D. W. Skagen

Enzyme Activities in the Duodenal Mucosa in Duodenal Ulcer Patients

The mucosal enzyme activities of 11 marker enzymes from the brush border, basolateral membrane, and lysosomes of 45 patients with an active duodenal ulcer (DU) were determined by analysis of homogenized biopsy specimens obtained from the duodenal bulb and descending duodenum at endoscopy. They were compared with activities measured in 22 controls. In the duodenal bulb lactase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.0005), and monoamine oxidase (p less than 0.0005) were significantly decreased in DU patients. In the descending duodenum all the brush border enzymes except sucrase were significantly decreased when compared with controls. DU patients with inflammation in the biopsy specimens from the duodenal bulb had decreased levels of lactase (p less than 0.05), sucrase (p less than 0.05), neutral-alpha-glucosidase (p less than 0.05), leucyl-beta-naphthylamidase (p less than 0.05), and acid phosphatases (p less than 0.05) when compared with DU patients with normal histology in this region. In the descending duodenum the activities of leucyl-beta-naphthylamidase (p less than 0.05) were decreased in patients with inflammation compared with those without such histologic changes. DU patients who had taken antacids before the investigation had decreased activities of lactase (p less than 0.05) in the descending duodenum when compared with those who had not taken antacids. Activities of lactase (p less than 0.005), sucrase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.05), and acid beta-glucuronidase (p less than 0.0005) in the descending duodenum were significantly lower in smokers than in non-smokers with active DU.

Flow Cytometric DNA Studies in Human Gastric Cancer and Polyps

Flow cytometric DNA studies were performed on cell suspensions of biopsy specimens from gastric tumors and neutral gastric mucosa in 18 patients with gastric cancer and 9 patients with gastric polyps. In cancer, aneuploidy was found in two tumors in the antral and five in the body part of the stomach (39%). The mean DNA index for aneuploid cancers was 1.57. In patients with aneuploid carcinomas three biopsy specimens from uninvolved mucosa also showed aneuploidy. In diploid carcinomas in the antral part of the stomach, the proliferative index (PI) was increased when compared with that of antral mucosa in controls (p less than 0.05). Increased PI was found in uninvolved mucosa in aneuploid carcinomas of the body part of the stomach when compared with that in diploid carcinomas (p less than 0.001). In uninvolved body mucosa in aneuploid carcinomas of the body part significantly reduced levels of acid-beta-glucuronidase (p less than 0.0001) were found when compared with diploid carcinomas. No polyps showed aneuploidy, and the PI in biopsy specimens from patients with gastric polyps did not differ from that in controls.

Enzyme Activities in the Gastric Mucosa in Duodenal Ulcer Patients

In a series of 45 consecutive duodenal ulcer patients (DU) the activities of 10 marker enzymes from the brush border, basolateral membrane, mitochondria, and lysosomes were determined by analysis of homogenized material taken with biopsy forceps through an endoscope from the antral and body part of the stomach. They were compared with the enzyme activities determined in controls with similar types of gastritis but without any evidence of peptic ulcer disease. All the DU patients had gastritis in the antral mucosa. In the body part, about 30% had gastritis. In the antral mucosa of DU patients the activities of the membrane and lysosomal enzymes were mostly increased when compared with the controls. In the gastric body mucosa of DU patients the activities of the lysosomal enzymes were mostly increased, whereas most of the membrane enzymes showed unchanged activities when compared with the corresponding controls. Monoamine oxidase activities were decreased or unaltered in both regions in these patients. The finding of enzymatic changes in the gastric mucosa of DU patients gives further support to an altered mucosal metabolism in these patients.

Enzymatic Activities in Jejunal Biopsy Specimens from Patients with the Stagnant-Loop Syndrome

The activity of the marker enzymes lactase, sucrase, neutral alpha-glucosidase, alkaline phosphatase, gamma-glutamyl transferase, leucyl-beta-naphthylamidase (brush border); 5-nucleotidase (basolateral membrane); and acid phosphatase and N-acetyl-beta-glucosaminidase (lysosomes) in jejunal biopsies from patients with the stagnant-loop syndrome and controls was studied. The activity of gamma-glutamyl transferase was increased in the patient group; the activity of the other enzymes did not differ significantly in patients and controls. The DNA to protein ratio was increased in the patient group. The results do not support the hypothesis of epithelial damage in the human stagnant-loop syndrome.

