Vitamin B12 deficiency may play an etiological role in atrophic glossitis and its grading: A clinical case-control study.

BACKGROUND: Existing studies have reported the significant association between atrophic glossitis (AG) and hematinic deficiencies, including iron, folate and vitamin B12 deficiency. However, these findings were inconsistent. AG can be graded as partial or complete atrophy. It is still unclear whether hematinic deficiencies are associated with the grading of AG. METHODS: 236 AG patients and 208 sex- and age-matched healthy controls were enrolled in this study. Hematological tests including complete blood count, and serum levels of folate, ferritin and vitamin B12 were performed. The AG group was divided into those with partial AG and those with complete AG according to the extent of papillary atrophy. Statistical analysis was performed to assess whether hematinic deficiencies are risk factors for AG and its grading. RESULTS: Compared with the healthy controls, AG patients had significantly higher frequencies of vitamin B12 deficiency (68.22%), ferritin deficiency (13.98%) and anemia (21.61%). The differences in hematinic deficiencies and anemia between AG patients and healthy controls changed according to gender and age. The frequencies of serum vitamin B12 deficiency and anemia in the complete AG subgroup were significantly higher than those in the partial AG subgroup. Logistic regression analysis revealed that vitamin B12 deficiency and anemia were significantly correlated with AG and its grading. The AG patients with vitamin B12 deficiency responded well to supplement therapy. CONCLUSION: AG could be an important clinical indicator for potential vitamin B12 deficiency, especially when the degree of tongue atrophy more than 50% and complete atrophy. Vitamin B12 deficiency might play an etiological role in the development of AG.

Characterization by Lectin Histochemistry of Two Subpopulations of Parietal Cells in the Rat Gastric Glands.

Parietal cells undergo a differentiation process while they move from the isthmus toward the pits and the base region of the gastric gland. The aim of this work was to analyze the rat gastric glands by lectin histochemistry to show the glycans expressed by upper (young) and lower (old) parietal cells. We used lectins recognizing the most frequent sugar moieties in mammals. Each lectin was assayed alone and in combination with several deglycosylation pretreatments: (1) ß-elimination, which removes O-linked oligosaccharides; (2) incubation with Peptide-N-glycosidase F, to remove N-linked glycans; (3) acid hydrolysis, which removes terminal sialic acid moieties; (4) methylation-saponification, to remove sulfate groups from sugar residues; and (5) glucose oxidase, a technique carried out with the lectin concanavalin A to convert glucose into gluconic acid. The lectins from Helix pomatia, Dolichos biflorus (DBA), Glycine max (soybean), Maclura pomifera, Arachis hypogaea (peanut), Bandeiraea simplicifolia (lectin I-B4), and Datura stramonium showed a different glycan expression in the parietal cells throughout the gastric gland. This difference supports that parietal cells undergo a maturation/degeneration process while the cells descend along the gland. The role of DBA as a marker of parietal cells previously reported should be taken with caution because these cells showed different reactivity for the lectin, ranging from negative to strong labeling.

Autoimmune Metaplastic Atrophic Gastritis: Recognizing Precursor Lesions for Appropriate Patient Evaluation.

