50 results on '"Yan, S. F."'
Search Results
2. Blockade von RAGE fördert die Leberregeneration nach subtotaler Hepatektomie
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Cataldegirmen, Güllü, Yan, S. F., Qu, W., Lu, Y., Bröring, D. C., Rogiers, X., Stern, D. M., Schmidt, A. M., Emond, J., Menger, M. D., editor, Haas, N. P., editor, Neugebauer, E., editor, and Bauer, H., editor
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- 2003
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3. Cyclocondensation of ethyl 3,3-diaminoacrylate with aromatic ketones and nitriles containing a labile halogen atom in the ortho position
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Yan, S. F., Dar’in, D. V., Lobanov, P. S., and Potekhin, A. A.
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- 2008
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4. RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease
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Bucciarelli, L. G., Wendt, T., Rong, L., Lalla, E., Hofmann, M. A., Goova, M. T., Taguchi, A., Yan, S. F., Yan, S. D., Stern, D. M., and Schmidt, A. M.
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- 2002
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5. RAGE AND EXPERIMENTAL DIABETIC NEUROPATHY: DOES RAGE DRIVE THE DEVELOPMENT OF DIABETIC AXONAL ATROPHY?
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Toth, C, Schmidt, A M, Brussee, V, Yan, S F, Rong, L L, and Zochodne, D W
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- 2005
6. Reaction of 2,4-dinitrofluorobenzene with enediamines. synthesis of cinnolines
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Vypolzov, A. V., Yan, S. F., Dar’in, D. V., and Lobanov, P. S.
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- 2010
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7. Direction of hydrolysis of esters of some pyrimidine-5-carboxylic acids
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Yan, S. F., Ivanov, A. Yu., Dar’in, D. V., Lobanov, P. S., and Potekhin, A. A.
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- 2007
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8. Preparation of Nd-doped manganese–zinc–ferrite/polyaniline composite materials
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Yan, S. F., primary, Xie, Y., additional, Liu, J. M., additional, Pan, J. F., additional, Yu, Y. F., additional, Shi, L., additional, Zhang, K., additional, Lai, Q., additional, Liu, F. M., additional, Gao, Y. H., additional, and Ling, Y., additional
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- 2013
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9. ChemInform Abstract: Reaction of 2,4-Dinitrofluorobenzene with Enediamines. Synthesis of Cinnolines (IV).
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Vypolzov, A. V., primary, Yan, S. F., additional, Dar'in, D. V., additional, and Lobanov, P. S., additional
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- 2011
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10. ChemInform Abstract: Cyclocondensation of Ethyl 3,3-Diaminoacrylate with Aromatic Ketones and Nitriles Containing a Labile Halogen Atom in the ortho Position.
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Yan, S. F., primary, Dar'in, D. V., additional, Lobanov, P. S., additional, and Potekhin, A. A., additional
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- 2009
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11. Preparation of Nd-doped manganese-zinc-ferrite/polyaniline composite materials.
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Yan, S. F., Xie, Y., Liu, J. M., Pan, J. F., Yu, Y. F., Shi, L., Zhang, K., Lai, Q., Liu, F. M., Gao, Y. H., and Ling, Y.
- Subjects
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DOPING agents (Chemistry) , *MANGANESE zinc ferrite , *POLYANILINES , *COMPOSITE materials , *MAGNETIC properties , *FOURIER transform infrared spectroscopy , *TRANSMISSION electron microscopy , *X-ray diffraction - Abstract
Mn0·4Zn0·6NdxFe2-xO4/polyaniline (PANI) nanocomposites with magnetic properties were prepared by in situ polymerisation of aniline in the presence of Mn0·4Zn0·6NdxFe2-xO4 nanoparticles. The structure and morphologies of nanocomposites were characterised by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM). X-ray diffraction analysis shows that the size of Mn0·4Zn0·6NdxFe2-xO4 nanocomposites increases with the increase in the Nd doped amount. The optimum doped amount of Nd was 0·075, and the optimum calcination temperature was 850°C. The ferrite particles are well embedded in PANI chains. The FTIR results further prove that the Nd doped manganese-zinc-ferrite/PANI composites have been synthesised. Images (TEM) showed that the nanocomposites presented a spherical structure with a magnetic core of Mn0·4Zn0·6NdxFe2-xO4 and a conducting shell of PANI. The results showed that the electromagnetic properties of the Mn0·4Zn0·6NdxFe2-xO4/PANI composites were related to the mass ratio of PANI, the amount of Nd, the calcination temperature and the precipitation time. [ABSTRACT FROM AUTHOR]
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- 2014
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12. Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition.
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Pinsky, D J, primary, Liao, H, additional, Lawson, C A, additional, Yan, S F, additional, Chen, J, additional, Carmeliet, P, additional, Loskutoff, D J, additional, and Stern, D M, additional
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- 1998
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13. Monocytes and tissue factor promote thrombosis in a murine model of oxygen deprivation.
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Lawson, C A, primary, Yan, S D, additional, Yan, S F, additional, Liao, H, additional, Zhou, Y S, additional, Sobel, J, additional, Kisiel, W, additional, Stern, D M, additional, and Pinsky, D J, additional
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- 1997
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14. CD18-mediated neutrophil recruitment contributes to the pathogenesis of reperfused but not nonreperfused stroke.
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Prestigiacomo, C J, Kim, S C, Connolly, E S Jr, Liao, H, Yan, S F, and Pinsky, D J
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- 1999
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15. Novel Statistical Approach for Primary High-Throughput Screening Hit Selection
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Yan, S. F., Asatryan, H., Li, J., and Zhou, Y.
- Abstract
The standard activity threshold-based method (the top X approach), currently widely used in the high-throughput screening (HTS) data analysis, is ineffective at identifying good-quality hits. We have proposed a novel knowledge-based statistical approach, driven by the hidden structure−activity relationship (SAR) within a screening library, for primary hit selection. Application to an in-house ultrahigh-throughput screening (uHTS) campaign has demonstrated it can directly identify active scaffolds containing valuable SAR information with a greatly improved confirmation rate compared to the standard top X method (from 55% to 85%). This approach may help produce high-quality leads and expedite the hit-to-lead process in drug discovery.
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- 2005
16. Accommodation of a 1S-(−)-Benzo[c]phenanthrenyl-N<SUP>6</SUP>-dA Adduct in the <BO>Y</BO>-Family Dpo4 DNA Polymerase Active Site: Structural Insights through Molecular Dynamics Simulations
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Wang, L., Wu, M., Yan, S. F., Patel, D. J., Geacintov, N. E., and Broyde, S.
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Molecular modeling and molecular dynamics simulations have been performed to elucidate feasible structures in the Y-family Dpo4 DNA polymerase for the 1S-(−)-trans-anti-B[c]Ph-N6-dA adduct, derived from the fjord region polycyclic aromatic hydrocarbon (PAH) benzo[c]phenanthrene. Three types of models were delineated as follows: an intercalation model, a model with the aromatic ring system in the polymerase major groove open pocket, and a −1 deletion major groove model. All four 2-deoxyribonucleoside 5-triphosphates (dNTPs) were considered in the first two cases, and a normal Watson−Crick partner positioned to have skipped the modified template was employed as the incoming dNTP in the −1 deletion case. The trajectories derived from the dynamics simulations were analyzed in detail to evaluate the extents of distortion for each system. Overall, our results suggest that the major groove model is the least distorted, followed by the −1 deletion model, while the intercalation model is perturbed the most. The syn-dGTP and syn-dATP mismatches opposite the lesion are well-accommodated in the major groove model, as is the normal Watson−Crick partner dTTP. The intercalation model appears most likely to impede the polymerase. More broadly, these models look reasonable for other PAH metabolite-derived adducts to adenine with similar 1S stereochemistry. Furthermore, these models suggest how error-prone translesion synthesis by Y-family polymerases might produce mutations that may play a role in the initiation of cancer.
