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At least 91 records · Page 5Linked to original sources
PubMed2006

TNF alpha production to TLR2 ligands in active IBD patients.

Strong evidence suggests that microbial components are involved in the etiopathology of inflammatory bowel diseases (IBD). Since pathogen-associated molecular patterns are recognized by TLRs, dysregulation of TLR-mediated microbial recognition could be taking place in IBD patients. An in vitro assay with different TLR agonists was used to reproduce the immunostimulation via TLR ligands. Elevated TNFalpha production was found in response to LTA and Zymosan in 48% of active Crohn's disease and ulcerative colitis patients when compared to inactive patients or controls. The expression of CD14 did not differ in active patients, whereas TLR2 was significantly upregulated on monocytes from 71% of those patients with high production of TNFalpha. The marked increase of TNFalpha response to TLR2 ligands correlated with a higher TLR2 expression in a group of IBD patients, suggesting that an abnormal mechanism may provide an excess of inflammatory mediators during the active phase of IBDs.

Cells, Cultured↗
PubMed2005

The probability density of the total IBD length over a single autosome in unilineal relationships.

Several authors have studied identity by descent (IBD) by way of a continuous recombination process along a chromosome. Despite its potential uses in, for example, gene mapping or delineation of biological relationships there has been no exact algebraic result given for the probability density function of the IBD proportion in any familial relationship. Other authors have derived algebraic approximations in the case of half-sibs by way of the Poisson clumping heuristic and used computational methods to compute the distribution function of the IBD sharing for unilineal relationships. Here we provide a general numerical method for finding the density of IBD sharing that could be applied to any unilineal relationship and more importantly we derive algebraically an expression for the density for a grandparent-grandchild relationship. Initially we assume that recombination events occur at random along a chromosome, then go on to show how the method could be extended to incorporate a form of genetic interference.

Crossing Over, Genetic↗
PubMed2004

Direct IBD mapping: identical-by-descent mapping without genotyping.

Direct identical-by-descent (IBD) mapping is a technique, that combines genomic mismatch scanning (GMS) and DNA microarray technology, for mapping regions shared IBD between two individuals without locus-by-locus genotyping or sequencing. The lack of reagents has limited its widespread application. In particular, two key reagents have been limiting, 1). mismatch repair proteins MutS, L and H, and 2). genomic microarrays for identifying the genomic locations of the GMS-selected IBD fragments. Here, we describe steps that optimized the procedure and resources that will facilitate the development of direct IBD mapping.

Base Pair Mismatch↗
PubMed1997

Analysis of cytokine profile in human colonic mucosal Fc epsilonRI-positive cells by single cell PCR: inhibition of IL-3 expression in steroid-treated IBD patients.

Mast cells can serve as a possible important source of cytokine production in inflamed tissue which can be regulated by stimuli different from those activating other immune system cells. To study the expression of specific genes in mast cells derived from small human colonic mucosal endoscopic biopsies, we first modified a previously reported procedure to achieve a significantly enriched mast cell fraction. Then, by using single-cell RT-PCR analysis the expression of the IgE Fc receptor (Fc epsilonRI) and c-kit mRNA was determined. It was observed that the Fc epsilonRI-positive cells also expressed c-kit. This observation provided further evidence that Fc epsilonRI-positive cells are indeed mast cells. Analysis of biopsies from 12 patients (four control and eight patients with inflammatory bowel disease (IBD)) was carried out, revealing that all of the Fc epsilonRI-positive cells expressed IL-3, while the expression of IL-4 was detected only in some of these positive cells. TNF alpha was not detected in these cells. Therefore, it would seem that most intestinal mast cells produce IL-3. Since it has been reported that IL-3 synthesis was down-regulated in steroid-treated cells, the expression pattern of IL-3 in intestinal mast cells derived from steroid-treated IBD patients was then determined. IL-3 mRNA was detected in only two out of 24 Fc epsilonRI-positive cells derived from these steroid-treated patients. These results lend strong support to the idea that the down-regulation of IL-3 in mast cells derived from steroid-treated IBD patients occurs in vivo and could be an important mechanism for immunomodulation in IBD.

