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Hideki Yoshikawa

Publications and source records attributed to Hideki Yoshikawa.

At least 163 records · Page 9Linked to original sources
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

Mechanical stress-induced apoptosis of endplate chondrocytes in organ-cultured mouse intervertebral discs: an ex vivo study.

STUDY DESIGN: Various amounts of static mechanical load were applied to mouse intervertebral discs in organ cultures. The apoptosis then was examined using nick end labeling. Two mitogen-activated protein kinase (MAPK) inhibitors were added to the medium. OBJECTIVES: To establish an experimental model for detecting factors regulating chondrocyte apoptosis induced by mechanical stress, and to determine the role of MAPK and p38 in the stress-induced apoptotic pathway of endplate chondrocytes. SUMMARY OF BACKGROUND DATA: The cause of degenerative change in the cartilaginous endplate (CEP) remains unclear. The authors' previous findings using a mouse model suggested that apoptosis in the cartilaginous endplate may play a role in intervertebral disc degeneration, and that mechanical stress may induce apoptosis. If apoptosis of endplate chondrocytes is involved in the cascade of intervertebral disc degeneration, then how apoptosis is induced by mechanical stress should be important in preventing disc degeneration. However, the mechanism of apoptosis induced by mechanical stress remains unclear. METHODS: Mouse coccygeal discs were harvested and organ cultured. Various static compression loads (0, 0.2, 0.4, 0.8, and 1.0 MPa) were applied on intervertebral discs placed in culture bottles for 24 hours. Paraffin-embedded sections of the harvested discs were stained using Safranin-O and the nick end labeling procedure. The apoptotic cells were counted in the cartilaginous endplate and junctional anulus fibrosus of each intervertebral disc. In addition, U0126 (MAPK inhibitor) and SB202190 (p38 inhibitor) were added to the culture medium to determine their regulatory roles in the apoptosis of endplate chondrocytes induced by mechanical load. RESULTS: Histologically, loaded discs became bulged, and the disc space became narrow. Apoptosis was absent in discs without load, but was particularly noticeable in loaded discs (load weight, 1.0 MPa). The number of apoptotic cells increased depending on the weight of the load. The two MAPK inhibitors significantly increased the number of apoptotic cells. CONCLUSIONS: Chondrocyte apoptosis was induced using a static mechanical load especially in the cartilaginous endplate in an organ culture. Apoptosis occurred similarly to previous findings using an in vivo model. This culture system thus reflected the apoptosis demonstrated in vivo. Because biologically active reagents such as MAPK inhibitors can be simply added to culture media, this system may be a useful method for detecting factors that influence apoptosis induced by mechanical stress. Both MAPK inhibitors increased the occurrence of apoptosis. This suggests that these two MAPKs can counteract the apoptotic pathway induced by mechanical stress.

Animals↗
PubMed2003

Non-existence of positive glitches in spectra using the YB(66) double-crystal monochromator of BL15XU at Spring-8.

YB(66) is suitable for dispersing synchrotron radiation in the 1-2 keV energy range with a 2d lattice spacing of 1.17 nm. When used with an undulator there are no positive glitches at 1385.6 and 1438 eV in spectra dispersed by a YB(66) 400 double-crystal monochromator as observed using bending-magnet or wiggler beamlines. The transmission function of a YB(66) double-crystal monochromator has been measured by means of a Si PIN photodetector, and X-ray absorption near-edge structure (XANES) of Mg, Al and Si were measured at high resolution. From all of these experiments it has been clarified that a YB(66) double-crystal monochromator is well suited for soft X-ray beamlines on third-generation light sources.

Journal Article↗
PubMed2003

Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury.

