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- Title
Decreased tyrosine kinase C expression may reflect developmental abnormalities in Hirschsprung's disease and idiopathic slow-transit constipation.
- Authors
Facer, P.; Knowles, C. H.; Thomas, P. K.; Tam, P. K. H.; Williams, N. S.; Anand, P.
- Abstract
Summary Background Some patients with Hirschsprung's disease have refractory constipation following excision of aganglionic bowel, as do patients with idiopathic slow-transit constipation (STC). Gut motility depends on enteric neuronal development in response to expression of trophic factors and their receptors. Recent studies indicate the importance of neurotrophin 3 (NT-3) and its high-affinity receptor tyrosine kinase C (trk C) in enteric neuronal development. Methods Blinded quantitative immunohistochemical analysis of colon from patients with Hirschsprung's disease (aganglionic, hypoganglionic and normoganglionic) (n = 5), STC (n = 6) and appropriate age-matched control tissues (n = 5) was performed for NT-3 and trk C. Sural nerve morphometry and immunostaining were undertaken in three patients with STC who had abnormalities on limb autonomic and sensory testing. Results A significantly higher proportion of submucous plexus neurones was trk C immunoreactive in control infant than adult colon (mean(s.e.m.) 73(9) versus 16(3) per cent of the total; P < 0·001), in accord with a role in development. The proportion of submucous plexus trk C-immunoreactive neurones was reduced in colon from patients with Hirschsprung's disease (28(7) per cent of total in normoganglionic Hirschsprung's disease; P < 0·007 versus infant controls) and STC (10(1) per cent of total; P = 0·053 versus adult controls). No abnormalities of STC sural nerves were detected by morphometry or immunostaining. Conclusion Decreased trk C expression may reflect developmental abnormalities in Hirschsprung's disease and idiopathic STC. Trk C activation by NT-3 or drugs may provide novel treatments. Presented in abstract form to the Pacific Association of Pediatric Surgeons, Las Vegas, Nevada, USA, May 2000.
- Subjects
HIRSCHSPRUNG'S disease; PROTEIN-tyrosine kinases; CONSTIPATION
- Publication
British Journal of Surgery, 2001, Vol 88, Issue 4, p545
- ISSN
0007-1323
- Publication type
Article
- DOI
10.1046/j.1365-2168.2001.01731.x