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PubMed1976

Uptake of 14C-labelled chloroquine and an 125I-labelled chloroquine analogue in some polypeptide hormone producing cell systems.

After the injection of 14C-labelled chloroquine and the 125I-labelled chloroquine analogue 4-(31-dimethylaminopropylamino)-7-iodoquinoline [125I]DAPQ into mice, rats and a monkey the distribution of the radioactivity was studied by autoradiographical methods. A high and persistent uptake occurred in some endocrine cell systems, such as the pancreatic islets, the hypophysis, the adrenal medulla and the thyroid (in cells that were probably identical with the parafollicular cells). The melanin-containing tissues were the only ones which showed a higher uptake and retention of radioactivity. The above mentioned endocrine cells and the melanocytes have a common embryological origin and common morphological and cytochemical characteristics. They have been called the APUD (Amine Precursor Uptake and Decarboxylation)-cell series. It is proposed that the polypeptide hormone producing cells and the melanocytes may use a similar mechanism for accumulating chloroquine and (as shown earlier) also some other drugs such as nicotine, alprenolol, local anesthetics and atropine. These drugs however, accumulate stronger within the melanocytes and become bound to the melanin for a long time. The ability to accumulate these drugs may be considered another characteristic of the APUD-cell series.

Adrenal Medulla↗

PubMed1973

Cellular localization of gastric inhibitory polypeptide in the duodenum and jejunum.

Indirect immunofluorescence studies using an antiserum to purified porcine gastric inhibitory polypeptide indicate, in the gastrointestinal tract of dog and man, that this polypeptide is present in cells situated predominantly in the mid-zone of the glands in the duodenum and, to a lesser extent, in the jejunum. Absolute correlation of the gastric inhibitory polypeptide cell with one or other of the known endocrine-like cells identified by electron microscopy awaits confirmation by electron immunocytochemistry. It is here identified as an endocrine polypeptide cell of the APUD series and, provisionally, as the D(1) cell. While the hormonal status of a given polypeptide depends ultimately on physiological experiments the present results strengthen the view that gastric inhibitory polypeptide is indeed a hormone.

Animals↗

PubMed1981

Ultrastructure of endocrine-like cells in lamina propria of human gastric mucosa.

Endocrine cells of gastric and gut mucosa are commonly thought to be present only within mucosal glands. In a previous report, we described argyrophilic cells in the lamina propria in 40% of surgical gastric specimens, using light microscopy. All these patients had chronic gastritis. Argyrophilia, however, is a non-specific reaction which could occur in other than endocrine cells. The present study was undertaken to describe the ultrastructure of argyrophil cells in the lamina propria. In five patients with chronic gastritis, endoscopic biopsies were taken from the fundic, intermediate, and pyloric areas of the stomach. Single and/or clustered argyophil cells were seen by light microscopy in the lamina propria of the intermediate and pyloric areas. On electron-microscopy, these cells had the following characteristics of endocrine-like cells: they were characterised by numerous electron dense granules in the cytoplasm, 100-300 nm in diameter; the cytoplasm contained poorly-developed rough endoplasmic reticulum and well-developed smooth endoplasmic reticulum with occasional vesicles. Immunostaining gave negative results for various gastrointestinal hormones. These ultrastructural characteristics of lamina propria cells are similar to endocrine cells of the APUD series. We conclude that endocrine-like cells occur in the lamina propria of the human stomach in the presence of chronic gastritis.

Adult↗

PubMed1999

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.

APUD Cells↗

PubMed1977

Malignant acanthosis nigricans--a para-endocrine syndrome?

A case is reported of acanthosis nigricans associated with a gastric carcinoma. The gastric cancer was of the diffuse, infiltrating type. Many tumour cells were identified by means of histochemistry and electron microscopy as neoplastic enterochromaffin-like cells. It is suggested that cancers associated with acanthosis nigricans might constitute a certain group of carcinomas in which parts of the tumour cells arise from the APUD-series of endocrine cells.

Acanthosis Nigricans↗

PubMed2004

Activity of thyroid parafollicular (C) cells in rats with hyperthyroidism--preliminary ultrastructural investigations.

In the thyroid gland of mammals, except the basic follicular (F) cells, parafollicular (C) cells are detected. They belong to disperse neuroendocrine cells of the APUD system. Co-localisation of F and C cells in the thyroid gland is not accidental. It seems possible that there is an interaction between them, mediated by the peptidergic hormones. Calcitonin (CT) is proposed as an essential indicator of C cells. The role of C cells in the function of the thyroid gland has been not clarified till now, especially in hyperthyroid state. There are only a few data which document the ultrastructure of C cells in the physiological and pathological state. In the present study, the ultrastructure of thyroid C cells in an experimental model of hyperthyroidism was evaluated. Our preliminary study may confirm the functional interaction between follicular and parafollicular cells in the thyroid gland.

