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Endocrine cells in the human colorectal mucosa: immunocytochemical observations on patients with prolapse or internal procidentia of the rectum.

We have examined the occurrence and distribution of endocrine cells storing serotonin and the regulatory peptides somatostatin, glicentin, peptide YY in rectal mucosa on 16 patients with prolapse or intussusception of the rectum. There were no significant differences compared with normal rectal mucosa. Our results do not support the assumption that these endocrine cells of the rectum are involved in the pathophysiology of rectal prolapse.

APUD Cells↗

[Differentiation and cytogenesis of endocrine elements of the rat duodenum in ontogenesis].

Duodenal endocrine apparatus was studied in rat during individual development using electron microscopy. Endocrinocyte differentiation was demonstrated to occur in embryonic period and it is characterised by fast cytotype number growth. During embryogenesis processes of endocrinocyte differentiation occur more intensely than in adult animals which is manifested by higher incidence of different types of incretory elements in embryos. By the moment of birth EC-, L-, S-, D-, D1-, P and I-cells can be identified in the duodenal epithelium at different stages of differentiation as well as "mixed" exo-endocrine cells. The presence of transitory cellular forms from agranular elements up to mature differentiated endocrinocytes and "mixed" exo-endocrine cells reflects cytogenetic processes in population of endocrine cells and allows to consider duodenal epithelium both structurally and functionally as a tissue with common histogenetic basis.

APUD Cells↗

[Gastroduodenal incretory cells in duodenal ulcer with different levels of gastric secretion].

Immunomorphological PAP method was used in 20 patients with duodenum ulcer and in 10 control individuals to study gastrin (G)-, somatostatin (D)- and calcitonin-gene-related peptide (CGRP) cells in biopsies of the stomach and duodenum. The gastrin and pepsinogen level in the blood, basal and acid production stimulated by pentagastrin were also studied. All patients are subdivided into two groups by their acid production: those with hypersecretion and those with normal secretion. The group with hypersecretion was not homogeneous: some patients had deficiency of D-cells (sometimes in combination with G-cell hyperplasia) and others had a relative and absolute decrease of the number of CGRP cells in combination with foci of parietal cells in pylorus. These patients showed a tendency to the hypergastrinemia and significant hyperpepsinogenemia I in the blood. Stomach hyperplasia in the duodenum, multiple duodenal ulcers, erosive gastroduodenitis and ulcers in close relatives occurred more frequently in these patients. G- and CGRP cells are found to be similar in the form and localization. It is not excluded that G-cell contains, apart from gastrin 1-17, calcitonin-gene related peptide.

APUD Cells↗

Endocrine pancreatic tumors: ultrastructure.

Endocrine pancreatic tumors are frequently multicellular and produce several hormones and peptides. A review of the basic concepts of hormone secretion, pancreatic islet cell composition and ultrastructural make-up of tumors is presented. The importance of correlating ultrastructural, immunocytochemical and biochemical studies of these tumors is emphasized.

APUD Cells↗

[Primary carcinoid tumor of the kidney associated with cystic malformation of the kidney].

We report a case of primary renal carcinoid tumor associated with kidney malformation. The carcinoid tumor contained cells which stained with anti-chromogranin, anti-serotonin and anti-somatostatin antibodies. The carcinoid tumor was developed on a cystic malformation with transitional epithelium. Immunohistochemical studies revealed positive chromogranin and serotonin cells within the epithelium. The 21 other cases of primary renal carcinoid were reviewed with a particular emphasis on the 2 other cases associated with renal lesions containing endocrine cells. These 3 cases could help to explain the development of primary renal carcinoid tumor.

APUD Cells↗

The endocrine cells of the digestive tract. General concepts and historic perspective.

