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At least 19 recordsLinked to original sources

Small cell (endocrine cell) carcinoma of the gallbladder with squamous and adenocarcinomatous components.

Small cell (endocrine cell) carcinoma of the gallbladder in a 62-year-old woman is reported. The palliative cholecystectomy specimen revealed a submucosally invading tumor with extensive hemorrhagic necrosis. At autopsy, performed five months after surgery, a huge tumor measuring 14 x 12 x 8 cm was located at the liver hilus. No signs or symptoms related to overproduction of hormones were recorded throughout her illness. Neither lung lesions nor gall stones were identified. Histologically, diffuse proliferation of small, spindle-shaped atypical tumor cells with numerous mitoses was evident. Intraepithelial tumor cell proliferation in the gallbladder mucosa was seen focally. The neuroendocrine nature of the tumor cells was confirmed by the histologic pattern of growth with pseudo-rosette formation, positive reaction for Grimelius' argyrophilia, neuron-specific enolase and Leu 7, and ultrastructural demonstration of neuroendocrine-type granules. Immunostaining for a variety of hormones was all negative. Characteristically, foci with squamous and adenocarcinomatous differentiation were identified in the tumor tissue. The glandular components were immunoreactive for carcinoembryonic antigen, secretory component, epithelial membrane antigen and CA19-9. The histogenesis and totipotentiality of the neoplasm were discussed.

Adenocarcinoma↗

An immunocytochemical and ultrastructural study of the larval anterior intestine of the frog Rana temporaria, with especial reference to endocrine cells.

Endocrine cells of the larval intestine of Rana temporaria tadpoles have been identified by argyrophilic, immunocytochemical and electron-microscopical techniques. Scarce endocrine cells have been found in both the short non-absorptive zone immediately following the stomach, and in the rest of the anterior intestine. Endocrine cells are frequently seen to extend a cytoplasmic process towards the lumen. Immunoreactivity for serotonin, somatostatin, bombesin and cholecystokinin-8 has been detected. According to the ultrastructural traits of the endocrine granules, three larval intestinal endocrine populations have been differentiated.

Animals↗

Distribution of microtubules and microfilaments in exocrine (ventral prostatic epithelial cells and pancreatic exocrine cells) and endocrine cells (cells of the adenohypophysis and islets of Langerhans). The relationship between cytoskeletons and epithelial-cell polarity.

We investigated the distribution of microtubules and microfilaments in some exocrine and endocrine cells in rats. Microtubules were stained by applying an immunofluorescent technique using antibodies against beta-tubulin, while microfilaments were stained with rhodamine-phalloidin, which binds selectively to polymerized actin filaments. In the cytoplasm of some exocrine cells (pancreatic acinar cells and ventral prostatic epithelial cells), the microtubules were distributed longitudinally from the apical region to the basal region, but no microtubules were found in the nuclear region. In exocrine cells, most of the microfilaments were localized beneath the apical plasma membrane. In some endocrine cells (those of the adenohypophysis and the islets of Langerhans), the microtubules exhibited a radial or reticular distribution in the cytoplasm, and intense fluorescence was observed in the perinuclear region. The immunofluorescence produced by the antibodies against beta-tubulin was more intense in endocrine cells than in exocrine cells. The microfilaments observed in the endocrine cells studied were homogenously distributed beneath the plasma membrane. Dot-like rhodamine-phalloidin staining was often observed in the cytoplasm of both the exocrine and endocrine cells. The present study clearly demonstrated marked differences in the distribution of cytoskeletal elements in exocrine and endocrine cells, and these may reflect differences in the secretory direction of such cells as well as in epithelial-cell polarity.

Actin Cytoskeleton↗

Investigations of endocrine cells in the gastrointestinal tract and pancreas during the metamorphosis of an anuran (Alytes obstetricans L.): histochemical detection of APUD cells.

Endocrine cells were detected at premetamorphosis, prometamorphosis, climax, and juvenile stages using an amine-inducing fluorescence technique with or without previous L-3,4-dihydroxyphenylalanine (L-DOPA) treatment. At premetamorphosis, serotonin cells exhibited yellow fluorescence in the gut primary epithelium of the L-DOPA untreated animals. In the treated animals, green fluorescent APUD cells could be seen in addition to the serotonin cells. In the pancreas, numerous clusters of fluorescent APUD cells were observed. At prometamorphosis the number of fluorescent cells increased in the intestinal primary epithelium and, close to the basal membrane, numerous small regenerative buds devoid of fluorescent cells appeared. In the pancreas of L-DOPA-treated animals, two types of APUD cells could be distinguished by their different fluorescence intensities. At the climax stage, the stomach developed and APUD cells were detectable in the gastric glandular buds. The degenerated primary intestinal epithelium was progressively removed in the intestinal lumen. At this stage, the regenerative buds of the secondary epithelium exhibited APUD cells. In the disorganized pancreas, the induced fluorescence decreased strongly. At the juvenile stage, cords of APUD cells displayed a cytoplasmic green fluorescence in the pancreas. In the stomach and intestine, serotonin and APUD cells were numerous.

