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Biomedical subjects

W A Walker

Publications and source records attributed to W A Walker.

At least 109 records · Page 6Linked to original sources

Parenteral protein-sparing modified fast in an obese adolescent with Prader-Willi syndrome.

A ventilator-dependent, extremely obese adolescent patient with Prader-Willi syndrome was nutritionally managed using a parenteral, protein-sparing modified fast. A solution containing only amino acids, electrolytes, vitamins, and macro- and micro-minerals helped create a ketotic state and facilitate weaning from the ventilator. This case demonstrates an unusual strategy for achieving weight loss and the challenge to provide adequate protein intake while limiting fluid intake.

Adolescent↗

Celiac disease.

Explore the source record for details and available documents.

Celiac Disease↗

Medical management of acute traumatic rupture of the aorta.

Surgical reconstruction is the treatment for acute traumatic aortic rupture and should be accomplished immediately in most patients. In patients in whom concomitant injuries or the development of life-threatening complications preclude safe and successful aortic reconstruction, pharmacological intervention to reduce the risk of free aortic rupture may be considered. Surgical reconstruction can then be more safely performed under controlled elective circumstances.

Abdominal Injuries↗

Uptake and transport of epidermal growth factor by the small intestinal epithelium of the fetal rat.

Epidermal growth factor may play an important part in postnatal gastrointestinal development. However, little is known of its role prenatally. The aim of this study was to detect epidermal growth factor in amniotic fluid and to study its uptake and transfer across the epithelium of fetal rat small intestine. Anesthetized 20-day gestation rats underwent caesarean section. Three fetuses were exteriorized, their abdomens were opened, and ligated loops of proximal and distal small intestine were infused with 100 micrograms epidermal growth factor. Infused segments were removed 30 min later and processed for electron microscopy, and tissue was embedded in LR gold resin. Sections were treated with rabbit anti-rat epidermal growth factor antibody, followed by 5 nm gold-labeled goat anti-rabbit immunoglobulin before staining. Epidermal growth factor was measured in amniotic fluid by radioimmunoassay. In the proximal and distal small intestine epidermal growth factor was found membrane-associated along the luminal surface of microvilli, within apical invaginations and endosomal compartments, free from the membrane in multivesicular bodies, within large clear vesicles, basal vesicles and in association with the basolateral membrane and beyond. Epidermal growth factor was found in amniotic fluid at a concentration of 0.38 +/- 0.07 (SD) ng/ml. This study shows that epidermal growth factor is present in amniotic fluid and is transported across the epithelium of fetal rats by an endocytotic process in both the upper and lower small intestine. It is likely that amniotic fluid epidermal growth factor plays a part in intestinal mucosal development, and may be active systemically after transepithelial passage in utero.

Amniotic Fluid↗

Divalent hapten-induced intestinal anaphylaxis in the mouse enhances macromolecular uptake from the stomach.

The capacity of the stomach to participate in anaphylaxis induced by the hapten N,N'-di-2,4,dinitrophenyllysine (di-DNP-lysine) was examined in BDF1 female mice immunized with dinitrophenylated Ascaris suum extract. Immunized animals underwent laparotomy and nontraumatic pyloric occlusion using a microvascular clamp. Following wound closure, animals were gavage-fed ovalbumin together with di-DNP-lysine. Other mice were subjected to systemic anaphylaxis by intravenous injection of di-DNP-lysine administered 1 min after gavage feeding of ovalbumin. The intravenous and intragastric administration of di-DNP-lysine led to a sixfold or greater increase in serum immunoreactive ovalbumin. Examination of 1-micron sections of gastric tissue from DNP-Asc-immunized and unimmunized mice showed an intact mucosal and submucosal architecture. A 75% increase in the number of mast cells below the muscularis mucosa was seen in immunized compared with unimmunized BDF1 mice. Gastric tissue sections from immunized mice challenged orally or intravenously with di-DNP-lysine showed compaction of erythrocytes in blood vessels, degranulation of mast cells, degenerative changes in the gastric epithelium, expulsion of mucus from gastric glands, and edema in the lamina propria. The present model may be useful for further defining the consequences of anaphylaxis on the development of immune responses to dietary antigens.