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- 2005
17. Genomic organization and functional characterization of the Leishmania major Friedlin ribosomal RNA gene locus
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Martinez-Calvillo, S., Sunkin, S. M., Yan, S. f., Fox, M., Stuart, K., and Myler, P. J.
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- 2001
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18. Protein kinase C-beta and oxygen deprivation. A novel Egr-1-dependent pathway for fibrin deposition in hypoxemic vasculature.
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Yan, S F, Lu, J, Zou, Y S, Kisiel, W, Mackman, N, Leitges, M, Steinberg, S, Pinsky, D, and Stern, D
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Fibrin deposition is a salient feature of hypoxemic vasculature and results from induction of tissue factor. Such tissue factor expression in an oxygen deficient environment is driven by the transcription factor Early Growth Response (Egr)-1. Using homozygous null mice for the protein kinase C beta-isoform gene (PKCbeta null), PKCbeta is shown to be upstream of Egr-1 in this oxygen deprivation-mediated pathway for triggering procoagulant events. Whereas wild-type mice exposed to hypoxia (6%) displayed a robust increase in tissue factor transcripts and antigen, and vascular fibrin deposition, PKCbeta null animals showed a markedly blunted response. Consistent with a central role for Egr-1 in hypoxia-induced expression of tissue factor, PKCbeta null mice subjected to oxygen deprivation displayed at most a minor elevation in Egr-1 transcripts, antigen, and intensity of the gel shift band by electrophoretic mobility shift assay, compared with normoxic animals. These data firmly establish PKCbeta as a trigger for events leading to induction of Egr-1 and tissue factor under hypoxic conditions, and provide insight into a biologic cascade whereby oxygen deprivation recruits targets of PKCbeta and Egr-1, thereby amplifying the cellular response.
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- 2000
19. Hypoxia-associated induction of early growth response-1 gene expression.
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Yan, S F, Lu, J, Zou, Y S, Soh-Won, J, Cohen, D M, Buttrick, P M, Cooper, D R, Steinberg, S F, Mackman, N, Pinsky, D J, and Stern, D M
- Abstract
The paradigm for the response to hypoxia is erythropoietin gene expression; activation of hypoxia-inducible factor-1 (HIF-1) results in erythropoietin production. Previously, we found that oxygen deprivation induced tissue factor, especially in mononuclear phagocytes, by an early growth response (Egr-1)-dependent pathway without involvement of HIF-1 (Yan, S.-F., Zou, Y.-S., Gao, Y., Zhai, C., Mackman, N., Lee, S., Milbrandt, J., Pinsky, D., Kisiel, W., and Stern, D. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 8298-8303). Now, we show that cultured monocytes subjected to hypoxia (pO2 approximately 12 torr) displayed increased Egr-1 expression because of de novo biosynthesis, with a approximately 10-fold increased rate of transcription. Transfection of monocytes with Egr-1 promoter-luciferase constructs localized elements responsible for hypoxia-enhanced expression to -424/-65, a region including EBS (ets binding site)-SRE (serum response element)-EBS and SRE-EBS-SRE sites. Further studies with each of these regions ligated to the basal thymidine kinase promoter and luciferase demonstrated that EBS sites in the element spanning -424/-375 were critical for hypoxia-enhanceable gene expression. These data suggested that an activated ets factor, such as Elk-1, in complex with serum response factor, was the likely proximal trigger of Egr-1 transcription. Indeed, hypoxia induced activation of Elk-1, and suppression of Elk-1 blocked up-regulation of Egr-1 transcription. The signaling cascade preceding Elk-1 activation in response to oxygen deprivation was traced to activation of protein kinase C-betaII, Raf, mitogen-activated protein kinase/extracellular signal-regulated protein kinase kinase and mitogen-activated protein kinases. Comparable hypoxia-mediated Egr-1 induction and activation were observed in cultured hepatoma-derived cells deficient in HIF-1beta and wild-type hepatoma cells, indicating that the HIF-1 and Egr-1 pathways are initiated independently in response to oxygen deprivation. We propose that activation of Egr-1 in response to hypoxia induces a different facet of the adaptive response than HIF-1, one component of which causes expression of tissue factor, resulting in fibrin deposition.
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- 1999
20. N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression.
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Kislinger, T, Fu, C, Huber, B, Qu, W, Taguchi, A, Du Yan, S, Hofmann, M, Yan, S F, Pischetsrieder, M, Stern, D, and Schmidt, A M
- Abstract
Recent studies suggested that interruption of the interaction of advanced glycation end products (AGEs), with the signal-transducing receptor receptor for AGE (RAGE), by administration of the soluble, extracellular ligand-binding domain of RAGE, reversed vascular hyperpermeability and suppressed accelerated atherosclerosis in diabetic rodents. Since the precise molecular target of soluble RAGE in those settings was not elucidated, we tested the hypothesis that predominant specific AGEs within the tissues in disorders such as diabetes and renal failure, N(epsilon)-(carboxymethyl)lysine (CML) adducts, are ligands of RAGE. We demonstrate here that physiologically relevant CML modifications of proteins engage cellular RAGE, thereby activating key cell signaling pathways such as NF-kappaB and modulating gene expression. Thus, CML-RAGE interaction triggers processes intimately linked to accelerated vascular and inflammatory complications that typify disorders in which inflammation is an established component.
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- 1999
21. Stability confidence for fuzzy matrices
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Wang, W.-J. and Yan, S.-F.
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- 1999
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22. Expression of plasma phospholipid transfer protein mRNA in normal and emphysematous lungs and regulation by hypoxia.
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Jiang, X C, D'Armiento, J, Mallampalli, R K, Mar, J, Yan, S F, and Lin, M
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The lung is the major site expressing plasma phospholipid transfer protein (PLTP) mRNA in humans and mice, suggesting that this protein might have an important role in maintaining normal function of this organ. In the lung of human collagenase transgenic mice, an emphysematous animal model, PLTP mRNA was 3-fold higher than in control mice. However, the mRNA in other tissues was not changed. To further assess the expression and function of PLTP, we measured PLTP mRNA level in lung tissue of two emphysematous patients and found that the mRNA was 4-fold higher than in control subjects. In situ hybridization on mouse lung suggested positive staining in alveolar type II epithelial cells. In addition, immortalized rat alveolar pre-type II epithelial cells and freshly isolated mature rat alveolar type II epithelial cells both highly expressed PLTP mRNA, and the former cells actively secreted PLTP activity into the medium. To examine the possible mechanisms leading to high levels of PLTP expression in vivo, we exposed the pre-type II cells to hypoxia and demonstrated induction of PLTP mRNA and a coordinate increase in secreted PLTP activity. Thus, the PLTP gene is highly expressed in alveolar type II epithelial cells and is induced during hypoxia and in emphysema. These observations suggest that a hypoxic stimulus occurring in emphysema may be a novel mechanism that contributes to enhanced expression of PLTP.