Autoimmune metaplastic atrophic gastritis (AMAG) is a significant risk factor for pernicious anemia and gastric neoplasia. Still, the histologic features of AMAG are frequently overlooked, especially in the early stages of the disease. The purpose of our study, therefore, was to catalogue the progression of histologic changes that precede the development of AMAG in affected individuals. Over a 2-year period (2012 to 2014), the diagnosis of AMAG was rendered on material from 113 patients seen at Johns Hopkins Hospital (∼1.8% of "in house" gastric biopsies). Prior gastric body biopsies had been performed on 54 (48%) patients in the cohort, and the majority of these specimens had also shown AMAG. Eighteen of the previous biopsies, however, carried a diagnosis other than AMAG: 13 inactive chronic gastritis, 2 acute Helicobacter pylori gastritis, and 1 each of eosinophilic gastritis, iron pill gastritis, and proton-pump inhibitor-like effect. Upon review of these 18 biopsies, the most common histologic findings were heavy full-thickness or deep lamina propria chronic inflammation (12), inflammatory destruction of oxyntic glands (12), metaplasia (intestinal, pyloric, or pancreatic acinar) (10), prominent lamina propria eosinophils (8), and parietal cell pseudohypertrophy (4). At least 2 of these features were present in the majority (13, 72%) of the biopsies. In addition, 7 (58%) of these patients were also found to have another autoimmune or inflammatory disorder before the diagnosis of AMAG. Although subtle, histologic features of developing AMAG are identifiable in routine gastric body biopsies. When metaplasia, full-thickness chronic inflammation, and/or oxyntic destruction are seen, a note suggesting laboratory testing and/or close clinical follow-up in this subset of patients may be warranted.

Oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor: A case report.

Gastric adenocarcinoma is one of the most common malignancies worldwide. Histochemical and immunohistologic analyses classify the phenotypes of gastric adenocarcinoma into several groups based on the variable clinical and pathologic features. A new and rare variant of gastric adenocarcinoma with chief cell differentiation (GA-CCD) has recently been recognized. Studies reporting the distinct clinicopathologic characteristics proposed the term oxyntic gland polyp/adenoma because of the benign nature of the GA-CCD. Typically, GA-CCD is a solitary mucosal lesion that develops either in the gastric cardia or fundus. Histologically, this lesion is characterized by tightly clustered glands and anastomosing cords of chief cells. Immunohistochemically, GA-CCD is diffusely positive for mucin (MUC) 6 and negative for MUC2 and MUC5AC. However, other gastric tumors such as a gastric neuroendocrine tumor or fundic gland polyp have been difficult to exclude. Because GA-CCD tends to be endoscopically misdiagnosed as a neuroendocrine tumor or fundic gland polyp, comprehensive assessment and observation by an endoscopist are strongly recommended. Herein, we report a rare case of oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor that was successfully removed by endoscopic mucosal resection.

The A2B adenosine receptor colocalizes with adenosine deaminase in resting parietal cells from gastric mucosa.

The A2B adenosine receptor (A2BR) mediates biological responses to extracellular adenosine in a wide variety of cell types. Adenosine deaminase (ADA) can degrade adenosine and bind extracellularly to adenosine receptors. Adenosine modulates chloride secretion in gastric glands and gastric mucosa parietal cells. A close functional link between surface A2BR and ADA has been found on cells of the immune system, but whether this occurs in the gastrointestinal tract is unknown. The goal of this study was to determine whether A2BR and ADA are coexpressed at the plasma membrane of the acid-secreting gastric mucosa parietal cells. We used isolated gastric parietal cells after purification by centrifugal elutriation. The membrane fraction was obtained by sucrose gradient centrifugation. A2BR mRNA expression was analyzed by RT-PCR. The surface expression of A2BR and ADA proteins was evaluated by Western blotting, flow cytometry and confocal microscopy. Our findings demonstrate that A2BR and ADA are expressed in cell membranes isolated from gastric parietal cells. They show a high degree of colocalization that is particularly evident in the surface of contact between parietal cells. The confocal microscopy data together with flow cytometry analysis suggest a tight association between A2BR and ADA that might be specifically linked to glandular secretory function.

Gastric adenocarcinoma with chief cell differentiation: a proposal for reclassification as oxyntic gland polyp/adenoma.

