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Biomedical subjects

Toshikazu Kubo

Publications and source records attributed to Toshikazu Kubo.

At least 19 recordsLinked to original sources
PubMed2007

GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing.

The healing of an injured musculoskeletal system requires an influx of mesenchymal cells that can differentiate into osteoblasts, fibroblasts, chondroblasts, and skeletal myoblasts. However, whether these mesenchymal cells arise from the circulation (bone marrow) or the injured tissues themselves has been controversial. To reveal the spatiotemporal characteristics of the reparative mesenchymal cells, we investigated the healing process after patellar tendon injury using two types of green fluorescent protein (GFP) chimeric rats; one expressing GFP in the circulating cells, and the other expressing it in the patellar tendon. We analyzed the behavior of GFP-positive cells after experimental tendon injury in both chimeric rats to clarify the origin of reparative cells. At 24 h after the injury, the wound contained circulation-derived cells but not tendon-derived cells. Tendon-derived cells first appeared in the wounded area at 3 days after the injury, and had significantly increased in number with time and had maintained a high level of proliferative activity until 7 days after the injury, whereas the circulation-derived cells had decreased in number and had been replaced by the tendon-derived cells. These findings suggest that circulation-derived and tendon-derived cells contribute to the healing of tendons in different periods as part of a biphasic process.

Animals↗
PubMed2007

Low molecular weight phenotype of Apo(a) is a risk factor of corticosteroid-induced osteonecrosis of the femoral head after renal transplant.

OBJECTIVE: Osteonecrosis of the femoral head (ONF) is a necrosis due to disruption of the blood flow. The disease often occurs in association with corticosteroid treatment. The pathology of corticosteroid-induced ONF is unclear, although abnormalities in the coagulation and fibrinolytic systems or in the lipid metabolism have been reported to be involved. We examined the relationships between development of ONF and genetic variations and plasma level of lipoprotein(a) (Lp(a)), which is closely involved in the coagulation and fibrinolytic systems and lipid metabolism. METHODS: The study population consisted of 112 renal transplant patients undergoing corticosteroid treatment. Their apolipoprotein (a) [apo(a)] isoform was determined by Western blotting, and patients were classified into low molecular weight (LMW) or high molecular weight (HMW) groups. The plasma Lp(a) level was measured. Patients were also examined for 3 single-nucleotide polymorphisms (SNP), -773 (G/A), +93 (C/T), and +121 (G/A). Relationships between these 3 genetic factors of Lp(a) and ONF development were examined using statistical methods including multivariate analysis. RESULTS: A strong relationship was observed between the apo(a) molecular weight phenotype and ONF development, with an increased risk of ONF development for the LMW group (adjusted odds ratio 5.75, 95% CI 1.76-18.74, p = 0.0038). No significant relationships were observed between ONF and plasma Lp(a) level and SNP. CONCLUSION: Apo(a) molecular weight phenotype would be a useful predictor of ONF that develops after corticosteroid treatment.

Apoprotein(a)↗
PubMed2006

Carpal tunnel syndrome caused by volar dislocation of the lunate in a patient with rheumatoid arthritis.

We report a case of carpal tunnel syndrome caused by volar dislocation of the lunate in a patient with rheumatoid arthritis. A 74-year-old woman complained of numbness in her fingers. Carpal tunnel syndrome was diagnosed, and carpal tunnel release was performed. However, the symptoms recurred. Three-dimensional computed tomography and magnetic resonance imaging revealed volar dislocation of the lunate and synovitis around the distal radioulnar joint, respectively. Resection of the lunate and the Sauvé-Kapandji procedure were effective.

Aged↗
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

Sulforaphane enhances TRAIL-induced apoptosis through the induction of DR5 expression in human osteosarcoma cells.

