeletal muscle is known to be set at an over-stretched length in clinical tendon transfer. Such chronic stretching of skeletal muscle increases the serial sarcomere number required for muscle adaptation. Passive tension of the muscle must be affected during the adaptation. Thus, the objective of this study was to clarify the origin of increased passive tension after stretched tendon transfer in an animal model. The distal tendon of the extensor digitorum of the second toe was transposed to the extensor retinaculum at 3.7 mm of muscle sarcomere length. The contralateral muscle served as control. Muscle passive length-tension curves were measured at 1 week and 4 weeks after the transfer to the bilateral muscles. After functional measurements were taken, the muscles were dissected into fiber bundles and single muscle fibers to measure their passive mechanical properties with a micro force transducer. Passive tension was increased in the transferred muscle with a steeper inclination and leftward shift of muscle length-tension curve. Elastic modulus of the transferred fiber bundle increased at both time points, while those of the transferred single fibers increased only at 1 week. Results of the study suggest that the transferred muscle increased passive tension mainly due to proliferation of extracellular connective tissue within the muscle. Increased passive tension was a characteristic feature for the transferred muscle, which may ultimately represent a target for therapeutic intervention to optimize muscle function.
(Keyword)
tendon transfer / 受動張力 / sarcomere / tendon transfer / passive tension / passive tension / interstitial connective tissue
Terai Tomoya, Koichi Sairyo, Goel K. Vijay, Ebraheim A. Nabil, Biyani Ashok, Faizan Ahmad, Kiapour Ali, Higashino Kosaku, Toshinori Sakai and Natsuo Yasui : Biomechanical rationale of sacral rounding deformity in pediatric spondylolisthesis: a clinical and biomechanical study., Archives of Orthopaedic and Trauma Surgery, Vol.131, No.9, 1187-1194, 2011.
(Summary)
Rounding surface of the sacral dome and wedging deformity of the vertebral body are commonly observed in patients with isthmic spondylolisthesis. Recently, an animal study showed that the deformity can be caused by the growth plate involvement in the immature pediatric vertebral body after biomechanical alteration due to the pars defects. However, the pathomechanism and biomechanics of these deformities have yet to be clarified. To demonstrate that the sacral rounding deformity observed in pediatric patients with spondylolisthesis can be reversed, and to understand the pathomechanism of the deformity from the biomechanical standpoint by analyzing changes of stress around the growth plate of the vertebral body due to spondylolysis. Three-dimensional finite element pediatric lumbar models of the L3-L5 segment were utilized. Unlike the adult model, this pediatric model had growth plates and apophyseal rings. We analyzed stress distribution in response to 351°N axial compression and 10 N m moment in flexion, extension, lateral bending, and axial rotation. Bilateral spondylolysis was created in the model at the L4 level. The stress in the bilateral defect model was compared to the intact model predictions and the results obtained in the pediatric patients with sacral rounding deformity. Two patients presented rounding deformity of the anterior upper corner at S1 at the initial visit. They were asked to stop sports activities and use a soft trunk brace. Twelve months later, no rounding deformity was observed on the radiographs indicating that this deformity was reversible in pediatric cases. The biomechanical study indicated that in the pediatric spondylolytic spine, mechanical stress increased at the anterior upper corner during lumbar motion. In the presence of spondylolysis, mechanical stress increases in the growth plate at the anterior upper corner. Repetitive increases of mechanical stress may cause rounding deformity of the sacral dome mediated by growth plate involvement. When mechanical stress at the growth plate is reduced by wearing a brace, the proper functioning of the growth plate can help to remodel the sacral dome to its normal shape.
Yoshinori TAKAHASHI, Mitsuhiko Takahashi, Hirofumi Kosaka, Shinsuke Katoh and Natsuo Yasui : One case of plexiform schwannoma of sciatic nerve ; A case report, 中部日本整形外科災害外科学会雑誌. 中部日本整形外科災害外科学会抄録, Vol.54, No.1, 43-44, 2011.
Ichiro Tonogai, Yoshitaka Hamada, Tatsuhiko Henmi and Natsuo Yasui : Trigger thumb of the dominant hand in identical twins., Journal of Pediatric Orthopaedics. Part B, Vol.20, No.1, 56, 2011.
Shinji Yoshioka, Koichi Sairyo, Toshinori Sakai, Tatsuya Tamura, Hirofumi Kosaka and Natsuo Yasui : Osseous erosion by herniated nucleus pulposus mimicking intraspinal tumor: a case report., Journal of Orthopaedics and Traumatology, Vol.11, No.4, 257-261, 2010.
(Summary)
Erosion of spinal osseous structure, so-called scalloping, has been rarely reported associated with herniated nucleus pulposus (HNP). We report a rare case of HNP causing erosion of the spinal osseous structure (including lamina). The patient was an 81-year-old woman with 3-year history of low-back pain and left leg radiating pain. Muscle weakness of the left leg was also apparent. Computed tomography following myelography showed severe compression of the dural sac at the level of L3-L4; furthermore, erosion of the lamina, pedicle, and vertebral body was noted, indicating that the space-occupying mass was most probably a tumorous lesion. The mass also showed calcification inside. During the surgery, the mass was confirmed to be an HNP with calcification. Following resection, the pain disappeared. Surgeons should be aware of the possibility of scalloping of the vertebrae caused by HNP mimicking a tumorous lesion.
In myxoid liposarcoma (MLS), the t(12;16)(q13;p11) chromosomal translocation and its resultant fusion transcript, the human translocation liposarcoma (TLS)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), are found in the majority of cases. On the other hand, the variant translocation, t(12;22)(q13;q12) creating the Ewing sarcoma (EWS)-CHOP fusion transcript, is detectable in a limited number of cases. Tissue from MLS arising in the left thigh of a 19-year-old female was analyzed for possible detection of chromosome translocation and fusion transcript. Fluorescent in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR) methods were used. FISH analysis demonstrated a rearrangement in the CHOP gene. RT-PCR analysis confirmed the presence of EWS-CHOP chimeric transcript type 1, in which exon 7 of EWS was in-frame fused to exon 2 of CHOP with a serine (AGT) to methionine (ATG) transition at the junction. The patient underwent a radical segmental resection including a left vastus medialis musclectomy. Sixty months following the surgical resection, the patient was alive with no evidence of disease. Analysis of MLS with EWS-CHOP variant transcripts, type 1 through type 4, including this case together with 15 cases in the literature, indicated that MLS with type 1 fusion transcript may show a more favorable clinical behavior than MLS with other types of fusion transcript.
Toshinori Sakai, Koichi Sairyo, Shoichiro Takao, Hirofumi Kosaka and Natsuo Yasui : Adolescents with symptomatic laminolysis. -Report of two cases-., Journal of Orthopaedics and Traumatology, Vol.11, No.3, 189-193, 2010.
(Summary)
Retroisthmic cleft refers to a cleft in the lamina and is rarely reported. It was first described by Brocher, and later Wick et al. proposed the term "laminolysis" to describe the retroisthmic cleft by analogy with the nomenclature of the applied stress fracture of the pars interarticularis (spondylolysis) and the pedicle (pediculolysis). In this paper, we describe two adolescent sports players with symptomatic lumbar laminolysis. Both improved significantly after adequate conservative treatment. Knowledge of laminolysis in adolescent patients with low back pain is necessary to avoid overlooking it and late diagnosis. For correct diagnosis, multidetector three-dimensional computed tomography (CT) is suggested. In addition, magnetic resonance imaging (MRI) also allows detection of inflammation in the defects.
(Keyword)
Adolescent / Follow-Up Studies / Humans / Image Interpretation, Computer-Assisted / Immobilization / Injections, Intra-Articular / Lidocaine / Low Back Pain / Lumbar Vertebrae / Magnetic Resonance Imaging / Male / Pain Measurement / Recovery of Function / Severity of Illness Index / Spondylolysis / Steroids / Tomography, X-Ray Computed / Treatment Outcome
Pedram Heidari, Aziz Abbaspour, Taghi Baghdadi, Ramin Espandar, Mahmoud Farzan, Saeid Amanpour, Mohammad Reza Rasouli, Mohammad Ali Mohagheghi, Hamid Reza Amiri and Natsuo Yasui : Effect of risedronate on bone resorption during consolidation phase of distraction osteogenesis: a rabbit model., Journal of Orthopaedic Surgery (Hong Kong), Vol.18, No.2, 228-234, 2010.
(Summary)
To evaluate the effects of continuous local injection of risedronate in the prevention of bone resorption in a lengthened segment. 11 male rabbits underwent subperiosteal osteotomy of the left tibia and an external fixator was applied anteromedially. After a lag phase of one week, a 2-week distraction phase and a 5-week consolidation phase followed. Risedronate was continuously injected into the centre of the distracted segment at a rate of 10 micro g/kg/day during the first 14 days of consolidation by a subcutaneously implanted osmotic pump. A control group received purified buffer solution (PBS) using the same protocol. The lengthened bone segments were evaluated using radiography, quantitative computed tomography, and 3-point bending mechanical test. Risedronate injection prevented osteopenia as compared to PBS injection. The mean bone mineral content, volumetric density and cross-sectional area of the lengthened segments were significantly higher in the risedronate group than in controls (as much as 65%, 30%, and 25%, respectively). There was no significant difference between the 2 groups regarding the ultimate load to failure. Continuous local injection of risedronate into the lengthened segment can prevent osteopenia during distraction osteogenesis but fails to enhance mechanical strength of newly distracted segments.
(Keyword)
Animals / Bone Density Conservation Agents / Bone Regeneration / Bone Resorption / Disease Models, Animal / Dose-Response Relationship, Drug / Etidronic Acid / Follow-Up Studies / Injections, Intralesional / Intraoperative Care / male / Osteogenesis, Distraction / Rabbits / Retrospective Studies / Tibia / Treatment Outcome
Tomoya Terai, Koichi Sairyo, VK Goel, N Ebraheim, A Biyani, A Faizan, Toshinori Sakai and Natsuo Yasui : Spondylolysis originates in the ventral aspect of the pars interarticularis: a clinical and biomechanical study., The Journal of Bone and Joint Surgery. British Volume, Vol.92, No.8, 1123-1127, 2010.
(Summary)
Lumbar spondylolysis is a stress fracture of the pars interarticularis. We have evaluated the site of origin of the fracture clinically and biomechanically. Ten adolescents with incomplete stress fractures of the pars (four bilateral) were included in our study. There were seven boys and three girls aged between 11 and 17 years. The site of the fracture was confirmed by axial and sagittal reconstructed CT. The maximum principal tensile stresses and their locations in the L5 pars during lumbar movement were calculated using a three-dimensional finite-element model of the L3-S1 segment. In all ten patients the fracture line was seen only at the caudal-ventral aspect of the pars and did not spread completely to the craniodorsal aspect. According to the finite-element analysis, the higher stresses were found at the caudal-ventral aspect in all loading modes. In extension, the stress was twofold higher in the ventral than in the dorsal aspect. Our radiological and biomechanical results were in agreement with our clinical observations.
Koichi Sairyo, Toshinori Sakai, Kousaku Higashino, M Inoue, Natsuo Yasui and A Dezawa : Complications of endoscopic lumbar decompression surgery., Minimally Invasive Neurosurgery : MIN, Vol.53, No.4, 175-178, 2010.
(Summary)
Endoscopic lumbar decompression is useful for the treatment of various spinal conditions and is being performed in an increasing number of patients worldwide. We reviewed the surgery-related complications in patients who underwent endoscopic surgery and discuss the learning curve for this procedure. Since the first case in August 2000, a total of 138 patients have undergone endoscopic posterior decompression surgery. Of these, there were 74 patients with Herniated Nucleus Pulposus (HNP), 57 with Lumbar Canal Stenosis (LCS), and 7 with other conditions. From 2003 to 2005, the senior surgeon took a sabbatical, and no endoscopic surgery was conducted. We divided the cases based on the date of surgery: there were 62 patients in the early (E) group (before September 2003), and 76 in the late (L) group (from January 2006 to April 2008). We compared the incidence of surgery-related complications between 2 disease types as well as between the E and L groups. We encountered 11 complications, which included 6 dural tears, 2 post-surgical hematomas, 2 neural complications and 1 fracture of the inferior articular process. The incidence of surgery-related complications was 8.6%. The incidences of complications were 8.1% and 9.3% for HNP and LCS, respectively, and 11.3%, and 5.3% in the E and L groups, respectively. The incidence was particularly high (16.7%) in the E group with LCS. There is a steep learning curve for endoscopic surgery. Based on the data, surgeons should start performing endoscopic techniques for LCS after gaining enough experience of endoscopic surgery for HNP.
Kiminori Yukata, Takahiro Kubo, Yoshito Matsui, Tomofumi Koizumi, Shinjiro Takata and Natsuo Yasui : Nonunion of capital femoral physeal fracture with a large metaphyseal fragment., Journal of Orthopaedic Trauma, Vol.24, No.8, e75-e77, 2010.
(Summary)
This report presents a case demonstrating the nonunion of a capital femoral physeal fracture with a large metaphyseal fragment in a 10-year-old boy. To our knowledge, there is no previously reported case of this type of nonunion. The treatment of this nonunion presented a potential risk of premature physeal closure and avascular necrosis of the femoral head, so internal fixation using cannulated screws and percutaneously drilling with a Kirschner wire to the metaphyseal fragment was used and was effective in bone union without these complications.
(Keyword)
Bone Screws / Bone Wires / Child / Femoral Neck Fractures / Fracture Fixation, Internal / Fractures, Ununited / Humans / Male / Treatment Outcome
Shinji Yoshioka, Koichi Sairyo, Toshinori Sakai and Natsuo Yasui : Congenital absence of lumbosacral articular facet joint associated with conjoined nerve root., Journal of Orthopaedics and Traumatology, Vol.11, No.3, 183-187, 2010.
(Summary)
We report a rare case of congenital absence of the L5-S1 facet joint, which was associated with a conjoined nerve root. Combination of these two anomalies has been quite rarely reported in the literature. A 39-year-old man presented with acute low back pain and right leg radiating pain. Muscle weakness and sensory disturbance of the right leg were also apparent in the region innervated by L5 and S1 nerve roots. Preoperative multidetector three-dimensional computed tomography (3D-CT) showed complete absence of the right S1 superior articular process. Magnetic resonance (MR) images showed lumbar disc herniation at right L5-S1 level that migrated cranially. Intraoperative findings revealed that the right L5 nerve root and S1 nerve root were conjoined, and the conjoined nerve root was compressed by L5-S1 disc herniation, which led to impairment of the conjoined nerve root by a single-level lumbar disc herniation. After removal of the disc herniation, his right leg pain immediately subsided, however muscle weakness and sensory disturbance persisted. Surgeons should be aware of this nerve root anomaly when examining a patient who shows an unusual clinical presentation and/or congenital osseous anomaly.
Toshinori Sakai, Koichi Sairyo, Naoto Suzue, Hirofumi Kosaka and Natsuo Yasui : Incidence and etiology of lumbar spondylolysis: review of the literature., Journal of Orthopaedic Science, Vol.15, No.3, 281-288, 2010.
(Summary)
Lumbar spondylolysis is a defect of the pars interarticularis known to occur as a stress fracture. Its incidence varies considerably depending on ethnicity, sex, and sports activity. However, there are few literature reviews describing its incidence in different ethnic groups or in people who engage in different sports. We reviewed the most relevant articles on spondylolysis published in scientific journals. First, we focused on its incidence in various ethnic groups distributed by sex, the familial occurrence, and in patients with relevant diseases. Second, we focused on the incidence of spondylolysis in relation to the sports practiced by the patients. Although placing special emphasis on the incidence of lumbar spondylolysis in the general population in Japan, we also reviewed the Japanese and English literature to investigate its incidence among those who engage in different sports. The incidence of lumbar spondylolysis in the general Japanese population was 5.9%. Most studies report that the incidence in higher in male subjects than in female subjects. We found that Japanese rugby and judo players were prone to suffer lumbar spondylolysis, at an incidence of about 20%. However, the incidence for Japanese professional soccer and baseball players was much higher, at 30%, which was more than five times the incidence in the general Japanese population. The incidence of lumbar spondylolysis varies depending on ethnicity, sex, family history, relevant disease, and sports activity.
(Keyword)
African Americans / Athletic Injuries / European Continental Ancestry Group / Female / Fractures, Stress / Humans / Incidence / Japan / Lumbar Vertebrae / Male / Spondylolysis / United States
Toshinori Sakai, Koichi Sairyo, Seiichi Mima and Natsuo Yasui : Significance of magnetic resonance imaging signal change in the pedicle in the management of pediatric lumbar spondylolysis., Spine, Vol.35, No.14, E641-645, 2010.
(Summary)
Prospective study. To investigate the time course of signal changes in the adjacent pedicle in fresh pediatric lumbar spondylolysis. A recent study reported that high signal change (HSC) on T2-magnetic resonance image (MRI) in the pedicle adjacent to the pars interarticularis could be an indicator of early spondylolysis. In addition, the HSC-positive pars defects showed significant better bony healing than the HSC-negative pars defects. However, there has been no report on the time course and the duration of HSC. We prospectively investigated 10 boys and 5 girls with fresh lumbar spondylolysis showing HSC in the adjacent pedicle. Their mean age was 15.1 years, ranging from 10 to 17 years. Two patients had multilevel unilateral spondylolysis. Among 15 patients, HSC was found in 22 (12 unilateral and 5 bilateral) pedicles. At the first presentation, the diagnosis of spondylolysis was made based on the plain radiograph findings, multidetector computed tomograms (CTs), and MRI. Every month from the first presentation, follow-up MRIs were taken. When HSC disappeared, multidetector CT was taken to confirm bony healing of the pars defect. Bony healing of the pars was obtained in 21 out of 22 defects. The bony healing rate was 95.6%. In 19 pedicles of 12 patients, HSC gradually diminished by every month until it disappeared 3 months later, and radiologic osseous healing was confirmed by CT in all but 1 patient. In the 3 remaining pedicles of 3 patients, HSC took more than 4 months to disappear. In this study, HSC disappeared in most pedicles on the 3-month follow-up MRI. In patients who did not comply with treatment, HSC tended to last longer. These results led us to hypothesize that MRI at the third month during follow-up can indicate whether the conservative treatment is being successful or not.
Mitsuhiko Takahashi, Yoshiteru Kawasaki, Yoshito Matsui and Natsuo Yasui : Fragmental bone transport in conjunction with acute shortening followed by gradual lengthening for a failed infected nonunion of the tibia., Journal of Orthopaedic Science, Vol.15, No.3, 420-424, 2010.
(Keyword)
Adult / Fractures, Ununited / Humans / Ilizarov Technique / Leg Length Inequality / Male / Osteomyelitis / Recovery of Function / Tibial Fractures / Young Adult
Madoka Inoue, Koichi Sairyo, Toshinori Sakai and Natsuo Yasui : Significance of surgical treatment for severe dystrophic changes in the cervical spine associated with neurofibromatosis type I: a case report., Journal of Pediatric Orthopaedics. Part B, Vol.19, No.3, 270-275, 2010.
(Summary)
There have been several reports about the treatments for dystrophic changes in the thoracic or lumbar spines owing to neurofibromatosis type-1. However, dystrophic changes in the cervical spine have been rarely reported. In this study, we present the case of a 13-year-old boy with severe dystrophic changes (dural ectasia) in the cervical spine owing to neurofibromatosis type-1. Although he had no neurological deficit, imaging studies revealed cervical kyphotic deformity and osteolysis of vertebral bodies. Thinning of vertebral bodies and laminae from C2 to C5 was remarkable, suggesting that the patient was at risk of suffering a spinal injury. The patient underwent cervical posterior fusion. At the 2-year follow-up examination, there was complete posterior bony fusion and no obvious progression.
Keizo Wada, Koichi Sairyo, Toshinori Sakai and Natsuo Yasui : Minimally invasive endoscopic bilateral decompression with a unilateral approach (endo-BiDUA) for elderly patients with lumbar spinal canal stenosis., Minimally Invasive Neurosurgery : MIN, Vol.53, No.2, 65-68, 2010.
(Summary)
Endoscopic spinal surgery has become increasingly common year for year because it is a minimally invasive procedure. In our hospital, we introduced endoscopic bilateral decompression with a unilateral approach (endo-BiDUA) in 2006. In this paper, we review clinically and radiographically the elderly patients who underwent the endo-BiDUA. Fifteen patients aged over 65 years were included in this review. They had undergone endo-BiDUA between January 2006 and July 2008. Operation time, blood loss, complications, clinical outcome using the Japanese Orthopedic Association (JOA) score, and enlargement ratio of the dural tube on magnetic resonance imaging (MRI), were evaluated. The mean operation time per level of endo-BiDUA was 144 min. Blood loss was about 60.2 mL. One patient had a post-surgical hematoma and required an additional laminectomy and removal of the hematoma 2 days after the surgery. No other complications such as dural tear, nerve root injury, or infection were encountered. All patients but one, who had a post-surgical hematoma, could start walking within 2 days following the surgery. Before surgery, the mean JOA score was 17.0 and it improved to about 23.3 after the surgery. The area of the dural tube increased to 408.0% after the surgery (range: 211-774%). Endo-BiDUA facilitated the return of elderly patients with lumbar spinal canal stenosis to their original daily activities.
(Keyword)
Aged / Aged, 80 and over / Decompression, Surgical / Endoscopy / Female / Humans / Lumbar Vertebrae / Magnetic Resonance Imaging / Male / Spinal Stenosis / Treatment Outcome
Kiminori Yukata, Yoshito Matsui, C Shukunami, A Takimoto, Nori Hirohashi, O Ohtani, T Kimura, Y Hiraki and Natsuo Yasui : Differential expression of Tenomodulin and Chondromodulin-1 at the insertion site of the tendon reflects a phenotypic transition of the resident cells., Tissue & Cell, Vol.42, No.2, 116-120, 2010.
(Summary)
The insertion site of the tendon to the skeletal element is hypovascular and is one of the most common sites of dysfunction in the musculoskeletal system. However, the resident cells have been poorly defined due to a lack of a specific marker for tenocytes. We previously reported that Tenomodulin (Tnmd) and Chondromodulin-1 (Chm1) are homologous angiogenesis inhibitors and predominantly expressed in the avascular region of tendons and cartilage, respectively. In this study, we analyzed the expression of Tnmd, Chm1, alpha 1 chain of the type I collagen (Col1a1) and alpha 1 chain of the type II collagen (Col2a1) at the insertion site of the Achilles, patellar, or rotator cuff tendons of 1-week-old rabbits by in situ hybridization analysis. Tnmd was co-expressed with Col1a1 in tenocytes of these tendons, while Chm1 and Col2a1 were detected in chondrocytes of the hyaline cartilage. Interestingly, the cell population between Tnmd/Col1a1 positive tenocytes and Chm1/Col2a1 positive chondrocytes expressed Col1a1 but none of the other markers (Tnmd, Chm1, and Col2a1). Red blood cells were exclusively present at the interface between the tendon substance and cartilage in the insertion site of the Achilles tendon. Lack of Tnmd and Chm1 in this newly characterized cell population may allow the transitional zone between the poorly vascularized tendon and cartilage to establish the unique vascular pattern for blood supply.
(Keyword)
Animals / Animals, Newborn / Cartilage / Chondrocytes / Cloning, Molecular / Collagen Type I / Collagen Type II / Connective Tissue Cells / Erythrocytes / In Situ Hybridization / Intercellular Signaling Peptides and Proteins / Membrane Proteins / Phenotype / RNA, Messenger / Rabbits / Tendons / Weight-Bearing
An ossified arachnoid membrane combined with cystic formation is rarely reported as a cause of spinal cord compression. We report the case of a 60-year-old man who presented with diffuse ossification of the arachnoid membrane (arachnoid ossification) and multiple cystic changes (arachnoid cyst) at the thoracic and lumbar spine. The lesions were surgically removed and progressive deterioration was prevented, although no marked improvement of neurological symptoms was attained.
Tatsuya Tamura, Toshinori Sakai, Koichi Sairyo, Shoichiro Takao, Seiko Kagawa, Shinsuke Katoh and Natsuo Yasui : Hematoma in the Cervical Ligamentum Flavum. Report of a Case and Review of the Literature., Skeletal Radiology, Vol.39, No.3, 289-293, 2010.
(Summary)
Hematoma of the cervical ligamentum flavum is very rare, and its pathogenesis is unknown. We describe a case of ligamentum flavum hematoma in the cervical spine causing severe myelopathy. Postoperative histological examination suggested it was the result of the rupture of a hemangioma or of an arteriovenous malformation in the ligamentum flavum. After removal of the lesion, the patient's condition immediately improved. Review of all three reported cases, including this one, showed that complete resection of the mass resulted in immediate relief of symptoms of incomplete paraplegia. The findings of magnetic resonance imaging (MRI) of the hematoma may vary with time, and they may show no characteristic intensity. However, MRI of this case revealed that the tissues surrounding the mass were enhanced with gadolinium diethylene triamine penta-acetic acid, and an area of homogeneous iso-intensity was clearly surrounded by a low-intensity area (flavum) on T2-weighed short-tau inversion recovery images. These findings could be characteristic of the ligamentum flavum hematoma and might help in the differentiation from a cervical epidural hematoma.
Koichi Sairyo, Toshinori Sakai, Rui Amari and Natsuo Yasui : Causes of radiculopathy in young athletes with spondylolysis., The American Journal of Sports Medicine, Vol.38, No.2, 357-362, 2010.
(Summary)
The main clinical symptom of lumbar spondylolysis is lower back pain. Radiculopathy rarely occurs without vertebral slippage. Hypothesis Spondylolysis in young athletes can cause lumbar radiculopathy. Case series; Level of evidence, 4. Ten patients (7 males and 3 females) were included in this study. The age of the patients ranged from 12 to 27 years. We employed plain radiography, computed tomography, magnetic resonance imaging, and selective radiculography if needed. The pathomechanism was classified into nonspondylolytic radiculopathy (3 cases) and spondylolytic radiculopathy (7 cases). In the nonspondylolytic group, 1 patient had a juxta-facet cyst at L4-5 and 2 patients had a herniated nucleus pulposus. In the other group, spondylolytic-related factors caused radiculopathy, and spondylolysis was in the early or progressive stage in all 7 patients. Radiologic findings indicated that radiculopathy was caused by extraosseous hematoma or edema in the vicinity of the fracture site. The radiculopathy disappeared within a month of nonoperative management, and radiologic abnormalities disappeared 3 to 6 months later. Radiculopathy can occur together with lumbar spondylolysis without slippage in young athletes. We propose extra-osseous hematoma or edema at the site of spondylolysis as the unique pathomechanism causing radiculopathy in young athletes. Radiculopathy is rare in athletes with spondylolysis. Magnetic resonance imaging is a useful tool to clarify the pathologic changes that induce the radiculopathy for both spondylolytic and nonspondylolytic factors.
(Keyword)
Adolescent / Adult / Athletes / Child / Female / Humans / Low Back Pain / Magnetic Resonance Imaging / Male / Radiculopathy / Spondylolysis / Tomography, X-Ray Computed / Young Adult
Shigetaka Nakao, Shinjiro Takata, Hirokazu Uemura, Michiharu Kashihara, Toshifumi Osawa, Koji Komatsu, Yuki Masuda, Tetsuya Okahisa, Koji Noshikawa, Shin Kondo, Megumi Yamada, Risa Takahara, Yoshimi Ogata, Yuka Nakamura, Sinji Nagahiro, Ryuji Kaji and Natsuo Yasui : Relationship between Barthel Index scores during the acute phase of rehabilitation and subsequent ADL in stroke patients., The Journal of Medical Investigation : JMI, Vol.57, No.1-2, 81-88, 2010.
(Summary)
The Barthel Index (BI) cannot be used to measure initial stroke severity or by extension, to stratify patients by severity in acute stroke trials because most patients are bedbound in the first few hours after stroke, either by their deficit or by medical directive. Our objectives were to clarify the threshold of acute BI for use in the prediction of subsequent independence in activities of daily living (ADL) and to assist in the definition of acute stroke rehabilitation goals. Subjects comprised 78 patients out of 191 inpatients admitted with acute stroke at our hospital during 2006-2007. The BI ADL score was divided into 2 ranges (BI> or =60 and < or =40), in a process similar to previous studies. During the acute period (from onset to approximately 3 weeks), all patients with a BI> or =40 could improve their ADL in 6 months. Patients with a BI< or =40 exhibited two ADL recovery outcomes (improved and no change) at 6 months. We also found that the skill level of basic activities related to standing was significant indicator of BI improvement (P<0.001). BI scores determined at approximately 3 weeks were reliable predictors of ADL disabilities at 6 months.
