Tsuyoshi Sugiura

Kinematics of the thoracic spine in trunk rotation: in vivo 3-dimensional analysis.

Study Design. In vivo 3-dimensional (3D) study of the thoracic spine. Objective. To demonstrate axial rotations (ARs) and coupled motions of the thoracic spine. Summary of Background Data. In vivo 3D kinematics of the thoracic spine in trunk rotation with intact thorax and soft tissues has not been well-known. There were no quantitative data of AR in the consecutive thoracic spinal segments. Patterns of coupled motion with AR have been controversial. Methods. Thirteen healthy volunteers underwent 3D computed tomography of the thoracic spine in 3 positions; neutral, right, and left maximum trunk rotation. Relative motions of vertebrae were calculated by automatically superimposing the vertebrae in a neutral position over images in rotational positions, using voxel-based registration. Motions were represented with 6 degrees of freedom by Euler angles and translations on the local coordinate system. Results. Mean (±SD) relative rotational angles of T1 with respect to L1 to 1 side were 24.9° ± 4.9° in maximum trunk rotation. AR of each thoracic segment with respect to the inferior adjacent vertebra to 1 side was 1.2° ± 0.8° at T1–T2, 1.6° ± 0.7° at T2–T3, 1.4° ± 0.9° at T3–T4, 1.6° ± 0.8° at T4–T5, 1.8° ± 0.7° at T5–T6, 1.9° ± 0.6° at T6–T7, 2.3° ± 0.7° at T7–T8, 2.5° ± 0.8° at T8–T9, 2.7° ± 0.6° at T9–T10, 2.6° ± 0.8° at T10–T11, 1.3° ± 0.7° at T11–T12, and 0.5° ± 0.4° at T12–L1. Significantly larger segmental AR was observed at the middle thoracic segments (T6–T11) than at the upper (T1–T6) and lower (T11–L1) segments. At the upper thoracic segments, coupled lateral bending with AR was observed in the same direction as AR. However, at the middle and lower thoracic segments, coupled lateral bending occurred both in the same and opposite directions. Conclusion. In vivo 3D ARs and coupled motions of the consecutive thoracic spinal segments in trunk rotation were investigated accurately for the first time.

Effects of human fibroblasts on invasiveness of oral cancer cells in vitro: Isolation of a chemotactic factor from human fibroblasts

Oral fibroblasts stimulated invasion of oral‐carcinoma cells into the collagen matrix. The mechanisms of the fibroblast‐induced stimulation of invasiveness was further investigated by examining cell motility and proteolytic activity of tumor cells, using mainly an adenoid‐cystic‐carcinoma cell line (ACCS) and normal fibroblasts from gingival tissues. Conditioned medium from the fibroblasts grown in serum‐free medium was fractionated on a Superdex 200 pg column, and Peak 1 eluted at 200 to 300 kDa and Peak 2 eluted at 50 to 100 kDa were found to contain different specific activity. Treatment of ACCS cells with Peak 1 resulted in an increase in the production of proteolytic enzymes. Peak 2 stimulated both chemotaxis and chemokinesis of ACCS cells. A chemotactic factor was purified from the heparin‐unbound fraction of Peak 2 by anion exchange and hydrophobic chromatography, and was named “fibroblastderived motility factor (FDMF)”. At 1 μg/ml, FDMF stimulated chemotaxis of ACCS cells by 4‐fold compared with unstimulated controls. Characterization of the physicochemical properties of FDMF suggested that it might be different from any known motility factors. Exposure of ACCS cells to FDMF resulted in reduced amounts of actin stress fiber in the cytoplasm and induction of tyrosine phosphorylation of several cellular proteins detectable 30 to 60 min after treatment. These FDMF‐induced changes were blocked by pre‐treatment either with genistein or with pertussis toxin. These findings suggest that FDMF may be a novel protein which stimulates cell motility via a signaling pathway mediated by a pertussis‐toxin‐sensitive G protein and tyrosine phosphorylation.

Effect of Intermittent Administration of Teriparatide (Parathyroid Hormone 1-34) on Bone Morphogenetic Protein-Induced Bone Formation in a Rat Model of Spinal Fusion.

