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Gastric mucosal damage was produced in 130 mice by forced ingestion of alcohol, followed by restraint in the cold. Animals were killed at intervals from six hours to 27 days following the stress. Linear hemorrhagic erosions and diffuse hemorrhagic patches were found grossly, predominantly in the glandular portion of the stomach, in about 75% of the animals 6 to 24 hours after stress. At later time intervals, the linear mucosal depressions persisted; these became progressively less prominent with time but substantial numbers were still readily discernible three weeks after injury. Microscopical examination of the fresh lesions showed a variable amount of mucosal necrosis and acute inflammation. Epithelial regeneration became prominent after three days and persisted for several weeks. The first regenerating epithelial cells were primitive, cuboidal elements followed by mucous cells, parietal cells, and zymogen cells, in that order. The morphological features and evolution of the lesions were similar to that described in human stress ulcers.

A new sulfated glycolipid has been isolated from the lipid extract of human gastric content by the procedure involving column fractionation on silicic acid and thin-layer chromatography. Degradation studies revealed the presence of glucose, sulfate, fatty acids and glyceryl monoethers. The structure of this glycolipid was identified by partial acid hydrolysis, oxidation with periodate and chromium trioxide, and permethylation studies, as: SO3H-6Glcalphal leads to 6Glcalphal leads to 6Glcalphal leads to 3-diglyceride. The diglyceride portion of this glycolipid consists mostly of 1-O-alkyl-2-O-acyl-glycerol.

This investigation was initiated to separately evaluate the roles of dose and concentration of ethanol ingestion in the development of acute gastric mucosal injury and to determine the significance of stress as a potentiating factor in ethanol damage. A total of 423 mice were used in this study. Alcohol at the low concentration of 10% and at any of the doses used (1-5 g/kh wt) did not cause gastric mucosal lesions. Similarly, alcohol at the low dose of 1 g/kg wt at any of the concentrations used (10-50%) did not produce any gross injury to the stomach. A single oral administration of ethanol, given at doses of 2-5 g/kg wt and at concentrations of 25-50%, resulted in hyperemia and multiple fundic erosions and, less frequently, antral erosion. The incidence, number, and severity of these lesions rapidly increased with increase in ethanol concentration, ethanol dose, or both. Healing was rapid; at best, lesions were only barely visible 72 hours after alcohol ingestion. Repeated daily doses of ethanol given for 3-5 days did not increase the incidence and number of lesions, probably due to their capacity for rapid healing. Mild stress, in the form of 1-hour restraint in the cold room at 8 degrees C, by itself caused very little mucosal injury in mice, but significantly potentiated the injurious effect of 35% ethanol administered in a 3 g/kh dose. Stress following alcohol intake potentiated gastric mucosal injury much more than if the stress preceded the alcohol ingestion. The incidence, number, and severity of erosions was here 3,4 and 11 times, respectively, greater than the additive effect of alcohol and stress together (P smaller than 0.001). Thus, the extent of ethanol damage to the stomach related both to the concentration and dose of ethanol infested. Stress, especially when following excessive ethanol intake, was a highly significant factor in the potentiation of acute alcoholic gastric mucosal injury.

An autologous "skin window test," used lately for the study of cellular immunity in cancer, was applied here successfully to 54 patients with upper-gastrointestinal ailments, 48 of whom had a coexistent fundic and/or antral chronic gastritis of varying severity. The diagnoses of gastritis were made by multiple fiber-gastroscopic biopsies. The ether-alcohol-fixed cryostat sections of fundic and antral biopsies were mounted on cover slides and placed on small cutaneous abrasions of the forearm of the same patients for 24--28 hr. The exudates on cover slides and on imprints of the abrasions were read blindly for the mononuclear cell response according to criteria set for this test by Black and Leis (10). A positive reaction was obtained in 8 of the 54 patients using autologous fundic mucosal biopsy. An autologous antral mucosal biopsy gave positive reaction in only 2 of the 26 of the patients in whom it was used. The positive yield of this autologous skin window test in chronic advanced fundic gastritis was somewhat higher than that obtained by other authors using lymphocytes blast transformation or macrophages migration inhibition test in vitro. It was much higher than the yield obtained by others who used skin tests in vivo, with homologous or heterologous gastric mucosal extracts as antigens. The autologous skin window is safe in regard to possible transmission of hepatitis. Its applicability for detection of cellular immunity derangement in chronic gastritis carries promise.

