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Endocrine cells in the gastrointestinal tracts of 3 teleostean species.

Endocrine cells of the gastrointestinal tracts of 3 teleostean species (Lepomis gibbosus, Morone americana and Notemigonus crysoleucas) were studied using several staining techniques: Masson-Hamperl argentaffin reaction, Singh's argyrophil reaction, Schmorl's ferricyanide test and MacConnail's lead hematoxylin; only the argyrophil method showed a positive reaction. In L. gibbosus and M. americana, endocrine cells of proximal (corporic) stomach were seen singly among the surface epithelial cells while those of distal (pyloric) stomach were more numerous and located in irregular patches. A small number of positive cells were found in the gastric glands of corporic stomach. A few argyrophil cells were seen among the surface intestinal epithelial cells of N. crysoleucas but none were seen in the intestines of L. gibbosus and M. americana.

Animals↗

Enteric nervous system and endocrine cells demonstrated in the gut in teratomas.

A case of retroperitoneal teratoma, showing considerable morphological development presented as an encapsulated and pedunculated tumour with a seemingly mature intestinal loop. Markedly complex intramural nerve plexuses and numerous epithelial endocrine cells were revealed immunohistochemically in the gut tissue. Ten other mature teratomas containing gastrointestinal tissues were examined for comparison, but neither intramural ganglia nor nervous networks were found in the gut components, despite the presence of amine- and/or peptide-containing endocrine cells in all intestinal mucosa linings. Enteric endocrine cells were found to occur irrespective of the differentiation of intestinal layers or the occurrence of neural elements. These findings suggest that the epithelial endocrine cells of intestinal mucosa do not have the same origin as enteric neurons, but are rather of endodermal origin. This invertebrate well-formed teratoma, containing a highly organized enteric nervous system, suggests that teratoma and fetus in fetus are related entities distinguished by the presence of a vertebral axis.

Choristoma↗

Endocrine cells producing regulatory peptides.

Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.

Animals↗

Endocrine cells in the caecum of the rabbit.

An ultrastructural study of the caecal mucosa of the rabbit revealed four endocrine cell types, distinguishable by their morphological features and by the size and appearance of the secretory granules which they contained. Endocrine cells occurred most frequently in the mid-region of the corpus ceci, with fewer cells in other regions of the caecum. The commonest cell type appeared to belong to the widely distributed enterochromaffin cells of the intestinal mucosa; less common were cells corresponding to the L cells of the colon, and more rare were endocrine cell types which corresponded to the M and (probably) S cells of the gastrointestinal tract. The secretions from these cell types may well be important in the diurnal physiological regimen of the rabbit caecum.

Animals↗

Endocrine cells of the colon in Hirschsprung's and control children.

The large intestine resected from 6 Hirschsprung's patients and surgical colonic biopsies from 6 control children were examined with light and electron microscopy. The presence and the relative distribution of various endocrine cell types in both groups of mucosa were determined. In light microscope studies endocrine cell data were expressed as number of cells per unit area of mucosa using a quantitative method after argentaffin and Grimelius's argyrophilic techniques and an immunoperoxidase reaction with glucagon and somatostatin (SRIF) antisera. The results indicate that endocrine cells are apparently not involved in Hirschsprung's disease, since their number and frequency did not differ significantly between the ganglionic and aganglionic segments of Hirschsprung's patients nor between the latter and control children. Glucagon immunoreactive cells were, on the average, 5-6 times and 7-9 times more numerous that SRIF cells in the rectum and the sigmoid, respectively. Ultrastructurally, five endocrine cell types could be distinguished. The fifth type, probably a transition type, apparently disappears in adults.

Child, Preschool↗

Immunohistochemical study of endocrine cells in the gastrointestinal tract of the Philippine carabao (Bubalus bubalis).

The distribution and frequency of occurrence of endocrine cells in the gastrointestinal tract of the Philippine carabao (Bubalus bubalis) were studied by immunohistochemistry. Fourteen types of immunoreactive (IR) endocrine cells were revealed. Among the cell types, only chromogranin, serotonin, and bovine pancreatic polypeptide (BPP) were present in the entire gut, while the others showed restricted distribution: somatostatin, gastrin, and cholecystokinin in the abomasum and small intestine; methionine-enkephalin-Arg6-Gly7-Leu8, motilin, neurotensin, secretin, gastric inhibitory peptide, and substance P in the small intestine; peptide tyrosine tyrosine (PYY) in the large intestine; and glucagon in the whole intestinal tract. Most of the cell types showed peak density in the pyloric, duodenal, or rectal region. The highest cell type heterogeneity was observed in the duodenum. The distribution profile of the gut endocrine cells in the carabao is closely related to that in the Holstein cattle. Important findings include the occurrence of BPP-IR cells in the entire gut and the high frequency of PYY-IR cells in the large intestine.

