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排序方式: 共有114条查询结果,搜索用时 587 毫秒
81.
Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands 总被引:26,自引:0,他引:26
82.
Huffman JW Miller JR Liddle J Yu S Thomas BF Wiley JL Martin BR 《Bioorganic & medicinal chemistry》2003,11(7):1397-1410
A series of 1',1'-dimethylalkyl-Delta(8)-tetrahydrocannabinol analogues with C-3 side chains of 2-12 carbon atoms has been synthesized and their in vitro and in vivo pharmacology has been evaluated. The lowest member of the series, 1',1'-dimethylethyl-Delta(8)-THC (8, n=0) has good affinity for the CB(1) receptor, but is inactive in vivo. The dimethylpropyl (8, n=1) through dimethyldecyl (8, n=8) all have high affinity for the CB(1) receptor and are full agonists in vivo. 1',1'-Dimethylundecyl-Delta(8)-THC (8, n=9) has significant affinity for the receptor (K(i)=25.8+/-5.8 nM), but has reduced potency in vivo. The dodecyl analogue (8, n=10) has little affinity for the CB(1) receptor and is inactive in vivo. A quantitative structure-activity relationship study of the side chain region of these compounds is consistent with the concept that for optimum affinity and potency the side chain must be of a length which will permit its terminus to loop back in proximity to the phenolic ring of the cannabinoid. 相似文献
83.
M D Lee G E Quinton R E Beeman A A Biehle R L Liddle D E Ellis RJ Buchanan Jr 《Journal of industrial microbiology & biotechnology》1997,18(2-3):106-115
For the full scale implementation of in situ anaerobic bioremediation of tetrachloroethene (PCE) in groundwater, the following issues must be addressed: which organic
substrates at which concentration would be most effective in promoting dechlorination and are economical; how far the substrate,
electron acceptor, and nutrients can be transported in the aquifer; and the placement of delivery and recovery wells for
distributing these amendments. In a microcosm study, almost all of the tested inexpensive substrates supported reductive
dechlorination of PCE through vinyl chloride (VC) under methanogenic conditions. A minimum of about 60 mg L−1 of organic carbon was needed to dechlorinate 23 μM PCE with a single feeding. In a second microcosm study dechlorination
stopped at 1,2-dichloroethene (DCE) in microcosms fed higher concentrations of several substrates. At the highest concentrations
the substrates inhibited DCE production. Three field tracer tests were conducted to evaluate methods to distribute the amendments
across the aquifer. The natural groundwater gradient is not sufficient to distribute substrate evenly. Groundwater injection
at 60 times the natural flux rate increased the distribution of substrate. A mixing strategy of cross-gradient injection
further increased the distribution of the substrate. Ammonia-nitrogen, sulfate, and phosphate were retarded relative to
the substrate and inorganic tracer.
Received 30 October 1995/ Accepted in revised form 07 June 1996 相似文献
84.
The primary nucleus of Batophora oerstedii J. Agardh like that of the related Acetabularia, undergoes a great increase in size throughout vegetative development. Formation of small secondary nuclei represents an irreversible stage in the development of reproductive structures in the gametangia. Changes observed in the course of the life cycle include: i) an increase from 3 to 200 μm diam, of the nucleus; ii) increase in number of nucleoli; iii) development of the perinuclear region; iv) increased pore density in the nuclear membrane; v) development of chromosomes in the nucleoplasm; vi) formation of secondary nuclei; and, vii) division of secondary nuclei. 相似文献
85.
Michael D. Barker John Liddle Francis L. Atkinson David Matthew Wilson Marion C. Dickson Cesar Ramirez-Molina Huw Lewis Rob P. Davis Donald O. Somers Margarete Neu Emma Jones Robert Watson 《Bioorganic & medicinal chemistry letters》2018,28(21):3458-3462
The discovery and lead optimisation of a novel series of SYK inhibitors is described. These were optimised for SYK potency and selectivity against Aurora B. Compounds were profiled in a human skin penetration study to identify a suitable candidate molecule for pre-clinical development. Compound 44 (GSK2646264) was selected for progression and is currently in Phase I clinical trials. 相似文献
86.
