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Ontogeny of small-granule APUD cells in hamster lung: a morphological study.

Development of small-granule APUD cells and cell clusters was studied in 13-day to 15-day fetal hamster lungs by periodic acid-Schiff (PAS)-lead hematoxylin staining, monoamine fluorescence, and transmission electron microscopy. We examined 11-day and 12-day fetal, early postnatal, and adult animals only by PAS-lead hematoxylin. Precursors of small-granule cells first appear as PAS-negative clear cells in proximal airways of 13-day lung, occurring singly or in clusters of 2-25 cells and standing out among their undifferentiated, glycogen-laden, PAS-positive neighbors. By 14 days, developing small-granule cell clusters are prominent in main and lobar bronchi, extending 2-3 airway generations into the periphery. Clear-cell clusters, similar to those seen in 13-day lung, appear in peripheral airways and reach within one generation of developing terminal sacs. By 15 days, a few small, small-granule cell clusters are located at bronchioloalveolar junctions. Comparatively mature clusters occur in proximal airways; they are characterized by specific formaldehyde-induced monoamine fluorescence demonstrable after exposure in vitro to 5-hydroxytryptophan. In early postnatal stages, PAS-positive granules are resolvable toward the base of some endocrine cells. Ultrastructurally, pulmonary APUD cells contain numerous membrane-limited granules (180-nm diameter) of varying electron density. In 13-day lung, granules sparsely populate the cytoplasm of clear cells, but as the cells mature, the granule population increases and becomes concentrated in the basal cytoplasm. Fetal development of small-granule cells is therefore compressed into the last 4 days before birth. Most clusters appearing in neonatal lungs are not yet fully mature, and not all subtypes of this population are present until some time later.

APUD Cells↗

APUD cells in teratomas.

The origin of the endocrine cells in the respiratory tract and the gastrointestinal tract is still a matter of debate. In the original concept of the amine precursor uptake and decarboxylation (APUD) system, all APUD cells were considered to be derived from the neural crest. More recently it has been proposed that the APUD cell types of the gastrointestinal and respiratory tracts originate from neuroendocrine-programmed ectoblast. Still other investigators have reported observations that favor a direct endodermal origin of these cell types. Based on the assumption that in teratomas different tissue types which in normal embryogenesis are derived from the neuroectoderm might be expected to occur together, we investigated a series of cystic ovarian teratomas and testicular teratocarcinomas for the presence of brain tissue and of different types of APUD cells. In the ovarian teratomas, intestinal and respiratory APUD cell types were found almost exclusively without coexistence of brain tissue, whereas melanocytes, which are of neuroectodermal origin, occurred mostly together with brain tissue. In the testicular teratocarcinomas, intestinal types of APUD cells occurred without brain tissue. Peptide hormone production was found in appropriate tissues. It can therefore be concluded that in teratomas appropriate intestinal and respiratory APUD cells differentiate in and presumably descend directly from intestinal and respiratory epithelium.

APUD Cells↗

Nerve growth factor and pancreatic APUD cells.

Pancreatic endocrine cells have been considered APUD cells and been thought to be of neural crest origin. Neonatal rats were passively immunized with nerve growth factor antiserum and the development of neural crest derived superior cervical ganglia was markedly inhibited. The pancreatic content of glucagon, insulin, and somatostatin was unaffected, suggesting that pancreatic A,B, and D cells are under different developmental control than are cells of known neural crest origin.

APUD Cells↗

The Merkel cell system and a comparison between it and the neurosecretory or APUD cell system.

The Merkel cell, a neural crest migrant to the skin, possesses a characteristic intranuclear rodlet, cytoplasmic membrane-bound granules, and horn projections and is usually associated with nerve terminations. It is also associated with all types of known organizations of sensory nerve endings in the skin and possesses characteristic enzyme reactions in relation to the ending. The Merkel cell is found in the skin and the oral mucous membranes, and similar cells are observed in the taste buds and pulmonary tissue. A comparison between the Merkel cell and the APUD cell system of polypeptide hormone and amine-producing cells reveals many structural and chemical similarities.