BACKGROUND Although clinical bone morphogenetic protein (BMP) therapy is effective at enhancing bone formation in patients managed with spinal arthrodesis, the required doses are very high. Teriparatide (parathyroid hormone 1-34) is approved by the U.S. Food and Drug Administration to treat osteoporosis and is a potent anabolic agent. In this study, intermittent administration of parathyroid hormone 1-34 combined with transplantation of BMP was performed to elucidate the effect of parathyroid hormone 1-34 on the fusion rate and quality of newly formed bone in a rat model. METHODS A total of forty-eight male Sprague-Dawley rats underwent posterolateral lumbar spinal arthrodesis with one of three different treatments with recombinant human (rh) BMP-2: (1) 0 μg (control), (2) 2 μg (low dose), or (3) 50 μg (high dose). Each of the rhBMP-2 treatments was studied in combination with intermittent injections of either parathyroid hormone 1-34 (180 μg/kg/wk) or saline solution starting two weeks before the operation and continuing until six weeks after the operation. Osseous fusion was assessed with use of radiographs and a manual palpation test. Microstructural indices of the newly formed bone were evaluated with use of micro-computed tomography. The serum markers of bone metabolism were also quantified. RESULTS The fusion rate in the group treated with 2 μg of rhBMP-2 significantly increased (from 57% to 100%) with the administration of parathyroid hormone 1-34 (p < 0.05). The fusion rates in the other groups did not change significantly with the administration of parathyroid hormone 1-34. The bone volume density of the newly formed bone significantly increased in both the 2-μg and 50-μg rhBMP-2 treatment groups with the administration of parathyroid hormone 1-34 (p < 0.01). Micro-computed tomography scans of the newly formed bone clearly demonstrated an abundance of trabecular bone formation in the group treated with parathyroid hormone 1-34. In addition, serum levels of osteocalcin were significantly increased in the parathyroid hormone 1-34 treatment group. CONCLUSIONS Intermittent administration of parathyroid hormone 1-34 significantly increased fusion rates in the group treated with low-dose rhBMP-2, and it improved the quality of the newly formed bone in both the high and low-dose groups in a rat model of rhBMP-2-induced spinal fusion. CLINICAL RELEVANCE Our results suggest that the combined administration of rhBMP-2 and parathyroid hormone 1-34 may lead to efficient bone regeneration.

The bone morphogenetic protein-2/7 heterodimer is a stronger inducer of bone regeneration than the individual homodimers in a rat spinal fusion model

BACKGROUND CONTEXT Bone morphogenetic proteins (BMPs) are a group of dimeric growth factors that belong to the transforming growth factor super family and are capable of eliciting new bone formation. Previous studies have suggested that the coexpression of two different BMP genes in a cell can result in the production of BMP heterodimers that are more potent than homodimers. However, because of the difficulty in optimizing the level of BMP gene expression, the coexpression of two different BMP genes also produces BMP homodimers as a by-product. These homodimers could, in theory, interact with the heterodimers. PURPOSE To elucidate the effects of a BMP-2/7 heterodimer, which were investigated in depth using purified BMP-2/7 heterodimers, BMP-2 homodimers, and BMP-7 homodimers in a rat spinal fusion model. METHODS Bilateral posterolateral fusion at L4-L5 was performed in four different groups: control group animals were implanted with collagen carriers alone; BMP-7 group animals with collagen carriers+1 μg of BMP-7 homodimer; BMP-2 group animals with collagen carriers+1 μg of BMP-2 homodimer; and BMP-2/7 group animals with collagen carriers+1 μg of the BMP-2/7 heterodimer. The following assessments were performed: bone microstructural analysis of the fusion mass and tissue volume (TV) with microcomputed tomography (micro-CT); fusion assessment with manual palpation testing and three-dimensional CT images; and bone histomorphometrical analysis of the fusion mass. RESULTS The fusion scores, as determined by radiography, and the TV of the newly formed bone, as determined by micro-CT, were significantly higher in the BMP-2/7 heterodimer group than the other groups (p<.0001). The microstructural indices of the newly formed bone did not differ between the groups. Moreover, histologic analysis of the fused spines revealed that the formation of the trabecular bone bridging the transverse process was the highest in this group. CONCLUSIONS This study demonstrated that BMP-2/7 heterodimer is a stronger inducer of bone regeneration than BMP-2 or -7 homodimers. The use of a purified BMP-2/7 heterodimer may represent an efficient alternative to the current clinical use of BMP-2 or -7 homodimers. Further studies as to the side effects of BMP-2/7 heterodimer are required.

