[The functional cytochemistry of amine precursor uptake and decarboxylation (APUD) cells and its uses in pathology].
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Amines↗
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[Apud-cell tumors (carcinoids)--immunohistochemical and pathomorphologic results].
47 carcinoid tumours originating from different sites were classified on a histological basis and immunohistochemically investigated by means of a modified PAP method using 10 different antisera. The biological behaviour and the extent of anaplasia were correlated. The results were compared with those described in the literature. 19 carcinoids showed a positive immune reaction with the antisera used. 5 hormone-producing tumours were poorly differentiated and in 9 cases metastases were recognized. More than one peptide hormone was detected in 7 carcinoids, 3 of which were malignant. Metastases or invasion of lymph and blood vessels were observed in 9 cases although the tumour cells showed no greater degree of cellular atypia. A good correlation between biological behaviour and cytological features was obtained in only 5 atypical carcinoids. Carcinoid tumours represent a group with complex biological, histological and immunohistochemical properties. The secreted peptide hormones might be of importance as tumour markers in some cases.
Carcinoid Tumor↗
[Comparative analysis of monoamine producers in the major duodenal papilla and lungs of rabbits].
By means of incubation of slices in 2% solution of glyoxylic, acid adrenergic nervous structures and endocrine cells (APUD cells) have been studied in the ampule wall of the duodenal large papilla and in the lungs in 6 mature male rabbits. Topographic proximity of APUD cells and adrenergic nervous fibers is noted. Contents of serotonin and catecholamines in the structures mentioned have been investigated microfluorometrically. Simultaneous revealing of producers of monoamines make possible to suppose that serotonin and catecholamines get paracrinically from the APUD cells into terminals of the adrenergic nervous fibers.
APUD Cells↗
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 electron microscopic radioautographic identification of the APUD endocrine cells in the rat gastric pyloric glands.
The rat stomach was shown some years ago to contain numerous endocrine cells with APUD ability--cells that could take up the amino acids L-5-hydroxytryptophan (5-HTP) or L-dihydroxyphenylalanine (L-DOPA) and could decarboxylate them to their respective amines, 5-hydroxytryptamine (5-HT, serotonin) and dopamine, by means of the enzyme DOPA-decarboxylase. In a recent study, most of the APUD endocrine cells in the rat oxyntic mucosa were shown by electron microscopic radioautography to be the enterochromaffinlike cells, while the A-like cells were shown to lack APUD ability. To identify the APUD cells in the pyloric mucosa, pieces of rat pylorus were incubated in organ culture with 3H-5-HTP and were processed for light microscopic and electron microscopic radioautography. Additional specimens were incubated with 3H-5-HTP and carbidopa, an inhibitor of DOPA-decarboxylase, used to block the decarboxylation of 3H-5-HTP to 3H-5-HT, or with 3H-5-HT, used to determine where exogenous 3H-5-HT localizes in the pyloric mucosa. The 3H-5-HTP labeled all three types of endocrine cells identified within the pyloric glands--the G, enterochromaffin, and D cells. As this labeling was inhibited by carbidopa, and as exogenous 3H-5-HT labeled these cells only lightly, the labeling must have resulted from the uptake and intracellular conversion of the 3H-5-HTP of 3H-5-HT. Thus despite their morphologic differences, all rat pyloric endocrine cells possess APUD ability, a property shared by many, but not all, of the peptide- and amine-producing endocrine cells located throughout the body.
5-Hydroxytryptophan↗
[Content of endocrine cells of the APUD-system of the lungs in cancer of that organ].
Pulmonary tissue samples were obtained from 17 patients operated on for cancer of the lungs. The samples were subjected to Grimelius argyrophil reaction to detect apud cells. These occurred in clusters and solitary cells in lung tissue adjacent to that involved with cancer. Numerous apud cells were found in 4 out of 12 patients with squamous cell carcinoma and in 1 out of 5 patients with adenocarcinoma. Apud cell hyperplasia occurred more frequently in large tumors with metastases to the lymph nodes of the root of the lung.
APUD Cells↗
Characterization of opioid peptides in guinea-pig heart and skin.
Using reverse phase HPLC separations, and assay of eluate fractions in the mouse vas deferens, extracts of heart and skin from guinea-pigs were shown to contain several species of opioid-active material in low amounts (3-20 pmol/g as [Met5]enkephalin). Immunohistochemical studies revealed in the heart a small number of enkephalin-immunoreactive nerve fibres, particularly in cardiac ganglia and some small cells (paraganglionic cells, APUD cells). In the skin, enkephalin-immunoreactivity was confined to Merkel cells. Cardiac and cutaneous opioid peptides may modulate peripheral cardiovascular and sensory functions.