(Keyword)
Activities of Daily Living / Acute Disease / Aged / Female / Geriatric Assessment / Humans / Male / Middle Aged / Severity of Illness Index / Stroke
Shigetaka Nakao, Shinjiro Takata, Hirokazu Uemura, Shunji Nakano, Hiroshi Egawa, Yoshiteru Kawasaki, Michiharu Kashihara and Natsuo Yasui : Early ambulation after total knee arthroplasty prevents patients with osteoarthritis and rheumatoid arthritis from developing postoperative higher levels of D-dimer., The Journal of Medical Investigation : JMI, Vol.57, No.1-2, 146-151, 2010.
(Summary)
This study aimed to clarify the therapeutic effects of postoperative ambulation after total knee arthroplasty (TKA) on deep venous thrombosis (DVT) in patients with osteoarthritis (OA) and rheumatoid arthritis (RA) after TKA. Subjects of this study were thirty-seven inpatients (21 inpatients: OA, 16 inpatients: RA) undergoing TKA (32 female and 5 male). Subjects were divided into two groups, deep venous thrombosis (DVT) group (n=25) and non-DVT group (N group, n=12). The cutoff value was 10.0 microg/ml plasma D-dimer level measured on 7(th) postoperative day. The N group was below the cutoff value. Another cutoff value divided into two groups, ambulatory group (n=26) and non-ambulatory group (n=11). Ambulatory group was the date of ambulation beginning below 7(th) day. Statistical analysis confirmed that all subjects showed a significant correlation to the date of ambulation. Postoperative ambulation beginning had strong association with the level of D-dimer (r=0.71). Group comparison showed that the non-ambulatory group had significant higher values of D-dimer than ambulatory group (P=0.022). Typical case supported these results. Postoperative early ambulation within a week after TKA kept patients with OA and RA after TKA lower level of D-dimer.
(Keyword)
Aged / Aged, 80 and over / Arthritis, Rheumatoid / Arthroplasty, Replacement, Knee / Early Ambulation / Female / Fibrin Fibrinogen Degradation Products / Humans / Male / Middle Aged / Osteoarthritis, Knee / Postoperative Period / Venous Thrombosis
In subsets of adipocytic tumors, specific chromosomal translocations lead to the generation of fusion genes. The high mobility group A2 (HMGA2)-lipoma preferred partner (LPP) and the reciprocal LPP-HMGA2 represent such fusion genes in lipoma, while the human translocation liposarcoma (TLS)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) and the Ewing sarcoma (EWS)-CHOP in liposarcoma. However, the specificity of these fusion genes has not been established in a variety of adipocytic tumors. One hundred and seventy-two cases of adipocytic tumors, comprising 98 cases of lipoma and 74 cases of liposarcoma, were analyzed for the possible expression of HMGA2-LPP, LPP-HMGA2, TLS-CHOP and EWS-CHOP fusion genes, using a reverse-transcription polymerase chain reaction method. In lipoma, twenty-two cases (22.4%) were associated with either HMGA2-LPP or LPP-HMGA2, while neither TLS-CHOP nor EWS-CHOP transcript was detectable. On the contrary, in liposarcoma, neither HMGA2-LPP nor LPP-HMGA2 transcript was detectable, although twenty-five cases (33.8%) were related to either TLS-CHOP or EWS-CHOP. HMGA2-LPP and LPP-HMGA2 were specific to lipoma, and TLS-CHOP and EWS-CHOP were specific to liposarcoma.
Shoichiro Takao, Toshinori Sakai, Koichi Sairyo, Tadashi Kondo, Junji Ueno, Natsuo Yasui and Hiromu Nishitani : Radiographic comparison between male and female patients with lumbar spondylolysis., The Journal of Medical Investigation : JMI, Vol.57, No.1-2, 133-137, 2010.
(Summary)
We studied the lumbar spines of 117 adults (39 women and 78 men) with spondylolysis unrelated to low back pain using multidetector computed tomography (CT). Of the 117 subjects with spondylolysis, including five with multiple-level spondylolysis, there were 124 vertebrae with spondylolysis. In adult lumbar spines with unilateral spondylolysis, there was no significant difference between the incidence of spondylolisthesis in female and male subjects. However, in those with bilateral spondylolysis, there was a significantly higher incidence of spondylolisthesis in female subjects (90.9%) than in males (66.2%). Furthermore, females with bilateral spondylolysis had significant more slippage than males. Lumbar index and lumbar lordosis were not significantly different between male and female subjects, and did not significantly correlate with slippage. In conclusion, to treat acute spondylolysis in adolescents, it is important to obtain bony union at least unilaterally, especially in female subjects, to prevent further slippage.
(Keyword)
Adult / Aged / Aged, 80 and over / Female / Humans / Incidence / Lumbar Vertebrae / Male / Middle Aged / Sex Characteristics / Spondylolisthesis / Spondylolysis / Tomography, X-Ray Computed
Tetsuya Matsuura, Shinji Kashiwaguchi, Takenobu Iwase, Tetsuya Enishi and Natsuo Yasui : The Value of Using Radiographic Criteria for the Treatment of Persistent Symptomatic Olecranon Physis in Adolescent Throwing Athletes., The American Journal of Sports Medicine, Vol.38, No.1, 141-145, 2010.
(Summary)
Previously published reports present a variety of nonoperative and operative treatments for a persistent olecranon physis. However, the radiographic indication for the operative treatment is not clear. Our radiographic classification of persistent olecranon physis is helpful in formulating treatment decisions. Cohort study; Level of evidence, 3. Sixteen male baseball players with persistent olecranon physis were retrospectively evaluated. The mean age at first presentation was 14.7 years (range, 12-17 years). The lesion was classified into 2 stages based on radiographic appearance. Stage I demonstrated widening of the olecranon epiphyseal plate when compared with the contralateral elbow on the lateral view. Sclerotic change indicated stage II. All patients underwent nonoperative treatment for at least 3 months. Follow-up radiographs were taken at 1-month intervals. Operative treatment was provided to the patients whose condition had failed to improve after nonoperative treatment. Of the 16 patients, 12 had stage I lesions and 4 had stage II lesions. Nonoperative management produced healing in 91.7% of patients with stage I lesions and none of the patients with stage II lesions. Our radiographic classification of persistent olecranon physis is useful for treatment decision making. In addition, our results demonstrated that sclerotic change is a high predictive indicator of the need for operative treatment.
(Keyword)
Adolescent / Baseball / children / Cohort Studies / decision making / Elbow / Elbow Joint / Growth Plate / Humans / male / Retrospective Studies / Time Factors
Shinji Yoshioka, Yoshitaka Hamada, Shinjiro Takata, Hiroaki Takai and Natsuo Yasui : An Osteochondroma Limiting Flexion of the Proximal Interphalangeal Joint in Hereditary Multiple Exostosis: a Case Report., Hand (New York, N.Y.), 2009.
(Summary)
We describe a patient in which an osteochondroma, which resulted from hereditary multiple exostoses, limited flexion of the proximal interphalangeal (PIP) joint at birth. The tumor grew over the original distal head of the proximal phalanx, and the early appearance of a second ossification center on the base of the middle phalanx was observed. The mass was removed surgically when the patient was 17 months old. There was an improvement in the range of motion at a follow-up evaluation 3 years later. The tumor shape and the growth of the affected PIP joint are examined in detail.
Toshinori Sakai, Koichi Sairyo, Shoichiro Takao, Hiromu Nishitani and Natsuo Yasui : Incidence of lumbar spondylolysis in the general population in Japan based on multidetector computed tomography scans from two thousand subjects., Spine, Vol.34, No.21, 2346-2350, 2009.
(Summary)
Epidemiological analysis using CTs. To investigate the true incidence of lumbar spondylolysis in the general population in Japan. Although there have been several reports on the incidence of lumbar spondylolysis, they had some weakness. One of them concerns the subjects investigated, because the incidence of lumbar spondylolysis varies considerably, and some patients are asymptomatic. In addition, most of the past studies used plain radiograph films or skeletal investigation. Therefore, the past reported incidence may not correspond to that of the general population. We reviewed the computed tomography (CT) scans of 2000 subjects (age: 20-92 years) who had undergone abdominal and pelvic CT on a single multidetector CT scanner for reasons unrelated to low back pain. We reviewed them for spondylolysis, spondylolytic spondylolisthesis, and spina bifida occulta (SBO) in the lumbosacral region. The grade (I-IV) of spondylolisthesis was measured using midsagittal reconstructions. Lumbar spondylolysis was found in 117 subjects (5.9%). Their male-female ratio was 2:1. Multiple-level spondylolysis was found in 5 subjects (0.3%). Among these 117 subjects, there were 124 vertebrae with spondylolysis. Of them, 112 (90.3%) corresponded to L5, and 26 (21.0%) had unilateral spondylolysis.SBO was found in 154 subjects. Of them, 25 had spondylolysis (16.2%), whereas, in 1846 subjects without SBO, 92 had spondylolysis (5.0%). The incidence of spondylolysis among the patients with SBO was significantly higher than that in subjects without SBO (Odd ratio was 3.7-fold).Of 124 vertebrae with spondylolysis, 75 (60.5%) showed low-grade (Meyerding grade I or II) spondylolisthesis, and no subject presented high-grade spondylolisthesis. Spondylolisthesis was found in 74.5% of the subjects with bilateral spondylolysis, and in 7.7% of those with unilateral spondylolysis. The incidence of lumbar spondylolysis in the Japanese general population was 5.9% (males: 7.9%, females: 3.9%).
(Keyword)
Adult / Aged / Aged, 80 and over / Female / Humans / Incidence / Japan / Lumbar Vertebrae / Male / Middle Aged / Spina Bifida Occulta / Spondylolisthesis / Spondylolysis / Tomography, X-Ray Computed / Young Adult
Yoshiteru Kawasaki, Naoyoshi Hanaoka, Mitsuhiko Takahashi, Hiroshi Egawa and Natsuo Yasui : Percutaneous opening wedge varus osteotomy with a multidrilling guide in Perthes' disease: a technical note on two cases., Journal of Pediatric Orthopaedics. Part B, Vol.18, No.5, 242-247, 2009.
(Summary)
We report a technique of percutaneous opening wedge intertrochanteric femoral osteotomy using a multidrilling guide with application of an Ilizarov external fixator in the management of Perthes' disease, and describe the early results obtained in two children. The average operative time was 96.5 min and the duration of external fixation was 51.5 days. Intraoperative blood loss was less than 20 ml. There were no significant complications. This percutaneous technique offers several advantages over currently available methods for surgical containment of Perthes' disease. These include a small incision, soft tissue preservation, sufficient stability, easy procedure, and short time in fixator.
Reiko Nakao, Katsuya Hirasaka, Jumpei Goto, Kazumi Ishidoh, Chiharu Yamada, Ayako Ohno, Yuushi Okumura, Ikuya Nonaka, Koji Yasutomo, KM Baldwin, Eiki Kominami, Akira Higashibata, Keisuke Nagano, Keiji Tanaka, Natsuo Yasui, EM Mills, Shinichi Takeda and Takeshi Nikawa : Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading., Molecular and Cellular Biology, Vol.29, No.17, 4798-4811, 2009.
(Summary)
Skeletal muscle atrophy caused by unloading is characterized by both decreased responsiveness to myogenic growth factors (e.g., insulin-like growth factor 1 [IGF-1] and insulin) and increased proteolysis. Here, we show that unloading stress resulted in skeletal muscle atrophy through the induction and activation of the ubiquitin ligase Cbl-b. Upon induction, Cbl-b interacted with and degraded the IGF-1 signaling intermediate IRS-1. In turn, the loss of IRS-1 activated the FOXO3-dependent induction of atrogin-1/MAFbx, a dominant mediator of proteolysis in atrophic muscle. Cbl-b-deficient mice were resistant to unloading-induced atrophy and the loss of muscle function. Furthermore, a pentapeptide mimetic of tyrosine(608)-phosphorylated IRS-1 inhibited Cbl-b-mediated IRS-1 ubiquitination and strongly decreased the Cbl-b-mediated induction of atrogin-1/MAFbx. Our results indicate that the Cbl-b-dependent destruction of IRS-1 is a critical dual mediator of both increased protein degradation and reduced protein synthesis observed in unloading-induced muscle atrophy. The inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy.
Shunji Nakano, Testuya Enishi, Yehya Mohamed Hasan, Naoyoshi Hanaoka, Yoshiteru Kawasaki, Hiroshi Egawa, Isamu Kinoshita and Natsuo Yasui : Arthoplasty using a custom-made cemented total hip prosthesis for an extensive giant cell tumor of the proximal femur: report of a patient followed up for over 30 years., Archives of Orthopaedic and Trauma Surgery, Vol.129, No.9, 1171-1175, 2009.
(Summary)
We report the case of a 26-year-old man who had a pathologic transtrochanteric fracture of the left femur due to a grade II giant cell tumor affecting the neck and the trochanteric area. This patient underwent complete resection of the tumor and arthroplasty using a custom-made cemented total hip prosthesis. The good radiologic and functional results of the surgery have been maintained for over 30 years without local recurrence or lung metastasis. Moreover, new bone formation was observed at the reattachment sites of abductors, iliopsoas tendons and vastus lateralis to the femoral component of the prosthesis although local bone resorption was detected at the upper lateral part of the femoral stem and zone I of the cup side.
Toshinori Sakai, Shinsuke Katoh, Koichi Sairyo, Tatsuya Tamura, Nori Hirohashi, Kousaku Higashino and Natsuo Yasui : Anterior transvertebral herniotomy for cervical disc herniation: a long-term follow-up study, Journal of Spinal Disorders & Techniques, Vol.22, No.6, 408-412, 2009.
(Summary)
Retrospective study. To investigate the efficacy and radiologic changes after anterior transvertebral herniotomy (ATH), in patients followed for at least 10 years after the surgery. The theoretical idea of ATH is to remove an extruded herniated mass while preserving disc motion. To our knowledge, no report has been published on the long-term outcome of this procedure. Twenty patients underwent single-level ATH at our institution between 1989 and 1995. Clinical outcome was evaluated by visual analog scale for neck and arm pain according to Japanese Orthopaedic Association (JOA) score, and range of motion (ROM) of the cervical spine. Radiologic outcome was evaluated by measuring disc height and range of intervertebral motion of the site on plain radiographs. We also evaluated the operated and the adjacent segments by magnetic resonance imaging (MRI) for degenerative changes. Fifteen of the 20 patients were evaluated. One patient required additional surgery, 3 patients were lost to follow-up, and 1 patient had died by the time of the evaluation. Therefore, we evaluated the clinical outcome of 15 patients. Both the plain radiographs and MRI were available from 10 patients, and for 3 patients only the plain radiographs were available. Two patients refused x-ray examination at the final follow-up. Regarding clinical outcome, no patient had suffered from neck pain or arm pain. The average visual analog scale was 7.8/100 (%) for neck pain, and 7.0/100 (%) for arm pain. JOA scores improved and remained at a good level. The improvement rate was 88.5%. The average ROM of the cervical spine was 42.7 degrees in flexion, 52.3 degrees in extension, 58.6 degrees in axial rotation, and 25.0 degrees in lateral bending. Although ROM in axial rotation and lateral bending was symmetric, the range was smaller than that in the healthy segments. On plain radiographs, although the disc height in the operated segment was not significantly decreased compared with the other segments, loss of intervertebral motion was noticed on the follow-up roentgenograms in most cases. Only 2 patients had mobility of the operated intervertebral levels (>10 degrees). There was no collapse of the drilled vertebral body in any patient. Four of the 10 patients who underwent MRI showed protrusion of intervertebral discs, including those adjacent to the affected discs. No recurrence of disk herniation at the involved level was seen on the follow-up MRI. In conclusion, ATH provided a good clinical outcome that was maintained for a long time. Although intervertebral motion at the operated level decreased to some extent, degenerative changes at the adjacent levels were not enhanced.
(Keyword)
Activities of Daily Living / Cervical Vertebrae / Diskectomy / Female / Follow-Up Studies / Humans / Intervertebral Disc / Intervertebral Disc Displacement / magnetic resonance imaging / Male / Middle Aged / Neck Pain / Patient Satisfaction / Postoperative Complications / Range of Motion, Articular / Retrospective Studies / Spinal Cord Compression / Spondylosis / time / Treatment Outcome
Kousaku Higashino, Koichi Sairyo, Shinsuke Katoh, Shunji Nakano, Tetsuya Enishi and Natsuo Yasui : The effect of rheumatoid arthritis on the anatomy of the female cervical spine: a radiological study., The Journal of Bone and Joint Surgery. British Volume, Vol.91, No.8, 1058-1063, 2009.
(Summary)
The effect of rheumatoid arthritis on the anatomy of the cervical spine has not been clearly documented. We studied 129 female patients, 90 with rheumatoid arthritis and 39 with other pathologies (the control group). There were 21 patients in the control group with a diagnosis of cervical spondylotic myelopathy, and 18 with ossification of the posterior longitudinal ligament. All had plain lateral radiographs taken of the cervical spine as well as a reconstructed CT scan. The axial diameter of the width of the pedicle, the thickness of the lateral mass, the height of the isthmus and internal height were measured. The transverse diameter of the transverse foramen (d1) and that of the spinal canal (d2) were measured, and the ratio d1/d2 calculated. The width of the pedicles and the thickness of the lateral masses were significantly less in patients with rheumatoid arthritis than in those with other pathologies. The area of the transverse foramina in patients with rheumatoid arthritis was significantly greater than that in the other patients. The ratio of d1 to d2 was not significantly different. A high-riding vertebral artery was noted in 33.9% of the patients with rheumatoid arthritis and in 7.7% of those with other pathologies. This difference was statistically significant. In the rheumatoid group there was a significant correlation between isthmus height and vertical subluxation and between internal height and vertical subluxation.
(Keyword)
Adult / Aged / Aged, 80 and over / Arthritis, Rheumatoid / Cervical Vertebrae / Disease Progression / Female / Humans / Internal Fixators / Middle Aged / Predictive Value of Tests / Vertebral Artery / Young Adult
Takahiro Kubo, Yoshito Matsui, Norifumi Naka, Nobuhito Araki, Tomohiro Goto, Kiminori Yukata, Kenji Endo, Natsuo Yasui, Akira Myoui, Hidehiko Kawabata, Hideki Yoshikawa and Takafumi Ueda : Expression of HMGA2-LPP and LPP-HMGA2 Fusion Genes in Lipoma: Identification of a Novel Type of LPP-HMGA2 Transcript in Four Cases, Anticancer Research, Vol.29, No.6, 2357-2360, 2009.
(Summary)
In a subset of lipoma, a specific t(3;12)(q27-28;q14-15) chromosomal translocation leads to the fusion of the high mobility group A2 (HMGA2) gene and the lipoma preferred partner (LPP) gene. Although the expression of HMGA2-LPP fusion gene has been reported in lipomas, the reciprocal LPP-HMGA2 fusion gene has rarely been described. Ninety-eight cases of lipoma were analyzed for the possible expression of HMGA2-LPP and LPP-HMGA2 fusion genes using a reverse-transcription polymerase chain reaction method. Ten lipomas (10%) revealed both HMGA2-LPP and LPP-HMGA2 fusion transcripts, nine (9%) only HMGA2-LPP, and three (3%) only LPP-HMGA2. DNA sequencing analysis demonstrated that the HMGA2-LPP transcript in 19 lipomas consisted of exons 1-3 of HMGA2 and exons 9-11 of LPP, which was described previously. Out of 13 lipomas with LPP-HMGA2 transcript, 9 were associated with a previously reported LPP-HMGA2 fusion transcript, which fuses exon 8 of LPP to exon 4 of HMGA2, while 4 with a novel type of LPP-HMGA2 fusion transcript, which fuses exon 7 of LPP to exon 4 of HMGA2. In addition to the HMGA2-LPP fusion gene, the LPP-HMGA2 fusion gene could have some specific roles for lipomagenesis. The biological implications of the expression and the variation of LPP-HMGA2 fusion transcripts need to be elucidated.
Abbaspour Aziz, Mitsuhiko Takahashi, Koichi Sairyo, Shinjiro Takata, Kiminori Yukata, Ami Inui and Natsuo Yasui : Optimal increase in bone mass by continuous local infusion of alendronate during distraction osteogenesis in rabbits, Bone, Vol.44, No.5, 917-923, 2009.
(Summary)
Several methods have been used to increase bone mass in distraction osteogenesis. Since bone resorption as well as regeneration is stimulated in the distracted segment, bisphosphonate can be a beneficial agent for distraction osteogenesis. Here, we examined the effects of bisphosphonate injected continuously into the regenerate on bone volume, and architectural and mechanical properties of distraction osteogenesis. The left tibia of Japanese White rabbits (n=66) was subjected to slow distraction using an external fixator. At the beginning of the consolidation phase, alendronate (7 microg/kg/day) was infused directly into the lengthened segment for 14 days using an osmotic pump. Control rabbits were infused with phosphate buffered saline (PBS). The tibiae were monitored weekly by soft X-ray and dual-energy X-ray absorptiometry (DXA). The animals were sacrificed at 4, 6, and 8 weeks after operation to examine bone mineral density (BMD) and cortical bone thickness (CBT) by peripheral quantitative computerized tomography (pQCT), while the mechanical property of the lengthened tibia was measured by three-point bending test. In PBS-infused control animals, bone mineral content around the lengthened segment began to decrease after the first week of consolidation phase, forming a tubular bone structure with thin cortex. Infusion of alendronate increased peak bone mineral content around the lengthened segment. At the end of the experiment, volumetric BMD, CBT and mechanical strength of the lengthened segment of the treatment group were approximately twice those of the control animals. Alendronate infused in this manner significantly prevented the osteopenia that critically began early in the consolidation phase, though the dose used in this study was relatively low and no adverse events were noted.
(Keyword)
Absorptiometry, Photon / Alendronate / Animals / Biomechanical Phenomena / Bone Density / Male / Osteogenesis, Distraction / Rabbits / Tibia / Tomography, X-Ray Computed
Koichi Sairyo, Toshinori Sakai and Natsuo Yasui : Minimally invasive technique for direct repair of pars interarticularis defects in adults using a percutaneous pedicle screw and hook-rod system., Journal of Neurosurgery. Spine, Vol.10, No.5, 492-495, 2009.
(Summary)
In this report, the authors described a new minimally invasive technique to repair pars interarticularis defects in adults. The well-established technique using the pedicle screw (PS) and hook-rod system was modified. First, bilateral PSs were inserted percutaneuosly using the Sextant system. Then, through a small skin incision (3-4 cm), an illuminated tubular retractor (Quadrant system; Medtronic Sofamore Danek) was inserted into the pars defect. When this system is used, it is not necessary to detach all the back muscles to access the lytic part. The bursa and fibrocartilaginous mass near the defects were removed. After decortication of the pseudarthrosis at the spondylolytic level, bone grafts were implanted. Finally, the hook part of a hook-rod system was attached to the lamina and the rod was secured at the tulip head of the PSs. The authors performed this procedure in 2 adult patients, 32 and 24 years of age. Immediately after surgery both patients' low-back pain disappeared, and by 3 months postoperatively both had returned to their original work or sports activities.
(Keyword)
Bone Screws / Humans / Lumbar Vertebrae / Male / Pseudarthrosis / Spondylolysis / Surgical Procedures, Minimally Invasive / Young Adult
Kiminori Yukata, Mitsuhiko Takahashi and Natsuo Yasui : [Bone fracture and the healing mechanisms. The mechanical stress for fracture healing in view of distraction osteogenesis][Article in Japanese], Clinical Calcium, Vol.19, No.5, 641-646, 2009.
(Summary)
It is generally accepted that moderate mechanical stress influences the course of fracture healing. A flexible fixation of the fractured site can induce fracture callus formation, whereas an unstable fixation can lead to a nonunion. The relationship between mechanical stress and the process of bone regeneration or healing remains incompletely understood. Distraction osteogenesis is a surgical technique that, using appropriate mechanical tension-stress, does not break the callus but rather it stimulates and maintains osteogenesis. The common principles of distraction osteogenesis are osteotomy and slow progressive distraction by an external fixation device. Interest in bone regeneration associated with mechanical stress might lead to better understanding of the fracture healing process.
Fumio Hayashi, Toshinori Sakai, Koichi Sairyo, Nori Hirohashi, Kousaku Higashino, Shinsuke Katoh and Natsuo Yasui : Intramedullary schwannoma with calcification of the epiconus., The Spine Journal, Vol.9, No.5, e19-e23, 2009.
(Summary)
There have been few reports on intramedullary ancient schwannoma. Schwann cells are generally present in the nerve root, not in the spinal cord. Thus, intramedullary schwannomas are rare, and in most cases there is cyst formation without calcification. To report a patient with intramedullary ancient schwannoma at the epiconus together with a review of the previously published cases. Case report. A 78-year-old woman. Retrospective case review. DESCRIPTION OF THE CASE: A 78-year-old woman had presented with severe weakness of the lower extremities, increased patellar reflex, and sensory disturbance of the entire lower extremities. Magnetic resonance imaging showed a tumorous mass in the intramedullary region of epiconus at T11-L1, and computed tomography revealed calcification in the tumor. She underwent total resection of the tumor. Histopathological findings were consistent with the diagnosis of ancient schwannoma. After the operation, although lower extremities weakness and sensory disturbance deteriorated transiently, lower leg pain disappeared. At the final follow-up of 10 months after the operation, lower leg pain did not relapse. We reported a rare case presenting epiconus syndrome due to intramedullary ancient schwannoma, which should be considered for the differential diagnosis of a tumor that shows calcification.
Kazumasa Nishimoto, Yuta Kochi, Katsunori Ikari, Kazuhiko Yamamoto, Akari Suzuki, Kenichi Shimane, Yusuke Nakamura, Koichiro Yano, Noriko Iikuni, So Tsukahara, Naoyuki Kamatani, Hiroshi Okamoto, Hirotaka Kaneko, Yasushi Kawaguchi, Masako Hara, Yoshiaki Toyama, Takahiko Horiuchi, Kayoko Tao, Koji Yasutomo, Daisuke Hamada, Natsuo Yasui, Hiroshi Inoue, Mitsuo Itakura, Hisashi Yamanaka and Shigeki Momohara : Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese., Annals of the Rheumatic Diseases, Vol.69, No.2, 368-373, 2009.
(Summary)
The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed. A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay. Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04). Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.
(Keyword)
Arthritis, Rheumatoid / Asian Continental Ancestry Group / Autoantibodies / Case-Control Studies / Cell Line / Complement C5 / Female / Genetic Predisposition to Disease / Genome-Wide Association Study / Genotype / Hand Joints / Humans / Lupus Erythematosus, Systemic / Male / Middle Aged / Polymorphism, Single Nucleotide / TNF Receptor-Associated Factor 1
Rui Amari, Toshinori Sakai, Shinsuke Katoh, Koichi Sairyo, Kosaku Higashino, Keizo Tachibana and Natsuo Yasui : Fresh stress fractures of lumbar pedicles in an adolescent male ballet dancer: case report and literature review., Archives of Orthopaedic and Trauma Surgery, Vol.129, No.3, 397-401, 2009.
(Summary)
Stress fracture in the pars interarticularis is a common cause of low back pain in young athletes. Pedicle stress fractures have also been reported in adolescent sport players, and most of them were associated with contralateral spondylolysis. Only a few cases with bilateral pedicle stress fractures have been reported. We report a 14-year-old ballet dancer with fresh bilateral pedicle fractures treated conservatively, together with a review of the literature.
(Keyword)
Adolescent / Dancing / Fractures, Stress / Humans / Low Back Pain / Lumbar Vertebrae / Male / Spinal Fractures
Koichi Sairyo, Toshinori Sakai and Natsuo Yasui : Conservative treatment of lumbar spondylolysis in childhood and adolescence: the radiological signs which predict healing., The Journal of Bone and Joint Surgery. British Volume, Vol.91, No.2, 206-209, 2009.
