小野通女筆「霊照女図」の解釈をめぐって

（付記）本稿は、平成二〇年一月に筑波大学大学院に提出した中間評価論文に基づき、加筆訂正を行ったものです。著作権保護のため、すべての掲載図版に墨消し処理を施しています

小野通女と公家との交流について : 「人麿図」等の和歌を伴う書画を中心に

本稿は2011年3月に筑波大学に提出した博士論文の一部の内容に加筆、修正したものです。著作権保護のため、すべての掲載図版に墨消し処理を施しています

Fermi surface topology and electronic transport properties of a chiral crystal NbGe2_2 with strong electron-phonon interaction

We report the electronic structures and transport properties of a chiral crystal NbGe$_2$, which is a candidate for a coupled electron-phonon liquid. The electrical resistivity and thermoelectric power of NbGe$_2$ exhibit clear differences compared to those of NbSi2 even though both niobium ditetrelides are isostructural and isoelectronic. We discuss the intriguing transport properties of NbGe$_2$ based on a van Hove-type singularity in the density of states. The analysis of de Haas-van Alphen oscillations measured by the field modulation and magnetic torque methods reveals the detailed shape of the Fermi surface of NbGe$_2$ by comparison with the results of energy band structure calculations using a local density approximation. The electron and hole Fermi surfaces of NbGe$_2$ split into two because of the anti-symmetric spin-orbit interaction. The temperature dependence of quantum oscillations indicates that the effective mass is isotropically enhanced in NbGe$_2$ due to strong electron-phonon interaction.Comment: 9 pages, 7 figures, To be published in Phys. Rev.

Identification of two novel activities of the Wnt signaling regulator Dickkopf 3 and characterization of its expression in the mouse retina

<p>Abstract</p> <p>Background</p> <p>The Wnt signaling pathway is a cellular communication pathway that plays critical roles in development and disease. A major class of Wnt signaling regulators is the Dickkopf (Dkk) family of secreted glycoproteins. Although the biological properties of Dickkopf 1 (Dkk1) and Dickkopf 2 (Dkk2) are well characterized, little is known about the function of the related Dickkopf 3 (Dkk3) protein in vivo or in cell lines. We recently demonstrated that Dkk3 transcripts are upregulated during photoreceptor death in a mouse model of retinal degeneration. In this study, we characterized the activity of Dkk3 in Wnt signaling and cell death.</p> <p>Results</p> <p>Dkk3 was localized to Müller glia and retinal ganglion cells in developing and adult mouse retina. Western blotting confirmed that Dkk3 is secreted from Müller glia cells in culture. We demonstrated that Dkk3 potentiated Wnt signaling in Müller glia and HEK293 cells but not in COS7 cells, indicating that it is a cell-type specific regulator of Wnt signaling. This unique Dkk3 activity was blocked by co-expression of Dkk1. Additionally, Dkk3 displayed pro-survival properties by decreasing caspase activation and increasing viability in HEK293 cells exposed to staurosporine and H₂O₂. In contrast, Dkk3 did not protect COS7 cells from apoptosis.</p> <p>Conclusion</p> <p>These data demonstrate that Dkk3 is a positive regulator of Wnt signaling, in contrast to its family member Dkk1. Furthermore, Dkk3 protects against apoptosis by reducing caspase activity, suggesting that Dkk3 may play a cytoprotective role in the retina.</p

IL10-driven STAT3 signalling in senescent macrophages promotes pathological eye angiogenesis

Macrophage dysfunction plays a pivotal role during neovascular proliferation in diseases of ageing including cancers, atherosclerosis and blinding eye disease. In the eye, choroidal neovascularization (CNV) causes blindness in patients with age-related macular degeneration (AMD). Here we report that increased IL10, not IL4 or IL13, in senescent eyes activates STAT3 signalling that induces the alternative activation of macrophages and vascular proliferation. Targeted inhibition of both IL10 receptor-mediated signalling and STAT3 activation in macrophages reverses the ageing phenotype. In addition, adoptive transfer of STAT3-deficient macrophages into eyes of old mice significantly reduces the amount of CNV. Systemic and CD163(+) eye macrophages obtained from AMD patients also demonstrate STAT3 activation. Our studies demonstrate that impaired SOCS3 feedback leads to permissive IL10/STAT3 signalling that promotes alternative macrophage activation and pathological neovascularization. These findings have significant implications for our understanding of the pathobiology of age-associated diseases and may guide targeted immunotherapy

