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Sites of prealbumin production in the human fetus using the indirect immunoperoxidase technique.

An indirect immunoperoxidase technique was used to investigate the site of prealbumin synthesis in the human fetus from between 8 and 43 weeks. Prealbumin staining was noted in the A cells of the fetal pancreas, both in the primary and secondary generations of the islets of Langerhans, from as early as 12 weeks gestation. Electron microscopy localized the staining to the cytoplasmic secretory granules. Prealbumin was also present in the gastrointestinal mucosa in cells which had a distribution similar to that of argentaffin cells. Positive staining was noted in the lining epithelium of the renal proximal convoluted tubules, but ultrastructural studies indicated that this was probably related to reabsorption, and not to synthesis.

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Tissue-specific and substrate-specific endoproteolytic cleavage of monkey pro-opiomelanocortin in heterologous endocrine cells: processing at Lys-Lys dibasic pairs.

This study compares the processing of pro-opiomelanocortin (POMC) at two Lys-Lys cleavage sites, located in the carboxy-terminal domain of the precursor, one site marking the amino terminus of beta-melanocyte-stimulating hormone (beta-MSH) and the other in the carboxy-terminus of beta-endorphin (beta E). These comparisons were carried out by transfecting monkey POMC cDNA into two heterologous cell lines: AtT-20, which endogenously expresses mouse POMC, and Rin m5F, which has been previously used as a host for transfected POMC. These cells lines are known to process POMC differently at Lys-Arg residues, though less is known about their Lys-Lys cleavage. Our results have demonstrated both tissue-specific and site-specific factors controlling Lys-Lys cleavage. The AtT-20 line appears not to perform either Lys-Lys cleavage. Rin m5F cells, on the other hand, fail to process the site at the carboxy terminus of beta E (beta E28-29) but do process, to a significant extent, the N-terminal site to beta-MSH. That this differential processing is unlikely to be due to a POMC conformation which would make the beta E site inaccessible was demonstrated by mutating the sites from Lys-Lys to Lys-Arg. With such mutants, Rin m5F cells fully processed at both locations. Interestingly, the mutant Lys-Arg sites were not fully processed by AtT-20 cells. These results are discussed in terms of the complement of processing enzymes expressed in each of the cell lines, as well as the role of residues surrounding the diabasic cleavage sites in determining the likelihood of proteolysis.

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Preliminary evaluation of neuroendocrine cells in the respiratory tract in rats with experimental uremia.

The goal of this study was to investigate the influence of experimetally induced chronic renal failure on endocrine cells in the respiratory tract in rats. After 30 days of uremia, the fragments of rat lungs were collected. Paraffin sections were stained using H+E, silver impregnation and immunohistochemistry with specific antibodies against calcitonin (CT), synaptophysin (SY), somatostatin (ST), and neuron-specific enolase (NSE). A large number of endocrine cells with a strong calcitonin immunoreactivity were observed in the respiratory tract of rats with experimental uremia, as compared with the control group. Other immunoreactions were weakened.

APUD Cells↗

Chromogranin-A expression in gastric and colon cancer tissues.

UNLABELLED: We studied the expression of chromogranin A (CgA) in human gastric (n = 17) and colorectal (n = 18) adenocarcinomas by nucleic acid hybridization and immunohistochemical analyses using a specific monoclonal antibody (MAb) to human chromogranin A (CgA). Some corresponding adjacent non-malignant mucosal tissues were also examined. RESULTS: (1) Northern blotting: of 3 normal gastric mucosas examined, 2 (67%) had an easily detected signal for expression of CgA. Only one of 14 gastric carcinomas (7%) and one of 18 colorectal carcinomas (6%) had easily detected RNA signals. (2) Immunohistochemical staining: all non-malignant samples of gastric and colonic mucosa contained CgA-positive neuroendocrine (NE) cells. Two of 17 (12%) gastric adenocarcinomas, and 3 of 18 (17%) of colorectal adenocarcinomas contained CgA-positive tumor cells. Interestingly, the positive cases detected by immunohistochemistry included both cases detected by Northern blotting. Of the 5 cases detected by immunohistochemistry, 2 gastric cancers and 1 rectal carcinoma contained many diffusely scattered positive cells, occurring singly or in small clusters, while 2 colorectal carcinomas contained only occasional single CgA-positive tumor cells. In one of the positive gastric cases, a well-differentiated adenocarcinoma arising in a tubular adenoma, both the adenomatous and the carcinomatous elements contained positively staining cells. Our specific assays for CgA indicate that (1) a NE cell component, either diffusely scattered or occasional, occurs in about 15% of gastric and colorectal tumors; (2) there is no correlation between the presence of NE cells and degree of tumor differentiation; and (3) because only a minority of the tumor cells in positive cases stain for CgA, immunohistochemistry is a more sensitive method than Northern blotting.

