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Basal chromogranin A and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-A gastritis.

BACKGROUND: It is not known whether plasma chromogranin analysis could be a complement to histology for detection and grading of gastric fundic mucosal endocrine cell proliferation in hypergastrinemic (type-A) atrophic gastritis. METHODS: Gastric biopsy sections (body and antrum) from 43 patients with type-A gastritis (9 with gastric carcinoid) were examined for density and micronodules of argyrophil endocrine cells. Fasting blood samples were analyzed for chromogranin A and B, gastrin, and somatostatin. RESULTS: All patients with carcinoid and 17 of the 34 without carcinoid had micronodules in the gastric fundic mucosa. The median plasma chromogranin A concentration was 5.7 (3.5-40.0) nmol/l in patients with carcinoid, 4.5 (3.0-9.5) nmol/l in patients with micronodules, and 3.7 (0.8-6.0) nmol/l in patients without micronodules. Overall, chromogranin A concentrations correlated to endocrine cell densities in the fundic mucosa (r = 0.64, P < 0.001) and to gastrin concentrations (r = 0.71, P < 0.001). Plasma somatostatin and chromogranin B concentrations did not differ significantly between the groups. CONCLUSION: In type-A gastritis, analysis of plasma chromogranin A may be a useful complement to histology in estimating the endocrine cell mass. Moreover, subclinical type-A gastritis may be a source of error when chromogranin A analysis is used in the search for neuroendocrine neoplasia.

Aged↗

[The duration of hormone synthesis by cultures of human fetal endocrine cells].

It is stated as possible to cultivate and accumulate endocrine cells by regular passages in vitro over a long period of time. In this case endocrine cells of human fetus don't loose the ability to synthesize hormone. Such cultures can be used to study some general-biological problems out of influence of the neurohumoral organism factors.

APUD Cells↗

Exposure to ionizing radiation modifies circulating gastrin levels and gastrointestinal endocrine cell densities in the rat.

PURPOSE: Gastrointestinal functions, controlled partly by gut peptides, are disturbed by ionizing radiation exposure. The effect of whole-body irradiation on circulating gastrin levels, densities of gastrointestinal endocrine cells and gastric acid secretion was investigated. MATERIALS AND METHODS: Rats were exposed to 2 or 6 Gy gamma-radiation. They were killed 3 or 7 days later and compared with shams. Plasma gastrin and basal acid output were measured. Endocrine cells were identified by argyrophilia or immunohistochemistry and their densities estimated. RESULTS: Radiation exposure significantly increased gastrinaemia and gastric acid output at the times studied (p<0.05-p<0.001). Endocrine cells displayed different sensitivities to irradiation. In the gastric mucosa, a 6 Gy dose induced a decrease in fundic argyrophil cell, antral gastrin and somatostatin cell densities, always accentuated 7 days after irradiation, while in the intestinal mucosa it induced an increase, with highest values often at 7 days post-irradiation (p<0.01-p<0.001). This was true for neurotensin cells in the jejunum and ileum, substance P cells in ileum and enteroglucagon cells in the descending colon. CONCLUSIONS: Whole-body irradiation in rats significantly alters plasma gastrin levels, and several gut endocrine cell densities. This has repercussions on hormonal function, such as that exerted on acid secretion, and may explain gastrointestinal dysfunction observed following radiation exposure.

Animals↗

The effect of Zollinger-Ellison syndrome and omeprazole therapy on gastric oxyntic endocrine cells.

In 1983, all trials of omeprazole in humans were stopped because rats given the drug developed gastric endocrine cell hyperplasia and carcinoid tumors. Further studies in rats showed that drug-induced achlorhydria and hypergastrinemia caused these changes. Because data in humans are limited, we compared the numbers of endocrine cells, as judged by silver staining (argyrophilia), in the gastric mucosa of patients with Zollinger-Ellison syndrome, who are hypergastrinemic, and in normogastrinemic patients with idiopathic acid-peptic diseases. In addition, we analyzed the number of gastric endocrine cells in patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years. Patients with Zollinger-Ellison syndrome had 15.7% +/- 6.9% argyrophil cells in biopsies of gastric oxyntic mucosa, and patients with idiopathic acid-peptic disease had 7.8% +/- 2.3% (P less than 0.01). In patients with Zollinger-Ellison syndrome, the percentage of argyrophil cells was not related to serum gastrin concentration, duration of symptoms, time since diagnosis, basal or maximal acid output, extent of tumor, or age. There was a tendency for patients with multiple endocrine neoplasia type 1 to have a greater percent of argyrophil cells than patients with sporadic Zollinger-Ellison syndrome. Considering the biopsies from both normogastrinemic and hypergastrinemic patients, there was a significant relationship between the percentage of argyrophil cells and the serum concentration of gastrin (P less than 0.01). Patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years developed no significant changes in percentage of argyrophil cells, no carcinoid tumors, and no changes in serum concentrations of gastrin. The present study shows that patients with Zollinger-Ellison syndrome have an increased percentage of argyrophil cells in oxyntic mucosa and that omeprazole does not increase this percentage. In periods of up to 3 years, omeprazole had no effects on gastric morphology in patients with Zollinger-Ellison syndrome.

