gastrins and Hypertrophy

The role of gastrin in the pathophysiology of two diseases affecting the human stomach, the Zollinger Ellison syndrome (ZES) and the pernicious anemia (PA), is reviewed. Both diseases present chronic hypergastrinemia but from different origins. The ZES is characterized by the occurrence of ectopic endocrine gastrin-secreting tumors and PA by a fundic atrophic gastritis leading to complete atrophy of fundus and resulting in achlorhydria. In PA, the lack of acid induces continuous gastrin cell activation and is responsible for the subsequent gastrin hypersynthesis and secretion. In ZES, hypergastrinemia causes hypertrophy of the oxyntic mucosa, which, in addition, displays hyperplasia of parietal and mucus cells. In both diseases, hypergastrinemia also induces the hyperproliferation of enterochromaffin-like endocrine cells in the fundic mucosa, which can offer all aspects from hyperplasia, then dysplasia, until true carcinoid tumor. The influence of antisecretory treatments and MEN 1 in the ZES as well as that of several other factors and antrectomy in PA on the behavior of the different gastric cells is evoked. Finally, the role that gastrin and its receptor play in the maintenance of the normal development of gastric mucosa and gastric acid secretion is emphasized by results observed in gene knockout models.

Topics: Anemia, Pernicious; Animals; Atrophy; Autoimmune Diseases; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Hypertrophy; Mice; Mice, Knockout; Multiple Endocrine Neoplasia Type 1; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Gastrins; Gastrointestinal Hormones; Hyperplasia; Hypertrophy; Male; Pancreas; Pancreatic Juice; Rats; Rats, Inbred Strains

Recent advances in the medical therapy of duodenal ulcer support the long held concept that acid hypersecretion is an important pathophysiological abnormality in the majority of patients with duodenal ulcer. The origin of acid hypersecretion is heterogeneous (Table 1). Certain specific physiologic abnormalities that lead to acid hypersecretion may have a genetic basis. The various physiologic abnormalities, alone or in combination, may lead to two final common pathways: abnormally large meal-stimulated and nocturnal acid secretion. Indeed, the success of medical therapy aimed at the control of postprandial acid secretion alone or that of nocturnal acid secretion alone strongly support the significance of these two final acid hypersecretory pathways.

Topics: Circadian Rhythm; Duodenal Ulcer; Eating; Enterochromaffin Cells; Ethnicity; Gastric Acid; Gastrins; Gastrointestinal Motility; Humans; Hypertrophy; Parietal Cells, Gastric; Pyloric Antrum; Secretory Rate; Vagus Nerve; Zollinger-Ellison Syndrome

The lining of the intestinal tract is constantly renewed in a brisk but orderly fashion. Further acceleration of cell renewal is elicited by various stimuli, notably surgical shortening of the intestine and hyperphagia, which lead to prompt but persistent increases in mucosal mass. Progressive hypoplasia ensues when the small and large bowel are deprived of their normal contents, either by fasting (with or without parenteral nutrition) or by exclusion from intestinal continuity. All atrophic changes are reversed by refeeding or restoration of the normal anatomical disposition. Intestine responds to mucosal damage by regeneration from the crypts. Pancreatobiliary secretions mediate some of the tropic effects of chyme; systemic influences, both neurovascular and humoral, also play a part in the adaptive response of the gut.

Topics: Adaptation, Physiological; Adult; Animals; Cell Division; Colectomy; Colostomy; Female; Gastrins; Glucagon-Like Peptides; Humans; Hyperphagia; Hyperplasia; Hypertrophy; Ileum; Intestinal Diseases; Intestinal Mucosa; Intestines; Jejunum; Obesity; Parenteral Nutrition; Rats; Starvation

A review of the publications on mediators of pyloric contraction, together with experimental lesions in animals, suggest that the lesions characteristic of hypertrophic pyloric stenosis in infants (hypertrophy of Torgersen's circular muscle and degenerative changes in Auerbach's myenteric plexus) are probably functional in nature. The hypothesis of a double mechanism is discussed. The primary defect would be an excess of pyloric contraction agonists, such as duodenal hormones and acetylcholine. This would be followed by self-maintenance of the lesions, where pyloric spasm and subsequent distension of the antrum would induce gastrin release with secondary stimulation of duodenal hormone release by oxyntic secretion and acidification of the duodenum.

Topics: Gastrins; Humans; Hypertrophy; Infant; Pyloric Stenosis

Topics: Cholecystokinin; Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Hypertrophy; Intestinal Mucosa; Pepsin A; Secretory Rate; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Hydrogen-Ion Concentration; Hypertrophy; Intubation, Gastrointestinal; Stomach Neoplasms

Topics: Anemia, Pernicious; Antibodies; Atrophy; Autoimmune Diseases; Capillaries; Chronic Disease; Dyspepsia; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Hypertrophy; Intrinsic Factor; Metaplasia; Mitosis; Pentagastrin; Pepsin A; Peptic Ulcer; Pyloric Antrum; Radiography; Stomach; Stomach Neoplasms; Thyroid Diseases; Vagotomy

An account is given of the process by which the Primary Hyperacidity pathogenesis of Pyloric Stenosis of Infancy (PS) evolved. The initial discovery that fasting gastrins were high at birth and continued to rise within the first 4 days was the starting point. Since acidity was also rising at the same time it was proposed that the usual negative feed-back between gastrin and stomach acidity was not mature in the first few weeks of life. The gastrin model for producing PS in puppy dogs was a further incentive to believe that relatively high gastrins, and secondary high acidity would thereby repeatedly cause sphincter contraction and lead to hypertrophy. When gastrin was found to be normal in PS babies we considered and accepted, the less complicated hypothesis that a Primary Inherited Hyperacidity itself was the driving force. Such a theory explained nearly all the clinical features. When we further considered the expected consequences of an initially ineffective negative feed -back and its later maturation, the known peak acidity in neonatal development was explained. This phenomenon also provided an explanation for the remaining previously unexplained time sensitive features of the condition.

Topics: Animals; Disease Models, Animal; Dogs; Fasting; Gastrins; Humans; Hypertrophy; Infant; Pyloric Stenosis

The cause of pyloric stenosis of infancy (PS) is at present unknown. A theory of causation is proposed which is consistent with all the known clinical features of this condition. It is based on the knowledge that PS babies are hypersecretors of acid which pre-dates the development of PS and is an inherited constitutional feature. This acidity will become temporarily and dangerously high due to an insensitivity of the negative feed-back between gastrin and gastric acidy within the first few weeks of life. Normal babies who have inherited normal acidity will also experience peak acid secretions at that time but will be much less acid than babies destined to develop PS. Acid entering the duodenum causes contraction of the pyloric sphincter. Hyperacidity will naturally lead to repeated pyloric sphincter contractions and sphincter hypertrophy. Inappropriate repeated feeding of the vomiting PS baby by a first-time overanxious mother to her ever hungry baby, by provoking feed related sphincter contraction is considered to play a significant part in pathogenesis. Should the baby with PS survive beyond the age of around 6weeks, the matured negative feed-back between gastrin and acid will ensure that dangerous hyperacidity is kept in check. This coupled with the natural pyloric canal widening with age, will lead then to an long lasting cure. This theory explains satisfactorily all the known and hitherto unexplained features of this condition.

Topics: Child; Female; Gastric Acid; Gastrins; Humans; Hypertrophy; Infant; Pyloric Stenosis; Pylorus

Huntingtin interacting protein 1 related (Hip1r) is an F-actin- and clathrin-binding protein involved in vesicular trafficking that is crucial for parietal cell function and epithelial cell homeostasis in the stomach. Gastric parietal cells in Hip1r-deficient mice are lost by apoptotic cell death, which leads to a progressive epithelial cell derangement, including glandular hypertrophy, zymogenic cell loss and expansion of a metaplastic mucous cell lineage known as spasmolytic polypeptide-expressing metaplasia (SPEM). The epithelial cell changes are associated with infiltration of inflammatory cells. As inflammatory mediators, such as IFNγ, have been shown to contribute to the development of the gastric epithelial cell metaplasia after Helicobacter infection, we tested whether IFNγ played a role in the spontaneous progressive epithelial metaplasia observed in Hip1r-deficient mice. Hip1r-deficient mice were crossed with IFNγ-deficient mice and single- and double-mutant mice were analyzed at 3 and 12 months of age. Histopathology scoring showed that loss of IFNγ tempered the spontaneous development of metaplastic lesions in Hip1r-deficient mice. Loss of IFNγ was observed to abrogate the glandular hypertrophy evident in Hip1r mutant stomach, although increased epithelial cell proliferation and elevated gastrin levels were not affected by the presence or absence of this pro-inflammatory cytokine. An analysis of cell lineage markers in the double-mutant mice demonstrated that IFNγ specifically affected the development of metaplastic mucous cells in the neck region, whereas the parietal cell, surface mucous cell and zymogenic cell alterations remained similar to the histopathology in the Hip1r mutant. Morphometric analysis showed that IFNγ was required for the mucous cell hypertrophy and hyperplasia observed in Hip1r-deficient mice. Together, these findings demonstrate that IFNγ is critical for the development of the gastric epithelial cell metaplasia that results from parietal cell atrophy in the Hip1r-deficient mice.

Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Proliferation; DNA-Binding Proteins; Female; Gastric Mucosa; Gastrins; Hypertrophy; Interferon gamma Receptor; Interferon-gamma; Male; Metaplasia; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Microfilament Proteins; Receptors, Interferon; Stomach Neoplasms

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to increase the histamine release from gastric enterochromaffin-like (ECL) cells and promote gastric acid secretion in rats. In contrast, in mice, PACAP has been demonstrated to induce a decrease of gastric acid secretion, an effect presumably due to somatostatin release. To more clearly define the role of PACAP in the regulation of gastric acid output, a knockout mouse model for the PACAP-specific receptor PAC1 was applied in this study. Measurements of the basal and stimulated gastric acid secretion and morphological studies on the gastric mucosa were performed in both wild-type and PAC1-deficient mice. Compared with the wild-type mice, the PAC1-deficient mice showed a nearly threefold higher basal gastric acid output, increased gastric mucosa thickness and glands height, and proportional increases in parietal and total cell counts in the gastric mucosa. The PAC1-deficient mice also showed a trend of increased plasma gastrin levels and gastrin gene expression in the gastric mucosa. This study indicates that the expression of PAC1 is clearly important for maintaining the homeostasis of gastric acid secretion. Loss of PACAP receptor during development may lead to a compensatory mechanism regulating gastric acid secretion.

