Autoimmune gastritis. A clinicopathologic study of 25 cases

The histopathological diagnosis of autoimmune gastritis (AG) in its early stages can be a diagnostic challenge. Even some advanced cases with complete atrophy of the corpus mucosa may be difficult to recognize. To establish the diagnosis of autoimmune gastritis, several histological features should be assessed and combined with immunostains for enterochromaffin cell-like (ECL) cells and G-cells. The main histological criteria include a mononuclear infiltrate within the lamina propria, foci of destruction of oxyntic glands, intestinal metaplasia (IM), pyloric metaplasia, and parietal cell pseudohypertrophy. These criteria were evaluated in our series of 25 patients with achlorhydria and/or megaloblastic anemia. Some of our patients presented with nonspecific gastrointestinal symptoms. The age ranged between 46 and 79 years; one male patient was only 31 years old. Histologically, the corpus mucosa displayed in all cases chronic inflammation with focal complete IM and advanced pyloric metaplasia. In 4 patients, oxyntic glands were destructed in some sites. There was a pancreatic metaplasia of acinar type in 2 patients and a minimal focal pseudohypertrophy of parietal cells in the 31-year-old man. A tubular adenoma with a low-grade dysplasia was found in one female patient. Immunohistochemically, chromogranin-A highlighted linear or nodular hyperplasia of ECL cells in 19 patients, and adenomatoid ECL hyperplasia in one case (80%). In the remaining cases hyperplasia of ECL cells could not be recognized from their normal count. In 13 cases (52%) a few ECL cells were seen also in IM. Regarding associated pathology, in one woman with nodular ECL cell hyperplasia, a gastric carcinoid was removed endoscopically. The reaction with gastrin antibody revealed in 11 cases (44%) a small number of G cells in IM in the corpus mucosa. In 18 patients, antral mucosa was examined as well. In 8 patients, the mucosa was normal; in 10 cases, a mild chronic inactive gastritis was diagnosed, and in 15 patients G-cell hyperplasia was found. In accordance with other studies, we show that the diagnosis of AG may be established microscopically in endoscopic specimens of the gastric body mucosa when histologic features and immunohistochemical detection of ECL and G cell hyperplasia are combined.     

Expression of glycoprotein hormone alpha-subunit by endocrine cells of the oxyntic mucosa is associated with hypergastrinemia

Previous studies have shown that hyperplastic endocrine cells of the oxyntic mucosa in patients with atrophic gastritis may express immunoreactivity for the alpha-subunit of human chorionic gonadotropin (alpha-HCG, common to all glycoprotein hormones). Since this endocrine proliferation is regarded as dependent on the trophic effect of the concomitant hypergastrinemia, the relation between immunohistochemical expression of alpha-HCG by oxyntic endocrine cells and serum levels of gastrin were investigated. The study was performed on endoscopic gastric biopsies of the oxyntic mucosa from 49 patients subdivided into the following groups: A) with histologically normal mucosa and normogastrinemia (22 cases), B) with atrophic gastritis and normogastrinemia (12 cases), C) with normal mucosa and hypergastrinemia (Zollinger-Ellison syndrome, retained antrum) (7 cases) and D) with atrophic gastritis and hypergastrinemia (with or without pernicious anemia) (8 cases). The alpha-HCG immunoreactive cells were found in all hypergastrinemic patients (groups C and D), regardless of the concomitant pathological condition of the mucosa. These cells accounted for 7.8% to 44.7% of the number of Grimelius argyrophil cells in consecutive serial sections. In contrast, alpha-HCG-containing cells were exceptional or absent in most normogastrinemic patients. Their number was sizable in only two cases of group A and three cases of group B, where it ranged from 2.5% to 14.8% of the number of argyrophil cells. It was concluded that expression of alpha-HCG is another feature of oxyntic endocrine cells associated with hypergastrinemia in addition to those previously recognized such as development of hyperplasia and/or carcinoid tumors.     