Robinson John P. Derreberry Sandra Liddle Rodger A. Ascoli Mario Puett David 《Molecular and cellular biochemistry》1977,15(1):63-66
Summary Nephrectomy of mature male rats was found to result in a significant increase in the circulatory half-life of tritiated ovine lutropin. The interaction of the glycoprotein hormone with the kidneys was studied in a more direct fashion using electron microscopic autoradiography. Evidence is presented showing the transfer of the hormone from microvilli into tubular epithelia (probably via vesicular transport), where radioactivity then becomes associated with lysosomes. This provides direct support for related results based on subcellular fractionation in which renal lysosomal catabolism was suggested as being important in the degradation of tritiated lutropin (M. Ascoli,R. A. Liddle, andD. Puett, Molecular and Cellular Endocrinology 4, 297, 1976). These results add substantial weight to the growing evidence that the kidneys assume a major role in controlling the concentration of circulating macromolecules.Research Career Development Awardee (AM-00055). 相似文献
87.
Liddle RA 《Biochimica et biophysica acta》2007,1772(8):869-878
Premature activation of digestive enzymes within the pancreas which leads to autodigestion of the gland is an early step in the pathogenesis of pancreatitis. Pancreatic injury is followed by other manifestations of inflammation including plasma extravasation, edema, and neutrophil infiltration which constitute the features of pancreatitis. Recent studies indicate that neural innervation of the pancreas may play an important role in the initiation and maintenance of the inflammatory response to injury. The pancreas is innervated by vagal, sympathetic and parasympathetic neurons, as well as sensory neurons. Activation of pancreatic primary sensory neurons causes the release of inflammatory neuropeptides both in the spinal cord to signal pain and in the pancreas itself where they produce plasma extravasation and neutrophil infiltration. Recent studies indicate that primary sensory neurons of the pancreas express transient receptor potential V1 (TRPV1) channels whose activation induces pancreatic inflammation. Moreover, blockade of these TRP channels significantly ameliorates experimental pancreatitis. This review describes our current understanding of the role of TRPV1 channels in pancreatitis and illustrates how this mechanism might be used to direct future treatments of pancreatic diseases. 相似文献
88.
John Liddle Paul Bamborough Michael D. Barker Sebastien Campos Rick P.C. Cousins Geoffrey J. Cutler Heather Hobbs Duncan S. Holmes Chris Ioannou Geoff W. Mellor Mary A. Morse Jeremy J. Payne John M. Pritchard Kathryn J. Smith Daniel T. Tape Caroline Whitworth Richard A. Williamson 《Bioorganic & medicinal chemistry letters》2009,19(9):2504-2508
The synthesis and SAR of a novel series of IKK2 inhibitors are described. Modification around the hinge binding region of the 7-azaindole led to a series of potent and selective inhibitors with good cellular activity. 相似文献
89.
The peptide tyrosine tyrosine (PYY) is produced and secreted from L cells of the gastrointestinal mucosa. To study the anatomy
and function of PYY-secreting L cells, we developed a transgenic PYY-green fluorescent protein mouse model. PYY-containing
cells exhibited green fluorescence under UV light and were immunoreactive to antibodies against PYY and GLP-1 (glucagon-like
peptide-1, an incretin hormone also secreted by L cells). PYY-GFP cells from 15 μm thick sections were imaged using confocal
laser scanning microscopy and three-dimensionally (3D) reconstructed. Results revealed unique details of the anatomical differences
between ileal and colonic PYY-GFP cells. In ileal villi, the apical portion of PYY cells makes minimal contact with the lumen
of the gut. Long pseudopod-like basal processes extend from these cells and form an interface between the mucosal epithelium
and the lamina propria. Some basal processes are up to 50 μm in length. Multiple processes can be seen protruding from one
cell and these often have a terminus resembling a synapse that appears to interact with neighboring cells. In colonic crypts,
PYY-GFP cells adopt a spindle-like shape and weave in between epithelial cells, while maintaining contact with the lumen and
lamina propria. In both tissues, cytoplasmic granules containing the hormones PYY and GLP-1 are confined to the base of the
cell, often filling the basal process. The anatomical arrangement of these structures suggests a dual function as a dock for
receptors to survey absorbed nutrients and as a launching platform for hormone secretion in a paracrine fashion. 相似文献