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991.
Enterococcal surface protein (Esp) is a cell wall-associated protein of Enterococcus faecalis that has been identified as a potential virulence factor. We used a mouse model to examine whether Esp facilitates intestinal colonization or translocation of E. faecalis to mesenteric lymph nodes. After clindamycin treatment, similar levels of high-density colonization were established after orogastric inoculation of an E. faecalis isolate containing the esp gene within a large pathogenicity island and an isogenic mutant created by allelic replacement of the esp gene with a chloramphenicol resistance cassette (P=0.7); translocation to mesenteric lymph nodes was detected in 3 of 12 (25%) mice in both groups. Isogenic mutants of FA2-2 (a plasmid-free derivative of E. faecalis strain JH2) with or without the esp gene failed to establish colonization of clindamycin-treated mice. These results suggest that Esp does not facilitate intestinal colonization or translocation of E. faecalis. 相似文献
992.
993.
Kaur K Aeron S Bruhaspathy M Shetty SJ Gupta S Hegde LH Silamkoti AD Mehta A Chugh A Gupta JB Sarma PK Kumar N 《Bioorganic & medicinal chemistry letters》2005,15(8):2093-2096
Novel derivatives of Tolterodine (1) and Oxybutynin (2) have been designed using conformationally restricted azabicyclics as replacement for open-chain amines. The synthesis and structure-activity relationships are presented. 相似文献
994.
Shankar BB Lavey BJ Zhou G Spitler JA Tong L Rizvi R Yang DY Wolin R Kozlowski JA Shih NY Wu J Hipkin RW Gonsiorek W Lunn CA 《Bioorganic & medicinal chemistry letters》2005,15(20):4417-4420
We recently reported that compound 1 is a potent inhibitor of the CB2 receptor with high selectivity over CB1. This paper describes the SAR development for this class of compounds. Variation of the substitution pattern on the aromatic rings, as well as the groups linking them together, led to sub-nanomolar inhibitors of the CB2 receptor, with high selectivity over CB1. 相似文献
995.
Sinha N Jain S Tilekar A Upadhayaya RS Kishore N Jana GH Arora SK 《Bioorganic & medicinal chemistry letters》2005,15(6):1573-1576
A new series of antituberculosis agents 6-9 was designed, synthesized and evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv and clinical isolates in an agar dilution method. Compound 9h showed comparable in vitro activity (MIC) to isoniazid against M. tuberculosis H37Rv and clinical isolates (sensitive strains) and superior activity against resistant strains of M. tuberculosis. 相似文献
996.
Chemical oscillation in glycolysis induced by glucose is an universal feature in all living cells. In beta-cells this is accompanied by sustained oscillations of concentration of insulin, which helps to keep the blood glucose level within optimum limits. Experiments in this regard had shown that the glycolytic and insulin oscillations are almost consistently in phase and their time periods are very close to each other at both high and low initial concentration of glucose. Experiments have also demonstrated the dynamical transition between the states of glycolytic oscillations indicating a saturation behaviour of glucose transporters at a higher glucose flow rate. We propose a phenomenological model to understand these simultaneous oscillations and how glycolysis provides a mechanism for pulsatory insulin secretion in the light of these basic experimental issues. 相似文献
997.
Malik ZA Thompson CR Hashimi S Porter B Iyer SS Kusner DJ 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(6):2811-2815
One-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), and three million people die of tuberculosis each year. Following its ingestion by macrophages (MPs), Mtb inhibits the maturation of its phagosome, preventing progression to a bactericidal phagolysosome. Phagocytosis of Mtb is uncoupled from the elevation in MP cytosolic Ca(2+) that normally accompanies microbial ingestion, resulting in inhibition of phagosome-lysosome fusion and increased intracellular viability. This study demonstrates that the mechanism responsible for this failure of Ca(2+)-dependent phagosome maturation involves mycobacterial inhibition of MP sphingosine kinase. Thus, inhibition of sphingosine kinase directly contributes to survival of Mtb within human MPs and represents a novel molecular mechanism of pathogenesis. 相似文献
998.
Electrostatic interactions play a key role in enzyme catalytic function. At long range, electrostatics steer the incoming ligand/substrate to the active site, and at short distances, electrostatics provide the specific local interactions for catalysis. In cases in which electrostatics determine enzyme function, orthologs should share the electrostatic properties to maintain function. Often, electrostatic potential maps are employed to depict how conserved surface electrostatics preserve function. We expand on previous efforts to explain conservation of function, using novel electrostatic sequence and structure analyses of four enzyme families and one enzyme superfamily. We show that the spatial charge distribution is conserved within each family and superfamily. Conversely, phylogenetic analysis of key electrostatic residues provide the evolutionary origins of functionality. 相似文献
999.
Murine CD4 and CD8 T cells express predominantly types 1 and 4 sphingosine 1-phosphate (S1P) G protein-coupled receptors (designated S1P1 and S1P4 or previously endothelial differentiation gene-encoded 1 and 6) for S1P, which has a normal plasma concentration of 0.1-1 microM. S1P now is shown to enhance chemotaxis of CD4 T cells to CCL-21 and CCL-5 by up to 2.5-fold at 10 nM to 0.1 microM, whereas 0.3-3 microM S1P inhibits this chemotaxis by up to 70%. Chemotaxis of S1P(1), but not S1P(4), transfectants to CXCL1 and CXCL4 was similarly affected by S1P. Activation of CD4 T cells, which decreases S1P receptor expression, suppressed effects of S1P on chemotaxis. Pretreatment of labeled CD4 T cells with S1P before reintroduction into mice inhibited by a maximum of 75% their migration into chemokine-challenged s.c. air pouches. The S1P-S1P(1) receptor axis thus controls recruitment of naive T cells by maintaining their response threshold to diverse lymphotactic factors. 相似文献
1000.
Influence of connection geometry and SVC-IVC flow rate ratio on flow structures within the total cavopulmonary connection: a numerical study 总被引:5,自引:0,他引:5
Khunatorn Y Mahalingam S DeGroff CG Shandas R 《Journal of biomechanical engineering》2002,124(4):364-377
The total cavopulmonary connection (TCPC) is a palliative cardiothoracic surgical procedure used in patients with one functioning ventricle that excludes the heart from the systemic venous to pulmonary artery pathway. Blood in the superior and inferior vena cavae (SVC, IVC) is diverted directly to the pulmonary arteries. Since only one ventricle is left in the circulation, minimizing pressure drop by optimizing connection geometry becomes crucial. Although there have been numerical and in-vitro studies documenting the effect of connection geometry on overall pressure drop, there is little published data examining the effect of SVC-IVC flow rate ratio on detailed fluid mechanical structures within the various connection geometries. We present here results from a numerical study of the TCPC connection, configured with various connections and SVC:IVC flow ratios. The role of major flow parameters: shear stress, secondary flow, recirculation regions, flow stagnation regions, and flow separation, was examined. Results show a complex interplay among connection geometry, flow rate ratio and the types and effects of the various flow parameters described above. Significant changes in flow structures affected local distribution of pressure, which in turn changed overall pressure drop. Likewise, changes in local flow structure also produced changes in maximum shear stress values; this may have consequences for platelet activation and thrombus formation in the clinical situation. This study sheds light on the local flow structures created by the various connections andflow configurations and as such, provides an additional step toward understanding the detailed fluid mechanical behavior of the more complex physiological configurations seen clinically. 相似文献