[Eutopic and ectopic hormone formation in the APUD endocrine cell system].
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APUD Cells↗
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Asbestos-related increase in pulmonary levels of vasoactive intestinal peptide (VIP).
Vasoactive intestinal peptide (VIP), leucine-enkephalin (Leu-Enk), dynorphin (Dyn), neurotensin (NT) and substance P (SP) were measured by radioimmunoassay in lung and bronchoalveolar lavage (BAL) fluids of sham operated control rats and rats exposed to asbestos (5 and 10 mg, single intratracheal injections) for 3 and 6 months. Among these peptides, VIP, Leu-Enk and Dyn were the most abundant with 6 to 25 pmoles per g of lung tissue as compared with 0.95 to 1.2 pmoles per g for the other neuropeptides. In the presence of asbestos, VIP levels were selectively increased up to 2.7 times in lung tissue and 4.3 times in BAL fluids. On high pressure liquid chromatography (HPLC), the immunoreactive VIP coeluted with synthetic VIP. It is concluded that this selective increase may be involved in the pathogenesis of asbestos-related diseases. Exposure to asbestos causes chronic inflammatory reactions in the lung which may lead to fibrosis (1) and increase the incidence of pleuropulmonary cancers (2). Little is known concerning the biochemical changes responsible for the deleterious effects of asbestos on pulmonary functions. Previous studies have documented the vast complexity and diversity of lung biochemistry including its ability to metabolize lipids, inactivate certain enzymes and produce physiologically active amines (3-6). Recently, the lung has been recognized as an important source of peptidergic substances. VIP and SP were reported to be localized in nerve terminals of the main airways and in axons of the parasympathetic conducts (7-11). Other neuropeptides including bombesin (12, 13), calcitonin (13, 14) and Leu-Enk (13) were also detected in the lung. However, these latter peptides were mainly confined to diffuse granule-containing cells also known as APUD cells (amine precursor uptake and decarboxylation cells) (15). The role of these neuropeptides in normal lung function and in pulmonary diseases is unknown. However, it has recently been demonstrated that APUD cells proliferate in the rat lung following asbestos inhalation (16) and lung exposure to carcinogens (17, 18). In addition, Moody et al. (19) and Sorenson et al. (20) have observed high levels of bombesin in human cell lines derived from small-cell lung carcinoma. It was then of particular interest to verify if lung exposure to asbestos can induce some changes in the levels of various neuropeptides. In the present study, we report that VIP is significantly increased in the lungs and BAL fluids of rats exposed to asbestos while no significant change in the levels of Leu-Enk, Dyn, NT and SP is observed.
Animals↗
[Fluorescent detection of APUD-type cells in the digestive tract of the rabbit fetus. Correlative study in electron microscopy].
Previous studies performed on different species have shown that these cells could be recognized by their morphologic and immuno-histological features. In early stages, these cells are able to take up and decarboxylate amine precursors. Therefore the aim of the present work was to determine if this uptake could be correlated with ultrastructural modifications. A processing technique allowing amine detection and correlative ultrastructural examination was used. Rabbit foetuses 13, 14, 17 and 21 day old were studied. The gastro-intestinal tracts of L-DOPA treated or untreated foetuses were removed in a glutaraldehyde-formaldehyde mixture and embedded in epoxy-resin. Semi-thin sections allowed to locate fluorescent cells in U.V light microscopy; adjacent thin sections were observed in electron microscopy. The first green fluorescent cells appeared in the 13 day old foetuses treated with L-DOPA. By this stage, these cells were very scarce and appeared poorly differentiated in electron microscopy. Between the 15th and the 18th day, the green fluorescent cells contained only small round granules. By the day 19, orange-yellow cells can be observed in L-DOPA treated and untreated foetuses. These cells possessed characteristic enterochromaffin granules. The green fluorescent cells of 21 day old foetuses, treated with L-DOPA, exhibited various fluorescence intensities correlated with the heterogeneity of the secretory granules. Some foetuses of each stage were treated with Falck's technique. This method gave similar results concerning the chronology of fluorescent cell detection.
APUD Cells↗
Chemodectoma of the larynx. A clinico-pathological study.
The present case report is concerned with a clinico-pathological study, including ultrastructural investigation, of a rare and uncommon laryngeal tumour, a chemodectoma, in a 62 year old patient. There have been 23 cases of laryngeal chemodectomas reported in the literature, and only three of them, including our own report, were investigated by electron microscopy. The tumours arise from the superior and inferior larynegeal nonchromaffin paraganglia or possibly from Kultschitzky-cells of the normal bronchial mucosa. Ultrastructurally they have all the characteristics of apudomas whose parent cells (APUD-cells), usually show endocrine function and probably have their origin in the neural crest. The tumours show an aggressive type of behaviour, despite usually benign histological features when compared to chemodectomas at other sites in the head and neck region. Surgery is thus the therapy of choice.
