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Biomedical subjects

D G Gall

Publications and source records attributed to D G Gall.

At least 37 records · Page 2Linked to original sources

Effect of luminal epidermal growth factor on enterocyte glucose and proline transport.

The effect of luminal epidermal growth factor (EGF; 60 ng/ml) and tyrphostin-51 (TYR; 10 microM), a tyrosine kinase inhibitor, on rabbit jejunal brush-border and basolateral membrane transport was investigated. In separate experiments, the effect of EGF, EGF and TYR, or TYR alone was examined in in vivo loops. In addition, Na+ permeability in brush-border membrane vesicles (BBMV) and the effect of Ca2+ channel blockade on EGF-stimulated glucose uptake were examined. Luminal EGF significantly (P < 0.0001) increased the maximal rate of transport (Vmax) for glucose and proline uptake in BBMV. TYR and Ca2+ channel blockade completely abolished the EGF-induced increase in glucose transport and in the case of TYR resulted in a significant reduction in Vmax compared with controls (P < 0.0001). The Michaelis-Menten constant did not differ in any experimental group. EGF had no effect on brush-border Na+ permeability or basolateral membrane glucose transport. The findings indicate a role for EGF in the acute regulation of jejunal brush-border membrane nutrient uptake. Furthermore, tyrosine kinase activity appears to be involved both in mediating EGF-induced alterations in transport function and in the maintenance of basal brush-border membrane function.

Animals↗

Intestinal secretory response to atrial natriuretic peptide during postnatal development in the rabbit.

The postnatal development of atrial natriuretic peptide (ANP) stimulus-secretion coupling was examined in rabbit ileum. A positive correlation between age and ANP-induced secretory responsiveness was observed. The short circuit current (Isc) response in 14-day animals was significantly (p < 0.05) less than that seen in 21-day, 28-day and adult animals. Animals at 21 days of age were less responsive (p < 0.05) than either 28-day or adult animals which did not differ. The Isc response of infant animals (day 14) to the Cl- secretagogue 3-isobutyl-1-methylxanthine was blunted in the infant, as was the response to electrical field stimulation. The infant animals had higher basal levels of mucosal cGMP, but were still able to respond to ANP with an elevation in cGMP. The ability of the immature ileum to generate the second messenger molecule cGMP in response to ANP, but not to produce an appropriate Isc response to ANP, indicates infant animals possess underdeveloped secretory mechanisms and lack the ability to effectively couple secretory stimuli to a secretory response.

1-Methyl-3-isobutylxanthine↗

Intraluminal pH modulates gastric prostaglandin synthesis.

Prostaglandins play an important role in modulating gastric mucosal integrity and in regulating gastric acid secretion, but little is known regarding regulation of prostaglandin synthesis by the stomach. We have therefore examined the effects of changes in gastric intraluminal pH on the capacity of gastric tissue to synthesize prostaglandin E2. Oral administration of solutions with a pH of 8.3 or 10 markedly reduced the capacity of the gastric tissue to synthesize prostaglandin E2, but did not affect synthesis of leukotriene B4. This phenomenon was observed in three strains of rats. Administration of the same solutions subcutaneously did not affect gastric prostaglandin synthesis. On the other hand, oral administration of a solution of pH 1 significantly increased prostaglandin synthetic capacity, while a solution with a pH of 3 had no effect. The effects observed were not attributable to differences in the osmolarity of the test solutions. These studies suggest that changes in gastric intraluminal pH result in changes in gastric prostaglandin synthesis. It is possible that this represents a physiological response aimed at maintaining gastric mucosal integrity when intraluminal pH is low, while also providing a feedback inhibition of gastric acid secretion.

Animals↗

Polyamines alter intestinal glucose transport.

