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Kaoru Sugimoto

Publications and source records attributed to Kaoru Sugimoto.

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The role of XBtg2 in Xenopus neural development.

In early neural development, active cell proliferation and apoptosis take place concurrent with cell differentiation, but how these processes are coordinated remains unclear. In this study, we characterized the role of XBtg2 in Xenopus neural development. XBtg2 transcripts were detected at the edge of the anterolateral neural plate and the neural crest region at the midneurula stage, and in eyes and in part of the neural tube at the tailbud stage. Translational inhibition of XBtg2 affected anterior neural development and impaired eye formation. XBtg2 depletion altered the expression patterns of the early neural genes, Zic3 and SoxD, at the midneurula stage, but not at the early neurula stage. At the midneurula stage, XBtg2-depleted embryos exhibited a marked decrease in the expression of anterior neural genes, En2, Otx2, and Rx1, without any changes in neural crest genes, Slug and Snail, or an epidermal gene, XK81. These results suggest that XBtg2 is required for the differentiation of the anterior neural plate from the midneurula stage, but not for the specification of the fate and patterning of the neural plate. XBtg2-depleted embryos also exhibited an increase in both proliferation and apoptosis in the anterior neural plate; however, the altered expression patterns of neural markers were not reversed by inhibition of either the cell cycle or apoptosis. Based on these data, we propose that XBtg2 plays an essential role in the anterior neural development, by regulating neural cell differentiation, and, independently, cell proliferation and survival.

Animals↗

Immunoadsorption plasmapheresis using a phenylalanine column as an effective treatment for lupus nephritis.

Immunoadsorption plasmapheresis (IAPP) is effective for eliminating pathogenic molecules such as anti-DNA antibody (anti-DNA Ab) and immune complexes from the serum of patients with systemic autoimmune diseases. The purpose of this study was to assess patients with lupus nephritis (LN) treated by IAPP using a phenylalanine column and determine its efficacy with respect to conventional therapies. Six patients (M = 1, F = 5) with histologically proven LN associated with proteinuria and abnormal sedimentation on urinalysis were the subjects for this study. All were treated with oral corticosteroid (prednisolone 1 mg/kg/day) and IAPP (Immusorba PH - 350; 2 L of plasma twice weekly for 2 weeks). Serum anti-DNA Ab and complement, urinary protein, and creatinine clearance were measured over 6 weeks (pretreatment, before and after each of 2 IAPP sessions, and 1 and 4 weeks after the second IAPP session). Clinical efficacy of IAPP was compared with conventional pharmacotherapy regimes by conducting a retrospective review of 23 LN patients treated at our hospital using corticosteroid pulse therapy (CSPT, N = 7, intravenous methylprednisolone 500 mg/day for 3 days), intravenous cyclophosphamide pulse therapy (IVCY, N = 7), or corticosteroid monotherapy (CSMT, N = 9, oral prednisone 1 mg/kg body weight daily, for 4 weeks). Immunosuppressants and anticoagulants were not used. With IAPP, mean urinary protein excretion decreased from 2.2 +/- 1.7 g/day pretreatment to 0.4 +/- 0.6 g/day post-treatment (P < 0.001). Mean serum anti-DNA Ab also decreased from 84.0 +/- 88.1 U/mL pretreatment to 5.8 +/- 5.5 U/mL post-treatment (P < 0.05). In combination with corticosteroid therapy, IAPP would appear to be an effective and safe treatment for LN.

Adult↗

XBtg2 is required for notochord differentiation during early Xenopus development.

The notochord is essential for normal vertebrate development, serving as both a structural support for the embryo and a signaling source for the patterning of adjacent tissues. Previous studies on the notochord have mostly focused on its formation and function in early organogenesis but gene regulation in the differentiation of notochord cells itself remains poorly defined. In the course of screening for genes expressed in developing notochord, we have isolated Xenopus homolog of Btg2 (XBtg2). The mammalian Btg2 genes, Btg2/PC3/TIS21, have been reported to have multiple functions in the regulation of cell proliferation and differentiation but their roles in early development are still unclear. Here we characterized XBtg2 in early Xenopus laevis embryogenesis with focus on notochord development. Translational inhibition of XBtg2 resulted in a shortened and bent axis phenotype and the abnormal structures in the notochord tissue, which did not undergo vacuolation. The XBtg2-depleted notochord cells expressed early notochord markers such as chordin and Xnot at the early tailbud stage, but failed to express differentiation markers of notochord such as Tor70 and 5-D-4 antigens in the later stages. These results suggest that XBtg2 is required for the differentiation of notochord cells such as the process of vacuolar formation after determination of notochord cell fate.

Animals↗

Axial protocadherin is a mediator of prenotochord cell sorting in Xenopus.

Prenotochord cell sorting is regarded as one of the first cell sorting events in early chordate development. We recently demonstrated that this sorting event occurs in vitro, although the mediator of this activity remains unidentified. Herein, we report the isolation of a full-length cDNA clone of Axial protocadherin (AXPC), the homologue of human protocadherin-1 (PCD1). AXPC encodes a transmembrane protein (AXPC) that is expressed exclusively in the notochord at the neurula stage and in the pronephros, somites, heart, optic vesicle, otic vesicle, and distinct parts of the brain at the tailbud stage. Cell dissociation and reaggregation assays and in vivo microinjection experiments demonstrated that cells overexpressing a membrane-tethered form of AXPC (MT-AXPC) acquired the same adhesive properties as prenotochord cells. Moreover, microinjection of either mRNA encoding the dominant negative form of AXPC (DN-AXPC) or morpholino oligonucleotides interferes with the sorting activity of prenotochord cells and normal axis formation. This study suggests that AXPC is necessary and sufficient for prenotochord cell sorting in the gastrulating embryo, and may also mediate sorting events later in development.

Animals↗

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