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Pulmonary endocrine cells in various species in the Himalaya.

The numbers, morphology and distribution of pulmonary endocrine cells in goats, sheep and the yak and its interbreeds with cattle, dzos and stols, were studied after their demonstration by means of the peroxidase-antiperoxidase technique with a polyclonal antiserum raised in the rabbit to human neuron-specific enolase, a marker for neuroendocrine cells. The numbers, morphology and distribution were related to species and not to residence at high altitude. Pulmonary endocrine cells were common and mainly distributed as solitary cells in the epithelium of the bronchial tree in sheep. They were much less common and found mainly as clusters in the alveolar capillary walls in goats and in the yak and its interbreeds with cattle.

Altitude↗

Epithelial changes following bone marrow transplantation: cytological atypia and epithelial endocrine cells.

This report describes the histological and immunocytochemical findings in gastrointestinal biopsies and skin of a patient with chronic granulocytic leukaemia which progressed to blastic transformation, who was then treated with chemotherapy and total body irradiation followed by allogeneic bone marrow transplantation. The gut showed endocrine cells in the lamina propria and these had an immunophenotype similar to the glandular epithelium at the sites studied (stomach, duodenum and rectum), supporting the idea that the endocrine cells of the gut are more resistant to the effect of radiation, chemotherapy and graft-versus-host disease (GVHD) than are other cell types in the epithelium, and that lamina proprial endocrine cells are epithelially derived in this situation. Epidermis and gut epithelium also showed marked atypia due to the conditioning regimen and GVHD, and this case illustrates the possibility of misdiagnosis of carcinoma in this increasingly common situation. An additional, unusual feature of this case was the presence of a B-cell UCHL1 + ve lymphoma of the colon at autopsy, 122 days post-transplantation.

Bone Marrow Transplantation↗

Morphometry of gastric endocrine cells in hypergastrinemic patients treated with the somatostatin analogue octreotide.

The aim of the study was to evaluate whether treatment with 200 micrograms/d of the somatostatin analogue octreotide (SMS 201-995) for three months can influence the trophic action exerted by hypergastrinemia on endocrine cells of the oxyntic mucosa, a condition potentially leading to hyperplasia and carcinoid tumors. Endocrine cells were morphometrically investigated in Grimelius silver stained sections of endoscopic biopsies of oxyntic mucosa collected from 13 hypergastrinemic patients with Zollinger-Ellison syndrome (ZES) (n = 5), antral G cell hyperfunction (AGCH) (n = 4) and atrophic gastritis type A (AG-A) (n = 4) before and after 3 months treatment and 3 months after drug discontinuance. The treatment induced a reduction of the volume density (P < 0.015), profile cross sectional area (P < 0.05) and number of cell profiles per unit area (P < 0.015) of argyrophil cells. A rebound of all these parameters was observed 3 months after drug withdrawal with values usually exceeding those at the entry, except in cases of AG-A. The patients' plasma gastrin concentrations presented similar variations showing a significant relation with all morphometric parameters of argyrophil cells. Also, the cell content in alpha subunit of human chorionic gonadotropin was related to the plasma gastrin levels, a finding confirming the close gastrin dependence of the expression of this protein by oxyntic endocrine cells. No significant changes were observed in mucosal somatostatin D cells. These results indicate that variations in circulating gastrin levels are the most likely factor responsible for the hypotrophic effect of octreotide on oxyntic argyrophil cells (mostly corresponding to the ECL cells) of hypergastrinemic patients.

Adult↗

Changes of gastrointestinal argyrophil endocrine cells in the COLO205 tumor-implanted Balb/c-nu/nu mice.

The regional distributions and frequencies of argyrophil endocrine cells in gastrointestinal (GI) tract of Balb/c-nu/ nu mouse were studied using Grimelius silver stain after abdominal subcutaneous implantation of COLO205. The experimental animals were divided into two groups, one is non-implanted group (Sham) and the other is COLO205- implanted group. Samples were collected from GI tract (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) at 21 days after implantation of COLO205 cells (1 x 10(6) cell/mouse). In this study, argyrophil cells were detected throughout the entire GI tract with various frequencies regardless of implantation. Most of these argyrophil cells in the mucosa of GI tract were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were found occasionally in gastric and/or intestinal gland regions. The regional distributions of argyrophil cells in COLO205 were similar to those of Sham. However, significant decreases of argyrophil cells were detected in COLO205 compared to those of Sham except for the jejunum and ileum. In the jejunum and ileum, argyrophil cells in COLO205 showed similar frequencies compared to those of Sham. In the pylorus, the most dramatically decreasement of argyrophil cells were detected in COLO205 compared to that of Sham. Implantation of COLO205 tumor cell line induced severe quantitative changes of argyrophil cell density, and the abnormality in density of GI endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.

