Frank Weiler

Publications of Frank Weiler

• Human rectal mucosal gene expression after consumption of digestible and non-digestible carbohydrates.

  Authors: Jürgen Schauber, Frank Weiler, Andrea Gostner, Ralph Melcher, Theodor Kudlich, Hardi Lührs, Wolfgang Scheppach

  Molecular nutrition & food research. 12/2006; 50(11):1006-12.

  The effect of regular consumption of the low-digestible and prebiotic isomalt versus the digestible sucrose on gene expression in rectal mucosa was examined in a randomized double-blind crossoverThe effect of regular consumption of the low-digestible and prebiotic isomalt versus the digestible sucrose on gene expression in rectal mucosa was examined in a randomized double-blind crossover trial. Nineteen healthy volunteers received 30 g isomalt per day or 30 g sucrose as part of a controlled diet over two 4-week test periods with a 4-week washout period in between. At the end of each test phase rectal biopsies were obtained. After RNA extraction mucosal gene expression was assayed using GeneChip microarrays. In addition, expression of cathelicidin hCap18/LL37, cellular detoxification enzymes GSTpi, UGT1A1 and CYP3A4, cyclooxygenase 2 and barrier factors MUC2 and ZO-1 were determined by real-time RT-PCR. Microbiological analyses of fecal samples revealed a shift of the gut flora towards an increase of bifidobacteria following consumption of the diet containing isomalt. Isomalt consumption did not affect rectal mucosal gene expression in microarray analyses as compared to sucrose. In addition, the expression of cathelicidin LL37, GSTpi, UGT1A1, CYP3A4, COX-2, MUC2 and ZO-1 was not changed in rectal biopsies. We conclude that gene expression of the human rectal mucosa can reliably be measured in biopsy material taken at endoscopy. Dietary intervention with the low digestible isomalt compared with the digestible sucrose did not affect gene expression in the lining rectal mucosa.

• Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases.

  Authors: Jürgen Schauber, Daniel Rieger, Frank Weiler, Jan Wehkamp, Matthias Eck, Klaus Fellermann, Wolfgang Scheppach, Richard L Gallo, Eduard F Stange

  European journal of gastroenterology & hepatology. 07/2006; 18(6):615-21.

  BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by a breakdown of colon epithelial barrier function. Antimicrobial peptides like cathelicidins are molecules of the innate immuneBACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by a breakdown of colon epithelial barrier function. Antimicrobial peptides like cathelicidins are molecules of the innate immune system located at epithelial surfaces. Cathelicidins influence microbial growth and inflammation and may play a role in IBD. In this study, the expression of human cathelicidin hCAP18/LL-37 was investigated in the intestinal mucosa from patients suffering from ulcerative colitis or Crohn's disease. METHODS: Biopsy material from colon and ileal mucosa of a total of 89 patients (34 with Crohn's disease, 27 with ulcerative colitis, 28 control patients) was evaluated for cathelicidin expression by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. Colon epithelial cells were stimulated in vitro with various cytokines to evaluate mechanisms that influence cathelicidin production. RESULTS: Cathelicidin expression was significantly increased in inflamed and non-inflamed colon mucosa from ulcerative colitis patients compared to non-inflamed control mucosa. In patients with Crohn's disease cathelicidin expression was not changed in inflamed or non-inflamed colon or ileal mucosa independent of NOD2 status. Biopsies evaluated by immunohistochemistry showed epithelial cathelicidin expression in the upper crypt that was diffuse in controls and only basal in IBD patients. Inflammation mediators, alone or in combination with the known cathelicidin inducer butyrate, had no effect on cathelicidin expression in cultured colon cells. CONCLUSIONS: In IBD the colonic expression of human cathelicidin is altered: cathelicidin expression is increased in inflamed and non-inflamed mucosa in patients suffering from ulcerative colitis but not in Crohn's disease. This deficiency may further compromise the antimicrobial barrier in Crohn's disease.

• Influence of protein kinase C on transcription of the tight junction elements ZO-1 and occludin.

  Authors: Frank Weiler, Theresa Marbe, Wolfgang Scheppach, Jürgen Schauber

  Journal of cellular physiology. 08/2005; 204(1):83-6.

