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D G Gall

Publications and source records attributed to D G Gall.

At least 73 records · Page 4Linked to original sources

Intestinal anaphylaxis in the rat: mediators responsible for the ion transport abnormalities.

Antigen challenge of jejunal epithelium from rats sensitized to egg albumin induces an active Cl- secretory process secondary to release of mucosal mast cell mediators. The present study was designed to define the relative role of these mast cell mediators and the enteric nervous system in the transport abnormalities associated with intestinal anaphylaxis. Net ion transport of stripped jejunal tissue from sensitized and sham-treated animals was studied in Ussing chambers. The Cl- secretory response induced by egg albumin during intestinal anaphylaxis was similar to that after addition of 5-hydroxytryptamine (5-HT), histamine, and prostaglandins D2 and E2 to jejunal tissue. Cinanserin, a 5-HT2-receptor antagonist, virtually abolished the response to 5-HT and totally abolished the response to egg albumin. Methysergide, a 5-HT1-receptor antagonist had no effect on either response. Indomethacin, an inhibitor of prostaglandin synthesis, significantly inhibited the 5-HT and egg albumin response. Diphenhydramine, an H1-receptor antagonist and cimetidine, an H2-receptor antagonist both significantly inhibited the histamine response but neither altered the response to egg albumin. Atropine, an anticholinergic, and tetrodotoxin, a nerve blocker, did not inhibit the antigen induced anaphylactic response. These results indicate that 5-HT, acting through 5-HT2 receptors is largely responsible for the transport abnormalities seen in intestinal anaphylaxis induced by egg albumin while prostaglandins appear to play a partial role. The findings do not support a role for the enteric nervous system for the egg albumin induced changes in Cl- secretion.

Anaphylaxis↗

Binding of Yersinia enterocolitica to rabbit intestinal brush border membranes, mucus, and mucin.

Mucus and its gel-forming glycoprotein component, mucin, are thought to protect the gastrointestinal tract from enteric pathogens by inhibiting their attachment to enterocytes. In this study, we investigated interactions between Yersinia enterocolitica (isogenic strains of virulent and nonvirulent organisms) and crude mucus, highly purified mucin, and brush border membranes (BBMs) isolated from the upper mid-, and distal small intestine and the proximal colon of the rabbit. Adherence of radiolabeled bacteria was assessed to BBMs, mucus, and mucin immobilized in polystyrene microtiter plate wells. Virulent Y. enterocolitica showed saturable binding to mucus, mucin, and BBMs from all four regions of the intestinal tract, although adherence to BBMs was appreciably greater than that to mucus or mucin. Maximal binding of bacteria was higher to BBMs from the distal small intestine and the proximal colon than to those from the upper and mid-small intestine, which may in part explain why the organism localizes to the ileo-caecal regions of the gut. Adherence of virulent Y. enterocolitica to BBMs was significantly reduced in the presence of homologous mucus or mucin preparations. Binding of virulent bacteria appears to depend on plasmid-encoded proteins located on the outer surface membrane, since (i) the isogenic strain lacking the virulence plasmid showed markedly less binding to all BBM, mucus, and mucin preparations; (ii) growth of the virulent strain at 25 degrees C, which inactivates its plasmid, significantly diminished binding to BBMs, mucus, and mucin; and (iii) mild proteolysis substantially decreased adherence of virulent bacteria to BBMs. Compared with rabbit intestinal and colonic mucins, binding of virulent Y. enterocolitica was significantly greater to purified human intestinal mucin and significantly less to rat intestinal mucin. These findings provide support for the role of mucus and mucin in host defense by preventing adherence of virulent Y. enterocolitica to epithelial cell membranes.

Animals↗

Intestinal motility during acute Yersinia enterocolitica enteritis in rabbits.

