Masafumi Machida

Murayama Medical Center, Edo, Tōkyō, Japan

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Publications (44)95.15 Total impact

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    ABSTRACT: Controversy still exists around surgical strategies for Lenke type 1C and 2C curves with primary thoracic and compensatory lumbar curves in adolescent idiopathic scoliosis (AIS). The benefit of selective thoracic fusion (STF) for these curve types is spontaneous lumbar curve correction while saving more mobile lumbar segments. However, a risk of postoperative coronal decompensation after STF has also been reported. This multicenter retrospective study was conducted to evaluate postoperative behavior of thoracolumbar/lumbar (TLL) curve and coronal balance after posterior thoracic fusion for Lenke 1C and 2C AIS.
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. 10/2014;
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    ABSTRACT: Abstract Purpose Post-traumatic spinal deformities are well-recognized sequelae of spinal cord injuries (SCIs). Despite the devastating complications for SCI patients with trunk imbalance, the incidence, clinical outcomes, and independent risk factors of scoliosis after SCI remain controversial. Te purpose of this study is to assess the incidence and risk factors of spinal deformity in a large sample of patients with SCIs. Materials and Methods. We assessed 214 consecutive adult compressive SCI patients who were hospitalized in our hospital. We compared patients who developed spinal deformities with those who did not. Univariate and multivariate analyses to determine the independent risk factors were performed. Age, gender, etiology, ASIA grade (American Spinal Injury Association) surgery, and other demographic data were analyzed to determine the risk factors for developing a spinal deformity. Results. The average patient age was 58.3 years (20-86 years). The etiology was trauma (n=158), ossification of ligament (n=22), infectious (n=17), and others. 152 patients had cervical spine involved, 62 had thoracic spine involved. 26 patients classified as ASIA A, 54 were ASIA B, 96 were ASIA C, and 42 were ASIA D 4. 135 patients had either decompression or decompression and fusion surgery. The incidence of spinal deformities was 21% (44/214). The mean Cobb angle was 28.9 degrees (13-38 degrees). ASIA grade and surgery predicted the occurrence of spinal deformity in both the univariate model (ASIA grade, OR: 1.59 [95% CI: 1.04-2.44; P=0.032]; Surgery, OR: 4.47 [95% CI: 1.89-10.06; P=0.0007]) and the multivariate model (ASIA grade, OR: 1.63 [95% CI: 1.04-2.57; P=0.033]; Surgery, OR: 4.59 [95% CI: 1.91-11.04; P=0.0006]), whereas surgery was the most important risk factor in the Cox model (HR: 3.50 [95% CI: 1.56-7.88; P=0.0025]). Conclusions. The SCI patients with high ASIA grades and those who had undergone surgery had a higher likelihood of developing a spinal deformity. Of these risk factors, surgery was the stronger risk factor.
    European Spine Journal 08/2014; · 2.47 Impact Factor
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    ABSTRACT: Background Context During quiet standing, the gravity line (GL) can be located according to the sum of the ground reaction forces (GRF) measured with a force platform. C7 plumb line (C7PL) is an easy method to estimate sagittal trunk balance, but discordance between C7PL and the GL is widely recognized. However, the prevalence of occiput-trunk (O-T) discordance (GL-C7PL > 3 cm) and the factors affecting this type of discordance have not yet been determined. Purpose The purpose of this study was to report the prevalence of O-T discordance in adult spinal deformity (ASD) patients and identify the factors affecting this type of discordance. Study Design This was a retrospective consecutive case series of ASD. Patient Sample This retrospective case series included 300 consecutive ASD patients. The inclusion criteria were age > 50 years, Cobb angle of the main curve > 20°, and C7PL > 5 cm. The exclusion criteria consisted of inappropriate radiography; syndromic, neuromuscular, or other pathological conditions; and previous joint replacement. Outcome Measures The outcome measures included self-reported measures (SRS22 and ODI) and radiographic measures. Methods Study funding sources and a study-specific appraisal of potential conflict of interest. No