Failure to detect gastric campylobacter-like organisms in a group of ferrets in New Zealand.
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Biomedical subjects
Publications and source records attributed to C Tasman-Jones.
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Mucin has been purified from nude mouse xenografts of SW1990 human pancreatic cancer cells. The mucin was eluted at the void volume of Sepharose CL-4B and was of density greater than 1.3 in CsCl gradients. The isolated mucin had a high content of threonine, serine, and proline, with 31% of the amino acid residues O-glycosylated. The average oligosaccharide composition was NeuAc1.8Fuc0.7Gal2.0GlcNAc1.7GalNAc1.4. Polyclonal rabbit antibodies prepared against the purified mucin recognized primarily mucin polypeptide, and there was extensive immunological cross-reaction between SW1990 pancreatic cancer mucin and LS174T colon cancer mucin. However, using carbohydrate-specific monoclonal antibodies, the two mucins were found to differ. SW1990 mucin had more Lewis, sialyl Lewis, and sialyl Lewis activity, while the colon cancer mucin had more sialyl T antigen. Since pancreatic mucins, whether from normal pancreas or pancreatic cancer, have not previously been well characterized, the availability of SW1990 pancreatic cancer mucin may be useful as a model for studying the expressing of organ-specific or cancer-associated antigens.
The distribution of Campylobacter pylori, its prevalence, and its relationship to gastritis and urease activity have been studied in 54 postmortem stomachs. Infection was confirmed by finding C. pylori in a Gram-stained smear of gastric mucus harvested from the entire stomach. Eight tissue specimens were obtained from predetermined sites from each stomach and examined for histologic gastritis and urease activity. Thirty-seven per cent of stomachs were infected, and of these 80% had widespread histologic gastritis. The detection of urease activity provided information on the distribution of the organism and had a high correlation with histologic gastritis. The organism is capable of infecting any area of the stomach. Infection is common and is more prevalent in Polynesian subjects (60%) than in Caucasians (19%).
The Na+/H+ ion-exchange property of human gastric mucus and its relationship to age has been studied. Mucus was collected from 40 postmortem human stomachs (age range, 21-83 years) within 24 h of traumatic death. Twenty-one stomachs (age range, 21-76 years) were free of Campylobacter pylori infection and histologic gastritis. Mucus from these stomachs was consistently a cation exchanger at pH 6 in an in vitro system. The cation-exchange capacity of mucus from seven stomachs within the age range 55-70 years was 50% less than the cation-exchange capacity of mucus from eight stomachs within the age range 20-35 years. This study shows that human gastric mucus at pH 6 is a cation exchanger and that the ion-exchange capacity decreases with age.
Peptic ulcer disease occurs when there is an imbalance between aggressive factors and mucosal resistance. Mucus plays a key role in mucosal resistance. The mucus layer is relatively resistant to peptic digestion, it provides a layer through which there is a movement of hydrogen ions from the parietal cell to the lumen but a resistance to back-diffusion of hydrogen ions in the opposite direction. It maintains a pH gradient by 'sequestering' secreted bicarbonate and by its resistance to H+ back-diffusion. Colloidal bismuth subcitrate (De-Nol) binds to mucus to stabilize the mucous layer and increase the resistance to back-diffusion of hydrogen ions without significantly modifying the ion-exchange properties of mucus.
Mucus, a hydrated complex consisting mainly of glycoproteins, forms a layer over the epithelial surface of the gastrointestinal tract. The usual preparative procedures for histological and scanning electron microscopic examination of the gut result in the loss or distortion of this mucus layer. Careful evaluation of two new methods reported to stabilize the mucus layer showed that acrolein vapor did not provide adequate fixation, but application of heat-inactivated antiserum raised in rabbits against rat colon mucus reliably preserved a continuous layer closely adherent to the epithelium. This stabilized layer is continuous with the mucus in the colonic crypts.
