Identification of Antigenic Site Within hsc 70 by Serum Autoantibody in Patients with Cancer-associated Retinopathy

In our previous studies, both recoverin and heat shock cognate protein 70 (hsc 70) were found as autoantigens recognized by sera from four patients with cancer-associated retinopathy (CAR) . In the present study on the mole-cular mechanism of antibody generation in CAR, we identified the antigenic site within hsc 70 by the patients\u27 sera using deletion mutants of hsc 73. We expressed a series of deletion mutants of hsc 73 proteins and subjected then to western blot analysis. In western blot analysis, CAR patient\u27s serum reacted with wild type hsp 70, but not with the C-terminal truncated mutants. This data demonstrated that the antigenic site was located within the C-terminus region of hsc 73 as identified by CAR patient\u27s serum

A Safe Surgical Procedure for Old Distractive Flexion Injuries of the Subaxial Cervical Spine

Study DesignRetrospective review.PurposeTo describe a safe and effective surgical procedure for old distractive flexion (DF) injuries of the subaxial cervical spine.Overview of LiteratureSurgical treatment is required in old cases when a progression of the kyphotic deformity and/or persistent neck pain and/or the appearance of new neurological symptoms are observed. Since surgical treatment is more complicated and dangerous in old cases than in acute distractive-flexion cases, the indications for surgery and the selection of the surgical procedure must be carefully conducted.MethodsTo identify a safe and effective surgical procedure, the procedure selected, reason(s) for its selection, and associated neurological complications were investigated in 13 patients with old cervical DF injuries.ResultsNo neurological complications were observed in nine patients (DF stage 2 or 3) who underwent the anterior-posterior-anterior (A-P-A) method and two patients (DF stage 1) who underwent the posterior method. It was initially planned that two patients (DF stage 2) who underwent the P-A method would be treated using the Posterior method alone; however, anterior discectomy was added to the procedure after the development of a severe spinal cord disorder.ConclusionsThe A-P-A method (anterior discectomy, posterior release and/or partial facetectomy, reduction and instrumentation, anterior bone grafting) is considered to be a suitable surgical procedure for old cervical DF injuries

Immunolocalization of Adhesion Molecules in Rheumatoid and Osteoarthritic Synovial Tissues

To elucidate the potential role of adhesion molecules in the pathogenesis of rheumatoid arthritis (RA), we stained specimens of synovial tissue from patients with RA and osteoarthritis (OA) with monoclonal antibodies against adhesion molecules using an immunohistochemical method. Positive staining with anti-ICAM-1 monoclonal antibody was detected on the synovial lining cells, the sublining cells and the capillary endothelial cells in the synovium from patients with RA, and, to a lesser degree, in that from patients with OA. The capillary endothelial cells from patients with RA intensively expressed both ELAM-1 and VLA-5α molecules, in contrast to that from OA patients. The intensity of both ICAM-1 and ELAM-1 on the capillary endothelial cells in RA synovium was comparable to disease activity and to the degree of synovial proliferation. A high density of expression of LFA-1α , VLA-4α and VLA-5α was observed on the mononuclear cells that infiltrated the RA synovium, especially in the lesions with aggregated mononuclear cells. The findings clearly demonstrated an up-regulation of the expression of adhesion molecules on synovial cells, capillary endothelial cells and infiltrated mononuclear cells in the synovial tissues of patients with RA. This enhanced expression of adhesion molecules may play an important role in the migration of mononuclear cells into the synovial tissues and thus perpetuate the inflammatory response in these tissues

Clinical Influence of Cervical Spinal Canal Stenosis on Neurological Outcome after Traumatic Cervical Spinal Cord Injury without Major Fracture or Dislocation

Study DesignRetrospective case series.PurposeTo clarify the influence of cervical spinal canal stenosis (CSCS) on neurological functional recovery after traumatic cervical spinal cord injury (CSCI) without major fracture or dislocation.Overview of LiteratureThe biomechanical etiology of traumatic CSCI remains under discussion and its relationship with CSCS is one of the most controversial issues in the clinical management of traumatic CSCI.MethodsTo obtain a relatively uniform background, patients non-surgically treated for an acute C3–4 level CSCI without major fracture or dislocation were selected. We analyzed 58 subjects with traumatic CSCI using T2-weighted mid-sagittal magnetic resonance imaging. The sagittal diameter of the cerebrospinal fluid (CSF) column, degree of canal stenosis, and neurologic outcomes in motor function, including improvement rate, were assessed.ResultsThere were no significant relationships between sagittal diameter of the CSF column at the C3–4 segment and their American Spinal Injury Association motor scores at both admission and discharge. Moreover, no significant relationships were observed between the sagittal diameter of the CSF column at the C3–4 segment and their neurological recovery during the following period.ConclusionsNo relationships between pre-existing CSCS and neurological outcomes were evident after traumatic CSCI. These results suggest that decompression surgery might not be recommended for traumatic CSCI without major fracture or dislocation despite pre-existing CSCS

RUNX1 transactivates BCR-ABL1 expression in Philadelphia chromosome positive acute lymphoblastic leukemia

The emergence of tyrosine kinase inhibitors as part of a front-line treatment has greatly improved the clinical outcome of the patients with Ph⁺ acute lymphoblastic leukemia (ALL). However, a portion of them still become refractory to the therapy mainly through acquiring mutations in the BCR-ABL1 gene, necessitating a novel strategy to treat tyrosine kinase inhibitor (TKI)-resistant Ph⁺ ALL cases. In this report, we show evidence that RUNX1 transcription factor stringently controls the expression of BCR-ABL1, which can strategically be targeted by our novel RUNX inhibitor, Chb-M'. Through a series of in vitro experiments, we identified that RUNX1 binds to the promoter of BCR and directly transactivates BCR-ABL1 expression in Ph⁺ ALL cell lines. These cells showed significantly reduced expression of BCR-ABL1 with suppressed proliferation upon RUNX1 knockdown. Moreover, treatment with Chb-M' consistently downregulated the expression of BCR-ABL1 in these cells and this drug was highly effective even in an imatinib-resistant Ph⁺ ALL cell line. In good agreement with these findings, forced expression of BCR-ABL1 in these cells conferred relative resistance to Chb-M'. In addition, in vivo experiments with the Ph⁺ ALL patient-derived xenograft cells showed similar results. In summary, targeting RUNX1 therapeutically in Ph⁺ ALL cells may lead to overcoming TKI resistance through the transcriptional regulation of BCR-ABL1. Chb-M' could be a novel drug for patients with TKI-resistant refractory Ph⁺ ALL