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Quantitative characteristics of the Feyrter (APUD) cells of the neonatal rabbit lung in normoxia and chronic hypoxia.

Our studies show that the apparent number of Feyrter cells in the lung declines during the neonatal period in normoxic rabbits, and that in hypoxic animals a uniformly and significantly lower number of cells occurs as compared with the normoxic rabbits. There is some indication of degranulation of cells in the hypoxic groups. It is suggested that environmental and/or physiological factors associated with the start of extrauterine life, or lung development, may affect the apparent number and probable level of activity of these cells. These changes seem to be enhanced by hypoxia. Mast cells are scarce, and Feyrter cells are relatively more numerous along the airways. These cell types could possibly represent storage sites for 5-hydroxytryptamine, as suggested also by other investigators. Intraepithelial nerve fibres in bronchi and bronchioles were found but they were not limited to innervations of Feyrter cells or related cell bodies.

APUD Cells

[The APUD cells].

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Catecholamines

Quantitative characteristics of the Feyrter cells and neuroepithelial bodies of the fetal rabbit lung in normoxia and short term chronic hypoxia.

We report here quantitative data on the Feyrter (single) cells (APUD cells) and neuroepithelial bodies (grouped Feyrter cells), in the lungs of rabbit fetuses at 26, 27.5 and 29 days gestational age, during normoxia and short term chronic hypoxia. The apparent number of these cells declines during this period; we suggest that this might be due to increased hypoxemia. Moreover, the number of cells in the lungs of fetuses from short term chronically hypoxic mothers is lower than in the normoxic animals. These findings are in agreement with our previous studies in short term chronically hypoxic neonatal rabbits, and suggest that the increased hypoxemia in the fetus, caused by the induction of hypoxia in the mother, constitutes a stimulus for secretory activity of the Feyrter cells and neuroepithelial bodies (NEBs). This in turn could be part of the mechanism responsible for maintaining the pulmonary vasoconstriction due to hypoxemia. Our results from fetuses of normoxic does provide base line data on the chronological importance of the Feyrter cells and NEBs.

APUD Cells

An experimental investigation into the possible neural crest origin of pancreatic APUD (islet) cells.

It has recently been contended that pancreatic APUD cells are neural crest derivatives. In an experimental investigation, isotopic grafts of neural tube containing neural crest cells were transplanted from chick and quail embryos labelled with tritiated thymidine, and from unlabelled quail embryos, to host chick embryos at the same stage of development. Transplantations were performed at various levels between somites 5 and 24 in embryos at 6- to 24-somite stages. In operated embryos at 3 3/4 days of incubation, the pancreatic APUD cells were not labelled; nor did their nuclei show quail features. Migration of cells from the graft was evidenced by the presence of quail nuclei and/or radioactive label in autoradiographs, in spinal and sympathetic ganglia in the operated region. It is concluded that the pancreatic APUD cells of the 3 3/4-day-old chick embryo are not derived from the trunk neural crest up the level of somite 24. It is unlikely that more caudal levels contribute, because APUD cells are already concentrated in the dorsal pancreatic bud region at the 24-somite stage, by which time no migration of crest cells has occurred caudal to somite 24. This conclusion probably concerns A, B and D pancreatic endocrine cells.

Animals

Dissociation of epithelial cells from rabbit trachea and small intestine with demonstration of APUD endocrine cells.

In this study the entire epithelial lining of tracheas and a 15-cm segments of small intestine were dissociated into individual cell components after 45-minute incubation with 1% pronase. Light and electron microscopy of isolated cells confirmed good morphologic preservation of various epithelial cell types dissociated from the trachea and small intestinal mucosa. Of particular interest was the recovery and preservation of APUD endocrine cells, which are known to be widely dispersed amongst various non-endocrine epithelial cells in both the trachea and small intestine. The APUD cells were demonstrated in dissociated cell preparations by a formaldehyde-induced fluorescence method, Grimelius' silver nitrate stain, and electron microscopy. The isolated APUD cells retained their characteristic features, e.g., amine-handling properties, argyrophilia and cytoplasmic dense-core vesicles. The cell dissociation method described in this report provides high yields of viable epithelial cells in single cell suspensions which are suitable for further cell separation into homogeneous populations of single kinds of cells, including the APUD endocrine cells. Availability of methods for isolation of tracheal and intestinal APUD cells will facilitate further studies, in vitro, on secretory, metabolic and functional aspects of these cells.

