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Biomedical subjects

Yoshiaki Toyama

Publications and source records attributed to Yoshiaki Toyama.

At least 19 recordsLinked to original sources
PubMed2007

Hyaline cartilage formation and enchondral ossification modeled with KUM5 and OP9 chondroblasts.

What is it that defines a bone marrow-derived chondrocyte? We attempted to identify marrow-derived cells with chondrogenic nature and immortality without transformation, defining "immortality" simply as indefinite cell division. KUM5 mesenchymal cells, a marrow stromal cell line, generated hyaline cartilage in vivo and exhibited enchondral ossification at a later stage after implantation. Selection of KUM5 chondroblasts based on the activity of the chondrocyte-specific cis-regulatory element of the collagen alpha2(XI) gene resulted in enhancement of their chondrogenic nature. Gene chip analysis revealed that OP9 cells, another marrow stromal cell line, derived from macrophage colony-stimulating factor-deficient osteopetrotic mice and also known to be niche-constituting cells for hematopoietic stem cells expressed chondrocyte-specific or -associated genes such as type II collagen alpha1, Sox9, and cartilage oligomeric matrix protein at an extremely high level, as did KUM5 cells. After cultured OP9 micromasses exposed to TGF-beta3 and BMP2 were implanted in mice, they produced abundant metachromatic matrix with the toluidine blue stain and formed type II collagen-positive hyaline cartilage within 2 weeks in vivo. Hierarchical clustering and principal component analysis based on microarray data of the expression of cell surface markers and cell-type-specific genes resulted in grouping of KUM5 and OP9 cells into the same subcategory of "chondroblast," that is, a distinct cell type group. We here show that these two cell lines exhibit the unique characteristics of hyaline cartilage formation and enchondral ossification in vitro and in vivo.

Animals↗
PubMed2007

Factors of thoracic cage deformity that affect pulmonary function in adolescent idiopathic thoracic scoliosis.

STUDY DESIGN: This clinical study examined the association between pulmonary function and thoracic cage deformities in scoliosis. OBJECTIVE: To determine the factors in spinal and thoracic cage deformities that affect pulmonary function in scoliosis. SUMMARY OF BACKGROUND DATA: Pulmonary function in scoliosis has generally been evaluated in terms of lateral spinal curvature. No previous report has evaluated changes in pulmonary function taking into consideration measurements reflecting not only spinal curvature but also thoracic cage deformities, although scoliosis is a three-dimensional deformity. METHODS: A total of 109 patients (mean age, 14.2 years) with adolescent idiopathic right thoracic scoliosis (mean lateral spinal curvature, 37.7 degrees) had full assessment of pulmonary function and a radiographic evaluation from radiographs of the whole spine, Moiré topography, and thoracic computed tomography. RESULTS: Multiple regression analysis (stepwise method) was performed at each vertebral level from T3-T12 to identify the factor that most strongly affects %VC. The correlation coefficient was highest at T9 and next highest at T8, with values of 0.641 (r2 = 0.411, P < 0.0001) and 0.625 (r2 = 0.390, P < 0.0001), respectively. At T9, multiple regression analysis showed that the sagittal diameter of the thoracic cage and the total lung area were identified as factors that most strongly affect %VC. Similarly, the sagittal diameter of the thoracic cage and the rotation angle to the sagittal plane were identified at T8. CONCLUSIONS: The factors that reduced %VC were the sagittal diameter of the thoracic cage, total lung area and vertebral rotation at the T8 and T9 levels.

Adolescent↗
PubMed2006

Long-term results of expansive open-door laminoplasty for cervical myelopathy--average 14-year follow-up study.

