Anthony Weiss

GLUT1 glucose transporter expression in colorectal carcinoma

Malignant cells exhibit increased glycolytic metabolism, and in many cases increased glucose transporter gene expression. The authors hypothesized that GLUT1 glucose transporter expression is increased in colorectal carcinoma, and that the degree of expression might have prognostic significance.

Early gallbladder cancer associated with idiopathic splenomegaly, splenic vein thrombosis and gastroesophageal varices

Purpose: A 77 year-old male presented with an upper GI hemorrhage secondary to gastric ulcers noted on two prior endoscopies in a period of 4 months at an outside hospital. He was transferred to our facility due to recurrent ulcer bleeding despite a high dose of omeprazole. Initial biopsies from the ulcer were negative for malignancy and H-pylori. A serum gastrin level was determined and a secretin provocative test was performed. The fasting serum gastrin level was 302 pg/ml on PPI treatment. After PPI therapy was discontinued for 10 days, the gastrin level decreased to 214 pg/ml and the peak serum gastrin level on IV secretin stimulation testing climbed to 3408 pg/ml. Upon repeat EGD in the duodenal bulb a centrally, umbilicated, submucosal mass (1.0 cm in diameter) was found on the posterior wall of the duodenum with normal appearing overlying mucosa. Endoscopic ultrasonography confirmed this lesion disclosing a well-circumscribed, solid hypoechoic mass in the submucosa measuring 1 3 2.5 cm. The abdominal CT scan, however, revealed no evidence of pancreatic or duodenal tumor and the octreotide scan was also negative. In order to rule out a duodenal gastrinoma upper GI endoscopy was repeated and the duodenal bulb was examined using a retroflexed maneuver. At exploratory laparotomy, the tumor in the bulb was confirmed and regional lymphadenopathy was found. A Whipple procedure was preformed. Histological examination of the tumor confirmed a gastrinoma, immunohistochemically. Postoperatively, his serum gastrin level decreased to ,50 pg/ml. At 6-month follow-up repeat secretin stimulation testing was negative ( ,50 pg/ml) and he was doing well clinically. Repeat EGD showed healed gastric ulceration. We report a case of duodenal gastrinoma which was diagnosed by endoscopy and endoscopic ultrasound despite a negative abdominal CT scan and octreotide scan. A careful examination of the duodenum by endoscopy and endoscopic ultrasound are useful and essential diagnostic methods for duodenal gastrinoma detection.

558 Outcomes After Retreatment with Cyclosporine a (CsA) in Hospitalized Ulcerative Colitis (UC) Patients: A 7-Year Review from a Single Institution

Background and Aims: Although expression of the di/tripeptide transporter PepT1 has been observed in colon under inflammatory conditions, the inducing factors and underlying mechanisms have not yet been investigated. Here, we addressed the role of pathogenic bacteria in the regulation of colonic PepT1 expression/function and the potential role of PepT1 in bacterial-epithelial interaction. Methods: Colonic HT29-Cl.19A cells were infected with enteropathogenic E. coli (EPEC). PepT1 promoter activity and PepT1 expression/activity were analyzed using the luciferase assay, RT-PCR, nuclear run-on assay, immunoblotting, immunofluorescence staining and uptake experiments. Cdx2-PepT1 promoter binding was assessed by gel-shift and chromatin immunoprecipitation assay. In Vitro experiments were validated by ex vivo and In Vivo infection of wild type and PepT1 over-expressing mice with Citrobacter rodentium. Interleukin (IL)-8 and keratinocyte-derived chemokine (KC) expression levels were quantified by real-time RT-PCR and ELISA. Results: EPEC transcriptionally induced PepT1 expression/activity in HT29-Cl.19A cells. Cdx2 over-expression in HT29-Cl.19A cells induced PepT1 expression and Cdx2 silencing markedly reduced EPECinduced PepT1 expression, indicating the importance of Cdx2 in PepT1 expression. Furthermore, PepT1 expression required intimate adherence of EPEC to host cells through lipid rafts (LRs). Importantly, PepT1 expressed upon EPEC infection is functionally localized in LRs, and PepT1 associated with LRs delayed EPEC-LR binding as monitored in real time by an electric cell-substrate impedance-sensing technique. Remarkably, PepT1 over-expression in HT29-Cl.19A cells reduced EPEC-triggered NF-κB and MAP kinase activation and IL-8 production. In agreement with In Vitro data, ex vivo and In Vivo experiments showed that C. rodentium increased PepT1 mRNA and protein expression levels in mouse colon. Furthermore, PepT1 over-expression in mouse colon reduced C. rodentium adherence and C. rodentium-induced KC production. Conclusions: We demonstrate that i) EPEC transcriptionally induces functional PepT1 expression in LRs of colonocytes by intimately attaching to host cell membranes through LRs, ii) the transcription factor Cdx2 is crucial for EPECinduced PepT1 expression, and iii) PepT1 associated with LRs is involved in bacterialepithelial interaction and intestinal inflammation. Our findings not only reveal a novel mechanism underlying the regulation of colonic epithelial PepT1 expression/function under pathological conditions, but also highlight the potential contribution of this transporter to host defense mechanisms in response to pathogenic attack.

