Decreased tyrosine kinase C expression may reflect developmental abnormalities in Hirschsprung's disease and idiopathic slow-transit constipation

被引:13
作者
Facer, P
Knowles, CH
Thomas, PK
Tam, PKH
Williams, NS
Anand, P
机构
[1] Hammersmith Hosp, Imperial Coll, Sch Med, Peripheral Neuropathy Unit, London W12 0NN, England
[2] Univ Hong Kong, Med Ctr, Queen Mary Hosp, Dept Surg,Div Paediat Surg, Hong Kong, Hong Kong, Peoples R China
[3] St Bartholomews & Royal London Sch Med & Dent, Acad Dept Surg, London, England
关键词
D O I
10.1046/j.1365-2168.2001.01731.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
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.
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页码:545 / 552
页数:8
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