In this study of 48 successfully operated rats, we evaluated the applicability of the Ghosh-Lai stomach preparation to the quantitation of the HCl output following stimulation with histamine and pentagastrin and inhibition with gastrone and atropine. The usefulness of this rat preparation was well demonstrated and good duplication of results was obtained with various doses of histamine and pentagastrin. In this rat preparation, the HCl output following an optimal pentagastrin dose of 6 mug/kg/30 min i.v. was almost twice higher than that after an optimal histamine dose - for this rat preparation - of 0.2 mg/kg/30 min i.v. The inhibitory effect of gastrone B on histamine-stimulated HCl output has been confirmed in this rat preparation and shown to extend also on the pentagastrin-stimulated HCl secretion. The comparison of the atropine and gastrone inhibition of the pentagastrin-stimulated HCl output in the Ghosh-Lai preparation indicates that the inhibitory effect of 40 mug gastrone i.v. is similar in rat to that of 0.4 mg atropine sulfate i.v. under these conditions.

Seven individual glycolipids (I--VII) have been isolated from the lipid extract of human saliva. All glycolipids contained glucose, glyceryl ethers and fatty acids, and differed from each other primarily with respect to the number of glucose residues. In addition, glycolipid V contained also the sulfate ester group. The structures of these glycolipids were identified by partial acid and alkaline hydrolysis, oxidation with periodate and chromium trioxide and methylation studies, as: Glc(alpha1 leads to 3)-diglyceride (glycolipid I), Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipids II and III), Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipid IV), SO3H-6Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipid V), Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipid VI) and Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 lead to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipid VII). Diglyceride portion of these compounds consists of 1-O-alkyl-2-O-acyl-glycerol with the docosanoate and glyceryl-monodocosyl being the predominant acyl and alkyl components.

The authors evaluated the applicability of the rat with gastric fistula to the bioassay of gastrone, endogenous inhibitor of gastric acid secretion and the role of anticholinergic mechanism in this inhibition. 104 individual bioassays were performed on 25 rats with chronic gastric fistula out of which 34 tests were performed with gastrone, 49 controls with saline and 21 with atropine. In rats serving as their own controls, a statistically significant reduction of the volume of basal gastric secretion and of the basal HCl output by 56 and 59%, respectively, occurred after intravenous administration of 40 mug gastrone B. This was demonstrated in the first 4 h after gastrone and was statistically highly significant (p less than 0.001). There was no significant difference, however, in the concentration of HCl in the gastric juice after gastrone and after saline. The inhibitory effect of gastrone on HCl output at the intravenous dose of 40 mug was greater than that of 0.1 mg/kg atropine intravenously, while that of 50 mug gastrone was about equal to that of 0.4 mg/kg atropine. The gastrone inhibitory activity on gastric acid secretion in rats appears to be unrelated to anticholinergic mechanism. The advantages of the bioassay of gastrone activity using rats with chronic gastric fistula over the rats with pyloric ligation are discussed.

The lipid composition of the "mucous barrier" of rat stomach was investigated. Cellular mucus of the mucous cells from gastric epithelium and surface mucus from gastric mucosa were obtained by perfusion in vivo of Ghosh-Lai rat stomachs with 2 M NaCl. Lipids extracted from dialyzed and lyophilized 2 M NaCl perfusates and 0.9% NaCl (saline) controls were quantitatively separated into single components by means of two-dimensional thin layer chromatography and compared. Significant differences in the level of cholesterol esters, di- and triglycerides, and glycolipids were found. Three to 4 times greater quantities of cholesterol esters and di- and triglycerides, and 2 to 6 times greater quantities of glycolipids were found in 2 M NaCl perfusates as compared to saline controls. The glycolipid fraction consisted of neutral and acidic glyceroglucolipids and was devoid of glycosphingolipids. The phospholipids constituted the smallest portion of the lipids present in 2 M NaCl and saline perfusates and were 2 times higher in 2 M NaCl. These data indicate that mucous barrier in addition to mucins contains considerable quantities of lipids of which glyceroglucolipids are the most prominent components.

Our main purpose in this review article is to present some of the vast amount of information on the subject of atrophic gastritis available at the present time. Various areas of research pertaining to this entity, including that from the author's laboratory, are reviewed in this article, encompassing histological and ultrastructural abnormalities, enzyme histochemistry, and exfoliative cytology and cytochemistry of chronic gastritis, with emphasis on the diagnostic significance of these laboratory methods. The altered cell proliferation kinetics in atrophic gastric lesions is also discussed, as well as its significance in the proliferation and reduction of glandular cells of the gastric mucosa. Furthermore, some of the more recent evidence of immunological mechanisms and other causes of chronic gastritis, such as chronic alcoholism and bile reflux, is reviewed, as well as the effects of partial gastrectomy on the gastric mucosa. The important associations and sequellae of atrophic gastritis, such as gastric ulcer, gastric polyps, and gastric cancer, are discussed in detail.

The origin of blood group ABH activity in human gastric content was investigated. Dialyzed and lyophilized samples of ten individual gastric secretions were assayed for ABH antigen under various conditions. The native activity persisted in delipidated residue of the respective secretions, but was completely missing in the lipid extracts of the analyzed samples. The alkaline degradation of the native and delipidated samples led to total loss of blood group activity of the analyzed materials, but no effect on A-active glycosphingolipid was evolved. Purified glycolipid portion of the lipid extract was lacking ABH activity and was shown to have distinct composition. This fraction contained only glyceroglucolipids and neither sphingosine nor other carbohydrates were present. On the basis of blood group activity assays of the native, delipidated, alkaline degraded samples and also on glycolipid analysis it was established that the ABH blood group activity of stomach secretion originated entirely from the glycoprotein portion of these samples.

