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Articles 1 - 8 of 8
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Caspase 3-Dependent Cell Death Of Neurons Contributes To The Pathogenesis Of West Nile Virus Encephalitis, M. A. Samuel, John D. Morrey, M. S. Diamond
Caspase 3-Dependent Cell Death Of Neurons Contributes To The Pathogenesis Of West Nile Virus Encephalitis, M. A. Samuel, John D. Morrey, M. S. Diamond
John D. Morrey
West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that has become a significant global cause of viral encephalitis. To examine the mechanisms of WNV-induced neuronal death and the importance of apoptosis in pathogenesis, we evaluated the role of a key apoptotic regulator, caspase 3. WNV infection induced caspase 3 activation and apoptosis in the brains of wild-type mice. Notably, congenic caspase 3–/– mice were more resistant to lethal WNV infection, although there were no significant differences in the tissue viral burdens or the kinetics of viral spread. Instead, decreased neuronal death was observed in the cerebral cortices, brain stems, …
Defining Limits Of Treatment With Humanized Neutralizing Monoclonal Antibody For West Nile Virus Neurological Infection In A Hamster Model, John D. Morrey, V. Siddharthan, Aaron L. Olsen, H. Wang, Justin G. Julander, Jeffery O. Hall, H. Li, J. L. Nordstrom, S. Koenig, S. Johnson, M. S. Diamond
Defining Limits Of Treatment With Humanized Neutralizing Monoclonal Antibody For West Nile Virus Neurological Infection In A Hamster Model, John D. Morrey, V. Siddharthan, Aaron L. Olsen, H. Wang, Justin G. Julander, Jeffery O. Hall, H. Li, J. L. Nordstrom, S. Koenig, S. Johnson, M. S. Diamond
John D. Morrey
A potent anti-West Nile virus (anti-WNV)-neutralizing humanized monoclonal antibody, hE16, was previously shown to improve the survival of WNV-infected hamsters when it was administered intraperitoneally (i.p.), even after the virus had infected neurons in the brain. In this study, we evaluated the therapeutic limit of hE16 for the treatment of WNV infection in hamsters by comparing single-dose peripheral (i.p.) therapy with direct administration into the pons through a convection-enhanced delivery (CED) system. At day 5 after infection, treatments with hE16 by the peripheral and the CED routes were equally effective at reducing morbidity and mortality. In contrast, at day 6 …
Efficacy Of Orally Administered T-705 On Lethal Avian Influenza A (H5n1) Virus Infections In Mice, R. W. Sidwell, Dale L. Barnard, C. W. Day, Donald F. Smee, K. W. Bailey, M. H. Wong, John D. Morrey, Y. Furuta
Efficacy Of Orally Administered T-705 On Lethal Avian Influenza A (H5n1) Virus Infections In Mice, R. W. Sidwell, Dale L. Barnard, C. W. Day, Donald F. Smee, K. W. Bailey, M. H. Wong, John D. Morrey, Y. Furuta
John D. Morrey
T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) was inhibitory to four strains of avian H5N1 influenza virus in MDCK cells, with the 90% effective concentrations ranging from 1.3 to 7.7 µM, as determined by a virus yield reduction assay. The efficacy was less than that exerted by oseltamivir carboxylate or zanamivir but was greater than that exerted by ribavirin. Experiments with mice lethally infected with influenza A/Duck/MN/1525/81 (H5N1) virus showed that T-705 administered per os once, twice, or four times daily for 5 days beginning 1 h after virus exposure was highly inhibitory to the infection. Dosages from 30 to 300 mg/kg of body weight/day …
Neutralizing Viruses In Suspensions By Copper Oxide-Based Filters, G. Borkow, R. W. Sidwell, Donald F. Smee, Dale L. Barnard, John D. Morrey, H. H. Lara-Villegas, Y. Shemer-Avni, J. Gabbay
Neutralizing Viruses In Suspensions By Copper Oxide-Based Filters, G. Borkow, R. W. Sidwell, Donald F. Smee, Dale L. Barnard, John D. Morrey, H. H. Lara-Villegas, Y. Shemer-Avni, J. Gabbay
John D. Morrey
We report the capacity of copper oxide-containing filters to reduce infectious titers of a panel of viruses spiked into culture media. Enveloped, nonenveloped, RNA, and DNA viruses were affected, suggesting the possibility of using copper oxide-containing devices to deactivate a wide spectrum of infectious viruses found in filterable suspensions.