Gastric adenocarcinoma with chief cell differentiation (GA-CCD) has been reported as a new, rare variant of gastric adenocarcinoma. Only 12 cases in Japanese patients have been described to date, but they demonstrate distinct clinicopathologic features. To further characterize these lesions, we have collected 10 additional cases. Patients ranged in age from 44 to 79 years (mean, 64.2 y) with a relatively equal sex distribution (6 women and 4 men). Stratified by race, 4 patients were Hispanic, 2 were White, 2 were African American, 1 was Asian (Chinese), and the race was unknown for 1 patient. All patients presented with gastroesophageal reflux that prompted an endoscopic examination. The majority of GA-CCDs were identified in the fundus (7 of 10, 70%) and the remaining in the cardia (n=3). Grossly, they were solitary and polypoid, ranging in size from 0.2 to 0.8 cm (mean, 0.4 cm). Histologically, all cases were centered in the deep mucosa, with focal involvement of surface foveolar epithelium in 3 (30%) cases but not the submucosa. The tumors consisted of clustered glands and irregular branching cords of oxyntic epithelium. Thin wisps of radiating smooth muscle separated the epithelium, but desmoplasia was distinctly absent in all cases. The oxyntic mucosa was 1 to 2 cells thick and composed of a mixture of mucous neck, parietal, and chief cells. In 7 of 10 (70%) cases, chief cells were the predominant cell type, whereas the remaining 3 cases consisted primarily of mucous neck cells. The nuclei were mildly enlarged with slight nuclear pleomorphism, but no mitotic figures were identified. In addition, necrosis, lymphovascular invasion, and perineural invasion were absent. Immunohistochemically, GA-CCDs were diffusely positive for MUC6 (10 of 10, 100%) and negative for MUC5AC (0%) and MUC2 (0%). Ki-67 immunolabeling demonstrated variable expression, with the highest areas ranging from 0.2% to 10%. Clinical follow-up was available for 9 of 10 (90%) patients and ranged from 6 to 39 months. One patient had persistence of lesion at 6 months because of incomplete removal, whereas the other 8 were disease free. In summary, GA-CCDs are solitary, mucosal lesions of the gastric cardia/fundus that arise in patients from multiple ethnic backgrounds. Considering that patients within this study and those reported previously have had neither true recurrence nor progression of disease, these lesions are best regarded as benign. Consequently, the term GA-CCD is contradictory and we prefer the descriptive term "oxyntic gland polyp/adenoma" until further studies can clarify the pathogenesis of these lesions and their natural history.

The Golgi apparatus in the endomembrane-rich gastric parietal cells exist as functional stable mini-stacks dispersed throughout the cytoplasm.

BACKGROUND INFORMATION: Acid-secreting gastric parietal cells are polarized epithelial cells that harbour highly abundant and specialized, H+,K+ ATPase-containing, tubulovesicular membranes in the apical cytoplasm. The Golgi apparatus has been implicated in the biogenesis of the tubulovesicular membranes; however, an unanswered question is how a typical Golgi organization could regulate normal membrane transport within the membrane-dense cytoplasm of parietal cells. RESULTS: Here, we demonstrate that the Golgi apparatus of parietal cells is not the typical juxta-nuclear ribbon of stacks, but rather individual Golgi units are scattered throughout the cytoplasm. The Golgi membrane structures labelled with markers of both cis- and trans-Golgi membrane, indicating the presence of intact Golgi stacks. The parietal cell Golgi stacks were closely aligned with the microtubule network and were shown to participate in both anterograde and retrograde transport pathways. Dispersed Golgi stacks were also observed in parietal cells from H+,K+ ATPase-deficient mice that lack tubulovesicular membranes. CONCLUSIONS: These results indicate that the unusual organization of individual Golgi stacks dispersed throughout the cytoplasm of these terminally differentiated cells is likely to be a developmentally regulated event.

Effects of extracts of oxyntic mucosa in rat on the biological activity of osteoblasts.