Animals↗
[Immunomorphological methods for identifying cells of the APUD system of the digestive organs].
Possibilities of application of immunomorphologic methods to gastrointestinal apud cells study were evaluated. These are: immunofluorescent, immunoenzyme, immune-peroxidase, peroxidase-antiperoxidase, avidinbiotin. Causes of immunologic and non-immunologic non-specific background staining and the means of its elimination are discussed, as well as problems of fixation and embedding of the material.
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↗
[Morphofunctional state of the APUD-system cells of the lungs in hyaline membrane disease of newborn infants].
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.
APUD Cells↗
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↗
Crypt cell carcinoma of the appendix (so-called adenocarcinoid tumor).
A series of 16 carcinoid tumors of the appendix, including four examples of so-called adenocarcinoid tumors, has been studied immunohistochemically for the presence of lysozyme, secretory component (SC) and IgA, within tumor cells. Stains for mucin, Paneth cells, and APUD cells were also performed. Of the conventional carcinoid tumors, eight showed focal tubule formation with production of PAS-positive material. In contrast to conventional carcinoids, including those showing tubule formation, adenocarcinoids contained few APUD cells and showed positive staining of tumor cells for lysozyme, SC, and IgA. Paneth cells, staining positively for lysozyme, were present in two cases and mucin-containing Paneth cells were observed. A parallel study of normal small intestinal mucosa demonstrated a population of lysozyme containing goblet cells within the crypts. It is suggested that so-called adenocarcinoid tumors are not derived from APUD cells but from lysozyme-producing cells of the type normally present in small intestinal crypts.
Adenocarcinoma↗
[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↗
Ultrastructure of the APUD-like cells of the frog thymus gland.
Within the thymus gland of the European common frog, Rana temporaria, cells with endocrine- like appearance have been found. At the ultrastructural level the most characteristic feature of their cytoplasm is the presence of secretory granules. Some cells possess irregular electron lucent granules with an eccentrically located dense core while others possess smaller electron dense granules. The cytoplasm contains also cisterns of rough endoplasmic reticulum, free ribosomes, and small mitochondria. The cells possess irregular nuclei with the pronounced nucleoli. These endocrine-like cells are connected by desmosomes with neighbouring non-granulated epithelial cells. Ultrastructural features of the cells described here resemble those seen in polypeptide hormone-secreting cells belonging to the family of cells of the APUD (Amine Precursor Uptake and Decarboxylation) series.
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↗
Identification of the APUD endocrine cells of rat fundic mucosa by means of combined amine fluorescence and electron microscopy.
Rat fundic mucosa contains numerous APUD endocrine cells that can take up 5-hydroxytryptophan (5-HTP) and decarboxylate it to 5-hydroxytryptamine (serotonin), detectable by its formaldehyde-induced yellow fluorescence. To identify these cells by electron microscopy, pieces of rat gastric mucosa were incubated with DL-5-HTP. Some specimens were fixed in 4% formaldehyde-0.5% glutaraldehyde, while others were frozen, freeze-dried, and exposed to paraformaldehyde vapors. Thick sections of the Epon-embedded specimens were examined and photographed by fluorescence microscopy, and fluorescing and nonfluorescing cells were identified by electron microscopy in serial thin sections. Control specimens, not incubated with 5-HTP, revealed fluorescence of only the mast cells and EC cells, which were abundant in the pylorus, but rare in fundic mucosa. Specimens incubated with 5-HTP also exhibited numerous yellow fluorescent endocrine cells in fundic mucosa, which cells were found to be the ECL cells; the A-like cells did not fluoresce. In pyloric mucosa, many G and D (D1) cells also exhibited weak or moderate fluorescence after 5-HTP incubation. Thus, this study supports the contention of previous radioautographic studies that the ECL, but not the A-like, cells are the APUD endocrine cells of rat fundic mucosa, that G and D cells also possess some APUD activity, and that EC cells represent the enterochromaffin cells, which normally synthesize and store demonstrable quantities of serotonin.
5-Hydroxytryptophan↗
Occurrence of APUD-type cells in the ciliated cyst of the parathyroid gland of ozone-exposed dogs.
Presence of APUD-type cells in the ciliated cysts of the parathyroid glands of ozonized dog is described in this report. These cells were present on the abluminal side of the cyst wall and contained secretory granules with dense core, homogeneous matrix and coated vesicles throughout the cytoplasm. Intermixed with the granules were sheaves of microfilaments which were mostly seen in the perinuclear area. The APUD cells formed hemidesmosomes with the basal lamina.
APUD Cells↗