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Yukihide Iwamoto

Publications and source records attributed to Yukihide Iwamoto.

At least 19 recordsLinked to original sources
PubMed2007

The effects of histone deacetylase inhibitors on the induction of differentiation in chondrosarcoma cells.

PURPOSE: Histologically, chondrosarcomas represent the degree of chondrogenic differentiation, which is associated with the prognosis of the disease. Histone acetylation and deacetylation play key roles in the regulation of chondrocytic differentiation. Here, we describe the antitumor effects of histone deacetylase (HDAC) inhibitors as differentiating reagents on chondrosarcomas. EXPERIMENTAL DESIGN: We examined the effects of a HDAC inhibitor, depsipeptide, on the growth of chondrosarcoma cell lines. We also investigated the modulation of the expression levels of extracellular matrix genes and the induction of phenotypic change in chondrosarcoma cells treated with depsipeptide. Finally, we examined the antitumor effect of depsipeptide on chondrosarcoma in vivo. RESULTS: Depsipeptide inhibited the growth of chondrosarcoma cells by inducing cell cycle arrest and/or apoptosis. HDAC inhibitors increased the expression of the alpha1 chain of type II collagen (COL2A1) gene due to the enhanced histone acetylation in the promoter and enhancer. Depsipeptide also up-regulated the expressions of aggrecan and the alpha2 chain of type XI collagen (COL11A2) mRNA in a dose-dependent manner. Moreover, long-term treatment with a low dose of depsipeptide resulted in the induction of differentiation into hypertrophic phenotype, as shown by the increment of the alpha1 chain of type X collagen (COL10A1) expression in chondrosarcoma cells. In vivo studies and histologic analyses confirmed that depsipeptide significantly inhibited tumor growth and induced differentiation into the hypertrophic and mineralized state in chondrosarcoma cells. CONCLUSIONS: These results strongly suggest that HDAC inhibitors may be promising reagents for use as a differentiating chemotherapy against chondrosarcomas.

Apoptosis↗
PubMed2007

Dysadherin expression as a significant prognostic factor and as a determinant of histologic features in synovial sarcoma: special reference to its inverse relationship with E-cadherin expression.

Dysadherin is a cancer-associated cell membrane glycoprotein, which down-regulates E-cadherin and promotes metastasis. Synovial sarcoma is a very rare mesenchymal tumor that exhibits an epithelial profile. To confirm the diagnosis of synovial sarcoma, we evaluated several immunohistochemical markers, or detected SYT-SSX fusion gene transcript. We studied the clinicopathologic features in 92 synovial sarcoma patients and also assessed the immunohistochemical expression of dysadherin and E-cadherin to examine their possible association with histologic subtype and biologic behavior. Moreover, among 30 patients, for whom frozen materials were available, dysadherin mRNA expression was examined by reverse transcription-polymerase chain reaction and real-time quantitative reverse transcription-polymerase chain reaction analysis. Dysadherin-positive expression was significantly correlated with E-cadherin-reduced expression (P=0.0004). Dysadherin-positive immunostaining was diffusely observed in the membranes of tumor cells in 30/68 (44%) patients with monophasic fibrous type and in 1/2 (50%) patients with poorly differentiated type. However, in biphasic tumors, dysadherin expression in the fibrous component was not diffusely observed, but often sporadically or focally observed [20/22 (91%) patients]. In addition, dysadherin mRNA expression in monophasic fibrous type was significantly higher than in biphasic type (P=0.0079). Synovial sarcoma patients with dysadherin expression survived for a significantly shorter time than those without dysadherin expression (P=0.0006). Patients with combined dysadherin-positive expression and E-cadherin-reduced expression had a significantly worse prognosis than those with other combinations of dysadherin and E-cadherin expression (P=0.0007). SYT-SSX fusion gene transcript was detected in 39 patients. In our series, SYT-SSX fusion type was found to have no correlation with histologic subtype, prognosis, or dysadherin expression. In multivariate analysis, dysadherin immunopositivity (P=0.0411) was an independent adverse prognostic factor, in addition to a high MIB-1 labeling index (> or =10%). We conclude that E-cadherin dysfunction by dysadherin is associated with reduced E-cadherin expression and morphologic change from epithelioid to spindle phenotype. Dysadherin expression is considered to be one of the determinants of histologic subtype in synovial sarcoma. Moreover, dysadherin expression is an excellent and independent prognostic indicator.

