平安時代における大堰川遊覧の和歌と序の表現―典拠の継承をめぐって―

The Oigawa River flowed from south to north through the western part of the Heian capital. Like nearby Sagano and Arashiyama, during the Heian Period it was a sightseeing excursion area that capital aristocrats frequently visited. On the morning of September 10, 907, the day after the Chrysanthemum Festival, retired Emperor Uda made a royal visit to the Oigawa River. On this occasion, the attendant poets composed Chinese poems and waka poetry, in addition to a preface based on nine themes united under the title “The Imperial Visit: Chinese and Japanese Poems and Preface” (shown below). Of the waka, two were selected for inclusion in the Kokin Wakashu. The kana preface, written by Ki no Tsurayuki, is known as the Oigawa Gyoko Waka-Jo (“Preface to Waka composed during the Imperial Visit to the Oigawa River”). “The Imperial Visit: Chinese and Japanese Poems and Preface” powerfully influenced works created during excursions to the Oigawa River throughout the Heian Period. The first unique feature of Emperor Uda’s royal visit is that it is linked to poetry recitation gatherings held the morning after the Chrysanthemum Festival, which were only customary during his years as a retired ruler. “The Imperial Visit: Chinese and Japanese Poems and Preface” is deeply associated with the reading of Chinese poems at poetry gatherings held the morning after the Chrysanthemum Festival. Examples of these connections include the fact that the Chinese poems, in addition to a preface composed by Sugawara no Michizane at a poetry reading party (held 10 years before the imperial visit), include the word shusui (crystal stream in autumn), which is the first theme of the “The Imperial Visit: Chinese and Japanese Poems and Preface.” The word shusui is often employed, taking the work of Zhuangzi as the authority. In the Chinese poems and preface of Michizane, the location of the poetry recitation concretely expresses the thoughts of Zhuangzi. The writings contained in “The Imperial Visit: Chinese and Japanese Poems and Preface,” composed with shunsui as the theme, also express the superimposition of the scenery along the Oigawa river, along with the world of Zhuangzi’s thinking, with him as the authority.Ope

Separation into polar and hydrogen-bonding factors of the effects of alcohols on the emission spectrum of 4-phenyl-1-N,N-dimethylaminobutane in THF

The effects of the additions of protic and aprotic polar solvents on the emission spectrum of 4-phenyl-1-N,N-dimethylaminobutane (PDAB) in THF have been studied under conditions of steady-state illumination. The fluorescence spectrum of PDAB in THF was reported to consist of three component bands (band A at 285 nm (fluorescence of the phenyl group), band B at 343 nm (fluorescence of the amino group) and band C at 385 nm (emission from an intramolecular exciplex)). The intensities of bands B and C decreased with increasing solvent polarity. They also decreased owing to the hydrogen-bonding interaction between the amino group in PDAB and protic solvents, but in this case the intensity of band A was found to increase. Acetonitrile has only a polar effect and trichloroacetic acid only a hydrogen-bonding (or protonation) effect, while alcohols have both effects. The equilibrium constants for the formation of intermolecular hydrogen-bonded complexes of the amino group with alcohols were estimated from the intensity change of band A. The hydrogen-bonding and polar effects of alcohols on the intensities of bands B and C could be separately evaluated. The decrease in the intensities of bands B and C with increasing solvent polarity in THF-AN and THF-alcohol mixtures is considered to be caused by the conversion of the exciplex to an ion-pair enhanced by the increase in solvent polarity.</p

Vaccination with Human Induced Pluripotent Stem Cells Creates an Antigen-Specific Immune Response Against HIV-1 gp160

