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W Allan Walker

Publications and source records attributed to W Allan Walker.

47 records · Page 3Linked to original sources

Distribution of the IgG Fc receptor, FcRn, in the human fetal intestine.

The intestinal Fc receptor, FcRn, functions in the maternofetal transfer of gamma globulin (IgG) in the neonatal rodent. In humans, most of this transfer is presumed to occur in utero via the placenta. Although the fetus swallows amniotic fluid that contains immunoglobulin, it is unknown whether this transfer also occurs via the fetal intestine. A human FcRn has been identified in the syncytiotrophoblast that mediates the maternofetal transfer of antibody. It has also been identified in human fetal intestine and is postulated to function in IgG transport. We hypothesize that the human fetal intestinal FcRn may play a role in IgG transport from the amniotic fluid into the fetal circulation. The aim of this study was to characterize the distribution of the FcRn along the human fetal intestine. Lysates prepared from human fetal intestine and from a nonmalignant human fetal intestinal epithelial cell line (H4) were subjected to Western blot analysis and probed using anti-FcRn antibodies. A 42-kD band, consistent with the known molecular weight of the FcRn, was detected along the human fetal intestine and in H4 cells. Expression of the human FcRn was confirmed with immunohistochemistry. Our study demonstrates the expression of FcRn along the human fetal intestine and in a human nonmalignant fetal intestinal epithelial cell line (H4), which by location indicates that FcRn could play a role in the uptake and transport of IgG in the human fetus.

Adult↗

Nutritional factors contributing to the development of cholestasis during total parenteral nutrition.

Parenteral nutrition-associated cholestasis is a major clinical problem in pediatrics, particularly during infancy in children with short bowel syndrome who require long-term use of total parenteral nutrition (TPN) for survival. Multifactorial theories regarding the origin of parenteral nutrition-associated cholestasis have not yet defined its pathogenesis or resulted in a solution to the problem. However, our knowledge of risk factors has helped develop new hypotheses as to the mechanisms of this disease. In this review, we consider the following potential risk factors that influence the development of this condition: (1) the gastrointestinal dysfunction associated with the absence of enteric nutrients while receiving TPN; (2) components of TPN solutions as potential hepatotoxins; and (3) the contribution of the underlying disease necessitating TPN for adequate nutrition. It is hoped that a better understanding of factors affecting hepatocyte secretion and bile formation and flow will help to prevent this life-threatening complication of TPN.

Child↗

The role of indigenous microflora in the development of murine intestinal fucosyl- and sialyltransferases.

Most enteric bacteria use intestinal brushborder glycoconjugates as their target host cell receptors. It has been postulated that resident microbes regulate specific glycosyltransferases that are responsible for synthesizing brushborder glycoconjugates. To investigate this hypothesis, we measured glycosyltransferase enzyme activities in intestine from different regions of maturing conventional (CONV), germ-free (GF), and ex-germ-free (XGF) mice and compared them to general enzyme markers of gut development, for example, disaccharidases. High alpha2,3/6-Sialyltransferase (ST) activity and low alpha1,2-fucosyltransferase (FT) activities were detected from duodenum to colon in suckling CONV mice, but the relative levels of these activities reversed during the third postnatal wk, rapidly reaching adult levels by the fourth wk. These age-related enzyme changes were significantly attenuated in GF mice, maintaining an immature pattern well past 3 wk. Introduction of gut microflora in GF mice rapidly initiated maturation of glycosyltransferase activity but had no significant affect on developmental programming of dissacharidases. Therefore, in mice, intestinal glycosyltransferase activities are under tissue and developmental control and microflora play a major role in their specific ontogeny but not in overall development. These findings may help explain the regional specificity of commensal bacteria and of enteric pathogens and may also relate age-related changes in microflora to susceptibility to enteropathogens.

Age Factors↗

Nutritional impact of pre- and probiotics as protective gastrointestinal organisms.

The health benefits of pre- and probiotics have been the subject of increased research interests. These food supplements have been demonstrated to alter the pre-existing intestinal flora so as to provide an advantage to the host. This review focuses on the scientific evidence both for and against their role in promoting health and treating disease. Specific attention is turned to their effects on immunomodulation, lipid metabolism, cancer prevention, diarrhea, Helicobacter pylori, necrotizing enterocolitis, allergy, and inflammatory bowel disease.

Diarrhea↗

Protective nutrients and functional foods for the gastrointestinal tract.