Intestinal Diffuse Large B-Cell Lymphoma in a Patient with Systemic Lupus Erythematosus

A 44-year-old Japanese woman with systemic lupus erythematosus (SLE) presented to our hospital with abdominal pain. Radiological and endoscopic examinations led to the diagnosis of diffuse large B-cell lymphoma of the jejunum, which was subsequently resected. Patients with SLE reportedly have an increased risk of non-Hodgkin lymphoma, as demonstrated by our patient. Hence, lymphoma should be considered in the differential diagnosis of neoplastic lesions emerging in SLE patients. In addition, flow cytometry using endoscopically biopsied fragments is useful for the immediate diagnosis of lymphoma, leading to timely and accurate preoperative staging

Safe and efficient method for cryopreservation of human induced pluripotent stem cell-derived neural stem and progenitor cells by a programmed freezer with a magnetic field

AbstractStem cells represent a potential cellular resource in the development of regenerative medicine approaches to the treatment of pathologies in which specific cells are degenerated or damaged by genetic abnormality, disease, or injury. Securing sufficient supplies of cells suited to the demands of cell transplantation, however, remains challenging, and the establishment of safe and efficient cell banking procedures is an important goal. Cryopreservation allows the storage of stem cells for prolonged time periods while maintaining them in adequate condition for use in clinical settings. Conventional cryopreservation systems include slow-freezing and vitrification both have advantages and disadvantages in terms of cell viability and/or scalability. In the present study, we developed an advanced slow-freezing technique using a programmed freezer with a magnetic field called Cells Alive System (CAS) and examined its effectiveness on human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs). This system significantly increased cell viability after thawing and had less impact on cellular proliferation and differentiation. We further found that frozen-thawed hiPSC-NS/PCs were comparable with non-frozen ones at the transcriptome level. Given these findings, we suggest that the CAS is useful for hiPSC-NS/PCs banking for clinical uses involving neural disorders and may open new avenues for future regenerative medicine

Cutaneous Angiosarcoma: The Possibility of New Treatment Options Especially for Patients with Large Primary Tumor

The most widely accepted treatment for cutaneous angiosarcoma (CAS) is wide local excision and postoperative radiation to decrease the risk of recurrence. Positive surgical margins and large tumors (T2, >5 cm) are known to be associated with poor prognosis. Moreover, T2 tumors are known to be associated with positive surgical margins. According to previous reports, the majority of CAS patients in Japan had T2 tumors, whereas less than half of the patients in the studies from western countries did so. Consequently, the reported 5-year overall survival of Japanese CAS patients without distant metastasis was only 9%, lower than that for stage-IV melanoma. For patients with T2 tumors, management of subclinical metastasis should be considered when planning the initial treatment. Several attempts to control subclinical metastasis have been reported, such as using adjuvant/neoadjuvant chemotherapy in addition to conventional surgery plus radiation. Unfortunately, those attempts did not show any clinical benefit. Besides surgery, new chemotherapeutic approaches for advanced CAS have been introduced in the past couple of decades, such as paclitaxel and docetaxel. We proposed the use of chemoradiotherapy (CRT) using taxanes instead of surgery plus radiation for patients with T2 tumors without distant metastasis and showed a high response ratio with prolonged survival. However, this prolonged survival was seen only in patients who received maintenance chemotherapy after CRT, indicating that continuous chemotherapy is mandatory to control subclinical residual tumors. With the recent development of targeted drugs for cancer, many potential drugs for CAS are now available. Given that CAS expresses a high level of vascular endothelial growth factor (VEGF) receptor, drugs that target VEGF signaling pathways such as anti-VEGF monoclonal antibody and tyrosine kinase inhibitors are also promising, and several successful treatments have been reported. Besides targeted drugs, several new cytotoxic anticancer drugs such as eribulin or trabectedin have also been shown to be effective for advanced sarcoma. However, most of the clinical trials did not include a sufficient number of CAS patients. Therefore, clinical trials focusing only on CAS should be performed to evaluate the effectiveness of these new drugs