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PubMed1994

Raphé neural cells immortalized with a temperature-sensitive oncogene: differentiation under basal conditions down an APUD cell lineage.

Dividing cells from the midline of the ventral rhombencephalon and medulla oblongata have been transduced with a modulatable oncogene, (ts)SV40-T, using retroviral gene transfer. At the permissive temperature of the oncogene (33 degrees C), cells replicated and were isolated as individual, homogeneous clones. The effects of simply raising the temperature to the oncogene's non-permissive value, namely 39 degrees C, were analyzed by immunohistochemical methods. In one clone in particular (921202-6), cells ceased replication and started to differentiate. Certain neuronal characteristics became apparent: neurone-specific enolase-like immunoreactivity developed, as did the ability to take up exogenously applied 5-hydroxytryptamine (5HT). In addition, the cells took up exogenous 5-hydroxytryptophan (5HTP), and subsequently decarboxylated it to 5HT. However, they were unable to synthesize immunohistochemically detectable amounts of 5HT using L-tryptophan as a precursor. No 5HT uptake was found either in mitotic cells of this clone held at 33 degrees C, or in several other neuronal clones differentiating at 39 degrees C. Neither the neuronal nor the serotoninergic characteristics of clone 921202-6 developed in the presence of retinoic acid. It is concluded that 921202-6 cells differentiate under basal conditions down a neuronal pathway typical of an APUD cell, and that the choice of this pathway is made prior to the end of cell cycling. Furthermore, predisposition of the precursor cells to the neuronal/APUD phenotype can be overridden by extraneous epigenetic factors.

5-Hydroxytryptophan↗
PubMed1977

APUD cells and the apudomas. A concept relevant to anaesthesia and endocrinology.

A variety of cells found in the pituitary and pineal glands, sympathetic nervous system and adrenal glands, the gut, pancreas, thyroid (C-cells), chemoreceptors (type I-Cells), lungs (P-cells), skin (melanocytes) and the urogenital tract have a common origin from the neural crest. These cells are programmed for neuro-endocrine function and, as a group, can be regarded as one of the physiological control systems. They secrete a variety of amine and peptide hormones and have common cytochemical characteristics from which the term APUD cell is derived. Tumours of these cells are referred to as 'apudomas' and may synthesise not only their own hormones but also those which are normally produced by other APUD cells. The relevant physiological properties of some of the peptides which have been described relatively recently are discussed and the principal clinical syndromes produced by the APUDomas are described.

APUD Cells↗
PubMed1980

APUD cells and neuroepithelial bodies in hamster lung: methods, quantitation, and response to injury.

A comparative study of the Falck-Hillarp Technique, a modification of Eaton-Fedde procedure and silver staining of aldehyde-fixed tissue was carried out to determine the most efficient procedure to demonstrate neuroendocrine cells of the hamster and rat lung. The modified Eaton-Fedde procedure is the most efficient method of observing these cells, and is also the easiest to perform. With this method, the normal hamster lung contains a total of 2.00 x 10(-1) to 3.00 x 10(-1) neuroendocrine cells/mm in the small and large bronchioles. In the larger airways approximately 3.51 x 10(-1) neuroepithelial bodies (NEB)/mm are observed. Immediately after 24-hour exposure to NO2 the number of APUD cells dropped to approximately 25% of the control levels. These cells were decreased to 50% of the control levels throughout the 28 days of exposure. The number of NEB decreased transiently after 24 hours of NO2 but returned to normal numbers by day 14. We recommend the application of fluorescence techniques coupled with standardised sections and quantitative methods of study for analysis of APUD cells and NEB.

APUD Cells↗
PubMed1980

The apud cells.

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APUD Cells↗
PubMed2000

Identification, localization and morphology of APUD cells in gastroenteropancreatic system of stomach-containing teleosts.

