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Tetsuya Tomita

Publications and source records attributed to Tetsuya Tomita.

At least 19 recordsLinked to original sources
PubMed2007

In vivo three-dimensional skeletal alignment analysis of the hindfoot valgus deformity in patients with rheumatoid arthritis.

The purpose of this study was to analyze the skeletal alignment of the hindfoot valgus deformity in patients with rheumatoid arthritis using bone models reconstructed from three-dimensional computerized tomography data. Computed tomography was performed on 21 feet of patients with rheumatoid arthritis, and magnetic resonance imaging was taken of 10 normal feet of eight volunteers. An image processing system was used to create bone models and analyze the three-dimensional displacement of the calcaneus, talus, navicular, and cuboid bones. With a standard coordinate system in the distal tibia and a local coordinate system in each bone of the hindfoot, three rotational parameters and three translational parameters were used to evaluate the relative displacement. The talus showed plantar flexion. Both the calcaneus and navicular bones had valgus and lateral shift displacements. However, the cuboid had no displacement relative to the calcaneus, and the navicular showed no displacement relative to the cuboid. The calcaneus, navicular, and cuboid bones have the same pattern of deformity in patients with rheumatoid arthritis. This three-dimensional image-based technique successfully quantified the hindfoot valgus deformity resulting from rheumatoid arthritis and is beneficial for better understanding the deformity pathomechanism.

Adult↗
PubMed2006

Radiographic study of joint destruction patterns in the rheumatoid elbow.

Knowledge of the pattern of joint destruction is important for planning the therapeutic approach to rheumatoid arthritis (RA) of the elbow. Accordingly, we carried out a large-scale radiographic study with the objective of elucidating the joint destruction pattern in rheumatoid elbows. From 2001 through 2003, we examined and took plain X-rays of both elbows of 193 RA patients (i.e., 386 elbows), consisting of 18 men and 175 women, with a mean age of 57.0 years. Radiographic images of the elbow joints were used to classify the degree of bone loss in various zones on the elbow joint surface into four grades of severity, and joint destruction was compared between the left and right elbows. In addition, correlation in the extent of bone loss between each of the zones of the same elbow and differences in the extent of bone loss were analyzed statistically. The results showed direct correlations for destruction of the elbow joint surface among the zones for the left and right elbow joints and in the same elbow joint. However, more severe destruction was observed on the radial side of the humeral trochlea, and it was surmised that destruction of the elbow joint must begin at that site and gradually spread mediolaterally. In addition, in the same elbow joint, the correlation in the degree of bone loss between the trochlea of humerus and the trochlear notch was especially strong, indicating that the bone destruction at both sites represented mirror lesions. We conclude that when performing radiographic diagnosis of the joint damage in the rheumatoid elbow, knowledge of this pattern of joint destruction will be useful for assessing whether there is joint destruction in the initial stage and for deciding the therapeutic approach.

Adult↗
PubMed2006

Enhanced expression of mRNA for nuclear factor kappaB1 (p50) in CD34+ cells of the bone marrow in rheumatoid arthritis.

Bone marrow CD34+ cells from rheumatoid arthritis (RA) patients have abnormal capacities to respond to tumor necrosis factor (TNF)-alpha and to differentiate into fibroblast-like cells producing matrix metalloproteinase (MMP)-1. We explored the expression of mRNA for nuclear factor (NF)kappaB in RA bone marrow CD34+ cells to delineate the mechanism for their abnormal responses to TNF-alpha. CD34+ cells were purified from bone marrow samples obtained from 49 RA patients and 31 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The mRNAs for NFkappaB1 (p50), NFkappaB2 (p52) and RelA (p65) were examined by quantitative RT-PCR. The expression of NFkappaB1 mRNA in bone marrow CD34+ cells was significantly higher in RA than in OA, whereas there was no significant difference in the expression of mRNA for NFkappaB2 and RelA. The expression of NFkappaB1 mRNA was not correlated with serum C-reactive protein or with the treatment with methotrexate or oral steroid. Silencing of NFkappaB1 by small interfering RNA abrogated the capacity of RA bone marrow CD34+ cells to differentiate into fibroblast-like cells and to produce MMP-1 and vascular endothelial growth factor upon stimulation with stem cell factor, granulocyte-macrophage colony stimulating factor and TNF-alpha without influencing their viability and capacity to produce beta2-microglobulin. These results indicate that the enhanced expression of NFkappaB1 mRNA in bone marrow CD34+ cells plays a pivotal role in their abnormal responses to TNF-alpha and, thus, in the pathogenesis of RA.