STUDY DESIGN: Retrospective case series on long-term follow-up results of original expansive open-door laminoplasty for cervical myelopathy due to cervical spondylosis (CSM) and ossification of posterior longitudinal ligament (OPLL). OBJECTIVES: To elucidate efficacy and problems of original open-door laminoplasty to improve future surgical outcomes. SUMMARY OF BACKGROUND DATA: Little information is available on long-term outcomes of original open-door laminoplasty without grafts, implants, or instruments. METHOD: The study group included 80 patients who underwent original open-door laminoplasty and were followed for minimum 10 years. Clinical results, including Japanese Orthopedic Association scores, recovery rates, occurrences of complications, and long-term deterioration were investigated. Cervical alignments, type of OPLL, cervical range of motion, anteroposterior diameter of spinal canal, and progression of OPLL were assessed on plain radiographs. Spinal cord decompression was verified on magnetic resonance imaging. RESULTS: Average Japanese Orthopedic Association score and recovery rate improved significantly until 3 years after surgery and remained at an acceptable level in both cervical spondylosis and OPLL patients with slight deterioration after 5 years. Segmental motor palsy developed in 8 patients. Late deterioration, mainly lower extremity motor score decline, developed in 8 CSM and 16 OPLL patients. Overall cervical range of motion decreased by 36%. Patients with cervical lordosis decreased gradually in both patient groups. Such changes in alignments did not affect surgical results in CSM patients, while OPLL patients with preoperative kyphosis had lower recovery rates than those with straight and lordotic alignments. OPLL progression that was detected in 66% of patients did not affect clinical results. Although infrequent, magnetic resonance imaging revealed atrophy of spinal cord, spinal cord compression at adjacent segments due to degenerative changes and OPLL progression. CONCLUSIONS: Long-term results of open-door laminoplasty without bone graft, graft substitutes, or instruments were satisfactory. However, segmental motor paralysis, kyphosis, established before and after surgery, OPLL progression, and late deterioration due to age-related degeneration remain challenging problems.

Adult↗
PubMed2006

Electrical stimulation modulates fate determination of differentiating embryonic stem cells.

A clear understanding of cell fate regulation during differentiation is key in successfully using stem cells for therapeutic applications. Here, we report that mild electrical stimulation strongly influences embryonic stem cells to assume a neuronal fate. Although the resulting neuronal cells showed no sign of specific terminal differentiation in culture, they showed potential to differentiate into various types of neurons in vivo, and, in adult mice, contributed to the injured spinal cord as neuronal cells. Induction of calcium ion influx is significant in this differentiation system. This phenomenon opens up possibilities for understanding novel mechanisms underlying cellular differentiation and early development, and, perhaps more importantly, suggests possibilities for treatments in medical contexts.

Animals↗
PubMed2006

A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord.

Axons in the adult mammalian central nervous system (CNS) exhibit little regeneration after injury. It has been suggested that several axonal growth inhibitors prevent CNS axonal regeneration. Recent research has demonstrated that semaphorin3A (Sema3A) is one of the major inhibitors of axonal regeneration. We identified a strong and selective inhibitor of Sema3A, SM-216289, from the fermentation broth of a fungal strain. To examine the effect of SM-216289 in vivo, we transected the spinal cord of adult rats and administered SM-216289 into the lesion site for 4 weeks. Rats treated with SM-216289 showed substantially enhanced regeneration and/or preservation of injured axons, robust Schwann cell-mediated myelination and axonal regeneration in the lesion site, appreciable decreases in apoptotic cell number and marked enhancement of angiogenesis, resulting in considerably better functional recovery. Thus, Sema3A is essential for the inhibition of axonal regeneration and other regenerative responses after spinal cord injury (SCI). These results support the possibility of using Sema3A inhibitors in the treatment of human SCI.

