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Development of neuroepithelial bodies in fetal rabbit lungs. I. Appearance and functional maturation as demonstrated by high-resolution light microscopy and formaldehyde-induced fluorescence.

Developing lungs of fetal rabbits aged 13 days through early postnatal stages were examined for periodic acid-Schiff (PAS)-lead hematoxylin staining, serotonin fluorescence, and argyrophilia, methods selective for small-granule (neuro) endocrine cells. Later stages were also studied by electron microscopy. These cells arise from precursors that first appear around days 18-19 in the endodermal epithelium; the latter stand out as clear cells from their undifferentiated, glycogen laden neighbors. The cells first form in the main and lobar bronchi, then continue to arise in the lining of newly laid down branches of the extending bronchial tree, tending to concentrate near points of branching. Some cells have been seen to divide, and clusters of two, four, or more soon appear. Morphologically mature neuroepithelial bodies begin to appear in larger bronchi around 23 days, although the largest examples occur in 25-day and older fetuses. After 23 days, additional bodies mature from clear-cell precursors in more recently laid down distal lung, so that by the terminal sac period (around days 28-29) all conducting airways contain them, and the clear cells and clear-cell clusters have virtually disappeared. A pinkish staining by PAS-lead hematoxylin and dense-core secretory granules, which begin to appear in the clear cells, are present in mature small-granule cells whether solitary or aggregated. Argyrophilia is less consistently demonstrable. Fluorescence for serotonin is first evident in mature neuroepithelial bodies at 23 days, increases considerably by 26 days, and reaches a prenatal peak around days 28-29, when neuroepithelial bodies and solitary small-granule cells along the whole conducting bronchial tree may participate. Fluorescence appears to decrease during days 30-31 but strengthens again after birth. Composed of these solitary small-granule cells and neuroepithelial bodies, the pulmonary APUD system of rabbits thus appears substantially functional during the final quarter of gestation.

APUD Cells↗

[Structural-functional characteristics of the renal endocrine system after alpha-1 adrenoreceptor blockade].

Research Institute of Cardiology, Uzbek Health Ministry Structural and functional peculiarities of the renal juxtaglomerular and interstitial cells were studied after alpha 1-adreno-blockers were used. The endocrine cells were studied after a single and prolonged introduction of the agents. Administration of a single dose of the drugs led to hypergranulation in juxtaglomerular cells thus decreasing their functional activity and release of the granules from the cells. The interstitial cells function intensified. Prolonged administration of alpha 1-adrenoblockers caused a degranulation process in the juxtaglomerular cells and a decrease in their protein-synthetizing structures, namely, renin synthesis, and elevation of synthetic process in the interstitial cells.

APUD Cells↗

Reproduction and the APUD system.

Substantial evidence for involvement of the APUD system in the normal reproductive tract is limited to the prostate gland and uterine cervix. Most supportive data simply documents the presence of neuro-endocrine cells in these tissues. A biological product(s) or role(s) remains to be discovered, but appears likely in the prostate. Tumors possessing cells with APUD characteristics have been described in many reproductive tissues including the prostate, cervix, endometrium, ovary, and testes. These tumors are generally aggressive in behavior, and optimum therapy needs to be determined.

APUD Cells↗

[The effect of choleragen poisoning on the intestinal apudocytes of gnotobiotic minipigs].

Intragastric administration of the cholera toxin to gnotobiotic mini-pigs results in cyclic morphofunctional alterations of intestinal apudocytes followed by their degranulation, a decrease in their number from 1 to 3 hrs and after 18 hrs, while a slight increase in their number occurred from 3 to 12 hrs. The response of APUD-system cells is similar in large and small intestine. Products of apudocyte secretion may be involved in the diarrheogenic effect of the cholera toxin.

APUD Cells↗

Ectopic hormone syndromes.

Ectopic hormone production is not always associated with endocrine manifestations and if extensive studies of tumour hormones are made it is found that asymptomatic hormone production is often concomitant with neoplasms. The nature of tumour hormones seems essentially indistinguishable from that of native hormones, although there exists in some cases an abundance of precursor or hormone fragments and unbalanced biosynthesis of subunits. Production of multiple hormones by a tumour is not uncommon. These facts may suggest abnormal gene expression as the basic mechanism responsible for ectopic hormone production. During the process of cellular differentiation, most of the genes are inactivated. Neoplastic transformation may activate repressed genes, thus producing hormones that are not produced by differentiated cells (derepression hypothesis). This hypothesis, however, makes it difficult to explain the higher incidence of ACTH-LPH-producing tumours among APUD tumours. Some investigators have postulated that only APUD tumours elaborate ACTH-LPH or other APUD hormones (neuro-endocrine cell hypothesis). However, there have been reported some definite non-APUD tumours which elaborate ACTH-LPH. These facts can be explained by the stepwise, irreversible repression hypothesis of cellular differentiation. In APUD cells, the gene for ACTH-LPH coding may be repressed at the terminal stage of differentiation and may, therefore, be very easily derepressed by neoplastic transformation. On the other hand, the ACTH-LPH gene may be repressed at a relatively early stage in non-APUD cells and be difficult to reactivate even after neoplastic transformation. Further studies on ectopic hormone producing tumours may clarify the mechanism of ectopic hormone production and yield new insights into the fundamental process of malignant change.