(Summary)
It has been noted that bony union of a pars defect can be achieved in children if they wear a trunk brace. Our aim was to evaluate how the stage of the defect on CT and the presence or absence of high signal change in the adjacent pedicle on T2-weighted MRI were related to bony healing. We treated 23 children conservatively for at least three months. There were 19 boys and four girls with a mean age of 13.5 years (7 to 17). They were asked to refrain from sporting activity and to wear a Damen soft thoracolumbosacral type brace. There were 41 pars defects in 23 patients. These were classified as an early, progressive or terminal stage on CT. The early-stage lesions had a hairline crack in the pars interarticularis, which became a gap in the progressive stage. A terminal-stage defect was equivalent to a pseudarthrosis. On the T2-weighted MR scan the presence or absence of high signal change in the adjacent pedicle was assessed and on this basis the defects were divided into high signal change-positive or -negative. Healing of the defect was assessed by CT. In all, 13 (87%) of the 15 early defects healed. Of 19 progressive defects, only six (32%) healed. None of the seven terminal defects healed. Of the 26 high signal change-positive defects 20 (77%) healed after conservative treatment whereas none of the high signal change-negative defects did so. We concluded that an early-stage defect on CT and high signal change in the adjacent pedicle on a T2-weighted MR scan are useful predictors of bony healing of a pars defect in children after conservative treatment.
Koichi Sairyo, Toshinori Sakai, Kousaku Higashino, Tatsuya Tamura, Shinsuke Katoh and Natsuo Yasui : Cervical and upper thoracic screwing for spinal fusion: strategy for its safe insertion to avoid major complications., Archives of Orthopaedic and Trauma Surgery, Vol.129, No.11, 1447-1452, 2009.
(Summary)
There are several screwing techniques to attain cervical fusion such as pedicle screw, lateral mass screw, facet screw, transarticular and laminar screw. Each screwing technique has advantages and disadvantages. In this study, we introduce our strategy for safe screwing and its clinical results. Our strategy is as follows: lateral mass screw for C1, 3, 4, 5, 6 and pedicle screw for C2, 7, and thoracic level. When the C2 pedicle is thinner than 3.5 mm, we use C2 laminar screws. We do not use Magerl transarticular screw or facet screw; 146 screws were inserted in 17 patients. There were no major complications such as spinal cord and nerve root injury. We did not observe vertebral arterial injury either. Of the 146 screws, 141 (97.0%) were accurately inserted. As for lateral mass screwing by Roy-Camille's technique and C2 laminar screwing, all screws were inserted in the appropriate site (100%) without any complications. Five pedicle screws were misplaced. Of the 57 pedicle screws, 5 showed a minor tear of the wall at C7, Th1 and Th3, the success rate for all pedicle screws was 91%. All showed solid fusion. For cervical screwing the most important aspect should be safety to avoid severe morbidity. Our strategy, which consists in the combined use of pedicle, lateral mass and laminar screwing, is safe and reliable.
Koichi Sairyo, Toshinori Sakai, Natsuo Yasui, Ali Kiapour, Ashok Biyani, Nabil Ebraheim and K Vijay Goel : Newly occurred L4 spondylolysis in the lumbar spine with pre-existence L5 spondylolysis among sports players: case reports and biomechanical analysis., Archives of Orthopaedic and Trauma Surgery, Vol.129, No.10, 1433-1439, 2009.
(Summary)
STUDY DESIGN: Case series and a biomechanical study using a finite element (FE) analysis. OBJECTIVES: To report three cases with multi-level spondylolysis and to understand the mechanism biomechanically. BACKGROUND: Multi-level spondylolysis is a very rare condition. There have been few reports in the literature on multi-level spondylolysis among sports players. METHODS: We reviewed three cases of the condition, clinically. These patients were very active young sports players and had newly developed fresh L4 spondylolysis and pre-existing L5 terminal stage spondylolysis. Thus, we assumed that L5 spondylolysis may have increased the pars stress at the cranial adjacent levels, leading to newly developed spondylolysis at these levels. Biomechanically, we investigated pars stress at L4 with or without spondylolysis at L5 using the finite element technique. RESULTS: L4 pars stress decreased in the presence of L5 spondylolysis, which does not support our first hypothesis. CONCLUSIONS: It seems that multi-level spondylolysis may occur due to genetic and not biomechanical reasons.
Chondromodulin-I (Chm-I) is a glycoprotein that stimulates the growth of chondrocytes and inhibits angiogenesis in vitro. Mice lacking the Chm1 gene show abnormal bone metabolism and pathological angiogenesis in cardiac valves in the mature stage although they develop normally without aberrations in endochondral bone formation during embryogenesis or in cartilage development during growth. These findings indicate that Chm-I is critical under conditions of stress such as bone repair through endochondral ossification of a fracture callus. We carried out the present study to examine the expression and role of Chm-I in bone repair using a stabilized tibial fracture model, and compared fracture healing in Chm1 knockout (Chm1(-/-)) mice with that in wild-type mice. Chm-I mRNA and protein localized in the external cartilaginous callus in the reparative phase of fracture healing. Radiological examination showed a delayed union in Chm1(-/-) mice although the fracture site was covered with both external and internal calluses. Chm1 null mutation reduced external cartilaginous callus formation as judged by marked decrease of type X collagen alpha 1 (Col10a1) expression and the total amount of cartilage matrix. Interestingly, the majority of chondrocytes in the periosteal callus failed to differentiate into mature chondrocytes in Chm1(-/-) mice, while the hypertrophic maturation of chondrocytes between the cortices was not affected. These results suggest that Chm-I is involved in hypertrophic maturation of periosteal chondrocytes. Although a direct effect of Chm-I on bones is still unclear, bony callus formation was increased while external cartilaginous callus decreased in Chm1(-/-) mice. We conclude that in the absence of Chm1, predominant primary bone healing occurs due to an indirect effect induced by reduction of cartilaginous callus rather than to a direct effect on osteogenic function, resulting in a delayed union.
Shinjiro Takata, Shoichiro Takao, Shusaku Yoshida, Fumio Hayashi and Natsuo Yasui : Therapeutic effects of one-year alendronate treatment in three cases of osteoporosis with parietal thinning of skull., The Journal of Medical Investigation : JMI, Vol.55, No.3-4, 297-302, 2008.
(Summary)
We studied the therapeutic effects of one-year alendronate treatment in three cases (two males and one female) of osteoporosis with parietal thinning of skull. Plain radiography and three dimensional computed tomography revealed asymmetric external thinning of the posteromedial part of the bilateral parietal bones. Technetium-99m methylenediphosphate bone scintigraphy did not show any changes in these three cases. Pretreatment levels of urinary type I collagen cross-linked N-telopeptides (NTX) in all three cases were high compared to the normal range. Pretreatment levels of serum bone-specific alkaline phosphatase (BAP) in the two male patients were high in contrast to the normal values in the female patient. Pretreatment mean bone mineral density (BMD) values of the 2nd to 4th lumbar vertebrae (L2-4BMD), head BMD, femoral neck BMD, and whole body BMD of all three patients were low compared with the respective normal ranges. One-year alendronate treatment decreased both urinary NTX and serum BAP in all three cases to normal values. Treatment also increased the whole body BMD in all three cases, the L2-4BMD of the female patient, the femoral neck BMD of the female patient and one male patient, and the head BMD of the female patient when compared to pretreatment levels.
(Keyword)
Aged / Alendronate / Bone Density / Bone Density Conservation Agents / Female / Humans / Male / Osteoporosis / Parietal Bone / Radiopharmaceuticals / Technetium Tc 99m Medronate / Time Factors
Shu Kobayashi, Katsunori Ikari, Hirotaka Kaneko, Yuta Kochi, Kazuhiko Yamamoto, Kenichi Shimane, Yusuke Nakamura, Yoshiaki Toyama, Takeshi Mochizuki, So Tsukahara, Yasushi Kawaguchi, Chihiro Terai, Masako Hara, Taisuke Tomatsu, Hisashi Yamanaka, Takahiko Horiuchi, Kayoko Tao, Koji Yasutomo, Daisuke Hamada, Natsuo Yasui, Hiroshi Inoue, Mitsuo Itakura, Hiroshi Okamoto, Naoyuki Kamatani and Shigeki Momohara : Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population., Arthritis and Rheumatism, Vol.58, No.7, 1940-1946, 2008.
(Summary)
OBJECTIVE: STAT4 encodes a transcriptional factor that transmits signals induced by several key cytokines, and it might be a key molecule in the development of autoimmune diseases. Recently, a STAT4 haplotype was reported to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in Caucasian populations. This was replicated in a Korean RA population. Interestingly, the degree of risk of RA susceptibility with the STAT4 haplotype was similar in the Caucasian and Korean populations. The present study was undertaken to investigate the effect of STAT4 on susceptibility to RA and SLE in the Japanese. METHODS: We performed an association study using 3 independent Japanese RA case-control populations (total 3,567 cases and 2,199 controls) and 3 independent Japanese SLE populations (total 591 cases). All samples were genotyped using the TaqMan fluorogenic 5' nuclease assay for single-nucleotide polymorphism (SNP) rs7574865, which tags the susceptibility haplotype. The association of the SNP with disease susceptibility in each case-control study was calculated using Fisher's exact test, and the results were combined, using the Mantel-Haenszel method, to obtain combined odds ratios (ORs). RESULTS: We observed a significant association of the STAT4 polymorphism with susceptibility to both RA and SLE. The combined ORs for RA and SLE, respectively, were 1.27 (P = 8.4 x 10(-9)) and 1.61 (P = 2.1 x 10(-11)) for allele frequency distribution; these ORs were quite similar to those previously observed in the Caucasian population. CONCLUSION: We conclude that STAT4 is associated with RA and SLE in the Japanese. Our results indicate that STAT4 is a common genetic risk factor for autoimmune diseases, with similar strength across major racial groups.
(Keyword)
Aged / Arthritis, Rheumatoid / Case-Control Studies / Female / Genetic Predisposition to Disease / Haplotypes / Humans / Japan / Lupus Erythematosus, Systemic / Male / Middle Aged / Polymorphism, Single Nucleotide / Risk Factors / STAT4 Transcription Factor
Kousaku Higashino, Shinsuke Katoh, Koichi Sairyo, Yuichiro Goda, Toshinori Sakai, Takashi Kitaichi, Tetsuya Kitagawa and Natsuo Yasui : Pseudoaneurysm of the thoracoabdominal aorta caused by the severe migration of an anterior spinal device. A case report., The Spine Journal, Vol.8, No.4, 696-699, 2008.
(Summary)
Case report. To describe the case of pseudoaneurysm of the thoracoabdominal aorta caused by the severe migration of an anterior spinal device 5 years after surgery. Case report. A 70-year-old woman was referred to us because of migrated anterior spinal devices and a pseudoaneurysm of the thoracoabdominal aorta. This patient had undergone anterior corpectomy and spinal fusion from Th12 to L2 because of delayed palsy after a burst fracture using a smooth rod Kaneda device (SRK) with bioactive ceramic (apatite-wollastonite containing glass ceramic) at a local hospital. She had persistent low back pain after the surgery. Five years after the initial surgery, the patient was referred to us because of increasing of her low back pain and the migrated SRK devices shown on plain X-ray films. An enhanced computed tomography scan taken in our hospital clearly showed a pseudoaneurysm of the thoracoabdominal aorta surrounding the SRK devices. The pseudoaneurysm was resected, the aortic defect was repaired with an artificial patch, and the migrated SRK devices were removed. The pseudoaneurysm of the aorta can occur secondary to a migrated anterior spinal fixation device and can be successfully treated by revision anterior surgery with vascular repair and implant removal.
Yuka Nagasaki, Maki Moritani, Toshihito Tanahashi, Dai Osabe, Kyoko Nomura, Yuka Fujita, Parvaneh Keshavarz, Kiyoshi Kunika, Naoto Nakamura, Toshikazu Yoshikawa, Eiichiro Ichiishi, Hiroshi Shiota, Natsuo Yasui, Hiroshi Inoue and Mitsuo Itakura : Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population., BMC Medical Genetics, Vol.9, 22, 2008.
(Summary)
BACKGROUND: Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The presence of T2D disease susceptibility variant(s) was assessed in the 21.8 Mb region between D15S118 and D15S117 in a Japanese population using a region-wide case-control association test. METHODS: A two-stage association test was performed using Japanese subjects: The discovery panel (Stage 1) used 372 cases and 360 controls, while an independent replication panel (Stage 2) used 532 cases and 530 controls. A total of 1,317 evenly-spaced, common SNP markers with minor allele frequencies > 0.10 were typed for each stage. Captured genetic variation was examined in HapMap JPT SNPs, and a haplotype-based association test was performed. RESULTS: SNP2140 (rs2412747) (C/T) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal p value (p = 0.0043 in the allelic test, OR = 1.26, 95% CI = 1.07-1.48 for combined samples) was weak in a single locus or haplotype-based association test. We failed to find any significant SNPs after correcting for multiple testing. CONCLUSION: The two-stage association test did not reveal a strong association between T2D and any common variants on chromosome 15q14-22.1 in 1,794 Japanese subjects. A further association test with a larger sample size and denser SNP markers is required to confirm these observations.
Kiminori Yukata, Shinsuke Katoh, Koichi Sairyo, Yoshito Matsui, Yoshitaka Hamada and Natsuo Yasui : Os odontoideum in achondroplasia: a case report., Journal of Pediatric Orthopaedics. Part B, Vol.17, No.2, 103-105, 2008.
(Summary)
The neurological complication in achondroplasia has been focused on the foramen magnum stenosis. We report the combination of os odontoideum in a patient with achondroplasia.
Koichi Sairyo, Toshinori Sakai, Kousaku Higashino, Bunji Hirao, Shinsuke Katoh and Natsuo Yasui : Minimally invasive excision of lumbar epidural lipomatosis using a spinal endoscope., Minimally Invasive Neurosurgery : MIN, Vol.51, No.1, 43-46, 2008.
(Summary)
In this report, we describe the case of a patient with a long-term radiculopathy due to epidural lipomatosis at the L3-4 intervertebral disc level. The fatty tissue was located on the dorsal side of the dural sac in the spinal canal and compressed the dural sac. The fatty tissue was removed endoscopically. After surgery, the symptoms disappeared, and neurological deficits normalized. We would like to state that epidural lipomatosis is a good candidate for minimally invasive endoscopic surgery because of its anatomic location.
(Keyword)
Aged / Cauda Equina / Decompression, Surgical / Dura Mater / Endoscopy / Epidural Space / Humans / Lipomatosis / Low Back Pain / Lumbar Vertebrae / Magnetic Resonance Imaging / Male / Polyradiculopathy / Spinal Canal / Surgical Procedures, Minimally Invasive / Treatment Outcome
Ichiro Tonogai, Toshinori Sakai, Shinsuke Katoh, Kousaku Higashino, Koichi Sairyo, Nori Hirohashi and Natsuo Yasui : Myelopathy in a 6-year-old girl caused by neurofibromatosis Type 1: a case report, The Spine Journal, Vol.8, No.5, 836-840, 2008.
(Summary)
Even when there is radiological evidence of spinal involvement, young patients with neurofibromatosis Type 1 (NF-1) seldom have symptoms. We report the case of a child who developed rapidly progressive myelopathy. To describe a technique used to prevent postoperative spinal deformity and instability, after removal of a dumbbell-shaped tumor in a 6-year-old child. Case report. A 6-year-old female. Retrospective case review. The patient underwent a resection of the cervical dumbbell tumor using an osteoplastic laminectomy technique to prevent postoperative spinal deformity. At 2-year follow-up, there was no clinical or radiographic evidence of complications or spinal kyphotic deformity. The case of a 6-year-old girl with cervical myelopathy caused by NF-1 was reported. The tumor was removed after osteoplastic laminectomy, which could prevent postoperative kyphotic deformity.
Tetsuya Matsuura, Shinji Kashiwaguchi, Takenobu Iwase, Yoshitsugu Takeda and Natsuo Yasui : Conservative treatment for osteochondrosis of the humeral capitellum., The American Journal of Sports Medicine, Vol.36, No.5, 868-872, 2008.
(Summary)
BACKGROUND: Conservative treatment is recommended for the early stage of osteochondrosis of the humeral capitellum. However, the outcome of conservative treatment has not been well documented. HYPOTHESIS: Osteochondrosis of the humeral capitellum detected at an early stage responds well to conservative treatment. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We retrospectively reviewed 176 patients with osteochondrosis of the humeral capitellum. There were 134 lesions that were stage I (radiolucent area) in patients with a mean age of 11.5 years and 42 lesions that were stage II (nondisplaced fragments) in patients with a mean age of 13.9 years based on anteroposterior radiographs of the elbow in 45 degrees of flexion. Conservative treatment was performed on 101 patients. The remaining 75 patients did not follow the authors' advice. Conservative treatment consisted of discontinuation of heavy use of the elbow for at least 6 months. Follow-up radiographs were taken at 1-month intervals. At a mean follow-up of 24 months, all patients were evaluated clinically and radiographically. RESULTS: Conservative management produced healing in 90.5% of stage I lesions and 52.9% of stage II lesions. The mean period required for healing was 14.9 months in stage I and 12.3 months in stage II. Sixty-six of 84 (78.6%) stage I patients and 9 of 17 (52.9%) stage II patients returned to competitive-level baseball. Of the 75 patients who did not follow our advice, healing was observed in 17 (22.7%). The healing rate was higher for the 101 patients who followed our advice as opposed to the 75 patients who did not. CONCLUSION: Osteochondrosis of the humeral capitellum can be successfully treated conservatively if treatment is begun in an early stage of the disease.
Shunji Nakano, Toshihiko Nishisyo, Daisuke Hamada, Hirofumi Kosaka, Kiminori Yukata, Kouichi Oba, Yoshiteru Kawasaki, Hideaki Miyoshi, Hiroshi Egawa, Isamu Kinoshita and Natsuo Yasui : Treatment of dysplastic osteoarthritis with labral tear by Chiari pelvic osteotomy: outcomes after more than 10 years follow-up., Archives of Orthopaedic and Trauma Surgery, Vol.128, No.1, 103-109, 2008.
(Summary)
The presence of a damaged labrum is one of many factors influencing the outcomes of Chiari pelvic osteotomy. However, there are few previous papers describing the long-term outcomes of Chiari pelvic osteotomy with labrectomy. The purpose of this study was to evaluate the long-term clinical and radiological outcomes of Chiari pelvic osteotomy for dysplastic hips with labral tears. We compared outcomes between labrectomy (+) and labrectomy (-) groups. Chiari pelvic osteotomies were performed by one surgeon on 34 dysplastic hips with labral tears between 1983 and 1996, in which labrectomy was performed on 23 hips but not on 11 hips. Three patients undergoing labrectomy were lost to follow-up evaluation within 5 years after surgery. The average age of the remaining 31 patients was 35.5 years (range, 16-54 years). The clinical and radiographic surveillance averaged 16.0 years (range, 10-23.3 years). In all patients, pain disappeared after the operation. At the end of the study, 8 of the 31 patients displayed clinical deterioration. Progression of osteoarthritis (OA) was observed in 11 hips. Patients with poor results have not opted for revision surgery except for one patient. In the labrectomy (+) group, 10 of the 20 hips showed progression of OA and the clinical outcomes of 6 patients deteriorated. In the labrectomy (-) group, 1 of the 11 hips showed progression of OA and 2 patients deteriorated clinically. Radiological outcomes differed significantly between the two groups. Labrectomy accompanying Chiari pelvic osteotomy is an acceptable procedure for relieving pain caused by the damaged labrum, but the outcomes have a tendency to deteriorate after 10 or more years postoperatively.
Aziz Abbaspour, Shinjiro Takata, Koichi Sairyo, Shinsuke Katoh, Kiminori Yukata and Natsuo Yasui : Continuous local infusion of fibroblast growth factor-2 enhances consolidation of the bone segment lengthened by distraction osteogenesis in rabbit experiment., Bone, Vol.42, No.1, 98-106, 2008.
(Summary)
Experimental tibial lengthening was achieved in 61 rabbits to examine the effect of continuous local infusion of recombinant human fibroblast growth factor-2 (rhFGF-2) on bone healing of the lengthened segment. The tibial diaphysis was separated by osteotomy and was subjected to slow progressive distraction (rate: 0.35 mm/12 h) using a monolateral external fixator. There were a lag phase for 1 week, a distraction phase for 2 weeks, and a consolidation phase for 5 weeks in this experiment. At various stages of distraction, rhFGF-2 was infused continuously for 2 weeks into the lengthened segment (rate: 14.28 microg/60 microl/day) using an osmotic pump implanted under the skin. Bone healing was significantly accelerated when rhFGF-2 was infused in the beginning of consolidation phase, but not in the distraction phase or in the lag phase. Infusion of normal saline (N/S) using the same osmotic pump had no effect. Dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT) studies demonstrated that rhFGF-2-treated tibia had increased bone mineral density (BMD), bone mineral content (BMC) and cortical bone thickness (CBT) when compared with N/S-treated tibia. Three-point bending test demonstrated that rhFGF-2-treated bone had significantly stronger mechanical properties than N/S-treated bone. Finally, distribution of the infused materials was checked by using Indian ink or radio-opaque. The dyes distributed widely but exclusively in the lengthened segment. Based on these results, we conclude that direct delivery of rhFGF-2 into the lengthened segment can shorten the consolidation phase of limb lengthening and the method is applicable to the clinical treatment.
(Keyword)
Absorptiometry, Photon / Animals / Bone Density / Disease Models, Animal / Fibroblast Growth Factor 2 / Fractures, Bone / Injections, Intralesional / Male / Osteogenesis / Osteogenesis, Distraction / Rabbits / Tomography, X-Ray Computed
Yoichiro Takata, Hiroshi Inoue, Aya Sato, Kazue Tsugawa, Katsutoshi Miyatake, Daisuke Hamada, Fumio Shinomiya, Shunji Nakano, Natsuo Yasui, Toshihito Tanahashi and Mitsuo Itakura : Replication of reported genetic associations of PADI4, FCRL3, SLC22A4 and RUNX1 genes with rheumatoid arthritis: results of an independent Japanese population and evidence from meta-analysis of East Asian studies., Journal of Human Genetics, Vol.53, No.2, 163-173, 2008.
(Summary)
We conducted population-based association tests for the four selected SNPs (rs2240340/padi4_94, rs7528684/fcrl3_3, rs3792876/slc2F2 and rs2268277/runx1) previously reported to be associated with rheumatoid arthritis (RA). The study population consisted of 950 unrelated Japanese subjects with RA and 507 controls, none of whom had previously been tested for these variants. Only the SNP rs2240340/padi4_94 was modestly associated with RA [allele odds ratio (OR) 1.22, 95% confidence interval (CI) 1.04-1.43, P=0.012]. The most significant association effect was found for genotype contrast between minor and major allele homozygotes (OR 1.53, 95% CI 1.10-2.12, P=0.010). No other SNPs showed a statistically significant association with RA in our population. Meta-analysis of published studies and our new data confirmed a highly significant association between PADI4 gene SNPs and increased risk of RA in East Asian populations (allele fixed-effects summary OR 1.31, 95% CI 1.22-1.41, P<0.0001). We found some evidence for an association of either rs7528684/fcrl3_3 or rs3792876/slc2F2 with RA; however, because the magnitudes of effects were apparently much weaker than those reported in the initial positive reports, and there were substantial levels of inter-study OR heterogeneity, we concluded that additional studies are needed to fully understand the present results.
Toshinori Sakai, Koichi Sairyo, Daisuke Hamada, Kousaku Higashino, Shinsuke Katoh, Yoichiro Takata, F Shinomiya and Natsuo Yasui : Radiological features of lumbar spinal lesions in patients with rheumatoid arthritis with special reference to the changes around intervertebral discs., The Spine Journal, Vol.8, No.4, 605-611, 2008.
(Summary)
Compared with the cervical spine, little attention has been paid to rheumatoid arthritis (RA)-related lumbar disorders. Only a few articles have described the status of the lumbar spine affected by RA based on plain X-ray films and magnetic resonance imaging (MRI). To describe the features and prevalence of radiological changes of the lumbar spine of patients with RA and to clarify the correlations of such features with disease activity. Transverse radiological study. We radiographically examined 104 patients with RA whose age ranged from 21 to 78 years (mean, 51.0). In each, the duration of RA exceeded 10 years (mean, 17.7 years). Clinical outcomes included Ochi's classification, Lansbury index, C-reactive protein (CRP) (mg/dL), rheumatoid factor (RF) (U/mL), and platelet (count/mm). Radiological outcomes included radiography and MRI. One hundred four RA patients were included in this study regardless of the presence/absence of low back pain. We examined discs from L1-2 to L5-S, including endplates, in each patient on plain X-ray films and magnetic resonance images and used a comprehensive grading system to evaluate each feature of the lumbar spine affected by RA based on the present findings and published reports. The correlations of these radiological features with RA activity and Ochi's classification were examined. To quantify disease activity, we determined the Lansbury index, serum CRP (mg/dL), RF (U/mL), and platelet count (count/mm) at the time of radiological examinations. Of the 104 patients, 47 (45.2%) exhibited a lumbar lesion. There were two types of lumbar disc lesions related to RA: disc narrowing and disc ballooning. The Lansbury index of patients with the most severe lesions was significantly higher than that of patients with less severe lesions (p<.01). The frequency of lumbar involvement also increased as the number of affected peripheral joints increased, and Ochi's classification appeared to be useful in predicting the occurrence of lumbar lesions. Of 104 patients, 47 (45.2%) exhibited abnormalities on X-ray films and MRI. There were two types of disorders, disc narrowing and disc ballooning. Both the Lansbury index and Ochi's classification reflected the severity of lumbar lesions in RA patients.
(Keyword)
Adult / Aged / Arthritis, Rheumatoid / Female / Humans / Intervertebral Disc / Lumbar Vertebrae / Magnetic Resonance Imaging / Male / Middle Aged / Severity of Illness Index / Spinal Stenosis
Aziz Abbaspour, Shinjiro Takata, Yoshito Matsui, Shinsuke Katoh, Mitsuhiko Takahashi and Natsuo Yasui : Continuous infusion of insulin-like growth factor-I into the epiphysis of the tibia., International Orthopaedics, Vol.32, No.3, 395-402, 2008.
(Summary)
We have developed a method to promote longitudinal bone growth at the level of a specific growth-plate (GP) in young rabbits. Insulin-like growth factor-I (IGF-I) was continuously infused by means of an osmotic pump into the bone marrow cavity of the proximal epiphysis of the tibia. Radiological measurement showed a 2-mm overgrowth of the tibia after 4 weeks of treatment, while histological analysis demonstrated a 15% increase in the thickness of the selected GP. The local infusion of IGF-I increased the numbers of both proliferative and hypertrophic chondrocytes and promoted hyperplasia of bony trabeculae within the epiphysis. The distribution of material infused locally into the epiphysis was simulated by the infusion of Indian ink using the same methodology (osmotic pump) as that for IGF-I. Most of the dye remained within the bone marrow cavity of the epiphysis, but a portion infiltrated into the GP, reaching the deep layer of the physeal chondrocytes and primary spongiosa of the metaphysis. These results suggest that the method reported here is a valid one for delivering cytokines or growth factors to the selected GP and for controlling the growth and differentiation of physeal chondrocytes.
(Keyword)
Animals / Bone Development / Cell Differentiation / Chondrocytes / Epiphyses / Growth Plate / Infusion Pumps, Implantable / Infusions, Intraosseous / Insulin-Like Growth Factor I / Male / Rabbits / Tibia / Tomography
Kousaku Higashino, Koichi Sairyo, Tadanori Sakamaki, Shinnji Komatsubara, Kiminori Yukata, Naohito Hibino, hirofumi Kosaka, Toshinori Sakai, Shinsuke Katoh, Toshiaki Sano and Natsuo Yasui : Vertebral rounding deformity in pediatric spondylolisthesis occurs due to deficient of endochondral ossification of the growth plate: radiological, histological and immunohistochemical analysis of a rat spondylolisthesis model., Spine, Vol.32, No.25, 2839-2845, 2007.
(Summary)
A study using rat spondylolisthesis models. To clarify pathomechanism of vertebral rounding deformity in pediatric spondylolisthesis. For high-grade slippage, rounding of sacrum surface associated with L5 spondylolisthesis is reported to be the most responsible risk factor. However, the exact pathomechanism of the rounding deformity is yet to be clarified. Spondylolisthesis rat model (4-week-old) was used. Radiographs were taken weekly for 5 weeks after the surgery. The lumbar spines were harvested for histology. Hematoxylin and eosin, alcian blue staining, and tartrate-resistant acid phosphatase staining were used. Immunohistochemically, the growth plate cartilage was studied for type II and X collagen. A modified bone histomorphometric analysis was also performed. Radiographs showed slippage 1 week after surgery. Rounding deformity was obvious 2 weeks after surgery. The rounding deformity progressed with time. Three weeks after surgery, the specific columns of growth plate were unclear at the anterior corner, which corresponded to the rounding surface observed on radiographs. Instead, a huge mass of cartilage was observed at that site. Tartrate-resistant acid phosphatase-positive cells were observed in the vicinity of the growth plate except in relation with the anterior corner. The growth plate and cartilage mass at the anterior corner stained positive for type II collagen. Chondrocytes in the hypertrophied layer stained positively for type X collagen; however, staining was faint at the anterior corner. The results suggested that the chondrocytes at the anterior did not form, morphologically and functionally, the normal growth plate. From histomorphometrical analysis, the normal posterior growth plate made endochondral bone growth in 510 +/- 20 microm for a week, whereas the anterior corner in 200 +/- 15 microm. Deficient endochondral ossification of the growth plate in the anterior upper corner of the vertebra could be the pathomechanism of the rounding deformity of the sacrum.