Adult↗
PubMed2006

Adventitial cystic disease of the popliteal vein: report of a case.

Adventitial cystic disease (ACD), also known as cystic mucoid or myxomatous degeneration, is a rare vascular disease seen mainly in arteries. It is very unusual for these cystic masses to develop in a vein. We report the case of a 56-year-old woman with leg swelling caused by ACD arising in the popliteal vein. The swelling appeared after a long period of standing. Magnetic resonance imaging (MRI) showed a popliteal cystic mass and venography showed disrupted venous flow. We resected the cyst wall without venous reconstruction, after which venous blood flow normalized and her symptoms subsided. To our knowledge, this is only the third documented case of ACD arising in the popliteal vein. A misdiagnosis could easily have been made, since the mass was not obvious on physical examination and the only symptom was intermittent swelling. Thus, it is important to be aware of ACD as a possible diagnosis when examining patients with a swelling in the leg.

Adult↗
PubMed2006

Subchondral insufficiency fracture of the femoral head in younger adults.

We report two cases of subchondral insufficiency fracture of the femoral head observed in younger adults without any history of overexertion. In both cases, MRI revealed an irregular, discontinuous low-intensity band on the T1-weighted images. Both patients were treated operatively, and histological examination confirmed the diagnosis of subchondral fracture. A diagnosis of subchondral insufficiency fracture needs to be put in as one of the diagnoses in younger patients with a hip pain.

Adult↗
PubMed2006

Age-related differences in muscle activity, stride frequency and heart rate response during walking in water.

This study aimed to examine whether walking in water produces age-related differences in muscle activity, stride frequency (SF), and heart rate (HR) response. Surface electromyography (EMG) was used to evaluate muscle activities in six older and six young subjects while they walked in water immersed to the level of the xiphoid process. The trials in water utilized the Flowmill which consists of a treadmill at the base of a water flume. The measurement of maximal voluntary contraction (MVC) of each muscle was made prior to the gait analysis. The %MVCs, which refer to the surface EMG measures, from the gastrocnemius of the older subjects were significantly lower than those of the young subjects, in every experimental condition (P<0.05). In contrast, the %MVCs from the rectus femoris (P<0.05) and the biceps femoris (P<0.001) of older subjects were significantly greater than those of young subjects in every experimental condition. Moreover, the SFs of older subjects were also significantly greater than those of young subjects (P<0.05), while the HR responses of older and young subjects were similar. In conclusion, the older subjects had increased hip musculature activity and decreased ankle plantar flexor activity while walking in water, compared with the young subjects.

Adult↗
PubMed2006

Intramuscular diffuse-type giant cell tumor within the hamstring muscle.

Diffuse-type giant cell tumor (D-TGCT) is known as a synonym for pigmented villonodular synovitis (PVS), a condition usually found in the large joints. We report an extremely rare case of D-TGCT which was located within the hamstring muscle. The lesion was an incidental finding in a 62-year-old man who underwent positron emission tomography (PET) as part of a staging evaluation for gastric cancer. The lesion was resected. There has been neither metastasis nor recurrence during the 6-month period since resection. This case demonstrates that PVS/D-TGCT may have a high SUV on PET imaging, and for this reason PET may be useful for detecting both the tumor and any recurrence.

Buttocks↗
PubMed2006

Dedifferentiated chondrosarcoma with leukocytosis and elevation of serum G-CSF. A case report.

