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1.
H. Furuya Yoh-ji Kukita Sukehisa Nagano Yasuyoshi Sakai Yoriaki Yamashita Hidenao Fukuyama Yuichiro Inatomi Yutaka Saito Ryoko Koike Shoji Tsuji Yasuyuki Fukumaki Kenshi Hayashi Takuro Kobayashi 《Human genetics》1997,100(3-4):450-456
We examined galactosylceramidase (GALC) cDNA in four Japanese patients with adult onset globoid cell leukodystrophy (Krabbe
disease; AO-GLD) by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis, subsequent sequence
determination, and restriction enzyme digestion of PCR products. Initial symptoms were the onset of slowly progressive spastic
paraplegia from the middle of the second decade, and all patients had diminished GALC activity in their leukocytes. We identified
three missense mutations (I66M, G270D, L618S) and one exon-6 skipping (535– 573del). Two of the patients had only the I66M
mutant mRNA, and one only the G270D mutant mRNA. The fourth patient carried a compound heterozygous mutation of 535–573del
and L618S. To determine the enzymatic activities produced by these mutations, we constructed mutated GALC cDNAs and expressed
them in COS-1 cells. Three mutations, viz., G270D, L618S, and exon-6 skipping (535–573del), produced diminished GALC activity
as expected. The I66M mutation in the wild-type GALC cDNA(I289) had normal activity, but when this mutation and the V289 polymorphism
were introduced into the same allele, it had decreased activity. Thus, the combination of a unique mutation and polymorphism
causes conformational change in the GALC enzyme, resulting in low enzymatic activity. AO-GLD mutations, including those found
here, are located in the N-terminus (I66M, G270D, 535–573del) or C-terminus (L618S) of the GALC enzyme, whereas the reported
mutations in the infantile form (IF-GLD) are in the central domain. This difference in mutation sites may affect the clinical
features of GLD.
Received: 4 February 1997 / Accepted: 28 April 1997 相似文献
2.
Human observers perceive illusory rotations after the disappearance of circularly repeating patches containing dark-to-light luminance. This afterimage rotation is a very powerful phenomenon, but little is known about the mechanisms underlying it. Here, we use a computational model to show that the afterimage rotation can be explained by a combination of fast light adaptation and the physiological architecture of the early visual system, consisting of ON- and OFF-type visual pathways. In this retinal ON/OFF model, the afterimage rotation appeared as a rotation of focus lines of retinal ON/OFF responses. Focus lines rotated clockwise on a light background, but counterclockwise on a dark background. These findings were consistent with the results of psychophysical experiments, which were also performed by us. Additionally, the velocity of the afterimage rotation was comparable with that observed in our psychophysical experiments. These results suggest that the early visual system (including the retina) is responsible for the generation of the afterimage rotation, and that this illusory rotation may be systematically misinterpreted by our high-level visual system. 相似文献
3.
Yuichiro Higuchi Kenji Kawai Masahumi Yamamoto Miyuki Kuronuma Yasuhiko Ando Ikumi Katano Masato Nakamura Hiroshi Suemizu 《Experimental Animals》2014,63(1):55-62
The interaction between transplanted cells and host tissues is important for the growth
and maintenance of transplanted cells. To analyze the mechanisms of these interactions, a
systemic fluorescent protein-expressing mouse is a useful recipient. In this study, we
generated a novel NOG strain, which strongly expresses enhanced green fluorescent protein
(EGFP; PgkEGFP-NOG), especially in the liver, kidney, gastrointestinal tract, and testis.
Because the host tissues expressed EGFP, xenotransplanted human cancer cells were clearly
identified as EGFP-negative colonies in PgkEGFP-NOG mice. Immunohistochemical analysis
revealed that EGFP-expressing stromal tissues formed a complicated tumor microenvironment
within xenograft tissues. Moreover, a similar microenvironment was observed in human iPS
cell-derived teratomas. Collectively, these results indicated that a suitable
microenvironment is essential for the growth and maintenance of xenotransplanted cells and
that PgkEGFP-NOG mice represent a useful animal model for analyzing the mechanisms of
microenvironment formation. 相似文献
4.
Masamitsu Konno Atsushi Hamabe Shinichiro Hasegawa Hisataka Ogawa Takahito Fukusumi Shimpei Nishikawa Katsuya Ohta Yoshihiro Kano Miyuki Ozaki Yuko Noguchi Daisuke Sakai Toshihiro Kudoh Koichi Kawamoto Hidetoshi Eguchi Taroh Satoh Masahiro Tanemura Hiroaki Nagano Yuichiro Doki Masaki Mori Hideshi Ishii 《Development, growth & differentiation》2013,55(3):309-318
Adipose tissue‐derived mesenchymal stem cells (ADSCs) are multipotent and can differentiate into various cell types, including osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β‐cells, and hepatocytes. Compared with the extraction of other stem cells such as bone marrow‐derived mesenchymal stem cells (BMSCs), that of ADSCs requires minimally invasive techniques. In the field of regenerative medicine, the use of autologous cells is preferable to embryonic stem cells or induced pluripotent stem cells. Therefore, ADSCs are a useful resource for drug screening and regenerative medicine. Here we present the methods and mechanisms underlying the induction of multilineage cells from ADSCs. 相似文献
5.
