Gastric proteolysis in disease. 2. The proteolytic activity of gastric juice and gastric mucosal extracts from patients with chronic gastric and duodenal ulcer.

The secretion of pepsin in the gastric juice of patients with peptic ulcer has been the subject of much investigation. Early work was carried out mainly on resting juices or on the aspirated products of an Ewald meal (Willcox, 1908; Boas, 1925; Hirsch-Mamroth and Rindfleisch, 1925; Polland and Bloomfield, 1930; Vanzant, Osterberg, Alvarez, and Rivers, 1933; Mullins and Flood, 1935), and appeared to establish that in both gastric and duodenal ulcer, but more strikingly so in the latter, the pepsin concentration of the gastric juice is increased. The total output of pepsin in response to a given stimulus is further increased because a greater volume of juice is secreted. Ihre (1938) found, however, in both chronic duodenal and gastric ulcer that the pepsin concentrations of the fasting and histamine secretions were normal and that only after insulin hypoglycaemia were they raised. Le Veen and Hallinger (1947) presented evidence that the absolute peptic activity of the fasting gastric juice in peptic ulcer was normal and only appeared raised because of the lower pH at which the fasting juice is usually secreted in this disease. Chinn, Book, and Beams (1951) also were unable to find any significant difference in the pepsin concentration of nocturnal or insulin juices between patients with duodenal ulcer and normal controls. Janowitz and Hollander (1951, 1952) determined the total pepsin content of the basal gastric secretion (" in the absence of all intentional and avoidable stimuli") over periods of one hour, and found that in duodenal ulcer the average basal output of pepsin is up to three times that of normal controls, whereas in gastric ulcer it is not significantly different from normal. Whilst, therefore, it is doubtful if the actual concentration of pepsin is increased, it seems established that, in duodenal ulcer at any rate, because of the increased volume of gastric secretion, the total output of pepsin by the mucous membrane both at rest and in response to a given stimulus is usually greater than in normal subjoets. The underlying assumption in these investigations has been that the gastric mucous membrane of patients with peptic ulcer secretes normal pepsin. Proteolytic activity has been determined only near pH 2. The possibility that modified pepsin, or enzymes different from pepsin, may be present has not been considered. An investigation of this possibility is now described.