Topics: Animals; Biomarkers; Gastric Acid; Gastric Mucosa; Gastrins; Hypertrophy; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Rats; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I

Mutations in TRPML1, a lysosomal Ca(2+)-permeable TRP channel, lead to mucolipidosis type IV, a neurodegenerative lysosomal storage disease. An unusual feature of mucolipidosis type IV is constitutive achlorhydria. We produced Trpml1(-/-) (null) mice to investigate the requirement for this protein in gastric acid secretion.. Trpml1-null mice were generated by gene targeting. The expression of Trpml1 and its role in acid secretion by gastric parietal cells were analyzed using biochemical, histologic, and ultrastructural approaches.. Trpml1 is expressed by parietal cells and localizes predominantly to the lysosomes; it was dynamically palmitoylated and dephosphorylated in vivo following histamine stimulation of acid secretion. Trpml1-null mice had significant impairments in basal and histamine-stimulated gastric acid secretion and markedly reduced levels of the gastric proton pump. Histologic and ultrastructural analyses revealed that Trpml1(-/-) parietal cells were enlarged, had multivesicular and multi-lamellated lysosomes, and maintained an abnormal intracellular canalicular membrane. The intralysosomal Ca(2+) content and receptor-mediated Ca(2+) signaling were, however, unaffected in Trpml1(-/-) gastric glands, indicating that Trpml1 does not function in the regulation of lysosomal Ca(2+).. Loss of Trpml1 causes reduced levels and mislocalization of the gastric proton pump and alters the secretory canaliculi, causing hypochlorhydria and hypergastrinemia. The lysosomal enlargement and defective intracellular canaliculi formation observed in Trpml1(-/-) parietal cells indicate that Trpml1 functions in the formation and trafficking of the tubulovesicles. This study provides direct evidence for the regulation of gastric acid secretion by a TRP channel; TRPML1 is an important protein in parietal cell apical membrane trafficking.

Topics: Achlorhydria; Animals; Calcium; Disease Models, Animal; Gastric Acid; Gastrins; H(+)-K(+)-Exchanging ATPase; Histamine; Hypertrophy; Lipoylation; Lysosomes; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucolipidoses; Parietal Cells, Gastric; Phosphorylation; Protein Transport; Time Factors; Transient Receptor Potential Channels; TRPM Cation Channels

Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS) to inject the Cytotoxin associated antigen (CagA) into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI) for the induction of gastric ulcer and precancerous conditions over time (2-64 weeks) using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT), or an isogenic B128DeltacagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4-8 weeks) occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies.

Topics: Achlorhydria; Animals; Antigens, Bacterial; Bacterial Proteins; Cytokines; Gastrins; Gastritis; Genomic Islands; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Hypertrophy; Immunoenzyme Techniques; Precancerous Conditions; Radioimmunoassay; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatostatin; Stomach Neoplasms; Stomach Ulcer

The orderly differentiation of cell lineages within gastric glands is regulated by a complicated interplay of local mucosal growth factors and hormones. Histamine secreted from enterochromaffin-like cells plays an important role in not only stimulated gastric acid secretion but also coordination of intramucosal growth and lineage differentiation. We have examined histidine-decarboxylase (HDC)-deficient mice, which lack endogenous histamine synthesis, to evaluate the influence of histamine on differentiation of fundic mucosal lineages and the development of metaplasia following induction of acute oxyntic atrophy. Stomachs from HDC-deficient mice and wild-type mice were evaluated at 8 wk and 12 mo of age. DMP-777 was administrated orally to 6-wk-old mice for 1 to 14 days. Sections of gastric mucosa were stained with antibodies against Mist1, intrinsic factor, H/K-ATPase, trefoil factor 2 (TFF2), chromogranin A, and Ext1 and for the cell cycle marker phospho-histone H3. HDC-deficient mice at 8 wk of age demonstrated a prominent increase in chief cells expressing Mist1 and intrinsic factor. Importantly Mist1-positive mature chief cells were present in the midgland region as well as at the bases of fundic glands, indicating a premature differentiation of chief cells. Mice dually deficient for both HDC and gastrin showed a normal distribution of chief cells in fundic glands. Treatment of HDC-deficient mice with DMP-777 led to loss of parietal cells and an accelerated and exaggerated emergence of mucous cell metaplasia with the presence of dual intrinsic factor and TFF2-expressing cells throughout the gland length, indicative of the emergence of spasmolytic polypeptide-expressing metaplasia (SPEM) from chief cells. These findings indicate that histamine, in concert with gastrin, regulates the appropriate differentiation of chief cells from mucous neck cells as they migrate toward the bases of fundic glands. Nevertheless, histamine is not required for emergence of SPEM following acute oxyntic atrophy.

Topics: Age Factors; Animals; Azetidines; Basic Helix-Loop-Helix Transcription Factors; Cell Count; Cell Differentiation; Chief Cells, Gastric; Chromogranin A; Enterochromaffin-like Cells; Enzyme Inhibitors; Gastric Fundus; Gastric Mucosa; Gastrins; Histamine; Histidine Decarboxylase; Hyperplasia; Hypertrophy; Intrinsic Factor; Metaplasia; Mice; Mice, Inbred BALB C; Mice, Knockout; Mucins; Muscle Proteins; N-Acetylglucosaminyltransferases; Parietal Cells, Gastric; Peptides; Piperazines; Trefoil Factor-2

Gastrin promotes gastric mucosal growth, and hypergastrinemia induces gastric mucosal hypertrophy. Recently, it has been reported that gastrin induces cyclooxygenase-2 (COX-2) in human gastric and colorectal cancer cell lines. However, whether COX-2 is involved in gastrin-induced gastric mucosal growth in vivo is unknown. We investigated the role of COX-2 in gastrin-induced gastric mucosal hypertrophy using gastrin transgenic mice. Hypergastrinemic mice [mice with mutated gastrin under the control of the beta-actin promoter (ACT-GAS mice)] received the COX-2 inhibitor celecoxib (0, 200, or 500 mg/kg of diet) from 5 wk of age and were killed at 16 or 24 wk. Some ACT-GAS mice received celecoxib from 16 wk and were killed at 24 wk. Eighty-week-old ACT-GAS mice without celecoxib treatment were also examined. The thickness of the gastric mucosa, cell populations, COX-2 expression, and PGE(2) levels were evaluated. All ACT-GAS mice showed gastric mucosal hypertrophy, and four of six 80-wk-old ACT-GAS mice developed gastric cancer. COX-2 was expressed in interstitial cells of the hypertrophic gastric mucosa and gastric cancers. Moreover, PGE(2) levels in the gastric mucosa of ACT-GAS mice were significantly higher than those of normal mice. With treatment with celecoxib, PGE(2) levels, the gastric mucosal thickness, and the number of total gastric cells per gastric gland of ACT-GAS mice were significantly decreased. The decrease in gastric mucosal thickness was caused by a reduction of foveolar hyperplasia. The thickness of glandules and the number of Ki67-positive cells were not significantly changed. In conclusion, COX-2 contributes to gastrin-induced mucosal hypertrophy of the stomach.

Topics: Animals; Apoptosis; Celecoxib; Cyclooxygenase 2; Dinoprostone; Gastric Mucosa; Gastrins; Gene Expression; Hypertrophy; Mice; Mice, Transgenic; Pyrazoles; Stomach Neoplasms; Sulfonamides

Genes in the KCNE family encode single transmembrane domain ancillary subunits that co-assemble with voltage-gated potassium (Kv) channel alpha subunits to alter their function. KCNE2 (also known as MiRP1) is expressed in the heart, is associated with human cardiac arrhythmia, and modulates cardiac Kv alpha subunits hERG and KCNQ1 in vitro. KCNE2 and KCNQ1 are also expressed in parietal cells, leading to speculation they form a native channel complex there. Here, we disrupted the murine kcne2 gene and found that kcne2 (-/-) mice have a severe gastric phenotype with profoundly reduced parietal cell proton secretion, abnormal parietal cell morphology, achlorhydria, hypergastrinemia, and striking gastric glandular hyperplasia arising from an increase in the number of non-acid secretory cells. KCNQ1 exhibited abnormal distribution in gastric glands from kcne2 (-/-) mice, with increased expression in non-acid secretory cells. Parietal cells from kcne2 (+/-) mice exhibited normal architecture but reduced proton secretion, and kcne2 (+/-) mice were hypochlorhydric, indicating a gene-dose effect and a primary defect in gastric acid secretion. These data demonstrate that KCNE2 is essential for gastric acid secretion, the first genetic evidence that a member of the KCNE gene family is required for normal gastrointestinal function.

