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The authors describe a case of multiple carcinoid tumours of stomach, which arose on an atrophic chronic gastritis. The case was studied in strict equipe cooperation by physicians, surgeons, radiologists, anatomopathologists, and, subsequently, it was surgically treated through total extended gastrectomy.
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The significance of the hormone calcitonin, ectopically produced, is evaluated as a tumour marker. Since 40 percent of an unselected sample of tumours is hypercalcitoninaemic, calcitonin may be useful as a tumour marker, though absence of specificity limits its diagnostic value.
Opiate peptides, encephalins and endorphins, originally isolated from the brain, have been detected by the immunocytochemistry and radioimmunoassay in the digestive system and localized in the distinctive endocrine-paracrine cells of APUD series of the gastrointestinal mucosa and the nerve fibers of the myenteric plexus. The physiological role of endogenous opiates is unknown but the spectrum of biological action on the digestive system resembles that of morphine and related drugs. They strongly affect gastrointestinal motility such as gastric and intestinal contractions, gastric emptying, intestinal transit, biliary pressure and defecation. They also increase gastric secretory activity and raise gastric mucosal microcirculation without affecting gastrin release. They inhibit pancreatic bicarbonate and enzyme secretion probably via suppressing the release of intestinal hormones, secretin and cholecystokinin. The actions of opiates on the motility and secretion can be reversed by specific opiate receptor antagonists, e.g. naloxone, indicating that opiate receptors may be involved in these actions.
Histotopography and content of argyrophilic and argentaffin endocrinocytes per 1 mm2 of section of the hen rectal mucosa in ontogenesis were studied by method of light microscopy. Endocrinocytes were demonstrated in a part of epithelial layer from 12 day of embryogenesis. By 21 day their number increased 23 times. By the 3rd day of postnatal development endocrinocyte number reaches definitive values. Endocrinocytes are evenly distributed in the rectal epithelium, their shape varies. Forming of the endocrine apparatus structural organization in the hen rectum deals with the processes of the early endocrinocyte differentiation in a part of the epithelial layer during embryogenesis.
Results of the morphofunctional examination of APUD and immune lung systems of 180 infants who have died from acute pneumonia are presented. Cooperative interactions between lung adipocytes and lymphocytes of the lymphoid system associated with bronchi are revealed. These interactions play an important role in the mechanisms of the pulmonary inflammatory processes development.
The method of light microscopy was used for studying the histotopography of endocrinocytes of the vermiform process mucosa of man. The direction of their distribution was found in distal, medial and proximal parts of the vermiform process mucosa. The greatest amount of endocrinocytes in normal conditions per 1 mm2 of the mucous membrane was found in the proximal part and it was getting less towards the distal one. In inflammation there occurs an increase of the amount of endocrinocytes (in acute ordinary appendicitis, it is 1.5 times higher, in the phlegmonous form--2 times). With the development of deep destructive processes in the mucous membrane the content of endocrinocytes is sharply decreased.
The original classification of neuroendocrine tumours proposed by Pearse was based on a common embryologic origin in the neuroectoderm. The term, carcinoid, literally means carcinoma-like, was coined in 1907 to describe the histologic similarity of these tumors to carcinomas on the one hand and their generally indolent biologic behaviour on the other hand. Neuroendocrine tumours represent a group with complex biological, histological, ultrastructural and immunocytochemical properties. This concept was replaced by another classification based on results of modern techniques (electron microscopy, immunocytochemistry, molecular and DNA analyses). This permits a more reliable classification of tumours, that can be used to determine their biological behaviour and prognosis.
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Apudomas, i.e. tumours deriving from apud system cells, comprise already known forms located in widely different organs at considerable distances one from the other. They present great cytochemical, biochemical and ultrastructural similarities and possess a common derivation in the neuroectodermal cells of the neural crest. They thus form part of that tumour group known as neurolophomas. They are also responsible for typical clinical pictures connected with the production of hormone-type substances, and are classified among multiple endocrine adenomatoses and in the ectopic hormone syndromes.