Enhanced Antiscrapie Effect Using Combination Drug Treatment, D. A. Kocisko, B. Caughey, John D. Morrey, R. E. Race
Enhanced Antiscrapie Effect Using Combination Drug Treatment, D. A. Kocisko, B. Caughey, John D. Morrey, R. E. Race
John D. Morrey
Combination treatment with pentosan polysulfate and Fe(III)meso-tetra(4-sulfonatophenyl)porphine in mice beginning 14 or 28 days after scrapie inoculation significantly increased survival times. This increase may be synergistic, implying that the compounds act cooperatively in vivo. Combination therapy may therefore be more effective for treatment of transmissible spongiform encephalopathies and other protein-misfolding diseases.
A Porphyrin Increases Survival Time Of Mice After Intracerebral Prion Infection, D. A. Kocisko, W. S. Caughey, R. E. Race, G. Roper, B. Caughey, John D. Morrey
A Porphyrin Increases Survival Time Of Mice After Intracerebral Prion Infection, D. A. Kocisko, W. S. Caughey, R. E. Race, G. Roper, B. Caughey, John D. Morrey
John D. Morrey
Prion diseases, including scrapie, are incurable neurodegenerative disorders. Some compounds can delay disease after a peripheral scrapie inoculation, but few are effective against advanced disease. Here, we tested multiple related porphyrins, but only Fe(III)meso-tetra(4-sulfonatophenyl)porphine injected into mouse brains after intracerebral scrapie inoculation substantially increased survival times.
Phosphorothioate Di- And Trinucleotides As A Novel Class Of Anti-Hepatitis B Virus Agents, R. P. Iyer, Y. Jin, A. Roland, John D. Morrey, S. Mounir, B. Korba
Phosphorothioate Di- And Trinucleotides As A Novel Class Of Anti-Hepatitis B Virus Agents, R. P. Iyer, Y. Jin, A. Roland, John D. Morrey, S. Mounir, B. Korba
John D. Morrey
Several nucleoside analogs are under clinical development for use against hepatitis B virus (HBV). Lamivudine (3TC), a nucleoside analog, and adefovir dipivoxil (ADV), an acyclonucleotide analog, are clinically approved. However, long-term treatment can induce viral resistance, and following the cessation of therapy, viral rebound is frequently observed. There continues to be a need for new antiviral agents with novel mechanisms of action. A library of more than 600 di- and trinucleotide compounds synthesized by parallel synthesis using a combinatorial strategy was screened for potential inhibitors of HBV replication using the chronically HBV-producing cell line 2.2.15. Through an iterative process of …
Anti-Hepatitis B Virus Activity Of Ori-9020, A Novel Phosphorothioate Dinucleotide, In A Transgenic Mouse Model, R. P. Iyer, A. Roland, Y. Jin, S. Mounir, B. Korba, Justin G. Julander, John D. Morrey
Anti-Hepatitis B Virus Activity Of Ori-9020, A Novel Phosphorothioate Dinucleotide, In A Transgenic Mouse Model, R. P. Iyer, A. Roland, Y. Jin, S. Mounir, B. Korba, Justin G. Julander, John D. Morrey
John D. Morrey
ORI-9020, a novel dinucleotide, evaluated in transgenic mice expressing hepatitis B virus (HBV), significantly reduced liver HBV DNA (P <= 0.001). Levels of HBeAg and HBsAg in serum and of HBcAg in liver were not affected by treatment. A minimal effective dosage was determined to be between 1.6 and 0.5 mg/kg of body weight/day, which was similar to that observed for adefovir dipivoxil.