APUD Cells↗

A fine structure study of the non-ciliated cells in the mouse tracheal epithelium with special reference to the relation of "brush cells" and "endocrine cells".

The non-ciliated epithelial cells in the air way of mice were examined by electron microscopy. They are flask-like or pyramidal cells dispersed singly or occasionally in pairs. The apical portion of the cells reaches the air way lumen with microvillous projections. Their cytoplasm always contains abundant and variable numbers of small granules (60-170 nm in diameter). Close appositions between non-ciliated cells and nerve fibers are frequently observed at their lateral or basal surfaces. Fine structures of the non-ciliated cells are similar to those previously reported in the cells under different designations such as brush cells, basal-granulated cells, cells of neuroepithelial bodies and endocrine cells. The present study proposes that these names express different features of the same cell group collectively called "non-ciliated cells" in this paper. Furthermore images indicating exocytotic granule release are obtained in this study, indicating an endocrine function of these cells.

Animals↗

Localization of inhibins and activins in normal endocrine cells and endocrine tumors of the gut and pancreas: an immunohistochemical and in situ hybridization study.

Activins and inhibins, which belong to the TGF beta family, are composed of different combinations of alpha-, betaA-, and betaB-subunits, resulting in inhibin A (alphabetaA), inhibin B (alphabetaB), activin A (betaAbetaA), activin B (betaBbetaB), and activin AB (betaAbetaB). They regulate several cell functions, acting as paracrine/autocrine factors. Their actions, which depend on binding to specific receptors, are also modulated by follistatin. Gastroenteropancreatic (GEP) endocrine cells and endocrine tumors (ETs) produce several growth factors, but it is not well known whether they express follistatin and the various inhibin/activin subunits. We studied their expression in 65 GEP ETs using immunohistochemistry (IHC) and in situ hybridization (ISH). The alpha-subunit and follistatin were not identified in normal GEP endocrine cells and were poorly expressed in ETs. A betaA-subunit immunoreactivity (IR) was detected in A-, G-, EC-, and GIP-cells, while betaB-chain IR was present only in D-cells. The mRNAs encoding for these molecules were poorly expressed in normal tissues. BetaA- and betaB-subunits were identified in several ETs by both IHC and ISH: betaA-subunit mainly in G-cell and A-cell ETs, and betaB-subunit in D-cell, A-cell, and EC-cell ETs. Our results demonstrate a differential expression of activin/inhibin subunits among different types of GEP endocrine cells and related tumors, suggesting a role in modulation of biological functions of these normal and neoplastic endocrine cells.

Activins↗

Mucin-producing cells and endocrine cells of gallbladder epithelium in patients with uncomplicated cholelithiasis.

In this study we have investigated various morphofunctional features of gallbladder mucosa in patients with uncomplicated cholelithiasis. The histological changes, endocrine cell types and their distribution, and mucin-producing cells were characterized by immunocytochemistry and mucin histochemistry; moreover, we attempted to correlate these findings to the number and size of gallbladder stones and the type of bacteria present in the bile. Our results indicate that, despite similar clinical parameters, a wide range of histological changes can occur in the gallbladder mucosa of these patients. Moreover, the presence of certain endocrine and mucin-producing cell types in so-called "pyloric metaplasia" led us to hypothesize that this finding may be a trivial event in the gallbladder epithelium.

Cholelithiasis↗

Transdifferentiation molecular pathways of neonatal pig pancreatic duct cells into endocrine cell phenotypes.

Restrictions in availability of cadaveric human donor pancreata have intensified the search for alternate sources of pancreatic endocrine tissue. We have undertaken to assess whether nonendocrine pancreatic tissue, with special regard to ducts, including epithelial cells, and retrieved from neonatal pig pancreata that are used for islet isolation, may under special in vitro culture conditions generate endocrine cell phenotypes. Special care was taken to identify the time-related appearance of molecular and biochemical markers associated with beta-cell specificity, in terms of glucose-sensing apparatus and insulin secretion. For this purpose, established ductal origin monolayer cell cultures were incubated with a battery of mono- or polyvalent growth factors. Morphological, immunocytochemical, molecular, and functional assays indicated that under special culture conditions ductal origin cells acquired an endocrine identity, based upon expression of key gene transcripts that govern the stimulus-coupled insulin secretory activity. Among factors eliciting transdifferentiation of ductal epithelial into endocrine cells, Sertoli cell (SC)-conditioned medium seemed to be the most powerful inducer of this process. In fact, the resulting cultures not only expressed beta-cell-oriented metabolic markers but also were associated with insulin and C-peptide output at equimolar ratios. This finding indicates that SC coincubation, more than other conditions, caused originally ductal cell cultures to gradually differentiate and mature into beta-cell-like elements. In vivo studies with this early cell differentiation product will test whether our approach may be suitable for correction of hyperglycemia in diabetic animal models.

