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Biomedical subjects

W A Walker

Publications and source records attributed to W A Walker.

At least 145 records · Page 8Linked to original sources
PubMed1987

The comparative immunoreactivities of brain amyloids in Alzheimer's disease and scrapie.

An antibody was raised to a synthetic peptide corresponding to a published sequence for the first 24 residues of a cerebrovascular amyloid peptide (CVAP). Immunohistochemical staining of tissue sections revealed that the antibody bound extensively to cerebrovascular amyloid in Alzheimer disease (AD/SDAT) and Down's syndrome cases. The antibody bound less extensively to neuritic plaques (primitive and mature) and indetectably to neurofibrillary tangles. The antibody did not label scrapie plaques, scrapie-associated fibrils, or Gerstmann-Sträussler syndrome plaques. Immunoblotting experiments showed that the cerebrovascular amyloid peptide epitopes contaminating the neurofibrillary tangle preparations could be extracted with urea, leaving the neurofibrillary tangles intact. These data confirm that the cerebrovascular amyloid peptide is a component of cerebrovascular amyloid, and suggest that its epitopes are also components of neuritic plaque amyloid. The reduced level of immunostaining on amyloid cores in tissue sections suggests that either the cerebrovascular amyloid peptide epitopes are a minor component of amyloid cores, or that their mode of packing or state of processing in amyloid cores renders them relatively inaccessible to the antibody. We also conclude that the cerebrovascular amyloid peptide is not a component of neurofibrillary tangles. The synthetic cerebrovascular amyloid peptide possesses amyloid-like properties: at neutral pH it forms insoluble aggregates consisting of 5-7-nm fibrils, which form red-green birefringent adducts with Congo red and fluoresce with thioflavine S.

Alzheimer Disease↗
PubMed1987

Differential binding kinetics of cholera toxin to intestinal microvillus membrane during development.

A complete randomized block design was used to compare the binding kinetics of cholera toxin to developing rat enterocyte microvillus membranes prepared from newborn, 2-week-old, 4-week-old, and adult animals. Saturation-binding isotherms were generated on 16 independent samples (four blocks) under steady-state and reversible conditions. Scatchard analyses suggested positive cooperative binding to a single class of receptors, and the isotherms were analyzed by both the Hill-Waud and Michaelis-Menten functions. Receptor density varied significantly with age (P = 0.013). An abrupt rise in receptor density occurred after the neonatal period and normalized in the adult animal. The half-dissociation constant also varied significantly with age (P = 0.019). Microvillus membranes from suckling animals had a slightly higher apparent affinity than those from weaned animals. Neither receptor concentration nor membrane purity confounded these observations. Whereas age-related changes in apparent affinity correlated with cellular responses, changes in receptor density did not. This study suggests that developmental changes in membrane structure which influence binding affinity but not receptor density may, in part, contribute to the increased sensitivity of suckling rats to cholera toxin exposure.

Age Factors↗
PubMed1987

Development of gastrointestinal surface. VIII. Lectin identification of carbohydrate differences.

Binding of microvillus membranes (MVM) from newborn and adult rats by concanavalin A (Con A), Ulex europaeus (UEA I), Dolichos bifluorus (DBA), and Triticum vulgaris (WGA) was examined to determine the availability of carbohydrate-containing sites for these lectins on the intestinal surface during development. Consistent patterns of differences in the reaction of MVM with these lectins were found. Con A and UEA had much higher reactivities to MVM of adult than newborn rats. 125I-labeled-UEA gel overlay experiments revealed the abundance of UEA-binding sites in MVM of adult rat in contrast to the two binding sites in MVM of a newborn rat. DBA bound only to MVM of the adults, and very few binding sites were found in immature MVM. In contrast to these lectins, WGA binding was much higher in MVM of the newborns and decreased with maturation. Additional experiments on the age dependence of UEA and DBA reactivities revealed that the most striking changes occur in animals from 2 to 4 wk of age. In MVM from 2-wk-old rats, there were only 13.9% and less than 0.2% of the adult binding capacities for UEA and DBA, respectively. By the time the animals were 4 wk old, the binding capacity for UEA had attained close to the level of the adults, whereas for DBA it reached 71.3% of the adult value. These results provide definite evidence of changes in the intestinal surface during perinatal development.

Animals↗
PubMed1987

Structural and functional maturation of rat gastrointestinal barrier with thyroxine.

It has been noted that the closure of the intestinal barrier to immunoglobulins is a normal maturational process in the rat. It has also been noted that the microvillus membrane (MVM) of newborn animals differs from adult MVM. The purpose of this study is to document whether thyroid hormone can induce closure in vivo in the rat and to relate this effect of thyroxine to the structural and functional maturation of the intestinal MVM. To assess closure, 2-wk-old rats were fed a rat immunoglobulin G (IgG), and serum antibody binding activity was measured 4 h later. The antibody binding activity of treated animals (T) was 1.5-2 times less than that of controls (C) (P less than 0.001), indicating that thyroxine stimulates closure. The MVM similarly showed signs of maturation. Structural maturation was demonstrated by the lower fluidity of the thyroid-treated animals' membranes. Under the influence of thyroxine, the number of receptors on the MVM for IgG had decreased [2.8 X 10(-7) M (C) vs. 1.7 X 10(-7) M (T)], while the Ka remained the same, demonstrating the functional maturation of the MVM. In conclusion, thyroid hormone can induce both structural and functional maturation of the intestinal MVM and can enhance the intestinal mucosal barrier by decreasing the penetration of antibodies.

Animals↗
PubMed1987

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.

