Birgit Hoyler

evaplan at the University Hospital Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (11)28.21 Total impact

  • 8th International Conference on Oncolytic Virus Therapeutics; 12/2014
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    ABSTRACT: Acetaminophen (APAP) is one of the most widely used analgesic and antipyretic pharmaceutical substances in the world and accounts for most cases of drug induced liver injury resulting in acute liver failure. Acute liver failure initiates a sterile inflammatory response with release of cytokines and innate immune cell infiltration in the liver. This study investigates, whether pharmacologic acetylcholinesterase inhibition with neostigmine diminishes liver damage in acute liver failure via the cholinergic anti-inflammatory pathway. Acute liver failure was induced in BALB/c mice by a toxic dose of acetaminophen (APAP). Neostigmine and/or N-acetyl-cysteine (NAC) were applied therapeutically at set time points and the survival was investigated. Liver damage was assessed by serum parameters, histopathology and serum cytokine assays 12 h after initiation of acute liver failure. Serum parameters, histopathology and serum cytokine assays showed pronounced features of acute liver failure 12 h after application of acetaminophen (APAP). Neostigmine treatment led to significant reduction of serum liver enzymes (LDH (47,147 ± 12,726 IU/l vs. 15,822 ± 10,629 IU/l, p = 0.0014) and ALT (18,048 ± 4,287 IU/l vs. 7,585 ± 5,336 IU/l, p = 0.0013), APAP-alone-treated mice vs. APAP + neostigmine-treated mice), inflammatory cytokine levels (IL-1β (147 ± 19 vs. 110 ± 25, p = 0.0138) and TNF-α (184 ± 23 vs. 130 ± 33, p = 0.0086), APAP-alone-treated mice vs. APAP + neostigmine-treated mice) and histopathological signs of damage. Animals treated with NAC in combination with the peripheral cholinesterase inhibitor neostigmine showed prolonged survival and improved outcome. Neostigmine is an acetylcholinesterase inhibitor that ameliorates the effects of APAP-induced acute liver failure in the mouse and therefore may provide new treatment options for affected patients.
    BMC Gastroenterology 08/2014; 14(1):148. DOI:10.1186/1471-230X-14-148 · 2.37 Impact Factor
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    ABSTRACT: To explore dendritic cells (DCs) multiple functions in immune modulation. We used bone-marrow derived dendritic cells from BALB/c mice pulsed with pseudo particles from the hepatitis C virus to vaccinate naive BALB/c mice. Hepatitis C virus (HCV) pseudo particles consist of the genotype 1b derived envelope proteins E1 and E2, covering a non-HCV core structure. Thus, not a single epitope, but the whole "viral surface" induces immunogenicity. For vaccination, mature and activated DC were injected subcutaneously twice. Humoral and cellular immune responses measured by enzyme-linked immunosorbent assay and interferon-gamma enzyme-linked immunosorbent spot test showed antibody production as well as T-cells directed against HCV. Furthermore, T-cell responses confirmed two highly immunogenic regions in E1 and E2 outside the hypervariable region 1. Our results indicate dendritic cells as a promising vaccination model for HCV infection that should be evaluated further.
    World Journal of Gastroenterology 02/2012; 18(8):785-93. DOI:10.3748/wjg.v18.i8.785 · 2.37 Impact Factor
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    ABSTRACT: Lentiviral vectors are vectors of choice for many gene therapy applications. Recently, efficient targeting of lentiviral vectors pseudotyped with the Measles virus (MV) glycoproteins has been reported. However, MV antibodies in patients might limit the clinical use of these vectors. We demonstrate here that lentiviral vectors can also be pseudotyped with the glycoproteins of Tupaia paramyxovirus (TPMV), the hemagglutinin (H) and fusion (F) protein. As this animal paramyxovirus has no known close relatives in humans, we do not expect TPMV antibodies in patients. Because TPMV normally does not infect human cells, 'detargeting' from natural receptors is unnecessary. Similar to the MV system, TPMV glycoproteins can mediate targeted cell entry by displaying different single-chain antibodies (scAb) directed against surface molecules on target cells on the viral hemagglutinin. We generated a panel of H and F proteins with truncated cytoplasmic tails and determined the variants that efficiently pseudotyped lentiviral vectors. The B-cell marker CD20 was used as a model antigen, and CD20-targeted TPMV vectors selectively transduced CD20-positive cells, including quiescent primary human B-cells. Lentiviral vectors pseudotyped with targeted TPMV envelope proteins might be a valuable vector choice when systemic application of targeted lentiviral vectors in humans is required.Gene Therapy advance online publication, 5 January 2012; doi:10.1038/gt.2011.209.
