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71.
Rho kinases regulate endothelial invasion and migration during valvuloseptal endocardial cushion tissue formation. 总被引:2,自引:0,他引:2
Masahide Sakabe Kazuo Ikeda Kazuki Nakatani Norifumi Kawada Kyoko Imanaka-Yoshida Toshimichi Yoshida Toshiyuki Yamagishi Yuji Nakajima 《Developmental dynamics》2006,235(1):94-104
Rho-associated kinase (ROCK) is a downstream effector of small Rho-GTPases, and phosphorylates several substrates to regulate cell functions, including actin cytoskeletal reorganization and cellular motility. Endothelial-mesenchymal transformation (EMT) is a critical event in the formation of valves and septa during cardiogenesis. It has been reported that ROCK plays an important role in the regulation of endocardial cell differentiation and migration during mouse cardiogenesis (Zhao and Rivkees [2004] Dev. Biol. 275:183-191). Immunohistochemistry showed that, during chick cardiogenesis, ROCK1 and -2 were expressed in the transforming and migrating endothelial/mesenchymal cells in the outflow tract (OT) and atrioventricular (AV) canal regions from which valvuloseptal endocardial cushion tissue would later develop. Treatment with Y27632, a specific ROCK inhibitor, of cultured AV explants or AV endothelial monolayers of stage 14-minus heart (preactivated stage for EMT) on three-dimensional collagen gel perturbed the seeding of mesenchymal cells into the gel lattice. In these experiments, Y27632 did not suppress the expression of an early transformation marker, smooth muscle alpha-actin. Moreover, Y27632 inhibited the mesenchymal invasion in stage 14-18 AV explants, in which endothelial cells had committed to undergo EMT. ML-9, a myosin light chain kinase inhibitor, also inhibited the mesenchymal invasion in cultured AV explants. These results suggest that ROCKs have a critical role in the mesenchymal cell invasion/migration that occurs at the late onset of EMT. 相似文献
72.
73.
Vitamin D receptor gene polymorphism is associated with serum total and ionized calcium concentration 总被引:1,自引:0,他引:1
Nakano Y Oshima T Sasaki S Yamaoka K Matsumoto T Hirao H Ozono R Matsuura H Kajiyama G Kambe M 《Journal of molecular medicine (Berlin, Germany)》2000,78(10):575-579
Restriction fragment length polymorphisms of the vitamin D receptor gene have recently been reported to be associated with changes in bone mineral density. Alterations in systemic calcium balance and Ca-regulating hormones such as 1,25(OH)2 vitamin D3 and parathyroid hormone have been demonstrated in essential hypertension. We investigated the relationship between polymorphisms of the vitamin D receptor gene and systemic Ca metabolism in patients with essential hypertension and in normotensives. We compared 147 subjects with essential hypertension and 100 normotensive control subjects. The genotype distribution and derived allele frequencies for the vitamin D receptor gene were similar in the two groups (genotype bb/Bb/BB and allele B/b: 60.1/32.6/7.2 and 0.24/0.76 in hypertensives vs. 56.0/36.0/8.0 and 0.26/0.74 in normotensive subjects). Serum concentrations of total Ca in the bb, Bb, and BB groups were, respectively, 4.5+/-0.3 vs. 4.5+/-0.4 vs. 4.4+/-0.5 mmol/l in normotensives and 4.6+/-0.3 vs. 4.6+/-0.4 vs. 4.4+/-0.5 mmol/l in hypertensives. Ionized Ca levels were 1.17+/-0.04 vs. 1.16+/-0.04 vs. 1.15+/-0.04 mmol/l in normotensives and 1.16+/-0.04 vs. 1.16+/-0.04 vs. 1.14+/-0.05 mmol/l in hypertensives, respectively. These results indicate that the BB genotype of the vitamin D receptor gene is associated with lower serum Ca levels but is not a useful predictive marker for the development of essential hypertension in Japanese subjects. 相似文献
74.
Toshiyuki Tanaka Yasuhiko Nagasaka Fujiko Kitamura Keisuke Kuida Hiroshi Suwa Masayuki Miyasaka 《European journal of immunology》1993,23(6):1378-1380
Autoimmune MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop a systemic lupus erythematosus-like disease accompanied by a profound lymphadenopathy that consists of CD4?8?B220+ a P T cells. By the use of cross-linking experiments with radiolabeled interleukin-2 (IL-2), these abnormal T cells have been reported to constitutively express the IL-2 receptor β chain (IL-2Rα), a signal transducing component of IL-2R, in the absence of the a chain (IL-2Rα).To critically reevaluate the role of the IL-2/IL-2R pathway in the pathogenesis of lymphadenophathy we examined expression of the IL-2Rα and IL-2Rβ in MRL/lpr mice by 125I-IL-2 binding analysis and also by flow cytometric analysis using monoclonal antibodies against each component of the receptor. We found that, contrary to the previous report, the CD4?8?B220+ α β T cells in lymph node (LN) of MRL/lpr mice were negative for both IL-2Rα and IL-2Rβ expression. The lpr liver CD4?8?B220+ a P T cells that had been implicated in the genesis of these abnormal LN T cells were also negative for IL-2Rβ expression. Therefore, our results indicate that the IL-2/IL-2R system plays little role, if any, in the expansion of abnormal CD4?8? B220+ α β T cells in MRL/lpr mice. 相似文献
75.
