Biomedical subjects

Yasushi Oshima

Publications and source records attributed to Yasushi Oshima.

15 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activity until 7 days after the injury, whereas the circulation-derived cells had decreased in number and had been replaced by the tendon-derived cells.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↗

PubMed2006

Negative regulation of osteoclastogenesis by ectodomain shedding of receptor activator of NF-kappaB ligand.

Receptor activator of NF-kappaB ligand (RANKL) is a transmembrane glycoprotein that has an essential role in the development of osteoclasts. The extracellular portion of RANKL is cleaved proteolytically to produce soluble RANKL, but definite RANKL sheddase(s) and the physiologic function of RANKL shedding have not yet been determined. In the present study, we found that matrix metalloproteinase (MMP) 14 and a disintegrin and metalloproteinase (ADAM) 10 have strong RANKL shedding activity. In Western blot analysis, soluble RANKL was detected as two different molecular weight products, and RNA interference of MMP14 and ADAM10 resulted in a reduction of both the lower and higher molecular weight products. Suppression of MMP14 in primary osteoblasts increased membrane-bound RANKL and promoted osteoclastogenesis in cocultures with macrophages. Soluble RANKL produced by osteoblasts from MMP14-deficient mice was markedly reduced, and their osteoclastogenic activity was promoted, consistent with the findings of increased osteoclastogenesis in vivo. RANKL shedding is an important process that down-regulates local osteoclastogenesis.

ADAM Proteins↗

PubMed2006

Erk pathways negatively regulate matrix mineralization.

Skeletal mineralization is an important step regulating the mechanical properties of the calcified tissues, but molecular events underlying mineralization still remain elusive. We examined the role of extracellular signal-regulated kinase (Erk) pathways in matrix mineralization of osteogenic cells both in vitro and in vivo. Matrix mineralization by preosteocytic MLO-A5 cells and osteoblastic MC3T3-E1 cells was increased by either PD98059 Mek inhibitor treatment or adenovirus vector-mediated dominant negative Ras (Ras(DN)) expression and was suppressed by Erk activation by platelet-derived growth factor (PDGF) treatment or constitutively active Mek1 (Mek(CA)) expression. Administration of adenovirus vectors carrying Ras(DN) gene onto the calvaria of 1-day-old mice increased the mineralization of the tissues, while that of the Mek(CA) adenovirus suppressed it. These results suggest that the Erk pathway is a negative regulator of the matrix mineralization both in vitro and in vivo.

Actins↗

PubMed2006

Usefulness of arterial blood gas analysis and D-dimer measurement in the assessment of pulmonary embolism after orthopedic surgery.

BACKGROUND: Deep venous thrombosis (DVT) and pulmonary embolism (PE) after spinal or lower extremity surgery are well recognized as common complications. Since 1995 we have investigated the incidence of PE after orthopedic surgery using ventilation-perfusion (V/Q) lung scans, and the prevalence of PE was about 10%. With a view to detecting early-stage PE by simple examinations, we evaluated the use of both the blood gas analysis and the D-dimer measurement after spinal or lower extremity surgery. METHODS: Altogether, 85 patients who underwent spinal or lower extremity surgery were eligible for the study. Pneumatic sequential leg compression devices (PSLCDs) were utilized continuously both intra- and postoperatively. Arterial blood gas analysis and D-dimer measurement were performed pre- and postoperatively on days 3 and 7. We set lung scan criteria as follows: postoperative decrease in Pa(O2) (deltaPa(O2) by > or = 10 torr (group G), postoperative D-dimer of > or = 1 microg/ml (group D), or both. Patients with the criteria went on to undergo lung scans, and PE was diagnosed by the existence of any mismatch between ventilation-perfusion (V/Q) lung scans. RESULTS: A total of 44 (51.8%) patients met the lung scan criteria and underwent perfusion lung scans, 10 (11.7%) of whom were diagnosed as PE. In groups G and D, about 30% showed PE. Moreover, six (85.7%) of the seven patients with both criteria showed a significant increase (83.7%) in the prevalence of PE. CONCLUSIONS: Patients with the above criteria showed a high prevalence of PE. Moreover, 10 (11.7%) of the 85 patients were diagnosed as having PE, which corresponded to the prevalence in our former studies where lung scans were performed in all patients. The blood gas analysis and the D-dimer measurement may be utilized as the first screening examinations.

Adolescent↗

PubMed2005

The fate of host and graft cells in early healing of bone tunnel after tendon graft.

BACKGROUND: The behavior of host and graft cells during the healing process after autologous tendon graft has not been elucidated. HYPOTHESIS: Host cells will integrate into the bone-tendon interface and contribute to cellular repopulation of the graft. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve-week-old, genetically identical, female green fluorescent protein transgenic rats (n = 20) and wild-type rats (n = 20) were used. The rats were divided into 2 experimental groups. In group A, the Achilles tendons of wild-type rats were harvested and transplanted into the transcondylar femoral bone tunnels of green fluorescent protein rats. In group B, the Achilles tendons of green fluorescent protein rats were transplanted into a transcondylar femoral bone tunnel of wild-type rats. Immediately after transplantation (time zero) and at 1, 2, and 4 weeks after the transplantation, distal femoral epiphyses were harvested and cut into 14-mum serial sagittal frozen sections. The sections were examined with a confocal laser-scanning microscope to quantify green fluorescent protein-positive cell survival. RESULTS: At time zero, only host cells in group A and only graft cells in group B demonstrated green fluorescent protein signals. At 1 week in group A, many green fluorescent protein-positive cells were found in the graft. In group B, a few green fluorescent protein-positive cells were found in the graft. At 2 and 4 weeks in group A, many green fluorescent protein-positive cells were detected in the graft, but green fluorescent protein-positive cells had disappeared completely in group B. CONCLUSION: Host cells, rather than graft cells, contribute to repair of the bone-tendon interface and the remodeling of grafts after simulated autologous tendon graft.

Achilles Tendon↗

PubMed2005

Central motor conduction in cervical dystonia with cervical spondylotic myelopathy.

OBJECTIVES: It has been known that cervical dystonia develops secondarily to spinal cord injuries as secondary dystonia. However, little is known about the pathophysiological mechanism. PATIENTS AND METHODS: We examined motor and sensory conduction in six patients with symptomatic cervical dystonia by transcranial magnetic stimulation (TMS). All of the patients exhibited unilateral head rotation. They had symptoms corresponding to cervical myelopathy and felt discomfort in the neck, shoulders or arms before involuntary movement occurred. RESULTS: Although the overall central motor conduction time (CMCT) was not different from that of normal controls, contralateral CMCT was significantly delayed compared to ipsilateral CMCT (p<0.05). The results of somatosensory evoked potential study demonstrated that contralateral central conduction time (CCT) was not significantly different from ipsilateral CCT. CONCLUSION: These findings indicate that there is a selective interference with the contralateral corticospinal tract in patients with symptomatic cervical dystonia.

Adult↗

PubMed2005

Pelvic ring reconstruction with a vascularized pedicle iliac bone graft for a large sacral schwannoma.

A case of pelvic ring reconstruction with a vascularized pedicle iliac bone graft for removal of a huge sacral schwannoma is reported. It is necessary to reconstruct a pelvic ring when its integrity is impaired. Spinal instrumentation is essential for a temporary stability of the pelvic ring in the course of complete healing, which at times results in instrumentation failure. Several cases of pelvic ring reconstruction using vascularized fibular bone grafts have also indicated positive results attributable to their good blood circulation, but techniques with them are relatively complicated. We applied a vascularized pedicle iliac bone graft to the pelvic ring reconstruction after resection of a huge sacral schwannoma. When a stable pelvic ring was regained by using a lumbosacral instrumentation technique, a tricortical iliac bone graft with its vascular pedicle was harvested, transported into the dead space, and tied to the right residual sacrum and the left ilium. The vascularized graft healed rapidly, and continuity of the pelvic ring was regained. This method is effective for pelvic ring reconstruction in that it does not require microvascular techniques and rapid bone healing can be obtained.

Bone Transplantation↗

PubMed2005

Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation.

To elucidate the behavior of autologously transplanted mesenchymal cells in osteochondral defects, we followed transplanted cells using green fluorescent protein (GFP) transgenic rats, in which all cells express GFP signals in their cytoplasm and nuclei as transplantation donors. Bone marrow-derived mesenchymal cells, which contain mesenchymal stem cells (MSCs), were obtained from transgenic rats. Then, dense mesenchymal cell masses created by hanging-drop culture were transplanted and fixed with fibrin glue into osteochondral defects of wild-type rats. At 24 weeks after surgery, the defects were repaired with hyaline-like cartilage and subchondral bone. GFP positive cells, indicating transplanted mesenchymal-derived cells, were observed in the regenerated tissues for 24 weeks although GFP positive cells decreased in number with time. Because GFP causes no immunological rejection and requires no chemicals for visualization, transplantation between transgenic and wild-type rats can be regarded as a simulation of autologous transplantation, and the survivability of transplanted cells are able to be followed easily and reliably. Thus, the behavior of transplanted mesenchymal cells was able to be elucidated in vivo by this strategy, and the results could be essential in future tissue engineering for the regeneration of osteochondral defects with original hyaline cartilage and subchondral bone.

