Hideto Inokuchi

Tritiated thymidine radioautographic study on the origin and renewal of secretin cells in the rat duodenum

The origin and renewal of secretin cells in the duodenum were investigated using the unlabeled antibody peroxidase-antiperoxidase technique and radioautography in rats killed at various times after single or multiple injections of [3H]thymidine. Secretin cells were spatially distributed from the upper crypt to the villus tip, being particularly numerous in the upper two-thirds of the duodenal villi. After a single injection of [3H]thymidine, there were no labeled secretin cells, indicating a lack of self-replicating activity. After repeated injections of the isotope, labeled secretin cells appeared and increased in number. They first occurred at the upper part of the crypt and the lower part of the villus, and later at the villus tip. All these cells were found to be labeled after continuous labeling for 120 h, which is considered to be the renewal time for this cell population.

Pancreatic arteriovenous malformation with pancreatitis involving a pancreatico-venous fistula.

SummaryAn arteriovenous malformation of the pancreas is a very rare disease, but its presentation is distinct and unique. In this report, we describe a patient who presented with this malformation which was localized in the tail of pancreas and demonstrated by abnormal angiography findings. The patient was a 60-year-old male with severe left hypochondralgia. Angiography revealed an increased blood volume in the tail of the pancreas with arteriovenous shunting. Secondary pancreatitis caused by the arteriovenous malformation was suspected by abnormal laboratory data, and confirmed by histology from the resected tail of the pancreas. This is a very rare report in which pancreatic arteriovenous malformation involving a pancreaticovenous fistula was confirmed by endoscopic retrograde cholangiopancreatography (ERCP).

Immunohistochemical study on the morphology of enterochromaffin cells in the human fundic mucosa

SummaryThe morphology of enterochromaffin (EC) cells in the human fundic mucosa was investigated at the lightmicroscopic level by means of the unlabeled peroxidase anti-peroxidase method, with the use of a highly specific anti-serotonin serum.EC-cells in the human fundic mucosa were sparsely distributed below the neck portion of the gland, but were found to be rather numerous in its lower half. Immunohistochemistry revealed marked pleomorphic and seemingly polynuclear EC-cells or cells with long, sometimes multipolar cytoplasmic processes. In addition, luminal contacts and contiguity between EC-cells, or interglandular connections were also encountered.The present immunohistochemical procedure permits, for the first time, a clear-cut morphological visualization of the entire population of EC-cells, and reveals the distinctive morphological features of these cells in the human fundic mucosa. These morphological findings imply that EC-cells in the fundic mucosa may be crucial in gastric function.

Serotonin immunohistochemistry reveals immature EC cells

SummaryRadioautographic studies of rat duodenal mucosa were carried out after single injections of 3H-thymidine, and the labelling indices of enterochromaffin (EC) cells identified by serotonin immunohistochemistry and by the diazo reaction were compared. The labelling index of EC cells by serotonin immunohistochemistry was 2.3% (mean percentage of 2 rats), while no labelled cells were found in diazo-positive EC cells. This finding indicates that serotonin immunohistochemistry reveals a less mature population of EC cells than conventional techniques such as the diazo reaction.

G-Cell population and serum gastrin response to cimetidine-oxo test meal in relation to histopathological alterations in resected stomachs from patients with peptic ulcer disease

SummaryThe relationship between histopathological alterations and G-cell population in the stomach was studied in 14 resected stomachs from patients with chronic peptic ulcer disease (6 with duodenal ulcer and 8 with gastric ulcer). G-cells were identified by indirect immunoperoxidase method. When atrophy was graded three steps (0, 1, 2), the average grade of DU and GU was 0.23 and 0.89, respectively. There was a significant correlation (r=-0.871, p<0.005) between atrophic grade and G-cell population in each stomach. The mean occupation rate with intestinal metaplasia was 0.9% in DU and 35.8% in GU. There was no correlation between total pyloric area and G-cell population, however residual pyloric area excluding intestinal metaplasia correlated significantly with G-cell population (r=0.557, p<0.05). There was a significant difference in the mean G-cell population which were 26.5 millions in DU and 8.9 millions in GU. The mean integrated gastrin response to Cimetidine-OXO test meal were 559±236 pg/ml in DU and 216±124 pg/ml in GU, and there was significant correlation (r=0.889, p<0.005) between G-cell population and integrated gastrin response. The average age of both groups, however, was 27.7 in DU and 52.8 in GU, so that these differences of G-cell population and functional G-cell mass in both groups might originate in the histopathological alterations accompanying with the aging.

