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Search Results: 1 - 10 of 153388 matches for " Gary H Posner "
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Recombinant luciferase-expressing human cytomegalovirus (CMV) for evaluation of CMV inhibitors
Ran He, Gordon Sandford, Gary S Hayward, William H Burns, Gary H Posner, Michael Forman, Ravit Arav-Boger
Virology Journal , 2011, DOI: 10.1186/1743-422x-8-40
Abstract: Infection with Cytomegalovirus (CMV) continues to be a major threat in organ transplant recipients and congenitally-infected children [1,2]. Although existing systemic therapies are effective in suppressing virus replication, serious side effects and the emergence of resistant viral strains pose significant treatment dilemmas [3]. The need to identify and develop new anti-CMV compounds coincides with the advancement of rapid, sensitive, and high-throughput methods for screening of lead compounds. While the plaque reduction assay remains the gold-standard for screening of anti-viral compounds, new techniques based on recombinant DNA technology and highly sensitive molecular assays have recently been suggested as alternatives [4-6]. Real-time PCR, the standard of care in the management of CMV disease in high- risk patient populations, may also provide a sensitive tool for drug screening [7-12]In earlier studies, a series of chloramphenicol acetyl transferase (CAT) recombinants expressing CAT under the control of UL54 (DNA polymerase, POL) or UL99 (pp28) promoters were constructed. The expression of CAT in infected cells highly mimicked the expression pattern of the endogenous UL54 and UL99 [4,13]. Thus, these two gene promoters were selected to construct luciferase-recombinant CMV for quatification of CMV replication in a rapid and reproducuble way. We report on the evaluation of two luciferase recombinant viruses (pp28 and POL) and the correlation of the pp28-luciferase system with plaque reduction and real-time PCR in evaluation of CMV inhibition by anti-CMV compounds.Recombinant CMV based on the laboratory-adapted strain, Towne, was constructed by homologous recombination in transfected-infected cells. A β- galactosidase (β -gal)-expressing Towne virus was first constructed using an intergenic insertion site between US9 and US10. Prior studies in which a β-glucuronidase expression cassette was inserted in this intergenic region of the laboratory-adapted AD169 virus
Malaria-Infected Mice Are Cured by a Single Low Dose of a New Silylamide Trioxane Plus Mefloquine
Lauren E. Woodard,Bryan T. Mott,Vandana Singhal,Nirbhay Kumar,Theresa A. Shapiro,Gary H. Posner
Pharmaceuticals , 2009, DOI: 10.3390/ph2030228
Abstract: Three thermally and hydrolytically stable silylamide trioxanes have been prepared from the natural trioxane artemisinin in only five simple chemical steps and in at least 56% overall yield. Two of these new chemical entities completely cured malariainfected mice at a single oral dose of only 8 mg/kg combined with 24 mg/kg of mefloquine hydrochloride. The high efficacy of this ACT chemotherapy is considerably better than the efficacy using the popular trioxane drug artemether plus mefloquine hydrochloride.
Inhibition of P-glycoprotein by two artemisinin derivatives
Babette Steglich,Anne Mahringer,Ying Li,Gary H. Posner,Gert Fricker,Thomas Efferth
Natural Products and Bioprospecting , 2012, DOI: 10.1007/s13659-012-0006-3
Abstract: P-Glycoprotein/MDR1 represents an important component of the blood brain barrier and contributes to multidrug resistance. We investigated two derivatives of the anti-malarial artemisinin, SM616 and GHP-AJM-3/23, concerning their ability to interact with P-glycoprotein. The ability of the two compounds to inhibit P-glycoprotein (P-gp) activity was examined in sensitive CCRF-CEM and P-gp over-expressing and multidrug-resistant CEM/ADR5000 cells as well as in porcine brain capillary endothelial cells (PBCEC) by means of calcein-AM assays. Verapamil as well-known P-gp inhibitor was used as control drug. CEM/ADR5000 cells exhibited cross-resistance to GHP-AJM-3/23, but slight collateral sensitivity to SM616. Furthermore, SM616 inhibited calcein efflux both in CEM/ADR5000 and PBCEC, whereas GHP-AJM-3/23 did only increase calcein fluorescence in PBCEC, but not CEM/ADR5000. This may be explained by the fact that CEM/ADR5000 only express P-gp but not other ATP-binding cassette transporters, whereas PBCEC are known to express several ABC transporters and calcein is transported by more than one ABC transporter. Hence, SM616 may be the more specific P-gp inhibitor. In conclusion, the collateral sensitivity of SM616 as well as the inhibition of calcein efflux in both CEM/ADR5000 cells and PBCEC indicate that this compound may be a promising P-gp inhibitor to treat cancer therapy and to overcome the blood brain barrier.