Topics: Achlorhydria; Animals; Cells, Cultured; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gene Targeting; Hyperplasia; Hypertrophy; KCNQ1 Potassium Channel; Mice; Mice, Inbred C57BL; Mice, Knockout; Parietal Cells, Gastric; Potassium Channels, Voltage-Gated; Protein Subunits; Stomach; Up-Regulation

Epidemiological studies suggest that atrophic corpus-dominant gastritis is an increased risk factor for gastric carcinogenesis. The role of the Helicobacter pylori type IV secretion system (T4SS) for pathogenesis in the Mongolian gerbil model was explored.. Mongolian gerbils were infected for 32 weeks either with H. pylori type I strain B128 or with isogenic mutant strain B128delta cytotoxin-associated gene (cagY) or B128delta cagA , defective in T4SS or in the production of its effector protein CagA, respectively. Quantitative H. pylori reisolation was performed from the gastric antrum and corpus separately, cytokines were measured by quantitative reverse-transcription polymerase chain reaction, and gastric pH and hormones were determined.. B128-infected gerbils harbored high numbers of bacteria in the gastric antrum and corpus, whereas B128delta cagY and B128delta cagA colonized the antrum more densely than the corpus. All infected animals showed a strong antral inflammation and epithelial cell proliferation. B128-infected, rather than mutant-infected, gerbils presented a severe transmural inflammation with huge lymph aggregates, increased proliferation, significant atrophy, and mucous gland metaplasia in the corpus. Plasma gastrin levels and gastric pH values were significantly increased only in B128-infected gerbils. In all infected animals, the expression of the proinflammatory cytokines interleukin 1beta, interferon gamma, and growth-regulated protein was considerably increased in the antrum, but only in wild type-infected animals was an increase seen in the corpus mucosa.. The presence of an intact T4SS allows H. pylori to colonize the gastric corpus. This results in atrophic corpus-dominant gastritis, a severe precancerous condition, thus highlighting T4SS and CagA as major risk factors for gastric cancer development.

Topics: Achlorhydria; Animals; Antigens, Bacterial; Atrophy; Bacterial Proteins; Cytokines; Female; Gastric Mucosa; Gastrins; Gastritis; Gerbillinae; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Helicobacter pylori; Hypertrophy; Mutation; Precancerous Conditions; Promoter Regions, Genetic; Pyloric Antrum; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Virulence

H+/K+-ATPase beta-subunit-deficient mice (129/Sv background) display numerous pathologies in the stomach. Expression of the mutation in BALB/cCrSlc mice results in the development of an aberrant 'mucus-rich' cell population. 'Mucus-rich' cells have been described in stomachs of mice with autoimmune gastritis, a disease mediated by CD4+ T cells. Other pathological features of autoimmune gastritis are similar to those in H+/K+ beta-deficient mice and include a mononuclear cell infiltrate in the gastric mucosa, non-functional or absent parietal cells, depletion of zymogenic cells, hypergastrinaemia, and gastric unit hypertrophy caused by immature cell hyperplasia. The present study investigates further the aberrant gastric 'mucus-rich' cell lineage and analyses the mRNA expression of mucus cell products TFF1 and TFF2. 'Mucus-rich' cells stained for both acidic and neutral mucins, and with a TFF2-specific antibody. Stomachs from both models expressed decreased TFF1 mRNA and reciprocally increased TFF2 mRNA. The involvement of gastrin in regulating trefoil mRNA expression was also investigated using gastrin-deficient mice. In contrast to previous findings, gastrin did not positively regulate TFF1 mRNA expression, but there was possible augmentation of TFF2. Additionally, a clear role for inflammation was established involving both polymorphonuclear and mononuclear cells in these models, and a link was found between mucosal hypertrophy and increased interleukin-11 (IL-11) expression.

Topics: Animals; Autoimmune Diseases; Cytokines; Disease Models, Animal; Gastric Mucosa; Gastrins; Gastritis; Gene Expression Regulation; H(+)-K(+)-Exchanging ATPase; Hyperplasia; Hypertrophy; Interleukin-11; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Mucins; Muscle Proteins; Peptides; RNA, Messenger; Species Specificity; Trefoil Factor-1; Trefoil Factor-2

A prominent pathological feature of murine autoimmune gastritis is a pronounced mucosal hypertrophy. Here, we examined factors that may be responsible for inducing this hypertrophy. Because gastrin is known to be both an inducer of gastric mucosal cell proliferation and is elevated in autoimmune gastritis, mice deficient in gastrin were thymectomised at day 3 and assessed for autoimmune gastritis. Gastrin-deficient mice showed all the characteristic features of murine autoimmune gastritis, including gastric unit hypertrophy due to hyperproliferation and accumulation of immature epithelial cells, decreases in the number of zymogenic and parietal cells, and autoantibodies to the gastric H+/K+-ATPase. Hence, gastrin is not required for either the establishment of chronic gastritis or development of the typical pathological features of this disease. We also examined mRNA levels of a number of gastric mucosal growth factors in RNA samples from mice with hypertrophic autoimmune gastritis. Members of the Reg family, RegIIIbeta and RegIIIgamma, were greatly elevated in mice with hypertrophic gastritis, whereas RegI and amphiregulin (an EGF receptor ligand) were more modestly and/or inconsistently induced. These data demonstrate that induction of gastric mitogenic factors, such as members of the Reg family, can be achieved in inflammatory situations by gastrin-independent pathways. Members of the Reg family, in particular RegIIIbeta and RegIIIgamma, are good candidates to be involved in inducing the mucosal hyperproliferation in autoimmune gastritis. These findings are likely to be of relevance to other gastric inflammatory conditions.

Topics: Amphiregulin; Animals; Autoantibodies; Autoimmune Diseases; Chronic Disease; EGF Family of Proteins; Epidermal Growth Factor; ErbB Receptors; Gastric Mucosa; Gastrins; Gastritis; Gene Expression; Glycoproteins; Growth Substances; H(+)-K(+)-Exchanging ATPase; Heparin-binding EGF-like Growth Factor; Hypertrophy; Intercellular Signaling Peptides and Proteins; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Proteins; RNA, Messenger; Transforming Growth Factor alpha

Stomach changes after major pancreatectomy (Px) are unclear. We previously reported that 90% Px increased stomach weight in rats similarly to endogenous hypergastrinemia by lansoprazole, a proton-pump inhibitor.. To investigate the role of endogenous gastrin in gastric hypertrophy after Px.. In male Wistar rats, we compared the wet weight of the stomach and serum gastrin levels between normal (n = 10) or sham-operated controls (n = 10) and 90% partially pancreatectomized rats (n = 7). Then, using Northern blot analysis, we compared gene expression of gastrin, cholecystokinin-B (CCK-B) receptor, and somatostatin in the stomach among normal controls (n = 7), sham-operated rats (n = 7), and 90% partially pancreatectomized rats (n = 8). The samples were obtained on the third and seventh postoperative days (POD).. Wet weight of the stomach was significantly heavier in the Px rats than in the sham-operated controls (3.90 +/- 0.12 mg/g vs 2.63 +/- 0.07mg/g; p< 0.0001) on the 14th POD. Serum gastrin levels were also higher in the Px rats than in controls (161.4 +/- 13.35 pg/mL vs 110.6 +/- 5.67 pg/mL; p< 0.005) on the 14th POD. Gene expression of gastrin in the stomach on the 7th POD was significantly higher in the Px rats than in the sham-operated rats (p < 0.05), and gene expression of CCK-B receptor clearly increased in the Px rats on the 7th POD, when compared with that of controls (p < 0.05). Gastric somatostatin gene expression in both operated groups increased approximately twice as much as in normal controls after operation (p < 0.005). However, on the 7th POD, it returned to control levels only in Px rats and not in sham-operate rats (p < 0.05).. Increased gene expression of gastrin and CCK-B receptor suggests that gastrin may act as a trophic factor on the stomach after partial Px. Moreover, the relative decrease in gastric somatostatin gene expression may also influence gastric hypertrophy after Px.

Topics: Animals; Blotting, Northern; Gastric Mucosa; Gastrins; Gene Expression Regulation; Hypertrophy; Male; Organ Size; Pancreatectomy; Rats; Rats, Wistar; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; RNA, Messenger; Somatostatin; Stomach; Time Factors

Gastrin/CCK-B receptors (CCKB-Rs) are present on parietal and enterochromaffin-like cells in the gastric mucosa but not on pit cells in the proliferative zone. Because serum gastrin levels are well correlated with the growth of the gastric pit, we examined whether pit precursor cells express CCKB-Rs using hypergastrinemic transgenic mice and a mouse pit precursor cell line, GSM06. In situ hybridization indicated that CCKB-R mRNA was limited to the lower one-third of the mucosa in control mice, whereas it was faintly distributed along the mid- to low glandular region in the hypergastrinemic transgenic mouse mucosa. CCKB-R-positive midglandular cells appear to have a pit cell lineage; therefore, GSM06 cells were used for an [(125)I]gastrin binding study. [(125)I]gastrin bound to the membrane fraction of the GSM06 cells when precultured with gastrin. Gastrin dose dependently induced CCKB-R expression in GSM06 cells and stimulated their growth. Thus these findings suggest that gastrin directly stimulates the growth of the pit cell lineage by inducing its own receptor in pit cell precursors.

Topics: Amino Acid Sequence; Animals; Cell Division; Gastric Mucosa; Gastrins; Gastritis; Gene Expression; Hypertrophy; In Situ Hybridization; Iodine Radioisotopes; Mice; Mice, Inbred ICR; Mice, Transgenic; Molecular Sequence Data; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sincalide; Stem Cells

Gastrin is known to have stimulatory effects on gastric mucosa; however, long-term effect of gastrin stimulation is not well known.. To investigate the long-term effect of hypergastrinaemia, we established hypergastrinaemic transgenic mice by introducing a mutated human gastrin gene. Homozygously transgene-expressing mice showed serum gastrin levels of more than 600 pg/mL.. Neither progastrin nor glycine-extended gastrin titre elevation were observed in hypergastrinaemic transgenic mice. Stomachs from the 30-35-week-old transgenic mice were 30-50% heavier and their mucosa were markedly thicker than those of the controls. The hypertrophic gastric mucosa of hypergastrinaemic transgenic mice consisted of elongated pits with widespread proliferative zones, and comprised depleted glandular regions. In situ hybridization study indicated that expression of H, K-ATPase mRNA in parietal cells of hypergastrinaemic transgenic mice was markedly decreased. By gastrin binding assay in vivo, specific gastrin binding sites were observed in the mid-glandular region of hypergastrinaemic transgenic mice that consisted mainly of prepit cells.. These results suggest that long-term stimulation of gastrin increases the expression of CCK-B/gastrin receptors in the less-differentiated pit cells that are the main component of elongated gastric units, and lessens the well-differentiated characteristics of parietal cells.