Economic evaluation of Helicobacter pylori eradication for the treatment of duodenal ulcer disease in Japan: A decision analysis to assess eradication strategy in comparison with a conventional strategy

To evaluate the socio‐economic effects of Helicobacter pylori eradication in the treatment of duodenal ulcer disease in Japan, a clinical decision analysis was performed to assess H. pylori eradication therapy compared with the conventional strategy of maintenance with histamine‐2 receptor antagonists. A decision tree‐based state transition model (Markov chain approach) implemented to simulate a 5 year period of follow up was constructed. The H. pylori eradication strategy was found to be superior to the conventional maintenance strategy with regard to clinical effectiveness and other dimensions of a patient’s outcome. Furthermore, in a long‐term perspective, the eradication strategy was less costly than the maintenance strategy. Helicobacter pylori eradication should be recommended as the first choice treatment of H. pylori‐positive duodenal ulcer patients. The clinical implication of H. pylori eradication entails an improvement in clinical effectiveness and other dimensions of a patient’s outcome and a significant reduction in the costs of duodenal ulcer treatment. The long‐term total costs do not depend on the initial drug cost of an eradication regimen. Pursuing a high eradication rate of H. pylori is essential in improving the patient’s outcome and the cost‐effectiveness of treatment.

Intra‐operative secretin test for the rapid evaluation of curative operation in a case of Zollinger‐Ellison syndrome

The intra‐operative measurements of serum gastrin levels and an intra‐operative secretin test were carried out as the rapid evaluation of curative operation in a case of Zollinger‐Ellison syndrome (ZES). In this case, pre‐operative investigations suggested that the tumours were located in the head of the pancreas and the duodenal wall. The surgeon planned a pan‐creato‐duodenectomy. Serum gastrin levels were reduced after the resection of the head of the pancreas and duodenum, and the secretin test after resection was negative. The surgeon ensured that gastrinomas were resected completely during the operation. The secretin test carried out 1 month post operatively was also negative. The patient has experienced no further complications, to date. This case suggests that intra‐operative secretin test is useful for the rapid evaluation of curative operation in case of ZES.

Neural and paracrine regulation of gastrin release using rat antral mucosa in tissue culture The effect of carbachol, bombesin, and anti-somatostatin antibody on gastrin release

SummaryGastrin release was significantly stimulated by the cholinergic agent carbachol at doses of 10-4 M, 10-5 M, and 10-6 M. Peak stimulation was observed at 10-5 M. Gastrin release was also significantly stimulated by bombesin at a dose of 10-8 M, and 10-6 M atropine which abolished the effect of carbachol in stimulating gastrin release had no effect on the bombesin-stimulated gastrin release. In addition, antisomatostatin antiserum significantly stimulated gastrin release. These findings suggest that gastrin release is regulated by cholinergic and noncholinergic neurons the latter being thought to be a bombesin-containing neuron, and that antral somatostatin exerts a continuous restraint on gastrin release by the paracrine mechanism.

Regulatory mechanism of bombesin on gastrin release

Bombesin has been demonstrated to stimulate gastrin release by an atropine‐resistant mechanism. In the present study, the effects of truncal vagotomy and chemical sympathectomy on the gastrin release by exogenous and endogenous bombesin using rat antral mucosa in tissue culture were studied. Exogenous bombesin 10‐8 mol/l significantly stimulated gastrin release. The stimulation of gastrin release by bombesin was abolished by truncal vagotomy, but not altered by chemical sympathectomy. Bombesin antiserum inhibited gastrin release by blocking the effect of endogenous bombesin. The inhibition of gastrin release by bombesin antiserum was abolished by truncal vagotomy, but not altered by chemical sympathectomy. In addition, the concentrations of bombesin‐like immunoreactivity in antral mucosa were not altered by truncal vagotomy. These results suggest that the mechanism of gastrin release by bombesin is influenced by non‐cholinergic local nerves under vagal control.

Occurrence and neonatal development of N-terminal (1-15) immunoreactivity of big gastrin in the rat antrum.

SummaryG34N (1–15) immunoreactive cells and C-terminal tetrapeptide immunoreactive cells in the antrum of rats of various ages were studied immunocytochemically in both naturally weaned and non-weaned conditions.Some of the C-terminal immunoreactive cells were found to lack G34N (1–15) immunoreactivity while the remainder showed both types of immunoreactivity.G34N (l–15)/C-terminal immunoreactive cell rates increased with age and reached adult values at 3 weeks after birth. The rates in a non-weaned condition were, however, significantly lower than those in a naturally weaned rats.These findings suggest that the development of G34N (1–15) immunoreactivity in rat antral gastrin cells is closely related to maturation of the gastrin cells, and weaning may enhance the maturation process.