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Quantitative study of pulmonary endocrine cells in anencephaly.

Quantitative studies of pulmonary endocrine cells in 8 male autopsy cases of anencephaly were performed. The densities of pulmonary endocrine cells were expressed as the number of the total argyrophil cells/100 bronchiolar cell nuclei and as the number of the total argyrophil cells/mm bronchiole. The average values in the 8 anencephalic cases were 1.26 cells/100 nuclei and 3.56 cells/mm, and did not differ from the 1.28 cells/100 nuclei and 3.24 cells/mm in the control cases without malformation of the brain and without severe hyaline membrane disease of the lung. Furthermore, there was no significant difference in the densities of neuroepithelial bodies between the 2 groups. Immunostaining for calcitonin, bombesin, adrenocorticotropic hormone, chromogranin, and neuron-specific enolase also revealed no qualitative differences between them. It is concluded that defect and hypofunction of the hypothalamus-pituitary-adrenal axes associated with anencephaly do not have significant effects on the proliferation and differentiation of pulmonary endocrine cells in the fetus.

Anencephaly↗

The distribution of endocrine cells along the mouse intestine: a quantitative immunocytochemical study.

The topographical distribution of endocrine cells in the crypt and villus epithelium along the length of the mouse intestine was studied. Argyrophil reactivity using the Grimelius stain was used to estimate the total endocrine population of the intestine. Comparisons were then made with the fraction of endocrine cells containing glucagon like material, stained immunocytochemically using rabbit anti-glucagon antisera. A highly significant reduction in the incidence of endocrine cells (argyrophil reactive) from the proximal to distal end of the intestine was noted. However, only 10-30% of these cells contained glucagon like material in the crypts of the duodenum, jejunum and ileum, compared to 30-60% in the crypts of the colon and rectum. The distribution of endocrine cells (argyrophil reactive) was maximal in the lower regions of the proliferative zone of the crypts but showed no significant variation along the length of the villi. Cells containing glucagon like material were also most frequent in the lower regions of the proliferative zone of the crypts, but were not generally found above the bottom third of the villi. Each crypt in the small intestine contains between 3 and 5 endocrine cells one of which contained glucagon like immunoreactive material. In the colon and rectum each crypt contains about 6-8 endocrine cells, of which 3-4 contained glucagon like immunoreactive material. These results indicate that a sub-set of cells containing glucagon like material, differentiate early in the lineage of endocrine cells within the proliferative zone of the intestinal crypts.

Animals↗

Endocrine cell carcinoma of extrahepatic bile duct.

An endocrine cell carcinoma of the extrahepatic bile duct in a 79-year-old man is described. The patient had complaints of jaundice and epigastric pain due to a small tumor located at the confluence of the common hepatic duct with the cystic duct. Microscopically, the tumor showed a well differentiated tubular adenocarcinoma and was confined to the mucosa. Numerous tumor cells showed argyrophil and/or argentaffin reactions. Immunoperoxidase staining revealed that the tumor tissue contained somatostatin-, gastrin-and serotonin-immunoreactive cells. From these findings the tumor was diagnosed as endocrine cell carcinoma. Four years later he remains well without any evidence of recurrence or metastasis. The histogenesis of endocrine cells in the biliary tract is briefly discussed.

Adenocarcinoma↗

Neoplastic endocrine cells in carcinomas of the small intestine: histochemical and immunohistochemical studies of 24 tumors.

Endocrine cells in 24 primary carcinomas and in the nonneoplastic mucosa of the small intestine were investigated histochemically and immunohistochemically with antisera against serotonin and 10 kinds of peptide hormones. Argyrophil-positive endocrine cells were found in four of eight duodenal, all of eight jejunal, and six of eight ileal carcinomas. The density of the positive cells was higher in the ileal tumors than in the duodenal and jejunal ones. Immunoreactive endocrine cells were detected in three duodenal, six jejunal, and five ileal carcinomas. Immunoreactive serotonin cells were present most frequently and most densely without respect to the site of origin of the carcinomas. In general, the population of endocrine cells among the tumor cells was higher in the ileal carcinomas than in the duodenal and jejunal ones. The ileal carcinomas frequently and densely demonstrated somatostatin, peptide YY, neurotensin, glucagon, and glicentin cells in addition to serotonin cells. The kinds of endocrine cells and the relative frequency of each kind of endocrine cell in carcinomas of the small intestine were similar to those in the nonneoplastic mucosa from which the carcinomas originated. This is the first systematic immunohistochemical study on endocrine cells in carcinoma of the small intestine.

