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51.
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52.
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
53.
Koichi Eguchi Yasuhide Yoshioka Hideki Yoshida Kazushige Morishita Seiji Miyata Hiroshi Hiai Masamitsu Yamaguchi 《Experimental cell research》2013
The Drosophila sponge (spg)/CG31048 gene belongs to the dedicator of cytokinesis (DOCK) family genes that are conserved in a wide variety of species. DOCK family members are known as DOCK1–DOCK11 in mammals. Although DOCK1 and DOCK2 involve neurite elongation and immunocyte differentiation, respectively, the functions of other DOCK family members are not fully understood. Spg is a Drosophila homolog of mammalian DOCK3 and DOCK4. Specific knockdown of spg by the GMR-GAL4 driver in eye imaginal discs induced abnormal eye morphology in adults. To mark the photoreceptor cells in eye imaginal discs, we used a set of enhancer trap strains that express lacZ in various sets of photoreceptor cells. Immunostaining with anti-Spg antibodies and anti-lacZ antibodies revealed that Spg is localized mainly in R7 photoreceptor cells. Knockdown of spg by the GMR-GAL4 driver reduced signals of R7 photoreceptor cells, suggesting involvement of Spg in R7 cell differentiation. Furthermore, immunostaining with anti-dpERK antibodies showed the level of activated ERK signal was reduced extensively by knockdown of spg in eye discs, and both the defects in eye morphology and dpERK signals were rescued by over-expression of the Drosophila raf gene, a component of the ERK signaling pathway. Furthermore, the Duolink in situ Proximity Ligation Assay method detected interaction signals between Spg and Rap1 in and around the plasma membrane of the eye disc cells. Together, these results indicate Spg positively regulates the ERK pathway that is required for R7 photoreceptor cell differentiation and the regulation is mediated by interaction with Rap1 during development of the compound eye. 相似文献
54.
Hideo Ochiai Hiroshi Eguchi Shunsuke Noguchi Yutaro Hayashi Hideaki Nishino Masaru Kawamura Chau H. Wu 《Journal of molecular recognition : JMR》2013,26(1):32-37
Glutathione S‐transferase (GST) was found to complex with the Na+,K+‐ATPase as shown by binding assay using quartz crystal microbalance. The complexation was obstructed by the addition of antiserum to the α‐subunit of the Na+,K+‐ATPase, suggesting the specificity of complexation between GST and the Na+,K+‐ATPase. Co‐immunoprecipitation experiments, using the anti‐α‐subunit antiserum to precipitate the GST‐Na+,K+‐ATPase complex and then using antibodies specific to an isoform of GST to identify the co‐precipitated proteins, revealed that GSTπ was complexed with the Na+,K+‐ATPase. GST stimulated the Na+,K+‐ATPase activity up to 1.4‐fold. The level of stimulation exhibited a saturable dose–response relationship with the amount of GST added, although the level of stimulation varied depending on the content of GSTπ in the lots of GST received from supplier. The stimulation was also obtained when recombinant GSTπ was used, confirming the results. When GST was treated with reduced glutathione, GST activity was greatly stimulated, whereas the level of stimulation of the Na+,K+‐ATPase activity was similar to that when untreated GST was added. When GST was treated with H2O2, GST activity was greatly diminished while the stimulation of the Na+,K+‐ATPase activity was preserved. The results suggest that GSTπ complexes with the Na+,K+‐ATPase and stimulates the latter independent of its GST activity. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
55.
Silvia Yuko Eguchi Naomichi Nishio Shiro Nagai 《Bioscience, biotechnology, and biochemistry》2013,77(12):2941-2943
Resting cells of the methanogen strain HU, a formate-utilizing methanogenic bacterium, was able to utilize formate or hydrogen as electron donor for the production of NADPH from NADP+ under suitable conditions. In the presence of 0.2% Triton X-100 and 0.3 m potassium phosphate, pH 9.0 at 30°C, the resting cells could convert ca. 60% of the exogenous NADP+ into NADPH yielding ca. 6 g NADPH/liter. Phosphate ions greatly enhanced the NADPH production. 相似文献
56.