Adult↗
PubMed2006

THR0921, a novel peroxisome proliferator-activated receptor gamma agonist, reduces the severity of collagen-induced arthritis.

THR0921 is a novel peroxisome proliferator-activated receptor gamma (PPARgamma) agonist with potent anti-diabetic properties. Because of the proposed role of PPARgamma in inflammation, we investigated the potential of orally active THR0921 to inhibit the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in DBA/1J mice by the injection of bovine type II collagen in complete Freund's adjuvant on days 0 and 21. Mice were treated with THR0921 (50 mg/kg/day) starting on the day of the booster injection and throughout the remaining study period. Both clinical disease activity scores as well as histological scores of joint destruction were significantly reduced in mice treated with THR0921 compared to untreated mice. Proliferation of isolated spleen cells, as well as circulating levels of IgG antibody to type II collagen, was decreased by THR0921. Moreover, spleen cell production of IFN-gamma, tumor necrosis factor (TNF)-alpha and IL-1beta in response to exposure to lipopolysaccharide or type II collagen was reduced by in vivo treatment with THR0921. Steady state mRNA levels of TNF-alpha, IL-1beta, monocyte chemotactic protein-1 and receptor activator of nuclear factor kappaB ligand (RANKL) in isolated joints were all decreased in mice treated with THR0921. Finally, THR0921 inhibited osteoclast differentiation of bone marrow-derived cells stimulated with macrophage colony-stimulating factor and RANKL. In conclusion, THR0921 attenuates collagen-induced arthritis in part by reducing the immune response. As such, PPARgamma may be an important therapeutic target for rheumatoid arthritis.

Animals↗
PubMed2006

Inhibitory effect of ribbon-type NF-kappaB decoy oligodeoxynucleotides on osteoclast induction and activity in vitro and in vivo.

In this study we examined the effect of ribbon-type (circular-type) NF-kappaB decoy oligodeoxynucleotides (RNODN) on osteoclast induction and activity. We extracted bone marrow cells from the femurs of rats and incubated non-adherent cells with receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). First, transfer efficiency into osteoclasts and their precursors, resistance to exonuclease, and binding activity of decoy to NF-kappaB were examined. Next, to examine the effect of RNODN on osteoclast induction and activity, osteoclast differentiation and pit formation assays were performed. RNODN were injected into the ankle joints of rats with collagen-induced arthritis. Joint destruction and osteoclast activity were examined by histological study. The resistance of RNODN to exonuclease and their binding activity on NF-kappaB were both greater than those of phosphorothionated NF-kappaB decoy oligodeoxynucleotides. The absolute number of multinucleate cells scoring positive for tartrate-resistant acid phosphatase was significantly decreased in the RNODN-treated group. The average calcified matrix resorbed area was significantly decreased in the RNODN-treated group. Histological study showed marked suppression of joint destruction and osteoclast activity by intra-articular injection of RNODN. These results suggest the inhibitory effect of RNODN on the induction and activity of osteoclasts. Direct intra-articular injection of RNODN into the joints may be an effective strategy for the treatment of arthritis.

Animals↗
PubMed2006

E2F decoy oligodeoxynucleotide ameliorates cartilage invasion by infiltrating synovium derived from rheumatoid arthritis.

