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961.
Yoko Beniyama Kenji Matsuno Hiroyuki Miyachi 《Bioorganic & medicinal chemistry letters》2013,23(6):1662-1666
We designed a series of pyrazole-based carboxylic acids as candidate ligands of heart fatty acid binding protein (H-FABP, or FABP3), based on a comparison of the X-ray crystallographic structures of adipocyte fatty acid binding protein (FABP4)–selective inhibitor (BMS309403) complex and FABP3–elaidic acid complex. Some of the synthesized compounds exhibited dual FABP3/4 ligand activity, and some exhibited selectivity for FABP3. 相似文献
962.
Kenji Matsumura Masahiro Ono Masashi Yoshimura Hiroyuki Kimura Hiroyuki Watanabe Yoko Okamoto Masafumi Ihara Ryosuke Takahashi Hideo Saji 《Bioorganic & medicinal chemistry》2013,21(11):3356-3362
This paper describes the synthesis and biological evaluation of styrylbenzimidazole (SBIM) derivatives as agents for imaging neurofibrillary tangles (NFT) in patients with Alzheimer’s disease (AD). SBIM derivatives were prepared with 4-iodobenzene-1,2-diamine and substituted cinnamaldehydes. In binding experiments using recombinant tau and Aβ1–42 aggregates, SBIM-3 showed higher affinity for the tau aggregates than Aβ1–42 aggregates (ratio of Kd values was 2.73). In in vitro autoradiography and fluorescent staining, [125I]SBIM-3 (or SBIM-3) bound NFT in sections of AD brain tissue. In biodistribution experiments using normal mice, all [125I]SBIM derivatives showed high initial uptake into (3.20–4.11%ID/g at 2 min after the injection) and rapid clearance from (0.12–0.33%ID/g at 60 min after the injection) the brain. In conclusion, appropriate structural modifications of SBIM derivatives could lead to more useful agents for the in vivo imaging of NFT in AD brains. 相似文献
963.
Yoko Shimoda Joji Yui Lin Xie Masayuki Fujinaga Tomoteru Yamasaki Masanao Ogawa Nobuki Nengaki Katsushi Kumata Akiko Hatori Kazunori Kawamura Ming-Rong Zhang 《Bioorganic & medicinal chemistry》2013,21(17):5316-5322
1-[2-(4-Methoxyphenyl)phenyl]piperazine (4) is a potent serotonin 5-HT7 receptor antagonist (Ki = 2.6 nM) with a low binding affinity for the 5-HT1A receptor (Ki = 476 nM). As a potential positron emission tomography (PET) radiotracer for the 5-HT7 receptor, [11C]4 was synthesized at high radiochemical yield and specific activity, by O-[11C]methylation of 2′-(piperazin-1-yl)-[1,1′-biphenyl]-4-ol (6) with [11C]methyl iodide. Autoradiography revealed that [11C]4 showed in vitro specific binding with 5-HT7 in the rat brain regions, such as the thalamus which is a region with high 5-HT7 expression. Metabolite analysis indicated that intact [11C]4 in the brain exceeded 90% of the radioactive components at 15 min after the radiotracer injection, although two radiolabeled metabolites were found in the rat plasma. The PET study of rats showed moderated uptake of [11C]4 in the brain (1.2 SUV), but no significant regional difference in radioactivity in the brain. Pretreatment with 5-HT7-selective antagonist SB269970 (3) did not decrease the uptake of [11C]4 in the rat brain. Further studies are warranted that focus on the development of PET ligand candidates with higher binding affinity for 5-HT7 and higher in vivo stability in brain than 4. 相似文献
964.
965.
An examination was performed on 16 intraductal proliferative breast lesions diagnosed as intraductal papillomas (IP) or usual ductal hyperplasia (UDH), which were followed up for more than 3 years. An immunohistochemical marker panel combining myoepithelial markers, high-molecular-weight keratin (HMWK) and neuroendocrine markers was used. Two of 11 IP cases were re-evaluated as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). These cases developed breast cancer after the first operation. One IP case showed repeated recurrences. None of the other IP and UDH cases had breast cancer or recurrence. The ADH, DCIS and the recurrent IP showing a solid growth lacked myoepithelia, but the recurrent IP expressed HMWK, immunohistochemically. Interestingly, these three lesions were weakly positive for neuroendocrine markers. All other IPs and UDHs, including lesions having solid components, were negative for neuroendocrine markers, and most of them were positive for myoepithelial markers and/or HMWK. A combination of the above immunohistochemical markers seems useful to evaluate intraductal proliferative lesions and to predict their prognosis. In particular, intraductal proliferative lesions with solid components exhibiting positivity for neuroendocrine markers should be followed up carefully to monitor breast cancer risk or recurrence. 相似文献
966.