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- 1998
23. Nuclear factor interleukin 6 motifs mediate tissue-specific gene transcription in hypoxia.
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Yan, S F, Zou, Y S, Mendelsohn, M, Gao, Y, Naka, Y, Du Yan, S, Pinsky, D, and Stern, D
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Activation of transcription at the nuclear factor interleukin 6 (NF-IL-6) DNA binding motif modulates expression of multiple genes important in host adaptive and developmental mechanisms. Studies showing that hypoxia-induced transcription of IL-6 in cultured endothelial cells was due to transcriptional activation by the NF-IL-6 motif in the promoter (Yan, S.-F., Tritto, I., Pinsky, D., Liao, H., Huang, J., Fuller, G., Brett, J., May, L., and Stern, D. (1995) J. Biol. Chem. 270, 11463-11471) led us to prepare transgenic mice using 115- or 14-base pair regions of the promoter encompassing the NF-IL-6 site ligated to the lacZ reporter gene and the basal thymidine kinase promoter. On exposure to hypoxia or induction of ischemia, mice bearing either of the constructs showed prominent expression of the transgene in lung and cardiac vasculature and in the kidney but not in the liver (parenchyma or vasculature). In contrast, transgenic mice bearing a mutationally inactivated NF-IL-6 site showed no increase in transgene expression in hypoxia. Gel retardation assays revealed time-dependent, hypoxia-enhanced nuclear binding activity for the NF-IL-6 site in nuclear extracts of the heart, lung, and kidney but not in the liver; the hypoxia-enhanced band disappeared on addition of antibody to C/EBPbeta-NF-IL-6. Consistent with the specificity of hypoxia-mediated activation of C/EBPbeta-NF-IL-6, gel retardation assays showed no change in the intensity of the hypoxia-enhanced gel shift band in the presence of excess unlabeled oligonucleotide probes or antibodies related to other transcription factors, including NFkappaB, AP1, cAMP response element-binding protein, SP1, and hypoxia-inducible factor 1. These data indicate that the transcription factor NF-IL-6 is sensitive to environmental oxygen deprivation, and the tissue-specific pattern of gene expression suggests that local mechanisms have an important regulatory effect.
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- 1997
24. Induction of interleukin 6 (IL-6) by hypoxia in vascular cells. Central role of the binding site for nuclear factor-IL-6.
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Yan, S F, Tritto, I, Pinsky, D, Liao, H, Huang, J, Fuller, G, Brett, J, May, L, and Stern, D
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The pathologic picture in ischemic tissue injury shares features with the inflammatory response, including production of proinflammatory cytokines. Hypoxia-mediated induction of interleukin-6 (IL-6), a cytokine with anti-inflammatory properties, could set in motion mechanisms limiting inflammation in ischemia. Exposure of cultured endothelial cells (ECs) to H (pO2 approximately 12-16 torr) increased transcription of IL-6, elevated levels of IL-6 mRNA, and induced elaboration of IL-6 antigen in a time-dependent manner. Exposure of mice to hypoxia increased IL-6 transcripts in the lung, and immunostaining revealed a striking increase in IL-6 antigen in pulmonary vasculature. Transfection of ECs with deletion chimeric IL-6 promoter-chloramphenicol acetyl-transferase (CAT) constructs showed hypoxia-mediated 9-11-fold induction with -1200/+13, -596/+13, and -225/+13 but no induction with -111/+13. Electrophoretic mobility shift assays (EMSAs) using -225/-111 as the labeled probe demonstrated enhanced binding activity in nuclear extracts of hypoxic ECs and lung; the appearance of the gel shift band was prevented by excess unlabeled probe (-225/-111), and hypoxia-mediated enhancement of the band was blocked by a probe corresponding to the nuclear factor (NF)-IL-6 site (-158/-145). The hypoxia-enhanced band on EMSA displayed a supershift with antibody to CCAAT-enhancer-binding protein beta (C/EBP-beta), but antibody to C/EBP-alpha or -delta was without effect. Transfection of ECs with a construct comprising thymidine kinase promoter, -225/-111 in either the 5' to 3' to 5' orientation, and the reporter CAT showed this region to be an enhancer (approximately 8-fold) under hypoxia. EMSA with the NF-IL-6 probe revealed a prominent induction of binding activity with nuclear extracts from hypoxic ECs and whole lung. Constructs with -158/-145 and the CAT reporter gene showed induction when transfected into hypoxic ECs, whereas a similar construct with the NF-IL-6 motif mutationally inactivated failed to display hypoxia-induced expression. Furthermore, the tumor necrosis factor (TNF) gene, whose product contributes to ischemic pathology and contains a putative regulatory NF-IL-6 site, demonstrated enhanced binding activity for its NF-IL-6 motif and induction of TNF mRNA based on analysis of hypoxic lung. These data indicate that hypoxia induces expression of IL-6, most likely a result of hypoxic activation at the NF-IL-6 site, and suggest that other genes with regulatory NF-IL-6 sites may also be induced by a similar mechanism.
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- 1995
25. On the direction of hydrolysis of some pyrimidine-5-carboxylic acid esters
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Yan, S. F., Alexander Yu. Ivanov, Dar In, D. V., Lobanov, P. S., and Potekhin, A. A.
26. Glycation and diabetes: The RAGE connection
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Hudson, B. I., Hofmann, M. A., Bucciarelli, L., Wendt, T., Bernhard Moser, Lu, Y., Qu, W., Stern, D. M., D Agati, V., Yan, S. D., Yan, S. F., Grant, P. J., and Schmidt, A. M.
27. [Determination of lutein and zeaxanthin in serum by high performance liquid chromatography]
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Huang, Y. M., Yan, S. F., Ma, L., Zhiyong Zou, Xu, X. R., Xiao, X., Wang, X., Huang, F. F., and Lin, X. M.
28. [Serotype distribution and antimicrobial resistance of Salmonella isolates from retail chicken carcasses in six provinces of China].
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Hu YJ, He YY, Wang YR, Liu C, Wang MM, Gan X, Wang W, Yan SF, Bai Y, Peng ZX, Li FQ, and Xu J
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- Animals, Anti-Bacterial Agents pharmacology, Cefotaxime pharmacology, China, Ciprofloxacin pharmacology, Drug Resistance, Bacterial, Meat microbiology, Microbial Sensitivity Tests, Salmonella drug effects, Salmonella isolation & purification, Serogroup, Chickens microbiology, Drug Resistance, Multiple, Bacterial, Salmonella pathogenicity
- Abstract
Objective: To obtain the serotype diversity and antimicrobial resistance of Salmonella isolates recovered from retail chicken carcasses for sale in six regions of China. Methods: From August 2010 to March 2012, each month 20 retail chicken carcasses including freshly slaughtered, chilled and frozen samples were collected from supermarkets and farmer's markets in 7 monitoring sites in Beijing, Jilin province, Inner Mongolia Autonomous, Shanxi province, Jiangsu province and Guangdong province, respectively. Samples were routinely collected for 12 months for each site. 1 680 chicken carcasses were collected in total and 2 629 Salmonella strains were isolated by PCR and biochemical method. Luminex xMAP method and classical slide agglutination method were carried out to determine isolates' serotypes. Minimal inhibitory concentrations (MICs) of 10 classes of antimicrobials including 14 agents were determined using broth micro-dilution method. Mocular methods were used to determine antimicrobial resistance genes of CIP-CTX-CT co-resistant isolates. Results: In all, 2 629 Salmonella isolates, there were 17 seorgroups and 58 serotypes, B and D1 were the dominant serogroups with rates of 34.7% ( n= 913) and 31.0% ( n= 815), Enteritidis (30.8%, n= 810), Indiana (17.6%, n= 463), Infantis (10.6%, n= 278) were the top three serovars. We found 224 CIP-CTX co-resistant S . Indiana containing 3 colistin resistant strains, one of them carrying mcr -1 gene and being ESBLs positive, which demonstrated a nine multi drug resistance against 11 antimicrobials tested. Conclusion: These data began to describe the complicated serovar diversity and heavy antimicrobial resistance of Salmonella isolates recovered from retail chicken carcasses in six regions of China. The findings highlight the emergence of ciprofloxacin and cefotaxime co-resistant S . Indiana and also a mcr -1 positive S . Indiana with heavy multi drug resistance.