Animals↗

[APUD cells in basal cell proliferative tissue of the prostate].

Basal cell hyperplasia involving intensive APUD cell proliferation should be distinguished among dyshormonal hyperplastic processes of the prostate. This form of hyperplasia can be considered a separate unit for its potential in the promotion of prostatic apudoma onset.

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Immunocytochemical identification and localization of APUD cells in the gut of seven stomachless teleost fishes.

AIM:To study the cell types, localization, distribution density and morphology of APUD cells in the intestinal mucosa of stomachless teleost fishes.METHOD:By using the peroxidase antiperoxidase complex (PAP) immunocytochemical staining technique the identification, localization and morphology of immunoreactive (IR) endocrine cells seattered in the intestinal mucosa of grass carp (Cyenopharyngodon idellus), black carp ( Mylopharyngodon piceus ) and common carp (Cyprinus carpio) were investigated with 20 kinds of antisera prepared against mammalian peptide hormones of APUD cells, and likewise by using avidin-biotin-peroxidase complex (ABC) method those of silver carp (Hypophthalmichthys molitrix), bighead (Aristichthys nobilis), silver crucian carp (Carassius gibelio) and bluntnose black bream (Megalobrama amblyocephala ) were also studied with 5 different antisera. The replacement of the first antiserum by phosphate buffered saline (PBS) was employed as a control. IR endocrine cells were counted with a square-mesh ocular micrometer from 10 fields selected randomly in every section of each part of the intestine specimen. The average number of IR endocrine cells per mm(2) was counted to quantify their distribution density.RESULT:Gastrin (GAS), Gastric inhibitory peptide (GIP), glucagon (GLU), glucagons like immunorea-ctants (GLI), bovine pancreatic polypeptide (BPP), leucine-enkephalin (ENK) and substance P (SP)-IR endocrine cells were found in the gut of grass carp, black carp and common carp, and somatostatin (SOM) IR endocrine cells were only seen in common carp. GAS, GIP and GLU-IR endocrine cells were found in the intestinal mucosa of silver carp, bighead, silver crucian carp and bluntnose black bream. Most of IR endocrine cells had the higher distribution density in the foregut and midgut, and were longer in shape. They had a long apical cytoplasmic process extended to the gut lumen and a basal process extended to adjacent cells or basement membrane and touched with it. Sometimes, the basal cytoplasmic process formed an enlarged synapse-like structure in the contiguous part with basement membrane. This phenomenon provided new morpho-logical evidence for neuroendocrine and paracrine secretory function of these enteroendocrine cells.CONCLUTION:At least 8 kinds of IR endocrine cells were found in the gut of stomachless teleost species for the first time in China. These IR endocrine cells scattering in the gut mucosa belong to the APUD system. Among them, the hormones secreted by SP-, ENK-, SOM- and GLU-IR endocrine cells belong to the peptides of dual distribution in the brain and gut. This provided new evidence for the concept of brain-gut peptide. According to the cell types, distribution density, morphological characteristics and variety in shape of APUD cells in the gut of stomachless teleost fishes, it is deemed that the digestive tract of fishes is also an endocrine organ of great importance and complexity.

Journal Article↗

APUD cells, apudomas and the neural crest.

The most characteristic feature of the APUD cell series is the ability to take up and decarboxylate amine precursors. Other features, regarded as characteristic by Pearse, are the secretion of polypeptide hormones and their origin from the neural crest. An increasing number of APUD cells is being shown to elaborate polypeptide hormones. It is acknowledged that some members are derived from the neural crest, but there is a good reason to believe that others are not, and no good reason to believe that yet others are so derived. It is therefore suggested that the common factor sought in the genesis of the APUD cell, and perhaps other tumours, may be the biochemical, rather than the embryological, relationship of the progenitor cell types.