This study examined the ability of E2F decoy oligodeoxynucleotides (ODN) to inhibit proliferation of synovial fibroblasts derived from patients with rheumatoid arthritis (RA). The effect of E2F decoy ODN on cartilage invasion by RA synovium in a murine model of human RA was also investigated. E2F decoy ODN were introduced into synovial tissue and synovial fibroblasts derived from patients with RA using hemagglutinating virus of Japan (HVJ)-liposomes. The effect of E2F decoy ODN on synovial fibroblast proliferation was evaluated by MTT assay and by RT-PCR for the cell cycle regulatory genes proliferating-cell nuclear antigen (PCNA) and cyclin-dependent kinase 2 (cdk2). Changes in production of inflammatory mediators by RA synovial tissue following transfection with E2F decoy ODN were assessed by ELISA. Human cartilage and RA synovial tissue transfected with E2F decoy ODN were co-transplanted in severe combined immunodeficient (SCID) mice. After 4 weeks, the mice were sacrificed and the implants histologically examined for inhibition of cartilage damage by E2F decoy ODN. E2F decoy ODN resulted in significant inhibition of synovial fibroblast proliferation, corresponding with reduced expression of PCNA and cdk2 mRNA in synovial fibroblasts. The production of interleukin-1beta (IL-1beta), IL-6 and matrix metalloproteinase (MMP)-1 by synovial tissue was also significantly inhibited by the introduction of E2F decoy ODN. Further, in an in vivo model, cartilage that was co-implanted with RA synovial tissue transfected with E2F decoy ODN exhibited no invasive and progressive cartilage degradation. These data demonstrate that transfection of E2F decoy ODN prevents cartilage destruction by inhibition of synovial cell proliferation, and suggest that transfection of E2F decoy ODN may provide a useful therapeutic approach for the treatment of joint destruction in arthritis.

Animals↗
PubMed2005

[Development of three-dimensional kinematic analysis system for artificial knee implants using X-ray fluoroscopic imaging].

To achieve quantitative assessment of 3D dynamic motion of artificial knee implants under clinical conditions, we developed a 3D kinematic analysis system using X-ray fluoroscopic imaging. The 3D pose-estimation technique for knee implants was built on a 2D/3D registration algorithm, which determines the spatial pose for each femoral and tibial component from the knee implant contours and computer-assisted design (CAD) models of the implant. In order to validate the accuracy of the 3D pose estimation and the system, computer simulation and in vitro tests were performed using images of knee implants taken in 10 different poses with respect to X-ray focus. Computer simulation tests showed that the root mean square errors (RMSE) for all variables were less than 1.0 mm 1.0 degrees. In vitro tests showed that the RMSE for translation perpendicular to the X-ray image plane was about 1.5 mm, while the accuracy of the remaining two translational and three rotational variables was found to be sufficient for analyzing knee kinematics. Computation time in 3D pose estimation was then obtained in less than 30 seconds for each frame. In clinical application, dynamic movement in deep knee bending was quantitatively analyzed, and the feasibility and effectiveness of the system was demonstrated.

Algorithms↗
PubMed2005

Visualization of femorotibial contact in total knee arthroplasty using X-ray fluoroscopy.

The purpose of this study was to build a visualization technique of the femorotibial contact in fixed-bearing total knee arthroplasty (TKA) using X-ray fluoroscopy, and to apply this technique to a TKA patient during dynamic motion. In vivo kinametcis of the metallic knee implant was determined using a 2D/3D registration technique, which uses computer assisted design (CAD) model of the implant to estimate the 3D pose of radiopaque metallic femoral and tibial components from a single-plane fluoroscopic image. In fixed-bearing TKA, a 3D pose of radiolucent tibial polyethylene insert can be determined from the estimated pose of the tibial component. To visualize femorotibial contact, the proximity between surfaces of femoral component and tibial insert was calculated, and mapped onto the insert surface model. For the clinical application, dynamic states of contact on the tibial insert were observed including axial rotation and unilateral loading during knee flexion, and post-cam contact of posterior stabilized TKA. The present technique provided us new information and enabled us to better understand the relationship between in vivo knee kinematics and articular shape of the implant.

Arthroplasty, Replacement, Knee↗
PubMed2004

Human interleukin-1-induced murine osteoclastogenesis is dependent on RANKL, but independent of TNF-alpha.

