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Biomedical subjects

Yuji Yasunaga

Publications and source records attributed to Yuji Yasunaga.

At least 19 recordsLinked to original sources
PubMed2006

Inhibitory effects of a new bisphosphonate, minodronate, on proliferation and invasion of a variety of malignant bone tumor cells.

Little is known about the biological effects of bisphosphonates on primary malignant bone tumors. The purpose of this study was to investigate the antitumor effects of newly developed minodronate (MIN) on a variety of human malignant bone tumors. We examined the effects of MIN and clinically relevant incadronate (INC) on the proliferation, apoptosis, and cell cycle of two osteosarcoma (Saos-2, MG-63), two chondrosarcoma (SW1353, OUMS27), and two Ewing's sarcoma (RD-ES, SK-ES-1) cell lines. Furthermore, we investigated the anti-invasion effects of MIN on sarcoma cells and the effects of MIN on tumor growth in nude mice. MIN inhibited the viability of all six cell lines in a dose-dependent manner with IC50 values of 2.7 to 5.0 microM, which were significantly lower than those of INC. Importantly, both bisphosphonates affected the viability of normal bone marrow stromal cells much less than sarcoma cells. Both bisphosphonates induced cell cycle perturbation in all sarcoma cells tested and apoptosis in Saos-2 and SW1353 cells, although they failed to induce apoptosis in RD-ES and SK-ES-1 cells. MIN significantly suppressed invasion, even at a low concentration of 1 microM (p < 0.01). Daily injection of 5 microg of MIN inhibited the growth of SK-ES-1 xenograft sarcoma in nude mice without loss of body weight. These findings suggest that MIN may have a beneficial adjuvant role in the treatment of patients with malignant bone tumors.

Animals↗
PubMed2006

Rotational acetabular osteotomy for advanced osteoarthritis secondary to dysplasia of the hip.

BACKGROUND: Satisfactory intermediate and long-term results of rotational acetabular osteotomy for the treatment of early osteoarthritis secondary to developmental dysplasia of the hip have been reported. The purpose of this study was to examine the results of rotational acetabular osteotomy in patients with advanced osteoarthritis secondary to developmental dysplasia of the hip. METHODS: We performed a retrospective review of the results of rotational acetabular osteotomy in forty-three patients (forty-three hips). All of the patients had radiographic evidence of advanced-stage osteoarthritis, defined as narrowing of the joint space with cystic radiolucencies and small osteophytes according to the staging system of the Japanese Orthopaedic Association. Forty-one patients were female, and two were male. The mean age was 43.8 years at the time of surgery, and the mean duration of follow-up was 8.5 years. Clinical follow-up was performed with use of the system of Merle d'Aubigné and Postel. The center-edge angle, acetabular roof angle, head lateralization index, and minimum width of the joint space were measured on radiographs made preoperatively, postoperatively, and at the time of final follow-up. Postoperative joint congruency was classified into four grades. RESULTS: The mean preoperative Merle d'Aubigné clinical score was 13.3 points, which improved to a mean of 15.4 points at the time of the latest follow-up (p < 0.0001). The mean center-edge angle improved from 0.7 degrees preoperatively to 29 degrees at three months postoperatively (p < 0.0001), the mean acetabular roof angle improved from 30 degrees to 11 degrees (p < 0.0001), the mean head lateralization index improved from 0.69 to 0.65 (p < 0.01), and the mean minimum width of the joint space improved from 2.2 to 2.5 mm (p < 0.0003). Ten hips had radiographic evidence of progression of osteoarthritis. Kaplan-Meier survivorship analysis, with radiographic signs of progression of osteoarthritis as the end point, predicted a ten-year survival rate of 72.2%. CONCLUSIONS: Rotational acetabular osteotomy for advanced osteoarthritis secondary to dysplasia of the hip in properly selected patients can improve clinical scores and is associated with a lack of radiographic signs of progression of osteoarthritis in most patients. LEVEL OF EVIDENCE: Therapeutic Level IV.

Acetabulum↗
PubMed2005

Prefabrication of vascularized bone graft using a combination of fibroblast growth factor-2 and vascular bundle implantation into a novel interconnected porous calcium hydroxyapatite ceramic.