Humans↗
Serotonin storage and chromogranins: an experimental study in rat gastric endocrine cells.
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.
5-Hydroxytryptophan↗
[The APUD concept and its clinical significance. 2. Effect of gastrointestinal hormones, polypeptides and neurotransmitters on the physiological course and disease processes of the intestinal tract and the nervous system].
The neurally programmed APUD-cells from ectodermal origin are of peculiar significance in two respects: 1. They represent the largest endocrine gland of the whole organism and the peptides, which are secreted by the different APUD-cells, exercise a great influence on most of the motoric and secretory processes within the whole gastrointestinal tract just as on many metabolic processes as demonstrated on the so-called "enteropancreatic axis". Neoplasias of these APUD-cells, the "Apudomes", give rise to peculiar clinical syndromes. Early diagnosis of an apudome can be reached today by radioimmunologic detection of high concentrations of the responsible peptide in the blood enabling us to initiate an effective therapy at least for some of the known apudomes. 2. Beyond that the APUD-cells and their corresponding peptides are representing the so-called "peptidergic" division of the nervous system which acts as third-line effector to modulate not only the actions of the autonomic division but also of each other. The given example of the modulating effect of substance P or of the endorphines on the perception of pain is only one single aspect of the broad functional spectrum of these neuropeptides. The discovery, that the very same peptide can be detected in endocrine cells as well as in neurones, has opened one of the most fascinating and provocative developments in biology of the present time and some surprising new details can be expected in the next future.
APUD Cells↗
Oat cell carcinoma as a malignant apudoma.
The neural crest origin of cells secreting amine and polypeptide hormones (APUD cells) is a unifying concept. The relationship of the classical endocrine system to that of tumor hormone secretion can be explained by the diffuse migration and later neoplasia of these unique cells. This paper describes the APUD cell origins of oat cell carcinoma.
Carcinoma, Adenoid Cystic↗
Immunohistochemical and electron-microscopic identification of neuroendocrine cells in the stomach of uremic rats.
Many disturbances in electrolyte and hormonal balance in the body induced by functional impairment of renal parenchyma may affect the activity of amine precursor uptake and decarboxylation (APUD) cells, which constitute a very important link in the regulation of homeostasis. The aim of the present study was the morphological, immunohistochemical and ultrastructural estimation of enteroendocrine cells in the stomach of uremic rats. Fragments of gastric pylorus were collected 1, 2 and 4 weeks after nephrectomy. Paraffin embedded sections were stained with H + E and by silver impregnation. For identification of neuroendocrine cells, immunohistochemical reactions were performed using specific antibodies against somatostatin, synaptophysin, neuron-specific enolase and anti-calcitonin gene related peptide. The analysis showed an increased number of APUD cells in the stomach of uremic rats compared to control rats, which may be a morphological expression of their hyperfunction in the functional impairment of renal parenchyma. These results suggest that chronic renal failure can modulate the secretory processes of APUD cells.
APUD Cells↗
Ultrastructure and fluorescence histochemistry of endocrine (APUD-type) cells in tracheal mucosa of human and various animal species.
This study describes distrinctive cells with ultrastructural and histochemical features of APUD-type endocrine cells within the tracheal epithelium of human fetuses, newborns and children as well as different animal species. These cells referred to as Kultschitzky cells (K cells) were found to be argyrophilic, but not argentaffin, and are considered analogous to the same type of cells in lung and gastro-intestinal tract. Fluorescence histochemistry demonstrated the presence of intracellular amine within tracheal K cells, but only after in-vitro or in-vivo administration of amine precursor (L-DOPA). Ultrastructurally, these cells are characterized by the presence of numerous cytoplasmic granules (dense core vesicles) which show species related morphologic variations. Two different types of K cells were found in trachea of lamb and armadillo, each type possessing morphologically different dense core vesicles. In human and rabbit tracheas, only one type of K cell was identified. K cells in the trachea are distributed as single cells between other epithelial cells; neuroepithelial bodies such as those found in bronchial mucosa were not identified. Well differentiated K cells were found in tracheas of early human fetuses and throughout gestation, infancy, and childhood. Preservation of K cells in human autopsy material and widespread occurence of these cells in various laboratory animals will permit further studies into the nature and function of tracheobronchial endocrine cells.
Animals↗
[Potentials and limits for the histologic diagnosis of apudomas].
One should differentiate apudomas, two-component tumors (a combination of apudoma with a non-endocrine tumor), apudoma-like tumors and non-endocrine ones with admixture of APUD cells among the tumors with cells possessing the properties of APUD cells. Apudomas in their turn are represented by microapudomas and high- and low-differentiated macroapudomas. Routine light microscopy in most cases provides for apudoma verification, estimation of its differentiation and tissue origin, occasional identification of a secreted hormone.