BACKGROUND: G-CSF is known to function as a hematopoietic growth factor and it is known to be responsible for leukocytosis. G-CSF-producing tumors associated with leukocytosis include various types of malignancies. CASE PRESENTATION: We report the case of a 72-year-old man with dedifferentiated chondrosarcoma characterized by dedifferentiated components of malignant fibrous histiocytoma- or osteosarcoma-like features in addition to conventional chondrosarcoma, arising from his pelvic bone. After hemipelvectomy, when local recurrence and metastasis were identified, leukocytosis appeared and an elevated level of serum granulocyte-colony-stimulating factor (G-CSF) was also recognized. The patient died of multiple organ failure 2 months after surgery. Autopsy specimens showed that the histological specimens of the recurrence and metastasis were dedifferentiated components, without any conventional chondrosarcoma components. G-CSF was expressed only in the dedifferentiated components, not in the chondrosarcoma components, immunohistochemically. CONCLUSION: This is the first report of chondrosarcoma, or any other primary bone tumor, with leukocytosis, probably stimulated by tumor-produced G-CSF from the dedifferentiated components.

Journal Article↗
PubMed2006

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

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

Animals↗
PubMed2006

Outcome of the contralateral hip in rapidly destructive arthrosis after total hip arthroplasty: a preliminary report.

We investigated the outcome of the contralateral hip in patients with rapidly destructive arthrosis of the hip after total hip arthroplasty. Twenty-four patients were included, and the mean duration of radiographic follow-up was 7.0 years (range, 3.8-17.8 years). To assess the capable parameters for predicting the development of osteoarthritis, we evaluated the receiver operating characteristic curves. Three (12.5%) of 24 patients developed osteoarthritis and underwent total hip arthroplasty within 3.8 to 6.5 years. In these 3 patients, both the acetabular-head index and the center-edge angle were significantly lower than those in patients without osteoarthritis (P < .005). Based on the receiver operating characteristic curves, both an acetabular-head index of less than 72% and a center-edge angle of less than 16 degrees were considered to be associated with the development of osteoarthritis.

Acetabulum↗
PubMed2006

Traumatic atlanto-occipital dislocation with atlantoaxial subluxation.

STUDY DESIGN: This is a case report of a patient who survived traumatic atlanto-occipital dislocation with atlantoaxial subluxation. OBJECTIVE: To describe the useful points of 3-dimensional computerized tomography (CT) and magnetic resonance imaging (MRI) for an evaluation of atlanto-occipital dislocation. SUMMARY OF BACKGROUND DATA: Atlanto-occipital dislocation is a severe ligamentous injury that usually results in either a fatal outcome or severe neurologic deficit. To our knowledge, no patient who has survived atlanto-occipital dislocation with atlantoaxial subluxation has yet been reported. METHODS: Three-dimensional CT was performed to confirm the diagnosis of atlanto-occipital dislocation and precisely evaluate the magnitude of displacement. MRI clearly showed a disruption of the ligamentous structures, which play a role as the primary stabilizers of the cranium on the cervical spine. RESULTS: As soon as the patient's general condition improved, the posterior spinal fusion with internal fixation was performed to maintain the stability of cervical spine. A significant degree of motor function was regained within 2 years after injury. CONCLUSIONS: In this case, the diagnosis was accurately confirmed, and the cervical spine was evaluated in detail using both 3-dimensional CT and MRI as a reliable examination for atlanto-occipital dislocation.

Adult↗
PubMed2006

A comparison of muscle activity and heart rate response during backward and forward walking on an underwater treadmill.

This investigation compared muscle activities and heart rate (HR) responses while subjects walked backward or forward in water, with and without a water current. Ten healthy males (23.5+/-1.4 years) volunteered for the study. Surface electromyography (EMG) was used to evaluate muscle activities while the subjects walked in water, immersed to the level of the xiphoid process. HR responses were monitored continuously by a telemetry method. A "Flowmill" was used for this study, which involves a treadmill at the base of a water flume. Measurement of maximal voluntary contraction (MVC) of each tested muscle was undertaken prior to gait analysis. The %MVCs obtained from the paraspinal muscles, vastus medialis and tibialis anterior were all significantly greater when walking backward than when walking forward, for every experimental condition (P<0.05). HR responses tended to be greater while walking backward than when walking forward, with a statistical significance at fast speed (P<0.05). In conclusion, walking backward in water resulted in significantly greater muscle activation of the paraspinal muscles, vastus medialis and tibialis anterior compared with walking forward in water. These findings may be helpful in developing water-based exercise programs.