Anaphylaxis↗

Prevention of necrotizing enterocolitis in the rat with prenatal cortisone.

Cortisone acetate is known to accelerate maturation of the immature intestine. The effect of prenatal administration of cortisone acetate on the morbidity and mortality of necrotizing enterocolitis was examined in a rat pup model. Pregnant rats were administered cortisone acetate, 20 mg/100 g of body weight, or normal saline by daily IP injection from day 18-21 of gestation. Rat pups were taken from the mothers before suckling was initiated, fed a simulated rat milk formula, and subjected to daily ischemic insults to produce an animal model of necrotizing enterocolitis. Both morbidity and the mortality rates were significantly improved with prenatal cortisone treatment. Maturation of the intestinal mucosal barrier was accelerated with the cortisone treatment as measured by decreased serum concentrations of a fed antigen, ovalbumin. Aerobic bacterial colonization of the small intestine and translocation of bacteria to the liver were decreased in the pups pretreated with steroids. These changes observed in a rat model of necrotizing enterocolitis may explain the decreased incidence of necrotizing enterocolitis in human infants born to mothers who received corticosteroids late in gestation.

Animals↗

Developmental changes in galactosyltransferase activity in the rat small intestine.

During postnatal development, UDP-Gal: GlcNAc(beta 1-4)-galactosyltransferase (4 beta-GT) and UDP-Gal:GalNAc(beta 1-3)-galactosyltransferase (3 beta-GT) activities were increased by 17- and 24-fold, respectively, in the rat small intestine. The injection of cortisone into suckling rats resulted in precocious induction of distal 4 beta- and 3 beta-GT activities by 2.7- and 1.8-fold, respectively. Injection of phorbol-12-myristate-13-acetate (PMA) resulted in precocious induction of distal 3 beta-GT by 2.7-fold. These results suggest that intestinal galactosyltransferase activities are under developmental regulation and can be modified by cortisone and PMA.

Aging↗

Prolactin is transported across the epithelium of the jejunum and ileum of the suckling rat.

Milk prolactin is transferred from the gastrointestinal tract to the circulation of the suckling rat. To identify the site of prolactin penetration and to determine the mechanism by which the hormone traverses the mucosal barrier, we followed the uptake of prolactin from ligated loops of jejunum or ileum in vivo by three methods: autoradiography, transport of prolactin-gold conjugates, and immunocytochemistry. Autoradiographic studies demonstrated specific binding sites for 125I-prolactin on apical membranes of the jejunum and ileum. Excess cold prolactin reduced radiolabel in apical and basal compartments. Gel autoradiography of portal sera showed the presence of intact prolactin and a prolactin fragment following jejunal transport but only a prolactin fragment following ileal transport. Uptake of prolactin-gold conjugates demonstrated that, in the jejunum, label was present at the luminal surface, within endosomal compartments and lysosomes, in basal coated and smooth vesicles, within basal coated pits, and beyond the basolateral surface. In the ileum, label was found at the luminal surface; within the tubulocisternae, endosomal vesicles, lysosomes, and basal smooth vesicles; and beyond the basolateral surface. Immunoreactive prolactin was present throughout the transepithelial pathways. This study demonstrates that prolactin is selectively and nonselectively absorbed in the jejunum and ileum and that the hormone is directed either to the lysosome for degradation or across the epithelium by means of a transcellular pathway.

Animals↗

Spontaneous rupture of the esophagus: a 30-year experience.

This retrospective review of 34 patients with spontaneous rupture of the esophagus, which spans a 30-year period, attempts to identify areas in diagnosis and therapy that might alter the dismal prognosis. The diagnosis and definitive surgical repair of Boerhaave's syndrome were frequently delayed. Delay resulted in a significant increase in complication rates. Pain (85%) and vomiting (71%) were the only common historical events suggesting the diagnosis. Physical examination was of aid in the diagnosis in only the 9 patients (27%) who demonstrated cervical or mediastinal emphysema. The initial chest roentgenogram was abnormal in 97% of the patients, but was interpreted as "compatible with perforation of the esophagus" in only 27%. Esophagography was diagnostic in 23 of 24 patients in whom it was used. Thoracentesis was of little diagnostic aid, but pleural fluid pH was measured in only 15% of the patients. Prompt surgical repair, regardless of time after onset, appears to be the indicated therapy.