Animals↗

PubMed1989

Ultrastructural architecture of pulmonary small-granule cell clusters in adult Syrian golden hamster.

Throughout the epithelial lining of the respiratory system is a class of cells with characteristics similar to Amine Precursor Uptake and Decarboxylation (APUD) polypeptide hormone-producing cells. In the intrapulmonary airways, these small-granule cells (SGCs) occur either singly or in organized clusters. Although no specific peptide has yet been identified, subclasses have been postulated based on granule geometry or light microscopic staining. The present study characterizes the architectonic and cellular organization of clustered SGCs in the adult Syrian golden hamster. Two morphologically distinct cells can be defined in such clusters, "light" and "dark." Thid distinction was based primarily on differences in the electron density of the cytoplasmic matrix rather than on the remarkable variations in cellular organelles or dense-core secretory vesicles. Both cell types were normal as judged by uniform spherical nuclei, chromatin organization, and distribution of cellular organelles. The "dark" cells, however, presented the profile of a cell actively involved in synthesis with a markedly dilated perinuclear cisterna and endoplasmic reticulum. Additionally, the "dark" cells contained membrane-delimited structures containing concentric membranous whorls, clear vacuoles, and lipofuscin granules. Occasionally, cells were observed to contain features of both cell types, suggesting that they may represent a continuum of common cell lineage. Accordingly, in the absence of additional morphologic or biochemical data, the "light" and "dark" cells most probably correspond to different stages of functional activity or age-related changes of a single type of cell. Unmyelinated nerve endings were occasionally interposed between cells, but synaptic specializations were not observed. Beneath the clusters, nerve fibers were also present, but they were never observed to penetrate the basal lamina or contact any of the SGCs. Of equal occurrence were elements of the vascular system and smooth muscle, suggesting that some SGCs in the adult hamster may function in a paracrine or endocrine manner. Such knowledge is essential to any study attempting to delineate the functional role or roles of these enigmatic organoids.

APUD Cells↗

PubMed1982

[The diffuse endocrine system and the carcinoids of the alimentary tract. Part I: Orthological aspects and common morphological features of the carcinoids (author's transl)].

Carcinoids arise from the so-called system of diffuse clear cells. Because of common histochemical properties it was proposed in the APUD-concept that these endocrine cells are of neural crest origin. As for the gastrointestinal tract endocrine cells this embryological derivation is disputed. Modern methods have led to the identification of about 18 distinct cell types. - According to the different localization of these cells in the alimentary canal the carcinoids show various histological structures i.e., a solid, trabecular, adenoid, undifferentiated and mixed growth. According to the reactivity to silver salts one can distinguish argentaffin, argyrophil and argyrophobe carcinoids. Biochemically and immunohistochemically some carcinoids are multihormonal, while others show paraendocrine hormone production. Small cell anaplastic carcinomas with endocrine granules are highly malignant variants of the carcinoids. There may be a mixed endo- and exocrine (amphicrine) differentiation in normal cells and in the so-called mucicarcinoids.

APUD Cells↗

PubMed1989

[Endocrine cells of the gastroduodenal area in duodenal ulcer].

A study has been carried out to substantiate the assumption that excessive proliferation of major gastroduodenal endocrine cells may be predetermined genetically. Hereditary predisposition to the hyperplasia of cells belonging to the APUD system may be inherited both through the male and female lines. Duodenal ulcers (DU) undoubtedly involves multifactorial inheritance. Acquired capacity for endocrine cell hyperplasia cannot be excluded in some of DU patients. The development of DU is, apparently, related to the formation of a pathological system, based on pathologic structure-linked neurohormonal relationships between the duodenum and peripheral and central nervous systems that enhance nerve impulses in the duodenal bulbar portion. A sudden "total" catecholamine release occurs at a certain stage and is followed by a change of production/utilization ratios of various hormones that weakens pathologic neurohormonal relationships, destroys the pathologic system and activates the healing process around the ulcer. The pathologic system, active in peptic ulcers, is doubtless counteracted by a system, whose activity must be determined by the number of endocrine cells with beta-endorphine-like and, perhaps, serotonin-like immunoreactivity. The antagonistic regulation principle is of great universal significance for general biology. It is essential for healing and chronization processes.

APUD Cells↗

PubMed1985

Ultrastructure of enterochromaffin cells and associated neural and vascular elements in the mouse duodenum.

