Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although pancreatic neuroendocrine tumors (NETs) in von Hippel-Lindau (VHL) disease have been reported, their pathological features have not been characterized. In addition, it is unknown whether alterations of the VHL gene are responsible for pancreatic NET development. To evaluate NETs in VHL patients, we performed histopathological analysis of 30 pancreatic tumors in 14 patients. In addition, DNA from NETs and normal pancreatic tissue from 6 patients with documented germ-line VHL gene mutations was studied for allelic deletions of the second copy of the VHL gene by fluorescence in situ hybridization and polymerase chain reaction-based single-strand conformational polymorphism analysis. Morphologically, the tumors were characterized by solid, trabecular, and/or glandular architecture and prominent stromal collagen bands. Sixty percent of the tumors revealed at least focally clear-cell cytology. All tumors were positive for panendocrine immunohistochemistry markers (chromogranin A and/or synaptophysin); 35% of NETs demonstrated focal positivity for pancreatic polypeptide, somatostatin, insulin, and/or glucagon; and no immunostaining for pancreatic and gastrointestinal hormones was observed in 65% of tumors. Dense core neurosecretory granules were evident by electron microscopic examination, and the clear cells additionally revealed abundant intracytoplasmic lipid. All NETs that were subjected to genetic analysis showed allelic loss of the second copy of the VHL gene. We conclude that multiple, nonfunctional pancreatic NETs occur in VHL patients. Stromal collagen bands and clear-cell morphology are important histological features of VHL-associated NETs. The presence of allelic deletions of the VHL gene in pancreatic NETs provides direct molecular evidence for a role of the gene in their tumorigenesis and establishes NET as an independent tumor type of VHL disease.
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PMID:Multiple neuroendocrine tumors of the pancreas in von Hippel-Lindau disease patients: histopathological and molecular genetic analysis. 966 83

The aim of the present study was to distinguish and describe the patterns of distribution of pancreatic islets within the pancreas of four species of laboratory animals, including rats, dogs, minipigs and monkeys, and furthermore, to identify immunohistochemically various islet cell types and characterize their content. Histopathological examinations were performed on sections stained with hematoxylin and eosin (H&E) and immunostained using rabbit polyclonal antibodies (pAb) against insulin, glucagon, pancreatic polypeptide (PP), somatostatin, chromogranin A, keratin, bombesin and gastrin, or mouse monoclonal antibodies (mAb) against synaptophysin, Leu-7 and proliferating cell nuclear antigen (PCNA) in three-step rabbit immunoperoxidase (PAP) and streptavidin/peroxidase (StreptABC/HRP) reactions. Positive immunohistochemical reactions were observed in the pancreatic islets of all animal species with all antibodies, except with anti-bombesin and anti-gastrin antibodies. Our results revealed that: 1) there is species specific regional arrangement of islets in the pancreas, 2) each species presents a characteristic distribution of cells producing different hormones. 3) immunoreactivity with immunohistochemical markers varies between species and/or age. The present comparative immunohistochemical study could be helpful for answering questions which are important for understanding some of the intricate mechanisms that govern the integrated function of the endocrine pancreas.
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PMID:A comparative immunohistochemical study of pancreatic islets in laboratory animals (rats, dogs, minipigs, nonhuman primates). 968 46

The occurrence, distribution and possible cellular colocalizations of chromogranin A (CgA) and of two synthetic secretogranin II peptides (SgIIC23-3 and SgIIC26-3) with serotonin, somatostatin, neurotensin, pancreatic polypeptide and bombesin have been investigated immunohistochemically in the amphibian gut. CgA or SgIIC26-3-immunostained enterocytes were found throughout along the frog intestine, while no immunoreaction for any of the tested antisera against granins was seen in the same organ of newts. Variable amounts of serotonin-immunoreactive cells co-storing CgA or SgIIC26-3, but never both granins, were encountered in all intestinal segments of the frogs investigated. In addition, CgA was co-localized with somatostatin in a few endocrine cells of the frog (genus Rana) duodenum and small intestine. In the duodenum of another frog (genus Xenopus) several enterocytes co-stored SgIIC26-3 and neurotensin. Pancreatic polypeptide- and bombesin-immunoreactive cells, the latter detected only in the duodenum of Xenopus, did not contain and granin. The results suggest that, in spite of their relatively restricted occurrence in the intestine of frogs and even of their absence in that of newts, the granins are well conserved during phylogeny. On the other hand, the heterogeneous distributions of these anionic glycoproteins, related to the entero-endocrine cell types, make their previously assigned usefulness as markers of all neuro-endocrine cells unlikely.
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PMID:Granin proteins (chromogranin A and secretogranin II C23-3 and C26-3) in the intestine of amphibians. 986 32