Gastrin has a specific proliferative effect on the rat enterochromaffin-like cell, but not on the parietal cell: a study by elutriation centrifugation

Gastrin has a general growth-promoting effect on gastric oxyntic mucosa, and a more pronounced one on the enterochromaffin-like (ECL) cell. Whether gastrin has a proliferative effect on the parietal cell lineage beyond the general effect is uncertain. Hypergastrinaemia was evoked in rats using pantoprazole (group II: 100 micromol kg-1, group III: 400 micromol kg-1) for 45 days. Plasma gastrin was 43 +/- 8 pmol L-1 (control), 283 +/- 54 pmol L-1 (group II) and 577 +/- 63 pmol L-1 (group III). Gastric mucosal cells were isolated and fractionated by elutriation centrifugation. Total cell number, percentage and number of ECL and parietal cells, and histamine were determined in each fraction. The number of mucosal cells increased 1.5-fold in both hypergastrinaemic groups. Enterochromaffin-like cell content was 2.6 +/- 0.5% (control), 6.0 +/- 0.6% (group II) and 9.0 +/- 0.8% (group III). Histamine concentration in oxyntic mucosal cells rose similarly. The size of the ECL cells was 8.5 +/- 0.1 microm (control), 10.8 +/- 0.2 microm (group II) and 12.1 +/- 0.2 microm (group III), and the increased size was confirmed by shifted distribution in elutriation fractions. Histamine per ECL cell increased with cell size. The number of parietal cells increased parallel to the total number of mucosal cells (1.5-fold). Parietal cell size and percentage, assessed by image analysis and distribution in elutriation fractions, were unchanged after pantoprazole dosing. Gastrin has a pronounced, concentration-dependent specific trophic effect on ECL cells and a general proliferative effect on gastric mucosa, including parietal cells.     

Development of gastric carcinoids inmastomys during histamine2-receptor blockade

We have investigated the effect of histamine₂-receptor blockade on gastric carcinoid formation inMastomys, a rodent prone to develop gastric carcinoids. During long-term treatment (8–24 weeks) with loxtidine, a 3–5 fold increase in plasma gastrin levels was observed. Oxyntic mucosal histamine and histidine decarboxylase activity were increased 2 times and 4–10 times respectively in loxitidine-treated animals, as compared to controls. An increase in oxyntic mucosal thickness was also noted in all treated animals, while gross tumors were only observed in animals treated for 24 weeks. Immunocytochemical analysis of treated animals revealed a marked proliferation of chromogranin-positive cells in the oxyntic mucosa. These cells were identified as ECL cells because they were labeled by histamine antibodies, but not by gastrin-, somatostatin-or serotonin-antibodies. Hyperplasia of endocrine cells was noted after 8 weeks of treatment, while dysplastic lesions were seen after 16 weeks and the first micro- or macrocarcinoids after 24 weeks of treatment. No tumors, or hyperplastic changes, were observed in control animals. The results demonstrate that histamine₂-receptor blockade significantly enhances the development of gastric carcinoids inMastomys and suggest that hypergastrinemia may be important for the development of these tumors.     

Endocrine cells and parietal cells in the stomach of the developing rat

Gastrin-immunoreactive cells were fairly numerous in the pancreas and upper duodenum of the rat at about the time of birth. A minor population of these cells stained with antibodies directed against the N-terminal region of gastrin-34 as well as with antibodies directed against the C-terminal region. The remainder of the cells stained with the C-terminally directed antibodies only. Within a fortnight after birth all gastrin-immunoreactive cells disappeared from the pancreas and were greatly reduced in number in the duodenum; those that remained were probably CCK cells. Gastrin cells were rare in the antrum at birth and remained rare during the first days after birth. They increased in number, slowly until after weaning (15-20 days of age) and then more rapidly, until 25-30 days of age when the gastrin cell density reached that in adult rats. At the time of birth the gastrin concentration in serum was low; the subsequent increase during the first 2 weeks paralleled the development of the antral gastrin cell system. Adult postprandial serum gastrin concentrations were reached 12 days after birth. Somatostatin cells were rare in both the antral and oxyntic mucosa at birth. They increased gradually in number until about a month after birth when the cell density reached that seen in adult rats. In the oxyntic mucosa the ECL and A-like cells are the predominant endocrine (argyrophil) cell types. They were not detected until about 4 days after birth. Their number increased slowly until about 30 days of age. They did not stain argyrophil until about 2-4 weeks after birth. Parietal cells were few at birth; ultrastructurally they appeared to be in an active state and histochemically they were shown to contain carbonic anhydrase. The pH of the gastric content of newborn rats was close to 5; 15-17 days after birth the pH was about 4 in freely fed rats. In fasted rats shortly after birth the pH was about 4. Two weeks later it was around 2, which is the pH measured in older rats. Hence, the full capacity for acid secretion is probably not established until weaning. Fasting greatly lowers the serum gastrin concentration and the histidine decarboxylase activity of the ECL cells in adult rats. Before weaning, fasting produced these effects only to a minor degree.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of portacaval shunt on the rat stomach

