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Biomedical subjects

W A Walker

Publications and source records attributed to W A Walker.

At least 127 records · Page 7Linked to original sources
PubMed1989

Divalent hapten-induced intestinal anaphylaxis in the mouse: uptake and characterization of a bystander protein.

We examined the mucosal barrier function during anaphylaxis induced by the hapten N,N'-di-2,4,dinitrophenyl-lysine (di-DNP-lysine) in BDF1 female mice immunized with dinitrophenylated Ascaris suum extract. Immunized mice were gavaged with 10 mg or 50 mg of ovalbumin (OVA) with or without N,N'-di-2,4,-DNP-lysine (di-DNP-lysine). Animals that received di-DNP-lysine underwent anaphylaxis and were observed to have significantly greater serum concentrations of immunoreactive OVA (iOVA) than control mice. The severity of anaphylaxis, which varied with the dose of di-DNP-lysine administered, influenced the uptake of OVA; greater amounts of iOVA were detected in serum of mice undergoing more severe anaphylaxis. On gel permeation of serum from both groups of mice, immunoreactive OVA was found to have a molecular size similar to native OVA. Di-DNP-lysine is a synthetic hapten that reliably induced anaphylaxis in sensitized animals challenged by gavage. Anaphylaxis resulted in the uptake into the circulation of greater quantities of an unrelated protein antigen present in the intestinal lumen. The protein antigen that was taken up into the circulation appeared to be intact and thus may have an influence on the development of the immune response, or lack thereof, to this bystander antigen.

Anaphylaxis↗
PubMed1989

Intestinal adaptation during lactation in the mouse. I. Enhanced intestinal uptake of dietary protein antigen.

Small quantities of dietary protein antigens cross the intestinal epithelium of the lactating mouse, enter the circulation, are transferred across the mammary gland into the milk and reach the suckling neonate. In this study, we sought to determine whether intestinal uptake of ovalbumin (OVA) was enhanced in lactating compared to control mice. OVA was administered by gavage under ether anaesthesia. Blood was obtained at 15, 30, 60 and 120 min and immunoreactive OVA (iOVA) measured by enzyme immunoassay. At 30 and 60 min, a three- to four-fold higher concentration of iOVA was detected in lactating compared to control mice. Because this increase in concentration of iOVA might be explained by changes in plasma volume, rate of clearance of OVA from the circulation or altered uptake from the intestine, plasma volume was measured by isotope dilution after i.v. injection of 125I-bovine serum albumin (BSA) and clearance was assessed by measuring elimination of OVA from the circulation after i.v. injection of OVA. In comparison to controls, plasma volume of Day 7-10 lactating mice was increased two-fold and no difference in clearance rate was noted. Because the increase in concentration of iOVA in lactating mice is several-fold greater than in controls, we suggest that increased intestinal uptake of the protein occurs during lactation.

Animals↗
PubMed1989

Differences between caries levels in 5-year-old children from fluoridated Anglesey and non-fluoridated mainland Gwynedd in 1987.

Using standard epidemiological techniques, several indicators of dental health showed significantly lower levels of caries experience in 5-year-old children from fluoridated Anglesey compared with a similar group from non-fluoridated mainland Gwynedd. The mean dmft was 0.80 in Anglesey and 2.26 in mainland Gwynedd. The mainland Gwynedd children had suffered more toothache and experienced more dental extractions. This study showed that fluoridation of water supplies remains an effective and relevant public health measure, and illustrates the value of a parental questionnaire in epidemiological surveys of younger children.

Child, Preschool↗
PubMed1989

Does open lung biopsy affect treatment in patients with diffuse pulmonary infiltrates?