Polyamines are required for the growth of all eukaryotic cells. Enterocytes respond to luminal nutrients with large increases in polyamine synthesis, even though they are mature, nonproliferating cells. The role of polyamines in these cells is unknown. The current experiments examined whether polyamines affected intestinal transport of glucose, since absorption is the primary activity of enterocytes and since polyamines are known to affect membrane function and stability. Glucose transport was examined in rabbit brush-border membrane vesicles (BBMV). BBMV from rabbits given 5% alpha-difluoromethylornithine (DFMO) in their drinking water 24 h before they were killed transported significantly less glucose than control vesicles [38% decrease in maximal transport rate (Jmax)]. Orogastric administration of spermine, spermidine, or putrescine to DFMO-treated animals 24 h before they were killed prevented the decrease. In rabbits receiving only orogastric spermine, glucose transport was significantly increased (64% increase in Jmax), whereas in vivo spermidine and putrescine decreased Jmax. This increase in Jmax caused by in vivo administration of spermine was not dependent on protein synthesis. Addition of polyamines whether in vivo or in vitro decreased Michaelis constant in vesicles from control and DFMO-treated animals. The change in glucose transport induced by DFMO or polyamines was not related to altered membrane lipid composition or fluidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Disruption of colonic electrolyte transport in experimental colitis.

The time course of disturbances of distal colonic electrolyte transport during experimental colitis in rats was compared with changes in the severity of inflammation and epithelial disruption. Colitis was induced by intracolonic administration of trinitrobenzenesulfonic acid (TNBS). At time points from 1 day to 8 wk thereafter, Na+ and Cl- transport was studied under short-circuited conditions in Ussing chambers, three indexes of tissue inflammation were measured, and histology was performed. Net absorption of Na+ and Cl- was abolished at 1 and 4 days after induction of colitis, but recovered to control levels by 1 wk. All unidirectional electrolyte fluxes were elevated at 1 day and fell significantly, generally to control levels, by 4 days. The indexes of inflammation, tissue myeloperoxidase, and synthetic capacities for prostaglandin E2 and leukotriene B4 were all significantly elevated from 1 day to 2 wk post-TNBS. At 1 and 4 days, there was widespread epithelial necrosis, and reepithelialization was consistently seen by 2 wk. In additional studies, 2 wk post-TNBS, the short-circuit current response to 3-isobutyl-1-methylxanthine was reduced compared with controls. These data suggest that abolition of electrolyte absorption early in this experimental colitis was largely attributable to epithelial damage. Despite demonstrable tissue inflammation 2 wk post-TNBS, basal electrolyte transport was not impaired, while the colitic epithelium was hyporesponsive to a Cl- secretagogue. The data also suggest that gross barrier function was restored prior to reepithelialization.

Animals↗

Structural and functional adaptation following jejunal resection in rabbits: effect of epidermal growth factor.

BACKGROUND/AIMS: Remnant small intestine undergoes adaptation following massive resection. The aim of this study was to examine the effect of epidermal growth factor (EGF) on ileal adaptation following proximal resection. METHODS: New Zealand white rabbits, aged 8 weeks, underwent 2/3 proximal resection, and ileal mucosal adaptation was assessed 10 and 21 days postsurgery. In a second series of experiments, animals with resection received oral EGF (40 micrograms.kg-1.day-1) for 5 days, and the effect on adaptation was assessed 10 days postsurgery. RESULTS: Transection alone stimulated mucosal hyperplasia, intestinal sucrase specific activity, and glucose transport at 10 days but not at 21 days. Resection resulted in mucosal hyperplasia at both time periods and increased disaccharidase specific activity at 10 days postresection. In contrast, 3 O-methyl-D-glucose transport was significantly decreased compared with both groups at both time periods. EGF treatment in animals with resection did not alter mucosal proliferation but did stimulate maltase specific activity and caused a 3-4-fold increase in glucose transport and phlorizin binding. CONCLUSIONS: Following proximal resection, adaptation of intestinal digestive and absorptive function does not parallel mucosal hyperplasia. Administration of EGF to resected animals enhances glucose absorption and may have a therapeutic role in the management of short gut syndrome.

