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Immunoreactive trypsin in serum can be divided into trypsinogen and trypsin-alpha 1-proteinase inhibitor (alpha 1PI) complexes. These were studied separately in serum from 204 patients with acute gastro-intestinal symptoms. Elevated levels of both trypsinogen and trypsin-alpha 1PI complexes were seen in patients with acute pancreatitis. Elevated levels of trypsinogen and normal or slightly elevated levels of trypsin-alpha 1PI complexes were seen in patients with biliary tract diseases. An isolated increase in the concentration of trypsin-alpha 1PI complexes with normal trypsinogen and amylase levels were seen in patients with perforated ulcer. This third cluster may result from an absorption of active trypsin from the peritoneal cavity. Small amounts of trypsin-alpha 1PI complexes were present also in serum from patients free from pancreatic disease. The results in this study show that high levels of trypsin-alpha 1PI complexes in serum are seen mainly in patients with acute pancreatitis. However, elevated levels are also seen in other pathological conditions in the upper gastrointestinal tract; therefore an assay for these complexes is not a specific diagnostic test for acute pancreatitis.

Lactic dehydrogenase (LDH) and its isoenzyme in the serum, gastric juice and mucosal tissue were studied in 83 patients with severe intestinal metaplasia, early and advanced gastric carcinoma, ulcer and superficial gastritis. The LDH activity in these tissues was lower in superficial gastritis and ulcer than in gastric carcinoma and intestinal metaplasia, while their isoenzyme activity was nearly normal. The LDH activity in the intestinal metaplasia was near to that in gastric carcinoma and its isoenzyme was transformed from H into M fraction, similar to gastric carcinoma. Thus, the relation between gastric carcinoma and intestinal metaplasia is reflected in the LDH activity. Because the differentiation of benign from malignant gastric disease by means of LDH assay is difficult and its isoenzyme possessing an individual characteristic distribution, this method may only be auxiliary in the differential diagnosis.

Using an immunoperoxidase technique the distribution of secretory component, IgA, and lysozyme has been investigated in normal, inflamed, dysplastic, and carcinomatous gastric mucosa. Apart from pyloric glands which contain lysozyme, normal gastric mucosa stains negatively for all three antigens. In gastric mucosa neck cells appear to adapt by synthesising secretory component and lysozyme and transporting IgA. Intense staining for the three antigens is seen in dysplastic gastric epithelium and in well-differentiated intestinal type carcinomas. With progressive de-differentiation the tumours lose the ability to synthesise secretory component and lysozyme. Carcinomas of the diffuse type stain positively for secretory component and lysozyme and individual cells appear to take up IgA even in the absence of surrounding IgA containing plasma cells. These functional properties are retained in lymph node metastases. It is suggested that secretory component synthesising malignant cells might take up circulating dimeric IgA and that this could be a reflection of an important physiological mechanism.

Biopsy specimens from the antral and body part of the stomach were studied for a range of marker enzymes in 11 patients with superficial gastritis, 9 patients with atrophic gastritis, and 31 Billroth-II-resected patients and compared with activities found in controls with normal gastric mucosa. In the antral part of the stomach increased gamma-glutamyltransferase activity was found in superficial (p less than 0.01) and atrophic gastritis (p less than 0.05), whereas monoamine oxidase activity was decreased in superficial (p less than 0.01) and atrophic gastritis (p less than 0.05). In the body part, increased activity of gamma-glutamyltransferase (p less than 0.01) and acid-beta-glucuronidase (p less than 0.01) was found in superficial gastritis. In atrophic gastritis increased activities for lactase (p less than 0.01), alkaline phosphatase (p less than 0.05), leucyl-beta-naphthylamidase (p less than 0.05), gamma-glutamyltransferase (p less than 0.05), 5'-nucleotidase (p less than 0.01), N-acetyl-beta-D-glucosaminidase (p less than 0.05), and acid-beta-glucuronidase (p less than 0.01) were found. Specimens from the gastric remnant showed an enzyme activity pattern similar to that seen in the body in atrophic gastritis, apart from a significantly decreased monoamine oxidase activity (p less than 0.004). Specimens with dysplasia in the gastric remnant showed decreased monoamine oxidase activity when compared with specimens without dysplasia (p less than 0.01).

