Biomedical subjects

Kanji Mori

Publications and source records attributed to Kanji Mori.

13 recordsLinked to original sources

PubMed2006

A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.

Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the chi (2) test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P=0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.

Adolescent↗

PubMed2006

RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells.

The POS-1 murine model of osteolytic osteosarcoma was used to elucidate the molecular and cellular mechanisms involved in the development of primary bone tumors and associated lung metastasis. The POS-1 cell line is derived from an osteosarcoma tumor which develops spontaneously in C3H mice. The POS-1 cell line was characterized in vitro by mineralization capacity and expression of bone markers by semi-quantitative RT-PCR, compared to primary osteoblasts and bone marrow cells. POS-1 cells showed no mineralization capacity and exhibited an undifferentiated phenotype, expressing both osteoblastic and unexpected osteoclastic markers (TRAP, cathepsin K and RANK). Thereby, experiments were performed to determine whether RANK was functional, by studying the biological activity of murine RANKL through the receptor RANK expressed on POS-1 cells. Results revealed a RANKL-induced increase in ERK phosphorylation, as well as BMP-2 induction at the mRNA and protein levels, and a decrease of POS-1 cell proliferation in the presence of 10 ng/ml RANKL. BMP-2 induction is dependent on the ERK 1/2 signal transduction pathway, as its expression is abolished in the presence of UO126, a specific synthetic inhibitor of the ERK 1/2 pathway. Moreover, a 2-fold molar excess of soluble RANK blocks the RANKL-induced BMP-2 expression, demonstrating that the biological effects of RANKL observed in POS-1 cells are mediated by RANK. This is the first report describing a functional RANK expressed on osteosarcoma cells, as shown by its ability to induce signal transduction pathways and biological activity when stimulated by RANKL.

Animals↗

PubMed2006

Osteosarcoma: current status of immunotherapy and future trends (Review).

Osteosarcoma is the most common primary bone tumor and represents a major therapeutic challenge in medical oncology. While the use of aggressive chemotherapy has drastically improved the prognosis of the patients with non-metastatic osteosarcomas, the very poor prognosis of patients with metastasis have led to the exploration of new, more effective and less toxic treatments, such as immunotherapy for curing osteosarcoma. Compared to the numerous reports describing successful immunotherapy for other solid tumors, the number of reports concerning immunotherapy for osteosarcoma is low. However, this therapeutic strategy opens new areas for the treatment of osteosarcoma. In this review, the reasons for delay and all elements essential to develop immunotherapy concerning osteosarcoma are defined. Several pieces of evidence strongly support the potential capability of new therapies such as cellular therapy and gene therapy to eradicate osteosarcoma. Thus, clinical human trials using peptides, cytokines and dendritic cells have been performed. Tumor-infiltrating lymphocytes and some tumor antigens have been identified in osteosarcoma and resulted in an important breakthrough in cellular immunotherapy. Also, RANKL/RANK/OPG, the key regulator of bone metabolism, is a hot spot in this field as therapeutic tools. Immunotherapy for osteosarcomas has great potential, promising improvement in the survival rate and better quality of life for the patients.

Bone Neoplasms↗

PubMed2005

[Meningioma].

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Diagnosis, Differential↗

PubMed2004

Association of CYP17 with HLA-B27-negative seronegative spondyloarthropathy in Japanese males.

Susceptibility genes for seronegative spondyloarthropathy (SNSA) other than HLA-B27 remain unclarified. Sex hormones are implicated in the pathogenesis of SNSA. Cytochrome P450c17a (CYP17) is a key regulator of androgen biosynthesis, and a single nucleotide polymorphism (SNP) in the 5'-untranslated region of the CYP17 gene (CYP17), -34C > T, is associated with variety of diseases. We have investigated the association between the CYP17 SNP and SNSA in Japanese males. Genomic DNA was extracted from 149 Japanese male SNSA patients and 380 controls. The CYP17 SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Allelic and genotypic frequencies of the SNP were compared between SNSA patients and controls, and within SNSA patients. We also computed haplotype frequencies using an expectation-maximization algorithm, analyzed the difference between SNSA and control groups, and examined the potential association of other known SNPs in the CYP17 gene. The frequency of the -34T allele was significantly increased in HLA-B27-negative SNSA, but not in total or HLA-B27-positive SNSA when compared to controls. The T allele was more prevalent in HLA-B27-negative SNSA than in HLA-B27-positive SNSA, and the T/T genotype was over-represented in HLA-B27-negative SNSA. Haplotype analysis did not demonstrate more significant association. The CYP17 SNP is associated with SNSA in HLA-B27-negative Japanese males.

Adolescent↗

PubMed2004

Type-selective muscular degeneration promotes infiltrative growth of intramuscular lipoma.