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- 2018
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29. [Antimicrobial susceptibility and drug-resistance genes of Yersinia spp. of retailed poultry in 4 provinces of China].
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Peng ZX, Zou MY, Xu J, Guan WY, Li Y, Liu DR, Zhang SS, Hao Q, Yan SF, Wang W, Yu DM, and Li FQ
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- Ampicillin, Animals, Anti-Infective Agents, China, Microbial Sensitivity Tests, Sulbactam, Yersinia drug effects, Yersinia isolation & purification, Yersinia Infections, Yersinia enterocolitica drug effects, Yersinia enterocolitica isolation & purification, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial, Poultry microbiology, Yersinia pathogenicity, Yersinia enterocolitica pathogenicity
- Abstract
Objective: To monitor the antimicrobial resistance and drug-resistance genes of Yersinia enterocolitis , Y. intermedia and Y. frederiksenii recovered from retailed fresh poultry of 4 provinces of China. Methods: The susceptibility of 25 isolated Yersinia spp. to 14 classes and 25 kinds of antibiotics was determined by broth microdilution method according to CLSI (Clinical and Laboratory Standards Institute). The antibiotic resistance genes were predicted with antibiotic resistance genes database (ARDB) using whole genome sequences of Yersinia spp. Results: In all 22 Y. enterocolitis tested, 63.7% (14 isolates), 22.8% (5 isolates), 4.6% and 4.6% of 1 isolates exhibited the resistance to cefoxitin, ampicillin-sulbactam, nitrofurantoin and trimethoprim-sulfamethoxazole, respectively. All the 25 isolates were multi-drug resistant to more than 3 antibiotics, while 64.0% of isolates were resistant to more than 4 antibiotics. A few Y. enterocolitis isolates of this study were intermediate to ceftriaxone and ciprofloxacin. Most Yersinia spp. isolates contained antibiotic resistance genes mdtG, ksgA, bacA, blaA, rosAB and acrB , and 5 isolates recovered from fresh chicken also contained dfrA 1, catB 2 and ant 3 ia . Conclusion: The multi-drug resistant Yersinia spp. isolated from retailed fresh poultry is very serious in the 4 provinces of China, and their contained many kinds of drug-resistance genes.
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- 2018
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30. [Molecular typing characterization of food-borne methicillin-resistant Staphylococcus aureus in China].
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Bai Y, Wang W, Yan L, Yang SR, Yan SF, Dong YP, Zhao BC, Zhao YY, Xu J, Hu YJ, and Li FQ
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- Animals, Anti-Bacterial Agents, China epidemiology, Electrophoresis, Gel, Pulsed-Field, Humans, Methicillin, Microbial Sensitivity Tests, Prevalence, Red Meat, Swine, Foodborne Diseases epidemiology, Foodborne Diseases microbiology, Methicillin-Resistant Staphylococcus aureus enzymology, Molecular Epidemiology, Multilocus Sequence Typing, Staphylococcal Infections
- Abstract
Objective: To analyses the antimicrobial resistance and molecular characterization of 21 MRSA isolates cultured from retail foods from different provinces in China, and evaluate the molecular typing methods. Methods: Twenty-one MRSA isolates were obtained from national foodborne pathogen surveillance network in 2012 (Chinese salad, n= 3; milk, n= 1; cake, n= 2; rice, n= 1; cold noodle, n= 1; spiced beef, n= 1; dumpling, n= 1; packed meal, n= 1; salad, n= 1; raw pork, n= 9). The antimicrobial resistance of 21 strains to 12 antimicrobial agents was tested by broth dilution method. Polymerase chain reaction (PCR) and DNA sequencing were performed to obtain the genetic types of MLST (ST) and spa typing. The clonal complex (CC) was assigned by eBURST soft and the MLVA type (MT) and MLVA complex (MC) were identified via the database of the MLVA website (http://www.mlva.net). Sma I pulsed-field gel electrophoresis ( Sma Ⅰ-PFGE) was also carried out to obtain the PFGE patterns of 21 strains. The genetic diversity and discriminatory power of typing were calculated by the Simpson's index of diversity (diversity index, DI) to find out the best genotyping method for MRSA. Results: All MRSA isolates showed multi-drug resistance(MDR), and were resistant to oxacillin, benzylpenicillin, clindamycin and erythromycin, and 71.4% (15/21), 47.6% (10/21), 42.9% (9/21) and 28.6% (6/21) of the MRSA isolates were resistant to tetracycline, ciprofloxacin, trimethoprim/sulfamethoxazole and gentamicin, respectively. Moreover, one strain was found to be resistant to all three antimicrobials of levofloxacin, moxifloxacin and rifampicin. Great diversity was found in these food-associated MRSA (6 STs, 7 spa types, and 9 MTs). PFGE patterns were more diverse than those of other three molecular typing methods (19 pulse types). The index of diversity (DI) of PFGE, MLVA, spa typing and MLST was 0.99, 0.80, 0.73, and 0.61, respectively. Among the MRSA isolates, CC9-ST9-t899-MT929-MC2236 (PFGE Cluster Ⅴ) was the most prevalent clone, which were all cultured from raw pork (9 isolates). Besides, two MRSA were identified as CC59-ST338-t437-MT621-MC621 (PFGE Cluster Ⅳ). Different clone had their own resistance spectrum profiles. Conclusion: The food-borne MRSA isolates were all MDR in this study. Different clones had their own resistance spectrum profiles. MLVA represented a promising tool for molecular epidemiology tracing of MRSA in foodborne disease events.
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- 2018
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31. Mitochondrial Perturbation in Alzheimer's Disease and Diabetes.
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Akhter F, Chen D, Yan SF, and Yan SS
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- Amyloid beta-Peptides metabolism, Animals, Humans, Mitochondria metabolism, Neurons metabolism, Neurons pathology, Synapses pathology, Alzheimer Disease metabolism, Diabetes Mellitus metabolism, Mitochondria pathology
- Abstract
Mitochondria are well-known cellular organelles that play a vital role in cellular bioenergetics, heme biosynthesis, thermogenesis, calcium homeostasis, lipid catabolism, and other metabolic activities. Given the extensive role of mitochondria in cell function, mitochondrial dysfunction plays a part in many diseases, including diabetes and Alzheimer's disease (AD). In most cases, there is overwhelming evidence that impaired mitochondrial function is a causative factor in these diseases. Studying mitochondrial function in diseased cells vs healthy cells may reveal the modified mechanisms and molecular components involved in specific disease states. In this chapter, we provide a concise overview of the major recent findings on mitochondrial abnormalities and their link to synaptic dysfunction relevant to neurodegeneration and cognitive decline in AD and diabetes. Our increased understanding of the role of mitochondrial perturbation indicates that the development of specific small molecules targeting aberrant mitochondrial function could provide therapeutic benefits for the brain in combating aging-related dementia and neurodegenerative diseases by powering up brain energy and improving synaptic function and transmission., (© 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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32. Extinguishing Egr-1-dependent inflammatory and thrombotic cascades after lung transplantation.
