Thomas Tschernig

Universität des Saarlandes, Saarbrücken, Saarland, Germany

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Publications (230)693.93 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial colonization and recurrent infections of the respiratory tract contribute to the progression of chronic obstructive pulmonary disease (COPD). There is evidence that exacerbations of COPD are provoked by new bacterial strains acquired from the environment. Using a murine model of colonization, we examined whether chronic exposure to cigarette smoke (CS) promotes nasopharyngeal colonization with typical lung pathogens and whether colonization is linked to inflammation in the respiratory tract. C57BL/6 N mice were chronically exposed to CS. The upper airways of mice were colonized with nontypeable Haemophilus influenzae (NTHi) or Streptococcus pneumoniae. Bacterial colonization was determined in the upper respiratory tract and lung tissue. Inflammatory cells and cytokines were determined in lavage fluids. RT-PCR was performed for inflammatory mediators. Chronic CS exposure resulted in significantly increased numbers of viable NTHi in the upper airways, whereas NTHi only marginally colonized air-exposed mice. Colonization with S. pneumoniae was enhanced in the upper respiratory tract of CS-exposed mice and was accompanied by increased translocation of S. pneumoniae into the lung. Bacterial colonization levels were associated with increased concentrations of inflammatory mediators and the number of immune cells in lavage fluids of the upper respiratory tract and the lung. Phagocytosis activity was reduced in whole blood granulocytes and monocytes of CS-exposed mice. These findings demonstrate that exposure to CS impacts the ability of the host to control bacterial colonization of the upper airways, resulting in enhanced inflammation and susceptibility of the host to pathogens migrating into the lung.
    Respiratory Research 12/2015; 16(1). DOI:10.1186/s12931-015-0204-8 · 3.09 Impact Factor
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    ABSTRACT: Objectives: Our previous data demonstrated that allergic airway inflammation induces migration of dendritic cells (DC) into airway sensory jugular and nodose ganglia (jugular-nodose ganglion complex; JNC). Here we investigated the effects of steroid treatment regarding the expression and migration of DC and calcitonin gene-related peptide (CGRP)-immunoreactive neurons of vagal sensory ganglia during allergic airway inflammation. Methods: A house dust mite (HDM) model for allergic airway inflammation was used. The mice received 0.3 mg fluticasone propionate per kilogram of body weight in the last 9 days. JNC slices were analyzed on MHC II, the neuronal marker PGP9.5, and the neuropeptide CGRP. Results: Allergic airway inflammation increased the numbers of DC and CGRP-expressing neurons in the JNC significantly in comparison to the controls (DC/neurons: HDM 44.58 ± 1.6% vs. saline 33.29 ± 1.6%, p < 0.05; CGRP-positive neurons/total neurons: HDM 30.65 ± 1.9% vs. saline 19.49 ± 2.3%, p < 0.05). Steroid treatment did not have any effect on the numbers of DC and CGRP-expressing neurons in the JNC compared to HDM-treated mice. Conclusions: The present findings indicate an important role of DC and CGRP-containing neurons in the pathogenesis of allergic airway inflammation. However, steroid treatment did not have an effect on the population of DC and neurons displaying CGRP in the JNC, whereas steroid treatment was found to suppress allergic airway inflammation.
    NeuroImmunoModulation 10/2015; DOI:10.1159/000440622 · 1.88 Impact Factor
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    ABSTRACT: Pannexins (Panx) are proteins with a similar membrane topology to connexins, the integral membrane protein of gap junctions. Panx1 channels are generally of major importance in a large number of system and cellular processes and their function has been thoroughly characterized. In contrast, little is known about channel structure and subcellular distribution. We therefore determine the subcellular localization of Panx1 channels in cultured cells and aim at the identification of channel morphology in vitro. Using freeze-fracture replica immunolabeling on EYFP-Panx1-overexpressing HEK 293 cells, large particles were identified in plasma membranes, which were immunogold-labeled using either GFP or Panx1 antibodies. There was no labeling or particles in the nuclear membranes of these cells, pointing to plasma membrane localization of Panx1-EYFP channels. The assembly of particles was irregular, this being in contrast to the regular pattern of gap junctions. The fact that no counterparts were identified on apposing cells, which would have been indicative of intercellular signaling, supported the idea of Panx1 channels within one membrane. Control cells (transfected with EYFP only, non-transfected) were devoid of both particles and immunogold labeling. Altogether, this study provides the first demonstration of Panx1 channel morphology and assembly in intact cells. The identification of Panx1 channels as large particles within the plasma membrane provides the knowledge required to enable recognition of Panx1 channels in tissues in future studies. Thus, these results open up new avenues for the detailed analysis of the subcellular localization of Panx1 and of its nearest neighbors such as purinergic receptors in vivo.