Sulforaphane (SFN), a naturally occurring isothiocyanate, is an attractive agent because of its potent anticancer effects. SFN suppresses the proliferation of various cancer cells in vitro and in vivo. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is also one of the most promising candidates for cancer therapeutics owing to its ability to selectively induce apoptosis in tumor cells. In this study, we report that SFN enhances TRAIL-induced apoptosis in human osteosarcoma cells, Saos2 and MG63. The apoptosis induced by co-treatment with SFN and TRAIL was markedly blocked by a dominant negative form of the TRAIL receptor or caspase inhibitors. The combined use of SFN and TRAIL effectively induced Bid cleavage and the activation of caspases 8, 10, 9 and 3 at ineffective concentrations for each agent. SFN upregulated the expression of death receptor 5 (DR5), a receptor for TRAIL, at mRNA and protein levels in a dose-dependent manner. In addition, the SFN-mediated sensitization to TRAIL was reduced by DR5 siRNA, suggesting that the sensitization was at least partially mediated through the induction of DR5 expression. Furthermore, SFN sensitized TRAIL-induced apoptosis in a p53-independent manner. On the other hand, SFN neither induced DR5 protein expression or enhanced TRAIL-induced apoptosis in normal human peripheral blood mononuclear cells. Thus, combined treatment with SFN and TRAIL might be a promising therapy for osteosarcoma.

Anticarcinogenic Agents↗
PubMed2006

Relationship between acetabular labrum evaluation by using radial magnetic resonance imaging and progressive joint space narrowing in mild hip dysplasia.

OBJECTIVE: The aim of this study was to investigate the relationship between abnormal acetabular labrum depicted by radial magnetic resonance and progressive joint space narrowing (JSN) of hip dysplasia. METHODS: Subjects were 23 joints [21 patients; mean age: 35.1 years (16-53 years)] that had acetabular dysplasia with lateral center-edge angle of Wiberg (CE angle) greater than 5 degrees and smaller than 25 degrees (mean, 16.4 degrees ), which did not show any arthrotic changes on plain radiograms and were followed up for 3 years or longer. Radial images of acetabular labrum were classified into three stages. RESULTS: Progression of JSN was not significantly related to CE angle but to progression of MRI stage (P=.006). In multivariate analysis, one rank progression of MRI stage was significantly associated with progression of JSN (adjusted OR=11.41, 95% CI: 1.51-86.24, P=.018). CONCLUSION: Our findings showed that in patients whose acetabular dysplasia has 5-25 degrees CE angle, MRI staging based on radial MRI is a better factor for prediction of progression of JSN than CE angle.

Acetabulum↗
PubMed2006

Transcriptional regulation of the cartilage intermediate layer protein (CILP) gene.

Cartilage intermediate layer protein (CILP) is an extracellular matrix protein abundant in cartilaginous tissues. CILP is implicated in common musculoskeletal disorders, including osteoarthritis and lumbar disc disease. Regulation of the CILP gene is largely unknown, however. We have found that CILP mRNA expression is induced by TGF-beta1 and dependent upon signaling via TGF-beta receptors. TGF-beta1 induction of CILP is mediated by Smad3, which acts directly through cis-elements in the CILP promoter region. Pathways other than Smad3 also are involved in TGF-beta1 induction of CILP. These observations, together with the finding that CILP protein binds and inhibits TGF-beta1, suggest that CILP and TGF-beta1 may form a functional feedback loop that controls chondrocyte metabolism.

Cell Line↗
PubMed2006

Utility of delayed gadolinium-enhanced MRI (dGEMRIC) for qualitative evaluation of articular cartilage of patellofemoral joint.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was used for the measurement of relative proteoglycan depletion of articular cartilage in the patellofemoral (PF) joint following a proprietary protocol, which was compared with the X-ray images, proton density weighted MR images (PDWI) and arthroscopic findings. The study examined 30 knees. The ages ranged from 16 to 74 (average 40.3) years. The Gd-DTPA(2-)containing contrast medium was used in a single dose. The subjects were made to exercise the knee joint for 10 min; and MR images were taken 2 h after intravenous injection of contrast medium. T1-calculated images were produced and the region of interest (ROI) was set as follows. (1) ROI1: entire articular cartilage in a slice through the center of the patella. (2) ROI2: low signal region in T1-calculated images, which were set in a blind fashion by two observers. (3) ROI3: articular cartilage on one side that includes ROI2 where low signal region were detected (medial or lateral). ROI3 was set to examine the contrast of ROI2 with surrounding articular cartilage. The average T1 values of ROI1 was 393.5+/-33.6 ms for radiographic grade 0 and 361.3+/-11.1 ms for grade I, which showed a significant difference (P=0.036). The T1 value of ROI2 was 351.6+/-28.2 ms for grade I, 361.9+/-38.3 ms for grade II, 362.1+/-67.7 ms for grade III, and 297.8+/-54.1 ms for grade IV according to arthroscopic Outerbridge classification. All cases, that demonstrated decrease of T1 values on dGEMRIC (ROI2), showed abnormal arthroscopic or direct viewing findings. The ratio (ROI3/ROI2) in cases of only slight damage classified as Outerbridge grade I (6 cases) was an average of 1.04+/-0.02 and was 1.0 or greater in all cases, thereby indicating well-defined contrast with the surrounding cartilage. The diagnosis of damage in articular cartilage was possible in all 16 cases with radiographic K-L grade I on dGEMRIC, while the intensity changes were not found in 10 of 16 cases on PDWI. The dGEMRIC with a single-dose would be useful on a diagnosis of the area demonstrating early relative proteoglycan depletion in the articular cartilage of the PF joint prior to any discernible changes in the subchondral bone on X-ray images and exceeds to plain MR images for examining deterioration of articular cartilage.