Adult↗

Staining procedures for the endocrine cells of the upper gastrointestinal mucosa: light-electron microscopic correlation for the gastrin-producing cell.

Although histochemical, immunohistochemical, and electron microscopic methods have led to the identification of a large variety of endocrine cells in the upper gastrointestinal mucosa, no conventional light microscopic technique capable of the simultaneous identification of these cells has been reported. Such a staining method would be of considerable value to the pathologist as the malfunction of the endocrine cells of the gut, which produce numerous digestive hormones and biogenic amines, is closely related to a number of clinical conditions afflicting man. In this work, after testing three different polychrome staining methods, it has been concluded that a slightly modified Herlant's tetrachrome in tissues fixed in Zenker-formol is the procedure of choice. This method allows the distinction of several different cell types in the upper gastrointestinal mucosa of man and dog and permits the easy identification of the gastrin-producing cells on a routine basis. This identification has been confirmed in the case of two patients with gastrin cell hyperplasia, seen by both light and electron microscopy. Herlant's tetrachrome has proven valuable in the screening of human as well as experimental gastrointestinal tissues and it has been found to be very suitable for recognizing gastrin-producing cell hyperplasias. The usefulness of this method is expected to increase with the establishment of further correlations between the light and electron microscopy of the endocrine cells of the gut.

Adenocarcinoma↗

Pathological features and their prognostic implications in colorectal endocrine cell tumours: a long-term follow-up study.

AIMS: Long-term follow-up studies of colorectal endocrine cell tumours (CRECTs) are rare. Our aim was to correlate pathological features with metastatic potential and long-term survival of CRECTs. METHODS: Pathological features of 35 CRECTs were reviewed. Features assessed were the tumour size, local and angio-invasion, growth pattern, cyto-nuclear morphology, mitotic count, mucin production and proliferative activity. CRECTs were also re-classified according to the World Health Organization (WHO) 2000 criteria. The follow-ups ranging from 60 to 132 months was obtained from Singapore National Cancer Registry data. RESULTS: There were five metastatic and 30 non-metastatic tumours. Three of five metastatic tumours resulted in death within 1 year of diagnosis. Features exclusively seen in these three tumours were large size (25mm or more), mitoses > 6/10 high power fields with abnormal forms necrosis and large cell morphology. The features which correlated significantly with metastases were size, local and angioinvasion, primitive growth pattern, coarse chromatin and mitotic count (p < 0.0005), large cells and prominent nucleoli (p = 0.017), MIB1 proliferative index (p = 0.001) and abnormal mitoses and necrosis (p = 0.02). Thirty tumours were reclassified as well-differentiated endocrine cell tumours (WETs), three as well-differentiated endocrine cell carcinomas (WECs) and two were large cell neuroendocrine cell carcinomas (LECs) according to WHO criteria. One of the WECs and both LECs resulted in death. CONCLUSIONS: All patients whose tumour was 25 mm or more, showing mitoses of more than 6 per 10 high power fields, with abnormal forms, necrosis and large cell morphology, died of the disease. Size, invasion, presence of discernible mitoses, coarse chromatin, 'primitive' growth pattern and MIB1 index of 4% or more were associated with metastases. LECs are rare but aggressive tumours resulting in early death. All WECs do not behave in the same fashion.

Adult↗

The endocrine cells of the pancreas and related tumours. Ultrastructural study and classification.