Naoshi Kaneko Tatsuyuki Muratake Hideki Kuwabara Takanori Kurosaki Mitsuru Takei Tsuyuka Ohtsuki Tadao Arinami Shoji Tsuji Toshiyuki Someya 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2007,(6):735-742
We analyzed a large multiplex schizophrenia pedigree collected in mid-eastern Japan using 322 microsatellite markers distributed throughout the whole autosome. Under an autosomal-dominant inheritance model, the highest pairwise LOD score (LOD = 1.69) was found at 4q (D4S2431: theta = 0.0), and LOD scores at two other loci 3q (ATA34G06) and 8q (D8S1128) were 1.62 and 1.46, respectively. In multipoint analysis, LOD scores of the regions on 4q and 3q remained at a similar level; however, the LOD score of the region on 8q apparently decreased. Additional dense map analysis revealed haplotypes on 4q and 3q regions shared by affected individuals. On chromosome 4q, the haplotype spanning about 8 centiMorgans (cM) was shared by four of six genotyped individuals with schizophrenia and one affected individual whose haplotype was estimated. On 3q, the haplotype spanning about 20 cM was shared by five genotyped individuals with schizophrenia. We obtained two candidate regions of major susceptibility loci for schizophrenia on chromosomes 3q and 4q. 相似文献
76.
Byoung Won Kang Kazuyuki Hattori Takashi Yoshida Makoto Hirai Yoon Soung Chio Toshiyuki Uryu 《Macromolecular chemistry and physics.》1997,198(5):1331-1345
Ring-opening polymerization of a new anhydro ribose-type monomer, 1,4-anhydro-3-azido-3-deoxy-2-O-tert-butyldimethylsilyl-α-D -ribopyranose (A3ASR), was investigated. The monomer was synthesized from 1,4-anhyro-α-D -xylopyranose by three steps comprising Walden inversion at the C3 position into ribose configuration. Ring-opening polymerization of A3ASR by Lewis acid catalysts such as boron trifluoride etherate and stannic chloride gave a stereoregular 3-azido-3-deoxy-2-O-tert-butyldimethylsilyl-(1→5)-α-D -ribofuranan having specific rotations of +246 ~ +271 deg · dm?1 · g?1 · cm3 and number-average molecular weights of 18,7 × 103 ~ 25,1 × 103. When the polymerization was carried out by antimony pentachloride at 0°C, the resulting polymer exhibited a negative specific rotation of ?6 deg · dm?1 · g?1 · cm3 and the C1 absorption in the 13C NMR spectrum shifted downfield to 107,5 ppm, suggesting that the polymer might consist of 1,5-β furanosidic unit. The reduction of the azido group of the 1,5-α and 1,5-β furanosidic polymers into amino group and subsequent desilylation gave 3-amino-3-deoxy-(1→5)-α- and -β-D -ribofuranans, respectively. In addition, copolymerization of A3ASR with 1,4-anhydro-2,3-di-O-tert-butyldimethylsilyl-α-D -ribopyranose (ADSR) in various feeds was performed by boron trifluoride etherate as catalyst to give copolymers with different monomeric components. The structural analysis of the homopolymers and copolymers was examined by means of 1H and 13C NMR spectroscopies, IR spectroscopy, and optical rotation. 相似文献
77.
Haruhiko Yoshida Tokichi Yumoto Yoichiro Hamada Toshiyuki Aki Kazuhito Nakai Juichi Ueki 《Pathology international》1989,39(1):55-66
Ffteen cases of peripheral T cell lymphoma were studied to evaluate the respective properties of various histologic types using enzyme histochemical and ultrastructural examinations in addition to immunological methods. Eleven cases in an ATLA negative group manifested various histologic patterns such as IBL like, pleomorphic and Lennert's lymphomas in comparison with the relatively monomorphic proliferation of neoplastic lymphoid cells in the 4 ATLA positive cases. The presence of neoplastic clear cells is characteristic of peripheral T-cell malignancies, and is likely to be found in CD4 lymphomas. There is an occasional reaction of epithelioid histiocytes and plasma cells with eosinophils, the former being designated Lennert's lymphoma and the latter IBL like T-cell lymphoma. Immunological examination revealed four immunophenotypic patterns: (1) CD2+ 3+ 4+ 8+ , (2) CD2+ 3− 4+ 8− , (3) CD2+ 3+ 4− 8+ , and (4) CD2+ 3+ 4+ 8+ , but did not provide information concerning the intimate relationship between histologic types and immuno phenotyes. β-Glucuronidase reactivity, however, contributed to the distinction between helper and suppressor T cell malignancies, suggesting its usefulness for distinguishing these two cell types and their malignant counterparts. 相似文献
78.
