Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Different types of colonic dysganglionosis, and in particular intestinal neuronal dysplasia (IND) have been blamed for certain postoperative complications after surgery for Hirschsprung's disease (HD). We prospectively assessed colon innervation above the aganglionic zone (AZ) before proceeding to pull-through (PT) in order to rule-out IND as a cause of those complications. We first used a two-stage procedure (TSP): Full-thickness biopsies were harvested above the AZ and a colostomy was established during a first stage. Biopsies were assessed postoperatively with conventional acetyl-cholinesterase (AChE) histochemistry and immunohistochemistry for protein gene product 9.5 (PGP 9.5) and antigen CD56 (CD56). Biopsies were repeated after 6 months if IND was found. When the innervation was normal, the PT was performed during a second stage. Since having refined a rapid AChE reaction, we now use a single-stage procedure (SSP). Biopsies are harvested above the AZ and assessed intraoperatively with rapid AChE staining, proceeding to PT during the same stage when the innervation is normal. Four patients underwent the TSP; 3 had normal innervation above the AZ and subsequently underwent PT. In 1 patient serial biopsies revealed IND-like dysganglionosis; 9 months later, the innervation was normal in repeat biopsies and PT was undertaken. Eleven patients underwent the SSP. Biopsies were normal in 9 but showed unclassifiable forms of dysganglionosis in 2. As these changes were not typical for IND, all patients underwent PT in the same stage. Both patients had a poor outcome of bowel function that required a colostomy in 1 and daily saline irrigations in the other. IND was found in repeat biopsies made during the colostomy in the 1st patient and markedly hypertrophied nerves in the submucosa as well as ectopic nerve cells in the lamina propria in the proximal border of the pulled-through colon in the other. All 13 other patients have normal bowel function. The assessment of colon innervation above the AZ before proceeding to PT allows safer surgical treatment of HD. Intraoperative AChE staining is reliable, but due to the size and number of the biopsies, IND might be overlooked. Non classifiable dysganglionosis should thus be taken into account in the diagnosis and follow-up of the patients, as it may be clinically significant.
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PMID:Assessment of the colon innervation with serial biopsies above the aganglionic zone before the pull-through procedure in Hirschsprung's disease. 1131 71

The association between the congenital absence of colonic ganglion cells and an increased acetylcholinesterase (AChE) expression in the affected tissue is of diagnostic importance in Hirschsprung's disease (HSCR). Investigation of AChE's function in development may also help unravel some of the complex pathophysiology in HSCR. Normal nerves do not stain for AChE, but increased AChE expression is associated with the hypertrophied extrinsic nerve fibres of the aganglionic segment in HSCR. Although a high degree of histochemical diagnostic accuracy exists, results are not always uniform, and false positives and false negatives are reported. False negative results are primarily related to age, and an absence of AChE reaction does not exclude HSCR in neonates within the first 3 weeks after birth. AChE staining results may lack uniformity, resulting in a number of technical modifications that have been made to improve standardization of AChE staining. At least two distinct histological patterns are described, types A and B. The interpretation of increased AChE staining patterns in ganglionated bowel at the time of surgical pull-through remains a problem in patients with HSCR. The development of rapid staining techniques has helped to identify normal ganglionated bowel with greater certainty. The presence of fine AChE neurofibrils in the ganglionated segment has contributed to the debate surrounding intestinal neuronal dysplasia. Quantitative assay of cholinesterase activity confirms the pattern of histochemical staining. AChE is particularly increased in relation to butrylcholinesterase, with one molecular form, the G4 tetrameric form, predominating. It is likely that the raised levels of AChE in aganglionic tissue are the transcriptional consequence of the abnormalities in signalling molecules that characterize HSCR. Evidence suggests that this AChE is functioning in a nonenzymatic capacity to promote cell adhesion and differentiation and that the hypertrophied nerves and neurofibrils may be the result of this increased AChE expression.
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PMID:Acetylcholinesterase in Hirschsprung's disease. 1575 43