Up to seven endocrine cell types have been identified ultrastructurally in the pancreas, including glucagon A cells, insulin B cells, somatostatin D cells, pancreatic peptide F cells and 5-hydroxytryptamine EC cells. In addition, D1 cells, which have been proposed as the cell type producing VIP and possible P cells of unknown function are seen. Various patterns of endocrine cell differentiation have been found in 20 endocrine pancreatic tumours. Well and poorly differentiated B cells have been identified in 6 insulinomas, diagnostic G cells in 3 out of 7 gastrinomas, D1 and/or F cells in 7 diarrheogenic tumours. Moreover, cells apparently unrelated to the prevalent clinical syndrome have been noted in 8 of the 20 tumours. Granular non diagnostic cells (poorly diagnostic gastrin cells? D1 cells?) were particularly frequent in gastrinomas; agranular or poorly granular cells, either by "active" or "Stem cell" type, were present in nearly all tumours, particularly in diarrheogenic tumours, gastrinomas and malignant insulinomas. A cytological classification of pancreatic endocrine tumours is proposed.

Adenoma, Islet Cell↗

Serotonin storage and chromogranins: an experimental study in rat gastric endocrine cells.

Chromogranins (Cg) and secretogranins (Sg) are acidic proteins localized in the secretory granules of a large variety of endocrine cells collectively named APUD cells (amine precursor uptake and decarboxylation). To examine the possible function of Cg/Sg as amine storage proteins, enteroendocrine cells of the rat gastric antral mucosa, i.e., serotonin-containing enterochromaffin (EC)-cells, gastrin (G)-, and somatostatin (D)-cells, were investigated immunohistochemically in serial semi-thin sections of controls and after intervention in serotonin synthesis. CgA and CgB immunoreactivity was determined semiquantitatively by optical density measurements. Experiments included inhibition of serotonin synthesis by p-chlorophenylalanine (pCPA), exogenous application of the serotonin precursor 5-hydroxytryptophan (5-HTP), and a combination of both treatments. The cellular distribution of Cg and the density of its immunoreactivity were closely related to the primary content of serotonin and the ability to store serotonin after 5-HTP application. Thus, Cg may act as amine-binding proteins in enteroendocrine cells, binding most probably being due to ionic interactions between Cg and the biogenic amines. EC- and G-cells, however, differed in their amine-handling properties and in the response of their Cg immunoreactivity after intervention in serotonin synthesis. We conclude, therefore, that the physiological function of Cg as amine storage proteins is restricted to endocrine cells with an endogenous content of amines. In other endocrine cells, exhibiting only a potential amine production, APUD may be considered as a kind of supravital staining without physiological significance.

5-Hydroxytryptophan↗

Widespread distribution of bronchopulmonary endocrine cells immunoreactive for calcitonin in the lung of the normal adult rat.

The nature and distribution of bronchopulmonary endocrine cells immunoreactive for calcitonin was studied in normal adult Wistar albino rats by immunoenzyme histochemistry with the peroxidase-antiperoxidase technique. A widespread distribution of both solitary endocrine cells and neuroepithelial bodies immunoreactive for calcitonin was found. Many, but not all, were also immunoreactive for neurone specific enolase. Although both classes of cells were present in airways and parenchyma, most of the solitary cells were found in alveolar ducts and alveoli whereas most of the neuroepithelial bodies were located in bronchi and bronchioles. Bronchopulmonary endocrine cells are generally regarded as being sparse in the adult rat. It is suggested that this may be a consequence of the use of inadequate methods in attempting to identify them. So far as is known, this is the first time that calcitonin has been demonstrated by immunohistochemical methods in the lungs of rats.

Animals↗

[Endocrine cells in the mucosal epithelium of the porcine large intestine].

Using the methods of light and electron microscopy, mucosal epithelium in the colon of adult pigs was studied with special reference to the amount and distribution of endocrine cells. The total amount of endocrine cells tended to increase caudally. Four types of these cells were demonstrated including EC, L, D and D1. The proportion of EC-cells was found to fall from cranial segments of the colon to caudal ones. According to the results of ultrastructural analysis, endocrine cells in the mucosal epithelium of porcine colon, as well as the cells of the adjacent tissues, are in the state of functional exertion.

Animals↗

An immunohistochemical study of the endocrine cells in the gastrointestinal mucosa of the Caiman latirostris.