(Keyword)
Acid Phosphatase / Age Factors / Animals / Cartilage / Chondrocytes / Collagen Type II / Collagen Type X / Disease Models, Animal / Female / Growth Plate / Immunohistochemistry / Isoenzymes / Lumbar Vertebrae / Ossification, Heterotopic / Rats / Rats, Wistar / Spondylolisthesis / Time Factors
Hirofumi Kosaka, Koichi Sairyo, Ashok Biyani, Douglas Leaman, Richard Yeasting, Kousaku Higashino, Toshinori Sakai, Shinsuke Katoh, Toshiaki Sano, Vijay K. Goel and Natsuo Yasui : Pathomechanism of loss of elasticity and hypertrophy of lumbar ligamentum flavum in elderly patients with lumbar spinal canal stenosis., Spine, Vol.32, No.25, 2805-2811, 2007.
(Summary)
A histologic, biologic, and immunohistochemical assessment using human samples of lumbar ligamentum flavum. To clarify the pathomechanism of loss of elasticity and hypertrophy of the lumbar ligamentum flavum (LF) in the elderly population. The most common spinal disorder in elderly patients is lumbar spinal canal stenosis, causing low back and leg pain, and paresis. Canal narrowing, in part, results from hypertrophy of the LF. Although histologic and biologic literature on this topic is available, the pathomechanism of loss of elasticity and hypertrophy of the LF is still unknown. One fetus, 5 young, and 5 elderly LF were obtained for histologic study. Hematoxylin and eosin, Alcian blue, Masson Trichrome, and Elastica Van Gieson stains were performed for each LF. Nine LF were collected and were used for biologic study of real time RT-PCR to quantitatively measure mRNA expression of Type I collagen and elastin in each LF. In the LF of the fetus, elastic fibers accounted for about 75% of the entire area. In the dural aspect of the LF in the young and elderly group, the ratio was also around 75%; however, the ratio of the dorsal aspect decreased with age. Almost half of the area showing loss of elastic fibers was shown to be converted to cartilaginous tissue producing Type II collagen and proteoglycan by Alcian blue and Type II collagen immunohistochemistry. The area, which did not stain black with EV nor blue with AB stain, was positively stained blue with T stain, indicating scarring. The area of the normal dural layer was 18.0 +/- 2.3 and 33.8 +/- 4.3 (mm2), for young and elderly group, respectively. Accordingly, it was 3.2 +/- 0.8 and 18.0 +/- 10.2 (mm2), for the dorsal abnormal layer. Elastin mRNA showed a relatively strong correlation (r = 0.44) with age; however, the slope was very gentle. Type I collagen mRNA showed a very strong correlation (r = 0.80) with age. The slope was steeper, and the value reached at 1000% (10-fold) around 65 years old when compared with the LF from younger patient. Elastin mRNA showed a weak correlation (r = 0.36) with thickness, and the slope was gentle. Type I collagen mRNA showed relatively strong correlation (r = 0.52) with thickness. The slope was steeper, and the line reached at 1000% (10-fold) around 6.5 (mm) when compared with a thin LF. Decreased elasticity of LF in the elderly is due to the loss of elastic fibers and a concomitant increase of collagenous fibers in the dorsal aspect. LF hypertrophy could be due to the thickening of the normal elastic layer as well as of the abnormal collagenous layer.
(Keyword)
Adult / Age Factors / aging / Collagen Type I / Collagen Type II / elasticity / Elastin / fetus / Humans / Hypertrophy / Ligamentum Flavum / Lumbar Vertebrae / Middle Aged / RNA, Messenger / Spinal Stenosis
Yoshitaka Hamada, Koichi Sairyo, Natsuo Yasui and Tokio Kasai : Intraneural heterotopic ossification of a digital nerve., The Journal of Hand Surgery, European Volume, Vol.32, No.6, 715, 2007.
Naohito Hibino, Yoshitaka Hamada, Koichi Sairyo, Kiminori Yukata, Toshiaki Sano and Natsuo Yasui : Callus formation during healing of the repaired tendon-bone junction. A rat experimental model., The Journal of Bone and Joint Surgery. British Volume, Vol.89, No.11, 1539-1544, 2007.
(Summary)
This study was undertaken to elucidate the mechanism of biological repair at the tendon-bone junction in a rat model. The stump of the toe flexor tendon was sutured to a drilled hole in the tibia (tendon suture group, n = 23) to investigate healing of the tendon-bone junction both radiologically and histologically. Radiological and histological findings were compared with those observed in a sham control group where the bone alone was drilled (n = 19). The biomechanical strength of the repaired junction was confirmed by pull-out testing six weeks after surgery in four rats in the tendon suture group. Callus formation was observed at the site of repair in the tendon suture group, whereas in the sham group callus formation was minimal. During the pull-out test, the repaired tendon-bone junction did not fail because the musculotendinous junction always disrupted first. In order to understand the factors that influenced callus formation at the site of repair, four further groups were evaluated. The nature of the sutured tendon itself was investigated by analysing healing of a tendon stump after necrosis had been induced with liquid nitrogen in 16 cases. A proximal suture group (n = 16) and a partial tenotomy group (n = 16) were prepared to investigate the effects of biomechanical loading on the site of repair. Finally, a group where the periosteum had been excised at the site of repair (n = 16) was examined to study the role of the periosteum. These four groups showed less callus formation radiologically and histologically than did the tendon suture group. In conclusion, the sutured tendon-bone junction healed and achieved mechanical strength at six weeks after suturing, showing good local callus formation. The viability of the tendon stump, mechanical loading and intact periosteum were all found to be important factors for better callus formation at a repaired tendon-bone junction.
Yoshitaka Hamada, Koichi Sairyo and Natsuo Yasui : Locking of the metacarpophalangeal joint as a result of the shape of the metacarpal head in achondroplasia., The Journal of Hand Surgery, European Volume, Vol.32, No.5, 588-590, 2007.
(Summary)
A 21 year-old woman with achondroplasia exhibited locking of the metacarpophalangeal joint of the right index finger which required surgery to release the joint. Locking was confirmed to be due to entrapment of the fan-like part of the radial collateral ligament on a metacarpal head prominence arising from epiphysial thickening.
Takanobu Nakase, Natsuo Yasui, Hidehiko Kawabata, Nobuyuki Shimizu, Keizi Ohzono, Kauzo Hiroshima and Hideki Yoshikawa : Correction of deformity and shortening due to post traumatic epiphyseal arrest by distraction osteogenesis., Archives of Orthopaedic and Trauma Surgery, Vol.127, No.8, 659-663, 2007.
(Summary)
Growth arrest in the epiphyseal plate during childhood often causes both periarticular deformities and limb length discrepancy, leading to compartmental osteoarthrosis and gait disturbance or spinal disorders, respectively. Distraction osteogenesis using external fixators with hinge systems appears to be useful for the simultaneous correction of deformity and shortening. In this paper, we evaluated cases of lower limbs with periarticular deformities and limb length discrepancy after epiphyseal plate injury that has been treated by distraction osteogenesis using external fixators. This is the first report regarding the outcomes of distraction osteogenesis for a group of patients having deformity and limb length discrepancy due to traumatic arrest of the physis. Successful outcomes may promise the use of this method as the first choice for the treatment of growth disorders after the arrest of the epiphyseal plate in the lower limbs. However, treatment under 20 years of age may provide a better outcome with a lower incidence of complications.
Yukiko Yamashita, Hiroshi Inoue, Keshavarz Parvaneh, Katsuyuki Miyawaki, Yuka Nagasaki, Maki Moritani, Kiyoshi Kunika, Naoto Nakamura, Toshikazu Yoshikawa, Natsuo Yasui, Hiroshi Shiota, Toshihito Tanahashi and Mitsuo Itakura : SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population., Journal of Human Genetics, Vol.52, No.10, 781-793, 2007.
(Summary)
Many genetic association studies support a contribution of genetic variants in the KCNJ11-ABCC8 gene locus to type 2 diabetes (T2D) susceptibility in Caucasians. In non-Caucasian populations, however, there have been only a few association studies, and discordant results were obtained. Herein, we selected a total of 31 SNPs covering a 211.3-kb region of the KCNJ11-ABCC8 locus, characterized the patterns of linkage disequilibrium (LD) and haplotype structure, and performed a case-control association study in a Japanese population consisting of 909 T2D patients and 893 control subjects. We found significant associations between eight SNPs, including the KCNJ11 E23K and ABCC8 S1369A variants, and T2D. These disease-associated SNPs were genetically indistinguishable because of the presence of strong LD, as found previously in Caucasians. For the KCNJ11 E23K variant, the most significant association was obtained under a dominant genetic model (OR 1.32, 95% CI 1.09-1.60, P = 0.004). A meta-analysis of East Asian studies, comprising a total of 3,357 T2D patients (77.4% Japanese) and 2,836 control subjects (77.8% Japanese), confirmed the significant role of the KCNJ11 E23K variant in T2D susceptibility. Furthermore, we found evidence suggesting that the KCNJ11 E23K genotype is independently associated with higher blood-pressure levels.
(Keyword)
ATP-Binding Cassette Transporters / Aged / Asian Continental Ancestry Group / blood pressure / Diabetes Mellitus, Type 2 / female / Humans / Japan / male / Middle Aged / Polymorphism, Single Nucleotide / Potassium Channels / Potassium Channels, Inwardly Rectifying / Receptors, Drug
Nori Hirohashi, Toshinori Sakai, Koichi Sairyo, Koichi Oba, Kousaku Higashino, Shinsuke Katoh and Natsuo Yasui : Lumbar radiculopathy caused by extradural rheumatoid nodules. A case report., Journal of Neurosurgery. Spine, Vol.7, No.3, 352-356, 2007.
(Summary)
The authors report on a 51-year-old woman with a 9-year history of rheumatoid arthritis (RA) who presented with symptomatic rheumatoid nodules in the lumbar extradural region with compression on the L-5 nerve roots bilaterally. She had also suffered from dysesthesia in the right lower leg and intermittent claudication. Magnetic resonance imaging revealed masses compressing the dural sac, and on lumbar myelography and computed tomography myelography a filling defect at L4-5 was revealed, which was compressing the dural sac posterolaterally on both sides. The masses were surgically removed. On histological examination the typical characteristics of rheumatoid nodules were found. Soon after the operation all of the patient's symptoms disappeared. There have been few reports on extradural rheumatoid nodules. Patients with RA usually complain of articular symptoms, and in fact the patient in the present study had been referred to the authors' institution for total hip arthroplasty. However, various symptoms other than those arising from articular lesions were found clinically. The authors believe that if patients with RA are also examined for extraarticular lesions, it is likely that these will be more frequently detected.
Katsutoshi Miyatake, Hiroshi Inoue, Kahoko Hashimoto, Hiroshi Takaku, Yoichiro Takata, Shunji Nakano, Natsuo Yasui and Mitsuo Itakura : PKC412 (CGP41251) modulates the proliferation and lipopolysaccharide-induced inflammatory responses of RAW 264.7 macrophages., Biochemical and Biophysical Research Communications, Vol.360, No.1, 115-121, 2007.
(Summary)
PKC412 (CGP41251) is a multitarget protein kinase inhibitor with anti-tumor activities. Here, we investigated the effects of PKC412 on macrophages. PKC412 inhibited the proliferation of murine RAW 264.7 macrophages through induction of G2/M cell cycle arrest and apoptosis. At non-toxic drug concentrations, PKC412 significantly suppressed the lipopolysaccharide (LPS)-induced release of TNF-alpha and nitric oxide, while instead enhancing IL-6 secretion. PKC412 attenuated LPS-induced phosphorylations of MKK4 and JNK, as well as AP-1 DNA binding activities. Furthermore, PKC412 suppressed LPS-induced Akt and GSK-3beta phosphorylations. These results suggest that the anti-proliferative and immunomodulatory effects of PKC412 are, at least in part, mediated through its interference with the MKK4/JNK/AP-1 and/or Akt/GSK-3beta pathways. Since macrophages contribute significantly to the development of both acute and chronic inflammation, PKC412 may have therapeutic potential and applications in treating inflammatory and/or autoimmune diseases.
(Keyword)
Animals / apoptosis / Cell Line / Cell Proliferation / Cytokines / Dose-Response Relationship, Drug / Drug Combinations / Immunologic Factors / Lipopolysaccharides / Macrophages / Mice / Staurosporine
Shinjiro Takata, Aziz Abbaspour, Michiharu Kashihara, Shigetaka Nakao and Natsuo Yasui : Unilateral chronic insufficiency of anterior cruciate ligament decreases bone mineral content and lean mass of the injured lower extremity., The Journal of Medical Investigation : JMI, Vol.54, No.3-4, 316-321, 2007.
(Summary)
We studied the effects of unilateral chronic anterior cruciate ligament (ACL) injury on bone size, bone mineral content (BMC), bone mineral density (BMD), soft tissue composition and muscle strength of the injured lower extremity in Japanese 21 men and 12 women aged 15 to 39 years. Bone area, BMD, BMC, lean mass and fat mass of lower extremity were measured using dual energy X-ray absorptiometry. The isometric and isokinetic muscle strength was assessed by an isokinetic machine.BMC, lean mass, circumference of the thigh and circumference of the lower leg of the injured lower extremity were significantly smaller than those of the intact lower extremity (p=0.0002, p<0.0001, p<0.0001, p=0.0131). In contrast, fat mass and %Fat of the injured lower extremity was significantly greater than that of the intact lower extremity (p=0.0301, p<0.0001). Bone area and BMD did not produce significant difference. These findings suggest that chronic insufficiency of ACL decreases BMC and lean mass of the injured lower extremity.
(Keyword)
Absorptiometry, Photon / Adolescent / Adult / Anterior Cruciate Ligament / Bone Density / Female / Humans / Leg / Male / Muscle Strength
Shunji Nakano, Takuya Mishiro, Sigeyuki Takahara, Hhiromiti Yokoi, Daisuke Hamada, Kiminori Yukata, Yoichiro Takata, Tomohiro Goto, Hiroshi Egawa, Susumu Yasuoka, H Furouchi, Katsuya Hirasaka, Takeshi Nikawa and Natsuo Yasui : Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis., Clinical Rheumatology, Vol.26, No.8, 1284-1292, 2007.
(Summary)
The objective of this study is to examine the differential expression of mast cell tryptase and its receptor, protease-activated receptor-2 (PAR-2), in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Biochemical and immunohistochemical analyses were performed to determine whether the trypsin-like protease in the synovium is identical to mast cell tryptase. The effects of mast cell tryptase on the proliferation of synovial fibroblast-like cells (SFCs) and the release of IL-8 thereof were evaluated by the [3H]-thymidine incorporation and ELISA, respectively. The trypsin-like protease in the synovium of RA patients was identical to human mast cell tryptase, which was composed of two subunits: 33 and 34 kDa. The 33- and 34-kDa proteins are different glycosylated forms of the 31-kDa protein, which was unglycosylated. Mast cell tryptase activity in RA synovial fluid was significantly higher than that in OA synovial fluid, while their activities and expression in the synovium were similar. Expression of PAR-2 mRNA in the synovium was higher in RA than in OA. Mast cell tryptase containing the unglycosylated 31-kDa subunit was the predominant form in synovial fluid. RA patients had higher amounts of this subunit in their synovial fluid than OA patients. Mast cell tryptase and PAR-2 activating peptide stimulated the proliferation of SFCs and release of IL-8 from these cells. Mast cell tryptase secretion into RA synovial fluid is higher than OA synovial fluid. Mast cell tryptase in synovial fluid stimulates the proliferation of SFCs and the release of pro-inflammatory cytokines via PAR-2, which may contribute to exacerbation of synovitis in RA.
Ichiro Tonogai, Koichi Sairyo, Kousaku Higashino, Toshinori Sakai, Shinsuke Katoh and Natsuo Yasui : Minimally invasive endoscopic removal of herniated nucleus pulposus that had migrated to the S1 nerve root foramen., Minimally Invasive Neurosurgery : MIN, Vol.50, No.3, 173-177, 2007.
(Summary)
In this report, we described an adult case with a lumbar herniated nucleus pulposus that had migrated to the S1 nerve root foramen from L5-S1 disc space. Endoscopically, the migrated mass was successfully removed after laminectomy at the S1 with a small skin incision of 20 mm in length. Unlike the other levels, the intraforaminally migrated mass along the S1 root can be excised without any removal of the facet joints; therefore, additional spinal fusion is not necessary. Thus, an S1 foraminal migrated mass can be a good surgical candidate for minimally invasive endoscopic surgery.
Ayako Tamura, Takako Ichihara, Shinjiro Takata, Takako Minagawa, Yumi Kuwamura, Takae Bando, Natsuo Yasui and Shinji Nagahiro : Study on factors related to loss of lower extremity muscle mass in elderly acute stroke patients, JNI : The Journal of Nursing Investigation, Vol.6, No.1, 23-27, 2007.
(Summary)
The present study investigated the factors contributing to the loss of upper and lower extremity muscle mass in three elderly stroke patients with right hemiplegia in whom our rehabilitation program could not be performed at 1‐2 weeks after onset. The results revealed common factors such as prolonged accurate microinjection of hypotensive agents, severe hemiplegia(Brunnstrom stage I or Ⅱ), diarrhea and delayed initiation of tube feeding at 3 to 8 days after onset. With regard to individual differences, while all patients were recovering in bed, the degree of decrease in muscle mass varied among patients because they moved their extremities differently.
(Keyword)
elderly / acute stroke patients / loss of lower extremity muscle mass / related factors
Takanobu Nakase, Natsuo Yasui, Kenzo Hiroshima, Kenji Ohzono, Chikahisa Higuchi, Nobuyuki Shimizu and Hideki Yoshikawa : Surgical outcomes after treatment of fractures in femur and tibia in pycnodysostosis., Archives of Orthopaedic and Trauma Surgery, Vol.127, No.3, 161-165, 2007.
(Summary)
Pycnodysostosis is a rare hereditary disease, characterized by systemic bone sclerosis. The most important orthopedic problem in this condition is the recurrent pathological fracture of long bones. In this paper, the surgical results for fractures of six limbs (three femurs and three tibias) in five cases of pycnodysostosis are reported. Five limbs achieved fracture union and union is developing in one tibia after intramedullary nail (IM) nailing or Ilizarov external fixation (IEF), although fracture line tends to persist for longer periods of time. One femoral fracture was treated by IM nailing, and one femoral and one tibial fracture were treated by IEF leading to final bone union. One femoral and one tibial fracture were initially treated by IEF, and were treated by IM nailing after re-fracture. One tibial fracture was initially treated by IEF leading to a failure of union, and was converted to IM nailing. All cases are able to walk; one case requires a single crutch. Infection was noted in two limbs after IM nailing following IEF. Fixation with IM nail was effective in preventing re-fracture as well as in alignment correction. Although the surgical technique is more difficult, IM nailing in the initial surgery may be a better choice for achieving successful union while reducing the risk of re-fracture or infection.
Ayako Tamura, Takako Minagawa, Shinjiro Takata, Takako Ichihara, Yumi Kuwamura, Takae Bando, Hiroko Kondo, Natsuo Yasui and Shinji Nagahiro : Effects of intervention with back-lying exercises with bent knees pointing upwards to prevent disuse muscle atrophy in patients with post-stroke hemiplegia, JNI : The Journal of Nursing Investigation, Vol.5, No.2, 53-58, 2007.
(Summary)
The present study measured lower extremity muscle mass using DXA (Dual energy X-ray Absorptiometry) in order to verify the effectiveness of intervention with a series of movements, including lying hip raise exercise with bent knees pointing upwards, among bedridden patients with post-stroke hemiplegia in the acute post-stroke period. Subjects in the intervention group were required to perform 10 repetitions of a series of back-lying exercises once a day with researchers, in addition to the exercises performed by those in a control group. The first measurement of muscle mass was conducted at three to five days after onset, and the second measurement was conducted seven days after the first. Muscle mass in the lower extremities was reduced by approximately 600g (decrease rate : 9%)on the paralyzed side and by 280g on the non-paralyzed side(decrease rate: 5%)in one week in the Brunnstrom stage ≤ II subgroup(site of measurement : lower extremities) (n＝8) of the control group (n＝23). The decrease in muscle mass in the Brunnstrom stage ≤ II subgroup (n＝4) of the intervention group (n＝15) was approximately 260g on the paralyzed side (decrease rate : 5%) and approximately 280g (decrease rate : 5%)on the non-paralyzed side. Thus, muscle mass decreased on both sides, and this occurred regardless of degree of paralysis. Comparison of the Brunnstrom stage ≥ III subgroups between the control and intervention groups also confirmed that the decease in muscle mass was smaller in the latter group. Thus, it was confirmed that back-lying exercises combining lower extremity movements, including hip raises with bent knees pointing upwards, prevented the decrease in lower extremity muscle mass on the paralyzed side in post-stroke patients. The present study also suggests that these exercise movements can be applied to preventive care for bedridden patients with other severe diseases.
(Keyword)
effects of intervention / acute post-stroke period / lower extremity muscle / prevent disuse muscle atrophy / hip raise exercises
Shinjiro Takata, Aziz Abbaspour, Hiroshi Yonezu and Natsuo Yasui : Differences of therapeutic effects on regional bone mineral density and markers of bone mineral metabolism between alendronate and alfacalcidol in Japanese osteoporotic women., The Journal of Medical Investigation : JMI, Vol.54, No.1-2, 35-40, 2007.
(Summary)
We studied the differences of therapeutic effects on regional bone mineral density (BMD) and markers of bone mineral metabolism between alendronate and alfacalcidol in Japanese osteoporotic women. Ninety-two Japanese women suffering from primary osteoporosis without osteoporotic fractures, aged 55 to 81 years, were divided into two groups: women treated orally with alendronate for one-year (5mg/day) (alendronate group, n=35) and women treated orally with alfacalcidol for one year (0.5 microg/day) (alfacalcidol group, n=57). The mean BMD of the 2nd to 4th lumbar vertebrae (L2-4BMD) and regional BMD were measured using dual energy X-ray absorptiometry. In the alendronate group, the percentage changes of L2-4BMD, lumbar spine BMD, thoracic spine BMD, pelvis BMD in the alendronate group were 106.3+/-4.6%, 104.2+/-6.6%, 107.1+/-10.4%, 107.1+/-10.5%, respectively. The percentage changes of L2-4BMD and regional BMD except for head BMD in the alendronate group were significantly greater than those in the alfacalcidol group. In the alfacalcidol group, L2-4BMD, thoracic spine BMD and lumbar spine BMD were maintained at respective pretreatment levels, whereas other regional BMD were decreased. Both serum bone-specific alkaline phosphatase and urinary type I collagen cross-linked N-telopeptide of the alendronate group were decreased, whereas these markers of bone mineral metabolism of alfacalcidol group were increased compared with the respective pre-treatment levels. The results suggest that one-year treatment with alendronate increased L2-4BMD, lumbar spine BMD, thoracic spine BMD and pelvis BMD, and that markers of both bone formation and bone resorption were decreased following one-year treatment with alendronate.
(Keyword)
Aged / Aged, 80 and over / Alendronate / Alkaline Phosphatase / Biological Markers / Bone Density / Bone Density Conservation Agents / Collagen Type I / Female / Humans / Hydroxycholecalciferols / Middle Aged / Osteoporosis, Postmenopausal / Peptides
Kousaku Higashino, Koichi Sairyo, Shinsuke Katoh, Toshinori Sakai, Hirofumi Kosaka and Natsuo Yasui : Minimally invasive technique for direct repair of the pars defects in young adults using a spinal endoscope. A technical note., Minimally Invasive Neurosurgery : MIN, Vol.50, No.3, 186-190, 2007.
(Summary)
Pars defect (spondylolysis) of the lumbar spine can cause chronic low back pain, and it sometimes requires surgical intervention. Direct repair is selected for the surgery if young adult patients do not present significant disc degeneration and lumbar instability. In order to lessen damages of back muscles during surgery, we added the use of a spinal endoscope to the "Buck's screwing procedure" the direct repair. There are four steps in this procedure: 1) identification of the defect, 2) curettage (refresh) of the defect, 3) percutaneous insertion of the annulated screws and 4) cancellous bone grafting. All these steps can be done endoscopically. We treated 3 young adults--a baseball player, a professional cycle-racer and a sculptor--using this endoscopic procedure. There were no complications during or after the operation. Union was obtained in all defects within 3 months, and they returned to their previous activities within 6 months after the surgery.
Yoichiro Takata, Daisuke Hamada, Katsutoshi Miyatake, Shunji Nakano, Fumio Shinomiya, Charles R. Scafe, Vincent M. Reeve, Dai Osabe, Maki Moritani, Kiyoshi Kunika, Naoyuki Kamatani, Hiroshi Inoue, Natsuo Yasui and Mitsuo Itakura : Genetic association between the PRKCH gene encoding protein kinase Ceta isozyme and rheumatoid arthritis in the Japanese population., Arthritis and Rheumatism, Vol.56, No.1, 30-42, 2007.
(Summary)
Analyses of families with rheumatoid arthritis (RA) have suggested the presence of a putative susceptibility locus on chromosome 14q21-23. This large population-based genetic association study was undertaken to examine this region. A 2-stage case-control association study of 950 unrelated Japanese patients with RA and 950 healthy controls was performed using >400 gene-based common single-nucleotide polymorphisms (SNPs). Multiple SNPs in the PRKCH gene encoding the eta isozyme of protein kinase C (PKCeta) showed significant single-locus disease associations, the most significant being SNP c.427+8134C>T (odds ratio 0.72, 95% confidence interval 0.62-0.83, P = 5.9 x 10(-5)). Each RA-associated SNP was consistently mapped to 3 distinct regions of strong linkage disequilibrium (i.e., linkage disequilibrium or haplotype blocks) in the PRKCH gene locus, suggesting that multiple causal variants influence disease susceptibility. Significant SNPs included a novel common missense polymorphism of the PRKCH gene, V374I (rs2230500), which lies within the ATP-binding site that is highly conserved among PKC superfamily members. In circulating lymphocytes, PRKCH messenger RNA was expressed at higher levels in resting T cells (CD4(+) or CD8(+)) than in B cells (CD19(+)) or monocytes (CD14(+)) and was significantly down-regulated through immune responses. Our results provide evidence of the involvement of PRKCH as a susceptibility gene for RA in the Japanese population. Dysregulation of PKCeta signal transduction pathway(s) may confer increased risk of RA through aberrant T cell-mediated autoimmune responses.
(Keyword)
Adult / Arthritis, Rheumatoid / Case-Control Studies / Chromosomes, Human, Pair 14 / Female / Genetic Predisposition to Disease / Humans / Isoenzymes / Japan / Linkage Disequilibrium / Male / Middle Aged / Polymorphism, Single Nucleotide / Protein Kinase C / RNA, Messenger / Signal Transduction / T-Lymphocytes / Zebrafish Proteins
Kousaku Higashino, Yoshito Matsui, Syoji Yagi, Yoichiro Takata, Tomohiro Goto, Toshinori Sakai, Shinsuke Katoh and Natsuo Yasui : The alpha2 type IX collagen tryptophan polymorphism is associated with the severity of disc degeneration in younger patients with herniated nucleus pulposus of the lumbar spine., International Orthopaedics, Vol.31, No.1, 107-111, 2007.
(Summary)
Tryptophan alleles in COL9A2 (Trp2) and COL9A3 (Trp3) have been linked to lumbar disc diseases in the Finnish population. Although such diseases consist of various pathogenetically different conditions, detailed analysis of each has not been well documented. The aim of this study was to clarify whether the collagen IX tryptophan alleles influence the symptomatic degeneration of the lumbar disc in Japanese patients with herniated nucleus pulposus. We performed a prospective study of 84 patients who underwent lumbar discectomy. The degree of disc degeneration was evaluated by magnetic resonance images in relation to the collagen IX genotype. Twenty patients (21.4%) had the Trp2 allele and no patients had the Trp3 allele. Patients under 40 years with the Trp2 allele showed more severe disc degeneration at the surgical level than did those without the Trp2 allele (odds ratio 6.00, P=0.043). In contrast, patients aged 40 years or over did not show significant association between disc degeneration and collagen IX genotype. Our results suggest that the Trp2 allele is an age-dependent risk factor for the severity of disc degeneration in younger patients with symptomatic herniated nucleus pulposus of the lumbar spine.