Toyoji Kakuchi Toshiyuki Hasegawa Hiroshi Sasaki Hiroshi Ohmori Kazumi Yamaguchi Kazuaki Yokota 《Macromolecular chemistry and physics.》1989,190(9):2091-2097
Chiral poly(crown ether)s were synthesized by cationic cyclopolymerization of (S)-2,2′-bis(2-vinyloxyethoxy)-3,3′-dimethyl-1,1′-binaphthyl [(S)- 1b ] and (R)-2,2′-bis[2-(2-vinyloxyethoxy)-ethoxy]-3,3′-dimethyl (or 3,3′-diphenyl)-1,1′-binaphthyl [(R)- 3b or (R)- 3c ]. The substituents in the 3,3′-positions of binaphthyl moiety disturb the intramolecular cyclization in the polymerization of monomer (S)- 1b , but have no influence on the cyclopolymerization tendency of monomers (R)- 3b and (R)- 3c . The polymers from (R)- 3b and (R)- 3c [(R)- 4b and (R)- 4c ] have a higher ability of chiral recognition towards a-amino acids, such as phenylglycine, phenylalanine, valine, and methionine, than the polymer from (R)- 3a [(R)- 4a ], which has no substituent in 3,3′-positions. The methyl and the phenyl substituents in the 3,3′-positions undoubtedly act as additional barrier causing an increase in the ability of chiral recognition, though the effect is less than expected from the result of model crown ethers. 相似文献
79.
Toshiyuki Uryu Katsuhiro Ito Ken-Ichi Kobayashi Kei Matsuzaki 《Macromolecular chemistry and physics.》1979,180(6):1509-1519
In order to elucidate the catalytic behavior of phosphorus pentafluoride in the polymerization of anhydro sugars, 13P and 19F NMR spectra were measured on a reaction mixture of 1,6-anhydro-2,3,4-tri-O-benzyl-β-D -glucopyranose (LGTBE) and PF5 with different mole ratios in a temperature range of ?40 to ?80°C. In the 31P NMR spectrum measured at low temperatures, there was a total of 16 peaks, which consisted of a broad quintet, a septet, and a sharp quartet, being assigned to the PF4O-group, to PF, and to POF3, respectively. These fluoro compounds were also determined by the 19F NMR spectrum of the reaction mixture. The concentration of PF ions was found to correspond to that of oxonium ions, which are assumed to be actual propagating species, by determining both the concentration of PF from 19F NMR spectrum and the degree of polymerization of 2,3,4-tri-O-benzyl-α-D -glucopyranan obtained. Formation of the PF5: LGTBE complex was observed from the 31P NMR spectrum of the polymerization system at ?80°C, which exhibits a broad sextet as well as absorptions due to POF3, PF4O–, and PF. To confirm the PF5:LGTBE complex, the NMR measurement of the PF5: tetrahydropyran complex was carried out. A polymerization mechanism of LGTBE by PF5 catalyst is discussed on the basis of the NMR measurement of the polymerization system. 相似文献
80.
Kunikata T Yamane H Segi E Matsuoka T Sugimoto Y Tanaka S Tanaka H Nagai H Ichikawa A Narumiya S 《Nature immunology》2005,6(5):524-531
Prostaglandins, including PGD(2) and PGE(2), are produced during allergic reactions. Although PGD(2) is an important mediator of allergic responses, aspirin-like drugs that inhibit prostaglandin synthesis are generally ineffective in allergic disorders, suggesting that another prostaglandin-mediated pathway prevents the development of allergic reactions. Here we show that such a pathway may be mediated by PGE(2) acting at the prostaglandin E receptor EP3. Mice lacking EP3 developed allergic inflammation that was much more pronounced than that in wild-type mice or mice deficient in other prostaglandin E receptor subtypes. Conversely, an EP3-selective agonist suppressed the inflammation. This suppression was effective when the agonist was administered 3 h after antigen challenge and was associated with inhibition of allergy-related gene expression. Thus, the PGE(2)-EP3 pathway is an important negative modulator of allergic reactions. 相似文献