Amines

[Distribution of the enterochromaffin ("EC") cells and those of the "APUD" series in the gastrointestinal tract of ruminants].

The research was carried out on the vorestomachs, abomasum and on the various tracts of gut of adult Cattle, Sheep and Goat, because Ruminants, not previously studied with respect to this problem, have, as is well known, particular morpho-functional characteristics of the digestive system. The results can be synthetized as follows: 1) either "EC" (5-HT-producing) or "APUD" cells (peptide hormones-producing) are not demonstrable in the vorestomachs. 2) "EC" cells are present in the various areas of abomasum (particularly numerous in the fundus glands) and in the different tracts of the gut (predominantly in the duodenum and in the rectum). 3) In the "APUD" cells of the abomasum gastrin-producing "G" cells are certainly demonstrable. They are present only in the pyloric glands, where they prevail in the middle third. Only in the cattle, cells which have all the histochemical characteristics of "G" cells, but are quite morphologically different, are also present in the same area. An interesting peculiarity seems to be the reduced number of "APUD" cells, compared with that of Monogastrics: it was impossible, in fact, to demonstrate some cells ("A", "A-like","X", "D", "D1", "ECL") which are described by other Authors in the stomach of various Mammals. 4) In the small intestine, endocrine cells, probably heterogenous are present, resulting more numerous in the duodenum. 5) In the coecum, colon and rectum, cells comparable to enteroglucagon-producing "EG" cells, are present; they are particularly numerous in the rectum, where cells similar to "H" cells are also present.

Abomasum

Small cell carcinoma of the lung: cellular origin and relationship to other neoplasms.

Many small cell carcinomas share morphological and physiological characteristics with normal and neoplastic cells of Pearse's APUD series, including pulmonary APUD cells and pulmonary carcinoid tumors. There is very likely more than one type of APUD cell in the lung, and conclusions that small cell carcinomas and carcinoids reflect neoplastic transformation of the same cell type are probably premature. The embryoogic lineage of pulmonary APUD cells is at present uncertain. The hypothesis that all APUD cells are derived from the neural crest is no longer tenable, and although some evidence does suggest a neural contribution to the pulmonary epithelium, additional embryologic studies are required. Some tumors that currently are classified as small cell carcinomas probably do not have APUD cell characteristics, and still others appear to have both APUD and non-APUD features. A subclassification of small cell carcinomas based on a combination of physiological and morphological features might prove to be of prognostic and therapeutic value, but current knowledge probably would not provide a sufficient foundation for a reliable or practical subclassification. Multidisciplinary studies of the differentiation and function of normal and neoplastic APUD cells in the lungs and elsewhere are needed.

APUD Cells

Sequential morphologic alterations in the bronchial epithelium of Syrian golden hamsters during N-nitrosomorpholine-induced pulmonary tumorigenesis.

N-nitrosomorpholine (NM)-induced pulmonary carcinogenesis was examined by light and electron microscopy in a 20-week serial sacrifice study using Syrian golden hamsters. First to be observed were a proliferation of endocrine APUD cells and a formation of lamellated inclusion bodies in the cytoplasm of Clara cells. After continued NM treatment, APUD cells underwent squamous metaplasia and Clara cells invaded the pulmonary tissues adjacent to the bronchi. Lung tumors consisted of cells possessing numerous lamellated inclusion bodies in their cytoplasm and a few squamous metaplastic and APUD cells. The observed pathologic alterations closely resembled those found after treatment with N-diethylnitrosamine (DEN) and N-dibutylnitrosamine (DBN) but were completely different from the cellular reactions induced by polycyclic aromatic hydrocarbons. It is concluded that the observed alterations of APUD cells and Clara cells are specific to nitrosamines.

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

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