Adaptation, Physiological↗

Rat gastric motor response to food protein-induced anaphylaxis.

BACKGROUND/AIMS: Antigen challenge of sensitized rats leads to delayed gastric emptying, but the mechanism (gastroparesis or prolonged trituration) and mediators are unknown. METHODS: Hooded Lister rats were sensitized by intraperitoneal injection of egg albumin as antigen, and control rats were sham-sensitized. On day 14, antral manometric and antroduodenal myoelectric activities in sensitized and sham-sensitized rats were recorded in response to antigen challenge, and the contractility of gastric antral circular muscle strips (mucosa intact) in standard tissue baths was measured in response to antigen or other agents. RESULTS: In vivo, the intragastric antigen challenge of sensitized (but not sham-sensitized) rats provoked diarrhea, reduction in the antral motility index, and disruption of the duodenal migrating motor complex. In vitro, antigen induced a tonic contraction of antral circular muscle segments from sensitized animals. Doxantrazole, but not disodium cromoglycate, inhibited antigen-induced contraction. Whereas histamine, 5-hydroxytryptamine, prostaglandins, leukotrienes, and platelet-activating factor contracted gastric muscle strips, neither specific antagonists, prostaglandin synthase, or 5-lipoxygenase inhibitors inhibited antigen-induced contraction. Tetrodotoxin increased antigen-induced contraction; however, the antigen-induced contraction was unaffected by atropine, guanethidine, or NG-nitro-L-arginine methyl ester. CONCLUSIONS: Food protein-induced, immunoglobulin E-mediated delayed gastric emptying in sensitized rats is associated with a transient reduction in gastric antral contractions. Antigen-induced contraction appears to be under nonadrenergic, noncholinergic, nonnitroxinergic inhibitory neural control.

Albumins↗

Allergic colitis in infancy: clinical and pathologic aspects.

This study prospectively evaluated 35 consecutive infants who presented with fresh blood mixed with stools. The mean age at onset of bleeding was approximately 4 weeks. All infants were otherwise asymptomatic and exhibited normal growth and physical examinations. None had evidence of a bleeding diathesis, viral or bacterial enteritis, or necrotizing enterocolitis. Consent for limited colonoscopy and biopsy was obtained for 34 infants. Twenty-five had macroscopic colitis and 10 infants had marked nodular lymphoid hyperplasia. Thirty-one infants had histopathological evidence of colitis characterized by a marked eosinophilic infiltrate. Compared with 19 controls (age, 4.1 +/- 3.6 months) the mean number of eosinophils per high-power field was greater in the patients with colitis. Patients with colitis also had an elevated mean absolute peripheral eosinophil count and a low mean serum albumin compared to control values. The 31 infants with colitis were receiving solely breast milk (10), cow's milk formula (9), soya formula (9), breast milk with cow's milk formula (2), or nutramigen (1) at the time of presentation. Nineteen infants had rapid resolution of frank bleeding and gradual correction of serum albumin with dietary change. While limited colonoscopy and biopsy were useful in establishing a definitive diagnosis, a low serum albumin and high peripheral eosinophil count suggested the diagnosis. Colitis characterized histologically by > 20 eosinophils per high-power field is a common cause of rectal bleeding in otherwise healthy young infants. Resolution of bleeding and increase in serum albumin after dietary change suggest that this is an allergic colitis: however, the pathogenesis of this disorder needs further clarification.

Animals↗

Transport of bovine serum albumin across rat jejunum: role of the enteric nervous system.