Topics: Animals; Cell Differentiation; Gastric Mucosa; Gastrins; Gene Expression; H(+)-K(+)-Exchanging ATPase; Hypertrophy; In Situ Hybridization; Mice; Mice, Inbred ICR; Mice, Transgenic; Parietal Cells, Gastric; RNA, Messenger

ECL cells in the oxyntic mucosa of stomach control gastric acid secretion by mobilizing histamine in response to gastrin. They respond to gastrin also with hypertrophy and hyperplasia. ECL cells exhibit functional impairment upon long-term gastrin stimulation. The impairment is manifested in a gradual decline of the activity of the histamine-forming enzyme per individual ECL cell and in a failure of gastrin to mobilize histamine. The mechanism behind this impairment is unknown. In the present study, rats were treated with the proton pump inhibitor pantoprazole for 45 days to induce sustained hypergastrinemia. The ECL cells were isolated from normogastrinemic and hypergastrinemic rats and size-separated from other mucosal cells by the elutriation technique. The total ECL cell number was twofold higher in hypergastrinemic rats than in normogastrinemic rats, and most of the cells appeared in elutriation fractions where large cells predominate. The ECL cells of the different fractions were analyzed by quantitative electron microscopy. Normal-sized ECL cells from hypergastrinemic rats displayed a reduced number of secretory vesicles (probably because of degranulation) compared with normal-sized ECL cells from normogastrinemic rats. Hypertrophic ECL cells from hypergastrinemic rats had an unchanged number of secretory vesicles, supporting the view that such cells fail to respond to gastrin with degranulation. Although both normal-sized and hypertrophic ECL cells from hypergastrinemic rats contained vacuoles, those in the hypertrophic ECL cells were larger and more numerous. In addition, hypertrophic ECL cells were found to contain numerous, prominent lipofuscin bodies which are the presumed end product of crinophagia. Conceivably therefore, large vacuoles and lipofuscin bodies cause functional impairment of the hypertrophic ECL cells.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Benzimidazoles; Cell Division; Cell Size; Enterochromaffin-like Cells; Enzyme Inhibitors; Female; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Histamine Release; Histidine Decarboxylase; Hypertrophy; Lipofuscin; Microscopy, Electron; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rats; Rats, Sprague-Dawley; Secretory Vesicles; Stomach; Sulfoxides; Time Factors; Vacuoles

Despite multiple and often contradictory research, no firm conclusions regarding the role of hypergastrinaemia in infantile hypertrophic pyloric stenosis (IHPS) have been established. Evaluation of somatostatin, the main physiological antagonist of gastrin, has not been assessed in previous studies. Long-term evaluation following pyloromyotomy suggests persistent abnormalities in gastrin and somatostatin in IHPS. The objective of this case-controlled study was to compare fasting serum gastrin and somatostatin levels in IHPS. Serum sample were collected from 39 children with IHPS at the time of pyloromyotomy and 20 age-matched controls with no evidence of gastrointestinal disease. Standard radioimmunoassay techniques were used to detect circulating levels of the hormones. A two-tailed t-test was used for statistical analysis. The levels of the two hormones (mean +/- SEM) revealed that there was no evidence of hypergastrinaemia in IHPS compared with controls (75.6 +/- 16.1 and 68.1 +/- 7.8 ng l(-1), respectively), but that the level of somatostatin was significantly elevated (38.9 +/- 6.4 and 30.5 +/- 5.8 ng l(-1), p = 0.016). An inverse trend in the gastrin/somatostatin levels could not be identified in IHPS.. Somatostatin but not gastrin is raised in IHPS. Somatostatin is known to inhibit the actions of inhibitory neurotransmitters in the pylorus and may explain the development of pylorospasm, which is believed to be important in the development of pyloric tumours. These results do not agree with a previous long-term follow-up study, but reflect the hormonal imbalance at the time of pyloric hypertrophy.

Topics: Biomarkers; Case-Control Studies; Fasting; Gastrins; Humans; Hypertrophy; Infant; Pyloric Stenosis; Somatostatin

The gastric H(+)/K(+)-ATPase is essential for normal development of parietal cells. Here we have directly assessed the role of the H(+)/K(+)-ATPase beta-subunit (H/K-beta) on epithelial cell development by detailed quantitation of the epithelial cell types of the gastric mucosa of H/K-beta-deficient mice. H/K-beta-deficient mice had a 3.1-fold increase in the number of immature cells per gastric unit; however, the numbers of surface mucous and parietal cells were similar to those in the gastric units of wild-type mice. The effect of elevated gastrin levels in the H/K-beta-deficient mice was determined by producing mice that are also deficient in gastrin. We demonstrated that the increased production of immature cells and resulting hypertrophy is caused by the overproduction of gastrin. However, the depletion of zymogenic cells, which is another feature of H/K-beta-deficient mice, is independent of hypergastrinemia. Significantly, parietal cells of H/K-beta- and gastrin-deficient mice had abnormal secretory membranes and were devoid of resting tubulovesicular membranes. Together these data suggest a homeostatic mechanism limiting the number of immature cells that can develop into end-stage epithelial cells and indicate a direct role for H/K-beta in the development of mature parietal cells.

Topics: Animals; Cell Count; Cell Death; Cell Division; Cyclins; Epithelial Cells; Gastric Mucosa; Gastrins; H(+)-K(+)-Exchanging ATPase; Hydrogen-Ion Concentration; Hypertrophy; Mice; Mice, Inbred BALB C; Mice, Knockout; Microscopy, Electron; Parietal Cells, Gastric; Phenotype; Proliferating Cell Nuclear Antigen

Gastrin has a growth-promoting effect on the oxyntic mucosa of the stomach but has been claimed also to affect other parts of the gastrointestinal tract and pancreas. This report describes the effects of the cholecystokinin, (CCK2) receptor antagonists YM022 and YF476 on various growth parameters in the gastrointestinal tract and pancreas of the rat. YM022 and YF476 were given subcutaneously in doses known to produce maximum and sustained CCK2 receptor blockade. The body weight was not affected. However, the oxyntic mucosal weight, thickness and protein and DNA contents were reduced by 15-20% already within 1-2 days and by about 30% after 4-8 weeks of CCK2 receptor blockade. Hence, the response of the oxyntic mucosa to CCK2 receptor blockade was in the form of hypotrophy (reduced protein content) and hypoplasia (reduced DNA content). There were no obvious effects of CCK2 receptor blockade on the intestine or pancreas (nor on liver, kidney or thyroid). The proton pump inhibitor omeprazole was used to induce hypergastrinaemia and was given with or without YM022. Omeprazole treatment for 4 weeks increased the oxyntic mucosal weight and thickness by 15-20%. YM022 prevented these effects. We conclude that while elevated circulating gastrin levels, acting on CCK2 receptors, exert a growth-promoting effect on the oxyntic mucosa (but not elsewhere), normal serum gastrin levels exert a mucosa-preserving effect.

Topics: Animals; Benzodiazepines; Benzodiazepinones; Digestive System; Drug Interactions; Gastrins; Hormone Antagonists; Hyperplasia; Hypertrophy; Male; Omeprazole; Pancreas; Parietal Cells, Gastric; Phenylurea Compounds; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin B; Receptors, Cholecystokinin

Hypergastrinemia occurs frequently in association with acid suppression and Helicobacter infection, but its role in the progression to gastric atrophy and gastric cancer has not been well defined.. The effects of hypergastrinemia, and possible synergy with Helicobacter felis infection, were investigated in insulin-gastrin (INS-GAS) transgenic mice.. INS-GAS mice initially showed mild hypergastrinemia, increased maximal gastric acid secretion, and increased parietal cell number but later progressed to decreased parietal cell number and hypochlorhydria. Development of gastric atrophy was associated with increased expression of growth factors, heparin-binding epidermal growth factor and transforming growth factor alpha. At 20 months of age, INS-GAS mice showed no evidence of increased enterochromaffin-like cell number, but instead exhibited gastric metaplasia, dysplasia, carcinoma in situ, and gastric cancer with vascular invasion. Invasive gastric carcinoma was observed in 6 of 8 INS-GAS mice that were >20 months old. Helicobacter felis infection of INS-GAS mice led to accelerated (< or = 8 mo) development of intramucosal carcinoma (85%), with submucosal invasion (54%) and intravascular invasion (46%; P < or = 0.05).. These findings support the unexpected conclusion that chronic hypergastrinemia in mice can synergize with Helicobacter infection and contribute to eventual parietal cell loss and progression to gastric cancer.

Topics: Animals; Cell Count; Epidermal Growth Factor; Epithelial Cells; Gastric Acid; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Heparin; Heparin-binding EGF-like Growth Factor; Hyperplasia; Hypertrophy; Intercellular Signaling Peptides and Proteins; Metaplasia; Mice; Mice, Transgenic; Stomach Neoplasms; Transforming Growth Factor alpha

Gastrin is a peptide hormone involved in the growth of both normal and malignant gastrointestinal tissue. Recent studies suggest that the glycine-extended biosynthetic intermediates mediate many of these trophic effects, but the in vivo relevance of glycine-extended gastrin (G-Gly) has not been tested. We have generated mice (MTI/G-GLY) that overexpress progastrin truncated at glycine-72 to evaluate the trophic effects of G-Gly in an in vivo model. MTI/G-GLY mice have elevated serum and colonic mucosal levels of G-Gly compared with wild-type mice. MTI/G-GLY mice had a 43% increase in colonic mucosal thickness and a 41% increase in the percentage of goblet cells per crypt. MTI/G-GLY mice exhibited increased colonic proliferation compared with wild-type controls, with an expansion of the proliferative zone into the upper third of the colonic crypts. Continuous infusion of G-Gly into gastrin-deficient mice for two weeks also resulted in elevated G-Gly levels, a 10% increase in colonic mucosal thickness, and an 81% increase in colonic proliferation when compared with gastrin-deficient mice that received saline alone. To our knowledge, these studies demonstrate for the first time that G-Gly's contribute to colonic mucosal proliferation in vivo.