The aim of this study was to create a prefabricated vascularized bone graft using a novel interconnected porous calcium hydroxyapatite ceramic (IP-CHA) by combining vascular bundle implantation and basic fibroblast growth factor (FGF)-2 administration in a rabbit model. Twenty-four Japanese white rabbits were used. The saphenous artery and vein were passed through the hole of the IP-CHA. In an experimental group, 100 microg of FGF-2 was administered into the IP-CHA before implanting the vascular bundle. In the control group, the saline was administered into the IP-CHA before implanting the vascular bundle. Finally, the IP-CHA was placed subcutaneously in the medial thigh. Neovascularization from the vascular bundle was evaluated at 2 weeks after surgery, and osteogenesis was evaluated at 4 weeks. At 2 weeks, the length and density of newly formed vessels were significantly greater in the experimental group than in the control group. Histological evaluation showed osteoid deposition in the pores of the IP-CHA at 4 weeks in the experimental group, whereas no evidence of osteoid deposition was noted in the control group. This study showed the potential of creating a vascularized bone graft of a predetermined size and shape using a combination of FGF-2 and vascular bundle implantation in the IP-CHA.

Animals↗
PubMed2005

Meniscal regeneration using tissue engineering with a scaffold derived from a rat meniscus and mesenchymal stromal cells derived from rat bone marrow.

The purpose of this study was to regenerate a meniscus using a scaffold from a normal meniscus and mesenchymal stromal cells derived from bone marrow (BM-MSCs). Thirty Sprague-Dawley rat menisci were excised and freeze-thawed three times with liquid nitrogen to kill the original meniscal cells. Bone marrow was aspirated from enhanced green fluorescent protein transgenic Sprague-Dawley rats. BM-MSCs were isolated, cultured for 2 weeks, and 2 x 10(5) cells were then seeded onto the meniscal scaffolds. Using a fluorescent microscope and immunohistochemical staining, repopulation of enhanced green fluorescent protein positive cells was observed in the superficial zone of the scaffold after 1 week of culture, and then in the deep zone after 2 weeks. At 4 weeks, expression of extracellular matrices was detected histologically and expression of mRNA for aggrecan and type X collagen was detected. Stiffness of the cultured tissue, assessed by the indentation stiffness test, had increased significantly after 2 weeks in culture, and approximated the stiffness of a normal meniscus. From this study, we conclude that a scaffold derived from a normal meniscus seeded with BM-MSCs can form a meniscus approximating a normal meniscus.

Animals↗
PubMed2005

Efficiency of magnetic liposomal transforming growth factor-beta 1 in the repair of articular cartilage defects in a rabbit model.

We evaluated the efficacy of a magnetic liposomal delivery system of transforming growth factor (TGF)-beta(1) in the treatment of articular cartilage defects in a rabbit model. Articular cartilage defects were created in the patellar groove of rabbits, and a permanent magnet or a nonmagnetic alloy was implanted in the defect site. Magnetic liposomal drugs, prepared by the conventional film method and sonication, were injected into the defect site 1 week after surgery. First, the efficacy of the magnetic liposomal delivery system was evaluated by using a model compound fluorescence-labeled dextran 40,000 (FD-40). Then, the therapeutic efficiency of magnetic liposomal TGF-beta(1) was evaluated by cartilage histological scoring at 4, 8, and 12 weeks after surgery. The injected magnetic liposomal FD-40 accumulated at the target site where a permanent magnet had been implanted. The histological score showed that the injection of magnetic liposomal TGF-beta(1) under magnetic force was significantly effective in the repair of the defect site over 12 weeks after surgery. Injection of TGF-beta(1) into the cartilage defect was effective as a magnetic liposomal preparation under magnetic force, resulting in acceleration of the cartilage repair, probably because of the desirable accumulation of TGF-beta(1) at the target site.

Animals↗
PubMed2005

Neovascularization and bone regeneration by implantation of autologous bone marrow mononuclear cells.

We examined whether transplantation of autologous bone marrow mononuclear cells (BM-MNCs) can augment neovascularization and bone regeneration of bone marrow in femoral bone defects of rabbits. Gelatin microspheres containing basic fibroblast growth factor (bFGF) were prepared for the controlled release of bFGF. To evaluate the in vivo effect of implanted BM-MNCs, we created bone defects in the rabbit medial femoral condyle, and implanted into them 5 x 10(6) fluorescent-labeled autologous BM-MNCs together with gelatin microspheres containing 10 microg bFGF on an atelocollagen gel scaffold. The four experimental groups, which were Atelocollagen gel (Col), Col + 5 x 10(6) BM-MNCs, Col + 10 microg bFGF, and Col + 5 x 10(6) BM-MNCs + 10 microg bFGF, were implanted into the sites of the prepared defects using Atelocollagen gel as a scaffold. The autologous BM-MNCs expressed CD31, an endothelial lineage cell marker, and induced efficient neovascularization at the implanted site 2 weeks after implantation. Capillary density in Col + BM-MNCs + bFGF was significantly large compared with other groups. This combination also enhanced regeneration of the bone defect after 8 weeks to a significantly greater extent than either BM-MNCs or bFGF on their own. In summary, these findings demonstrate that a combination of BM-MNCs and bFGF gelatin hydrogel enhance the neovascularization and the osteoinductive ability, resulting in bone regeneration.