The chromaffin cells of the digestive mucosa were discovered by Heidenhain in 1870, long before the hormone concept was formulated. Following the discovery of the first hormone, secretin, by Bayliss and Starling in 1902, the study of the cells producing such messengers acquired new impetus. After Masson, in 1914, showed that the digestive chromaffin cells were argentaffin and suggested their endocrine nature, a series of technological advances led to the gradual characterization of diverse cell types, their classification, and the discovery of their function. Histochemistry, including silver impregnations, fluorescence microscopy, and aniline stains, exposed the complexity of the digestive endocrine cells. Electron microscopy provided structural markers for their characterization and the basis for the formulation of the first universally accepted classifications. Light- and electron-microscopic immunocytochemistry contributed to the understanding of the function of many of these cells, thus opening the way for modern classifications. Many unsolved problems still remain. These include the existence of cells without defined function, of chemical messengers without known cell of origin, and the presence of multiple messengers in some cell types. Answers are expected to emerge from further application of immunocytochemistry and from the introduction of modern approaches, such as in-situ hybridization histochemistry.

APUD Cells↗

Pulmonary endocrine cells immunoreactive for calcitonin in the lungs of fetal and neonatal rats.

Previous studies have shown that the size of the population of bronchopulmonary endocrine (Feyrter) cells appears to be greatest in fetal and neonatal life. This has led to the logical assumption that these cells are important during this period and undergo a subsequent decline in number thereafter. In this study endocrine cells containing calcitonin or a closely related cross reacting peptide have been demonstrated in the lungs of fetal and neonatal rats by immunoenzyme histochemistry. They appear first about three days before birth and their number, expressed as immunoreactive cells per cm2 of histological section, remains relatively constant for up to three weeks after birth. It has been shown previously in this department that endocrine cells immunoreactive for calcitonin are present in the lungs of the normal adult rat. Their number in these adult animals is closely similar to the numbers of cells in the lungs of the developing animals of the present study. It is suggested that, at least in the rat, bronchopulmonary endocrine cells immunoreactive for calcitonin have a role that is not confined merely to the period of transition from fetal to neonatal life.

APUD Cells↗

[Seasonal changes in the endocrine cells of the gastric epithelium of Rana temporaria].

By means of the light and electron microscopy methods histotopography, quantity and ultramicroscopic organization of endocrine cells (EC) have been studied in gastric epithelium of the frog (Rana temporaria) during various periods of its life: hibernation, awakening, active life. At all the periods of life 8 types of EC are revealed. Depending on the season, certain changes both in their amount and ultrastructural organization are observed. Decreasing amount of EC is noted during hibernation and their increase in spring during awakening and in summer. Quantity of enterochromaffin cells is not subjected to seasonal fluctuations. This is explained by the fact that in hibernation these cells are also at their active functional state, since they produce serotonin necessary for maintaining deep hypothermia, specific for hibernating animals.

APUD Cells↗

[The physiology and pathophysiology of the small intestine].

An attempt is made in this review, to highlight recent concepts in the physiology and pathophysiology of intestinal absorption, to recollect the multiplicity of functions of the small intestine in the cellular and humoral immune response and to draw attention to the numerous endocrine and paracrine cells, residing in the intestinal mucosa, which produce peptides of mostly well defined biochemistry, the physiological and especially pathophysiological role of which, however, is still uncertain.

APUD Cells↗

Immunocytochemical detection of endocrine cells in the gut of Viviparus ater (Mollusca, Gastropoda).

The presence of endocrine cells was investigated by immunocytochemical procedures in the gut and salivary gland of Viviparus ater, a freshwater prosobranch gastropod. The endocrine cells were scanty and both of closed and open cell type. Most of them were located in the esophagus (immunostaining with anti-gastrin, anti-insulin, anti-serotonin and anti-substance P antisera), very few in the stomach (immunoreactive only to anti-gastrin antibody) and in proximal part of the intestine (immunoreactive to anti-serotonin and anti-substance P antibodies). In the salivary glands, occasional endocrine cells scattered among the glandular cells in the adenomera stained with anti-neuropeptide Y, anti-pancreatic polypeptide and anti-somatostatin sera were detected.