    Cell and Tissue Research 09/2015; DOI:10.1007/s00441-015-2281-x · 3.57 Impact Factor
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    ABSTRACT: Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection with Streptococcus pneumoniae being the most prevalent causal pathogen and hence, often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause in the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza infection might improve host defense against secondary bacterial pathogens. Here, we examined the effect of pulmonary immunostimulation with TLR-2 stimulating macrophage-activating lipopeptide-2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced recruitment of leukocytes, mainly neutrophils into the alveolar space of IAV-infected mice without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced bacterial numbers in the lung tissue without inducing exaggerated inflammation. Pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment in IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared with untreated co-infected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection.
    Infection and Immunity 09/2015; DOI:10.1128/IAI.00948-15 · 3.73 Impact Factor
  • Nadine Hainz · Sandra Wolf · Thomas Tschernig · Carola Meier
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    ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Neurological impairments are caused by axonal damage due to demyelination and neuroinflammation within the central nervous system. T cells mediate the neuroinflammation. The activation of T cells is induced by the release of adenosine triphosphate and involves purinergic receptors as well as pannexin (Panx) proteins. As Panx1 is expressed on T cells, we here propose that application of probenecid, a known Panx inhibitor, will prevent the onset of clinical symptoms in a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE) model. EAE-induced mice received daily injections of probenecid. Disease scores, T cell numbers, and microglia activation were compared between experimental groups. Probenecid treatment resulted in lower disease scores as compared to EAE animals. Probenecid-treated animals also displayed fewer inflammatory lesions. Microglia activation was not altered by treatment. In conclusion, probenecid prevented the onset of EAE.
    Inflammation 08/2015; DOI:10.1007/s10753-015-0230-1 · 2.21 Impact Factor
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    ABSTRACT: Janus kinase (JAK) inhibitors have recently been developed for allergic diseases. We focused on the 2 different JAK inhibitors, tofacitinib (selective for JAK3) and oclacitinib (selective for JAK1 and 2), to clarify the mechanism of anti-inflammatory and anti-itching potency of these drugs. In the process of detecting anti-itching potency, we observed that tofacitinib treated mice showed aggression behaviour. The objective of the study reported here was to investigate the aggressive behaviour induced by tofacitinib by using a mouse model of allergic dermatitis and the resident-intruder test. For the allergic dermatitis model, female BALB/c mice were sensitized and challenged topically with toluene-2,4-diisocyanate (TDI). Vehicle, tofacitinib or oclacitinib, was administered orally 30min before TDI challenge. Scratching, aggression and standing behaviours were monitored in the 60min period immediately following challenge of TDI. Another group of male BALB/c mice treated with vehicle, tofacitinib or oclacitinib was evaluated in the resident-intruder test and brains were obtained to determine blood brain barrier penetration. In the allergic dermatitis model, a significant increase in aggression and standing behaviour was only obvious in the tofacitinib treatment group. There was no effect in non-sensitized mice, but similar aggression was also induced by tofacitinib in male resident-intruder test. Penetration of blood-brain barrier was observed both in tofacitinib and oclacitinib treated mice. These results suggest that aggression was induced by tofacitinib under some kind of stressful environment. This study indicates a possible role of the JAK-STAT pathway in modulation of aggression behaviour. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 07/2015; 764. DOI:10.1016/j.ejphar.2015.06.060 · 2.53 Impact Factor
  • Der Chirurg 05/2015; DOI:10.1007/s00104-015-0025-9 · 0.57 Impact Factor
  • Pneumologie 04/2015; 69(04). DOI:10.1055/s-0035-1548642
  • Yulin Qi · Nadine Hainz · Thomas Tschernig · Carola Meier · Dietrich A Volmer
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    ABSTRACT: We demonstrate, by means of on-tissue mass spectrometry of tissue sections, that the drug probenecid can penetrate the blood-brain barrier. This method holds general promise for the detection and distribution of small molecule drugs within organ and tissue compartments.