Animals↗

PubMed2004

Oxidative stress-associated mitochondrial dysfunction in corticosteroid-treated muscle cells.

We analyzed the effects of corticosteroid on mitochondrial membrane potentials (DeltaPsi(m)), generation of reactive oxygen species (ROS), and apoptosis in a human rhabdomyosarcoma cell line, RD, and a dopaminergic neuroblastoma cell line, SH-SY5Y. The cell lines were cultured in the presence or absence of dexamethasone and superoxide dismutase (SOD) for up to 1 week. Dexamethasone treatment increased DeltaPsi(m), ROS generation, and apoptosis in proliferating RD cells. Treatment with SOD attenuated ROS generation and apoptosis, but not DeltaPsi(m). The increase in DeltaPsi(m) seemed to be the primary effect of dexamethasone on proliferating RD cells, which is probably mediated by mitochondrial transcription. In differentiated RD cells, but not differentiated SH-SY5Y cells, dexamethasone treatment showed a delayed effect of interfering with the DeltaPsi(m) and increasing ROS generation and apoptosis. Since these changes disappeared in the presence of SOD, dexamethasone primarily induced ROS generation, resulting in apoptosis. We speculate that this mechanism provides the basis of a pathophysiological model of corticosteroid myopathy.

Apoptosis↗

PubMed2004

Fate of transplanted bone-marrow-derived mesenchymal cells during osteochondral repair using transgenic rats to simulate autologous transplantation.

OBJECTIVE: The fate of transplanted cells used in tissue engineering strategies should be followed. With this aim in view, the survival of transplanted bone-marrow-derived mesenchymal cells within osteochondral defects was determined using transgenic rats to simulate autologous transplantation. DESIGN: An autologous transplantation model was simulated using transgenic rats - whose transgenes produce no foreign proteins - as donors, and wild-type rats as recipients. Dense masses of mesenchymal cells were prepared from the transgenic rats using the hanging-drop culture technique. These cell masses were then transplanted into osteochondral defects created within the medial femoral condyle of wild-type rats, wherein they are affixed with fibrin glue. The course of repair was assessed histologically. The survival of the transplanted cells was ascertained by in situ hybridization of the transgenes. RESULTS: Twenty-four weeks after transplantation, the defects were repaired with hyaline-like cartilage, which was thicker than normal, and with subchondral bone. Using the in situ hybridization technique, cells derived from the transplanted ones were detected within both the cartilaginous and the subchondral bone layers. CONCLUSION: Using this simulated autologous transplantation model, the survival of transplanted mesenchymal cells was monitored in vivo. The findings indicate that the transplanted mesenchymal cells contributed to the repair of the osteochondral defects.

Animals↗

PubMed2003

Dissociation between titer of anti-ganglioside antibody and severity of symptoms in a case of Guillain-Barré syndrome with treatment-related fluctuation.

Since plasma exchange (PE) and intravenous immunoglobulin (i.v.Ig) have been widely used in treatment for Guillain-Barré syndrome (GBS), early relapse and treatment-related fluctuation have been a potential problem, but little is known about the mechanism of relapse and fluctuation. We describe a patient who had GBS with treatment-related fluctuation. A 37-year-old Japanese man exhibited acute distal-dominant weakness in upper limbs after upper respiratory infection. His cranial nerve system was normal and muscle weakness was limited to upper limbs. Anti-GT1a IgG was strongly positive and anti-GQ1b IgG was also detected in his serum. Muscle weakness responded well to double-filtration plasmapheresis (DFPP) followed by i.v.Ig, but relapsed 45 days after the initial treatment. Although repeated treatments were effective, the patient showed additional minor deterioration twice. Motor nerve conduction velocities (MCVs) corresponded to the muscle weakness, but elevated level of cerebrospinal fluid (CSF) protein remained and anti-ganglioside antibody titers steadily decreased throughout the clinical course. These findings indicate that the clinical fluctuation was not due to changes in the production of anti-ganglioside antibodies but presumably to the transient beneficial effects of DFPP/i.v.Ig and the outlasting inflammatory response in peripheral nerves.