As part of a project to identify the endocrine cells ("EC" and "APUD" series) of the gastroenteric apparatus of ruminants, the ultrastructure of the mucosa of the pyloric glands of adult ox was studied morphologically and cytochemically, in parallel with a light microscope histochemical analysis. The results show that: the "EC" cells (producing 5-HT) are recognizable by their secretory granules which are heavily osmiophilic, argentaffin ("Masson") and argyrophilic ("Grimelius"). A further distinction is possible on the basis of their morphological features: the ""EC" cells of the gastric type (which belong to the "ECn" group) contain granules fairly homogeneous in shape and size, while the "EC" cells of the intestinal type (or "EC1") show granules which are more pleiomorphic and variable in size. Of particular interest is the presence in some cells of granules typical of the "EC" cells of the intestinal type, in the vicinity of a few others, which appear quite similar to those of the adjoining exocrine cells; the "G" cells (gastrin producing) contain medium sized granules, which are unreactive to "Masson" and poorly argyrophilic. Their morphology is rather diverse; some of them (these are the "typical" cells) have a granular and weakly electron dense content, others (which we consider "atypical") show a homogeneous and heavily osmiophilic core, with an eccentrical empty area. Also present are granules whose appearance is intermediate and empty vesicles; the "D cells" (somatostatin producting) show round, medium sized granules which have a granular, moderately osmiophilic core, tightly encircled by the membrane. These granules are unreactive to "Masson" and to "Grimelius"; the "D1" cells (whose function is yet unclear) contain small, round granules whose core is variously but discretely electron dense and not always homogeneous; they are unreactive to "Masson" and fairly argyrophilic. These granules may be numerous and packed, or scarce; in this latter instance the few granules are intermingled with variously running tufts of parallel filaments, thus resembling the "P" cells, whose function is still undefined. These data show therefore that the types of endocrine cells we have identified in the pyloric glands of adult ox correspond to those described in other mammals; "X" and "F" or "PP" cell appear to be lacking.
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Just as in other cyprinids, three zones can be distinguished in the digestive tract of Barbus conchonius. A fat absorptive zone (65--75%), including the intestinal bulb, is followed by a protein absorptive zone (25--35%) and a small ion and water absorptive zone (less than 5%). The main characteristics of these zones are described. Four types of enteroendocrine cells can be distinguished between the intestinal epithelial cells. The number decreases in the caudal direction, and there are very few in the protein absorptive zone. All the enteroendocrine cells are argyrophilic and differ mainly in the size and shape of their secretory granules. Serotonin producing and hence argentaffin cells have not been found. Amine precursor uptake and decarboxylation (APUD) by the enteroendocrine cells of adult fishes has not been observed. The possible functions of the enteroendocrine cells are discussed. (Auto-)phagosomes, common in epithelial cells of the gut of B. conchonius, show similar staining characteristics as the enteroendocrine cells; their function is discussed.
Psilocybin poisoning produces biphasic reactions composed of a schizophrenic phase and a panic attack-like phase. There is a time lag of several hours between phases, which may be considered an accumulation time in certain sites between the gut and the brain. So far as 5-hydroxytryptamine (5-HT) congeners are concerned, no sites are to be found except the amine precursor uptake and decarboxylation (APUD) system. It is postulated that argyrophil cells (AC) in the foregut, neuroepithelial bodies (NEB) in the lung, and raphe nuclei (RN) in the brainstem axis are relevant to mental disorders. Schizophrenia might be due to the massive destruction of APUD cells, and the paroxysmal release of 5-HT with peptides and panneuroendocrine markers from NEB might be the cause of panic attack.