external funding was used for this study. No appraisal of potential conflict of interest. In a retrospective consecutive case series, demographic and radiographic patient data were reviewed. Demographic data included age, gender, curve type, SRS22, and ODI. Radiographic data included GL, C7PL, C2-C7, T2-T5, T5-T12, T10-L2, T2 tilt, LL, SS, PT, and PI. Global sagittal alignment and spinopelvic alignment were also reviewed. Patients were categorized in either a concordance group (C group; GL-C7PL < 3 cm) or discordance group (D group; GL-C7PL > +3 cm), and the demographic, radiographic, and clinical outcome data were compared between these groups. One-way ANOVA, correlation coefficient tests, multiple regression analysis, and logistic regression analysis were performed for statistical analysis. P < 0.01 was considered statistically significant. Force platform analysis was performed to assess the relationship among GRF, GL, and C7PL. Results Among 300 consecutive ASD patients, 72 (24%) patients were categorized in the D group. There was no significant difference in terms of demographic data between the C and D groups. The SRS and ODI of patients with GL > 10 cm were significantly lower than those of patients with GL < 10 cm. Comparisons of regional sagittal alignment showed significantly higher T5-T12 values in the D group, and MRL analysis revealed significant correlations among T2-T5, T5-T12, and GL-C7PL. In contrast, the analysis of global sagittal alignment revealed a significantly large T2 sagittal tilt in the D group compared to the C group. Force platform analysis showed concordance between GRF and GL, whereas discordance was observed between GRF and C7PL. The D group could be classified into 2 groups based on the global sagittal alignment: 10 patients were classified as the hypo-compensation type (small SVA, small CL, small TK, and normal-to-small LL), whereas 62 patients were classified as the forward-leaning type (large SVA, large CL, large TK, and small LL). Conclusion The prevalence of discordance between GL and C7PL in ASD patients was 24%, and thoracic kyphosis and global sagittal alignment were significantly correlated with this discordance. The concordance of GRF and GL and the discordance of GRF and C7PL highlight the importance and necessity of accounting for GL when considering surgical treatment.
    The Spine Journal 08/2014; · 3.36 Impact Factor
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    ABSTRACT: Study Design. A retrospective, multicenter study.Objective. To investigate the relationship between postoperative shoulder balance and adding-on in Lenke type2 adolescent idiopathic scoliosis (AIS).Summary of Background Data. Postoperative shoulder imbalance (PSI) and adding-on are the main postoperative complications occurring at the proximal to upper instrumental vertebra (UIV) and the distal to the lower instrumental vertebra(LIV), respectively. Inadequate selection of LIV in the selective thoracic fusion surgery may result in postoperative distal adding-on. It remains unclear whether postoperative shoulder balance is associated with postoperative adding-on.Methods. Preoperative, postoperative and 2-year follow-up radiographs of 142 consecutive patients with Lenke type2 curves who underwent posterior fusion surgery were analyzed. The patients were grouped into PSI positive and negative at follow-up. Radiographic and categorical factors between patients with and without PSI were compared. The relationship between the radiographic shoulder height (RSH) and the parameters of adding-on were analyzed.Results. PSI occurred in 23 patients (16.2%) and distal adding-on was recognized in 20 patients (13.3%) at final follow-up. The occurrence of adding-on was significantly lower in the shoulder imbalance group at follow-up (p<0.01). There was no shoulder imbalance occurring in the patients with distal adding-on at final follow-up(p<0.01). Correlation analysis showed that the RSH was positively correlated with the change in the angulation of the first disc below LIV (r = 0.228, p≤0.01) and negatively correlated with the deviation change of the LIV+1 at follow-up (r = -0.254, p≤0.01).Conclusion. The postoperative shoulder balance and postoperative distal adding-on were weakly but significantly associated with each other, and both shoulder imbalance and adding-on need to be prevented in Lenke type2 curves.