Animals↗
PubMed2006

Effects of local administration of vascular endothelial growth factor on mechanical characteristics of the semitendinosus tendon graft after anterior cruciate ligament reconstruction in sheep.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. HYPOTHESIS: An application of VEGF may enhance angiogenesis in the grafted tendon in anterior cruciate ligament (ACL) reconstruction, and the application may affect mechanical characteristics of the ACL graft. STUDY DESIGN: Controlled laboratory study. METHODS: Eighteen sheep were divided into groups I and II. In group I, the harvested semitendinosus tendon was soaked in VEGF solution, and the right knee then underwent ACL reconstruction using this tendon. In group II, the right knee underwent identical procedures to those of group I except that the harvested tendon was soaked in phosphate-buffered saline. All animals were sacrificed 12 weeks after ACL reconstruction. RESULTS: Histologic findings showed that newly formed vessels and infiltrative fibroblasts were more abundant in group I than in group II. The anterior-posterior translation of the knee during an anterior-posterior force of +/- 100 N was significantly larger in group I than in group II by 2.58 mm (95% confidence interval, -1.76 mm to 1.76 mm) (P = .002). The linear stiffness of the femur-graft-tibia complex in group I was significantly lower than that in group II by 41.5 N/mm (95% confidence interval, -32.2 N/mm to 32.2 N/mm) (P = .017). CONCLUSION: This study has revealed that VEGF as administered in this study promotes angiogenesis in the ACL graft and significantly reduces the stiffness of the ACL graft with increased knee laxity at 12 weeks after ACL reconstruction. CLINICAL RELEVANCE: Exogenous VEGF application for ACL reconstruction can induce an increase in knee laxity and a decrease in the stiffness of the grafted tendon at least temporarily after ACL reconstruction. These potentially negative mechanical effects need to be taken into account when considering clinical use of VEGF.

Angiogenesis Modulating Agents↗
PubMed2006

Substrate selectivity of epidermal growth factor-receptor ligand sheddases and their regulation by phorbol esters and calcium influx.

Signaling via the epidermal growth factor receptor (EGFR), which has critical roles in development and diseases such as cancer, is regulated by proteolytic shedding of its membrane-tethered ligands. Sheddases for EGFR-ligands are therefore key signaling switches in the EGFR pathway. Here, we determined which ADAMs (a disintegrin and metalloprotease) can shed various EGFR-ligands, and we analyzed the regulation of EGFR-ligand shedding by two commonly used stimuli, phorbol esters and calcium influx. Phorbol esters predominantly activate ADAM17, thereby triggering a burst of shedding of EGFR-ligands from a late secretory pathway compartment. Calcium influx stimulates ADAM10, requiring its cytoplasmic domain. However, calcium influx-stimulated shedding of transforming growth factor alpha and amphiregulin does not require ADAM17, even though ADAM17 is essential for phorbol ester-stimulated shedding of these EGFR-ligands. This study provides new insight into the machinery responsible for EGFR-ligand release and thus EGFR signaling and demonstrates that dysregulated EGFR-ligand shedding may be caused by increased expression of constitutively active sheddases or activation of different sheddases by distinct stimuli.

ADAM Proteins↗
PubMed2006

Posterior instability near extension is related to clinical disability in isolated posterior cruciate ligament deficient patients.

The purpose of this study is to evaluate the relationship between the magnitude of knee laxity and posterior instability at different knee flexion angles and clinical disability in isolated posterior cruciate ligament (PCL) deficient patients. Knee laxity at 20 degrees and 70 degrees of knee flexion were evaluated using KT-2000 arthrometer, and the posterior instability at 20 degrees , 45 degrees and 90 degrees of flexion were evaluated using stress radiography. We assessed the differences in the knee laxity and the tibial translation between isolated PCL deficient knees and normal knees, and between the patients with giving-way during activities of daily living (ADL) and without giving-way. There were statistical differences in the knee laxity and the tibial translation at all knee flexion angles between the PCL deficient knees and normal knees. The magnitude of the knee laxity at 20 degrees of flexion measured with KT-2000 arthrometer was significantly larger in the patients with giving-way than those in the patients without giving-way although there was no significant difference in the tibial translation at 70 degrees between the two groups. The tibial translation in both medial and lateral compartments at 20 degrees and 45 degrees measured with stress radiography were significantly larger in the patients with giving-way than those in the patients without giving-way although there was not significant difference at 90 degrees between the two groups. These results suggested that the magnitude of the knee laxity and the posterior tibial translation at shallow knee flexion angles would be related to giving-way during ADL in isolated PCL deficient patients.

