Epitheliocytes of fundal glands and the relative volume of the parietal microflora of the stomach and small intestine mucosa in experimental chronic duodenal ulcer

The effect of experimental chronic duodenal ulcers and vagotomy on fundal gland epitheliocytes and membrane microflora has been studied in rats using light microscopy and stereometry on semithin sections. It is shown that in ulcers the relative amount of perietal and zymogen cells increases, while the volume of mucocytes decreases. Vagotomy leads to a decrease in the relative amount of parietal and zymogen cells and increases the relative amount of mucocytes. The relative volume of membrane microflora in gastric fundal and pyloroantral regions, duodenum and jejunum diminishes in ulcers and increases in vagotomy, as compared to the control.     

Prostaglandin E2 output by isolated rat gastric parietal cells and non-parietal epithelial cells

Prostaglandins have acid antisecretory and cytoprotective effects in gastric mucosa when given exogenously. This study's purpose was to isolate preparations of parietal and non-parietal cells from rat stomachs and to compare prostaglandin output by these cells. Gastric epithelial cells were isolated from rat stomachs using pronase. Cells from different incubation times were collected separately and enriched by discontinuous Percoll gradient. Cell types were identified by hematoxylin and eosin stain, succinic dehydrogenase activity (parietal cells), periodic acid Schiff staining (mucous cells), Bowie staining (chief cells) and electron microscopy. Prostaglandin E2 activity was measured by radio-immunoassay. Parietal cells were purified to over 90% while the non-parietal preparation contained 67% chief cells and over 31% mucous cells. By electron-microscopy, cell integrity was seen to be maintained. The parietal cell enriched fraction contained two and one-half times the amount of prostaglandin E2 that the non-parietal chief cell enriched fraction did, p less than 0.01. These results raise the question as to whether output of PGE2 by parietal cells could play a role in modulating gastric acid secretion directly by parietal cells as well as in protecting the deeper layers of gastric mucosa against damaging agents in-vivo.     

Genetic and evolutionary implications in peptic ulcer disease

The evidence for a genetic component in peptic ulcer disease has been based on twin, family, and blood group studies. A polygenic model for the inheritance of peptic ulcers has been displaced by a genetic heterogeneity model based on several lines of evidence, some of the most powerful being recent work using subclinical markers. One marker in particular, an elevated level of serum pepsinogen I (PG I), a pepsin precursor produced by the gastric mucosa, secreted into the stomach lumen and also appearing in the bloodstream, has been found to be associated with a subgroup of duodenal ulcer patients. Segregation analysis of elevated serum PG I in duodenal ulcer sibships demonstrates familial aggregation consistent with autosomal dominant inheritance. Elevated PG I is also accompanied by gastric hyperacidity and presumably indicates those individuals with an increased mass of chief and parietal cells, and thus an increased capacity for peptic activity, an important element in the pathogenesis of ulcer disease. An evolutionary hypothesis based on selection for peptic activity and acidity is offered to explain several of the epidemiologic and genetic elements of this group of chronic diseases.     

Morphological research on the effect of vagotomy on the parietal microflora of the stomach and duodenum

The effect of vagotomy on parietal microflora was studied in intact rats and rats with chronic experimental gastric ulcer using stereometry, as well as light, transmission and scanning electron microscopy. Vagotomy was found to increase the relative amount of parietal microflora on day 30 following denervation, especially in the duodenum and pylorus. Chronic gastric ulcers are also associated with a rise in the relative amount of parietal microflora.     