Enzyme Activities in Human Gastric Cancer and Polyps

Enzyme activities and the protein to DNA ratio in gastric biopsy specimens from patients with gastric cancer and polyps have been measured and compared with values from controls. In uninvolved mucosa in antral gastric cancer increased activities were found for several membrane and lysosomal enzymes, whereas the monoamine oxidase (MAO) activity was decreased (p less than 0.0005). In cancer tissue the MAO was also decreased (p less than 0.0003). In uninvolved mucosa in gastric cancer of the body, most membrane and lysosomal enzyme activities were increased. In the cancer tissue itself an increase in membrane enzyme activities was found for several enzymes, whereas the MAO activity was decreased (p less than 0.0001). Differences between activities in specimens from the gastric mucosa in patients with gastric polyps and those in controls were less pronounced than between gastric cancer and controls. A discriminant analysis, using the enzymes most sensitive to establish correct diagnosis, could identify normal gastric mucosa in 85-95%, atrophic gastritis in 56-63%, and uninvolved mucosa in gastric cancer in 66-78%.

Effect of Ranitidine on Gastric and Duodenal Mucosal Enzyme Activities in Duodenal Ulcer Patients

The activities of 11 marker enzymes from the gastric and duodenal mucosa were determined in 19 patients with active duodenal ulcer disease (DU) before therapy, after 4 weeks of therapy with ranitidine, 300 mg/day, and after another 4 weeks without treatment. The activities were measured in homogenized material obtained with forceps through an endoscope. The healing rate at 4 weeks was 68%. In the descending duodenum the activities of the membrane enzymes increased during the treatment period compared with pre-treatment activities. Although not as extensive as in the descending duodenum, an increase of membrane enzyme activities was also noted in the duodenal bulb during treatment. In the gastric mucosa only minor enzymic activity changes were seen. The altered enzyme activities in duodenum and stomach during treatment were independent of ulcer healing, smoking, antacids, and mucosal inflammation. Previously, significant differences in mucosal enzyme activities have been demonstrated between DU patients and controls. During ranitidine treatment the enzyme activities in the duodenal mucosa of the same DU patients tended to normalize, whereas they were mostly unchanged in the gastric mucosa. Four weeks after treatment the mucosal enzyme activities in the duodenum were as before treatment started, without occurrence of ulcer relapse. The altered enzymic activities of the duodenal mucosa in DU patients therefore seem to be largely independent of the presence of active ulcer.

Mucosal growth and enzyme activity during the early phase of adaptation after jejunal bypass in the rat.

Morphological variables and mucosal enzyme activities were measured in the bypassed and remaining parts of the small intestine 3, 7, and 14 days after a jejunal bypass operation. In the bypassed segment tissue mass, enzyme activity per unit intestinal length, and enzyme activity per unit DNA were gradually reduced. In sham-operated animals tissue mass increased, whereas enzyme activity per unit DNA was reduced. In the segment remaining in function, tissue mass increased, whereas enzyme activities decreased temporarily. In this part of the intestine, the changes were more or less parallel in bypassed and sham-operated animals. It may be concluded that the enzymatic changes are not correlated to the morphologic changes in the early phase of adaptation to intestinal bypass.

Effect of Perfusion of a Jejunal Blind Loop on Intestinal Thymidine Uptake in the Rat

The effect of perfusing a jejunal loop with saline or glucose solution on the thymidine uptake by the intestinal cells was studied in rats. Two weeks after the construction of the loop, it was perfused for 24 h with glucose or saline of either 280 or 450 mOsm/kg. A control group received no perfusion. The weight per unit length, the DNA concentration, and the DNA-specific activity of 3H-labeled thymidine was recorded in the duodenum, the loop, the remaining small intestine and the colon. The thymidine uptake in the perfused loop relative to the unperfused parts of the small intestine was higher in the groups that received glucose or hypertonic saline than in the groups that received isotonic saline and the control group. In the colon, the uptake relative to the uptake in the unperfused small-intestinal segments was reduced in all the perfused groups compared with the controls. The tissue DNA concentration and the weight per unit length of the intestinal segments were not changed by the perfusions. The results are discussed in relation to current hypotheses on the regulation of intestinal cell proliferation.