Adolescent↗
PubMed2006

The therapeutic effects of basic fibroblast growth factor contained in gelatin hydrogel microspheres on experimental osteoarthritis in the rabbit knee.

OBJECTIVE: To investigate the therapeutic effects of basic fibroblast growth factor (bFGF) contained in gelatin hydrogel microspheres on osteoarthritis (OA) development in rabbit knee joints. METHODS: (125)I-labeled bFGF contained in gelatin hydrogel microspheres was administered to the knee joints of normal rabbits to confirm the sustained-release kinetics of bFGF in the knee joint. In addition, the expression of proteoglycan core protein messenger RNA was examined using real-time polymerase chain reaction to confirm the anabolic effects on the cartilage treated with the sustained release of bFGF. The bFGF in gelatin hydrogel microspheres was administered to the knee joint once every 3 weeks (a total of twice) from 4 weeks after anterior cruciate ligament transection (ACLT). Ten weeks after ACLT, gross morphologic and histologic examinations were performed. RESULTS: Sustained release of bFGF in the knee joint continued for >7 days and induced the anabolic effects on the cartilage. Intraarticular injections of bFGF contained in gelatin hydrogel microspheres suppressed the progression of OA in the ACLT rabbit model. CONCLUSION: Our findings demonstrated that sustained release of bFGF into the joint had therapeutic effects on OA development in a rabbit model. Our results suggest the potential feasibility of a new conservative treatment for OA.

Animals↗
PubMed2006

Hydrostatic pressure induces apoptosis of chondrocytes cultured in alginate beads.

The purpose of this study was to investigate the influence of hydrostatic pressure (HP) on apoptosis and expression of heat-shock protein 70 (HSP70) in chondrocytes cultured in alginate beads. Chondrocytes were isolated from the articular cartilage of rabbit joints and seeded in alginate beads. The beads in Group A were cultured for less than 24 h after being embedded with the chondrocytes, while those in Group B were cultured for 2 weeks. Both groups were exposed to HP of 10 or 50 MPa for 12 or 24 h. The beads in Groups A and B that were not exposed to HP were regarded as controls. Apoptotic cells induced by exposure to HP were quantified using the TUNEL method. Immunohistochemical analysis for HSP70 and in situ TUNEL analysis were also performed. Apoptotic chondrocytes were not observed in the control cells under atmospheric pressure, whereas apoptosis was observed in the beads in Group A, and the number of apoptotic cells increased as the duration and magnitude of HP increased. On the other hand, we observed no significant population of apoptotic cells in the beads in Group B. Chondrocytes expressing HSP70 were not TUNEL positive in the histological analysis. Excessively strong HP could evoke apoptosis when the extracellular matrix did not accumulate around the chondrocytes. HSP70 expression was related to occurrence of apoptosis that resulted from HP. These findings suggest a mechanism for the pathogenesis of cartilage degeneration in osteoarthritis.

Alginates↗
PubMed2006

Surgical treatment for spinal accessory nerve injury.

