D. Hopwood

Evidence for hypomotility in non-ulcer dyspepsia: a prospective multifactorial study.

A prospective multifactorial study of symptoms and disturbance of gastrointestinal function has been undertaken in 50 patients with non-ulcer dyspepsia. Objective tests including solid meal gastric emptying studies, gastric acid secretion, E-HIDA scintiscan for enterogastric bile reflux, and hydrogen breath studies were carried out in all patients and validated against control data. Gastroscopy and biopsy were carried out in non-ulcer dyspepsia patients only. Non-ulcer dyspepsia patients were categorised on the basis of predominant symptoms as: dysmotility-like dyspepsia (n = 22); essential dyspepsia (n = 14), gastro-oesophageal reflux-like dyspepsia (n = 11); and ulcer-like dyspepsia (n = 3). In the total non-ulcer dyspepsia population, solid meal gastric emptying was delayed (T50 mean (SEM) = 102 (6) minutes (patients) v 64 (6) minutes (controls), (p less than 0.01) and high incidences of gastritis (n = 26) and Helicobacter pyloridis infection (n = 18) were found. An inverse correlation was observed between solid meal gastric emptying and fasting peak acid output (r = -0.4; p less than 0.01). Indeed gastric emptying was particularly prolonged in eight patients (T50 mean (SEM) = 139 (15) minutes) with hypochlorhydria. In the non-ulcer dyspepsia population oral to caecal transit time of a solid meal was delayed (mean SEM = 302 (14) minutes (patients) v 244 (12) minutes (controls) (p less than 0.01]. Seven patients had a dual peak of breath hydrogen suggestive of small bowel bacterial overgrowth. No association was observed between symptoms and any of the objective abnormalities. This multifactorial study has shown that hypomotility, including gastroparesis and delayed small bowel transit, is common in non-ulcer dyspepsia and may be related to other disorders of gastrointestinal function. No relation between symptoms and disorders of function, however, has been shown.

The Effects of Long-Term Feeding of Soya Flour on the Rat Pancreas

Rats were fed raw and heated soya flour for up to 2 years. The rats fed raw soya flour all developed pancreatic hypertrophy and hyperplastic and adenomatous nodules. Four of 26 rats fed raw soya flour continuously and 1 of 5 rats fed raw soya flour for 2 days each week developed pancreatic cancer. Preheating the soya flour seemed to protect against the pancreatic hyperplastic and neoplastic changes.

Epidermal growth factor receptors in the oesophagus.

The quantity and distribution of epidermal growth factor receptors (EGF-R) in oesophageal mucosa was studied in the oesophagus in order to determine its role in oesophageal disease. Fifty five biopsies were taken from different levels of the oesophagus in 25 consecutive patients undergoing endoscopy. Another group of eight patients with histologically proven Barretts oesophagitis had a biopsy taken from the area of columnar lined oesophagus. A peripheral, membranous pattern was seen predominantly confined to the basal and immediately suprabasal cells in all of the first group of patients. In the superficial cells a few granular cytoplasmic structures were positive. All patients with Barretts oesophagitis showed EGF-R staining of the surface epithelium. A computerised planimeter was used to determine the proportion of stained areas of squamous cells which were expressed as a percentage of the total area of squamous cells. The difference in the area of cells stained for EGF-R between normal and inflamed oesophageal mucosa (29.5% and 43.1% respectively) was significant (p less than 0.001).

Carbonic anhydrase isoenzymes I, II, III, and IV are present in human esophageal epithelium.

Carbonic anhydrase (CA) isoenzymes have been widely studied in the gastrointestinal tract, where they mediate membrane transport events and pH regulation. However, the esophagus has generally received scant attention. In an immunohistochemical study confirmed by Western blotting, we have detected four CA isoenzymes (CAI, II, III, and IV) in the epithelium of human esophagus. Isoenzymes I, III, and sometimes IV (<10%) were present in the cytoplasm of basal cells and II and IV in the cytoplasm and cell surface membranes, respectively, of suprabasal cells (prickle cells). The localization of CAIV to the plasma membranes was confirmed by electron microscopic immunocytochemistry. CA was effectively divided at the basal-suprabasal interface between low-activity CAI and III (basal) and high-activity CAII and IV (suprabasal). Carbonic anhydrase in esophageal epithelial cells may have several functions: elimination of CO2 and metabolites, participation in membrane transport events during active cell growth, and pH regulation as a protective mechanism against acidic gastric reflux.

Carcinogenic Effects of Di(2-hydroxypropyl)nitrosamine (DHPN) in Male Wistar Rats: Promotion of Pancreatic Cancer by a Raw Soya Flour Diet

Di(2-hydroxypropyl)nitrosamine was administered to rats fed raw or heated (control) soya flour diets. The group fed raw soya flour developed hyperplastic and adenomatous pancreatic nodules and pancreatic adenocarcinomata. We conclude that a diet of raw soya flour augments the carcinogenicity of pancreatic carcinogens in the rat.