In portacaval-shunted rats, basal but not pentagastrin-stimulated acid secretion was higher than in sham-operated controls. The basal serum gastrin concentration was unchanged and the postprandial serum gastrin concentration lowered following portacaval shunt. Thus, gastrin is not responsible for the elevated basal acid secretion. The present study provides evidence that there is no trophic effect on the oxyntic mucosa as a whole and that there is no change in parietal cell-associated gastrin receptors after portacaval shunting. Interestingly, however, endocrine cells in the oxyntic mucosa (the histamine-containing ECL cells) proliferated greatly and the pentagastrin- and cholecystokinin octapeptide-induced activation of the histamine-forming enzyme, histidine decarboxylase, in these cells was much greater than in control rats. Analysis of the dose-response curves for the enzyme-activating effect of pentagastrin and cholecystokinin-octapeptide indicated that the D50 values for these two stimulants were not altered by shunting but that the maximal enzyme activation was greatly elevated. The enhanced enzyme activation can be partly, but not fully, explained by the fact that the ECL cells were increased in number. The enhanced response following portacaval shunt probably reflects also an increased number of gastrin receptors per ECL cell. The effect of portacaval shunting on gastric ECL cells can perhaps be explained by impaired degradation in the liver of intestinal substance(s) exerting a highly specific trophic effect on the ECL cells or, alternatively, causing an enrichment of gastrin receptors on these cells, thereby making them more sensitive to the trophic effect of gastrin. The ECL cell hyperplasia is manifest about 4 weeks after the shunting. A modified procedure for portacaval shunting which left the gastroduodenal vein (otherwise ligated) drained to the liver produced the same trophic effect as conventional portacaval shunt, suggesting an intestinal rather than gastroduodenal origin of the agent(s) responsible for the trophic action.     

Omeprazole: its influence on gastric acid secretion, gastrin and ECL cells

The H+,K+-ATPase inhibitor omeprazole is a highly effective gastric antisecretory agent, both in animals and man, with a long duration of action. These properties are shared by a number of recently described histamine H2-receptor antagonists. In life-long oncogenicity studies of these H2-receptor antagonists, as well as with the H+,K+-ATPase inhibitor omeprazole, gastric enterochromaffin-like cell (ECL cell) hyperplasia and carcinoids have been found. The purpose of this paper is to summarize available evidence for the "Gastrin Hypothesis" to explain the development of ECL-cell hyperplasia. The hypothesis may be outlined as follows: 1) Inhibition of gastric acid secretion leads to elevated antral pH and, secondarily, to release of gastrin from the antral gastrin cells into the blood stream. 2) Gastrin causes both general hypertrophy of the oxyntic mucosa and hyperplasia of the ECL cells in the oxyntic mucosa. That this sequence of events occurs not only with omeprazole but also with other effective gastric antisecretory agents has been verified in the rat by giving the H2-receptor antagonist ranitidine as a continuous infusion. Ranitidine caused a hypergastrinemia of a similar magnitude as that seen after omeprazole, provided that the acid secretion was inhibited to a similar degree. At similar gastrin levels, ECL-cell hyperplasia of the same magnitude developed during both ranitidine and omeprazole treatment. Antrectomy prevented the development of ECL-cell hyperplasia during omeprazole treatment, indicating that the hyperplasia was not due to the drug treatment per se, but rather to the hypergastrinemia. Both the hypergastrinemia and the ECL-cell hyperplasia were found to be reversible.(ABSTRACT TRUNCATED AT 250 WORDS)     