Using a modified equilibrium dialysis cell the rate of diffusion of butyrate through pig colonic mucus has been compared with that through other gels and unstirred layers. Relative diffusion coefficients were calculated for each layer. Layers of 8% polyacrylamide, and of caecal, mid-colonic and terminal colonic mucus, had coefficients that were 50-60% of the apparent free diffusion coefficient for butyrate, determined using layers made up of Millipore filters alone. The apparent free diffusion coefficients for butyrate (layers of agarose or filters) were 70% of previously determined values in the literature. This discrepancy can be explained by elements of the experimental procedure. All mucus layers differed significantly from layers of 2% agarose and Millipore filters but were not significantly different from layers of 8% polyacrylamide or from each other. Diffusion coefficients for butyrate in the mucus samples correlated with water content and carbohydrate content but had no relationship to protein content. The rate of diffusion of butyrate in colonic mucus layers was significantly reduced when compared with unstirred layers (P less than 0.05). Whether this has an effect on the butyrate supply to colonocytes in vitro and whether mucus in colonic disease behaves differently are subjects for further investigation.
The distribution of microorganisms in the mid-colon of the rat was studied by light and scanning electron microscopy. An antiserum against rat colon mucus was used to stabilize the mucus in situ. In samples not incubated with antiserum, the mucus disintegrated and contracted into patchy strands only partly covering the luminal surface of the colon. Bacteria were seen within fecal pellets, tangled among the strands of mucus, and scattered on the epithelial surface. However, when incubated with antiserum, mucus almost completely filled the lumen and coated the fecal pellets. Bacteria in these stabilized preparations were limited mainly to the fecal pellets, and there were small numbers scattered in the luminal mucus, but none were observed on the epithelial surface or within the crypts. Latex particles introduced into the lumen with the antiserum or with phosphate-buffered saline showed the same distribution as the bacteria. These findings are at variance with previous reports that organisms occur in abundance in the mucous layer, adjacent to cell surfaces, and inside crypts. Our results suggest that conventional preparation for microscopy without prior stabilization of the mucus in situ may lead to artifactual redistribution of microorganisms and emphasize the importance of mucus in maintaining mucosal-floral homeostasis in the colon.
Acid production is a major gastric function. Second messengers (cyclic AMP and calcium) are released when parietal cell membrane receptors (H2, muscarinic and gastrin) are stimulated. The second messengers then stimulate the 'gastric proton pump' to produce hydrogen ions. New evidence suggests that there is a unidirectional flux of hydrogen ions into the lumen induced by unique physical properties of mucus and a sodium gradient from lumen to serosa. Luminal hydrogen ions, bile salts, ingested drugs, and ingested alcohol are potential gastric epithelial toxins. The stomach's protective mechanism includes a well-defined mucus layer, an epithelial bicarbonate secretion, a tight epithelium, and a good nutrient blood supply. Endogenous prostaglandins partly control these mechanisms. Modern therapeutics are increasingly directed towards improving gastric cytoprotection.
Feeding oleic acid to rabbits resulted in a progressive rise in bile concentration of allodeoxycholic acid, expansion of the bile salt pool, and depression of de novo hepatic bile acid synthesis. There was also an increase in cholesterol saturation in bile. The gallstones that formed contained traces of cholesterol but were composed mainly of salts of allodeoxycholic acid. The data suggest that oleic acid feeding results in increased rate of cholestanol and allodeoxycholic acid metabolism. Morphologically, these biochemical events were accompanied by early reactive changes in the gallbladder epithelium characterized by marked increase in cell proliferation and mucus hypersecretion. In addition, there was the early formation of interepithelial cell vacuoles and, later, Rokitansky-Aschoff sinuses. These cellular reactions reflect the dramatic and important changes that take place in the gallbladder before gallstone formation.
The relative frequency of acquired primary hypolactasia has been determined in adult Maoris, Samoans and Europeans by measuring an alteration in breath hydrogen concentration two hours after a 50 g oral lactose load. By this indirect measurement hypolactasia was present in 64% of Maoris, 54% of Samoans and 9% of Europeans. The differences between Maoris and Europeans (p less than 0.001) and between Samoans and Europeans (p less than 0.001) were significant.
Thirty-five patients with duodenal ulcers were treated with tripotassium dicitrato-bismuthate (TDB) in a double-blind, double-dummy endoscopically controlled trial. Healing rates were comparable in patients treated with either tablet or liquid, 74% and 72% at four weeks and 89% in both groups at eight weeks. It is concluded that the tablet formulation of TDB is as effective as the liquid in the treatment of acute duodenal ulceration.
