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181.
Toshio Watanabe Toshihisa Takeuchi Osamu Handa Yasuhisa Sakata Tetsuya Tanigawa Masatsugu Shiba Yuji Naito Kazuhide Higuchi Kazuma Fujimoto Toshikazu Yoshikawa Tetsuo Arakawa 《PloS one》2015,10(4)
Background
Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant.Aim
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy.Methods
We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks.Results
The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated.Conclusions
High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy.Trial Registration
UMIN Clinical Trials Registry UMIN000003463 相似文献182.
Deformation of the Outer Hair Cells and the Accumulation of Caveolin-2 in Connexin 26 Deficient Mice
Takashi Anzai Ichiro Fukunaga Kaori Hatakeyama Ayumi Fujimoto Kazuma Kobayashi Atena Nishikawa Toru Aoki Tetsuo Noda Osamu Minowa Katsuhisa Ikeda Kazusaku Kamiya 《PloS one》2015,10(10)
BackgroundMutations in GJB2, which encodes connexin 26 (Cx26), a cochlear gap junction protein, represent a major cause of pre-lingual, non-syndromic deafness. The degeneration of the organ of Corti observed in Cx26 mutant—associated deafness is thought to be a secondary pathology of hearing loss. Here we focused on abnormal development of the organ of Corti followed by degeneration including outer hair cell (OHC) loss.MethodsWe investigated the crucial factors involved in late-onset degeneration and loss of OHC by ultrastructural observation, immunohistochemistry and protein analysis in our Cx26-deficient mice (Cx26f/fP0Cre).ResultsIn ultrastructural observations of Cx26f/fP0Cre mice, OHCs changed shape irregularly, and several folds or notches were observed in the plasma membrane. Furthermore, the mutant OHCs had a flat surface compared with the characteristic wavy surface structure of OHCs of normal mice. Protein analysis revealed an increased protein level of caveolin-2 (CAV2) in Cx26f/fP0Cre mouse cochlea. In immunohistochemistry, a remarkable accumulation of CAV2 was observed in Cx26f/fP0Cre mice. In particular, this accumulation of CAV2 was mainly observed around OHCs, and furthermore this accumulation was observed around the shrunken site of OHCs with an abnormal hourglass-like shape.ConclusionsThe deformation of OHCs and the accumulation of CAV2 in the organ of Corti may play a crucial role in the progression of, or secondary OHC loss in, GJB2-associated deafness. Investigation of these molecular pathways, including those involving CAV2, may contribute to the elucidation of a new pathogenic mechanism of GJB2-associated deafness and identify effective targets for new therapies. 相似文献
183.
184.
Ida Bagus Andika Kazuyuki Maruyama Liying Sun Hideki Kondo Tetsuo Tamada Nobuhiro Suzuki 《Plant signaling & behavior》2015,10(8)
Eukaryotes employ RNA silencing as an innate defense system against invading viruses. Dicer proteins play the most crucial role in initiating this antiviral pathway as they recognize and process incoming viral nucleic acids into small interfering RNAs. Generally, 2 successive infection stages constitute viral infection in plants. First, the virus multiplies in initially infected cells or organs after viral transmission and then the virus subsequently spreads systemically through the vasculature to distal plant tissues or organs. Thus, antiviral silencing in plants must cope with both local and systemic invasion of viruses. In a recent study using 2 sets of different experiments, we clearly demonstrated the differential requirement for Dicer-like 4 (DCL4) and DCL2 proteins in the inhibition of intracellular and systemic infection by potato virus X in Arabidopsis thaliana. Taken together with the results of other studies, here we further discuss the functional specificity of DCL proteins in the antiviral silencing pathway. 相似文献
185.
186.