APUD Cells↗

[Morpho-functional characteristics of the pineal gland in patients with cancer at various sites].

Morphologic and histochemical changes in the pineal gland were studied in 60 autopsied cases of cancer of various sites. The changes were similar to those of the involutive pattern but appeared to be more pronounced and developed at an earlier stage. A decline in the gland activity was matched by a decrease in its size, specific weight of its parenchymal tissue and size of cell nuclei and nucleoli. Also, the gland's cells exhibited higher levels of lipids and lower concentrations of monoaminoxidase and RNA. The degree and extent of those changes were in correlation with tumor stage and duration of disease but did not depend on the site of tumor.

APUD Cells↗

[Struma ovarii and strumal carcinoid].

Seven ovarian tumours (3 mature teratomas, 2 strumas with malignancy 2 strumal carcinoids) have been examined histologically, hystochemically and electron-microscopically. It is shown that the cell composition of the strumal teratoma tissue is very similar to that of the ectopic thyroid. The follicular cells may proliferate either into the benign tumour (apudoma) or typical thyroid carcinoma. Parafollicular cells may give rise to C-cell hyperplasia with the amyloid deposits in the stroma. The so-called strumal carcinoid of the ovary represents probably the C-cell tumour. Its "strumal" component may be considered as preexisting follicles invaded by tumour apudocytes or as the site of tumour origin displaying the pattern of a non-medullary thyroid apudoma.

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Localization and possible function of polyamines in protein and peptide secreting cells.

Three different cytochemical methods, the formaldehyde-fluorescamine and the ortho-phtalaldehyde fluorescence cytochemical methods as well as immunocytochemistry have been developed for localising the polyamines spermidine and spermine in tissue. All three methods produce identical results and show polyamines to occur inter alia in high concentrations in certain protein- and peptide-secreting cells. Many of these cells also show the capacity to metabolise monoamines and belong to the amine content or amine precursor uptake and decarboxylation (APUD) series. In cell types where fluorescence microscopical resolution allows, most polyamines appear to be localised to secretory granules. Moreover, studies on isolated pancreatic islets reveal active and glucose-dependent polyamine biosynthesis to occur in insulin cells. Possible function of polyamines in secretory granules are discussed in the light of the above findings.

APUD Cells↗

Neuroendocrine differentiation in the precursors of prostate cancer.

OBJECTIVES: To review neuroendocrine differentiation in the precursors of prostatic carcinoma (prostatic intraepithelial neoplasia). METHODS: Background information is given on the prostatic neuroendocrine cell and neuroendocrine differentiation in prostatic carcinoma. Neuroendocrine differentiation in prostatic intraepithelial neoplasia is reviewed. RESULTS: Neuroendocrine differentiation occurs in prostatic intraepithelial neoplasia and is intermediate in degree between normal (which has the most cells with neuroendocrine differentiation) and carcinoma. CONCLUSION: Neuroendocrine differentiation in the precursors of prostatic carcinoma may play a role in the pathogenesis of cancer but is speculative at this time. Methods to better assess neuroendocrine differentiation are needed.

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Intestinal endocrine cells in radiation enteritis.

In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis.

APUD Cells↗

[The duration of hormone synthesis by cultures of human fetal endocrine cells].

It is stated as possible to cultivate and accumulate endocrine cells by regular passages in vitro over a long period of time. In this case endocrine cells of human fetus don't loose the ability to synthesize hormone. Such cultures can be used to study some general-biological problems out of influence of the neurohumoral organism factors.

APUD Cells↗

[C-cells (parafollicular) and medullary cancer of the thyroid gland].

In the human thyroid gland, less than 1% of the cell mass of the organ parenchyma is comprised of C-cells, the typical feature of which is the capacity of produce and accumulate a hypocalcemic hormone, calcitonin. Because of their function, these cells play an important role in the maintenance of homeostasis. Neoplastic proliferation of C-cells results in medullary carcinoma represented by the classical forms and non-medullary apudomas. Morphological, histochemical, and electron microscopic studies demonstrated cytological and histological inhomogeneity of thyroid apudomas and allowed the differential diagnosis criteria for their identification to be outlined.

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Increased intracellular levels of calcitonin gene-related peptide-like immunoreactivity in pulmonary endocrine cells of hypoxic rats.