Animals↗

Mixed ductal-endocrine carcinomas of the pancreas and ductal adenocarcinomas with scattered endocrine cells: characterization of the endocrine cells.

We compared the histological and immunohistochemical features of mixed ductal-endocrine carcinomas of the pancreas with those of ductal adenocarcinomas (DACs) containing scattered tumor-associated endocrine cells (SECs). Three pancreatic neoplasms fulfilled the WHO criteria for mixed ductal-endocrine carcinomas. Two of them showed moderately to poorly differentiated glandular structures composed of both mucin producing and neuroendocrine cells. The third mixed ductal-endocrine carcinoma was of the composite type showing DAC structures and a solid component with small epithelial cells, most of them of neuroendocrine nature. In 32 of 34 cases of DAC located in the head (30 cases) and body to tail (4 cases) of the pancreas and showing lymph-node metastases, SECs were found, but they were few in number and irregularly distributed in the tumors. In three DACs a few SECs were also detected in lymph-node metastases. Double staining for chromogranin A and the proliferation marker Ki-S5 revealed that all SECs that were not intimately integrated into the neoplastic glandular epithelium failed to show proliferative activity and changes of the expression of tumor suppressor genes (p53 and DPC 4). These findings suggest that only those SECs that belong to the proliferative cell fraction may be of neoplastic origin, while the majority of SECs probably constitute a tumor-associated but non-neoplastic cell population. These features contrast with those of mixed ductal-endocrine carcinomas, in which all endocrine cells are a component of the neoplasm.

Adenocarcinoma↗

Proliferative populations in intestinal metaplasia: evidence of deregulation in Paneth and goblet cells, but not endocrine cells.

In the small intestinal mucosa, four principal epithelial cell lineages are found - the Paneth, goblet, enterocytic, and endocrine cell lineages. These cell lineages are terminally differentiated, non-proliferative, and derive from multipotent stem cells near the bases of the crypts of Lieberkühn. Intestinal metaplasia of the stomach is considered to be a premalignant condition. Since proliferative populations in this condition are not well studied, this feature was examined using double-labelling immunohistochemical and histochemical methods; 20 paraffin blocks of small intestinal mucosa and 24 paraffin blocks of intestinal metaplasia of the human stomach were studied. Double-staining was carried out with MIB-1 as a proliferation marker, with Alcian blue for goblet cells, anti-chromogranin A for endocrine cells, and p-dimethylaminobenzaldehyde-nitrite for Paneth cells. Double-labelling showed that numerous Paneth cells and goblet cells in intestinal metaplasia were in the cell cycle, but endocrine cells appeared non-proliferative. Double-labelled Paneth or endocrine cells were not seen in the control small intestinal mucosa but scanty double-labelled goblet cells were observed in normal intestinal mucosa. In intestinal metaplasia of the stomach, there is evidence of cell-cycle deregulation in the goblet and Paneth cell lineages. These observations have considerable implications for the biology and histogenesis of Paneth cells, goblet cells, and endocrine cells, and the nature of intestinal metaplasia in the gastric mucosa.

Cell Division↗

[Muciparous cells and endocrine cells of the gallbladder epithelium in patients with uncomplicated cholelithiasis].

In this study the authors have investigated the different morphofunctional features of the gallbladder mucosa in patients with uncomplicated cholelithiasis. Histological changes, type and distribution of endocrine and mucin-producing cells were characterized by immunocytochemistry and mucin histochemistry. The authors attempted to correlate these findings to the number and size of gallbladder stones as well as type of bacteria present in the bile. The results indicate that, despite similar clinical parameters, a wide range of histological changes may occur in the gallbladder mucosa of these patients. Moreover, the presence of some endocrine and mucin-producing cell types in the so called "pyloric metaplasia" led the Authors to hypothesize that the latter may be a trivial event.

Cholelithiasis↗

Differentiation of adult hepatic stem-like cells into pancreatic endocrine cells.

