Floor de Kort

Academisch Medisch Centrum Universiteit van Amsterdam, Amsterdamo, North Holland, Netherlands

Are you Floor de Kort?

Claim your profile

Publications (8)48.71 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Different mouse models of inflammatory bowel diseases (IBD) demonstrate various aspects of the pathophysiology of IBD. We looked for overlapping gene expression profiles in three different mouse models of experimental colitis and analysed whether these overlapping genes are of help to find new genes that could be used as general markers in human IBD. Using Agilent mouse TOX oligonucleotide microarrays, we analysed the gene expression profiles in three widely used models of experimental colitis: 2,4,6-trinitrobenzene sulphonic acid, dextran sodium sulfate and CD4CD45RB transfer and looked for overlapping gene expression in these models. Overlapping genes were analysed using Lightcycler (Roche Diagnostics, Mannheim, Germany) in biopsy materials from human IBD and control tissue. Compared with control mice in dextran sodium sulfate, 2,4,6-trinitrobenzene sulphonic acid and the CD45RB transfer colitis mice five known genes, extracellular proteinase inhibitor (Expi), glutathione peroxidase 2 (Gpx2), mast cell protease 1 (Mcpt1), resistin-like beta (Retnlb) and sulphatase 2 (Sulf2), and two unknown genes were upregulated and the two genes aquaporin 8 (Aqp8) and kallikrein 5 (Klk5) were downregulated in all three models. In human Crohn's disease and ulcerative colitis biopsies, one of the upregulated glutathione peroxidase (Gpx2) and one of the downregulated Aqp8 genes in the mouse models were also differentially expressed in affected colonic tissue of patients with IBD. Experimental mouse models are suitable models for the search of new markers for human IBD. As both Gpx2 and Aqp8 are involved in H2O2 metabolism (Gpx2 as a radical scavenger whereas Aqp8 facilitates its diffusion), upregulation of Gpx2 and downregulation of Aqp8 could be a mechanism to defend against severe oxidative stress and indicate that H2O2 is a universal mediator in the inflammatory process in the colon. This provides a focus on homeostasis of the antioxidant pathway and its importance in IBD.
    No preview · Article · Jul 2008 · European Journal of Gastroenterology & Hepatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutations in the gene encoding the nucleotide-binding oligomerization domain 2 (NOD2) protein are associated with Crohn's disease (CD), but the mechanism underlying this is not completely understood. To study the mechanism of CD resulting from NOD2 mutations, we analyzed NOD2-dependent whole-genome expression profiles of patient-derived antigen-presenting cells. Monocyte-derived dendritic cells (DCs) from CD carriers of double-dose NOD2 mutations, wild-type CD patients, and wild-type healthy volunteers were stimulated with the NOD2 ligand muramyl dipeptide. Whole-genome microarrays were used to assess the differential gene expression. The clustering of significantly changed genes was analyzed by online gene ontology mapping software. In the DCs from the wild-type CD patient group, 683 genes were significantly changed, with most of the genes clustering in the pathways of inflammatory response. In addition, a significant number of genes clustered in the apoptosis regulation-related pathway. In the DCs from the healthy volunteer group, only 50 genes were significantly changed, predominantly those belonging to the response to pathogen pathway. Analysis of differentially expressed gene ontology pathways in the DCs from the NOD2 mutant CD patient group showed that the transcription of pathogen response genes was absent. In this group, 298 genes were significantly changed, predominantly clustering in the negative apoptosis regulation and cell organization and biogenesis pathways. Our results suggest that NOD2 mutations may result in perpetuation of mucosal inflammation through insufficient pathogen elimination. Further, these observations implicate a possible role of defective regulation of dendritic cell apoptosis in CD pathogenesis.
    Full-text · Article · Feb 2008 · Inflammatory Bowel Diseases
  • [Show abstract] [Hide abstract]
    ABSTRACT: Barrett's esophagus (BE) is a metaplastic condition in which normal squamous esophageal epithelium is replaced by columnar epithelium. It is proposed that one of the possible mechanisms is dedifferentiation of squamous epithelium into columnar epithelium. The pathophysiology through which this metaplasia occurs is unknown. A recent study by serial analysis of gene expression showed that bone morphogenetic protein 4 (BMP-4) is uniquely expressed in BE. In this study, the role of the BMP pathway in the metaplastic transformation of normal squamous cells into columnar cells was examined. Tissues from patients with esophagitis and BE and in an esophagitis-BE rat model were examined for the activation of the BMP pathway. Short-term cultures of primary normal squamous esophageal cells were treated with BMP-4, and cell biological changes were examined by Western blot analysis, immunohistochemistry, and microarrays. In both human and rat tissues, the BMP pathway proved to be activated in esophagitis and BE. Upon incubation of squamous cell cultures with BMP-4, the cytokeratin expression pattern showed a shift that was consistent with columnar epithelium. Involvement of the BMP pathway was suggested by up-regulation of Phosphorylated-Smad 1/5/8 (P-Smad 1/5/8) that was effectively blocked by Noggin, a BMP antagonist. Comparison of the gene expression profiles of squamous cells, BMP-4-treated squamous cells, and BE cells showed a significant shift in the profile of the BMP-4-treated squamous cells toward that of the cultured BE cells. These results suggest that the BMP pathway could play a role in the transformation of normal esophageal squamous cells into columnar cells.
    No preview · Article · Jun 2007 · Gastroenterology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mouse models of inflammatory bowel diseases (IBD) are used to unravel the pathophysiology of IBD and to study new treatment modalities, but their relationship to Crohn's disease (CD) or ulcerative colitis (UC) is speculative. Using Agilent mouse TOX oligonucleotide microarrays, we analyzed colonic gene expression profiles in three widely used models of experimental colitis. In 2 of the models (TNBS and DSS-induced colitis), exogenous agents induce the colitis. In the third model the colitis is induced after transfer of a T-cell population (CD4(+)CD45RB(high) T cells) that lacks regulatory cells into an immunodeficient host. Compared with control mice, in DSS, TNBS, and the CD45RB transfer colitis mice, 387, 21, and 582 genes were more than 2-fold upregulated in the intestinal mucosa. Analyses of exclusively shared gene expression profiles between the different models revealed that DSS/transfer colitis share 69 concordantly upregulated genes, DSS/TNBS 6, and TNBS/transfer colitis 1. Seven genes were upregulated in all three models. The CD45RB transfer model expression profile included the most genes that are known to be upregulated in IBD. Of 32 genes that are known to change transcriptional activity in IBD (TNF, IFN-gamma, Ltbeta, IL-6, IL-16, IL-18R1, IL-22, CCR2, 7, CCL2, 3, 4, 5, 7, 11, 17, 20, CXCR3, CXCL1, 5, 10, Mmp3, 7,9, 14, Timp1, Reg3gamma, and Pap, S-100a8, S-100a9, Abcb1, and Ptgs2), 2/32 are upregulated in TNBS, 15/32 are upregulated or downregulated in DSS and 30/32 are upregulated or downregulated in the CD45RB transfer colitis. The pattern of gene expression in the CD45RB transfer model most closely reflects altered gene expression in IBD.
    Full-text · Article · Mar 2007 · Inflammatory Bowel Diseases

  • No preview · Article · Apr 2006 · Inflammatory Bowel Diseases

  • No preview · Article · Jan 2006 · European Journal of Gastroenterology & Hepatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper presents a global test to be used for the analysis of microarray data. Using this test it can be determined whether the global expression pattern of a group of genes is significantly related to some clinical outcome of interest. Groups of genes may be any size from a single gene to all genes on the chip (e.g. known pathways, specific areas of the genome or clusters from a cluster analysis). The test allows groups of genes of different size to be compared, because the test gives one p-value for the group, not a p-value for each gene. Researchers can use the test to investigate hypotheses based on theory or past research or to mine gene ontology databases for interesting pathways. Multiple testing problems do not occur unless many groups are tested. Special attention is given to visualizations of the test result, focussing on the associations between samples and showing the impact of individual genes on the test result. An R-package globaltest is available from http://www.bioconductor.org
    Full-text · Article · Feb 2004 · Bioinformatics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Microarrays of oligonucleotide expression libraries can be hybridised with either cDNA, generated from mRNA during reverse transcription, or cRNA, generated in an Eberwine mRNA amplification procedure. While methods for fluorescent labelling of cDNA have been thoroughly investigated, methods for cRNA labelling have not. To this purpose, we developed an aminoallyl-UTP (aa-UTP) driven cRNA labelling protocol and compared it in expression profiling studies using spotted 7.5 K 65mer murine oligonucleotide arrays with labelling via direct incorporation of Cy-UTPs. The presence of dimethylsulfoxide during coupling of aa-modified cRNA with N-hydroxysuccinimide-modified, fluorescent Cy dyes greatly enhanced the labelling efficiency, as analysed by spectrophotometry and fluorescent hybridisation signals. Indirect labelling using aa-UTP resulted in 2- to 3-fold higher degrees of labelling and fluorescent signals than labelling by direct incorporation of Cy-UTP. By variation of the aa-UTP:UTP ratio, a clear optimal degree of labelling was found (1 dye per 20-25 nt). Incorporation of more label increased Cy3 signal but lowered Cy5 fluorescence. This effect is probably due to quenching, which is more prominent for Cy5 than for Cy3. In conclusion, the currently developed method is an efficient, robust and inexpensive technique for fluorescent labelling of cRNA and allows sensitive detection of gene expression profiles on oligonucleotide microarrays.
    Full-text · Article · Apr 2003 · Nucleic Acids Research

Publication Stats

913 Citations
48.71 Total Impact Points


  • 2007-2008
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Center for Experimental and Molecular Medicine
      • • Department of Gastroenterology and Hepatology
      Amsterdamo, North Holland, Netherlands
    • AMC Health
      New York City, New York, United States
  • 2003-2004
    • Leiden University Medical Centre
      • Department of Human Genetics
      Leyden, South Holland, Netherlands