[Role of neuroendocrine cells in prostate cancer progression]. / Ruolo delle cellule neuroendocrine nella progressionedel carcinoma prostatico.

Neuroendocrine (NE) cells represent the third epithelial cell type on normal prostatic tissue (in addition to basal and secretory cells). They are localized in all regions of the human prostate at birth but rapidly decrease in the peripheral prostate after birth, and then reappear at puberty. After puberty, their number seems to increase until an apparently optimum level is reached, which persists between the age of 25 and 54. NE cells were defined by Pearse as APUD to refer to chemical characteristics of amine precursor uptake and decarboxylation, common to the cells of this system. The most predominant product of prostatic NE cells is Chromogranin A, but they also produce serotonin, CgB, secretogranin or CgC, thyroid-stimulating hormone-like peptide, calcitonin, katacalcin, PTHrP and a-human chorionic gonadotropin-like peptide. NE cells in normal and neoplastic prostates are devoid of androgen receptors, but they express epidermal growth factor (EGF) receptor and c-erbB-2. For these reason NE cells are androgen-insensitive. The NE component of prostate adenocarcinoma is resistant to hormone therapy; some studies showed that the number of NE tumor cells and CgA serum levels increase with the recovery of human prostate tumor from hormonal therapy. Currently there are no clinical data available to support an active role of radiotherapy in NE differentiation.

Distribution and morphology of argyrophilic cells in the digestive tract of the African ostrich.

We used light microscopy to elucidate the morphological features of argyrophilic cells in the digestive tract of the African ostrich (Struthio camelus). The results indicated that argyrophilic cells were found to be distributed among the epithelial cells of the mucosa or glands throughout the digestive tract, except for the esophagus; two types of argyrophilic cells were found; i.e., closed-type cells and cells with triangular or elongated shapes and with their apical cytoplasmic process in contact with the lumen (open-type cells); the greatest number of argyrophilic cells was found in the proventriculus, and the argyrophilic cell density gradually decreased from the proventriculus to the rectum; Furthermore, the number of argyrophilic cells in the duodenum and ileum was higher than that in the jejunum. This text still combined the characteristics that the argyrophilic cells in digestive tract of ostrich maybe related to different digestive function of different region and the basis of their morphology to carry on a discussion. It was speculated that argyrophilic cells in the digestive tract may have both endocrine and exocrine functions.

[Positron emission tomography in neuroendocrine tumours]. / Positronemisjonstomografi ved nevroendokrine svulster.

BACKGROUND: Neuroendocrine tumours constitute a small group of malignancies; about 200 new patients are diagnosed in Norway annually. This article discusses problems associated with use of deoxyfluoroglucose (FDG) Positron Emission Tomography (PET) and other available options in patients with these conditions, as well as challenges related to introduction of new radiopharmaceutical agents. MATERIAL AND METHODS: The article is based on review of literature in connection with development of new guidelines for nuclear medicine examinations, supplemented with literature identified through a non-systematic search of Pubmed. RESULTS: A large proportion of these tumours grow slowly, and recent data show that 5-year survival is about 50 %. Neuroendocrine tumours are characterised by specific biochemical processes that enable tailoring of radiopharmaceutical agents for PET and consequently a more accurate diagnosis and improved follow-up of these patients. INTERPRETATION: As for other cancer types, diagnostics and detection of metastases are an important factor for correct treatment of neuroendocrine tumours. PET with FDG is of limited use for patients with this condition. New specific radiopharmaceutical agents for PET may imply detection of 90 % of all such tumours.

[The role of diffuse endocrine system and colonocytes cellular renovation in formation of clinical variants of irritable colon syndrome in young persons].

60 patients with irritable colon syndrome (ICS) were examined. They were divided into 2 groups. Group 1 included 30 patients who had ICS with dominating constipation (ICSc). Group 2 consisted of 30 patients with ICS and dominating diarrhea (ICSd). 12 practically healthy persons composed control group. The patients were being observed in dynamics (in periods of aggravation and remission), under uniform program including clinical, endoscopic, morphologic and immunohistochemical methods. It was established that ICSc development related to hyperplasia and hyperfunction serotonin producing cells together with decrease of number and functional activity of VIP-producing cells and mast cells. It was detected significant increase of colonocytes proliferative activity, shown throw number of immunopositive to cycline Dl epithelial cells, and compensatory increase of apoptosis activity. In patients with ICSd it was registered increase of number and functional activity of general population of apudocytes, serotonin-, melatonin- and VIP-produsing cells and mast cells. It was detected decrease of number of colonocytes immunopositive to cycline D1 and proliferating cell nuclear antigen, and growth of colon epithelial cells apoptosis activity. More significant changes of diffuse endocrine system in patients with ICSd set conditions for progress of changes of cell renovation with frequent colon mucous tunic atrophy, acting as a background for carcinogenesis.