To determine if Yersinia enterocolitica (YE) enteritis is associated with an alteration of intestinal myoelectric and motor activity, and with an increased rate of aboral transit, New Zealand white rabbits (500-900 g) were surgically prepared with ileal bipolar electrodes and a manometry catheter adjacent to the distal electrode. One week later animals were inoculated with 10(10) organisms of YE in 10 mL NaHCO3 (infected group) or 10 mL NaHCO3 (sham-infected pair-fed and control groups). Daily food intake, weight gain, YE excretion, and stool pattern were noted. Intestinal myoelectric and motor activity over a 6- to 8-h period before and 3, 6, and 14 days after inoculation was compared in infected (I), pair-fed (PF), and control (C) groups. Intestinal transit was evaluated in I and C animals on days 3 and 6 after inoculation by measuring the distribution in the intestinal lumen of 51Cr 20 min after it was instilled directly into the jejunum. Infected animals exhibited diarrhea, fecal excretion of YE, and significantly decreased food intake, weight gain, and survival (11.4 +/- 0.6 days). Infection was associated with a significant (p less than 0.05) decrease in both the cycle period of the migrating myoelectric complex (MMC) and the total number of single, paired, and (or) clustered contractions per MMC, and a significant (p less than 0.001) increase in duration of phase III of the MMC. There was no change in intestinal slow wave frequency (19 cycles/min), motility index per MMC, or the percentage of contractions that propagated in an orad (7%) or aboral (69%) direction or that appeared stationary (25%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of intestinal anaphylaxis on postprandial motility in the rat.

We have previously utilized a rat animal model to demonstrate that challenge of fasted sensitized animals with antigenic food protein is associated with diarrhea and altered intestinal myoelectric and motor activities. In this paper we examine the effect of intestinal anaphylaxis on postprandial motility in the same animal model. Hooded Lister rats were sensitized (S) by intraperitoneal injection of 10 micrograms egg albumin (i.e., antigen (Ag) and compared with sham-sensitized controls (C). Seven days later, three bipolar jejunal electrodes and a jejunostomy tube, for motility recording and Ag administration, were implanted. On day 14, intestinal myoelectric and motor activities were measured in fed animals before and after intraluminal challenge with Ag (100 mg egg albumin/0.5 mL saline) or placebo (P; 0.5 mL saline). Specific immunoglobulin E serum titres were greater than or equal to 1:64 in S animals, while C animals showed no response. None of the C animals challenged with P or Ag and none of the S animals challenged with P defecated after challenge, but all the S animals challenged with Ag developed diarrhea (p less than 0.001). There was no disruption or alteration of the fed motility pattern in C animals challenged with P or Ag, or S animals challenged with P. In fed S animals challenged with Ag the fed motility pattern persisted, but there was a significant (p less than 0.05) increase in the number of high-amplitude aborally propagating clustered contractions, where the phasic contractile activity was superimposed on a sustained tonic elevation of intraluminal pressure lasting 5-10 s.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗

The effect of food protein-induced intestinal anaphylaxis on rate of transit.

The aim of this study was to determine if the altered jejunal motility previously demonstrated in this animal model of food protein-induced intestinal anaphylaxis is (a) a localized (the jejunal site of challenge), or a generalized response of the small intestine, and (b) associated with more rapid aboral transit of intraluminal contents. Hooded-Lister rats, 100-150 g in weight, were sensitized by intraperitoneal injection of 10 micrograms egg albumin. Control rats were sham-sensitized. On day 7 rats were surgically prepared with six bipolar electrodes from duodenum to ileum and (or) a jejunostomy tube was positioned at the ligament of Treitz. On day 14, after an 18-h fast, recording of myoelectric activity were obtained from four sensitized animals with electrodes from duodenum to ileum during a control period for 45 min after saline challenge and for 45 min after antigen challenge. Control (n = 25) and sensitized (n = 31) animals with only a jejunostomy had Na2 51CrO4 instilled through the jejunostomy in 0.5 mL of saline, with or without egg albumin, either during a fast or after a standard meal. Propulsion of isotope through the small bowel was allowed to progress for 15 min, the animals were sacrificed, and their gut was removed for division into eight equal segments of small intestine, cecum, and remaining colon. The radioactivity of each segment was determined in a gamma counter.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗

Effect of Yersinia enterocolitica on intestinal mucin secretion.