Adult↗
PubMed2006

Direct GABAergic and glycinergic inhibition of the substantia gelatinosa from the rostral ventromedial medulla revealed by in vivo patch-clamp analysis in rats.

Stimulation of the rostral ventromedial medulla (RVM) is believed to exert analgesic effects through the activation of the serotonergic system descending to the spinal dorsal horn; however, how nociceptive transmission is modulated by the descending system has not been fully clarified. To investigate the inhibitory mechanisms affected by the RVM, an in vivo patch-clamp technique was used to record IPSCs from the substantia gelatinosa (SG) of the spinal cord evoked by chemical (glutamate injection) and electrical stimulation (ES) of the RVM in adult rats. In the voltage-clamp mode, the RVM glutamate injection and RVM-ES produced an increase in both the frequency and amplitude of IPSCs in SG neurons that was not blocked by glutamate receptor antagonists. Serotonin receptor antagonists were unexpectedly without effect, but a GABAA receptor antagonist, bicuculline, or a glycine receptor antagonist, strychnine, completely suppressed the RVM stimulation-induced increase in IPSCs. The RVM-ES-evoked IPSCs showed fixed latency and no failure at 20 Hz stimuli with a conduction velocity of >3 m/s (3.1-20.7 m/s), suggesting descending monosynaptic GABAergic and/or glycinergic inputs from the RVM to the SG through myelinated fibers. In the current-clamp mode, action potentials elicited by noxious mechanical stimuli applied to the receptive field of the ipsilateral hindlimb were suppressed by the RVM-ES in more than half of the neurons tested (63%; 10 of 16). These findings suggest that the RVM-mediated antinociceptive effects on noxious inputs to the SG may be exerted preferentially by the direct GABAergic and glycinergic pathways to the SG.

Animals↗
PubMed2006

The possible role of EWS-Fli1 in evasion of senescence in Ewing family tumors.

The chromosomal translocation t(11;22) yields the EWS-Fli1 fusion gene and is associated with oncogenesis of Ewing family tumors (EFT). In this study, using the RNA interference method, we show that EWS-Fli1-targeting small interfering RNAs (siRNA) depleted EWS-Fli1 protein and caused growth inhibition in EFT cells with the accumulation of p27 protein and the down-regulation of Skp2 protein in dose-dependent, time-dependent, and sequence-specific manners. Depletion of EWS-Fli1 subacutely elicited a senescence-like phenotype, but not apoptosis, in EFT cells. Furthermore, not only the knockdown of p27, but also the forced expression of Skp2, reduced the expression levels of p27 protein and partially rescued senescence-like phenotype caused by EWS-Fli1-targeting siRNAs. The accumulation of p27 protein in EWS-Fli1-depleted cells inhibited cdk2 kinase activity and was related to the stability of p27 protein, which resulted from a decrease in Skp2 protein. Immunohistochemical analysis of p27 and Skp2 proteins in EFT samples revealed that there was an inverse relationship between the expression profiles of p27 and Skp2 proteins. These findings indicate an important role of EWS-Fli1 in the prevention of senescence, leading to the unlimited growth and oncogenesis of EFT cells through a decrease in the stability of p27 protein due to increased action of Skp2-mediated 26S proteasome degradation.

Apoptosis↗
PubMed2006

Involvement of P-glycoprotein and MRP1 in resistance to cyclic tetrapeptide subfamily of histone deacetylase inhibitors in the drug-resistant osteosarcoma and Ewing's sarcoma cells.