Immunohistochemical and electron-microscopical identification of neuroendocrine cells in the respiratory tract of rats with experimental uraemia.

The aim of the present study was to characterise immunohistochemically and ultrastructurally the neuroendocrine cells in the pulmonary systems of uraemic rats. Pieces of lung and trachea were collected 1, 2 and 4 weeks after nephrectomy. Paraffin-embedded sections were stained with H+E and by silver impregnation. For the identification of neuroendocrine cells immunohistochemical reactions were performed with the use of specific antibodies against calcitonin (CT), somatostatin (SOM), synaptophysin (SYN), neuron-specific enolase (NSE) and calcitonin gene-related peptide (CGRP). For electron microscopy, ultrathin sections were used. The analysis showed an increased number of both the solitary neuroendocrine cells and of neuroepithelial bodies in uraemic rats when compared to control animals.

Review article--involvement of gastric APUD cells in chronic renal failure.

Uremia leads to a number of metabolic and hormonal disorders induced by renal failure with definite biological and clinical sequels. Most frequently, alimentary disorders are the first to appear, followed by symptoms from other organs and systems. The gastrointestinal tract is a site of synthesis of many compounds that have hormonal or hormonal-like biological activity. These substances are produced by highly-specialised receptor-effector cells, that are dispersed in the gastrointestinal mucosa and classified as APUD cells. The present review is an attempt to make a synthesis of current opinions and views concerning the effect of homeostatic dysfunction of the kidneys on the morphology and action of APUD cells in the stomach.

Incidence of neuroendocrine cells in the seminal vesicles and the prostate--an immunohistochemical study.

INTRODUCTION: Prostate and seminal vesicles (sv) are both androgen-dependent male sex accessory glands. The cancer incidence in these two organs is vastly different. Neuroendocrine (NE) cells are involved in the regulation of prostate growth, differentiation and in prostate cancer carcinogenesis. Thus, knowledge of the incidence of NE cells in sv may add to our understanding of prostate cancer etiology. METHODS: Samples of histologically confirmed normal prostate tissue and normal sv tissue from 20 men were immunostained for chromogranin A. The incidence of stained cells was evaluated semiquantitately. RESULTS: Neuroendocrine cells were detected in all prostate specimens, but not a single stained cell was found in any of the sv specimens. CONCLUSIONS: The lack of NE cells and, subsequently, of biogenic amines, peptides and growth factors may be a reason for the low cancer incidence in the seminal vesicles. Alternatively, the absence of NE cells can be seen as a hint that the stem cells of the prostate and sv react differently to endogenous and exogenous stimuli, and thus in the seminal vesicles, stem cells are not transformed into NE cells.

Preliminary evaluation of endocrine cells in the rat respiratory tract after thyroid and parathyroid gland removal.

The complete thyroid and parathyroid gland removal leads to the abrupt reduction of calcitonin, which can be a factor stimulating growth and intensified activity of APUD system cells in the respiratory tract. Thus, neuroendocrine cells in the lungs and trachea in rats after thyroid and parathyroid removal were evaluated. Paraffin specimens of the examined organs were stained with H+E and impregnated with silver. Calcitonin, synaptophysin, somatostatin, and neuronal-specific enolase were detected immunohistochemically by the use of rabbit specific antibodies. Antibodies used in the study immunostained neuroendocrine cells of the examined organs. Rats with removed thyroid and parathyroid glands presented weakened reaction compared to the control group.

[Melatonin and serotonin in inflammatory colon diseases and colorectal neoplasms]. / Melatonin i serotonin pri vospalitel'nykh zabolevaniiakh tolstoi kishki i kolorektal'nom rake.

Patients with inflammatory intestinal diseases and colorectal adenocarcinoma in sigmoid mucosa were examined using light and electron microscopy, immunohistochemical tests, radioimmunoassay and morphometry. Functional morphology of the general population of the endocrine cells and apudocytes producing melatonin and serotonin as well as urine excretion of 6-sulfatoxymelatonin changed in quality and quantity. The parameters showed specificity depending on clinicomorphological variant of colorectal pathology. The findings provide additional criteria in diagnosis and prediction of the course of different types of inflammatory and tumor affections of the colon.