Topics: Animals; Cell Division; Colon; Gastrins; Gastrointestinal Neoplasms; Gene Expression; Glycine; Goblet Cells; Humans; Hyperplasia; Hypertrophy; Male; Mice; Mice, Transgenic; Protein Precursors; Stomach; Tumor Cells, Cultured

Gastrin stimulates the growth of gastric mucosa by increasing mostly its glandular region but is not known to induce the growth of a pit region where its major constituent cells, gastric surface mucous (GSM) cells, turn over rapidly. To investigate the effect of gastrin on GSM cells, we generated hypergastrinemic mice by expressing a human gastrin transgene. We obtained a hypergastrinemic mouse line whose average serum gastrin level is 671 +/- 252 pg/ml (normal level <150 pg/ml). Gastrin-positive cells were found in the fundic mucosa. The gastric mucosa exhibited hypertrophic growth, which was characterized by an elongated pit with an active proliferative zone, but the glandular region containing parietal cells was normal or reduced in size. The GSM cells contained fewer mucous granules than those of control littermates and lost reactivity to the GSM cell-specific cholera toxin beta-subunit lectin. GSM cells along the foveolar region and many mucous neck cells became Alcian blue positive, suggesting the appearance of sialomucin in these cells. We suggest that gastrin stimulates the growth of the proliferative zone of gastric glands, which results in the elongation of the pit region whose GSM cells exhibit less-differentiated features.

Topics: Animals; Base Sequence; Cell Differentiation; Endocrine Glands; Gastric Mucosa; Gastrins; Humans; Hypertrophy; Mice; Mice, Transgenic; Molecular Sequence Data

To examine the effect of gastrin on spontaneous and induced pancreatic carcinogenesis in the hamster.. Two sets of experiments were carried out, one involving long term hypergastrinaemia and one involving cancer induction during hypergastrinaemia. The effect of hypergastrinaemia accomplished by gastric fundectomy was studied for eight months. Neither fundectomised hamsters nor sham operated controls developed premalignant or malignant pancreatic lesions. In the fundectomy group, the mean pancreatic weight, total protein content, and DNA content was increased by 28%, 25%, and 25% respectively. No such increases were found in fundectomised animals receiving a cholecystokinin-B receptor antagonist during the last 24 days of the experiment. In the cancer induction study, the effect of fundectomy on N-nitrosobis(2-oxopropyl) amine induced pancreatic carcinogenesis was studied for three months. There were no significant differences in the incidence or [3H]-thymidine labelling index of focal pancreatic lesions between fundectomised and sham operated control animals.. Fundectomy with chronic hypergastrinaemia induces pancreatic hypertrophy, but does not enhance N-nitrosobis (2-oxopropyl)amine induced pancreatic carcinogenesis in the hamster. The increases in growth were inhibited by a cholecystokinin-B receptor antagonist, indicating that the trophic effect of fundectomy is mediated by gastrin.

Topics: Animals; Benzodiazepinones; Carcinogens; Cholecystokinin; Cricetinae; Disease Models, Animal; Gastric Fundus; Gastrins; Hypertrophy; Male; Mesocricetus; Neoplasms, Experimental; Nitrosamines; Pancreas; Pancreatic Neoplasms; Phenylurea Compounds; Receptors, Cholecystokinin

Previously, we have investigated the effects of short-term (minutes to hours) and long-term (weeks to months) stimulation with gastrin on the histamine-producing enterochromaffin-like (ECL) cells in the oxyntic mucosa of rat stomach. The present study examines the response of the ECL cells of freely fed rats to sustained hypergastrinemia over a time span of a few hours to four weeks. Sustained hypergastrinemia was induced by the continuous subcutaneous infusion of human Leu15-gastrin-17. The histidine decarboxylase (HDC) activity and histamine concentration in the oxyntic mucosa were monitored throughout the study. ECL cell profiles in electron micrographs were analysed planimetrically. The HDC activity displayed a 4-fold increase within the first two days. Subsequently, it remained at a plateau. The histamine concentration increased 2- to 3-fold in response to gastrin. The rise in histamine was slower than the rise in HDC activity. At no time point was there a reduced concentration of histamine. The ECL cells increased in size after 4 days of hypergastrinemia, reaching a maximum cell profile area after 2 weeks and remaining enlarged for the duration of the study. The secretory vesicles were reduced in number after 1 day, returning gradually to the pre-stimulation value thereafter; their volume density remained reduced during the 6-day observation period. Vacuoles started to appear after 1 day of hypergastrinemia and their number and volume density increased, reaching a maximum after 4 days. The number and volume density of the microvesicles increased and plateaued after 2 days of hypergastrinemia. The number of granules per cell profile was unaffected but their volume density was greatly reduced after 4 days of hypergastrinemia (reflecting the ECL cell hypertrophy). The present findings establish the time course of activation of the ECL cells in response to sustained hypergastrinemia over a time span of a few hours to four weeks; a new "steady state" situation at a high level of activity has been established after about a week.

Topics: Animals; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Histidine Decarboxylase; Humans; Hypertrophy; Male; Rats; Time Factors

Many peptide hormone and neurotransmitter receptors belonging to the seven membrane-spanning G protein-coupled receptor family have been shown to transmit ligand-dependent mitogenic signals in vitro. However, the physiological roles of the mitogenic activity through G protein-coupled receptors in vivo remain to be elucidated. Here we have generated G protein-coupled cholecystokinin (CCK)-B/gastrin receptor deficient-mice by gene targeting. The homozygous mice showed a remarkable atrophy of the gastric mucosa macroscopically, even in the presence of severe hypergastrinemia. The atrophy was due to a decrease in parietal cells and chromogranin A-positive enterochromaffin-like cells expressing the H+,K(+)-ATPase and histidine decarboxylase genes, respectively. Oral administration of a proton pump inhibitor, omeprazole, which induced hypertrophy of the gastric mucosa with hypergastrinemia in wild-type littermates, did not eliminate the gastric atrophy of the homozygotes. These results clearly demonstrated that the G protein-coupled CCK-B/gastrin receptor is essential for the physiological as well as pathological proliferation of gastric mucosal cells in vivo.

Topics: Animals; Atrophy; Chromaffin Cells; Chromogranin A; Chromogranins; DNA Probes; Gastric Mucosa; Gastrins; Gene Expression; Genomic Library; H(+)-K(+)-Exchanging ATPase; Histidine Decarboxylase; Homozygote; Humans; Hypertrophy; Mice; Mice, Knockout; Omeprazole; Parietal Cells, Gastric; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Signal Transduction; Sincalide

Because somatostatin (SS) inhibits basal and stimulated gastric acid secretion and gastrin release, it is conceivable that decreased gastric SS concentration may be one of the factors responsible for hypergastrinemia found in patients formerly operated on for hypertrophic pyloric stenosis (HPS). To investigate this issue, the SS-like immunoreactivity (SLI) concentration was estimated in antral and fundic mucosal samples from control and HPS children. In addition, SS binding to cytosol from gastric mucosa (fundus and antrum), fasting serum gastrin levels, and serum gastrin response to a standard breakfast were studied. The mean fundic and antral SLI concentrations were significantly lower in HPS children than in controls. The depletion of fundic and antral SLI content was associated with an increase in the number of gastric SS binding sites. The fasting serum gastrin levels and serum gastrin responses to the standard breakfast (after 60 minutes) of HPS children were significantly higher than those of controls. Since, together with the increase of SS binding to gastric mucosa, there is an increase in the gastrin serum levels, despite the inhibitor effect of SS on gastrin release, the binding capacity cannot be the main factor determining the response to SS in children with HPS. The present results suggest that both SS and gastrin have a role in the pathogenesis of HPS.

Topics: Adolescent; Binding Sites; Child; Child, Preschool; Female; Follow-Up Studies; Gastric Fundus; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Hypertrophy; Male; Pyloric Antrum; Pyloric Stenosis; Radioimmunoassay; Somatostatin; Stomach

Mechanisms for the hypertrophy of rat pancreas induced by long-term administration of bethanechol were investigated. The administration of bethanechol, an acetylcholine receptor agonist, to male Wistar rats for 14 days induced significant increases in the pancreatic weight and contents of protein, amylase and RNA in the pancreas without altering the content of DNA and the incorporation of [3H]thymidine into DNA. Simultaneous administration of atropine with bethanechol suppressed the bethanechol-induced pancreatic hypertrophy. Long-term administration of other acetylcholine receptor agonists also showed similar effects as produced by bethanechol. CR1505 (loxiglumide; D,L-4-(3,4-dichlorobenzoyl-amino)-5-(N-3-methoxypropyl-pentylam ino)-5- oxopentanoic acid), an antagonist of cholecystokinin receptors, inhibited pancreatic growth induced by long-term administation of pentagastrin, whereas pancreatic hypertrophy induced by bethanechol was not inhibited by CR1505. These results suggest that long-term administration of bethanechol induces pancreatic hypertrophy through direct activation of muscarinic receptors in the pancreas.

