Molecular Interactions between MUC1 Epithelial Mucin, β-Catenin, and CagA Proteins

Interleukin (IL)-8-driven neutrophil infiltration of the gastric mucosa is pathognomonic of persistent Helicobacter pylori infection. Our prior study showed that ectopic over-expression of MUC1 in human AGS gastric epithelial cells reduced H. pylori-stimulated IL-8 production compared with cells expressing MUC1 endogenously. Conversely, Muc1 knockout (Muc1−/−) mice displayed an increased level of transcripts encoding the keratinocyte chemoattractant (KC), the murine equivalent of human IL-8, in gastric mucosa compared with Muc1+/+ mice during experimental H. pylori infection. The current study tested the hypothesis that a decreased IL-8 level observed following MUC1 over-expression is mediated through the ability of MUC1 to associate with β-catenin, thereby inhibiting H. pylori-induced β-catenin nuclear translocation. Increased neutrophil infiltration of the gastric mucosa of H. pylori-infected Muc1−/− mice was observed compared with Muc1+/+ wild type littermates, thus defining the functional consequences of increased KC expression in the Muc1-null animals. Protein co-immunoprecipitation (co-IP) studies using lysates of untreated or H. pylori-treated AGS cells demonstrated that (a) MUC1 formed a co-IP complex with β-catenin and CagA, (b) MUC1 over-expression reduced CagA/β-catenin co-IP, and (c) in the absence of MUC1 over-expression, H. pylori infection increased the nuclear level of β-catenin, (d) whereas MUC1 over-expression decreased bacteria-driven β-catenin nuclear localization. These results suggest that manipulation of MUC1 expression in gastric epithelia may be an effective therapeutic strategy to inhibit H. pylori-dependent IL-8 production, neutrophil infiltration, and stomach inflammation

Emphysematous gastritis due to Sarcina ventriculi infection in a diabetic liver-kidney transplant recipient

Emphysematous gastritis (EG) is a rare and potentially lethal process caused by invasive, gas-producing bacteria leading to inflammation and gas dissection of the stomach. The most common etiologic agents are Clostridium infections, but other organisms, including enterobacteria, staphylococcus, and fungi have also been identified. We report the first case of EG due to Sarcina ventriculi in a solid organ transplant recipient, who presented with epigastric pain and vomiting. The patient had a history of type 1 diabetes mellitus (DM) with recurrent episodes of ketoacidosis and systemic diabetic complications, including severe gastroparesis. CT scan studies demonstrated EG with venous air, and endoscopy showed severe gastritis and ulcerations. In the gastric biopsies, abundant Sarcina ventriculi were noted in areas of mucosal/submucosal necrosis. Antibiotic treatment was instituted at admission, and subsequent endoscopy demonstrated the disappearance of Sarcina, with some improvement of the gastric inflammation; however, the patient developed septic shock with multiorgan failure and expired. This case highlights the need to consider other infectious etiologies in transplant patients, in addition to the well-known opportunistic infections

SlimQuick™ - associated hepatotoxicity in a woman with alpha-1 antitrypsin heterozygosity

Green tea (Camellia sinensis)-associated hepatotoxicity is reported. However, the presence of alpha-1 antitrypsin MZ phenotype as a predisposing factor to green tea-associated drug-induced liver injury (DILI) is unknown. A previously healthy woman with alpha-1 antitrypsin MZ phenotype who took SlimQuick™, an herbal supplement containing green tea extract, developed severe hepatotoxicity requiring corticosteroid treatment. Green tea-associated hepatotoxicity is reviewed and alpha-1 antitrypsin MZ phenotype as a predisposing factor to green tea-associated DILI is discussed. Liver biopsy demonstrated marked inflammation with necrosis suggestive of toxic injury with diffuse alpha-1 antitrypsin globule deposition on immunostaining. Corticosteroid therapy resulted in rapid clinical improvement. Alpha-1 antitrypsin MZ phenotype may increase vulnerability to herbal hepatotoxicity

Barrett's esophagus:Treatments of adenocarcinomas II

The following topics are explored in this collection of commentaries on treatments of adenocarcinomas related to Barrett's esophagus: the importance of intraoperative frozen sections of the margins for the detection of high dysplasia; the preferable way for sentinel node dissection; the current role of robotic surgery and of video-endoscopic approach; the value of the Siewert's classification of adenocarcinomas; the indications of two-step esophagectomy; the evaluation of pathological complete response; the role of PET scan in staging and response assessment; the role of p53 in the selection of adenocarcinomas patients; chemotherapy regimens for adenocarcinomas; the use of monoclonal antibodies in the control of cell proliferation; he attempt to define a stage-specific strategy, and the possible indications of selective therapy; and changes in mortality rates from esophageal cancer.</p