Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interstitial cystitis (IC) is a sterile, inflammatory bladder condition characterized by urinary frequency and urgency, as well as burning and suprapubic pain, which occurs more frequently in women who may suffer for years before diagnosis. An increased number of mast cells have been associated with IC, but the published reports are inconclusive and often conflicting. Human bladder biopsies were analysed blindly for the degree of activation of mast cells in control and IC patients. It was found that mast cells from IC patients averaged as high as 34 cells/mm2 as compared to less than 16/mm2 in controls. Electron microscopy revealed that over 90% of mast cells from IC patients were activated to various degrees. It is concluded that mast cell activation is a pathologic characteristic for IC.
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PMID:Activation of bladder mast cells in interstitial cystitis. 130 30

Mast cells have been studied extensively for their involvement in allergic reactions, where they secrete numerous powerful mediators in response to immunoglobulin E and specific antigens. However, they are also triggered by neuropeptides, they have been found in close contact with neurons, and they are activated in diseases such as angioedema, interstitial cystitis and irritable bowel disease, the prevalence of which is much higher in women. When tested on purified rat peritoneal mast cells, 17 beta-estradiol augmented secretion of histamine and serotonin, starting at 1 microM and in a dose-dependent manner, whether stimulated by the mast cell secretagogue compound 48/80 or the neuropeptide substance P. However, 17 beta-estradiol did not augment mast cell secretion stimulated by immunoglobulin E and specific antiserum indicating that immunologic stimulation is under different regulation. Testosterone inhibited secretion induced by compound 48/80. Tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibited serotonin and histamine release from purified rat peritoneal mast cells triggered by compound 48/80 or substance P. Tamoxifen also inhibited the increase in intracellular free Ca2+ originating from an influx of extracellular Ca2+ in response to compound 48/80. Moreover, tamoxifen antagonized the synergistic effect of phorbol myristate and the cation ionophore A23187 on mast cell secretion, suggesting that tamoxifen's inhibition may be due to regulation of protein kinase C activity. Tamoxifen may, therefore, have a beneficial effect in other neuroimmunoendocrine disorders both through estrogen receptor blockade and inhibition of mast cell secretion.
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PMID:Estradiol augments while tamoxifen inhibits rat mast cell secretion. 138 69

Interstitial cystitis is an inflammatory disease of unknown etiology. To facilitate the study of the pathophysiology of interstitial cystitis, an animal model that correlates with the clinical features of interstitial cystitis and expresses histologic features consistent with those observed in interstitial cystitis patients was developed. Various strains of mice were immunized with a syngeneic bladder homogenate to determine their susceptibility to the induction of autoimmune cystitis. Of 3 mouse strains tested, only the Balb/cAN mice reproducibly developed the clinical correlates and histological features consistent with those observed in interstitial cystitis. In a blinded pathologic review, autoreactive Balb/cAN bladders were correctly distinguished from chronic bacterial cystitis, sham treated bladders and normal control bladders. Edema, fibrosis, perivascular lymphocytic infiltrations and detrusor mast cell accumulation were apparent in 75% of the Balb/cAN mice 2 weeks after immunization and 100% at 4 weeks. These histologic features plateaued and remained stable for at least 6 months. Grossly, the immunized mouse bladders were fibrotic and contracted with a significantly (p < .05) decreased fluid capacity. On hydrodistension, increased vascular prominence and petechial hemorrhage (glomerulations) were evident. Instillation of 14C-urea demonstrated increased permeability in immunized bladders compared with controls. A cellular autoimmune basis for the cystitis is supported by adoptive transfer studies. Spleen cells from experimental mice but not controls transferred the histological features of the disease to naive mice. These studies outline the development of a new experimental autoimmune cystitis model that expresses features similar to those frequently observed in human interstitial cystitis, and may provide a model for the study of the inflammatory process associated with interstitial cystitis. Furthermore, these data suggest a possible role for cellular immune components in interstitial cystitis.
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PMID:Experimental autoimmune cystitis: a potential murine model for ulcerative interstitial cystitis. 143 51

The diagnosis of interstitial cystitis (IC) is not usually considered in patients with idiopathic instability. Because histamine provokes detrusor contractions in vitro, we assessed detrusor mast cell counts in 29 females with refractory instability. Raised mast cell counts (greater than 28/mm2 of detrusor muscle, consistent with a histological diagnosis of IC) were found in 29% of such cases. Thus cystoscopy and bladder biopsy should be considered in patients with idiopathic instability which fails to respond to anticholinergic drugs, as alternative therapy may be useful. Patients with refractory instability and normal detrusor mast cell counts often gave a history of prolonged childhood nocturnal enuresis (55% of cases); in contrast, patients with intractable instability and abnormally high mast cell counts seldom gave such a history (12%). These trends may give some insight into the aetiology of idiopathic instability--"congenital" or acquired?
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PMID:Detrusor mast cells in refractory idiopathic instability. 163 68

