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Bud C. Tennant - One of the best experts on this subject based on the ideXlab platform.

  • Hepatocellular carcinoma in the woodchuck model of hepatitis B virus infection. Gastroenterology 2004
    2016
    Co-Authors: Bud C. Tennant, James R Jacob, Ilia Toshkov, Stephan Menne, Simon F. Peek
    Abstract:

    The Eastern woodchuck (Marmota monax) harbors a DNA virus (Woodchuck hepatitis virus [WHV]) that is similar in structure and replicative life cycle to th

  • The Laboratory Woodchuck (Marmota monax)
    Laboratory Animal Medicine, 2015
    Co-Authors: Christine A. Bellezza, L. Roth, William E. Hornbuckle, Betty H Baldwin, Sandra Sexton, Leslie Curtin, Patrick W. Concannon, Lou Ann Graham, Bud C. Tennant
    Abstract:

    The Eastern woodchuck, Marmota monax, is in the family Sciuridae of the order Rodentia. Common names include groundhog, whistle-pig, and chuck. Natural distribution includes the Eastern and Midwestern United States, Southeastern Alaska, and Southern Canada. The woodchuck is a large, burrow- digging animal with a thickset body, short legs, long claws, broad flat head, almost no neck, small, round ears, and a short, hairy tail. Adults in captivity reach an average body size of 3–5 kg in males, and 2.5–5 kg in females. Colors vary from a grizzly gray-brown to reddish, with a darker head and black feet. Black as well as white (presumably albino) woodchucks have been reported. The fur consists of a soft dense undercoat and a longer, coarse upper fur.

  • Quantitative evaluation of 2-deoxy-2[F-18]fluoro-D-glucose-positron emission tomography imaging on the woodchuck model of hepatocellular carcinoma with histological correlation.
    Molecular imaging and biology, 2007
    Co-Authors: Nicolas Salem, Bud C. Tennant, Gregory T. Maclennan, Yu Kuang, Paul W. Anderson, Steve J. Schomisch, Ilia A. Tochkov, Zhenghong Lee
    Abstract:

    Purpose The Eastern woodchuck (Marmota monax) is considered as a naturally occurring animal model of hepatocellular carcinoma (HCC). The performance of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) for imaging HCC on the woodchuck using Positron emission tomography (PET) was investigated in this study.

  • Seasonal changes in serum leptin, food intake, and body weight in photoentrained woodchucks.
    American journal of physiology. Regulatory integrative and comparative physiology, 2001
    Co-Authors: Patrick W. Concannon, Bud C. Tennant, K. Levac, Richard E. Rawson, André Bensadoun
    Abstract:

    Male woodchucks (Marmota monax) were maintained in northern vs. southern hemisphere photoperiods, provided feed and water ad libitum, and evaluated every 2 wk for 23 mo for body weight, absolute an...

  • antiviral activity of clevudine l fmau 1 2 fluoro 5 methyl β l arabinofuranosyl uracil against woodchuck hepatitis virus replication and gene expression in chronically infected woodchucks Marmota monax
    Hepatology, 2001
    Co-Authors: Simon Peek, William E. Hornbuckle, Bud C. Tennant, Frances V Wells, Paul J Cote, John L Gerin, James R Jacob, Betty H Baldwin, Ilia Toshkov, Brent E Korba
    Abstract:

    L-FMAU [1-(2-fluoro-5-methyl-β,L-arabinofuranosyl) uracil] has been shown to be an effective inhibitor of hepatitis B virus (HBV) and duck hepatitis B virus replication in cell culture and duck hepatitis B virus replication in acutely infected Peking ducks. The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmota monax), have been established as a predictive model for the evaluation of antiviral therapies against chronic HBV infection. In this report, the antiviral activity of l-FMAU against WHV replication in chronically infected woodchucks is described. Four weeks of once-daily oral administration of L-FMAU significantly reduced viremia, antigenemia, intrahepatic WHV replication, and intrahepatic expression of woodchuck hepatitis virus core antigen (WHcAg) in a dose-dependent manner. At the highest dose administered (10 mg/kg/d), significant reductions of intrahepatic WHV RNA and covalently closed circular (ccc)WHV-DNA levels also were observed. The reduction in viremia was remarkably rapid at the higher doses of L-FMAU, with greater than 1,000-fold reductions in WHV-DNA serum levels observed after as little as 2 to 3 days of therapy. Following the withdrawal of therapy, a dose-related delay in viremia rebound was observed. At the highest doses used, viremia remained significantly suppressed in at least one half of the treated animals for 10 to 12 weeks' posttreatment. No evidence of drug-related toxicity was observed in the treated animals. L-FMAU is an exceptionally potent antihepadnaviral agent in vitro and in vivo, and is a suitable candidate for antiviral therapy of chronic HBV infection. (HEPATOLOGY 2001;33:254-266)

J.e. Heath - One of the best experts on this subject based on the ideXlab platform.

  • An infrared thermographic study of surface temperature in the euthermic woodchuck (Marmota monax).
    Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2001
    Co-Authors: P.k. Phillips, J.e. Heath
    Abstract:

    Abstract Surface temperatures were measured in euthermic woodchucks (Marmota monax) using infrared thermography across a range of ambient temperatures from −10°C to 32°C. The woodchuck keeps surface temperature of the peripalpebral region uniformly high, while head and body surfaces change proportionally with ambient temperature. When ambient temperature was below 0°C, all surface temperatures increased which prevents freezing. At no point did the animals appear to be unable to regulate heat exchange. This species appears to be especially well adapted to the higher temperatures it encounters in its range. Vasomotion in the feet and to a lesser extent in the pinnae was used to regulate heat loss. At ambient temperature of 32°C, mean temperatures of nose surfaces were 0.2°C and 0.3°C less than ambient temperature suggesting a type of counter current cooling mechanism may be present.

  • An infrared thermographic study of surface temperature in the euthermic woodchuck (Marmota monax).
    Comparative biochemistry and physiology. Part A Molecular & integrative physiology, 2001
    Co-Authors: P.k. Phillips, J.e. Heath
    Abstract:

    Surface temperatures were measured in euthermic woodchucks (Marmota monax) using infrared thermography across a range of ambient temperatures from -10 degrees C to 32 degrees C. The woodchuck keeps surface temperature of the peripalpebral region uniformly high, while head and body surfaces change proportionally with ambient temperature. When ambient temperature was below 0 degrees C, all surface temperatures increased which prevents freezing. At no point did the animals appear to be unable to regulate heat exchange. This species appears to be especially well adapted to the higher temperatures it encounters in its range. Vasomotion in the feet and to a lesser extent in the pinnae was used to regulate heat loss. At ambient temperature of 32 degrees C, mean temperatures of nose surfaces were 0.2 degrees C and 0.3 degrees C less than ambient temperature suggesting a type of counter current cooling mechanism may be present.

James R Jacob - One of the best experts on this subject based on the ideXlab platform.

  • Hepatocellular carcinoma in the woodchuck model of hepatitis B virus infection. Gastroenterology 2004
    2016
    Co-Authors: Bud C. Tennant, James R Jacob, Ilia Toshkov, Stephan Menne, Simon F. Peek
    Abstract:

    The Eastern woodchuck (Marmota monax) harbors a DNA virus (Woodchuck hepatitis virus [WHV]) that is similar in structure and replicative life cycle to th

  • antiviral activity of clevudine l fmau 1 2 fluoro 5 methyl β l arabinofuranosyl uracil against woodchuck hepatitis virus replication and gene expression in chronically infected woodchucks Marmota monax
    Hepatology, 2001
    Co-Authors: Simon Peek, William E. Hornbuckle, Bud C. Tennant, Frances V Wells, Paul J Cote, John L Gerin, James R Jacob, Betty H Baldwin, Ilia Toshkov, Brent E Korba
    Abstract:

    L-FMAU [1-(2-fluoro-5-methyl-β,L-arabinofuranosyl) uracil] has been shown to be an effective inhibitor of hepatitis B virus (HBV) and duck hepatitis B virus replication in cell culture and duck hepatitis B virus replication in acutely infected Peking ducks. The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmota monax), have been established as a predictive model for the evaluation of antiviral therapies against chronic HBV infection. In this report, the antiviral activity of l-FMAU against WHV replication in chronically infected woodchucks is described. Four weeks of once-daily oral administration of L-FMAU significantly reduced viremia, antigenemia, intrahepatic WHV replication, and intrahepatic expression of woodchuck hepatitis virus core antigen (WHcAg) in a dose-dependent manner. At the highest dose administered (10 mg/kg/d), significant reductions of intrahepatic WHV RNA and covalently closed circular (ccc)WHV-DNA levels also were observed. The reduction in viremia was remarkably rapid at the higher doses of L-FMAU, with greater than 1,000-fold reductions in WHV-DNA serum levels observed after as little as 2 to 3 days of therapy. Following the withdrawal of therapy, a dose-related delay in viremia rebound was observed. At the highest doses used, viremia remained significantly suppressed in at least one half of the treated animals for 10 to 12 weeks' posttreatment. No evidence of drug-related toxicity was observed in the treated animals. L-FMAU is an exceptionally potent antihepadnaviral agent in vitro and in vivo, and is a suitable candidate for antiviral therapy of chronic HBV infection. (HEPATOLOGY 2001;33:254-266)

  • Antiviral activity of clevudine [L‐FMAU, (1‐(2‐fluoro‐5‐methyl‐β, L‐arabinofuranosyl) uracil)] against woodchuck hepatitis virus replication and gene expression in chronically infected woodchucks (Marmota monax)
    Hepatology (Baltimore Md.), 2001
    Co-Authors: Simon F. Peek, William E. Hornbuckle, Frances V Wells, Paul J Cote, John L Gerin, James R Jacob, Betty H Baldwin, Ilia Toshkov, Chung K. Chu, Bud C. Tennant
    Abstract:

    L-FMAU [1-(2-fluoro-5-methyl-β,L-arabinofuranosyl) uracil] has been shown to be an effective inhibitor of hepatitis B virus (HBV) and duck hepatitis B virus replication in cell culture and duck hepatitis B virus replication in acutely infected Peking ducks. The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmota monax), have been established as a predictive model for the evaluation of antiviral therapies against chronic HBV infection. In this report, the antiviral activity of l-FMAU against WHV replication in chronically infected woodchucks is described. Four weeks of once-daily oral administration of L-FMAU significantly reduced viremia, antigenemia, intrahepatic WHV replication, and intrahepatic expression of woodchuck hepatitis virus core antigen (WHcAg) in a dose-dependent manner. At the highest dose administered (10 mg/kg/d), significant reductions of intrahepatic WHV RNA and covalently closed circular (ccc)WHV-DNA levels also were observed. The reduction in viremia was remarkably rapid at the higher doses of L-FMAU, with greater than 1,000-fold reductions in WHV-DNA serum levels observed after as little as 2 to 3 days of therapy. Following the withdrawal of therapy, a dose-related delay in viremia rebound was observed. At the highest doses used, viremia remained significantly suppressed in at least one half of the treated animals for 10 to 12 weeks' posttreatment. No evidence of drug-related toxicity was observed in the treated animals. L-FMAU is an exceptionally potent antihepadnaviral agent in vitro and in vivo, and is a suitable candidate for antiviral therapy of chronic HBV infection. (HEPATOLOGY 2001;33:254-266)

  • Characterization and Immortalization of Woodchuck Hepatocytes Isolated from Normal and Hepadnavirus-Infected Woodchucks (Marmota monax)
    Experimental cell research, 1994
    Co-Authors: James R Jacob, Joseph H Hotchkiss, Rui Hai Liu, Carol A. Roneker, Fernando De Noronha, Bud C. Tennant
    Abstract:

    Primary woodchuck (Marmota monax) hepatocytes from normal woodchucks and woodchucks with chronic woodchuck hepatitis virus (WHV) infection were cultured in either a conventional serum-containing medium or a serum-free medium. The de novo synthesis of the plasma proteins albumin, transferrin, fibrinogen, and complement C3 were identical under both conditions. However, expression of the WHV and the synthesis of nitric oxide were diminished under serum-free conditions. Primary woodchuck hepatocytes cultured in conventional, serum-containing medium were immortalized utilizing the simian virus 40 T antigen oncogene. Immortalized hepatic cell lines retained differentiated functions of nitric oxide synthesis and expression of complement C3. The woodchuck hepatocyte culture model will supplement current experimental methods, allowing investigation of hepadnaviral pathogenesis, including hepatocarcinogenesis in vitro.

