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

Interstitial cystitis, a sterile bladder condition, is characterized by urinary frequency, urgency, burning and suprapubic pain. Increasing evidence indicates that interstitial cystitis is a heterogeneous syndrome that reflects an immune response to a variety of triggers. More than 50% of the patients have allergies, 30% have the irritable bowel syndrome and almost 20% suffer from migraine headaches. Increased numbers of mast cells have been reported in interstitial cystitis. Mast cell activation, which is critical if these cells were to be implicated in this syndrome, has been investigated by electron microscopy, which definitively shows mast cell secretion. Recently, methylhistamine, the major metabolite of histamine, and the specific mast cell marker, tryptase, were shown to be significantly elevated in urine of interstitial cystitis patients. Bladder biopsies from 53 patients were analyzed blindly for the number and degree of activation of mast cells using 4 different stains for light microscopy, as well as electron microscopy. Controls included 16 patients with incontinence and chronic bacterial cystitis. Mast cells in controls were less than 10/mm.2 and were all nearly intact. Surprisingly, mast cells from 11 cancer patients averaged 50/mm.2 but almost all were intact. In contrast, mast cells from 26 interstitial cystitis patients averaged 40/mm.2 and more than 90% were activated to various degrees. Therefore, bladder mast cell activation is a characteristic pathological finding in at least a subset of patients with interstitial cystitis.
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PMID:Activation of bladder mast cells in interstitial cystitis: a light and electron microscopic study. 786 1

Many patients with interstitial cystitis (IC) also have irritable bowel syndrome (IBS), both of which occur overwhelmingly in women, are characterized by pain, and worsen under stress. Bladder and colon biopsies of a female patient with both IC and IBS were evaluated immunohistochemically. There were 40 +/- 10 mast cells (MC)/mm2 (normal, less than 10) in the bladder, which were degranulated. The colon contained 148 +/- 11 MC/mm2 (normal, less than 50), mostly close to numerous substance P (SP)-positive nerves. Histamine, methylhistamine, and the unique MC enzyme tryptase were evaluated in 24-hour urine during two flare-ups. These results may help explain the concurrent presentation and the painful nature of these syndromes.
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PMID:Mast cell and substance P-positive nerve involvement in a patient with both irritable bowel syndrome and interstitial cystitis. 863 18

We have shown that the number of tryptase-positive mast cells in the duodenal mucosa in psoriasis is increased and that a subgroup of psoriasis patients showed elevated levels of antibodies to gliadin (some of whom also had increased lymphocytes in the duodenal epithelium). Duodenal biopsy specimens from 37 patients with psoriasis (eight mild, 13 moderate and 16 severe) and 22 patients with irritable bowel syndrome (IBS) were examined regarding the presence of tryptase + mast cells. Intraepithelial infiltration by lymphocytes was evaluated and scored from 0 to 3. Patients with psoriasis had 131 +/- 58 mast cells/mm2 (mean +/- SD) and those with IBS 28 +/- 18. Only in four of the 37 psoriasis patients was the number within the range of that in the IBS group. There were no signs of stromal inflammation except in one psoriasis patient. No relationship was found between degree of severity of psoriasis and number of mast cells. In 25 of the 37 specimens from psoriasis patients there was no increase in intraepithelial lymphocytes, whereas seven showed a slight increase (score 1-2) and five a moderate increase (score > or = 2-3). The number of tryptase + mast cells was similar in patients with or without increased intraepithelial lymphocytes. The number of mast cells showed no relation to the presence or absence of antibodies to gliadin. We hypothesize that there are at least two types of abnormalities in the duodenal mucosa in psoriasis, one type that is present in most psoriasis patients and characterized by an increase in mast cells and eosinophils, and another that is present in a subgroup of patients with antibodies to gliadin and an increased number of duodenal intraepithelial lymphocytes. The mechanisms underlying the increase in the number of mast cells and its relevance are not yet known.
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PMID:Psoriasis patients have highly increased numbers of tryptase-positive mast cells in the duodenal stroma. 921 18

Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P < 0.05) higher in IBS (0.91 +/- 0.18; CI 0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.
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PMID:Increased mast cells in the irritable bowel syndrome. 1101 45