Adult↗

Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells.

Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synthesizing the pancreatic hormones insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm, gut-tube endoderm, pancreatic endoderm and endocrine precursor--en route to cells that express endocrine hormones. The hES cell-derived insulin-expressing cells have an insulin content approaching that of adult islets. Similar to fetal beta-cells, they release C-peptide in response to multiple secretory stimuli, but only minimally to glucose. Production of these hES cell-derived endocrine cells may represent a critical step in the development of a renewable source of cells for diabetes cell therapy.

Cell Differentiation↗

Immunohistochemical study of the pancreatic endocrine cells of the ray, Dasyatis akajei.

The pancreatic endocrine cells of the ray, Dasyatis akajei was studied by aldehyde-fuchsin-Masson-Goldner's staining and by immunohistochemical methods. The pancreatic endocrine cells of the ray do not form islets by represent the most primitive distribution among elasmobranchs, occupying the outer layer of the double-layered duct epithelium of the pancreas. The endocrine cells showed no evidence of reaching the duct lumen, i. e., they are closed in type. By the use of immunohistochemical techniques, insulin-, glucagon-, somatostatin-and pancreatic polypeptide (PP)-like immunoreactivities were detected in the endocrine cells. The PP-positive cells could not be differentiated from the somatostatin-immunoreactive cells, although the former were smaller in number. The possible reasons for this result were discussed. The present finding supports the view that those four peptides are essential regulatory substances of the endocrine system of the pancreas at a fairy early stage of vertebrate evolution.

Animals↗

Endocrine cells in human cardial glands.

The presence of argentaffin cells (possibly of endocrine nature) in the human cardiac mucosa has been reported. The nature of these cells has not been characterized further. Biopsies of cardiac mucosa taken immediately distal to esophageal epithelium were studied ultrastructurally and immunohistochemically in seven healthy volunteers. Of 62 ultrastructurally-examined endocrine cells 21 % were enterochromaffin cells (EC) of the gastric type, 13 % were enterochromaffin (EC2) cells, 56% were enterochromaffin-like (ECl) cells and 10 % were D1 cells. All endocrine cells studied were of the "closed" type, which never reached the lumen of the cardiac glands, being separated from the lumen by the cytoplasm of mucous cells. Immunohistochemical examinations were performed using antibodies to gastrin, glucagon, somatostatin, VIP, secretin, motilin, pancreatic polypeptide, insulin and substance Pl Studies were performed simultaneously on human pancreatic, pyloric and duodenal tissue. Positive reactions were obtained for all antibodies on human tissue. Cardiac glands endocrine cells gave negative reactions for all hormones studied. In conclusion, human cardiac mucosa contains a relatively large number of endocrine cells. The function of these cells remains to be determined.

Adult↗

Neuroepithelial bodies (NEB) and solitary endocrine cells in the hamster lung.

Periodic acid-Schiff (PAS)-positive small-granule endocrine cells identified in serial plastic sections through 95% of the infracardiac lobe of a Syrian golden hamster lung were marked on a 70X cardboard reconstruction of the airways and recorded for computerized analysis as described in the preceding paper in this volume [1]. When airways were subdivided into thirds and the resulting small pieces of airway surface were analyzed statistically, endocrine cell loci appeared to be randomly distributed in the epithelial layer. Nevertheless, loci were absent from only 10 of 209 unit airways, far short of the 28 predicted from a random distribution. Solitary endocrine cells accounted for 37% of 980 loci but only 6% of all endocrine cells; 63% of loci consisted of endocrine cell clusters, broadly defined as "neuroepithelial bodies," of from 2 to 107 cells. Although small groups were preponderant, no significant discontinuity occurred in the size distribution between 1 and 56 cells per locus. Neuroepithelial bodies predominated everywhere, but especially in the lobar bronchus and at bronchioloalveolar portals, where cuboidal bronchiolar epithelium gives way to the attenuated epithelium of the respiratory zone; 45% were related to peribronchial smooth muscle and 18% to pulmonary capillaries. Only 3.3% of solitary cells were related to capillaries, 29% to airway muscle; 68% occurred in muscle-free regions of the airway, associated preferentially with ciliated epithelial cells. We conclude that endocrine cells are distributed in such a way that virtually all airways have at least one locus. This nonrandomness suggests that these cells are in fact important to normal lung function. Furthermore, because solitary endocrine cells and "neuroepithelial" cell clusters have different intrapulmonary distributions, they may well have distinct identities and functions.

