[Paget disease of bone].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Shu Takahashi.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
This study assessed the potential application and the effectiveness of functional magnetic stimulation (FMS) for preventing skeletal muscle atrophy in adult rats. FMS using magnetic stimulator was performed to rat soleus muscle by placing a round magnetic coil on the back of 3rd-5th lumbar vertebral level at 20 Hz frequency for 60 min/day up to 10 days. A reverse transcriptase-polymerase chain reaction was applied to evaluate relative amounts of mRNAs specific to four myosin heavy chain (MHC) isoforms [MHCIbeta, MHCIIa, MHCIIb, and MHCIId(x)] in rat soleus muscle during contractile activity by magnetic stimulation. Ten-day unloading by hindlimb suspension induced a drastic decrease of MHCIbeta and MHCIIa mRNA expressions, while MHCIIb and MHCIId(x) mRNA was not decreased. The magnetic stimulation resuscitated the down-regulation of the mRNA levels of MHCIbeta and MHCIIa. These results suggest that magnetic stimulation on acute atrophied muscles is useful for preventing the muscle atrophy.
Retinoic acid (RA) plays an important role in bone metabolism in vivo through osteoclast activation and bone resorption. Retinoid X-activated receptor beta (RXRbeta) has been implicated in the genetic spinal defect of ossification of the posterior longitudinal ligament (OPLL). In this study, we examined the effects of 9-cis RA and all-trans RA (ATRA) on the proliferation, differentiation, and RXRbeta expression of the murine preosteoblastic cell line MC3T3-E1. Both 9-cis RA and ATRA dose-dependently inhibited the increase in total soluble protein content at concentrations of 10 and 100 nM after 4 and 8 d co-culture with MC3T3-E1 cells. The inhibitory effect of 9-cis RA was slightly stronger than that of ATRA. Histone H4 mRNA expression was dose-dependently suppressed by both RAs on day 1. Alkaline phosphatase activity was increased by both RAs at 10 and 100 nM concentrations on day 4, with 9-cis RA-induced activity slightly stronger than that of ATRA. Osteopontin mRNA expression was increased by both RAs on day 1, but was suppressed on day 4. Bone Gla protein mRNA expression was inhibited by 10 and 100 nM 9-cis RA and by 100 nM ATRA on day 14. RXRbeta mRNA expression was increased by 9-cis RA, an RXRbeta ligand, in a dose-dependent manner. Our results suggested that while both RAs suppressed proliferation and stimulated the maturation of preosteoblastic MC3T3-E1 cells, 9-cis RA was slightly more potent than ATRA. It also appeared that RAs may contribute to the development of heterotopic ossification, including OPLL.
Stress fractures are usually encountered in athletes; however, only eight such cases involving the metacarpal bones have been reported in the English literature. We report on the rare case of a 15-year-old female tennis player with a stress fracture of the second metacarpal bone.
We describe a case history of a 24-year-old male with osteogenesis imperfecta (OI) who developed osteosarcoma of the left thigh. High-dose ifosfamide therapy caused marked tumor regression of multiple lung metastases. Immunohistochemically, the tumor cells were diffusely positive for the p53 protein. Mutation of the p53 gene was not detected by direct genomic sequencing of exons 4-8. The radiographic characteristics, including irregularly distributed osteolytic lesions and cortical discontinuity, should not be confused with hyperplastic callus formation, a benign process. A biopsy is critical to establish the differential diagnosis between osteosarcoma and common hyperplastic callus formation in OI; however, it must be applied with great care.
There have been only three previous reports of women with Ewing sarcoma who received chemotherapy while pregnant. A 17-year-old woman with Ewing sarcoma was treated with a combination of doxorubicin (Adriamycin) and ifosfamide during the 25th to 30th week of gestation, and the baby was delivered at the 32nd week. The baby was developing normally at follow-up at 8 months of age. This case report supports the idea that in this situation, the pregnancy can be continued to await fetal growth, and second-trimester chemotherapy may not have a deleterious effect on the fetus.