Animals↗
PubMed2005

Bone remodeling of a femoral head after transtrochanteric rotational osteotomy for osteonecrosis associated with slipped capital femoral epiphysis: a case report.

A rare case of a 12-year-old boy on whom a joint-preserving operation for osteonecrosis after slipped capital femoral epiphysis (SCFE) was performed, is described. Firstly, in situ pinning was performed for acute-on-chronic SCFE. However, osteonecrosis and collapse of the femoral head occurred at 7 months after surgery. Secondly, transtrochanteric rotational osteotomy (TRO) was performed against progression of the collapse of the femoral head. Eight years of X-ray observation revealed bone remodeling at the osteonecrotic region. No documentation has been reported about the potential of bone remodeling of a femoral head with osteonecrosis after SCFE. This case indicates that a joint-preserving operation such as TRO is capable of promoting bone remodeling in such circumstances.

Bone Remodeling↗
PubMed2005

Functional diagnosis using multimodal spinal cord evoked potentials in cervical myelopathy.

The electrophysiological measurement of spinal cord evoked potentials (SCEPs) has been established as a tool for diagnosing the spinal level responsible for cervical myelopathy. Only a few studies, however, employed multimodal SCEPs for this purpose. The objective of this study was to investigate the correlation between multimodal SCEPs recorded during cervical laminoplasty and magnetic resonance imaging (MRI) abnormalities in 18 patients aged 70 years and older versus 32 patients less than 65 years of age. Both the SCEPs and MRIs showed higher incidences of multiple-level cord involvement in the older group than in the younger group. Discrepancies in the spinal levels involved between the SCEPs and the MRIs were found in 12 patients (67%) for the older group and 6 patients (19%) for the younger group. The accuracy of the MR images in localizing the lesion site was significantly lower in the older group than in the younger group, indicating that MR images tend to show clinically silent cord compression in elderly patients. Because spinal cord compression can appear without functional change in elderly patients, electrophysiological evaluations with intraoperative multimodal SCEP studies are a useful addition to MRI for understanding the pathology of myelopathy.

Adult↗
PubMed2005

Natural course of the minimally symptomatic nonoperated hip in patients with bilateral hip dysplasia treated with contralateral rotational acetabular osteotomy.

BACKGROUND: The purpose of this study was to investigate the natural course of the minimally symptomatic nonoperated hip in patients with pre-osteoarthritis or early osteoarthritis in bilaterally dysplastic hips. METHODS: The material consisted of 61 patients with bilaterally dysplastic hips who underwent rotational acetabular osteotomy in their symptomatic hip and nonoperative treatment in their asymptomatic or minimally symptomatic hip. The average follow-up was 10.1 years (range 7.0-15.6 years), and the average age at the time of surgery was 38.2 years (range 20-58 years). All patients were divided into two groups by joint congruity of the nonoperated hip at surgery with rotational acetabular osteotomy. RESULTS: On radiographic assessment, 1 of the 35 pre-osteoarthritis hips had developed early osteoarthritis, and 6 of the 26 early osteoarthritis hips had progressed to advanced osteoarthritis. The Kaplan-Meier survivorship analysis for the whole group of nonoperated hips, with radiographic progression of osteoarthritis as the endpoint, predicted a 10-year survival rate of 83.7% (95% confidence interval 70%-98%). Significant differences were observed in the radiographic stage (pre- and early osteoarthritis group, P=0.015) and joint congruity (good and fair group, P=0.005). CONCLUSIONS: If the contralateral nonoperated hip has good joint congruity, minimal symptoms, and no or little radiographic change in patients with pre- or early osteoarthritis and bilateral acetabular dysplasia, the probability of radiographic progression is low.