Free glutamine content and phosphate-dependent glutaminase activity were studied in the biopsy specimens from the tissue of ulcer, polyps, carcinoma and the surrounding gastric mucosa of patients with precancerous diseases and carcinoma of the stomach. The glutamine content in carcinoma was not significantly different from that in the normal gastric mucosa. The glutamine level in the gastric mucosa remote from the tumour was considerably higher than normal. In case of polyposis of the stomach glutamine was present in the polyps and absent in the remote gastric mucosa. A marked glutaminase activity was revealed in the carcinoma of the stomach, but its level did not differ from the normal or in the case of precancerous diseases.

Using a method of electrophoretic separation on agar gel, the hexokinase (HK) isoenzymes were determined in biopsies from patients with gastric and esophageal cancer and nonmalignant diseases (gastric benign tumors and gastritis) as well as in biopsies from healthy people. In the malignant neoplasms studied, a significant elevation of HK-II and the appearance of additional anodal bands (HK-IIf and HK-III) have been demonstrated. As a rule, the HK isoenzyme spectrum in gastric polyps was similar to that of normal mucosa and characterized by a predominance of HK-I. Changes in the HK isoenzyme composition in gastric mucosa with intestinal metaplasia were expressed in lesser degree but had similar cancerous tendency. The HK isoenzyme analysis in biopsy samples may be used for differential diagnosis of malignant and benign tumors, and/or as definite diagnostic implication of an early sign of malignancy in the study of premalignant lesions.

Lactic dehydrogenase (LDH) and beta-glucuronidase (bGLU) levels are elevated in the gastric juice of patients with gastric cancer, and these enzymes have been used as a screening test for gastric cancer. False positives are common, however, and we have measured enzyme levels, including LDH isoenzyme fraction, in tissue homogenates from resected stomach specimens and compared these with histological features. Increases in bGLU were found in carcinoma and chronic gastritis, an increase in LDH was found in carcinoma, whilst mLDH fraction was increased in chronic gastritis, carcinoma and intestinal metaplasia, particularly the sulphomucin variant. These findings indicate the basis for the screening test, and also the reason for the false positives. An elevated mLDH fraction may be a useful marker of a group at increased risk of developing gastric cancer, and worthy of long-term follow-up.

Seventy patients were diagnosed to have chronic atrophic gastritis, because an atrophic border was distinguished by the endoscopic Congo red method. The atrophic border was furthermore classified into the closed type and the open type. Specimens of the gastric mucosa were obtained by biopsy to measure tissue kallikrein as a marker of inflammation. The sandwich-type ELISA showed that kallikrein significantly increased with the extension of the atrophic area. Histopathological investigations also revealed that kallikrein markedly increased with the appearance of intestinal metaplasia. The peroxidase-antiperoxidase method located (1) a large amount of kallikrein in the mucous granules which filled the goblet cells found in the mucosa showing intestinal metaplasia and (2) a small amount discharged into lumens. These findings suggested that atrophy of the gastric mucosa might be an inflammatory change, and that the kallikrein-kinin system might be associated with gastric inflammation regardless of the pathological stage.

A metalloproteinase was extracted from a medium of cultured gastric tissues following acetic acid-induced ulcer or taurocholic acid-induced gastritis, and the enzyme was partially purified by Sephadex G-200 column chromatography. This proteinase was released in active and latent forms with apparent molecular weights of 170,000 and 210,000, respectively. Its activity was abolished by treatment with ethylenediaminetetraacetic acid or 1,10-phenanthroline, but not with phenylmethylsulfonyl fluoride or soybean trypsin inhibitor. This enzyme degraded type I gelatin and type IV collagen but did not attack type I collagen. In contrast, very little of this enzyme was released from gastric tissue following erosion caused by water-immersion stress or from normal gastric tissue. These results suggest that this metalloproteinase plays an important role in gastric lesions by breaking down the basement membrane.