Induced pluripotent stem cells (iPSCs) are artificially derived from somatic cells that have been transduced with defined reprogramming factors. A previous report has indicated the possibility of using iPSCs as an immune stimulator to generate antigen-specific immunity. In our current study, we have investigated whether human iPSCs (hiPSCs) have the ability to enhance specific immune response against a human immunodeficiency virus type 1 (HIV-1) antigen in a xenogenic mouse model. Our results show that BALB/c mice immunized with hiPSCs transduced with an adenoviral vector encoding HIV-1 gp160 exhibited prominent antigen-specific cellular immune responses. We further found that pre-treatment of hiPSCs with ionizing radiation promotes the secretion of pro-inflammatory cytokines such as interleukin-1 alpha (IL-1α), IL-12, and IL-18. These cytokines might promote the activation of antigen-presenting cells and the effective induction of cellular immunity. Our present findings thus demonstrate that a hiPSCs-based vaccine has the potential to generate cellular immunity against viral antigens such as HIV-1 gp160 in a xenogenic condition

Psoriatic Inflammation Facilitates the Onset of Arthritis in a Mouse Model

Psoriatic arthritis (PsA) is a seronegative, inflammatory joint disease associated with psoriasis. In most patients with PsA, skin lesions precede arthritis; however, the causality of skin inflammation for the development of arthritis remains unclear. Gp130F759/F759 knock-in (F759) mice develop autoimmune arthritis after 1 year of age through persistent signal transducer and activator of transcription 3 (Stat3) activation due to impairment in SOCS3-dependent negative regulation. Here, we crossed F759 mice with K5.Stat3C transgenic mice, in which keratinocytes express constitutive active Stat3 (Stat3C), leading to generation of psoriasis-like skin change. F759 mice harboring the K5.Stat3C transgene not only had aggravated skin lesions but also spontaneously developed arthritis with high penetrance in adjacent paws as early as 3 weeks of age. The joint lesions included swelling of the peripheral paws and nail deformities contiguous with the skin lesions, closely resembling PsA. Histopathologic study revealed enthesitis and bone erosions, with mononuclear cell infiltrates. Quantitative reverse transcriptase–PCR (RT–PCR), immunohistochemical analyses, and flow cytometry showed upregulation of the IL-23/T helper type 17 (Th17) pathway in affected joints. Furthermore, enforced generation of psoriasis-like skin inflammation by topical treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) in F759 mice induced swelling of the underlying joints. This animal model renders psoriatic inflammation as the driver of arthritis and helps to further understand the pathogenesis of PsA

Secondary autoimmune hypothalamitis with severe memory impairment 7 years after the onset of diabetes insipidus due to lymphocytic hypophysitis: a case report

Background Autoimmune hypothalamitis is a very rare neuroendocrine disorder that causes central diabetes insipidus, headache, visual impairment, and sometimes cognitive impairment. Autoimmune hypothalamitis may occur in association with autoimmune hypophysitis, including lymphocytic hypophysitis, or in isolation. It is not known whether autoimmune hypothalamitis and autoimmune hypophysitis are consecutive diseases. Case presentation A 52-year-old woman developed autoimmune hypothalamitis 7 years after developing central diabetes insipidus due to lymphocytic hypophysitis, resulting in severe memory impairment. High-dose intravenous methylprednisolone therapy improved her cognitive function and decreased the size of the lesion. Conclusion This case presented a unique clinical course, with a long period of time between the onset of autoimmune hypopituitaritis and the development of autoimmune hypothalamitis

Induced cancer stem-like cells as a model for biological screening and discovery of agents targeting phenotypic traits of cancer stem cell

Cancer stem cells (CSCs) retain the capacity to propagate themselves through self-renewal and to produce heterogeneous lineages of cancer cells constituting the tumor. Novel drugs that target CSCs can potentially eliminate the tumor initiating cell population therefore resulting in complete cure of the cancer. We recently established a CSC-like model using induced pluripotent stem cell (iPSC) technology to reprogram and partially differentiate human mammary epithelial MCF-10A cells. Using the induced CSC-like (iCSCL) model, we developed a phenotypic drug assay system to identify agents that inhibit the stemness and self-renewal properties of CSCs. The selectivity of the agents was assessed using three distinct assays characterized by cell viability, cellular stemness and tumor sphere formation. Using this approach, we found that withaferin A (WA), an Ayurvedic medicine constituent, was a potent inhibitor of CSC stemness leading to cellular senescence primarily via the induction of p21Cip1 expression. Moreover, WA exhibited strong anti-tumorigenic activity against the iCSCL. These results indicate that our iCSCL model provides an innovative high throughput platform for a simple, easy, and cost-effective method to search for novel CSC-targeting drugs. Furthermore, our current study identified WA as a putative drug candidate for abrogating the stemness and tumor initiating ability of CSCs