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Gastric mucus is thought to protect the underlying mucosal cells from mechanical hazards and back-diffusion of luminal H+. In health, a pH gradient exists across the mucus layer from the variable low pH of the lumen to a pH approaching neutrality at the epithelial cell surface. By current hypotheses this gradient is maintained by the combined effects of an unstirred layer, restricted or slowed diffusion of H+ in the mucus, and the epithelial cell secretion of bicarbonate, which is confined to the cell surface by the mucus layer. These mechanisms do not explain how H+ is secreted through mucus in the first place. Using a modified diffusion chamber we have shown that pig gastric mucus facilitates a low-efficiency Na+/H+ exchange--a property that helps to clarify some previously unexplained components of H+ secretion. When a solution containing Na+ was separated by a layer of fresh pig gastric mucus from a solution of similar pH containing a much lower concentration of sodium, the sodium-rich solution was electrically negative relative to the sodium-poor solution and its pH decreased significantly with time. A similar pH gradient developed when the barrier was a synthetic cation-exchange membrane, and one of opposite sign when it was an anion exchanger; no pH gradient developed across neutral barriers. It is suggested that similar electrical coupling of H+ diffusion to active Na+ transport might in vivo ensure that secreted H+ moves into the gastric lumen.
Groups of rats were given a fibre-free diet containing none or one of the three fibre components: pectin, cellulose or galactomannan. After feeding for 16 weeks, total protein level and beta-glucuronidase (EC 3.2.1.31) activity in the contents and mucosa of jejunum and ileum, and in the contents only of the caecum, were determined. The pectin supplement reduced protein concentration in jejunal contents while cellulose reduced protein concentration in the ileal and caecal contents. beta-Glucuronidase activity of caecal contents was significantly reduced in both the pectin- and cellulose-fed groups. Cellulose affected the beta-glucuronidase activity of both the ileal contents while pectin reduced the beta-glucuronidase of the ileal but not the jejunal contents. Dietary fibre components did not significantly affect jejunal or ileal mucosal beta-glucuronidase activity.
When Dark Agouti rats were changed from a conventional pellet diet containing 3.3% crude fibre and 4% fat to the experimental diet containing 5% pectin and 17% fat, the levels of n-butyrate in the caecum rapidly decreased more than fivefold. Such a change could be important as n-butyrate is known to be a major energy source for colonocytes, and to affect colon tumour cell development in vitro. Striking decreases in the caecal concentrations of the short chain fatty acids isobutyrate, n-valerate and isovalerate occurred when Wistar rats were fed an experimental diet containing 5% pectin as the only dietary fibre, compared to rats fed the experimental diet containing no dietary fibre. These large changes in the short chain fatty acid profile, caused by pectin supplementation, have important implications for the metabolism and health of the colon.
The digestibility of pectin, a component of dietary fiber was investigated in humans. The groups studied comprised healthy people with intact gastrointestinal tracts, and patients who had undergone total colectomy followed by ileostomy in the management of ulcerative colitis. The pectin content of the individual plant foods in the diet and the pectin content of the excreta were determined. Some loss of pectin occurred in the small intestine but most of the pectin was degraded in the large intestine.
Wistar rat jejunal disaccharidases were measured after feeding low fat, low fat + 5% pectin, low fat + 0.4% galactomannan, high fat, high fat + 5% pectin and high fat + 0.4% galactomannan diets for 16 weeks. All rats fed high fat diet had significantly lower jejunal sucrase and maltase levels when compared with their respective low fat groups. Lactase was significantly lowered in the high fat pectin group compared with the low fat pectin group, but was not significantly different when comparing the high fat or high fat galactomannan with their respective low fat groups. There was no significant difference in lactase, sucrase or maltase levels between the low fat groups, or between the high fat groups. We conclude that in Wistar rats an increased dietary fat level lowers jejunal sucrase, maltase and lactase levels, while the gel-forming substances pectin and galactomannan added at the levels of 5% and 0.4%, respectively, have no effect.