Undiagnosed food allergies have been proposed as possible causes of promoting and perpetuating irritable bowel syndrome . Our aim was to find out if sensitization could induce chronic functional motor disturbances in the intestine and the mechanisms implicated. Rats were sensitized to ovalbumin (OVA) following three hypersensitivity induction protocols, two parenteral and one oral. Rat mast cell protease II (RMCP II) release in response to OVA challenge and immunoglobulin E (IgE) concentration were measured in serum. At least 1 week after challenge, small intestinal motility was evaluated using strain gauges. Intestinal tissue samples from orally sensitized rats were checked for in vitro stimulation with OVA. Mucosal mast cells were counted from duodenum sections. All sensitized rats showed intestinal hypermotility. Only rats sensitized by parenteral procedure showed an increase in RMCP II after OVA challenge in serum. IgEs increased only in the Bordetella pertussis sensitized group. Small intestine sections from orally sensitized rats released more RMCP II than sections from control rats. All sensitized rats showed an increase in the number of mucosal mast cells in duodenum. In conclusion, hypersensitivity to food proteins induces chronic motor alteration that persists long after antigen challenge and an excited/activated state of sensitized mucosal mast cells.
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PMID:Hypersensitivity to ovalbumin induces chronic intestinal dysmotility and increases the number of intestinal mast cells. 1567 Feb 71

Protease-activated receptors (PARs) are a family of four G-protein-coupled receptors (PAR-1 to PAR-4) activated by the proteolytic cleavage of their N-terminal extracellular domain. This activation first involves the recognition of the extracellular domain by proteases, such as thrombin, but also trypsin or tryptase which are particularly abundant in the gastrointestinal tract, both under physiological circumstances and in several digestive diseases. Activation of PARs, particularly of PAR-1 and -2, modulates intestinal functions, such as gastrointestinal motility, visceral nociception, mucosal inflammatory response, and epithelial functions (intestinal secretion and permeability). As these physiological properties have been shown to be altered in various extents and combinations in different clinical presentations of irritable bowel syndrome, PARs appear as putative targets for future therapeutic intervention in these patients.
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PMID:Protease-activated receptors: potential therapeutic targets in irritable bowel syndrome? 1618 59

The pathophysiology of functional gastrointestinal disorders is poorly understood. Accepted common mechanisms include psychosocial factors, abnormal gastrointestinal motility and disturbed visceral sensory perception, but the underlying causes remain unclear. Mast cells (MCs) are immunocytes widely distributed throughout the gastrointestinal tract. Several stimuli (e.g. allergens, neuropeptides and stress) lead to MC activation with consequent mediator release (e.g. histamine, tryptase and prostanoids). The MC mediators interact with nerves supplying the gut leading to altered gut physiology and increased sensory perception. The intestinal mucosa of irritable bowel syndrome patients contains on average an increased number of MCs. These cells release an increased amount of mediators in close vicinity to mucosal innervation. The MC activation and their close proximity to nerve fibres is correlated with the severity of perceived abdominal painful sensations. These data provide a strong basis for considering MCs as important participants in visceral hypersensitivity and pain perception in irritable bowel syndrome. Inhibition of MC function may ameliorate irritable bowel symptoms. Novel drugs with an increased potential in the control of MC function (e.g., anti-IgE antibodies, the intracellular protein tyrosine kinase inhibitor Syk) and mediator release (e.g., second generation antihistamines, proteinase-activated receptor antagonists) may be useful pharmacological tools for these common disorders.
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PMID:Functional gastrointestinal disorders and mast cells: implications for therapy. 1637 Oct 78