The mammalian respiratory tract contains innervated groups of endocrine cells which are believed to respond to hypoxia. We have demonstrated the involvement of a specific regulatory peptide produced by the cells, calcitonin gene-related peptide (CGRP), in this response. Cells immunoreactive for CGRP or for protein gene product 9.5 (PGP 9.5), a general marker of nerves and endocrine cells, were quantified in sections of lungs from hypoxic (21 days, 10 per cent O2) and normoxic rats. An immunostaining method employing supra-optimal dilutions of primary antiserum was used. This detects variations in antigen concentration which may be masked if the routine, optimal dilution is used. The number of CGRP-immunoreactive endocrine cells was significantly (P less than 0.001) greater in the lungs of hypoxic rats (76.9 +/- 10.1 cells/cm2, mean +/- SEM) compared with controls (19.7 +/- 2.4). However, the numbers of PGP 9.5-immunoreactive cells were the same in both groups (81.3 +/- 12.2, hypoxic; 79.5 +/- 9.8 control), suggesting that the total number of endocrine cells did not change. It is concluded therefore that the apparent increase in CGRP-immunoreactive endocrine cells in hypoxic rat lungs is due to increased intracellular levels of the peptide. Since CGRP is a vasodilator, this could have important implications in the vasoconstrictor response to hypoxia.

APUD Cells↗

[The morphological characteristics of the intestinal endocrine cells in mice].

Ultrastructural investigation and quantitative analysis of endocrine cells of intestine were studied in mice. The results obtained allow the quantitative composition and cytotopography of endocrine cells in different sections of small and large intestine in mice. The combination of these methods obtained allow to describe 15 types of endocrinocytes, and to demonstrate these localizations and electron microscopy characteristics.

APUD Cells↗

Amine-containing cells of the lung.

In many vertebrates, including mammals, there are amine-containing cells in the walls of the airways and the lungs. Despite a plethora of names for these cells, there is a general agreement about their structure. They occur singly or in groups (NEBs), but the functional distinction between the two types of distribution is uncertain. In spite of ultrastructural similarities, the cells may be physiologically heterogenous. The cells are characterised by their staining characteristics and content of electron-dense-core vesicles, which are believed to contain a biogenic amine. They also have additional cytoplasmic features common to other sensory paraganglia. They may be more numerous in certain species and also in the neonate. The NEBs may be innervated with afferent and/or efferent nerves, though physiological evidence of their innervation is scanty. The most popular hypothesis is that they can be stimulated by hypoxia to release mediators or to induce reflex activity. In the healthy animal, the amine-cells may control local ventilation/perfusion (V/Q) ratios via an action on the pulmonary vasculature. In disease, they may cause pulmonary hypertension. They can also give rise to three forms of tumour. Their full significance has yet to be established.

APUD Cells↗

[Identification of endocrine cells in the gastrointestinal tract].

The gastric and duodenal endocrine cells (apudocytes) of children and immature rats were studied by electron microscopy. It is shown that every cell type has its own morphological peculiarities of secretory granules formation, maturation and disintegration. This feature together with the size and morphology of mature granules is recommended to be used as a classification criterion for the identification of apudocyte types.

APUD Cells↗

The diffuse neuroendocrine (APUD) system.

The bulk of experimental evidence indicates that the APUD series of cells is a distinct system based upon common pathophysiological features. The diffuse nature of this system with elements in the central and peripheral nervous system suggests a more complex interaction of the body's homeostasis than has been established. It is probable that as radioimmunological and radioenzymatic assays become more widely available and standardized, other apudomas will be described. Finally, an understanding of the APUD concept, with its peculiar pluripotential for the production of biogenic amines and peptides, the multicentric nature of the disease and the possibility of multiple cell involvement, is of key importance in managing patients. Studies of the apudomas will also advance the understanding of the normal physiologic interrelationships of the APUD cells.

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[Apudocytes and mast cells in chronic inflammation of colon: clinicomorphological correlations].

AIM: To study functional morphology of a total population of endocrine cells of colon mucosa, mast and enterochromaffine cells. MATERIALS AND METHODS: Light and electrone microscopy, immunohistochemical methods, morphometry were used to study endocrine and mast cells of the sigmoid colon in inflammation. RESULTS: Changes of functional morphology and size of endocrine and mast cell population as well as apudocytes producing serotonin, melatonin, vasointestinal peptides were stated. Apudocyte and mass cell functional morphology, clinical symptoms and mucosal structural changes correlated. Specificity of some parameters in Chron's disease is shown. CONCLUSION: The results may provide additional criteria in diagnosis of different variants of chronic colitis.

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[Morpho-functional characteristics of the adenohypophysis in cardiovascular pathology].

Morphologic examination of the adenohypophysis of 46 subjects who died from cardiovascular diseases has shown a restructuring of the gland, including changes in its nonspecific signs and alterations typical of certain cardiovascular conditions. Analysis of the ratios between various types of endocrine cells and different types of basophil tropocytess in health and disease has revealed variability of these parameters in cardiovascular diseases and in various types of the same disease. Fluctuations in adenohypophysis cellular composition are explained by specific features of the pathogenesis of these conditions.

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