Mucin and glycoprotein synthesis and secretion were evaluated in the upper, mid, and distal small intestine and in the proximal colon of rabbits infected with Yersinia enterocolitica (YE). Infected (INF) animals were examined on day 6 and compared with pair-fed controls and unmanipulated weight-matched rabbits. Tissue mucin content in vivo and mucin secretion in vitro, measured by a specific immunoassay, were significantly elevated in all four regions of the gut of INF rabbits compared with both control groups. In vitro secretion of stored glycoprotein, prelabeled with [3H]glucosamine, was not increased in the upper and mid small intestine of INF animals but was significantly elevated in the distal small intestine and proximal colon. In vitro incorporation of [14C]glucosamine was increased in all four regions of the gut of INF rabbits, but secretion of newly synthesized [14C]glycoprotein was only significantly elevated in the distal small intestine and proximal colon. A graded response was observed down the intestinal tract of INF rabbits, with the greatest increase in mucin content, synthesis and secretion occurring in the distal small intestine and proximal colon where the morphological impact of disease is also most severe.

Animals↗

Gastric response to mucosal IgE-mediated reactions.

The effect of immunoglobulin E (IgE)-mediated anaphylaxis has been extensively studied in the small intestine, but little information is available on the response of the stomach to IgE-mediated mucosal reactions to food proteins. The effect of luminal antigenic challenge on gastric acid secretion, gastric emptying, and mucosal mast cell degranulation was examined in rats sensitized to egg albumin or in sham-treated controls. Intraluminal challenge of the stomach with egg albumin in sensitized animals significantly increased gastric acid secretion and delayed gastric emptying. The response was specific for the sensitizing antigen as challenge with bovine serum albumin was without effect. Sham-treated animals showed no response to egg albumin or bovine serum albumin. The increase in gastric acid secretion was reproduced by antigen challenge in naive animals passively transferred with hyperimmune serum. This effect was abolished by prior heat treatment of the serum. In sensitized animals challenged with egg albumin, there was histological evidence of mast cell degranulation in the stomach mucosa, increased intraluminal release of histamine, and increased serum levels of rat mast cell protease II, a marker specific for mucosal mast cell degranulation. The findings indicate that the stomach is a target organ for IgE-mediated reactions to food proteins. Antigen challenge in sensitized animals leads to increased gastric acid secretion and delayed emptying and evidence of mucosal mast cell activation.

Animals↗

Effect of acute Yersinia enterocolitica infection on in vivo and in vitro small intestinal solute and fluid absorption in the rabbit.

The impact of acute Yersinia enterocolitica infection on jejunal and ileal solute and water transport was examined. New Zealand White rabbits (500-600 g) were infected with Y. enterocolitica and compared with unmanipulated controls and pair-fed controls. Transport studies were performed 6 days after infection on jejunum and ileum by an in vivo single-pass perfusion technique and in vitro under short-circuited conditions in Ussing chambers. When studied in vivo, Y. enterocolitica infection resulted in decreased water and electrolyte absorption in the jejunum under basal conditions and in both jejunum and ileum in the presence of glucose. Glucose absorption was also decreased in jejunum and ileum. When studied in vitro, net basal Na+ and Cl- transport was not altered in jejunal or ileal epithelium from infected animals. Glucose-stimulated Na+ absorption was decreased in ileal epithelium, and absorption of 3-O-methyl-D-glucose was decreased in both jejunum and ileum. Secretory capacity of Cl-, as assessed by isobutylmethyl xanthine stimulation, was unimpaired in both jejunum and ileum. Decreased food intake alone, in the pair-fed animals, had little effect on intestinal transport. The results indicate that malabsorption, rather than active intestinal secretion, is the major small intestinal transport defect in acute Y. enterocolitica infection. Furthermore, the abnormalities can be directly attributed to injury induced by the organism itself, rather than malnutrition.

