[Disperse endocrine system and APUD concept].

This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

[Morphofunctional regeneration of epithelial cells in the colon and apudocytes in the pathogenesis and prognosis of the course of non-specific ulcerous colitis].

One hundred twenty patients with nonspecific ulcerative colitis (NUC) were examined. The patients were divided into three groups equal in number according to the severity of the disease. The controls were 24 practically healthy individuals, 64 patients with irritated bowel syndrome (IBS) without pathological changes in the colon mucosa, and 64 IBS patients with atrophic or inflammatory changes in the colon mucosa. The study showed that the development of NUC was associated with an abrupt decrease in the level of proliferation markers (cycline D, and proliferating cell nuclear antigen - PCNA) in the epithelial cells of the sigmoid colon. Their number progressively decreases in more severe cases, while cell apoptosis intensifies. Such changes in cell renewal are closely connected with the functional and structural rebuilding of the diffuse endocrine system, which manifests in an increase of the total number of apudocytes as well as serotonin- and melatonin-producing cells together with a decrease in the number of VIP-producing cells.

Endocrine cells of bronchial and bronchiolar epithelium.

Among the epithelial elements of the pulmonary airways are cells with features suggestive of endocrine function. Although these cells share a number of properties with the intestinal endocrine (argentaffine) cells, peptide hormones analogous to the multitude of those present in the gastrointestinal tract have yet to be identified in the lung. The oat cell carcinoma, which arises from this cell type, is of importance clinically, yet investigations into the basic properties and functions of this cell have been difficult and sparse, in part due to a lack of appreciation of the problem.

Innervation of the adrenal cortex, its physiological relevance, with primary focus on the noradrenergic transmission.

The current knowledge of the catecholaminergic innervation of the mammalian adrenal cortex is summarized, and macro- and microscopic neuromorphology, including the central nervous system connections of the adrenal cortex, is briefly discussed. Morphological and functional data on the catecholaminergic (i.e., noradrenergic) innervation of the adrenal cortex are reviewed. Experimental data suggest that in addition to the regulation of adrenal blood flow, the noradrenergic innervation has a primary influence on zona glomerulosa cells possibly via beta 1 adrenergic and dopaminergic receptors (DA2 subtype via inhibiting T-type Ca2+ channels) It is concluded that the local, modulatory effect of noradrenergic nerve fibres, terminating in the close vicinity of the zona glomerulosa cells, on the systemic renin-angiotensin-aldosterone and other peptide cascade may be influenced by neuropeptides, particularly neuropeptide Y and vasoactive intestinal peptide.

Peptides of the APUD system in amphibian skins.

Methanol extracted skins from 84 species of amphibia were screened, measuring by RIAs: gastrin-CCK, VIP, calcitonin, GIP, PP and motilin. G-CCK-like immunoreactivity was found in 97.6%; VIP-like immunoreactivity in 41%; CT-like immunoreactivity in 34%; GIP-like immunoreactivity in 10%; PP-like immunoreactivity in 40% and MT-like immunoreactivity in 60% of the samples. The use of a sequence-specific radioimmunoassay and of gel-chromatography confirmed the caerulein-CCK-8-like nature of the immunoreactive material. Detected amounts of the other peptides (VIP, CT, GIP, PP, MT) were too low for bioassay or chromatographic studies, thus leaving the question open if they are due to some kind of unspecific interferences or, most likely, to species-specificity differences of the used antisera.

The diffuse neuroendocrine (APUD) system.

The bulk of experimental evidence indicates that the APUD series of cells is a distinct system based upon common pathophysiological features. The diffuse nature of this system with elements in the central and peripheral nervous system suggests a more complex interaction of the body's homeostasis than has been established. It is probable that as radioimmunological and radioenzymatic assays become more widely available and standardized, other apudomas will be described. Finally, an understanding of the APUD concept, with its peculiar pluripotential for the production of biogenic amines and peptides, the multicentric nature of the disease and the possibility of multiple cell involvement, is of key importance in managing patients. Studies of the apudomas will also advance the understanding of the normal physiologic interrelationships of the APUD cells.

The pineal gland as an APUD organ: supporting evidence and implications.

It is only in recent years that the pineal gland has emerged from being thought of as non-functional and unimportant. The rise from obscurity has been the result of the interest of investigators of multidisplinary origins; such approaches, whilst clearly advancing understanding, also tend to leave knowledge fragmentary. In the last decade, a new neuroendocrine axis known as the APUD system has been delineated and scientifically accepted. The essence of the concept has been to link a physically widely dispersed and apparently unconnected series of glandular structures by a common embryological derivation and their secretion of closely similar functional products. The present proposal collates evidence for the inclusion of the pineal gland within the APUD system. In addition, because of the proven connections and response of the pineal gland to environmental changes, it is hypothesised that pineal products may provide the link between the environment and other members of the widely dispersed APUD system and thereby temper body homeostasis.