    Spine 04/2014; · 2.16 Impact Factor
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    ABSTRACT: Study Design. A retrospective case series of patients treated surgically for degenerative lumbar scoliosis (DLS).Objective. To determine incidence and risk factors of progressive global thoracic kyphosis (pGTK) after surgery for DLS.Summary of Background Data. Sagittal balance affects the surgical treatment of spinal deformity in adults. Little is known about the loss of sagittal balance due to pGTK, or about the risk factors for pGTK, after surgery for DLS.Methods. We reviewed records from a multi-center database of adults with DLS, treated with posterior spinal fusion. Inclusion required an age of 50 years or more at the time of surgery, an upper instrumented vertebrae (UIV) at T9 and below, more than 5 fused segments, and at least 2 years of follow-up. We included 73 patients with a mean age of 68.3 years (range 51-77 years) and a mean follow-up period of 3.6 years (range 2-11 years). Independent risk factors for pGTK were identified by logistic regression analysis.Results. Significant pGTK, defined as an increase in thoracic kyphosis of more than 10° from before surgery to the time of final follow-up, was observed in 41% of the patients. Loss of the sagittal vertical axis (SVA) was larger in patients with pGTK than without (4.7 vs. 1.5 cm; p = 0.02). Risk analysis showed larger lumbar lordosis correction in patients with pGTK. Multivariate logistic regression analysis identified an age greater than 75 (odds ratio [OR], 5.53; p = 0.02, 95% confidence interval [CI] [1.4-22.4]) and sacro-pelvic fusion (OR = 2.66, p = 0.02, 95% CI [1.5-11.1]) as independent risk factors for pGTK.Conclusion. The pGTK incidence after surgery for DLS was 41%. Age, sacro-pelvic fusion, and a larger sagittal correction were identified as pGTK risk factors. Long-term follow-up will provide more data on the clinical impact of pGTK in elderly patients.
    Spine 01/2014; · 2.16 Impact Factor
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    ABSTRACT: The use of intrasacral rods has been previously reported for posterior lumbosacral fixation. However, problems associated with this technique include poor stability of the rod in the sacrum, difficulty in contouring the rod to fit the lateral sacral mass, and the complicated assembly procedure for the rod and pedicle screws in the thoracolumbar segments after insertion of the rod into the sacrum.
    Scoliosis 01/2014; 9:8. · 1.31 Impact Factor
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    ABSTRACT: Study Design. A retrospective, observational multicenter study.Objective. To identify the ideal lower instrumented vertebra (LIV) to prevent distal adding-on after surgical correction of Lenke type 2A curve.Summary of Background Data. LIV level may affect the risk of post-surgical adding-on. The choice of the last touching vertebra (LTV)-the most caudal vertebra of the main thoracic curve that touches the central sacral vertical line when standing-as an appropriate LIV has been validated for Lenke type 1A but not type 2A curve.Methods. Radiographs taken before, immediately after, and 2 years after surgery were evaluated for 116 consecutive patients who underwent posterior thoracic fusion surgery for Lenke type 2A curve. The LIV was proximal to the LTV in 18 patients (PLTV), distal in 43 (DLTV), and at the LTV in 55 (ALTV). Significant independent factors associated with adding-on were analyzed first by univariate analysis, and then by stepwise logistic regression analysis.Results. Distal adding-on was present in 16 patients (13.8%) at follow-up: 9 PLTV (50.0%), 3 DLTV (7.0%), and 4 ALTV (7.3%) patients. Adding-on was significantly more common in the PLTV group. One PLTV-group patient required revision surgery to treat adding-on. Univariate analysis identified the following significant factors associated with adding-on: the T2-5 kyphosis angle and shoulder height before, immediately after, and 2 years after surgery; the lumbar Cobb angle at the 2-year follow-up; the 2-year postoperative lumbar curve correction rate; and the difference between the LIV and the end vertebra, neutral vertebra, and LTV levels. Significant independent risk factors identified by stepwise logistic regression analysis included the clavicle angle at follow-up, the correction rate of the lumbar curve immediately after surgery, and the difference between the LIV and LTV levels.Conclusion. A LIV at or distal to the LTV may prevent postoperative adding-on in Lenke type 2A curve.
    Spine 11/2013; · 2.16 Impact Factor
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    ABSTRACT: Study Design. Retrospective case series of surgically treated adolescent scoliosis patients. Objective. To assess the radiographic changes of cervical kyphosis and to identify the possible factors affecting post-op sagittal cervical kyphosis in a surgically treatment patients with adolescent idiopathic scoliosis. Summary of Background Data. Cervical kyphosis is a well recognized phenomenon in patient with adolescent idiopathic scoliosis. Despite recent reports, the prevalence, radiographic changes and the possible factors affecting post-op sagittal cervical kyphosis are still controversial. Materials and Methods. A retrospective review of a single center database was performed on 133 consecutive patients with adolescent idiopathic scoliosis treated with long instrumented (>5 levels) spine fusion. (minimum 2yrs. mean 3.3 years, range from 2 years to 5.5 years). 89 patients met all the inclusion criteria. The pre-op and post-op radiographic measurement and patient demographics were investigated. Results. Post-op cervical kyphosis was observed in 46 patients. Cobb angle decreased from 48.1+/-13.1 ° to 15.4+/-11.1 ° at the final follow-up. Cervical kyphosis significantly decreased from 5.5+/-8.9° pre-op to -1.5+/-8.9 degrees at the final follow-up. No difference was observed for T2-T5, T5-T12, LL, SS, PI, PT and SVA during the follow-up. Notably, T2 sagittal tilt was significantly increased from pre-op to the final follow-up. Pearson’s correlation coefficient test showed strong correlation between post-op cervical lordosis and T2 sagittal tilt (r=0.73, p<0.001). Conclusion. Despite the significant increase of cervical lordosis, 85% of patients still have a kyphotic or less lordotic spine. The strong positive association between cervical lordosis and T2 sagittal tilt suggests that the sagittal cervical alignment of adolescent idiopathic scoliosis patients is closely related to the global sagittal spine balance rather than thoracic kyphosis.