Acute Disease↗

Mast cell protease release and mucosal ultrastructure during intestinal anaphylaxis in the rat.

Intestinal anaphylaxis is associated with disturbances in gut function that are antigen-specific and dependent on mast cell degranulation. Using an animal model of intestinal anaphylaxis, we have correlated alterations in water and electrolyte transport, associated with intraluminal challenge, with specific intestinal mucosal mast cell degranulation by following systemic as well as local release of rat mast cell protease II. This protease is specific for intestinal mucosal mast cells and is known to selectively attack type IV collagen, which is found in basement membranes. Intraluminal antigen challenge in sensitized animals dramatically increased serum and intraluminal levels of rat mast cell protease II. Serum levels continued to rise throughout the duration of antigen challenge. Although light microscopy of challenged intestine demonstrated little distortion of mucosal architecture, ultrastructural examination revealed significant disruption to the basement membrane and underlying collagenous matrix of the intestinal mucosa. Our findings indicate that during mucosal immunoglobulin E-mediated reactions, rat mast cell protease II is released and is associated with ultrastructural changes in the intestinal mucosa. The systemic appearance of this specific protease provides a serum marker of intestinal anaphylaxis.

Anaphylaxis↗

Metoclopramide in gastroesophageal reflux of infancy.

This study examined the effect of metoclopramide on lower esophageal sphincter (LES) pressure, and frequency and duration of reflux episodes in 28 children (mean age (+/- SD) 9 +/- 11 months) referred for evaluation of gastroesophageal reflux (GER). Esophageal manometry was performed before and after one intravenous dose of metoclopramide (0.125 mg/kg), and esophageal pH was monitored over a 24-hour baseline period, followed by oral metoclopramide therapy (0.125 mg/kg four times a day, for 24 hours.) During pH monitoring, patients received diet for age and were kept in the prone position with the head elevated 45 degrees while sleeping. Eight patients entered a 6-month double-blind, placebo-controlled trial of metoclopramide. Metoclopramide significantly (P = 0.04) increased end-expiratory LES pressure, from 14.9 +/- 7.5 mm Hg to 18.6 +/- 6.8 mm Hg. However, there was a significant (P less than 0.05) increase in the number of reflux episodes/24 hours, and no significant change in percentage of time pH was less than 4, number of episodes lasting greater than 5 minutes, or the longest episode of reflux between the 24-hour baseline and M periods. LES pressure did not correlate well with any of these measurements (r = 0.2). In the controlled trial, the three patients receiving metoclopramide, but none of those receiving placebo, were withdrawn by their parents because of exacerbation of GER symptoms and marked irritability (P = 0.01). In the placebo group, symptoms improved in four infants, but did not change in one. The use of metoclopramide in the treatment of GER of infancy needs to be reconsidered.

Double-Blind Method↗

Protein intolerance and immunocyte and enterocyte interaction.

Food allergy is an untoward immunologic reaction to food. The number of conditions that need to be considered in the differential diagnosis is large and includes adverse reactions to foods that do not have an immunologic basis. Intestinal immune elements are an integral feature of the intestinal mucosa and, besides modulating gastrointestinal function, represent a significant part of the host's overall immune system. Despite increasing knowledge, the precise disturbances in immune function that lead to the appearance of food allergy are still unclear. Food allergy will remain primarily a clinical diagnosis, relying on history and response to dietary elimination and rechallenge until more specific tests become available.

Dietary Proteins↗

Intestinal anaphylaxis: in vivo and in vitro studies of the rat proximal colon.