The decision to perform open lung biopsy in the evaluation of a diffuse pulmonary infiltrate is based on the probability that this examination will yield specific information that may lead to a change in treatment. The role of this procedure remains controversial and many clinicians are reluctant to allow this invasive procedure without assurances that results will lead to a change in therapy for a significant number. To evaluate the impact of open lung biopsy on diagnosis and treatment of diffuse pulmonary infiltrates, we conducted a retrospective review of 61 patients undergoing this procedure at three university-affiliated hospitals during a recent 7-year period. There were 37 men and 24 women; average age was 57 years. Biopsy yielded a specific diagnosis in 21 (34%) patients and a change in therapy in 33 (54%) patients. A complication developed in 11 (18%) patients, directly related to the biopsy procedure in six (10%). Eight patients died. The immune status in 22 (36%) patients was compromised. A specific diagnosis was obtained in 13 (59%) immunocompromised patients and a change in therapy occurred in 17 (77%) of these patients after biopsy. A specific diagnosis was obtained in only eight (21%) of the 39 noncompromised patients and therapy was changed in 16 (41%) patients in this group (p less than 0.02 compromised versus noncompromised). Morbidity and mortality were not significantly different between the two groups. A nonspecific diagnosis led to a change in therapy as frequently as a specific diagnosis in both compromised and noncompromised groups. Open lung biopsy in the patient with a diffuse pulmonary infiltrate is an accurate diagnostic tool and frequently leads to a change in patient treatment. The procedure can be performed with acceptable morbidity and mortality in immunocompromised and noncompromised patients.

Adult↗
PubMed1988

Host defense development in gut and related disorders.

The gastrointestinal tract serves as an important interface between ingested elements from the external environment and the internal milieu of the person. Maturation of this intestinal barrier appears to occur along with the normal development of other organ systems. Evidence is presented for this maturational process, and the relation of this immature barrier to certain disease states seen in the neonatal period (e.g., infectious diarrhea, necrotizing enterocolitis, and allergic disease) is discussed.

Celiac Disease↗
PubMed1988

Redistribution of blood flow after thermal injury and hemorrhagic shock.

Diminished mucosal mass and a diminished rate of DNA synthesis by the intestinal mucosa have been identified in the rat after thermal injury. Because these changes may be associated with ischemia, the distribution of intestinal blood flow was studied after a thermal injury and compared with the blood flow distribution after hemorrhagic shock. For the thermal injury, anesthetized animals received a standardized 20% body surface area, full-thickness injury and were given intraperitoneal saline resuscitation. By the use of 46Sc- or 141Ce-labeled microspheres, no changes in intestinal and hepatic blood flow occurred after thermal injury. In contrast, a marked redistribution of blood flow was identified after hemorrhagic shock in which a decrease in arterial blood flow was identified to the stomach and to the small and large intestine. Although clinical shock was not present, the cardiac output decreased to a comparable degree in the hemorrhagic shock and the thermal injury. These studies indicate that although physiological changes in intestinal mucosa can be demonstrated after burn injury, these changes are not due to decreases in mesenteric arterial blood flow.

Animals↗
PubMed1988

Development of the gastrointestinal mucosal barrier: changes in phospholipid head groups and fatty acid composition of intestinal microvillus membranes from newborn and adult rats.

Phospholipids in microvillus membrane (MVM) prepared from the proximal small intestine of newborn (less than 24 h of age) and adult rats were characterized to determine if differences in composition existed. Our hypothesis is that developmental differences in composition of the MVM may account for mucosal barrier differences to microorganisms and antigens during the perinatal period. Lipid analysis showed that both cholesterol and total phospholipids, per mg of membrane protein, were much higher in the newborn MVM than the adult, but the molar ratio of these two lipid classes remained unchanged. Increased phosphatidylcholine and decreased phosphatidylinositol levels were found in the newborn MVM compared to the adult. In addition, the major difference in fatty acid composition of total lipid extracts and three major membrane phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol appeared to be an increased ratio of palmitate (16:0) to stearate (18:0) and of oleate (18:1) to linoleate (18:2) in the newborn. These data suggest that changes in the proportion of phospholipid polar head groups and fatty acyl groups as well as changes in the amount of total phospholipids and cholesterol exist in the newborn MVM. These observations are consistent with differences in MVM fluidity previously noted and may help explain the increased uptake of antigens and other mucosal barrier defects in the newborn intestine.

Age Factors↗
PubMed1988

Gastrointestinal syndromes associated with food sensitivity.

A wide range of clinical syndromes exist that are related to adverse reactions to dietary proteins and that affect predominantly the gastrointestinal tract of infants and children. Experimental data suggest a critical role for developmental alterations affecting intestinal permeability and the mucosal immune response that predispose to these conditions. The diagnostic and therapeutic approach to these disorders varies depending on the nature of the presumed offending antigen, the anatomic site affected, the severity of the inflammatory process, and the implications for future dietary and medical management. Ultimately, the proof that a particular dietary antigen is responsible is dependent on observing the response to oral challenge.

