Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021390 (inflammatory bowel disease)
 23,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats transgenic for HLA-B27 and human beta 2-microglobulin develop a spontaneous, multisystem, inflammatory disease that resembles human B27-associated disease and that involves the gut mucosa. This model predominantly affects the colon and is characterized by an extensive infiltration of the mucosa by inflammatory cells, largely composed of mononuclear cells. In addition, an increased plasma level of nitric oxide (NO)-derived metabolites was described in this model. Deficiency in the anti-inflammatory cytokine, interleukin-10 (IL-10), leads to the development of colitis in IL-10 knockout mice, suggesting that IL-10 plays a major role in the control of gut inflammation. The objectives of this work were to study the mechanisms of the inflammatory bowel disease (IBD) in HLA-B27 rats and to determine the effects of treatment with IL-10. The 33-3 line of HLA-B27 recombinant rats with established disease was treated in two consecutive experiments with murine recombinant IL-10 for five weeks. Assessment of the effect of this treatment was performed, based on clinical, histological and biological (myeloperoxidase and inducible NO synthase activities; tumor necrosis factor-alpha, interferon-delta, CD3, iNOS and beta-actin mRNA expression. In 33-3 rats with established disease, mesenteric lymph nodes were hyperplastic, and colonic cellularity and MPO and iNOS activities in the colonic mucosa were increased without any detectable effects of IL-10 administration. IFN-gamma and iNOS mRNA were only detected in the colon of transgenic rats. Despite a lack of effect on disease expression, IL-10 strikingly reduced the level of IFN-gamma mRNA in gut mucosa. Up-regulation of IFN-gamma mRNA suggests that the IBD of HLA-B27 rats is mediated by T-helper 1 lymphocytes. Sustained administration of IL-10, in HLA-B27 rats with established disease, efficiently inhibited IFN-gamma mRNA expression but did not influence disease expression: these results indicate that IFN-gamma may exert a critical role at an earlier stage of the disease rather in the maintenance of the lesions.
 ...
PMID:Effects of murine recombinant interleukin-10 on the inflammatory disease of rats transgenic for HLA-B27 and human beta 2-microglobulin. 968 92

In the 25 years since the initial reports of the association of HLA-B27 with ankylosing spondylitis (AS) and subsequently with Reiter's syndrome, psoriatic spondylitis, and the spondylitis of inflammatory bowel disease, the association of HLA-B27 with the seronegative spondyloarthropathies has remained one of the best examples of a disease association with a hereditary marker. HLA-B27 has been recognized as representative of a spectrum of diseases, ranging from the majority of HLA-B27-positive individuals who have no disease at all, through those with isolated eye or skin involvement, to those with critical eye, heart, and peripheral joint compromise of full-blown AS. Yet HLA polymorphism has evolved in response to environmental stresses, and even the presence of HLA-B27 itself appears to confer advantages in certain infectious diseases, such as acquired immune deficiency syndrome (AIDS). This article will review what is currently known about HLA-B27 and disease, especially in the seronegative spondyloarthropathies. The structure-function relationship of HLA-B27 will be presented, including differences between the B27 subtypes both in their ethnic variation and possible disease implications. The disease spectrum conferred by the presence of HLA-B27 will also be discussed, and the theories of how HLA-B27 contributes to the pathogenesis of the spondyloarthropathies will be considered.
 ...
PMID:HLA-B27 and the seronegative spondyloarthropathies. 976 85

Eye inflammation, especially uveitis, is a prominent feature of spondyloarthropathies. Uveitis associated with ankylosing spondylitis and Reiter's syndrome usually is a unilateral acute anterior uveitis with a high tendency to recur sometimes in the contralateral eye. Uveitis associated with undifferentiated spondyloarthropathy, inflammatory bowel disease, and psoriasis may be less characteristic in its presentation, with a higher tendency to posterior pole involvement, bilaterality, and chronicity. Although acute anterior uveitis is grouped into the spectrum of human leukocyte antigen B27-related disease, other genetic and environmental factors including infections by gram-negative bacteria and gut inflammation can play a role in its pathogenesis. The prognosis of uveitis usually is excellent with topical treatment, and only those with posterior pole involvement or a high tendency to recur or to chronicity might benefit from immunosuppressive therapy.
 ...
PMID:Eye involvement in the spondyloarthropathies. 989 10