    Spine Deformity. 11/2013;
  • Mitsuru Yagi, Masakazu Takemitsu, Masafumi Machida
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    ABSTRACT: Study Design. Retrospective case series of surgically treated adolescent scoliosis patientsObjective. To assess the prevalence and independent risk factors of post-operation shoulder imbalance in surgically treated adolescent patients with idiopathic scoliosisSummary of Background Data. Despite recent reports that have identified risk factors for post-operation shoulder imbalance, the relative risks remain unclear.Methods. A retrospective review of 85 consecutive patients treated with thoracic fusion with a minimum 2-year follow-up (mean 3.1 years) was conducted to investigate the patient radiographic measurements and demographics. Shoulder height difference (SHD) was measured as the graded height difference of the soft tissue shadows. A SHD>2 cm indicated an unbalanced shoulder. Patient demographics and radiographic data were studied to determine risk factors for post-operation SHD. The potential risk factors included age, gender, Risser sign, Cobb angle, flexibility, apical vertebral rotation (AVR) of the main curve, UIV level, SHD, and clavicle chest cage angle difference (CCAD). Uni-variate and multi-variate logistic regression analyses were performed to determine the independent risk factors for post-operation shoulder imbalance.Results. Of the 85 patients, 21 patients presented post-operation shoulder imbalance. The uni-variate analysis indicated age, Risser sign, Cobb angle of the main curve, AVR of the main curve, and CCAD as risk factors, but the multi-variate logistic regression analysis showed that only AVR of the main curve and CCAD were independent risk factors for post-operation shoulder imbalance (AVR, p = 0.04, OR: 3.54; CCAD, p = 0.01, OR: 5.10).Conclusions. Post-operation shoulder imbalance was observed in 25% of the surgically treated adolescent patients. The CCAD and AVR of the main thoracic curve were independent risk factors for post-operation shoulder imbalance in surgically treated AIS patients. The significant correlation between CCAD and post-operation shoulder imbalance seen in the present study strongly suggests that the relationship of the shoulder girdle and chest cage has a role in maintaining shoulder balance.
    Spine 06/2013; · 2.16 Impact Factor
  • Mitsuru Yagi, Masakazu Takemitsu, Masafumi Machida
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    ABSTRACT: Study Design. Retrospective case series of surgically treated adolescent scoliosis patients.Objective. To establish a new radiographic measurement method to determine the best preoperative predictor of post-operation shoulder balance.Summary of Background Data. Shoulder balance is an important aspect of the overall cosmetic balance in patients with adolescent idiopathic scoliosis. Despite recent reports, it is still difficult to accurately estimate the post-operation shoulder balanceMaterials and Methods. A retrospective review of 89 consecutive patients who had thoracic fusion with a minimum 2-year follow-up (mean 3.1 years) was conducted to investigate the radiographic measurements and patient demographics. The shoulder height difference (SHD) was measured as the graded height difference of the soft tissue shadows. SHD>2 cm was considered an unbalanced shoulder. The clavicle chest cage angle difference (CCAD) was established and evaluated. The CCAD was graded as Grade A: no imbalance (<0 degrees), Grade B: mild imbalance (0-10 degrees), and grade C: significant imbalance (> 10 degrees).Results. Of 89 patients, 22 patients had a moderate or significant shoulder height difference at 2 yrs post-operation and were categorized as the unbalanced shoulder group (unbalanced SD). A significant difference was observed in pre-operation CCAD between the balanced and unbalanced SD groups (p = 0.01). The intra-class correlation coefficient for CCAD was 0.94 among the observers. CCAD was consistent from the pre-operation to the final post-operation follow-ups in both groups. The classification of the CCAD pre-operation indicated that 12/22 (54.4%) patients who were classified in the post-operation unbalanced SD group showed Grade 3 CCAD pre-operation, while only 9/67 (13.4%) patients who were classified in the post-operation balanced SD group had Grade 3 CCAD pre-operation.Conclusion. The developed method to predict postoperative shoulder balance was demonstrated to be easy to perform, reliable, and practical. Additionally, we classified the estimation of post-operation shoulder imbalance by pre-operation CCAD. The results of this comprehensive review will guide spinal surgeons in their pre-operative planning and in the surgical management of AIS to reduce post-operative shoulder imbalance.