The regulation of gastric acid secretion – clinical perspectives

The purpose of this review, based upon 40 years of research, is to clear old controversies. The gastric juice is a strong acid with active enzymes (pepsin and lipase); ideal for killing swallowed microorganisms. Totally isolated rat stomach and histamine determination. Human gastric carcinomas were examined for ECL cell differentiation because tumours found in rodents after dosing with inhibitors of acid secretion were reclassified to be of ECL cell origin. The gastrin receptor is localized to the ECL cell only, where gastrin stimulates the function and growth. Drug‐induced hypo‐acidity induces hypergastrinaemia and ECL cell hyperplasia responsible for rebound acid hypersecretion. Every condition with long‐term hypergastrinaemia disposes to ECL cell neoplasia. In man, both atrophic gastritis and gastrinoma lead to ECL cell carcinoids. Proton pump inhibitors induce hypergastrinaemia with ECL cell hyperplasia and ECL cell carcinoids that disappear when stopping treatment. The gastrin antagonist netazepide induces regression of ECL cell carcinoids due to atrophic gastritis. Human gastric carcinomas of diffuse type, particularly the signet‐ring subtype, show ECL cell differentiation, suggesting involvement of gastrin in the carcinogenesis. Helicobacter pylori (Hp) causes gastritis and peptic ulcer, and when infecting the antrum only gives a slight hypergastrinaemia with acid hypersecretion predisposing to duodenal ulcer, but protecting from gastric cancer. When Hp infection spreads to oxyntic mucosa, it induces atrophy, reduced acid secretion and marked hypergastrinaemia and cancer.It is remarkable that the interaction between Hp and gastrin may explain the pathogenesis of most diseases in the upper gastrointestinal tract.     

胃内分泌细胞的超微结构及定量免疫组织化学研究

应用透射电镜、免疫组化及图像分析系统对9例正常人胃粘膜的内分泌细胞进行研究.结果显示:超微结构下胃泌酸区粘膜可见ECL细胞、EC细胞、X细胞、偶见D细胞;胃窦粘膜可见G细胞、D细胞、EC细胞、P细胞.应用CgA及9种激素抗体免疫组化BA法观察胃内分泌细胞及激素的分布,发现胃窦GAST阳性细胞约占胃窦内分泌细胞总数的75%,SS、5-HT、CT、BOM、ACTH阳性细胞在胃窦均可见到;胃体粘膜主要为5-HT、SS阳性细胞,CgA阳性细胞有相当数量在文内所用激素抗体染色中不显色,如ECL细胞.结果提示形态与功能检测相结合将有助于加深对胃内分泌细胞的认识.对胃内分泌细胞进行定量图像测量,为某些疾病的病理研究提供了定量对比参数.     

The origin of subdural neomembranes. I. Fine structure of the dura-arachnoid interface in man.

A patient with atrophic gastritis and excessively raised serum gastrin concentrations (4000 to 5000 pg/ml) was found to have multiple polypous tumors of the gastric corpus mucosa. Following gastrectomy, serum gastrin concentrations decreased to undetectable levels. The tumors consisted of a mixed population of endocrine cells. The majority of tumor cells were of the ECL type, but, in addition, enterochromaffin cells of various subtypes as well as agranular cells were found. The tumors were locally invasive and invaded the walls of submucosal blood vessels. The surrounding mucosa showed a severe atrophic gastritis with intestinalization and contained numerous goblet cells, enterochromaffin cells, and cholecystokinin cells. Cholecystokinin cells do not occur in the normal oxyntic mucosa. Hence, the observation of this cell type in intestinalized gastric epithelium suggests that "intestinalization also is associated with changes in endocrine cell populations. Gastrin has been shown to affect the function of the ECL cells. Indications for a trophic action of gastrin on these cells have been obtained. It is discussed whether greatly raised serum gastrin levels in patients with atrophic gastritis may be associated with increased risks for the development of certain types of gastric tumors.     

Gastrin has a specific proliferative effect on the rat enterochromaffin‐like cell,but not on the parietal cell: A study by elutriation centrifugation

Gastrin has a general growth‐promoting effect on gastric oxyntic mucosa, and a more pronounced one on the enterochromaffin‐like (ECL) cell. Whether gastrin has a proliferative effect on the parietal cell lineage beyond the general effect is uncertain. Hypergastrinaemia was evoked in rats using pantoprazole (group II: 100 μmol kg^–1, group III: 400 μmol kg^–1) for 45 days. Plasma gastrin was 43 ± 8 pmol L^–1 (control), 283 ± 54 pmol L^–1 (group II) and 577 ± 63 pmol L^–1 (group III). Gastric mucosal cells were isolated and fractionated by elutriation centrifugation. Total cell number, percentage and number of ECL and parietal cells, and histamine were determined in each fraction. The number of mucosal cells increased 1.5‐fold in both hypergastrinaemic groups. Enterochromaffin‐like cell content was 2.6 ± 0.5% (control), 6.0 ± 0.6% (group II) and 9.0 ± 0.8% (group III). Histamine concentration in oxyntic mucosal cells rose similarly. The size of the ECL cells was 8.5 ± 0.1 μm (control), 10.8 ± 0.2 μm (group II) and 12.1 ± 0.2 μm (group III), and the increased size was confirmed by shifted distribution in elutriation fractions. Histamine per ECL cell increased with cell size. The number of parietal cells increased parallel to the total number of mucosal cells (1.5‐fold). Parietal cell size and percentage, assessed by image analysis and distribution in elutriation fractions, were unchanged after pantoprazole dosing. Gastrin has a pronounced, concentration‐dependent specific trophic effect on ECL cells and a general proliferative effect on gastric mucosa, including parietal cells.     