UNLABELLED: We explored the relationship between extracts of oxyntic mucosa (EOM) and the biological activity of osteoblasts in rats. We found that EOM could enhance the activity of bone formation in osteoblast. Our results suggest that EOM likely play a role in the cases of osteopenia induced by gastrectomy. INTRODUCTION: Surgical removal of the stomach (gastrectomy) leads to osteopenia in animals and in humans. It was demonstrated that EOM could induce transient hypocalcaemia and stimulate an uptake of Ca(2+) into bone in rats. The main aim of this study has been to clarify whether this procedure was performed through osteoblast, which is responsible for bone formation. METHODS: Osteoblasts were isolated, cultured, and identified in vitro. Preparing the rats' EOM and diluting into low, middle, and high concentrations, respectively. After osteoblasts were treated by different concentration EOMs or saline (for control), the intracytoplasm [Ca(2+)]i was measured by laser scanning confocal microscopy; the proliferation of osteoblast cells were detected with cell counting kit 8 (CCK-8); and the expressions of collagen type I and osteocalcin were assayed by reverse transcriptase polymerase chain reaction and Western blot. RESULTS: EOMs were found to induce a dose-related rapid increase of intracytoplasm [Ca(2+)]i in osteoblasts and could stimulate osteoblasts to enhance proliferation and upregulate the expressions of collagen type I and osteocalcin significantly (p < 0.05) compared with the control group. CONCLUSIONS: It was confirmed that EOM could stimulate osteoblasts to elevate the cytoplasm [Ca(2+)]i and promote the multiplication and the activity of bone formation in osteoblasts.

Novel insights of the gastric gland organization revealed by chief cell specific expression of moesin.

ERM (ezrin, radixin, and moesin) proteins play critical roles in epithelial and endothelial cell polarity, among other functions. In gastric glands, ezrin is mainly expressed in acid-secreting parietal cells, but not in mucous neck cells or zymogenic chief cells. In looking for other ERM proteins, moesin was found lining the lumen of much of the gastric gland, but it was not expressed in parietal cells. No significant radixin expression was detected in the gastric glands. Moesin showed an increased gradient of expression from the neck to the base of the glands. In addition, the staining pattern of moesin revealed a branched morphology for the gastric lumen. This pattern of short branches extending from the glandular lumen was confirmed by using antibody against zonula occludens-1 (ZO-1) to stain tight junctions. With a mucous neck cell probe (lectin GSII, from Griffonia simplicifolia) and a chief cell marker (pepsinogen C), immunohistochemistry revealed that the mucous neck cells at the top of the glands do not express moesin, but, progressing toward the base, mucous cells showing decreased GSII staining had low or moderate level of moesin expression. The level of moesin expression continued to increase toward the base of the glands and reached a plateau in the base where chief cells and parietal cells abound. The level of pepsinogen expression also increased toward the base. Pepsinogen C was located on cytoplasmic granules and/or more generally distributed in chief cells, whereas moesin was exclusively expressed on the apical membrane. This is a clear demonstration of distinctive cellular expression of two ERM family members in the same tissue. The results provide the first evidence that moesin is involved in the cell biology of chief cells. Novel insights on gastric gland morphology revealed by the moesin and ZO-1 staining provide the basis for a model of cell maturation and migration within the gland.

The gastric H,K ATPase as a drug target: past, present, and future.

The recent progress in therapy if acid disease has relied heavily on the performance of drugs targeted against the H,K ATPase of the stomach and the H2 receptor antagonists. It has become apparent in the last decade that the proton pump is the target that has the likelihood of being the most sustainable area of therapeutic application in the regulation of acid suppression. The process of activation of acid secretion requires a change in location of the ATPase from cytoplasmic tubules into the microvilli of the secretory canaliculus of the parietal cell. Stimulation of the resting parietal cell, with involvement of F-actin and ezrin does not use significant numbers of SNARE proteins, because their message is depleted in the pure parietal cell transcriptome. The cell morphology and gene expression suggest a tubule fusion-eversion event. As the active H,K ATPase requires efflux of KCl for activity we have, using the transcriptome derived from 99% pure parietal cells and immunocytochemistry, provided evidence that the KCl pathway is mediated by a KCQ1/KCNE2 complex for supplying K and CLIC6 for supplying the accompanying Cl. The pump has been modeled on the basis of the structures of different conformations of the sr Ca ATPase related to the catalytic cycle. These models use the effects of site directed mutations and identification of the binding domain of the K competitive acid pump antagonists or the defined site of binding for the covalent class of proton pump inhibitors. The pump undergoes conformational changes associated with phosphorylation to allow the ion binding site to change exposure from cytoplasmic to luminal exposure. We have been able to postulate that the very low gastric pH is achieved by lysine 791 motion extruding the hydronium ion bound to carboxylates in the middle of the membrane domain. These models also allow description of the K entry to form the K liganded form of the enzyme and the reformation of the ion site inward conformation thus relating the catalytic cycle of the pump to conformational models. The mechanism of action of the proton pump inhibitor class of drug is discussed along with the cysteines covalently bound with these inhibitors. The review concludes with a discussion of the mechanism of action and binding regions of a possible new class of drug for acid control, the K competitive acid pump antagonists.

