Allan Walker

Breast milk as the gold standard for protective nutrients.

In this introductory overview, I explore the observation that breast milk is the gold standard for protective nutrients fed to newborn infants and present clinical evidence of its strong protective effect against age-related infectious gastroenteritis. The composition of breast milk changes according to the newborn infants needs for passive protection. In addition, substances in breast milk can actively stimulate development of the newborns host defenses to provide continued mucosal protection after breastfeeding is terminated. Later I present several specific examples of the development of intestinal host defenses due to breastfeeding. An important function of early breastfeeding is its anti-inflammatory effect on the immature, excessive inflammatory response in newborns. Several components of breast milk can reduce the inflammatory response to stimuli in the newborn intestine. These include transforming growth factor (TGF)-beta, interleukin (IL)-10, erythropoietin, and lactoferrin. These components of breast milk can act individually or in concert to contain the neonatal immature anti-inflammatory response.

Structure and Function of Intestinal Mucin: Developmental Aspects

Mucin glycoproteins are thought to play an important role in protecting the intestine from chemical or physical injury but the mechanisms of protection and the possible relationship between mucin structure and function are incompletely understood. Structurally, purified intestinal mucins are a heterogeneous and polydisperse group of large-molecular-weight glycoproteins which have regional and developmental differences in composition. Newborn mucin contains more protein and less carbohydrate than adult mucin and differs from adult mucin in buoyant density and mobility on electrophoresis. The primary function of mucin, protection of the intestine, appears to be dependent upon at least four factors: the rate and quantity of mucin release; the physical barrier of the viscous mucus blanket; the provision of specific inhibitory binding sites to infectious agents and proteins, and the inclusion of secretory immunoglobulins to provide a link to the immunologic component of the intestinal host defense system. Immune as well as infectious and chemical agents appear to play an important role in mucus release but developmental effects have not been studied. Preliminary studies indicate that developmental differences may exist in the provision of inhibitory binding sites and the inclusion of secretory immunoglobulins in mucin. These studies indicate that mucus may provide a link between the physical and immunological components of the intestinal host defense system and point to the need for further studies in this area.

Establishment of a Human Fetal Small Intestinal Epithelial Cell Line

Human enterocytes Karyotype Nonmalignant Keratin Matrigel Correspondence to: Dr. Ian R. Sanderson, MD, Developmental Gastroenterology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, 149 13th Street (1493404), Charlestown, MA 02129-2060 (USA) Introduction The manifestations of gastrointestinal disorders often result from a failure of the intestinal epithelium to interact beneficially with the luminal milieu. The function of the en-terocyte can radically alter according to its state of differentiation. However, the mechanisms which control this process are ill defined. This is, in part, because small intestinal epithelial cells have proven awkward to grow in vitro, making the external influences on enterocyte differentiation difficult to study. Furthermore, intestinal epithelial cells are increasingly recognized to be an integral part of the mucosal immune system. They express class IIMHC molecules [1, 2] and may secrete cytokines [3]. The mechanisms underlying this activity in the human could be studied more effectively in isolated enterocyte cell lines. To date, the only human epithelial cells that have remained viable in culture for indefinite periods have been derived from colonic carcinomas [4]. However, nonmalignant cell lines (IEC6) have been successfully developed from the rat [5], which can differentiate when grown in the presence of connective tissue elements [6, 7]. Clearly, a nontransformed human cell line in culture would increase our ability to study epithelial cell function, particularly with regard to genetic control when carcinoma cell lines may be abnormal. Results We have established epithelial cell lines from human fetal intestine. Morphologic, immunochemical and molecular techniques suggest that these cells originated from intestinal epithelial cells and retain features of small intestinal enterocytes. Furthermore, extracellular basement matrix induces brush border enzyme activity. Characterization has been extensive in one particular line, H-4. Examination of the chromosomes of the H-4 cell line demonstrated a normal 46 XY karyotype. The morphology of the viable cell lines was similar to that of rat IEC-6