Child↗
PubMed1987

Trichloroacetic acid (TCA) precipitability of 125I in the blood of mice fed 125I.

A recent study showed that after feeding 125I-labelled proteins or free 125I to mice, as much as 40% of total radioactivity in the circulation precipitated upon mixing whole blood with 10% trichloroacetic acid. We examined this potential limitation to the use of radiolabelled tracers for studies on intestinal digestion of proteins and protein uptake, and identified its mechanism. BALB/c mice were gavage-fed or injected intravenously (i.v.) with Na125I. Blood obtained at 15 min was added directly to 10% trichloroacetic acid (TCA) or was processed to obtain serum or plasma. On mixing with 10% TCA, 25-33% of the radioactivity in whole blood was precipitated; less than 2% of the radioactivity in plasma or serum was precipitated. In vitro studies identified hemoglobin as the primary carrier protein participating in this reaction. If hemoglobin was replaced by methemoglobin or cyanomethemoglobin, then the reaction with 125I did not occur, suggesting that iron in the heme group may be the site for 125I binding and that iron must be in its reduced or ferrous form (Fe2+). The administration of non-radioactive NaI in vivo or its addition to reaction mixtures in vitro completely inhibited the precipitation of 125I by hemoglobin in the presence of TCA. Thus the addition of non-radioactive iodide to TCA stock solutions may effectively prevent non-specific binding of 125I to free hemoglobin released unintentionally during venipuncture or at other stages of blood processing.

Animals↗
PubMed1987

myo-inositol action on gerbil intestine: alterations in alkaline phosphatase activity upon phosphatidylinositol depletion and repletion in vivo.

The influence of phosphatidylinositol (PI) on intestinal alkaline phosphatase activity was studied in myo-inositol deficient gerbils. A reduction of membrane PI in intestinal mucosa to 30-40% of the control was produced by feeding female gerbils a myo-inositol-deficient diet containing coconut oil for 2 weeks. As expected, the animals developed typical intestinal lipodystrophy with abnormal fat accumulation. In the PI-depleted animal, intestinal alkaline phosphatase activity was reduced to 20-30% of the control group. The levels of both membranous and soluble enzymes in intestinal mucosa were affected, but there were no changes in liver, kidney and plasma levels. When the lipodystrophic gerbils were given dietary myo-inositol, the complete repletion of intestinal membrane PI to the control level occurred 36 h later, whereas membrane-bound alkaline phosphatase activity in intestine was not restored to the control level until 72 h later. Administration of cycloheximide or actinomycin D did not block this enzyme induction. Lymphatic output of triacylglycerol into the bloodstream was stimulated 10-fold at 18 h of myo-inositol repletion, but there was no parallel increase in the activity of alkaline phosphatase in plasma during this early phase of intestinal recovery. Thus, these data suggest a possible regulatory role of PI in the processing and/or turnover of alkaline phosphatase in vivo, but a negative role of alkaline phosphatase in lipid transport across gerbil intestine.

Alkaline Phosphatase↗
PubMed1987

Screening tests for enteropathy in children.

Three widely used screening tests for enteropathy in childhood are the lactose breath hydrogen test, the one-hour serum D-xylose absorption test, and the 72-hour fecal fat determination. To our knowledge, no study has compared these three tests and jejunal biopsy results. A retrospective survey of all jejunal biopsy results at Children's Hospital, Boston, from July 1983 to July 1984 was undertaken to evaluate which test best predicted a normal biopsy result. None of the screening tests was ideal. The lactose breath test had low sensitivity and specificity and did not correlate significantly with biopsy results. The D-xylose and fecal fat tests were each significantly correlated with biopsy results; a normal result of either test was highly predictive of a normal biopsy result. Combining the results of two or more screening tests did not improve predictive value. The xylose test is preferable on the basis of greater sensitivity and ease of patient compliance.

Adolescent↗
PubMed1987

Development of intestinal mucosal barrier function to antigens and bacterial toxins.

In this paper, we have tried to provide evidence for the association between the microvillus membrane immaturity of young infants/animals and the enhanced attachment and uptake of intestinal antigens and toxins. Finally, we have reviewed observations that growth factors that alter the newborn MVM composition towards maturity may also affect the handling of antigens by the intestinal surface.

Age Factors↗