Epithelial and other cells of the gastrointestinal mucosa rely on both luminal and bloodstream sources for their nutrition. The term functional food is used to describe nutrients that have an effect on physiologic processes that is separate from their established nutritional function, and some of these nutrients are proposed to promote gastrointestinal mucosal integrity. We review the recent in vitro, animal, and clinical experiments that evaluated the role of several types of gastrointestinal functional foods, including the amino acids glutamine and arginine, the essential micronutrients vitamin A and zinc, and 2 classes of food additives, prebiotics and probiotics. Many of the data from preclinical studies support a strong role for enteral nutrients in gastrointestinal health; in comparison, the data from human studies are limited. In some cases, impressive data from in vitro and animal studies have not been replicated in human trials. Other clinical trials have shown positive health benefits, but some of those studies were plagued by flaws in study design or analysis. The methods available to detect important changes in human gastrointestinal function and structure are still limited, but with the development of more sensitive measures of gastrointestinal function, the effects of specific nutrients may be more easily detected. This may facilitate the development of phase 3 clinical trials designed to more rigorously evaluate the effects of a particular nutrient by focusing on valid and reliable outcome measures. Regulatory changes in the way in which health claims can be made for dietary supplements should also be encouraged.

Animals↗

Immunology.

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Editorial↗

T helper cell subclasses and clinical disease states.

The functionally different CD4 T helper cell subsets known as T helper 1 (Th1) and T helper 2 (Th2) display a unique and different cytokine profile. Abnormal skewing toward Th1 or Th2 cells has been suggested to play an important role in the pathogenesis of autoimmune disorders and in inflammatory and allergic diseases. The Th1/Th2 paradigm continues to serve as a model to understand the pathogenesis of several pathologic conditions and provides the rationale for the development of new strategies for treating and preventing these diseases. Over the past year, efforts have continued to increase our understanding of the mechanisms underlying the development and regulation of Th cells and their pathogenic role and therapeutic potential in the induction and treatment of clinic diseases. Several teams of researchers have further examined the association of Th1/Th2 inducing factors and allergic disease and intestinal inflammatory diseases. The protective effect of helminth infection on allergy and the role of regulatory T cells in both Th1- and Th2-mediated diseases have been further examined.

Journal Article↗

Region-specific ontogeny of alpha-2,6-sialyltransferase during normal and cortisone-induced maturation in mouse intestine.

Regional differences in the ontogeny of mouse intestinal alpha-2,6-sialyltransferase activities (alpha-2,6-ST) and the influence of cortisone acetate (CA) on this expression were determined. High ST activity and alpha-2,6-ST mRNA levels were detected in immature small and large intestine, with activity increasing distally from the duodenum. As the mice matured, ST activity (predominantly alpha-2,6-ST) in the small intestine decreased rapidly to adult levels by the fourth postnatal week. CA precociously accelerated this region-specific ontogenic decline. A similar decline of ST mRNA levels reflected ST activity in the small, but not the large, intestine. Small intestinal sialyl alpha-2,6-linked glycoconjugates displayed similar developmental and CA induced-precocious declines when probed using Sambucus nigra agglutinin (SNA) lectin. SNA labeling demonstrated age-dependent diminished sialyl alpha2,6 glycoconjugate expression in goblet cells in the small (but not large) intestine, but no such regional specificity was apparent in microvillus membrane. This suggests differential regulation of sialyl alpha-2,6 glycoconjugates in absorptive vs. globlet cells. These age-dependent and region-specific differences in sialyl alpha-2,6 glycoconjugates may be mediated in part by altered alpha-2,6-ST gene expression regulated by trophic factors such as glucocorticoids.

Aging↗

Review: the role of omega 3 fatty acids in intestinal inflammation.

The role of polyunsaturated fatty acids (PUFAs) in inflammatory lesions of the intestines is the subject of increasing research. This review begins with a background discussion of the source, elongation, and desaturation of PUFAs, as well as the role they have played in the human diet through evolution. The available data and hypotheses as to how manipulation of PUFAs might effect the various components of the immune system are then provided. Possible mechanisms by which PUFAs result in immunomodulation include alterations in eicosanoid synthesis, membrane fluidity, signal transduction, intraluminal bacteria, and gene expression. Attention is then turned to the known effects that these polyunsaturated fatty acids have on the various individual components of the immune system including lymphocytes, neutrophils, and antigen presenting cells, as well as the immunoregulatory process of apoptosis. Finally, laboratory data on the role of PUFAs in necrotizing enterocolitis, and to a greater extent inflammatory bowel disease, first as demonstrated in animal models of the disease, and second in human studies are then summarized.

Journal Article↗

Probiotics as flourishing benefactors for the human body.

This article provides a comprehensive review of the beneficial effects of various strains of probiotics in preventing and treating certain diseases. Currently, changed lifestyles as well as the increased use of antibiotics are significant factors challenging the preservation of a healthy intestinal microflora. The concept of probiotics is to restore and uphold a microflora advantageous for the human body. Probiotics are found in a number of fermented dairy products, infant formula, and dietary supplements. In the presence of prebiotics, which are nondigestible food ingredients favorable for probiotic growth, their survival in the intestine is ameliorated.

Diarrhea↗