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Okada M, Fujita T, Sakaguchi T, Olson KE, Collins T, Stern DM, Yan SF, and Pinsky DJ
- Subjects
- Animals, Blotting, Northern, Blotting, Western, DNA, Antisense pharmacology, DNA-Binding Proteins genetics, Early Growth Response Protein 1, Fibrin drug effects, Fibrin metabolism, Gene Expression, Gene Expression Regulation drug effects, Graft Survival drug effects, Graft Survival physiology, Interleukin-1 genetics, Plasminogen Activator Inhibitor 1 genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Signal Transduction, Thromboplastin genetics, Transcription Factors genetics, DNA-Binding Proteins physiology, Immediate-Early Proteins, Inflammation physiopathology, Lung Transplantation, Thrombosis physiopathology, Transcription Factors physiology
- Abstract
Hypoxic induction of the early growth response-1 (Egr-1) transcription factor initiates proinflammatory and procoagulant gene expression. Orthotopic/isogeneic rat lung transplantation triggers Egr-1 expression and nuclear DNA binding activity corresponding to Egr-1, which leads to increased expression of downstream target genes such as interleukin-1b, tissue factor, and plasminogen activator inhibitor-1. The devastating functional consequences of Egr-1 up-regulation in this setting are prevented by treating donor lungs with a phosphorothioate antisense oligodeoxyribonucleotide directed against the Egr-1 translation initiation site, which blocks expression of Egr-1 and its gene targets. Post-transplant graft leukostasis, inflammation, and thrombosis are consequently diminished, with marked improvement in graft function and recipient survival. Blocking expression of a proximal transcription factor, which activates deleterious inflammatory and coagulant effector mechanisms, is an effective molecular strategy to improve organ preservation.
- Published
- 2001
- Full Text
- View/download PDF
33. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses.
- Author
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Schmidt AM, Yan SD, Yan SF, and Stern DM
- Subjects
- Amyloidosis immunology, Amyloidosis metabolism, Animals, Diabetes Mellitus, Experimental immunology, Diabetes Mellitus, Experimental metabolism, Glycation End Products, Advanced metabolism, HMGB1 Protein metabolism, Humans, Membrane Proteins metabolism, Neoplasms immunology, Receptor for Advanced Glycation End Products, Receptors, Immunologic metabolism, Glycation End Products, Advanced immunology, Membrane Proteins immunology, Receptors, Immunologic immunology
- Published
- 2001
- Full Text
- View/download PDF
34. Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression.
- Author
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Guha M, O'Connell MA, Pawlinski R, Hollis A, McGovern P, Yan SF, Stern D, and Mackman N
- Subjects
- DNA-Binding Proteins genetics, Early Growth Response Protein 1, Enzyme Activation drug effects, Enzyme Inhibitors pharmacology, Flavonoids pharmacology, Humans, MAP Kinase Kinase 1, MAP Kinase Kinase 2, Mitogen-Activated Protein Kinase 1 antagonists & inhibitors, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Mitogen-Activated Protein Kinase Kinases metabolism, Mitogen-Activated Protein Kinases antagonists & inhibitors, Mitogen-Activated Protein Kinases metabolism, Monocytes enzymology, NF-kappa B metabolism, Phosphorylation drug effects, Protein Processing, Post-Translational drug effects, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein Serine-Threonine Kinases metabolism, Protein-Tyrosine Kinases antagonists & inhibitors, Protein-Tyrosine Kinases metabolism, Recombinant Fusion Proteins metabolism, Thromboplastin genetics, Transcription Factors genetics, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha pharmacology, ets-Domain Protein Elk-1, DNA-Binding Proteins biosynthesis, Gene Expression Regulation drug effects, Immediate-Early Proteins, Lipopolysaccharides pharmacology, MAP Kinase Signaling System drug effects, Monocytes drug effects, Proto-Oncogene Proteins metabolism, Thromboplastin biosynthesis, Transcription Factors biosynthesis, Tumor Necrosis Factor-alpha biosynthesis
- Abstract
Lipopolysaccharide (LPS) induces human monocytes to express many proinflammatory mediators, including the procoagulant molecule tissue factor (TF) and the cytokine tumor necrosis factor alpha (TNF-alpha). The TF and TNF-alpha genes are regulated by various transcription factors, including nuclear factor (NF)-kappaB/Rel proteins and Egr-1. In this study, the role of the MEK-ERK1/2 mitogen-activated protein kinase (MAPK) pathway in LPS induction of TF and TNF-alpha gene expression in human monocytic cells was investigated. The MAPK kinase (MEK)1 inhibitor PD98059 reduced LPS induction of TF and TNF-alpha expression in a dose-dependent manner. PD98059 did not affect LPS-induced nuclear translocation of NF-kappaB/Rel proteins and minimally affected LPS induction of kappaB-dependent transcription. In contrast, PD98059 and dominant-negative mutants of the Ras-Raf1-MEK-ERK (extacellular signal-regulated kinase) pathway strongly inhibited LPS induction of Egr-1 expression. In kinetic experiments LPS induction of Egr-1 expression preceded induction of TF expression. In addition, mutation of the Egr-1 sites in the TF and TNF-alpha promoters reduced expression of these proinflammatory genes. It was demonstrated that LPS induction of the Egr-1 promoter was mediated by 3 SRE sites, which bound an LPS-inducible complex containing serum response factor and Elk-1. LPS stimulation transiently induced phosphorylation of Elk-1 and increased the functional activity of a GAL4-Elk-1TA chimeric protein via the MEK-ERK1/2 pathway. The data indicate that LPS induction of Egr-1 gene expression is required for maximal induction of the TNF-alpha and TF genes in human monocytic cells.
- Published
- 2001
- Full Text
- View/download PDF
35. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice.
- Author
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Goova MT, Li J, Kislinger T, Qu W, Lu Y, Bucciarelli LG, Nowygrod S, Wolf BM, Caliste X, Yan SF, Stern DM, and Schmidt AM
- Subjects
- Animals, Becaplermin, Binding Sites, Cytokines biosynthesis, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 pathology, Endothelial Growth Factors metabolism, Gene Expression Regulation, Granuloma pathology, Granuloma physiopathology, Lymphokines metabolism, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 3 metabolism, Matrix Metalloproteinase 9 metabolism, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Models, Biological, Neovascularization, Physiologic, Platelet-Derived Growth Factor metabolism, Proto-Oncogene Proteins c-sis, Receptor for Advanced Glycation End Products, Receptors, Immunologic antagonists & inhibitors, Time Factors, Tumor Necrosis Factor-alpha biosynthesis, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Wound Healing genetics, Wounds and Injuries physiopathology, Diabetes Mellitus, Type 1 physiopathology, Glycation End Products, Advanced physiology, Receptors, Immunologic physiology, Receptors, Immunologic therapeutic use, Wound Healing physiology, Wounds and Injuries pathology
- Abstract
Receptor for advanced glycation end-products (RAGE), and two of its ligands, AGE and EN-RAGEs (members of the S100/calgranulin family of pro-inflammatory cytokines), display enhanced expression in slowly resolving full-thickness excisional wounds developed in genetically diabetic db+/db+ mice. We tested the concept that blockade of RAGE, using soluble(s) RAGE, the extracellular ligand-binding domain of the receptor, would enhance wound closure in these animals. Administration of sRAGE accelerated the development of appropriately limited inflammatory cell infiltration and activation in wound foci. In parallel with accelerated wound closure at later times, blockade of RAGE suppressed levels of cytokines; tumor necrosis factor-alpha; interleukin-6; and matrix metalloproteinases-2, -3, and -9. In addition, generation of thick, well-vascularized granulation tissue was enhanced, in parallel with increased levels of platelet-derived growth factor-B and vascular endothelial growth factor. These findings identify a central role for RAGE in disordered wound healing associated with diabetes, and suggest that blockade of this receptor might represent a targeted strategy to restore effective wound repair in this disorder.
- Published
- 2001
- Full Text
- View/download PDF
36. Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis.