OBJECTIVE: SR-PSOX/CXCL16 is a transmembrane chemokine and is implicated in activated CD8+ T cell trafficking. In the present study, we examined the expression pattern of SR-PSOX/CXCL16 in the heart and investigated a potential role of SR-PSOX/CXCL16 in inflammatory valvular heart disease. METHODS AND RESULTS: Initial expression of SR-PSOX/CXCL16 in murine embryos was detected in endothelial cells lining endocardial cushions in the forming heart at E11.5. From mid-gestation to adult, expression of this gene in the heart was exclusively observed in valvular endothelial cells. Examination of SR-PSOX/CXCL16 expression in human cardiac valves demonstrated that SR-PSOX/CXCL16 was strongly expressed in valvular and neocapillary endothelial cells in patients with infective endocarditis. SR-PSOX/CXCL16 expression in neocapillary endothelial cells was also observed in patients with rheumatic and atherosclerotic valvular disease. Moreover, CD8+ T cells were distributed closely to endothelial cells expressing SR-PSOX/CXCL16. In vitro adhesion assays showed that SR-PSOX/CXCL16 induced adhesion of activated CD8+ T cells to vascular cell adhesion molecule-1 (VCAM-1) through very late antigen-4 (VLA-4) activation. Furthermore, SR-PSOX/CXCL16 stimulated interferon-gamma (IFN-gamma) production by CD8+ T cells. CONCLUSIONS: SR-PSOX/CXCL16 may be involved in CD8+ T cell recruitment through VLA-4 activation and stimulation of IFN-gamma production by CD8+ T cells during inflammatory valvular heart disease.
Direct contacts between dendritic cells (DCs) and T cells or natural killer T (NKT) cells play important roles in primary and secondary immune responses. SR-PSOX/CXC chemokine ligand 16 (CXCL16), which is selectively expressed on DCs and macrophages, is a scavenger receptor for oxidized low-density lipoprotein and also the chemokine ligand for a G protein-coupled receptor CXC chemokine receptor 6 (CXCR6), expressed on activated T cells and NKT cells. SR-PSOX/CXCL16 is the second transmembrane-type chemokine with a chemokine domain fused to a mucin-like stalk, a structure very similar to that of fractalkine (FNK). Here, we demonstrate that SR-PSOX/CXCL16 functions as a cell adhesion molecule for cells expressing CXCR6 in the same manner that FNK functions as a cell adhesion molecule for cells expressing CX(3)C chemokine receptor 1 (CX(3)CR1) without requiring CX(3)CR1-mediated signal transduction or integrin activation. The chemokine domain of SR-PSOX/CXCL16 mediated the adhesion of CXCR6-expressing cells, which was not impaired by treatment with pertussis toxin, a Galphai protein blocker, which inhibited chemotaxis of CXCR6-expressing cells induced by SR-PSOX/CXCL16. Furthermore, the adhesion activity was up-regulated by treatment of SR-PSOX/CXCL16-expressing cells with a metalloprotease inhibitor, which increased surface expression levels of SR-PSOX/CXCL16. Thus, SR-PSOX/CXCL16 is a unique molecule that not only attracts T cells and NKT cells toward DCs but also supports their firm adhesion to DCs.
SR-PSOX and CXC chemokine ligand (CXCL)16, which were originally identified as a scavenger receptor and a transmembrane-type chemokine, respectively, are indicated to be identical. In this study, we demonstrate that membrane-bound SR-PSOX/CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria. Importantly, our prepared anti-SR-PSOX mAb, which suppressed chemotactic activity of SR-PSOX, significantly inhibited bacterial phagocytosis by human APCs including dendritic cells. Various scavenger receptor ligands inhibited the bacterial phagocytosis of SR-PSOX. In addition, the recognition specificity for bacteria was determined by only the chemokine domain of SR-PSOX/CXCL16. Thus, SR-PSOX/CXCL16 may play an important role in facilitating uptake of various pathogens and chemotaxis of T and NKT cells by APCs through its chemokine domain.
The receptor for parathyroid hormone (PTH) and PTH-related protein (PTHrP) regulates calcium homeostasis, bone remodeling and skeletal development. 14-3-3 proteins bind to signaling proteins and act as molecular scaffolds and regulators of subcellular localization. We show that the parathyroid hormone receptor (PTHR) interacts with 14-3-3 and the proteins colocalize within the cell. 14-3-3 interacts with the C-terminal tail of the receptor containing a consensus 14-3-3 binding motif, but additional binding sites are also used. Protein kinase-A treatment of the receptor and especially the C-terminal tail reduces 14-3-3 binding. The expressed C-terminal tail is primarily localized in the nucleus, supporting the function of a putative nuclear localization signal that could be involved in the previously described nuclear localization of PTHR. The observed interaction between PTHR and the 14-3-3 protein implies that 14-3-3 could contribute to regulation of PTHR signaling.