Despite recent improvements in multimodal therapies for osteosarcoma (OS) and Ewing's family of tumors (EFTs), the prognosis of relapsed cases remains very poor because of the resistance to chemotherapy. Histone deacetylase inhibitors (HDACIs), including members of the cyclic tetrapeptide family such as FK228 and apicidin, are novel antitumor agents that can induce cell cycle arrest and apoptosis in various cancer cells. HDACIs also exhibit potent antitumor effects on OS and EFTs. However, to date there have been no studies to our knowledge reporting the effects of HDACIs on drug-resistant OS and EFTs. Here, we demonstrated that FK228 and apicidin exhibited strong resistance in doxorubicin-resistant clones of OS and EFTs expressing P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) and that P-gp and MRP1 might play a crucial role in the resistance mechanism to FK228 and apicidin. A P-gp inhibitor (verapamil) and an MRP1 inhibitor (MK571) could independently reverse the resistance to FK228 and apicidin in the drug-resistant clones. Moreover, the combination of verapamil and MK571 could enhance HDACI-induced cell number reduction in drug-resistant clones to a similar extent as that in their parental clones. Although these findings suggest the difficulty in treating drug-resistant tumors expressing P-gp and/or MRP1 with these HDACIs, the combination of P-gp and MRP1 inhibitors might reverse the resistance to the HDACIs in the treatment of those tumors. Because HDACIs are potent and promising antitumor drugs and seem to be close to clinical use, it is necessary to pay attention to the resistance mechanisms against HDACIs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Asymmetry of mediolateral laxity of the normal knee.

BACKGROUND: Understanding the normal kinematics of the joints is important for reconstructive surgery. However, only a few extensive studies have been done on medial and lateral laxity of the normal knee. METHODS: Radiographs of 50 normal knees were obtained under varus and valgus stress in both extension and flexion and the relative angle of the articular surface was measured. RESULTS: In extension, the mean angle was 4.9 degrees in varus stress and 2.4 degrees in valgus stress. In flexion, the mean angle was 4.8 degrees in varus stress and 1.7 degrees in valgus stress. Lateral laxity was significantly greater than medial laxity in both extension and flexion. CONCLUSIONS: Lateral laxity may be necessary for the medial pivot movement of the normal knee. There is some disagreement regarding the importance of pursuing the perfect rectangular gaps during total knee arthroplasty (TKA). The methods for measuring the tension of soft tissues during the operation are not accurate and do not always reflect the postoperative tensions of dynamic phases, such as walking and standing. Slight lateral laxity can be accepted with TKA, and further studies are necessary to determine whether prosthesis lift-off occurs in the replaced knee with slight lateral laxity similar to that in the normal knee.

Adult↗
PubMed2006

In vivo banking for vascularized autograft bone by intramuscular inoculation of recombinant human bone morphogenetic protein-2 and beta-tricalcium phosphate.

BACKGROUND: The gold standard of bone graft substitutes is vascularized autologous bone. Our strategy to acquire this bone substitute is using recombinant human bone morphogenetic protein (rhBMP)-2 with beta-tricalcium phosphate (TCP) as carrier to induce bone tissue in muscle and grafting as a muscle-pedicled bone flap. In our previous studies, morphologically controlled living bone was successfully induced in a rat muscular pedicle. Moreover, concurrent administration of bisphosphonate controlled the subsequent resorption of the induced bone. This study was conducted (1) to confirm that when the size of carrier is increased, the induced bone can form the same in the center as well as on the periphery of the carrier, and (2) to simulate in vivo banking for vascularized autograft bone. METHODS: In experiment 1200 microg rhBMP-2 and 10(-5) M bisphosphonate (Minodronate) were applied to a 1-cm-diameter sphere of beta-TCP. This sphere was then inoculated into rabbit quadriceps and harvested 5 weeks later (n = 3). In experiment 2, beta-TCP was generated as a one-third hollow cylinder with 4-mm outer radius, 2-mm inner radius, and 10-mm length. After 50 microg rhBMP-2 and 10(-5) M Minodronate were applied, this structure was then inoculated into rat quadriceps. Four weeks later, the induced bone was transplanted as a muscle-pedicled flap onto the adjacent femur and harvested after 4 and 8 weeks more (n = 3). RESULTS: In experiment 1, good bone formation was observed at the central as well as the peripheral region of the sphere. In experiment 2, good bone formation and bony union to the femur at both 4 and 8 weeks were detected on the X-ray film. The presence of new bone formation around the screw was observed. CONCLUSIONS: Transplantation of the beta-TCP carrier treated with rhBMP-2 and bisphosphonate into the muscular tissue may have clinical potential for in vivo banking for muscle-pedicled bone flaps.

Animals↗