[Apudocytes and mast cells in chronic inflammation of colon: clinicomorphological correlations]. / Apudotsity i tuchnye kletki pri khronicheskikh vospalitel'nykh zabolevaniiakh tolstoi kishki: kliniko-morfologicheskie sopostavleniia.

AIM: To study functional morphology of a total population of endocrine cells of colon mucosa, mast and enterochromaffine cells. MATERIALS AND METHODS: Light and electrone microscopy, immunohistochemical methods, morphometry were used to study endocrine and mast cells of the sigmoid colon in inflammation. RESULTS: Changes of functional morphology and size of endocrine and mast cell population as well as apudocytes producing serotonin, melatonin, vasointestinal peptides were stated. Apudocyte and mass cell functional morphology, clinical symptoms and mucosal structural changes correlated. Specificity of some parameters in Chron's disease is shown. CONCLUSION: The results may provide additional criteria in diagnosis of different variants of chronic colitis.

Gut endocrine cells in birds: an overview, with particular reference to the chemistry of gut peptides and the distribution, ontogeny, embryonic origin and differentiation of the endocrine cells.

This review deals with gut endocrine cells in birds. It focuses on both morphological and developmental aspects of these cells, which were included members of Pearse's APUD series. They comprise many cell types, which, in birds as in mammals, produce serotonin and a range of regulatory peptides. The chemical structure of most avian gut peptides has been established. These peptides and their functions are outlined here. The types and distribution of avian gut endocrine cells are detailed and compared with the situation in mammals. In birds, ultrastructural work has been limited to certain types of gut endocrine cell and not as widely applied as in mammals. However, immunocytochemistry has found widespread application in studies on birds: the hatching chick and also the adult chicken and certain other species such as the quail and duck have been studied. Gut endocrine cells showing immunoreactivity for the following peptides/serotonin have been identified: somatostatin, pancreatic polypeptide (PP), peptide YY, glucagon, secretin, vasoactive intestinal peptide, gastrin, cholecystokinin (CCK), neurotensin, motilin, gastrin-releasing peptide, substance P, enkephalin and serotonin. The colocalization of different peptides (including chromogranins) and of peptides and serotonin in the same gut endocrine cells is reviewed: notable amongst such associations are glucagon with PP and gastrin/CCK with neurotensin in the same cells. On morphological grounds cells have been identified as endocrine in avian gut from at least 9 days of incubation. Immunocytochemical studies show the majority of the various types first to appear between 12 to 14 days of incubation, with substantial numbers being recorded from 17 days onwards. Experimental studies on chicken and quail embryos have determined the embryonic origin of gut endocrine cells: evidence is unequivocal that such cells arise from the endoderm, not the neural crest, other ectoderm or the mesoderm. Studies on avian embryos have also contributed to our knowledge of mechanisms controlling the differentiation of gut endocrine cells: evidence shows that gut mesenchyme plays an important role in provoking (or inhibiting) the development of gut endocrine cells and there are indications that the endocrine cell pattern in gut is established early and that an axially-derived factor may be important in this process. The kinds of genetic mechanism possibly involved are mentioned but full elucidation of the processes concerned is awaited. A better understanding of the formation of endocrine tumours of the gut should result from the findings.

[Changes in the neuromediator system of the thymus in rats after splenectomy]. / Izmeneniia neiromediatornoi sistemy timusa u krys posle splenectomy.

Removal of spleen leads to compensatory activation of the function of central immunogenetic organ and increase of hyperplastic processes in it on d 3 postoperatively which is accompanied by growth of biogenic amine concentration, appearance of bioaminergic areas and lobules-satellites as well as formation of new cloe correlative links. Transitory inhibition of immunogenesis occurs on d 15 and d 30 peaking on d 45 following splenectomy. At this period glycosaminoglycan composition of mast cells and their functional activity changes which is manifested by appearance of juvenile T-0 forms and new metachromatic types of mast cells. In 2 months decrease of APUD cells number and their mono- and diamine content and weakening of correlative interconnections is accompanied by true significant disturbance in T lymphocytes differentiation, their release in peripheral blood and further insufficiency of cellular immunity.

Exocytotic release of vasoative intestinal polypeptide and serotonin from mucosal nerve fibres and endocrine cells of the intestine of the goldfish (Carassius auratus) and the tilapia (Oreochromis mossambicus): an ultrastructural study.