- Author
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Fujita T, Toda K, Karimova A, Yan SF, Naka Y, Yet SF, and Pinsky DJ
- Subjects
- Animals, Base Sequence, Carbon Monoxide therapeutic use, Cell Line, DNA Primers, Female, Fibrinolysis, Heme Oxygenase (Decyclizing) genetics, Immunohistochemistry, Lipopolysaccharides administration & dosage, Lung blood supply, Male, Mice, Plasminogen Activator Inhibitor 1 biosynthesis, Carbon Monoxide administration & dosage, Reperfusion Injury prevention & control
- Abstract
Carbon monoxide (CO) can arrest cellular respiration, but paradoxically, it is synthesized endogenously by heme oxygenase type 1 (Ho-1) in response to ischemic stress. Ho-1-deficient (Hmox1-/-) mice exhibited lethal ischemic lung injury, but were rescued from death by inhaled CO. CO drove ischemic protection by activating soluble guanylate cyclase and thereby suppressed hypoxic induction of the gene encoding plasminogen activator inhibitor-1 (PAI-1) in mononuclear phagocytes, which reduced accrual of microvascular fibrin. CO-mediated ischemic protection observed in wild-type mice was lost in mice null for the gene encoding PAI-1 (Serpine1). These data establish a fundamental link between CO and prevention of ischemic injury based on the ability of CO to derepress the fibrinolytic axis. These data also point to a potential therapeutic use for inhaled CO.
- Published
- 2001
- Full Text
- View/download PDF
37. The biology of the receptor for advanced glycation end products and its ligands.
- Author
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Schmidt AM, Yan SD, Yan SF, and Stern DM
- Subjects
- Amyloidosis metabolism, Animals, Capillary Permeability drug effects, Cells, Cultured, Diabetes Mellitus, Experimental metabolism, Diabetic Neuropathies metabolism, Disease Models, Animal, Erythrocytes metabolism, Glycation End Products, Advanced chemistry, Humans, Ligands, Lung metabolism, Lysine chemistry, Membrane Proteins chemistry, Receptor for Advanced Glycation End Products, Receptors, Immunologic administration & dosage, Receptors, Immunologic chemistry, Serum Amyloid A Protein metabolism, Tumor Cells, Cultured, Endothelium, Vascular metabolism, Glycation End Products, Advanced metabolism, Lysine analogs & derivatives, Membrane Proteins metabolism, Receptors, Immunologic metabolism
- Abstract
Receptor for advanced glycation end products (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface molecules whose repertoire of ligands includes advanced glycation end products (AGEs), amyloid fibrils, amphoterins and S100/calgranulins. The overlapping distribution of these ligands and cells overexpressing RAGE results in sustained receptor expression which is magnified via the apparent capacity of ligands to upregulate the receptor. We hypothesize that RAGE-ligand interaction is a propagation factor in a range of chronic disorders, based on the enhanced accumulation of the ligands in diseased tissues. For example, increased levels of AGEs in diabetes and renal insufficiency, amyloid fibrils in Alzheimer's disease brain, amphoterin in tumors and S100/calgranulins at sites of inflammation have been identified. The engagement of RAGE by its ligands can be considered the 'first hit' in a two-stage model, in which the second phase of cellular perturbation is mediated by superimposed accumulation of modified lipoproteins (in atherosclerosis), invading bacterial pathogens, ischemic stress and other factors. Taken together, these 'two hits' eventuate in a cellular response with a propensity towards tissue destruction rather than resolution of the offending pathogenic stimulus. Experimental data are cited regarding this hypothesis, though further studies will be required, especially with selective low molecular weight inhibitors of RAGE and RAGE knockout mice, to obtain additional proof in support of our concept.
- Published
- 2000
- Full Text
- View/download PDF
38. Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress.
- Author
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Yan SF, Fujita T, Lu J, Okada K, Shan Zou Y, Mackman N, Pinsky DJ, and Stern DM
- Subjects
- Animals, Blood Coagulation Factors biosynthesis, Chemokines biosynthesis, DNA-Binding Proteins genetics, Early Growth Response Protein 1, Endothelial Growth Factors biosynthesis, Genes, Switch, Immediate-Early Proteins genetics, Immediate-Early Proteins metabolism, Intercellular Adhesion Molecule-1 biosynthesis, Lipopolysaccharides toxicity, Lung blood supply, Lymphokines biosynthesis, Mice, Mice, Mutant Strains, Transcription Factors genetics, Up-Regulation, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Zinc Fingers genetics, DNA-Binding Proteins metabolism, Lung pathology, Reperfusion Injury etiology, Transcription Factors metabolism
- Abstract
Activation of the zinc-finger transcription factor early growth response (Egr)-1, initially linked to developmental processes, is shown here to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Chemokine, adhesion receptor, procoagulant and permeability-related genes are coordinately upregulated by rapid ischemia-mediated activation of Egr-1. Deletion of the gene encoding Egr-1 strikingly diminished expression of these mediators of vascular injury in a murine model of lung ischemia/reperfusion, and enhanced animal survival and organ function. Rapid activation of Egr-1 in response to oxygen deprivation primes the vasculature for dysfunction manifest during reperfusion. These studies define a central and unifying role for Egr-1 activation in the pathogenesis of ischemic tissue damage.
- Published
- 2000
- Full Text
- View/download PDF
39. Expression of Egr-1 in late stage emphysema.
- Author
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Zhang W, Yan SD, Zhu A, Zou YS, Williams M, Godman GC, Thomashow BM, Ginsburg ME, Stern DM, and Yan SF
- Subjects
- Aged, Blotting, Northern, Cells, Cultured, DNA, Complementary metabolism, DNA-Binding Proteins genetics, Disease Progression, Early Growth Response Protein 1, Emphysema genetics, Emphysema pathology, Humans, Lung metabolism, Lung pathology, Middle Aged, RNA, Messenger metabolism, Transcription Factors genetics, DNA-Binding Proteins metabolism, Emphysema metabolism, Immediate-Early Proteins, Transcription Factors metabolism
- Abstract
The transcription factor early growth response (Egr)-1 is an immediate-early gene product rapidly and transiently expressed after acute tissue injury. In contrast, in this report we demonstrate that lung tissue from patients undergoing lung reduction surgery for advanced emphysema, without clinical or anatomical evidence of acute infection, displays a selective and apparently sustained increase in Egr-1 transcripts and antigen, compared with a broad survey of other genes, including the transcription factor Sp1, whose levels were not significantly altered. Enhanced Egr-1 expression was especially evident in smooth muscle cells of bronchial and vascular walls, in alveolar macrophages, and some vascular endothelium. Gel shift analysis with (32)P-labeled Egr probe showed a band with nuclear extracts from emphysematous lung which was supershifted with antibody to Egr-1. Egr-1 has the capacity to regulate genes relevant to the pathophysiology of emphysema, namely those related to extracellular matrix formation and remodeling, thrombogenesis, and those encoding cytokines/chemokines and growth factors. Thus, we propose that further analysis of Egr-1, which appears to be up-regulated in a sustained fashion in patients with late stage emphysema, may provide insights into the pathogenesis of this destructive pulmonary disease, as well as a new facet in the biology of Egr-1.