Colocalisation of synaptophysin has been studied in different neuroendocrine cell types in histologically normal mucosa from human gastrointestinal tract (corpus, antrum, duodenum, ileum and colon) using double-immunofluorescence stainings. Numerous synaptophysin immunoreactive cells were seen in the antrum, while a smaller number were found in the intestinal tract. Synaptophysin immunoreactivity was strong in the antrum but weak in the intestine. In the intestinal colocalisation studies the synaptophysin immunoreactivity was enhanced by using the tyramide amplification method. Synaptophysin and chromogranin A were colocalised but the latter occurred mainly basally, whereas synaptophysin was found to occur diffusely throughout the cytoplasm. Synaptophysin immunoreactivity occurred in the serotonin cells throughout the gastrointestinal tract, and in the antral gastrin and somatostatin cells. In the intestinal tract only a small fraction of somatostatin, gastrin, cholecystokinin, enteroglucagon, enteroglucagon/ peptide tyrosine tyrosine displayed synaptophysin immunoreactivity. In the gastrointestinal tract (except the antrum), chromogranin A is a better general neuroendocrine marker than synaptophysin. The functional role of synaptophysin is unclear but it may be involved in the intracellular transport and release of hormones. Based on the distribution background of synaptophysin, it seems to be of greater importance in the antrum than in the intestinal tract as a whole.
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PMID:Co-localization of synaptophysin with different neuroendocrine hormones in the human gastrointestinal tract. 993 Aug 83

A pancreatic endocrine carcinoma with lung metastases was found in a 15-year-old male raccoon. This tumour was characterized by great variation in cell size and production of multiple polypeptide hormones. Endocrine markers expressed by the neoplastic cells were, in descending order of frequency, chromogranin A, pancreatic polypeptide (PP), glucagon, somatostatin and insulin. Co-expression of PP and glucagon, somatostatin or insulin was demonstrated immunohistochemically with consecutive sections, and cells with both glucagon and insulin were also observed. The pattern of co-expression was similar to that in the earliest stages of murine pancreatic development. Amyloid deposits in the islets of Langerhans, which reacted with antibody to islet amyloid polypeptide, were thought to be associated with age.
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PMID:Pancreatic endocrine carcinoma with multiple hormone production in a raccoon (Procyon lotor). 1021 74

The ECL cell is the predominant endocrine cell type in the oxyntic mucosa, displaying typical ultrastructure with numerous cytoplasmic vesicles and electron-dense granules. ECL cells have many features in common with neurons and other peptide hormone-producing endocrine cells, including the ability to produce, store, and secrete chromogranin-A and chromogranin A-derived peptides. In addition, they produce and store histamine and respond with activation and growth to a gastrin challenge. ECL cells are stimulated to secrete histamine as well as other products by gastrin and PACAP and are inhibited by somatostatin, galanin, and prostaglandins. The cytoplasmic vesicles are thought to contain histamine and other secretory products. Mature secretory vesicles occur in the docking zone of the ECL cells, where they constitute the releasable pool of secretory products. Gastrin stimulation will induce exocytosis and degranulation. Histamine released from ECL cells plays a key role in the regulation of parietal cell activity (the gastrin-ECL cell-parietal cell axis). In response to long-term gastrin stimulation, vacuoles and lipofuscin bodies develop in the ECL cells, forming part of a crinophagic pathway by which the ECL cell strives to eliminate superfluous secretory products.
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PMID:Rat stomach ECL cells up-date of biology and physiology. 1032 81

The occurrence, distribution and the possible cellular co-localizations of chromogranin A (CgA) and of two synthetic secretogranin II-peptides (SgIIC23-3 and SgIIC26-3) with several enteric neuropeptides and serotonin have been investigated immunohistochemically in turtles, lizards and snakes. The distribution of CgA-immunoreactivity was restricted only to the enteroendocrine cells in all the reptiles studied. SgII-immunoreactivity--absent in turtle--revealed nerve cells and fibers, besides enteroendocrine cells in lizard and snake guts. Moreover, the two antisera (C23-3 and C26-3) raised against the different regions of the SgII-molecule yielded distinct distribution patterns of immunoreactivity both in the lizard and snake organs. Small amounts of enteric serotonin cells co-stored CgA or SgIIC23-3 in lizards and snakes and only SgIIC26-3-peptide in snakes. CgA was found co-stored with somatostatin in a few enterocytes of the turtle duodenum. In the same gut segment of lizards and throughout the snake organ, neurotensin and the SgIIC23-3-peptide co-existed in a small number of endocrine cells. The pancreatic polypeptide-containing cells were devoid of immunoreactivity both for CgA and SgII. Bombesin immunopositive cells were absent throughout the intestines of the reptiles investigated. The above findings entirely support the heterogenous distribution of granins in neuroendocrine organs and tissues and also within the same neuroendocrine cell population. They further support the concept of a good conservation of granins during phylogeny.
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PMID:Granin proteins (chromogranin A and secretogranin II C23-3 and C26-3) in the intestine of reptiles. 1036 8