Possible mechanisms of panic attack and schizophrenia via APUD system.

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.

[APUD- and RAA- regulatory systems in acute radiation injury]. / APUD- i RAA-sistemy reguliatsii pri ostrom radiatsionnom porazhenii.

An experimental morpho-functional assessment of rat APUD and RAA systems status in acute radiation injury (cerebral form) was performed. The named regulatory systems were found to display an actual momentary post-exposure reaction, followed by subsequent functional changes of a distinct phase character. The latter were shown to determine in many respects the clinical picture and in some cases the outcome of the disease.

[Differentiation and cytogenesis of endocrine elements of the rat duodenum in ontogenesis]. / Differentsirovka i tsitogenez éndokrinnykh élementov dvenadtsatiperstnoi kishki krysy v ontogeneze.

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

[Medullary carcinoma of the thyroid gland and the APUD system]. / Medulární karcinom stítné zlázy a APUD systém.

Medullary thyroid carcinoma, MTC, accounts for 8-10% of all thyroid malignancies. It occurs in the sporadic form (70-75%) and the familial variant (25-30%). In familial MTC the autosomal dominant type of heredity is involved. This variant is found frequently in association with other endocrine hyperplasias or tumours within the framework of the APUD system and is thus an indispensible condition of the MEN 2 syndrome, either MEN 2A (MTC and pheochromocytoma and/or hyperparathyroidism) or MEN 2B with the frequent concurrent presence of pheochromocytoma and a typical phenotype, in particular multiple neurofibromas on the lips and tongue. The type of MTC determines also to a certain extent the prognosis of the disease. MTC in the framework of MEN 2A are usually most benign, while the prognosis is poorest for MEN 2B. The sporadic variant has a poorer prognosis, as compared with differentiated thyroid carcinoma. The only effective and rational treatment of MTC is radical surgery. In all instances where we confirm the diagnosis before surgery we indicate bilateral total thyroidectomy. In the familial variant where the tumour is usually multifocal and in both lobes this indication is absolute, in sporadic forms with possible early intrathyroid dissemination of the primary tumour also to the other side, bilateral surgery is also indicated. Moreover we know that a certain ratio of assumed sporadic forms are genetically conditioned tumours and thus are familial. The histological finding of hyperplasia of the C-cells suggests the familial variant even when tumourous transformation did not occur yet.(ABSTRACT TRUNCATED AT 250 WORDS)

[Peptidergic innervation and the APUD system in normal conditions and in various pathological states]. / Peptidergicheskaia innervatsiia i APUD-sistema v norme i pri patologii.

The use of highly sensitive and selective methods (autoradiography, light and electron microscopy, radioimmunoassay) allowed identification of peptide hormones in both the specialized endocrine cells (apudocytes) of some internal organs and various structural elements of the central and peripheral nervous system. Current knowledge permits one to suggest the existence of a peptidergic innervation as one of the parts of the nervous system and to demonstrate the direct participation of these peptides in the pathogenesis of some diseases. Biological significance of these substances in supporting homeostasis determines the urgent need for a combined investigation of the structural-functional relationship between apudocytes and peripheral nerves under normal and pathologic conditions. This will promote new opportunities in the elucidation of the mechanisms of some pathologic processes.

[APUD system (problems of structural and functional organization, histogenesis and pathology)]. / APUD-sistema (voprosy strukturno-funktsional'noi organizatsii, gistogeneza, patologii).

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.

[The APUD-system function of the intestines and the morphological changes in the internal organs of adult rabbits infected with toxigenic Vibrio cholerae]. / Sostoianie APUD-sistemy kishechnika i morfologicheskie izmeneniia vo vnutrennikh organakh vzroslykh krolikov, zarazhennykh toksigennymi kholernymi vibrionami.

V. cholerae infection with clearly pronounced diarrhea was reproduced in adult rabbits with the use of the RITARD system. The state of the APUD system of the intestine of the animals and morphological changes in internal organs in experimental cholera were described. As noted in this study, the manifestation of changes in the intestine and other organs, as well as the reaction of apudocytes to V. cholerae infection, were linked with the intensity of diarrhea and the time of the death of the animals.