To assess the mechanisms for movement of antigenically intact macromolecules across small intestinal mucosa, transport kinetics of bovine serum albumin (BSA) uptake and the effect of neural and metabolic inhibition were examined in stripped short-circuited rat jejunum. The mucosa was exposed to BSA, and, after a 50-min equilibration, mucosal-to-serosal movement of immunologically intact BSA was determined by enzyme-linked immunosorbent assay and total BSA by radiolabeled 125I-BSA. Intact BSA uptake demonstrated saturable kinetics. Immunologically intact BSA crossed the intestinal mucosa as 4.5% of total 125I-BSA flux. Colchicine and 4 degrees C significantly reduced uptake of immunologically intact BSA. NaF significantly reduced uptake of immunologically intact BSA and 125I-BSA. Treatment with tetrodotoxin significantly reduced intact BSA uptake, but did not significantly alter total BSA uptake. The muscarinic cholinoceptor antagonist atropine also significantly inhibited transport of intact BSA, whereas the nicotinic cholinoceptor antagonist hexamethonium had no effect. These findings indicate that transport of intact macromolecules across small intestinal mucosa is a saturable energy-dependent process that utilizes the microtubular network and is regulated by the enteric nervous system primarily through cholinergic nerves acting on muscarinic receptors.

Animals↗

Electrolyte transport responses to secretagogues in neonatal versus adult rabbit jejunum.

The ability of the neonatal and adult rabbit jejunum to respond to different exogenous stimuli of electrolyte transport was investigated in vitro. When mounted in Ussing chambers, jejunum from neonatal rabbits exhibited a higher basal short circuit current and lower potential difference compared to jejunum from adult rabbits. As a result, basal conductance was approximately 50% higher in the neonatal group. When the tissue was subjected to electrical field stimulation, neonatal jejunum was significantly less responsive to stimulation with respect to change in short circuit current, particularly at submaximal stimulus strength and stimulus duration. The neonatal jejunum was less responsive than adult jejunum to exogenous application of prostaglandin E2 and 5-hydroxytryptamine, and more responsive to histamine. There was no significant difference in the responses to carbachol, epinephrine, leukotriene D4 or platelet-activating factor. The neonatal rabbit jejunum exhibited a greater capacity to synthesize prostaglandin E2 and the peptidoleukotrienes, and had a higher tissue content of 5-hydroxytryptamine than the adult rabbit jejunum.

Animals↗

Adaptation of the small intestine in desert-dwelling animals: morphology, ultrastructure and electrolyte transport in the jejunum of rabbits, rats, gerbils and sand rats.

1. The aim of this study was to characterize adaptive alterations of the small intestine in desert-dwelling animals by comparing jejunal morphology, ultrastructure and function in mammalian species with or without desert habitat origins. 2. Crypt-villus architecture, brush border surface area, and electrolyte transport were measured and compared in the jejunum of rabbits (Oryctolagus cuniculus), rats (Rattus rattus), gerbils (Meriones unguiculatus) and sand rats (Psammomys obesus). 3. In addition, transport of 3-0-methyl-D-glucose was compared in rats, rabbits and gerbils. 4. Gerbils and sand rats had significantly longer microvilli and villi (P < 0.01), increased brush border surface area (P < 0.01), and greater absorption of Na+ and Cl- (P < 0.05) than rabbits and rats. 5. Absorption of 3-0-methyl-D-glucose was also significantly (P < 0.05) greater in gerbils than in rabbits or rats. 6. The findings demonstrate enhanced small intestinal absorption of electrolytes and nutrients in desert-dwelling animals. 7. This increase was associated with an enlarged mucosal absorptive surface area. 8. The findings suggest that intestinal mucosal adaptation allows desert-dwelling animals to compensate for the limited availability of water and nutrients in an arid environment.

3-O-Methylglucose↗

Effect of epidermal growth factor on enterocyte brush-border surface area.