Although interleukin-1 (IL-1) has been implicated in the pathogenesis of inflammatory osteolysis, the means by which it recruits osteoclasts and promotes bone destruction are largely unknown. Recently, a cytokine-driven, stromal cell-free mouse osteoclastogenesis model was established. A combination of macrophage colony stimulating factor (M-CSF) and receptor activator of NFkappaB ligand (RANKL) was proven to be sufficient in inducing differentiation of bone marrow hematopoietic precursor cells to bone-resorbing osteoclasts in the absence of stromal cells or osteoblasts. This study utilizes this model to examine the impact of human IL-1beta on in vitro osteoclastogenesis of bone marrow progenitor cells. We found that osteoclast precursor cells failed to undergo osteoclastogenesis when treated with IL-1 alone. In contrast, IL-1 dramatically up-regulated osteoclastogenesis by 2.5- to 4-folds in the presence of RANKL and M-CSF. The effect can be significantly blocked by IL-1 receptor antagonist (p < 0.01). Tumor necrosis factor-alpha (TNF-alpha) was undetectable in the culture medium of differentiating osteoclasts induced by IL-1. Adding exogenous TNF-alpha neutralizing antibody had no influence on the IL-1-induced effect as well. These results show that in the absence of stromal cells, IL-1 exacerbates osteoclastogenesis by cooperating with RANKL and M-CSF, while TNF-alpha is not involved in this IL-1-stimulated osteoclast differentiation pathway.

Animals↗
PubMed2004

Enhanced generation of endothelial cells from CD34+ cells of the bone marrow in rheumatoid arthritis: possible role in synovial neovascularization.

OBJECTIVE: To examine the capacity of bone marrow CD34+ cells to generate endothelial cells, in order to assess the role of bone marrow in neovascularization in the synovium of rheumatoid arthritis (RA). METHODS: CD34+ cells purified from the bone marrow of 13 patients with active RA and 9 control subjects (7 osteoarthritis [OA] patients and 2 healthy individuals) were cultured in the presence of stem cell factor (10 ng/ml) and granulocyte-macrophage colony-stimulating factor (1 ng/ml). After 18 days of incubation, the generation of endothelial cells was assessed by flow cytometry. The generation of endothelial cells was compared with the degree of vascularization in the synovial tissues and with the microvessel densities in the synovium, as determined by microscopy. The expression of vascular endothelial growth factor receptor 2/kinase insert domain receptor (KDR) messenger RNA (mRNA) in CD34+ cells was examined by quantitative reverse transcription-polymerase chain reaction. RESULTS: The generation of CD14+ cells from bone marrow-derived CD34+ cells from RA patients was comparable to that from control subjects. However, the generation of von Willebrand factor (vWF)-positive cells and CD31+/vWF+ cells from RA bone marrow-derived CD34+ cells was significantly higher than that from control subjects (P = 0.004 and P = 0.030, respectively). The generation of vWF+ cells from bone marrow CD34+ cells correlated significantly with the microvessel densities in the synovial tissues (r = 0.569, P = 0.021). Finally, RA bone marrow CD34+ cells expressed KDR mRNA at higher levels than OA bone marrow CD34+ cells. CONCLUSION: These results indicate that RA bone marrow CD34+ cells have enhanced capacities to differentiate into endothelial cells in relation to synovial vascularization. The data therefore suggest that bone marrow CD34+ cells might contribute to synovial neovascularization by supplying endothelial precursor cells and, thus, play an important role in the pathogenesis of RA.

Aged↗
PubMed2004

Localization of RANKL in osteolytic tissue around a loosened joint prosthesis.

Osteoclastogenesis is a key event of the cellular reaction in prosthetic loosening. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) were used to study the localization and expression of receptor activator of nuclear factor kappa B ligand (RANKL), a potent factor for osteoclastogenesis in the membranous tissue formed around loosened prosthetic joint implants. RANKL was identified in a wide variety of cells appearing in this membranous tissue. At least three types of RANKL-positive cells were identified, including prolyl 4-hydroxylase (PH)-positive fibroblast lineage cells, CD68 cells, and tartrate-resistant acid phosphatase (TRAP)-positive mononuclear and multi-nucleated macrophage lineage cells. Tumor necrosis factor (TNF)-alpha-converting enzyme (TACE) was colocalized with RANKL in these cells, suggesting the in-situ release of this factor. RT-PCR confirmed the actual expression of the RANKL and TACE genes in the tissues around the loosened implant. These observational findings indicate the possible synthesis of RANKL by fibroblast and macrophage lineage cells, and suggest the in-situ involvement of RANKL in both osteoclastogenesis and osteoclastic bone resorptive events occurring in prosthetic joint loosening.