Potentiation of the action of azaserine on the rat pancreas by raw soya bean flour.

Rats were treated with raw soya flour to produce pancreatic hypertrophy and also received azaserine, a pancreatic carcinogen. The combined treatment resulted in the development of large numbers of hyperplastic nodules in the acinar tissue of the rat pancreas. We conclude that the pancreas of the rat stimulated to proliferate by raw soya flour provides a sensitive model for detecting and studying pancreatic carcinogens.

Histochemical studies of mucosubstances and lipids in normal human oesophageal epithelium

SynopsisThe histochemistry of lipids and mucosubstances in normal human oesophageal epithelium were studies in biopsies obtained from 24 patients undergoing investigations of the upper gastro-intestinal tract. Neutral fat droplets, 1–2 gmm in diameter, were present in all layers, the greatest number being in the functional layer cells. No unsaturated lipids or fatty acids were demonstrable. Much glycogen was present in the cytoplasm of the prickle and functional cell layers as demonstrated by PAS (and diastase digestion) techniques. The intercellular space of the most superfical of the functional cell layer contained neutral and sialic acid-rich acid mucopolysaccharides. These may be important in protecting the epithelium against physical and chemical trauma.

The reactions of glutaraldehyde with nucleic acids

SynposisThe kinetics of the reactions between glutaraldehyde, RNA and DNA have been investigated. At temperatures up to 64°C no reaction occurred between native DNA and glutaraldehyde. At temperatures above 75°C the reaction followed pseudofirst order kinetics, proceeding more quickly at higher temperatures. Reactions between RNA and glutaraldehyde were similar, except that they began above 45°C. These findings were corroborated by thermal transition profiles. There was little evidence for the formation of cross-links between nucleic acid molecules even at elevated temperatures.

Flow-Cytometric Analysis of Growth-Regulatory Peptides and Their Receptors in Barrett's Oesophagus and Oesophageal Adenocarcinoma

The conventional assessment of the premalignant potential of Barretts oesophagus is unsatisfactory. However, it has recently been shown that abnormalities of growth-regulatory peptides and their receptors may be important in the pathogenesis of this condition. In an attempt to improve the diagnostic and prognostic criteria we have studied 21 consecutive patients with Barretts oesophagus and 7 others with adenocarcinoma of the oesophagus. In each patient biopsy specimens were taken from the columnarlined oesophagus or the adenocarcinoma and from the gastric cardiac mucosa for routine histologic evaluation. Immediately adjacent specimens were taken from both the Barretts mucosa or adenocarcinoma and from the gastric mucosa for flow-cytometric study. The latter samples were disaggregated and labelled with antibodies to epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and epidermal growth factor receptor (EGF-R). The flow cytometer selected cells labelled with each antibody and expressed them as a percentage of the total number of disaggregated cells (average, 5500 cells). Epidermal growth factor receptors were expressed in a greater number of cells from Barretts mucosa, with the intestinal type or those with dysplasia, than in gastric cardiac mucosa (p less than 0.05). All seven adenocarcinoma had many more cells expressing EGF, TGF-alpha, and EGF-R than normal gastric mucosa (p less than 0.01). We conclude that flow-cytometric evaluation of EGF-R can help in the understanding of the pathogenesis of Barretts oesophagus.

Expression of Epidermal Growth Factor, Transforming Growth Factor Alpha and Their Receptor in Gastro-Oesophageal Diseases

This article is a review of aspects of the expression of the regulatory peptides; epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and their receptor (EGF-R) in the epithelium of the human oesophagus and stomach in health and disease. It has become clear that TGF-alpha has increased expression in metaplastic, dysplastic and neoplastic tissue of the oesophagus compared with normal mucosa. The degree of abnormal expression becomes more marked as dysplasia increases. TGF-alpha expression is also increased in gastric neoplasias. EGF has a different pattern of expression, being decreased in oesophagitis and increased in gastritis. Although EGF is present in Barretts oesophagitis, the expression of EGF does not discriminate between dysplastic and neoplastic epithelium. EGF-R is normally expressed on all gastro-intestinal epithelia, but its expression is increased in Barretts epithelium, as well as in adenocarcinomas of the oesophagus and the stomach. The two peptides bind to their receptors on the mucosal cell membranes, and the co-expression of peptide and receptor is positively associated with varying degrees of cellular proliferation. The density of receptor expression may modulate the proliferative stimulus, leading to either mitogenic (regulated) or oncogenic (unregulated) growth.