  • nitrite and nitrosamine synthesis by hepatocytes isolated from normal woodchucks Marmota monax and woodchucks chronically infected with woodchuck hepatitis virus
    Cancer Research, 1992
    Co-Authors: James R Jacob, Bud C. Tennant, Joseph H Hotchkiss
    Abstract:

    Abstract Hepatocytes isolated from woodchucks (Marmota monax) were shown to produce nitrite in vitro from l-arginine after stimulation with lipopolysaccharide (LPS). Hepatocytes isolated from woodchucks that were chronic carriers of woodchuck hepatitis virus formed twice as much nitrite as hepatocytes from noninfected animals. Nitrite synthesis by hepatocytes was directly related to l-arginine and LPS concentrations in the tissue culture medium and reached a plateau at 0.5 mml-arginine and 1.0 µg/ml LPS. LPS-stimulated hepatocytes nitrosated morpholine to form N-nitrosomorpholine in the presence of l-arginine at a physiological pH of 7.4. There was a 10-fold increase in N-nitrosomorpholine production when hepatocytes were stimulated with LPS compared to unstimulated hepatocytes under similar conditions when both nitrite and morpholine were directly added to the medium. NG-monomethyl-l-arginine, a selective inhibitor of nitric oxide synthase, inhibited formation of both nitrite and N-nitrosomorpholine. These results demonstrate that nitrosating agents are formed in hepatocytes via the l-arginine-nitric oxide pathway. This suggests that endogenous formation of carcinogenic N-nitroso compounds could influence the process of hepatocarcinogenesis in woodchucks with chronic woodchuck hepatitis virus infection.

P.k. Phillips - One of the best experts on this subject based on the ideXlab platform.

  • An infrared thermographic study of surface temperature in the euthermic woodchuck (Marmota monax).
    Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2001
    Co-Authors: P.k. Phillips, J.e. Heath
    Abstract:

    Abstract Surface temperatures were measured in euthermic woodchucks (Marmota monax) using infrared thermography across a range of ambient temperatures from −10°C to 32°C. The woodchuck keeps surface temperature of the peripalpebral region uniformly high, while head and body surfaces change proportionally with ambient temperature. When ambient temperature was below 0°C, all surface temperatures increased which prevents freezing. At no point did the animals appear to be unable to regulate heat exchange. This species appears to be especially well adapted to the higher temperatures it encounters in its range. Vasomotion in the feet and to a lesser extent in the pinnae was used to regulate heat loss. At ambient temperature of 32°C, mean temperatures of nose surfaces were 0.2°C and 0.3°C less than ambient temperature suggesting a type of counter current cooling mechanism may be present.

  • An infrared thermographic study of surface temperature in the euthermic woodchuck (Marmota monax).
    Comparative biochemistry and physiology. Part A Molecular & integrative physiology, 2001
    Co-Authors: P.k. Phillips, J.e. Heath
    Abstract:

    Surface temperatures were measured in euthermic woodchucks (Marmota monax) using infrared thermography across a range of ambient temperatures from -10 degrees C to 32 degrees C. The woodchuck keeps surface temperature of the peripalpebral region uniformly high, while head and body surfaces change proportionally with ambient temperature. When ambient temperature was below 0 degrees C, all surface temperatures increased which prevents freezing. At no point did the animals appear to be unable to regulate heat exchange. This species appears to be especially well adapted to the higher temperatures it encounters in its range. Vasomotion in the feet and to a lesser extent in the pinnae was used to regulate heat loss. At ambient temperature of 32 degrees C, mean temperatures of nose surfaces were 0.2 degrees C and 0.3 degrees C less than ambient temperature suggesting a type of counter current cooling mechanism may be present.