- Published
- 2000
- Full Text
- View/download PDF
40. Pulmonary expression of early growth response-1: biphasic time course and effect of oxygen concentration.
- Author
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Yan SF, Lu J, Xu L, Zou YS, Tongers J, Kisiel W, Mackman N, Pinsky DJ, and Stern DM
- Subjects
- Animals, Blotting, Northern, DNA-Binding Proteins genetics, Early Growth Response Protein 1, Female, Immunohistochemistry, Mice, Mice, Inbred C57BL, Osmolar Concentration, Oxygen metabolism, RNA, Messenger metabolism, Thromboplastin metabolism, Time Factors, Transcription Factors genetics, DNA-Binding Proteins metabolism, Hypoxia metabolism, Immediate-Early Proteins, Lung metabolism, Transcription Factors metabolism
- Abstract
Hypoxia induces complex adaptive responses. In this report, induction of early growth response-1 (Egr-1) transcripts in lungs of mice subjected to hypoxia is shown to be dose and time dependent. Within 30 min of hypoxia, Egr-1 transcripts were approximately 20-fold elevated in 6% oxygen, approximately 5.2-fold increased by 10% oxygen, and returned to the normoxic baseline by 12% oxygen. Time course studies up to 48 h showed a biphasic profile with an initial steep rise in Egr-1 transcripts after 0.5 h of hypoxia and a second elevation beginning after 20-24 h. Hypoxic induction of Egr-1 was paralleled by enhanced expression of the downstream target gene tissue factor. Egr-1 and tissue factor antigen were visualized in bronchial and vascular smooth muscle and in alveolar macrophages. Egr-1 has the capacity to modulate expression of genes involved in the remodeling of the extracellular matrix and properties of smooth muscle, thus possibly contributing to the pulmonary response to chronic hypoxia.
- Published
- 2000
- Full Text
- View/download PDF
41. Egr-1: is it always immediate and early?
- Author
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Yan SF, Pinsky DJ, Mackman N, and Stern DM
- Subjects
- Animals, Arteriosclerosis pathology, DNA-Binding Proteins genetics, Early Growth Response Protein 1, Endothelium, Vascular pathology, Humans, Ischemia pathology, Mice, Mice, Knockout, Platelet-Derived Growth Factor genetics, Thromboplastin metabolism, Transcription Factors genetics, Zinc Fingers, DNA-Binding Proteins metabolism, Immediate-Early Proteins metabolism, Transcription Factors metabolism
- Published
- 2000
- Full Text
- View/download PDF
42. A pathway leading to hypoxia-induced vascular fibrin deposition.
- Author
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Yan SF, Pinsky DJ, and Stern DM
- Subjects
- Animals, Humans, Hypoxia metabolism, Thromboplastin metabolism, Thrombosis blood, Thrombosis etiology, Blood Vessels pathology, Fibrin metabolism, Hypoxia pathology
- Abstract
Hypoxemia has long been associated with vascular fibrin formation leading to thrombosis. This review describes a pathway through which mononuclear phagocytes and vascular smooth muscle cells upregulate tissue factor under hypoxic conditions. Increased expression of tissue factor triggers events leading to vascular fibrin deposition, providing insight into a novel mechanism potentially underlying thrombosis in ischemic vasculature.
- Published
- 2000
- Full Text
- View/download PDF
43. Hypoxia/Hypoxemia-Induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis.
- Author
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Yan SF, Mackman N, Kisiel W, Stern DM, and Pinsky DJ
- Subjects
- Animals, Humans, Blood Coagulation, Hypoxia complications, Hypoxia physiopathology, Ischemia complications, Thrombosis etiology
- Abstract
Although oxygen deprivation has long been associated with triggering of the procoagulant pathway and venous thrombosis, blood hypoxemia and stasis by themselves do not lead to fibrin formation. A pathway is outlined through which diminished levels of oxygen activate the transcription factor early growth response-1 (Egr-1) leading to de novo transcription/translation of tissue factor in mononuclear phagocytes and smooth muscle cells, which eventuates in vascular fibrin deposition. The procoagulant response is magnified by concomitant suppression of fibrinolysis by hypoxia-mediated upregulation of plasminogen activator inhibitor-1. These data add a new facet to the biology of thrombosis associated with hypoxemia/stasis and imply that interference with mechanisms causing Egr-1 activation in response to oxygen deprivation might prevent vascular fibrin deposition occurring in ischemia without directly interfering with other pro/anticoagulant pathways.
- Published
- 1999
- Full Text
- View/download PDF
44. Tissue factor transcription driven by Egr-1 is a critical mechanism of murine pulmonary fibrin deposition in hypoxia.
- Author
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Yan SF, Zou YS, Gao Y, Zhai C, Mackman N, Lee SL, Milbrandt J, Pinsky D, Kisiel W, and Stern D
- Subjects
- Animals, DNA-Binding Proteins metabolism, Early Growth Response Protein 1, HeLa Cells, Humans, Leukocytes, Mononuclear metabolism, Mice, Mice, Knockout, Oxygen metabolism, Transcription Factors metabolism, DNA-Binding Proteins genetics, Fibrin metabolism, Hypoxia genetics, Hypoxia metabolism, Immediate-Early Proteins, Lung metabolism, Lung physiopathology, Thromboplastin genetics, Thromboplastin metabolism, Transcription Factors genetics, Transcription, Genetic
- Abstract
Local hypoxemia and stasis trigger thrombosis. We have demonstrated previously that in a murine model of normobaric hypoxia pulmonary fibrin deposition is a result of expression of tissue factor, especially in oxygen-deprived mononuclear phagocytes (MPs). We now show that transcription factor early-growth-response gene product (Egr-1) is rapidly activated in hypoxia, both in vitro and in vivo, and is responsible for transcription and expression of tissue factor in hypoxic lung. MPs and HeLa cells subjected to hypoxia (pO2 approximately 13 torr) had increased levels of tissue factor transcripts (approximately 18-fold) and an increased rate of transcription (approximately 15-fold), based on nuclear run-on analysis. Gel-shift analysis of nuclear extracts from hypoxic MPs and HeLa cells demonstrated increased DNA-binding activity at the serum response region (SRR; -111/+14 bp) of the tissue factor promoter at Egr-1 motifs. Using 32P-labeled Egr consensus oligonucleotide, we observed induction of DNA-binding activity in nuclear extracts from hypoxic lung and HeLa cells because of activation of Egr-1, by means of supershift analysis. Transient transfection of HeLa cells with chimeric plasmids containing wild-type or mutant SRR from the tissue factor promoter showed that intact Sp1 sites are necessary for basal promoter activity, whereas the integrity of Egr-1 sites was required for hypoxia-enhanced expression. A central role for Egr-1 in hypoxia-mediated tissue factor expression was confirmed by experiments with homozygous Egr-1 null mice; wild-type mice subjected to oxygen deprivation expressed tissue factor and showed fibrin deposition, but hypoxic homozygous Egr-1 null mice displayed neither tissue factor nor fibrin. These data delineate a novel biology for hypoxia-induced fibrin deposition, in which oxygen deprivation-induced activation of Egr-1, resulting in expression of tissue factor, has an unexpected and central role.
- Published
- 1998
- Full Text
- View/download PDF
45. Hypoxia-mediated modulation of vascular function--implications for organ preservation and thrombogenesis: Roger S. Mitchell lecture.
- Author
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Yan SF, Lawson CA, Stern DM, and Pinsky DJ
- Subjects
- Animals, Cyclic AMP physiology, Fibrin metabolism, Interleukin-6 metabolism, Leukostasis physiopathology, Mice, Myocardial Reperfusion Injury physiopathology, Myocardium cytology, P-Selectin physiology, Rats, Second Messenger Systems, Translocation, Genetic, Heart physiology, Heart Transplantation physiology, Hypoxia physiopathology, Organ Preservation