A population of cells containing the enzymes tyrosine hydroxylase (TH) and dopa-decarboxylase (L-AADC) but not dopamine-B-hydroxylase (DBH) nor phenylethanolamine-N-methyltransferase (PNMT) can be detected with immunocytochemical techniques in the pancreas of mouse embryos at the 11th day of development (E 11). The presence of TH in embryonal pancreas is transient: TH is not observed after E 15. By use of a method for simultaneously detecting two antigens in the same section both TH and glucagon were visualized in the same cell on E 12. Double labelled cells comprised 10% of all stained cells. At E 14.5, some of the cells stained for TH also contained insulin. However, at the time somatostatin appeared no embryonal cells containing TH remained. We conclude that two cell types of the APUD series, i.e., the glucagon and insulin cells of pancreas, arise from transformation, in situ, of cells that transiently express a dopaminergic phenotype. These results suggest that peptide-containing cells in skin, brain and gut are linked by a common embryonic origin. They also raise the prospect that other peptidergic cells of the APUD series may have aminergic precursors.
This report concerns a 49 year old asymptomatic male who had a mediastinal mass demonstrated on routine radiography. A large encapsulated tumour composed of small regular cells arranged in clumps and acini with fine vascular stroma was removed. The differential diagnosis on routine H&E section included parathyroid tumor, medullary carcinoma arising in ectopic thyroid tissue, epithelial thymoma or carcinoid tumor of the thymus. The presence of compressed thymic tissue around the tumor, and of argentaffin granules together with the electron microscopic appearance characteristic of the "enterochromaffin" or "APUD" group of cells allowed the diagnosis of carcinoid tumor of the thymus to be made. Electron microscopy showed that the cell cytoplasm contained electron dense membrane bound granules, together with bundles of microfilaments. Vesicles of smooth surfaced reticulum were present but rough surfaced reticulum was inconspicuous. No desmosomes were demonstrated. Special stains for amyloid and glycogen were negative.
The isoenzymes of the glycolytic enzyme enolase have been separated and purified. The structural and functional properties of two brain enolases are described. Immunocytochemical techniques have established that one brain enolase is restricted to neuronal cells (neuron-specific enolase, NSE) while the other is localized in glial cells (nonneuronal enolase, NNE). The brain enolases, therefore, represent the first example of functional markers for neuronal and glial cell types in brain. The two enzymes are structurally distinct with the evidence establishing that they are products of separate genes. Functionally, the neuronal enolase has been demonstrated to be uniquely stable to concentrations of chloride salts that rapidly inactivate the glial enzyme. NSE may therefore represent an adaptation of this enzyme that is specifically suited to the neuronal milieu. A specific radioimmunoassay is described for NNE and NSE with the studies reported indicating that neuronal enzyme levels vary considerably when different brain areas are compared, suggesting a relationship between functional activity and levels of NSE. In addition to being a marker for neuronal cells, NSE has also been found to be present in various glands. The cells of the APUD series (amine precursor uptake and decarboxylation cells) in the pituitary, adrenal medulla, pineal, thyroid, and pancreas have been shown to contain NSE. NSE is, therefore, also a marker for these neuronlike endocrine cells since they are the only cells other than neurons that contain this protein.
The neural crest cells give rise to a large variety of derivatives including neural, mesenchymal, APUD and/or paraneuron cell types. A better knowledge of these derivatives was partly achieved through studies using Le Douarin's quail/chick marker system. We review here evidences which were thus provided for a neural crest origin of calcitonin containing cells, carotid body, aortic paraganglia, adrenomedulla, and against a neurectodermal origin of enterogastric and respiratory tract endocrine cells. The role of neural crest cells in Pearse's APUD system is discussed. The results implicate that an explanation for the common properties of these cell types and their pathological and biochemical significance should not be looked for in a common embryological origin but at another level. The place of neural crest and, more generally, neurectoderm derivatives in the paraneuron concept of Fujita is examined. The relevance of the epithelial origin of these cell types to their "receptosecretory" function is stressed. Considering neural crest itself as a unique system is still questioned and discussed here. Its ubiquity and penetration of other systems is pointed out as a widespread phenomenon which is not restricted to APUD and paraneuron systems.