To investigate the intracellular signal transduction pathways involved in regulating the gene expression of brain-derived neurotrophic factor (BDNF) in primary afferent neurons, we examined the activation of extracellular signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons after peripheral inflammation and sciatic nerve transection. Peripheral inflammation induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase A-containing small-to-medium-diameter DRG neurons. The treatment of the mitogen-activated protein kinase (MAPK) kinase 1/2 inhibitor U0126 reversed the pain hypersensitivity and the increase in phosphorylated-ERK (p-ERK) and BDNF in DRG neurons induced by complete Freund's adjuvant. On the other hand, axotomy induced the activation of ERK mainly in medium-and large-sized DRG neurons and in satellite glial cells. U0126 suppressed the axotomy-induced autotomy behavior and reversed the increase in p-ERK and BDNF. The intrathecal application of nerve growth factor (NGF) induced an increase in the number of p-ERK-and BDNF-labeled cells, mainly small neurons, and the application of anti-NGF induced an increase in p-ERK and BDNF in some medium-to-large-diameter DRG neurons. The activation of MAPK in the primary afferents may occur in different populations of DRG neurons after peripheral inflammation and axotomy, respectively, through alterations in the target-derived NGF. These changes, including the changes in BDNF expression, might be involved in the pathophysiological changes in primary afferent neurons.

Activating Transcription Factor 3↗
PubMed2003

PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts.

Although a large number of studies have been carried out on the diverse effects mediated by the common neurotrophin receptor p75(NTR), little is known about the molecular mechanisms by which p75(NTR) initiates intracellular signal transduction. We identified a variant of the beta catalytic subunit of cAMP-dependent protein kinase (PKACbeta) as a p75(NTR)-interacting protein, which phosphorylates p75(NTR) at Ser304. Intracellular cAMP in cerebellar neurons was accumulated transiently by ligand binding to p75(NTR). Activation of cAMP-PKA is required for translocation of p75(NTR) to lipid rafts, and for biochemical and biological activities of p75(NTR), such as inactivation of Rho and the neurite outgrowth. Proper recruitment of activated p75(NTR) to lipid rafts, structures that represent specialized signaling organelles, is of fundamental importance in determining p75(NTR) bioactivity.

Amino Acid Sequence↗
PubMed2003

Extraskeletal myxoid chondrosarcoma: a Multi-Institutional Study of 42 Cases in Japan.

BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm. Despite a consensus for the distinct clinicopathologic entity of EMC, its clinical features remain controversial. In addition, most studies have contained a small number of patients who underwent definitive surgical treatment. METHODS: Forty-two cases of EMC, which had been identified from files of eight affiliated hospitals and confirmed for histologic diagnosis at the Pathology Center, were analyzed for histologic grade, demographics, treatments, outcomes, and prognostic factors. The average follow-up period was 7.4 years. RESULTS: Included in the study were 20 men and 22 women with a mean age at diagnosis of 52.1 years. The tumors were located mainly in the lower extremities (69%). Thirty-three tumors (79%) were classified as Grade 1 and nine as Grade 2 according to the modified French System. Overall survival was 100% at 5 years and 88% at 10 years. Disease-free survival was 45% at 5 years and 36% at 10 years. Inadequate initial surgery was defined as a significant risk factor for local recurrence by univariate analysis of all 42 patients but not by the analysis of those 30 patients who had undergone wide tumor excision or amputation. Wide excision led to the recurrence rate of 14%. CONCLUSIONS: These findings supported the role of wide excision in the local control of EMC, irrespective of the previous excision procedure or recurrence. The protracted clinical course of the tumors and the presence of patients who had distant metastasis develop after definitive surgery of the primary tumor represented EMC as intermediate malignancy.

Adult↗
PubMed2003

Functional inhibition of the p75 receptor using a small interfering RNA.

The neurotrophin receptor p75(NTR) mediates a wide variety of biological effects. Consistent with the function in controlling the survival and neurite formation, p75(NTR) is expressed during the developmental stages of the nervous system. Importantly, p75(NTR) is re-expressed in various pathological conditions and is suggested to contribute to the inhibition of neuronal regeneration and the death of the neurons. Here we develop a tool to knock down the expression of p75(NTR) by employing a small interfering RNA (siRNA). The siRNA for p75(NTR) effectively reduces the expression of endogenous p75(NTR) both in Schwann cells and dorsal root ganglion neurons in vitro. NGF-induced cell death in Schwann cells and the neurite retraction in DRG neurons induced by myelin-associated glycoprotein are attenuated by the siRNA. Inhibition of p75(NTR) in specific pathological conditions by the siRNA may provide a potential therapeutic agent.

Animals↗
PubMed2003

COL11A2 collagen gene transcription is differentially regulated by EWS/ERG sarcoma fusion protein and wild-type ERG.