The effect of acute in vivo epidermal growth factor (EGF) exposure on intestinal absorptive surface area was examined in blind jejunal loops in New Zealand White rabbits (500-900 g). Brush-border surface area was assessed by electron microscopy at 30 and 120 min, and total surface area was assessed by the fluorophore 1-[4-(trimethylamino)phenyl)]-6-phenylhexatriene (TMA-DPH) at 10 and 60 min after EGF exposure. Mucosa obtained at 120 min was also used for morphometrics and analysis of membrane composition and fluidity. Brush-border surface area was significantly increased in EGF-treated tissue after 30 (42%) and 120 min (60%). Total absorptive surface area measured by TMA-DPH was increased more than twofold after 10 and 60 min EGF exposure. The increase in absorptive surface area was abolished by pretreatment with intravenous verapamil. Mucosal morphometrics and membrane sucrase activity, total phospholipids, cholesterol content, cholesterol-to-phospholipid ratio, phospholipid species (wt%), phospholipid fatty acid composition, and fluidity did not differ between control and EGF-treated tissue. These findings indicate that EGF can rapidly increase brush-border surface area by a mechanism that appears to be due to a redistribution of existing performed microvillus plasma membrane.

Animals↗

Effect of cyclooxygenase inhibition on macromolecular transport in rat gastric mucosa.

We have shown that the rat gastric mucosa takes up antigenically intact protein in vitro. The present study investigated the effect of two cyclooxygenase inhibitors, indomethacin and piroxicam, on gastric transport of BSA. Fasted rats were given indomethacin, piroxicam, or vehicle. After 30 min, the stomach was removed, stripped, and mounted in a Ussing chamber. Each side was bathed with Krebs buffer. Bovine serum albumin (BSA), 125I-labeled BSA (125I-BSA), and 51Cr-labeled EDTA (51Cr-EDTA) were added to the mucosal fluid and equilibrated for 30 min. Serosal fluids were sampled for two subsequent 30-min periods, and mean fluxes for immunologically intact BSA (enzyme-linked immunoabsorbent assay), total BSA (125I-BSA), and 51Cr-EDTA were calculated. Cyclooxygenase inhibition significantly (P < 0.01) reduced tissue prostaglandin E2 synthetic capacity (indomethacin, 97%; piroxicam, 92%) but did not cause either macroscopic or microscopic mucosal injury. Both inhibitors significantly (P < 0.05) decreased uptake of immunologically intact BSA (indomethacin, 91%; piroxicam, 81%) and 51Cr-EDTA. In contrast, the movement of degraded BSA was not altered by indomethacin. These findings suggest that a selective pathway exists for the uptake of intact proteins in gastric mucosa and that the pathway is modulated by cyclooxygenase metabolites.

Animals↗

The effect of TGF alpha on intestinal solute transport.

The effect of transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) on 3-O-methylglucose transport was examined in vitro under short-circuited conditions in stripped rabbit jejunum. Mucosal EGF, 60 ng/ml, stimulated a significant increase in net 3-O-methylglucose transport (Jnet 0.67 +/- 0.15 vs. 0.90 +/- 0.15 microEq/cm2/h; P less than 0.03; n = 6) due to an increased mucosal to serosal flux (Jms 1.2 +/- 0.2 vs. 1.5 +/- 0.2 microEq/cm2/h; P less than 0.03). In contrast, TGF alpha, when applied to both mucosal and serosal surfaces at concentrations of either 60 (n = 6) or 150 (n = 9) ng/ml had no effect on either mucosal to serosal (Jms) or net transport (Jnet) of 3-O-methylglucose. TGF alpha did induce a significant increase in the serosal to mucosal flux (Jsm 60 ng/ml 0.44 +/- 0.02 vs. 0.51 +/- 0.03, 150 ng/ml 0.55 +/- 0.03 vs. 0.64 +/- 0.05 microEq/cm2/h; P less than 0.05). When brush border surface area was examined after exposure to either 60 ng/ml TGF alpha or saline vehicle for 2 h in in vivo isolated jejunal loops no significant difference was found (control 53 +/- 1.9; n = 35 vs. TGF alpha 52 +/- 1.9 microns 2; n = 29). Bioactivity of transforming growth factor alpha was assessed by an gastric acid secretion bioassay and found to be intact. These data provide further evidence for separate and distinct functional roles for these peptides in some biological systems.

3-O-Methylglucose↗

Pathophysiology of small intestinal malabsorption in gerbils infected with Giardia lamblia.