Enterochromaffin cells of adult mouse duodenum were studied with light- and electron-microscopical techniques. They were distinguished from other enteroendocrine cells by their pleomorphic, electron-dense secretory granules in the basal cytoplasm. At the apices of enterochromaffin cells, tufts of short microvilli bordered the gut lumen. At their bases, irregular cytoplasmic extensions were either in contact with or passed through the basal lamina. The presence of cytoplasmic extensions in close proximity to fenestrated capillaries and subepithelial nerves suggested an endocrine or paracrine function. Electron micrographs of serial thin sections were used to reconstruct an enterochromaffin cell from the crypt epithelium in three dimensions and to determine its relationship with the underlying neural plexus. Although extensions from the serially sectioned and reconstructed cell and other enterochromaffin cells studied in crypt epithelia protruded through the basal lamina, no synaptic contacts were seen. Evidence of a synaptic contact between a neurite and another type of enteroendocrine cell (possibly an intestinal A cell), suggested a neurocrine role for some of the basally-granulated cells. Possible functions of enterochromaffin cells are discussed in the light of recent literature on the system of enteroendocrine cells, also known as APUD (amine precursor uptake and decarboxylation) cells and/or paraneurons.

Animals↗

PubMed1985

[Histochemical and immunohistochemical identification of endocrine cells in the internal ear].

The authors describe the results of the study of rabbit decalcified temporal bones and guinea-pig membranous cochlea treated according to the Grimelius argyrophil method and immunohistochemical technique with the use of a number of specific antisera. The study revealed the cells of the diffuse endocrine system (APUD system) in various parts of the internal ear: in the main membrane, receptor elements of the spiral chorda, and spiral ligament. Serotonin and melatonin were identified in the cells of the APUD system. The data obtained may form a theoretical basis of a basically new trend in the study of the function of the internal ear in health and disease.

APUD Cells↗

PubMed1975

APUD characteristics and immunocytochemistry of avian pituitary corticotrophs.

L-DOPA is taken up and decarboxylated by cells in the avian adenohypophysis, which are situated largely in the cephalic lobe. These APUD cells have been shown by sequential formaldehyde-induced and immunofluorescence to be corticotrophs and the relationship between the two procedures has been found to have a reciprocal quality.

Adrenocorticotropic Hormone↗

PubMed1984

Morphologic and cytochemical characteristics of amine-containing globule leukocytes in rat tracheal epithelium.

Amine-containing cells in the tracheal epithelium are typically of the small-granule type (diameter approximately 100 nm). However, in the rat, another amine-containing cell type has been identified that possesses the amine-handling features of the APUD-series of cells (amine precursor uptake and decarboxylation) but not the ultrastructural characteristics. It has been postulated that these cells may be related to cutaneous melanocytes. In this study, fluorescent cells were present in the laryngeal and tracheal epithelial lining of adult Sprague-Dawley rats following freeze-drying and exposure to formaldehyde vapor (FIF or formaldehyde-induced fluorescence). Microspectrofluorimetry revealed an emission maximum at 493 nm. The excitation maximum could not be calculated but appeared to be around or below 350 nm (to record spectra below requires the use of quartz optics). Yellow fluorescence also emanated from serotonin-containing mast cells (excitation and emission maxima: 401/515 nm). Tracheal segments processed according to the aqueous formaldehyde ( AFIF ) technique, for the demonstration of 5- hydroxytryptophan (5-HTP) or serotonin (5-HT), failed to identify fluorescent cells in the epithelial lining even though connective-tissue mast cells were evident. Subsequent treatment of AFIF -fixed sections with formaldehyde and HCl vapors ( AFIF -HCl) resulted in the formation of a fluorogenic compound within numerous cells in the tracheal lining (455/537 nm). This spectral shift and increase in intensity of fluorescence following acidification are characteristic for standards and/or cells that contain tryptamine, tryptophan, or peptides with NH2-terminal tryptophan and are markedly different from microspectrofluorimetric data reported for the phenylethylamines or serotonin. It is therefore postulated that these cells contain a closely related beta-(3-indolyl) ethylamine-like compound, serotonin excluded. The morphology of the fluorescent cells was similar when prepared according to the FIF or AFIF -HCl techniques. Conjunctive staining, the examination of a single section first by fluorescence microscopy and subsequently by other histochemical and cytochemical methods, demonstrated that the fluorescent granules were also methylene blue, alcian blue, periodic-acid Schiff, and ferric- fericyanide positive. Subsequent correlative electron microscopic examination of Epon-embedded AFIF -HCl-treated tracheal sections demonstrated that these amine-containing cells were globule leukocytes.

Animals↗

PubMed1985

Application of markers in the diagnosis of soft tissue tumours.