In a retrospective study we compared the outcome of 39 patients with interstitial cystitis to the histological findings at initial diagnostic bladder biopsy. The degree of inflammation and fibrosis and the mast cell counts were assessed on each biopsy. The prognostic relevance of the clinical features of age, duration of symptoms, frequency, nocturia, pain and bladder capacity was assessed. The study showed no statistical correlation between the severity of histological findings at diagnosis and the eventual outcome of the disease. Over 50% of patients with severe histological abnormalities responded to conservative treatment. Although the majority of patients with mild pathological changes responded to conservative treatment, some did require surgical intervention. The clinical features of pain, nocturia and bladder capacity showed significant differences between the 2 patient groups. However, the former 2 features are subject to many variables and the latter probably has too wide a range to be useful as a prognostic indicator. Only the response of patients to conservative treatment will indicate those who are not being helped and who may eventually require surgical treatment.
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PMID:Can histological assessment predict the outcome in interstitial cystitis? 170 76

An analysis was made of the numbers and characteristics of mast cells in lateral bladder wall biopsies from 22 patients with interstitial cystitis, 6 with bacterial cystitis and 8 normal controls, using toluidine blue stains and computerised video image analysis techniques. A significantly greater number of mast cells were found within the detrusor muscle in interstitial cystitis than in bacterial cystitis or normal controls. Within the urothelium and submucosa, mast cell numbers were significantly greater than in normal controls in both interstitial and bacterial cystitis. In interstitial cystitis mast cells were significantly larger within the detrusor than in the urothelium/submucosa and they appeared to degranulate predominantly within the superficial layers. Differential staining techniques, using long and short toluidine blue stains, failed to reveal statistically significant evidence of mast cell heterogeneity within the bladder wall in interstitial cystitis.
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PMID:Characteristics of mast cells in normal bladder, bacterial cystitis and interstitial cystitis. 172 Sep 92

The aetiology of pain in interstitial cystitis is not understood, although it has been reported to be due to release of mediators from mast cell granules. Cystolysis and intravesical instillation of dimethyl sulphoxide have been shown to relieve pain in this condition. We have studied the nerve population within the bladder wall using immunohistochemical stains for protein gene product 9.5. A group of 18 cases of chronic interstitial cystitis and 12 controls; neuropathic bladder (n = 1), chronic bacterial cystitis (n = 3), systemic lupus erythematosus cystitis (n = 2) and normals (n = 6), were investigated. There were significantly more nerve fibres within the sub-urothelial and detrusor muscle layers in chronic interstitial cystitis than there were in normals. Patients with chronic cystitis of other aetiology did not have a significant increase in nerve fibre density within the bladder wall suggesting a specific association between nerve fibre proliferation and interstitial cystitis. Cystolysis is shown to deplete selectively the submucosal nerve plexuses without altering the nerve density within detrusor muscle. This finding explains the desensitisation of the bladder without impairment of detrusor function after this procedure.
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PMID:Nerve fibre proliferation in interstitial cystitis. 210 33

Interstitial cystitis is rarely considered as a cause of urinary symptoms in referrals to gynaecology clinics. Recent concepts in the diagnosis of this condition mean that it is emerging as a much more common entity, with both early and late forms of the disease being described. Mast cell density in the detrusor muscle has been reported to be useful as a disease marker to substantiate the diagnosis of interstitial cystitis where no classical diagnostic features exist. We assessed mast cell counts in bladder biopsies from 27 women with idiopathic sensory urgency and 10 control patients about to undergo a colposuspension procedure for pure genuine stress incontinence; 30% of the study group had a clear increase in the detrusor muscle mast cell population (detrusor mastocytosis). No control patient showed such an increase. Early interstitial cystitis should be considered as a possible cause of lower urinary tract symptoms in patients with apparently idiopathic sensory urgency.
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PMID:Do women with idiopathic sensory urgency have early interstitial cystitis? 220 41

We reviewed clinical and histological findings in 55 patients with interstitial cystitis and 21 with voiding dysfunction secondary to other pathological conditions. Of our interstitial cystitis patients 36% would fail to meet the research definition proposed at a recent National Institutes of Health workshop. Detrusor mastocytosis was present in 64% of our interstitial cystitis patients compared to 80% of the noninterstitial cystitis group. There was no statistically significant difference in mean detrusor mast cell counts between interstitial cystitis and noninterstitial cystitis patients. Biopsies of 12 patients who did meet the proposed National Institutes of Health research definition were evaluated by immunohistochemical techniques. Early results are inconclusive. These studies indicate that interstitial cystitis is a complex disease whose diagnosis presently still must be made from a symptom complex rather than from objective histological criteria, including mastocytosis or the presence of any specific immunoreactive cell.
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PMID:Diagnosis of interstitial cystitis. 200 13

Transurethral resection material from a series of 64 patients with classical (ulcer) interstitial cystitis (60 women and 4 men, with a mean age of 64 years), 44 with nonulcer interstitial cystitis (40 women and 4 men, with a mean age of 39 years) and 20 control women (mean age 49 years) were studied by light microscopy. Patients with classical disease had mucosal ulceration and hemorrhage, granulation tissue, intense inflammatory infiltrate, elevated mast cell counts and perineural infiltrates. Patients with nonulcer disease, despite the same severe symptoms, had a relatively unaltered mucosa with a sparse inflammatory response, the main feature being multiple, small, mucosal ruptures and suburothelial hemorrhages that were noted in a high proportion of the patients. It is suggested that these features are characteristic, specific and prevalent enough to allow for morphological differentiation of the 2 clinical subtypes of interstitial cystitis.
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PMID:Clinical features and spectrum of light microscopic changes in interstitial cystitis. 234 71


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