ADAM Proteins↗
PubMed2004

In vivo kinematics of mobile-bearing knee arthroplasty in deep knee bending motion.

The current study aimed to analyze kinematics during deep knee bending motion by subjects with fully congruent mobile-bearing total knee arthroplasties allowing axial rotation and anteroposterior (AP) gliding. Twelve subjects were implanted with Dual Bearing Knee prostheses (DBK, slot type: Finsbury Orthopaedics, Surrey, UK). These implants include a mobile-bearing insert that is fully congruent with the femoral component throughout flexion and allows axial rotation and limited AP translation. Sequential fluoroscopic images were taken in the sagittal plane during loaded knee bending motion. In vivo kinematics were analyzed using a two- to three-dimensional registration technique, which uses computer-assisted design models to reproduce the spatial position of femoral and tibial components from single-view fluoroscopic images. The average femoral component demonstrated 13.4 degrees external axial rotation for 0-120 degrees flexion. On average, the medial condyle moved anteriorly 6.2 mm for 0-100 degrees flexion, then posteriorly 4.0 mm for 100-120 degrees flexion. On average, the lateral condyle moved anteriorly 1.0 mm for 0-40 degrees flexion, then posteriorly 8.7 mm for 40-120 degrees flexion. The typical subject exhibited a lateral pivot pattern from extension to 60 degrees flexion and a central pivot pattern from 60 degrees to 100 degrees flexion, patterns that are not usually observed in normal knees. Subsequently from 100 degrees to 120 degrees flexion, a rollback pattern was reproduced in which bilateral condyles moved backward.

Aged↗
PubMed2004

Improvement of depth position in 2-D/3-D registration of knee implants using single-plane fluoroscopy.

Two-dimensional (2-D)/three-dimensional (3-D) registration techniques using single-plane fluoroscopy are highly important for analyzing 3-D kinematics in applications such as total knee arthroplasty (TKA) implants. The accuracy of single-plane fluoroscopy-based techniques in the determination of translation perpendicular to the image plane (depth position), however, is relatively poor because a change in the depth position causes only small changes in the 2-D silhouette. Accuracies achieved in depth position using conventional 2-D/3-D registration techniques are insufficient for clinical applications. Therefore, we propose a technique for improving the accuracy of depth position determination in order to develop a system for analyzing knee kinematics over the full six degrees of freedom (6 DOF) using single-plane fluoroscopy. In preliminary experiments, the behaviors of errors for each free variable were quantified as evaluation curves by examining changes in cost function with variations in the free variable. The evaluation curve for depth position was more jagged, and the curve peak less pointy, compared to the evaluation curves of the other five variables, and the curve was found to behave differently. Depth position is therefore optimized independently of the other variables, using an approximate evaluation curve of depth position prepared after initial registration. Accuracy of the proposed technique was evaluated by computer simulation and in vitro tests, with validation of absolute position and orientation performed for each knee component. In computer simulation tests, root-mean-square error (RMSE) in depth position was improved from 2.6 mm (conventional) to 0.9 mm (proposed), whereas for in vitro tests, RMSE improved from 3.2 mm to 1.4 mm. Accuracy of the estimation of the remaining two translational and three rotational variables was found to be almost the same as that obtained by conventional techniques. Results of in vivo tests are also described in which the possibility of full 6 DOF kinematic analysis of TKA implants is shown.

Algorithms↗
PubMed2003

Total ankle replacement in rheumatoid arthritis.