The authors describe a method designed by them for assessing gastric juice proteolysis relative to different protein-containing foods, commonly used in nutrition (beef, pork, mutton, etc). Investigations involved the use of gastric juice from healthy persons and patients with chronic gastritis associated with low secretory gastric function and ulcer disease. The proteolytic activity of gastric juice turned out to be different both in healthy persons and in patients with ulcer disease. In patients suffering from chronic gastritis associated with low secretory gastric function, proteolysis of protein-containing foods was reduced to a different degree in respect to a concrete food. Out of all foods investigated, egg yolk, beef liver and mintai were assimilated better whereas egg white and mutton to a worse degree. Addition of hydrochloric or citric acid raised the proteolytic activity of gastric juice.

By using an original method of electrophoresis separation, the normal relative values of each one of the LDH isoenzymes in the gastric body and antral mucosa were determined. It has been shown in gastric tumors that there is a significance rise in the relative values of "type M" isoenzymes (iso-LDH-4-5). With intestinal metaplasia as well as gastritis, a significant elevation of the relative value of iso-LDH-5 has been demonstrated in the antral mucosa. In 6 benign gastric polyps we found a similar disturbance. This would confirm the known precancerous condition of these lesions. In the normal mucosa of subtotal gastrectomy specimens, 19 patients with antral cancer had 2 types of LDH isoenzyme patterns: one normal and the other with an increase in the relative proportion of "type M" isoenzymes. These LDH isoenzyme pattern shifts in the gastric mucosa could be an early sign of malignancy prior to the morphologic changes.

The authors studied the acid-proteolytic profile of the stomach using an original method in 9 patients with superficial gastritis, in 38 patients with atrophic gastritis and in 25 of the control group without gastroduodenal pathology. It was established that in patients with atrophic gastritis associated with secretory insufficiency, proteolytic activity is maintained due to entering of pancreatic enzymes in the process of digestion and is characterized by an increase of the intensity of proteolysis from the cardia to the pylorus, by low values of hydrolysis of proteins resistant to the effect of pancreatic proteinases.

A correlation was sought between changes in enzymes involved in gastric acid secretion (Mg-, NaK-, K- and HCO3-stimulated ATPases) and histological changes in gastric biopsies. Alkaline phosphatase was also studied. Mg- and NaK-stimulated ATPase activities increased significantly in biopsies from the pylorus and antrum which showed moderate or severe gastritis. NaK ATPase levels increased and HCO3 ATPase decreased in incisural, body and fundic mucosa which had intestinal metaplasia and atrophic gastritis. No K+ ATPase was found in normal mucosa. The total activity of alkaline phosphatase did not vary with histological changes in the gastric mucosa. Results indicate that the ATPase enzyme systems are sensitive indicators of gastric mucosal disease.

An immunogenic acid stable esterase of gastric origin was purified from normal gastric juice. Specific antibodies were obtained by solid immunoadsorbents and were used for indirect immunoenzyme histology on gastric resection specimens. This esterase proved to be a cell specific marker for gastric chief cells. Different patterns of chief cell alterations in gastritis and cancer were observed.