The concept of spondyloarthropathies gathers together a group of chronic diseases in which not only the locomotor system is involved but also other organs, especially the gastrointestinal tract. In humans, ileocolonoscopic studies demonstrated the presence of inflammatory gut lesions in all the diseases in the spondyloarthropathy group; their presence varied in the different diseases between 20% and 70%. The inflammation could be related to specific disease features in the spondyloarthropathies. Further research supports the hypothesis of subclinical inflammatory bowel disease in some patients with spondyloarthropathy, in which the locomotor inflammation was the only clinical manifestation. The link between gut inflammation and arthropathy has also been demonstrated in animal models, notably the human leukocyte antigen B27 transgenic rats. The temporal relationship between activity and severity of colonic involvement and flares of peripheral arthritis directs treatment of choice. For all forms of enterogenic arthropathies, nonsteroidal anti-inflammatory drugs remain the acute treatment form. Caution is in order, however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation.
 ...
PMID:Bowel inflammation and the spondyloarthropathies. 989 11

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD: two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3 to approximately 3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 mg/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.
 ...
PMID:Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease. 1048 73

There are large differences in the antigenicity and biology of the ReA-associated bacteria. For induction of arthritis, the relevance seems to be only that antigenic material reaches the joint, alive or dead. If there is a common antigen, it has to be a highly conserved one. Bacterial hsp60 seems to be an immunodominant T cell antigen in ReA, but there must be other relevant antigens shared by these different bacteria. An ineffective immune response (for example, low production of TNFalpha) seems to contribute to the manifestations and course of ReA. Although arthritis can also occur in its absence, HLA-B27 plays an important role in the pathogenesis of ReA and the other SpA. Current data suggest that B27 probably acts as an antigen-presenting molecule for a still-unknown arthritogenic molecule. Comparison of ReA with IBD-associated arthritis suggests that there might indeed be a common antigen shared by ReA-associated bacteria and bacteria of the gut flora. CD8+ T cells seem to be important in ReA and other SpA. In some parts of the world, such as in Mexico, ReA could be a major predisposing cause of the development of AS. Antibiotic treatment is not effective, probably because the triggering bacteria are already dead or in a partly latent state at the time arthritis occurs. Based on this knowledge and on new technologies, it should be possible in future years to derive answers to the questions about ReA and the other SpA and, as a consequence, to find a cure.
 ...
PMID:Report on the Fourth International Workshop on Reactive Arthritis. 1076 16

The aim of this study was to evaluate the clinical features, evolution and reliability of spondyloarthropathy criteria in a subset of patients with subclinical sacroiliitis and inflammatory bowel disease (IBD). All patients with IBD (n 62) attending a gastroenterology clinic from a referral centre were included to assess the prevalence of articular involvement. Patients were evaluated according to a specific protocol designed for the study, which included epidemiological and clinical variables, physical examination and radiological assessment. Only those with subclinical sacroiliitis were followed prospectively for 4 years. This group was visited every 6 months with the same initial protocol. Sacroiliac joints were studied using frontal and oblique X-ray views and graded according to New York criteria. HLA B27 typing was performed by serological methods in all patients and in 80 healthy controls. The reliability of Amor and ESSG criteria for spondyloarthropathy was evaluated. Fifteen patients (24%) presented with isolated subclinical sacroiliitis. In this group a higher frequency of peripheral arthritis and erythema nodosum was observed (p = NS compared to those without sacroiliitis). Most cases (60%) were grade II unilateral sacroiliitis. Three patients were HLA B27+ (p>0.05 compared to healthy controls). The resultant sensitivity of Amor's and ESSG criteria ranged from 40% to 46%. An unexpectedly high freuqency (9.5%) of psoriasis was observed in the whole group. There is a high prevalence of isolated subclinical sacroiliitis in IBD. This may represent a forme fruste of enteropathic ankylosing spondylitis, a stunted form of axial involvement because of therapy, or a third category of rheumatic disease associated with IBD. It may also represent a common characteristic of spondyloarthropathies, rather than a specific finding of IBD. The recently developed spondyloarthropathy criteria are not particularly helpful for the diagnosis of this milder form of spondyloarthropathy.
 ...
PMID:Subclinical sacroiliitis in inflammatory bowel disease: a clinical and follow-up study. 1114 53