Amyloid↗
Endocrine-paracrine (APUD, neuroendocrine) cells in the normal and pathologic prostate.
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APUD Cells↗
Proliferation of endocrine (APUD-type) cells during early N-diethylnitrosamine-induced lung carcinogenesis in hamsters.
Pronounced proliferation of amine precursor uptake and decarboxylase activity (APUD-type) cells was found in the segmental bronchi and bronchioles of Syrian golden hamsters during N-diethylnitrosamine (DEN)-induced lung carcinogenesis. Since similar epithelial alterations did not occur in previous experiments after benzo(a)pyrene (B(a)P) treatment, it is concluded that the initial stages of lung carcinogenesis differ with respect to the carcinogen administered.
Animals↗
APUD-like cells in the primitive gut of a 27 day old human embryo.
A 27 +/- 1 days old human embryo arising from an ectopic pregnancy was incubated with 3,4, L-dihydroxyphenylalanine (L-DOPA) to investigate whether cells of the gut primordium have at this early stage of development, the ability to take up the amine precursors. We could observe that a few cells exhibiting greenish fluorescence were located in the epithelium wall of the fore gut. Most of them were situated in contact with the basal lamina and possessed a long apical process extending over towards the gut lumen. The uptake of amine precursor, the morphology and the location of these cells strongly suggest that they represent the gut endocrine precursor cells of the human embryo.
APUD Cells↗
Neurone specific enolase: an aid to the diagnosis of melanoma and neuroblastoma.
Melanoma and neuroblastoma are diagnosed by their clinical and histological features, including evidence of melanogenesis and neural differentiation respectively, by tumour cells. These criteria are occasionally inadequate. Melanoma and neuroblastoma are derived from a system of cells characterized by the content, precursor uptake and decarboxylation of particular amines (APUD cells). Neurone specific enolase (NSE) has been proposed as a specific marker for neural elements and APUD cells. Immunohistochemical cytoplasmic and fibrillary localization of this enzyme was demonstrated in formalin-fixed, paraffin-processed sections of melanoma and neuroblastoma, constituting and additional aid to the identification of these tumours. The demonstration of an enzyme of the glycolytic pathway within tumour cells has implications following the effects of anti-tumour agents and these are discussed.
APUD Cells↗
[Endocrine function of apudocytes in immunocompetent organs during different forms of immune response].
Histochemical methods devised by Masson, Sevka and Dominichi and immunohistochemical methods were used to establish that immunization markedly changes both qualitative and quantitative characteristics of the hormonal production of APUD cells in immune organs. The differences in the function of the APUD-system of immunocompetent organs were recorded on the primary and secondary immune responses as well as during sensitization in the development of the immediate type hypersensitivity. The most intense changes occurring in different forms of immune response were noticed at the level of serotonin- and catecholamine-containing APUD cells of the immune system.
APUD Cells↗
Ovarian carcinoid composed of argyrophil and argentaffin cells.
A rare case of ovarian carcinoid tumor composed of both argyrophil and argentaffin cells is reported. The tumor cells were arranged in solid-trabecular or glandular fashion. Electron microscopically, each of the argyrophil and argentaffin tumor cells had intracytoplasmic neurosecretory granules possessing their own characteristics. Immunoflourescent and immunohistological procedures failed to demonstrate thyroglobulin, calcitonin, and CEA in the tumor. No structures suggestive of a struma ovarii were identifiable. Scattered in the tumor were mucinous cysts with APUD cells lying between the lining epithelial cells. These APUD cells are thought to be the origin of this pure ovarian carcinoid tumor.
Adult↗
A light and electron microscopic study of an ovarian and rectal carcinoid.
An ovarian and rectal carcinoid within the same person is described. The ovarian carcinoid is non-argentaffinic with typical regular granules. The rectal tumour consists of two types of APUD cells, some argentaffinic and diazo-positive, whilst others are non-argyrophilic. These features are mirrored ultrastructurally, some cells containing the large pleomorphic argentaffinic granules while others have smaller regular granules. In addition, focal aggregates of microfilaments were found in both tumour types. These findings are discussed in terms of the APUD concept. The similarities of the APUD tumour cells to D1 APUD cells of the duodenum is highlighted, and an alternative explanation for their derivation is proposed.
APUD Cells↗
Identification of carcinoembryonic antigen in the C-cell of the normal thyroid.
Carcinoembryonic antigen (CEA) activity was confirmed in the C-cell of the normal thyroid by immunohistochemical techniques. This suggests that CEA production in medullary carcinoma of the thyroid is not initiated by carcinogenesis, but reflects a function of the normal C-cell. It is not yet clear whether CEA production in the C-cell may be influenced by carcinogenesis. The C-cell is the first APUD cell that was confirmed to have CEA activity.
APUD Cells↗