Animals↗

Ultrastructural studies of endocrine cell populations showing an argentaffin reaction and/or serotonin immunoreactivity in the rat antral mucosa.

On the basis of staining results in closely related semi-thin sections from rat antral mucosa immunostained with polyclonal serotonin antibodies and silver-stained for the argentaffin reaction, respectively, three different cell populations could be distinguished. One of these cell populations showed both serotonin immunoreactivity and an argentaffin reaction, a second one serotonin immunoreactivity alone, and a third one only an argentaffin reaction. These cell populations were studied electron microscopically in ultra-thin sections located between the stained semi-thin sections. The cell population displaying an agentaffin reaction and serotonin immunoreactivity showed secretory granules of the enterochromaffin cell type. A similar granular appearance was observed in cells which only exhibited an argentaffin reaction. Serotonin immunoreactivity in the absence of an argentaffin reaction was evident in some G (gastrin) cells, and in some D1 and possibly also some D (somatostatin) cells; but not all the endocrine cells of the non-enterochromaffin type displayed serotonin immunoreactivity. The significance of the different reactions in the three cell populations is discussed.

Animals↗

Gastric endocrine cells and gastritis in patients receiving long-term omeprazole treatment.

Both argyrophil endocrine cells and gastritis were investigated in 2,120 biopsies of gastric corpus mucosa from 443 out of 448 patients receiving long-term (for periods ranging from several months to 4 years) omeprazole treatment. None of the patients showed neoplasia or dysplasia, either endocrine or non-endocrine. In 123 out of 443 patients (27.8%), endocrine hyperplasia of diffuse (9.3%), linear (4.1%) or micronodular (14.4%) type was detected either before or at some time during treatment. Chronic atrophic gastritis was found in 45 (10.2%) patients, 60% of whom also showed micronodular hyperplasia. In patients with chronic atrophic gastritis, micronodular hyperplasia occurred in 49% of 96 biopsies, compared with 6% of 1,083 biopsies from patients with non-atrophic chronic gastritis and 2% of 941 biopsies from patients with no evidence of gastritis. In 202 patients treated with omeprazole for at least 330 days, the incidence of micronodular hyperplasia increased from 2.5% at the first biopsy to 10.4% at the final biopsy, while the incidence of chronic atrophic gastritis increased from 1.0% to 13.0%. The present and parallel studies suggest that progression of gastritis is inherent in the natural history of acid-related diseases, while endocrine cell changes are mostly secondary to gastritis-related gland atrophy and have no tumorigenic potential.

Adult↗

Experimental ultrastructural study on stimulation of the rat gastric endocrine cells. In vitro distension of the stomach by air inflation.

The effect of distension of the stomach by air (in vitro) upon the ultrastructural picture of gastric endocrine cells in rats starved for 72 hours was investigated. Distension of the stomach by air in vitro, lasting for 5, 10, 15 and 20 minutes, resulted in massive dissolution of gastrin granules that had accumulated in the course of starvation. In AL, D1, EC and ECL cells distension of the stomach by air failed to induce dissolution of granular content or release of granules by any other mechanism. In AL and D1 cells accumulation of secretory granules caused by starvation was observed, the ultrastructure of EC and ECL cells remained unchanged both under the effect of starvation and distension. Dilatation of endoplasmic reticulum profiles as well as other changes on some cell organelles observed on endocrine cells after distension of the stomach by air in vitro are due to the effect of autolysis.

Air↗

Metallothionein does not protect mouse endocrine cells from damage induced by alloxan injection.

