鶏卵法によるヒト癌転移巣に対する抗癌剤および腫瘍壊死因子の抗腫瘍活性ならびに温熱併用効果に関する検討

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1067号, 学位授与年月日：平成5年3月25日,学位授与年：199

AAD-2004, a potent spin trapping molecule and microsomal prostaglandin E synthase-1 inhibitor, shows safety and efficacy in a mouse model of ALS

While free radicals and inflammation constitute major routes of neuronal injury occurring in neurodegenerative diseases, neither antioxidants nor nonsteroidal anti-inflammatory drugs (NSAIDs) have shown significant efficacy in human clinical trials. To explore the possibility that concurrent blockade of free radicals and PGE2-mediated inflammation might constitute a safe and effective therapeutic approach to certain neurodegenerative diseases, we have developed 2-hydroxy-5-[2-(4-trifluoromethylphenyl)-ethylaminobezoic acid (AAD-2004) as a derivative of aspirin. AAD-2004 completely removed free radicals at 50 nM as a potent spin trapping molecule and inhibited microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 230 nM. Oral administration of AAD-2004 blocked free radical formation, PGE2 formation, and microglial activation in the spinal motor neurons of SOD1G93A mice. As a consequence, AAD-2004 reduced autophagosome formation, axonopathy, and motor neuron degeneration, improving motor function and increasing life span. In these assays, AAD-2004 was superior to ibuprofen or riluzole. Gastric bleeding was not induced by AAD-2004 even at a dose 400-fold higher than that required to obtain maximal therapeutic efficacy in SOD1G93A mice. Targeting both mPGES-1 and free radicals may be a promising approach to reduce neurodegeneration in ALS and possibly other neurodegenerative diseases

The Extended Virgo Cluster Catalog

We present a new catalog of galaxies in the wider region of the Virgo cluster, based on the Sloan Digital Sky Survey (SDSS) Data Release 7. The Extended Virgo Cluster Catalog (EVCC) covers an area of 725 deg^2 or 60.1 Mpc^2. It is 5.2 times larger than the footprint of the classical Virgo Cluster Catalog (VCC) and reaches out to 3.5 times the virial radius of the Virgo cluster. We selected 1324 spectroscopically targeted galaxies with radial velocities less than 3000 kms^-1. In addition, 265 galaxies that have been missed in the SDSS spectroscopic survey but have available redshifts in the NASA Extragalactic Database are also included. Our selection process secured a total of 1589 galaxies of which 676 galaxies are not included in the VCC. The certain and possible cluster members are defined by means of redshift comparison with a cluster infall model. We employed two independent and complementary galaxy classification schemes: the traditional morphological classification based on the visual inspection of optical images and a characterization of galaxies from their spectroscopic features. SDSS u, g, r, i, and z passband photometry of all EVCC galaxies was performed using Source Extractor. We compare the EVCC galaxies with the VCC in terms of morphology, spatial distribution, and luminosity function. The EVCC defines a comprehensive galaxy sample covering a wider range in galaxy density that is significantly different from the inner region of the Virgo cluster. It will be the foundation for forthcoming galaxy evolution studies in the extended Virgo cluster region, complementing ongoing and planned Virgo cluster surveys at various wavelengths.Comment: 69 pages, 29 figures, 4 tables, accepted for publication in the ApJ

Large-scale filamentary structures around the Virgo cluster revisited

We revisit the filamentary structures of galaxies around the Virgo cluster, exploiting a larger dataset based on the HyperLeda database than previous studies. In particular, this includes a large number of low-luminosity galaxies, resulting in better sampled individual structures. We confirm seven known structures in the distance range 4~$h^{-1}$~Mpc~$<$ SGY~$<$ 16~$h^{-1}$ Mpc, now identified as filaments, where SGY is the axis of the supergalactic coordinate system roughly along the line of sight. The Hubble diagram of the filament galaxies suggests they are infalling toward the main-body of the Virgo cluster. We propose that the collinear distribution of giant elliptical galaxies along the fundamental axis of the Virgo cluster is smoothly connected to two of these filaments (Leo~II~A and B). Behind the Virgo cluster (16~$h^{-1}$~Mpc~$<$ SGY~$<$ 27~$h^{-1}$~Mpc), we also identify a new filament elongated toward the NGC 5353/4 group ("NGC 5353/4 filament") and confirm a sheet that includes galaxies from the W and M clouds of the Virgo cluster ("W-M sheet"). In the Hubble diagram, the NGC 5353/4 filament galaxies show infall toward the NGC 5353/4 group, whereas the W-M sheet galaxies do not show hints of gravitational influence from the Virgo cluster. The filamentary structures identified can now be used to better understand the generic role of filaments in the build-up of galaxy clusters at z~$\approx$~0.Comment: 8 pages, 4 figures, accepted for publication in Ap

A Novel Mutation in the XLRS1 Gene in a Korean Family with X-linked Retinoschisis

Purpose: To report a novel missense mutation in the XLRS1 gene in a Korean family with X-linked retinoschisis. Methods: Observation case report of a family with a proband with X-linked retinoschisis underwent complete ophthalmologic examination. Genomic DNA was excluded from the family's blood and all exons of the XLRS1 gene were amplified by polymerase chain reaction and analyzed using a direct sequencing method. Results: A novel Leu103Phe missense mutation was identified. Conclusions: A novel Leu103Phe mutation is an additional missense mutation which is responsible for the pathogenesis of X-linked retinoschisis.ope

Mouse genetics: Catalogue and scissors

Phenotypic analysis of gene-specific knockout (KO) mice has revolutionized our understanding of in vivo gene functions. As the use of mouse embryonic stem (ES) cells is inevitable for conventional gene targeting, the generation of knockout mice remains a very time-consuming and expensive process. To accelerate the large-scale production and phenotype analyses of KO mice, international efforts have organized global consortia such as the International Knockout Mouse Consortium (IKMC) and International Mouse Phenotype Consortium (IMPC), and they are persistently expanding the KO mouse catalogue that is publicly available for the researches studying specific genes of interests in vivo. However, new technologies, adopting zinc-finger nucleases (ZFNs) or Transcription Activator-like Effector (TALE) Nucleases (TALENs) to edit the mouse genome, are now emerging as valuable and effective shortcuts alternative for the conventional gene targeting using ES cells. Here, we introduce the recent achievement of IKMC, and evaluate the significance of ZFN/TALEN technology in mouse genetics. [BMB Reports 2012; 45(12): 686-692]

AKARI Detection of the Infrared-Bright Supernova Remnant B0104-72.3 in the Small Magellanic Cloud

We present a serendipitous detection of the infrared-bright supernova remnant (SNR) B0104-72.3 in the Small Magellanic Cloud by the Infrared Camera (IRC) onboard AKARI. An elongated, partially complete shell is detected in all four observed IRC bands covering 2.6-15 um. The infrared shell surrounds radio, optical, and X-ray emission associated with the SNR and is probably a radiative SNR shell. This is the first detection of a SNR shell in this near/mid-infrared waveband in the Small Magellanic Cloud. The IRC color indicates that the infrared emission might be from shocked H2 molecules with some possible contributions from ionic lines. We conclude that B0104-72.3 is a middle-aged SNR interacting with molecular clouds, similar to the Galactic SNR IC 443. Our results highlight the potential of AKARI IRC observations in studying SNRs, especially for diagnosing SNR shocks.Comment: 12 pages with 3 figures, accepted for publication in AKARI PASJ special issu