title: Distribution of interstitial cells of Cajal in the internal anal sphincter of patients with internal anal sphincter achalasia and Hirschsprung disease.
abstract: BACKGROUND
  Interstitial cells of Cajal (ICCs) are pacemaker cells in the smooth muscles of the gut. The internal anal sphincter (IAS) is the most caudal part of gastrointestinal tract. It has the important function of maintaining fecal continence. It has been proposed that ICCs in the IAS mediate the inhibitory innervation of the recto-anal reflexes.
  
  
  OBJECTIVE
  To investigate the distribution of ICCs in the normal IAS and in the IAS of children diagnosed with internal anal sphincter achalasia (IASA) and Hirschsprung disease (HD).
  
  
  METHODS
  At the time of IAS myectomy, specimens of the IAS were taken from 8 patients with IASA, 4 patients with HD, and 4 normal controls. All specimens were examined using anti-c-Kit and antiperipherin antibodies; immunolocalization was detected with light microscopy. Density of the ICCs was graded by computerized image analysis.
  
  
  RESULTS
  There was strong peripherin immunoreactivity in the ganglia cells and nerve fibers in the normal IAS. The number of peripherin-positive nerve fibers was markedly reduced in the IAS in patients with IASA. In HD patients, there was lack of peripherin immunoreactivity in the IAS, but hypertrophic nerve trunks stained strongly. Many c-Kit-positive ICCs were present among the muscle fibers and between the muscle bundles in the normal IAS. In HD and IASA patients, ICCs were absent or markedly reduced.
  
  
  CONCLUSIONS
  Altered distribution of ICCs in the internal sphincter in IASA and HD may contribute to motility dysfunction in these patients.
authors.affiliation: Children's Research Centre, Our Lady's Hospital for Sick Children, University College Dublin, Dublin, Ireland.
authors.forename: Anna Piaseczna
authors.initials: AP
authors.lastname: Piotrowska
authors.forename: Valeria
authors.initials: V
authors.lastname: Solari
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D000293:Adolescent; D001003:Anal Canal / Q000737:chemistry / Q000473:pathology*; D001004:Anus Diseases / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D006627:Hirschsprung Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007381:Intermediate Filament Proteins / Q000032:analysis; D008562:Membrane Glycoproteins; D009130:Muscle, Smooth / Q000737:chemistry / Q000473:pathology; D009412:Nerve Fibers / Q000737:chemistry / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis; D064531:Peripherins; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis
chemical_list: D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; D064531:Peripherins; D019009:Proto-Oncogene Proteins c-kit