APUD Cells↗

Identification of R-GRAMP, a membrane glycoprotein of regulated secretory granules in primate cells.

Investigation of membrane assembly and traffic in the regulated secretory pathway may be facilitated by identification of membrane components that are unique to regulated secretory granules. To identify such markers, we isolated integral membrane proteins by Triton X-114 extraction from well-differentiated monolayers of an exocrine cell line, the goblet cell subclone (18N2) of the human colon carcinoma cell line HT29, and used the extracts as immunogens to produce monoclonal antibodies (mAbs). Immunofluorescence microscopy of HT29 goblet cell monolayers identified one mAb (MG-1) that labeled a component of mucin granule membranes. Immunofluorescence of frozen semithin sections of normal intestine, and various other human and monkey tissues, showed that this antigen is present in regulated secretory granule membranes of primate exocrine cells, endocrine cells, and tissue granulocytes. EM immunogold labeling of goblet cells, enteroendocrine cells and eosinophils confirmed that the antigen is associated with secretory granule membranes and not with plasma membranes. The antigen was identified by SDS-PAGE autoradiography of immunoprecipitates from HT29 goblet cells metabolically labeled with [35S]methionine and [35S]cysteine or [3H]glucosamine, as a glycoprotein with an apparent molecular mass ranging from 23 to 37 kDa. Digestion of immunoprecipitates with N-glycosidase F reduced the apparent mass to 16 to 19 kDa. This small, highly-glycosylated protein was named "R-GRAMP" (for regulated granule-associated membrane protein) to reflect its wide distribution in secretory granule membranes of regulated exocrine, endocrine and granulocytic cell types. This distribution suggests that it may play a common functional role in regulated secretion.

APUD Cells↗

Immunocytochemical and ultrastructural characterization of endocrine cells and nerves in the intestine of Rana temporaria.

Endocrine cells have been identified in the intestine of the frog Rana temporaria after application of the Grimelius and Masson-Fontana techniques. These endocrine cells were examined using immunocytochemical techniques on paraffin and semithin sections for light microscopy. After testing 19 antisera, 12 immunoreactivities were identified. Numerous serotonin-, somatostatin- and GLP-1-immunoreactive cells; a moderate number of PYY-, glucagon-, VIP-, gastrin/CCK-immunoreactive cells and few human PP-, bombesin-, substance P- and neurotensin-immunoreactive cells were found. VIP- and met-enkephalin were identified in nerve fibers of the muscular layer. Using semithin-thin sections five types of endocrine cells (serotonin-, somatostatin-, gastrin/CCK-, glucagon- and bombesin-immunoreactive cells) have been characterized according to their immunocytochemical reaction and the ultrastructure of the secretory granules.

APUD Cells↗

The prevalence, prognostic significance and hormonal content of endocrine cells in gastric cancer.

Twenty-six of 100 cases of gastric adenocarcinoma contained argyrophil cells. All these tumours were carcino-embryonic antigen positive and 13 contained variable amounts of gastro-enteropancreatic peptides and amines. There was no significant difference in mucin type, extent or incidence of intestinal metaplasia between tumours with and those without endocrine cells. The prognosis for both groups was similarly poor, contrasting with that for carcinoid and atypical carcinoid. Endocrine cell hyperplasia was evident in the adjacent mucosa in some of the cases of endocrine positive tumours. There was no association between achlorhydria and the presence of endocrine cells in the tumours. The origin of the neoplastic endocrine cells remains speculative, occurring either as a mutation of a single stem cell or as a synchronous malignant transformation of two epithelial cell types exposed to a particular carcinogenic factor(s). Adenocarcinomas containing endocrine cells appear to be as biologically aggressive as the usual adenocarcinomas of the stomach and therefore should be treated in a like manner.

APUD Cells↗

Medullary carcinoma of the human thyroid in monolayer culture: morphological and cytochemical correlations.