A specific t(21;22) chromosomal translocation creates the chimeric EWS/ERG gene in some cases of Ewing's sarcoma. In the resultant EWS/ERG fusion protein, the N-terminal part of the ETS family protein ERG is replaced by the N terminus of the RNA-binding protein EWS. We found that both the EWS/ERG and COL11A2 genes are expressed in the Ewing's sarcoma cell line, CADO-ES1. To investigate a potential role for EWS/ERG in COL11A2 gene expression, we characterized the COL11A2 promoter and tested the ability of wild-type ERG and EWS/ERG sarcoma fusion protein to transactivate COL11A2 promoter using a luciferase assay. We found that expression of EWS/ERG, but not wild-type ERG, transactivated the COL11A2 promoter and that this transactivation required not only the N-terminal region of EWS but also an intact DNA-binding domain from ERG. Electrophoretic mobility shift assay using COL11A2 promoter sequence showed involvement of EWS/ERG in the formation of DNA-protein complexes, and chromatin immunoprecipitation assay revealed direct interaction between COL11A2 promoter and EWS/ERG fusion protein in vivo. EWS/ERG, but not wild-type ERG, bound to RNA polymerase II. Treatment of cells with the histone deacetylase inhibitor trichostatin A enabled ERG to transactivate the COL11A2 promoter, therefore abolishing the differential effects of EWS/ERG and ERG. Taken together, these findings indicate that the COL11A2 gene is regulated both by potential ERG association with a histone deacetylase complex and by direct EWS/ERG recruitment of RNA polymerase II.

Animals↗
PubMed2003

Isolation and identification of indigestible pyroglutamyl peptides in an enzymatic hydrolysate of wheat gluten prepared on an industrial scale.

An enzymatic hydrolysate of wheat gluten was further digested in vitro with porcine pepsin and pancreatin to obtain an indigestible peptide. Indigestible pyroglutamyl peptide was isolated from the digest by strong cation-exchange, size-exclusion, and reversed-phase chromatographies. The pyroglutamyl peptide was digested with pyroglutamate aminopeptidase, and the digest was reacted with phenyl isothiocyanate. The resultant phenylthiocarbamyl (PTC) peptides were purified by reversed-phase HPLC by using binary gradient elution with ammonium acetate buffer, pH 6.0, and acetonitrile. The PTC peptides were analyzed with an automatic peptide sequencer on the basis of the Edman degradation method with a modified program. Some pyroglutamyl peptides were also analyzed by fast-atom bombardment ionization mass spectrometry without the pyroglutamate amino peptidase digestion. Consequently, pyroGlu-Asn-Pro-Gln, pyroGlu-Gln-Gln-Pro-Gln, pyroGlu-Gln-Pro-Gln, pyroGlu-Gln-Pro-Gly-Gln-Gly-Gln, pyroGlu-Gln, pyroGlu-Gln-Pro, pyroGlu-Ile-Pro-Gln, pyroGlu-Ile-Pro, pyroGlu-Gln-Pro-Leu, pyroGlu-Gln-Phe-Pro-Gln, pyroGlu-Ser-Phe-Pro-Gln, pyroGlu-Phe-Pro-Gln, and pyroGlu-Gln-Pro-Pro-Phe-Ser were identified.

Amino Acid Sequence↗
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

Unusual skeletal metastases from myxoid liposarcoma only detectable by MR imaging.

We present two cases of skeletal metastases from myxoid liposarcoma, occurring several years after treatment of the primary tumors in the lower limb. The present two case reports have unusual radiological features only detectable by MR imaging and not by plain radiographs or bone scans. From the present two cases, we found that a negative plain radiograph of the spine or a negative bone scan could not exclude skeletal metastases from myxoid liposarcoma, and MRI was a more sensitive screening procedure for their detection, especially in T1-weighted images. Unusual radiological features of skeletal metastases from myxoid liposarcoma are not well documented and only a few cases have been previously reported. Our aim is to document two more patients exhibiting the unusual radiological features of skeletal metastases from myxoid liposarcoma to improve their early detection and management.

Adult↗
PubMed2003

Correlation between femoral neck version and strain on the femur after insertion of femoral prosthesis.