6.
Koichi Hirabayashi Masaaki Shiohara Kazuhiro Yamada Akane Sueki Yuichiro Ide Koichi Takeuchi Rokuro Hagimoto Tatsuya Kinoshita Akihiko Yabuhara S. Harvey Mudd Kenichi Koike 《Gene》2013
Background
There is not much information on established standard therapy for patients with severe methionine adenosyltransferase (MAT) I/III deficiency.Case presentation
We report a boy with MAT I/III deficiency, in whom plasma methionine and total homocysteine, and urinary homocystine were elevated. Molecular genetic studies showed him to have novel compound heterozygous mutations of the MAT1A gene: c.191T>A (p.M64K) and c.589delC (p.P197LfsX26). A low methionine milk diet was started at 31 days of age, and during continuing dietary methionine restriction plasma methionine levels have been maintained at less than 750 μmol/L. He is now 5 years old, and has had entirely normal physical growth and psychomotor development.Conclusions
Although some severely MAT I/III deficient patients have developed neurologic abnormalities, we report here the case of a boy who has remained neurologically and otherwise normal for 5 years during methionine restriction, suggesting that perhaps such management, started in early infancy, may help prevent neurological complications. 相似文献7.
Ki-Sung Kim Yuichiro Arima Taro Kitazawa Koichi Nishiyama Rieko Asai Yasunobu Uchijima Takahiro Sato Giovanni Levi Sachiko Kitanaka Takashi Igarashi Yukiko Kurihara Hiroki Kurihara 《Mechanisms of development》2013,130(11-12):553-566
Endothelin-1 (Edn1), originally identified as a vasoconstrictor peptide, is involved in the development of cranial/cardiac neural crest-derived tissues and organs. In craniofacial development, Edn1 binds to Endothelin type-A receptor (Ednra) to induce homeobox genes Dlx5/Dlx6 and determines the mandibular identity in the first pharyngeal arch. However, it remains unsolved whether this pathway is also critical for pharyngeal arch artery development to form thoracic arteries. Here, we show that the Edn1/Ednra signaling is involved in pharyngeal artery development by controlling the fate of neural crest cells through a Dlx5/Dlx6-independent mechanism. Edn1 and Ednra knock-out mice demonstrate abnormalities in pharyngeal arch artery patterning, which include persistent first and second pharyngeal arteries, resulting in additional branches from common carotid arteries. Neural crest cell labeling with Wnt1-Cre transgene and immunostaining for smooth muscle cell markers revealed that neural crest cells abnormally differentiate into smooth muscle cells at the first and second pharyngeal arteries of Ednra knock-out embryos. By contrast, Dlx5/Dlx6 knockout little affect the development of pharyngeal arch arteries and coronary arteries, the latter of which is also contributed by neural crest cells through an Edn-dependent mechanism. These findings indicate that the Edn1/Ednra signaling regulates neural crest differentiation to ensure the proper patterning of pharyngeal arch arteries, which is independent of the regional identification of the pharyngeal arches along the dorsoventral axis mediated by Dlx5/Dlx6. 相似文献
8.
Michiyo Takahara Haruka Sakaue Yukiko Onishi Marifu Yamagishi Yuichiro Kida Masao Sakaguchi 《Biochemical and biophysical research communications》2013,430(2):567-572
Nascent chain release from membrane-bound ribosomes by the termination codon was investigated using a cell-free translation system from rabbit supplemented with rough microsomal membrane vesicles. Chain release was extremely slow when mRNA ended with only the termination codon. Tail extension after the termination codon enhanced the release of the nascent chain. Release reached plateau levels with tail extension of 10 bases. This requirement was observed with all termination codons: TAA, TGA and TAG. Rapid release was also achieved by puromycin even in the absence of the extension. Efficient translation termination cannot be achieved in the presence of only a termination codon on the mRNA. Tail extension might be required for correct positioning of the termination codon in the ribosome and/or efficient recognition by release factors. 相似文献
9.
10.
Takaaki Kubota Yuichiro Ishiguro Azusa Takahashi-Nakaguchi Jane Fromont Tohru Gonoi Jun’ichi Kobayashi 《Bioorganic & medicinal chemistry letters》2013,23(1):244-247
Three new polyketides, manzamenones L–N (1–3), have been isolated from an Okinawan marine sponge of the genus Plakortis. The structures of 1–3 were elucidated on the basis of spectroscopic data. Manzamenones L–N (1–3) were new dimeric fatty-acid derivatives consisting of a tetrahydroindenone with three carboxy groups and two hexadecanyl chains. Manzamenones M (2) and N (3) showed antimicrobial activity against several bacteria and fungi. 相似文献