Biopsy↗
PubMed2000

Influence of quality of care on quality of life in inflammatory bowel disease (IBD): literature review and studies planned.

Inflammatory bowel disease (IBD) is a chronic disorder with an early onset in life. Therefore, it is reasonable to assume that IBD patients are in considerable need of health care. The quality of life of IBD patients is reported to be impaired. Whether optimizing the quality of health care for these patients may positively influence their quality of life is a question that has been raised often during recent years. This review of the literature on health care research discusses different concepts regarding the quality of care assessment in chronic disease, stresses the need to see things from the patient's perspective, and provides recommendations to optimize health care research. The two most important conclusions that can be drawn are that: (1) the relationship between quality of health care and quality of life in IBD is one that is certainly worth studying; and (2) when developing a means to assess patient data on quality of care, it is essential to involve patients from the very start.

Journal Article↗
PubMed2001

Does better disease-related education improve quality of life? A survey of IBD patients.

The importance of health-related quality of life (HRQOL) assessment in patients with chronic disorders such as inflammatory bowel disease (IBD) is now acknowledged by researchers. Of the many factors that may influence HRQOL, patient knowledge of the condition and disease-related information provision have hitherto not been studied. In all, 250 patients with inactive IBD (UC = 128, CD = 122) were randomly chosen from our IBD clinic. Two sets of questionnaires [initially a standard questionnaire to assess level of disease-related information by a patient information score (PIS), followed by a HRQOL questionnaire] were sent to each patient. In the PIS, a score of 7 or more indicated satisfactory disease-related knowledge and in the HRQOL, a score less than 51 suggested a normal QOL, and a score above 60 significantly impaired QOL. A total of 168 patients (66%) returned both the questionnaires (UC = 91, CD = 77). The mean QOL in patients with UC and CD was 62.2+/-8.3 and 63.9+/-9.5 respectively, (P = NS). 99 patients (59%) had significantly impaired QOL (mean score 65+/-7.6) with only 12 patients (8%), 6 in each group, having a normal QOL. Mean PIS score for the patients was 7.04+/-0.1; 53% of the UC patients and 75% of the CD patients (P = 0.006) were considered well informed (ie, PIS scores of 7 or more). The mean PIS for UC patients was 6.5+/-0.4 vs 7.5+/-0.2 for the CD group (P = 0.001). There was, however, no correlation seen between the QOL and PIS scores, both for UC and CD patients (R = 0.3). In conclusion, most patients with IBD have impaired QOL, despite of having inactive disease. The level of disease-related knowledge appears to be better in patients with CD, although that does not seem to affect QOL.

Adult↗
PubMed2001

The CC chemokine receptor 5 delta32 mutation is not associated with inflammatory bowel disease (IBD) in NE England.

Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract of unknown aetiology. Evidence of abnormalities in immune regulation and cytokine production in patients with IBD has led to investigations of various immuno-regulatory genes as potential candidate susceptibility loci. Studies using whole genome scanning have highlighted chromosomes 3, 7, 12 and 16. A 32 base-pair deletion in the CC-chemokine receptor-5 gene (CCR5-A32, chromosome 3p21.3) has been associated with susceptibility to IBD. We have investigated CCR5 as a candidate susceptibility gene in 350 patients (251 with ulcerative colitis and 99 with Crohn's disease) and 103 controls using polymerase chain reaction. There were no significant differences in the distribution of CCR5 genotypes or frequencies comparing patients and controls, or associations with extent of colitis. In contrast to preliminary data, these findings suggest no evidence for involvement of this mutation in susceptibility/resistance or disease progression in IBD.

Colitis, Ulcerative↗
PubMed1997

Differential distribution of B7.1 (CD80) and B7.2 (CD86) costimulatory molecules on mucosal macrophage subsets in human inflammatory bowel disease (IBD).