Effects of metallothionein (MT) on pancreatic endocrine cells of mice, injected with alloxan and at different zinc status were studied. Mice were given drinking water containing four different concentrations of zinc (0, 0.05, 0.1 or 0.5%) for 18 days, and alloxan was injected once on the 14th day. When zinc was added to the drinking water, pancreatic zinc and MT contents increased after injection of alloxan, but did not change with injection of vehicle alone, except in the group of mice drinking 0.5% zinc in water. However, plasma glucose level was increased in all the alloxan injected groups, and was independent of their zinc status. In mice given water with 0.5% of zinc, both pancreatic zinc and MT contents were higher than control mice given water alone. There was no difference in zinc and MT contents of the pancreas in mice drinking 0.5% zinc in groups injected with either alloxan or vehicle. The increase in plasma alpha-amylase activity, an indicator of pancreatic exocrine toxicity, was observed only in mice drinking water with 0.5% zinc after injection of both alloxan and vehicle. Histochemically, degranulation of zymogen and duct-like structures of exocrine cells and atrophy and disappearance of islet cells were observed in alloxan-injected mice drinking 0.5% zinc in water. The zymogen degranulation was observed on the vehicle-injected mice drinking 0.5% zinc in water. MT was immunohistochemically detected in the exocrine cells of both alloxan- and vehicle-injected mice given 0.5% zinc in water. No MT was detected in islet cells of mice in any group. The results show that an increase of zinc content may be followed by induction of MT synthesis in the pancreas of mice given increasing amounts of zinc in drinking water. However, MT dose not provide any protection against damage caused by alloxan to endocrine cells of the pancreas.

Alloxan↗

Quantitative morphology of endocrine cells in human fetal pancreas.

Sections of pancreas from human fetuses, 6-20 weeks gestation, were stained with immunoperoxidase for insulin (B cells), glucagon (A cells), pancreatic polypeptide or somatostatin (D cells). Morphometric analyses were performed on sections from head and tail regions of each fetus. No stained cells were found at 7 weeks. A, B, pancreatic polypeptide and D cells were found at 9 weeks in primitive islets or as isolated cells adjacent to duct cells. There was no relationship between the density of each endocrine cell type and fetal age, but there was a significant increase in the relative density (percentage total endocrine cells) of D cells from 10-20 weeks (p less than 0.01). The tail contained significantly more A cells (p less than 0.05) and less pancreatic polypeptide cells (p less than 0.01) than the head but similar densities of B and D cells. Lobules containing a high density of pancreatic polypeptide cells and few A cells were found in the posterior part of the head in six fetuses, aged 10-20 weeks.

Cell Count↗

Immunocytochemical identification of endocrine cells in the pancreas of the fruit bat, Rousettus aegyptiacus.

The fruit bat, Rousettus aegyptiacus, is able to absorb large amounts of glucose in very short periods of time. This ability is partly reflected by the structure of the gastrointestinal tract and pancreas. The aim of this study was to confirm preliminary histochemical studies of the bat pancreas and to identify and quantitate endocrine cells by immunocytochemical techniques in order to understand the ability of the bat to absorb these large amounts of glucose. Endocrine cells were distributed in islets throughout the gland and also occurred as discrete cells in the exocrine ducts. Three-dimensional reconstruction and quantitation showed that the endocrine component of the pancreas occupied 9.1% of the total volume. This is far more than that reported in any other species. Four endocrine cell types were demonstrated. Insulin (beta) cells (51.4%) were located throughout the islet and extended between the glucagon (alpha) cells (30.6%). Somatotostatin (delta) cells (8.8%) and pancreatic polypeptide (PP) cells (17.1%) were irregularly scattered throughout the islets. While the percentage of alpha, beta, and delta cells was similar to that in other species, the percentage of PP cells was higher. The high percentage of endocrine tissue found in the pancreas of the fruit bat may reflect metabolic adaptations involved in the absorption of the high carbohydrate diet of this animal.

Animals↗

[Differentiation of human pancreatic endocrine cells in the period of fetal development].

The stereological analysis of electron micrographs of pancreatic endocrine cells (A and B) obtained from human fetuses at gestational months 4 to 7 was performed to assess the volume densities of membranous organelles (mitochondria, rough endoplasmic reticulum, Golgi complex), polysomes and secretory granules. The differences were established in the ratios of the volume densities of organelles and secretory granules in the process of differentiation. The morphometric characteristics of total A- and B-cell populations as well as the quantitative data on the structural organization of endocrine cells at various stages of differentiation are presented.

Cell Differentiation↗

Neuron specific enolase: a common marker for the endocrine cells and innervation of the gut and pancreas.