Adult↗

Food allergy: facts and fiction.

Hypersensitivity reactions to dietary products are especially common in the pediatric population, yet food allergy as a distinct clinical entity remains poorly defined. The clinicopathologic features of this syndrome can vary considerably from patient to patient; no reliable diagnostic laboratory tests are available, and some of the treatment regimens are controversial. The pathogenesis of this condition is not well understood. An important factor is the role of the intestinal mucosal barrier in the regulation of uptake of dietary antigen from the intestinal tract. Recently, significant differences have been observed between the features of the immature newborn and the mature adult intestinal mucosal barriers. These findings may be of fundamental importance to the pathogenesis of food allergy and are currently an area of intense research.

Aging↗

Short term neonatal starvation altered cholera toxin binding in rabbits.

Acute neonatal malnutrition alters lumenal glycoproteins as demonstrated by altered lectin binding. To determine the effect of a 72-h fast on lumenal glycolipids, specifically the monosialoganglioside GM1, we quantitated cholera toxin (CT) binding and adenylate cyclase activity. The calculated number of specific sites for CT binding to microvillus membrane (MVM) from newborn rabbits fasted for 72 h was decreased in MVM from proximal small bowel (7 +/- 0.8 x 10(8)/micrograms protein) compared to 72-h control neonatal rabbits (18 +/- 3.3 x 10(8) micrograms protein). In distal small bowel there was no difference in the calculated receptor sites/micrograms MVM protein between fasted (8 +/- 1.7 x 10(8)) and fed (11 +/- 4 x 10(8)) groups. MVM prepared from proximal small bowel of fed animals bound significantly more CT than MVM prepared from distal small bowel of fed animals. The affinity for CT was the same in all MVM preparations. Neuraminidase treatment of MVM resulted in increased CT binding in fed and fasted rabbit proximal and distal MVM preparations, but the greatest increase occurred in MVM prepared from proximal small bowel from fasted animals. There was no difference in adenylate cyclase activity in fed, fasted, and proximal or distal small bowel crude membrane preparations. Refeeding (120 h) resulted in normalization of CT binding in MVM from proximal small bowel of fasted animals. We conclude a 72-h fast in neonatal rabbits resulted in decreased regional CT binding in MVM prepared from proximal small bowel of fasted animals, but no change in adenylate cyclase activity. Refeeding reverses CT binding abnormalities.

Adenylyl Cyclases↗

High-pressure water injury: case report.

High-pressure water jets are commonly used for complex industrial cleaning jobs, yet we found few reports of injuries attributed to these potentially dangerous devices. We present a case of severe laceration to the lower extremity caused by a high-pressure water jet with concomitant major vascular injury, apparently the first reported. Principles of evaluation and treatment are reviewed and documented.

Accidents, Occupational↗

Changes in the gastrointestinal tract during enteral or parenteral feeding.

Intestinal adaptation, in terms of increasing intestinal length and weight, usually occurs rapidly after small-bowel resection. However, this response depends on provision of enteral nutrients. If total parenteral nutrition without enteral feeding is prolonged, hypoplasia of the intestinal mucosa results. Adaptation is probably mediated through the presence of luminal nutrients, particularly glutamine, which is preferentially used by the intestine. However, systemic hormonal factors, possibly gastrin, cholecystokinin, and glucagon, also influence intestinal adaptation. Thus, in the management of short-bowel syndromes, enteral nutrition should be added to total parenteral nutrition as soon as possible.

Adaptation, Physiological↗

Host response to Escherichia coli heat-labile enterotoxin via two microvillus membrane receptors in the rat intestine.

