294 research outputs found

    JOURNAL OF NEUROINFLAMMATION

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    A novel autoantibody against ephrin type B receptor 2 in acute necrotizing encephalopath

    An Innovative Method to Identify Autoantigens Expressed on the Endothelial Cell Surface: Serological Identification System for Autoantigens Using a Retroviral Vector and Flow Cytometry (SARF)

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    Autoantibodies against integral membrane proteins are usually pathogenic. Although anti-endothelial cell antibodies (AECAs) are considered to be critical, especially for vascular lesions in collagen diseases, most molecules identified as autoantigens for AECAs are localized within the cell and not expressed on the cell surface. For identification of autoantigens, proteomics and expression library analyses have been performed for many years with some success. To specifically target cell-surface molecules in identification of autoantigens, we constructed a serological identification system for autoantigens using a retroviral vector and flow cytometry (SARF). Here, we present an overview of recent research in AECAs and their target molecules and discuss the principle and the application of SARF. Using SARF, we successfully identified three different membrane proteins: fibronectin leucine-rich transmembrane protein 2 (FLRT2) from patients with systemic lupus erythematosus (SLE), intercellular adhesion molecule 1 (ICAM-1) from a patient with rheumatoid arthritis, and Pk (Gb3/CD77) from an SLE patient with hemolytic anemia, as targets for AECAs. SARF is useful for specific identification of autoantigens expressed on the cell surface, and identification of such interactions of the cell-surface autoantigens and pathogenic autoantibodies may enable the development of more specific intervention strategies in autoimmune diseases

    Wave Measurements Using GPS Velocity Signals

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    This study presents the idea of using GPS-output velocity signals to obtain wave measurement data. The application of the transformation from a velocity spectrum to a displacement spectrum in conjunction with the directional wave spectral theory are the core concepts in this study. Laboratory experiments were conducted to verify the accuracy of the inversed displacement of the surface of the sea. A GPS device was installed on a moored accelerometer buoy to verify the GPS-derived wave parameters. It was determined that loss or drifting of the GPS signal, as well as energy spikes occurring in the low frequency band led to erroneous measurements. Through the application of moving average skill and a process of frequency cut-off to the GPS output velocity, correlations between GPS-derived, and accelerometer buoy-measured significant wave heights and periods were both improved to 0.95. The GPS-derived one-dimensional and directional wave spectra were in agreement with the measurements. Despite the direction verification showing a 10° bias, this exercise still provided useful information with sufficient accuracy for a number of specific purposes. The results presented in this study indicate that using GPS output velocity is a reasonable alternative for the measurement of ocean waves

    Clinical efficacy of tocilizumab in patients with active rheumatoid arthritis in real clinical practice

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    The previous clinical studies have demonstrated tocilizumab monotherapy to be highly effective in rheumatoid arthritis (RA). The objectives of the present article are to report the efficacy and safety of tocilizumab in patients with active RA in real clinical practice. In total, 61 patients with RA were treated with tocilizumab. Any comorbidities they had, especially infections, were treated thoroughly before they were given the drug. We provided guidance on infection control and prevention. Mean age of the patients was 60.9 ± 12.4 years, and their mean disease duration 10.9 ± 9.2 years. The patients remained on steroids, methotrexate, and tacrolimus as before, but were taken off any other drugs they had been using prior to the treatment. Mean of the 28-joint disease activity score using erythrocyte sedimentation rate was 4.75 ± 1.15 initially and fell to 2.21 ± 0.97 after two doses (n = 50). After four doses, the remission rate was 83.8% (31/37). All patients responded well to the therapy and there was no decrease in the efficacy of tocilizumab during the treatment. Even in the real clinical setting, treatment with tocilizumab can rapidly induce remission in RA in a high proportion of patients and is generally safe and well tolerated. Tocilizumab would seem to be promising as a first-line choice for the treatment of RA

    GATA-1 testis activation region is essential for Sertoli cell-specific expression of GATA-1 gene in transgenic mouse

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    Background: The erythroid transcription factor GATA-1 is also expressed in Sertoli cells of the testis. The testicular expression of GATA-1 is regulated in a developmental and spermatogenic stage-specific manner. To further clarify the regulatory mechanisms of testicular GATA-1 gene expression, we carried out transgenic reporter gene expression analyses. Results: We found that GATA-1 expression in Sertoli cells is markedly decreased concomitant with the emergence of elongated spermatids in the seminiferous tubules. Transgenic reporter mouse analyses revealed that a 15 kb GATA-1 genomic region is sufficient to recapitulate the gene expression profile in Sertoli cells. While the GATA-1 haematopoietic enhancer and the proximal first exon are included within the 15 kb genomic region, these regulatory elements are not essential for GATA-1 expression in Sertoli cells. Further analyses using deletion constructs revealed that a 1.5 kb region 5′ to the GATA-1 haematopoietic enhancer is essential for gene expression in Sertoli cells and this region is referred to as the GATA-1 testis activation region. Conclusion: These results thus demonstrated that the GATA-1 testis activation region is essential for Sertoli cell-specific expression of GATA-1 gene. The 15 kb genomic region is applicable and useful for the expression vector system specific for adult Sertoli cells in stage VII to IX.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71393/1/j.1365-2443.2003.00658.x.pd

    Molecular cloning and preliminary function study of iron responsive element binding protein 1 gene from cypermethrin-resistant Culex pipiens pallens

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    <p>Abstract</p> <p>Background</p> <p>Insecticide resistance jeopardizes the control of mosquito populations and mosquito-borne disease control, which creates a major public health concern. Two-dimensional electrophoresis identified one protein segment with high sequence homology to part of <it>Aedes aegypti </it>iron-responsive element binding protein (IRE-BP).</p> <p>Method</p> <p>RT-PCR and RACE (rapid amplification of cDNA end) were used to clone a cDNA encoding full length IRE-BP 1. Real-time quantitative RT-PCR was used to evaluate the transcriptional level changes in the Cr-IRE strain <it>Aedes aegypti </it>compared to the susceptible strain of <it>Cx. pipiens pallens</it>. The expression profile of the gene was established in the mosquito life cycle. Methyl tritiated thymidine (<sup>3</sup>H-TdR) was used to observe the cypermethrin resistance changes in C6/36 cells containing the stably transfected IRE-BP 1 gene of <it>Cx. pipiens pallens</it>.</p> <p>Results</p> <p>The complete sequence of iron responsive element binding protein 1 (IRE-BP 1) has been cloned from the cypermethrin-resistant strain of <it>Culex pipiens pallens </it>(Cr-IRE strain). Quantitative RT-PCR analysis indicated that the IRE-BP 1 transcription level was 6.7 times higher in the Cr-IRE strain than in the susceptible strain of 4th instar larvae. The IRE-BP 1 expression was also found to be consistently higher throughout the life cycle of the Cr-IRE strain. A protein of predicted size 109.4 kDa has been detected by Western blotting in IRE-BP 1-transfected mosquito C6/36 cells. These IRE-BP 1-transfected cells also showed enhanced cypermethrin resistance compared to null-transfected or plasmid vector-transfected cells as determined by <sup>3</sup>H-TdR incorporation.</p> <p>Conclusion</p> <p>IRE-BP 1 is expressed at higher levels in the Cr-IRE strain, and may confer some insecticide resistance in <it>Cx. pipiens pallens</it>.</p
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