Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, I hope to have highlighted that cytokines are of crucial importance in the normal homeostasis of the gut immune system, the interactions of the gut immune system with enteric antigens and also in tissue injury associated with IBD. There is evidence from a number of different systems that the response to nominal non-replicating antigens, administered nasally or orally, is skewed towards a non-Th1 type of response. To say that the response is Th2, Th3 or Tr is premature. IL-10 and TGF beta seem to be important in downregulating potentially tissue-damaging Th1 responses to the normal flora and possibly food antigens. However, it need to be seen whether the mouse results also apply to humans. A consistent pattern in disease states, whether it be human or mouse, is an exaggerated Th1 type response with excess local production of IFN-gamma and TNF alpha, and its association with tissue injury. An important question to address is whether this represents a switch from the Th2, Th3, or Tr pathway towards a Th1 pathway, or whether the Th1 pathway is in fact always present in the gut, but is kept in check and non-pathogenic by regulatory cells. Equally important is the need to discover where regulation occurs: is it in the PP or the lamina propria? Intriguing results from Kronenberg and colleagues have shown that SCID mice reconstituted with CD45RBhi or CD45RBlo cells show no difference in the re-population of the gut prior to disease (ARANDA et al. 1997). The reason for colitis developing in those mice reconstituted with CD45RBhi cells is therefore more complex than merely differential re-population kinetics. No matter what the outcome is, these and other related questions dealing with the induction and expression of mucosal T-cell responses are going to produce some surprises in the next few years.
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PMID:Effector and regulatory lymphoid cells and cytokines in mucosal sites. 989 58

To evaluate the therapeutic effects of the new synthetic sphingosine-1-phosphate (S1P) receptor modulator, FTY720, we investigated how FTY720 affects the development of dextran sulfate sodium (DSS)-induced colitis and CD4+CD62L+ T cell transfer colitis. BALB/c mice were fed a chow containing 3.5% (wt/wt) DSS to induce colitis. The CD4+CD62L+ T cell transfer colitis was induced by an intraperitoneal injection of CD4+CD62L+ spleen T cells into recipient CB17 SCID mice. The FTY720 was administered by lavage at a dose of 0.3 mg/kg/day. FTY720 was effective in preventing the body weight loss in the DSS-colitis model and the CD4+CD62L+ T cell transfer model. The disease activity index, histological colitis score, and MPO activity were all significantly lower in FTY720-treated mice than in the non-treated mice. Microscopically, mucosal edema, cellular infiltration and epithelial disruption were much more moderate in the FTY720-treated mice than in the non-treated mice. In both colitis models, FTY720 prevented the infiltration of CD4+ T cells into the inflamed colonic lamina propria. In conclusion, the development of DSS-colitis and CD4+CD62L+ T cell transfer colitis were significantly attenuated by FTY720. Since FTY720 is an immunosuppressive product that does not modulate T cell functions, it could be useful in the treatment of IBD patients.
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PMID:The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice. 1696 82

In the present study we have characterized T cell-driven immune function in mice that are genetically deficient in PKC theta. In response to simple immunologic stimulation invoked by in vivo T cell receptor (TCR) cross-linking, these mice showed significantly depressed plasma cytokine levels for IL-2, IL-4, IFNgamma, and TNFalpha compared to wild-type (WT) mice. In parallel, spleen mRNA levels for these cytokines were reduced, and NF-kappaB activation was also reduced in PKC theta knockouts (KO). Injection of allogeneic cells into the footpad of PKC theta deficient mice provoked a significantly diminished local T cell response compared to WT mice similarly challenged. Unlike comparable cells from wild type mice, CD45RBhi T cells harvested from PKC theta deficient mice failed to induce colitis in the SCID-CD45RB cell transfer model of IBD. In another T cell-dependent model of inflammatory disease, PKC theta deficient animals developed far less severe neurologic signs and reduced spinal cord inflammatory cell infiltrate compared to WT controls in the MOG-induced EAE model. A fundamental role for PKC theta in T cell activation and in the development of T cell-mediated inflammatory diseases is indicated by these results.
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PMID:Mice deficient in PKC theta demonstrate impaired in vivo T cell activation and protection from T cell-mediated inflammatory diseases. 1706 26

Partial or total CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain are among the autosomally inherited SCID presenting with T-B+NK+ phenotype with lymphopenia. The clinical findings are generally severe in all except for CD3 gamma deficiency. Here we present a 10-month-old CD3 gamma deficient boy with IBD. The patient had suffered from intractable diarrhea, recurrent pulmonary infections and oral moniliasis since two months of age. Following the first allogeneic HSCT from his HLA-identical (6/6) sister after a reduced intensity regimen, a second transplantation was performed five months later. On day +19 after second transplantation, the CD3 TCR alpha/beta chain expression increased to 66% with development of full donor chimerism (98.6%). A significant improvement in diarrhea, perianal lesions, and rectal fistula was observed suggesting an improvement in inflammatory bowel disease. The patient died at home on day +50 with a sudden respiratory failure secondary to an undetermined infection. The case was interesting being the first reported case with SCID and inflammatory bowel disease who responded very well to HSCT by full recovery of intractable diarrhea, failure to thrive, laboratory findings, and improvement of fistula formation.
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PMID:Hematopoietic stem cell transplantation in a CD3 gamma-deficient infant with inflammatory bowel disease. 1848 19

Objective: To determine if presence of co-existing medically unexplained syndromes or psychiatric diagnoses affect symptom frequency, severity or activity impairment in Chronic Fatigue Syndrome.Patients: Sequential Chronic Fatigue Syndrome patients presenting in one clinical practice.Design: Participants underwent a psychiatric diagnostic interview and were evaluated for fibromyalgia, irritable bowel syndrome and/or multiple chemical sensitivity.Main Measures: Structured Clinical Interview [SCID] for DSM-IV; SF-36, Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Short Form; Patient Health Questionnaire-8; Multidimensional Fatigue Inventory (MFI-20), CDC Symptom InventoryResults: Current and lifetime psychiatric diagnosis was common (68%) increasing mental fatigue/health but no other illness variables and not with diagnosis of other medically unexplained syndromes. 81% of patients had at least one of these conditions with about a third having all three co-existing syndromes. Psychiatric diagnosis was not associated with their diagnosis. Increasing the number of these unexplained conditions was associated with increasing impairment in physical function, pain and rates of being unable to work.Conclusions: Patients with Chronic Fatigue Syndrome should be evaluated for current psychiatric conditions because of their impact on patient quality of life, but they do not act as a symptom multiplier for the illness. Other co-existing medically unexplained syndromes are more common than psychiatric co-morbidities in patients presenting for evaluation of medically unexplained fatigue and are also more associated with increased disability and the number and severity of symptoms.Key messagesWhen physicians see patients with medically unexplained fatigue, they often infer that this illness is due to an underlying psychiatric problem.This paper shows that the presence of co-existing psychiatric diagnoses does not impact on any aspect of the phenomenology of medically unexplained fatigue also known as chronic fatigue syndrome. Therefore, psychiatric status is not an important causal contributor to CFS.In contrast, the presence of other medically unexplained syndromes (irritable bowel syndrome; fibromyalgia and/or multiple chemical sensitivity) do impact on the illness such that the more of these that co-exist the more health-related burdens the patient has.
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PMID:The effect of comorbid medical and psychiatric diagnoses on chronic fatigue syndrome. 3164 45