Abomasum↗

Endocrine cells in rectal biopsy specimens from patients with familial amyloidotic polyneuropathy.

BACKGROUND: A decreased amount of duodenal endocrine cells has recently been found in patients with familial amyloidotic polyneuropathy (FAP), and it has been suggested that this may contribute to the development of the gastrointestinal symptoms. The present study was performed to establish whether the endocrine cells in the lower gastrointestinal tract are also affected. METHODS: The endocrine cells in rectal biopsy specimens from 13 patients (7 women and 6 men) with FAP were investigated by means of immunocytochemistry and computed image analysis. These specimens were taken early during the disease. As controls, rectal specimens from 13 patients (7 women and 6 men) with rectal bleeding caused by haemorrhoids or polyps were included. RESULTS: The amount of both serotonin- and pancreatic polypeptide (PP)-immunoreactive cells was significantly decreased compared with the controls. There was no significant difference between patients and controls with regard to the amount of chromogranin A-, polypeptide YY (PYY)-, enteroglucagon- and somatostatin-immunoreactive cells. CONCLUSION: It has been suggested that serotonin depletion may contribute to the development of the severe constipation encountered in FAP patients in early stages of the disease. This constipation may promote bacterial overgrowth in the small intestine, with diarrhoea and malabsorption as a result.

Adult↗

Effects of food nutrient content, insect age and stage in the feeding cycle on the FMRFamide immunoreactivity of diffuse endocrine cells in the locust gut.

We have studied the influence of variations in dietary protein and digestible carbohydrate content, of insect age and of time during the feeding cycle on the endocrine cells of the ampullar region of the midgut in the African migratory locust Locusta migratoria L. Morphometric analysis of FMRFamide-like immunoreactivity was used as an indirect measure of the amount of FMRFamide-related peptides (FaRPs) stored in the gut endocrine cells. There was a highly significant correlation between FaRP content and the nutritional quality of the food, measured relative to the concentrations and ratio of protein to digestible carbohydrate in a nutritionally optimal diet. The direction of the relationship between FaRP content and diet quality varied with age during the fifth stadium. On day 1, FaRP levels increased with the nutritional quality of the food, while on day 4 the opposite relationship was observed. Release of peptide was triggered by the onset of a meal during ad libitum feeding, with cell FaRP levels returning to premeal values within 15 min of the meal ending. The results also suggested that cell contents were released during food deprivation beyond the normal intermeal interval. Locusts switched for a single meal during ad libitum feeding on day 4 from a low- to a high-carbohydrate food did not respond by reducing endocrine cell FaRP content. Our results show a relationship between the diffuse gut endocrine system and feeding and nutrition in locusts. The ampullar endocrine cells are in three-way contact with the midgut luminal contents, with the primary urine from the Malpighian tubules and with the haemolymph. They are thus ideally positioned to play an integrative receptor-secretory function in the regulation of a variety of post-ingestive processes, such as enzyme secretion, absorption, gut motility or nutrient metabolism.

Age Factors↗

Identification of the endocrine cells detected by the monoclonal antibody HISL-19 in human tissues.

The human endocrine cells reacting with the monoclonal antibody HISL-19 were identified with hormone antisera of proven specificity using a double immunostaining procedure. The epitope for HISL-19 was found in all types of pituitary cells except ACTH cells, in thyroid C cells, in all types of adrenal medullary and pancreatic islet cells and in somatostatin and pancreatic polypeptide cells of the gastrointestinal mucosa. No staining was found in parathyroid cells and in most gastrointestinal endocrine cells. Either paranuclear focal accumulation or diffuse cytoplasmic distribution of immunoreactive material were found. The spectrum of HISL-19 immunoreactive cells was found to be only in part complementary to that of cells immunoreactive for chromogranin A. Thus, it is concluded that the monoclonal antibody HISL-19 is a useful addition to other immunohistochemical markers for the detection of cells showing neuroendocrine features.

Adrenal Medulla↗

Ultrastructure of endocrine cells from the abdominal midgut epithelium of Lutzomyia longipalpis (Diptera: Psychodidae).

Transmission electron microscopy (TEM) was used to study two types of endocrine cells front the midgut of adult female Luttzomyia longipalpis (Lutz & Neiva). Endocrine cells rarely have been observed in Nematocera, even using TEM, and were present in small numbers dispersed among the monolayer of midgut digestive epithelial cells. Triangular shaped "closed" cells were observed along the basement membrane, bounded on each side by digestive cells; these cells closed distally before reaching the epithelial lumen. These endocrine cells appeared to deliver active granules that were secreted through a cellular membrane into the hemolymph. A second cell type occupied a similar position to the closed cells, but opened into the midgut lumen via microvilli, where the secretory products may be delivered. Each cell type possessed both electron-lucent and electron-dense vesicles with secretory granules which may indicate different stages in maturation and activity. These granular secretory products are probably peptidergic substances, with secretion mediated by diet via basal and baso-lateral receptors that were bound to membranes or microvilli.