The responsiveness of enterocytes to Escherichia coli heat-labile enterotoxin (LT) was studied in the small intestine of 6- to 7-week-old rats. Dose-effect analysis showed the dose required for a 50% maximal LT-induced secretory response to be at 8 nM. After the well-documented glycolipid GM1 receptor was blocked with the cholera toxin B subunit, LT still activated the second messenger cascade, measured in terms of heightened cellular adenylate cyclase activity, and caused fluid to be secreted into ligated intestinal loops. Furthermore, Scatchard analysis of binding kinetics suggested that LT bound to two receptor sites on the intestinal microvillus membrane. The toxin also bound to delipidated membrane but was competitively inhibited by a galactose-specific lectin, RCA60, suggesting that the additional receptor is a galactoglycoprotein. Western blot analysis of toxin binding to membrane proteins revealed a group of binding components around 85 to 150 kilodaltons. When measured at 2.2 nM LT, approximately 70% of LT-binding activity took place through a high-affinity (Kd1, 0.38 nM) GM1 receptor and 30% of LT-binding activity took place through a low-affinity (Kd2, 3.3 nM) glycoprotein receptor. These results suggest that LT functions through two microvillus membrane receptors in the mature rat small intestine.

Adenylyl Cyclases↗

Age and cortisone alter host responsiveness to cholera toxin in the developing gut.

To assess the influence of immaturity on the responsiveness of enterocytes to specific pathogens, a dose-response curve for cholera toxin (CT)-induced fluid secretion was determined in the proximal small intestine of rats at 2 and 4 wk of age. The suckling rat was approximately 50 times more sensitive to CT in triggering the secretory response than the weaned rat, when estimated by the medium-effective dose (ED50, 0.8 vs. 38.9 nM). Cortisone, known to promote enterocyte maturation, when injected into suckling rats, decreased host sensitivity approximately 1,000 times. Neither age nor cortisone decreased the receptor binding of 125I-labeled CT to intestinal microvillus membranes. In contrast, cortisone treatment caused a threefold increase in receptor density from 14.5 to 43.0 pmol/mg protein. The enzyme responsible for the sodium pump, Na+-K+-ATPase, showed a threefold increase in activity both after weaning and after a cortisone treatment. These data indicate that the immature gut exhibited an increased host sensitivity to CT stimulation that was not correlated with initial receptor binding but was related to a lowered Na+-K+-ATPase activity, suggesting that an underdeveloped sodium pump may be partially responsible for the high incidence of secretory diarrhea in neonates.

Aging↗

Responses of antigen-specific long-term murine T cell lines to wheat gliadin fractions.

Recent evidence suggests that the four electrophoretically defined gliadin subfractions (alpha, beta, gamma and omega) of wheat can induce the typical pathological finding of coeliac disease. We have prepared long-term murine T cell lines to gliadin and its four major subfractions. The cell lines were tested in proliferative assays with each homologous gliadin subfraction, and to the other gliadin subfractions. There was some cross-reactivity, with unfractionated gliadin and its alpha-subfraction being the most antigenic, while omega-gliadin was the least. These data demonstrate that gliadin components are effective stimuli for specific T cell responses, and further suggest that the alpha-gliadin subfraction generates the highest specific responses. This accords with observations in man that all four gliadin subfractions exacerbate coeliac mucosa, but that the alpha-subfraction is the most active.

Animals↗

Development of intestinal host defense: an increased sensitivity in the adenylate cyclase response to cholera toxin in suckling rats.

To determine if developmental variations existed in the second messenger system that mediates cholera toxin (CT) action, the adenylate cyclase (AC) response was studied in 2-wk-old suckling and 6-wk-old weaned rats. AC was assayed in the proximal small intestine 4 h after intraduodenal administration of various doses of CT. Dose-effect analysis showed a 9-fold increase in the sensitivity of the CT-activated cyclase response in suckling rats when measured by the ED50, expressed as microgram CT/g body wt (0.03 for 2 wk, 0.27 for 6 wk). When the CT dose was expressed as microgram/animal, suckling rats were 50 times more sensitive than 6-wk-old rats. In addition, the CT-induced fluid secretion was closely correlated with the elevated cyclase activities (correlation coefficient: 0.83 for 2 wk, 0.93 for 6 wk). Furthermore, more fluid seemed to be secreted/unit wt of gut in the sucklings, even when the same level of enzyme activity was compared. A maximum of 3- to 4-fold rise in AC activation occurred at 0.5 microgram CT/g body wt, but both the basal and the maximal stimulated levels of AC were not developmentally different. This study demonstrates an in vivo increase in AC responsiveness to CT that may be in part responsible for the increased incidence of toxigenic diarrhea in neonates.

Adenylyl Cyclases↗