Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the late changes associated with radiation enteropathy in mice over a period of 224 days following single or split doses of gamma radiation delivered to the total abdomen (TAI). We focused on the importance of adhesion formation as a cause of strictures and gut-associated deaths following TAI. Gut-associated peritoneal adhesions were found in mice 2-7 months after receiving 13.5-17.5 Gy TAI and appeared to constitute the most consistent serious late effect of irradiation. There was a good correlation between adhesion formation and death for both the single and split-doses of radiation. Adhesions primarily involved the large gut, normally near the cecum. They appeared to result from serosal breakdown and were the major cause of partial gut obstruction. Submucosal fibrosis was present but seemed to be a comparatively minor cause of strictures. Local lymphoid hyperreactivity was also seen following TAI and may have contributed to the late sequelae. The complexity of the pathogenesis of chronic radiation enteropathy was indicated by finding three successive waves of non-scheduled deaths following TAI. The first wave (28-70 days) was not related to adhesion formation and may have been due to localized failure of mucosa to regenerate after irradiation with consequent ulceration. The second wave (98-140 days) occurred over the period when adhesion formation and fibrosis were most marked. In the third wave (168-224 days), the additional complication of fluid exudation was seen. Further experimentation is obviously needed to better define the complex pathogenesis of radiation enteropathy with dose and time after radiation but our data strongly support a multifactorial causation with an important role for adhesion formation in the disease complex.
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PMID:Adhesion formation in experimental chronic radiation enteropathy. 292 Nov 72

Intestinal injury caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased mucosal permeability, microvascular injury, focal intravascular thrombus formation, fibrin deposition, and neutrophil infiltration. Ulcerations and adhesions are also prominent feature of this injury. Although NSAID-induced inhibition of prostaglandin formation has been suggested to produce ischemic injury and inflammation, no studies have directly assessed intestinal blood flow in experimental NSAID-induced enteropathy. This study tested the hypothesis that indomethacin-induced small bowel injury and inflammation result from intestinal ischemia. With the use of pulsed Doppler flowmetry, superior mesenteric artery blood flow was continuously monitored in conscious rats after doses of indomethacin known to promote acute and then chronic small bowel inflammation (7.5 mg/kg, 2 sc doses spaced 24 h apart). After 72 h, rats were anesthetized and a section of small bowel was removed for histology and intestinal myeloperoxidase activity measurements. Mean arterial blood pressure was not affected until 32 h after indomethacin, when it decreased 20% (P < 0.05) to P < 0.01). Sustained blood flow changes first occurred at 20 h, when an increase of 15% (P < 0.01) was observed, whereas flow resistance decreased. Flow resistance continued to decrease for the remainder of the 72-h period, and there was an accompanying blood flow increase to +40% (P < 0.05 to P < 0.01). Intestinal ulcers developed in 86% of indomethacin-treated rats. Adhesions, dilation, and thickening of the distal jejunum and proximal ileum were observed in most indomethacin-treated rats. Histological grading of intestinal injury yielded scores of 7.1 +/- 1.2 and zero for indomethacin-treated and vehicle-injected rats, respectively (P < 0.01). Myeloperoxidase activity was greater in indomethacin-treated rats (6.7 +/- 1.9 vs. 1.8 +/- 0.3 U/cm, P < 0.05). These results suggest that indomethacin-induced enteropathy is associated with an increase, not a decrease, in superior mesenteric artery blood flow. Therefore, ischemia dose not appear to be a mechanism by which subcutaneous indomethacin administration produces small intestinal injury and inflammation.
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PMID:Superior mesenteric artery blood flow and indomethacin-induced intestinal injury and inflammation. 889 79

Epithelial Cell Adhesion Molecule (EpCAM) has been discovered as one of the first tumor-specific antigens overexpressed in epithelial cancer. The present review focuses on the role of EpCAM in physiology and homeostasis of epithelia. Recent research pointed to a close interaction of EpCAM with other cell-cell contact molecules like E-cadherin and claudins and an intimate crosstalk with Wnt and TGF-beta signaling in the regulation of cell growth. Moreover, EpCAM has been shown to modulate trans-epithelial migration processes of white blood cells. Mutations of the EpCAM gene lead to disturbances of epithelial homeostasis and cellular differentiation from the stem cell compartment. In the intestinal tract EpCAM mutations contribute to congenital tufting enteropathy. Regarding tumorigenesis EpCAM can act as an oncogene still depending on additional driver mutations and epithelial phenotype of tumor cells. Tumor cells display increased EpCAM expression that often correlates with the loss of strict basolateral localization. Many tumors show enhanced regulated intramembrane proteolysis (RIP) of EpCAM and loose EpCAM expression under conditions of epithelial to mesenchymal transition. The resulting extracellular EpEX and intracellular EpICD fragments mediate proliferative signals to the cell. Resulting fragments can be validated either by sensitive enzyme-linked immune-sandwich assays (EpEX) or by immunohistochemistry (EpICD). The present review gives an overview on the detection of EpCAM fragments as predictive markers for disease progression and survival of cancer patients.
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PMID:The role of EpCAM in physiology and pathology of the epithelium. 2649 39