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 an esophageal motor disorder characterized by abnormal relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Previous studies evaluating esophagomyotomy and esophageal resection specimens have shown the presence of myenteric inflammation to be a consistent and early pathologic change in patients with achalasia. Thus, the goal of this study was to determine the immunohistochemical characteristics of the inflammatory infiltrate within the myenteric plexus in patients with clinically early and end-stage achalasia. Using formalin-fixed tissue, we analyzed the immunohistochemical features of the myenteric lymphocytes using antibodies that recognize B cells (CD20), T cells (CD3), T cell subsets (CD8), and the activation state of T cell subpopulations (TIA-1 and granzyme B) in nine patients with clinically early achalasia who underwent esophagomyotomy and 13 patients with clinically endstage achalasia who underwent esophageal resection. The myenteric infiltrate in all nine esophagomyotomy specimens was composed predominantly of T cells (CD3-positive), the majority of which also stained for CD8. In five of nine specimens, the majority of CD8-positive cells stained for TIA-1. In the esophageal resection specimens, the myenteric infiltrate was composed predominantly of CD3-positive T cells in seven of 13 cases. In three cases, there was a predominance of CD20-positive B cells, and in the remaining three cases there were relatively equal numbers of T and B cells. In eight of 13 cases, the majority of T cells stained for CD8. TIA-1 immunoreactivity was found in the majority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy and esophageal resection specimens studied, rare granzyme B-positive cells were detected. In conclusion, the majority of myenteric inflammatory cells in patients with achalasia are CD3-positive T cells, most of which are also CD8-positive, although the relative percentage of such cells appears to decrease with disease progression. Furthermore, many of the CD3-positive/CD8-positive myenteric lymphocytes also express TIA-1, suggesting they are resting or activated cytotoxic T cells. The immunohistochemical demonstration of granzyme B in a subpopulation of these cells supports the contention that achalasia is an immune-mediated disease, although the inciting antigen remains an enigma.
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PMID:The nature of the myenteric infiltrate in achalasia: an immunohistochemical analysis. 1093 57

Achalasia is an esophageal motor disorder in which the primary morphologic changes are found in the myenteric plexus. However, a number of secondary alterations are characteristically found in esophagectomy specimens, including the mucosa. In addition, these patients are at increased risk of developing esophageal squamous cell carcinoma. We studied the squamous mucosal alterations in 35 esophagectomy specimens from patients with end-stage achalasia and compared them with those found in the squamous mucosa near the esophagogastric junction from pediatric autopsies (</=18 years) from patients with no known esophageal disease. A representative block was immunostained for p53 (DO7), CD3, and CD20. p53 immunoreactivity was graded as follows: 0 = no staining; 1+ = rare basal cell staining; 2+ = extensive basal cell staining; 3+ = suprabasilar staining. Intraepithelial lymphocyte counts were performed by counting five high power fields (HPF) and calculating an average/HPF. Ages of achalasia patients at esophagectomy ranged from 21 to 78 years (mean 56 years), including 20 men and 15 women. Disease duration ranged from 1 to 44 years (mean 17 years). In all cases the squamous mucosa from achalasia patients was markedly hyperplastic with papillomatosis and basal cell hyperplasia. p53 staining in the squamous mucosa from achalasia patients was significantly more common than in controls (32 of 35 [91%] vs 1 of 17 [6%]; p <0.05). In all achalasia cases CD3+ cells far outnumbered CD20+ cells. There was a significantly greater number of CD3+ cells in achalasia cases (range 32-239/HPF; mean 107/HPF) compared with controls (range 0.8-12/HPF; mean 6/HPF) (p <0.05). In conclusion, the squamous mucosa in esophagectomy specimens from patients with end-stage achalasia shows significant alterations including marked squamous hyperplasia, an increased frequency of p53 immunoreactivity, and increased numbers of CD3+ cells when compared with controls. These changes may be related to the increased risk of squamous cell carcinoma in these patients.
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PMID:Squamous mucosal alterations in esophagectomy specimens from patients with end-stage achalasia. 1168 58