Topics: Amylases; Animals; Atropine; Bethanechol; Cholinergic Agonists; Cholinergic Antagonists; Drug Administration Schedule; Drug Interactions; Gastrins; Hypertrophy; Male; Organ Size; Pancreas; Pentagastrin; Proglumide; Rats; Rats, Wistar; Receptors, Cholecystokinin; Sincalide

Omeprazole, a long-acting inhibitor of gastric acid secretion, is able to increase the circulating concentrations of gastrin. Daily treatment with high doses of omeprazole cause sustained hypergastrinemia. Long-standing hypergastrinemia can be expected to exert numerous effects in the body. For instance, gastrin has been proposed to promote growth in the digestive tract and pancreas. The present study is concerned with the effect of omeprazole on parathyroid glands in the chicken.. Chickens were treated with omeprazole (400 mumol/kg/day) in methylcellulose (2.5 ml/kg) for 5 or 10 weeks. Controls received vehicle. Blood calcium and serum gastrin concentrations were studied. The weight gain of the animals and of various organs (proventriculus, antrum, thyroids, parathyroids, ultimobranchial glands, and femur) were determined. The DNA content and the size of the parathyroid chief cells were also determined.. Omeprazole reduced the body weight gain while greatly increasing the weight of the proventriculus and the parathyroid glands. The weight and density of the femur were reduced. The circulating concentrations of calcium were unaffected. The DNA content of the parathyroid glands was increased, and morphometric analysis of the parathyroid chief cells showed an increased cell size. Thus, the increased parathyroid gland weight seems to reflect both hypertrophy and hyperplasia. There was a slight increase in the weight of the ultimobranchial glands (expressed per kilogram body weight). The weight of the thyroids was unaffected (expressed in relation to body weight).. The results indicate that omeprazole treatment in chickens leads not only to trophic effects in the acid-producing gastric mucosa (probably because of the ensuing hypergastrinemia), as reported earlier, but also to growth of the parathyroid glands (both hypertrophy and hyperplasia) and to bone loss without affecting blood calcium values. The mechanism behind these effects remains unknown.

Topics: Animals; Bone Density; Chickens; DNA; Gastrins; Hyperplasia; Hypertrophy; Omeprazole; Organ Size; Parathyroid Glands; Proventriculus; Thyroid Gland; Weight Gain

The effect of gastric fundectomy with hypergastrinaemia on the pancreas in rats was studied for 14 months. Rats with hypercholecystokininaemia that had had a pancreaticobiliary diversion (PBD) operation and sham operated rats served as controls. Fundectomised rats showed a significant increase in pancreatic weight and total DNA and protein content compared with sham operated rats. DNA flow cytometry showed a significantly higher ratio of tetraploid to diploid nuclei in pancreatic tissue after fundectomy than after sham operation. Mean values of all these variables were significantly lower after fundectomy than after PBD. Acidophilic atypical acinar cell foci of the pancreas were diagnosed in both fundectomised and PBD operated rats, but not in sham operated controls. The volume density and 3H-thymidine labelling index of the acidophilic atypical acinar cell foci were significantly lower after fundectomy than after PBD. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. In conclusion, fundectomy lasting about half of the life span in rats causes pancreatic hyperplasia and hypertrophy, as well as development of acidophilic atypical acinar cell foci. Although hypergastrinaemia is a prominent feature, it may not be the only factor responsible for this pancreaticotrophical effect of fundectomy.

Topics: Animals; Autoradiography; Body Weight; Cholecystokinin; DNA; Gastric Fundus; Gastrins; Hypertrophy; Male; Organ Size; Pancreas; Ploidies; Rats; Rats, Wistar; Time Factors

The histamine-producing enterochromaffin-like (ECL) cells in the acid-producing portion of the rat stomach responded to long-standing hypergastrinemia (omeprazole treatment daily for 8-10 weeks) with hypertrophy (and hyperplasia) and with a reduced number of granules and vesicles per unit cytoplasm. There was a reduction in the ratio of electron-dense granules versus vesicles and an increase in the profile diameter of the vesicles. Also, portacaval shunting (PCS) induced changes in the ECL cells, manifesting (i) as an increase in cell number and size, and (ii) as a reduced number of granules and vesicles per unit area. The cytoplasmic granules and vesicle profiles were enlarged, and the ratio of granules versus vesicles was reduced. The combination of PCS and long-standing hypergastrinemia (omeprazole treatment) produced a greatly enhanced ECL cell hypertrophy (and hyperplasia) and a marked reduction in the number of granules. The ratio of granules versus vesicles was markedly reduced while the profile diameters of both granules and vesicles were increased. The relative predominance of very large vesicles (vacuoles) was a prominent feature of the ECL cells in these rats.

Topics: Animals; Enterochromaffin Cells; Gastrins; Hyperplasia; Hypertrophy; Male; Microscopy, Electron; Omeprazole; Portacaval Shunt, Surgical; Rats; Rats, Sprague-Dawley; Stomach

Gastrin is an important trophic hormone for the acid-producing part of the stomach. There is no solid evidence that gastrin is physiologically important as a trophic agent outside the stomach. The trophic effects in the stomach are manifested as an increased weight and thickness of the oxyntic mucosa and can be induced by both exogenous and endogenous gastrin--that is, in situations of long-lasting hypergastrinemia (treatment with effective antisecretagogues, partial fundectomy, or antrum exclusion). Removal of endogenous gastrin by antrectomy induces the opposite effects--that is, diminished weight and thickness of the oxyntic mucosa. Unlike all other peptide hormone-producing endocrine cells in the oxyntic mucosa, the so-called enterochromaffin-like (ECL) cells respond readily to gastrin. An acute gastrin challenge results in release of stored products from the ECL cells (such as histamine) and activation of cytoplasmic enzymes (such as histidine decarboxylase). Sustained elevation of circulating gastrin over days results in hypertrophy of the ECL cells and over weeks results in marked hyperplasia (at most a fivefold increase in the rat). The results in other species are similar but often somewhat less marked than in the rat.

Topics: Animals; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Histamine Release; Hyperplasia; Hypertrophy; Parietal Cells, Gastric; Rats

Studies in the rat have shown that partial gastric corpectomy, in which about 75% of the acid-producing oxyntic mucosa was removed, leads to markedly reduced acid secretion and a feedback increase in the plasma gastrin levels. Ten weeks after operation, the gastric enterochromaffin (ECL)-like cell density in the remaining part of the oxyntic mucosa had increased significantly. In the present study, the effects on the gastric ECL cells of lifelong persistent hypergastrinemia induced by partial (75%) corpectomy have been investigated. Seventy-five partially corpectomized rats and 40 control rats were investigated for plasma gastrin and oxyntic mucosal changes in a 124-week study. The partially corpectomized rats showed increased plasma gastrin levels after the operation; the mean increase compared with the controls was almost 10-fold during the entire study. The remaining oxyntic mucosa of the partially corpectomized rats differed from that of control rats in two respects, showing first general hypertrophy and second a marked hyperplasia of argyrophil ECL cells. The degree and incidence of these changes increased towards the end of the study, i.e., in the aging rats. An age-related increase in ECL-cell density occurred spontaneously also in the control rats but to a lesser extent than in the partially corpectomized group. ECL-cell carcinoids were found in the oxyntic mucosa of 26 of the 75 partially corpectomized rats. The first carcinoid was found 78 weeks after the beginning of the study. Six rats with carcinoids (23%) were found before week 104 (2 years) and the remainder, 20 (77%), were discovered later. No carcinoid tumor was found in the control rats. It is concluded that lifelong hypergastrinemia induced by partial corpectomy leads to the development of ECL-cell carcinoids in the oxyntic mucosa of some rats towards the end of their life span. This observation strongly supports the hypothesis that the gastric ECL-cell carcinoids found in rats treated with antisecretory drugs are caused by long-standing hypergastrinemia developing secondary to inhibition of gastric acid secretion.

Topics: Animals; Body Weight; Carcinoid Tumor; Enterochromaffin Cells; Feedback; Female; Gastric Mucosa; Gastrins; Hyperplasia; Hypertrophy; Parietal Cells, Gastric; Rats; Rats, Inbred Strains; Stomach; Stomach Neoplasms; Time Factors

Topics: Child, Preschool; Follow-Up Studies; Gastrins; Humans; Hypertrophy; Infant; Infant, Newborn; Postoperative Period; Pyloric Stenosis; Time Factors

Since little is known about the pathophysiology of pyloric stenosis, we created a partial gastric outlet obstruction in 13 Wistar rats by placing a nonabsorbable ligature of defined size around the pylorus. Sham operations were performed in 10 rats. The animals from both groups were killed after four months. G-cell count and gastrin content were determined in 10 parallel strips, which were cut by razor blades mounted on a handle. Gastric size and weight as well as thickness of mucosal and muscular layers and serum gastrin concentration were also determined. Body weight of the animals with pyloric stenosis was lower and gastric weight higher than that of the controls. Furthermore, we found an enlarged G-cell area and G-cell hyperplasia, an increased surface area and thickness of the mucosal and muscular layers of the stomach, and in the majority of rats, elevated serum gastrin levels. Total G-cell count was 583,720 +/- 90,561 in the rats with pyloric stenosis and 385,775 +/- 15,820 (mean +/- SEM) in the control rats (P less than 0.04). We conclude that partial gastric outlet obstruction in rats leads to G-cell hyperplasia and that this experiment may serve as a model for pyloric stenosis in man.

Topics: Animals; Body Weight; Cell Count; Chromaffin System; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Hyperplasia; Hypertrophy; Male; Organ Size; Pyloric Stenosis; Rats; Rats, Inbred Strains; Stomach

The effect of ileo-jejunal transposition (IJT) on the intestinal adaptation after total colectomy was investigated in 4 mongrel dogs. Hyperenteroglucagonemia was observed in the IJT with colectomy group, especially in postprandial state. Obvious hyperplastic changes were observed in all part of the small intestinal mucosa in the colectomy with IJT group. However, there were no significant differences in body weight changes between the colectomy with IJT group and the colectomy group. Postprandial plasma gastrin levels were lower in the colectomy with IJT group compared to the control. These results suggest that IJT causes hyperenteroglucagonemia and intestinal mucosal hypertrophy in colectomized dogs. Enteroglucagon may have an inhibitory effect on postprandial gastrin release.