Animals↗

Quantitative studies of APUD cells in airways of rats. The effects of diethylnitrosamine and NO2.

A method of quantitating the airways amine precursor uptake decarboxylase (APUD) cells is proposed that relates these cells to total airway epithelial cells or airway length. In control rats, these values were 0.13 APUD cells/100 epithelial cells in the trachea, 0.03 in the large airways, and 0.02 in the small airways. In order to evaluate the ability of this method to determine changes in number of APUD cells, rats were exposed to diethylnitrosamine (DEN) and nitrogen dioxide (NO2), which have been reported to increase the number of airways APUD cells. The NO2 exposure was associated with a twofold increase in APUD cells of the trachea only without associated epithelial hyperplasia; DEN produced marked epithelial hyperplasia in the trachea and bronchi with a disproportionate increase in APUD cells in the bronchial epithelium only. The basis of this differential effect requires further study.

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Diffuse neuroendocrine system: structural and functional effects of radiation injury to amine precursor uptake and decarboxylation (APUD) cells.

The paper presents a review of the results obtained by the authors on the study of external (gamma) and internal (I-131) radiation effects on the functional morphology and linkage of the diffuse neuroendocrine system (DNES) and amine precursor uptake and decarboxylation (APUD) cells of the stomach and duodenum. The investigations performed enabled us to determine that the morphological changes noted in APUD cells had a dose and time dependency. The present study supports the point of view that the radiation initiates serotonin release from APUD cells, which appears to initiate the mechanism of early postirradiation dysfunctions of the gastrointestinal tract and the subsequent adaptive response of DNES. Analysis of our results, together with a review of the literature, indicates that APUD cells actively participate both in pathogenesis of radiation injury and development of organ and tissue radiosensitivity.

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[Apud cells and apudomas of the prostate, breast and uterus].

Morphofunctional features of apud cells in the prostatic, mammalian and uterine parenchyma have been studied inadequately and their further comprehensive study is needed. It will help to estimate fully enough those pathologic changes in which apud cells are involved. Dyshormonal hyperplastic processes and, especially, tumours, are of greatest importance among them. It is essential to consider not only morphologic, but functional peculiarities of tumour tissue, that will enable one to study the biological activity, long-term results of reproductive organ apudoma treatment, as well as to solve the problem of their histogenesis sources.

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APUD cells in normal and hyperplastic prostates.

Argyrophilia and argentaffinity, as basic properties of APUD cells, were investigated in 50 normal and hyperplastic prostates, which included both autopsy and surgical specimens from patients of various ages. Normal prostates (including glands from 3 foetuses) had 62% of argyrophil-positive granules in the glandular epithelia, while only 44% of the hyperplastic glands were positive. Argentaffin-positive cells were found in 12% of the surgical hyperplastic cases. Both argyrophil and argentaffin cells were distributed in zones, often in lobule-like shapes, lying along the basal membrane. On the basis of these findings, there is a discussion on the possible roles played by the so-called APUD cells in hyperplastic and neoplastic growths of the prostate, such as carcinoid tumours (apudomas) or endocrine-associated syndromes in the course of prostatic cancer.

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[Functional morphology of breast APUD cells in dysplasia and neoplastic processes].

Histochemical and immunohistochemical methods were used to examine 29 malignant tumors (18 lobular and 11 invasive carcinomas) and 34 fibroadenomas of the mammary gland (MG). APUD cells containing serotonin, melatonin, and beta-endorphine were shown to be present in the duct epithelium of the normal MG and its pericanalicular fibroadenoma. APUD cells were detected in 21 of the 29 malignant tumours of MG. Hormonal differences of APUD cells were found in poorly and well differentiated carcinomas: the former contained serotonin, melatonin, and beta-endorphine (inhibitors of proliferation), the latter--insulin and adrenocorticotropic hormone (stimulators of cell division). Such differences in the endocrine function of MG malignant tumors are likely to be significant in the clinical course and determination of prognosis for carcinomas of various differentiation.