Glycoconjugate distribution in the human fundic mucosa revealed by lectin- and glycoprotein-gold cytochemistry

The glycoconjugates of the human fundic mucosa were characterized at the ultrastructural level by means of direct (Helix pomatia agglutinin-gold complex) and indirect lectin techniques (Concanavalin A and horseradish peroxidase-gold complex; wheat germ agglutinin and ovomucoid-gold complex). Surface mucous cells and mucous neck cells secreted O-glycoproteins with N-acetylgalactosamine and N-acetylglucosamine residues at the non reducing terminus of the saccharidic chain. The secretory granules of the mucous neck cells showed condensed areas slightly reactive to ConA. The results obtained in the chief cells suggest that these cells secrete N-glycoproteins rich in mannose and/or glucose residues. "Transitional cells", presenting both morphological characteristics and lectin binding pattern intermediate to the mucous neck and chief cells have been observed. The surface of the intracellular canaliculi of the parietal cell was labelled by HPA, WGA and ConA. In the neck region of the gastric glands, immature parietal cells containing abundant mucous granules reactive to HPA, WGA and ConA were observed. The present results further corroborate the existence of a common cell precursor for surface mucous, mucous neck and parietal cells. In a further step, mucous neck cells gradually differentiate into chief cells the transitional cells being an intermediate stage.     

Light and electron microscope observations on the gastric mucosa of the frog (Rana esculenta)

Summary The structure of the frog gastric and esophageal mucosa was studied in the course of a complete hibernation period and compared with that in summer frogs (see preceding article).It appeared that especially chief cells and parietal cells are liable to cytoplasmic remodelling. Thus, in chief cells the rough endoplasmic reticulum (RER) undergoes disorganization, the number of free ribosomes increases and the Golgi system becomes transformed into a compact vesicular structure. The number of pepsinogen granules in chief cells of late winter frogs is only 20% of that in frogs studied at the onset of hibernation. The loss of pepsinogen granules is at least partly due to autophagy. In addition, lysosomes are involved in focal degradation of the cytoplasm, which may ultimately result in complete degeneration of some chief cells. The presence of zymogen granules containing fibrocyte-like cells in the tunica propria proved heterophagocytosis by these cells.In parietal cells, the area occupied by smooth endoplasmic reticulum becomes reduced. The basal cytoplasm of both chief cells and parietal cells contains numerous lipid droplets, which, in contrast to those in summer frogs, are continuous with RER cisternae. The juxtaposition of lipid droplets and mitochondria seen in summer frogs is eventually lost in hibernating animals.Apart from the appearance of supra-nuclear lipid droplets, the mucous cells of the surface epithelium show no striking alterations. However, in the glandular pits both surface mucous cells and mucous neck cells contain less mucous granules than in summer frogs.The results are discussed in connection with parallel biochemical work and available literature, and in the light of our previous studies on the exocrine pancreas in hibernating frogs.     

Autoradiographic demonstration of gastrin binding sites in rat gastric mucosa

The location of 125I-iodotyrosyl gastrin I binding sites in rat gastric mucosa was studied. Peptide specificity was demonstrated by competitive binding studies through the addition of a large dose of cold human gastrin I or cholecystokinin-octapeptide. Autoradiography of the stomach tissue was carried out by freeze-drying, embedding in Epon, wet-sectioning with ethylene glycol, and dry-mounting the emulsion film by means of the wire-loop method to prevent loss of the labeled substance. Specific binding sites for gastrin were found on parietal and chief cells, whereas few binding sites were seen on the surface mucous or mucous neck cells. Binding sites on the parietal cells were dispersed in the cytoplasm, while those on the chief cells were found near the basal plasma membrane.     

Gastric mucosal cellular changes induced by indomethacin (NSAID) in male albino rats

Indomethacin (2 mg/100 g body weight), induces haemorrhagic gastric ulcers in albino rats. The incidence and severity of ulceration increased with starvation period. Indomethacin caused little or no effect on the cellular and the nuclear diameter of parietal and chief cells while reduction was observed in mucus and endocrine cells. The effect was enhanced with increased duration of starvation. Both mucous and endocrine cells decreased in their number after 72 hr of starvation. Thus prolonged starvation enhanced the gastric mucosal damage induced by indomethacin.     