(Keyword)
Adult / Collagen Type IX / Female / Genetic Predisposition to Disease / Humans / Intervertebral Disc / Intervertebral Disc Displacement / Lumbar Vertebrae / Magnetic Resonance Imaging / Male / Odds Ratio / Polymorphism, Genetic / Prospective Studies / Risk Factors
Toshinori Sakai, Shinsuke Katoh, Koichi Sairyo, Kousaku Higashino, Nori Hirohashi and Natsuo Yasui : Extension of contained rupture of an abdominal aortic aneurysm into a lumbar intervertebral disc. Case report., Journal of Neurosurgery. Spine, Vol.7, No.2, 221-226, 2007.
(Summary)
Chronic contained rupture of an abdominal aortic aneurysm (AAA) is a rare event, making its diagnosis difficult. A delayed diagnosis and delayed surgical repair compromise the outcome. In this paper the authors report the case of a chronic contained rupture of an AAA causing spinal destruction, in which diagnosis was difficult because the lesion produced symptoms mimicking those of pyogenic spondylitis.
Maki Moritani, Kyoko Nomura, Toshihito Tanahashi, Dai Osabe, Yuka Fujita, Shinohara Syuichi, Yuka Nagasaki, Parvaneh Keshavarz, Eiji Kudo, Naoto Nakamura, Toshikazu Yoshikawa, Eiichiro Ichiichi, Yoichiro Takata, Natsuo Yasui, Hiroshi Shiota, Kiyoshi Kunika, Hiroshi Inoue and Mitsuo Itakura : Genetic association of single nucleotide polymorphisms in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population., Diabetologia, Vol.50, No.6, 1218-1227, 2007.
(Summary)
In order to identify type 2 diabetes disease susceptibility gene(s) in a Japanese population, we applied a region-wide case-control association test to the 20.4 Mb region between D3S1293 and D3S2319 on chromosome 3p24.3-22.1, supported by linkage to type 2 diabetes and its related traits in Japanese and multiple populations. We performed a two-stage association test using 1,762 Japanese persons with 485 gene-centric, evenly spaced, common single nucleotide polymorphism (SNP) markers with minor allele frequency >0.1. For mouse studies, total RNA was extracted from various organs of BKS.Cg-+Lepr(db)/+Lepr(db) and control mice, and from MIN6, NIH3T3 and C2C12 cell lines. We detected a landmark SNP375 (A/G) (rs2051211, p = 0.000046, odds ratio = 1.33, 95% CI 1.16-1.53) in intron 5 of the endonuclease G-like 1 (ENDOGL1) gene. Systematic dense SNPs approach identified a susceptibility linkage disequilibrium (LD) block of 116.5 kb by |D'|, an LD units map and a critical region of 2.1 kb by r (2) in ENDOGL1. A haplotype-based association test showed that an at-risk haplotype is associated with disease status (p = 0.00001). The expression of ENDOGL1 was rather ubiquitous with relatively abundant expression in the brain and also in a pancreatic islet beta cell line. Mouse Endogl1 expression increased in pancreatic islets of hyperglycaemic BKS.Cg-+Lepr(db)/+Lepr(db) mice compared with that in control mice. Based on the population genetics, fine mapping of LD block and haplotype analysis, we conclude that ENDOGL1 is a candidate disease-susceptibility gene for type 2 diabetes in a Japanese population. Further analysis in a larger sample size is required to substantiate this conclusion.
(Keyword)
Adult / Aged / Body Mass Index / Case-Control Studies / Diabetes Mellitus, Type 2 / Endodeoxyribonucleases / Endonucleases / Female / Genetic Predisposition to Disease / Hemoglobin A, Glycosylated / Humans / Japan / Male / Middle Aged / Polymorphism, Single Nucleotide / Reference Values
Takayuki Ogawa, Harumi Furochi, Mai Mameoka, Katsuya Hirasaka, Yuko Onishi, Naoto Suzue, Motoko Oarada, Motoki Aakamatsu, Hiroshi Akima, Tetsuo Fukunaga, Kyoichi Kishi, Natsuo Yasui, Kazumi Ishidoh, Hideoki Fukuoka and Takeshi Nikawa : Ubiquitin ligase gene expression in healthy volunteers with 20-day bedrest., Muscle & Nerve, Vol.34, No.4, 463-469, 2006.
(Summary)
In animal models, several ubiquitin ligases play an important role in skeletal muscle atrophy caused by unloading. In this study we examined protein ubiquitination and ubiquitin ligase gene expression in quadriceps femoris muscle from healthy volunteers after 20-day bedrest to clarify ubiquitin-dependent proteolysis in human muscles after unloading. During bedrest, thickness and cross-sectional area of the quadriceps femoris muscle decreased significantly by 4.6% and 3.7%, respectively. Ubiquitinated proteins accumulated in these atrophied human muscles. A real-time reverse transcription-polymerase chain reaction system showed that bedrest significantly upregulated expression of two ubiquitin ligase genes, Cbl-b and atrogin-1. We also performed DNA microarray analysis to examine comprehensive gene expression in the atrophied muscle. Bedrest mainly suppressed the expression of muscle genes associated with control of gene expression in skeletal muscle. Our results suggest that, in humans, Cbl-b- or atrogin-1-mediated ubiquitination plays an important role in unloading-induced muscle atrophy, and that unloading stress may preferentially inhibit transcriptional responses in skeletal muscle.
(Keyword)
Adaptor Proteins, Signal Transducing / Adult / Bed Rest / Body Weight / DNA / Gene Expression Profiling / Gene Expression Regulation, Enzymologic / Humans / Male / Muscle Proteins / Muscle, Skeletal / Muscular Atrophy / Oligonucleotide Array Sequence Analysis / Organ Size / Proteins / Proto-Oncogene Proteins c-cbl / SKP Cullin F-Box Protein Ligases / Ubiquitin-Protein Ligases
Ayako Tamura, Takako Ichihara, Shinjiro Takata, Takako Minagawa, Yumi Kuwamura, Takae Bando, Hiroko Kondo, Natsuo Yasui and Shinji Nagahiro : Changes in lower extremity muscle mass among bedridden patients with post-stroke hemiplegia in the acute post-stroke period, JNI : The Journal of Nursing Investigation, Vol.5, No.1, 18-21, 2006.
(Summary)
The present study analyzed16patients who were bedridden for one week immediately after onset of post-stroke hemiplegia. We used DXA(dual energy X-ray absorptiometry)to determine changes in muscle mass in the lower extremities on both paralyzed and non-paralyzed sides. The first measurement was conducted 3 to 5 days after the onset, and the second measurement was conducted 7 days after the first. Muscle mass in the lower extremities was reduced by approximately 600g (9%) on the paralyzed side with and by 200g on the non-paralyzed side (3%) in the Brunnstrom stage≤II group (n＝5). Although the decrease of muscle mass in the Brunnstrom stage≥III group(n＝11, relatively slight degree of functional motion impairment)was not significant, a decrease of approximately 300g (decrease rate : 5%)was observed on the paralyzed side and approximately 100g (decrease rate : 1．5%)was seen on the non-paralyzed side. Hence, muscle mass declined on both sides, and this occurred regardless of degree of paralysis. The findings suggested that conventional range of motion exercises, functional position maintenance, and postural changes are inadequate to prevent disuse muscle atrophy in post-stroke patients ; thus, it is necessary to develop a new rehabilitation program which adopts different exercises such as trunk motion, even for patients in the acute stage after stoke onset.
(Keyword)
acute post-stroke period / hemiplegia / lower extremity muscle / disuse muscle atrophy / dual energy X-ray Absorptiometry(DXA)
Takanobu Nakase, Natsuo Yasui, Kenji Ohzono, Nobuyuki Shimizu and Hideki Yoshikawa : Treatment of relapsed idiopathic clubfoot by complete subtalar release combined with the Ilizarov method., The Journal of Foot and Ankle Surgery, Vol.45, No.5, 337-351, 2006.
(Summary)
This study presents the clinical and radiographic outcomes of 6 feet (4 patients) with relapsed idiopathic clubfoot that were treated with a combination of subtalar release and the Ilizarov method. The mean patient age at the time of the surgery was 7.4 years (range, 4.5-10.5 years), and the mean follow-up was 5.1 years (range, 2.0-7.3 years). All cases achieved a plantigrade foot, better walking ability, and parental satisfaction with the result. Ankle joint range of motion increased from a mean of 17 degrees (range, 10-30 degrees) preoperatively to 45 degrees (range, 35-65 degrees) at final follow-up. The talocalcaneal angle improved from a mean of 26 degrees (range, 15-34 degrees) preoperatively to 55 degrees (range, 47-65 degrees) at follow-up. The mean tibiocalcaneal angle improved from 95 degrees (range, 87-115 degrees) preoperatively to 80 degrees (77-83 degrees) at follow-up, whereas the talometatarsal angle improved from a preoperative mean of -19 degrees (range, -35 to -10 degrees) to 3.5 degrees (range, -5 to 7 degrees) at follow-up. Recurrence was observed in only 1 foot with forefoot adductus, caused by a pin tract infection and early fixator removal. These cases suggest the Ilizarov method combined with subtalar release are beneficial for the treatment of relapsed idiopathic clubfoot.
Shinji Komatsubara, Koichi Sairyo, Shinsuke Katoh, Tadanori Sakamaki, Kousaku Higashino and Natsuo Yasui : High-grade slippage of the lumbar spine in a rat model of spondylolisthesis: effects of cyclooxygenase-2 inhibitor on its deformity., Spine, Vol.31, No.16, 528-534, 2006.
(Summary)
Radiographic and histologic evaluation of spondylolisthesis in a rat model. To investigate the effects of etodolac, a cox-2 inhibitor, on the severity of spondylolisthesis in a 4-week-old rat model. Spondylolisthesis occurs associated with spondylolysis in some pediatric patients. In such patients, the percent of forward slippage varies individually ranging between 0% and 100%. The factors determining the severity of forward slippage have not been clarified as yet. In earlier studies, we found that growth plate stress fracture was the basic lesion and that slippage was a consequence of the stress fracture. Hence, we hypothesized that the capacity of bone healing might be an important determinant of the degree of forward slippage. A lumbar spine slippage model was prepared in 4-week-old rats with vertebral physis fracture. To disrupt the fracture healing, the cyclooxygenase-2 (cox-2) inhibitor etodolac was used, and its effects on slippage and deformity were evaluated radiologically and histologically. In the etodolac group, forward slip significantly increased (P < 0.05) to the Meyerding Grade III while in the control rats it was Grade I or II. Bone remodeling of the vertebral body was suppressed by etodolac. Histologically, epiphyseal separation with slippage was observed in all the control and etodolac-treated rats. However, in the etodolac-treated group, the epiphyseal plate was greatly separated and did not present periosteal thickening at the physis fracture site. Vertebral forward slippage occurred in young rats after epiphyseal separation. In the etodolac group, slippage increased as deterioration of the bone healing capacity increased. Poor bony healing is suggested as one of the determinants of high-grade spondylolisthesis in children and adolescents.
(Keyword)
Animals / Bone Remodeling / Cyclooxygenase 2 Inhibitors / Dose-Response Relationship, Drug / Etodolac / Female / Growth Plate / Lumbar Vertebrae / Rats / Rats, Wistar / Severity of Illness Index / Spinal Fractures / Spondylolisthesis / Wound Healing
Yoshito Matsui, Takafumi Ueda, Takahiro Kubo, Tadashi Hasegawa, Yasuhiko Tomita, Mina Okamoto, Akira Myoui, Shigeki Kakunaga, Natsuo Yasui and Hideki Yoshikawa : A novel type of EWS-CHOP fusion gene in myxoid liposarcoma., Biochemical and Biophysical Research Communications, Vol.348, No.2, 437-440, 2006.
(Summary)
The cytogenetic hallmark of myxoid type and round cell type liposarcoma consists of reciprocal translocation of t(12;16)(q13;p11) and t(12;22)(q13;q12), which results in fusion of TLS/FUS and CHOP, and EWS and CHOP, respectively. Nine structural variations of the TLS/FUS-CHOP chimeric transcript have been reported, however, only two types of EWS-CHOP have been described. We describe here a case of myxoid liposarcoma containing a novel EWS-CHOP chimeric transcript and identified the breakpoint occurring in intron 13 of EWS. Reverse transcription-polymerase chain reaction and direct sequence showed that exon 13 of EWS was in-frame fused to exon 2 of CHOP. Genomic analysis revealed that the breaks were located in intron 13 of EWS and intron 1 of CHOP.
(Keyword)
Adult / Base Sequence / Chimera / Female / Gene Fusion / Humans / In Situ Hybridization, Fluorescence / Liposarcoma, Myxoid / Molecular Sequence Data / RNA-Binding Protein EWS / Reverse Transcriptase Polymerase Chain Reaction / Transcription Factor CHOP
Yoichiro Takata, Yoshito Matsui, Daisuke Hamada, Tomohiro Goto, Takahiro Kubo, Hiroshi Egawa, Shunji Nakano, Fumio Shinomiya, Hiroshi Inoue, Mitsuo Itakura and Natsuo Yasui : The alpha 2 type IX collagen gene tryptophan polymorphism is not associated with rheumatoid arthritis in the Japanese population, Clinical Rheumatology, Vol.25, No.4, 491-494, 2006.
(Summary)
The aim of this study was to investigate whether the alpha 2 type IX collagen (COL9A2) polymorphism that introduces tryptophan residue into the collagen triple-helix is a marker of susceptibility to, or severity of, rheumatoid arthritis (RA). The study included 749 Japanese patients with RA. One hundred twenty-four unrelated healthy individuals served as the control subjects. The relationship between the COL9A2 gene polymorphism and clinical manifestations of RA was evaluated. For the number of subjects positive for COL9A2 tryptophan polymorphism, there was no statistically significant difference between RA patients and normal controls. Furthermore, we did not detect any association of COL9A2 tryptophan polymorphism with disease status, least erosive subset, more erosive subset, or mutilating disease. The lack of association of COL9A2 tryptophan polymorphism with RA and the clinical findings in our study implies that the polymorphism may not function as a candidate gene marker for screening RA patients.
(Keyword)
Polymorphism - Rheumatoid arthritis / Severity - Susceptibility / Type IX collagen
Mitsuhiko Takahashi, Kenji Endo, Yoshito Matsui, Kenji Mori and Natsuo Yasui : A remarkable large hamartoma around the knee in a patient with tuberous sclerosis., Pediatrics International, Vol.48, No.3, 340-341, 2006.
Takahiro Kubo, Yoshito Matsui, Tomohiro Goto, Kiminori Yukata, Kenji Endo, Ryosuke Sato, Takahiro Tsutsui and Natsuo Yasui : MRI Characteristics of Parosteal Lipomas Associated with the HMGA2-LPP Fusion Gene., Anticancer Research, Vol.26, No.3B, 2253-2257, 2006.
(Summary)
The magnetic resonance (MR) characteristics of parosteal lipomas with the HMGA2-LPP fusion transcripts are described. The expression of HMGA2-LPP fusion transcripts was determined using the reverse transcription-polymerase chain reaction method. MR images of two cases with the fusion transcripts, a 56-year-old man and a 50-year-old woman, revealed heterogeneous high signal intensities on T1- and T2-weighted images, showing heterogeneous curvilinear enhancement on fat-suppressed T1-weighted images after Gd-DTPA injection, which resembled those of well-differentiated liposarcomas. Since the HMGA2-LPP fusion transcripts are exclusively detectable in benign mesenchymal tumors, testing HMGA2-LPP expression may be useful for differential diagnosis in cases of radiologically-suspected well-differentiated liposarcomas.
Tomoya Terai, Noriyuki Nishimura, Ikuno Kanda, Natsuo Yasui and Takuya Sasaki : JRAB/MICAL-L2 is a junctional Rab13-binding protein mediating the endocytic recycling of occludin., Molecular Biology of the Cell, Vol.17, No.5, 2465-2475, 2006.
(Summary)
The dynamic turnover of tight junctions (TJs) is essential for epithelial-mesenchymal transitions and/or mesenchymal-epithelial transitions during epithelial morphogenesis. We previously demonstrated that Rab13 specifically mediates the endocytic recycling of occludin. Here, we identified MICAL-L2 (molecule interacting with CasL-like 2) as a novel Rab13-binding protein. Immunoprecipitation and immunofluorescence microscopy showed that MICAL-L2 specifically bound to the GTP-bound form of Rab13 via its C terminus, which contained a coiled-coil domain, and localized at TJs in epithelial MTD-1A cells. Recycling assay demonstrated that a MICAL-L2 mutant lacking the Rab13-binding domain (MICAL-L2-N) specifically inhibited the endocytic recycling of occludin but not transferrin receptor. Ca2+ switch assay further revealed that MICAL-L2-N as well as Rab13 Q67L inhibited the recruitment of occludin to the plasma membrane, the development of transepithelial electrical resistance, and the formation of a paracellular diffusion barrier. MICAL-L2 was displaced from TJs upon actin depolymerization and was distributed along radiating actin cables and stress fibers in Ca2+-depleted MTD-1A and fibroblastic NIH3T3 cells, respectively. These results suggest that MICAL-L2 mediates the endocytic recycling of occludin and the formation of functional TJs by linking Rab13 to actin cytoskeleton. We rename MICAL-L2 as JRAB (junctional Rab13-binding protein).
Tomohiro Goto, Yoshito Matsui, J Russell Fernandes, A Dennis Hanson, Ttakahiro Kubo, Kiminori Yukata, Toshimi Michigami, Toshihisa Komori, Takashi Fujita, Liu Yang, R David Eyre and Natsuo Yasui : Sp1 Family of Transcription Factors Regulates the Human 2(XI) Collagen Gene (COL11A2) in Saos-2 Osteoblastic Cells., Journal of Bone and Mineral Research, Vol.21, No.5, 661-673, 2006.
(Summary)
Genes encoding type XI collagen, normally associated with chondrogenesis, are also expressed by osteoblasts. By studying Saos-2 cells, we showed that the transcription factors, Sp1, Sp3, and Sp7 (Osterix), regulate COL11A2 expression through its proximal promoter. The findings indicate both ubiquitous and osteoblast-specific mechanisms of collagen gene regulation. Type XI collagen is essential for skeletal morphogenesis. Collagen XI gene regulation has been studied in chondrocytes but not in osteoblasts. We cultured Saos-2 cells, a human osteosarcoma-derived line of osteoblasts, and analyzed them for alpha2(XI) protein and COL11A2 regulatory mechanisms. Although types I and V were the dominant collagens deposited by Saos-2 cells, they expressed COL11A2 mRNA, and alpha2(XI) chains were present in the extracellular matrix. The COL11A2 promoter region (from -149 to -40) containing three Sp1 binding sites was required for promoter activity in transient transfection assays. All three Sp1 sites were critical for binding by nuclear proteins in electrophoretic mobility shift assays. Further analysis using consensus oligonucleotides and specific antibodies as well as chromatin immunoprecipitation assay implicated Sp1 and Sp3 in binding to this promoter region. Overexpressing Sp1 or Sp3 significantly increased COL11A2 promoter activity and endogenous COL11A2 gene expression, an effect that was suppressed by the Sp1-binding inhibitor mithramycin A. Further experiments showed that Sp1, Sp3, CREB-binding protein (CBP), p300, and histone deacetylase (HDAC) were physically associated and HDAC inhibitors (trichostatin A or NaB) upregulated COL11A2 promoter activity and endogenous gene expression. Another Sp1 family member, Sp7 (Osterix), was expressed in Saos-2 cells, but not in chondrocytes, and was shown by chromatin immunoprecipitation to occupy the COL11A2 promoter. Overexpressing Sp7 increased COL11A2 promoter activity and endogenous gene expression, an effect also blocked by mithramycin A. Using siRNA to knockdown Sp1, Sp3, or Sp7, it was shown that depression of any of them decreased COL11A2 promoter activity and endogenous gene expression. Finally, primary cultures of osteoblasts expressed COL11A2 and Sp7, upregulated COL11A2 promoter activity and endogenous gene expression when Sp1, Sp3, or Sp7 were overexpressed, and downregulated them when Sp1, Sp3, or Sp7 were selectively depressed. The results establish that Sp1 proteins regulate COL11A2 transcription by binding to its proximal promoter and directly interacting with CBP, p300, and HDAC.
(Keyword)
Base Sequence / Binding Sites / Blotting, Western / Cell Line / Collagen Type XI / DNA Primers / Electrophoretic Mobility Shift Assay / Gene Expression Regulation / Histone Deacetylase Inhibitors / Humans / Immunoprecipitation / Plasmids / Promoter Regions, Genetic / RNA, Messenger / Sp1 Transcription Factor
Naoto Suzue, Takeshi Nikawa, Yuko Onishi, Chiharu Yamada, Katsuya Hirasaka, Takayuki Ogawa, Harumi Furochi, Hirofumi Kosaka, Kazumi Ishidoh, Gu Hua, Shin'ichi Takeda, Naozumi Ishimaru, Yoshio Hayashi, Hironori Yamamoto, Kyoichi Kishi and Natsuo Yasui : Ubiqitin Ligase Cbl-b Downregulates Bone Formation Through Suppression of IGF-I Signaling in Osteoblasts During Denervation, Journal of Bone and Mineral Research, Vol.21, No.5, 722-734, 2006.
(Summary)
Unloading can prevent bone formation by osteoblasts. To study this mechanism, we focused on a ubiquitin ligase, Cbl-b, which was highly expressed in osteoblastic cells during denervation. Our results suggest that Cbl-b may mediate denervation-induced osteopenia by inhibiting IGF-I signaling in osteoblasts. Unloading, such as denervation (sciatic neurectomy) and spaceflight, suppresses bone formation by osteoblasts, leading to osteopenia. The resistance of osteoblasts to growth factors contributes to such unloading-mediated osteopenia. However, a detailed mechanism of this resistance is unknown. We first found that a RING-type ubiquitin ligase, Cbl-b, was highly expressed in osteoblastic cells after sciatic neurectomy in mice. In this study, we reasoned that Cbl-b played an important role in the resistance of osteoblasts to IGF-I. Cbl-b-deficient (Cbl-b(-/-)) or wildtype (Cbl-b(+/+)) mice were subjected to sciatic neurectomy. Bone formation in these mice was assessed by calcein labeling and histomorphometric analyses. We examined IGF-I signaling molecules in femora of these mice by Western blot and immunohistochemical analyses. We also examined the mitogenic response of Cbl-b-overexpressing or -deficient osteoblastic cells to various growth factors. In Cbl-b(+/+) mice, denervation decreased femur mass and bone formation, whereas it increased the expression of Cbl-b protein in osteoprogenitor cells and in osteocalcin-positive cells (osteoblastic cells) in hindlimb bone. In contrast, in Cbl-b(-/-) mice, bone mass and bone formation were sustained during denervation. Denervation inhibited the mitogenic response of osteoprogenitor cells most significantly to IGF-I. Therefore, we focused on Cbl-b-mediated modification of IGF-I signaling. Denervation decreased the amounts of insulin receptor substrate-1 (IRS-1), phosphatidly inositol 3-phosphate kinase (PI3K), and Akt-1 proteins in femora of Cbl-b(+/+) mice, whereas the amounts of these IGF-I signaling molecules in femora of Cbl-b(-/-) mice were constant after denervation. On a cellular level, primary osteoblastic cells from Cbl-b(-/-) mice were more stimulated to proliferate by IGF-I treatment compared with those from Cbl-b(+/+) mice. Furthermore, overexpression of Cbl-b increased ubiquitination and degradation of IRS-1 in primary Cbl-b(-/-) osteoblastic cells, leading to their impaired mitogenic response to IGF-I. These results suggest that Cbl-b induces resistance of osteoblasts to IGF-I during denervation by increasing IRS-1 degradation and that Cbl-b-mediated modification of IGF-I signaling may contribute to decreased bone formation during denervation.
(Keyword)
Animals / Base Sequence / Blotting, Western / Bone Development / Cells, Cultured / DNA Primers / Denervation / Down-Regulation / Hydrolysis / immunohistochemistry / Insulin-Like Growth Factor I / Mice / Mice, Inbred C57BL / Osteoblasts / Protein Binding / Reverse Transcriptase Polymerase Chain Reaction / signal transduction / Ubiquitin / Ubiquitin-Protein Ligases
Yoshitaka Hamada, Shinsuke Katoh, Naohito Hibino, Hirofumi Kosaka, Daisuke Hamada and Natsuo Yasui : Effects of monofilament nylon coated with basic fibroblast growth factor on endogenous intrasynovial flexor tendon healing., The Journal of Hand Surgery, Vol.31, No.4, 530-540, 2006.
(Summary)
We developed a monofilament nylon thread that can release various growth factors to enhance intrinsic reparative processes after flexor tendon injury. We evaluated the properties of this thread in vitro and in vivo. Nylon threads were coated with gelatin that subsequently was cross-linked in glutaraldehyde. The thread was soaked in basic fibroblast growth factor (bFGF) solution (400 microg/mL). Exogenous bFGF in the thread was released constantly over the course of 1 week. The biologic activity of bFGF and the biomechanical strength of the thread were examined in vitro and its efficacy was investigated in an in vivo rabbit tendon repair model after early flexion exercises. The sutured sites were examined histologically (hematoxylin-eosin, immunohistochemistry, in situ hybridization), biochemically (Western blot test), and biomechanically (ultimate load) after surgery. This gelatin-coated thread absorbed iodine 125-labeled bFGF in a time-dependent manner. The total amount of bFGF absorbed by the thread within the tendon tissue was between 3 and 15 mug depending on the concentration of bFGF solution. Basic fibroblast growth factor protein was delivered selectively-not in the surrounding scar but in the repaired tendon-for 3 weeks. Histologic analysis showed that the cellular density at the repaired site increased in accordance with the expression of bFGF messenger RNA and protein in the tendon. Endogenous bFGF expression seemed to be enhanced transiently by exogenous bFGF during the first few weeks. The epitenon showed a vigorous fibroblastic response to the coated thread and the ultimate load also was increased significantly at 3 weeks after surgery. This bFGF-coated nylon suture gave excellent results in delivering a drug selectively to tendon; it also induced an increase of biomechanical strength and a thickening of the epitenon layer in vivo during a 3-week period, thereby accelerating cellular proliferation, initially peripherally and later centrally. This system may become a therapeutic tool to be used in hand surgery.
Shinjiro Takata, Gen Nishimura, Shiro Ikegawa, Yasuhiro Kuroda, Mizuho Nishino, Yoshito Matsui and Natsuo Yasui : Metaphyseal Dysplasia of Braun-Tinschert Type: Report of a Japanese Girl., American Journal of Medical Genetics. Part A., Vol.140, No.11, 1234-1237, 2006.
(Summary)
We report on a 7-year-old Japanese girl with metaphyseal dysplasia (MD) of Braun-Tinschert type, a recently recognized, autosomal dominant sclerosing bone dysplasia. All individuals with the disorder from four families in the literature originated from a small town in Bohemia or its vicinity. The occurrence of the disorder in a Japanese girl indicates that it is not restricted to Germans. The radiographic hallmarks of the disorder include metaphyseal undermodeling (Erlenmeyer-flask deformity); osteosclerosis of the chondroosseous junctions, metaphyseal cortices, and epiphyseal margins; and exostosis-like bone excrescences at the metaphyseal-diaphyseal junctions. In the girl we described, the latter two findings were conspicuous at age 4 years, but became less prominent with increasing age. The metaphyseal trabeculae were somewhat coarse. The humeri exhibited varus deformity, and the ulnae and fibulae mild bowing. The mean bone mineral density of the lumbar spine was lower than that of age-matched controls. The patient exhibited premature loss of primary teeth, likely to be a sign of increased periodontal bone resorption. Markers of bone formation and resorption were both increased, an indication of a high rate of bone turnover.
(Keyword)
Abnormalities, Multiple / Bone Diseases, Metabolic / Bone and Bones / Child / Female / Femur / Humans / Osteochondrodysplasias / Tibia / Tooth Abnormalities
Ami Inui, Koichi Sairyo, Shinsuke Katoh, Kousaku Higashino, Toshinori Sakai, M Shiiba and Natsuo Yasui : Extruded lumbar osseous endplate causing long-term radiculopathy in an adult: an endoscopic excision., Minimally Invasive Neurosurgery : MIN, Vol.49, No.1, 55-57, 2006.