Mechanically or enzymatically dissociated cells from three human medullary thyroid carcinomas (MTC) were grown in monolayer culture for periods up to seven months. Cultures of each tumor contained clusters of small epithelial-like cells which were readily identified by phase contrast microscopy. Immunocytochemical studies and electron microscopy showed that these cells contained abundant calcitonin and numerous secretory granules. Amine-storing mechanisms were also demonstrable in these cells by formaldehyde-induced fluorescence. Homogeneous cultures of epithelial-like cells showed no evidence of transitions into fibroblast-like cells. Addition of thyroxin to the tissue culture medium appeared to promote survival of epithelial-like cells in cultures of one tumor. The ability to morphologically recognize cultured cells with endocrine activity should facilitate establishment of human MTC lines for biochemical and physiological studies.

APUD Cells↗

Indium-111 pentetreotide in the diagnostic work-up of patients with bronchogenic carcinoma.

In a prospective study we examined 38 patients with primary bronchogenic carcinoma to validate the use of indium-111 pentetreotide (IPT) as a diagnostic tool. Of these 38 patients, 25 had small cell lung cancer (SCLC) and 13, non-small cell lung cancer (NSCLC). The aim of the study was to investigate whether (a) the disease can be reliably detected, (b) IPT allows differentiation between SCLC and NSCLC and (c) IPT provides further information on metastatic disease. After giving their informed consent the patients were injected and imaged 4 and 24 h later using a planar whole-body technique. In addition single-photon emission tomography of the thorax and, if necessary, other areas of the body was performed at 24 h. In the 25 patients with SCLC 22 sites of primary tumour were correctly identified (true-positive, TP); one was false-negative (FN) and two were true-negative (TN), the patients being in full remission. Metastases were correctly identified in ten instances (lung, bone and brain), while the findings were FN in five cases. An additional six FN findings resulted in the area of the upper abdomen due to the physiological uptake in the liver, spleen and kidneys. In the 13 patients with NSCLC, ten findings were TP and 3 FN with respect to the primary tumour. Two FNs were squamous cell carcinoma, and one, adenocarcinoma. Metastases were TP in nine cases and FN in one.(ABSTRACT TRUNCATED AT 250 WORDS)

APUD Cells↗

Regulatory peptides in gastric endocrine cells of the rainbow trout Oncorhynchus mykiss: general distribution and colocalizations.

The endocrine cells of the rainbow trout (Oncorhynchus mykiss) stomach have been investigated using the immunocytochemical techniques of peroxidase-anti-peroxidase and avidin-biotin-peroxidase complexes on paraffin sections. 33 antisera were tested and eight immunoreactivities were detected: somatostatin-, glucagon- bombesin-, substance P-, serotonin-, met-enkephalin-, CCK/gastrin-, and chromogranin-like containing cells. All of them were present throughout the gastric mucosa except CCK/gastrin-like containing cells that were restricted to the pyloric epithelium. Somatostatin 25 and chromogranin immunoreactive cells are described for the first time in fish stomach. Serotonin immunoreactive cells were also positive for the Grimelius technique and some of them were immunoreactive to anti substance P or anti CCK/gastrin. Immunoreactivities for gastrin 17, gastrin 34 and CCK appeared in the same cells and the absorption controls showed that a molecule containing the carboxi-terminal pentapeptide of this family was present in trout stomach.

APUD Cells↗

[Detection of CgA mRNA in neuroendocrine cells in gastric carcinoma by in situ hybridization].

Fresh gastric carcinoma specimens from 17 cases were collected. The neuroendocrine (NE) cells in gastric carcinoma (GC) and gastric mucosa adjacent to the carcinoma (GMAC) were observed using in situ hybridization of chromogranin A (CgA) oligonucleotide probe and compared with immunohistochemistry of CgA antibody. 5 of the 17 cases of GC showed CgA mRNA positive expression and 7 of the 17 cases expressed CgA protein positively. The simultaneous expression of mRNA and protein of CgA was present in 4 cases. The NE cells in GC not only can store and secrete CgA protein products but also possess the ability to synthesize NE products from gene expression.

APUD Cells↗