[Morphofunctional state of the APUD-system cells of the lungs in hyaline membrane disease of newborn infants]. / Morfofunktsional'noe sostoianie kletok APUD-sistemy legkikh pri bolezni gialinovykh membran novorozhdennykh detei.

Examination of these cells in newborn infants with hyaline membrane disease. (HMD) has demonstrated involvement of neuroendocrine elements in its patho- and morphogenesis. A crucial factor in HMD development is immaturity of the lungs, one sign of which is the presence of numerous serotonin-containing cells. Degranulation of APUD cells and serotonin lease under exposure to pathogenic factors initiate pathologic reactions in the lungs and account for the earliest manifestations of the disease.

[Effect of pineal peptides on neuroendocrine system after pinealectomy]. / Vliianie peptidov pineal'noi zhelezy na neiroéndokrinnye vzaimosviazi posle pinealéktomii.

Removal of the pineal gland leads to structural and functional rearrangement of gastric endocrine cells and thyroid C-cells in albino rats, as was shown by immunohistological methods and morphometry. Injection of pineal peptides epithalone and epithalamine eliminated these changes. Biological activity of epithalone is believed to be higher than that of epithalamine.

[Local neuroendocrine regulation of the cerebral vessels in acute disorders of cerebral blood circulation]. / Mestnaia neiroéndokrinnaia reguliatsiia sosudov golovnogo mozga pri ostrom narushenii mozgovogo krovoobrashcheniia.

The functional condition of lateral endocrine (melanocytes, mast cells) and neurogenic (adrenergic plexus) arterial apparatus of the cat brain during occlusion of the right common carotid artery for 5, 20, 35 min, was studied. The maximal decrease of the melanocytes occurred on the 20th min in the vessels of the right side of the Willis circle. An increased concentration of the mast cells and nervous fibers was found on the 20th min followed by its reduction by the 35th min on the side of ischemia. The reaction of the blood supply was evident as a gradual increase of the mast cells, longitudinal and transversal adrenergic fibers on the 35th min of the experiment.

Morphological aspects of endocrine cells in human fetal gastrointestinal mucosa. Microscopical, electronmicroscopical and immunohistochemical studies.

This paper describes the morphological features and distribution of endocrine cells in the human fetal gastrointestinal mucosa between the 8-9th and the 36th the weeks of gestation. We used techniques of argentic impregnation, techniques with chromogranine and neuron specific enolase, electronmicroscopical techniques and immunohistochemical techniques as well (PAP and ABC) with antibodies for G cells, EG cells, D cells, S cells CCK (I) cells and EC cells. The first argyrophilic and/or argentaffin cells appear in the fetal gut of 8-9 weeks old. We describe the appearance, distribution, morphology of the identified endocrine cells with immunohistochemical techniques and we discuss the possible morphofunctional interrelations between them, but also with the neighbouring structures like lymphoid tissue in ileum, colon and appendix in embryofetal period.

[Importance of the morphofunctional status of APUD cells in the prognosis of duodenal ulcer hemorrhage]. / Znachenie morfofunktsional'nogo sostoianiia apudotsitov dlia prognoza krovotecheniia pri iazvennoi bolezni dvenadtsatiperstnoi kishki.

In 24 patients with uncomplicated duodenal ulcer and 40 patients with acute bleeding duodenal ulcer morphofunctional status of the local paraendocrine adjusting system of the duodenal mucous membrane in the periulcer, ulcer and remote zones was studied with histochemical and electron-microscopic techniques. It is established, that ECL- and G-apudocytes hyperplasia and hyperfunction and vice versa D-cells reduction of the number and suppression of the secretory activity are reliable prognostic criteria of duodenal ulcer bleeding.

C and APUD cells and endocrine tumours. Pearse's laboratory in the years 1965-1969: a personal recollection.

This paper is a personal recollection of the studies, conducted in Prof. Pearse's laboratory in London in the years 1965-1969, which led to the discovery of production of calcitonin by parafollicular C cells and medullary carcinomas of the thyroid. The author's intention is to underline the combination of technical excellence, brilliant intuition, dedication and serendipity which led to a series of major discoveries and, historically, established the pivotal role to be played by immunohistochemistry in endocrine research and diagnosis. The formulation of Pearse's APUD cell theory gave a formal credence to the existence of common endocrine mechanisms, molecular markers and structural features in dispersed cells, all belonging to a diffuse endocrine system. This represented a major breakthrough which primed, in the following years, the studies on polypeptide hormone-producing cells and tumours, thus paving the way to the endocrine histology and pathology as we know, and practice them today.