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排序方式: 共有313条查询结果,搜索用时 15 毫秒
51.
Kathleen Woodruff Teresa Defrancesco Sandra Tou Christina M. Williams Mathew Breen Kathryn Meurs Bruce Keene Ke Cheng 《Journal of cellular and molecular medicine》2017,21(8):1503-1512
Cardiosphere‐derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non‐ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c‐kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells. 相似文献
52.
The process of mRNA localization typically utilizes cis-targeting elements and trans-recognition factors to direct the compartmental organization of translationally suppressed mRNAs. mRNA localization to the endoplasmic reticulum (ER), in contrast, occurs via a co-translational, signal sequence/signal recognition particle (SRP)-dependent mechanism. We have utilized cell fractionation/cDNA microarray analysis, shRNA-mediated suppression of SRP expression, and mRNA reporter construct studies to define the role of the SRP pathway in ER-directed mRNA localization. Cell fractionation studies of mRNA partitioning between the cytosol and ER demonstrated the expected enrichment of cytosolic/nucleoplasmic protein-encoding mRNAs and secretory/integral membrane protein-encoding mRNAs in the cytosol and ER fractions, respectively, and identified a subpopulation of cytosolic/nucleoplasmic protein-encoding mRNAs in the membrane-bound mRNA pool. The latter finding suggests a signal sequence-independent pathway of ER-directed mRNA localization. Extending from these findings, mRNA partitioning was examined in stable SRP54 shRNA knockdown HeLa cell lines. shRNA-directed reductions in SRP did not globally alter mRNA partitioning patterns, although defects in membrane protein processing were observed, further suggesting the existence of multiple pathways for mRNA localization to the ER. ER localization of GRP94-encoding mRNA was observed when translation was disabled by mutation of the start codon/insertion of a 5'UTR stem-loop structure or upon deletion of the encoded signal sequence. Combined, these data indicate that the mRNA localization to the ER can be conferred independent of the signal sequence/SRP pathway and suggest that mRNA localization to the ER may utilize cis-encoded targeting information. 相似文献
53.
Anionic PAMAM dendrimers as drug delivery vehicles for transition metal-based anticancer drugs 总被引:1,自引:0,他引:1
Michelle J. Pisani Nial J. Wheate F. Richard Keene J. Grant Collins 《Journal of inorganic biochemistry》2009,103(3):373-380
The use of anionic half-generation poly(amidoamine) dendrimers as drug delivery vehicles for [Pt(S,S-dach)(5,6-Me2phen)]2+ (56MESS) (where S,S-dach = 1S,2S-diaminocyclohexane; 5,6-Me2phen = 5,6-dimethyl-1,10-phenanthroline) and [{Δ,Δ-Ru(phen)2}2(μ-bb7)]4+ (Rubb7) (where phen = 1,10-phenanthroline; bb7 = 1,7-bis[4-(4′-methyl-2,2′-bipyridyl)heptane]) has been studied by nuclear magnetic resonance spectroscopy. From one- and two-dimensional 1H NMR spectra both 56MESS and Rubb7 were found to bind to the surface of generation 3.5, 4.5, 5.5 and 6.5 dendrimers through electrostatic interactions. The higher charge and larger size of Rubb7 resulted in stronger binding to all dendrimer generations (Kb ? 2 × 105 M−1) compared with 56MESS (Kb ? 1 × 104 M−1). Interestingly, there appeared to be no observable trend between dendrimer size and binding constant strength. The size of the free and 56MESS-bound dendrimers were examined using pulsed-gradient spin-echo NMR. The dendrimers ranged in hydrodynamic diameter from 11 to 20 nm and in all cases were larger than their corresponding full-generation dendrimer. Upon the addition of 56MESS the diameter of the dendrimers increased, consistent with surface binding. 相似文献
54.
Boys ML Schretzman LA Chandrakumar NS Tollefson MB Mohler SB Downs VL Penning TD Russell MA Wendt JA Chen BB Stenmark HG Wu H Spangler DP Clare M Desai BN Khanna IK Nguyen MN Duffin T Engleman VW Finn MB Freeman SK Hanneke ML Keene JL Klover JA Nickols GA Nickols MA Steininger CN Westlin M Westlin W Yu YX Wang Y Dalton CR Norring SA 《Bioorganic & medicinal chemistry letters》2006,16(4):839-844
We describe a series of 1,2,4-oxadiazoles, which are potent antagonists of the integrin alpha(v)beta3 and, in addition, show selectivity relative to the other beta3 integrin alpha(IIb)beta3. In whole cells, the majority of these analogs also demonstrated modest selectivity against other alpha(v) integrins such as alpha(v)beta1 and alpha(v)beta6. 相似文献
55.