Adrenocorticotropic Hormone↗

Chromaffin cells as models of endocrine cells and neurons.

Chromaffin cells have many functional similarities to amine- and peptide-producing endocrine cells throughout the body and to both peripheral and central neurons. The hypothesis of a shared, neural origin for chromaffin cells and most other endocrine cells is not tenable. However, chromaffin cells and their neoplastic counterparts, known as pheochromocytomas, are valuable models for studies of endocrine and neural properties. In this session, PC12 rat pheochromocytoma cells are used in two novel applications: to identify profiles of gene expression that may mediate cell death in neurodegenerative disorders and to study mechanisms for transduction of hypoxic signals. Recently described pheochromocytoma cell lines from neurofibromatosis knockout mice are shown to be novel models for signaling by the receptor tyrosine kinase ret, and purified enterochromaffin-like (ECL) cells are shown to offer new opportunities to study the shared and distinctive aspects of neuroendocrine function using a normal cell type.

APUD Cells↗

Monoamine-containing granulated cells in the frog lung.

The epithelium of the primary bronchus of the frog lung has been studied by fluorescence and electron microscopy. Clusters of five to ten, ovoid, brilliantly yellow fluorescent cells were observed in the basal portion of the epithelium. These cells contained numerous electron-dense granules of variable shape and size. The granules gave a positive argentaffin reaction at the ultrastructural level, suggesting a possible existence of monoamines in the granules. In addition, synaptic contact between the intraepithelial nerves and the cells, which was characterized by the aggregation of the granules toward the presynaptic membrane thickening of the cell, was also noted. These data are discussed in relation to similar studies in birds and mammals, and a possible function of these cells suggested.

APUD Cells↗

Co-occurrence of immunoreactive calcitonin and calcitonin gene-related peptide in neuroendocrine cells of rat lungs.

Neuroendocrine cells of the lung, occurring singly or in clusters known as neuroepithelial bodies, contain a variety of biologically active compounds, including several neuropeptides. We have investigated the localization of calcitonin and calcitonin gene-related peptide (CGRP) within single and grouped neuroendocrine cells in the respiratory epithelium of rats by an immunohistochemical double-staining technique which uses specific antisera raised in heterogeneous animal species. Calcitonin- and CGRP-immunoreactivities were nearly totally co-localized in both single neuroendocrine cells and neuroepithelial bodies. CGRP-immunoreactivity was also present in neurons in the jugular, nodose and dorsal root ganglia. The calcitonin-immunoreactivity in neuroendocrine cells, as in thyroid parafollicular (C) cells, was abolished by preincubation of the anti-calcitonin serum with synthetic calcitonin. The CGRP-immunoreactivity in neuroendocrine cells and in the neuronal cells was abolished by preincubation of anti-CGRP serum with synthetic CGRP. Thus, while the calcitonin gene is expressed exclusively or predominantly as either calcitonin or CGRP in all other tissues except thyroid C-cells, our results strongly suggest that both peptides are expressed in the rat bronchopulmonary neuroendocrine cells.

APUD Cells↗

[The ultrastructure of the epithelial endocrinocytes of the appendiceal mucosa in the human fetus].

An electron microscope study of the epithelium of vermiform processes of 11-26 week old human fetuses showed seven types of endocrinocytes differing in ultrastructure and dimensions of secretory granules. In addition to the six known types of endocrinocytes (EC, D, D1, I, L and P), endocrinocytes of a 7th type were discovered which are beyond the International classification of endocrinocytes of the gastroenteropancreatic system. The overwhelming majority of endocrinocytes of the vermiform process epithelium form EC-cells. Besides, cells of a "mixed" type, both exo-endocrine and endo-endocrine cells, were revealed.

APUD Cells↗

Carcinoid tumor with uterine location. Case report.

A carcinoid is defined as a tumor arising from endocrine cells with neurosecretory characteristics belonging to the APUD system. These cells are most frequently observed in the digestive tract and lungs. Uterine location is rare. This paper presents the case of a 21-year old patient with uterine carcinoid tumor. In order to establish the histopathologic diagnosis of the carcinoid tumor, we used optical microscopy examination in haematoxylin-eosin, argentic impregnation in Fontana-Masson staining and an immunohistochemical reaction using monoclonal antibody to the S100 protein. Due to the intracytoplasmatic granulations shown in Fontana-Masson staining and in the immunohistochemical reaction to S100 protein which confirm the neurosecretory character of the tumoral cells, we included this tumor in the group of tumors with neuroendocrine differentiation.

APUD Cells↗

Neuron specific enolase in human small cell carcinoma cultures.

Continuous cell lines of human lung cancers were analyzed for neuron specific enolase (NSE). The levels of NSE in the small cell carcinoma cells were in every case much higher than those derived from other forms of lung cancer. Since NSE is strictly localized to neurons and neuroendocrine cells of the amine precursor uptake and decarboxylation (APUD) series, the data provided further evidence that small cell carcinoma is an APUD cell tumor and is distinct from other forms of lung cancer.

APUD Cells↗