The molecules B7.1 and B7.2 deliver costimulatory signals of critical importance to naive T cells, and may thus be involved in abrogation of oral tolerance in IBD. Functional disparity apparently exists among antigen-presenting cells in vivo. We wanted to examine if differential B7 expression occurs on mucosal macrophage subsets. Cryosections of bowel specimens from patients with IBD and normal controls were subjected to immunofluorescence and immunoperoxidase staining. In normal mucosa, selective subepithelial accumulation of B7.2+ cells was found. In inflamed IBD mucosa, however, subsets appeared consisting of both B7.2(hi) and B7.1(hi) cells as well as CD14(hi) macrophages. Notably, outside lymphoid aggregates the prominent fraction of recently recruited CD14(hi) macrophages comprised most (approximately 80%) of the B7.1(hi) cells, whereas most (approximately 70%) B7.2(hi) cells were identified as resident mucosal macrophages (CD14(lo) or CD14-). Differential expression of B7.1 and B7.2 on two functionally different subsets of intestinal macrophages implies separate immunoregulatory roles for the two molecules. This finding is in keeping with recent experimental data demonstrating that monocyte-derived cells are crucial for immune responses at mucosal surfaces. Preferential B7.1 up-regulation might be critical in breaking the immunological tolerance to luminal antigens in IBD, but it cannot be excluded that it is a secondary pathogenic event.

Antigens, CD↗
PubMed1998

Contribution of the IL-2 and IL-10 genes to inflammatory bowel disease (IBD) susceptibility.

Although the importance of genetic susceptibility to IBD has been established by epidemiological studies, the genes involved remain poorly characterized. Important candidate genes include those encoding the immunoregulatory cytokines IL-2 and IL-10. The aim of this study was to assess the contribution of the IL-2 and IL-10 genes to IBD susceptibility. One hundred and ninety-eight pairs of siblings with IBD were genotyped at dinucleotide repeat polymorphisms within the IL-2 and IL-10 genes, and data analysed by the affected sib-pair method of linkage analysis and the transmission disequilibrium test (TDT). A subset of 89 affected sibling pairs was genotyped at markers flanking the IL-2 gene as part of a genome-wide search. The IL-2 polymorphism showed no linkage to IBD overall, but modest evidence for linkage to the ulcerative colitis (UC) data set (P = 0.028). A microsatellite 4 cM distal to the IL-2 gene showed a similar distortion in the ulcerative colitis subgroup (P = 0.006). The TDT showed some distortion of allelic transmission for the IL-2 polymorphism in the UC group, but this did not reach statistical significance (P = 0.09). Results for the IL-10 polymorphism were not significant. Thus the gene encoding IL-2 may contribute to UC susceptibility, but the effect is modest and must await replication in other data sets. The IL-10 gene does not appear to contribute to the risk of developing UC or Crohn's disease.

Alleles↗
PubMed1999

Are anti-neutrophil cytoplasmic antibodies (ANCA) clinically useful in inflammatory bowel disease (IBD)?

Since the first detection of ANCA in IBD, numerous studies have dealt with their prevalence, antigenic specificities, clinical significance, pathophysiological role, and their induction. This review summarizes the information obtained from those studies and shows that ANCA are not directly useful as diagnostic and prognostic factors in IBD. ANCA were detected in 50-85% of patients with ulcerative colitis (UC) and 10-20% of patients with Crohn's disease (CD). Multiple target antigens are recognized by these autoantibodies, including both cytoplasmic and nuclear proteins. A pathophysiological role for ANCA in IBD is far from clear. On the one hand, it is suggested that ANCA are genetic markers of susceptibility for IBD, and on the other hand, the induction of ANCA in those diseases may just be an epiphenomenon of chronic inflammation. We discuss recent evidence that ANCA may be induced by a break-through of tolerance towards bacterial antigens.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2003

The interleukin-25 gene located in the inflammatory bowel disease (IBD) 4 region: no association with inflammatory bowel disease.