BACKGROUND: Intramuscular lipoma is a relatively common benign neoplasm that is occasionally described as an infiltrating lipoma. Typical benign tumors show a clear margin, however, the infiltrative growth pattern of this lipoma mimics that of a malignant tumor. Although its growth has an effect on muscle bundles and it is known to never metastasize, the mechanism of infiltrative growth is not well understood. Previously, little attention has been paid to pathogenic features of muscle fibers around an intramuscular lipoma. METHODS: In the present study, we focused on pathologic changes of the surrounding skeletal muscles especially to the degenerative features of involving muscular types, and evaluate the role of type-selective muscular degeneration for the infiltrative growth of intramuscular lipomas. Following a review of the medical records in our institute, 17 lesions containing muscle tissues in their specimens (15 infiltrating lipomas, 2 well-circumscribed lipomas) were analyzed immunohistochemically. The tumor from the most recent case was also subjected to ultrastructural analysis. Two cases of the traumatic muscle damage were also evaluated as the control experiments. RESULTS: These analyses revealed type-selective muscle involution in 11 of 17 intramuscular lipomas and in 10 of 11 of the infiltrative type, with an involving pattern that resembled that of a neurogenic or myogenic disorder. Immunoreactivity to cathepsin-D, a lysosomal catabolic enzyme, was increased in the involved muscle fibers. Subsarcolemmal vacuoles in the muscle fibers of the peripheral areas were also positive for cathepsin-D, while degenerative findings were not visually apparent in these areas. Ultrastructural analysis revealed degenerative changes in those fibers. Neither positive staining for cathepsin-D nor type-selective atrophy was detected in the sections of traumatic muscle damage. CONCLUSIONS: Our findings suggest that type-selective muscular degeneration and endomysial fatty growth as a result of atrophy may modulate the infiltrating growth characteristic of intramuscular lipoma.

Adipocytes↗

PubMed2004

Evaluation of standard nucleotomy for lumbar disc herniation using the Love method: results of follow-up studies after more than 10 years.

A retrospective analysis of long-term follow-up results more than 10 years after a standard nucleotomy for lumbar disc herniation with the Love method was done to determine the effectiveness of this procedure. Nucleotomy according to Love was the standard treatment for lumbar disc herniation before the various minimally invasive alternatives were recently introduced. Without long-term follow-up analysis of Love operations, evidence-based evaluation of those new methods is impossible. We believe that the standard nucleotomy procedure should now be evaluated precisely. In this study we present a comparison of 1-year follow-up results to the results more than 10 years after lumbar nucleotomy. Seventy-six consecutive patients who had undergone lumbar nucleotomy were identified. It was possible to assess 54 (71.1%) of the cases more than 10 years after surgery. The initial and final outcomes were assessed using the MacNab classification and the Japanese Orthopaedic Association (JOA) score. With the MacNab classification a successful outcome 1 year after surgery was achieved in 87.0% of the cases. At the final follow-up, this result was reduced to 74.1%. Seven patients required a second operation and patients under 21 years of age were at risk for reoperation. Patient overall satisfaction with the results of the standard nucleotomy was high. The disc height of the operation site significantly decreased after surgery; nevertheless, this did not affect the clinical outcome. A standard lumbar nucleotomy according to Love is a safe and reliable method of treating selected patients with lumbar disc herniations.

Adult↗

PubMed2004

Bath ankylosing spondylitis functional index (BASFI) evaluation of postoperative patients with OPLL.

Although surgical decompression of the involved spinal cord achieves a good recovery of neurological conditions, one of the most important complaints of patients with ossification of the posterior longitudinal ligament (OPLL) is disability as a result of spinal immobility. The activities of daily living (ADL) of postoperative patients with OPLL were examined. To evaluate the ADL of postoperative patients with OPLL in the cervical spine, we utilized the Bath Ankylosing Spondylitis Functional Index (BASFI), one of the most widely used functional indexes for ankylosing spondylitis. We investigated consecutive cases that underwent surgery for OPLL of the cervical spine in our department from 1978 to 1998. The latest and postoperative scores were compared to the preoperative Japanese Orthopaedic Association (JOA) scores (range, 0-17) to assess neurological recovery. We also evaluated ADL at the latest follow-up, using BASFI scores. Significant recoveries of JOA scores were confirmed; however, 77% of patients complained of disability. In BASFI, questions that seemed to reflect spinal condition received low scores in the present study. BASFI scoring was not sufficient in the present form; however, it is one of the candidate functional indexes for evaluating ADL in postoperative patients with OPLL. Establishment of an ideal functional index for such evaluation is needed.

Activities of Daily Living↗

PubMed2004

Expression of macrophage inflammatory protein-1alpha in Schwann cell tumors.