557 colectomy rate in hospitalized ulcerative colitis patients undergoing therapy with cyclosporine (csa)

Background and Aims: Although expression of the di/tripeptide transporter PepT1 has been observed in colon under inflammatory conditions, the inducing factors and underlying mechanisms have not yet been investigated. Here, we addressed the role of pathogenic bacteria in the regulation of colonic PepT1 expression/function and the potential role of PepT1 in bacterial-epithelial interaction. Methods: Colonic HT29-Cl.19A cells were infected with enteropathogenic E. coli (EPEC). PepT1 promoter activity and PepT1 expression/activity were analyzed using the luciferase assay, RT-PCR, nuclear run-on assay, immunoblotting, immunofluorescence staining and uptake experiments. Cdx2-PepT1 promoter binding was assessed by gel-shift and chromatin immunoprecipitation assay. In Vitro experiments were validated by ex vivo and In Vivo infection of wild type and PepT1 over-expressing mice with Citrobacter rodentium. Interleukin (IL)-8 and keratinocyte-derived chemokine (KC) expression levels were quantified by real-time RT-PCR and ELISA. Results: EPEC transcriptionally induced PepT1 expression/activity in HT29-Cl.19A cells. Cdx2 over-expression in HT29-Cl.19A cells induced PepT1 expression and Cdx2 silencing markedly reduced EPECinduced PepT1 expression, indicating the importance of Cdx2 in PepT1 expression. Furthermore, PepT1 expression required intimate adherence of EPEC to host cells through lipid rafts (LRs). Importantly, PepT1 expressed upon EPEC infection is functionally localized in LRs, and PepT1 associated with LRs delayed EPEC-LR binding as monitored in real time by an electric cell-substrate impedance-sensing technique. Remarkably, PepT1 over-expression in HT29-Cl.19A cells reduced EPEC-triggered NF-κB and MAP kinase activation and IL-8 production. In agreement with In Vitro data, ex vivo and In Vivo experiments showed that C. rodentium increased PepT1 mRNA and protein expression levels in mouse colon. Furthermore, PepT1 over-expression in mouse colon reduced C. rodentium adherence and C. rodentium-induced KC production. Conclusions: We demonstrate that i) EPEC transcriptionally induces functional PepT1 expression in LRs of colonocytes by intimately attaching to host cell membranes through LRs, ii) the transcription factor Cdx2 is crucial for EPECinduced PepT1 expression, and iii) PepT1 associated with LRs is involved in bacterialepithelial interaction and intestinal inflammation. Our findings not only reveal a novel mechanism underlying the regulation of colonic epithelial PepT1 expression/function under pathological conditions, but also highlight the potential contribution of this transporter to host defense mechanisms in response to pathogenic attack.

M2071 Innate Immune Defects in IRGM1, TLR2, and NOD2 Contribute to Crohn's Disease Risk and Severity in Ashkenazi Jews

ively). Furthermore, IL-17A -197A allele was significantly associated with chronic relapsing phenotype (OR, 2.36; 95%CI, 1.34-4.15; p=0.0028) and steroid-dependent cases (OR, 2.14; 95%CI, 1.03-4.45; p=0.040), whereas IL-17F 7488T allele was associated with chronic continuous phenotype (OR, 2.71; 95%CI, 1.13-6.49; p=0.025). [Conclusion] Our results provided the first evidence that IL-17A and -17F gene polymorphism was significantly associated with the development of UC. IL-17A -197A and -17F 7844T alleles may influence the susceptibility to and pathophysiological features of UC independently.

Yield of screening sigmoidoscopy in Puerto Rican born immigrants to the mainland United States

Yield of screening sigmoidoscopy in Puerto Rican born immigrants to the mainland United States