Motility and secretory disorders of the gastrointestinal tract and associated glands increase with ageing. The duodenum contains several peptide/amine producing cells that play an important role in regulating gastrointestinal motility and secretion. The present study was performed to elucidate changes in these cells that may have arisen as a result of ageing. A total of four age groups of subjects, aged 1-2, 20-29, 40-49 and 60-69 years were studied. The various endocrine cell types were identified by immunohistochemistry and quantified by computerized image analysis, and two parameters were determined; the number of cells/mm3 epithelial cells and the cell secretory index (CSI), which indicates the immunoreactive secretory granule content of the endocrine cells. Chromogranin A- and serotonin-immunoreactive (IR) cells were fewer in 1-2-year-olds than in 20-29-year-olds. Gastrin/CCK-IR cells were significantly more numerous in 1-2-year-olds and 60-69 years-olds than in 20-29-year-olds. Somatostatin-IR cells were more numerous in the 40-49-year-olds than in the 20-29 years-olds. The CSI was higher in chromogranin A-, gastric inhibitory polypeptide (GIP)-, somatostatin- and gastrin/CCK-IR cells in 1-2-year-olds than in 20-29-year-olds. There was no significant sex difference regarding the numbers and CSI of other endocrine cell types. This study established the absence of sex-related differences in all endocrine cell types investigated, regarding numbers and physiological activity. Age, on the other hand, was shown to be associated with changes in the numbers of CCK-, somatostatin- and serotonin-IR, which may have some bearing on the gastrointestinal disorders of the elderly.
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PMID:Ageing and endocrine cells of human duodenum. 1036 38

Neuroendocrine gut and pancreatic tumors are rather rare malignant diseases which has gained increased attraction through the last decennium, possibly through development of new diagnostic and therapeutic methods. Histopathology demonstrating the common neuroendocrine features of these tumors has been the diagnostic corner stone for long, but today it should be supplemented with information about the tumor biology. An excellent biochemical marker which is easy to analyze in serum or plasma is chromogranin A, which is a glycoprotein that is stored and released from neuroendocrine cells. This marker can be used for diagnosis and follow-up of the patients. Somatostatin receptor scintigraphy has been one of the most important diagnostic tools for staging of the disease and also indicating sensitivity to treatment with somatostatin analogues. It is a general agreement that almost every patient should be subjected to this procedure before or during the treatment course. From the therapeutic point of view, surgery is nowadays more extensive aiming at reducing the tumor mass in patients who could not be cured by surgery alone. Other means of tumor reduction is liver dearterialization by embolization with starch spheres. The medical treatment of neuroendocrine tumors has made a real break through with the introduction of somatostatin analogues, particularly octreotide, and today most of the hormonally related symptoms can be controlled by this kind of treatment. Somatostatin analogues have also shown to be inhibitors of tumor growth and the latest development is tumor targeted radioactive treatment with Ytrium or Indium labelled octreotide. Long-acting formulation of somatostatin analogues have come into clinical use and significantly improved quality of life for patients with neuroendocrine tumors. Other means of medical treatment are alpha interferons, which have shown particular effect in patients with midgut carcinoid tumors giving both biochemical and tumor responses. Chemotherapy such as streptozotocin plus 5-fluorouracil (5-FU) or doxorubicin is still considered as first-line treatment in malignant endocrine pancreatic tumors but is combined with concomitant somatostatin analogue treatment. In the future a multimodal treatment will further develop combining different agents and also somatostatin receptor subtype specific analogues will come into clinical use.
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PMID:Neuroendocrine gastrointestinal tumors--a condensed overview of diagnosis and treatment. 1039 26

The enterochromaffin-like (ECL) cells of the oxyntic mucosa (fundus) of the stomach produce, store and secrete histamine, chromogranin A-derived peptides such as pancreastatin, and an unanticipated but as yet unidentified peptide hormone. The cells are stimulated by gastrin and pituitary adenylate cyclase activating peptide and suppressed by somatostatin and galanin. Choline esters and histamine seem to be without effect on ECL cell secretion. The existence of a gastrin-ECL cell axis not only explains how gastrin stimulates acid secretion but also may help to explore the functional significance of the ECL cells with respect to the nature and bioactivity of its peptide hormone. From the results of studies of gastrectomized/fundectomized and gastrin-treated rats, it has been speculated that the anticipated ECL-cell peptide hormone acts on bone metabolism.
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PMID:Physiology of the ECL cells. 1046 54


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