Twelve endocrine cell types immunoreactive for either 5-hydroxytryptamine (5-HT), somatostatin, gastrin, motilin, neurotensin, bovine pancreatic polypeptide (BPP), avian pancreatic polypeptide (APP), pancreatic glucagon, enteroglucagon, glicentin, secretin or cholecystokinin (CCK) were found in gastrointestinal mucosa of Caiman latirostris. Moderate numbers of enteroglucagon-immunoreactive cells, a few 5-HT-, somatostatin- and motilin-immunoreactive cells and rare pancreatic glucagon-immunoreactive cells were found in the fundic stomach. Numerous gastrin-immunoreactive cells and moderate numbers of somatostatin- and motilin-immunoreactive cells were seen in the pyloric stomach. Moderate numbers of 5-HT-, gastrin-, motilin- and enteroglucagon-immunoreactive cells, a few somatostatin-, neurotensin- and BPP-immunoreactive cells, and rare APP-, pancreatic glucagon-, glicentin-, secretin- and CCK-immunoreactive cells were observed in the proximal intestine. Moderate numbers of 5-HT-immunoreactive cells, small to moderate numbers of neurotensin- and enteroglucagon-immunoreactive cells and occasional somatostatin-, motilin- and BPP-immunoreactive cells were seen in the distal intestine. Moderate numbers of neurotensin-immunoreactive cells and a few 5-HT-immunoreactive cells were found also in the cloaca. Cells immunoreactive for gastrin releasing polypeptide, bombesin and gastric inhibitory peptide were not observed in the caiman gastrointestinal epithelium. The differences in endocrine cell types between the caiman and alligator are discussed in terms of their topographic distribution.

Alligators and Crocodiles↗

Neuro-endocrine cells--a new prognostic parameter in prostate cancer.

Neuro-endocrine cells are a recognised component of prostatic ducts and acini. Half of all clinically manifest cancers show neuro-endocrine differentiation. Occult carcinomas have a lower incidence of such differentiation. Neuro-endocrine cells are of major prognostic importance and appear more reliable in predicting patients' survival than do conventional histological grading systems.

Adenocarcinoma↗

Expression of the Neural Cell Adhesion Molecule NCAM by Peptide- and Steroid-Producing Endocrine Cells and Tumors: Alternatively Spliced Forms and Polysialylation.

The adhesive properties of neural cell adhesion molecules (NCAMs) can be modified by alternative splicing of the primary transcript or by posttranslational modifications, such as sialylation. In this article, we describe distinct forms of alternative splicing and posttranslational modification of the extracellular domain of NCAM of various endocrine tissues and derived tumor cells of the rat and of steroid- and peptide-hormone producing endocrine cells in humans. NCAM-140 is the major isoform expressed in the rat adrenal gland, adenohypophysis, and in granulosa and granulosa-lutein cells. NCAM-180 is predominant in the neurohypophysis. Polysialylated NCAM is expressed in different endocrine tissues and tumor cells of the rat. Different amounts of NCAM mRNA containing the "extra-exon" VASE at the exon 7/8 splice boundary were detected in endocrine cells of rats. Human granulosa cells in culture undergo luteinization. During this process, the VASE-containing NCAM isoform is supplemented by an alternatively spliced isoform without this insert. Thus, modifications of NCAM may be important for adhesive interactions in normal and neoplastic endocrine cells. In addition, the differential expression and the alternative splicing of NCAM during luteinization of granulosa cells raise the possibility that NCAM could be involved in folliculogenesis and the formation of the corpus luteum in humans.

Journal Article↗

[Endocrine cells in the cardial glands of the esophagus in man].

Distribution of endocrine cells in composition of the secretory epithelium of the cardial glands of the human esophagus in both sex and at various age has been investigated. In spiral paraffin slices the endocrine cells have been revealed by means of different silver impregnation methods (after Grimelius, Masson--Hamperl, Sevier--Munger), Sevke technique, ferry-ferrocyanide method. Some cells have been revealed, which according to the specific signs of their granule staining resemble very much G-, EC-, ECL-cells of the stomach. They can be triangular, flatten or polygonal and are stained in the cardial gland epithelium as single diffuse cells, or as groups of cells. Staining of the slices with aldehyde-fuchsin in various modifications reveals dark cells with dark-violet granules and lighter cells with acidophilic granules. Sometimes among these cells certain cells with light-violet cytoplasm are revealed. All these cells can be arranged both in composition of the secretory epithelium of the glands and in conglomerates of cells, resembling pancreatic islands. According to their tinctorial properties they resemble A-, B-, D-cells of these islands.

APUD Cells↗

Pulmonary endocrine cells in chronic bronchitis and emphysema.

