Repeated adenoviral administration into the biliary tract can induce repeated expression of the original gene construct in rat livers without immunosuppressive strategies

Tominaga, K.; Kuriyama, S.; Yoshiji, H.; Deguchi, A.; Kita, Y.; Funakoshi, F.; Masaki, T.; Kurokohchi, K.; Uchida, N.; Tsujimoto, T.; Fukui, H.
August 2004
Gut;Aug2004, Vol. 53 Issue 8, p1167
Academic Journal
Background: Systemic adenoviral readministration appears to be limited by immunogenicity. Aims: We examined the feasibility of repeated adenovirus mediated gene transfer into the liver via the biliary tract. Methods: Recombinant adenoviruses carrying a reporter IacZ gene were infused retrogradely into the common bile duct of rats. Transduction efficiency of the IacZ gene was estimated histochemically and quantitatively. Results: Retrograde administration of recombinant adenoviruses into the common bile duct of rats resulted in efficient transgene expression in the liver, specifically in hepatocytes, but not in biliary epithelia. Transduction efficiency induced by intrabiliary adenoviral administration was not substantially different from that induced by intraportal adenoviral infusion. Transgene expression in the liver was however transient, and development of neutrolising antibodies against adenovirus was observed in serum but not in bile. When adenoviruses were readministered into the common bile duct, successful re-expression of the transgene in the liver was achieved despite the existence of neutralising antibodies in serum. Interestingly, although proliferation of adenovirus specific I cells in response to adenoviral readministration was suppressed significantly by immunosuppressive FK506 treatment, levels of transgene expression in the liver achieved by intrabiliary adenoviral readministration were not significantly different between animals treated with and without FK506. Furthermore, third adenoviral administration into the common bile duct also induced successful transgene expression in the liver. Conclusions: These results suggest that adenovirus mediated gene transfer into the liver may be repeatable without immunosuppressive strategies in clinical settings by means of endoscopic retrograde cholangiography.


Related Articles

  • Tacrolimus (FK 506), a Treatment for Primary Sclerosing Cholangitis: Results of an Open-Label Preliminary Trial. Van Thiel, David H.; Carroll, Patricia; Abu-Elmagd, Kareem; Rodriguez-Rilo, Horacio; Irish, William; McMichael, John; Starzl, Thomas E. // American Journal of Gastroenterology;Mar1995, Vol. 90 Issue 3, p455 

    Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the liver that is characterized by progressive cholestasis and the development of secondary biliary cirrhosis. There is no widely recognized therapy for this disease, although anti-inflammatory agents (steroids),...

  • Is there an association between immunosuppressant therapy medication adherence and depression, quality of life, and personality traits in the kidney and liver transplant population? Gorevski, Elizabeth; Succop, Paul; Sachdeva, Jyoti; Cavanaugh, Teresa M.; Volek, Paul; Heaton, Pamela; Chisholm-Burns, Marie; Martin-Boone, Jill E. // Patient Preference & Adherence;2013, Vol. 7, p301 

    Objectives: To measure the association of transplant patients' personality, depression, and quality of life with medication adherence in kidney and liver transplant recipients. Methods: A cross-sectional study of liver and kidney transplant recipients greater than 1 year post-transplant was...

  • IgG 4-Positive Sclerosing Cholangitis Following Autoimmune Pancreatitis With Deranged CA19.9. Ong, Seok L.; Garcea, Guiseppe; Puls, Florian; Richards, Cathy; Mulcahy, Kevin; Grant, Allister; Dennison, Ashley R.; Berry, David P. // International Journal of Surgical Pathology;03/01/2011, Vol. 19 Issue 1, p84 

    Sclerosing cholangitis is an autoimmune condition characterized by lymphocytic infiltration within the biliary epithelium leading to multifocal stricturing of the biliary tree. Primary sclerosing cholangitis (PSC) is the most common type encountered clinically. However, a similar process may...

  • Prevalence of primary biliary cirrhosis in adults referring hospital for annual health check-up in Southern China. Haiying Liu; Yunfeng Liu; Luxia Wang; Dexing Xu; Bingliang Lin; Renqian Zhong; Sitang Gong; Podda, Mauro; Invernizzi, Pietro // BMC Gastroenterology;2010, Vol. 10, p100 

    Background: Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of antimitocondrial autoantibodies (AMA) which has an essential role also for diagnosis. In addition, also some antinuclear antibodies (ANA) have been shown to be highly specific PBC. The...

  • Metabolic effects of trekrezan during adaptation of rats to intermittent hypoxic hypoxia. I. Zarubina // Bulletin of Experimental Biology & Medicine;Jan2008, Vol. 145 Issue 1, p47 

    Abstract  The animals were adapted to intermittent hypoxic hypoxia in a flow pressure chamber for 3 days. Each one-day training session consisted of 4 elevations to an altitude of 6000 m for 20 min (15 m/sec, 20-min intervals between assents). Trekrezan (25 mg/kg intraperitoneally) was...

  • Stochastic vs. deterministic uptake of dodecanedioic acid by isolated rat livers. Ditlevsen, Susanne; de Gaetano, Andrea // Bulletin of Mathematical Biology;May2005, Vol. 67 Issue 3, p547 

    Abstract: Deterministic and stochastic differential equations models of the uptake of dodecanedioic acid (C12) are fitted to experimental data obtained on nine isolated, perfused rat livers. 11500 μg of C12 were injected as a bolus into the perfusing liver solution. The concentrations of...

  • Drug metabolizing enzyme expression in rat choroid plexus: effects of in vivo xenobiotics treatment. Gradinaru, Daniela; Minn, Anne-Laure; Artur, Yves; Minn, Alain; Heydel, Jean-Marie // Archives of Toxicology;Jun2009, Vol. 83 Issue 6, p581 

    The presence of drug metabolizing enzymes in extrahepatic tissues such as the choroid plexus (CP) suggests that the CP, like the blood–brain barrier, affords a metabolic protection to the brain against xenobiotics. The CP, which is the principal site of formation of the cerebrospinal...

  • Transient mTOR Inhibition Facilitates Continuous Growth of Liver Tumors by Modulating the Maintenance of CD133+ Cell Populations. Zhaojuan Yang; Li Zhang; Ma, Aihui; Liu, Lanlan; Li, Jinjun; Gu, Jianren; Liu, Yongzhong // PLoS ONE;2011, Vol. 6 Issue 12, p1 

    The mammalian target of the rapamycin (mTOR) pathway, which drives cell proliferation, is frequently hyperactivated in a variety of malignancies. Therefore, the inhibition of the mTOR pathway has been considered as an appropriate approach for cancer therapy. In this study, we examined the roles...

  • SIGNIFICANCE OF THE ROKITANSKY-ASCHOFF SINUSES. Halpert, Béla // American Journal of Gastroenterology;Nov1961, Vol. 36 Issue 5, p534 

    Elaborates the nature of Rokitansky-Aschoff sinuses, epithelial structures in the gallbladder. Characteristics of the structures; Purpose of the sinuses; Kinds of gallbladder diseases which alter morphology of the structures.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics