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  • 1
    Electronic Resource
    Electronic Resource
    HLA-DRB1 * 03, but not the TNFA -308 promoter gene polymorphism, confers protection against fistulising Crohn’s disease (1998)
    Springer
    Immunogenetics 47 (1998), S. 451-455 
    Details
    ISSN: 1432-1211
    Keywords: Key words Crohn’s disease ; Fistula ; HLA association ; DRB1 ; TNF polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Crohn’s disease (CD) appears in forms so diverse that it has been hypothesized CD might be a syndrome, with different pathogenic mechanisms leading to the various clinical phenotypes. This may plausibly explain the conflicting and inconclusive results with regard to HLA associations in unselected groups of patients. The power of these association studies may increase when disease heterogeneity is taken into account. As fistulising CD has been proposed as a separate subgroup of patients with CD, we studied the carrier frequencies (CF) of the DRB1 alleles in 35 unrelated Caucasian Dutch CD patients with proven peri-anal fistulas. A striking decrease in the frequency of the DRB1 * 03 allele was found in those patients with peri-anal fistulas when compared with a panel of 2400 healthy controls (HC) (3% vs 25%; P = 0.005; Odds Ratio [OR] = 0.09). The DRB1 * 03 allele is in strong linkage disequilibrium with a polymorphism at position –308 in the promoter region of the gene encoding TNFα (TNFA-308 * 2). We investigated whether this allele frequency was decreased as well. Surprisingly, the CF of TNFA-308 * 2 was 29%, not different from the CF of 98 HC (34%; P = 0.7; OR = 0.8). This study is the first showing a significant negative association between DRB1 * 03 and a particular subgroup of CD patients. Thus, patient selection may largely determine the outcome of genetic association studies in CD, as we previously observed no association with this allele in an unselected population of CD patients. As DRB1 * 03 frequency, but not the closely linked TNFA-308 * 2, was decreased, this suggests recombination between the DRB1 and TNFA loci in this group of patients, and may help to define the biological basis of fistula formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050382
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  • 2
    Electronic Resource
    Electronic Resource
    IL1B gene polymorphisms influence the course and severity of inflammatory bowel disease (1999)
    Springer
    Immunogenetics 49 (1999), S. 527-531 
    Details
    ISSN: 1432-1211
    Keywords: Key words Inflammatory bowel disease ; IL1B gene polymorphism ; Crohn's disease ; Ulcerative colitis ; Disease susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  There is evidence of a disbalance in the inflammatory regulation of patients with inflammatory bowel diseases (IBD). Interleukin-1β plays an important role in the pro-inflammatory response. Our aim was to study the influence which IL1B gene polymorphisms may have on the severity and course of these diseases. Ninety-six patients with ulcerative colitis (UC), 98 patients with Crohn's disease (CD), and 132 ethnically matched healthy individuals (HC) were typed for the polymorphic sites in the promoter region (position –511) and in exon 5 (position +3953) of the IL1B gene, using polymerase chain reaction (PCR)-based methods. In the CD group a significant association (P=0.009) was found in this pair of genes. Homozygotes for allele 1 at position +3953 were more often present (69% vs 31%) in the subgroup of patients carrying at least one copy of allele 2 at position –511. This association was significant in patients with non-perforating disease (P=0.002), but was not present in patients with perforating-fistulizing disease. The distribution of both allelic pairs in the non-fistulizing group proved to be significantly different from HC (P〈0.05), UC (P〈0.03), and the fistulizing group (P〈0.05). There was a similar association in non-operated patients (P=0.024), whereas no such association was found in surgically treated patients. Among carriers of allele 2 at position –511, UC patients with more severe bleeding symptoms (P=0.006) were less frequently found. These results suggest that IL1B gene polymorphisms participate in determining the course and severity of inflammatory bowel disease and contribute to explain the heterogeneity of these diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050530
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  • 3
    Electronic Resource
    Electronic Resource
    No allelic variant associations of the IL-1 and TNF gene polymorphisms in the susceptibility to duodenal ulcer disease (2005)
    Oxford, UK : Blackwell Science Ltd
    International journal of immunogenetics 32 (2005), S. 0 
    Details
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Recent studies have reported the association of a pro-inflammatory profile of genetic polymorphisms in IL-1B, IL-1RN, TNF-A, and IL-10 genes with an increased risk of non-cardia gastric cancer. Because gastric cancer and duodenal ulcer are mutually exclusive outcomes of Helicobacter pylori infection, we aimed to investigate possible allelic variant associations of several functional polymorphisms in the IL-1B, IL-1RN, TNFA, and LTA genes in the susceptibility to duodenal ulcer. Genomic DNA from 118 patients with duodenal ulcer and 97 healthy controls was typed for the IL-1B polymorphisms at positions −511, −31, and +3954, the VNTR polymorphism in intron 2 of the IL-1RN gene, the TNFA−308, TNFA −238, and the NcoI and BsI LTA polymorphisms by PCR, SSCP and TaqMan assays. H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) use was investigated in patients and controls. Logistic regression analysis identified H. pylori infection (OR: 12.86; 95%CI: 3.85–43), NSAID use (OR: 11.95; 95%CI: 4.19–34.05), and family history-ulcer (OR: 3.79; 95%CI: 1.68–8.54) as independent risk factors for duodenal ulcer. When the effect of the combinations of IL-1 and TNF genotypes was studied we found that the distribution of all possible combinations of these eight polymorphisms was similar in duodenal ulcer patients and controls. The simultaneous carriage of alleles IL-1RN*2/IL-1B −31T/IL-1B −511C/IL-IB +3954C/TNF-HaplotypeE negative (termed in some studies as ‘low-producing’ alleles) was increased in H. pylori-positive duodenal ulcer patients compared to H. pylori-infected healthy controls (10.5% vs. 5.9%) although the difference did not reach statistical significance (OR: 1.85; 95%CI: 0.57–5.99, P = 0.41). Moreover, no differences were found with respect to H. pylori status, NSAID use, age, gender, smoking habit, type of complication, recurrence of the ulcer, and need for surgical treatment. Our data show no association between allelic variants of IL-1 and TNF gene polymorphisms in the susceptibility to and final outcome of duodenal ulcer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1744-313X.2005.00528.x
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  • 4
    Electronic Resource
    Electronic Resource
    CARD15 gene mutations in periodontitis (2004)
    Oxford, UK : Munksgaard International Publishers
    Journal of clinical periodontology 31 (2004), S. 0 
    Details
    ISSN: 1600-051X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objectives: The CARD15 gene encodes the Nod2 protein, which is involved in intracellular recognition of bacterial products like peptidoglycan, activates inflammation and regulates apoptosis through nuclear factor-kappa B, a transcription factor that plays a central role in the innate immunity. Two functional mutations, an insertion mutation at nucleotide 3020 (3020insC) and a missense mutation C2104T in the CARD15 gene (originally NOD2 gene) have been reported to be associated with Crohn's disease. Our aim was to investigate the occurrence of CARD15 gene polymorphisms in adult patients with periodontitis taking into account smoking and presence of putative periodontal pathogens as additional variables.Material and methods: A case–control study was performed in 104 Dutch Caucasian patients with severe adult periodontitis (54 non-smokers and 50 smokers, mean age 46 years) and in 97 ethnically matched, periodontal healthy controls (73 non-smokers and 24 smokers, mean age 40 years). DNA isolated from a mouthwash was typed with PCR technology. Presence of putative periodontal pathogens was established by culture technique.Results: Frequencies of the CARD15 3020insC and 2104T mutations were similar in the periodontitis group and in the control group (5.1% and 13.3%; 5.2% and 10.3%, respectively). The highest carrier frequency of CARD15 mutations was found in non-smoking patients without Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans (29.4% versus 17.4% in controls); however it did not reach statistical significance.Conclusion: Our results suggest no role for CARD15 3020insC and C2104T mutations in adult periodontitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-051X.2004.00577.x
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  • 5
    Electronic Resource
    Electronic Resource
    A critical approach to new forms of treatment of Crohn's disease and ulcerative colitis (2002)
    Oxford, UK : Blackwell Science, Ltd
    Alimentary pharmacology & therapeutics 16 (2002), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Most patients with inflammatory bowel disease can be managed with conventional immunosuppressive therapy. The choice of agents to prevent relapses of inflammatory bowel disease must be based on efficacy, toxicity and cost. Studies in animal models of inflammatory bowel disease indicate that chronic intestinal inflammation results from enhanced immune responses to bacteria that are present normally in the lumen. Loss of tolerance, an abnormal function or defective healing of the mucosal barrier may all give raise to chronic intestinal inflammation. This hypothesis is the basis of new therapies aimed at either decreasing the levels of luminal bacterial antigens and/or selectively blocking detrimental mucosal immune responses. Anti-TNF is an example of this novel approach that is very effective in Crohn's disease. The use of biological therapy is costly, however, and the long-term complications are not yet known. The recent increase of tuberculosis in patients treated with anti-TNF indicates that careful monitoring is necessary. It is clear that the new forms of treatment may play an important role in tailoring the appropriate drug to a specific group of patients. However, for the time being, fine-tuning in the use of conventional immunosuppression is necessary. New knowledge in the pharmacogenetics of these compounds allows improvements to be made in their use. It is to be hoped that a critical approach in the use of current and future drugs, taking into account the advances in the aetiopathogenesis of inflammatory bowel disease, will contribute to the quality of life of patients with inflammatory bowel disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.16.s4.8.x
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  • 6
    Electronic Resource
    Electronic Resource
    Effect of zinc therapy on natural killer cell activity in inflammatory bowel disease (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 7 (1993), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Disturbances in zinc metabolism have been documented in patients with inflammatory bowel disease. In this study we evaluated the effect of in vivo treatment with zinc on the in vitro natural killer cell activity in thirteen inflammatory bowel disease patients, with stable disease and mild–moderate disease activity, in a double-blind randomized cross-over trial. The results of our study show a long-lasting effect of in vivo zinc administration, which decreased peripheral blood natural killer cell activity in inflammatory bowel disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.1993.tb00099.x
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  • 7
    Electronic Resource
    Electronic Resource
    Secretion of Tumour Necrosis Factor α and Lymphotoxin α in Relation to Polymorphisms in the TNF Genes and HLA-DR Alleles. Relevance for Inflammatory Bowel Disease (1996)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 43 (1996), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The genes for tumour necrosis factor alpha (TNFα) and lymphotoxin alpha (LTα; TNFβ) are tandemly arranged in the central region of the MHC. They may, therefore, be of importance for the aetiology of MHC-associated diseases. The authors have prospectively studied the secretion of TNFα and LTα in relation to polymorphisms at positions -308 and -238 in the TNFα gene (TNFA), and two polymorphisms in the first intron of the LTα gene (LTA), as well as HLA-DR in 30 patients with chronic inflammatory bowel diseases (IBD) and 12 healthy controls. In the Dutch population, the alleles of these four polymorphisms are present in only five combinations, called TNF-haplotypes: TNF-C, -E, -H, -I, and -P. Significant associations between TNF haplotypes and TNFα and LTα secretion were found when PBMC were cultured with T-cell activators, irrespective of disease. Mean TNFα secretion of individuals carrying the HLA-DR3 associated TNF-E haplotype was significantly higher, as compared to individuals without this haplotype (26 441 pg/ml versus 19 629 pg/ml; P = 0.014). Individuals carrying the TNF-C haplotype produced the lowest amount of TNFα (17 408 pg/ml; P = 0.022). The TNF-C and TNF-E haplotypes differ only at position -308 in the promoter of TNFA. Individuals carrying the HLA-DR1 associated TNF-I haplotype produced significantly less LTα when compared to those who lack this haplotype (1979 pg/ml versus 3462 pg/ml; P = 0.006). As the TNF-I haplotype is also associated with low TNFα secretion, this haplotype thus defines a ‘low secretor phenotype’. In conclusion, this is the first study to show associations between TNF haplotypes and TNFα and LTα secretion when T-cell stimulators are used. These findings will contribute to define disease heterogeneity in IBD and may be of relevance for understanding the pathogenesis of autoimmune diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1996.d01-65.x
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  • 8
    Electronic Resource
    Electronic Resource
    Image quality and radiopharmaceutical parameters of Indium-111 granulocytes in scintigraphy of inflammatory bowel disease (1989)
    Springer
    European journal of nuclear medicine 15 (1989), S. 197-200 
    Details
    ISSN: 1619-7089
    Keywords: 111In-granulocytes ; Image quality ; Inflammatory bowel disease ; Leukoscintigraphy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was undertaken to investigate the influence of various parameters of injected autologous 111In labelled granulocytes on scintigraphic image quality. Forty-two scintigrams of 37 patients with inflammatory bowel disease were evaluated. The images were divided into three groups according to quality: good, intermediate and poor. The relationships between image quality and such radiopharmaceutical parameters as injected dose of 111In, number of injected cells and specific activity were investigated. It appeared that in order to obtain interpretable images, a specific activity of at least 85 kBq 111In/million cells was necessary. The activity of the injected dose must exceed 7 MBq if poor quality images and very long acquisition times are to be avoided.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253794
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  • 9
    Electronic Resource
    Electronic Resource
    Presence ofHelicobacter pylori in the oral cavity, oesophagus, stomach and faeces of patients with gastritis (1995)
    Springer
    European journal of clinical microbiology & infectious diseases 14 (1995), S. 234-237 
    Details
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The presence ofHelicobacter pylori in the oral cavity (6 sites), oesophagus, stomach and bowel of 20 dyspeptic patients was investigated. Samples were cultured on three selective media and analyzed by 16S rDNA polymerase chain reaction (PCR) and southern hybridization.Helicobacter pylori DNA was detected by PCR from oral-cavity samples of three (20 %) and from faeces samples of only one (7 %) of the patients whose stomach biopsies were positive forHelicobacter pylori. When culture was used, the microorganism's rate of recovery from the oral cavity and faeces was 13 % and 7%, respectively. One patient had aHelicobacter pylori-like organism in samples collected from the tongue and palate. Both strains were urease, catalase and oxidase positive and grew microaerophilically but were negative on PCR analysis. This demonstrates the possibility of false identification ofHelicobacter pylori by use of routine enzyme reactions. Interestingly, specimens collected from the cheeks of three patients were positive forHelicobacter pylori by PCR analysis. This is the first instance of detection of this micro-organism in the cheek.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02310363
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  • 10
    Electronic Resource
    Electronic Resource
    The immunoglobulin-bearing cells in the lamina propria and the clinical response to a gluten-free diet in dermatitis herpetiformis (1977)
    Springer
    Archives of dermatological research 258 (1977), S. 223-230 
    Details
    ISSN: 1432-069X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 17 Patienten mit DH wurden vielfältige Duodenum- und Jejunum-Biopsien verrichtet. Die Dünndarm-Biopsien aller dieser Patienten zeigten histopathologische Änderungen, die cöliakie-ähnlich waren. Vierzehn dieser Patienten hielten eine glutenfreie Diät (GFD) während mehr als 8 Monaten. Bei allen untersuchten Patienten, die Diät hielten, verbesserten sich die Dünndarmerscheinungen. Die Dosierung von Dapsone, nötig für die Kontrolle der Hauterscheinungen, konnte reduziert werden um mehr als 50% bei 4 Patienten, und 5 andere Patienten, die die glutenfreie Diät auch hielten, brauchten diese Dapsone nicht mehr. Die Immunoglobulin enthaltenden Zellen in der Lamina propria wurden gezählt bei 8 Patienten, die nicht eine GFD hielten, bei 6 Patienten mit dieser GFD und bei 8 gesunden Kontroll-Personen. Die Zahl der IgA, IgM und IgG enthaltenden Zellen hat bei den meisten der DH-Patienten, die keine GFD hielten, zugenommen. Die Zahl der IgM enthaltenden Zellen bei den DH-Patienten, die eine GFD hielten, war dieselbe wie die Zahl dieser IgM enthaltenden Zellen bei den gesunden Kontroll-Personen. Aus dieser Untersuchung könnte man schließen, daß Gluten hauptsächlich eine IgM-Stimulierung in der Lamina propria hervorruft.
    Notes: Summary In 17 patients with DH, multiple duodenal and jejunal biopsies were performed. In all patients the small-intestinal biopsy-specimens showed histopathological changes compatible with coeliac disease. Fourteen of the patients maintained a gluten-free diet (GFD) for more than 8 months. The small-intestinal lesions improved in all patients investigated during the GFD. The dosage of Dapsone needed to control the skin lesions could be reduced by more than 50% in 4 patients and the Dapsone could be stopped in 5 other patients on GFD. The immunoglobulin-bearing cells in the lamina propria were counted in 8 patients not on a gluten-free diet, in 6 patients on gluten-free diet, and in 8 healthy controls. The numbers of IgA-, IgM- and IgG-bearing cells were increased in most of the DH patients who were not on a gluten-free diet. The number of IgM-bearing cells in the DH patients who were on a gluten-free diet was the same as that in the control group. This may indicate a mainly IgM response in the lamina propria induced by gluten.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561123
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