Tsukasa Ikemura Akane Miyaji Hideaki Kashima Yuji Yamaguchi Naoyuki Hayashi 《Journal of physiological anthropology》2013,32(1):23
Background
Heat stress induces various physiological changes and so could influence ocular circulation. This study examined the effect of heat stress on ocular blood flow.Findings
Ocular blood flow, end-tidal carbon dioxide (PETCO2) and blood pressure were measured for 12 healthy subjects wearing water-perfused tube-lined suits under two conditions of water circulation: (1) at 35°C (normothermia) for 30 min and (2) at 50°C for 90 min (passive heat stress). The blood-flow velocities in the superior temporal retinal arteriole (STRA), superior nasal retinal arteriole (SNRA), and the retinal and choroidal vessels (RCV) were measured using laser-speckle flowgraphy. Blood flow in the STRA and SNRA was calculated from the integral of a cross-sectional map of blood velocity. PETCO2 was clamped at the normothermia level by adding 5% CO2 to the inspired gas. Passive heat stress had no effect on the subjects’ blood pressures. The blood-flow velocity in the RCV was significantly lower after 30, 60 and 90 min of passive heat stress than the normothermic level, with a peak decrease of 18 ± 3% (mean ± SE) at 90 min. Blood flow in the STRA and SNRA decreased significantly after 90 min of passive heat stress conditions, with peak decreases of 14 ± 3% and 14 ± 4%, respectively.Conclusion
The findings of this study suggest that passive heat stress decreases ocular blood flow irrespective of the blood pressure or arterial partial pressure of CO2. 相似文献57.
Yusuke Sakai Makiko Koike Hideko Hasegawa Kosho Yamanouchi Akihiko Soyama Mitsuhisa Takatsuki Tamotsu Kuroki Kazuo Ohashi Teruo Okano Susumu Eguchi 《PloS one》2013,8(7)
Cell sheet engineering is attracting attention from investigators in various fields, from basic research scientists to clinicians focused on regenerative medicine. However, hepatocytes have a limited proliferation potential in vitro, and it generally takes a several days to form a sheet morphology and multi-layered sheets. We herein report our rapid and efficient technique for generating multi-layered human hepatic cell (HepaRG® cell) sheets using pre-cultured fibroblast monolayers derived from human skin (TIG-118 cells) as a feeder layer on a temperature-responsive culture dish. Multi-layered TIG-118/HepaRG cell sheets with a thick morphology were harvested on day 4 of culturing HepaRG cells by forceful contraction of the TIG-118 cells, and the resulting sheet could be easily handled. In addition, the human albumin and alpha 1-antitrypsin synthesis activities of TIG-118/HepaRG cells were approximately 1.2 and 1.3 times higher than those of HepaRG cells, respectively. Therefore, this technique is considered to be a promising modality for rapidly fabricating multi-layered human hepatocyte sheets from cells with limited proliferation potential, and the engineered cell sheet could be used for cell transplantation with highly specific functions. 相似文献
58.
Exposure to high‐concentration oxygen in the neonatal period induces abnormal retinal vascular patterning in mice
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Akane Morita Hiroko Ushikubo Asami Mori Kenji Sakamoto Tsutomu Nakahara 《Birth defects research. Part B, Developmental and reproductive toxicology》2016,107(6):216-224
The interruption of vascular development could cause structural and functional abnormalities in tissues. We have previously reported that short‐term treatment of newborn mice with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors induces abnormal retinal vascular growth and patterns. An exposure of neonatal mice to high‐concentration oxygen disturbs normal retinal vascular development. The present study aimed to determine (1) whether vascular abnormalities are observed in the retina of newborn mice exposed to high concentrations of oxygen, and (2) how astrocyte network formation is affected following the exposure to hyperoxia. Newborn (postnatal day 0) mice were exposed to 75% oxygen for 48 or 96 hr. During hyperoxia exposure, VEGF expression decreased, and the onset of retinal vascularization was completely suppressed. After completion of the hyperoxic period, retinal vascularization occurred, but it was delayed in a hyperoxic exposure duration‐dependent manner. In retinas of hyperoxia‐exposed mice, dense capillary plexuses were found, and the number of arteries and veins decreased. The astrocyte network formation was slightly delayed under hyperoxic conditions, and the network became denser in retinas of mice with an episode of hyperoxia. Expression of VEGF levels in the avascular retina of mice that were exposed to hyperoxia was higher than that of control mice. These results suggest that short‐term interruption of the onset of vascular development resulting from the reduction in VEGF signals induces abnormal vascular patterns in the mouse retina. The abnormalities in retinal astrocyte behavior might contribute to the formation of an abnormal retinal vascular growth. 相似文献
59.