    Cell and Tissue Research 03/2015; 360(2). DOI:10.1007/s00441-015-2153-4 · 3.57 Impact Factor
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    ABSTRACT: Asthma is the consequence of allergic inflammation in the lung compartments and lung-draining lymph nodes. Dendritic cells initiate and promote T cell response and drive it to immunity or allergy. However, their modes of action during asthma are poorly understood. In this study, an allergic inflammation with ovalbumin was induced in 38 mice versus 42 control animals. After ovalbumin aerosol challenge, conventional dendritic cells (CD11c/MHCII/CD8) were isolated from the lungs and the draining lymph nodes by means of magnetic cell sorting followed by fluorescence-activated cell sorting. A comparative transcriptional analysis was performed using gene arrays. In general, many transcripts are up- and downregulated in the CD8(-) dendritic cells of the allergic inflamed lung tissue, whereas few genes are regulated in CD8(+) dendritic cells. The dendritic cells of the lymph nodes also showed minor transcriptional changes. The data support the relevance of the CD8(-) conventional dendritic cells but do not exclude distinct functions of the small population of CD8(+) dendritic cells, such as cross presentation of external antigen. So far, this is the first approach performing gene arrays in dendritic cells obtained from lung tissue and lung-draining lymph nodes of asthmatic-like mice.
    International Journal of Genomics 02/2015; 2015:638032. DOI:10.1155/2015/638032 · 0.95 Impact Factor
  • Ebru Diler · Stephanie Saul · Ivan Bogeski · Carola Meier · Thomas Tschernig
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    ABSTRACT: The influence of extracellular calcium on phagocytosis is limited, and the involvement of extracellular magnesium is unclear. The role of extracellular calcium and magnesium on phagocytosis efficiency was investigated. Extracellular calcium had no influence on the internalization of 1 μm polystyrene particles by primary monocytes as has been shown before for the human lymphoma-derived, differentiated cell line U937 and murine alveolar macrophage-derived MH-S cells. In contrast, the phagocytosis by differentiated U937 cells was positively affected by the presence of extracellular magnesium whereas that of MH-S cells was not. An extracellular increase in the magnesium level did not cause an increase in the free cytosolic magnesium concentration in either cell line. In contrast to magnesium, extracellular calcium caused an increase in intracellular divalent cation levels in differentiated U937 cells. A phagocytosis-enhancing effect in the extracellular space was observed in relation to extracellular magnesium rather than with an intracellular increase in magnesium levels, indicating that murine and human immune cells might be regulated differently.
    Magnesium research: official organ of the International Society for the Development of Research on Magnesium 02/2015; 28(1):23-31. DOI:10.1684/mrh.2015.0378 · 0.77 Impact Factor
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    ABSTRACT: Abundant microbial colonization is a hallmark of COPD and smoke exposure likely increases the susceptibility to colonization and infection. The aim of the present study was to characterize the pulmonary changes of a combined exposure to cigarette smoke (CS) and microbial challenge in a preclinical murine COPD model. Animals were exposed to CS for 2 weeks, 3, and 6 months. Low and high doses of heat inactivated nontypeable Haemophilus influenzae (NTHi) were administered by inhalation during the whole exposure time. Pulmonary changes were analyzed by stereology, pulmonary function tests, measurements of inflammatory cells and mediators, and histopathology.
    Experimental and Toxicologic Pathology 01/2015; 67(3). DOI:10.1016/j.etp.2015.01.002 · 1.86 Impact Factor
  • N T Veith · T Tschernig · B J Braun · T Pohlemann · G Aßmann
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    ABSTRACT: A 51-year-old female patient with history of longterm drug abusus, was admitted to our hospital with large, stocking-shaped areas of painful, non-displaceable confluent bruising reaching up to the groin. The emergency laboratory tests showed leucopenia, thrombocytopenia and anemia as well as a distinct protein C deficiency. Purpura fulminans was diagnosed and treated with an initial dose of protein C. The patient survived and the skin necrosis can be treated. Purpura fulminans is an internistic and dermatological emergency situation which can lead to shock through consumptive coagulopathy. The serious course of disease can be prevented by rapid treatment with protein C. © Georg Thieme Verlag KG Stuttgart · New York.
    DMW - Deutsche Medizinische Wochenschrift 12/2014; 139(50):2597-601. DOI:10.1055/s-0034-1387428 · 0.54 Impact Factor
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    ABSTRACT: Surfactant proteins (SP) secreted by alveolar type 2 cells, play an essential role in maintaining the air-liquid barrier of the lung and are also involved in the opsonisation and clearance of bacteria by phagocytes. We have recently described a novel surfactant protein, SP-H (SFTA3). Expression of SP-H was earlier demonstrated to be upregulated by LPS and negatively regulated by IL-1beta and IL-23 in vitro. The influence of SP-H on phagocytosis was measured using a murine and a human phagocytic cell line and fluorescent latex beads. SP-H markedly increases phagocytosis in vitro in the murine-derived alveolar macrophage cell lines MH-S and in human-derived differentiated U937 cells. It can be assumed that SP-H is involved in regulating phagocytic activity of macrophages. SP-H is a new player in pulmonary host defence.