Stress analysis on the femur after insertion of a femoral prosthesis with a modular interchangeable neck with adjustable neck version was performed using in vitro experimental procedures and cemented strain gauges. Although strain on the anterior and posterior aspects was less than on the medial and lateral aspects, it was more markedly affected by adjusting the interchangeable neck from straight to anteverted (or retroverted) than strain on the medial and lateral aspects, particularly around the stem tip. There was a highly significant correlation between compressive strain on the side toward which the prosthetic neck was oriented and the extent of neck version, whether anteverted or retroverted. Insertion of a femoral implant in excessive anteversion (or retroversion) may cause noticeably increased stress on the anterior and posterior aspects of the proximal femoral shaft.

Arthroplasty, Replacement, Hip↗
PubMed2003

Comparison of the fit and fill between the Anatomic Hip femoral component and the VerSys Taper femoral component using virtual implantation on the ORTHODOC workstation.

The purpose of this study was to evaluate differences in fit and fill between an anatomic femoral component and a straight tapered femoral component, both of which were designed for proximal fit and fill using the preoperative planning workstation of the ROBODOC system (ORTHODOC). Anatomic Hip (Zimmer) and VerSys Taper (Zimmer) femoral components were each virtually implanted into 50 femora (25 dysplastic femora and 25 anatomically normal femora) using the ORTHODOC workstation. The fit and fill of the femoral components were measured on cross-sectional images. The VerSys Taper femoral components showed significantly better fit and fill than the Anatomic Hip femoral components at the lower corner of the femoral neck cut and the middle of the femoral component in both the dysplastic femora and the anatomically normal femora. The Anatomic Hip femoral components showed significantly better fit and fill than the VerSys Taper femoral components 1 cm proximal from the femoral component tip in both dysplastic femora and anatomically normal femora. There was no significant difference in fit and fill between the two types of femoral component at the center of the lesser trochanter or 1 cm distal from the center of the lesser trochanter in either dysplastic femora or anatomically normal femora. Overall, VerSys Taper femoral components appear to provide better proximal fit and fill than Anatomic Hip femoral components in both dysplastic and anatomically normal femora.

Adult↗
PubMed2003

Contribution of injured and uninjured dorsal root ganglion neurons to pain behavior and the changes in gene expression following chronic constriction injury of the sciatic nerve in rats.

Neuropathic pain models, such as the chronic constriction injury (CCI) model, are partial nerve injury models where there exist both intact and injured peripheral axons. Recent studies suggested that dorsal root ganglion (DRG) neurons with intact axons also show the alteration of excitability and gene expression and might have some role in the pathophysiological mechanisms of neuropathic pain. The incidence of pain-related behavior after the CCI is unstable and variable. In the present study, we used activating transcription factor 3 (ATF3) expression as a neuronal injury marker, and analyzed a relationship between the number of axotomized neurons and the incidence of pain-related behavior. We divided all rats into three groups according to the percentage of ATF3-immunoreactive (IR) neurons, group 1 (<12.5%), group 2 (12.5-25%), and group 3 (>25%). We found that rats in groups 2 and 3 showed thermal hyperalgesia, whereas only the rats in group 2 developed tactile allodynia from the third day to the fourteenth day after surgery. Rats in group 1 did not show thermal hyperalgesia or tactile allodynia. The DRG neurons in group 2 contained ATF3-IR neurons mainly in medium- and large-sized neurons. In order to investigate brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid(A)-receptor (GABA(A)-R) regulation in both intact and injured primary afferent neurons after the CCI, we used a double-labeling method with immunohistochemistry and in situ hybridization, as well as double immunofluorescent staining. The CCI induced an increased number of BDNF-labeled neurons in the ipsilateral DRG and the increase in BDNF expression was observed mainly in small- and medium-sized neurons that were mainly ATF3-negative. On the other hand, the number of GABA(A)-Rgamma2 subunit mRNA-positive neurons decreased in the ipsilateral DRG and GABA(A)-R- and ATF3-labeled neurons rarely overlapped. These changes in molecular phenotype in intact and injured primary afferents may be involved in the pathophysiological mechanisms of neuropathic pain produced by partial nerve injury.

Activating Transcription Factor 3↗
PubMed2003

The triquetrum-hamate joint: an anatomic and in vivo three-dimensional kinematic study.

