Background & Aims Cytokine signaling pathways play a central role in the pathogenesis of inflammatory bowel disease (IBD). Ulcerative colitis (UC) and Crohn’s disease (CD) have unique as well as overlapping phenotypes, susceptibility genes, and gene expression profiles. This study aimed to delineate patterns within cytokine signaling pathways in colonic mucosa of UC and CD patients, explore molecular diagnostic markers, and identify novel immune-mediators in IBD pathogenesis. Methods We quantified 70 selected immune genes that are important in IBD signaling from formalin-fixed, paraffin-embedded (FFPE) colon biopsy samples from normal control subjects and UC and CD patients having either severe colitis or quiescent disease (n=98 subjects). We utilized and validated a new modified real-time RT-PCR technique for gene quantification. Results Expression levels of signaling molecules including IL-6/10/12/13/17/23/33, STAT1/3/6, T-bet, GATA3, FOXp3, SOCS1/3, and downstream inflammatory mediators such as chemokines CCL-2/11/17/20, oxidative stress inducers, proteases, and mucosal genes were differentially regulated between UC and CD and between active and quiescent disease. We also document the possible role of novel genes in IBD, including SHP-1, IRF-1,TARC, Eotaxin, NOX2, Arginase I, and ADAM 8. Conclusions This comprehensive approach to quantifying gene expression provides insights into the pathogenesis of IBD by elucidating distinct immune signaling networks in CD and UC. Furthermore, this is the first study demonstrating that gene expression profiling in FFPE colon biopsies might be a practical and effective tool in the diagnosis and prognosis of IBD and may help identify molecular markers that can predict and monitor response to individualized therapeutic treatments.

. Pancreatic exocrine enzyme deficiency associated with asphyxiating thoracic dystrophy. Asphyxiating thoracic dystrophy, a constrictive thoracic chondrodystrophy present at birth, is associated with tachypnoea, recurrent pulmonary infections, and failure to thrive. In our patient, a successful surgical procedure for the alleviation of the thoracic constriction resulted in improvement of ventilatory function and reduction in the frequency of respiratory infections, but did not improve the growth rate. Further investigation disclosed chronic diarrhoea, steatorrhoea, and neutropenia with impaired pancreatic zymogen secretion, suggesting the presence of a second congenital abnormality. The association of exocrine pancreatic insufficiency with asphyxiating thoracic dystrophy has not been previously described.

A five-month-old white male was admitted to Children's Hospital of Philadelphia. He was the product of a normal pregnancy and delivery; birth weight was 2.8 kg. At birth, an imperforate anus was found for which a diverting colostomy was performed at the local hospital. He then gained weight normally, and was referred to us for definitive surgery. On arrival his weight was 6.54 kg. A functioning double loop colostomy was present in the right upper quadrant of the abdomen. There were no other abnormal findings.Prior to surgery, enemas were ordered to be given through both segments of the colostomy. A 60 ml Fleet enema was introduced into the upper colon segment and another 60 ml into the lower segment. There was immediate return of large amounts of fluid. Five and nine hours later the same volumes were again administered. Both enemas again produced a copious return of fluid. Soon thereafter the child became lethargic, with rigid extremities. His temperature rose to 39 C, respirations to 76 per minute, and pulse to 196 per minute. His BUN level was 15 mg/100 ml (Table 1). As soon as tetany was recognized, 108 mg of elemental calcium was given intravenously. The child became alert and the clinical signs of tetany disappeared. The child was rehydrated with intravenous fluids which included calcium gluceptate 2.2 gm/1. Ten hours later another episode of tetany recurred. This was treated with 54 mg of elemental calcium intravenously. Thirty ml of amphogel, by mouth, was then given every two hours. The lower segment of the colon was irrigated every

ABSTRACT. Little is known about the role of oral prostaglandins and maintenance of intestinal epithelial cell membrane integrity in suckling animals. The presence of prostaglandins in milk suggests that they may have potential cytoprotective effects. Thus, experiments were performed to determine whether indomethacin causes inflammation in the gastrointestinal tract of suckling animals. Rats were treated with daily intraperitoneal injections of indomethacin (10 mg/kg) starting on the 1st day of life. Unlike adult animals which develop intestinal lesions within 72 h, these rats did not develop intestinal ulcerations until weaning started on days 15 to 16. Indomethacintreated suckling animals prevented from weaning did not develop intestinal lesions until they had access to solid food on day 23. Indomethacin-treated rats had large reductions in jejunal prostaglandin E2 content. In addition, prostaglandin E2 was present in rat milk in relatively large concentration as determined by radioimmunoassay. These studies suggest that exogenous prostaglandins present in milk may protect the intestine of suckling rats from indomethacin-induced inflammation; however, once weaning commences, prostaglandin insufficiency may develop lea& ing to intestinal lesions. We s~eculate that suckling rats treated with indomethacin did-not develop ulcerat6e lesions, despite a marked reduction in intestinal prostaglandin content, possibly due to prostaglandins present in milk. (Pediatr Res 20: 598-601,1986) glandin F,, have also been found in significant amounts, suggesting that milk contains the parent compounds thromboxane A2 and prostacyclin (4-6). They are also found in commercially obtained whole milk and low-fat milk (7), but not in infant formulas (6). Prostaglandin in milk has been demonstrated to be effective in promoting healing of peptic ulcers and in protecting the gastroduodenal mucosa against experimentally induced ulcers (7). In addition, administration of oral prostaglandin E2 to humans has been demonstrated to protect the gastrointestinal mucosa from blood loss induced by indomethacin (8). Thus, considerable information exists about the importance of oral prostaglandins in maintaining integrity of the gastrointestinal epithelial cell membrane in adults. However, very little is known about similar functions of prostaglandins in suckling animals. The presence of prostaglandins in milk suggest that they may play an important role in the function and adaptation of the gastrointestinal tract to extrauterine life. The significance of prostaglandin cytoprotection in the gastrointestinal tract of stressed newborns has not been determined. Exogenous prostaglandin in breast milk could have cytoprotective effects on the gastrointestinal tract. Thus, to evaluate the role of oral prostaglandins in maintenance of gastrointestinal mucosal integrity in suckling animals, experiments were performed in suckling rats to explore whether indomethacin causes inflammation in the immature gastrointestinal tract. A preliminary report has been publish...