Electron microscopic immunohistochemical investigation of chromogranin A in endocrine cells in human oxyntic gastric mucosa

Human oxyntic gastric mucosa harbours 6 types of endocrine cells: enterochromaffin-like (ECL) cells, enterochromaffin (EC) cells, somatostatin (D) cells, and cells with an unknown secretory product (P cells, D1 cells and X (A-like) cells). In the present study, intracellular localization and granular content of chromogranin A (CGA) in these cells have been investigated by electron microscopic immunohistochemistry. The content of CGA in granules of the various types of endocrine cells was evaluated and compared with the content of serotonin and somatostatin in EC cells and D cells, respectively. ECL cells, EC cells, P cells, D1 cells and X cells contained CGA in their granules, whereas D cells did not. CGA granular content in ECL cells, P cells, D1 cells and X cells was 3.39 +/- 0.17, 3.41 +/- 0.21, 3.58 +/- 0.18, and 3.55 +/- 0.09, respectively. In ECL cells, CGA was also found in a nongranular form. The CGA content in EC cells (2.95 +/- 0.21) was not significantly different from the serotonin content (2.82 +/- 0.11; p > 0.05) which is in line with the basic significance of CGA as potential amine storage and release protein. The somatostatin content in D cells was 3.30 +/- 0.15. Our study has established high content of CGA in granules of all types of endocrine cells in human oxyntic gastric mucosa except in D cells.     

Effects of antrectomy or porta-caval shunting on the histamine-storing endocrine-like cells in oxyntic mucosa of rat stomach. A fluorescence histochemical, electron microscopic and chemical study.

1. The argyrophil (enterochromaffin-like) cells in the oxyntic gland area of the rat stomach contain histamine, which can be demonstrated fluorescence microscopically after exposure to gaseous OPT. After administration of L-dopa (or L-5-hydroxytryptophan), these cells produce and temporarily store dopamine (or 5-hydroxytryptamine), demonstrable by its characteristic formaldehyde-induced fluorescence. Ultrastructurally, the enterochromaffin-like cells, which have the appearance of polypeptide hormone-secreting cells, comprise two main cell types, the most predominant one having vesicular type granules (EGL cells), the second most predominant one having smaller, uniformly electron dense granules (A-like cells). 2. Rats were subjected to the following surgical treatments: antrectomy; porta-caval shunting; antrectomy+porta-caval shunting; or sham-operation. Three to eight weeks after surgery the histamine-storing cells (enterochromaffin-like cells) of the oxyntic mucosa were analysed by fluorescence histochemistry, light and (quantitative) electron microscopy, and fluorometric determination of amines. 3. After antrectomy, fluorescence histochemistry and silver staining revealed a reduced number of enterochromaffin-like cells. The histamine content in the oxyntic mucosa was reduced by about 50%. As in unoperated injection of pentagastrin seemed to mobilize histamine. Feeding or injection of insulin failed to do so in antrectomized as opposed to control rats. Ultrastructurally, the cytoplasmic granules of both endocrine-like cell types were less numerous than in the unoperated rats. The reduction in cell number and granularity was particularly conspicuous with regard to the EGL cells. 4. After porta-caval shunting the number of enterochromaffin-like cells increased markedly. Chemical determination revealed a twofold increase in the histamine concentration of the oxyntic mucosa. Feeding or injection of insulin or pentagastrin lowered the histamine concentration. As judged by electron microscopy, the proliferation of endocrine-like cells induced by porta-caval shunting was restricted to the ECL cell type. Besides occurring in greater number, these cells were larger than those in unoperated controls, and their cytoplasm was densely packed with granules that were increased in size. 5. Following antrectomy of the porta-caval shunted rats the number of enterochromaffin-like cells and the oxyntic histamine concentration was reduced. 6. The results support the idea that gastrin exerts trophic as well as excitatory effects on oxyntic endocrine-like cells.     