Genetic predisposition has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). Linkage studies have identified a Crohn's disease susceptibility locus on chromosome 14 (14q11-12; IBD4). Interleukin-25 (IL-25) is a newly identified proinflammatory cytokine that has been shown to promote Th2 responses by inducing cytokines such as IL-4, IL-5 and IL-13. The IL-25 gene is located within this susceptibility region at 14q11.2. As IBDs are characterized by an imbalance of the Th1/Th2 cytokine response, we hypothesized that genetic alterations within the IL-25 gene might contribute to IBD. First, direct sequencing of the coding regions of the IL-25 gene in 40 patients with Crohn's disease or ulcerative colitis revealed only a newly reported polymorphism (c424C/A) in exon 2. Next, the frequency of this polymorphism was further investigated in 151 patients with Crohn's disease, 111 patients with ulcerative colitis, and 119 healthy controls to determine its clinical relevance. The genotypes of the c424C/A polymorphism did not reveal any significant differences between patients with Crohn's disease or ulcerative colitis and controls. Genoytype-phenotype relations in patients with Crohn's disease showed a comparable distribution of the c424C/A polymorphism in all subgroups of the Vienna classification. In summary, our data indicate that genetic alterations in the coding regions of the IL-25 gene are unlikely to play a role in IBDs, but the c424C/A polymorphism in the IL-25 gene should be investigated for a potential association with other chronic inflammatory and inherited disorders such as autoimmune diseases.

Adolescent↗
PubMed2004

Assessing whether an allele can account in part for a linkage signal: the Genotype-IBD Sharing Test (GIST).

To fine map genes, investigators often test for disease-marker association in chromosomal regions with evidence for linkage. Given a marker allele tentatively associated with disease, one would ask if this allele, or one in linkage disequilibrium (LD) with it, could account in part for the observed linkage signal. This question can be addressed by determining if families selected on the basis of the presence of the tentatively associated allele show stronger evidence of linkage as measured by increased allele sharing identical by descent (IBD) by affected family members. However, common selection strategies can be biased for or against linkage in the marker region, even given no disease-marker association. We define unbiased selection schemes and extend the definition to allow weighted selection on the basis of all genotyped family members. For affected-sibship data, we describe three genotype-based weight variables, corresponding to dominant, recessive, and additive models. We then introduce a test for association of a family weight variable with excess IBD sharing. This test allows us to determine if the linkage signal in a region can be attributed in part to the presence of a marker allele, either because of direct involvement in disease etiology or because of LD with a predisposing genetic variant. For samples of 500 affected sib pairs, the tests are powerful in detection of genotype-IBD sharing association, even for disease models with sib relative risk as low as lambda S=1.1, or when evidence for linkage is absent because of sampling variation. This makes our method a new tool for detecting linkage as well as association, especially in regions harboring a candidate gene. We have implemented these methods in the software package GIST (Genotype-IBD Sharing Test).

Computer Simulation↗
PubMed2002

Use of complementary therapies by patients with IBD may indicate psychosocial distress.

BACKGROUND: Complementary and alternative medicine (CAM) is used increasingly by patients with chronic diseases. We have assessed the use of CAM in general medicine and gastrointestinal outpatients focusing particularly on factors predisposing to its use in patients with inflammatory bowel disease (IBD). METHODS: 239 consecutive patients attending gastrointestinal and general medical outpatient clinics answered a questionnaire about their use of CAM: patients with IBD also completed a validated disease-specific quality of life (QOL) inflammatory bowel disease questionnaire (IBDQ). RESULTS: 26% of all patients used CAM, most commonly herbal remedies (43%). CAM was used significantly more by younger than older patients and by single than married or widowed ones. There were no differences by gender or ethnicity. More patients with irritable bowel syndrome used CAM than those with other diagnoses. In IBD patients, CAM users had significantly poorer QOL scores for emotional and social factors than nonusers. 53% of users stated that CAM alleviated their symptoms. CONCLUSIONS: Use of CAM is common in gastroenterological outpatients, particularly if they are young, single, or have irritable bowel syndrome (IBS). Most patients deem it helpful. In IBD, poor QOL predisposes to use of CAM. Conversely, use of CAM may serve as a marker of emotional or social unease in these patients. Physicians need to be aware of widespread usage of CAM by their patients.

Adult↗
PubMed2005

The diagnostic accuracy of serologic markers in children with IBD: the West Virginia experience.

