Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Achalasia is dominated by injury to inhibitory nerves. As intramuscular interstitial cells of Cajal (ICC-IM) are proposed to form functional units with nitrergic nerves, their fate in achalasia may be critically important. We studied the relationship between loss of nitrergic nerves and injury to ICC-IM in patients with achalasia and determined associations between ICC-IM and mast cells (MC), using quantitative immunohistochemistry and electron microscopy. Loss of neuronal nitric oxide synthase (nNOS) immunoreactivity was completed within 3 years of acquiring achalasia. Thereafter, progressive ultrastructural injury to remaining nerve structures was evident. Within the first 2 years, the number of ICC-IM did not decline although ultrastructural injury was already present. Thereafter, loss of ICC-IM occurred unrelated to duration of disease. Damage to ICC-IM appeared unrelated to nerve injury. A significant MC infiltration was observed in the musculature; the number of MC was positively related to the persistent number of ICC-IM. Mast cell formed close contacts with ICC-IM and piecemeal-degranulation occurred towards ICC-IM. In conclusion, injury to ICC-IM in achalasia is variable, but not related to duration of disease and injury to nitrergic nerves. MC are prominent and form close functional contact with ICC-IM which may be responsible for their relatively long survival.
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PMID:Intramuscular interstitial cells of Cajal associated with mast cells survive nitrergic nerves in achalasia. 1677 71

Interstitial cells of Cajal (ICCs) have, in the past 2 decades, been recognised as important elements in the regulation of gastrointestinal motility. Specifically, they have been shown to be critical for the generation and propagation of electrical slow waves that regulate the phasic contractile activity of gastrointestinal smooth muscle, and for mediating neurotransmission from enteric motor neurons to smooth muscle cells. These different functional roles are carried out by different phenotypic classes of ICC that have discrete distributions within the tunica muscularis. Identifying the functional roles of ICC within the gut has been facilitated by studying mutant mice deficient in ICC, either as a consequence of loss of the tyrosine kinase receptor, Kit, or its ligand, stem cell factor, both of which are necessary for normal ICC development. In humans, under certain pathophysiological conditions, loss or defects in ICC networks appear to play a role in the generation of certain motility disorders. Alterations in ICC distribution have been reported in conditions such as achalasia, chronic intestinal pseudoobstruction, Hirschsprung disease, inflammatory bowel diseases, and slow transit constipation. Molecular and genetic techniques are helping researchers to determine whether defects in ICC networks are the cause of motility disorders, or whether the disrupted ICC networks are a consequence of gut dysfunction.
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PMID:Disorders of interstitial cells of Cajal. 1818 68

Oesophageal achalasia is a disease known to result from reduced relaxation of the lower oesophageal sphincter (LES). Nitric oxide (NO) is one of the main inhibitory transmitters. NO-sensitive guanylyl cyclase (NO-GC) acts as the key target of NO and, by the generation of cGMP, mediates nitrergic relaxation in the LES. To date, the exact mechanism of nitrergic LES relaxation is still insufficiently elucidated. To clarify the role of NO-GC in LES relaxation, we used cell-specific knockout (KO) mouse lines for NO-GC. These include mice lacking NO-GC in smooth muscle cells (SMC-GCKO), in interstitial cells of Cajal (ICC-GCKO) and in both SMC/ICC (SMC/ICC-GCKO). We applied oesophageal manometry to study the functionality of LES in vivo. Isometric force studies were performed to monitor LES responsiveness to exogenous NO and electric field stimulation of intrinsic nerves in vitro. Cell-specific expression/deletion of NO-GC was monitored by immunohistochemistry. Swallowing-induced LES relaxation is strongly reduced by deletion of NO-GC in ICC. Basal LES tone is affected by NO-GC deletion in either SMC or ICC. Lack of NO-GC in both cells leads to a complete interruption of NO-induced relaxation and, therefore, to an achalasia-like phenotype similar to that seen in global GCKO mice. Our data indicate that regulation of basal LES tone is based on a dual mechanism mediated by NO-GC in SMC and ICC whereas swallow-induced LES relaxation is mainly regulated by nitrergic mechanisms in ICC.
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PMID:Dominant role of interstitial cells of Cajal in nitrergic relaxation of murine lower oesophageal sphincter. 2563 Feb 61