Topics: Adaptation, Physiological; Animals; Body Weight; Colectomy; Dogs; Gastrins; Glucagon; Glucagon-Like Peptides; Hypertrophy; Ileum; Intestinal Mucosa; Intestines; Jejunum; Peptides

The gastrointestinal tract harbors several populations of peptide containing nerve fibers. Among the gut neuropeptides are vasoactive intestinal peptide (VIP), substance P, enkephalin, and gastrin releasing peptide (GRP). We have examined specimens from five patients with pyloric stenosis and from five controls immunocytochemically with respect to the density of nerve fibers containing VIP, substance P, enkephalin, or GRP. In the control specimens VIP and enkephalin fibers were fairly numerous, whereas substance P and GRP fibers were few. In the pyloric stenosis patients the density of VIP fibers and enkephalin fibers was reduced in the smooth muscle. In the myenteric ganglia there was no such reduction. Substance P and GRP fibers were rare as in controls. The results indicate a reduction of VIP and enkephalin fibers in smooth muscle in pyloric stenosis patients and may be interpreted to support the view that an impaired neuronal function is involved in the pathophysiology of pyloric stenosis.

Topics: Enkephalins; Female; Fluorescent Antibody Technique; Gastrin-Releasing Peptide; Gastrins; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Muscle, Smooth; Nerve Fibers; Peptides; Pyloric Stenosis; Substance P; Vasoactive Intestinal Peptide

Omeprazole is a long acting inhibitor of gastric acid secretion in different species including rat and dog. Due to the long duration of action, steady state inhibition at repeated once daily administration is reaches within 4-5 days in dogs and in about 3 days in rats. Daily dosing at high dose levels results in virtually complete 24-hour inhibition of acid secretion in experimental animals. The elimination of the inhibitory feedback effect of acid on gastrin secretion leads to hypergastrinaemia. Because gastrin has a trophic effect on the oxyntic mucosa, the hypergastrinaemia results in a reversible hypertrophy of the oxyntic mucosa and an increased capacity to produce acid following maximal stimulation with exogenous secretagogues after discontinuing treatment. Despite the increased capacity to produce acid, basal acid secretion seems to be unchanged. The pronounced hypergastrinaemia which occurs during long-term treatment with high doses rapidly normalizes after discontinuing treatment. The hyperplasia of the oxyntic endocrine ECL cells, and the eventual development of gastric ECL cell carcinoids after lifelong treatment of rats with high doses, can also be attributed to the hypergastrinaemia developing after almost complete elimination of gastric acid secretion in these animals.

Topics: Animals; Anti-Ulcer Agents; Benzimidazoles; Carcinoid Tumor; Dogs; Female; Gastric Acid; Gastric Mucosa; Gastrins; Hypertrophy; Male; Omeprazole; Rats; Stomach Neoplasms; Time Factors

Hypo- or anacidity, caused by antisecretagogues, stimulates gastrin release and leads to hypergastrinaemia. If drug treatment is maintained over a period of time, the hypergastrinaemia can be expected to give rise to trophic effects. We examined the trophic consequences of the very marked hypergastrinaemia produced by long-term treatment (16-20 weeks) of rats with large doses of the substituted benzimidazole, omeprazole, a potent and long-acting blocker of acid secretion. The weight of the stomach and the oxyntic mucosal thickness were increased, whereas the weight of the pancreas and the intestines and the thickness of the mucosa of the antrum and small and large intestine were unaffected. The number of exocrine cells (parietal, zymogen and mucous cells) were uniformly increased by 25-30%. The density of parietal and zymogen cells, expressed as number of cell nuclei per mm2 epithelium, was unchanged. The volume density of parietal cells, expressed as % of epithelial volume, was also unchanged, implying that the volume of the individual parietal cell had not increased. The density of endocrine ECL cells in the stomach increased 5-fold. Thus, the findings demonstrate a growth-promoting effect of the hypergastrinaemia on the oxyntic mucosa, the ECL cells in particular, and the lack of such an effect on the antrum, pancreas and intestines.

Topics: Animals; Benzimidazoles; Cytoplasmic Granules; Female; Gastric Acid; Gastric Mucosa; Gastrins; Hypertrophy; Intestinal Mucosa; Intestines; Male; Omeprazole; Pancreas; Parietal Cells, Gastric; Rats; Rats, Inbred Strains; Secretory Rate; Stomach

Hypertrophic gastritis, histologically characterized by a depletion of parietal and chief cells and by varying degrees of lymphocyte infiltration along the thickened muscularis mucosa, could be induced by neonatal thymectomy (Tx) without any additional treatment in about 50% of mice (C3H/HeMs X 129/J)F1 (C3.129). The thickness of the mucosa in gastritic mice increased with age, forming giant folds. In Tx mice with an early stage of abnormal mucosal folds at 6 months of age, numbers of parietal cells per mucosal tissue unit area (parietal cell densities) and ratios of parietal cells to mucous cells became lower than in control mice, and serum gastrin levels became contrastingly higher with the increasing severity of gastritis. Circulating antibodies against parietal cells (APA) were detected by indirect immunofluorescence (IFL) in the mice. A good correlation was observed between APA and gastritis: APA with high titers (more than 1,000-fold dilutions) appeared when severe lesions were found. In mice with giant mucosal folds at 18 months of age, serum protein levels were within normal limits, but fecal clearance rates of 125I-labelled polyvinylpyrrolidone (125I-PVP) were significantly increased. These results suggest that the hypertrophic gastritis induced by neonatal Tx is characterized by hypergastrinemia due to parietal cell depletion caused by the presence of circulating APA and the protein loss from the hypertrophic mucosa. Both histological and physiopathological similarities were found between the gastritis in the mice and Menetrier's disease in man.

Topics: Animals; Animals, Newborn; Autoantibodies; Blood Proteins; Disease Models, Animal; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Hypertrophic; Hypertrophy; Immunoglobulin G; Male; Mice; Thymectomy

Antral somatostatin-immunoreactive cells (D cells) were counted pre- and postoperatively in 20 patients with duodenal ulcer and in 8 patients with gastric ulcer. Counts were obtained either over a 2-yr postoperative period (duodenal ulcer patients) at intervals of 0.5, 1, and 2 yr or over a greater than or equal to 4-yr postoperative period (gastric ulcer patients) at intervals of 1-2 yr. In patients with a normal population of gastrin-immunoreactive cells (G cells), the D cells were within the normal range (mean value 0.53% in duodenal ulcer patients and 0.67% in gastric ulcer patients). High G-cell values were accompanied by high D-cell values (e.g., in gastrin-cell hyperplasia) and low G-cell values were accompanied by low D-cell values. The G-cell to D-cell ratio was 8:1 and 6.6:1 in duodenal and gastric ulcer patients, respectively. After selective proximal vagotomy and pyloroplasty, the following observations were made: the relation of number of G cells to number of D cells remained unchanged; the postoperative rise in G-cell population was accompanied by a rise in D-cell population; hypertrophy of the D cells was apparent as was postoperative hyperplasia, with a postoperative increase in D-cell size. Morphologic coupling of the gastrin-somatostatin system in the antrum is assumed. This is constant in ulcer disease both before and after vagotomy.

Topics: Adult; Cell Count; Duodenal Ulcer; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Hyperplasia; Hypertrophy; Immunoenzyme Techniques; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer; Vagotomy

Topics: Adaptation, Physiological; Animals; Gastrectomy; Gastrins; Hypertrophy; Ileum; Intestinal Mucosa; Jejunum; Mitotic Index; Pentagastrin; Rats

Serum gastrin levels in 16 patients with congenital hypertrophic pyloric stenosis (CHPS) were measured and oesophageal manometric studies were performed in 14 of these 16 patients before and after pyloromyotomy. Hypergastrinaemia was found in the patients with CHPS, and the 7th postoperative serum gastrin level was much higher than the preoperative pressure. However, there was no significant correlation between the LES pressure change and the serum gastrin change. These results indicate that competence of LES after pyloromyotomy in patients with CHPS is maintained not only by endogenous gastrin rise but also by other factors.

Topics: Esophagogastric Junction; Female; Gastrins; Humans; Hypertrophy; Infant; Male; Manometry; Postoperative Complications; Pyloric Stenosis

Topics: Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Hypertrophy; Infant; Infant, Newborn; Neurotensin; Pyloric Stenosis; Radioimmunoassay; Somatostatin

Topics: Animals; Disease Models, Animal; Equipment Design; Foreign Bodies; Gastrins; Hypertrophy; Male; Obesity; Rats; Stomach; Stomach Diseases

Topics: Adult; Animals; Gastrins; Humans; Hypertrophy; Infant; Infant, Newborn; Pyloric Stenosis

Topics: Adult; Female; Fetal Blood; Gastrins; Humans; Hypertrophy; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Neoplastic; Pyloric Stenosis; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Hypertrophy; Infant; Pyloric Stenosis; Radioimmunoassay

Genitourinary anomalies were looked for in patients with congenital hypertrophic pyloric stenosis. In a prospective series of 64 patients investigated by intravenous pyelography, 13 were abnormal (20.6%). In a retrospective series of 232 patients, 6 had anomalies of the upper urinary tract (2.7%). In this latter series the incidence of inguinal hernia (3.4%), undescended testes (3.0%), and hypospadias (0.9%) was determined. In another 10 patients urinary tract anomalies (5), urinary infection (2), and a significant family history (3) were found associated with congenital pyloric stenosis. As the incidence of these anomalies is greater than expected, which suggests an interrelationship, a hypothesis has been proposed linking genetic factors and the metabolism of gastrin with the etiology of congenital hypertrophic pyloric stenosis.

Topics: Female; Gastrins; Hernia, Inguinal; Humans; Hypertrophy; Kidney Neoplasms; Male; Prospective Studies; Pyloric Stenosis; Retrospective Studies; Urogenital Abnormalities; Wilms Tumor

Topics: Female; Gastrins; Gastroenteritis; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Pyloric Stenosis; Secretin

Blood serum immunoreactive gastrin level (IRG) was measured in infants with hypertrophic pyloric stenosis before and after corrective surgery and in a control group children of corresponding age. No significant difference in IRG level was found between the stenotic infants and the control group. In the stenotic infants IRG values were higher at the seventh day after than before the operation and significantly higher in those infants in whom gain of body weight was noted during that time as compared with the infants without gain of weight. These observations remain in agreement with the view that the main role of gastrin in infants is trophic action on the mucosa of the upper gastrointestinal tract.