An Artemisinin-Derived Dimer Has Highly Potent Anti-Cytomegalovirus (CMV) and Anti-Cancer Activities
Ran He, Bryan T. Mott, Andrew S. Rosenthal, Douglas T. Genna, Gary H. Posner, Ravit Arav-Boger
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024334
Abstract: We recently reported that two artemisinin-derived dimers (dimer primary alcohol 606 and dimer sulfone 4-carbamate 832-4) are significantly more potent in inhibiting human cytomegalovirus (CMV) replication than artemisinin-derived monomers. In our continued evaluation of the activities of artemisinins in CMV inhibition, twelve artemisinin-derived dimers and five artemisinin-derived monomers were used. Dimers as a group were found to be potent inhibitors of CMV replication. Comparison of CMV inhibition and the slope parameter of dimers and monomers suggest that dimers are distinct in their anti-CMV activities. A deoxy dimer (574), lacking the endoperoxide bridge, did not have any effect on CMV replication, suggesting a role for the endoperoxide bridge in CMV inhibition. Differences in anti-CMV activity were observed among three structural analogs of dimer sulfone 4-carbamate 832-4 indicating that the exact placement and oxidation state of the sulfur atom may contribute to its anti-CMV activity. Of all tested dimers, artemisinin-derived diphenyl phosphate dimer 838 proved to be the most potent inhibitor of CMV replication, with a selectivity index of approximately 1500, compared to our previously reported dimer sulfone 4-carbamate 832-4 with a selectivity index of about 900. Diphenyl phosphate dimer 838 was highly active against a Ganciclovir-resistant CMV strain and was also the most active dimer in inhibition of cancer cell growth. Thus, diphenyl phosphate dimer 838 may represent a lead for development of a highly potent and safe anti-CMV compound.
Monetary and Fiscal Policies for a Finite Planet
Joshua Farley,Matthew Burke,Gary Flomenhoft,Brian Kelly,D. Forrest Murray,Stephen Posner,Matthew Putnam,Adam Scanlan,Aaron Witham
Sustainability , 2013, DOI: 10.3390/su5062802
Abstract: Current macroeconomic policy promotes continuous economic growth. Unemployment, poverty and debt are associated with insufficient growth. Economic activity depends upon the transformation of natural materials, ultimately returning to the environment as waste. Current levels of economic throughput exceed the planet’s carrying capacity. As a result of poorly constructed economic institutions, society faces the unacceptable choice between ecological catastrophe and human misery. A transition to a steady-state economy is required, characterized by a rate of throughput compatible with planetary boundaries. This paper contributes to the development of a steady-state economy by addressing US monetary and fiscal policies. A steady-state monetary policy would support counter-cyclical, debt-free vertical money creation through the public sector, in ways that contribute to sustainable well-being. The implication for a steady-state fiscal policy is that any lending or spending requires a careful balance of recovery of money, not as a means of revenue, but as an economic imperative to meet monetary policy goals. A steady-state fiscal policy would prioritize targeted public goods investments, taxation of ecological “bads” and economic rent and implementation of progressive tax structures. Institutional innovations are considered, including common asset trusts, to regulate throughput, and a public monetary trust, to strictly regulate money supply.
Tagungsbericht: The Rhetoric of Gestures, Centro Internazionale di Semiotica e di Linguistica, Urbino, Italien, Juli 2000 Conference Report: The Rhetoric of Gestures, Centro Internazionale di Semiotica e di Linguistica, Urbino, Italy Nota sobre la conferencia: The Rhetoric of Gestures [La retórica de los gestos], Centro Internazionale di Semiotica e di Linguistica, Urbino, Italia
Roland Posner
Forum : Qualitative Social Research , 2000,
Abstract: URN: urn:nbn:de:0114-fqs0003509 URN: urn:nbn:de:0114-fqs0003509 URN: urn:nbn:de:0114-fqs0003509
Cómo me convertí en keynesiano
Richard Posner
Revista de Economía Institucional , 2010,
Founding Editorial: Higher Level Brain Function
Michael Posner
The Scientific World Journal , 2002, DOI: 10.1100/tsw.2002.165
Founding Editorial: Cognition
Michael Posner
The Scientific World Journal , 2002, DOI: 10.1100/tsw.2002.164
The Response of Creatine Kinase Specific Activity in Rat Pituitary to Estrogenic Compounds and Vitamin D Less-Calcemic Analogs
D. Somjen,N. Mirsky,S. Tamir,J. Vaya,G. H. Posner,A. M. Kaye
International Journal of Cell Biology , 2009, DOI: 10.1155/2009/273651
Abstract: We examined the response of rat female pituitary at different metabolic stages to treatments with estrogenic compounds and vitamin D analogs. Immature or ovariectomized (Ovx) female rats responded by increased creatine kinase specific activity (CK) to estradiol-17 (E2), genistein (G), daidzein (D), biochainin A (BA), quecertin (Qu), carboxy- G (cG), carboxy- BA (cBA), and raloxifene (Ral). The response was inhibited when Ral was injected together with the estrogens. CK was increased when hormones were injected daily into Ovx rats for 4 different time periods. Pretreatment with the less-calcemic vitamin D analogs JK 1624 F2-2 (JKF) or QW 1624 F2-2 (QW) followed by estrogenic injection resulted in increased response and sensitivity to E2 and loss of inhibition of E2 by Ral. CK was also increased by feeding with E2 or licorice or its components dose- and time- dependent in immature or Ovxrats. Diabetic female rats did not respond to increased doses of E2. In conclusion, rat female pituitary is estrogens-responsive organ, suggesting to considerits response for HRT in postmenopausal women for both beneficial and hazardous aspects.
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