Norio Tani

The effect of omeprazole on ultrastructural changes in gastric parietal cells

SummaryThis study was designed to compare the effects of omeprazole and cimetidine on ultrastructural changes in parietal cells of guinea pigs during histamine stimulation. Both omeprazole and cimetidine remarkably inhibited acid secretion induced by histamine stimulation. Omeprazole, however, failed to prevent the morphological transition of parietal cells to an active stage during histamine stimulation, in contrast to cimetidine which inhibited the morphological transition. In addition, it was noticed that administration of omeprazole caused vacuolation in approximately 27% of all parietal cells. This phenomenon was not seen in control animals with histamine stimulation alone and only very rarely in cimetidine treated animals. Ultrastructural findings suggested that vacuoles originated in secretory canaliculi of parietal cells. These results may be the key to explain the difference of the inhibitory mechanism between omeprazole which acts on the final step of the intracellular process (so-called proton pump) and cimetidine which acts on the H2-receptor site of plasma membrane.

Immunohistochemical localization of calcitonin gene-related peptide in the human gastric mucosa

Background/Aim: There have been only a few studies on the distribution of calcitonin gene-related peptide (CGRP) in the human stomach, in which it was stated that CGRP fibers are rare in that organ. The aim of the present study was to investigate the immunohistochemical localization of CGRP in the human gastric mucosa obtained by endoscopic biopsy from patients with gastric ulcers. Methods: Immunohistochemistry was carried out according to the indirect immunoperoxidase method using an anti-human CGRP antibody. Biopsies were taken from the ulcer margin in 18 patients (age 37–78, average 57.4 years) and from two endoscopically normal portions (antrum and body) in 7 other patients (age 36–65, average 51.0 years). One biopsy specimen was obtained from each portion. Results: Twelve of the eighteen biopsy specimens from the ulcer margin, 6 of the 7 biopsy specimens from normal portions of the antrum and 3 of the 7 biopsy specimens from normal portions of the body showed CGRP-immunoreactive staining. Intense staining was more marked in the specimens from the ulcer margin compared to those of the normal portions. Conclusions: CGRP immunoreactivity was observed in the human gastric mucosa in considerable abundance, and it is presumed that CGRP might participate in a restoration mechanism of the ulcer.

Gastric emptying in normal subjects and patients with peptic ulcer

SummaryGastric emptying in patients with peptic ulcer and normal subjects was studied using the acetaminophen method. The subjects consisted of 15 normal subjects, 52 gastric ulcer patients and 65 duodenal ulcer patients, who were studied in active stage of the ulcer. As an indicator of gastric emptying rate, the plasma acetaminophen concentration was measured by dye method (diphenylhydrazyl), as meg/ml, at 45 minutes after ingestion of a high calory pasty test meal (200 ml) with 1.5gr of acetaminophen.In normal subjects, the plasma acetaminophen concentration was 9.4±3.6mcg/ml. In gastric ulcer patients, the concentration was 7.4±3.2mcg/ml, which showed significantly delayed gastric emptying (P< 0.05). In duodenal ulcer patients, the concentration was 11.6±3.3mcg/ml, which suggested significantly rapid gastric emptying (P< 0.05).In consideration of gastric acid secretion, gastric ulcer cases with lower acid secretion have more delayed gastric emptying. In duodenal ulcer cases with hypersecretion, gastric emptying is more rapid than normoand/or hyposecretory cases (P< 0.005).The delayed gastric emptying may play a role in etiology of gastric ulcer. On the other hand, the rapid gastric emptying with gastric acid hypersecretion may be important in the pathogenesis of duodenal ulcer.

Lesions of the upper gastrointestinal tract in patients with chronic renal failure

SummaryEndoscopy of the upper gastrointestinal tract was performed on 84 patients with end-stage chronic renal failure undergoing hemodialysis. Gastric acid secretion and fasting plasma gastrin levels were also examined in these patients.Hemorrhagic gastritis was most frequently observed (23 cases) followed by erosive gastritis (18 cases). No patients had gastric ulcers. Duodenal ulcers were observed in only two patients. Gastrointestinal bleeding was observed in 15 cases (17.9%). Thirteen of these 15 cases had hemorrhagic gastritis, one of which had a duodenal ulcer as a complication.Fasting plasma gastrin levels (359.6 ± 336.5 pg/ml) were significantly higher than those of normal subjects (35.2 ± 37.1 pg/ml), but no acceleration in gastric acid secretion was observed either in the basal condition (BAO 0.8± 0.7 mEq/h) or following tetragastrin stimulation (MAO 9.0 ± 6.9 mEq/h).Our results were inconsistent with the previous reports that high frequencies of peptic ulcers and increased gastric acid secretion were observed in patients with chronic renal failure.Our data suggest that the defensive factors rather than the aggressive factors of the gastroduodenal mucosa may be involved in chronic renal failure.