On personal invitation, which is here gratefully acknowledged, of Professor C. Burg, the general director of the Institut National de la Santé et de la Récherche Médicale (INSERM), I had the privilege and pleasure to spend the month of October 1976 in France touring Gastroenterology INSERM Units. The INSERM is the French analog of the National Institute of Health (NIH) in the United States. The purpose of my visit was to see the organization and performance of these research units, compare them with what I know about the gastroenterology research laboratories in the United States, and exchange scientific information with the French researchers on the topics of mutual interest. Professor Serge Bonfils was chosen with his kind approval as the host of my visit. His INSERM Unit (number 10) at the Hospital Bichat in Paris, was elected as the "Host Unit" where my visit started and ended, and where the visits to the other units were organized. I owe him sincere gratitude for his guidance and help. After completing my tour, I was left with the feeling that what I had seen would be of interest to American gastroenterologists. Dr. John Farrar, the editor of this journal, encouraged me to review my tour and my impressions.

In order to determine the possible effects of the circulating intrinsic factor antibodies (IFA) on gastric morphology and secretory function, four groups of 12 rats each received intravenous injection daily for 8 to 12 weeks of immunoglobulin G (IgG) fractions separated on DEAE-cellulose columns from various sources: (1) sera of patients with pernicious anemia, containing both IFA and parietal cell antibodies (PCA), (2) sera from patients with atrophic gastritis, containing parietal cell antibody only, and (3) and (4) sera of rabbits immunized with semipurified human or rat intrinsic factor (IF). In addition three control groups of 12 rats each received intravenous injections daily for 8 to 12 weeks of either (5) saline or (6) and (7) IgG processed from human or rabbit normal sera. Still another group of 12 rats (8) did not receive any injections whatsoever for the same duration of time. One-third of the rats were intubated biweekly after histamine stimulation and the hourly outputs of CHl pepsin, and IF were determined. At conclusion of the experiments, rats were killed, the mucosal surface and thickness of the mucosa were measured, and parietal cell and peptic cell masses were counted. The control groups showed either progressive growth of the cellular mass in gastric mucosa and increase of the HCl, pepsin, and IF outputs, or no significant changes. In contrast, rats injected with IgG containing IFA to human or rat IF showed a statistically significant thinning of the gastric mucosa, reduction of peptic cells, which are known to secret IF in this species, and corresponding decreases in the ouputs of pepsin and IF. These became reduced by about 50% from initial values, and by 62 or 75%, respectively, when compared to rats injected with normal human or rabbit IgG's. In rats injected with IgG's from pernicious anemia sera, which contained both IFA and PCA, the outputs of IF, pepsin, and HCl decreased signigicantly, as well as the peptic and parietal cell masses. The rats injected with PCA only demonstrated thinning of the gastric mucosa, reduction of parietal cell mass, and a significant decrease of the HCl output. These findings imply an active role of the circulating gastric.

One hundred fifty alcoholic men and women and 150 age and sex-matched nonalcoholic controls (after exclusion of pernicious anemia and cancer of the stomach) were evaluated for the presence of parietal cell antibodies (PCA). Blocking and binding intrinsic factor antibodies (IFA) were determined in the PCA positive sera. The prevalence and age and sex distribution of PCA in the alcoholics and nonalcoholics was identical. In alcoholics above the age of 60 years, the incidence of PCA, although higher than in those of the younger age group was similar to that in the nonalcoholics of the same age group (in men 6.3 percent and 7.3 percent and in women 7.5 percent and 10.0 percent respectively). Antral gastritis of moderate or severe degree was the frequent lesion in alcoholics. This form of gastritis was not associated with any significant increase in the incidence of PCA. No patients with sera positive for IFA were detected among the 22 PCA positive patients. There is no evidence for humoral derangement of the gastric autoimmunity in chronic alcoholics.

Two major neutral glyceroglucolipids (A and B) have been isolated from lipid extract of human gastric content by the procedure involving column fractionation on DEAE-Sephadex, silicic acid, and thin-layer chromatography. Both glycolipids contained glucose, glyceryl ethers, and fatty acids. The structures of these glycolipids were identified by mild alkaline methanolysis, oxidation with periodate and chromium trioxide, and permethylation studies. Based on the obtained data, we propose that glycolipid A is a monoalkylmonoacylglyceryl hexaglucoside and glycolipid B is a monoalkylmonoacylglyceryl octaglucoside. The diglyceride portion of these glycolipids consists mostly of 1-O-alkyl-2-O-acylglycerol.