In situ measurement of pH in the secreting canaliculus of the gastric parietal cell and adjacent structures.

The gastric H(+)/K(+)-ATPase is located within an infolding (secretory canaliculus) of the apical plasma membrane of gastric parietal cells. Our aim was to measure the pH values in the cytosol and canaliculus of the acid-secreting parietal cell and the adjacent gland lumen in situ. We used ultrafine double-barreled tip-sealed microelectrodes at high acceleration rates for intracellular and canalicular measurements. Immunohistochemical staining of the parietal cells was used to identify the track of the electrode and to estimate the position of the electrode tip at the time of the last intracellular measurement. En route to the deepest regions of the mucosa, where the average gland lumen pH was approximately 3, and on advancing in steps of 2 mum, the electrode entered the cytosol of the parietal cells, where the pH value was 7.4. Advancing the electrode further resulted, in several instances, in a sharp decrease in pH to an average value of 1.7 +/- 0.2, which we interpreted as the measurement within the canaliculus. When the electrode was advanced even further, the pH reading returned to the cytosolic value. From the difference in pH between the secreting canaliculus and the adjacent gland lumen, we concluded that the released acid was immediately buffered. Thus, the only cellular structure directly exposed to the highly acidic canalicular content is the apical membrane forming the canaliculus in the parietal cell.

Immunocytochemical identification of low-affinity NTS2 neurotensin receptors in parietal cells of human gastric mucosa.

The biological effects of neurotensin (NT) are mediated by two distinct G protein-coupled receptors, NTS(1) and NTS(2). Although it is well established that neurotensin inhibits gastric acid secretion in man, the plasma membrane receptor mediating these effects has not been visualized yet. We developed and characterized a novel antipeptide antibody to the carboxy-terminal region of the human NTS(2) receptor. The cellular and subcellular distribution of NTS(2) receptors was evaluated in various human gastrointestinal tissues. Specificity of the antiserum was demonstrated by (1) detection of a broadband migrating at M(r) 90 000-100 000 in Western blots of membranes from NTS(2)-expressing tissues; (2) cell-surface staining of NTS(2)-transfected cells; (3) translocation of NTS(2) receptor immunostaining after agonist exposure; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with its immunizing peptide. In the gastrointestinal tract, NTS(2) receptor immunoreactivity was highly abundant in parietal cells of the gastric mucosa, in neuroendocrine cells of the stomach small and large intestine, and in cells of the exocrine pancreas. NTS(2) receptors were clearly located in the plasma membrane and uniformly present on nearly all target cells. The presence of NTS(2) receptors was rarely detected in human tumors. This is the first localization of NTS(2) receptors in human formalin-fixed, paraffin-embedded tissues at the cellular level. The abundant expression of low-affinity NTS(2) receptors on the plasma membrane of human parietal cells provides a morphological substrate for the direct inhibition of gastric acid secretion observed after i.v. administration of neurotensin.

[A pH-probe for endoscopic parietal topographical pH-metry].