GOAL: To assess the sensitivity/specificity of the serologic markers: perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti-saccharomyces cerevisiae antibody (ASCA) in children diagnosed with inflammatory bowel disease (IBD), living in West Virginia. BACKGROUND: In recent years, serologic markers have been used to differentiate between CD and UC diseases in children. The clinical usefulness of these markers in children was restricted by their low sensitivity and specificity. Racial and ethnic diversity may alter the accuracy of these markers in children. The demographic homogeneity of the West Virginia population may offer a better clinical setup to reassess the utility of those markers in children with IBD. STUDY: A retrospective analysis of all the charts of children diagnosed with IBD was performed at the gastroenterology clinics of Marshall University, Huntington, WV; and West Virginia University, Charleston Division, Charleston, WV. The diagnosis of IBD was established according to clinical, radiologic, and endoscopic data. Laboratory data and serum markers were recorded, and their accuracy to diagnose UC or CD was assessed. RESULTS: A total of 101 charts were reviewed, of which only 90 (89%) included serologic markers and were considered for further analysis. Disease distribution included: UC-41, CD-44, and indeterminate colitis (IC)-7 (2 patients changed diagnosis after colectomy). Serum antibody pANCA had a sensitivity of 73% and specificity of 84% for UC, but only 16% and 35% for CD, respectively. Serum antibody ASCA had a sensitivity of 58% and specificity of 92% for CD, but only 7% and 49% for UC, respectively. The outer membrane porin to Escherichia coli antibody (anti-OmpC) was available in 54 (59%) children and demonstrated a very poor sensitivity for both diseases (sensitivity<11%). CONCLUSION: Despite our homogeneous patient population, pANCA and ASCA antibodies had an inadequate sensitivity/specificity for children with UC or CD. Those antibodies were not useful for our small number of patients with IC.

Adolescent↗
PubMed2006

Recent understanding of IBD pathogenesis: implications for future therapies.

The inflammatory bowel diseases (IBD) are comprised of two major phenotypes, Crohn's disease (CD) and ulcerative colitis (UC). Research over the last couple of years has led to great advances in understanding the inflammatory bowel diseases and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses to a subset of luminal bacteria. Susceptibility to disease is thereby determined by genes encoding immune responses which are triggered by environmental stimuli. Based on extensive research over the last decade, there are several new and novel pathways and specific targets on which to focus new therapeutics. The following review summarizes the current view on the four basic tenets of the pathophysiological basis of IBD and its implications for therapies of IBD: genetics, immune dysregulation, barrier dysfunction and the role of the microbial flora.

Bacterial Infections↗
PubMed1995

Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)

Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non-inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co-culture with sonicates of bacteria from autologous intestine (BsA). Proliferation was inhibitable by anti-MHC class II MoAb, suggesting that it was driven by antigen. LPMC from adjacent non-inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non-inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate. PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co-culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12, interferon-gamma (IFN-gamma), and IL-10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD.

Adult↗
PubMed1989

The status of guinea fowls (Numida meleagris) in the epidemiology of infectious bursal disease (IBD) of poultry in Nigeria.

A serological survey for IBD in market guinea fowls gave a total prevalence rate of 44.3% from five different locations in Nigeria. Guinea fowl keets were susceptible to experimental IBD infection and transmitted it to in-contact sentinel chickens. The infected guinea fowl keets showed the typical clinical-pathology and seroconversion for IBD. These results suggest that guinea fowls could play an active part in the epidemiology of IBD.

Animals↗
PubMed2003

Aminosalicylates and colorectal cancer in IBD: a not-so bitter pill to swallow.

Inflammatory bowel disease (IBD) is associated with an increased risk of developing intestinal cancer at sites of chronic inflammation. Aminosalicylates, including both sulfasalazine and mesalamine, are the most commonly prescribed anti-inflammatory agents prescribed in IBD. On balance, the body of literature to date suggests that aminosalicylates confer some protection against the development of colonic neoplasia in patients with IBD and in a variety of models, including in the noninflamed gut. This latter observation implies that aminosalicylates may be of chemopreventive value in normal as well as IBD individuals. The current review examines and gives an overview of the evidence from a variety of sources, including epidemiological, in vivo and in vitro studies that have investigated the potential anticancer effects of aminosalicylates.

Aminosalicylic Acids↗