PURPOSE: To obtain anatomic and kinematic information regarding the relative motion of the triquetrum-hamate (TqH) joint. METHODS: In this anatomic study the contact surface constraints of the TqH joint that affect TqH motion were investigated by passively simulating TqH motion according to the kinematic data. Two fresh and 28 embalmed cadaver wrists were dissected. In the kinematic study we studied the in vivo 3-dimensional (3D) kinematics of the TqH joint during radioulnar deviation (RUD) and wrist flexion and extension motion (FEM) in 5 healthy wrists using a magnetic resonance image (MRI)-based markerless bone registration algorithm. Animations of the relative motion of the TqH joint were created and accurate estimates of the relative positions and orientations of the bones and axes of rotation of TqH motion during RUD and FEM were obtained. RESULTS: The anatomic study revealed that the contact surface constraints of the TqH joint include primarily the oval convex surface of the hamate. In the kinematic study TqH motion was likely to be not helicoidal but rotational around an oval convex surface of the hamate. In RUD the triquetral movement was rotation in an ulnoflexion-radial extension plane of the wrist. In FEM it was rotation in an almost flexion-extension plane of the wrist. The axes of rotation of the TqH joint in all wrist motions always ran distal to the TqH joint. CONCLUSIONS: Typical motion of the TqH joint in functional range of motion is not a helicoidal motion on the saddle, but rather a rotational motion on an oval, whose axes of rotation are located on the distal side of the joint.

Aged↗
PubMed2003

Evaluation of femoral perfusion in a non-traumatic rabbit osteonecrosis model with T2*-weighted dynamic MRI.

We evaluated femoral perfusion in a non-traumatic rabbit serum sickness osteonecrosis (ON) model, using serial repetitive T2*-weighted (T2*W) dynamic magnetic resonance imaging (MRI) and investigated prediction of ON occurrence in early stages, comparing T2*W dynamic MRI with non-enhanced (T2-, T1- and fat suppression T1-weighted) and contrast-enhanced MRI. Early microcirculatory injury or necrotic lesion was detected in 0% of femora (extravasation, 0/6) at 72 h, 33% (necrotic, 4/12) at 1 week and 100% (necrotic, 14/14) at 3 weeks using non-enhanced MRI, and in 67% of femora (extravasation, 4/6) at 72 h, 58% (necrotic, 7/12) at 1 week and 100% (necrotic, 14/14) at 3 weeks using contrast-enhanced MRI. In contrast, microcirculatory injury or necrotic lesion was detected in 83% of femora (extravasation, 5/6) at 72 h, 92% (necrotic, 11/12) at 1 week and 100% (necrotic, 14/14) at 3 weeks using T2*W dynamic MRI as no transient decrease or less marked transient decrease in signal intensity of regions of interest (ROIs), compared to normal femora, which showed a clear transient decrease in signal intensity of ROIs. These results indicate that T2*W dynamic MRI with optimal imaging parameters and a dose of contrast agent is the most sensitive of these three MRI methods and may be clinically useful for evaluating femoral perfusion in artery phase and predicting ON occurrence.

Animals↗
PubMed2003

Measurement of lesion area and volume by three-dimensional spoiled gradient-echo MR imaging in osteonecrosis of the femoral head.

The purpose of this investigation is to evaluate the diagnostic ability of three-dimensional spoiled gradient-echo (3D SPGR) magnetic resonance (MR) imaging in cases of osteonecrosis of the femoral head (ONFH), and to determine the accuracy of 3D SPGR imaging in area and volume measurement of ONFH. T1-weighted spin-echo (SE) and 3D SPGR imaging were performed on 20 femoral heads obtained from patients with ONFH. After MR imaging, the femoral heads were cut parallel to the imaging plane and were evaluated histologically. Areas and volumes of necrotic lesions were measured with a computer program and the deviation between MR images and anatomical measurements was evaluated. A low signal intensity band on 3D SPGR MR images was observed in all femoral heads and corresponded histologically to repaired marrow with viable fibrous mesenchymal tissue. The area proximate to the low band area coincided with the necrotic region. Both area and volume measurements by T1-weighted SE and 3D SPGR images showed a strong correlation to histological measurements. The discrepancies between histological and imaging results were minimal in 3D SPGR imaging, especially at the anterior and posterior portions of the femoral head. Three-dimensional SPGR imaging provides more accurate measurements of the area and volume of a necrotic lesion than T1-weighted SE imaging.

Bone Marrow Diseases↗