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231.
Kensuke Kobayashi Minaho Uchiyama Hirobumi Takahashi Hiroshi Kawamoto Satoru Ito Takashi Yoshizumi Hiroshi Nakashima Tetsuya Kato Atsushi Shimizu Izumi Yamamoto Masanori Asai Hiroshi Miyazoe Akio Ohno Mioko Hirayama Satoshi Ozaki Takeshi Tani Yasuyuki Ishii Takeshi Tanaka Takanobu Mochidome Kiyoshi Tadano Osamu Okamoto 《Bioorganic & medicinal chemistry letters》2009,19(11):3096-3099
The synthesis and biological evaluation of new potent opioid receptor-like 1 (ORL1) antagonists are presented. Conversion of the thioether linkage of the prototype [It is reported prior to this communication as a consecutive series.: Kobayashi, K.; Kato, T.; Yamamoto, I.; Shimizu, A.; Mizutani, S.; Asai, M.; Kawamoto, H.; Ito, S.; Yoshizumi, T.; Hirayama, M.; Ozaki, S.; Ohta, H.; Okamoto, O. Bioorg. Med. Chem. Lett., in press] to the carbonyl linker effectively reduces susceptibility to P-glycoprotein (P-gp) efflux. This finding led to the identification of 2-cyclohexylcarbonylbenzimizole analogue 7c, which exhibited potent ORL1 activity, excellent selectivity over other receptors and ion channels, and poor susceptibility to P-gp. Compound 7c also showed satisfactory pharmacokinetic profiles and brain penetrability in laboratory animals. Furthermore, 7c showed good in vivo antagonism. Hence, 7c was selected as a clinical candidate for a brain-penetrable ORL1 antagonist. 相似文献
232.
A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family
Miyamoto Y Matsuda T Kitoh H Haga N Ohashi H Nishimura G Ikegawa S 《Human genetics》2007,121(5):625-629
Legg-Calvé-Perthes disease (LCPD) is a common childhood hip disorder characterized by sequential stages of involvement of
the capital femoral epiphyses, including subchondral fracture, fragmentation, re-ossification and healing with residual deformity.
Most cases are sporadic, but familial cases have been described, with some families having multiple affected members. Genetic
factors have been implicated in the etiology of LCPD, but the causal gene has not been identified. We have located a missense
mutation (p.G1170S) in the type II collagen gene (COL2A1) in a Japanese family with an autosomal dominant hip disorder manifesting as LCPD and showing considerable intra-familial
phenotypic variation. This is the first report of a mutation in hereditary LCPD. COL2A1 mutations may be more common in LCPD patients than currently thought, particularly in familial and/or bilateral cases. 相似文献
233.
A novel small protein of Bacillus subtilis involved in spore germination and spore coat assembly 总被引:1,自引:0,他引:1
Kodama T Matsubayashi T Yanagihara T Komoto H Ara K Ozaki K Kuwana R Imamura D Takamatsu H Watabe K Sekiguchi J 《Bioscience, biotechnology, and biochemistry》2011,75(6):1119-1128
Two small genes named sscA (previously yhzE) and orf-62, located in the prsA-yhaK intergenic region of the Bacillus subtilis genome, were transcribed by SigK and GerE in the mother cells during the later stages of sporulation. The SscA-FLAG fusion protein was produced from T(5) of sporulation and incorporated into mature spores. sscA mutant spores exhibited poor germination, and Tricine-SDS-PAGE analysis showed that the coat protein profile of the mutant differed from that of the wild type. Bands corresponding to proteins at 59, 36, 5, and 3 kDa were reduced in the sscA null mutant. Western blot analysis of anti-CotB and anti-CotG antibodies showed reductions of the proteins at 59 kDa and 36 kDa in the sscA mutant spores. These proteins correspond to CotB and CotG. By immunoblot analysis of an anti-CotH antibody, we also observed that CotH was markedly reduced in the sscA mutant spores. It appears that SscA is a novel spore protein involved in the assembly of several components of the spore coat, including CotB, CotG, and CotH, and is associated with spore germination. 相似文献
234.