We report on the surgical results of spinal accessory nerve injuries between 1992-2003. We operated on 10 patients (9 female, and 1 male) who had injuries of the spinal accessory nerve. All injuries were iatrogenic. The mean age of patients was 39.2 years (range, 20-57 years). The average interval between date of injury and surgery was 7 months (range, 4-12 months). All patients had stiffness and pain in the shoulder girdle. The average active abduction of the shoulder joint was 79.5 degrees (range, 60-100 degrees ) before surgery. End-to-end repairs were performed in 7 cases, and graft repairs were indicated in 3 cases. The mean follow-up period was 18.4 months (range, 8-36 months). The average active abduction of the shoulder joint was 171 degrees (range, 140-180 degrees ) at time of final follow-up.

Accessory Nerve↗
PubMed2006

Age-related changes in the hemodynamics of the femoral head as evaluated by early phase of bone scintigraphy.

OBJECTIVE: The femoral head is reported to be in a markedly hypoemic state as compared with other tissues even under normal conditions, and it is therefore necessary to understand its hemodynamics to investigate the pathogenesis of hip disorders. It is known that aspects of intraosseous hemodynamics including blood flow and blood pool can be evaluated soon after radioisotope administration. In this study, hemodynamic changes in the femoral head according to gender and age were examined by investigating accumulation of radioisotope in the tissue during the early phase of bone scintigraphy. METHODS: The subjects of this study consisted of 58 joints of 31 men and 75 joints of 41 women, whose ages ranged from 15 to 87 years (average age: 67.9 years). Images of bone scintigraphy were obtained for 15 to 20 minutes at 5 minutes and at 3 hours after radioisotope administration. The ratio of accumulation in the femoral head to that in the diaphysis (head-to-diaphysis ratio, HD ratio) was calculated. RESULTS: HD ratios obtained 15-20 minutes later ranged from 0.01 to 7.35 (1.88 +/- 0.91, mean +/- SD). HD ratios decreased with age, and a significant inverse correlation was observed between age and HD ratio, demonstrating a correlation coefficient of -0.27 (p = 0.001). The HD ratio among men was 0.01-3.57 (1.66 +/- 0.71), while that among women was 0.53-7.35 (2.05 +/- 1.01), and a significant difference was observed in HD ratio between men and women (p = 0.02). There was a significant difference in HD ratios between men and women in their teens to forties (p = 0.03), while no significant differences was observed in the other age groups.. HD ratios obtained 3 hours later ranged from 0.44 to 6.32 (1.95 +/- 0.79, mean +/- SD), and no significant correlation was observed between age and HD ratio, demonstrating a correlation coefficient of -0.14. CONCLUSION: The present study demonstrated that blood flow and blood pool of the femoral head decrease with aging particularly in women. This hemodynamic deterioration of the femoral head caused by aging may have an effect on the onset and progression of hip disorders by influencing bone metabolism.

Adolescent↗
PubMed2006

Atlantoaxial subluxation in different intraoperative head positions in patients with rheumatoid arthritis.

BACKGROUND: Disorders of the cervical spine are often observed in patients with rheumatoid arthritis (RA). However, the best head position for RA patients with atlantoaxial subluxation in the perioperative period is unknown. This study investigated head position during general anesthesia for the patients with RA and proven atlantoaxial subluxation. METHODS: During anesthesia of patients with RA and proven atlantoaxial subluxation, the authors used fluoroscopy to obtain a lateral view of the upper cervical spine in four different positions: the mask position, the intubation position, the flat pillow position, and the protrusion position. Copies of the still fluoroscopic images were used to determine the anterior atlantodental interval, the posterior atlantodental interval, and the angle of atlas and axis (C1-C2 angle). RESULTS: The anterior atlantodental interval was significantly smaller in the protrusion position (2.3 mm) than in the flat pillow position (5.1 mm) (P < 0.05). The posterior atlantodental interval was significantly greater in the protrusion position (18.9 mm) than in the flat pillow position (16.2 mm) (P < 0.05). The C1-C2 angle was, on average, 9.3 degrees greater in the protrusion position than in the flat pillow position (P < 0.05). CONCLUSION: This study showed that the protrusion position using a flat pillow and a donut-shaped pillow during general anesthesia reduced the anterior atlantodental interval and increased the posterior atlantodental interval in RA patients with atlantoaxial subluxation. This suggests that the protrusion position, which involves support of the upper cervical spine and extension at the craniocervical junction, might be advantageous for these patients.

