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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.

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., (Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.)

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.

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.

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., (Copyright 2004 Via Medica)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Endocrine-paracrine cells of the prostate (also known as APUD or neuroendocrine cells) constitute, in addition to the basal and exocrine secretory cells, a third population of highly specialized epithelial cells in the prostate gland. These endocrine-paracrine cells contain, and most likely secrete, serotonin and calcitonin, as well as variety of other peptides. Little is known of the functional role of these cells, but they probably subserve a paracrine or local regulatory role. They may also regulate via endocrine, lumencrine, or neurocrine mechanisms. These endocrine-paracrine cells probably play a significant role during prostatic growth and differentiation as well as regulating the secretory process of the mature gland. Neuroendocrine differentiation in prostatic carcinoma occurs in the form of the relatively rare small cell carcinoma and carcinoid or carcinoid-like tumor, but most commonly as focal neuroendocrine differentiation in a conventional prostatic adenocarcinoma that is a very frequent, if not ubiquitous phenomenon, and reflects tumor cell heterogeneity mimicking the normal differentiation process. The world's literature on neuroendocrine differentiation in prostatic carcinoma is reviewed. Neuroendocrine differentiation in all types of prostatic carcinoma appears to correlate with a poor prognosis. This correlation is probably multifactorial and may relate to a positive correlation with grade, a direct resistance to hormonal manipulation, and/or autocrine/paracrine growth factor activity due to the secretion of neuroendocrine products. Neuron-specific enolase and chromogranin, as well as other neuroendocrine products, may be useful as serum markers in patients with prostatic carcinoma with neuroendocrine differentiation. New therapeutic strategies need to be developed to treat these tumors. This includes the use of specialized protocols that have been effective against neuroendocrine carcinomas arising in other organ systems.

Bioptates of the stomach mucous membrane (SMM) have been investigated in 169 patients suffering from duodenal ulcer (DU). According to the nocturnal gastric secretion test among them there are "hypersecretors" and persons with moderate elevation of acid formation. In conformity with the efficiency of the operative treatment among the patients examined, groups are defined: those with recurrent disease and those recovered after vagotomy. The DU endocrine apparatus undergoes both qualitative and quantitative alterations after vagotomy. When recovery after vagotomy takes place, the number of endocrine cells only slightly exceeds these parameters in the patients with a moderately manifested acid production. These alterations are adaptive. The recurrence of DU in patients with moderately manifested acid production before the operation can be explained by hyperplasia of G-cells. A high degree of hyperplasia of all elements of the endocrine apparatus in the "hypersecretors" can be one of the causes of the DU recurrence. The data about the state of G-, Ec- and EcL-cells before and after vagotomy can be used at prognostication the results of surgical treatment of patients with DU.

The organization peculiarities of APUD-system in the lungs of rabbits, rats and guinea pigs has been studied. The endocrine system in the lungs of rabbits in pre- and postnatal ontogenesis is presented by the adipocytes and neuroepithelial bodies (NEB) containing a considerable number of monoamines. The number of argyrophil adipocytes and NEBs in the lungs of 21 and more day-old adult rats seem to be less than in fetuses and newborns. Monoamines are not revealed in the endocrine rat lung structures by means of the glyoxylic acid. In the lungs of guinea pigs the single argyrophil adipocytes and NEBs are determined in the gestation period.

By means of incubation of slices in 2% solution of glyoxylic, acid adrenergic nervous structures and endocrine cells (APUD cells) have been studied in the ampule wall of the duodenal large papilla and in the lungs in 6 mature male rabbits. Topographic proximity of APUD cells and adrenergic nervous fibers is noted. Contents of serotonin and catecholamines in the structures mentioned have been investigated microfluorometrically. Simultaneous revealing of producers of monoamines make possible to suppose that serotonin and catecholamines get paracrinically from the APUD cells into terminals of the adrenergic nervous fibers.

The lungs of 40 children who had died at the age of 1 month to 3 years were studied using special immunohistochemical and morphometric methods. Destructive lung processes were registered more frequently in children below one year of age with acute pneumonia having a similar viral-bacterial etiology. The content of apud-cells with an argyrophilic reaction, amine-containing APUD-cells and lymphocytes with cyclic nucleotides was significantly decreased and indices of the lymphocyte functional activity lowered comparing to the older age group. An essential role of the physiological immaturity of the biogenic amine synthesis by apud-cells is attributed in the acute pneumonia pathogenesis in children of early age. This aggravates immune deficiency and the development of the destructive forms of inflammation.