    Spine 03/2013; · 2.16 Impact Factor
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    ABSTRACT: STUDY DESIGN.: Retrospective, observational study. OBJECTIVE.: To assess the efficacy and safety of tranexamic acid (TXA) in decreasing operative blood loss and the need for transfusion during posterior spinal fusion for the treatment of idiopathic scoliosis in adolescents. SUMMARY OF BACKGROUND DATA.: Blood loss associated with spinal surgery is a common potential cause of morbidity and often requires a blood transfusion, which subjects patients to the known risks of blood transfusion including transmission of diseases. Since the 1990s, intraoperative administration of antifibrinolytics has gained popularity. This study assesses the efficacy and safety of TXA in controlling blood loss during posterior spinal fusion for the treatment of idiopathic scoliosis in adolescents at 1 institution. METHODS.: A retrospective comparative analysis of 106 consecutive adolescents undergoing posterior spinal fusion procedures at 1 institution was performed. Patients were analyzed according to treatment group: controls (63) and TXA (43). There were no significant differences in demographic (age, sex, and comorbidities) or surgical traits (surgical time, number of fused vertebrae, preoperative hematocrit and hemoglobin) between the 2 groups. RESULTS.: TXA group had significantly less intraoperative blood loss (613 ± 195 mL) than the control group (1079 ± 421 mL; P < 0.001) as well as postoperative blood loss (155 ± 86 mL and 263 ± 105 mL, respectively; P < 0.001). TXA group received significantly less blood during the surgical procedure than the control group (258 ± 246 mL and 377 ± 200 mL, respectively; P < 0.001). There were no major intraoperative complications for any of the treatment groups. CONCLUSION.: TXA treatment group lost significantly less blood and received significantly fewer blood transfusions than the control group without significant differences in intra- and postoperative complications. A multicenter randomized prospective analysis would provide additional information of the efficacy and safety of TXA.
    Spine 07/2012; 37(21):E1336-42. · 2.16 Impact Factor
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    ABSTRACT: To clarify the mechanism of osteoporosis in adolescent idiopathic scoliosis (AIS), we investigated radiological and histological changes in the cervical vertebrae of a chicken thoracic scoliosis model. Forty newly hatched broiler chicks were randomly divided into four equal groups: sham-operated chickens serving as control (CON), pinealectomized chickens (PNX), sham-operated (CON + MLT) and pinealectomized chickens (PNX + MLT) that received intraperitoneal administration of melatonin. Pinealectomy was performed at the age of 3 days, and the chickens were killed at 2 months of age. Postmortem X-rays were examined for the presence of scoliosis, and micro-computed tomography (micro-CT) images were taken to evaluate the microstructure of the cervical vertebrae. Histological specimens of the scanned cervical vertebra were prepared, and a midsagittal section was stained with hematoxylin and eosin and tartrate-resistant acid phosphatase to evaluate the numbers of osteoblasts and osteoclasts, respectively. Scoliosis developed at the thoracic spine in all chickens of the PNX and in two of the PNX + MLT group. Micro-CT data revealed that chickens in the PNX group had a greater degree of generalized osteoporosis compared with the other birds. The number of osteoblasts was significantly decreased in the PNX group, while no significant difference was observed among chickens in the numbers of osteoclasts. Our results suggest that melatonin deficiency reduces osteoblast proliferation and leads to the development of scoliosis and osteoporosis. The restoration of melatonin prevented the development of scoliosis and osteoporosis, indicating that melatonin levels may be crucial to the development of deformity and osteoporosis in AIS.