Adult↗

PubMed2003

Complicated paraneoplastic neurological syndromes: a report of two patients with small cell or non-small cell lung cancer.

Paraneoplastic neurological syndromes are frequently associated in patients with small cell lung cancer (SCLC) and antineuronal antibodies are involved in the autoimmune mechanism. Multiple syndromes are sometimes complicated in a single patient with SCLC. However, little is known about non-SCLC-associated neurological manifestations. We report two patients with complicated paraneoplastic neurological syndromes. Patient 1 showed paraneoplastic limbic encephalitis (PLE), paraneoplastic sensory neuropathy (PSN) and Lambert-Eaton myasthenic syndrome (LEMS) associated with SCLC. Patient 2 developed opsoclonus-ataxia and probable PLE associated with non-SCLC. Analysis of various antineuronal antibodies revealed that anti-Hu and P/Q-type voltage-gated calcium channel (VGCC) antibodies were positive in Patient 1 but any antibodies were not in Patient 2. Brain MRI demonstrated high intensity signals in temporal lobes particularly on fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted images. These findings suggest that complicated paraneoplastic neurological syndromes occur in non-SCLC as well as SCLC and that unidentified antineuronal autoantibodies may underlie the pathophysiology.

Autoantibodies↗

PubMed2003

Dermatomyositis with peripheral nervous system involvement: activation of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) in vasculitic lesions.

We describe two cases of dermatomyositis (DM) with nervous system involvement. Polyneuropathy was observed in both patients, and cerebral vasculitis was suspected in one patient. Histological examination of biopsied specimens of skeletal muscles, skin and sural nerves revealed vasculitis. Furthermore, vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) were overexpressed in vasculitic lesions. Although, VEGF and VEGFRs were not detected in biopsied specimens of skeletal muscle from normal subjects, they were observed in one of two patients with DM who did not exhibit neuropathy. These findings suggest the possibility that VEGF overproduction is associated with development of vasculitis in some cases of DM complicated with peripheral neuropathy.

Aged↗

PubMed2002

Behavior of graft and host cells in underlying subchondral bone after transplantation of osteochondral autograft.

Transplantation of osteochondral autograft is widely used as a therapeutic strategy for the defect of articular cartilage. In the repair process, although underlying subchondral bone becomes necrotic and then is followed by bone reconstruction, the fate of graft and host cells during remodeling of underlying subchondral bone has not been elucidated. The objectives of this study were to establish a method to follow graft and host cells after transplantation of osteochondral autograft, and to elucidate the fate of both graft and host cells during remodeling of underlying subchondral bone. For these purposes, autologous transplantation models employing transgenic rats and wild-type rats, which were genetically identical to each other except for transgenes, were used. Two transplantation models were designed so that either the graft or the host cells had transgenes. Model I: transgenic rats were the donor, and wild-type rats were the recipient; model II: conversely, wild-type rats were the donor, and transgenic rats were the recipient. The grafted bone marrow cells and osteocytes in the trabeculae survived in the graft at 3 weeks after transplantation. Invasion of the host bone marrow cells into the graft was also found. Thus, bone marrow cells in the host as well as both bone marrow cells and osteocytes in the graft could potentially participate in the remodeling of underlying subchondral bone. Furthermore, the interface between graft and host was consisted with both graft and host derived cells. Since new bone formation was found in this space, both graft and host cells could have the potential to contribute to remodeling of underlying subchondral bone. The two models of the transplantations using the transgenic rats were found to be beneficial in following graft cells as well as host cells and in understanding their function on healing after autologous transplantation.

Animals↗

PubMed2002

Diurnal fluctuation of edema synchronized with plasma VEGF concentration in a patient with POEMS syndrome.

A case of POEMS syndrome in a 49-year-old Japanese woman is reported. The patient exhibited prominent edema in her legs at night, but her edema usually improved by the following morning. The plasma concentrations of VEGF in the patient showed diurnal fluctuations; plasma VEGF levels peaked at night and decreased in the daytime. Immunocytochemical study demonstrated the expression of VEGF in IgA- and lambda-positive plasma cells in bone marrow. The results indicate that VEGF was produced at least by plasma cells and that VEGF production was regulated by circadian rhythm in synchronization with the development of edema.

Anti-Inflammatory Agents↗