Kou Kayamori Ken-ichi Katsube Kei Sakamoto Yoshio Ohyama Hideaki Hirai Akane Yukimori Yae Ohata Takumi Akashi Masao Saitoh Kiyoshi Harada Hiroyuki Harada Akira Yamaguchi 《PloS one》2016,11(4)
Recent studies have shown that Notch signaling is involved in many types of cancers, including oral squamous cell carcinomas (OSCCs). However, the role of Notch signaling in the tumor microenvironment is not yet fully understood. In this study, we investigated the roles of NOTCH3 signaling in cancer associated fibroblasts (CAFs) in OSCCs. Immunohistochemical study of 93 human tongue OSCC cases indicated that about one third of OSCCs showed NOTCH3 expression in CAFs, and that this expression significantly correlated with tumor-size. In vitro study showed that OSCC cell lines, especially HO1-N-1 cells stimulated NOTCH3 expression in normal human dermal fibroblasts (NHDFs) through direct cell-to-cell contact. Immunohistochemical and morphometric analysis using human OSCC samples demonstrated that NOTCH3 expression in CAFs significantly correlated with micro-vessel density in cancer stroma. In vitro angiogenesis assays involving co-culture of NHDFs with HO1-N-1 and human umbilical endothelial cells (HUVECs), and NOTCH3 knockdown in NHDFs using siRNA, demonstrated that HO1-N-1 cells significantly promoted tube formation dependent on NOTCH3-expression in NHDFs. Moreover, NOTCH3 expression in CAFs was related to poor prognosis of the OSCC patients. This work provides a new insight into the role of Notch signaling in CAFs associated with tumor angiogenesis and the possibility of NOTCH3-targeted molecular therapy in OSCCs. 相似文献
60.
Tomohiro Iguchi Sho Nambara Takaaki Masuda Hisateru Komatsu Masami Ueda Shinya Kidogami Yushi Ogawa Qingjiang Hu Kuniaki Sato Tomoko Saito Hidenari Hirata Shotaro Sakimura Ryutaro Uchi Naoki Hayashi Shuhei Ito Hidetoshi Eguchi Keishi Sugimachi Yoshihiko Maehara Koshi Mimori 《PloS one》2016,11(11)
miR-146a plays important roles in cancer as it directly targets NUMB, an inhibitor of Notch signaling. miR-146a is reportedly regulated by a G>C polymorphism (SNP; rs2910164). This polymorphism affects various cancers, including colorectal cancer (CRC). However, the clinical significance of miR-146a polymorphism in CRC remains unclear. A total of 59 patients with CRC were divided into 2 groups: a CC/CG genotype (n = 32) and a GG genotype (n = 27), based on the miR-146a polymorphism. cDNA microarray analysis was performed using 59 clinical samples. Significantly enriched gene sets in each genotype were extracted using GSEA. We also investigated the association between miR-146a polymorphism and miR-146a, NUMB expression or migratory response in CRC cell lines. The CC/CG genotype was associated with significantly more synchronous liver metastasis (p = 0.007). A heat map of the two genotypes showed that the expression profiles were clearly stratified. GSEA indicated that Notch signaling and JAK/STAT3 signaling were significantly associated with the CC/CG genotype (p = 0.004 and p = 0.023, respectively). CRC cell lines with the pre-miR-146a/C revealed significantly higher miR-146a expression (p = 0.034) and higher NUMB expression and chemotactic activity. In CRC, miR-146a polymorphism is involved in liver metastasis. Identification of this polymorphism could be useful to identify patients with a high risk of liver metastasis in CRC. 相似文献