Adult↗
PubMed2006

Life expectancy and functional prognosis after femoral neck fractures in hemodialysis patients.

OBJECTIVES: To identify whether differences exist in the outcomes between patients undergoing hemodialysis and elderly nonhemodialysis patients with a femoral neck fracture. DESIGN: Retrospective review. SETTING: Level 1 trauma center. PATIENTS/INTERVENTIONS: A total of 71 femoral neck fractures in 62 patients undergoing hemodialysis treated nonoperatively or operatively. MAIN OUTCOME MEASUREMENTS: Clinical outcomes were analyzed to identify factors that may be correlated with life expectancy and functional prognosis. RESULTS: The overall survival rates in this study at 1-year and 5-years postfracture were found to be 89.8% and 51.5%, respectively. There were significant correlations among the survival rate, patients' age, type of treatment, prefracture ambulation status, and prefracture activities of daily living status. However, using multivariate analysis, the only significant predictor of life expectancy was prefracture ambulation status. As for functional prognosis, the rates of total ambulation recovery and total activities of daily living recovery at 1-year postfracture were 50.0% and 71.2%, respectively. Both patients' age and age at the onset of hemodialysis may contribute considerably to functional prognosis in patients undergoing hemodialysis after femoral neck fracture. CONCLUSIONS: The present study suggests that the clinical outcomes of patients with femoral neck fractures who undergo hemodialysis are considerably superior to those of previous studies. In addition, when those fractures are treated surgically with specific management in patients undergoing hemodialysis, it may be possible to expect a life expectancy and functional prognosis similar to elderly nonhemodialysis patients with hip fractures.

Adult↗
PubMed2006

Radiological grading of cervical destructive spondyloarthropathy in long-term hemodialysis patients.

On the basis of the radiological findings of dialysis patients, we made a radiological grading and analyzed the progression of destructive spondyloarthropathy (DSA) using this grading system. In this system, the radiological features of the vertebral endplates and intervertebral disc spaces were divided into 4 grades (grade 0 to grade III). Grades II and III were defined as DSA. In this study, out of the 787 dialysis patients (447 men and 340 women, mean age: 60.0 years) examined, 133 patients (16.9%) were diagnosed with DSA. During 7 years follow-up, 108 dialysis patients were examined to investigate the clinical characteristics of DSA. Fifteen of 90 non-DSA cases progressed to DSA. Six of 18 DSA cases showed grade progression. The duration required for progression of each grade was analyzed. A new classification of DSA, namely, degenerative DSA and classical DSA, was applied in this study. The degenerative DSA showed faster grade progression than the classical DSA. Therefore, great attention should be paid in the radiological follow-up of elderly patients with grade I who start dialysis at an old age.

Adult↗
PubMed2006

Outcomes of new pogo-stick brace for Legg-Calvé-Perthes' disease.

In 1992, the authors developed a non-weightbearing unilateral ambulatory hip abduction brace, which was named the new pogo-stick brace for unilateral Legg-Calve -Perthes' disease. The hip abduction angle of the new pogo-stick brace was adjustable 45 degrees . The advantage of this brace was that even in the sitting position, the hip abduction angle was maintained. Twenty patients were treated with unilateral LCPD using the new pogo-stick brace. In the Catterall classification, one patient was classified as group 2, 17 as group 3, two as group 4. In Herring classification, one patient was classified as group A, 17 as group B, two as group C. Ultrasonography was performed to determine containment of the hip joints, and the abduction angle of the new pogo-stick brace was adjusted to get better containment, every 2 months. Mose's and acetabular head index methods were used for radiographic evaluation, and classified into good, fair and poor groups both at the primary healing and at the final follow-up. Total evaluation was defined as worse group between Mose's method and acetabular head index method. The average time from onset of disease to the primary healing was 25 months. The average bracing period was 21 months. The average follow-up period was 94 months. At the final follow-up appointment, patients who were classified into good and fair groups were 85% in Mose's method, 95% in acetabular head index method, 85% in total evaluation. In Stulberg classification, the total number of patients who were classified into classes I and II was 85%. The outcome of the new pogo-stick brace was not worse than that of any other treatment method, and was better than that of other unilateral ambulatory braces.

Braces↗