Difference in the structures of alanine tri‐ and tetra‐peptides with antiparallel β‐sheet assessed by X‐ray diffraction,solid‐state NMR and chemical shift calculations by GIPAW
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Tetsuo Asakura Koji Yazawa Kumiko Horiguchi Furitsu Suzuki Yusuke Nishiyama Katsuyuki Nishimura Hironori Kaji 《Biopolymers》2014,101(1):13-20
Alanine oligomers provide a key structure for silk fibers from spider and wild silkworms.We report on structural analysis of l ‐alanyl‐l ‐alanyl‐l ‐alanyl‐l ‐alanine (Ala)4 with anti‐parallel (AP) β‐structures using X‐ray and solid‐state NMR. All of the Ala residues in the (Ala)4 are in equivalent positions, whereas for alanine trimer (Ala)3 there are two alternative locations in a unit cell as reported previously (Fawcett and Camerman, Acta Cryst., 1975, 31, 658–665). (Ala)4 with AP β‐structure is more stable than AP‐(Ala)3 due to formation of the stronger hydrogen bonds. The intermolecular structure of (Ala)4 is also different from polyalanine fiber structure, indicating that the interchain arrangement of AP β‐structure changes with increasing alanine sequencelength. Furthermore the precise 1H positions, which are usually inaccesible by X‐ray diffraction method, are determined by high resolution 1H solid state NMR combined with the chemical shift calculations by the gauge‐including projector augmented wave method. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 13–20, 2014. 相似文献
187.
Tetsu Yamane Masako Mitsumata Noriko Yamaguchi Tadao Nakazawa Kunio Mochizuki Tetsuo Kondo Tomonori Kawasaki Shin-ichi Murata Yoji Yoshida Ryohei Katoh 《Cell and tissue research》2010,340(3):471-479
Remodeling of endothelial basement membrane is important in atherogenesis. Since little is known about the actual relationship
between type IV collagen and matrix metalloprotease−2 (MMP-2) in endothelial cells (ECs) under shear stress by blood flow,
we performed quantitative analysis for type IV collagen and MMP-2 in ECs under high shear stress. The mRNA of type IV collagen
from ECs exposed to high shear stress (10 and 30 dyn/cm2) had a higher expression compared to ECs exposed to a static condition or low shear stress (3 dyn/cm2) (P < 0.01). 3H-proline uptake analysis and fluorography revealed a remarkable increase of type IV collagen under high shear stress (P < 0.01). In contrast, zymography revealed that exposing to high shear stress, however similar positivity was leveled in the
intracellular MMP-2 in the control and high shear stress-exposed ECs, reduced the secretion of MMP-2 in ECs. The results of
Northern blotting, gelatin zymography and monitoring the intracellular trafficking of GFP-labeled MMP-2 revealed that MMP-2
secretion by ECs was completely suppressed by high shear stress, but the intracellular mRNA expression, protein synthesis,
and transport of MMP-2 were not affected. In conclusion, we suggest that high shear stress up-regulates type IV collagen synthesis
and down-regulates MMP-2 secretion in ECs, which plays an important role in remodeling of the endothelial basement membrane
and may suppress atherogenesis. 相似文献
188.
Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure,synthesis, and SAR
Tetsuo Takayama Hiroki Umemiya Hideaki Amada Tetsuya Yabuuchi Fumiyasu Shiozawa Hironori Katakai Akiko Takaoka Akie Yamaguchi Mayumi Endo Masakazu Sato 《Bioorganic & medicinal chemistry letters》2010,20(1):108-111
We have described the synthesis, enzyme inhibitory activity, structure–activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC50s <10 nM) for Lck kinase inhibition. 相似文献
189.
Masaki Asada Tetsuo Obitsu Atsushi Kinoshita Yoshihiko Nakai Toshihiko Nagase Isamu Sugimoto Motoyuki Tanaka Hiroya Takizawa Ken Yoshikawa Kazutoyo Sato Masami Narita Shuichi Ohuchida Hisao Nakai Masaaki Toda 《Bioorganic & medicinal chemistry letters》2010,20(8):2639-2643
A series of novel N-acylsulfonamide analogs were synthesized and evaluated for their binding affinity and antagonist activity for the EP3 receptor subtype. Representative compounds were also evaluated for their inhibitory effect on PGE2-induced uterine contraction in pregnant rats. Among those tested, a series of N-acylbenzenesulfonamide analogs were found to be more potent than the corresponding carboxylic acid analogs in both the in vitro and in vivo evaluations. The structure activity relationships (SAR) are also discussed. 相似文献