Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little is known about lineage relationships and differentiation programs of various epithelial cells present in mouse gastric units. We have previously used rat liver fatty acid binding protein/human growth hormone (L-FABP/hGH) transgenes to define epithelial cell lineages relationships in the small intestine of fetal and adult mice and to examine regulation of their terminal differentiation programs along the crypt-to-villus and duodenal-to-ileal axes. We have now used these transgenes to explore similar issues in the stomach. Immunocytochemical studies of fetal and adult transgenic L-FABP/hGH animals and their normal littermates revealed that the intact endogenous mouse L-FABP gene (Fabpl) is not expressed in gastric epithelium. Nucleotides-596 to +21 of the rat L-FABP gene direct "inappropriate" expression of hGH in the gastric epithelium as early as fetal day 15. From 1 to 13 mo, L-FABP-596 to +21/hGH expression occurs only in surface mucous cells of zymogenic and mucous gastric units; the reporter is not detectable in the enteroendocrine, parietal and chief cell populations of zymogenic glands. Electron microscopic immunocytochemistry revealed that hGH is directed to apical secretory granules in surface and pit mucous cells expressing the transgene. hGH levels vary widely among surface mucous cells both within single pits and between gastric units in a given animal. The heterogeneity noted in reporter expression suggests that there are marked differences in the regulatory environments of individual cells of a single type within a given gastric unit. This raises the possibility that cell differentiation programs in the stomach may not be as tightly coupled to cellular translocation as in the small intestine. Finally, the lack of expression of L-FABP-596 to +21/hGH in gastrin- and serotonin-immunoreactive cells of the stomach contrasts with its efficient expression in comparable cell types located in the duodenum; providing a model system for examining differential regulation of gene expression in terminally differentiated cell types represented in both gastric and intestinal epithelium.
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PMID:Regulation of gene expression in gastric epithelial cell populations of fetal, neonatal, and adult transgenic mice. 151 30

HPLC-purified 125I-labeled vasoactive intestinal peptide (VIP) bound in a specific, saturable, and reversible manner to pancreatic plasma membranes isolated from newborn calves, from milk-fed calves at 28 and 119 days, and from weaned calves at 119 days. A series of VIP analogues, including pituitary adenylate cyclase-activating polypeptide (PACAP), displaced 125I-VIP binding and activated adenylate cyclase in the same order of relative potency: PACAP-38 greater than helodermin greater than VIP, PACAP-27 greater than PHM (human peptide with NH2-terminal histidine and COOH-terminal methionine amide). At maximally effective concentrations, these five peptides produced the same two- to threefold increase of adenylate cyclase activity in pancreatic membranes from newborn and 28-day-old calves, and fourfold in ruminant or preruminant animals at 119 days. The activation constant for PACAP-38 ranged from 0.1 to 0.34 nM throughout the postnatal development. Helospectin I and II were three times less potent than VIP in inhibiting 125I-VIP binding. At concentrations up to 0.1 microM, secretin, rat and human growth hormone-releasing factors, glucagon, oxyntomodulin, the truncated form of glucagon-like peptide-1 lacking the 6 NH2-terminal amino acid sequence (TGLP-1), GLP-2, gastric inhibitory peptide, gastrin, CCK, and insulin had no effect on binding. Scatchard plots from 28- and 119-day-old calves were compatible with the presence of two classes of 125I-VIP binding sites: one with a high affinity for VIP and a low binding capacity (Kd = 0.11-0.4 nM, Bmax = 66-174 fmol/mg protein) and the other with a low affinity and high binding capacity. At birth, only one class of binding sites was observed (Kd = 0.4 nM, Bmax = 858 fmol/mg protein). The covalently cross-linked PACAP-preferring 125I-VIP binding site is a glycoprotein of 55 kDa with higher sensitivity to PACAP vs. helodermin and VIP. Our results suggest that calf pancreatic functions might be regulated at an early stage of postnatal development by PACAP receptors linked to cAMP generation.
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PMID:Characterization of binding sites for VIP-related peptides and activation of adenylate cyclase in developing pancreas. 184 91