A pH-probe for endoscopic parietal topographical pH-metry was developed. The probe has a circular measuring electrode and a cutaneous silver chloride reference electrode. Clinical testing of the developed probe was performed to compare it with a conventional end electrode. It was found that the new pH-probe with circular antimonial electrode for pH measurement at the surface of the mucous coat of upper gastrointestinal tract in a fasting patient considerably increases the accuracy of pH measurement at the site of acid glands. Recommendations for examination of acid-forming and alkalizing functions of stomach and determination of the boundaries of the main regions of stomach during endoscopic examination are given.

Ghrelin cell density in the gastrointestinal tracts of animal models of human diabetes.

Ghrelin cell density in the gastrointestinal tract of animal models of human diabetes type 1 and 2 was investigated. The animals used were non-obese diabetic (NOD) mice and obese diabetic mice. Ghrelin cells were detected by immunohistochemistry and quantified by computerized image analysis. Ghrelin-immunoreactive cells were detected in all animals studied. They were abundant in the oxyntic mucosa, patchy and few in the duodenum and rare in the colon. The density of ghrelin-immunoreactive cells decreased in diabetic, pre-diabetic NOD mice and in obese diabetic mice as compared to controls, though not statistically significant. It was concluded that the reduced density of ghrelin-immunoreactive cells in animal models of human diabetes type 1 and 2 might explain the slow gastric emptying and slow intestinal transit found in diabetes gastroenteropathy.

Immunohistochemical study on the distribution and relative frequency of endocrine cells in the stomach of the Malayan Pangolin, Manis javanica.

The distribution and relative frequency of six kinds of endocrine cells in the stomach of the Malayan pangolin, Manis javanica were studied immunohistochemically using the avidin-biotin-peroxidase complex method. The stomach of the pangolin has three regions of mucous gland, one oxyntic gland and one pyloric gland. Cells immunoreactive for chromogranin, serotonin, somatostatin, BPP and glucagon were detected in all of the gastric glands, while gastrin-immunoreactive cells were found in the entire gastric gland except for the oxyntic gland. The distribution pattern of endocrine cells in the mucous gland and pyloric gland was mainly from the middle to apical portions of the glands. The endocrine cells were rare or not detected in the basal portion of all of the mucous glands and pyloric gland, but they were also found in the basal portion of the oxyntic gland. The distribution pattern of the endocrine cells in the mucous and pyloric glands suggested that this position facilitates a quick response to the luminal ingesta. The wide distribution of gastrin-immunoreactive cells in all of the mucous glands and pyloric gland was the most remarkable finding. This distribution suggests a major function of gastrin-immunoreactive cells for the digestive process in the Malayan pangolin stomach.

Evaluation of the ordering of membranes in multilayer stacks built on an ATR-FTIR germanium crystal with atomic force microscopy: the case of the H(+),K(+)-ATPase-containing gastric tubulovesicle membranes.

Polarized attenuated total reflection Fourier transform infrared spectra were recorded on multilayer stacks of native gastric tubulovesicle membranes. The spectral intensity and linear dichroism were measured for average thicknesses ranging between 0 and 100 bilayers. Atomic force microscopy was used to investigate the orientation of the membranes at the top of the stack. Height profiles were obtained along randomly drawn lines and slopes were computed over various distances. Orientation distribution functions were obtained from the slopes and decomposed into Legendre polynomials. It was found that the second Legendre polynomials coefficient characterizing the membrane orientation was always larger than 0.9. It could therefore be concluded that the membrane tilt does not significantly contribute to the infrared dichroism, even for the largest thicknesses tested.

Co-secretion of soluble caveolin-1 and pepsinogen in the oesophagus of the red-legged frog Rana aurora aurora.