APUD Cells↗

Gastrointestinal endocrine cell hyperplasia in celiac disease: a selective proliferative process of serotonergic cells.

Untreated celiac disease is characterized by gastrointestinal endocrine cell hyperplasia (ECH). This study investigated the constitutive nature of the ECH. Ten duodenal biopsies showing villous atrophy from adult celiacs were evaluated against ten sex- and age-matched controls. The mean number of endocrine cells per unit length of mucosa in the celiacs was compared with the control group using the Student t test. These values, respectively, were as follows: Churukian-Schenk method, 52.4 versus 29.6 (P = 0.001); Fontana-Masson, 32.5 versus 18.4 (P = 0.016); chromogranin, 33.4 versus 23.6 (P = 0.017); serotonin, 44.7 versus 26.7 (P = 0.006); somatostatin, 5.0 versus 5.4 (P = 0.631); and gastrin, 0.37 versus 0.37 (P = 1.000). There was thus ECH as shown by the first four stains with, in some areas, the endocrine cells continuously abutting against each other to form linear profiles. With respect to specific hormonal products, only serotonin showed ECH. These results suggest that the ECH in celiac disease is not a haphazard process but, instead, a selective proliferation of certain endocrine cell types.

Adult↗

Interactions between autonomic nerves and endocrine cells of the gastroenteropancreatic system.

Autonomic nerves and endocrine cells of both the gastrointestinal tract and the pancreatic islets participate in the control of several processes related to the digestion and metabolism of nutrients. While it was once thought that they acted separately to regulate these processes, it is now appreciated that numerous interactions exist between the functions of autonomic nerves and GEP endocrine cells. Recent studies show that autonomic signals play a role in the secretory activity of various GEP cells, thus providing a mechanism by which the central nervous system can integrate digestive and metabolic functions. It also has been shown that nerves and endocrine cells frequently share certain common peptides and/or amines. Therefore, in functional terms, it is often difficult to determine whether a specific peptide of amine should be considered a neurotransmitter or a hormone. Within the next few years, one can reasonably expect that new techniques and methods of investigation will clarify the roles of putative chemical messengers such as the peptides found within autonomic nerves and the amines found within endocrine cells. It also seems likely that future studies will demonstrate that the specific chemical messenger and the mechanism by which it reaches its target cells are far more important factors in the understanding of gastrointestinal and endocrine pancreatic function, than whether or not these signals are neural or endocrine in origin.

Amines↗

An immunohistochemical study on the endocrine cells in the gastrointestinal tract of domestic duck.

Endocrine cells in the gastrointestinal tract of the domestic duck were identified immunocytochemically using antisera specific to bombesin, chromogranin A, cholecystokinin (CCK), gastrin, glucagon, neuron specific enolase (NSE), neurotensin, secretin, 5-hydroxytryptamine (5-HT), somatostatin, substance P and vasoactive intestinal polypeptide (VIP). Chromogranin A, 5-HT and somatostatin immunoreactive cells were widespread throughout the gastrointestinal tract. Bombesin immunoreactive cells were observed only in the proventriculus and the gizzard. CCK, substance P and neurotensin immunoreactive cells were present in the intestinal tracts from the duodenum to the colorectum. The latter were numerous also in the antrum. Gastrin cells were peculiar to the antrum but present also in the gizzard and small intestine. Glucagon immunoreactive cells were present in the jejunum-ileum and above all in the large intestine. Only few secretin cells were present in the duodenum. The highest frequency of endocrine cells was found in the antrum, while the lowest was observed in the caeca. Antisera to somatostatin and substance P showed numerous nerve cells and fibers besides endocrine cells, whereas NSE and VIP immunopositivity was found in the nervous structures only of the gut wall.

APUD Cells↗

Characterization of the endocrine cells in the pancreatic-bile duct system of the rat.

