Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030794 (pelvic pain)
 4,056 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peritoneal fluid (PF) lines the abdomen and pelvis and is believed to contain growth factors that stimulate endometriosis, a benign gynecological condition associated with pelvic pain and infertility, in which endometrial cells proliferate and differentiate on the pelvic peritoneum, outside of their normal location within the uterus. In this study, we examined the insulin-like growth factor (IGF) system in seven paired samples of PF and serum from normally cycling women and examined the mitogenic potential of this fluid on cultured endometrial stromal cells. IGF-I, IGF-II, and IGF-binding protein-1 (IGFBP-1), -2, -3, and -4 were identified in PF by immunoassays. PF IGF levels, determined by RIA, were approximately 60% of paired serum levels, and PF levels of IGFBP-2 and IGFBP-3, determined by Western ligand blotting and RIA, respectively, were approximately half of their serum concentrations. IGFBP-4 was barely detectable by Western ligand blotting in PF, and levels of IGFBP-1, determined by immunoassay, were not appreciably different in PF and serum. Incubation of [125I]IGF-II with serum and PF and subsequent size-exclusion chromatography at neutral pH revealed approximately equal incorporation of radiolabel in the IGFBP regions of 150 and 44 kilodaltons (kDa) in serum and primarily in the 44-kDa region in PF. RIA of IGFBP-3 in the IGFBP regions of column effluent revealed that the majority of IGFBP-3 was in the 150-kDa region in both serum and PF, suggesting the presence of the ternary complex in PF. Western ligand blotting of column effluent samples revealed 37-/43-kDa IGFBP-3 primarily in the 150-kDa complex in serum and a marked reduction in the amount of the 37-/43-kDa IGFBP in PF. Western immunoblotting of column effluent with IGFBP-3 antiserum revealed immunoreactive IGFBP-3 forms of 37-43 kDa (major) and 28 kDa (minor) in serum and almost exclusively the 28-kDa band in PF, suggesting that IGFBP-3 in PF may be proteolytically processed. The presence of an IGFBP-3 protease was confirmed using [125I]IGFBP-3 as substrate and was not appreciably present in paired serum samples. Inhibitor profiles demonstrated that this protease is a metal-independent serine protease, and its approximate relative molecular mass was estimated to be 69 kDa, determined by size-exclusion chromatography. The mitogenic potential of IGF peptides and PF was assessed on cultured endometrial stromal cells to test the hypothesis that IGFs in PF may stimulate the growth of endometrium in the pelvic cavity, for example in the disorder of endometriosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The insulin-like growth factor system in human peritoneal fluid: its effects on endometrial stromal cells and its potential relevance to endometriosis. 752 31

We describe a solitary fibrous tumour of the urinary bladder wall removed from a 50-year-old man with a history of pelvic pain, dysuria, and urinary bleeding. Anamnesis revealed a weight increase during the preceding 3 months, but no apparent episodes of biochemical hypoglycaemia or hormonal abnormalities. The patient is alive and well 18 months after surgery. Pathological examination revealed a 6.5-cm well-circumscribed nodular mass composed of uniform spindle cells arranged in bundles and fascicles with varying amounts of collagen and a typical haemangiopericytoma-like vascular pattern. The tumour cells were positive for bcl-2, CD34, and vimentin and ultrastructurally showed mesenchymal-myofibroblastic traits. These cells produced insulin-like growth factor type II mRNA as demonstrated by non-isotopic in situ hybridization. This rare case with a solitary fibrous tumor suggests that insulin-like growth factor type II could join CD34 and bcl-2 as markers for postoperative differential diagnosis.
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PMID:Solitary fibrous tumour of the urinary bladder with expression of bcl-2, CD34, and insulin-like growth factor type II. 1130 91

Endometriosis is a common incurable inflammatory disorder that is associated with debilitating pelvic pain in women. Macrophages are central to the pathophysiology of endometriosis: they dictate the growth and vascularization of endometriosis lesions and more recently have been shown to promote lesion innervation. The aim of this study was to determine the mechanistic role of macrophages in producing pain associated with endometriosis. Herein, we show that macrophage depletion in a mouse model of endometriosis can reverse abnormal changes in pain behavior. We identified that disease-modified macrophages exhibit increased expression of IGF-1 in an in vitro model of endometriosis-associated macrophages and confirmed expression by lesion-resident macrophages in mice and women. Concentrations of IGF-1 were elevated in peritoneal fluid from women with endometriosis and positively correlate with their pain scores. Mechanistically, we demonstrate that macrophage-derived IGF-1 promotes sprouting neurogenesis and nerve sensitization in vitro. Finally, we show that the Igf-1 receptor inhibitor linsitinib reverses the pain behavior observed in mice with endometriosis. Our data support a role for macrophage-derived IGF-1 as a key neurotrophic and sensitizing factor in endometriosis, and we propose that therapies that modify macrophage phenotype may be attractive therapeutic options for the treatment of women with endometriosis-associated pain.-Forster, R., Sarginson, A., Velichkova, A., Hogg, C., Dorning, A., Horne, A. W., Saunders, P. T. K., Greaves, E. Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis.
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PMID:Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis. 3201 99