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Search Results: 1 - 10 of 486 matches for " Britta Siegmund "
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Innate and adaptive immunity in inflammatory bowel disease
Britta Siegmund,Martin Zeitz
World Journal of Gastroenterology , 2011, DOI: 10.3748/wjg.v17.i27.3178
Abstract: Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time. Functional studies from in vivo models of intestinal inflammation as well as results from genome-wide association studies strongly suggest a cross-regulation of both arms. The present review will illustrate this interaction by selecting examples from innate immunity and adaptive immunity, and their direct impact on each other. Broadening our view by focusing on the cross-regulated areas of the mucosal immune system will not only facilitate our understanding of disease, but furthermore will allow identification of future therapeutic targets.
Extraluminal factors contributing to inflammatory bowel disease
Arvind Batra,Thorsten Stroh,Britta Siegmund
World Journal of Gastroenterology , 2011,
Abstract: Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease (IBD). The genome-wide association studies clearly support the earlier developed concept that IBD occurs in genetically predisposed individuals who are exposed to distinct environmental factors, which together result in dysregulation of the mucosal immune system. Thus, the majority of previous studies have focused on the immune response within the intestinal wall. The present review aims to emphasize the contribution of three extraluminal structures to this inflammatory process, namely the mesenteric fat tissue, the lymphatics and the microvasculature. Broadening our view across the intestinal wall will not only facilitate our understanding of the disease, but will also us to identify future therapeutic targets.
Bacterial Translocation – Impact on the Adipocyte Compartment
Tassilo Kruis,Arvind Batra,Britta Siegmund
Frontiers in Immunology , 2014, DOI: 10.3389/fimmu.2013.00510
Abstract: Over the last decade it became broadly recognized that adipokines and thus the fat tissue compartment exert a regulatory function on the immune system. Our own group described the pro-inflammatory function of the adipokine leptin within intestinal inflammation in a variety of animal models. Following-up on this initial work, the aim was to reveal stimuli and mechanisms involved in the activation of the fat tissue compartment and the subsequent release of adipokines and other mediators paralleled by the infiltration of immune cells. This review will summarize the current literature on the possible role of the mesenteric fat tissue in intestinal inflammation with a focus on Crohn’s disease (CD). CD is of particular interest in this context since the transmural intestinal inflammation has been associated with a characteristic hypertrophy of the mesenteric fat, a phenomenon called “creeping fat.” The review will address three consecutive questions: (i) What is inducing adipocyte activation, (ii) which factors are released after activation and what are the consequences for the local fat tissue compartment and infiltrating cells; (iii) do the answers generated before allow for an explanation of the role of the mesenteric fat tissue within intestinal inflammation? With this review we will provide a working model indicating a close interaction in between bacterial translocation, activation of the adipocytes, and subsequent direction of the infiltrating immune cells. In summary, the models system mesenteric fat indicates a unique way how adipocytes can directly interact with the immune system.
Combined Pulse Electroporation – A Novel Strategy for Highly Efficient Transfection of Human and Mouse Cells
Thorsten Stroh,Ulrike Erben,Anja A. Kühl,Martin Zeitz,Britta Siegmund
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009488
Abstract: The type of a nucleic acid and the type of the cell to be transfected generally affect the efficiency of electroporation, the versatile method of choice for gene regulation studies or for recombinant protein expression. We here present a combined square pulse electroporation strategy to reproducibly and efficiently transfect eukaryotic cells. Cells suspended in a universal buffer system received an initial high voltage pulse that was continuously combined with a subsequent low voltage pulse with independently defined electric parameters of the effective field and the duration of each pulse. At comparable viable cell recoveries and transfection efficiencies of up to 95% of all cells, a wide variety of cells especially profited from this combined pulse strategy by high protein expression levels of individual cells after transfection. Long-term silencing of gene expression by transfected small interfering RNA was most likely due to the uptake of large nucleic acid amounts as shown by direct detection of fluorochromated small interfering RNA. The highly efficient combined pulse electroporation strategy enables for external regulation of the number of naked nucleic acid molecules taken up and can be easily adapted for cells considered difficult to transfect.
The Selective Phosphodiesterase 4 Inhibitor Roflumilast and Phosphodiesterase 3/4 Inhibitor Pumafentrine Reduce Clinical Score and TNF Expression in Experimental Colitis in Mice
Florian Rieder, Britta Siegmund, Daniela S. Bundschuh, Hans-Anton Lehr, Stefan Endres, Andreas Eigler
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056867
Abstract: Objective The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. Methods The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. Results Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. Conclusions These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice.
Characterization of Chromosomal Instability in Murine Colitis-Associated Colorectal Cancer
Marco Gerling,Rainer Glauben,Jens K. Habermann,Anja A. Kühl,Christoph Loddenkemper,Hans-Anton Lehr,Martin Zeitz,Britta Siegmund
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0022114
Abstract: Patients suffering from ulcerative colitis (UC) bear an increased risk for colorectal cancer. Due to the sparsity of colitis-associated cancer (CAC) and the long duration between UC initiation and overt carcinoma, elucidating mechanisms of inflammation-associated carcinogenesis in the gut is particularly challenging. Adequate murine models are thus highly desirable. For human CACs a high frequency of chromosomal instability (CIN) reflected by aneuploidy could be shown, exceeding that of sporadic carcinomas. The aim of this study was to analyze mouse models of CAC with regard to CIN. Additionally, protein expression of p53, beta-catenin and Ki67 was measured to further characterize murine tumor development in comparison to UC-associated carcinogenesis in men.
