Decreased interstitial cell of Cajal volume in patients with slow-transit constipation

He, C Y; Burgart, Larry J.; Wang, Linan; Pembérton, John H.; Young‐Fadok, Tonia M.; Szurszewski, Joseph H.; Farrugia, Gianrico

doi:10.1016/s0016-5085(00)70409-4

Cited by 370 publications

(272 citation statements)

References 27 publications

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“…ICC generate a pacing signal that drives smooth muscle, mediates neuronal input to smooth muscle, and establishes a smooth muscle membrane potential gradient across the thickness of the circular smooth muscle layer (Huizinga et al, 1995;Farrugia et al, 2003;Strege et al, 2003;Ward et al, 2004;Sanders et al, 2006). Disturbances in ICC distribution have been correlated with GI dysmotilities in animal model systems, and in humans (He et al, 2000(He et al, , 2001Huizinga et al, 2001;Lyford et al, 2002;Sanders et al, 2006). The zebrafish is a well-established model system for studies on development, and is an important model system for human disease (Dodd et al, 2000;Goldsmith, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Identification of ICC in the GI tract may be accomplished using Kit as a selective and specific marker (Huizinga et al, 1995;Burns et al, 1997;Kluppel et al, 1998;Faussone-Pellegrini and Thuneberg, 1999;Komuro, 1999;He et al, 2000He et al, , 2001Lyford et al, 2002) The proto-oncogene c-kit is expressed by ICC located within the tunica muscularis of the GI tract of mice, guinea pigs, rats, dogs, and humans. Antibodies specific for this protein label ICC within GI tissues in several species, including humans, and have been widely utilized to both determine ICC cellular morphology, and to characterize sub-populations of ICC located in distinct layers of the muscular wall of the GI tract (Ward and Sanders, 1992;Ward et al, 1994;Burns et al, 1997;Ozaki et al, 2004;Komuro, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Kit‐like immunoreactivity in the zebrafish gastrointestinal tract reveals putative ICC

Rich

Leddon

Hess

et al. 2007

Developmental Dynamics

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kit‐like immunoreactivity in the zebrafish gastrointestinal tract reveals putative ICC

Rich

Leddon

Hess

et al. 2007

Developmental Dynamics

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“…Only a few specific histopathological abnormalities have been found and described to date [12] . Concerning ICCs, there have been two studies of patients with idiopathic megabowl [5,13] and four studies of patients with idiopathic constipation with decreased ICC density [6,[14][15][16] . By contrast, another study of 63 patients with megacolon has shown no consistent alterations in colonic ICC histology [17] .…”

Section: Discussionmentioning

confidence: 99%

Therapy-refractory gastrointestinal motility disorder in a child with c-kit mutations

Breuer

Oh²,

Molderings³

et al. 2010

WJG

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Constipation and fecal impaction are frequent and distressing complaints in pediatric gastroenterology. Especially in neurologically handicapped children, treatment of severe forms of slow-transit constipation (STC) can be difficult. In the majority of cases, STC is of unknown etiology. However, in recent years, there is growing evidence that interstitial cells of Cajal (ICCs), which serve as electrical pacemakers and generate spontaneous electrical slow waves in the gastrointestinal tract, might play an important role in the pathophysiology of STC. It remains unclear whether morphological ICC alterations seen in affected patients are based on congenital developmental anomalies, or whether they are a consequence of long-term constipation with secondary damage of the gastrointestinal nervous system. To the best of our knowledge, we present the first case of a patient with histological alterations in ICC morphology who displayed multiple alterations of c-kit at the level of mRNA. The protein encoded by c-kit is the receptor tyrosine kinase Kit (CD117), which is crucial for development and function of ICCs. Therefore, these findings provide a new explanation for congenital alterations of ICC development that result in gastrointestinal motility disorders.

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“…Histopathological changes in nerves (Schuffler et al 1982), smooth muscle ) and interstitial cells of Cajal (ICC) (Huizinga 1998;He et al 2000;Farrugia 2008) have been variably described in most and have received recent attention by an international working group (Knowles et al 2010).…”

Section: Gastrointestinal Neuromuscular Diseasesmentioning

confidence: 99%

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Hubball

Martin

Lang

et al. 2009

Progress in Neurobiology

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Dysfunction of the gastrointestinal neuromuscular apparatus (including interstitial cells ofCajal) is presumed to underlie a heterogeneous group of disorders collectively termed gastrointestinal neuromuscular diseases (GINMDs). Humoral (antibody)-mediated autoimmunity directed against ligand-or voltage-gated ion channels or associated proteins involved in neuromuscular transmission is associated with several acquired neuromuscular diseases of the periphery and is now implicated in an increasing number of less well-characterised diseases. Anti-channel antibodies have been reported in small numbers of patients with GINMD, particularly in those with GI dysfunction secondary to an underlying disease such as neoplasia or infection. However, little is known of humoral autoimmunity in primary GINMDs.This thesis investigated the association between anti-channel antibodies and GINMD, and the human GI tract as a potential target of anti-channel antibodies. The presence of antivoltage-and ligand-gated antibodies was investigated in the serum of patients with primary achalasia, enteric dysmotility and intestinal pseudo-obstruction, and in those with GINMD secondary to Chagas' disease. The functional effect of sera from some of these patients on colonic smooth muscle contractility was also characterised. Finally, the distribution of six voltage-gated potassium channels (VGKCs), which serve essential roles in the peripheral and central nervous systems and are known targets of pathological autoantibodies, were investigated in all layers of the human GI tract.Our findings suggest that currently recognised anti-channel antibodies are not a common pathogenic factor in primary GINMDs. Anti-channel antibodies, in particular anti-VGKC antibodies, were however found in a significant number of individuals with Chagas' disease. Furthermore, circulating factors in patients with chagasic GI disease altered GI smooth muscle contractility in vitro which may have pathological relevance to GI

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Decreased interstitial cell of Cajal volume in patients with slow-transit constipation

Cited by 370 publications

References 27 publications

Kit‐like immunoreactivity in the zebrafish gastrointestinal tract reveals putative ICC

Kit‐like immunoreactivity in the zebrafish gastrointestinal tract reveals putative ICC

Therapy-refractory gastrointestinal motility disorder in a child with c-kit mutations

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

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