    Journal of Pineal Research 04/2011; 51(4):387-93. · 7.30 Impact Factor
  • Masafumi Machida, Jean Dubousset, Thoru Yamada, Jun Kimura
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    ABSTRACT: The correlation of serum melatonin levels and curve progression in adolescent idiopathic scoliosis, and the effects of melatonin therapy in scoliotic patients with reduced levels of endogenous melatonin were studied in 40 adolescent patients with moderate to severe idiopathic scoliosis. Of the scoliotic subjects, 28 had stable scoliosis and 12 had progressive scoliosis. Normal melatonin levels were derived from 25 age-matched control patients. Serum melatonin levels were monitored yearly in scoloiotic patients for a period ranging from 3 to 6 yr, revealing a diurnal pattern with low values during the day and high at night. Scoliotic patients with normal levels were not treated or were treated with a brace, and all but two patients with low endogenous melatonin were treated with oral supplements of the indole. Of the 22 patients with a normal melatonin level, 16 had stable scoliosis and six had progressive scoliosis. Of the 16 patients treated for a low melatonin level, 12 had stable scoliosis and four had a progressive course. The two untreated cases had a progressive course. Of the 12 patients who had progressive scoliosis, nine had >35 degrees of curve at initial examination. These findings suggest that melatonin deficiency plays a role in the prognosis of idiopathic scoliosis. Therefore, melatonin supplements may prevent the progression of scoliosis, especially in mild cases with less than a 35 degrees curve.
    Journal of Pineal Research 05/2009; 46(3):344-8. · 7.30 Impact Factor
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    ABSTRACT: The Hedgehog family of proteins are powerful morphogens mediating embryonic development as well as adult morphogenesis and carcinogenesis. For example, excess hedgehog activity has been implicated in basal cell carcinoma, medulloblastoma and rhabdomyosarcoma. More recently, hedgehog signalling has been implicated in angiogenesis. While hedgehog signalling in adult angiogenesis may constitute a simple recapitulation of that in embryonic development, it should be appreciated that Hedgehog signalling occurs in embryonic angiogenesis in different developmental contexts. This article reviews the role of Hedgehog signalling in both embryonic and postnatal vascular development. The temporal importance of a window of hedgehog dependent angiogenesis during development is emphasised and illustrated using a whole mouse embryo culture system.
    Angiogenesis 02/2008; 11(1):71-7. · 4.41 Impact Factor
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    ABSTRACT: Microscopic computed tomography (microCT) has been recently applied to morphological evaluation of mouse embryos with or without congenital malformations, and 3-dimensional (3D) digital images of the whole embryo can be obtained. In the present study, the authors report a modified, rapid technique of 3D embryonic microCT without processing with osmium tetroxide. Normal embryonic days 10.5 to 11 mouse embryos, as well as those with craniofacial anomalies treated with teratogens, were examined. After fixation, we processed the embryo samples with hexamethyldisilazane, instead of highly toxic osmium tetroxide in the original method. Our protocol enabled clear 3D craniofacial imaging of the normal and anomalous mouse embryos within a short period of 20 minutes or 1 hour. In addition, some anatomical landmarks were clearly detected in the reconstituted craniofacial section images. Our present data suggest a possible role of microCT for high-throughput morphological screening of the mouse embryos with craniofacial anomalies.
    Journal of computer assisted tomography 01/2008; 32(5):816-21. · 1.38 Impact Factor
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    ABSTRACT: Although embryonic development is inevitably affected by biophysical or biomechanical processes, it has yet to be elucidated to what extent molecular mechanisms of development are modulated by such physical factors. The hedgehog family, including Sonic hedgehog (Shh), is the most well-known morphogens involved in the developmental pattern formation of various organs, such as the nervous system, face, limbs, and skin appendages. There are several unique features in hedgehog signaling including long-range diffusion or positive and negative feedback loops, suggesting the possible modification of hedgehog signaling by biophysical or biomechanical factors. Especially, the period of embryonic day 8-10 is characterized by various biomechanically regulated processes in mouse development, such as axial rotation and vasculoangiogenesis. We executed a series of experiments using a mouse whole embryo culture system to investigate the biomechanical roles of hedgehog signaling during this period. In this review, we examine various examples in which biophysical and biomechanical aspects of hedgehog signaling in development are revealed, including our own data using the mouse whole embryo culture system.