APUD Cells↗

Review article--involvement of gastric APUD cells in chronic renal failure.

Uremia leads to a number of metabolic and hormonal disorders induced by renal failure with definite biological and clinical sequels. Most frequently, alimentary disorders are the first to appear, followed by symptoms from other organs and systems. The gastrointestinal tract is a site of synthesis of many compounds that have hormonal or hormonal-like biological activity. These substances are produced by highly-specialised receptor-effector cells, that are dispersed in the gastrointestinal mucosa and classified as APUD cells. The present review is an attempt to make a synthesis of current opinions and views concerning the effect of homeostatic dysfunction of the kidneys on the morphology and action of APUD cells in the stomach.

APUD Cells↗

[Study of the APUD cells of the gastric mucosa].

The results of an histochemical and microscopic study of the APUD cells carried on gastric biopsies are reported. Endocrine cell hyperplasia, microscopically detected, was particularly evident in atrophic gastritis (type A chronic gastritis) and adenomas. The presence of the APUD cells confirmed by electronmicroscopy, which revealed granules of 200 NM with a central nucleus and a membrane-separating electron-lucent ring, gives a further contribution to the hypothesis of a possible association between endocrine cell hyperplasia and intestinal metaplasia.

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[Morphofunctional characteristics of the APUD-cell and lymphocyte reactions in the lungs of children with acute pneumonia].

The lungs of 40 children who had died at the age of 1 month to 3 years were studied using special immunohistochemical and morphometric methods. Destructive lung processes were registered more frequently in children below one year of age with acute pneumonia having a similar viral-bacterial etiology. The content of apud-cells with an argyrophilic reaction, amine-containing APUD-cells and lymphocytes with cyclic nucleotides was significantly decreased and indices of the lymphocyte functional activity lowered comparing to the older age group. An essential role of the physiological immaturity of the biogenic amine synthesis by apud-cells is attributed in the acute pneumonia pathogenesis in children of early age. This aggravates immune deficiency and the development of the destructive forms of inflammation.

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Ultrastructural alterations of APUD cells during nitrosamine-induced lung carcinogenesis.

Groups of Syrian golden hamsters were treated twice weekly for life with 1/10 LD50 DEN, or once weekly for life with 1/5 LD50 DBN. The sequential alterations in the ultrastructure of Apud cells in their bronchial lining were examined. Both carcinogens caused pronounced proliferation of this cell type during the initial treatment period. Thereafter, the formation of increasing numbers of filamentous bundles was observed in the cytoplasm of the Apud cells, whereas their neurosecretory granules decreased in number. The present findings suggest that after an initial phase of proliferation, the Apud cells undergo squamous metaplasia when treated with the two nitrosamines investigated.

Animals↗

Is there a ventral neural ridge in chick embryos? Implications for the origin of adenohypophyseal and other APUD cells.

Two- to ten-somite chick embryos were studied in order to ascertain whether, as has been proposed, there exists a 'ventral neural ridge' which gives rise to the hypophyseal (Rathke's) pouch. Serial sections and stereo-microscopy were used. The neural ridges arch around the rostral end of the embryo onto the ventral surface of the head, but no evidence was found for their extension to form a 'ventral neural ridge' reaching the stomodaeum: in fact a considerable expanse of non-thickened surface ectoderm was seen to separate the ventral portions of the neural ridges from the stomodaeum. The thickening of neural ectoderm which does appear on the ventral surface of the head results from apposition and fusion of the opposite neural ridges flanking the neural plate and thus the tip of the anterior neuropore--the classically accepted mode of closure of the neuropore. These findings are in accord with the generally accepted concept of the origin of the hypophyseal pouch rather than with its derivation from a 'ventral neural ridge'. No sign of neural crest formation was encountered ventrally; this observation excludes the possibility that endocrine cells of the APUD series could originate from neural crest in this region.

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