The response of the rat proximal colon to an immunoglobulin E (IgE)-mediated hypersensitivity reaction was examined. Rats were sensitized to egg albumin (EA) by intraperitoneal injection, and serum titers of specific anti-EA IgE were measured at 14 days. Sensitized animals had titers of greater than or equal to 1:64, whereas no anti-EA IgE antibodies were detected in controls. Water and electrolyte absorption in the proximal colon, before and during antigen challenge, was measured by in vivo marker perfusion. Antigen challenge resulted in significant inhibition of water, Na+, Cl-, and K+ absorption in vivo. Proximal colonic tissue from sensitized and control animals was studied in Ussing chambers under short-circuited conditions. Antigen challenge of sensitized tissue resulted in significant increases in short-circuit current due to the induction of active Cl- secretion. No such changes were seen in control tissue. The abnormalities induced by antigen challenge in tissue from sensitized animals was blocked by doxantrazole (10(-3) M), a mast cell stabilizer. The findings indicate that IgE-mediated reactions in rat proximal colon to a food protein cause pertubations in water and electrolyte transport secondary to active Cl- secretion and these abnormalities appear to be due to mast cell degranulation.

Anaphylaxis↗

Motility effects of intestinal anaphylaxis in the rat.

Intestinal motility was examined in an animal model of intestinal anaphylaxis. Hooded-Lister rats were sensitized (S) by intraperitoneal injection of 10 micrograms egg albumin (Ag) and compared with sham-sensitized controls (C). Seven days later three bipolar jejunal electrodes and a jejunostomy tube for motility recording and Ag administration were implanted. On day 14 intestinal myoelectric and motor activity were measured in fasted animals before and after intraluminal administration of either 10 mg egg albumin in 0.5 ml saline, 10 mg bovine serum albumin (BSA) in 0.5 ml saline, or placebo (P) challenge with 0.5 ml saline. Specific immunoglobulin E serum titers were greater than or equal to 1:64 in S animals, whereas C animals showed no response. None of the C animals challenged with P or Ag and none of the S animals challenged with P or BSA defecated after challenge, but all the S animals challenged with Ag developed diarrhea (P less than 0.001). In S animals challenged with Ag, the fasting motility pattern was disrupted, the migrating motor complex was abolished (P = 0.002), and the frequency of aborally propagating clustered contractions was increased (P less than 0.01). In this animal model an immune-mediated reaction to food protein was associated with diarrhea and altered intestinal myoelectric and motor activity.

Anaphylaxis↗

Effects of chronic protein-calorie malnutrition on small intestinal repair after an acute bacterial enteritis: a study in infant rabbits.

The aim of this study was to determine if recovery of intestinal function in infant rabbits subjected to protein-calorie malnutrition was delayed as a result of inflammatory injury induced by an experimental bacterial enteritis. Rabbits were malnourished by expanding litter size at 7 days of age and infecting undernourished animals and dietary controls with Yersinia enterocolitica at either 17 or 21 days of age. Intestinal morphology and function were evaluated in infected and noninfected animals from both dietary groups at 27 days of age. Undernutrition alone significantly reduced animal weight, small intestinal weight, segmental jejunal and ileal mucosal weight, villus height, crypt depth, disaccharidase activities, mucosal protein and DNA contents, but increased ileal short-circuited glucose-stimulated Na+ absorption compared to controls. The jejunum of undernourished rabbits at 6 days postinfection exhibited an intestinal injury, as evidenced by a mild inflammatory infiltrate and further reductions in villus height, mucosal weight, lactase activity, protein and DNA content, not seen in infected dietary controls. Jejunal recovery was complete by 10 days postinfection. In the ileum of infected animals of both dietary groups at 6 days post-infection, a severe inflammatory response, decreased villus height, elongated crypts, and depressed stimulation of Na+ absorption by glucose was observed. By 10 days after infection, while recovery was nearly complete in dietary controls, intestinal damage persisted in the undernourished rabbits, as evidenced by absent glucose-stimulated Na+ absorption, continued severe inflammation and microabscess formation. We conclude that intestinal injury is more severe and chronic in the undernourished, compared to dietary control infant rabbits subjected to an acute bacterial enteritis.

Acute Disease↗

The effect of protein-calorie malnutrition on the developing liver.

