OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors.

MYC genes have both essential roles during normal development and exert oncogenic functions during tumorigenesis. Expression of a dominant-negative allele of MYC, termed OmoMYC, can induce rapid tumor regression in mouse models with little toxicity for normal tissues. How OmoMYC discriminates between physiological and oncogenic functions of MYC is unclear. We have solved the crystal structure of OmoMYC and show that it forms a stable homodimer and as such recognizes DNA in the same manner as the MYC/MAX heterodimer. OmoMYC attenuates both MYC-dependent activation and repression by competing with MYC/MAX for binding to chromatin, effectively lowering MYC/MAX occupancy at its cognate binding sites. OmoMYC causes the largest decreases in promoter occupancy and changes in expression on genes that are invaded by oncogenic MYC levels. A signature of OmoMYC-regulated genes defines subgroups with high MYC levels in multiple tumor entities and identifies novel targets for the eradication of MYC-driven tumors.

Controversies in the composition of infant formulas.

Available infant formulas contain a vast assortment of carbohydrate, protein, and fat sources in an effort to emulate the composition of human milk. Although infants receiving commercial formulas thrive, physicians should be cognizant of differences in formula composition and the research that has resulted in the differences. Such awareness permits rational and scientific recommendations both in prescription of formulas and in direction of research on the optimal formula composition for infants.

Intestinal button implantation for obstipation and fecal impaction in children.

Chronic obstipation and fecal impaction in children can be difficult management problems for pediatricians. We describe a novel approach to the management of obstipation and fecal impaction: the implantation of the button gastrostomy device in the appendiceal stump or the terminal ileum. We report the procedure in two children. One child had pseudoobstruction syndrome complicated by recurrent obstipation; the other had cystic fibrosis complicated by recurrent obstruction from meconium ileus equivalent. Both children received a polyethylene glycol/electrolyte solution, with or without pancreatic enzymes, which was administered through the button. The children have remained essentially asymptomatic for at least 10 months. We believe that this is the first report of the use of a button gastrostomy device to successfully manage chronic obstipation and recurrent fecal impaction in children.

Bolus versus continuous feedings stimulate small-intestinal growth and development in the newborn pig.

Although bolus and continuous tube feedings are common, little is known about their effect on the developing small intestine. To compare their effect on small-intestinal growth and differentiation, six pairs of 3-day-old piglet littermates were randomized to receive similar volumes of sow milk replacer, either by bolus (four times daily, group B) or continuous feedings (over 24 h, group C) for 7 days. The piglets were then killed and small-intestinal length, weight, protein mass, and disaccharidase activities were determined. Small-intestinal mucosal weight and ileal protein mass were greater in group B than in group C (p = 0.0024 and 0.019, respectively). No differences were noted between groups in jejunal mucosal protein mass. Ileal maltase activity also was greater in group B than group C (p = 0.02). Although ileal lactase activity in group B was twice that in group C, the differences did not quite reach statistical significance (p = 0.11). No differences between groups were noted in ileal or jejunal sucrase activity. Our study demonstrated that bolus feedings increased mucosal mass, protein mass, and maltase activity to a greater degree than continuous feedings. These results may have clinical significance for infants receiving long-term tube feedings.

Determinants of lactose digestion in the miniature pig.

Although lactose is an important nutrient in the diet of the infant and child, the factors contributing to its digestion have not been clarified adequately. We sought to determine the degree to which lactase activity and small intestinal transit explain lactose digestion, the average error (SEE) in estimating lactose digestion using these parameters, and the effect of age. We compared lactose digestion from both a 7% lactose-containing formula and a solution by determining lactose in ileostomy output in pig littermates at 10 days, 4 weeks, and 10 weeks of age. The entire small intestinal mucosa was assayed for lactase specific activity (micromol x min-1 x g protein-1), total activity (micromol x min-1), and whole-villus lactase activity. Transit time (min), and transit rate (cm/min) were measured. Meal type did not affect lactose digestion. Lactose digestion was explained best by lactase specific activity (formula, R2 = 0.73, SEE = 1.1; solution, R2 = 0.69, SEE = 1.0; P < 0.001). The next best parameter was total transit rate (formula, R2 = 0.69, SEE = 2.0; solution, R2 = 0.46, SEE = 1.3). The relationship with lactase specific activity was age related and there appeared to be a critical value of lactase specific activity above which essentially all the lactose was digested.

Helicobacter pylori gastritis in a child with sickle cell anemia and recurrent abdominal pain.

PURPOSE: Recurrent abdominal pain is a common complaint in children with sickle cell disease. Helicobacter pylori gastritis has recently been described in association with recurrent abdominal pain in children. PATIENTS AND METHODS: A case report is given of a 16-year-old black male with hemoglobin SS disease presenting with recurrent abdominal pain and hematemesis. RESULTS: Endoscopic exam of the upper gastrointestinal tract revealed gastritis, and biopsy confirmed H. pylori infection. Serology studies demonstrated increased anti-H. pylori antibody titers. The young man responded well to treatment, with resolution of his symptoms. CONCLUSION: Helicobacter pylori infection is a new diagnostic consideration for children with recurrent abdominal pain and should be included in the differential diagnosis of children with sickle cell disease, especially when abdominal pain is recurrent and accompanied by vomiting. Larger case studies will be necessary to determine the true incidence of H. pylori in children with sickle cell disease and recurrent abdominal pain.