AIM:To identify the type localization and morphology of APUD endocrine cells in the gastroenteropancreatic (GEP) system of stomach-containing teleosts, and study APUD endocrine system in the stomach, intestine and pancreas of fish species.METHODS:Two kinds of immunocytochemical (ICC) techniques of the streptavidin biotin-peroxidase complex (SABC) and streptavidin-peroxidase (S-P) method were used. The identification, localization and morphology of APUD endocrine cells scattered in the mucosa of digestive tract, intermuscular nerve plexus and glandular body of northern snakehead (Channa argus), ricefield eel (Monopterus albus), yellow catfish (Pelteobagrus fulvidraco), mandarinfish (Siniperca chuatsi), largemouth bass (Micropterus salmoides),oriental sheatfish (Silurus asotus), freshwater pomfret (Colossoma brachypomum) and nile tilapia (Tilapia nilotica) were investigated with 8 kinds of antisera.RESULTS:The positive reaction of 5-hydroxytryptamine (5-HT) immunoreactive endocrine (IRE) cells was found in the digestive tract and glandular body of 8 fish species in different degree.Only a few gastrin (GAS)-IRE cells were seen in C.argus,M.albusand P.fulvidraco. Glucagon (GLU)IRE cells were not found in the digestive tract and glandular body but existed in pancreatic island of most fish species. The positive reaction of growth hormone (GH)IRE cells was found only in pancreatic island of S. Chuatsi and S. Asotus, no positive reaction in the other 6 fish species. Somatostatin (SOM), calcitonin (CAL), neurofilament (NF) and insulin (INS)-IRE cells in the stomach, intestine and pancreas of 8 kinds of fish were different in distribution and types. The distribution of all 8 APUD cells was the most in gastrointestinal epithelium mucosa and then in digestive glands. The positive reaction of SOM and 5-HT-IRE cells was found in intermuscular nerve plexus of intestine of P.fulvidraco and S.chuatsi. Only GH-IRE cells were densely scattered in the pancreatic islands of S.chuatsi and S. asotus, and odd distribution in the pancreas of S. asotus.SOM-IRE cells were distributed in the pancreatic islands of S. asotus, C. Brachypomumand T. nilotica. There were INS-IRE cells in the pancreatic islands of S. chuatsi and S. asolus. Eight kinds of APUD cells had longer cell body and cytoplasmic process when they were located in the gastrointestinal epithelium, and had shorter cell body and cytoplasmic process in the gastric gland, and irregular shape in the esophagus and pancreatic island.CONCLUSION:Eight kinds of IRE cells were identified in the GEP system of stomach-containing teleosts. These endocrine cells were scattered in gastrointestinal mucosa, intermuscular nerve plexus, gland body, pancreatic gland and islands under APUD system. CAL and GH-IRE cells in the pancreatic islands of fishes showed functional diversity for these two hormones. Their morphological feature provides evidence of endocrine-paracrine and endocrine-exocrine acting mode. This research can morphologically prove that the GEP endocrine system of fish (the lowest vertebrate) is almost the same as of mammal and human.

Journal Article↗
PubMed1971

Neural crest origin of the endocrine polypeptide (APUD) cells of the gastrointestinal tract and pancreas.

A method of labelling known to be appropriate for the demonstration of endocrine polypeptide (APUD) cells was found to label the cells of the neural crest in the chick embryo after as little as 72 hours' development. The method depends on the production, from an exogenous precursor, of an amine which is stored in specific granules and which is convertible by treatment with hot formaldehyde vapour into a fluorescent derivative. The whole technique is described as APUD-FIF. The application of APUD-FIF to mouse embryos shows that at the 7-8 somite stage (eight days) labelled neural crest cells migrate in large masses in a ventrad direction. At around the ninth day they colonize the developing foregut and its derivatives, including pharynx, stomach, duodenum, ultimobranchial body, and pancreas. In subsequent stages of development (up to 12 days) the cells are seen in comparatively large numbers in the gastrointestinal tract and in the pancreas. Complete proof that these early APUD cells, which demonstrably arise from the neural crest, are the precursors of all the endocrine polypeptide cells of the adult pancreas, stomach, duodenum, and small and large intestine, is not at present available. Notwithstanding a great deal of earlier evidence to the contrary, the premise seems likely to be true.

Amines↗
PubMed1979

[2 cases of Apud cell tumors of the rectum and colon].

Two cases of Apud cell tumour of the rectosigmoid are presented. The question of gross diagnosis and the therapeutic efficacy of polypectomy are discussed. Lastly, an account is given of the morphological, functional and embryogenetic features of these tumours.

Apudoma↗
PubMed1985

Small-granule APUD cells in relation to airway branching and growth: a quantitative, cartographic study in Syrian golden hamsters.

Small-granule APUD cell clusters and their clear-cell precursors were mapped in serial 2-micron glycol methacrylate-embedded, periodic acid-Schiff (PAS)-lead hematoxylin-stained sections of 13-, 14-, and 15-day fetal hamster lungs. Every sixth section was drawn from a camera lucida projection on tracing paper. Each tracing included the profiles of nonalveolated air passages and the locations of small-granule cell clusters and solitary clear cells. Airways containing ciliated cells and those surrounded by condensed mesoderm were also labeled. Single clear cells were rare in fetal hamster lung. Of 2,368 endocrine cell loci identified in the three fetal age groups examined, only 14 were single clear cells. A preliminary survey of the entire left and right lungs showed that the pattern of airway and small-granule cell development in the infracardiac lobe was similar to that occurring in the remainder of the lung; this lobe was accordingly considered a model for the whole lung, and the ontogeny of its small-granule cell population was quantitated and compared with results of similar quantitative mapping of this lobe in an adult animal (Hoyt et al., 1982a,b). Along the lobar bronchus of the 13-day infracardiac lobe and proximal portions of its main branches, small-granule cell clusters occurred most often near airway intersections. As the number and density increased in subsequent fetal stages, small-granule cell clusters became conspicuous along internodal bronchial segments. In distributing bronchioles, the population density of small-granule cell clusters decreased between 13 and 14 days but more than doubled by day 15. Unlike human lungs, where centrifugally developing small-granule cell clusters are firmly established in terminal bronchioles well before birth, most peripheral bronchioles in fetal hamster were devoid of small-granule cell clusters, even at 15 days, one day before birth. Comparison of numerical population densities in this lobe of fetal and adult lungs indicates that small-granule cell clusters continue to form past day 15 and suggests that they are considerably more numerous in adult than fetal lung.