One thousand three hundred and forty clinically suspected patients of Ankylosing Spondylitis (AS) and other autoimmune diseases and 5000 controls were studied to detect the association of HLA B27 antigen amongst them. Other alleles studied include HLA B7, B40 (B60), B22(B55), B13, etc. Our findings show a considerable and consistent association of HLA B27 with AS irrespective of the community to which the patient, belonged his hygiene or socio-economic conditions. We also found that people in the age group of 21-39 were the most vulnerable, when number of affected individuals or severity of the disease were taken into consideration. Male members showed a preponderance over females in HLA B27 positivity. Detection of HLA B27 could help in the diagnosis of AS. Patients suffering from other autoimmune diseases such as rheumatoid arthritis, psoriasis, Reiter's syndrome and uveitis and patients with inflammatory bowel disease, colitis, eczema, bacillary or fungal infection were also found to be HLA B27 positive. A study of other alleles shows that even they sometimes associate AS and other autoimmune diseases.
 ...
PMID:Association of HLA B27 antigen in Indian patients of ankylosing spondylitis and other autoimmune diseases. 1127 14

The distribution of B27 alleles (B*2701-23) was characterized by PCR-SSP in ankylosing spondylitis and related spondyloarthropathies (SpA) in a sample of B27 positive patients from northern Spain. Six B27 alleles were identified: B*2705,02,03,07,08 and B*2713. B*2705 and 02 were the most common alleles in the SpA studied: ankylosing spondylitis (AS) (n = 89), reactive arthritis (ReA) (n = 11), psoriatic arthritis (PsA) (n = 29), and inflammatory bowel disease (IBD) (n = 21). B*2707 and B*2708 were found in PsA patients and B*2703 in one patient with IBD. B*2713 was identified in a healthy control family. B*2713 has not been reported to be represented in either ethnic group. Thus, this population shows higher levels of B27 diversity than other Caucasian groups.
 ...
PMID:High variability of HLA-B27 alleles in ankylosing spondylitis and related spondyloarthropathies in the population of northern Spain. 1212 75

Epidemiological studies on the spondyloarthritides have been hindered in the past by the lack of adequate classification criteria for the whole group of these diseases. Using the Amor and the European Spondyloathropathy Study Group (ESSG) criteria the total prevalence of such diseases has been found to be higher than estimated in the past. The prevalence of ankylosing spondylitis varies across populations, but closely parallels the frequency of HLA B27-associated subtypes. The lack of well established criteria for reactive arthritis and the varying expression of its clinical manifestations are the principal reasons for the under-reporting of the true prevalence and incidence of this type of spondyloarthritis. Few data exist on the prevalence and incidence of psoriatic arthritis. A recent European study on an inception cohort of patients having inflammatory bowel disease has evaluated the prevalence of spondyloarthritis using the ESSG criteria. Of the patients studied, 18% met these criteria. Undifferentiated spondyloarthritis is one of the most frequent spondyloarthritides. It also includes a number of different subtypes.
 ...
PMID:Seronegative spondyloarthritides. 1247 70


<< Previous 1 2 3 4 5 6 7 8 Next >>