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41.
Asaki T Sugiyama Y Hamamoto T Higashioka M Umehara M Naito H Niwa T 《Bioorganic & medicinal chemistry letters》2006,16(5):1421-1425
A series of 3-substituted benzamide derivatives structurally related to STI-571 (imatinib mesylate), a Bcr-Abl tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML), was prepared and evaluated for antiproliferative activity against the Bcr-Abl-positive leukemia cell line K562. About ten 3-halogenated and 3-trifluoromethylated benzamide derivatives were identified as highly potent Bcr-Abl kinase inhibitors. One of these, NS-187 (9b), is a promising new candidate Bcr-Abl inhibitor for the therapy of STI-571-resistant chronic myeloid leukemia. 相似文献
42.
BACKGROUND: Sepsis causes diaphragmatic dysfunction, which can lead to the development of respiratory failure. We previously reported that isoproterenol, non-selective beta-adrenergic agonist, improved contractility of the diaphragm in a septic rat model. Since beta(2)-adrenoceptor agonists are widely used in the treatment of chronic respiratory disease, we investigated the effect of terbutaline, a selective beta(2)-adrenergic agonist, on contractility of the septic rat diaphragm and the contribution of intracellular Ca(2+) to the effect of terbutaline in vitro. METHODS: Forty-eight rats were divided into a sham group (in which sham laparotomy was performed) and a CLP group (in which peritonitis was induced by cecal ligation and perforation). The left hemidiaphragm was removed at 16 h after the operation. The effect of terbutaline (10(-)(6) M) on contractility of the diaphragm was assessed by twitch characteristics (twitch tension, contraction time and contraction velocity) and force-frequency relationship. In addition, to investigate the role of calcium ions in the effect of terbutaline on contractility of the diaphragm, contractility of the diaphragm was assessed after the pre-incubation of the diaphragm with methoxy-verapamil (10(-)(5) M), Ca(2+)-free Krebs-Ringer's solution buffered with 2 mM of ethylene glycol tetra-acetic acid (EGTA), and ryanodine (10(-)(6) M). RESULTS: Terbutaline significantly improved twitch characteristics and force-frequency relationship of the diaphragm in the CLP group (P<0.01). Incubation with methoxy-verapamil or calcium-free solution with EGTA did not show any changes in the inotropic effect of terbutaline in the CLP group. However, incubation with ryanodine completely abolished the inotropic effect of terbutaline in the CLP group. CONCLUSIONS: The present study demonstrated that terbutaline increased contractility of the diaphragm in the septic rats. Since this inotropic effect was abolished by ryanodine administration, calcium release from the sarcoplasmic reticulum may contribute to the terbutaline-induced improvement in dysfunction of the septic diaphragm. 相似文献
43.
Ou K Kesuma D Ganesan K Yu K Soon SY Lee SY Goh XP Hooi M Chen W Jikuya H Ichikawa T Kuyama H Matsuo E Nishimura O Tan P 《Journal of proteome research》2006,5(9):2194-2206
The identification of drug-responsive biomarkers in complex protein mixtures is an important goal of quantitative proteomics. Here, we describe a novel approach for identifying such drug-induced protein alterations, which combines 2-nitrobenzenesulfenyl chloride (NBS) tryptophan labeling with two-dimensional gel electrophoresis (2DE)/mass spectrometry (MS). Lysates from drug-treated and control samples are labeled with light or heavy NBS moiety and separated on a common 2DE gel, and protein alterations are identified by MS through the differential intensity of paired NBS peptide peaks. Using NBS/2DE/MS, we profiled the proteomic alterations induced by tamoxifen (TAM) in the estrogen receptor (ER) positive MCF-7 breast cancer cell line. Of 88 protein spots that significantly changed upon TAM treatment, 44 spots representing 23 distinct protein species were successfully identified with NBS-paired peptides. Of these 23 TAM-altered proteins, 16 (70%) have not been previously associated with TAM or ER activity. We found the NBS labeling procedure to be both technically and biologically reproducible, and the NBS/2DE/MS alterations exhibited good concordance with conventional 2DE differential protein quantitation, with discrepancies largely due to the comigration of distinct proteins in the regular 2DE gels. To validate the NBS/2DE/MS results, we used immunoblotting to confirm GRP78, CK19, and PA2G4 as bona fide TAM-regulated proteins. Furthermore, we demonstrate that PA2G4 expression can serve as a novel prognostic factor for disease-free survival in two independent breast cancer patient cohorts. To our knowledge, this is the first report describing the proteomic changes in breast cancer cells induced by TAM, the most commonly used selective estrogen receptor modulator (SERM). Our results indicate that NBS/2DE/MS may represent a more reliable approach for cellular protein quantitation than conventional 2DE approaches. 相似文献
44.
Seiichiro Ogawa Yoshikazu Iwasawa Tatsushi Toyokuni Tetsuo Suami 《Carbohydrate research》1985,141(1):29-40
The synthesis is described of adiposin-1 (2a), isolated from an α-d-glucosidase inhibitor complex, adiposin, produced by Streptomyces caluvs TM-521. The synthesis involved the coupling of 1,6-anhydro-4-O-(3,4-anhydro-α-d-galactopyranosyl)-β-d-glucopyranose (13) with the di-O-isopropylidene derivative (7) of dl-(1,4,)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexenylamine. All possible diastereoisomers of the secondary amine were isolated by chromatography on silica gel. Their structures were tentatively assigned on the basis of 1H-n.m.r. spectroscopy and optical rotation. Likewise, both the core-structure (4) of adiposin and the saturated analog (22) of 2a were synthesized. 相似文献
45.
