Expression of the short-chain fatty acid receptor, GPR43, in the human colon.

Short-chain fatty acids (SCFAs), 2-4 carbon monocarboxylates including acetate, propionate and butyrate, are known to have a variety of physiological and pathophysiological effects on the intestine. Previously, we reported that the SCFA receptor, G-protein coupled receptor 43 (GPR43), is expressed by enteroendocrine and mucosal mast cells in the rat intestine. In the present study, expression and localization of GPR43 were investigated in the human large intestine. Gene and protein expression of GPR43 in the human ascending colon was analyzed by reverse transcriptase/polymerase chain reaction and Western blotting, respectively. In addition, localization of GPR43 was investigated by immunohistochemistry. In RT-PCR analysis, GPR43 mRNA was detected in whole wall mRNA samples. Western blotting analysis revealed the expression of GPR43 protein in whole wall and scraped mucosa protein samples, but not in muscle or submucosa. GPR43 immunoreactivity was observed in the intracellularly in enterocytes and in the peptide YY-immunoreactive enteroendocrine cells. These results indicate that the short chain fatty acid receptor, GPR43 is expressed by enteroendocrine L cells containing peptide YY in the human large intestine.

Platelet-activating factor, a critical mediator in the pathogenesis of dextran sulfate sodium-induced colitis in rats.

PURPOSE: Disorder of mucosal immunity based on an imbalance between proinflammatory and anti-inflammatory cytokines is believed to be a major factor in the pathogenesis of ulcerative colitis. Platelet-activating factor potentially stimulates the production of proinflammatory cytokines and recruits inflammatory cells. The aim of this study was to determine whether and to what extent platelet-activating factor plays a role in the pathogenesis of ulcerative colitis. METHODS: Using dextran sulfate sodium-induced colitis in rats as a model of ulcerative colitis, we analyzed the composition of cellular infiltrates and the local tissue expression of messenger ribonucleic acid for cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha. To directly assess the impact of platelet-activating factor on the development of colitis, we also determined the efficacy of a specific platelet-activating factor receptor antagonist for preventing dextran sulfate sodium-induced colitis. RESULTS: The activity of colitis was well correlated with the upregulation of cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha messenger ribonucleic acid in local tissues and infiltration of cytokine-induced neutrophil chemoattractant-positive neutrophils and ED1-positive macrophages. The platelet-activating factor receptor antagonist effectively ameliorated colitis, along with causing a decrease in the tissue cytokine-induced neutrophil chemoattractant messenger ribonucleic acid level and a decline in neutrophil and macrophage infiltration. However, the antagonist did not alter tissue levels of tumor necrosis factor-alpha messenger ribonucleic acid. CONCLUSION: Platelet-activating factor plays a critical role in the pathogenesis of dextran sulfate sodium-induced colitis through recruitment of cytokine-induced neutrophil chemoattractant-positive neutrophils and macrophages and/or stimulation of cytokine-induced neutrophil chemoattractant release from activated neutrophils. The tissue level of tumor necrosis factor-alpha messenger ribonucleic acid does not closely reflect the activity of colitis.

Duodenal cancer in a patient with Peutz-Jeghers syndrome: molecular analysis.

We experienced an unusual case of duodenal adenocarcinoma associated with Peutz-Jeghers syndrome (PJS). A 34-year-old woman was admitted to our hospital with abdominal pain. She had been diagnosed as having PJS at 21 years of age, based on the presence of mucocutaneous pigmentation of the lip and fingertips, and colonic hamartomatous polyps. Abdominal computed tomography revealed a tumor in the third portion of the duodenum extending into the pancreas head. As the tumor was pathologically determined to be adenocarcinoma at the time of surgery, pylorus-preserving pancreaticoduodenectomy was performed. We carried out molecular analyses of this patient to examine the pathway of carcinogenesis in PJS. The tumor did not show somatic mutation of the APC and K-ras genes, which is a critical step for the adenoma-carcinoma sequence in colon cancer. Importantly, a germline mutation of the STK11 gene was detected at codon 281 delC in exon 6. Moreover, the tumor showed loss of heterozygosity of the 19p marker near STK11 and somatic mutation of the p53 gene. These findings suggest that STK11 is a tumor suppressor gene regulating the development of hamartomas, and that somatic mutation of p53 subsequently promotes gastrointestinal cancer at a later stage in PJS.

Diverticulitis causing a high serum level of carbohydrate antigen 19-9: report of a case.

We report herein a rare case of diverticulitis causing a high serum level of carbohydrate antigen (CA) 19-9. A 52-year-old man was admitted to our hospital with lower abdominal pain. Laboratory data showed evidence of inflammation and a high serum level of CA 19-9 (370 U/ml). Computed tomography demonstrated thickening of the wall of the sigmoid colon. He was diagnosed as having diverticulitis of the sigmoid colon and was treated with antibiotics. Although his symptoms improved, the presence of a malignancy such as colorectal cancer could not be completely ruled out because of the persistently high serum level of CA 19-9. A laparotomy was performed and the sigmoid colon was found to be adherent to the bladder. Under a diagnosis of diverticulitis, a sigmoidectomy was performed. Pathological examination revealed diverticulitis of the sigmoid colon, but there was no evidence of malignancy in the resected specimen. The serum CA 19-9 level decreased to normal postoperatively and immunohistochemical staining revealed CA 19-9 antigen in the cytoplasm of the diverticular epithelium. Therefore, a possible explanation for the high level of this tumor marker was diverticulitis of the sigmoid colon.

Aggressive angiomyxoma of the perineum originating from the rectal wall.

Aggressive angiomyxoma (AA) is a rare mesenchymal tumor that preferentially involves the pelvic and perineal regions, and is characterized by frequent local recurrences. We describe here a case of large AA in a 31-year-old woman. The patient was admitted to our hospital with a mass in the perineal region, associated with severe menstrual pain. Although her past medical history was unremarkable, she had spotty pigmentation on the lips. Magnetic resonance imaging showed a large mass in the abdominal pelvis traversing the pelvic diaphragm just to the right of the anus, and the border between the tumor and the rectal wall was indistinct. Pathology examination of a frozen intraoperative specimen suggested AA, and, therefore, we completely resected the tumor, using a combined abdominoperineal approach. The tumor was attached to the right wall of the rectum and the pelvic diaphragm between the anus and the puborectalis. The patient recovered uneventfully and there has not been any evidence of local recurrence for 3 years postoperatively. We consider that abdominoperineal resection may be an appropriate treatment for a large AA infiltrating to the perirectal tissues, because the high recurrence rate of this disease has been attributed to incomplete surgical excision.