Rapid induction of enterochromaffinlike cell tumors by histamine2-receptor blockade.

The effect of acid inhibition on gastric endocrine cells was investigated in Praomys (Mastomys) natalensis. Long-term treatment (1 to 32 weeks) with an irreversible histamine 2-receptor blocker (loxtidine) caused a sustained increase in plasma gastrin levels, which was accompanied by a gradual increase in histamine and histidine decarboxylase activity of the gastric oxyntic mucosa. The density of endocrine cells in the oxyntic mucosa increased gradually, doubled by 8 weeks, and was three times that of controls after 24 weeks of treatment. Hyperplastic changes in the endocrine cell population were evident after 2 to 8 weeks in all animals, whereas dysplastic or neoplastic lesions were observed in half the animals after 16, 24, and 32 weeks of treatment. Gross tumors in the oxyntic mucosa were observed in 1/4 of the animals treated for 24 or 32 weeks. Proliferating cells were identified as enterochromaffinlike cells because they were argyrophilic and immunopositive for chromogranin A and histamine. The results demonstrate that histamine 2-receptor blockade initiated by loxtidine promotes a rapid development of enterochromaffinlike cell tumors in Mastomys and suggest a critical role for gastrin in the formation of these tumors. However, the rate and frequency by which carcinoid tumors appeared in Mastomys after acid inhibition was much greater than that reported in other species, indicating that several factors, including hormonal and genetic factors, are important in the development of gastric endocrine tumors.     

Comparison of the ECL-cell frequency in the stomachs of 3 different rat strains.

Three different rat strains, Sprague-Dawley, Wistar and Fischer 344, were treated for 3 months with 2 doses (0.8; 4 mg/kg) of the gastric acid suppressing ATPase inhibitor pantoprazole. The gastrin levels were determined, the height of the mucosa measured and the number of enterochromaffin-like (ECL) cells counted. Because these cells were stained according to the method of Grimelius they were designated as GPC (Grimelius positive cells). Under 4 mg/kg, the gastrin levels were increased 8 hours after administration, but fell again after 24 h. The Fischer rats showed the highest value. Also the height of the mucosa was increased under 4 mg/kg. A trend towards an increased mucosal height was noticeable even at 0.8 mg/kg. The number of GPC was determined in 2 ways: 1) without taking the mucosal height into account, 2) taking the height into account. An increase in GPC was observed at 4 mg/kg with both methods.     

Ultrastructural characterization of fundic endocrine cell hyperplasia associated with atrophic gastritis and hypergastrinaemia

Summary Clinical and experimental evidence indicates that carcinoid tumours of the stomach fundic mucosa represent another example of hormone-dependent neoplasm, gastrin being the hormone involved in tumour induction. In this context hyperplasia of fundic endocrine cells associated with chronic atrophic gastritis (CAG) and hypergastrinaemia is regarded as the most frequent preneoplastic lesion. However, the cell type involved in this hyperplasia has not been clarified. To elucidate this problem fundic endocrine cells were characterized ultrastructurally in 9 patients from which endoscopic gastric biopsies were obtained. ECL cells were the most frequent cell type in 8 cases, in 4 of which they were more numerous than all other cell types taken together. D₁ cells were the most frequent type in one case while they were inconspicuous in the other cases. P cells were found with a frequency in each case intermediate between that of ECL cells and that of D₁ cells. These results indicate that fundic endocrine cell hyperplasia occurring in hypergastrinaemic CAG is in most cases cytologically similar to that found in other hypergastrinemic conditions, in which the gastrin-dependent ECL cells were already found to prevail. They also explain why fundic carcinoids arising in CAG are mostly composed of ECL cells. The relation between ECL, D₁ and P cells, if any, remains obscure.Abbreviations EC enterochromaffin cells, producing 5-hydroxytryptamine - ECL enterochromaffin-like cells - D somatostatin producing cells - D₁ cells with small granules showing some characteristics of granules of D cells - P cells with small granules similar to those of pulmonary (P) endocrine cells - X gastric endocrine cells with large, dense granules. Unless specified, the secretory product of these cells is unknown Supported by grants from the Italian Ministry of Public Education and from the A.I.R.C. (Associazione Italiana per la Ricerca sul Cancro)     