    BMC Research Notes 11/2014; 7(1):851. DOI:10.1186/1756-0500-7-851
  • M.W. Laschke · V. Augustin · S. Kleer · T. Tschernig · M.D. Menger
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    ABSTRACT: Porous polyethylene (Medpor(®)) is frequently used in craniofacial reconstructive surgery. Rapid vascularization of the biomaterial crucially contributes to its adequate incorporation without complications. Macrophage-activating lipopeptide-2 (MALP-2) is a toll-like receptor (TLR)-2/6 agonist with pro-angiogenic properties. Herein we analyzed, whether local single-shot application of MALP-2 improves the angiogenic host tissue response to Medpor(®). Medpor(®) (3 x 3 x 0.25mm) was implanted into dorsal skinfold chambers of BALB/c mice topically exposed to different MALP-2 doses (0.1μg and 0.5μg) or vehicle (control). The vascularization of the implants and the inflammatory foreign body reaction was analyzed using intravital fluorescence microscopy, histology and immunohistochemistry over 14 days. MALP-2 treatment dose-dependently improved the vascularization of Medpor(®), as indicated by a significantly higher functional microvessel density at the border and center of the implants when compared to controls. This was associated with a temporary increase of adherent leukocytes in host tissue venules during the first 3 days after implantation. At day 14, implants in MALP-2-treated chambers were surrounded by a granulation tissue, which exhibited a significantly higher density of CD31-positive microvessels and number of F4/80-positive macrophages when compared to controls. Additional biomaterial-free chambers did not show any signs of angiogenesis when treated with MALP-2. This indicates that locally applied MALP-2 effectively stimulates the early vascularization of Medpor(®) without inducing any local or systemic side effects. Accordingly, this easy approach may further improve the rapid incorporation of this biomaterial at the implantation site.
    Acta Biomaterialia 11/2014; 10(11). DOI:10.1016/j.actbio.2014.07.004 · 6.03 Impact Factor
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    ABSTRACT: Surfactant protein A has been shown to enhance opsonization and clearance of Staphylococcus aureus in vitro. Here, the phagocytosis of alveolar S. aureus was investigated in vivo using intravital microscopy. Fluorescence labelled S. aureus Newman cells were intratracheally administered to anesthetized mice and the alveolar surface was observed for fifteen minutes. Confirming previously reported in vitro data, surfactant protein A-deficient mice showed a significantly reduced uptake of bacteria compared to wild-type mice.
    Respiratory Research 08/2014; 15(1):85. DOI:10.1186/s12931-014-0085-2 · 3.09 Impact Factor
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    ABSTRACT: Background Moxifloxacin is a synthetic antibacterial agent belonging to the fluoroquinolone family. The antimicrobial activity of quinolones against Gram-positive and Gram-negative bacteria is based on their ability to inhibit topoisomerases. Quinolones are described to have immunomodulatory features in addition to their antimicrobial activities. It was the goal of this study to examine whether a short term treatment with moxifloxacin modulates the inflammation during a subsequently induced bacterial infection in an animal model. Methods Mice were treated with moxifloxacin or saline for two consecutive days and were subsequently intranasally infected with viable or heat-inactivated bacterial pathogens (Streptococcus pneumoniae, Pseudomonas aeruginosa) for 6 and 24 hours. Measurements of cytokines in the lungs and plasma were performed. Alveolar cells were determined in bronchoalveolar lavage fluits. Results The inflammation was increased after the inoculation of viable bacteria compared to inactivated bacteria. Numbers of total immune cells and neutrophils and concentrations of inflammatory mediators (e.g. KC, IL-1β, IL-17A) were significantly reduced in lungs of moxifloxacin-treated mice infected with inactivated and viable bacterial pathogens as compared to infected control mice. Plasma concentrations of inflammatory mediators were significantly reduced in moxifloxacin-treated mice. Immunohistochemistry showed a stronger infiltrate of TNF-α-expressing cells into lungs of saline-treated mice infected with viable P. aeruginosa as compared to moxifloxacin-treated mice. Conclusions These data show that in this pneumonia model moxifloxacin has anti-inflammatory properties beyond its antibacterial activity.