In this review we describe the application of markers which are useful for the diagnosis of soft tissue tumours in paraffin sections. Detection of intermediate filament proteins appears to be most useful for first screening of these neoplasms because all, except neuroblastomas, express vimentin; cytokeratin is expressed in synovial sarcomas, epithelioid sarcomas and mesotheliomas; desmin in myogenic tumours and glial fibrillary acidic protein in astrocytomas and gliomas. Tissue-specific markers are: factor VIII--related antigen-endothelial cells; myoglobulin and skeletal muscle myosin--skeletal muscle cells; neuron specific enolase--neurons and cells of the APUD systems; and leukocyte-associated antigen--leukocytes. Markers which are present in a variety of cell types and therefore do not serve as tissue-specific markers are; S-100 proteins, alpha-1-antichymotrypsin, creatine kinase M and actin. The S-100 antigens have been detected in melanomas, granular cell tumours, chondrosarcomas and in some schwannomas and liposarcomas. Alpha-1-antichymotrypsin has been found in fibrohistiocytic and 'true' histiocytic tumours and creatine kinase M and actin in myogenic tumours. No specific markers have, as yet, been described for fibrosarcomas, Ewing's sarcomas and hemangiopericytomas.

Carcinoma↗

PubMed1988

Small cell carcinoma of the esophagus: report of a case treated with chemotherapy.

A 54-year-old man with small cell carcinoma of the esophagus and extensive metastases to the liver and bone is presented herein. Ectopic hormone production and a high level of serum NSE (neuron specific enolase), as revealed by biochemical and radioimmunoassay, suggested that this tumor was derived from the cells of the APUD (amine precursor and dehydroxylation) series. He was treated with a combination chemotherapy, resulting in a prompt remission with significant palliation lasting five months. Small cell carcinoma of the esophagus is as responsive to chemotherapy as small cell carcinoma of the lung. Although this is an uncommon tumor, recognition is important because of its responsiveness to chemotherapy and the potential for significant palliation of symptoms without surgical intervention.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Preliminary immunohistochemical investigations of thyroid C cells in an experimental model of hyperthyroidism.

The role of the parafollicular (C) cells, the second most important cells in the thyroid gland, has not hitherto been clarified. They are considered to be disperse neuroendocrine cells of the APUD system and synthesise and release many of the regulatory peptides. Few publications are concerned with the evaluation of the structure and function of C cells in the thyroid gland or the probable relationship between these cells and the follicular cells in physiological and pathological conditions. For this reason immunohistochemical investigations were carried out into the activity of the C cells in rats in an experimental model of hyperthyroidism caused by chronic thyroxine influence. This C-cell activity was then evaluated. Differences in the quantity, distribution and calcitonin immunoreactivity of C cells were observed in hyperthyroid rats in comparison to the control group, together with a significant diminution of plasma TSH and calcitonin levels. Our preliminary study may indicate a functional interaction between follicular and parafollicular cells in the thyroid gland.

Animals↗

PubMed2006

Quantitative characteristics of somatostatin-like cells in the stomach of uraemic rats.

Metabolic disorders induced by impairment of renal parenchyma functions affect the activity of the endocrine cells of the APUD system, which are of importance in the intrinsic regulatory system in the digestive tract. For this reason, the author decided to investigate the behaviour of neuroendocrine cells in experimental uraemia, taking somatostatin-producing cells as an example. The aim of the present study was to examine the number and distribution of somatostatin-containing cells in the pylorus of rats with uraemia. Segments of the gastric pylorus were collected 1, 2 and 4 weeks after nephrectomy. Paraffin-embedded sections were stained with H+E and by silver impregnation. To identify the neuroendocrine cells, on immunohistochemical reaction was performed with a specific antibody against somatostatin. It was found that the number of ST-immunoreactive cells in the stomach of the rats significantly decreased one week after nephrectomy and then considerably increased two and four weeks after the uraemia-inducing surgery as compared with the values in the control animals. The results can be regarded as a morphological manifestation of the hyperreaction of somatostatin-producing endocrine cells in the rat stomach to disorders in the internal environment of the body induced by impairment of renal parenchyma function.

Animals↗

PubMed1981

[APUD system (problems of structural and functional organization, histogenesis and pathology)].

The aspects of structure and function of the APUD-system under normal and pathological conditions are analysed. New terms and concepts (apudocyte, apudoblast, apudogenesis, apudopathies) applicable to the APUD-system are introduced. It is suggested that some apudocytes originate from polypotential stem cells. The dysfunctions of the APUD-system (apudopathies) are described, their classification is suggested, and the role of apudocytes in the endogenous mechanisms of oncogenesis is analysed.

APUD Cells↗