Haploidentical Stem Cell Transplantation Using Post-Transplant Cyclophosphamide for T-Cell Prolymphocytic Leukemia after Alemtuzumab Induction Therapy: A Case Report

T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive disease with a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) followed by alemtuzumab administration is the most promising treatment for T-PLL but is associated with a high risk of infections as alemtuzumab strongly suppresses cellular immunity, leading to high transplant-related mortality and unsatisfactory survival rates. In addition, for patients without human leukocyte antigen-matched donors, haploidentical stem cell transplantation (haplo-SCT) using post-transplant cyclophosphamide (PTCy) has been used because of the ready availability of donors and achievement of results comparable to those of transplantation with human leukocyte antigen-matched donors. However, there are no reports on the efficacy and safety, including infectious complications, of haplo-SCT with PTCy after alemtuzumab therapy in patients with. Here, we describe a 66-year-old Japanese male patient with T-PLL treated successfully with haplo-SCT after induction therapy of alemtuzumab for T-PLL. Approximately 3 months after the achievement of complete remission with alemtuzumab for T-PLL, haplo-SCT with reduced-intensity conditioning and PTCy was performed. Infectious complications were improved by early therapeutic interventions, and peripheral T cell counts gradually recovered. The patient was alive for more than 16 months after allo-SCT with no signs of relapse. Thus, haplo-SCT using PTCy should be considered as an option after alemtuzumab treatment for T-PLL

miR-155, a Modulator of FOXO3a Protein Expression, Is Underexpressed and Cannot Be Upregulated by Stimulation of HOZOT, a Line of Multifunctional Treg

MicroRNAs (miRNAs) play important roles in regulating post-transcriptional gene repression in a variety of immunological processes. In particular, much attention has been focused on their roles in regulatory T (Treg) cells which are crucial for maintaining peripheral tolerance and controlling T cell responses. Recently, we established a novel type of human Treg cell line, termed HOZOT, multifunctional cells exhibiting a CD4+CD8+ phenotype. In this study, we performed miRNA profiling to identify signature miRNAs of HOZOT, and therein identified miR-155. Although miR-155 has also been characterized as a signature miRNA for FOXP3+ natural Treg (nTreg) cells, it was expressed quite differently in HOZOT cells. Under both stimulatory and non-stimulatory conditions, miR-155 expression remained at low levels in HOZOT, while its expression in nTreg and conventional T cells remarkably increased after stimulation. We next searched candidate target genes of miR-155 through bioinformatics, and identified FOXO3a, a negative regulator of Akt signaling, as a miR-155 target gene. Further studies by gain- and loss-of-function experiments supported a role for miR-155 in the regulation of FOXO3a protein expression in conventional T and HOZOT cells

PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation

Lentiviruses have evolved to acquire an auxiliary protein Vpx to counteract the intrinsic host restriction factor SAMHD1. Although Vpx is phosphorylated, it remains unclear whether such phosphorylation indeed regulates its activity toward SAMHD1. Here we identify the PIM family of serine/threonine protein kinases as the factors responsible for the phosphorylation of Vpx and the promotion of Vpx-mediated SAMHD1 counteraction. Integrated proteomics and subsequent functional analysis reveal that PIM family kinases, PIM1 and PIM3, phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1. Inhibition of the PIM kinases promotes the antiviral activity of SAMHD1, ultimately reducing viral replication. Our results highlight a new mode of virus–host cell interaction in which host PIM kinases facilitate promotion of viral infectivity by counteracting the host antiviral system, and suggest a novel therapeutic strategy involving restoration of SAMHD1-mediated antiviral response