Background:Neurogenin-3(NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine.The NEUROG3 gene(NEUROG3) is therefore a candidate for the cause...Background:Neurogenin-3(NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine.The NEUROG3 gene(NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells.Methods:We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3.We then tested the ability of the observed mutations to alter NEUROG3 function,using in vitro and in vivo assays.Results:The patients had few intestinal enteroendocrine cells positive for chromogranin A,but they had normal numbers of Paneth’s,goblet,and absorptive cells.We identified two homozygous mutations in NEUROG3,both of which rendered the NEUROG3 protein unable to activate NEUROD1,a downstream target of NEUROG3,and compromised the ability of NEUROG3 to bind to an E-box element in the NEUROD1 promoter.The injection of wild-type but not mutant NEUROG3 messenger RNA into xenopus embryos induced NEUROD1 expression.Conclusions:A newly discovered disorder characterized by malabsorptive diarrhea and a lack of intestinal enteroendocrine cells is caused by loss-of-function mutations in NEUROG3.展开更多
Cholecystocolonic fistula (CF) is an uncommon type of internal biliary-enteric fistulas, which comprise rare complications of cholelithiasis and acute cholecystitis, with a prevalence of about 2% of all biliary tree d...Cholecystocolonic fistula (CF) is an uncommon type of internal biliary-enteric fistulas, which comprise rare complications of cholelithiasis and acute cholecystitis, with a prevalence of about 2% of all biliary tree diseases. We report a case of a spontaneous CF in a 75-year-old diabetic male admitted to hospital for the investigation of chronic watery diarrhea and weight loss. Massive pneumobilia demonstrated on abdominal ultrasound and computerized tomography, along with chronic, bile acid-induced diarrhea and a prolonged prothrombin time due to vitamin K malabsorption, led to the clinical suspicion of the fistula. Despite further investigation with barium enema and magnetic resonance cholangio-pancreatography, diagnosis of the fistulous tract between the gallbladder and the hepatic flexure of the colon could not be established preoperatively. Open cholecystectomy with fistula resection and exploration of the common bile duct was the preferred treatment of choice, resulting in an excellent postoperative clinical course. The incidence of biliary-enteric fistulas is expected to increase due to the parallel increase of iatrogenic interventions to the biliary tree with the use of endoscopic retrograde cholangio-pancreatography and the increased rate of cholecystectomies performed. Taking into account that advanced imaging techniques fail to demonstrate the fistulas tract in half of the cases, and that CFs usually present with non-specific symptoms, our report could assist physicians to keep a high index of clinical suspicion for an early and valid diagnosis of a CF.展开更多
Celiac disease(CD) is a type of intestinal malabsorption syndrome,in which the patients are intolerant to the gliadin in dietary gluten,resulting in chronic diarrhea and secondary malnutrition. The disease is common i...Celiac disease(CD) is a type of intestinal malabsorption syndrome,in which the patients are intolerant to the gliadin in dietary gluten,resulting in chronic diarrhea and secondary malnutrition. The disease is common in Europe and the United States,but only sporadic reports are found in East Asia including China. Is CD really rare in China? We examined 62 patients by capsule endoscopy for chronic diarrhea from June 2003 to March 2008. Four patients with chronic diarrhea and weight loss were diagnosed to have CD. Under the capsule endoscopy,we observed that the villi of the proximal small bowel became short,and that the mucous membrane became atrophied in these four patients. Duodenal biopsies were performed during gastroscopy and the pathological changes of mucosa were confirmed to be Marsh 3 stage of CD. A gluten free diet significantly improved the conditions of the four patients. We suspect that in China,especially in the northern area where wheat is the main food,CD might not be uncommon,and its under-diagnosis could be caused by its clinical manifestations that could be easily covered by the symptoms from other clinical situations,particularly when it came to subclinical patients without obvious symptom or to patients with ex-traintestinal symptoms as the initial manifestations.展开更多
文摘Background:Neurogenin-3(NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine.The NEUROG3 gene(NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells.Methods:We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3.We then tested the ability of the observed mutations to alter NEUROG3 function,using in vitro and in vivo assays.Results:The patients had few intestinal enteroendocrine cells positive for chromogranin A,but they had normal numbers of Paneth’s,goblet,and absorptive cells.We identified two homozygous mutations in NEUROG3,both of which rendered the NEUROG3 protein unable to activate NEUROD1,a downstream target of NEUROG3,and compromised the ability of NEUROG3 to bind to an E-box element in the NEUROD1 promoter.The injection of wild-type but not mutant NEUROG3 messenger RNA into xenopus embryos induced NEUROD1 expression.Conclusions:A newly discovered disorder characterized by malabsorptive diarrhea and a lack of intestinal enteroendocrine cells is caused by loss-of-function mutations in NEUROG3.
文摘Cholecystocolonic fistula (CF) is an uncommon type of internal biliary-enteric fistulas, which comprise rare complications of cholelithiasis and acute cholecystitis, with a prevalence of about 2% of all biliary tree diseases. We report a case of a spontaneous CF in a 75-year-old diabetic male admitted to hospital for the investigation of chronic watery diarrhea and weight loss. Massive pneumobilia demonstrated on abdominal ultrasound and computerized tomography, along with chronic, bile acid-induced diarrhea and a prolonged prothrombin time due to vitamin K malabsorption, led to the clinical suspicion of the fistula. Despite further investigation with barium enema and magnetic resonance cholangio-pancreatography, diagnosis of the fistulous tract between the gallbladder and the hepatic flexure of the colon could not be established preoperatively. Open cholecystectomy with fistula resection and exploration of the common bile duct was the preferred treatment of choice, resulting in an excellent postoperative clinical course. The incidence of biliary-enteric fistulas is expected to increase due to the parallel increase of iatrogenic interventions to the biliary tree with the use of endoscopic retrograde cholangio-pancreatography and the increased rate of cholecystectomies performed. Taking into account that advanced imaging techniques fail to demonstrate the fistulas tract in half of the cases, and that CFs usually present with non-specific symptoms, our report could assist physicians to keep a high index of clinical suspicion for an early and valid diagnosis of a CF.
文摘Celiac disease(CD) is a type of intestinal malabsorption syndrome,in which the patients are intolerant to the gliadin in dietary gluten,resulting in chronic diarrhea and secondary malnutrition. The disease is common in Europe and the United States,but only sporadic reports are found in East Asia including China. Is CD really rare in China? We examined 62 patients by capsule endoscopy for chronic diarrhea from June 2003 to March 2008. Four patients with chronic diarrhea and weight loss were diagnosed to have CD. Under the capsule endoscopy,we observed that the villi of the proximal small bowel became short,and that the mucous membrane became atrophied in these four patients. Duodenal biopsies were performed during gastroscopy and the pathological changes of mucosa were confirmed to be Marsh 3 stage of CD. A gluten free diet significantly improved the conditions of the four patients. We suspect that in China,especially in the northern area where wheat is the main food,CD might not be uncommon,and its under-diagnosis could be caused by its clinical manifestations that could be easily covered by the symptoms from other clinical situations,particularly when it came to subclinical patients without obvious symptom or to patients with ex-traintestinal symptoms as the initial manifestations.