The effects of protein-calorie malnutrition on bile salt metabolism and liver function were studied. Malnutrition was induced in rabbits by combining litters at 7 days of age (13-16 animals) and results compared to control litters (six-eight animals). At age 29-30 days biliary output from the common bile duct was measured directly for three 1-h periods: under basal conditions, and in response to intravenous infusion of exogenous glycodeoxycholic acid at 0.75 and 1.5 mumol/min/kg, respectively. The bile salt pool size was measured by isotope dilution. Final mean body weight and liver weight were significantly decreased in malnourished animals compared to controls. Liver weight/body weight was also less in the malnourished group. Total liver DNA and protein content, as well as the protein to DNA ratio, were less in the malnourished animals compared to controls. Bile flow and bile salt secretion were reduced in the malnourished group when calculated per kg body weight or per mg liver DNA. Bile salt-dependent flow did not differ significantly, but bile salt-independent flow was significantly less in malnourished animals. Bile salt pool size was decreased in the malnourished group. These findings indicate that malnutrition has a greater impact on liver weight than on total body weight in the preweaning period. In addition, malnutrition reduces bile flow, bile salt secretion, and bile salt pool size which, along with the decrease in bile salt-independent flow, may reflect either an impairment of hepatic uptake function or a delay in postnatal development.

Animals↗

Supplemental calories improve essential fatty acid deficiency in cystic fibrosis patients.

Fatty acid composition of plasma lipids was analyzed in malnourished cystic fibrosis patients undergoing 6 months of nutritional rehabilitation. There were three males and five females (mean age 15.1 yr); five patients had pancreatic insufficiency. Nutritional rehabilitation in seven of eight patients was accomplished by nocturnal nasogastric infusion of a high-carbohydrate semisynthetic diet, in addition to daily meals. One patient received high-energy food supplements as snacks in addition to regular meals. All patients were moderately to severely malnourished on entry to the study and showed significant improvement over the 6 months in (means +/- SE) energy intake (96 +/- 8.0 to 126 +/- 11% recommended daily allowance) and body composition (80 +/- 4 to 90 +/- 4% ideal body weight). Daily intakes of linoleic acid were not significantly different before or during nutritional rehabilitation either as an absolute amount (383 +/- 45 to 557 +/- 124 mg/kg/day) or as a percentage of total calories (4.50 +/- 0.40 to 4.73 +/- 0.14%). In comparison to the controls, the relative percentage of plasma cholesterol ester fatty acids of the CF patients on entry into the study showed a marked decrease of linoleic acid (52.7 +/- 1.0 versus 42.3 +/- 2.7%) with elevated palmitoleic (2.34 +/- 0.2 versus 5.64 +/- 0.7%) and oleic (18.7 +/- 1.0 versus 25.2 +/- 1.4%) acids; a pattern consistent with essential fatty acid deficiency. However, this pattern is not truly characteristic of a pure linoleic acid deficiency as the metabolites of linoleic acid were not decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Colonic function in acute Yersinia enterocolitica infection in rabbits.

The impact of acute Yersinia enterocolitica infection on colonic fluid and electrolyte absorption was studied. New Zealand White rabbits (500-600 g), were infected with Yersinia enterocolitica and compared to unmanipulated controls and pair-fed controls. Water and electrolyte transport were measured in proximal and distal colon by an in vivo single pass perfusion technique and in proximal colon in vitro under short-circuited conditions in Ussing chambers. Infection resulted in severe histologic damage in proximal colon but only mild alterations in distal colon. Pair-fed controls demonstrated decreased absorption in vivo in both proximal and distal colon and Na+ and Cl- secretion in vitro in proximal colon compared to unmanipulated controls. In contrast infection did not alter water and electrolyte absorption in vivo compared to unmanipulated controls despite evidence of net secretion of Na+ and Cl- in vitro. These results indicate that Yersinia enterocolitica infection of the colon does not contribute to fluid and electrolyte losses despite mucosal damage, but rather there appears to be a degree of compensatory colonic salvage.

Animals↗