Adult↗
PubMed2005

The HU knot: a new sliding knot for arthroscopic surgery.

Sliding knots are commonly used in arthroscopic knot tying. The Surgical knot as a hand-tied knot is very secure. We found that the Surgical knot could be used as a sliding knot. We have modified the Surgical knot to include a self-locking loop. A new sliding knot for arthroscopic surgery, the HU knot, is described. By tensioning the loop strand, the self-locking loop creates a snug knot without sliding backward. The HU knot provides great security.

Arthroscopy↗
PubMed2005

Effective repair of a fresh osteochondral defect in the rabbit knee joint by articulated joint distraction following subchondral drilling.

PURPOSE: Joint distraction has been used to treat osteoarthritis and was found to delay the need for arthrodesis or joint replacement. However, there has been little basic research on articulated joint distraction for the repair of osteochondral defects. We investigated the effects of joint distraction with motion after drilling on a fresh osteochondral defect in the weight bearing area of the rabbit knee joint. METHODS: A full thickness osteochondral defect was created in the weight bearing area of both medial femoral condyles of an adult Japanese white rabbit. After drilling of the defect, the experimental knee joint was distracted for 1.5 mm using a pair of external fixators to decrease compression force. The contralateral knee joint was used as a control with no apparatus. Gross findings and histological evaluation were assessed to study morphology of the repaired cartilage. RESULTS: A partial repair with cartilage-like tissue was observed in the joints of the experimental group at 4 weeks. While cartilage-like tissue stained with Safranin O was found in the experimental group at 8 and 12 weeks, destructive changes were observed in the control joints. Morphological changes were evaluated using the histological grading scale [Wakitani S, Goto T, Pineda SJ, et al. Mesenchymal cell-based repair of large, full-thickness defect of articular cartilage. J Bone Joint Surg Am 1994;76(4):579-92]. There was no significant difference between experimental and control groups at 4 weeks (mean 11.2 and 13.8 points, respectively). However, the mean scores of the experimental groups at 8 and 12 weeks (mean 6.8 and 7.5, respectively) were significantly better than those of the control groups at the same time points (mean 14 points each). Between the experimental groups, the scores at 8 and 12 weeks were both significantly better than those at 4 weeks. CONCLUSION: A combination of subchondral drilling, joint motion and distraction by an articulated external fixator promoted repair of a fresh osteochondral defect in the weight bearing area. Although distraction for 4 weeks was not a long enough period to repair the defect, distraction for 8 and 12 weeks resulted in a good outcome.

Animals↗
PubMed2005

Role of simple cold storage in preventing epiphyseal growth plate impairment after replantation surgery in immature rats.

The purpose of this study was to investigate the effect of ischemia time on longitudinal bone growth after replantation, and to evaluate the usefulness of simple cold storage of an amputated limb in preventing epiphyseal growth-plate impairment. A hind-limb replantation model was produced with 5-week-old rats after various ischemia times. With more than 6 hr of warm ischemia, growth disturbance was observed, and extensive necrosis was histologically apparent in the central region of the growth plate of the proximal tibia, even at 1 week postoperatively. Destruction of the growth plate was complete at 4 weeks after surgery. By simple cold storage of the amputated limb, growth disturbance was not observed, even following ischemia for 9 hr, and no abnormal findings were observed histologically. Segmental necrosis and destruction of the growth plate observed histologically suggested the possibility of indirect impairment of the epipyseal chondrocytes due to disturbance of the epiphyseal arterial system, attributable to ischemia. The study confirmed experimentally that cold storage of the amputated part may prevent longitudinal bone-growth disturbance after extension of ischemia time.

Amputation, Traumatic↗
PubMed2005

The cellular origin of cartilage-like tissue after periosteal transplantation of full-thickness articular cartilage defects: an experimental study using transgenic rats expressing green fluorescent protein.