    Respiratory Research 07/2014; 15(1):82. DOI:10.1186/1465-9921-15-82 · 3.09 Impact Factor
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    ABSTRACT: The activation of inflammasome signaling mediates pathology of acute Pseudomonas aeruginosa pneumonia. This suggests that the inflammasome might represent a target to limit the pathological consequences of acute P. aeruginosa lung infection. Pannexin-1 (Px1) channels mediate the activation of caspase-1 and release of IL-1β induced by P2X7 receptor activation. The approved drug probenecid is an inhibitor of Px1 and ATP release. In this study, we demonstrate that probenecid reduces infection and inflammation in acute P. aeruginosa pneumonia. Treatment of mice prior to infection with P. aeruginosa resulted in an enhanced clearance of P. aeruginosa and reduced levels of inflammatory mediators, such as IL-1β. In addition, probenecid inhibited the release of inflammatory mediators in murine alveolar macrophages and human U937 cell-derived macrophages upon bacterial infection but not in human bronchial epithelial cells. Thus, Px1 blockade via probenecid treatment may be a therapeutic option in P. aeruginosa pneumonia by improving bacterial clearance and reducing negative consequences of inflammation.
    International Journal of Medical Microbiology 07/2014; 304(5-6). DOI:10.1016/j.ijmm.2014.05.002 · 3.61 Impact Factor
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    Le DD · Rochlitzer S · Fischer A · Heck S · Tschernig T · Sester M · Bals R · Welte T · Braun A · Dinh QT
    Respiratory research 06/2014; 15(1):73. · 3.09 Impact Factor
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    ABSTRACT: Background A neuroimmune crosstalk between dendritic cells (DCs) and airway nerves in the lung has recently been reported. However, the presence of DCs in airway sensory ganglia under normal and allergic conditions has not been explored so far. Therefore, this study aims to investigate the localisation, distribution and proliferation of DCs in airway sensory ganglia under allergic airway inflammation. Methods Using the house dust mite (HDM) model for allergic airway inflammation BALB/c mice were exposed to HDM extract intranasally (25 μg/50 μl) for 5 consecutive days a week over 7 weeks. With the help of the immunohistochemistry, vagal jugular-nodose ganglia complex (JNC) sections were analysed regarding their expression of DC-markers (MHC II, CD11c, CD103), the neuronal marker PGP 9.5 and the neuropeptide calcitonin gene-related peptide (CGRP) and glutamine synthetase (GS) as a marker for satellite glia cells (SGCs). To address the original source of DCs in sensory ganglia, a proliferation experiment was also carried in this study. Results Immune cells with characteristic DC-phenotype were found to be closely located to SGCs and vagal sensory neurons under physiological conditions. The percentage of DCs in relation to neurons was significantly increased by allergic airway inflammation in comparison to the controls (HDM 51.38 ± 2.38% vs. control 28.16 ± 2.86%, p < 0.001). The present study also demonstrated that DCs were shown to proliferate in jugular-nodose ganglia, however, the proliferation rate of DCs is not significantly changed in the two treated animal groups (proliferating DCs/ total DCs: HDM 0.89 ± 0.38%, vs. control 1.19 ± 0.54%, p = 0.68). Also, increased number of CGRP-positive neurons was found in JNC after allergic sensitisation and challenge (HDM 31.16 ± 5.41% vs. control 7.16 ± 1.53%, p < 0.001). Conclusion The present findings suggest that DCs may migrate from outside into the ganglia to interact with sensory neurons enhancing or protecting the allergic airway inflammation. The increase of DCs as well as CGRP-positive neurons in airway ganglia by allergic airway inflammation indicate that intraganglionic DCs and neurons expressing CGRP may contribute to the pathogenesis of bronchial asthma. To understand this neuroimmune interaction in allergic airway inflammation further functional experiments should be carried out in future studies.
    Respiratory Research 06/2014; 15(1):73. DOI:10.1186/1465-9921-15-73 · 3.09 Impact Factor

Publication Stats

3k Citations
693.93 Total Impact Points


  • 2010–2015
    • Universität des Saarlandes
      • Institut für Medizinische Mikrobiologie und Hygiene
      Saarbrücken, Saarland, Germany
  • 1995–2011
    • Hannover Medical School
      • Institute for Functional and Applied Anatomy
      Hanover, Lower Saxony, Germany
  • 2006
    • VU University Amsterdam
      • Department of Molecular Cell Biology and Immunology
      Amsterdamo, North Holland, Netherlands
  • 2005–2006
    • Fraunhofer Institute for Toxicology and Experimental Medicine ITEM
      Hanover, Lower Saxony, Germany
  • 2002
    • University of Pittsburgh
      • Department of Environmental and Occupational Health
      Pittsburgh, Pennsylvania, United States
    • University Hospital Essen
      Essen, North Rhine-Westphalia, Germany
  • 1998
    • Technische Universität Dresden
      • Institut für Pathologie
      Dresden, Saxony, Germany