Activities of Daily Living↗
PubMed2006

Association study of COL9A2 with lumbar disc disease in the Japanese population.

Lumbar disc disease (LDD) is a common musculo-skeletal disease with strong genetic determinants. In a Finnish population, a single nucleotide polymorphism (SNP) causing an amino-acid substitution (Trp2 allele) in COL9A2, which encodes the alpha2 (IX) chain of type IX collagen, has been reported to associate with LDD. However, replication studies in different populations have produced controversial results. To further investigate the association of COL9A2 with LDD in Japanese, we examined SNPs in COL9A2, including Trp2, in 470 LDD patients (mean age 35) along with 658 controls (mean age 48). We identified a total of 43 sequence variations in COL9A2. Nine SNPs, including Trp2, were selected and genotyped. After Bonferroni's correction, none of these SNPs showed association. Unlike observations in the Finnish population, Trp2 was common in Japanese, and no association with LDD was apparent. However, we did see association of a COL9A2 specific haplotype with LDD (P=0.025; permutation test); this association is more significant in patients with severe lumbar disc degeneration (P=0.011). Thus, the association of Trp2 with LDD was not replicated, but COL9A2 susceptibility allele(s) other than Trp2 may be present in Japanese LDD.

Adult↗
PubMed2006

Clinical disability in posterior cruciate ligament deficient patients does not relate to knee laxity, but relates to dynamic knee function during stair descending.

We investigated the factors which influence clinical subjective symptoms during activities in Posterior cruciate ligament (PCL) deficient patients by evaluating knee laxity, muscle strength and knee mechanics during level walking, stair ascent and descent. Twenty-two subjects with isolated PCL deficient knees and 20 healthy volunteers were involved. The PCL deficient patients were divided into two subgroups based on previous history of experiencing giving-way during stair descent; a giving-way group (10 subjects) and a nongiving-way group (12 subjects). Giving-way during activities of daily living is a key symptom in isolated PCL deficient patients. No statistically significant differences in the knee laxity, muscle strength and knee mechanics during level walking and were observed between the giving-way group and the nongiving-way group. However, we found significant differences in the knee mechanics during stair ascent and descent between the two groups, and these differences were more remarkable during stair descent. Peak values of knee flexion angle, external knee flexion moment and posterior knee force during early stance phase were significantly lower in the giving-way group than in the nongiving-way group. This study indicated that the symptom of giving-way during stair descent was related to knee mechanics during stair descent, unlike other quantitative evaluations such as KT-2000 or Biodex.

Activities of Daily Living↗
PubMed2006

Clinical disability in posterior cruciate ligament deficient patients does not relate to knee laxity, but relates to dynamic knee function during stair descending.

We investigated the factors which influence clinical subjective symptoms during activities in PCL deficient patients by evaluating knee laxity, muscle strength and knee mechanics during level walking, stair ascent and descent. Twenty-two subjects with isolated PCL deficient knees and 20 healthy volunteers were involved. The PCL deficient patients were divided into two subgroups based on previous history of experiencing giving-way during stair descent; a giving-way group (10 subjects) and a non giving-way group (12 subjects). Giving-way during activities of daily living is a key symptom in isolated PCL deficient patients. No statistically significant differences in the knee laxity, muscle strength and knee mechanics during level walking and were observed between the giving-way group and the non giving-way group. However, we found significant differences in the knee mechanics during stair ascent and descent between the two groups, and these differences were more remarkable during stair descent. Peak values of knee flexion angle, external knee flexion moment and posterior knee force during early stance phase were significantly lower in the giving-way group than in the non giving-way group. This study indicated that the symptom of giving-way during stair descent was related to knee mechanics during stair descent, unlike other quantitative evaluations such as KT-2000 or Biodex.

Activities of Daily Living↗
PubMed2006

Posterior osteotomy and instrumentation for thoracolumbar kyphosis in patients with achondroplasia.