New era in cancer immunotherapy: Twenty years to the discovery of monoclonal antibodies harnessing the immune system to eradicate tumors  [PDF]
Britta Hardy, Annat Raiter
Advances in Bioscience and Biotechnology (ABB) , 2013, DOI: 10.4236/abb.2013.44A005

The better understanding of the mechanism in which the immune system responds to the developing cancer provided the outcome in a new era in cancer immunotherapy. The tumor suppressive effect on the immune system is caused by negative T cell receptor signaling that abrogate immunity against the cancer cells. Novel monoclonal antibodies that target co-inhibitory receptors on T cells block the tumor induced inhibition of the immune system and enable the immune system to eradicate the tumors. The development of such antibodies started twenty years ago by the preparation of a monoclonal antibody termed BAT. A single administration of the antibody to tumor bearing mice resulted in striking anti tumor activity that was mediated by the lymphocytes. These studies provided a basis for the new era of cancer immunotherapy. The present review summarizes twenty years to the discovery of monoclonal antibodies harnessing the immune system to eradicate tumors.

Sensorik und Lebensmitteltechnologie: Salzreduktion - M glichkeiten und Grenzen
Siegmund B
Journal für Ern?hrungsmedizin , 2013,
Abstract: Die in der westlichen Welt aus gesundheitlichen Gründen angestrebte Reduktion der Kochsalzmenge vor allem in verarbeiteten Lebensmitteln stellt die Lebensmittelindustrie vor gro e Herausforderungen, da Kochsalz nicht nur aus sensorischen Gründen zugesetzt wird, sondern wegen verschiedener lebensmitteltechnologischer und mikrobiologischer Gründe einen schwer ersetzbaren Lebensmittelbestandteil darstellt.
Shift Towards Pro-inflammatory Intestinal Bacteria Aggravates Acute Murine Colitis via Toll-like Receptors 2 and 4
Markus M. Heimesaat, André Fischer, Britta Siegmund, Andreas Kupz, Julia Niebergall, David Fuchs, Hannah-Katharina Jahn, Marina Freudenberg, Christoph Loddenkemper, Arvind Batra, Hans-Anton Lehr, Oliver Liesenfeld, Michael Blaut, Ulf B. G?bel, Ralf R. Schumann, Stefan Bereswill
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000662
Abstract: Background Gut bacteria trigger colitis in animal models and are suspected to aggravate inflammatory bowel diseases. We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling. Methodology and Principal Findings Because knowledge on shifts in the intestinal microflora during colitis is limited, we performed a global survey of the colon flora of C57BL/10 wild-type (wt), TLR2-/-, TLR4-/-, and TLR2/4-/- mice treated for seven days with 3.5% dextrane-sulfate-sodium (DSS). As compared to wt animals, TLR2-/-, TLR4-/-, and TLR2/4-/- mice displayed reduced macroscopic signs of acute colitis and the amelioration of inflammation was associated with reduced IFN-gamma levels in mesenteric lymph nodes, lower amounts of neutrophils, and less FOXP3-positive T-cells in the colon in situ. During acute colitis E. coli increased in wt and TLR-deficient mice (P<0.05), but the final numbers reached were significantly lower in TLR2-/-, TLR4-/- and TLR2/4-/- animals, as compared to wt controls (P<0.01). Concentrations of Bacteroides/ Prevotella spp., and enterococci did not increase during colitis, but their numbers were significantly reduced in the colon of DSS-treated TLR2/4-/- animals (P<0.01). Numbers of lactobacilli and clostridia remained unaffected by colitis, irrespective of the TLR-genotype of mice. Culture-independent molecular analyses confirmed the microflora shifts towards enterobacteria during colitis and showed that the gut flora composition was similar in both, healthy wt and TLR-deficient animals. Conclusions and Significance DSS-induced colitis is characterized by a shift in the intestinal microflora towards pro-inflammatory Gram-negative bacteria. Bacterial products exacerbate acute inflammation via TLR2- and TLR4-signaling and direct the recruitment of neutrophils and regulatory T-cells to intestinal sites. E. coli may serve as a biomarker for colitis severity and DSS-induced barrier damage seems to be a valuable model to further identify bacterial factors involved in maintaining intestinal homeostasis and to test therapeutic interventions based upon anti-TLR strategies.
Franchising: An adequate Business Model for the "Proactive University"? A Public-Private Perspective on German HE
Leusing, Britta;
Sinéctica , 2011,
Abstract: public higher education institutions (heis) are experiencing circumstantial changes due to increasing financial pressure, higher autonomy and diversified actors on an increasingly challenging "market". these changes have led to forms of "entrepreneurial behavior" in public heis, such as franchising arrangements, which have become prominent in the context of internationalization and the export of study programs. over the last decade, a growing number of franchising arrangements on an intrastate level can be observed between public universities as franchisors and private, non-state recognized heis as franchisees in the german he sector. the german situation is of special interest because the he system is traditionally state-run and emphasizes the university as a prestige and sound institution. students pay almost no tuition fees for a public university degree except those students enrolled in a franchise model, where the fees are about 9 times higher. special organizational structures like intermediary stock companies and either the lack of or not commonly interpreted regulatory instruments lead to critical discussions of these models. the most crucial assumptions are that financial motives dominate decision making rather than pedagogical considerations and that public services are exploited to mask the interests of individuals. although these presumptions cannot be rejected through the empirical results of case study analyses, the opportunities of such strategic alliances are not to be underestimated. with adequate external and internal quality assurance mechanisms, franchising models can be used to strengthen the market position of public universities through a higher number of students and an extended portfolio of products and services. additionally, he programs can be offered more flexibly in regions with minimal he infrastructure and / or with programs particularly designed for "non-traditional students".
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