(Summary)
In this report, we described an adult case that had a long-term radiculopathy due to an extruded osseous endplate of the lumbar spine at the L5-S1 intervertebral disc level. The osseous material inside the extruded material was not absorbed, and it had continued compressing the nerve root for one year. Endoscopically, the bony fragment was successfully removed. After the surgery, the patient's symptom disappeared, and neurological deficits became normalized. In conclusion, we propose that surgical intervention should be taken into account for the treatment of HNP, when the extruded material contains bony fragment such as osseous endplate.
Koichi Sairyo, Shinsuke Katoh, Yoichiro Takata, Tomoya Terai, Natsuo Yasui, K Vijay Goel, Akiyoshi Masuda, Sasidhar Vadapalli, Ashok Biyani and Nabil Ebraheim : MRI signal changes of the pedicle as an indicator for early diagnosis of spondylolysis in children and adolescents. A clinical and biomechanical study., Spine, Vol.31, No.2, 206-211, 2006.
(Summary)
Clinical review of pediatric patients with lumbar spondylolysis and biomechanical analysis using finite-element lumbar spine model. To evaluate the usefulness of the signal changes observed on MR images of the pedicle for the early diagnosis of spondylolysis, and to investigate the pathomechanism of the signal changes based on the stresses in pedicles, as predicted using finite-element analyses. Furthermore, to evaluate the usefulness of the signal change to predict the bony healing following conservative treatment. Since early-stage spondylolysis can achieve osseous healing conservatively, it is important to diagnose this disorder as early as possible. Presently, there is no well-established, noninvasive, and reliable diagnostic tool for the early diagnosis. Thirty-seven pediatric patients with spondylolysis were included. Sixty-eight defects were examined and their stages as revealed on CT scans were recorded. High signal changes (HSC) of the pedicles on axial T2-weighted MRI were compared with the CT-based stages of the defect. Among them, 16 patients, including 15 boys and 1 girl, were treated conservatively for at least a 3-month period. Bony healing of the fracture site was evaluated on CT, and the results were compared between two groups with or without HSC at the initial consultation. Using a three-dimensional nonlinear finite-element model of the L3-L5 segment, stress distributions in the pars and pedicle regions were analyzed in response to 400 N compression and 10.6 Nm moment. Based on CTs, 68 pars defects were classified as follows: 8 very early, 24 late-early, 16 progressive, and 20 terminal stages. All defects in very early and late-early stages (100%) showed HSC on T2-weighted MRI at the ipsilateral pedicle. Among 16 progressive stages, eight (50%) showed HSC, while no defects of the terminal stage (0%) were found to have HSC. In total, 29 pars defects were treated conservatively out of 16 patients. In 19 of the HSC positive defects, 15 (79%) showed bony healing after the conservative treatment, whereas none of the 10 HSC negative defects (0%) showed any healing. The results were statistically significant at P < 0.05 (chi). Stress results from the finite-element model indicated that pars interarticularis showed the highest value in all loading modes, and the pedicle showed the second highest. The correlation between the high stresses in the pedicle and the corresponding HSC suggest that signal changes in MRI could be used as an indicator for early diagnosis of spondylolysis. The HSC of the pedicle provided useful information to diagnose early stage spondylolysis. Furthermore, the HSC may be a good indicator as to whether a bony union will result from conservative treatment.
(Keyword)
Adolescent / biomechanics / Child / Early Diagnosis / Female / Follow-Up Studies / Humans / Lumbar Vertebrae / magnetic resonance imaging / Male / Retrospective Studies / Spondylolysis
Hitoshi Kato, Kyoko Nomura, Dai Osabe, Shuichi Shinohara, Osamu Mizumori, Rumi Katashima, Shoji Iwasaki, Koichi Nishimura, Masayasu Yoshino, Masato Kobori, Eiichiro Ichiishi, Naoto Nakamura, Toshikazu Yoshikawa, Toshihito Tanahashi, Parvaneh Keshavarz, Kiyoshi Kunika, Maki Moritani, Eiji Kudo, Kazue Tsugawa, Yoichiro Takata, Daisuke Hamada, Natsuo Yasui, Tatsuro Miyamoto, Hiroshi Shiota, Hiroshi Inoue and Mitsuo Itakura : Association of single nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese., Genomics, Vol.87, No.4, 446-458, 2006.
(Summary)
Several previous linkage scans in type 2 diabetes (T2D) families indicated a putative susceptibility locus on chromosome 12q15-q22, while the underlying gene for T2D has not yet been identified. We performed a region-wide association analysis on 12q15-q22, using a dense set of >500 single-nucleotide polymorphisms (SNPs), in 1492 unrelated Japanese individuals enrolled in this study. We identified an association between T2D and a haplotype block spanning 13.6 kb of genomic DNA that includes the entire SOCS2 gene. Evolutionary-based haplotype analysis of haplotype-tagging SNPs followed by a "sliding window" haplotypic analysis indicated SNPs that mapped to the 5' region of the SOCS2gene to be associated with T2D with high statistical significance. The SOCS2 gene was expressed ubiquitously in human and murine tissues, including pancreatic beta-cell lines. Adenovirus-mediated expression of the SOCS2 gene in MIN6 cells or isolated rat islets significantly suppressed glucose-stimulated insulin secretion. Our data indicate that SOCS2 may play a role in susceptibility to T2D in the Japanese.
Suguru Ohsawa, Kazuya Hukuda, Yasuaki Inamori and Natsuo Yasui : High tibial osteotomy for osteoarthritis of the knee with varus deformity utilizing the hemicallotasis method., Archives of Orthopaedic and Trauma Surgery, Vol.126, No.9, 588-593, 2006.
(Summary)
A hemicallotasis method has been developed utilizing an external fixator as high tibial osteotomy (HTO), and satisfactory results of this method with the external fixator have been reported. This external fixator has a universal joint that moves in all directions. We have recently designed a hemicallotasis device for this operation. HTO for the knee with varus deformity utilizing the hemicallotasis method was performed on 44 knees. The patients had a mean age at operation of 65 years (range 49-82 years), a mean follow-up period of 68 months (range 36-119 months), and a mean preoperative knee score of 66 points (range 27-90 points). The operated knees had a mean knee score at the final follow-up of 86 points (range 51-98 points), but the mean range of knee motion was not changed as follows. Before surgery, the mean flexion was 129 degrees (range 90-150 degrees) and the mean extension was -5 degrees (range -30 to 0 degrees), whereas at the final follow-up, the corresponding values were 127 degrees (range 85-150 degrees) and -4 degrees (range -25 to 0 degrees), respectively. Radiographically, the femorotibial joint was classified as grade 2 in 9 knees, grade 3 in 21 knees, and grade 4 in 14 knees according to the classification of osteoarthritis (Kellgren and Laurence). The patellofemoral joint was also classified as grade 1 in 39 knees, grade 2 in 2 knees, and grade 3 in 3 knees. The mean femorotibial angle was 184 degrees (4 degrees varus) before surgery, 169 degrees (11 degrees valgus) after pin extraction, and was maintained at the final follow-up. The complications of this method were relatively few and consisted of pin-tract infection (8 knees), deep vein thrombosis (3 knees), and delayed union (2 knees). No peroneal nerve palsy or compartment syndrome was encountered. No knee was converted to total arthroplasty. However, administration of analgesics was necessary in ten knees at the final follow-up. The hemicallotasis method easily determined the angle of correction even in the knees with ligamentous laxity. Nevertheless, one of the major demerits of this method was a longer period of application of the external fixator. The level of evidence was level IV (case series).
Keisuke Yagi, Yoshitaka Hamada and Natsuo Yasui : A Leiomyoma Arising from the Deep Palmar Arterial Arch., The Journal of Hand Surgery, British and European Volume, Vol.31, No.6, 680-682, 2006.
(Summary)
Vascular leiomyomas, or angioleiomyomas, are benign tumours originating from smooth non-striated muscle. Leiomyomas in the hand are uncommon and their pre-operative diagnosis is difficult. We report a 65 year-old woman who developed a vascular leiomyoma arising from the deep palmar arterial arch.
Mitsuhiko Takahashi, Yoshito Matsui, Tomohiro Goto, Gen Nishimura, Shiro Ikegawa, Hirofumi Ohashi and Natsuo Yasui : Intrafamilial phenotypic diversity in multiple epiphyseal dysplasia associated with a COL9A2 mutation (EDM2), Clinical Rheumatology, Vol.25, No.4, 591-595, 2006.
(Summary)
We describe a Japanese family with an autosomal dominant multiple epiphyseal dysplasia (MED EDM2) showing significant phenotypic diversity among the five affected members. Genomic analysis for COL9A2 identified an Ex3-1A>G heterozygous mutation, which has been proved to result in skipping of exon 3. The proband was a 9-year-old boy, who presented with ulnar club hands due to severe epiphyseal dysplasia in the distal ulnae. Radiological examination showed multiple epiphyseal dysplasias, predominantly involving the knee and the wrist. The hip appeared almost normal. The malalignment of the wrist was successfully treated with a limb lengthening procedure. The phenotype of the asymptomatic 12-year-old brother was similar to, but milder than, that of the proband. The asymptomatic 39-year-old mother, the 35-year-old uncle, and the 65-year-old grandmother with bilateral painful knees showed radiographically mild and severe osteoarthritis of the knee, respectively, and none of them had wrist deformity.
(Keyword)
Base Sequence / children / Collagen Type IX / Disease Progression / family / Hand Deformities, Congenital / Humans / Japan / Male / Molecular Sequence Data / Mutation / Osteochondrodysplasias / Pedigree / Phenotype / Ulna
Yoshito Matsui, Tadashi Hasegawa, Takahiro Kubo, Tomohiro Goto, Kiminori Yukata, Kenji Endo, Yoshio Bando and Natsuo Yasui : Intrapatellar tendon lipoma with chondro-osseous differentiation: detection of HMGA2-LPP fusion gene transcript., Journal of Clinical Pathology, Vol.59, No.4, 434-436, 2006.
(Summary)
A 54 year old man developed an unusual lipoma in the patellar tendon, consisting of a fibro-adipose component and a chondro-osseous component. The fibro-adipose component contained mature adipocytes, lipoblasts, and fibroblasts; the chondro-osseous component showed typical endochondral bone formation. Molecular analysis showed that the identical HMGA2-LPP fusion transcript-characteristic of lipoma, parosteal lipoma, and pulmonary chondroid hamartoma-was detectable in the both components.
Parvaneh Keshavarz, Hiroshi Inoue, Yukiko Yamashita, Kiyoshi Kunika, Toshihito Tanahashi, Naoto Nakamura, Toshikazu Yoshikawa, Natsuo Yasui, Hiroshi Shiota and Mitsuo Itakura : No evidence for association of ENPP1(PC-1)K121Q variant with risk of Type 2 diabetes in a Japanese population., Journal of Human Genetics, Vol.51, No.6, 559-566, 2006.
(Summary)
Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, also known as PC-1) inhibits insulin signal transduction pathway(s). Previous studies have demonstrated the K121Q variant of the ENPP1 gene to have a significant functional role in determining susceptibility to insulin resistance and type 2 diabetes (T2D). To assess whether the K121Q variant has any impact on T2D in Japanese, we undertook an extensive case-control association study using a total of 911 unrelated Japanese T2D patients and 876 control subjects. No significant difference was observed in either genotype distribution (P=0.95) or allele frequency (P=0.83) between T2D and control groups. Notably, the frequency of the ancestral Q121 allele, which is also present in other primates, was quite high in African-Americans, and showed a marked ethnic variation (77.3% in African-Americans, 16.7% in European Americans, 10.5% in Japanese and 4.2% in Han Chinese). Consequently, the pairwise F(ST )value (a classic measure of genetic distance between pairs of population) showed highly significant differentiations between African-American and non-African-American populations (F(ST)>0.3). Our results indicated that the K121Q variant of the ENPP1 gene has very little, if any, impact on T2D susceptibility in Japanese, but may play a role in the inter-ethnic variability in insulin resistance and T2D.
(Keyword)
African Americans / Alleles / Amino Acid Substitution / Asian Continental Ancestry Group / Case-Control Studies / Diabetes Mellitus, Type 2 / European Continental Ancestry Group / Female / Gene Frequency / Genetic Variation / Humans / insulin resistance / Japan / Male / Phosphoric Diester Hydrolases / Pyrophosphatases / Risk Factors
Mitsuhiko Takahashi, Kiminori Yukata, Yoshito Matsui, Aziz Abbaspour, Shinjiro Takata and Natsuo Yasui : Bisphosphonate Modulates Morphological and Mechanical Properties in Distraction Osteogenesis through Inhibition of Bone Resorption., Bone, Vol.39, No.3, 573-581, 2006.
(Summary)
Despite the general clinical acceptance of distraction osteogenesis and much attention to bone formation in this method, little is recognized about activated bone resorption in the regenerated bone. The purpose of this study was to demonstrate the simultaneously activated bone resorption with activated bone formation and to investigate the role and efficacy of bisphosphonate in distraction osteogenesis. Left tibiae of 54 immature rabbits were lengthened for 3 weeks at a rate of 0.7 mm/day after a 1-week lag. Regenerated bone was quantitatively investigated by radiographic bone density, bone histomorphometry, and three-point bending testing. Animals received either vehicle or nitrogen-containing bisphosphonate (N-BP), YM529/ONO5920 at doses of 0.4 mg/kg/w or 0.004 mg/kg/w for 6 weeks. Regenerated bone of the vehicle group showed a radiologically characteristic zone structure containing the osteopenic zones adjacent to the sclerotic zones. The regenerated bone of the 0.4-mg/kg/w group showed no osteopenic zones during the course and eventually became homogeneously radiodense. The bone volume corresponding to the osteopenic zone of this group was 5.6-fold greater compared with that of the vehicle group. The lengthened bone strength of this group was 3.3-fold greater in ultimate force than that of the vehicle group and equivalent to the contralateral tibia. The 0.004-mg/kg/w group had no substantial differences compared with the vehicle group, despite radiological enhancement of the mineralized front as well as somewhat delayed bone resorption. These results demonstrate that not only bone formation but also bone resorption is highly activated in the regenerated bone, implying high bone turnover. Sufficient N-BP caused a notable modulation in morphological properties of the regenerated bone through inhibition of highly activated bone resorption and eventually increased mechanical properties.
(Keyword)
Absorptiometry, Photon / Animals / Bone Resorption / Calcification, Physiologic / Diphosphonates / Male / Osteogenesis / Rabbits
Takahiro Kubo, Yoshito Matsui, Tomohiro Goto, Kiminori Yukata and Natsuo Yasui : Overexpression of HMGA2-LPP fusion transcripts promotes expression of the alpha 2 type XI collagen gene., Biochemical and Biophysical Research Communications, Vol.340, No.2, 476-481, 2006.
(Summary)
In a subset of human lipomas, a specific t(3;12) chromosome translocation gives rise to HMGA2-LPP fusion protein, containing the amino (N)-terminal DNA binding domains of HMGA2 fused to the carboxyl (C)-terminal LIM domains of LPP. In addition to its role in adipogenesis, several observations suggest that HMGA2-LPP is linked to chondrogenesis. Here, we analyzed whether HMGA2-LPP promotes chondrogenic differentiation, a marker of which is transactivation of the alpha 2 type XI collagen gene (Col11a2). Real-time PCR analysis showed that HMGA2-LPP and COL11A2 were co-expressed. Luciferase assay demonstrated that either of HMGA2-LPP, wild-type HMGA2 or the N-terminal HMGA2 transactivated the Col11a2 promoter in HeLa cells, while the C-terminal LPP did not. RT-PCR analysis revealed that HMGA2-LPP transcripts in lipomas with the fusion were 591-fold of full-length HMGA2 transcripts in lipomas without the fusion. These results indicate that in vivo overexpression of HMGA2-LPP promotes chondrogenesis by upregulating cartilage-specific collagen gene expression through the N-terminal DNA binding domains.
Kousaku Higashino, Shinsuke Katoh, Koichi Sairyo, Toshinori Sakai, Hirofumi Kosaka and Natsuo Yasui : Preservation of C7 spinous process does not influence the long-term outcome after laminoplasty for cervical spondylotic myelopathy., International Orthopaedics, Vol.30, No.5, 362-365, 2006.
(Summary)
Axial pain is one of the major complications after laminoplasty, and preservation of C7 spinous process during the procedure can reduce the axial pain. However, it has not been elucidated whether laminoplasty preserving the C7 spinous process can maintain neurological improvement for a long time. The purpose of our retrospective study was to investigate the long-term neurological outcome after open-door laminoplasty preserving the C7 spinous process for cervical spondylotic myelopathy (CSM). Clinical and radiological outcomes were analysed in 42 patients who underwent open-door laminoplasty preserving C7 spinous process and followed up for more than 5 years. Neurological function was evaluated by means of the Japanese Orthopaedic Association (JOA) scoring system for cervical myelopathy. Axial pain was assessed using a visual analog scale (VAS) at the last examination. Alignment and motion of the cervical spine were measured from radiographs, and magnetic resonance imaging (MRI) was used to evaluate postoperative compression at C7. The mean JOA score was 9.4 before surgery and 12.0 at the latest follow-up. The mean VAS score in 26 patients score was 9.7/100. No compression of the spinal cord was observed in any MRI at the latest follow-up. Preservation of the C7 spinous process does not influence the long-term outcome of CSM after laminoplasty. Although we did not have a comparative group, the procedure described here should be considered as the solution.
Hiroshi Egawa, Shunji Nakano, Daisuke Hamada, Ryosuke Sato and Natsuo Yasui : Total hip arthroplasty in osteopetrosis using computer-assisted fluoroscopic navigation., The Journal of Arthroplasty, Vol.20, No.8, 1074-1077, 2005.
(Summary)
Hybrid total hip arthroplasty with computer-assisted fluoroscopic navigation was performed on a patient with osteoarthritis due to an autosomal dominant form of osteopetrosis. The surgical procedures were difficult because the bone was extremely hard and brittle with obliteration of the medullary cavity. Especially, preparation of a femoral canal for the stem was technically challenging and required changes from a conventional surgical procedure. Therefore, we used a computer-assisted fluoroscopic navigation system to create the femoral cavity for the stem, and an accurate placement of the prosthesis was achieved. Navigation guidance can be a useful tool when performing arthroplasty in patients with hip osteoarthritis associated with osteopetrosis.
(Keyword)
Arthroplasty, Replacement, Hip / Fluoroscopy / Hip Prosthesis / Humans / Male / Middle Aged / Osteopetrosis / Radiography, Interventional / Surgery, Computer-Assisted
We report the case of a 42-year-old Japanese woman with unusual diaphyseal dysplasia of bilateral femora. Radiographs showed thickening and sclerosis of the cortex with resultant enlargement of the diaphysis, unclear demarcation of the surface of the cortex, and no periosteal reaction. These changes were found on the left femur at the first presentation, and those on the right femur developed within several years. Although this patient partly presented characteristics of Ribbing disease and Camurati-Engelmann disease, the focal involvement of bilateral femora suggested an unknown pathogenesis.
Kenji Endo, Mitsuhiko Takahashi, Yoshito Matsui, Tadashi Hasegawa and Natsuo Yasui : Bone Tumor of the Distal Femur in a 67-Year-Old Woman, Clinical Orthopaedics and Related Research, Vol.440, 262-268, 2005.
Takayuki Ogawa, Takeshi Nikawa, Harumi Furochi, Miki Kosyoji, Katsuya Hirasaka, Naoto Suzue, Koichi Sairyo, Shunji Nakano, Takashi Yamaoka, Mitsuo Itakura, Kyoichi Kishi and Natsuo Yasui : Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice, American Journal of Physiology, Cell Physiology, Vol.289, No.3, C697-C707, 2005.
(Summary)
In this study, we examined pathophysiological roles of osteoactivin, a functionally unknown type I membrane glycoprotein, in mouse skeletal muscle atrophied by denervation (sciatic neurectomy). Denervation increased the amounts of osteoactivin, vimentin, matrix metalloproteinase-3 (MMP-3), and MMP-9 in mouse gastrocnemius muscle. Interestingly, immunohistochemical analysis revealed that vimentin, MMP-3, and MMP-9 were mainly present in fibroblast-like cells infiltrated into denervated mouse gastrocnemius muscle, whereas osteoactivin was expressed in the sarcolemma of myofibers adjacent to the fibroblast-like cells. On the basis of these findings, we reasoned that osteoactivin in myocytes was involved in activation of the infiltrated fibroblasts. To address this issue, we examined effects of osteoactivin on expression of MMPs in fibroblasts in vitro and in vivo. Overexpression of osteoactivin in NIH-3T3 fibroblasts induced expression of MMP-3, but not in mouse C(2)C(12) myoblasts, indicating that osteoactivin might functionally target fibroblasts. Treatment with recombinant mouse osteoactivin increased the amounts of collagen type I, MMP-3, and MMP-9 in mouse NIH-3T3 fibroblasts. The upregulated expression of these fibroblast marker proteins was significantly inhibited by heparin, but not by an integrin inhibitor, indicating that a heparin-binding motif in the extracellular domain might be an active site of osteoactivin. In osteoactivin-transgenic mice, denervation further enhanced expression of MMP-3 and MMP-9 in fibroblasts infiltrated into gastrocnemius muscle, compared with wild-type mice. Our present results suggest that osteoactivin might function as an activator for fibroblasts infiltrated into denervated skeletal muscles and play an important role in regulating degeneration/regeneration of extracellular matrix.
Cyclooxigenase-2 (COX-2) inhibitors have been reported to delay fracture healing. To investigate the major inhibitory period of COX-2 inhibitors in fracture healing, we administrated etodolac, a COX-2-specific inhibitor, to a rat fracture model by altering the period of administration from early to late. After closed fractures had been created at the middle of the femoral shafts in 12-week-old Wister rats, a standardized dose of etodolac was administrated in three ways: group I received it for 3 weeks, group II for just the first week after operation, and group III for just the third (final) week. Group IV was the vehicle control group. Bone maturation was estimated by radiographic scoring system, and mechanically by a three-point bending test. In both the radiographic and mechanical studies, groups I and II showed lower scores than group IV, indicating that even a short period of administration of a COX-2-specific inhibitor in the early phase of fracture healing creates a risk of delayed healing. blacksquare, square, filled.
Daisuke Hamada, Yoichiro Takata, Dai Osabe, Kyoko Nomura, Syuichi Shinohara, Hiroshi Egawa, Shunji Nakano, Fumio Shinomiya, Charles R Scafe, Vincent M Reeve, Tatsuro Miyamoto, Maki Moritani, Kiyoshi Kunika, Hiroshi Inoue, Natsuo Yasui and Mitsuo Itakura : Association Between Single-Nucleotide Polymorphisms in the SEC8L1 Gene,Which Encodes a Subunit of the Exocyst Complex,and Rheumatoid Arthritis in a Japanese Population, Arthritis and Rheumatism, Vol.52, No.5, 1371-1380, 2005.
(Summary)
To identify rheumatoid arthritis (RA) susceptibility genes in a Japanese population by conducting a large-scale case-control association analysis and linkage disequilibrium (LD) mapping on chromosome 7q31-34, a candidate susceptibility locus identified in a preliminary genome-wide scan in 53 Japanese families, using single-nucleotide polymorphisms (SNPs). We prepared 728 dense, evenly spaced SNPs with a minor allele frequency >0.15 in each gene locus on chromosome 7q31-34. Using these SNPs, a 2-stage case-control analysis was performed on 760 RA patients (157 men and 603 women) and 806 non-RA controls (189 men and 617 women). Haplotypes and LD mapping results were assessed based on SNP genotypes in 380 controls. Forty-eight SNPs showed allele associations (P < 0.05) in the first set of DNA samples (380 RA cases and 380 non-RA controls; first-stage analysis). For 4 of the SNPs in the SEC8L1 gene, the association was replicated (P < 0.05) in the second, independent set of DNA samples (an additional 380 RA cases and 380 non-RA controls; second-stage analysis). When data from the 2 groups were combined, the most significant allele association was observed with SNP 441, an intronic SNP of the SEC8L1 gene (P = 0.000059). The SEC8L1 SNPs with significant allele associations were all located in a single conserved LD block (block 4). Haplotype analysis revealed the disease-risk (P = 0.0015) and disease-protective (P = 0.0000062) haplotypes. Resequencing of coding exons within block 4 did not identify any nonsynonymous SNPs. Real-time quantitative polymerase chain reaction revealed that SEC8L1 was expressed ubiquitously in human tissues, including fibroblast-like synoviocytes from RA patients. Our locus-wide association and LD analyses identified intronic SNPs and haplotypes in the SEC8L1 gene that are strongly associated with RA. We propose that SEC8L1, which encodes a component of the exocyst complex, is a candidate susceptibility gene for RA in the Japanese population.
(Keyword)
Adult / Aged / Arthritis, Rheumatoid / Carrier Proteins / Case-Control Studies / Female / Haplotypes / Humans / Japan / Linkage Disequilibrium / Male / Membrane Proteins / Middle Aged / Polymorphism, Single Nucleotide / Vesicular Transport Proteins
Kiminori Yukata, Yoshito Matsui, Tomohiro Goto, Takahiro Kubo and Natsuo Yasui : Differential Expression of VEGF Isoforms and VEGF Receptors in Cartilaginous Tumors, Anticancer Research, Vol.25, No.2A, 955-958, 2005.
(Summary)
Vascular endothelial growth factor (VEGF), which is known to have at least five isoforms and four receptors, is integral to tumor-induced neovascularization. In order to determine whether VEGF signaling is modulated in the development of cartilaginous tumors, we analyzed osteochondrogenic tumors for the expression of VEGF isoforms and VEGF receptors using the reverse transcription-polymerase chain reaction method. Although mRNA for VEGF121, VEGF165, VEGFR-1 and NRP-2 was widely expressed, mRNA expression for VEGF189, VEGFR-2 and NRP-1 was linked to a malignant phenotype such as local invasion. These results indicated that VEGF signaling was fine-tuned by the differential expression of the VEGF isoforms and VEGF receptors.
(Keyword)
Alternative splicing / angiogenesis / cartilaginous tumors / VEGF
(Link to Search Site for Scientific Articles)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15868933
Koichi Sairyo, Shinsuke Katoh, Takahiro Sasa, Natsuo Yasui, K Vijay Goel, Sasidhar Vadapalli, Akiyoshi Masuda, Ashok Biyani and Nabil Ebraheim : Athletes With Unilateral Spondylolysis Are at Risk of Stress Fracture at the Contralateral Pedicle and Pars Interarticularis, --- A Clinical and Biomechanical Study ---, The American Journal of Sports Medicine, Vol.33, No.4, 583-590, 2005.
(Summary)
Unilateral spondylolysis is common in youths; its clinical and biomechanical features, especially effects on the contralateral side, are not fully understood. Unilateral spondylolysis predisposes the contralateral side to stress fracture, especially in athletes actively engaged in sporting activities involving torsion of the trunk. Case series and descriptive laboratory study. Thirteen athletes younger than age 20 with unilateral spondylolysis were included. The contralateral pedicle and pars of spondylolytic vertebrae were examined using computed tomography and magnetic resonance imaging. Using a finite element model of the intact ligamentous L3-S1 segment, stress distributions were analyzed in response to 400-N axial compression and 10.6-N.m moment in flexion, extension, lateral bending, and axial rotation. Unilateral spondylolysis was created in the model at L5. The stress results from the unilateral defect model were compared to the intact model predictions and correlated to the contralateral defects seen in patients. Among 13 patients, there were 6 early-, 2 progressive-, and 5 terminal-stage defects. Three (23.1%) showed contralateral stress fracture. Among them, 2 belonged to the progressive-stage and 1 to the terminal-stage spondylolysis group. The remaining 4 patients in the terminal defect group showed stress reactions, such as sclerosis at the contralateral pedicle. In the finite element analysis model with an L5 left spondylolysis, the stresses at the contralateral and pars interarticularis were found to increase in all loading modes, with increases as high as 12.6-fold compared to the intact spine. Unilateral spondylolysis could lead to stress fracture or sclerosis at the contralateral side due to an increase in stresses in the region. Surgeons should be aware of possibility of contralateral stress fractures in cases in which patients, especially athletes engaged in active sports, show unilateral spondylolysis and persistent low back pain complaints.
Koichi Sairyo, Shinsuke Katoh, Shinji Komatsubara, Ttomoya Terai, Natsuo Yasui, K Vijay Goel, Sasidhar Vadapalli, Ashok Biyani and Nabil Ebraheim : Spondylolysis fracture angle in children and adolescents on CT indicates the facture producing force vector A biomechanical rationale., The Internet Journal of Spine Surgery, Vol.1, No.2, 2005.