Six types of endocrine cells showing immunolabelling against gut or pancreatic islet hormones were identified in the pancreatic-bile duct system of the normal adult rat at the light and electron microscopic levels. They were located within the epithelial lining of the duct system from the intercalated portion to its duodenal opening. However, the distribution and frequency of each endocrine cell varied along the length of the duct system. While insulin, glucagon, somatostatin, and pancreatic polypeptide cells were widely distributed along the entire duct system, small numbers of cholecystokinin and serotonin cells were confined to the terminal portion. A considerable number of somatostatin cells were concentrated in gland-like pouches of the terminal portion of the common pancreatic-bile duct. When the accessory pancreatic duct was present, insulin, glucagon, and somatostatin cells were also found in its epithelial lining. Electron microscopically, the specific content of the secretory granules of all endocrine cells was confirmed by immunolabelling or cytochemical staining. Further the characteristics of the secretory granules of each endocrine cell type corresponded to those present in the same kind of endocrine cells in gut or pancreatic islet. The duct endocrine cells displayed a particular ultrastructural appearance. The "open type cells" were highly polarized, with their apical cytoplasmic process reaching the duct lumen, whereas "closed type cells" showed long basal cytoplasmic processes with no connection with the duct lumen. In general, insulin, and somatostatin cells were of the "open type", while no morphological connection with the duct lumen was found for glucagon and pancreatic polypeptide cells. The presence of various duct endocrine cells with their particular ultrastructural appearance implies that they may take part in modulating the function of the duct system.

Animals↗

[Endocrine cells in human laryngeal tumors (ectopic hormone secretion)].

Hormone-producing cells (apudocytes) were found immunohistochemically in 3 out of 15 squamous cell carcinomas of the larynx. In one tumor these cells synthesized melatonin and a thyrotropic hormone, in the other insulin, and in the third insulin and somatotropic hormone. The appearance of tumor cells with endocrine function in nonendocrine neoplasias is considered to be not ectopic but the result of malignization at the level of polypotent cells followed by their differentiation into epithelial or endocrine cells.

Carcinoma, Squamous Cell↗

A fine structural characterization of the proliferated endocrine cells in atrophic gastric mucosa.

This study shows that most of the proliferated endocrine cells in nonintestinalized epithelium in the body of stomachs in patients with pernicious anemia have the fine structure of ECL (enterochromaffin-like) cells, the principal endocrine cell in the body of normal stomachs, and notes an absence of G (gastrin) cells, the principal endocrine cell in the normal pylorus. Since gastrin has been identified in many of these proliferated cells by immunofluorescence, these findings question the position that gastrin synthesis in the stomach is only associated with G cells.

Anemia, Pernicious↗

Oxyntic endocrine cells of hypergastrinaemic patients. Differential response to antrectomy or octreotide.

BACKGROUND/AIMS: To evaluate the response of endocrine cells of the gastric oxyntic mucosa in hypergastrinaemic patients to either antrectomy or treatment with the somatostatin analogue octreotide. PATIENTS: (a) Two patients with enterochromaffin-like (ECL) cell carcinoid and chronic atrophic gastritis, treated with antrectomy; (b) four patients with Zollinger-Ellison syndrome, treated with octreotide. METHODS: Oxyntic endocrine cells were examined by ultrastructural morphometry on full thickness biopsy specimens taken: (a) before and four months after antrectomy, (b) before and after three months' treatment with octreotide 200 micrograms daily. RESULTS: Both treatments induced prompt, significant reduction of gastrinaemia and a significant decrease of the volume density of the whole endocrine cell mass and of the cross sectional area of all nucleated endocrine cell profiles (antrectomy: -38%, p < 0.04 and -31%, p < 0.04, respectively; octreotide: -59%, < 0.007 and -26%, < 0.04, respectively). Assessment of the relative proportion of individual endocrine cell types showed a different response to antrectomy or octreotide. After antrectomy, in fact, only the volume fraction of ECL cells was significantly reduced, from 56.5% to 22.5% (-60%, p < 0.04). After octreotide treatment, in contrast, the proportion of all endocrine cell types remained remarkably constant, showing that all cell types took part in the observed overall decrease. CONCLUSIONS: Postantrectomy reduction of oxyntic endocrine cells mostly reflects the withdrawal of the specific trophic stimulus of hypergastrinaemia on ECL cells. In contrast, the inhibitory response to octreotide seems to be exerted on virtually all types of oxyntic endocrine cells, probably reflecting a universal occurrence of somatostatin receptors.