Naoki Nishizawa Yoko Kanematsu-Yamaki Masaaki Funata Hiroaki Nagai Ayako Shimizu Hisashi Fujita Junichi Sakamoto Shiro Takekawa Taiji Asami 《Bioorganic & medicinal chemistry letters》2017,27(20):4626-4629
Neuromedin U (NMU) mediates various physiological functions via NMUR1 and NMUR2 receptors. NMUR2 has been considered a promising treatment option for diabetes and obesity. Although NMU-8, a shorter peptide, has potent agonist activity for both receptors, it is metabolically unstable. Therefore, NMU-8 analogs modified with long-chain alkyl moieties via a linker were synthesized. An octadecanoyl analog (17) with amino acid substitutions [αMePhe19, Nle21, and Arg(Me)24] and a linker [Tra-γGlu-PEG(2)] dramatically increased NMUR2 selectivity, with retention of high agonist activity. Subcutaneous administration of 17 induced anorectic activity in C57BL/6J mice. Owing to its high metabolic stability, 17 would be useful in clarifying the physiological role and therapeutic application of NMU. 相似文献
235.
236.
Cytological analysis of the mother cell death process during sporulation in Bacillus subtilis 下载免费PDF全文
We have identified the following events during the late stage in the mother cell in Bacillus subtilis: spore detachment from the polar site of the mother cell, membrane rupture, cell wall collapse, and release of the free spore. The membrane rupture was followed by mother cell lysis. Moreover, we found that NucB, an extracellular nuclease, is involved in DNA degradation after mother cell lysis. 相似文献
237.
238.
Torihashi S Ozaki H Hori M Kita M Ohota S Karaki H 《Histochemistry and cell biology》2000,113(2):73-80
A great number of macrophages is found to be evenly distributed in the muscle layer of the gastrointestinal tract. We investigated
their effects on smooth muscle contraction and the initiation of immune reactions such as inflammatory responses. Macrophages
were demonstrated by the uptake of FITC-dextran and their ultrastructural features were elucidated by electron microscopy.
Muscle layers of rats’ ileums were incubated with lipopolysaccharide (LPS) for 4–8 h and the force of smooth muscle contraction
was measured. The induction effect of inducible nitric oxide synthase (iNOS) on macrophages was then checked by immunohistochemistry.
The expression of major histocompatibility complex (MHC) class II was also examined. Macrophages in the muscle layer were
confirmed as resident macrophages and were different from a population of dendritic cells. After incubation with LPS, macrophages
began to express iNOS and produced NO, and it reduced smooth muscle contraction. iNOS-immunopositive cells increased in a
time-dependent manner. Macrophages also began to express MHC class II. The total number of macrophages did not alter after
incubation. Results indicate that resident macrophages in the muscle layer induced iNOS as an inflammatory reaction, affected
smooth muscle contraction, and initiated immune response in the smooth muscle layer of the gastrointestinal tract, when activated
by LPS.
Accepted: 24 November 1999 相似文献
239.
240.
Ikuta K Yamada T Shimomura T Kuratsune H Kawahara R Ikawa S Ohnishi E Sokawa Y Fukushi H Hirai K Watanabe Y Kurata T Kitani T Sairenji T 《Microbes and infection / Institut Pasteur》2003,5(12):1096-1102
To investigate the association of viral infections with chronic fatigue syndrome (CFS), we assayed 2', 5'-oligoadenylate synthetase (2-5AS) activities in peripheral blood mononuclear cells from CFS patients in Japan. These patients were diagnosed in two hospitals, H1 and H2, located in different areas of the country. The activities were detected in 19 (86%) and 7 (32%) of each of the 22 patients in H1 and H2, respectively, while they were detected in only four (11%) out of the 38 healthy controls. IFN-alpha was similarly detected in a few CFS patients and healthy controls. We also assayed the antibody titers against Epstein-Barr virus (EBV) and Coxiella burnetii in these patients. The EBV anti-EA-IgG antibodies were detected in two (9%) and seven (32%) of each of the 22 patients in H1 and H2, respectively. Anti-C. burnetii IgG antibodies were detected in six (27%) out of 22 patients in H1 but not in 22 patients in H2, while they were detected in one (11%) of the nine healthy controls. Some CFS patients may be associated with EBV or C. burnetii infection. There were some statistical correlations between the 2-5AS activities and antibody titers of EA-IgG (P < 0.05, Student's t-test) but not to the antibody titers of C. burnetii. The up-regulation of 2-5AS activities suggests immunological dysfunctions with some virus infections in the CFS patients. Our results indicate that 2-5AS activities are useful for a diagnostic marker of CFS and for exploring the complicated pathogenesis of CFS. 相似文献