Glycoconjugate cytochemistry of the rat fundic gland using lectin/colloidal-gold conjugates and Lowicryl K4M. Helix pomatia lectin is a specific marker for mucous neck cells in fundic glands of the rat gastric mucosa

The fundic gland of the rat stomach was studied using the low-temperature embedding resin Lowicryl K4M and postembedding staining with lectin/colloidal-gold (CG) conjugates. Intense labeling with Ricinus communis agglutinin I was observed not only in mucous-producing cells but also in parietal cells. In contrast, Helix pomatia agglutinin (HPA) only labeled mucous neck cells and intermediate cells between mucous neck cells and chief cells. The other epithelial cells present in the rat fundic gland showed virtually no reaction with this lectin. Our results indicate that HPA might be a marker lectin of mucous neck cells and their derivatives. The combination of embedding in the hydrophilic resin Lowicryl K4M and postembedding staining with lectin-CG conjugates provided satisfactory staining results, and made it possible to visualize the precise distribution of terminal glycoconjugates in intracellular components as well as on the plasma membrane.     

Localization of pepsinogen (A and C) and cellular differentiation of pepsinogen-synthesizing cells in the human gastric mucosa

The localization of pepsinogens (PG A and PG C) was studied intracellularly in human gastric biopsies embedded in Lowicryl K4M, using affinity-purified antibodies and protein A-gold. The homogeneous secretory granules of the chief cells contained both PG A and PG C, as was proved by serial sections. Identical reaction was also seen in the core of the biphasic mucous neck cell granules, whereas the mantle did not label. The rough endoplasmic reticulum (RER) and Golgi complex of the chief cells and mucous neck cells contained ample label. Transitional cells identified by the presence of granules of both chief cells and mucous neck cells were recognized. This type of mucous neck cell is thought to transform into a chief cell. However, an increase of RER that could explain an increase of the pepsinogen production was not observed. A mixture of these granules was also found in cells morphologically characterized as young parietal cells, suggesting a common precursor for these three cell types. These observations make the transformation from mucous neck to chief cells questionable. Antral gland cells contained only PG C, as was shown in serial section, too.     

Glycoconjugate cytochemistry of the rat fundic gland using lectin/colloidal-gold conjugates and Lowicryl K4M

Summary The fundic gland of the rat stomach was studied using the low-temperature embedding resin Lowicryl K4M and postembedding staining with lectin/colloidal-gold (CG) conjugates. Intense labeling with Ricinus communis agglutinin I was observed not only in mucous-producing cells but also in parietal cells. In contrast, Helix pomatia agglutinin (HPA) only labeled mucous neck cells and intermediate cells between mucous neck cells and chief cells. The other epithelial cells present in the rat fundic gland showed virtually no reaction with this lectin. Our results indicate that HPA might be a marker lectin of mucous neck cells and their derivatives. The combination of embedding in the hydrophilic resin Lowicryl K4M and postembedding staining with lectin-CG conjugates provided satisfactory staining results, and made it possible to visualize the precise distribution of terminal glycoconjugates in intracellular components as well as on the plasma membrane.     

Localization of pepsinogen and cellular differentiation in the human gastric mucosa using lowicryl K4M

The localization of pepsinogens (PG A and PG C) was studied intracellularly in human gastric biopsies embedded in Lowicryl K4M, using affinity purified antibodies and protein A-gold. The homogeneous secretory granules of the chief cells contained both PG A and PG C, as was proved in serial sections. Identical reaction was seen in the core of the biphasic mocous neck cell granules, whereas the mantle did not label. Even the rough endoplasmic reticulum (RER) and Golgi complex of the chief- and mucous neck cells contained label. Transitional cells identified by the presence of granules of both chief- and mucous neck cells were seen. This type of mucous neck cell is thought to transform into a chief cell. However an increase of RER that could explain an increase of the pepsinogen production was not observed. A mixture of these granules were also found in morphologically characterized young parietal cells, suggesting a common precursor for these three cell-types. These observations makes the transformation from mucous neck- into chief cells questionable. In conclusion Lowicryl K4M appeared to be a significant improvement compared to the Epon 812. Its shows a better preservation of both cytoplasmic antigens and cellular fine structure. This improvement adds information on the transformation hypothesis. Lowicryl K4M enables us, firstly to distinguish PG A and C synthesizing RER in different types of cell and secondly to recognize immature cells with the characteristics of chief-, mucous neck-, and parietal cells in the fundic gland. Very likely these three cell-types all arise from a common precursor. It is questionable that in normal human gastric mucosa the mucous neck cells transform into chief cells.     