  Tight junctions as an epithelial barrier against paracellular diffusion have mainly been investigated on the protein level with particular respect to subcellular localization. In this study,Tight junctions as an epithelial barrier against paracellular diffusion have mainly been investigated on the protein level with particular respect to subcellular localization. In this study, real-time PCR has been established to investigate the influence of protein kinase C (PKC) modulation on the transcription of tight junction elements occludin and ZO-1 in the cell line T84. Activation of PKC by the phorbol ester TPA induced ZO-1 and occludin transcription, whereas PKC inhibition lead to decreased expression levels. Activation of PKC exerted its effect on transcript level directly. PKC signal was partially transduced via MEK1/MEK2 but depended strongly on MAPK independent pathways probably involving nuclear localized PKC, whereas p38 signaling was not implicated. TPA induced loss of function concomitant with a dislocation of ZO-1 and occludin could be prevented by inhibition of MEK1 by PD98059. Overall ZO-1 and occludin seem to be identically regulated in colonic epithelium on the transcript level.

• The butyrate story: old wine in new bottles?

  Authors: Wolfgang Scheppach, Frank Weiler

  Current opinion in clinical nutrition and metabolic care. 10/2004; 7(5):563-7.

  PURPOSE OF REVIEW: Short-chain fatty acids are important end products of bacterial carbohydrate fermentation in the colon. In particular, n-butyrate is thought to play a regulatory role in thePURPOSE OF REVIEW: Short-chain fatty acids are important end products of bacterial carbohydrate fermentation in the colon. In particular, n-butyrate is thought to play a regulatory role in the maintenance of a physiological environment. Disturbances in the interplay between the microflora and the lining epithelium may lead to mucosal inflammation and promote carcinogenesis. The purpose of this article is to review the literature between March 2003 and February 2004 and to determine if recent studies have improved the understanding of butyrate effects in health and disease. RECENT FINDINGS: Preclinical studies (cell culture experiments, animal studies) using modern molecular biological tools (including cDNA arrays) have provided new insights into the action of butyrate on colonic epithelial, vascular endothelial and extracolonic cell types. The new information adds pieces of evidence to the assumption that butyrate may ameliorate colonic inflammation and may be chemopreventive in carcinogenesis. In contrast, new data from clinical studies have been limited in the review period. SUMMARY: In the era of molecular biology our understanding of subcellular processes that ultimately lead to inflammatory bowel disease or colorectal cancer has widened considerably. The new powerful technology of genomics and proteomics, however, raises new questions without easy answers. With this new information in mind, we will have to go back to human intervention trials to test the hypotheses generated in vitro. The preclinical data from the review period justify the need for carefully designed clinical trials to test the benefits derived from butyrate production.

• Zygocin, a secreted antifungal toxin of the yeast Zygosaccharomyces bailii, and its effect on sensitive fungal cells.

  Authors: Frank Weiler, Manfred J Schmitt

  FEMS yeast research. 04/2003; 3(1):69-76.

  Zygocin, a protein toxin produced and secreted by a killer virus-infected strain of the osmotolerant yeast Zygosaccharomyces bailii, kills a great variety of human and phytopathogenic yeasts andZygocin, a protein toxin produced and secreted by a killer virus-infected strain of the osmotolerant yeast Zygosaccharomyces bailii, kills a great variety of human and phytopathogenic yeasts and filamentous fungi. Toxicity of the viral toxin is envisaged in a two-step receptor-mediated process in which the toxin interacts with cell surface receptors at the level of the cell wall and the plasma membrane. Zygocin receptors were isolated and partially purified from the yeast cell wall mannoprotein fraction and could be successfully used as biospecific ligand for efficient one-step purification of the 10-kDa protein toxin by receptor-mediated affinity chromatography. Evidence is presented that zygocin-treated yeast cells are rapidly killed by the toxin, and intensive propidium iodide staining of zygocin-treated cells indicated that the toxin is affecting cytoplasmic membrane function, most probably by lethal ion channel formation. The presented findings suggest that zygocin has potential as a novel antimycotic in combating fungal infections.

• The Zygosaccharomyces bailii antifungal virus toxin zygocin: cloning and expression in a heterologous fungal host.

  Authors: Frank Weiler, Klaus Rehfeldt, Frank Bautz, Manfred J Schmitt

  Molecular microbiology. 12/2002; 46(4):1095-105.