The duodenum of four species of monkeys, belonging to the genera Macaca and Papio, has been investigated. In order to reveal argyrophil and argentaffin Ec-cells, Grimelius and Masson-Hamperl methods have been used, respectively. In all the species studied in the terminal parts and in the ducts of the duodenal glands presence of endocrine cells is noted; their amount, however, is considerably less than in crypts. Open and close types of endocrine cells++ have been revealed in the glands. A part of the endocrine cells population is argentaffin Ec-cells (about 40% in Papio and 80% in Macaca). This demonstrates participation of serotonin they produce in regulation of the duodenal glands functional activity. Dependence between taxonomic position of the species and degree of endocrine cells++ development in the duodenal glands has been followed. In particular, in representatives of Macaca amount of argyrophil and argentaffin in the glands is greater than in Papio. Possible reasons of the differences are discussed. Comparing the results on investigation of the glands in the primates with those previously obtained for representatives of Carnivora, a suggestion is made concerning some general principles in organization of the proper endocrinic apparatus of the mammalian duodenal glands.

In experiment on 25 cats reproducing small intestinal obstruction it has been established that the number of endocrine cells (EC) and the degree of their saturation with secretory granules increase in 3 and 6 h after the experiment. These indices decrease by 12 and 25 h after the experiment. The results obtained enable to reveal the EC participation in acute intestinal obstruction pathogenesis and to suppose the influence of released serotonin by paracrine way on mucous membrane as well as distant action on peristalsis and blood flow through intramural nerve plexus.

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.

It was found that in patients with gastroduodenal hemorrhage the number of serotonin-, histamine-, and melatonin-producing apudocytes in the gastric mucosa increases while the number of cells producing gastrin, adrenaline, and noradrenaline reduces. In timely arrest of hemorrhage, the primarily increased number of melatonin-producing apudocytes diminishes with time from the onset of bleeding and reaches normal values gradually. The essential differences in the content of melatonin- and noradrenaline- producing apudocytes in patients with and without hemorrhage allow this morphological sign to be used as diagnostic and prognostic criteria in gastroduodenal hemorrhages.

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.

Morphologic examination of the adenohypophysis of 46 subjects who died from cardiovascular diseases has shown a restructuring of the gland, including changes in its nonspecific signs and alterations typical of certain cardiovascular conditions. Analysis of the ratios between various types of endocrine cells and different types of basophil tropocytess in health and disease has revealed variability of these parameters in cardiovascular diseases and in various types of the same disease. Fluctuations in adenohypophysis cellular composition are explained by specific features of the pathogenesis of these conditions.

There are now increasing evidences suggesting that GABA is able of direct interaction with certain endocrine cells. In the present study, highly specific anti-GABA-glutaraldehyde antibodies and 3H-GABA uptake were used at the light and electron microscope levels to investigate the occurrence of cells containing endogenous GABA or taking up exogenous GABA in the mucosal antrum and corpus of the rat stomach. Only certain endocrine cell types of both regions were immunostained or grain-labelled. However, the morphology of their secretory granules did not allow to identify the nature of their hormone with certainty but suggested that somatostatin-like cells could interact with GABA. The combination of gastrin and somatostatin immunodetection with 3H-GABA uptake autoradiography at the light microscope level, revealed that a subpopulation of somatostatin-like cells and other still unidentified endocrine cells are able to take up GABA, while the gastrin-like cells are not. These results reinforce the hypothesis that certain endocrine cell types of the diffuse endocrine system of the digestive tract are able to directly interact with GABA.