STUDY DESIGN: A retrospective case series of surgically treated achondroplastic patients with severe thoracolumbar kyphosis. OBJECTIVE: To evaluate the outcome of surgical treatment for thoracolumbar kyphosis in patients associated with achondroplasia presenting with paraparesis. SUMMARY OF BACKGROUND DATA: Thoracolumbar kyphosis is one of the frequent skeletal manifestations in patients with achondroplasia. Few papers have been published on the surgical treatment of this condition, especially in skeletally mature patients. METHODS: Four patients with achondroplasia who developed neurologic deficit due to severe thoracolumbar kyphosis and underwent surgical treatment were evaluated (mean age, 32.5 years; mean follow-up, 3.0 years). Posterior osteotomy with segmental instrumentation was performed in all cases. The surgical procedures included pedicle subtraction osteotomy in 2 patients without a hypoplastic apical vertebra and spondylectomy with reconstruction of the anterior column in 2 patients with a hypoplastic apical vertebra. Neurologic outcomes (JOA scores), correction of kyphosis, and operative complications were assessed. RESULTS: All patients had gait disturbance, and 2 patients were unambulatory before surgery. The average preoperative JOA score was 5.8 points, which was improved to 9.3 points at the final follow-up (mean recovery rate, 75%). All patients obtained neurologic improvement and became ambulatory either with or without crutches after surgery. The mean preoperative kyphotic angle was 96.3 degrees (range, 57 degrees -117 degrees ). The postoperative angles averaged 55.3 degrees (range, 30 degrees -110 degrees ), yielding a mean correction rate of 43.6%. Neither loss of correction nor pseudarthrosis has been observed during the follow-up period. Partial nerve root laceration and dural tear resulting in transient postoperative muscle weakness were observed in 2 patients as complications. CONCLUSIONS: Posterior spinal osteotomy with segmental instrumentation is a reasonable surgical option for thoracolumbar kyphosis in patients with achondroplasia. Modification of the surgical procedures depending on the presence or absence of the dysplastic changes of the apical vertebra is necessary to obtain optimal results.

Achondroplasia↗
PubMed2006

Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury.

In the injured central nervous system (CNS), reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here we show that reactive astrocytes have a crucial role in wound healing and functional recovery by using mice with a selective deletion of the protein signal transducer and activator of transcription 3 (Stat3) or the protein suppressor of cytokine signaling 3 (Socs3) under the control of the Nes promoter-enhancer (Nes-Stat3(-/-), Nes-Socs3(-/-)). Reactive astrocytes in Nes-Stat3(-/-) mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury (SCI). On the contrary, we observed rapid migration of reactive astrocytes to seclude inflammatory cells, enhanced contraction of lesion area and notable improvement in functional recovery in Nes-Socs3(-/-) mice. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.

Animals↗
PubMed2006

Open-door laminoplasty for cervical myelopathy resulting from adjacent-segment disease in patients with previous anterior cervical decompression and fusion.

STUDY DESIGN: This is a retrospective study of patients with cervical myelopathy resulting from adjacent-segment disease who were treated by open-door expansive laminoplasty. OBJECTIVES: The purpose of this study was to evaluate the effectiveness of laminoplasty for cervical myelopathy resulting from adjacent-segment disease. SUMMARY OF BACKGROUND DATA: Adjacent-segment disease is one of the problems associated with anterior cervical decompression and fusion. However, the optimal surgical management strategy is still controversial. METHODS: Thirty-one patients who underwent open-door expansive laminoplasty for cervical myelopathy resulting from adjacent-segment disease and age- and sex-matched 31 patients with myelopathy who underwent laminoplasty as the initial surgery were enrolled in the study. The pre- and postoperative Japanese Orthopedic Association scores (JOA scores) and the recovery rate were compared between the two groups. RESULTS: The average JOA scores in the patients with adjacent-segment disease and the controls were 9.2 +/- 2.6 and 9.4 +/- 2.3 before the expansive laminoplasty and 11.9 +/- 2.8 and 13.3 +/- 1.7 at the follow-up examination, respectively; the average recovery rates in the two groups were 37.1 +/- 22.4% and 50.0 +/- 21.3%, respectively (P = 0.04). The mean number of segments covered by the high-intensity lesions on the T2-weighted magnetic resonance images was 1.87 and 0.9, respectively (P = 0.001). CONCLUSIONS: Moderate neurologic recovery was obtained after open-door laminoplasty in patients with cervical myelopathy resulting from adjacent-segment disc disease, although the results were not as satisfactory as those in the control group. This may be attributed to the irreversible damage of the spinal cord caused by persistent compression at the adjacent segments.