  Zygocin, a monomeric protein toxin secreted by a virus-infected killer strain of the osmotolerant spoilage yeast Zygosaccharomyces bailii, kills a broad spectrum of human and phytopathogenic yeastsZygocin, a monomeric protein toxin secreted by a virus-infected killer strain of the osmotolerant spoilage yeast Zygosaccharomyces bailii, kills a broad spectrum of human and phytopathogenic yeasts and filamentous fungi by disrupting cytoplasmic membrane function. The toxin is encoded by a double-stranded (ds)RNA killer virus (ZbV-M, for Z. bailii virus M) that stably persists within the yeast cell cytosol. In this study, the protein toxin was purified, its N-terminal amino acid sequence was determined, and a full-length cDNA copy of the 2.1 kb viral dsRNA genome was cloned and successfully expressed in a heterologous fungal system. Sequence analysis as well as zygocin expression in Schizosaccharomyces pombe indicated that the toxin is in vivo expressed as a 238-amino-acid preprotoxin precursor (pptox) consisting of a hydrophobic N-terminal secretion signal, followed by a potentially N-glycosylated pro-region and terminating in a classical Kex2p endopeptidase cleavage site that generates the N-terminus of the mature and biologically active protein toxin in a late Golgi compartment. Matrix-assisted laser desorption mass spectrometry further indicated that the secreted toxin is a monomeric 10.4 kDa protein lacking detectable post-translational modifications. Furthermore, we present additional evidence that in contrast with other viral antifungal toxins, zygocin immunity is not mediated by the toxin precursor itself and, therefore, heterologous pptox expression in a zygocin-sensitive host results in a suicidal phenotype. Final sequence comparisons emphasize the conserved pattern of functional elements present in dsRNA killer viruses that naturally infect phylogenetically distant hosts (Saccharomyces cerevisiae and Z. bailii) and reinforce models for the sequence elements that are in vivo required for viral RNA packaging and replication.

• Knowledge Based Automated Feature Extraction to Categorize Secondary Digitized Radiographs

  Authors: Michael Kohnen, Frank Vogelsang, Berthold B. Wein, Markus Kilbinger, Rolf W. Gunther, Frank Weiler

  02/2000;

  An essential part of the IRMA-project (Image Retrieval in Medical Applications) is the categorization of digitized images into predened classes using a combination of dierent independent features. ToAn essential part of the IRMA-project (Image Retrieval in Medical Applications) is the categorization of digitized images into predened classes using a combination of dierent independent features. To obtain an automated and content-based categorization, the following features are extracted from the image data. Fourier coecients of normalized projections are computed to supply a scale- and translation-invariant description of the projections. Furthermore histogram information and Co-occurrence matrices are calculated to supply information about the grey value distribution and textural information. But the key part of the feature extraction is the shape information of the objects represented by an Active Shape Model. The Active Shape Model supports various form variations given by a representative training set; we use one particular Active Shape Model for each image class. These dierent Active Shape Models are matched on precomputed image data with a simulated annealing optimization. The dierent extracted features were chosen with regard to the dierent aspects of the image contents. They give a good measure of what is visible in the image described by a low number of dierent features. Using a combination of dierent features for classication, results in a robust categorization of image data, which is a basic step towards medical archives that allow retrieval results for queries of diagnostic relevance.

• Kategorisierung von digitalen Röntgenbildern mit parametrisierbaren Formmodellen.

  Authors: Michael Kohnen, Frank Vogelsang, Frank Weiler, Jörg Bredno, Jörg Dahmen

  01/2000

• Modell- und wissensbasierte Segmentierung und Bildanalyse von Rötgenbildern.

  Authors: Frank Vogelsang, Frank Weiler, Michael Kohnen, Michael van Laak, Markus Kilbinger, Berthold B. Wein, Rolf W. Günther

  01/1999

• Detektion von Rippenschatten in digitalen Röntgenbildern durch synergetische Algorithmen - Diagnoseunterstützung durch Schattenkompensation.

  Authors: Frank Vogelsang, Frank Weiler, Thomas Lesch

  Bildverarbeitung für die Medizin: Algorithmen, Systeme, Anwendungen, Proceedings des Aachener Workshops am 8. und 9. November 1996; 01/1996

• Automatische Erkennung von Bildinhalten bei Standardröntgenaufnahmen.

  Authors: Frank Weiler, Frank Vogelsang

  Bildverarbeitung für die Medizin: Algorithmen, Systeme, Anwendungen, Proceedings des Aachener Workshops am 8. und 9. November 1996; 01/1996