BACKGROUND: Periosteal transplantation is commonly used for the treatment of articular cartilage defects. However, the cellular origin of the regenerated tissue after periosteal transplantation has not been well defined. The objective of this study was to investigate the cellular origin of the regenerated tissue after periosteal transplantation. METHOD: Free periosteum was harvested from the tibia of 10-week-old adolescent enhanced green fluorescent protein (GFP-) expressing transgenic Sprague Dawley (SD) rats and was transplanted to full-thickness articular cartilage defects of the patellar groove in normal 10-week-old adolescent SD rats. The periosteum was sutured to the defect with the cambium layer facing the joint cavity. 8 SD rats were killed at 4 weeks and 8 SD rats were killed at 8 weeks after surgery. The repaired tissue was assessed histologically and histochemically. GFP-positive cells derived from the donor periosteum could easily be detected in the repaired tissue by use of a fluorescent microscope. RESULTS: At both 4 and 8 weeks after transplantation, the entire area of the defects had been repaired, with the regenerated tissue being well stained histologically with safranin-O. Most cells in the whole area of the regenerated tissue were GFP-positive, indicating that very few of the cells were GFP-negative cells originating from the recipient rats. INTERPRETATION: This experiment demonstrates that most cells in regenerated tissue after periosteal transplantation using adolescent animals do not originate from recipient cells but from the periosteal cells of the donor.

Animals↗
PubMed2005

Hyperbaric oxygen as an adjuvant for athletes.

There has recently been a resurgence in interest in hyperbaric oxygen (HBO) treatment in sports therapy, especially in Japan. Oxygen naturally plays a crucial role in recovery from injury and physiological fatigue. By performing HBO treatment, more oxygen is dissolved in the plasma of the pulmonary vein via the alveolar, increasing the oxygen reaching the peripheral tissues. HBO treatment is therefore expected to improve recovery from injury and fatigue. HBO treatment has been reported to reduce post-injury swelling in animals, and in humans; swelling was also mitigated, but to a lesser extent. Positive results have also been reported regarding tissue remodelling after injury, with injuries involving bones, muscles and ligaments showing improved recovery. Furthermore, HBO treatment has effectively increased recovery from fatigue. This was clearly seen at the Nagano Winter Olympics, where sports players experiencing fatigue were successfully treated, enabling the players to continue performing in the games. Despite its potential, HBO treatment does have its risks. Increasing oxygen levels in tissues poses a risk to DNA through oxidative damage, which can lead to pathological changes in the CNS and the lungs. Regarding the operating of HBO systems, safer administration should be advised. Further research into HBO treatment is required if this therapy is to become more widespread. It should become possible to tailor treatment to an individual's condition in order to use HBO treatment efficiently.

Animals↗
PubMed2004

Intravenously injected neural progenitor cells of transgenic rats can migrate to the injured spinal cord and differentiate into neurons, astrocytes and oligodendrocytes.

Transplantation of neural progenitor cells (NPCs) has been reported recently to promote regeneration of the injured spinal cord. In the majority of these reports, cell transplantation was performed by local injection with a needle. However, direct injection might be too invasive for clinical use; therefore, the authors investigated a new method of delivering NPCs for the treatment of spinal cord injury. In this study, NPCs were obtained from E15 fetal hippocampus of transgenic rats expressing green fluorescent protein and 100,000 cells were transplanted intravenously into each animal 24h after contusion injury. It was found that the injected NPCs migrated to the lesion site widely and demonstrated nestin at an early phase after transplantation. These NPCs differentiated into neurons, astrocytes and oligodendrocytes, and survived at least for 56 days. These results indicated that intravenously injected neural stem cells migrated into the spinal cord lesion while preserving their potential as NPCs, and that this procedure is a potential method of delivering cells into the lesion for the treatment of spinal cord injury.

Animals↗
PubMed2004

Bone formation using novel interconnected porous calcium hydroxyapatite ceramic hybridized with cultured marrow stromal stem cells derived from Green rat.

The clinical use of cultured marrow stromal stem cells (MSCs) has recently attracted attention in the field of tissue engineering. For the clinical use of the MSCs, a prominent scaffold is needed. A scaffold hybridized with MSCs is transformed into a "bioactive bone substitute," and this provides good osteoconduction. In this study, a novel calcium hydroxyapatite ceramic with an interconnected porous structure (IP-CHA) was used as a scaffold. MSCs were harvested from Green rats containing Green Fluorescent Protein (GFP), and then these hybrids were implanted into the tibias of Sprague-Dawley rats. The purposes of this study were to examine the osteogenic ability of these hybrids without coculture, and to evaluate whether the resulting bone formation originated from the grafted MSCs or the recipient's cells. The hybridized group showed excellent bone formation compared with the IP-CHA-only implant group. Observation of the implanted MSCs revealed that they survived 8 weeks after surgery, and differentiated into osteoblast-like cells, thus providing bone formation. This implantation of the MSCs/IP-CHA composite provides excellent osteoconduction, and is expected to have extensive clinical applications.

Animals↗