Adult↗

Ultrastructural colocalization of the bioactive mediators 5-hydroxytryptamine and bombesin in endocrine cells of human fetal airways.

Endocrine cells in the airway epithelium of human fetal lungs are known to contain an amine, 5-hydroxytryptamine (5HT), and a peptide, bombesin (BOM). These mediators may be involved in regulating smooth muscle and secretory activity in the airways as well as in development of the fetal lung. However, the exact endocrine cell type that contains 5HT and BOM has not been described at the ultrastructural level. This investigation provides immunocytochemical evidence that 5HT and BOM are stored in a single cell type, the P1 cell. Thin sections of airways from human fetal lungs were incubated either in anti-5HT antiserum (diluted 1:3000) or in anti-BOM antiserum (diluted 1:600) and then labeled with affinity purified goat anti-rabbit IgG coupled to 16 nm gold particles. For colocalization, thin sections were incubated on one side to demonstrate 5HT and on the other side to demonstrate BOM. Two different sizes of gold particles (10 and 30 nm) were coupled to IgGs and used for the labeled second antibodies. Controls consisted of absorbing of the primary antiserum with an excess of either 5HT or BOM. 5HT- and BOM -like immunoreactivities were observed in the dense-core vesicles (DCV) of P1 cells, and it was apparent from serial sections that 5HT and BOM labeling was sometimes present in the same P1 cells. Sections labeled for 5HT on one side with large gold particles and for BOM on the other side with small gold particles revealed that 5HT- and BOM-like immunoreactivities were located in the same DCV.(ABSTRACT TRUNCATED AT 250 WORDS)

Bombesin↗

Proliferative activity of gastric and duodenal endocrine cells in the rat.

The replicative activity and migration of gastrin, somatostatin and serotonin cells in rat stomach and duodenum was studied using combined immunocytochemistry and autoradiography after 3H thymidine pulse-labeling. Our results show that a small proportion of gastrin, somatostatin and serotonin immunoreactive cells displays proliferative activity. The overall labeling index ranged from 1.3% for gastric endocrine cells to 3.2% for duodenal endocrine cells. In a pulse chase experiment, labeling indices of immunoreactive cells were estimated at several time intervals after 3H thymidine administration. Significant differences in labeling index were not found. Migration of 3H thymidine labeled endocrine cells towards the luminal surface was not found in the stomach nor in the duodenum. It is concluded that 1) these endocrine cells have replicating activity; 2) the replicative activity of endocrine cells is higher in the duodenum than in the stomach; 3) the various cell types do not show significant differences in replicating activity and 4) endocrine cells did not seem to migrate to the luminal surface of the mucosa along with the other epithelial cells.

Animals↗

Large intestinal endocrine cells in non-obese diabetic mice.

Colonic endocrine cells from prediabetic and diabetic non-obese diabetic mice as well as of the sister strain, BALB/cJ, were investigated by immunocytochemistry and computer image analysis. In prediabetic mice, enteroglucagon-and serotonin-immunoreactive cells were significantly increased in number, whereas the cell secretory index of these two cell types was significantly reduced. No significant differences were found in numbers or cell secretory index of peptide YY (PYY)-immunoreactive cells. In diabetic mice, PYY-immunoreactive cells were significantly fewer, but there were no significant differences in the numbers of enteroglucagon-and serotonin-immunoreactive cells. Whereas the cell secretory index was reduced in serotonin-producing cells, no significant differences were found between diabetic and control mice regarding the cell secretory index of PYY- and enteroglucagon-immunoreactive cells. Nor was any statistically significant difference found between controls, prediabetic and diabetic non-obese diabetic mice, regarding the thickness of submucosa, of circular and longitudinal-muscle layers, or of the mucosal area/microm baseline. The present study showed that abnormalities in colonic endocrine cells do occur, in both prediabetic and diabetic mice, but they are different in nature and can be divided into primary and secondary to the diabetes onset. The present findings of abnormal colonic endocrine cells in non-obese diabetic mice, an animal model for human insulin-dependent diabetes mellitus, might help explain the gastrointestinal disorders observed in patients with diabetes. The study also showed that the change in the colonic endocrine cells is dynamic and started before the onset of the diabetic condition.

Animals↗