Visualization of the secretory canaliculi of human parietal cells with a peroxidase-labelled peanut lectin

Summary Peanut lectin reactivity was examined in normal fundic glands from human gastric samples, both at light- and electron-microscopic levels, using a peroxidase conjugate. Positive reaction was observed in the glycocalyx of parietal cell secretory canaliculi as well as in the mucous globules of mucous cells and in the luminal cell coat of chief cells. The presence of terminal galactose in the canalicular glycocalyx may be connected with the peculiar function of hydrochloric acid secretion. Peroxidase-labelled peanut lectin is proposed as a marker for visualizing the secretory canaliculus of parietal cells.     

Muscarinic acetylcholine receptors in rat gastric mucosa

Summary The muscarinic cholinergic innervation of the rat gastric mucosa was investigated by localizing the muscarinic receptors using a tritiated muscarinic antagonist, pirenzepine. Radioautography was performed by freeze drying stomach tissue, which was then embedded in Epon and wet sectioned with ethylene glycol, and dry mounting on emulsion film by the wire-loop method to prevent loss of the labelled substance during fixation and the radioautographic procedure. Light and electron microscopy showed that the specific pirenzepine-binding sites were localized predominantly on parietal cells, chief cells and perivascular plexuses. Analysis of the grain distribution on parietal cells revealed that the silver grains corresponding to the pirenzepine-binding sites were mainly on the basolateral plasma membrane. On the other hand, the surface mucous or mucous neck cells had few pirenzepine-binding sites.     

The origin of pre-neoplastic metaplasia in the stomach: chief cells emerge from the Mist

The digestive-enzyme secreting, gastric epithelial chief (zymogenic) cell is remarkable and underappreciated. Here, we discuss how all available evidence suggests that mature chief cells in the adult, mammalian stomach are postmitotic, slowly turning over cells that arise via a relatively long-lived progenitor, the mucous neck cell, The differentiation of chief cells from neck cells does not involve cell division, and the neck cell has its own distinct pattern of gene expression and putative physiological function. Thus, the ontogeny of the normal chief cell lineage exemplifies transdifferentiation. Furthermore, under pathophysiogical loss of acid-secreting parietal cell, the chief cell lineage can itself trasndifferentiate into a mucous cell metaplasia designated Spasmolytic Polypeptide Expressing Metaplasia (SPEM). Especially in the presence of inflammation, this metaplastic lineage can regain proliferative capacity and, in humans may also further differentiate into intestinal metaplasia. The results indicate that gastric fundic lineages display remarkable plasticity in both physiological ontogeny and pathophysiological pre-neoplastic metaplasia.     

Muscarinic acetylcholine receptors in rat gastric mucosa. A radioautographic study using a potent muscarinic antagonist, 3H-pirenzepine

The muscarinic cholinergic innervation of the rat gastric mucosa was investigated by localizing the muscarinic receptors using a tritiated muscarinic antagonist, pirenzepine. Radioautography was performed by freeze drying stomach tissue, which was then embedded in Epon and wet sectioned with ethylene glycol, and dry mounting on emulsion film by the wire-loop method to prevent loss of the labelled substance during fixation and the radioautographic procedure. Light and electron microscopy showed that the specific pirenzepine-binding sites were localized predominantly on parietal cells, chief cells and perivascular plexuses. Analysis of the grain distribution on parietal cells revealed that the silver grains corresponding to the pirenzepine-binding sites were mainly on the basolateral plasma membrane. On the other hand, the surface mucous or mucous neck cells had few pirenzepine-binding sites.     