Proliferation and growth of gastroduodenal mucosal cells represent important elements of mucosal defense and any alterations in the balance between cell proliferation and cell loss may lead to trophic changes in mucosa. Acute mucosal lesions induced by local irritants such as bile salts, ethanol, aspirin, or stress are accompanied by widespread damage of surface epithelium followed by almost immediate repair due to mucosal cell restitution, which is unrelated to cell proliferation but does depend on the intrinsic property of mucosal cells to cover superficial defects. Cytoprotection involves the protection of the regeneration zone and the maintenance of blood flow to the mucosa. Various factors that exhibit mucosal growth-promoting action include EGF, gastrin, growth hormone, and GH-releasing factor. These factors protect the mucosa against acute injury but the mechanism of this effect is not clear. These trophic agents, especially EGF, accelerate the healing of chronic gastroduodenal ulceration and may contribute to the healing effects of sucralfate or De-Nol. These effects of trophic substances are related to their stimulation of cell proliferation and DNA, RNA, and protein synthesis and can be reversed by the suppression of mucosal growth. Prostaglandins, especially their stable methylated analogs, display trophic effects on the gastric mucosa but neither gastroprotective nor ulcer healing actions of PG can be attributed to their trophic effect. With increasing attention being paid to mucosal growth and repair as components of mucosal defense, the emphasis of drug therapy of acute or chronic gastroduodenal lesions is likely to move toward strengthening mucosal defense rather than the inhibition of aggressive factors.
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PMID:Role of growth factors in gastroduodenal protection and healing of peptic ulcers. 197 Mar 37

The somatostatinergic system has proven to be one of the best models of neuropeptide biology. Originally characterized as a hypothalamic regulator of growth hormone secretion, somatostatin also regulates the secretion of several other pituitary, pancreatic, and gastrointestinal (GI) hormones including thyrotropin-stimulating hormone, insulin, glucagon, and gastrin. Disorders in somatostatin metabolism have been proposed to contribute to the pathogenesis of Alzheimer's disease, epilepsy, GI motility disorders, and diabetes. On a more basic level, studies of somatostatin action have integrated divergent concepts of intracellular signal transduction. Advances in the understanding of somatostatin biosynthesis have had an impact on areas outside the field of endocrinology by providing new concepts of eukaryotic gene regulation. This report focuses on the transcriptional regulation of somatostatin gene expression. Two aspects of somatostatin gene transcription will be considered--regulated expression by second messengers and tissue-specific basal expression.
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PMID:Somatostatin gene regulation: an overview. 197 13

Transgenes consisting of segments of the rat liver fatty acid-binding protein (L-FABP) gene's 5' non-transcribed domain linked to the human growth hormone (hGH) gene (minus its regulatory elements) have provided useful tools for analyzing the mechanisms that regulate cellular and spatial differentiation of the continuously renewing gut epithelium. We have removed the jejunum from normal and transgenic fetal mice before or coincident with, cytodifferentiation of its epithelium. These segments were implanted into the subcutaneous tissues of young adult CBY/B6 nude mouse hosts to determine whether the bipolar, migration-dependent differentiation pathways of gut epithelial cells can be established and maintained in the absence of its normal luminal environment. Immunocytochemical analysis of isografts harvested 4-6 wk after implantation revealed that activation of the intact endogenous mouse L-FABP gene (fabpl) in differentiating enterocytes is perfectly recapitulated as these cells are translocated along the crypt-to-villus axis. Similarly, Paneth and goblet cells appear to appropriately differentiate as they migrate to the crypt base and villus tip, respectively. The enteroendocrine cell subpopulations present in intact 4-6-wk-old jejunum are represented in these isografts. Their precise spatial distribution along the crypt-to-villus axis mimics that seen in the intact gut. A number of complex interrelationships between enteroendocrine subpopulations are also recapitulated. In both "intact" and isografted jejunum, nucleotides -596 to +21 of the rat L-FABP gene were sufficient to direct efficient expression of the hGH reporter to enterocytes although precocious expression of the transgene occurred in cells located in the upper crypt, before their translocation to the villus base. Inappropriate expression of hGH occurred in a high percentage (greater than 80%) of secretin, gastrin, cholecystokinin, and gastric inhibitory peptide producing enteroendocrine cells present in the intact jejunum of 4-6-wk-old L-FABP-596 to +21/hGH transgenics. Addition of nucleotides -597 to -4,000 reduced the percentage of cells co-expressing this reporter four- to eightfold in several of the subpopulations. Jejunal isografts from each transgenic pedigree studied contained a lower percentage of hGH positive enteroendocrine cells than in the comparably aged intact jejunum.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epithelial cell differentiation in normal and transgenic mouse intestinal isografts. 204 Jun 47