APUD Cells↗
PubMed1978

Primary malignant melanoma of the small intestine and the APUD cell concept.

A primary melanoma of the small intestine is reported. A possible explanation of its origin according to the APUD cell concept is suggested. This concept may lessen the doubts and confusion whenever an intestinal melanoma is discovered and a primary tumor at one of the more common sites can reasonably be excluded.

APUD Cells↗
PubMed1981

[APUD cells and apudomas].

Synthesis of biologically active amines and peptides, and accumulation of them in the cytoplasm in the form of secretory granules of "neuroendocrine" type are among the most important characteristics of APUD cells. Apudomas, tumors consisting of cells with the properties of APUD elements, have many common morphological and functional features, although they are quite heterogeneous by clinical behavior and histogenesis. Histological diagnosis of apudomas requires the assessment of the endocrine function of the tumor cells for which histochemical and electron microscopic methods must be employed, as well as consideration of the clinical and biochemical indices of the hormonal activity of the tumors.

APUD Cells↗
PubMed1987

Endocrine-paracrine (APUD) cells of the human female urethra and paraurethral ducts.

The distribution, immunostaining profile and ultrastructural morphology of human female urethral and paraurethral endocrine-paracrine (APUD) cells was studied. Five urethras obtained from radical cystectomy specimens were stained with antisera to serotonin, neuron-specific enolase, chromogranin, bombesin, calcitonin, somatostatin, prostatic acid phosphatase, prostatic specific antigen and with the Churukian-Schenk argyrophil method. Numerous endocrine-paracrine cells were observed along the entire length of resected urethra, with these cells most numerous in the paraurethral ducts. The endocrine-paracrine cells were positive for serotonin, neuron-specific enolase, chromogranin and the argyrophil reaction. Scattered bombesin and very rare calcitonin immunoreactive cells were noted. The endocrine-paracrine cells were of the open (luminal extensions) and closed cell types and often had multiple long dendritic processes suggesting a primarily paracrine function. By electron microscopy the secretory granule morphology was highly variable. Autonomic innervation of endocrine-paracrine cells was noted. The relationship of female urethral and paraurethral endocrine-paracrine cells to those of the male prostate and urethra is discussed with speculation as to the functional role these cells may play.

APUD Cells↗
PubMed1976

Pancreatic APUD cells in older chick embryos, with special reference to their identity.

Pancreatic APUD cells showing formaldehyde-induced fluorescence in Black Australorp chick embryos of nine to eighteen days of incubation, proved, on subsequent staining and silver impregnation, to be A, B, D and, from sixteen days, enterochromaffin (EC) cells. EC and D cells were scattered in the exocrine parenchyma, the latter cells increasing with time. Some group of B cells were associated with large A islets from the ninth day of incubation onwards. The composition of A islets (A and some D cells) and B islets (B and some D cells) and the distribution attained (A islets in the splenic and third lobes; B islets in all lobes), accords with the situation reported for adults.

Age Factors↗
PubMed1978

Enteroendocrine APUD cells in the digestive tract of larval Barbus conchonius (Teleostei, Cyprinidae).

The development of Barbus conchonius is described with special attention to the differentiation of the gut. Amine precursor uptake and decarboxylation (APUD) are present in enteroendocrine cells during development, whereas these processes are lacking in adult specimens. The first APUD cells originate on the fourth day of development in the anterior part of the gut and on the fifth day in the caudal areas. The APUD facility of the cells disappears within 2 days, and after the 6th day APUD cells can no longer be distinguished in the intestinal epithelium. The first APUD cells were obsserved when four types of enteroendocrine cells were recognized with the electron microscope. These enteroendocrine cells contain granules of different electron densities, and microtubules and cilia can be observed. Some enteroendocrine-like cells are found below the basement membrane of the intestinal epithelium, indicating a possible extra-endodermal origin. APUD cells, except melanoblasts, have not been found migrating from the neural crest in ventral direction. The origin of the enteroendocrine cells of B. conchonius is discussed.

APUD Cells↗