Neuron specific enolase, the most acidic isoenzyme of the glycolytic enzyme enolase, was first believed to be present exclusively in central neurons. More recently, it has been found in peripheral autonomic nerves and in a number of endocrine cells. An immunocytochemical study was carried out concerning the distribution of neuron specific enolase in the gastrointestinal tract and pancreas of humans and rats. In addition, immunocytochemistry and histochemistry were used to obtain a characterization of the different types of cells and nerves in which neuron specific enolase can be detected. Neuron specific enolase was found in all currently identifiable endocrine cell types and nerves of the gut and pancreas. Neuron specific enolase is therefore a common marker for both endocrine cells and enteric nerves, thus providing a simple means for their simultaneous demonstration and examination of their morphologic characteristics and integration.

Animals↗

Histological and immunocytochemical data on the differentiation of intestinal endocrine cells in human fetus.

The differentiation of the argyrophil, argentaffin, 5-hydroxytryptamine (5-HT)-, somatostatin (SOM)-, cholecystokinin (CCK)-, substance P (SP)-, methionine-enkephalin (Met-Enk)- and vasoactive intestinal polypeptide (VIP)-immunoreactive entero-endocrine cells (EECs) was examined in human fetuses. A great increase in the frequency of EECs in the duodenum and the rectum was observed between the 7th and 12th gestation week. The differentiation of the EECs advanced distally in the small intestine and proximally in the large intestine. In 24-25-week-old fetuses the frequency of the EECs was also increased in the ileum and the colon. A different time-course of the appearance and differentiation of the types of EECs was observed. Met-Enk- and VIP-immunoreactive endocrine cells were not detected at any age. A regional difference in the frequency and morphology of the endocrine cell types was observed in the eldest fetuses.

Cell Differentiation↗

Exocytotic release of secretory granules from endocrine cells in the midgut of insects.

Exocytotic release of the secretory granules of the endocrine cells in the midgut of a cockroach, Periplaneta americana, was studied by means of fixation with tannic acid in combination with glutaraldehyde and osmium tetroxide. A sequence of images indicative of exocytosis suggests the following steps in this process: (1) A delicate connection appears between the granule-limiting membrane and the plasma membrane. (2) The plasma membrane approaches the granule, forming a concave indentation. (3) The granule-limiting membrane fuses with the plasma membrane and opens to give rise to an omega profile. (4) The granule content is voided into extracellular space. Exocytosis occurs not only at the base of the cell but occasionally at its side facing adjacent cells. (5) The exocytotic invagination after release becomes smaller and narrower; sometimes a coated pit with bristles appears. Multiple exocytosis, and exocytosis in the endocrine cells of the nidus, i.e., the regenerative cell mass, are also described.

Animals↗

An immunohistochemical study of the gastrointestinal endocrine cells in the C57BL/6 mice.

The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the eight portions (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) of the gastrointestinal tract of C57BL/6 mouse was studied with immunohistochemical method using seven types of specific anti-sera against chromogranin A (CGA), serotonin, somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and cholecystokinin (CCK)-8. In this study, all these seven types of immunoreactive (IR) cells were identified. Most of these IR cells in the intestinal portion were generally spherical or spindle in shape (open-type cell) while cells showing round in shape (closed-type cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of gastrointestinal tract. CGA-IR cells were demonstrated throughout the whole gastrointestinal tract and they showed most predominant in the pylorus and duodenum. Serotonin-IR cells were detected throughout whole gastrointestinal tract and they showed highest frequency in the stomach and colon. Somatostatin-IR cells were demonstrated throughout whole gastrointestinal tract except for large intestine and showed highest frequency in the fundus. HPP-IR cells were found in the fundus with rare frequency. Peculiarly, glucagon-IR cells were restricted to the fundus, ileum and colon with a few frequencies. Gastrin-IR cells were restricted to the pylorus with numerous frequency and CCK-8-IR cells were observed in the pylorus, duodenum and jejunum with numerous and/or a few frequencies, respectively. In conclusion, some peculiar distributional patterns of gastrointestinal endocrine cells were found in C57BL/6 mouse.

Animals↗

An immunohistochemical study of the pancreatic endocrine cells of the nude mouse, Balb/c-nu/nu.