Trichinella spiralis infection in rats induces hypermotility and an abnormal response to cholecystokinin (CCK) similar to motor disturbances observed in irritable bowel syndrome. Mast cell hyperplasia is also characteristic of this experimental model. The aim of our study was to correlate mast cell activity with the development of dysmotility and to demonstrate whether the mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] could prevent the development of intestine hypermotility. Sprague-Dawley rats were infected with T. spiralis and, 5 days after infection, treated with the mast-cell stabilizer ketotifen (10 mg/kg/day). Twelve days after infection, intestinal spontaneous motor activity and response to CCK were evaluated by means of strain-gauge transducers. Immunohistochemistry for rat mast cell protease II (RMCPII), cyclooxygenase (COX)-2, and inducible nitric-oxide synthase (iNOS) was performed in intestinal specimens. In addition, RMCPII and myeloperoxidase were determined in serum. Infected control rats showed hypermotility, mast cell hyperplasia, increased RMCPII levels, increased myeloperoxidase, and overexpression of COX-2 and iNOS. In contrast, ketotifen-treated rats showed spontaneous intestinal motility and CCK response similar to the noninfected control rats. Mast cell hyperplasia and RMCPII were reduced in ketotifen-treated rats. Inflammatory parameters were less modified by ketotifen, but those animals that received the longest ketotifen treatment showed a slight amelioration in these parameters. These results indicate that mast cells are implicated in the development of hypermotility. The treatment with ketotifen prevented hypermotility and mast cell hyperplasia and diminished mucosal mast cell activity.
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PMID:Mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4h-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] prevents mucosal mast cell hyperplasia and intestinal dysmotility in experimental Trichinella spiralis inflammation in the rat. 1698 56

Mediators involved in the generation of symptoms in patients with irritable bowel syndrome (IBS) are poorly understood. Here we show that colonic biopsy samples from IBS patients release increased levels of proteolytic activity (arginine cleavage) compared to asymptomatic controls. This was dependent on the activation of NF-kappaB. In addition, increased proteolytic activity was measured in vivo, in colonic washes from IBS compared with control patients. Trypsin and tryptase expression and release were increased in colonic biopsies from IBS patients compared with control subjects. Biopsies from IBS patients (but not controls) released mediators that sensitized murine sensory neurons in culture. Sensitization was prevented by a serine protease inhibitor and was absent in neurons lacking functional protease-activated receptor-2 (PAR2). Supernatants from colonic biopsies of IBS patients, but not controls, also caused somatic and visceral hyperalgesia and allodynia in mice, when administered into the colon. These pronociceptive effects were inhibited by serine protease inhibitors and a PAR2 antagonist and were absent in PAR2-deficient mice. Our study establishes that proteases are released in IBS and that they can directly stimulate sensory neurons and generate hypersensitivity symptoms through the activation of PAR2.
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PMID:Role for protease activity in visceral pain in irritable bowel syndrome. 1730 51

Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are common in both SM and cutaneous mastocytosis [urticaria pigmentosa (UP)], and are usually caused by the release of histamine and other inflammatory mediators. Occasionally, neoplastic mast cells may also directly infiltrate the GI tract. Previous studies have suggested that enumeration of the mast cells in GI biopsies may help establish the diagnosis of SM. However, mast cells have been reported to be increased in various inflammatory diseases, and mast cell density has not been systematically evaluated in other GI disorders. Recently, expression of CD25 by mast cells in bone marrow has been shown to be specific for SM. The purpose of this study was (1) to quantitate and compare mast cells in mucosal biopsies from patients with SM involving the GI tract, UP with GI symptoms, and a control group of diverse inflammatory disorders, and (2) to determine whether immunostaining for CD25 can be used to distinguish neoplastic from reactive mast cells in GI biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5 patients with UP; and 157 control cases including 10 each normal stomach, duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16 patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells were quantitated, and the presence or absence of CD25 expression on mast cells was determined. In SM patients, mast cells in the small intestine and colon numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74 to 339). This was significantly higher than in GI biopsies from UP patients (mean 17/HPF; range 8 to 32, P<0.0001) and all inflammatory diseases (P<0.01). Mast cell density in other disorders ranged from a mean of 12/HPF in H. pylori gastritis to 47/HPF in parasitic infections. Interestingly, all SM biopsies (and none of the other cases) contained aggregates or confluent sheets of mast cells. In addition, mast cells in all SM cases were positive for CD25, whereas GI mucosal mast cells in UP and all other control cases were negative. In conclusion, quantitation of mast cells can be helpful to diagnose SM in GI mucosal biopsies, although mast cells are also markedly increased in parasitic infections. Aggregates or sheets of mast cells are only seen in SM. Immunoreactivity for CD25 in GI mucosal mast cells is specific for SM and can be used to confirm the diagnosis.
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PMID:Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis. 1805 23


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