A 16-year-old Japanese boy was admitted to our institution in September 2000 because no apparent callus had appeared around a fracture after 6 weeks of cast fixation. Physical examination revealed a tenderness of the right lower leg, and multiple small subcutaneous tumors and café-au-lait spots in extremities and trunk. Radiographs showed the fracture of the right lower tibia with bony sclerosis and a localized fusiform osteolytic lesion at the fracture site. The affected tibia bowed anteriorly and the medullary space in the lower tibia was narrow. A diagnosis of Boyd type IV congenital pseudoarthrosis of the tibia was made. Treatment with low-intensity pulsed ultrasound (US) stimulation (LIPUS) was administered for 20 min/day, and a nonweight-bearing gait was continued with a cast or brace fixation. At 6 months after the treatment, a small amount of bridging callus was seen. We continued the treatment for 1 year until the solid fusion was observed on radiographs and the patient started full-weight-bearing.
Topochemical [2 + 2] cycloaddition polymerization of methyl p-phenylenediacrylate and 2,5-distyrylpyridine in nanocrystals, prepared by the reprecipitation method, were investigated in comparison with those in bulk crystals. The bulk single crystals, larger than 1 mum in size, broke into microcrystals with variety of size and shape in the course of polymerization. Interestingly, however, these nanocrystals show single-crystal-to-single-crystal transformation.
Rotator cuff tendon cells (RCC) derived from surgical samples showed fibroblast-like morphology. Histological staining demonstrated collagen secretion by RCC. Immunohistological findings revealed that RCC secreted type I and III collagen, but not type II collagen. In addition, the SDS-PAGE analysis suggested that RCC predominantly produced type I collagen. Basic fibroblast growth factor (bFGF) had a stimulatory effect on the proliferation of RCC dose-dependently up to 1 ng/ml. Administration of bFGF suppressed the secretion of collagens from RCC in a dose-dependent manner.
Explore the source record for details and available documents.
The purpose of this study was to investigate the histopathology, including apoptosis, in the supraspinatus tendon with stage II subacromial impingement. Samples from the critical zone of the supraspinatus tendon were obtained from 5 patients with subacromial impingement syndrome and 10 autopsy cases without shoulder diseases as controls. Three-micrometer-thick sections were cut and stained with hematoxylin-eosin (H-E) for routine histologic examination. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method and single-stranded deoxyribonucleic acid (ssDNA) assay in which the frequency of the apoptotic cells was expressed by the apoptotic index. Control supraspinatus tendons showed normal morphology, whereas supraspinatus tendons from shoulders with impingement showed significant mucoid degeneration. Correspondingly, few apoptotic cells were observed in control tendons, whereas a large number of apoptotic cells were observed in the degenerative area of tendons from impingement shoulders. The apoptotic indices were significantly higher in the impingement shoulders (ssDNA, 18.84% +/- 1.75%; TUNEL, 24.92% +/- 2.79%) than in the control shoulders (ssDNA, 5.22% +/- 1.30%; TUNEL, 7.01% +/- 1.05%) (P = .04 for ssDNA and P = .017 for TUNEL). Mechanical impingement seems to cause tendon degeneration and apoptosis of the tendon cells in the supraspinatus tendon in stage II impingement.
Growth factors are known to appear during wound healing. We hypothesized that growth factors would also appear during the healing process of a rotator cuff tear. We determined the expression of various growth factors during healing of acute rotator cuff tears in the rabbit. We made a full-thickness defect in the supraspinatus tendon of 27 Japanese white rabbits. The shoulders were harvested on days 1, 3, 5, 7, 9, 11, 14, 21, and 28 postoperatively (n = 3 at each time point). We assessed the expression of basic fibroblast growth factor, insulin-like growth factor 1, platelet-derived growth factor, and transforming growth factor beta. Basic fibroblast growth factor appeared with its peak on days 7 and 9, insulin-like growth factor 1 appeared with its peak on day 5, platelet-derived growth factor appeared with a mild expression between days 7 and 14, and transforming growth factor beta appeared with constant mild expression throughout the observation period. It is likely that each of these growth factors plays a role in the early phase of healing of the supraspinatus tendon in rabbits.
Several materials have been used as drug delivery systems to maintain a high concentration of anticancer drugs at localized sites. The feasibility of using doxorubicin-loaded calcium phosphate cement (CPC) as a new material, which can release the drug as well as fill a postoperative bony defect, was investigated. The mechanical strength of cylinders of doxorubicin-loaded CPC was not lower than that of CPC alone. Culture medium incubated with doxorubicin-loaded CPC from 1 to 7 days suppressed the proliferation of RMT-1 E4 rat breast cancer cells. In rabbits with doxorubicin-loaded CPC in their femurs, histological examinations showed diffuse edematous changes in the medullary space, but neither fracture nor skin necrosis occurred. Doxorubicin-loaded CPC markedly inhibited the proliferation of sarcoma 180 cells in the mouse air-pouch model. These results indicate that doxorubicin-loaded CPC may be useful in the local treatment of malignant bone and soft tissue tumors.