Mongolian gerbils were infected with a human pathogenic Giardia lamblia strain and compared with sham-treated control animals 6 days after inoculation. Infection resulted in crypt hyperplasia associated with an increased enterocyte migration rate. Villus height was decreased in the duodenum, unchanged in the jejunum, and increased in the ileum of infected animals. Epithelial microvilli were markedly shortened, and brush border surface area decreased in the jejunum and ileum of infected animals. Thymidine kinase activity was increased in isolated duodenal villus enterocytes but did not differ in the jejunum and ileum. In vitro and in vivo experiments showed that the infection resulted in decreased jejunal glucose-stimulated electrolyte, water, and 3-O-methyl-D-glucose absorption, whereas in the ileum in vitro electrolyte and 3-O-methyl-D-glucose absorption was similar in infected and control animals. Thus, in the jejunum infection causes electrolyte, solute, and fluid malabsorption associated with decreased brush border surface area. The results indicate that the diarrhea associated with giardiasis is caused by malabsorption rather than active secretion.

Animals↗

Macromolecular transport by rat gastric mucosa.

We previously demonstrated that the stomach is capable of mounting a type I hypersensitivity reaction to luminal antigen challenge. These findings imply that antigenically intact macromolecules cross the gastric mucosa. To test this hypothesis, rat gastric mucosa was mounted in Ussing chambers, and bovine serum albumin (BSA, 0.5 mg/ml) and 125I-labeled BSA (10 microCi) were added to mucosal fluids. After equilibration, serosal fluids were sampled for two 30-min periods, and fluxes of immunologically intact BSA (determined by an enzyme-linked immunosorbent assay) and total BSA (125I-BSA) were calculated under basal conditions and in the presence of NaF and colchicine, and at 4 degrees C. Additional experiments examined macromolecular permeability in sensitized-challenged tissues. Immunologically intact BSA (21.3 +/- 4.5 ng.30 min-1.cm-2) crossed the gastric mucosa as approximately one-fourth of the total BSA flux (78.2 +/- 7.5 ng.30 min-1.cm-2). The uptake of immunologically intact BSA was significantly reduced by NaF, an inhibitor of ATP production and endocytosis; colchicine, which inhibits polymerization of cytoskeletal microtubules; and at 4 degrees C, a general metabolic inhibitor. The transmural passage of antigen was not significantly altered by immunoglobulin E-mediated anaphylaxis. These findings indicate that intact protein antigens cross the gastric mucosa by an active, energy-dependent mechanism that uses the microtubular network.

Anaphylaxis↗

Effect of bombesin on the development of the neonatal rabbit gastrointestinal tract.

The effect of bombesin on the postnatal development of the gastrointestinal tract was examined in New Zealand white rabbits. Bombesin (1.25, 12.5, 30 micrograms/kg body weight) or vehicle was administered intraperitoneally to suckling rabbits for 13 days starting on day 4 of life. The animals were killed at day 17. There was no significant effect of bombesin at doses of 1.25 or 12.5 micrograms/kg in any region of the gut studied. Bombesin administered at 30 micrograms/kg induced a widespread trophic effect in the gastrointestinal tract characterized by significant increases in the wet weight of the stomach, liver and whole small intestine, as well as in 10-cm segments of the proximal, middle, and distal small intestine. There was also a significant increase in the mucosal weight of 10-cm segments of the proximal, middle and distal small intestine, and the colon in the bombesin-treated group. Bombesin significantly increased the protein and DNA contents of the liver, the fundus of stomach, all segments of the small intestine and the distal colon. Maximal stimulation was seen in DNA content, suggesting that bombesin has a primarily hyperplastic effect. Bombesin increased the activities of small intestinal sucrase and maltase but not lactase. Bombesin did not alter hepatic glucokinase activity. These findings suggest that bombesin can promote the growth of the neonatal rabbit gastrointestinal tract and liver.

Animals↗