Reiter LA Freeman-Cook KD Jones CS Martinelli GJ Antipas AS Berliner MA Datta K Downs JT Eskra JD Forman MD Greer EM Guzman R Hardink JR Janat F Keene NF Laird ER Liras JL Lopresti-Morrow LL Mitchell PG Pandit J Robertson D Sperger D Vaughn-Bowser ML Waller DM Yocum SA 《Bioorganic & medicinal chemistry letters》2006,16(22):5822-5826
Using SAR from two related series of pyrimidinetrione-based inhibitors, compounds with potent MMP-13 inhibition and >100-fold selectivity against other MMPs have been identified. Despite high molecular weights, clogPs, and polar surface areas, the compounds are generally well absorbed and have excellent pharmacokinetic (PK) properties when dosed as sodium salts. In a rat fibrosis model, a compound from the series displayed no fibrosis at exposures many fold greater than its MMP-13 IC50. 相似文献
56.
57.
Stephen R. Williams Qiong Yang Fang Chen Xuan Liu Keith L. Keene Paul Jacques Wei-Min Chen Galit Weinstein Fang-Chi Hsu Alexa Beiser Liewei Wang Ebony Bookman Kimberly F. Doheny Philip A. Wolf Michelle Zilka Jacob Selhub Sarah Nelson Stephanie M. Gogarten Bradford B. Worrall Sudha Seshadri Michèle M. Sale the Genomics Randomized Trials Network the Framingham Heart Study 《PLoS genetics》2014,10(3)
58.
59.
Direct demonstration of duvatrienediol biosynthesis in glandular heads of tobacco trichomes 总被引:6,自引:2,他引:4
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Biosynthesis of the diterpenes, α and β 4,8,13-duvatriene-1,3-diol, has been observed in detached, intact glandular heads from trichomes of Nicotiana tabacum, Tobacco Introduction 1068. This result shows directly that the glandular head portion of the trichome is capable of duvatrienediol biosynthesis. In additional experiments, all of the [14C] duvatrienediol formed from sodium [2-14C]acetate by leaf midrib sections was recovered with trichome exudate and surface washes. None was found in trichome stalk, epidermal or subepidermal tissue extracts. Also, removal of glandular heads and exudate from midrib sections reduced or eliminated duvatrienediol biosynthetic capacity. Together these results strongly suggest that glandular heads are the primary, and perhaps the only, site of duvatrienediol biosynthesis in this plant.
Incubation of detached, intact glandular heads with sodium [14C]acetate in the dark or incubation in the light in the presence of DCMU reduced incorporation into duvatrienediols by 97%. These results suggest that chloroplasts which are abundant in glandular heads are involved in the biogenesis of these compounds.
相似文献60.
Type II achondrogenesis-hypochondrogenesis: morphologic and immunohistopathologic studies. 总被引:9,自引:5,他引:4
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M Godfrey D R Keene E Blank H Hori L Y Sakai L A Sherwin D W Hollister 《American journal of human genetics》1988,43(6):894-903
A 32-wk-gestation female with type II achondrogenesis-hypochondrogenesis has been studied. The clinical features were typical, and radiographs revealed short ribs, hypoplastic ilia, absence of ossification of sacrum, pubis, ischia, tali, calcanei, and many vertebral bodies; the long bones were short with mild metaphyseal flaring. The femoral cylinder index was 6.3. Comparison with previous cases placed the patient toward the mild end of the achondrogenesis-hypochondrogenesis spectrum (Whitley-Gorlin prototype IV). Light microscopy revealed hypercellular cartilage with decreased matrix traversed by numerous fibrous vascular canals. The growth plate was markedly abnormal. Ultrastructural studies revealed prominently dilated rough endoplasmic reticulum containing a fine granular material with occasional fibrils in all chondrocytes. Immunohistologic studies indicated irregular large areas of cartilage matrix staining with monoclonal antibody to human type III collagen. The relative intensity of matrix staining for type II collagen appeared diminished. More striking, however, were intense focal accumulations of type II collagen within small rounded perinuclear structures of most chondrocytes but not other cell types. These results strongly suggest intracellular retention of type II collagen within vacuolar structures, probably within the dilated rough endoplasmic reticulum observed in all chondrocytes by electron microscopy (EM), and imply the presence of an abnormal, poorly secreted type II collagen molecule. Biochemical studies (see companion paper) suggest that this patient had a new dominant lethal disorder caused by a structural abnormality of type II collagen. 相似文献