Topics: Body Weight; Gastrins; Humans; Hypertrophy; Infant; Pyloric Stenosis; Radioimmunoassay

Topics: Female; Gastrins; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Peptones; Pyloric Stenosis; Stomach

This case describes an extraordinarily elevated total bilirubin level that reverted to normal 9 1/2 wk after Fredet-Ramstedt pyloromyotomy. Although the etiology of jaundice occurring in patients with IHPS remains uncertain, theories implicating inhibition of the glucuronyl transferase system have been proposed. Infants with IHPS have a documented hypergastrinemia. An hypothesis is offered, illustrated by this case, to explain the inhibition of the glucuronyl transferase system with resultant hyperbilirubinemia by the hypergastrinemia of idiopathic hypertrophic pyloric stenosis.

Topics: Exchange Transfusion, Whole Blood; Gastrins; Glucuronosyltransferase; Humans; Hypertrophy; Infant, Newborn; Jaundice, Neonatal; Male; Methods; Pyloric Stenosis

A 58-year-old patient with hypergastrinemia (basal and after stimulation by means of protein food, calcium, glucagon, and secretin), acid hypersecretion, recurrent anastomotic ulcer, gastrocolonic fistula, steatorrhea, and malabsortion (hypocalcemia, hypocholesterolemia and a rather elevated 5-HIAA) is reported. The definite preoperative diagnosis of Zollinger-Ellison syndrome was established after the intravenous secretin test (75 U) which produced a significant stimulation peak 5 minutes after being injected. The possible existence of a multiple endocrine adenomatosis syndrome type I was discarded. During the operation no pancreatic or extrapancreatic macroscopic tumor was found. A total gastrectomy, transverse colectomy, splenectomy, and subtotal pancreatic resection were performed; Rosanow's techniques was used to re-established the gastrointestinal continuity. The morphological study of the excised pancreatic tissue showed a diffuse hyperplasia of the Langerhans islet cells; indirect immunofluorescence in the presence of antigastrin antibodies was faintly positive and difficult to evaluate. However, gastrin levels clearly decrease after the operation may be because the inhibitory effect of total gastrectomy or because of the partial pancreatectomy. Furthermore, the inhibitory effect of tyrocalcitonine onthe pre- and postoperative gastrin levels measured by radioimmunoassay could be verified. For the moment the importance of this test in the diagnosis of Zollinger-Ellison syndrome, and especially in the diagnosis of ZES-type II, is not known.

Topics: Calcium; Gastrectomy; Gastrins; Glucagon; Humans; Hypertrophy; Injections, Intravenous; Islets of Langerhans; Male; Middle Aged; Pancreatectomy; Secretin; Stimulation, Chemical; Zollinger-Ellison Syndrome

The effects of endogenous hypergastrinemia and hypogastrinemia on the exocrine and endocrine pancreas were studied in the rat. Hypergastrinemia was induced by antral exclusion, and hypogastrinemia by antral resection. The studies were made 14 weeks after surgery. The total weight of the pancreas was increased both in hypergastrinemic and hypogastrinemic animals, due to hypertrophy of the exocrine cells. In contrast, the volume and total weight of the pancreatic islets were decreased. There was no numerical difference in the A-, D-, PP-cells between the hyper- and hypogastrinemic animals, respectively, and the controls. The number of insulin-producing (B-) cells was certainly reduced after the induction of hypogastrinemia. There was, however, signs of increased B-cell activity, which might contribute to an underestimation of the number of B-cells with the technique used. These findings do not support the hypothesis that antral gastrin has trophic influence on either exocrine or endocrine pancreas.

Topics: Animals; Body Weight; Gastrins; Hypertrophy; Islets of Langerhans; Male; Organ Size; Pancreas; Pyloric Antrum; Rats

The aim of this study was to look for a difference in fasting serum gastrin levels or in serum gastrin response to oral feeding between infants with hypertrophic pyloric stenosis and normal controls. Fasting serum gastrin levels were measured by radioimmunoassay in 10 patients with pyloric stenosis, before pyloromyotomy and 7 and 15 days after it, and in 11 controls. In addition, the serum gastrin responses to a casein hydrolysate meal were studied in both groups (in the patients, 7 days after operation). The fasting serum gastrin levels in the patients did not differ from those in the controls before operation, but they did so after it. The serum gastrin response to feeding in patients after pyloromyotomy was no greater than in controls.

Topics: Caseins; Female; Gastrins; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Postoperative Period; Protein Hydrolysates; Pyloric Stenosis

A study was designed and carried out to determine if the canine model of hypertrophic pyloric stenosis is applicable to other species and to demonstrate the transplacental passage of gastrin. Results of the study show that (1) pentagastrin does not induce hypertrophic pyloric stenosis in the rabbit; (2) human gastrin does not cross the canine placenta, and (3) gastrin has no documented and little inferred role in the etiology of CHPS.

Topics: Animals; Dogs; Female; Gastrins; Hypertrophy; Pentagastrin; Placenta; Pregnancy; Pyloric Stenosis; Rabbits

In order to evaluate the potential role of gastrin in the etiology of pyloric stenosis, serum gastrin levels were measured in cord blood of affected infants, matched controls, and mothers of both. No differences were identified when values from infants with pyloric stenosis were compared with those from control infants. Mean cord serum gastrin levels of the infants were significantly greater than the mean maternal gastrin levels. The data effectively dismiss the possibility that elevated serum gastrin concentration in mother or infant at the time of delivery can be implicated as a cause of pyloric stenosis.

Topics: Fetal Blood; Gastrins; Humans; Hypertrophy; Infant, Newborn; Pyloric Stenosis

Topics: Age Factors; Duodenal Ulcer; Female; Gastrins; Humans; Hypertrophy; Infant; Male; Pyloric Stenosis; Radioimmunoassay

The serum immunoreactive gastrin (IRG) level in infants with confirmed idiopathic hypertrophic pyloric stenosis (IHPS) has been determined and compared to that found in vomiting infants without IHPS, in normal infants, and in normal adults. The mean serum IRG level of normal infants (103 +/- 9 pg/ml (mean +/- SEM) exceeded that of normal adults (28 +/- 5 pg/ml). The preoperative mean serum IRG level in IHPS infants (256 +/- 26 pg/ml) was significantly higher than that of both normal infants and vomiting infants without IHPS (93 +/- 9 pg/ml). Twenty-five per cent (5/20) of the IHPS infants had serum IRG levels within the upper range of normal infants. Fasting serum IRG levels in IHPS infants were not altered immediately by pyloromyotomy. The results from this study suggest a relationship between gastrin and idiopathic hypertrophic pyloric stenosis.

Topics: Adolescent; Adult; Antigens; Female; Gastrins; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Pyloric Stenosis; Vomiting

Recently attempts have been made to demonstrate the possible role of hypergastrinemia in the production of congenital hypertrophic pyloric stenosis in infants. Eleven infants with congenital hypertrophic pyloric stenosis, ranging in age from three to 11 weeks, were evaluated for fasting and postprandial serum gastrin levels. Two to ten weeks following successful pyloromyotomy, a similar evaluation was undertaken to demonstrate the possible role of elevated serum gastrin levels in the etiology of congenital hypertrophic pyloric stenosis. The average fasting and postprandial serum gastrin levels in infants with congenital hypertrophic pyloric stenosis did not differ significantly from levels noted in control infants. Similarly, no statistically significant difference was noted between the pre- and postoperative levels of serum gastrin in the affected infants. Several experimental studies have been reported within the past few years describing the production of hypertrophic pyloric stenosis in the offspring of dogs injected with pentagastrin during pregnancy. The results of our study minimize the direct importance of serum gastrin in the production of congenital hypertrophic pyloric stenosis. The role of the hormone secretin in the etiology of this condition is hypothesized.

Topics: Female; Gastrins; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Pyloric Stenosis; Secretin

Topics: Animals; Cell Count; Gastric Juice; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Hypertrophy; In Vitro Techniques; Metiamide; Pentagastrin; Rats; Receptors, Histamine H2; Sodium Chloride; Stimulation, Chemical; Thiourea; Time Factors

Pentagastrin and acetyl choline were shown to contract isolated strips of the circular pyloric muscle from baboons. These findings are compatible with the hypothesis that gastrin may have a part to play in the development or maintenance of congenital hypertrophiic pyloric stenosis of infancy.

Topics: Acetylcholine; Animals; Gastrins; Haplorhini; Hypertrophy; Papio; Pentagastrin; Pyloric Stenosis; Pylorus

Topics: Adaptation, Physiological; Animals; Epithelium; Female; Gastrectomy; Gastrins; Hypertrophy; Ileum; Jejunum; Rats

Topics: Animals; Gastrins; Humans; Hypertrophy; Infant; Pentagastrin; Pyloric Stenosis; Rabbits

Serial morphological, secretory, and serological observations of a patient with Ménétrier's disease disclosed hypergastrinemia, antibodies to parietal cells and dietary substances, and an acute reduction of gastrointestinal protein loss after atropine administration. Transformation of the gastric mucosa from hypertrophy to atrophic gastritis was associated with disappearance of the protein-losing gastroenteropathy and serum antibodies and reduction of the serum gastrin concentration.

Topics: Antibodies; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Hypertrophy; Male; Middle Aged; Protein-Losing Enteropathies

Topics: Gastric Mucosa; Gastrins; Gastritis; Humans; Hypertrophy; Male; Middle Aged

Topics: Achlorhydria; Chronic Disease; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Histamine; Humans; Hydrogen-Ion Concentration; Hypertrophy; Insulin; Intubation, Gastrointestinal; Protein-Losing Enteropathies; Stimulation, Chemical; Stomach; Stomach Diseases; Stomach Ulcer; Zollinger-Ellison Syndrome