It is well known that tumors originating from Schwann cells often demonstrate degeneration, such as myxoid areas in Schwannoma (Antoni B) and granular cell tumors. However, the mechanism has never been understood in detail. Recruitment of circulating macrophages plays a role in degeneration, however, the factors leading to that process are not well known. Macrophage inflammatory protein-1alpha (MIP-1alpha), which belongs to the C-C family of chemokines, is thought to be involved in the recruitment of inflammatory cells and might play a role in the degenerative change of Schwann cell tumors. To elucidate the role of MIP-1alpha in such conditions, we employed immunohistochemistry and in situ hybridization analyses. Strongly positive staining of MIP-1alpha was revealed in the myxoid areas of tested tumors and in situ hybridization detected the existence of MIP-1alpha mRNA in some of the tumor cells. These results suggest that MIP-1alpha produced from tumorigenic cells plays a role in the auto-degenerative process of Schwann cell tumors. Furthermore, various levels of MIP-1alpha expression in these tumors were implicated to be correlated with histological variations.

Adult↗

PubMed2004

Differentially expressed genes in multidrug resistant variants of U-2 OS human osteosarcoma cells.

Multidrug resistance (MDR) to anticancer agents is a major barrier to the successful treatment of human osteosarcomas. Current understanding of the genes that contribute to the features of MDR is limited, and the mechanisms remain unclear. Here we applied differential display reverse transcription-polymerase chain reaction (DDRT-PCR) to parental and MDR-variants of U-2 OS human osteosarcoma cells, to clarify the genes involved in the MDR cells, and identified five candidate genes. These are BCRP (breast cancer resistance protein) encoding a transmembrane efflux pump; RB1CC1 (RB1-inducible coiled-coil 1), a tumor suppressor regulating RB1 (retinoblastoma 1) expression; a novel transcriptional variant of dUTPase; SSR2 (beta-signal sequence receptor), which is associated with protein translocation across ER membrane; and HSP105 encoding high molecular mass heat shock proteins. Molecular and biological characterization of these genes will yield further insight into the features between MDR and tumor progression in human osteosarcomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Traumatic bilateral locked facet at L4-5: report of a case associated with incorrect use of a three-point seatbelt.

We present a case of traumatic L4-5 bilateral facet dislocation, without neurological deficit, in a 32-year-old female patient, as an unusual seatbelt injury caused by positioning the shoulder harness improperly under her armpit. Open reduction, posterior interbody fusion, and posterior segmental instrumentation were carried out. The aim of this report is to describe this rarely encountered condition and speculate regarding automotive shoulder harness misuse as a potential cause of bilateral locked facet at L4-5, and to emphasize the importance of multidirectional X-ray on first examination. The unusual L4-5 level facet interlocking was attributed to misuse of the automobile shoulder harness. We propose the importance of recognizing this injury and following up on such clues as transverse process fractures and/or widened posterior elements.

Adult↗

PubMed2002

Expression of E-cadherin in chordomas: diagnostic marker and possible role of tumor cell affinity.

Chordoma is a relatively rare malignant bone tumor thought to arise from the remnants of the fetal notochord. Chordomas express epithelial cell markers such as cytokeratin and epithelial membrane antigen (EMA), which strongly suggests that the tumor cells grow via the mechanism of epithelial characterized cell-cell interactions. However, there are no known reports that have studied epithelial characterized cell-adhesion molecules such as E-cadherin or epithelial cell adhesion molecule (Ep-CAM) in chordomas. An immunohistochemical investigation was performed in seven cases of chordoma to determine the expression of pan-cytokeratin, Ep-CAM, and E-cadherin. Histological specimens showed the typical appearance of conventional chordoma but for two cases of chondroid chordoma. Cytokeratin was constantly expressed in conventional chordomas, but it was detected among a few cells with physaliphorous appearance in chondroid chordoma cases. Although no Ep-CAM expression was noted, E-cadherin was detected in most chordoma cells irrespective of histological subtypes. The expression of E-cadherin was negative among chondrosarcoma cells in this study as previously reported, and thus constant E-cadherin expression of chordoma cells suggests a role as a useful diagnostic marker to distinguish chondroid chordoma from chondrosarcoma. Furthermore, we speculate that E-cadherin may play a role in tumor cell adhesion and is also involved with histological and clinical features in chordomas.

Adult↗

PubMed2002

Brain-specific angiogenesis inhibitor 1 (BAI1) is expressed in human cerebral neuronal cells.

Brain-specific angiogenesis inhibitor 1 (BAI1) is a p53-target gene specifically expressed in the brain. We examined the distribution of the endogenous BAI1 protein in normal human brain tissue using a polyclonal antibody against the extracellular region of BAI1. Immunohistochemical study demonstrated that BAI1 was expressed in neuronal cells of the cerebral cortex but not in astrocytes. BAI1 protein was localized in the cellular cytoplasm and membrane. It was predominantly localized in the cellular membrane when expressed in cultured cells by means of gene transfection. BAI1 protein may play an important role in neuronal functions such as synapse formation and signal transduction.

Adult↗