Animals↗
PubMed1987

Pathophysiology of intestinal uptake and absorption of antigens in food allergy.

An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of proteins and protein fragments. To combat the potential danger of invasion across the mucosal barrier, the infant must develop within the lumen and on the luminal mucosal surface an elaborate system of defense mechanisms that act to control and maintain the epithelium as an impermeable barrier to the uptake of macromolecular antigens. These defenses include a unique local immunologic system adapted to function in the complicated milieu of the intestine as well as other nonimmunologic processes such as a gastric barrier, intestinal surface secretions, peristaltic movement, etc, all of which help to provide maximum protection for the intestinal surface. Unfortunately, during the immediate postpartum period, especially for premature and "small-for-date" infants, this elaborate local defense system is incompletely developed. As a result of the delay in the maturation of the mucosal barrier, newborn infants are particularly vulnerable to pathologic penetration by harmful intraluminal substances. The consequences of altered defense are susceptibility to infection and the potential for hypersensitivity reactions and the formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis, and hepatitis. Fortunately, nature has provided a means for passively protecting the "vulnerable" newborn against the dangers of a deficient intestinal defense system: human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leukocytes, but many other substances that can interfere with bacterial colonization and prevent antigen penetration.

Antigens↗
PubMed1986

Developmental changes in the activities of sialyl- and fucosyltransferases in rat small intestine.

To study an enzymatic basis for the postnatal changes in intestinal glycosylation, the activities of sialyl- and fucosyltransferases were determined in the particulate fraction of mucosal cells prepared from rat small intestine of various ages. The results show that sialyltransferase activity was present in increased levels compared to adults during the preweaning period (1-2 weeks) and subsequently declined 5-fold to adult levels after weaning, while fucosyltransferase activity was decreased compared to adults in the first 3 weeks of life, rapidly increased at 4 weeks, and reached adult levels (10-fold) by 5 weeks. The changes in both sialyl- and fucosyltransferase activities were reflected by the membranous content of glycosidic-bound sialic acid and fucose, respectively. Cortisone injection precociously induced a decreased sialyltransferase activity and an increased fucosyltransferase activity in 2-week-old suckling rats. This study indicates that the activities of sialyl- and fucosyltransferases were reciprocally related and modulated by cortisone action in the developing intestine. These enzyme changes may be responsible for the previously noted shift from sialylation to fucosylation of the intestinal mucosa during maturation.

Animals↗
PubMed1986

Immune complex-induced enteropathy in the rat. I. Clinical and histological features.

Adult male Sprague-Dawley rats injected with preformed rat anti-bovine serum albumin antibody-bovine serum albumin complexes prepared in fivefold antigen excess, developed intestinal lesions consisting of annular bands of serosal hyperemia alternating with nonhyperemic bands, causing a striped appearance. Histologically, vascular congestion and mucosal edema were observed; more severe lesions were accompanied by hemorrhage, epithelial necrosis and sloughing, and modest polymorphonuclear leukocyte infiltration. The lesions developed rapidly and were accompanied by hemoconcentration. A correlation between the dose of immune complexes injected and the intensity and extent of intestinal lesions was noted. The pathogenetic mechanism of the lesions was not determined. The similarity of the lesions to those observed in systemic anaphylaxis in the rat and experimental and clinical shock was cited. The implications of immune complex-induced enteropathy for studies of immune complex clearance by the mononuclear phagocyte system were considered.

Animals↗
PubMed1986

Food proteins and gut mucosal barrier. IV. Effects of acute and chronic ethanol administration on handling and uptake of bovine serum albumin by rat small intestine.

The effects of ethanol exposure on small intestinal handling and uptake of radiolabeled bovine serum albumin were investigated using everted gut sacs. There was less breakdown of BSA after acute ethanol administration in vitro and after acute and chronic in vivo exposure. Thus, the vascular compartment of the small intestine was confronted with more complete and potentially more antigenic material after ethanol. Changes in BSA binding and uptake after acute exposure were shown to be reversible after 4-6 hr. In all groups, there was more BSA binding when the small intestine was exposed to ethanol. This difference was most pronounced after chronic exposure. In the same group, uptake of BSA was correlated with binding and significantly increased. Combined effects of ethanol on the gut mucosal barrier may account for changes in food antigen handling and uptake.

Alcoholism↗
PubMed1986

Increased permeability to polyethylene glycol 4000 in rabbits with experimental colitis.

Little information is available regarding colonic permeability to macromolecules in health or disease states. In vivo permeability of rabbit colon to [14C]polyethylene glycol 4000 (14C-PEG) was examined in the presence of immune complex-mediated experimental colitis and compared with that of partially treated (control) and normal rabbits. Permeability was assessed by urinary 14C-PEG excretion after intrarectal administration of 0.1 mM solution of 14C-PEG (1 ml/kg, 7.5 X 10(6) cpm/ml). Experimental colitis greatly increased colonic permeability (p less than 0.001 in two-way analysis of variance) compared with control and normal groups (2.06% +/- 0.19%, 0.14% +/- 0.04%, and 0.01% +/- 0.004%, respectively, of rectally administered counts). Gel diffusion chromatography showed that absorbed 14C-PEG was excreted into urine unchanged, demonstrating its applicability as an inert, nonmetabolizable macromolecular probe. Urinary clearance after mesenteric vein administration of 14C-PEG was similar in normal animals and animals with colitis, implicating colonic absorption as the source of the group differences. Postmortem histology confirmed the acute colitis lesions in the experimental group. These findings support the hypothesis that nonspecific colonic inflammation is associated with significant alterations of mucosal permeability.

Animals↗