In earlier studies were determined the effect, presence and ultrastructure of vasoactive intestinal polypeptide (VIP) and 5-hydroxytryptamine (5-HT)-containing nerve fibres in the tilapia and goldfish intestinal mucosa. 5-HT-labelled varicosities were found close to the epithelial cells; however, synaptic membrane specializations have never been observed. VIP-like immunoreactive nerve fibres appear to be located less frequently close to the goldfish epithelium, as in the tilapia intestine, in which the distance between the VIP- or 5-HT-labelled varicosities and the epithelial cells was also rather large (more than 2 micros). To establish a possible role of VIP and 5-HT as neurotransmitters involved in the regulation of fish intestinal epithelium both electron microscopical and immunoelectron microscopical methods were used to visualize the release of 5-HT and VIP from nerve fibres. We found exocytoses from VIP-ergic and serotonergic varicosities in the muscle layers of both fish. Directly underneath the intestinal epithelium of the goldfish, it was demonstrated that 5-HT could be released from scarce varicosities. The release of 5-HT in the tilapia intestinal mucosa could only be observed from endocrine cells.

[Current methods for studying the functional morphology of apud cells]. / Sovremennye metody izucheniia funktsional'noi morfologii éndokrinnykh kletok.

The paper reviews methods for studying functional morphology of endocrine cells histochemistry and immunohistochemistry, radioautography and methods of ultrastructural verification of secretory granules. Methodological approach is illustrated by the authors' results on the influence of ionizing radiation and tumor growth on the cells of the diffuse endocrine system.

[Helicobacter pylori, endocrine cells of the gastric mucosa, and their function in duodenal ulcer]. / Helicobacter pylori, éndokrinnye kletki slizistoi obolochki zheludka i ikh funktsiia pri iazvennoi bolezni dvenadtsatiperstnoi kishki.

Antral biopsies of 33 duodenal ulcer patients (15 with hypergastrinemia, group 1 and 18 with normal fasting serum gastrin, group 2) and also 13 healthy volunteers were studied for D- and G-cell density and HP-status. Basal acid output (BAO), maximal acid output (MAO) and serum somatostatin were also evaluated. G- and D-cell density was measured by PAP-immunostaining technique. Serum gastrin and somatostatin levels were studied by radioimmunoassay. HP-status was evaluated histologically with the use of semiquantitative enhanced method. Both groups of patients had decreased D-cell density compared with control (p < 0.05). Patients from group 1 had significantly increased BAO, MAO, G-cell density, index of infective load of HP, index of adherence of HP, comparing with group 2 (p < 0.05), and decreased serum somatostatin level and D-cell density compared with group 2. There were no significant differences found in serum somatostatin level, BAO, G-cell density, serum gastrin level between group 2 and control (p > 0.05). Hyperfunction of G-cells arose from impaired paracrine secretion of somatostatin, that strongly associated with increased index of infective load and increased index of adherence of HP to epitheliocytes of gastric antrum.

[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.

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.

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.

Tissue-specific and substrate-specific endoproteolytic cleavage of monkey pro-opiomelanocortin in heterologous endocrine cells: processing at Lys-Lys dibasic pairs.

This study compares the processing of pro-opiomelanocortin (POMC) at two Lys-Lys cleavage sites, located in the carboxy-terminal domain of the precursor, one site marking the amino terminus of beta-melanocyte-stimulating hormone (beta-MSH) and the other in the carboxy-terminus of beta-endorphin (beta E). These comparisons were carried out by transfecting monkey POMC cDNA into two heterologous cell lines: AtT-20, which endogenously expresses mouse POMC, and Rin m5F, which has been previously used as a host for transfected POMC. These cells lines are known to process POMC differently at Lys-Arg residues, though less is known about their Lys-Lys cleavage. Our results have demonstrated both tissue-specific and site-specific factors controlling Lys-Lys cleavage. The AtT-20 line appears not to perform either Lys-Lys cleavage. Rin m5F cells, on the other hand, fail to process the site at the carboxy terminus of beta E (beta E28-29) but do process, to a significant extent, the N-terminal site to beta-MSH. That this differential processing is unlikely to be due to a POMC conformation which would make the beta E site inaccessible was demonstrated by mutating the sites from Lys-Lys to Lys-Arg. With such mutants, Rin m5F cells fully processed at both locations. Interestingly, the mutant Lys-Arg sites were not fully processed by AtT-20 cells. These results are discussed in terms of the complement of processing enzymes expressed in each of the cell lines, as well as the role of residues surrounding the diabasic cleavage sites in determining the likelihood of proteolysis.