A rôle for pulmonary endocrine cells has been suggested in the response of the lungs to hypoxia, the control of the pulmonary vasculature and inflammatory pulmonary disease. Since hypoxia, inflammation and vascular remodelling are all central to the pathology of chronic bronchitis and emphysema, we have studied these cells in the lungs of subjects with this condition. In comparison with lungs of matched controls, there was a modest uniform increase in endocrine cells containing gastrin-releasing peptide, possibly associated with vascular remodelling, and a marked increase in cells containing calcitonin, which was particularly seen in consolidated lobes and possibly related to inflammation.

Aged↗

Endocrine cell populations in the pancreas of diabetic WBN/Kob rats.

Numerical changes of insulin-, glucagon- and somatostatin-positive cells in the pancreas of WBN/Kob male rats with spontaneously occurring diabetes were examined. The rats examined were divided into three different age groups: Groups I (12 weeks old) and II (33 weeks old) were clinically prediabetic and group III (60-90 weeks old) was diabetic. Serum glucose value was in the normal range in groups I and II, while it was much higher in group III. B and A cells were markedly decreased in number in groups II and III. In group II, the ratio of B to A cells was normally preserved, though the total endocrine cell number was markedly decreased as compared with that in group I. In group III, the percentage of B cells was decreased significantly. The normal ratio in group II seemed to keep serum glucose within the normal level. In addition to the total endocrine cell reduction, an altered ratio of B and A cells was considered to cause the diabetic condition.

Animals↗

Ontogeny of endocrine cells in the respiratory system of Syrian golden hamsters. I. Larynx and trachea.

The ontogeny of protein gene product 9.5 (PGP 9.5), serotonin (5-HT), calcitonin gene-related peptide (CGRP), and calcitonin (CT) immunoreactivity was evaluated in small-granule endocrine cells of hamster laryngotracheal epithelium from fetal day 11 to adulthood. Two centrifugal (proximal-to-distal) patterns of differentiation occur. The first pattern begins during fetal life. Endocrine cells, single and clustered in groups (presumptive- or protoneuroepithelial bodies, pNEBs), initially colocalize immunostaining for PGP 9.5, 5-HT, and CGRP in the larynx and proximal 2/3 of the trachea on day 12 and spread to the caudal trachea on day 13. 5-HT disappears fleetingly during the 24 h preceding birth; otherwise immunoreactivity for all three substances persists into adulthood. The clusters of endocrine cells survive beyond birth but are so diluted by expansion of the nonendocrine epithelium as to become inconspicuous. Since innervation was not actually observed, these clusters may persist as pNEBs, without developing connections to afferent or efferent nerve fibers. The second pattern concerns single small-granule cells stainable for CGRP but not for 5-HT. These cells first appear in the larynx and cartilaginous part of the cranial trachea on postnatal day 3, and in the middle and caudal trachea, on day 5. The cells increase in number on day 7. In adults, they predominate among endocrine cells of the cartilaginous region. A subset of these cells begins to co-express CT proximally on postnatal day 10, reaching the caudal end of the trachea by 3 weeks. A few elements of the older 5-HT-positive population may also become immunoreactive for CT in juvenile hamsters.

Animals↗

Pulmonary endocrine cells in hypoplastic lungs due to foetal urinary tract obstruction: a microscopic immunohistochemical study.

METHODS: We performed a urinary tract obstruction (UTO) surgical procedure at 93-107 days' gestation in lambs to investigate the relationship between pulmonary hypoplasia and the appearance of pulmonary endocrine cells by quantitative analysis of respiratory tract cells using light microscopic immunohistochemistry. RESULTS: UTO produced a significant reduction in lung weight, lung/body weight ratio, air capacity, air capacity/body weight ratio (p < 0.01) and radial alveolar count (p < 0.05), which indicated the presence of lung hypoplasia. These foetuses also showed a significant increase in the number of neuron-specific enolase (NSE)-positive pulmonary endocrine cells, expressed as the number of NSE-positive cells per bronchus (p < 0.01) or bronchiole (p < 0.05), the number of NSE-positive cells per unit perimeter of bronchus or bronchiole (p < 0.01), and the number of NSE-positive cells per unit bronchial or bronchiolar surface area (p < 0.01). CONCLUSION: These results suggest that UTO significantly retards and modifies the structural growth and functional development of pulmonary endocrine cells in NSE expression. We speculate that pulmonary endocrine cells and their mediators may play a role in the problems associated with UTO during intrauterine life.

Animals↗