Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune impairment and destruction of the enteric nervous plexus are thought to play a central role in the pathogenesis of paraneoplastic motility disorders. We present a case of a small-cell lung carcinoma-related paraneoplastic motility disorder associated with abnormal interstitial cells of Cajal networks. Antibodies against c-Kit and protein gene product 9.5 were used to selectively stain interstitial cells of Cajal and the enteric nervous plexus, respectively. A 68-yr-old man presented with anorexia, early satiety, nausea, and weight loss. Investigations revealed gastroparesis, delayed small intestinal transit, and mediastinal lymphadenopathy. The patient was seropositive for type 1 antineuronal nuclear autoantibody and P/Q-type calcium channel antibody. Biopsy of mediastinal lymph nodes revealed metastatic small-cell carcinoma cells that were immunoreactive for c-Kit. Immunohistochemical staining of a full-thickness small intestinal biopsy revealed a relatively intact myenteric plexus but a sparse and disorganized interstitial cells of Cajal network. The histopathology of this case suggests that interstitial cells of Cajal may be a target in the pathogenesis of paraneoplastic motility disorders.
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PMID:Paraneoplastic dysmotility: loss of interstitial cells of Cajal. 1213 44

The interstitial cells of Cajal (ICCs) are fundamental in the generation of gastric slow waves. The role of these cells in gastroparesis has not been established. We studied 14 gastroparetic patients (9 diabetic, 4 idiopathic, and 1 postsurgical) for whom standard medical therapy had failed and who had been treated with a gastric electrical stimulator for at least 3 months. All patients had a full-thickness antral gastric wall biopsy at the time of surgery. The biopsy samples were stained with c-kit and scored for the presence of ICCs. Baseline electrogastrogram recordings were obtained for 30 minutes in the fasting state and for 2 hours after a test meal. The patients assessed their total symptom score at baseline and at 3 months. Five patients had almost no ICCs and were compared with nine patients with 20% to normal cell numbers. Both groups did respond symptomatically to gastric electrical stimulation. However, patients with depleted ICCs had significantly more tachygastria and had significantly greater total symptom scores at baseline and after 3 months of gastric electrical stimulation. ICCs are absent in some patients (up to a third) with diabetic or idiopathic gastroparesis, and the absence of these cells is associated with abnormalities of gastric slow waves, worse symptoms, and less improvement with gastric electrical stimulation.
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PMID:Absence of the interstitial cells of Cajal in patients with gastroparesis and correlation with clinical findings. 1562 50

Damage to interstitial cells of Cajal (ICC), pacemakers, and mediators of neuromuscular neurotransmission in the gastrointestinal tract contributes to the pathogenesis of diabetic gastroenteropathy in both patients and animal models. ICC depletion in diabetes may result from chronic hyperglycemia or lost/ineffective insulin signaling. Because independent control of insulin and glucose concentrations is difficult in chronic in vivo studies, we used long-term organotypic cultures to address this problem. Murine gastric muscles were cultured in normoglycemic or hyperglycemic basal media with or without insulin or IGF-I for 1-3 months, the time required for gastroparesis and ICC damage to develop in diabetic mice. ICC were assessed by c-Kit immunohistochemistry and quantitative analysis of c-kit expression. Electrical pacemaking was studied by intracellular recording of slow waves. ICC survived for at least 34 days in unsupplemented normoglycemic media, but their networks, c-kit expression, and slow waves were profoundly reduced after 68 days. These changes could be entirely prevented by insulin or IGF-I supplementation. ICC networks were completely resistant to hyperglycemia for at least 72 days. Thus, hyperglycemia is unlikely to be responsible for the diabetes-associated depletion of ICC. In contrast, maintenance of ICC requires insulin or IGF-I, which are reduced or ineffective in diabetes.
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PMID:Reduced insulin and IGF-I signaling, not hyperglycemia, underlies the diabetes-associated depletion of interstitial cells of Cajal in the murine stomach. 1585 42

Our goal was to investigate associations between the status of interstitial cells of Cajal (ICC) and electrogastrogram (EGG) parameters, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty-one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c-kit and scored for the presence of ICC based on criteria obtained from 10 controls. All patients underwent EGG recordings, a 4-h standardized scintigraphic gastric emptying study and symptom assessment prior to the surgery. Based on antral biopsy, 15 patients (36%) had almost no ICC (ICC- group) and 26 patients had adequate cell numbers (ICC+ group). EGG recordings in the ICC- group displayed significantly less normal slow waves than in the ICC+ group both in the fasting and fed states. Tachygastria in the ICC- group was significantly more than in the ICC+ group both in the fasting (32 +/- 8%vs 11 +/- 2%) and fed states (27 +/- 9%vs 12 +/- 2%). There was no statistical difference in gastric emptying, symptom severity of gastroparesis, aetiology, age and gender between the two groups. Severely depleted ICC occurs in up to 36% of gastroparetic patients and significantly correlates with an abnormal EGG. Severely depleted ICC does not correlate with the severity of gastroparesis as assessed by gastric emptying or symptom status but did result in a poorer symptomatic response to GES. These data suggest that the EGG may have a role for predicting ICC status during clinical evaluation of gastroparetic patients.
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PMID:Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis. 1961 68

The aim of the present study was to observe the effect of electroacupuncture (EA) on the gastric interstitial cells of Cajal (ICCs) in a rat model of diabetic gastroparesis (DGP). The gastric tissues were collected from 75 rats, which had been divided into three equal groups (n=25/group): Blank, model and EA. Hematoxylin and eosin and immunohistochemical staining were used to observe the cellular morphology and distribution of c-kit-positive gastric ICCs; light microscopy was used to count the number of ICCs; and electron microscopy was used to observe the ultrastructure of the rat ICCs. Compared with the model group, the gastromucosal glandular and smooth muscle cells of the EA group were more regularly arranged, with fewer vacuoles; there was an increased cellular gap and the vacuolar degeneration on the gastric walls was mild. Image analysis showed that the blank group exhibited the greatest number of c-kit-positive ICCs, and the number of c-kit-positive ICCs in the blank group was significantly different from that in the model and EA groups (P<0.01): Blank group > EA group > model group. In conclusion, DGP rats exhibited a reduced number of gastric ICCs, altered ultrastructural morphology and a reduced number of cell organelles, particularly mitochondria, compared with the blank group. EA may help to reverse the various pathological changes of gastric ICCs in rat models of DGP.
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PMID:Effect of electroacupuncture on gastric interstitial cells of Cajal in a rat model of diabetic gastroparesis. 2728 37