Caveolin-1, an integral membrane protein, is the principal component of caveolae, which are specialised vesicular microdomains of the plasma membrane. Caveolae are found in most cell types, but they are most abundant in adipocytes, endothelial cells, fibroblasts, and muscle cells. Functionally, they have been implicated in endothelial transcytosis, potocytosis, and signal transduction. Recently, caveolin-1 has been found unexpectedly in the cytoplasm, mitochondria and elements of the secretory pathways of exocrine secretory cells. We have co-localised caveolin-1 and pepsinogen immunohistochemically in serous cells of oesophageal glands of the red-legged frog, Rana aurora aurora. Thus, according to its intracellular localisation pattern, caveolin-1 may be either a soluble protein, located in secretory droplets, or a protein that is inserted in caveolar membranes. Soluble caveolin-1, which is probably embedded in a lipid particle surrounded by a phospholipid shell, may be involved in intracellular and extracellular lipid transport. In the gut, caveolin-1-rich lipid particles can act as donor particles to facilitate (protein-mediated) intestinal uptake of cholesterol and phospholipids. Our findings strengthen the hypothesis that caveolin-1 has a physiological autocrine/paracrine function and demonstrate that secretion of this protein also occurs in vertebrates other than mammals, such as amphibians, which may be a useful alternative animal model to study caveolin-1.

Cytochemistry of gastric parietal cells with high-pressure freezing followed by freeze-substitution.

Gastric parietal cells were examined for changes in their ultrastructure and distribution of the proton pump during feeding and fasting states in rats. The fundic glands from rats fed ad libitum or fasted with free access to water were cryofixed using high-pressure freezing followed by freeze-substitution in acetone containing osmium or acrolein and then embedded in Epon 812 or Lowicryl K4M resin, respectively. Excellent ultrastructural preservation was achieved. During the feeding state, intracellular canaliculi and numerous microvilli were well developed, while tubulovesicles were poorly developed. In contrast, during the fasting state, the microvilli in the narrowed space of the intracellular canaliculi were tightly packed and the tubulovesicles were enlarged. Ultrathin sections were immunostained with antibodies against the alpha- and beta-subunits of the proton pump, H+ x K(+)-ATPase, using the immunogold method. The labelling was strong and clearly localized in comparison with that obtained using the conventional chemical-fixation method. Each subunit was localized on the membrane of the microvilli, intracellular canaliculi and tubulovesicles. The distribution of subunit proteins varied between the two states. During ad libitum feeding, the immunolabelling was localized strongly on the membranes of the microvilli and intracellular canaliculi. In contrast, the labelling was strong on the tubulovesicle membrane in the fasting state. The results obtained with each anti-subunit antibody by H+ x K(+)-ATPase immunostaining revealed differences in distribution and labelling density between the feeding and fasting states.

Pancreatic acinar cell metaplasia in autoimmune gastritis.

OBJECTIVE: To determine the frequency and significance of pancreatic acinar cells in the gastric oxyntic mucosa. DESIGN: One hundred gastric oxyntic mucosal biopsy specimens from patients with chronic active gastritis (n = 30), multifocal atrophic gastritis (n = 15), autoimmune gastritis (n = 18), and normal gastric oxyntic mucosa (n = 37) were evaluated for the presence of pancreatic acinar cells. Formalin-fixed, paraffin-embedded tissues were stained with hematoxylin-eosin, and those positive for pancreatic acinar cells were immunostained with antibodies against trypsin and pancreatic amylase. RESULTS: Eleven (11%) of 100 oxyntic mucosal tissue samples contained pancreatic acinar cells. These samples came from 9 of the 18 (50%) specimens of autoimmune gastritis, 1 of the 15 (6.6%) specimens of multifocal atrophic gastritis, and 1 of the 37 (2.7%) specimens of normal oxyntic mucosa. None of the samples with chronic active gastritis contained pancreatic acinar cells. CONCLUSIONS: Pancreatic acinar cells were found in the oxyntic mucosa of patients with autoimmune gastritis significantly more frequently (P <.001) than in individuals with multifocal atrophic gastritis, normal oxyntic mucosa, or chronic active gastritis. Our study supports a metaplastic origin for pancreatic acinar cells in the oxyntic mucosa. Furthermore, detection of pancreatic acinar cells in the oxyntic mucosa of patients with gastritis strongly suggests an autoimmune pathogenesis.