A novel endocrine cell type has been identified in the guinea-pig gastric mucosa which preferentially occurs in the oxyntic area. Cells of this type exhibit immunoreactivities for bovine adrenal medulla dodecapeptide (BAM-12P) and in many cases for Met-enkephalin and are thus presumed to contain a pro-enkephalin-like precursor protein. Systematic immunohistochemical investigations show that these cells do not contain immunoreactivities for various enteric hormones, neuropeptides and biogenic amines (serotonin, histamine). However, they do contain immunoreactivity for chromogranin A, an acidic glycoprotein which is common to the majority of entero-endocrine cells. Using silver impregnation techniques BAM-12P immunoreactive cells prove to be argyrophil, but fail to react argentaffin. On the electron microscopical level, these cells contain a well-developed endoplasmic reticulum and Golgi apparatus and numerous polymorphous secretion granules which measure about 290 nm in diameter. The secretion granules are ovoid or pear-shaped but largely plump compared to those of enterochromaffin cells. Light and electron microscopical findings indicate that BAM-12P immunoreactive cells constitute an endocrine cell population of the gastric epithelium in addition to the "established" endocrine cells hitherto known in this location.

Modified Grimelius method of the apudocyte identification on the semithin sections is described and used for the study of the duodenum endocrine cells. The method gives the possibility to study the distribution of secretory granules in the endocrine cell cytoplasm and increases the possibilities of taking samples for the ultrastructural analysis of apudocytes.

It was shown in 25 experiments on anesthetized spontaneously breathing and immobilized artificially ventilated cats that the cooling of the intermediate chemosensitive area of the ventral surface of medulla oblongata to 20-22 degrees C is followed by depressor reaction that is more pronounced after preliminary occlusion of the sinocarotid and vagus nerves. Two types of apudocytes were revealed in this brain area with the use of the histochemical and immunohistochemical techniques. The first type cells are typically nervous and contain noradrenaline. The second type apudocytes adjacent to the microvascular wall showed melatonin and its precursors. It is assumed that the cells detected participate in the arterial pressure control.

The rat stomach was shown some years ago to contain numerous endocrine cells with APUD ability--cells that could take up the amino acids L-5-hydroxytryptophan (5-HTP) or L-dihydroxyphenylalanine (L-DOPA) and could decarboxylate them to their respective amines, 5-hydroxytryptamine (5-HT, serotonin) and dopamine, by means of the enzyme DOPA-decarboxylase. In a recent study, most of the APUD endocrine cells in the rat oxyntic mucosa were shown by electron microscopic radioautography to be the enterochromaffinlike cells, while the A-like cells were shown to lack APUD ability. To identify the APUD cells in the pyloric mucosa, pieces of rat pylorus were incubated in organ culture with 3H-5-HTP and were processed for light microscopic and electron microscopic radioautography. Additional specimens were incubated with 3H-5-HTP and carbidopa, an inhibitor of DOPA-decarboxylase, used to block the decarboxylation of 3H-5-HTP to 3H-5-HT, or with 3H-5-HT, used to determine where exogenous 3H-5-HT localizes in the pyloric mucosa. The 3H-5-HTP labeled all three types of endocrine cells identified within the pyloric glands--the G, enterochromaffin, and D cells. As this labeling was inhibited by carbidopa, and as exogenous 3H-5-HT labeled these cells only lightly, the labeling must have resulted from the uptake and intracellular conversion of the 3H-5-HTP of 3H-5-HT. Thus despite their morphologic differences, all rat pyloric endocrine cells possess APUD ability, a property shared by many, but not all, of the peptide- and amine-producing endocrine cells located throughout the body.

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.

Immunohistochemical studies in medullary thyroid carcinoma demonstrate the presence of C cells secreting calcitonin but also of other cells secreting other peptides or proteins. These different cells exist in the tumor as well as in metastases. These results and other reported in the literature suggest a common ultimobranchial and endodermal origin for these cells.

Melanin production by a medullary thyroid carcinoma (MTC) is reported and discussed. Immunohistochemically, the tumor cells contained calcitonin; by electron microscopy, they bore numerous, heterogeneous granules similar to those described previously in MTCs. One small focus of tumor was pigmented. Here, melanosomes in different stages of maturation were found in dendritic cells that ramified among granule-bearing cells. The remarkable phenotypic divergence in this solitary, nongerm cell neoplasm is unusual but not so surprising in light of the APUD nature and neural crest origin of both the melanocyte and the thyroid C cell, which gives rise to MTC. The authors view the calcitonin and melanosome phenotypes as closely related tumor clones evolving from a common precursor neoplastic cell. This unique "experiment of nature" adds to the set of rare human tumors that make melanin "ectopically."