GASTRIC METAPLASIA IN DUODENAL ULCER. Histochemical Considerations of Its Pathophysiological Significance

Gastric metaplasia of the duodenal mucosa in biopsy specimens of healed duodenal ulcer and in surgical specimens of perforated duodenal ulcer was investigated using mucin histochemistry and the indirect immunoperoxidase method. Endoscopic methylene blue test was performed prior to biopsy. All specimens from areas showing no dye absorption revealed varying degrees of gastric metaplasia characterized by heterotopic occurrence of gastric‐type foveolar cells mainly at the tips of stunted intestinal villi. On average, 31.8% of the total surface length of duodenal mucosa taken from areas showing no dye absorption was occupied by the metaplastic cells. They showed strong reactivities for periodic acid‐Schiff (PAS) and galactose oxidase‐Schiff sequences, while alcian blue and paradoxical concanavalin A staining, class III, were negative. Immunoperoxidase‐PAS double staining revealed a few gastrin and somatostatin cells in foci of gastric metaplasia, but almost no cells containing motilin, secretin, cholecystokinin and gastric inhibitory peptide. Such endocrine cells were scattered in nonmetaplastic mucosa. While such metaplastic change has been regarded as a self‐defence mechanism or adaptation of the duodenal mucosa against acid, a local decrease of normal endocrine cells, which allegedly function as acid receptors, may lead to alterations of gastroduodenal interaction. It is suggested that gastric metaplasia is important as one of the pathophysiological mechanisms involved in the recurrence of duodenal ulcer. ACTA PATHOL JPN 38 : 1011 ∼ 1018, 1988.

SOLITARY GASTRIC POLYPS IN THE FUNDIC GLAND AREA A Histochemical Study

Six solitary gastric polyps in the acid‐secreting fundic mucosa were histo‐chemically investigated using the mucin histochemistry, immunoperoxidase method, and silver methods for endocrine cells. Histologically, the polyps were grouped into three types : they largely consisted of either hyperplastic foveolar cells (group 1), normal‐appearing fundic gland cells with mild cystic changes (group 2) or hyperplastic fundic gland cells with cystic dilatation (group 3). The presence of parietal cells and mucous neck cells was confirmed in all polyps by the immunoperoxidase method using parietal cell autoantibody and the paradoxical Concanavalin A staining, respectively. Regarding the endocrine component, somatostatin‐containing cells, Grimelius‐positive argyrophil cells, and Fontana‐Masson‐positive enterochromaffin cells were scattered in the fundic gland area of the polyps as well as in the surrounding normal‐appearing fundic mucosa. Gastrin‐containing cells were absent. In one of the group 2 polyps and both group 3 polyps, a varying number of glicentin‐containing cells were found among the fundic gland components : In one polyp in group 3, glucagon immunoreactivity was detected in the glicentin‐containing cells. These findings suggest that some of the polyps express characteristics of the fetal fundic mucosa, since glicentin and glucagon immunoreactivities in normal human stomach have been detected exclusively in the fetal fundus. ACTA PATHOL. JPN. 35: 831–840, 1985.

Study on the Phenomenon of Locational Variation in the Speed of Discoloration During the Endoscopic Congo Red Test The Second Report: Ultrastructural Studies on Parietal Cell Populations

Both quantitative and morphological studies of parietal cells were done in order to investigate the cause of the phenomenon of locational variation in the speed of discoloration during the endoscopic Congo red test. The endoscopic Congo red test was performed in twelve patients with a peptic ulcer and/ or chronic gastritis. In each case, at the times when spotty discoloration was observed, five biopsy specimens were obtained from both the quickly discolored portion (already discolored portion) –Q and the slowly discolored portion (not yet discolored portion) –S of the greater curvature of the middle body at the same time and were separated into two groups (the Q‐group and the S–group). Quantitative studies of the parietal cells were performed using the cell isolation method described in our first report. A morphological study was performed with an electron microscope. Two specimens were fixed in glutaraldehyde and osmium tetroxide, and finally embedded in Epon resin. Ultra‐thin secretions contrasted with uranyl acetate and lead citrate were viewed with a JEOL‐1200EX electron microscope. Each parietal cell was classified according to the classification of ultrastructual stages put forward by Black et al. The number of parietal cells per milligram wet weight of the quickly discolored portion was significantly larger than that of the slowly discolored portion similar to the results of our first report. However the ultrastructural aspects of the parietal cells were not found to be different between the Q–group and S–group portion. It is concluded that the locational variation of the speed of discoloration during the endoscopic Congo red test may be due to the unequal distribution of parietal cells and that the sensitivity and responsiveness of parietal cells to the stimulation may be almost the same in all of the acid secreting area.

Studies on the Phenomenon of Locational Variation in the Speed of Discoloration During the Endoscopic Congo Red Test. The First Report: Quantitative Study of Parietal Cell Populations by Cell Isolation Method

A quantitative study of parietal cell populations was done using the cell isolation method designed by the authors in order to investigate the cause of the phenomenon of locational variation in the speed of discoloration during the endoscopic Congo red test. The endoscopic Congo red test was performed in three mongrel dogs and five patients with peptic ulcers. In each case, at the time when spotty discoloration was observed, three biopsy specimens were obtained from both the quickly discolored portion (Q) and the slowly discolored portion (S) of the greater curvature of the middle body. After determination of wet weight, the biopsy specimens, having been separated into two groups (the Q‐group and the S‐group), were digested simultaneously with collagenase and dispose in the same way in each case. The number of parietal cells per microlitre in the obtained cell suspensions were counted using Neubauers hemocytometer, staining with tetranitroblue tetrazolium. The number of parietal cells per milligram tissue wet weight was calculated for each sample from both groups. The number of parietal cells per milligram wet weight of the quickly discolored portion was 2.0 times (on average) as large as that of the slowly discolored portion in the case of the dogs. In the case of patients, the former was 1.7 times (on average) as large as the latter, with a statistically significant difference. We concluded that the locational variation of the speed of discoloration during the endoscopic Congo red test may be mainly due to the unequal distribution of parietal cells.