Peptidases, phosphatases, glycosidases, non-specific esterases, succinate dehydrogenase, cholinesterases, and carbohydrate components were studied in bioptic material of the normal and diseased human stomach using well established older, modified older, and new qualitative histochemical methods. For the first time, an enzyme pattern is reported for all regions of the human mucosa. Local and regional enzyme histochemical differences existed between the cardiac, fundic, body, and pyloric mucosa. Differences were absent, however, in the same region, and no differences were found between the anterior and posterior wall and the large and small curvature of the stomach. In cases of histologically less severe gastritis as a rule, enzyme histochemical changes were not found. They were numerous, however, in biopsies of patients with severe gastritis; only amino-peptidases A and M were unchanged. Dipeptidyl peptidase IV was absent; gamma-glutamyl transpeptidase exhibited individual differences. Alkaline phosphatase occurred in the pericapillary stroma and adenosine phosphates were not hydrolysed in atrophic glandular epithelia. Activity increases of lysosomal dipeptidyl peptidase I and beta-D-glucuronidase were typical for inflammatory infiltration processes of the gastric mucosa. Severe atrophy was accompanied by an activity decrease of glandular non-specific esterases, dipeptidyl peptidase II, and beta-N-acetyl-D-glucosaminidase and an activity decrease of the stromal peptidases and glycosidases. Enzyme activity was absent in the gastric glands proper in cases of total atrophy. An increase in macrophage number was primarily linked with an increase in acid phosphatase activity. Alkaline phosphatase, aminopeptidase M and gamma-glutamyl transpeptidase activities were enhanced in malignant neoplasms. High activities of all peptidases and alkaline phosphatase were found in the brush border of surface epithelial cells in cases of intestinal metaplasia. Except for dipeptidyl peptidase I and II, the enzyme pattern corresponds to that of small intestinal enterocytes. Compared with histological routine procedures for gastric diagnosis and assessment of the course enzyme histochemical methods deliver additional information; practically, however, the enzyme histochemical analysis of gastric biopsies are only useful in special cases.

Assay of creatine kinase MB isoenzyme plays an important role in the diagnosis of acute myocardial infarction. An increase in CK-MB is frequently interpreted by the clinician as objective evidence of myocardial cell damage. However, increases of CK-MB may be found in several circumstances in which patients have not sustained an acute myocardial infarction. An important cause of elevated CK-MB values unrelated to acute MI is the presence of macro-creatine kinases in the patient's plasma. With immuno-inhibition procedures macro-CK is often measured as CK-MB, leading to falsely elevated CK-MB. In this paper macro-CKs, their clinical importance and their interference with CK-MB determination are discussed.

Adenylate cyclase (AC) in response to prostaglandin E2 (PGE2) and histamine was studied in morphologically different biopsy specimens from human gastric mucosa. The activities of the enzyme were log-normally distributed and did not differ between males and females. PGE2 activated AC in a concentration-dependent manner in normal gastric mucosa (n = 57), chronic superficial gastritis (GI, 18), chronic gastritis with beginning atrophy (GII, 10), chronic atrophic gastritis (GIII, 24), gastric ulcer (GU, 39), duodenal ulcer (DU, 32), and biopsies of patients operated according to Billroth II (BII, 20) and was most efficacious in GIII and BII. Histamine, which was studied in normal gastric mucosa (n = 27), DU (n = 20), GU (n = 13), and BII (n = 18), stimulated AC most efficaciously and potently in DU, was less effective in normal gastric mucosa and GU, and had no effect at all in BII. Cimetidine treatment of DU patients did not change the PGE2 action, while the degree of stimulation by histamine was reduced. The data indicate characteristic differences of the PGE2- and histamine-sensitive AC in the mucosal samples of these patients.

Flow cytometric measurements of cellular DNA have been performed on biopsy specimens obtained by gastroscopy in patients with normal gastric mucosa (controls), superficial and atrophic gastritis, and resected stomachs. Aneuploidy was found in two biopsy specimens from a patient with superficial gastritis and in one specimen from a resected stomach. The fractional number of cells with a DNA content corresponding to the DNA synthetic and (G2 + M) phases of the cell cycle was defined as the 'proliferative index' (PI). No difference between the antral and body part of the stomach was found for the PI in controls or between controls and superficial and atrophic gastritis. PI was weakly but significantly correlated to a selection of mucosal enzymes. In resected stomachs increased PI was found when compared with that in the body part of the stomach in controls (p less than 0.01). Biopsy specimens with intestinal metaplasia (p less than 0.01) or atrophy (p less than 0.05) in the resected stomach showed significantly higher PI when compared with specimens with such findings from the body part of the stomach in atrophic gastritis.