Having demonstrated by indirect methods that the immature gastrointestinal tract of newborn infants is more permeable to cow milk antigens than the mature intestine of older infants, we extend these studies in man and in an experimental animal model in order to determine by direct radioimmunoassay techniques the extent of antigen transport from the gastrointestinal lumen into the serum. The degree of antigen uptake will be compared with prematurity of infants and with maturational criteria (mitotic index, morphologic features and DNA content) in the intestine of experimental animals. We also plan to characterize the enteromammary secretory immune system with respect to function in control of antigen uptake from the small intestine. Since the newborn infant is devoid of an active secretory system (SIgA system) during infancy, we plan to determine if human colostrum/milk can adequately function as a passive local protective process to prevent penetration of antigens from the intestinal lumen. The exact mechanism of colostral antibody function on the intestinal surface will be investigated and the distribution of colostral antibodies on the gut surface will be determined using a combination of morphologic, physiologic and immunologic techniques. Finally, the """"""""trophic"""""""" effect of human colostrum in limited absorption studies on premature infants will be examined using organ culture techniques as well as in vivo studies, we will also examine the effect of colostrum on the fetal/newborn rabbit intestine by using quantitate techniques of maturation of epithelial cells using villus/crypt enzyme markers and cell turnover techniques and morphologic assessment of epithelial cell states. These studies may help to revise our concepts of feeding practices in premature infants. If positive, the studies will support the use of colostrum in premature infants as a protective and """"""""trophic"""""""" substance as well as a nutrient.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Unknown (R22)
Project #
5R22HD012437-07
Application #
3445109
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1979-05-01
Project End
1987-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
Beck, P L; Ihara, E; Hirota, S A et al. (2010) Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3. Am J Physiol Gastrointest Liver Physiol 299:G43-53
Savidge, Tor C; Newman, Paul; Pothoulakis, Charalabos et al. (2007) Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology 132:1344-58
Bao, Yuanwu; Zhu, Libin; Newburg, David S (2007) Simultaneous quantification of sialyloligosaccharides from human milk by capillary electrophoresis. Anal Biochem 370:206-14
Meng, Di; Newburg, David S; Young, Cheryl et al. (2007) Bacterial symbionts induce a FUT2-dependent fucosylated niche on colonic epithelium via ERK and JNK signaling. Am J Physiol Gastrointest Liver Physiol 293:G780-7
Nanthakumar, N Nanda; Dai, Dingwei; Meng, Di et al. (2005) Regulation of intestinal ontogeny: effect of glucocorticoids and luminal microbes on galactosyltransferase and trehalase induction in mice. Glycobiology 15:221-32
Dai, Dingwei; Nanthakumar, N Nanda; Savidge, Tor C et al. (2002) Region-specific ontogeny of alpha-2,6-sialyltransferase during normal and cortisone-induced maturation in mouse intestine. Am J Physiol Gastrointest Liver Physiol 282:G480-90
Fernandez, I M; Silva, M; Schuch, R et al. (2001) Cadaverine prevents the escape of Shigella flexneri from the phagolysosome: a connection between bacterial dissemination and neutrophil transepithelial signaling. J Infect Dis 184:743-53
Dai, D; Nanthkumar, N N; Newburg, D S et al. (2000) Role of oligosaccharides and glycoconjugates in intestinal host defense. J Pediatr Gastroenterol Nutr 30 Suppl 2:S23-33
Siafakas, C G; Anatolitou, F; Fusunyan, R D et al. (1999) Vascular endothelial growth factor (VEGF) is present in human breast milk and its receptor is present on intestinal epithelial cells. Pediatr Res 45:652-7
Capano, G; Bloch, K J; Carter, E A et al. (1998) Polyamines in human and rat milk influence intestinal cell growth in vitro. J Pediatr Gastroenterol Nutr 27:281-6

Showing the most recent 10 out of 61 publications