Masaru Kobayashi, Natsuo Yasui, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Development of Autoimmune Arthritis With Aging Via Bystander T Cell Activation in the Mouse Model of Sjogren's Syndrome, Arthritis and Rheumatism, Vol.50, No.12, 3974-3984, 2004.
(Summary)
A wide spectrum of extraglandular manifestations may occur in patients with Sjogren's syndrome (SS), but the mechanisms responsible for in vivo progression are still obscure. We undertook this study to evaluate the age-related changes during the development of extraglandular autoimmune lesions, including arthritis, in the murine model of primary SS, and to evaluate the possible relationship between age-related disturbance of activation-induced cell death and the in vivo kinetics against autoantigens. A total of 126 NFS/sld mice were investigated at ages 2, 4, 6, 10, 12, 18, 20, and 24 months. Cytokine production was tested using culture supernatants from anti-CD3 monoclonal antibody-stimulated T cells. Anti-single-stranded DNA (anti-ssDNA) antibodies, Ig isotypes (IgG1, IgG2a), rheumatoid factor (RF), and anti-type II collagen (anti-CII) antibodies were detected by enzyme-linked immunosorbent assay. Proliferative T cell responses against each of 3 recombinant alpha-fodrin proteins and against CII were analyzed. Autoimmune arthritis developed in SS model mice until age 24 months. Significant elevations in serum levels of RF, anti-ssDNA antibodies, and anti-CII antibodies were found in aging SS model mice. A high titer of serum autoantibodies against alpha-fodrin fragments (containing different epitopes that were originally identified in primary SS model mice) was frequently detected in young and aged SS model mice. Moreover, we found that alpha-fodrin autoantigen induced Th1 immune responses and accelerated disturbance of Fas-mediated T cell apoptosis in aged SS model mice. These results indicate that age-related disturbance of activation-induced cell death via bystander T cell activation may play a crucial role in the development of autoimmune arthritis in a murine model of SS.
Kenji Endo, Kiminori Yukata and Natsuo Yasui : Influence of age on scapulo-thoracic orientation, Clinical Biomechanics, Vol.19, No.10, 1009-1013, 2004.
(Summary)
Scapular activity during shoulder motion is critical for normal shoulder function. With aging, muscle function deteriorates in almost all people, which may lead to shoulder impingement syndrome. Forty-four normal subjects, 23 men and 21 women aged from 16 to 73 years with a mean age 48, were enrolled in the study. Static antero-posterior radiography at both 0 degrees and 90 degrees of abduction were undertaken and correlation between age and scapular orientations were evaluated by Pearson's correlation coefficient test. The purpose of this study is to investigate the relationship between aging and scapulo-thoracic orientation. Significant correlation coefficients were observed between aging and scapular orientations. With the shoulder at 0 degrees abduction, posterior tilt showed significant negative correlation with aging. At 90 degrees abduction, both posterior tilt and upward rotation angle correlated negatively with aging. The correlation was apparent at 90 degrees abduction. The results indicate that shoulder aging closely relates to changes of scapular orientation, which consist of decreases of the posterior tilt at 0 degrees and 90 degrees abduction and the upward rotation angle at 90 degrees. The current study indicated that one of the effects of aging on the shoulder is a decrease of posterior tilt and upward rotation angle as seen in an abducted position; and that these alterations are similar to the scapular kinematics of shoulder impingement syndrome. By taking this concept into consideration, the effects of aging on shoulder kinematics can be appropriately evaluated.
Takahiro Sasa, Koichi Sairyo, Naoyuki Yoshida, Mari Fukunaga, Keiko Koga, Makoto Ishikawa and Natsuo Yasui : Continuous muscle stretch prevents disuse muscle atrophy and deterioration of its oxidative capacity in rat tail-suspension models, American Journal of Physical Medicine & Rehabilitation, Vol.83, No.11, 851-856, 2004.
(Summary)
The purpose of this study was to evaluate the effect of continuous muscle stretch on disuse-atrophied muscles. Sprague-Dawley rats were used and divided into five groups: control group, hind limb suspended for 3 and 7 days, and hind-limb suspension plus strenuous continuous muscle stretch for 3 and 7 days. In the hind-limb suspension plus strenuous continuous muscle stretch groups, the gastrocnemius-plantaris-soleus muscles were stretched using a plastic plate that immobilized the ankle joint at the maximum dorsal flexed position during the hind-limb suspension period. The intracellular energy metabolism of the working muscle during electric stimulation was evaluated by phosphorus-31 magnetic resonance spectroscopy in vivo. Changes in phosphocreatine, inorganic phosphate, and the intracellular pH were monitored to evaluate intramuscular oxidative capacity. Maximum tension and muscle wet mass were also measured. The oxidative capacity, muscle wet weight, and maximum tension decreased after hind-limb suspension. The muscle oxidative capacity at control levels was maintained during the first 3 days in muscles subjected to continuous strenuous stretch. It was also effective to prevent the decrease in muscle mass and maximum twitch tension during the initial 3 days. However, the effects did not persist. Continuous strenuous stretch was effective to prevent disuse muscle atrophy and its functional deterioration; however, its effects did not last long.
Shinjiro Takata, Natsuo Yasui, Kiyoshi Nakatsuka and Stuart H Ralston : Evolution of understanding of genetics of Paget's disease of bone and related diseases, Journal of Bone and Mineral Metabolism, Vol.22, No.6, 519-523, 2004.
(Keyword)
Paget's disease of bone / genetics / familial expansile osteolysis / expansile skeletal hyperphosphatasia
Takuya Mishiro, Shunji Nakano, Shigeyuki Takahara, Mari Miki, Yoichi Nakamura, Susumu Yasuoka, Takeshi Nikawa and Natsuo Yasui : Relationship Between Cathepsin B and Thrombin in Rheumatoid Arthritis, The Journal of Rheumatology, Vol.31, No.7, 1265-1273, 2004.
(Summary)
To investigate the pathophysiological significance of cathepsin B and thrombin in synovial fluid (SF) from patients with rheumatoid arthritis (RA). Thrombin and cathepsin B activities of samples from patients with RA and osteoarthritis (OA) were measured using fluorogenic synthetic substrates. The concentration of interleukin 8 (IL-8) in SF was measured by ELISA. The effect of thrombin on the proliferation of synovial fibroblast-like cells (SFC) was examined by measuring 3H-thymidine incorporation. The effect of thrombin on the release of IL-8 and cathepsin B from SFC was investigated. The expression of IL-8 mRNA in SFC after stimulation with thrombin was evaluated using real-time quantitative RT-PCR. The effect of recombinant IL-8 on the activation of cathepsin B was examined using the knee joints of rabbits. In SF supernatants, cathepsin B and thrombin-like activity was significantly higher in RA than in OA, and there was a significant correlation between them. Cathepsin B activity was also significantly higher in SF cells and synovial tissue extracts from RA patients than in those from OA patients. There was a significant correlation between cathepsin B activity and the concentration of IL-8 in RA SF. Thrombin enhanced the proliferation of SFC in a dose-dependent manner. Thrombin significantly enhanced the release of IL-8 from SFC as well as the expression of IL-8 mRNA in SFC. IL-8 induced activation of cathepsin B in the knee joints of rabbits. However, thrombin did not directly increase cathepsin B activity in SFC. In RA, thrombin was found to be related to the enhanced growth of SFC and the release of IL-8 from these cells; thus thrombin is probably related to worsening of inflammation through the recruitment of leukocytes (neutrophils), which release cathepsin B into the SF. Thrombin can induce activation of cathepsin B in SFC via increased expression of IL-8.
Koichi Sairyo, Shinsuke Katoh, Tadanori Sakamaki, Megumi Inoue, Shinji Komatsubara, Takayuki Ogawa, Toshiaki Sano, K. Vijay Goel and Natsuo Yasui : Vertebral forward slippage in immature lumbar spine occurs following epiphyseal separation and its occurence is unrelated to disc degeneration. Is the pediatric spondylolisthesis a physis stress fracture of vertebral body?, Spine, Vol.29, No.5, 524-527, 2004.
(Summary)
Radiographic and histologic evaluation of a rat model of lumbar spine slippage. To clarify the pathomechanism of slippage in the immature spine. There are controversial hypotheses regarding the pathogenesis of slippage of the pediatric spine with pars defects. Some studies supported that disc degeneration was its cause, while others indicated the growth plate injury was the cause. An immature lumbar spine slippage model in 4-week-old rats was used. Following posterior destabilizing surgery, the lumbar spine was radiographically and histologically examined at 1, 3, 5, and 7 days after surgery. Radiographically, slippage occurred about 7% in the % slip on day 7, and no slippage was observed before day 5. Histologically, epiphyseal separation also appeared on day 7; before day 5, the growth plate showed no abnormalities. Within 7 days after the operation, the anulus fibrosus did not show any sign indicating degeneration. The nucleus pulposus was also normal up to day 7. The findings of this study support the hypothesis that vertebral forward slippage of the immature spine occurs following epiphyseal separation and its occurrence is unrelated to disc degeneration.
K Fujii, Shinsuke Katoh, Koichi Sairyo, T Ikata and Natsuo Yasui : Union of defects in the pars interarticularis of the lumbar spine in children and adolescents. Radiological outcome after conservative treatment., The Journal of Bone and Joint Surgery. British Volume, Vol.86, No.2, 225-231, 2004.
(Summary)
Lumbar spondylolysis can heal with conservative treatment, but few attempts have been made to identify factors which may affect union of the defects in the pars. We have evaluated, retrospectively, the effects of prognostic variables on bony union of pars defects in 134 young patients less than 18 years of age with 239 defects of the pars who had been treated conservatively. All patients were evaluated by CT scans when first seen and more than six months later at follow-up. The results showed that the spinal level and the stage of the defects were the predominant factors. The site of the defects in the pars, the presence or development of spondylolisthesis, the condition of the contralateral pars, the degree of lumbar lordosis and the degree of lumbar inclination all significantly affected union.
Takeshi Nikawa, Kazumi Ishidoh, Katsuya Hirasaka, Ibuki Ishihara, Madoka Ikemoto, Mihoko kano, Eiki Kominami, Ikuya Nonaka, Takayuki Ogawa, Gregory R. Adams, kenneth M. Baldwin, Natsuo Yasui, Kyoichi Kishi and Shinichi Takeda : Skeletal muscle gene expression in space-flown rats, The FASEB journal, Vol.18, No.3, 522-524, 2004.
(Summary)
Skeletal muscles are vulnerable to marked atrophy under microgravity. This phenomenon is due to the transcriptional alteration of skeletal muscle cells to weightlessness. To further investigate this issue at a subcellular level, we examined the expression of approximately 26,000 gastrocnemius muscle genes in space-flown rats by DNA microarray analysis. Comparison of the changes in gene expression among spaceflight, tail-suspended, and denervated rats revealed that such changes were unique after spaceflight and not just an extension of simulated weightlessness. The microarray data showed two spaceflight-specific gene expression patterns: 1) imbalanced expression of mitochondrial genes with disturbed expression of cytoskeletal molecules, including putative mitochondria-anchoring proteins, A-kinase anchoring protein, and cytoplasmic dynein, and 2) up-regulated expression of ubiquitin ligase genes, MuRF-1, Cbl-b, and Siah-1A, which are rate-limiting enzymes of muscle protein degradation. Distorted expression of cytoskeletal genes during spaceflight resulted in dislocation of the mitochondria in the cell. Several oxidative stress-inducible genes were highly expressed in the muscle of spaceflight rats. We postulate that mitochondrial dislocation during spaceflight has deleterious effects on muscle fibers, leading to atrophy in the form of insufficient energy provision for construction and leakage of reactive oxygen species from the mitochondria.
Takahiro Sasa, Koichi Sairyo, Naoyuki Yoshida, Makoto Ishikawa, Mari Fukunaga and Natsuo Yasui : Muscular oxidative capacity in ovariectomized rats discussion on the endurance performance of female athletes with sports-related-amenorrhea, Journal of Sports Science & Medicine, Vol.3, 15-22, 2004.
Rieko Arakaki, Naozumi Ishimaru, Ichiro Saito, Masaru Kobayashi, Natsuo Yasui, Takayuki Sumida and Yoshio Hayashi : Development of Autoimmune Exocrinopathy Resembling Sjogren's Syndrome in Adoptively Transferred Mice With Autoreactive CD4+ T Cells, Arthritis and Rheumatism, Vol.48, No.12, 3603-3609, 2003.
(Summary)
The pathologic mechanisms responsible for organ-specific tissue damage in primary Sjögren's syndrome (SS) remain unclear, but it has been suggested that the pathology is mediated by autoreactive CD4+ T cells infiltrating the salivary and lacrimal glands. This study was undertaken to investigate whether alpha-fodrin autoantigen-specific autoreactive CD4+ T cells are capable of inducing autoimmune lesions. A total of 45 synthetic alpha-fodrin peptides designed to be 20 amino acid residues in length were generated. To establish an autoreactive T cell line, limiting dilution analysis (LDA) was performed on lymph node cells (LNCs) in the presence of alpha-fodrin peptides. The effects of adoptive transfer of autoreactive CD4+ T cells into normal syngeneic recipients were investigated. Autoreactive CD4+ T cell lines that recognize synthetic alpha-fodrin peptide, which produced Th1 cytokines and showed cytotoxic activities, were established in a murine model for SS. T cell receptor V(beta) usage and third complementarity-determining region (CDR3) sequences indicated that in some cases V(beta)6-CDR3 genes matched between the tissue-infiltrating T cells and the autoreactive T cell lines. Adoptive transfer of the autoreactive CD4+ T cells into normal syngeneic recipients induced autoimmune lesions quite similar to those of SS. Our data help to elucidate the pathogenic mechanisms responsible for tissue destruction in autoimmune exocrinopathy and indicate that autoreactive CD4+ T cells play a pivotal role in the development of murine SS.
(Keyword)
Adoptive Transfer / Amino Acid Sequence / Animals / Base Sequence / CD4-Positive T-Lymphocytes / Carrier Proteins / Complementarity Determining Regions / Disease Models, Animal / Mice / Mice, Mutant Strains / Microfilament Proteins / Molecular Sequence Data / Sjogren's Syndrome / Specific Pathogen-Free Organisms
Mohamed Yehya Hasan, Fumio Shinomiya, Masahiko Okada, Yosiaki Hamada, Takuya Fijimura, Daisuke Hamada, Shunji Nakano, Hiroshi Egawa, Ibrahim Elhawari and Natsuo Yasui : Intracapsular hip fractures in patients with rheumatoid arthritis, International Orthopaedics, Vol.27, No.5, 294-297, 2003.
(Summary)
We reviewed the treatment of 43 patients with rheumatoid arthritis and femoral neck fracture. Patients' average age was 66.4 (36-80) years and average duration of RA was 20.3 (4-42) years. Thirteen patients were treated with primary total hip arthroplasty (THA), and the clinical results were comparable to patients treated conservatively or by osteosynthesis. Eighteen patients were treated with primary bipolar hip prosthesis and after an average of 6.1 (1-13) years there was no acetabular destruction. However, long-term results were inferior to patients treated with THA. Nine patients were treated with osteosynthesis, of which two later had a hip prosthesis. Three cases with impacted fractures were treated conservatively with successful union in all.
(Keyword)
Adult / Aged / Aged, 80 and over / Arthritis, Rheumatoid / Arthroplasty, Replacement, Hip / Female / Femoral Neck Fractures / Fracture Fixation, Internal / Humans / Male / Middle Aged / Treatment Outcome
Nori Hirohashi, Kenji Endo, Mitsuhiko Takahashi, Shinsuke Katoh, Natsuo Yasui and Tsutomu Watanabe : Ewing Sarcoma of the Pelvis Treated with Internal Hemipelvectomy:A Cace Report, The Journal of the Chugoku-Shikoku Orthopaedic Association, Vol.15, No.2, 281-286, 2003.
(Keyword)
Ewing's Sarcoma / Surgery / Peivis / Wide resection
Koichi Sairyo, Shinsuke Katoh, T Sakamki, S. Komatsubara and Natsuo Yasui : Three successive stress fractures at the same vertebral level in an adolescent baseball player, The American Journal of Sports Medicine, Vol.31, No.4, 606-610, 2003.
(Keyword)
Adolescent / Baseball / Bone Transplantation / Fractures, Stress / Humans / Low Back Pain / Lumbar Vertebrae / magnetic resonance imaging / Male / Physical Examination / Spinal Fractures / Tomography, X-Ray Computed / Treatment Outcome
(Link to Search Site for Scientific Articles)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12860553
Tadanori Sakamaki, Koichi Sairyo, Shinsuke Katoh, Hideko Endo, Shinji Komatsubara, Toshiaki Sano and Natsuo Yasui : The Pathogenesis of Slippage and Deformity in the Pediatric Lumbar Spine, --- A Radiographic and Histologic Study using a New Rat In Vivo Model ---, Spine, Vol.28, No.7, 645-651, 2003.
Koichi Sairyo, Shinsuke Katoh, Tadanori Sakamaki, Shinji Komatsubara and Natsuo Yasui : A new endoscopic technique to decompress lumbar nerve roots affected by spondylolysis. Technical note, Journal of Neurosurgery, Vol.98, No.3 Suppl, 290-293, 2003.
(Summary)
The authors describe a new endoscopic technique to decompress lumbar nerve roots affected by spondylolysis. Short-term clinical outcome was evaluated. Surgery-related indications were: 1) radiculopathy without low-back pain; 2) no spinal instability demonstrated on dynamic radiographs; and 3) age older than 40 years. Seven patients, four men and three women, fulfilled these criteria and underwent endoscopic decompressive surgery. Their mean age was 60.9 years (range 42-70 years). No subluxation was present in four patients, whereas Meyerding Grade I slippage was demonstrated in three. For endoscopic decompression, a skin incision of 16 to 18 mm in length was made, and fenestration was performed to identify the affected nerve root. The proximal stump of the ragged edge of the spondylotic lesion, and the fibrocartilaginous mass compressing the nerve root were removed. The follow-up period ranged from 6 to 22 months (mean 11.7 months). Clinical outcome was evaluated using Gill criteria; in three patients the outcome was excellent, and in four it was good. This new endoscopic technique was useful in the decompression of nerve roots affected by spondylolysis, the technique was minimally invasive, and the clinical results were acceptable.
Naoyuki Yoshida, Koichi Sairyo, Takahiro Sasa, Mari Fukunaga, Keiko Koga, Takaaki Ikata and Natsuo Yasui : Electrical Stimulation Prevents Deterioration of the Oxidative Capacity of Disuse-Atrophied Muscles in Rats, Aviation, Space, and Environmental Medicine, Vol.74, No.3, 207-211, 2003.
(Summary)
The purpose of this study was to evaluate the effects of electrical stimulation on disuse-atrophied muscles. Sprague-Dawley rats were used and divided into three groups: control (C), hind-limb suspended for 7 d (HS), and HS plus transcutaneous electrical stimulation for 7 d (ES). In the ES group, transcutaneous electrical stimulation was induced at 1 Hz for 1 h every day to condition the gastrocnemius-plantaris-soleus muscles. Muscle oxidative capacity was evaluated by 31P-MRS in vivo. Maximum tension and muscle wet mass were also measured. Muscle oxidative capacity decreased within 1 wk in HS; however, it was maintained when electric stimulation was applied to the suspended limb. The maximum twitch tension in HS was significantly smaller than that in C (p < 0.05), while in ES it did not differ from that in C. The muscle mass was significantly smaller in the HS and ES groups compared to C (p < 0.05). These data indicated that twitch electrical stimulation was effective in preventing deterioration of muscle functions, such as maximum tension and oxidative capacity, induced by 1 wk of disuse.
(Keyword)
disuse / muscle / oxidative / capacity / 31P-MRS
(Link to Search Site for Scientific Articles)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12650266
Tomohiko Fukuda, Nobuaki Yoshida, Yuki Kataoka, Ri-ichiroh Manabe, Yoko Mizuno-Horikawa, Motohiko Sato, Kohji Kuriyama, Natsuo Yasui and Kiyotoshi Sekiguch : Mice lacking the EDB segment of fibronectin develop normally but exhibit reduced cell growth and fibronectin matrix assembly in vitro, Cancer Research, Vol.62, No.19, 5603-5610, 2002.
(Summary)
Fibronectins (FNs) are major cell-adhesive proteins in the extracellular matrix and are essential for embryonic development. FNs are encoded by a single gene, but heterogeneity is introduced by alternative pre-mRNA splicing. One of the alternatively spliced segments, extra domain B (EDB), is prominently expressed during embryonic development and in tumor tissues, although it is mostly eliminated from FN in normal adult tissues. To examine the function of the EDB segment in vivo, we generated mice lacking the EDB exon using the Cre-loxP system. Although EDB-containing FNs are highly expressed throughout early embryogenesis, EDB-deficient mice developed normally and were fertile. Despite the absence of any significant phenotypes observed in vivo, however, fibroblasts obtained from EDB-deficient mice grew slowly in vitro and deposited less FN in the pericellular matrix than fibroblasts from wild-type mice. These results indicate that expression of EDB-containing isoforms is dispensable during embryonic development, yet may play a modulating role in the growth of connective tissue cells via the FN matrix.
(Keyword)
Amino Acid Sequence / Animals / Cartilage / Cell Division / Chimera / Extracellular Matrix / Fibroblasts / Fibronectins / Male / Mice / Mice, Inbred C57BL / Molecular Sequence Data / Protein Isoforms / Protein Structure, Tertiary
(Link to Search Site for Scientific Articles)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12359774
Shinjiro Takata, Hiroshi Yonezu and Natsuo Yasui : Intergenerational comparison of total and regional bone mineral density and soft tissue composition in Japanese women without vertebral fractures, The Journal of Medical Investigation : JMI, Vol.49, No.3,4, 142-146, 2002.
(Summary)
We measured total and regional bone mineral density (BMD) and soft tissue mass in 115 healthy Japanese women without vertebral fractures. The subjects, aged 20 to 75 years, were divided into four age groups: 20's to 40's group (n=33), 50's group (n=26), 60's group (n=26), and 70's group (n=30). BMD was measured by dual energy X-ray absorptiometry (DXA). The evaluated regions were the head, arms, legs, ribs, thoracic vertebrae, lumbar vertebrae and pelvis. The total and regional BMDs were the highest in the 20's to 40's group, and they decreased with age, and reached their respective lowest values in the 70's group. The decrease in BMDs of the spine and pelvis was the most prominent of all regional BMDs. Total and regional lean mass and fat mass were the highest in the 20's to 40's group, and they decreased to their respective lowest values in the 70's group. The results showed that the decrease in BMD of the spine and pelvis was the most prominent of all regional BMDs associated with a decrease in the total and regional lean mass and total and regional fat mass.
(Keyword)
bone mineral density / soft tissue / aging / dual energy X-ray absorptiometry
Hidehiko Kawabata, Toru Shibata, Yoshito Matsui and Natsuo Yasui : Use of intercostal nerves for neurotization of the musculocutaneous nerve in infants with birth-related brachial plexus palsy, Journal of Neurosurgery, Vol.94, No.3, 386-391, 2001.
(Summary)
The use of intercostal nerves (ICNs) for the neurotization of the musculocutaneous nerve (MCN) in adult patients with traumatic brachial plexus palsy has been well described. However, its use for brachial plexus palsy in infants has rarely been reported. The authors surgically created 31 ICN-MCN communications for birth-related brachial plexus palsy and present the surgical results. Thirty-one neurotizations of the MCN, performed using ICNs, were conducted in 30 patients with birth-related brachial plexus palsy. In most cases other procedures were combined to reconstruct all upper-extremity function. The mean patient age at surgery was 5.8 months and the mean follow-up period was 5.2 years. Intercostal nerves were transected 1 cm distal to the mammary line and their stumps were transferred to the axilla, where they were coapted directly to the MCN. Two ICNs were used in 26 cases and three ICNs in five cases. The power of the biceps muscle of the arm was rated Grade M4 in 26 (84%) of 31 patients. In the 12 patients who underwent surgery when they were younger than 5 months of age, all exhibited a grade of M4 (100%) in their biceps muscle power. These results are better than those previously reported in adults. Neurotization of the MCN by surgically connecting ICNs is a safe, reliable, and effective procedure for reconstruction of the brachial plexus in patients suffering from birth-related palsy.
Yu-Wen Zhang, Natsuo Yasui, Kosei Ito, Gang Huang, Makiko Fujii, Jun-ichi Hanai, Hiroshi Nogami, Takahiro Ochi, Kohei Miyazono and Yoshiaki Ito : A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia., Proceedings of the National Academy of Sciences of the United States of America, Vol.97, No.19, 10549-10554, 2000.
(Summary)
Cleidocranial dysplasia (CCD), an autosomal-dominant human bone disease, is thought to be caused by heterozygous mutations in runt-related gene 2 (RUNX2)/polyomavirus enhancer binding protein 2alphaA (PEBP2alphaA)/core-binding factor A1 (CBFA1). To understand the mechanism underlying the pathogenesis of CCD, we studied a novel mutant of RUNX2, CCDalphaA376, originally identified in a CCD patient. The nonsense mutation, which resulted in a truncated RUNX2 protein, severely impaired RUNX2 transactivation activity. We show that signal transducers of transforming growth factor beta superfamily receptors, Smads, interact with RUNX2 in vivo and in vitro and enhance the transactivation ability of this factor. The truncated RUNX2 protein failed to interact with and respond to Smads and was unable to induce the osteoblast-like phenotype in C2C12 myoblasts on stimulation by bone morphogenetic protein. Therefore, the pathogenesis of CCD may be related to the impaired Smad signaling of transforming growth factor beta/bone morphogenetic protein pathways that target the activity of RUNX2 during bone formation.
Natsuo Yasui, Takanobu Nakase, Wataru Sahara, Takahiro Ochi, Eiichiro Okumura and Motohiko Sato : Congenital transverse deficiency of the tibia and fibula, Skeletal Radiology, Vol.29, No.4, 243-246, 2000.
(Summary)
We report two similar, but unrelated, patients with congenital bilateral partial deficiencies of the tibia and fibula associated with intact feet. In both patients, the tibia and fibula were absent on initial radiographs, while the femur and the tarsal bones were well developed and there was bilateral teratologic dislocation of the hips. Ultrasound and magnetic resonance imaging (MRI) studies suggested the presence of cartilaginous remnants of the tibia and fibula. There were multidirectional instabilities in the knees and ankles. The clinical and radiological features of these cases are distinct from those of congenital longitudinal deficiency of the tibia, in which the fibula is always preserved, and from longitudinal deficiency of the fibula, in which the tibia is present and the foot is usually involved. We suggest that the bilateral partial deficiencies of the tibia and fibula associated with the intact foot and teratologic dislocation of the hips is a single-entity disorder, possibly categorized as an intercalary transverse deficiency of the lower limb.
(Keyword)
Abnormalities, Multiple / female / Fibula / Hip Dislocation, Congenital / Humans / infant / magnetic resonance imaging / male / Tibia
Yu-Wen Zhang, Natsuo Yasui, Naoki Kakazu, Tatsuo Abe, Kenzo Takada, Shosuke Imai, Motohiko Sato, Shintaro Nomura, Takahiro Ochi, Shigeharu Okuzumi, Hiroshi Nogami, Hirhofumi Ohashi and Yoshiaki Ito : PEBP2aA/CBFA1 mutations in Japanese cleidocranial dysplasia patients., Gene, Vol.244, No.1-2, 21-28, 2000.
(Summary)
Cleidocranial dysplasia (CCD) is an autosomal dominant human bone disease whose genetic locus has been located on chromosome 6p21, where the PEBP2alphaA/CBFA1 gene essential for osteogenesis also maps. Previously, several heterozygous mutations in PEBP2alphaA/CBFA1 were found in CCD patients. In this study, we identified six different types of mutations in PEBP2alphaA/CBFA1 in Japanese CCD patients. Four cases were similar to those reported previously: two were nonsense mutations in the Runt domain, one was a hemizygous deletion, and the other was a missense mutation in the Runt domain which abolished the DNA-binding activity of Runx2/PEBP2alphaA/CBFA1. The remaining two mutations were novel: one had a heterozygous gt-to-tt mutation at the splice donor site (gt) between the exon3-intron junction, which resulted in abnormal exon3 skipping, and the other had a mutation in exon7, which led to the introduction of a translational stop codon in the middle of the transactivation domain. Thus, defects in either the DNA-binding domain or transactivation domain of Runx2/PEBP2alphaA/CBFA1 can cause CCD. The results not only provide a strong genetic evidence that mutations involving in PEBP2alphaA/CBFA1 contribute to CCD, but also provide a useful tool to study how Runx2/PEBP2alphaA/CBFA1 plays its pivotal role during osteoblastic differentiation.