- Published
- 1998
- Full Text
- View/download PDF
46. Amyloid-beta peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease.
- Author
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Du Yan S, Zhu H, Fu J, Yan SF, Roher A, Tourtellotte WW, Rajavashisth T, Chen X, Godman GC, Stern D, and Schmidt AM
- Subjects
- Alzheimer Disease cerebrospinal fluid, Animals, Cells, Cultured, Humans, Inflammation, Macrophage Colony-Stimulating Factor cerebrospinal fluid, Mice, NF-kappa B metabolism, Neuroblastoma, Neurons drug effects, Oxidative Stress, Receptor for Advanced Glycation End Products, Recombinant Fusion Proteins biosynthesis, Reference Values, Transfection, Tumor Cells, Cultured, Vascular Cell Adhesion Molecule-1 biosynthesis, Alzheimer Disease physiopathology, Amyloid beta-Peptides metabolism, Amyloid beta-Peptides pharmacology, Glycation End Products, Advanced metabolism, Macrophage Colony-Stimulating Factor biosynthesis, Neurons physiology, Receptors, Immunologic physiology
- Abstract
In Alzheimer disease (AD), neurons are thought to be subjected to the deleterious cytotoxic effects of activated microglia. We demonstrate that binding of amyloid-beta peptide (Abeta) to neuronal Receptor for Advanced Glycation Endproduct (RAGE), a cell surface receptor for Abeta, induces macrophage-colony stimulating factor (M-CSF) by an oxidant sensitive, nuclear factor kappaB-dependent pathway. AD brain shows increased neuronal expression of M-CSF in proximity to Abeta deposits, and in cerebrospinal fluid from AD patients there was approximately 5-fold increased M-CSF antigen (P < 0.01), compared with age-matched controls. M-CSF released by Abeta-stimulated neurons interacts with its cognate receptor, c-fms, on microglia, thereby triggering chemotaxis, cell proliferation, increased expression of the macrophage scavenger receptor and apolipoprotein E, and enhanced survival of microglia exposed to Abeta, consistent with pathologic findings in AD. These data delineate an inflammatory pathway triggered by engagement of Abeta on neuronal RAGE. We suggest that M-CSF, thus generated, contributes to the pathogenesis of AD, and that M-CSF in cerebrospinal fluid might provide a means for monitoring neuronal perturbation at an early stage in AD.
- Published
- 1997
- Full Text
- View/download PDF
47. Hypoxia-induced modulation of endothelial cell properties: regulation of barrier function and expression of interleukin-6.
- Author
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Yan SF, Ogawa S, Stern DM, and Pinsky DJ
- Subjects
- Animals, CCAAT-Enhancer-Binding Protein-delta, Capillary Permeability, Cyclic AMP metabolism, DNA-Binding Proteins metabolism, Gene Expression, Humans, Interleukin-6 genetics, Nuclear Proteins metabolism, CCAAT-Enhancer-Binding Proteins, Endothelium, Vascular physiopathology, Hypoxia physiopathology, Interleukin-6 biosynthesis, Transcription Factors
- Abstract
The endothelial cell response to hypoxia involves a range of adaptive mechanisms that reflect an active response of the cell's biosynthetic and metabolic apparatus. Hypoxia-mediated suppression of endothelial barrier function, resulting in increased vascular leakage, is likely to contribute to pulmonary and cerebral edema associated with high altitude and is closely associated with a fall in intracellular cyclic AMP levels. Buttressing of this second messenger pathway in the endothelium using membrane permeant cyclic AMP analogs prevents increased vascular leakage due to hypoxia. Application of this principle to organ preservation has shown that supplementation with cyclic AMP analogs or inhibition of endogenous cAMP metabolism enables extension of the time a harvested organ can remain extracorporeally, after which transplantation is successful. The underlying mechanism through which cyclic AMP exerts its effects appears to be maintenance of vascular homeostasis in the graft. A distinct adaptive mechanism triggered in the endothelium by hypoxia is expression of the cytokine interleukin-6 (IL-6) by a novel mechanism involving transcription driven by the nuclear factor IL-6 (NF-IL-6) DNA binding site in the promoter. IL-6 may exert protective effects on vascular function, thereby limiting vascular injury by a different mechanism than those recruited by elevated cAMP levels. These studies provide insights into tow independent mechanisms through which endothelium responds to oxygen deprivation, and suggest possible new approaches to attentuate vascular injury associated with ischemia.
- Published
- 1997
- Full Text
- View/download PDF
48. Hypoxia and modification of the endothelium: implications for regulation of vascular homeostatic properties.
- Author
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Pinsky DJ, Yan SF, Lawson C, Naka Y, Chen JX, Connolly ES Jr, and Stern DM
- Subjects
- Animals, Base Sequence, Cell Hypoxia, Cytokines biosynthesis, Endothelium, Vascular physiopathology, Homeostasis, Humans, Molecular Sequence Data, Organ Preservation methods, Endothelium, Vascular metabolism, Oxygen metabolism
- Abstract
Hypoxia is a common denominator of ischemic microenvironments. Endothelium subjected to oxygen deprivation maintains cell viability and basic biosynthetic mechanisms, but displays multiple changes in properties relevant to vascular homeostasis, including suppression of the anticoagulant cofactor thrombomodulin, decreased barrier function, and generation of proinflammatory cytokines. Diminished intracellular cAMP during the period of hypoxia and lowered nitric oxide/cGMP in the subsequent reperfusion period are proposed as fundamental mechanisms driving vascular dysfunction impacting on coagulation, permeability, vasomotor tone and leukocyte adhesivity. The period of organ preservation for transplantation, recognized to be associated with hypoxia, primes mechanisms leading to subsequent vascular dysfunction which can be ameliorated by buttressing cAMP and nitric oxide/cGMP intra- and intercellular second messenger systems. A mechanism likely to contribute to hypoxia-mediated generation of cytokines, such as interleukin 6, is activation of the transcription factor NF-IL-6, which occurs in oxygen deprivation. These data indicate that study of cellular mechanisms of endothelial perturbation in hypoxia is likely to provide insights ultimately applicable to ischemia-induced vascular damage.
- Published
- 1995
- Full Text
- View/download PDF
49. Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide.
- Author
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Yan SD, Yan SF, Chen X, Fu J, Chen M, Kuppusamy P, Smith MA, Perry G, Godman GC, and Nawroth P
- Subjects
- Alzheimer Disease genetics, Amyloid beta-Protein Precursor genetics, Animals, Animals, Newborn, Cerebral Cortex cytology, Cerebral Cortex metabolism, Cytochrome c Group metabolism, Feedback, Glycosylation, Humans, Interleukin-6 genetics, Neuroblastoma pathology, Rats, Superoxide Dismutase metabolism, Temporal Lobe metabolism, Transfection, Tumor Cells, Cultured, tau Proteins chemistry, Alzheimer Disease metabolism, Amyloid beta-Protein Precursor biosynthesis, Gene Expression Regulation, Interleukin-6 biosynthesis, Oxidative Stress, Protein Processing, Post-Translational, Reactive Oxygen Species metabolism, tau Proteins metabolism
- Abstract
Paired helical filament (PHF) tau is the principal component of neurofibrillary tangles, a characteristic feature of the neurodegenerative pathology in Alzheimer's disease (AD). Post-translational modification of tau, especially phosphorylation, has been considered a major factor in aggregation and diminished microtubule interactions of PHF-tau. Recently, it has been recognized that PHF-tau is also subject to non-enzymatic glycation, with formation of advanced glycation end products (AGEs). We now show that as a consequence of glycation, PHF-tau from AD and AGE-tau generate oxygen free radicals, thereby activating transcription via nuclear factor-kappa B, increasing amyloid beta-protein precursor and release of approximately 4 kD amyloid beta-peptides. These data provide insight into how PHF-tau disturbs neuronal function, and add to a growing body of evidence that oxidant stress contributes to the pathogenesis of AD.
- Published
- 1995
- Full Text
- View/download PDF
50. [Studies on enterotoxin plasmids. III. Analysis of plasmids in resistant and enterotoxigenic Escherichia coli by gel electrophoresis].
- Author
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Dai GS, Zhan LQ, Yan SF, Chen JZ, Lin CS, Guo WZ, and Zeng NM
- Subjects
- Conjugation, Genetic, Electrophoresis, Enterotoxins genetics, Escherichia coli genetics, Plasmids
- Published
- 1985
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