We reviewed 21 patients with rheumatoid arthritis who had a total ankle replacement between 1984 and 2000. The average follow-up was 72 (15-169) months. Clinical results were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score. At the latest review, three ankles had been revised. Two ankles were excellent, seven good, three fair, and 12 poor. Eleven patients with 13 ankles had residual pain, with radiographs showing a high incidence of radiolucent lines. Migration of the tibial component was seen in 13 ankles and collapse of talus in nine. Although clinical results were poor, patient satisfaction was not.

Adult↗
PubMed2003

Monoclonal antibody to parathyroid hormone-related protein induces differentiation and apoptosis of chondrosarcoma cells.

We investigated the effects of treatment with anti-parathyroid hormone-related protein (1-34) monoclonal murine antibody (anti-PTHrP MoAb) on apoptosis and the differentiation of chondrosarcoma HTB-94 cells. Treatment with anti-PTHrP MoAb accelerated apoptosis of HTB-94 cells in a dose-dependent manner, and anti-PTHrP MoAb also promoted the chondrogenic differentiation of HTB-94 cells. The induction of apoptosis by anti-PTHrP MoAb via imbalance of Bcl-2/Bax ratio and activation of caspase-3 may provide a mechanistic explanation for its potential antitumor effects. Our results suggest the possibility that anti-PTHrP MoAb may be beneficial as a new treatment for chondrosarcoma.

Antibodies, Monoclonal↗
PubMed2003

Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653.

OBJECTIVE: FR167653 is a potent inhibitor of p38 mitogen-activated protein kinase (MAPK) and inhibits tumor necrosis factor alpha (TNFalpha) and interleukin-1 beta (IL-1 beta) production in inflammatory cells. In this study we investigated the effect of FR167653 on collagen-induced arthritis (CIA). METHODS: Rats with CIA were subcutaneously injected with FR167653 (32 mg/kg/day) starting on the day of the booster injection (day 7) in the prophylactic treatment group and after the onset of arthritis (day 21) in the therapeutic treatment group. Hind-paw swelling, body weight, radiographic and histologic scores, and osteoclast number were evaluated. Cytokine levels in the serum and tissue were assessed by enzyme-linked immunosorbent assays. Flow cytometric analysis of T lymphocytes from bone marrow was performed. The effect of FR167653 on in vitro osteoclast formation induced by soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and TNFalpha was examined. RESULTS: Swelling of hind paws and loss of weight occurred in the CIA rats, but this was not evident in the prophylactic treatment group. Therapeutic treatment also significantly reduced paw swelling. The mean radiographic and histologic scores as well as the osteoclast numbers were significantly lower in the treatment group than in the CIA rats without treatment. FR167653 treatment reduced the serum levels of TNFalpha and IL-1 beta, lowered the IL-1 beta concentration in the ankle joints, and decreased the CD4-,CD8a+ T cell population in bone marrow. Furthermore, FR167653 inhibited the osteoclast-like cell differentiation induced by both sRANKL and TNFalpha in vitro. CONCLUSION: FR167653 prevents the onset of arthritis in a prophylactic treatment model and suppresses the progression of joint destruction in a therapeutic treatment model, suggesting that p38 MAPK is a potential therapeutic target for rheumatoid arthritis.

Animals↗
PubMed2003

Gene therapy for arthritis.

Recent progress in molecular biology has provided application of gene transfer methods in arthritis. Two clinical trails using ex vivo retrovirus mediated delivery of interleukin -1 receptor antagonist gene for rheumatoid arthritis has begun in USA and Germany. However, there are still many issues to be elucidated; one is the development of gene delivery system, and the other is the selection of therapeutic gene. Arthritis is nonlethal disease, and safety is one of the important issues. Currently viral mediated vectors are major even in clinical trials however, non viral efficient gene transfer system should be developed in future. Recently the application of DNA technologies, such as antisense oligonucleotide (ODN) strategies to regulate the transcription of disease-related genes in vivo, has significant therapeutic potential. Transfection of cis-clement double-stranded oligonucleotides (decoy ODN) for nuclear factor kappaB binding site has been reported as a new powerful tool in arthritis. The concept of regulation the disease related gene expression at the level of transcriptional factor may be more therapeutic effects compared with monotherapy in arthritis.

Animals↗