To apply cell transplantation for treatment of diabetes mellitus, a sufficient number of beta-cell sources are required. In the present study, we examined whether an epithelial cell line obtained from normal adult rat liver, namely hepatic stem-like (HSL) cells, which can be converted to both hepatocytes and billiary epithelial cells, could be a potential beta-cell source. The growth speed of HSL cells was rapid and these cells were easily expanded in vitro. Bipotential hepatic stem cells, HSL cells, also expressed PGP9.5, which is expressed in neurons, beta-cells, and progenitor cells of the pancreatic endocrine cells as well. Sodium butyrate induced morphological changes in HSL cells and converted them into flattened cells with large cytoplasm. When HSL cells were incubated with a combination of 5 mM sodium butyrate and 1 nM betacellulin, most of the cells were converted into morphologically neuron-like cells. RT-PCR analysis revealed that a series of transcriptional factors involved in differentiation of pancreatic endocrine cells was induced by the treatment with sodium butyrate and betacellulin. mRNAs for insulin, pancreatic polypeptide, and somatostatin were also observed. Immunoreactive pancreatic polypeptide, somatostatin, and insulin were detected in sodium butyrate and betacellulin-treated HSL cells. In conclusion, HSL cells obtained from adult normal liver also have the potential to differentiate into pancreatic endocrine cells in vitro. HSL cells may be one of the potential beta-cell sources for cell transplant therapy for insulin-dependent diabetes.

Animals↗

Chromogranin A immunoreactivity and Grimelius' argyrophilia. A correlative study in mammalian endocrine cells.

Various endocrine cells can be stained by the argyrophil reaction of Grimelius. This silver stain has recently been attributed to chromogranin A, an acidic glycoprotein, that is present in many endocrine cells. Using serial sections of plastic-embedded tissues (adrenal medulla, pancreas, gastric mucosa) various endocrine cells were investigated for their content of chromogranin A immunoreactivity and for their argyrophilia. The findings in four species (man, cattle, pig, guinea pig) showed that chromogranin A immunoreactivity and argyrophil stain partly overlap in identical endocrine cells, but do not necessarily coincide in the majority of endocrine cells. We found that endocrine cells could be positive for chromogranin A and argyrophilia (e.g., aminergic endocrine cells); or positive for chromogranin A but negative for argyrophilia (e.g., insulin cells of all species; somatostatin cells of cattle and pig); or negative for chromogranin A but positive for argyrophilia (e.g., glucagon cells of pig and guinea pig); or negative for chromogranin A and argyrophilia (e.g., somatostatin cells of man and guinea pig). Such heterogeneities of the staining pattern for chromogranin A and argyrophil silver reaction were also observed in individual endocrine cells of a given population (e.g., gastrin cells). Hence, although recent dot-blot tests have shown that chromogranin A is an argyrophilic substance, in tissue sections chromogranin A immunostaining and Grimelius' silver staining did not coincide in various endocrine cells, for unknown reasons. Therefore, it is recommended to use both chromogranin A immunohistochemistry and the classical Grimelius' silver stain to "mark" that vast majority of endocrine cells in tissue sections.

Adrenal Medulla↗

Effects of various gastrointestinal peptides on parietal cells and endocrine cells in the oxyntic mucosa of rat stomach.

1. The effects of secretin, glucagon, cholecystokinin-pancreozymin (CCK-PZ), gastric inhibitory peptide (GIP), vasoactive intestinal peptide (VIP), somatostatin, neurotensin and enkephalin on basal, pentagastrin- and histamine-stimulated gastric acid secretion were investigated in the conscious fistula rat. 2. Glucagon and GIP were ineffective inhibitors of basal and pentagastrin-stimulated secretion. CCK-PZ stimulated acid secretion at a low dose level but at higher doses it inhibited both pentagastrin- and histamine-induced secretions. VIP was ineffective at low doses and at high doses its action was complicated by reflux of stimulated pancreatic and intestinal secretions into the stomach. Met-enkephalin inhibited histamine- but not pentagastrin-stimulated secretion. Neurotensin inhibited the response to pentagastrin but had no effect on histamine-stimulated secretion. Secretin and somatostatin were potent inhibitors of basal and pentagastrin-stimulated acid secretion with little or no effect on the response to histamine. 3. At doses completely inhibitory to pentagastrin-stimulated secretion secretin and somatostatin did not block the mobilization of gastric mucosal histamine by pentagastrin, although somatostatin caused partial competitive inhibition at lower doses of pentagastrin. Thus secretin and somatostatin inhibited pentagastrin-induced secretion neither by blocking gastric mucosal histamine mobilization nor by abolishing the direct action of histamine on the parietal cell -- findings which are inconsistent with the proposed role of histamine as the mediator of the action of gastrin on the parietal cell.

Animals↗