Animals↗

Persistent expression of HNF6 in islet endocrine cells causes disrupted islet architecture and loss of beta cell function.

We used transgenesis to explore the requirement for downregulation of hepatocyte nuclear factor 6 (HNF6) expression in the assembly, differentiation, and function of pancreatic islets. In vivo, HNF6 expression becomes downregulated in pancreatic endocrine cells at 18. 5 days post coitum (d.p.c.), when definitive islets first begin to organize. We used an islet-specific regulatory element (pdx1(PB)) from pancreatic/duodenal homeobox (pdx1) gene to maintain HNF6 expression in endocrine cells beyond 18.5 d.p.c. Transgenic animals were diabetic. HNF6-overexpressing islets were hyperplastic and remained very close to the pancreatic ducts. Strikingly, alpha, delta, and PP cells were increased in number and abnormally intermingled with islet beta cells. Although several mature beta cell markers were expressed in beta cells of transgenic islets, the glucose transporter GLUT2 was absent or severely reduced. As glucose uptake/metabolism is essential for insulin secretion, decreased GLUT2 may contribute to the etiology of diabetes in pdx1(PB)-HNF6 transgenics. Concordantly, blood insulin was not raised by glucose challenge, suggesting profound beta cell dysfunction. Thus, we have shown that HNF6 downregulation during islet ontogeny is critical to normal pancreas formation and function: continued expression impairs the clustering of endocrine cells and their separation from the ductal epithelium, disrupts the spatial organization of endocrine cell types within the islet, and severely compromises beta cell physiology, leading to overt diabetes.

Animals↗

Malignant potential regarding mucin phenotypes and endocrine cell differentiation in gastric adenocarcinoma.

BACKGROUND: This study was designed to define the relationship between the mucin phenotype and differentiation in endocrine cells, including their biological behavior in gastric adenocarcinoma. MATERIALS AND METHODS: A total of 337 cases of solitary gastric adenocarcinoma were studied. The depth of tumor invasion was the mucosa in 58 cases, the submucosa in 206 cases and the muscularis propria in 73 cases. The mucin phenotype was divided into four phenotypes (gastric, intestinal, mixed and null types) based on immunohistochemical staining (HGM, Muc2 and CD10) and histochemical staining (PCS). Endocrine cells were identified by immunohistochemical staining (serotonin, gastrin, pancreatic polypeptide and Chromogranin A staining) in order to examine their relationship to mucin phenotype. Lymph node metastasis was used as a major indicator of the malignant potential. RESULTS: When lymph node metastasis was analyzed for tumors with submucosa(sm) or muscularis propria invasion, the incidence was significantly higher in the endocrine cell-positive [ECs(+)] group than in the endocrine cell-negative [ECs(-)] group. Namely, in gastric type, the incidence was 22.7% for the ECs(+) group and 0% for the ECs(-) group (p < 0.05). In intestinal type it was 26.9% for the ECs(+) group and 4.5% for the ECs(-) group (p < 0.05). When the 5-year survival rate of patients with a depth of sm or mp carcinoma was analyzed in relation to the mucin phenotype, no significant difference was seen in the survival rate according to the mucin phenotype, but the prognosis tended to be less favorable in the ECs(+) group than in the ECs(-) group (p = 0.06). CONCLUSION: The expression of endocrine cells was thus found to be more important as a prognostic factor than the mucin phenotype.

Adenocarcinoma↗

Evidence for polarization of plasma membrane domains in pancreatic endocrine cells.

Polarization of plasma membrane domains is an essential feature of secretory epithelial cells from exocrine glands. The surface of exocrine cells (a typical example is the acinar cell of the pancreas) is separated into an apical domain, where secretion occurs by exocytosis, and a basolateral domain, which senses variations of the internal milieu and is enriched with receptors for various hormones and secretagogues. It is unknown whether secretion is polarized in endocrine cells (except for thyroid follicular cells, which are organized into cavitary structures). To determine whether distinct plasma membrane domains exist in endocrine cells, we infected monolayer cultures of pancreatic endocrine cells with enveloped RNA viruses known to bud selectively from either the apical or basolateral domain in polarized epithelial cells. This asymmetrical budding is thought to reflect the polarized nature of the infected cells, as in non-polarized cells such as fibroblasts, the same viruses bud nonselectively from the entire cell surface. We show here that influenza virus and vesicular stomatitis virus (VSV) emerge asymmetrically from cultured pancreatic islet cells; this represents the first evidence for polarization of plasma membrane domains in pancreatic endocrine cells.

Animals↗

Mixed (composite) glandular-endocrine cell carcinoma of the stomach. Report of a case and review of literature.