Effect of dexamethasone on invasion of human squamous cell carcinoma cells into collagen gel

The effect of dexamethasone (Dex) on the ability to invade type I collagen gel was investigated in two cell lines of oral squamous cell carcinoma (SCC). At concentrations higher than 10(-8) M, Dex significantly suppressed the invasive growth of SCC cells into the gel. The same concentrations of Dex led to a decrease in urokinase type plasminogen activator (u-PA) synthesis and an increase in plasminogen activator inhibitor type 1 (PAI-1) synthesis by SCC cells. These findings suggest that Dex inhibits the invasiveness of SCC cells by decreasing their proteolytic activity.

Spinopelvic sagittal imbalance as a risk factor for adjacent-segment disease after single-segment posterior lumbar interbody fusion.

Objective The importance of spinopelvic balance and its implications for clinical outcomes after spinal arthrodesis has been reported in recent studies. However, little is known about the relationship between adjacent-segment disease (ASD) after lumbar arthrodesis and spinopelvic alignment. The purpose of this study was to clarify the relationship between spinopelvic radiographic parameters and symptomatic ASD after L4–5 single-level posterior lumbar interbody fusion (PLIF). Methods This was a retrospective 1:5 matched case-control study. Twenty patients who had undergone revision surgery for symptomatic ASD after L4–5 PLIF and had standing radiographs of the whole spine before primary and revision surgeries were enrolled from 2005 to 2012. As a control group, 100 age-, sex-, and pathology-matched patients who had undergone L4–5 PLIF during the same period, had no signs of symptomatic ASD for more than 3 years, and had whole-spine radiographs at preoperation and last follow-up were selected. Mean age at the time of primary surgery was 68.9 years in the ASD group and 66.7 years in the control group. Several radiographic spinopelvic parameters were measured as follows: sagittal vertical axis (SVA), thoracic kyphosis (TK), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), and segmental lordosis at L4–5 (SL) in the sagittal view, and C7–central sacral vertical line (C7-CSVL) in the coronal view. Radiological parameters were compared between the groups. Results No significant change was found between pre- and postoperative radiographic parameters in each group. In terms of preoperative radiographic parameters, the ASD group had significantly lower LL (40.7° vs 47.2°, p < 0.01) and significantly higher PT (27° vs 22.9°, p < 0.05) than the control group. SVA ≥ 50 mm was observed in 10 of 20 patients (50%) in the ASD group and in 21 of 100 patients (21%, p < 0.01) in the control group. PI-LL ≥ 10° was noted in 15 of 20 patients (75%) in the ASD group and in 40 of 100 patients (40%, p < 0.01) in the control group on preoperative radiographs. Postoperatively, the ASD group had significantly lower TK (22.5° vs 30.9°, p < 0.01) and lower LL (39.3° vs 48.1°, p < 0.05) than the control group had. PI-LL ≥ 10° was seen in 15 of 20 patients (75%) in the ASD group and in 43 of 100 patients (43%, p < 0.01) in the control group. Conclusions Preoperative global sagittal imbalance (SVA > 50 mm and higher PT), pre- and postoperative lower LL, and PI-LL mismatch were significantly associated with ASD. Therefore, even with a single-level PLIF, appropriate SL and LL should be obtained at surgery to improve spinopelvic sagittal imbalance. The results also suggest that the achievement of the appropriate LL and PI-LL prevents ASD after L4–5 PLIF.

Kinematics of the thoracic spine in trunk lateral bending: in vivo three-dimensional analysis