    Annals of the New York Academy of Sciences 05/2007; 1101:412-38. · 4.38 Impact Factor
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    ABSTRACT: The authors report 4 cases of Charcot spine treated surgically. In the surgical treatment, combined anterior and posterior with extensive debridement, autogenous bone grafting, and posterior instrumentation is the main therapeutic modality. Some cases with mild bone destruction could be treated by posterior interbody fusion. For the unstable, symptomatic Charcot spine, surgical treatment can provide excellent results.
    Journal of Spinal Disorders & Techniques 03/2007; 20(1):85-8. · 1.77 Impact Factor
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    ABSTRACT: Adipose-derived stromal cells (ASCs) are one of the most promising stem cell populations that differentiate into the mesodermal as well as neural lineages in vitro. In this study, we examined the neural differentiating potential of human ASCs by a neurosphere culture method. Neurospheres derived from human ASCs expressed Nestin and Musashi-1 genes, which are marker genes for neural stem cells. When these cells were labeled with green fluorescent protein gene transfection by Sendai virus vector and transplanted into the head region of mouse embryos using a whole embryo culture system, these cells were incorporated into the craniofacial development. Some transplanted cells appeared to migrate along the second branchial arches, implicating some similarity to the cranial neural crest cells. Although preliminary, our results support an idea that ASC-derived neurospheres have properties of neural progenitors in vitro and in vivo.
    Journal of Craniofacial Surgery 02/2007; 18(1):49-53; discussion 60-1. · 0.69 Impact Factor
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    ABSTRACT: The etiology of idiopathic scoliosis is unknown. Scoliosis with many characteristics closely resembling those seen in idiopathic scoliosis has been produced in young chickens and bipedal rats after pinealectomy. In this study, we induced experimental scoliosis in C57BL/6J mice without pinealectomy and melatonin treatment suppressed the development of scoliosis. A total of 100 mice were divided into four groups: 20 quadrupedal mice served as controls; 30 mice underwent resection of two forelegs and tail at 3 wk of age (bipedal mice); the remaining 20 quadrupedal and 30 bipedal mice received intraperitoneal melatonin (8 mg/kg BW) at 19:00 hr daily. Before killing, blood samples were collected in the middle of dark cycle and melatonin levels were measured by radioimmunoassay. Spine X-ray and helical 3D-CT were examined after killing at 5 months of age. The bipedal mice without a tail were able to walk with standing posture, whereas the quadrupedal mice did not walk with standing posture. In C57BL/6J mice, the serum melatonin was reduced to nearly zero; however, the normal level was restored in both bipedal and quadrupedal mice after the injection of melatonin. Scoliosis with rib humps developed in 29 of 30 bipedal and in five quadrupedal mice. None of mice with melatonin treatment developed scoliosis. The results suggest that melatonin deficiency in bipedal mice appears to play crucial role for development of scoliosis. Also the restoration of melatonin levels prevents the development of scoliosis.
    Journal of Pineal Research 09/2006; 41(1):1-7. · 7.30 Impact Factor
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    ABSTRACT: Sonic hedgehog (Shh) is a well-known morphogen indispensable in facial and nervous development, and recently it has also garnered much attention as a potent angiogenic factor. We previously created an animal model of holoprosencephaly by administration of cyclopamine, a specific inhibitor of hedgehog signaling, to the mouse embryos cultured in vitro, and found several types of angiogenic defects. In this study, we focused on other angiogenic phenotypes in the same model. When cyclopamine was added for embryonic day (E) 8.0-9.5, a pair of immature dorsal aortae, which normally fuse to form the single aorta by E9.5, remained to be separated. Expressions of vascular endothelial growth factor and bone morphogenetic protein 4, putative mediators of aortic fusion, were also reduced around the aorta by blockade of Shh signaling. When cyclopamine was added for E8.5-10.5, vessels on the surface of craniofacial region (possibly external cardinal veins) were extended and malformed. These results suggest that Shh signaling is essential for some aspects of embryonic angiogenesis, and that pathophysiology of holoprosencephaly may involve, at least in part, the Shh-dependent angiogenesis.
    Journal of Craniofacial Surgery 08/2006; 17(4):736-44. · 0.69 Impact Factor

Publication Stats

687 Citations
95.15 Total Impact Points

Institutions

  • 2005–2014
    • Murayama Medical Center
      Edo, Tōkyō, Japan
  • 1988–2005
    • Nihon University
      • Department of Orthopaedic Surgery
      Tokyo, Tokyo-to, Japan