A case of mixed (composite) glandular-endocrine cell carcinoma of the stomach is presented. Whereas the admixture of rare endocrine cells in ordinary adenocarcinoma of the stomach is a rather frequent occurrence, gastric tumors with an approximately equal proportion of glandular and endocrine cells are rare, and only 20 well-documented cases have been reported. Our case is unique in its range of histopathologic patterns, including well-differentiated and poorly differentiated adenoendocrine carcinoma as well as amphicrine differentiation. Immunohistochemical and electron microscopic findings are documented and the clinical characteristics of all reported cases tabulated. From the limited experience of these 21 cases, glandular-endocrine carcinoma of the stomach is found to have the following clinicopathologic features: It affects adults aged 32 to 74 years, (mean, 52.5 years) and has a male:female ratio of 1.3:1. It is located with almost equal frequency in the gastric body and antrum and has a poor prognosis, similar to that of advanced ordinary gastric carcinoma.

Adult↗

Ageing and endocrine cells of human duodenum.

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.

Adult↗

Multiple gastric carcinoids and endocrine cell micronests in type A gastritis: Nuclear morphometric and immunohistochemical analysis.

While the hyperplasia-neoplasia sequence of enterochromaffin-like (ECL) cells has been proposed in the pathogenesis of type I gastric carcinoids, the criteria for distinction between hyperplastic endocrine cell micronest (ECM) and neoplastic ECM have not been established. The aims of this study were to clarify differences between the hyperplasia and neoplasia of ECL cells and determine the optimal classification system for gastric ECL cell proliferations in type A gastritis. Endocrine cell lesions (n=531) from 8 surgically-resected stomachs with type A gastritis were reclassified as either atrophic ECM (n=333), hyperplastic ECM (n=168), neoplastic ECM (all ECM > or =0.1 mm in size, n=15), or typical carcinoid (n=15). Hematoxylin and eosin-stained sections were semiautomatically analyzed by nuclear morphometry. Immunohistochemical expression of bcl-2, p53 and Ki-67 was also investigated. As the histologic grade of histology advanced, the morphometric values of area, circumference and largest diameter of the nuclei significantly increased (p<0.0005), while the frequency of diffuse expression of bcl-2 significantly decreased (p<0.0001). Significant differences were also observed in all morphometric parameters and in bcl-2 positivity between the hyperplastic ECM and neoplastic ECM group. There was no expression of p53 in any of the lesions. The Ki-67 index did not differ between the neoplastic ECM and typical carcinoid groups. These results suggest that our system of classification for gastric endocrine cell proliferations in type A gastritis is appropriate. Nuclear morphometry and bcl-2 immunoexpression are useful parameters for the distinction of neoplastic ECMs from hyperplastic ECMs.

Adult↗

Expression of fucose residues in entero-endocrine cells.

The binding of the fucose-specific lectin, Ulex europaeus agglutinin (UEA-I), to entero-endocrine cells was studied in the ileum and caecum of humans, rabbits, rats, and mice. In all species investigated, numerous cells scattered in the crypt and villus epithelia intensely bound the UEA-I lectin. These cells proved to be argyrophilic and were identified as enterochromaffin cells and peptide tyrosine tyrosine cells by immunohistochemistry. They mostly reached the gut lumen ("open type") by slender cellular processes. At the ultrastructural level, fucose binding sites were located in the matrix of the electron-dense secretory granules of these cells and in the glycocalyx covering their apical membrane. The results show that in various mammalian species entero-endocrine cells of defined types express fucose-bearing glycoconjugates. The presence of fucose residues in the apical membrane of entero-endocrine cells indicates that this membrane domain has a specialized composition of intramembranous glycoconjugates which could be involved in receptive and/or secretory functions.

Adult↗

On argyrophil reactions of endocrine cells in the human fetal pancreas: a light and electron microscopic study.

The endocrine cells in the pancreas of five human fetuses with gestational ages of 18-20 weeks were examined by light and electron microscopy with special regard to argyrophil reactions. B-cells and typical A- and D-cells were easily identified electron microscopically on the basis of their typical secretory granules. In the Grimelius argyrophil silver stain, a concentration of silver grains over the less electron dense peripheral mantle of the A-cell secretory granules was observed by electron microscopy. In the Hellerström and Hellman modification of the argyrophil Davenport alcoholic silver stain, silver grains were concentrated over the internal structures of the D-cell secretory granules. With this stain an accumulation of silver grains was also seen at the surface of the A-cell secretory granules. The argyrophil reaction of the A-granules was less pronounced than in the D-cells. In addition to B-cells and A- and D-cells, two other types of endocrine cell were observed by electron microscopy. These cells were argyrophil with the silver impregnation method of Grimelius. The electron microscopic findings at least partly explain the frequent overlapping between the two staining methods observed at the light microscope level.

Cytoplasmic Granules↗