Adult↗
PubMed2006

A novel hydroxyapatite fiber mesh as a carrier for recombinant human bone morphogenetic protein-2 enhances bone union in rat posterolateral fusion model.

STUDY DESIGN: An experimental study, in which spinal fusion in rats was conducted using a hydroxyapatite fiber mesh (HAM) as a carrier for recombinant human bone morphogenetic protein (rhBMP)-2. OBJECTIVES: To study the usefulness of the HAM as a carrier and seek the possibility of clinical application in spinal fusion. SUMMARY OF BACKGROUND DATA: Several biomaterials have been used as a carrier for BMP to achieve spine fusion, however, to our knowledge, the most effective carrier has not been established. METHODS: In experiment No. 1, HAMs and the controls (commercially available hydroxyapatite ceramic body), loaded with rhBMP-2, were immersed in phosphate-buffered saline to evaluate the time course of the release of rhBMP-2. In experiment No. 2, posterolateral fusion was conducted in rats using HAM and the control loaded with rhBMP-2. The fusion status was evaluated radiologically and histologically after surgery. RESULTS: In experiment No. 1, HAMs released a larger amount of rhBMP-2 for up to 28 days than the controls (49.5% vs 7.8%). In experiment No. 2, the fusion rate was significantly higher in the HAM group (>80%) than in the control group (20%). Dense new bone formed close to the spine, and the HAMs were markedly absorbed compared with the controls. CONCLUSION: HAM provided more solid fusion mass than the control, suggesting that HAM is an efficient carrier for BMP.

Animals↗
PubMed2006

How much sterile saline should be used for efficient lavage during total knee arthroplasty? Effects of pulse lavage irrigation on removal of bone and cement debris.

Bone and polymethyl methacrylate (PMMA) debris particles generated during total knee arthroplasty (TKA) reportedly cause third-body wear. The present study investigated the volume of pulse lavage sufficient for removal of intraoperative PMMA and bone particles. Subjects comprised 8 patients who underwent cemented TKA. Pulse lavage with 8 L of sterile saline was performed using a pulsatile irrigator. During pulse lavage, aspirated fluid was collected in a 1-L aliquot, and the number and size of bone and PMMA particles in each fluid were measured. Image analysis revealed that the number of particles peaked at first lavage and gradually decreased until eighth lavage. Significant differences were found between the first vs second, second vs third, and third vs fourth lavage. However, no significant differences were found beyond the fourth lavage. This study indicated that 4 L of pulse lavage is effective for removing the particles during cemented TKA.

Aged↗
PubMed2006

Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1.

UNLABELLED: Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression of bone matrix proteins. We found that expression of Thbs1 and Thbs2 was reduced in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1-/-Thbs2-/- mice share an edge-to-edge bite. Therefore, reduced expression of thrombospondins may contribute to craniofacial dysmorphism independently of osteosclerosis. INTRODUCTION: Tg mice overexpressing Fra1, a component of the transcription factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell autonomous abnormalities in osteoblasts. The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts. MATERIALS AND METHODS: In osteoblastogenic cultures, altered bone matrix production by Fra1 overexpression was monitored using Alizarin red staining, quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was examined by bone histomorphometry. Craniofacial parameters were measured on radiographs and using CT. RESULTS: Thrombospondin-1 (Thbs1) and thrombospondin-2 (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg mice, as well as Thbs1-/- Thbs2-/- mice, which do not show osteosclerosis, exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism. CONCLUSIONS: These data suggest that reduced expression of thrombospondins in Fra1 Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis.

Animals↗