BACKGROUND CONTEXT In vivo three-dimensional kinematics of the thoracic spine in trunk lateral bending with an intact rib cage and soft tissues has not been well documented. There is no quantitative data in the literature for lateral bending in consecutive thoracic spinal segments, and there has not been consensus on the patterns of coupled motion with lateral bending. PURPOSE To demonstrate segmental ranges of motion (ROMs) in lateral bending and coupled motions of the thoracic spine. STUDY DESIGN In vivo three-dimensional biomechanics study of the thoracic spine. PATIENT SAMPLE Fifteen healthy male volunteers. OUTCOME MEASURES Computed analysis by using voxel-based registration. METHODS Participants underwent computed tomography of the thoracic spine in three supine positions: neutral, right maximum lateral bending, and left maximum lateral bending. The relative motions of vertebrae were calculated by automatically superimposing an image of vertebrae in a neutral position over images in bending positions, using voxel-based registration. Mean values of lateral bending were compared among the upper (T1-T2 to T3-T4), the middle-upper (T4-T5 to T6-T7), the middle-lower (T7-T8 to T9-T10), and the lower (T10-T11 to T12-L1) parts of the spine. RESULTS At lateral bending, the mean ROM (±standard deviation) of T1 with respect to L1 was 15.6°±6.3° for lateral bending and 6.2°±4.8° for coupled axial rotation in the same direction as lateral bending. The mean lateral bending of each spinal segment with respect to the inferior adjacent vertebra was 1.4°±1.3° at T1-T2, 1.3°±1.2° at T2-T3, 1.4°±1.3° at T3-T4, 0.9°±0.9° at T4-T5, 0.8°±1.0° at T5-T6, 1.1°±1.1° at T6-T7, 1.7°±1.2° at T7-T8, 1.3°±1.2° at T8-T9, 1.6°±0.7° at T9-T10, 1.8°±0.8° at T10-T11, 2.3°±1.0° at T11-T12, and 2.2°±0.8° at T12-L1. The smallest and the largest amounts of lateral bending were observed in the middle-upper and the lower parts, respectively. There was no significant difference in lateral bending between the upper and the middle-lower parts. Coupled axial rotation of each segment was generally observed in the same direction as lateral bending. However, high variability was found at the T2-T3 to T5-T6 segments. Coupled flexion was observed at the upper and middle parts, and coupled extension was observed at the lower part. CONCLUSIONS This study revealed in vivo three-dimensional motions of consecutive thoracic spinal segments in trunk lateral bending. The thoracolumbar segments significantly contributed to lateral bending. Coupled axial rotation generally occurred in the same direction with lateral bending. However, more variability was observed in the direction of coupled axial rotation at T2-T3 to T5-T6 segments in the supine position. These results are useful for understanding normal kinematics of the thoracic spine.

In vivo 3D kinematic changes in the cervical spine after laminoplasty for cervical spondylotic myelopathy.

OBJECT Cervical laminoplasty is an effective procedure for decompressing the spinal cord at multiple levels, but restriction of neck motion is one of the well-known complications of the procedure. Although many authors have reported on cervical range of motion (ROM) after laminoplasty, they have focused mainly on 2D flexion and extension on lateral radiographs, not on 3D motion (including coupled motion) nor on precise intervertebral motion. The purpose of this study was to clarify the 3D kinematic changes in the cervical spine after laminoplasty performed to treat cervical spondylotic myelopathy. METHODS Eleven consecutive patients (6 men and 5 women, mean age 68.1 years, age range 57-79 years) with cervical spondylotic myelopathy who had undergone laminoplasty were included in the study. All patients underwent 3D CT of the cervical spine in 5 positions (neutral, 45° head rotation left and right, maximum head flexion, and maximum head extension) using supporting devices. The scans were performed preoperatively and at 6 months after laminoplasty. Segmental ROM from Oc-C1 to C7-T1 was calculated both in flexion-extension and in rotation, using a voxel-based registration method. RESULTS Mean C2-7 flexion-extension ROM, equivalent to cervical ROM in all previous studies, was 45.5° ± 7.1° preoperatively and 35.5° ± 8.2° postoperatively, which was a statistically significant 33% decrease. However, mean Oc-T1 flexion-extension ROM, which represented total cervical ROM, was 71.5° ± 8.3° preoperatively and 66.5° ± 8.3° postoperatively, an insignificant 7.0% decrease. In focusing on each motion segment, the authors observed a statistically significant 22.6% decrease in mean segmental ROM at the operated levels during flexion-extension and a statistically insignificant 10.2% decrease during rotation. The most significant decrease was observed at C2-3. Segmental ROM at C2-3 decreased 24.2% during flexion-extension and 21.8% during rotation. However, a statistically insignificant 37.2% increase was observed at the upper cervical spine (Oc-C2) during flexion-extension. The coupling pattern during rotation did not change significantly after laminoplasty. CONCLUSIONS In this first accurate documentation of 3D segmental kinematic changes after laminoplasty, Oc-T1 ROM, which represented total cervical ROM, did not change significantly during either flexion-extension or rotation by 6 months after laminoplasty despite a significant decrease in C2-7 flexion-extension ROM. This is thought to be partially because of a compensatory increase in segmental ROM at the upper cervical spine (Oc-C2).