GGA (geranylgeranoic acid) is a natural polyprenoic acid, derivatives of which has been shown to prevent second primary hepatoma. GGA induces mitochondria-mediated PCD (programmed cell death), which may be relevant to cancer prevention. To gain further insights into GGA-induced PCD, autophagy processes were examined in human hepatoma-derived HuH-7 cells. Treatment of HuH-7/GFP (green fluorescent protein)-LC3 cells with GGA induced green fluorescent puncta in the cytoplasm within 30 min and their massive accumulation at 24 h. After 15 min of GGA treatment, a burst of mitochondrial superoxide production occurred and LC3β-I was appreciably converted into LC3β-II. GGA-induced early stages of autophagy were unequivocally confirmed by electron-microscopic observation of early/initial autophagic vacuoles. On the other hand, LC3β-II as well as p62/SQSTM1 (sequestosome 1) continuously accumulated and co-localized in the cytoplasmic puncta after GGA treatment. Furthermore, GGA treatment of HuH-7/mRFP (monomeric red fluorescent protein)-GFP-LC3 cells showed yellow fluorescent puncta, whereas glucose deprivation of the cells gave red fluorescent puncta. These results strongly suggest that GGA induces the initial phase of autophagy, but blocks the maturation process of autolysosomes or late stages of autophagy, insomuch that GGA provides substantial accumulation of autophagosomes under serum-starvation conditions in human hepatoma cells. 相似文献
967.
Esteves-Pedro NM Rodas AC Dal Belo CA Oshima-Franco Y dos Santos MG Lopes PS 《Alternatives to laboratory animals : ATLA》2011,39(2):189-196
In Brazil, medicinal plants are widely used by the indigenous people, which leads to a constant requirement for toxicity tests to be performed on the plant extracts. Although the current Brazilian Directive 90/2004 on the preclinical toxicity testing of phytotherapeutics recommends only in vivo tests, some Brazilian researchers would like to change this situation by implementing the Three Rs in the toxicological testing of medicinal plants. The present study evaluated the cytotoxic and genotoxic potentials of bark extracts from Dipteryx alata Vogel, a medicinal plant of the Brazilian cerrado, by using CHO-K1 (Chinese hamster ovary) cells. An IC50 value was obtained, which corresponded to 0.16mg/ml of plant extract, and from this the equivalent LD50 was determined as 705mg/kg. In order to determine the genotoxic potential of the sample, the frequency of micronucleus formation was assessed. CHO-K1 cells were exposed, during targeted mitosis, to different concentrations of plant extract and cytochalasin B, in the presence and absence of an appropriate metabolic activation system (an S9 mix). The results obtained indicated that it might be possible to implement the Three Rs in assessing the potential human hazard of medicinal plants. The publication of such data can increase awareness of the Three Rs by showing how to optimise the management of animal use, if in vivo toxicological experiments are required. 相似文献
968.
Kage A Asato E Chiba Y Wada Y Katsu-Kimura Y Kubota A Sawai S Niihori M Baba SA Mogami Y 《Zoological science》2011,28(3):206-214
Bioconvection emerges in a dense suspension of swimming protists as a consequence of their negative-gravitactic upward migration and later settling as a blob of density greater than that of water. Thus, gravity is an important parameter governing bioconvective pattern formation. However, inconsistencies are found in previous studies dealing with the response of bioconvection patterns to increased gravity acceleration (hypergravity); the wave number of the patterns has been reported to decrease during the hypergravity phases of parabolic aircraft flight, while it increases in centrifugal hypergravity. In this paper, we reassess the responses of bioconvection to altered gravity during parabolic flight on the basis of vertical and horizontal observations of the patterns formed by Tetrahymena thermophila and Chlamydomonas reinhardtii. Spatiotemporal analyses of the horizontal patterns revealed an increase in the pattern wave number in both pre- and post-parabola hypergravity. Vertical pattern analysis was generally in line with the horizontal pattern analysis, and further revealed that hypergravity-induced changes preceded at the top layer of the suspensions while microgravity-induced changes appeared to occur from the bottom part of the settling blobs. The responses to altered gravity were rather different between the two sample species: T. thermophila tended to drastically modify its bioconvection patterns in response to changes in gravity level, while the patterns of C. reinhardtii responded to a much lesser extent. This difference can be attributed to the distinct physical and physiological properties of the individual organisms, suggesting a significant contribution of the gyrotactic property to the swimming behavior of some protists. 相似文献
969.
Tracking epigenetic histone modifications in single cells using Fab-based live endogenous modification labeling 总被引:1,自引:0,他引:1
Hayashi-Takanaka Y Yamagata K Wakayama T Stasevich TJ Kainuma T Tsurimoto T Tachibana M Shinkai Y Kurumizaka H Nozaki N Kimura H 《Nucleic acids research》2011,39(15):6475-6488
Histone modifications play an important role in epigenetic gene regulation and genome integrity. It remains largely unknown, however, how these modifications dynamically change in individual cells. By using fluorescently labeled specific antigen binding fragments (Fabs), we have developed a general method to monitor the distribution and global level of endogenous histone H3 lysine modifications in living cells without disturbing cell growth and embryo development. Fabs produce distinct nuclear patterns that are characteristic of their target modifications. H3K27 trimethylation-specific Fabs, for example, are concentrated on inactive X chromosomes. As Fabs bind their targets transiently, the ratio of bound and free molecules depends on the target concentration, allowing us to measure changes in global modification levels. High-affinity Fabs are suitable for mouse embryo imaging, so we have used them to monitor H3K9 and H3K27 acetylation levels in mouse preimplantation embryos produced by in vitro fertilization and somatic cell nuclear transfer. The data suggest that a high level of H3K27 acetylation is important for normal embryo development. As Fab-based live endogenous modification labeling (FabLEM) is broadly useful for visualizing any modification, it should be a powerful tool for studying cell signaling and diagnosis in the future. 相似文献
970.