    Gene therapy 01/2012; 20(1). DOI:10.1038/gt.2011.209 · 3.10 Impact Factor
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    ABSTRACT: Eradication of chronic Hepatitis B virus (HBV) infection, marked by HBs seroconversion, is very rarely achieved by treatment with nucleoside and nucleotide analogs. Therapeutic cell based approaches, like interferon therapy, have a higher chance of seroconversion. Dendritic cells (DC) are key players in the cellular immune response and have been shown to play an important role in controlling HBV infection. In this study, the potential of ex vivo activated DC to induce specific immune responses against HBV was examined. DC derived from bone-marrow of BALB/c or C56BL/6 mice were pulsed with HBV subviral particles (HBVsvp), derived from the HepG2.2.15 cell line. HepG2.2.15 produces subviral particles consisting of the HBc and HBs proteins. Thus, the entire "viral surface" is presented to DC to induce an immune reaction. In vitro pulsation with HBVsvp successfully activated bone-marrow derived DC, demonstrated by FACS analysis showing increased MHCII, CD 86 and CCR-7. Immunization of mice, via subcutaneous injection of the activated DC, induced HBV specific immune reactions which were measured by ELISA, ELISPOT and T-cell proliferation analysis. Vaccination with ex vivo activated DC may be a promising tool for therapeutic or prophylactic approaches against the Hepatitis B virus.
    Vaccine 11/2010; 29(2):200-6. DOI:10.1016/j.vaccine.2010.10.056 · 3.62 Impact Factor
  • Zeitschrift für Gastroenterologie 04/2009; 50. DOI:10.1016/S0168-8278(09)60589-4 · 1.05 Impact Factor
  • F Voigt · C Eisenbach · J Encke · B Hoyler · W Stremmel · K Weigand
    Zeitschrift für Gastroenterologie 01/2008; 46(01). DOI:10.1055/s-2008-1037623 · 1.05 Impact Factor
  • Journal of Viral Hepatitis 12/2007; 14(11):817-9. DOI:10.1111/j.1365-2893.2007.00872.x · 3.91 Impact Factor
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    ABSTRACT: Current cancer gene therapies aim at the induction of systemic antitumor immune responses. Tumors may deliver antigens to T-cells, but may lack the costimulatory signals necessary for mounting an effective response. The purpose of this study was to evaluate the efficacy of an adenoviral delivery of the B7-H3 costimulatory molecule in mice to induce antitumor immune responses. Colon cancers were established by orthotopic injection of syngeneic colon cancer cells into the cecum on Balb/c mice. After two weeks, these mice were treated by intratumoral injection of an adenovirus expressing mouse B7-H3 (Ad-B7-H3-GFP) or a control virus (Ad-GFP). Ad-B7-H3-GFP treatment resulted in a reduction of tumor size compared to the controls. In addition, the occurrence of secondary metastasis was significantly reduced in B7-H3 treated mice compared to control animals (lymph node 7/10 vs. 10/10; liver 2/10 vs. 8/10, p<or=0.05). Ad-B7-H3-GFP treated animals showed significantly higher frequencies of tumor-specific interferon-gamma producing CD8+ T-cells (p<or=0.05) and higher interleukin-12 levels (p<or=0.01) than control animals. This study demonstrates that adenoviral B7-H3 transfer is able to induce a specific cellular antitumor immune response leading to primary tumor regression and reduction of secondary metastasis in vivo.
    Oncology Reports 09/2007; 18(3):745-8. DOI:10.1055/s-2007-988177 · 2.30 Impact Factor
  • F Voigt · K Weigand · C Eisenbach · B Hoyler · W Stremmel · J Encke
    Zeitschrift für Gastroenterologie 01/2007; 45(01). DOI:10.1055/s-2007-967881 · 1.05 Impact Factor
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    ABSTRACT: Surrogate infections with HCV-recombinant vaccinia viruses (HCV-rVV) are a standard method to test the efficacy of hepatitis C virus (HCV) vaccine candidates in the mouse model. We established a panel of 16 HCV-rVV expressing the nonstructural protein 3 (NS3) of HCV genotypes 1a, 1b, 2, 3 and 4. Mice immunized with recombinant NS3 protein derived from HCV genotype 1b were challenged with the rVV. rVV-titers decreased up to 54-fold after subtype 1b challenge and up to 8.5-fold after subtype 1a challenge. No change was detected for genotype 2, 3, or 4. Our model is a convenient and reliable tool to analyze the induction of cross-genotype immunity by experimental vaccination of mice.
    Vaccine 07/2006; 24(24):5140-8. DOI:10.1016/j.vaccine.2006.04.013 · 3.62 Impact Factor

Publication Stats

54 Citations
28.21 Total Impact Points


  • 2014
    • evaplan at the University Hospital Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2006–2012
    • Universität Heidelberg
      • • IV. Medical Clinic
      • • General pediatrics, pediatric neurology, metabolism, gastroenterology, nephrology
      Heidelburg, Baden-Württemberg, Germany