3D morphometric analysis of laminae and facet joints in patients with degenerative spondylolisthesis.

Abstract Objective. To clarify the three-dimensional (3D) morphometric characteristics of the spine in patients with degenerative spondylolisthesis (DS). Methods. 3D morphometric analyses of laminae and facets were performed and compared for a DS group, an age-matched spinal canal stenosis (LCS) group, and a control group of young persons without spinal disease. 3D facet sagittal angles (3D-FSAs), 3D facet axial angle (3D-FAAs), and 3D-FAA tropism at L3 and at L4 were measured by extracting the 3D inferior articular process. The 3D lamina inclination angles (3D-LIAs) of L3 and L4 were also measured by extracting the ventral surface of the laminae. Results. The 3D-FSAs at L4 in the DS group were significantly higher than for the other groups, but the difference in 3D-FSAs at L3 was not statistically significant among the groups. The 3D-FAAs at L4 in the DS group were significantly lower than in the control group. There was no significant difference in other factors. Conclusions. 3D morphometric analysis clarified that DS is significantly correlated with horizontalization (higher 3D-FSA), but is not correlated with sagittalization (lower 3D-FAA) and tropism (3D-FAA tropism) of facet joints or horizontalization of laminae (3D-LIA). There were no morphometric characteristics at the cranial adjacent segment of DS.

Sacroiliac joint motion in patients with degenerative lumbar spine disorders

OBJECT Usually additional anchors into the ilium are necessary in long fusion to the sacrum for degenerative lumbar spine disorders (DLSDs), especially for adult spine deformity. Although the use of anchors is becoming quite common, surgeons must always keep in mind that the sacroiliac (SI) joint is mobile and they should be aware of the kinematic properties of the SI joint in patients with DLSDs, including adult spinal deformity. No previous study has clarified in vivo kinematic changes in the SI joint with respect to patient age, sex, or parturition status or the presence of DLSDs. The authors conducted a study to clarify the mobility and kinematic characteristics of the SI joint in patients with DLSDs in comparison with healthy volunteers by using in vivo 3D motion analysis with voxel-based registration, a highly accurate, noninvasive method. METHODS Thirteen healthy volunteers (the control group) and 20 patients with DLSDs (the DLSD group) underwent low-dose 3D CT of the lumbar spine and pelvis in 3 positions (neutral, maximal trunk flexion, and maximal trunk extension). SI joint motion was calculated by computer processing of the CT images (voxel-based registration). 3D motion of the SI joint was expressed as both 6 df by Euler angles and translations on the coordinate system and a helical axis of rotation. The correlation between joint motion and the cross-sectional area of the trunk muscles was also investigated. RESULTS SI joint motion during trunk flexion-extension was minute in healthy volunteers. The mean rotation angles during trunk flexion were 0.07° around the x axis, -0.02° around the y axis, and 0.16° around the z axis. The mean rotation angles during trunk extension were 0.38° around the x axis, -0.08° around the y axis, and 0.08° around the z axis. During trunk flexion-extension, the largest amount of motion occurred around the x axis. In patients with DLSDs, the mean rotation angles during trunk flexion were 0.57° around the x axis, 0.01° around the y axis, and 0.19° around the z axis. The mean rotation angles during trunk extension were 0.68° around the x axis, -0.11° around the y axis, and 0.05° around the z axis. Joint motion in patients with DLSDs was significantly greater, with greater individual difference, than in healthy volunteers. Among patients with DLSDs, women had significantly more motion than men did during trunk extension. SI joint motion was significantly negatively correlated with the cross-sectional area of the trunk muscles during both flexion and extension of the trunk. CONCLUSIONS The authors elucidated the mobility and kinematic characteristics of the SI joint in patients with DLSDs compared with healthy volunteers for the first time. This information is useful for spine surgeons because of the recent increase in spinopelvic fusion for the treatment of DLSDs.