新生小鼠胃内组胺免疫反应细胞的形态及分布

目的：观察出生后小鼠胃内组胺免疫反应细胞的个体发生、分布、形态及数量变化。方法：免疫组织化学技术。结果：小鼠出生后第5天,胃体部粘膜上皮中出现组胺阳性细胞,此后随着胃体部粘膜的发育,组胺阳性细胞数量明显增多,密集分布于胃体部粘膜下1/3处的上皮内。胃粘膜下层中也可见少量组胺弱阳性细胞。上皮内的组胺阳性细胞多为闭合型,胞体较小,常聚集、环抱壁细胞。结论：小鼠胃体部粘膜中组胺阳性细胞出现的时间较G细胞、D细胞、EC细胞晚,随着小鼠的生长发育,其数量呈显著性增加。位于胃粘膜下1/3处上二皮内的组胺阳性细胞可能为肠嗜铬样细胞（ECL细胞）,ECL细胞释放的组胺,有可能通过旁分泌的方式作用于壁细胞。     

Autoimmune gastritis: distinct histological and immunohistochemical findings before complete loss of oxyntic glands.

Autoimmune gastritis (AG) can be easily recognized when the histological features are fully developed, but recognizing AG before the complete loss of the oxyntic mucosa is more challenging. One feature of fully developed AG is enterochromaffin cell-like (ECL) hyperplasia, but its presence or absence in earlier stages of AG has not been fully evaluated. A retrospective study of biopsy specimens from 40 patients was performed; all of the patients were originally diagnosed with possible AG based on the presence of lymphocytic infiltration and damage to oxyntic glands and/or the presence of metaplastic epithelium that disproportionately involved the body mucosa. Nineteen cases had follow-up serological studies for anti-parietal cells and/or anti-intrinsic factor antibodies: 13 were positive and 6 negative. The remaining 21 cases were indeterminate because of incomplete testing. The histological findings were similar in the patients who were serologically positive and those who were indeterminate for AG. In all of these cases, the oxyntic mucosa showed lymphoplasmacytic infiltrates within the lamina propria with focal gland infiltration and damage. Sixty-five percent (22/34) of the cases showed intestinal and/or pyloric metaplasia, and 85% (29/34) showed parietal cell pseudohypertrophy. Chromogranin stains were performed in 11 of 13 cases with positive serological markers for AG, and all showed at least linear ECL cell hyperplasia. In contrast, none of the six cases with negative serological studies had linear ECL cell hyperplasia, P <.001. In conclusion, the following constellation of findings supports a diagnosis of AG before the complete loss of oxyntic mucosa: deep or diffuse lymphoplasmacytic infiltrates within the lamina propria with foci of gland infiltration and damage, epithelial metaplasia, parietal cell pseudohypertrophy, and ECL cell hyperplasia at the linear or greater level.     

Histamine storage and formation in canine gastric mucosa--effect of pentagastrin stimulation

Histamine storage and formation in the dog gastric mucosa were studied during basal conditions and after pentagastrin stimulation. Histamine formation (histidine decarboxylase activity), histamine content as well as the density of mast cells of the oxyntic gland mucosa were evenly distributed. Histamine content of the mucosa was significantly correlated to the density of mucosal mast cells. In the basal secretory state, histamine formation and histamine content of the oxyntic gland mucosa were of the same magnitude as in the antral mucosa. Pentagastrin stimulation induced a small but significant decrease in histamine content of the oxyntic gland mucosa and a subsequent acceleration in the rate of amine formation. Neither histamine content nor histidine decarboxylase activity of the antral mucosa was affected by pentagastrin infusion.     

Histamine storage and formation in canine gastric mucosa - effect of pentagastrin stimulation

Histamine storage and formation in the dog gastric mucosa were studied during basal conditions and after pentagastrin stimulation. Histamine formation (histidine decarboxylase activity), histamine content as well as the density of mast cells of the oxyntic gland mucosa were evenly distributed. Histamine content of the mucosa was significantly correlated to the density of mucosal mast cells. In the basal secretory state, histamine formation and histamine content of the oxyntic gland mucosa were of the same magnitude as in the antral mucosa. Pentagastrin stimulation induced a small but significant decrease in histamine content of the oxyntic gland mucosa and a subsequent acceleration in the rate of amine formation. Neither histamine content nor histidine decarboxylase activity of the antral mucosa was affected by pentagastrin infusion.