Findings from animal experiments are sometimes contradictory to the idea that the tendon structure is a simple elastic spring in series with muscle fibers, and suggest influence of muscle contraction on the tendon mechanical properties. The purpose of the present study was to investigate the influence of muscle contraction levels on the force-length relationship of the human Achilles tendon during lengthening of the triceps surae muscle-tendon unit. For seven subjects, ankle dorsiflexion was performed without (passive condition) and with contraction of plantar flexor muscles (eccentric conditions, at 3 contraction levels) on an isokinetic dynamometer. Deformation of the Achilles tendon during each trial was measured using ultrasonography. The Achilles tendon force corresponding to the tendon elongation of 10mm in the passive condition was significantly smaller than those in the eccentric conditions (p<0.05 or p<0.01). Within the eccentric conditions, the Achilles tendon force corresponding to the tendon elongation of 10mm was significantly greater in the maximal contraction level than those in submaximal eccentric conditions (p<0.05 or p<0.01). In addition, the tendon stiffness was greater in higher contraction levels (p<0.05 or p<0.01). Present results suggest that the human tendon structure is not a simple elastic spring in series with muscle fibers. 相似文献
46.
Kunimoto K Yamazaki Y Nishida T Shinohara K Ishikawa H Hasegawa T Okanoue T Hamada H Noda T Tamura A Tsukita S Tsukita S 《Cell》2012,148(1-2):189-200
Highlights? Mice expressing truncated Odf2 cough and sneeze due to primary ciliary dyskinesia ? Full-length Odf2 is needed for the formation of basal body-associated basal feet ? In the absence of basal feet, basal bodies fail to align with planar polarity cues ? Polarization of basal bodies by Odf2 is required for coordinated ciliary beating 相似文献
47.
Yukie Sato Yoshiaki Tsuda Hironori Sakamoto Martijn Egas Tetsuo Gotoh Yutaka Saito Yan‐Xuan Zhang Jian‐Zhen Lin Jung‐Tai Chao Atsushi Mochizuki 《Ecology and evolution》2019,9(4):1590-1602
When males fight for access to females, such conflict rarely escalates into lethal fight because the risks and costs involved, that is, severe injury or death, are too high. The social spider mite, Stigmaeopsis miscanthi, does exhibit lethal male fights, and this male–male aggressiveness varies among populations. To understand the evolution of lethal fighting, we investigated aggressiveness in 42 populations and phylogenetic relationships in 47 populations along the Japanese archipelago. By analysis of the male weapon morph, a proxy for aggressiveness, we confirmed the existence of a mildly aggressive (ML) form, besides the low aggression (LW) and high aggression (HG) forms reported earlier. To evaluate demographic history of these three forms, we employed the approximate Bayesian computation approach using mtCOI sequences and taking into consideration the postlast glacial expansion history of the host plant, Miscanthus sinensis. As results, hierarchical split models are more likely to explain the observed genetic pattern than admixture models, and the ML form in the subtropical region was considered the ancestral group. The inferred demographic history was consistent with the one reconstructed for the host plant in a previous study. The LW form was split from the ML form during the last glacial period (20,000–40,000 years BP), and subsequently, the HG form was split from the ML form at the end of or after the last glacial period (5,494–10,988 years BP). The results also suggest that the mite invaded Japan more than once, resulting in the present parapatric distribution of LW and HG forms in eastern Japan. 相似文献
48.
Taxonomic status of Gerres limbatus Cuvier in Cuvier and Valenciennes, 1830 and G. lucidus Cuvier in Cuvier and Valenciennes, 1830 was studied. The two species were reassessed as the same species, the latter corresponding to young of the former, on the basis of examination of their eight syntypes and other comparative specimens. Gerres limbatus clearly differs from other congeners in having 2½–3 (usually 2½) scales between the 5th dorsal fin spine base and the lateral line, and four or five diffuse, dark saddle patches mainly along the back in life (more apparent in small specimens less than ca. 65 mm in standard length, or preserved and stressed live specimens) (vs. usually more than 3½ scales between fifth dorsal fin spine base and lateral line, and and no such body color pattern of G. limbatus in other congeners). The species is currently known from the southern and western coasts of India including Sri Lanka, the Malay Peninsula, Gulf of Thailand, and Indonesia, becoming rare in occurrence eastward. 相似文献
49.
50.
The heterogeneity of human fibroblasts as determined from the effects of hydrocortisone on cell growth and specific dexamethasone binding 总被引:1,自引:0,他引:1
To elucidate the heterogeneity of human fibroblasts from lung and skin, the effects of hydrocortisone on cell proliferation and the specific dexamethasone binding to cells were studied. Hydrocortisone at physiological concentrations stimulated the proliferation in three strains of human fetal lung fibroblasts and inhibited it in two strains. There are two kinds of fibroblasts in the human fetal lung in addition to the human skin fibroblasts reported previously. Dexamethasone-binding experiments showed that human fibroblasts may be classified into two groups with respect to the dissociation constant (Kd) of the binding reaction. The heterogeneity of human fibroblasts shown by Kd could not be correlated to classification on the basis of the effects of hydrocortisone on cell proliferation. The differences in Kd for the binding reactions suggest differences in donor tissues from which human fibroblasts are derived. 相似文献