Pulmonary tumourlets are focal aggregates of neuroendocrine cells that occur in the periphery of the lung and may be associated with chronic inflammation and scarring. Six such lesions were seen in five lungs from a series of 35 pairs of lungs studied at necropsy. All were immunoreactive for neurone-specific enolase, protein gene product 9.5, and a range of neuroendocrine products. Of the peptides found in neuroendocrine cells in normal human lungs, gastrin releasing peptide was present in all tumourlets and calcitonin in all but one; none contained leucineenkephalin. Of a series of peptide and protein hormones not present in the neuroendocrine cells of healthy human lungs, growth hormone was present in all six tumourlets and adrenocorticotrophin in two. Identical patterns of peptide expression were displayed by neuroendocrine cells in the airway associated with the tumourlets in two cases. Such cells were increased in number and abnormally clustered. Aberrant expression of peptides might accompany the morphological changes in the pulmonary neuroendocrine cells seen in diseased lungs, their florid focal proliferation occasionally resulting in the formation of a tumourlet.
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PMID:Appropriate and inappropriate neuroendocrine products in pulmonary tumourlets. 214 55

Based on observations of five of own patients the author analyzes the causes of spontaneous hypoglycaemia in malignant tumours and assumes three mechanisms of development: 1. Metastatic affection of the liver reduces the reserves of homeostatically usable glycogen and can reduce also the amount of utilized insulin and glucagon, and this weakens the effectivity of contraregulating hormones. 2. In case of large mesenchymal tumours it is assumed that the cause of hypoglycaemia is the neoplastic formation of IGF II. For these hypoglycaemic states a low concentration of C-peptide, IRI (immunoreactive insulin), absence of response of growth hormone to hypoglycaemia, high IGF II in the tumour and plasma and high mRNA for IGF II in the tumour is typical. 3. In hypoglycaemic states with massive metastases in the liver, high IRI and C-peptide it is assumed the cause of hypoglycaemia is a metastatizing insular tumour or a nes.dioblastoma. In those instances concurrent peptic ulcers (gastrin production) are frequent.
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PMID:[Neuroglycopenic syndromes in malignant tumors]. 225 61

Available techniques for light and electron microscopical double immunocytochemical staining are all associated with certain problems. We have developed a novel multiple staining procedure, which allows use of antibodies of differing specificities, raised in the same species (e.g. rabbit). Its essential features include 1) saturation of antigenic epitopes on the first layer primary antiserum by second (fluorophor- or gold-) labelled anti-IgG antibodies and 2) denaturation of free anti-IgG binding sites by formaldehyde vapour treatment. Various combinations of gastrin, somatostatin, glucagon, ACTH, growth hormone and enkephalin/endorphin antibodies have been tested at the light and electron microscopical level and have been found to give highly reproducible double- and triple-staining results. The technique has also been evaluated by use of cytochemical paper models. The method is simple and very useful for multiple staining of a wide variety of antigens.
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PMID:Simultaneous demonstration of multiple antigens by indirect immunofluorescence or immunogold staining. Novel light and electron microscopical double and triple staining method employing primary antibodies from the same species. 241 88

The pathophysiological structure shows aggressors like increased acid and pepsin, an impaired defence system of the mucosa (mucus, mucosal circulation and possibly PG's and epidermal growth hormone). Disturbances in the interdigestive and digestive motility brings about most clearly the pathophysiological differences between GU and DU. Therapeutic corrections of the high secretion lead to pathological reactions in other parts of the system (gastrin). SPV is the only therapeutic procedure which reduces irreversibly the enlarged secretory capacity of the gastric mucosa (parietal cell reduction). This surgical treatment should therefore have priority in the treatment also of uncomplicated duodenal ulcers and with some exceptions of GU.
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PMID:[Pathophysiology of ulcer disease]. 241 23

The purpose of the study was to evaluate some of the hormones in 20 patients with alcoholic cirrhosis. We investigated the diurnal rhythmicity of some of the hormones (cortisol, follicle-stimulating hormone-FSH, luteinizing hormone-LH, growth hormone-LH, prolactin-PRL) and basal serum concentrations of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4) and testosterone, as well as gastrin and insulin, using provocative tests. Statistical analysis of the results obtained from the observed patients compared with controls, showed significantly lower concentrations of T3 (p less than 0.05), cortisol (p less than 0.05), testosterone (p less than 0.05) and FSH (p less than 0.05), and significantly higher (p less than 0.01) serum concentration of prolactin. Then, in the cirrhotic group the serum concentrations of gastrin and insulin increased significantly (p less than 0.01), together with the disorders of carbohydrate metabolism (impaired glucose tolerance and diabetes mellitus. The described disturbances of some of the observed hormones are complex, particularly in their relationship by which the clinical picture of the cirrhotic patients can be explained.
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PMID:[Hormone levels in patients with alcoholic liver cirrhosis]. 249 Sep 94


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