(Keyword)
Amino Acid Substitution / Base Sequence / Binding Sites / Chromosomes, Human, Pair 6 / Cleidocranial Dysplasia / Core Binding Factor Alpha 1 Subunit / DNA / DNA Mutational Analysis / DNA-Binding Proteins / Family Health / female / Heterozygote / Humans / In Situ Hybridization, Fluorescence / Japan / male / Mutation / Mutation, Missense / Pedigree / Protein Binding / Sequence Deletion / Transcription Factor AP-2 / Transcription Factors
Yoshi Fujita, Ken Nakata, Natsuo Yasui, Yoshito Matsui, Eiichiro Kataoka, Kazuo Hiroshima, Ryoichi Shibata and Takahiro Ochi : Novel mutations of the cathepsin K gene in patients with pycnodysostosis and their characterization., The Journal of Clinical Endocrinology and Metabolism, Vol.85, No.1, 425-431, 2000.
(Summary)
Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acroosteolysis, bone fragility, and skull deformities. Recently, mutations in the gene encoding cathepsin K (CK), a lysosomal cysteine protease localized exclusively in osteoclasts, were found to be responsible for this disease. We analyzed genomic DNA from four unrelated Japanese patients with this disorder and identified three different mutations of their CK genes: a previously reported missense mutation (A277 V), a novel single base deletion mutation (531 del T) causing a frame shift from codon 142 that results in a premature termination codon, and a novel missense mutation (L9P) in the signal peptide region. To investigate whether the L9P mutation disrupts signal peptide function and decreases protein synthesis, mutant and wild-type CK complementary DNAs driven by the cytomegalovirus promoter were transfected into COS-7 cells, and their gene products were detected by immunohistochemistry and Western blotting. Expression of the mutant protein was markedly reduced, suggesting decreased mature CK production in this patient, which may have been due to dysfunction of the signal peptide. These results provide evidence that a structural change in the signal peptide of the CK protein was involved in the pathogenesis of pycnodysostosis.
(Keyword)
Adult / Amino Acid Substitution / Animals / Blotting, Western / Bone and Bones / COS Cells / Cathepsin K / Cathepsins / DNA / Epitopes / female / Humans / immunohistochemistry / male / Middle Aged / Mutation / Osteosclerosis / Pedigree / Protein Sorting Signals / RNA, Messenger / Reverse Transcriptase Polymerase Chain Reaction
Natsuo Yasui, Hidehiko Kawabata, Takanobu Nakase, Toru Shibata, H Ohno and Takahiro Ochi : Oberarm verlangerungen und Deformitatenkorrektur (Humeral lngthening and deformity correction), Orthopade, Vol.29, No.1, 58-62, 2000.
194.
Motohiko Sato, Takahiro Ochi, Takanobu Nakase, Seiichi Hirota, Yukihiko Kitamura, Shintaro Nomura and Natsuo Yasui : Mechanical tension-stress induces gene expression of BMP-2 and -4, but not of BMP-6, -7 and GDF-5, during bone lengthening by distraction osteogenesis, Journal of Bone and Mineral Research, Vol.14, No.7, 1084-1095, 1999.
Mitsuhiko Takahashi, Yoshiteru Kawasaki, 高砂 智哉, Toshihiko Nishisho and Natsuo Yasui : Treatment Strategy for Congenital Pseudarthrosis of the Tibia, The Journal of the Japanese Orthopaedic Association, Vol.87, No.1, 32-37, 2013.
(Keyword)
congenital pseudarthrosis of the tibia / Ilizarov / neurofibromatosis type I (NF1)
Mitsuhiko Takahashi, Natsuo Yasui, Koichi Sairyo, Shinsuke Katoh, 三代 卓哉 and 三橋 雅 : 軟骨無形成症に対する四肢骨延長術の合併症, The Central Japan Journal of Orthopaedic Surgery & Traumatology, Vol.58, No.4, 759-760, Jul. 2015.
山田 千晴, Katsuya Hirasaka, Natsuo Yasui and Takeshi Nikawa : Ubiquitin Ligase Cbl-B Mediates the Atrophy of Bone and Skeletal Muscle during Unloading(Elucidation of Mechanisum of Muscular Atrophy and Rehabilitation,43rd Annual Meeting of the Japanese Association of Rehabilitation Medicine), The Japanese Journal of Rehabilitation Medicine, Vol.44, No.3, 163-170, Mar. 2007.
Kousaku Higashino, Shinsuke Katoh, Toshinori Sakai, Hiroshi Kosaka and Natsuo Yasui : Preservation of C7 spinous process does not influence on the long-term neurologic outcome after laminoplasty for cervical spodylotic myelopathy, Journal of Musculaskeletal System, Vol.18, No.4, 325-330, Apr. 2005.
Shinjiro Takata, Akira Shibata, Hiroshi Yonezu, Toshihide Yamada, Mitsuhiko Takahashi, Aziz Abbaspour and Natsuo Yasui : Biophysic evaluation of bone quality, --- application of Fourier transfrom infrared spectroscopy and phosphorus-31 solid-state nuclear magnetic resonance spectroscopy ---, The Journal of Medical Investigation : JMI, Vol.51, No.3,4, 133-138, Aug. 2004.
(Summary)
In this review, we focus on findings obtained with biophysic techniques, Fourier transformed infrared (FTIR) spectroscopy and phosphorus-31 solid-state nuclear magnetic resonance (31P solid-state NMR) spectroscopy, which may allow us to evaluate bone quality and to predict bone strength. FTIR measures the absorption energy that produces an increase in the vibrational or rotational energy of atoms or groups of atoms within the molecule. FTIR spectroscopy allows us to examine the relative amount of minerals and matrix content and the arrangement of apatite and organic matrix. FTIR spectroscopy should become an important tool, because the relative amount of minerals and the arrangement of apatite and organic matrix could be a measure for evaluating bone quality. 31P solid-state NMR spectroscopy is useful for evaluating the quality of bone and predicting bone strength by calculating the spine-lattice relaxation time (T1) of bone. 31P solid-state NMR imaging can be used to measure quantitatively the mass of hydroxyapatite. The T1 relaxation time of both bone and deficient hydroxyapatite was much longer than that of pure hydroxyapatite. T1 relaxation time is one of the promising indices of bone quality.
Shinjiro Takata and Natsuo Yasui : Disuse Osteoporosis, The Journal of Medical Investigation : JMI, Vol.48, No.3,4, 147-156, Aug. 2001.
(Summary)
Reduction of mechanical stress on bone inhibits osteoblast-mediated bone formation and accelerates osteoclast-mediated bone resorption, and leads to what has been called disuse osteoporosis. Prolonged therapeutic bed rest, immobilization due to motor paralysis from injury of the central nervous system or peripheral nerves, application of cast to treat fractures, a common causes of disuse osteoporosis. Imaging diagnosis shows coarse trabecular pattern and thinning of cortical bones. Bone metabolism markers have been used to evaluate bone metabolism. From the viewpoint of bone metabolism, antiresorptive agents should be administered to inhibit bone resorption. Rehabilitation, including bed positioning, therapeutic exercise and electrical stimulation, should be prescribed to subject the atrophied bone to an appropriate level of mechanical stress. In spite of these aggressive and continuous treatments, most cases of disuse osteoporosis require a long time for bone to recover its bone mineral density and strength. Hence, we have to keep in mind that there are no treatments better than prophylaxis of disuse osteoporosis.
(Keyword)
Disuse / osteoporosis / bone metabolism / treatment / prophylaxis
Yuichiro Goda, Nori Sato, Takako Taniguchi, Yoichiro Takata, Hirofumi Kosaka, Toshinori Sakai, Kousaku Higashino, Koichi Sairyo, Shinsuke Katoh, Hisaaki Taniguchi and Natsuo Yasui : Proteomic analysis of ligamentum flavum, 52nd International Spinal Cord Society (ISCoS), Oct. 2013.
2.
Yuichiro Goda, Nori Sato, Takako Taniguchi, Yoichiro Takata, Hirofumi Kosaka, Toshinori Sakai, Kousaku Higashino, Koichi Sairyo, Shinsuke Katoh, Hisaaki Taniguchi and Natsuo Yasui : Proteomic analysis of ligamentum flavum from lumbar spinal canal stenosis, International Society for Study of the Lumbar Spine (ISSLS) 2013, May 2013.
3.
Yuichiro Goda, Nori Sato, Takako Taniguchi, Yoichiro Takata, Hirofumi Kosaka, Toshinori Sakai, Kousaku Higashino, Koichi Sairyo, Shinsuke Katoh, Hisaaki Taniguchi and Natsuo Yasui : Proteomic Analysis of Ligamentum Flavum from Lumbar Spinal Canal Stenosis., 2013 Annual meeting of the Orthopaedic Research Society, January 26-29, 2013 (Poster Presentation ), San Antonio, TX, Jan. 2013.
4.
Natsuo Yasui : Bone lengthening without osteotomy, ASAMI and BR 7th International Congress, Thessaloniki Greece, Jun. 2012.
5.
Yuichiro Goda, Tadanori Sakamaki, Toshinori Sakai, Natsuo Yasui and Koichi Sairyo : Analysis of adolescent patients with MRI signal changes in the adjacent pedicle in fresh lumbar spondylolysis., The 35nd Annual meeting of ISSLS, SPINEWEEK 2012,May 28- June 1,2012 (E-poster), Geneva, May 2012.
6.
Ryo Miyagi, Koichi Sairyo, Toshinori Sakai, Natsuo Yasui and Akira Dezawa : Symptomatic laminolysis in adolescent athletes., The 35nd Annual meeting of ISSLS, SPINEWEEK 2012,May 28- June 1,2012 (E-poster), Geneva, May 2012.
7.
Toshinori Sakai, Shoichiro Takao, Koichi Sairyo, Hiromu Nishitani and Natsuo Yasui : Gender differences of radiographic findings in patients with lumbar spondylolysis., The 35nd Annual meeting of ISSLS, SPINEWEEK 2012,May 28- June 1,2012 (Special E-poster), Geneva, May 2012.
8.
Masatoshi Morimoto, Kousaku Higashino, Hiroaki Manabe, Hirofumi Kosaka, Shinsuke Katoh, WC Hutton and Natsuo Yasui : The association between age and the orientation of the lumbar facet joints, disc height and degenerative spondylolisthesis (DS) in patients without low back pain, Spine Week 2012, Amsterdam,Netherlands, May 2012.
9.
Natsuo Yasui : Bone lengthening without osteotomy, Agenda of the 1st Beijing International Congress on External Fixation and Bone Reconstruction, Beijing, Apr. 2012.
10.
Natsuo Yasui : History of bone lengthening technique in Japan, Agenda of the 1st Beijing International Congress on External Fixation and Bone Reconstruction, Beijing, Apr. 2012.
11.
Hirofumi Kosaka, Kousaku Higashino, Shinsuke Katoh and Natsuo Yasui : Anatomical analysis of cervical posterior fusion (Roy-Camille lateral mass screw) with enhanced cervical CT scan., 58th Annual Meeting of the Orthopaedic Research Society, San Francisco, Feb. 2012.
12.
Nori Sato, Takako Taniguchi, Yuichiro Goda, Hirofumi Kosaka, Kousaku Higashino, Toshinori Sakai, Koichi Sairyo, Shinsuke Katoh, Hisaaki Taniguchi and Natsuo Yasui : Quantitative proteomic analysis of human tendon and ligament, 2012 Annual Meeting of the Orthopaedic Research Society, Feb. 2012.
13.
T Hirano, Kousaku Higashino, S Toki, Hirofumi Kosaka and Natsuo Yasui : Epidemiologic analysis of the ossification of the posterior longitudinal ligament in cervical spine using reconstructive computed tomography: a study of female non-symptomatic patients, The 39th Annual meeting of CSRS, Scottsdale, Arizona, USA, Dec. 2011.
14.
Shoichiro Takao, Koichi Sairyo, Tadashi Kondo, Junji Ueno, Natsuo Yasui and Hiromu Nishitani : Lumbar spondylolysis: clinical significance of gender difference, International Skeletal Society 2011 Annual Meeting, San Diego, Sep. 2011.
15.
Miyagi Ryo, Koichi Sairyo, Toshinori Sakai, Bhatia N. Nitin, Yoshioka Hiroshi, Natsuo Yasui and Dezawa Akira : Symtopmatic Laminolysis in Adolescents Sports Players., The International Skeletal Society, San Diego, California, Sep. 2011.
16.
Shoichiro Takao, Toshinori Sakai, Koichi Sairyo, Junji Ueno, Natsuo Yasui and Hiromu Nishitani : Lumbar spondylolysis: clinical significance of gender difference., The International Skeletal Society, San Diego, California, Sep. 2011.
17.
Toshihiko Nishisho, N Hanaoka, Kenji Endo, Mitsuhiko Takahashi and Natsuo Yasui : Locally administered zoledronic acid therapy for giant cell tumor of bone, ASBMR 33rd Annual Meeting, San Diego, Sep. 2011.
18.
Hiroshi Egawa, Tomohiro Goto, Daisuke Hamada and Natsuo Yasui : Accuracy of the three dimensional planning for the uncemented tapered wedge femoral stem., The 24th International Society for Technology in Arthroplasty, Brugge, Belgium, Sep. 2011.
19.
Mitsuhiko Takahashi, Tetsuya Enishi, Shinjiro Takata, Toshihiko Nishisho, T Takao and Natsuo Yasui : Fate of the chondrocyte-like cells in chondroid bone during distraction osteogenesis in the rabbits., ASBMR 33rd Annual Meeting, San Diego, Sep. 2011.
20.
Shinjiro Takata, Tetsuya Enishi, N Sato, Mitsuhiko Takahashi and Natsuo Yasui : Mechanisms of longitudinal overgrowth following circumferential periosteal division of rat femur., ASMBR 33rd Annual Meeting, San Diego, Sep. 2011.
21.
Enishi Tetsuya, Shinsuke Katoh, Sogo Toshiharu and Natsuo Yasui : Significant fracture-dislocation of the thoracic or lumbar spine without neurologic deficit: a report of two cases, --- 50th Annual Meeting of International Spinal Cord Society ---, Topics in Spinal Cord Injury Rehabilitation, Vol.16, No.suppl 1, 76, Washington, D.C., Jun. 2011.
22.
Hirofumi Kosaka, Shinsuke Katoh, Kousaku Higashino, Satoh Nori, Goda Yuji and Natsuo Yasui : Anatomical analysis of cervical posterior fusion (Roy-Camille lateral mass screw with enhanced cervical CT scan, --- 50th Annual Meeting of International Spinal Cord Society ---, Topics in Spinal Cord Injury Rehabilitation, Vol.16, No.suppl 1, 55-56, Washington, D.C., Jun. 2011.
23.
Mitsuhiko Takahashi and Natsuo Yasui : Impaired Architectural Adaptations in Plantarflexor Muscles to Accelerated Limb Lengthening, 2011Annual Meeting of the Orthopaedic Research Society(2011.1.13-16), Long Beach, California, Jan. 2011.
24.
Nori Sato, T Taniguchi, Yuichiro Goda, Hirofumi Kosaka, Kousaku Higashino, Toshinori Sakai, Koichi Sairyo, Shinsuke Katoh, H Taniguchi and Natsuo Yasui : Establishment of a Method for Proteomic Analysis of Human Achilles Tendon, 2011Annual Meeting of the Orthopaedic Research Society(2011.1.13-16), Long Beach Conbention Center (Long Beach,California), Jan. 2011.
25.
Tetsuya Enishi, Mitsuhiko Takahashi, Shinjiro Takata and Natsuo Yasui : Fate of the chondrocyte-like cells in chondroid bone during distraction osteogenesis in the rabbits, 2011Annual Meeting of the Orthopaedic Research Society(2011.1.13-16), Long Beach Conbention Center (Long Beach,California), Jan. 2011.
26.
Nori Sato, Takako Taniguchi, Yuichiro Goda, Hirofumi Kosaka, Kosaku Higashino, Toshinori Sakai, Koichi Sairyo, Shinsuke Katoh, Hisaaki Taniguchi and Natsuo Yasui : Establishment of a Method for Proteomic Analysis of Human Achilles Tendon., 2011 Annual meeting of the Orthopaedic Research Society, Long Beach, California, Long Beach, California, Jan. 2011.
27.
Nori Sato, Taniguchi Takako, Goda Yuichiro, Kosaka Hirofumi, Higashino Kosaku, Toshinori Sakai, Koichi Sairyo, Shinsuke Katoh, Hisaaki Taniguchi and Natsuo Yasui : Development of a Method for Proteomic Analysis of Human Yellow Ligament., 2011 Annual meeting of the Orthopaedic Research Society, Long Beach, California, Long Beach, California, Jan. 2011.
28.
Natsuo Yasui, Mitsuhiko Takahashi and Yoshiteru Kawasaki : A special drill guide for percutaneous multidriling osteotomy for limb lengthening, 6th Meeting of the A.S.A.M.I International & 3rd World Congress on External Fixation(Hesperia Tower Hotel & Convention Center Gran Via), Barcelona, Oct. 2010.
29.
Mitsuhiko Takahashi, Yoshiteru Kawasaki and Natsuo Yasui : Strategy and outcome of limb reconstruction for fibular hemimelia type, 6th Meeting of the A.S.A.M.I International & 3rd World Congress on External Fixation, Barcelona, Oct. 2010.
30.
Natsuo Yasui, Mitsuhiko Takahashi, Kiminori Yukata, Aziz Abbaspour, Shinjiro Takata and Koichi Sairyo : Enhanced bone healing by local infusion of FGF-2 and bisphosphonate during distraction osteogenesis, 6th Meeting of the A.S.A.M.I International & 3rd World Congress on External Fixation(Hesperia Tower Hotel & Convention Center Gran Via (Barcelona)), Oct. 2010.
31.
Natsuo Yasui : Orthofix-MBA Symposium Biological techniques for accelerating consolidation of regenerate, 6th Meeting of the A.S.A.M.I International & 3rd World Congress on External Fixation(Hesperia Tower Hotel & Convention Center Gran Via), Barcelona, Oct. 2010.
32.
Shinjiro Takata, Enishi Tetsuya, Mitsuhiko Takahashi, Nishisho Toshihiko and Natsuo Yasui : Circumferential periosteal stripping of femoral diaphysis of developing rat produces longitudinal overgrowth and cortical hypertrophy, ASBMR 32nd Annual Meeting, Oct. 2010.
33.
Daisuke Hamada, Tomohiro Goto, Hiroshi Egawa and Natsuo Yasui : Navigation-assisted total knee arthroplasty in patient with extra-articular valgus deformity of the femur., The 23rd International Society for Technology in Arthroplasty (October 6-9, 2010), Dubai, UAE, Oct. 2010.
34.
Hiroshi Egawa, Daisuke Hamada, Yoshiteru Kawasaki and Natsuo Yasui : Accuracy of CT based navigation system for acetabular component placement in cementless total hip arthroplasty., The 23rd International Society for Technology in Arthroplasty (October 6-9, 2010), Dubai, UAE, Oct. 2010.
35.
Yoshiteru Kawasaki, Daisuke Hamada, Hiroshi Egawa and Natsuo Yasui : Visualization of the pelvic vascular structures through the pelvis using 3D-CT angiography., The 77th Annual Meeting of the American Academy of Orthopaedic Surgeons (March 10-13), New Orleans, USA,, Mar. 2010.
36.
Takashi Iwase, Hirotsugu Kurobe, Masashi Akaike, Shunji Nakano, Sumiko Yoshida, Sumitomo Yuka, Shusuke Yagi, Ken-ichi Aihara, Shuji Ozaki, Masahiro Abe, Natsuo Yasui, Toshio Matsumoto, Tetsuya Kitagawa and Masataka Sata : Erythropoietin administration with autologous blood donation - a novel strategy to enhance mobilization of circulating progenitor cells, American Heart Association Sessions 2008, New Orleans, Nov. 2008.
37.
Takashi Iwase, Masashi Akaike, Shunji Nakano, Takayuki Ise, Sumiko Yoshida, Sumitomo Yuka, Shusuke Yagi, Ken-ichi Aihara, Natsuo Yasui and Toshio Matsumoto : Single erythropoietin administration with autologous blood donation - a novel strategy to enhance mobilization of endothelial progenitor cells, 22nd Scientific Meeting of the International Society of Hypertension 2008, Berlin, Germany, Berlin, Jun. 2008.
Tetsuya Matsuura, Naoto Suzue, 西尾 進, 岩目 敏幸 and Natsuo Yasui : 上腕骨小頭骨軟骨障害の病態解明における超音波検査の役割, The Journal of the Japanese Orthopaedic Association, Vol.87, No.8, 1294, Aug. 2013.
9.
Tetsuya Matsuura, Naoto Suzue, 西尾 進, 岩目 敏幸 and Natsuo Yasui : 上腕骨小頭骨軟骨障害の病態解明における超音波検査の役割, The Journal of the Japanese Orthopaedic Association, Vol.87, No.8, 1294, Aug. 2013.
Natsuo Yasui : 私の出会った小児整形外科の巨星たち, 第118回 和歌山臨床整形外科医会研修会, Mar. 2013.
16.
Tetsuya Matsuura, Naoto Suzue, 岩目 敏幸, Shinji Kashiwaguchi, 岩瀬 毅信, Kokichi Arisawa and Natsuo Yasui : 野球障害予防ガイドラインの検証, The Journal of the Japanese Orthopaedic Association, Vol.87, No.3, 952, Mar. 2013.
17.
Tetsuya Matsuura, Naoto Suzue, 岩目 敏幸, Shinji Kashiwaguchi, 岩瀬 毅信, Kokichi Arisawa and Natsuo Yasui : 野球障害予防ガイドラインの検証, The Journal of the Japanese Orthopaedic Association, Vol.87, No.3, 952, Mar. 2013.
18.
Tetsuya Matsuura, Naoto Suzue, 岩目 敏幸, 西尾 進, Shinji Kashiwaguchi, 岩瀬 毅信 and Natsuo Yasui : 少年野球選手の超音波による上腕骨小頭の経年的変化, The Journal of the Japanese Orthopaedic Association, Vol.87, No.3, 951, Mar. 2013.
19.
Tetsuya Matsuura, Naoto Suzue, 岩目 敏幸, 西尾 進, Shinji Kashiwaguchi, 岩瀬 毅信 and Natsuo Yasui : 少年野球選手の超音波による上腕骨小頭の経年的変化, The Journal of the Japanese Orthopaedic Association, Vol.87, No.3, 951, Mar. 2013.
Tetsuya Matsuura, Naoto Suzue, 岩目 敏幸, Shinji Kashiwaguchi and Natsuo Yasui : 上腕骨小頭骨軟骨障害の早期発見に対する超音波を用いた少年野球検診の意義, The Journal of the Japanese Orthopaedic Association, Vol.87, No.2, 183, Feb. 2013.
Yuka Ueda, Takayuki Ise, Takashi Iwase, K Maeda, K Nishikawa, M Kadota, T Hara, Y Kawabata, R Ota, Toshiyuki Niki, Koji Yamaguchi, Shusuke Yagi, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Shinsuke Katoh, Natsuo Yasui and Masataka Sata : 心臓リハビリテーションにおける禁煙継続効果の検討, 第101回日本循環器学会四国地方会, Dec. 2012.
Tetsuya Matsuura, Naoto Suzue, T Iwame, Shinji Kashiwaguchi, T Iwase and Natsuo Yasui : Prospective study of elbow pain and verification of guideline in schoolchild baseball players, 第61回東日本整形災害外科学会(H24.9.21-22), Sep. 2012.
Yuka Ueda, Takashi Iwase, Takayuki Ise, K Maeda, K Nishikawa, Mika Bando, K Ogasawara, S Bando, Toshiyuki Niki, J Hotchi, Koji Yamaguchi, N Tomita, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Shinsuke Katoh, Natsuo Yasui and Masataka Sata : 喫煙継続者における心臓リハビリテーションの効果の検討, 第18回心臓リハビリテーション学会, Jul. 2012.
42.
K Maeda, Yuka Ueda, Takayuki Ise, Takashi Iwase, K Nishikawa, Mika Bando, K Ogasawara, S Bando, Toshiyuki Niki, J Hotchi, Koji Yamaguchi, N Tomita, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Shinsuke Katoh, Natsuo Yasui and Masataka Sata : 患者の気持ちを汲んだ患者教育の実際, 第18回心臓リハビリテーション学会, Jul. 2012.
43.
A Takashima, Takayuki Ise, Yuka Ueda, K Maeda, K Nishikawa, K Ogasawara, Mika Bando, N Tomita, Toshiyuki Niki, J Hotchi, Koji Yamaguchi, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Shinsuke Katoh, Masashi Akaike, Natsuo Yasui and Masataka Sata : 心臓リハビリテーションは酸化LDLを低下させる, 第18回心臓リハビリテーション学会, Jul. 2012.
44.
K Maeda, Yuka Ueda, Takayuki Ise, Takashi Iwase, K Nishikawa, Mika Bando, K Ogasawara, S Bando, Toshiyuki Niki, J Hotchi, Koji Yamaguchi, N Tomita, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Shinsuke Katoh, Natsuo Yasui and Masataka Sata : チーム医療で取り組む重症心不全に対する心臓リハビリテーション, 第100回日本循環器学会中国・四国合同地方会, Jun. 2012.
45.
Natsuo Yasui : 経皮的骨切りと経皮的腱切り, 第55回広島大学整形外科学教室開講記念会教育研修会, May 2012.
46.
Natsuo Yasui : 特別講演3「小児整形外科の未来」, 第85回日本整形外科学会学術総会, May 2012.
47.
Shinsuke Katoh, Kousaku Higashino, Toshinori Sakai, Hirofumi Kosaka, Yoichiro Takata and Natsuo Yasui : 脊椎脊髄疾患による痛みとしびれの病態, 第85回日本整形外科学会学術総会, May 2012.
48.
Tetsuya Matsuura, Naoto Suzue, 岩目 敏幸, Shinji Kashiwaguchi, 岩瀬 毅信 and Natsuo Yasui : 上腕骨小頭骨軟骨障害の早期発見に対する少年野球検診の意義, 第85回日本整形外科学会学術総会(H24.5.17-20), May 2012.
Tetsuya Matsuura, Naoto Suzue, 柏口 新二, 岩瀬 毅信 and Natsuo Yasui : 少年野球肘検診の現状, Japanese Journal of Clinical Sports Medicine, Vol.19, No.4, 91, Nov. 2011.
61.
Tetsuya Matsuura, Naoto Suzue and Natsuo Yasui : 肘離断性骨軟骨炎でみられる小頭の扁平化は骨端核の成長障害である, The Journal of the Japanese Orthopaedic Association, Vol.85, No.8, 1343, Oct. 2011.
Hiroshi Egawa, Daisuke Hamada, Yoshiteru Kawasaki and Natsuo Yasui : ナビゲーション使用(CT based navigation system)THAにおけるカップ設置の精度検証, 第37回日本股関節学会, Oct. 2010.
100.
Shinsuke Katoh, Kousaku Higashino, Hirofumi Kosaka, Hiroaki Manabe and Natsuo Yasui : Anterior decompression of the thoracic spinal cord via postero-lateral approach. a report of 4 cases., 49th Annual Meeting of International Spinal Cord Society, Oct. 2010.
Natsuo Yasui, Koichi Sairyo, Takeshi Nikawa and Kyoichi Kishi : Osteoactivin : A novel glycoprotein inhibiting adhesion of osteoblastic cells to bone matrix, ラット宇宙実験サンプルシェア研究, 2002.
Clarification of the pathophysiological significance of mast cell tryptase and protease activated receptor-2 (PAR-2) in articular destruction (Project/Area Number: 15591581 )
Pathomechanism of the verbetral slippage of the juvenile spine with spondylolysis (Project/Area Number: 15591580 )
Molecular mechanism of unloading-mediated insulin resistance (Project/Area Number: 15500449 )
Effect of tension-stress on gene expression of one and cartilage cells. Molecular mechanism of distraction osteogenesis (Project/Area Number: 12671413 )
Molecular mechanism of distraction osteogenesis : Effect of tension-stress on bone formation. (Project/Area Number: 10671360 )
We focused on the cartilage differentiation and regulation by tissue-specific transcription factors during the period of this Grant-in-Aid for Scientific Research (Project/Area Number: 09671491 )
Abnormality of Cartilage development by gene defectsin cartilage collagens (Project/Area Number: 06454428 )