The regional distribution and frequency of the pancreatic endocrine cells in the nude mouse, Balb/c-nu/nu were studied by immunohistochemical (peroxidase anti-peroxidase; PAP) methods using specific antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (hPP). The pancreas of the mouse was divided into two lobes, the splenic and duodenal lobes, and each lobe was subdivided into three regions, the pancreatic islets (central and peripheral regions), the exocrine region and the pancreatic duct region (consisting of duct epithelium and surrounding connective tissue--sub-epithelial connective tissue). In the pancreatic islets, most of insulin-immunoreactive (IR) cells were located in the central region, and glucagon-, somatostatin and hPP-IR cells were located in the peripheral region regardless of the lobe. In the splenic part, glucagon-IR cells were also located in the central regions, and more numerous somatostatin-IR cells were detected in the central regions compared to those of the duodenal part. hPP-IR cells were restricted to the peripheral regions in both lobes but more numerous cells were detected in the duodenal portion as compared to those of the splenic portion. In the exocrine parenchyma of the splenic lobe, only insulin-, glucagon- and somatostatin-IR cells were detected.. Here, the insulin- and glucagon-IR cells formed cell clusters, while somatostatin-IR cells were present as solitary cells. In the exocrine region of the duodenal portion, only insulin-, somatostatin- and hPP-IR cells were observed, with the same distributional pattern as that found in the splenic lobe. However, clusters of cells consisting only of hPP-IR cells were distributed in the pancreas parenchyma as small islets. In the pancreatic duct region, only solitary hPP-IR cells were demonstrated in the sub-epithelial connective tissue regions of the splenic portion. In conclusion, some strain-dependent characteristic distributional patterns of pancreatic endocrine cells, especially of the hPP-IR cells, were found in the nude mouse. In addition, somewhat different distributional patterns were found between the two pancreatic lobes.

Animals↗

Immunolocalisation of serotonin, gastrin, somatostatin and glucagon in entero-endocrine cells of the goose (Anser anser).

The processes of digestion in the avian gastrointestinal tract depend on sophisticated control systems that co-ordinate secretion of digestive juices and movement of the luminal contents. In the current study, the distribution of serotonin-, gastrin-, glucagon- and somatostatin-immunoreactive endocrine cells was investigated by immunocytochemical methods in the intestinal tract of the goose. The number of cells immunoreactive for each antiserum was evaluated in different regions of the intestinal tract. Serotonin-, glucagon- and somatostatin-immunoreactive endocrine cells were seen throughout the intestinal tract, but somatostatin-immunoreactive cells were not detected in the colon of the goose. Gastrin-immunoreactive cells were detected only in the duodenum, jejunum and colon mucosa. It is concluded that the distribution pattern of the entero-endocrine cells in the goose is similar to that of most of the mammalian and other poultry species.

Animals↗

Enterostatin in gut endocrine cells--immunocytochemical evidence.

The presence of enterostatin, a pentapeptide acting as a potential satiety signal in rats, was investigated in rat intestine by immunocytochemical methods. Using antibodies directed against the C-terminal part of enterostatin, the peptide was identified in endocrine cells in the antral part of the stomach and in the small intestine of rat. The immunoreactive cells were more frequent in the antrum and duodenum and became gradually fewer towards the distal small intestine. In some of the labeled endocrine cells, a coexistence of enterostatin with serotonin was revealed by immunocytochemical double staining, implying that the cells were enterochromaffin cells. In the pancreas, no enterostatin-immunoreactive cells were detected, indicating enterostatin to be included in its parent molecule, procolipase. In addition, the existence of procolipase in the gastrointestinal tract, including the pancreas, was investigated. Procolipase immunoreactivity was also identified, except in the pancreas, in chief cells in the fundus region of the stomach. The number of labeled cells declined distally in the stomach, finally being absent in the intestine. Immunoreactive enterostatin was measured with a specific ELISA method. Intestinal content and serum were found to average 540 +/- 70 and 50 +/- 4 nM, respectively. Pancreatic duct ligation strongly reduced the levels of enterostatin in intestinal content to 5.4 +/- 1.5 nM (p < 0.001), and also reduced the serum enterostatin level to 35 +/- 5 nM (p < 0.05). It is concluded that the peptide enterostatin in the rat is produced both in the exocrine pancreas, as part of pancreatic procolipase, and in gut endocrine cells, both sources of peptide being important for the circulating enterostatin.

Amino Acid Sequence↗