Role of bone marrow derived-mesenchymal stem cells against gastric ulceration: Histological,immunohistochemical and ultrastructural study

The current study aimed to assess the antiulcerogenic impact of mesenchymal bone marrow stem cells (BMMSCs) against gastric ulcer induced by the use of piroxicam in rats and to compare this effect with the antiulcer drug “Pantoloc ®” proton pump inhibitors. The study included histological, histochemical, immunohistochemical and ultrastructural examination in stomach of rats in different study groups. In the ulcerated group, the glandular region of the stomach displayed clear mucosal lesions occurring as perforations along the stomach axis. In addition, stomach displayed degeneration of surface mucous cells accompanied by pyknosis, vacuolation among parietal cells in ishmus region, basal region with vacuolated chief cells and karyolitic nucleus of parietal cells. Moreover, Stomach sections of ulcer model rats showed intensive immunoreactivity to cytokeratin 20, Cox 2 and PCNA. Findings of the present study have shown that BMMSCs have an ameliorative effect against piroxicam-induced gastric ulcer in rats. Collectively, the proposed work has shown that BMMSCs have a curative capacity as an antiulcer due to their high antioxidant activity. Further studies are required in molecular levels to understand the mechanism of action during treatment.     

Glycoconjugate distribution in the human fundic mucosa revealed by lectin- and glycoprotein-gold cytochemistry

Summary The glycoconjugates of the human fundic mucosa were characterized at the ultrastructural level by means of direct (Helix pomatia agglutinin-gold complex) and indirect lectin techniques (Concanavalin A and horseradish peroxidase-gold complex; wheat germ agglutinin and ovomucoid-gold complex). Surface mucous cells and mucous neck cells secreted O-glycoproteins with N-acetylgalactosamine and N-acetylglucosamine residues at the non reducing terminus of the saccharidic chain. The secretory granules of the mucous neck cells showed condensed areas slightly reactive to ConA. The results obtained in the chief cells suggest that these cells secrete N-glycoproteins rich in mannose and/or glucose residues. Transitional cells, presenting both morphological characteristics and lectin binding pattern intermediate to the mucous neck and chief cells have been observed. The surface of the intracellular canaliculi of the parietal cell was labelled by HPA, WGA and ConA. In the neck region of the gastric glands, immature parietal cells containing abundant mucous granules reactive to HPA, WGA and ConA were observed. The present results further corroborate the existence of a common cell precursor for surface mucous, mucous neck and parietal cells. In a further step, mucous neck cells gradually differentiate into chief cells the transitional cells being an intermediate stage.     

Ultrastructural changes in the parietal cells of persons suffering gastric ulcers

Ultrastructural changes taking place in various phases of secretion in the gastric fundus parietal cells after histamine adminstration were studied in patients suffering from gastric and duodenal ulcers, having different gastric acidity. Parietal cells of patients with normal and hyperacidity of the gastric juice after histamine administration were found to have such ultrastructural alterations in which were characteristic of the intensively functioning cells, with the retention of phasic character of the process; as to patients with hypoacidity, the secretory phases of the parietal cells were not marked, and no alterations indicating intensification of the cellular functional activity were noted.     

Recent Advances in the Physiology of Gastric Acid Secretion

The classic scheme of gastric acid secretion which divided the digestive period into cephalic, gastric and antral phases has become obsolete in the last 10 years. These “phases” are now seen as concurrently acting mechanisms which depend upon one another to be fully efficient. About half of all gastrin released during a meal is dependent upon vagal stimulation of the antrum. Also, vagotomy desensitizes the acid-secreting parietal cells to the effect of all other types of stimuli.The number of parietal cells (parietal cell mass) varies greatly according to the gastric secretory activity of each individual. It is highest with duodenal ulcer and lowest with gastric ulcer.Parietal cell hyperplasia or atrophy can be induced experimentally, but the factors controlling the size of the parietal cell mass in man have not been studied.A scheme of acid secretion which incorporates recent advances is presented.