Brent E Korba - One of the best experts on this subject based on the ideXlab platform.

  • antiviral activity of clevudine l fmau 1 2 fluoro 5 methyl β l arabinofuranosyl uracil against woodchuck hepatitis virus replication and gene expression in chronically infected woodchucks Marmota monax
    Hepatology, 2001
    Co-Authors: Simon Peek, William E. Hornbuckle, Bud C. Tennant, Frances V Wells, Paul J Cote, John L Gerin, James R Jacob, Betty H Baldwin, Ilia Toshkov, Brent E Korba
    Abstract:

    L-FMAU [1-(2-fluoro-5-methyl-β,L-arabinofuranosyl) uracil] has been shown to be an effective inhibitor of hepatitis B virus (HBV) and duck hepatitis B virus replication in cell culture and duck hepatitis B virus replication in acutely infected Peking ducks. The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmota monax), have been established as a predictive model for the evaluation of antiviral therapies against chronic HBV infection. In this report, the antiviral activity of l-FMAU against WHV replication in chronically infected woodchucks is described. Four weeks of once-daily oral administration of L-FMAU significantly reduced viremia, antigenemia, intrahepatic WHV replication, and intrahepatic expression of woodchuck hepatitis virus core antigen (WHcAg) in a dose-dependent manner. At the highest dose administered (10 mg/kg/d), significant reductions of intrahepatic WHV RNA and covalently closed circular (ccc)WHV-DNA levels also were observed. The reduction in viremia was remarkably rapid at the higher doses of L-FMAU, with greater than 1,000-fold reductions in WHV-DNA serum levels observed after as little as 2 to 3 days of therapy. Following the withdrawal of therapy, a dose-related delay in viremia rebound was observed. At the highest doses used, viremia remained significantly suppressed in at least one half of the treated animals for 10 to 12 weeks' posttreatment. No evidence of drug-related toxicity was observed in the treated animals. L-FMAU is an exceptionally potent antihepadnaviral agent in vitro and in vivo, and is a suitable candidate for antiviral therapy of chronic HBV infection. (HEPATOLOGY 2001;33:254-266)

  • treatment of chronic woodchuck hepatitis virus infection in the eastern woodchuck Marmota monax with nucleoside analogues is predictive of therapy for chronic hepatitis b virus infection in humans
    Hepatology, 2000
    Co-Authors: Brent E Korba, William E. Hornbuckle, Bud C. Tennant, Paul J Cote, John L Gerin
    Abstract:

    : The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmota monax), have been established as a model of hepatitis B virus (HBV)-induced disease. Several published studies have used this experimental animal model system to demonstrate potential antiviral therapies for chronic HBV infections. However, there has been little comparative information available on compounds used in clinical anti-HBV studies in WHV-infected woodchucks, thereby making interpretations of the potential relative effectiveness of new antiviral agents in humans more difficult. In this report, using a series of placebo-controlled studies, we compared the relative effectiveness of several nucleoside analogues that have been used in clinical trials for the treatment of chronic HBV infection against WHV replication in chronically infected woodchucks. Adenine-5'-arabinoside monophosphate (Ara-AMP [vidarabine]), ribavirin, (-)beta-L-2',3'-dideoxy-3'-thiacytidine (3TC [lamivudine]), and famciclovir (oral prodrug of penciclovir) induced depressions in viremia and intrahepatic WHV-DNA replication that were consistent with their relative effectiveness in anti-HBV human clinical trials. As observed in HBV-infected patients, 3' azido-3'-deoxythymidine (AZT [zidovudine]) had no effect on WHV replication in these studies. These experimental results more firmly establish chronic WHV infection in woodchucks as an accurate and predictive model for antiviral therapies against chronic HBV infection in humans and provide a baseline for comparative antiviral effects of other experimental antiviral agents in the WHV/woodchuck model system.