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Storage granules of thyroid C cells in the dog: a cytochemical and ultrastructural study, in relation to the masked metachromasia reaction.

Masked metachromasia can be demonstrated in thyroid C cells, and other cells of the APUD series, by staining with a metachromatic basic dye after hydrolysis of suitably fixed tissue. The reaction is thought to be due to the presence of polypeptides with a high concentration of side-chain acidic groups. Since most APUD cells possess storage granules, presumed to contain a polypeptide hormone, it has been assumed that the masked metachromasia reaction gives information concerning the contents of these granules. However, there has been an increasing suspicion that the reaction might actually be due to the membrane bounding these granules, rather than to the contents. We have examined, cytochemically and ultrastructurally, dog thyroid tissue which has been subjected to fixation and hydrolysis as in the usual method for masked metachromasia. We found that the membrane surrounding the C cell granules is removed by hydrolysis, confirming the hypothesis that the reaction is due to the contents (hormone and/or matrix)rather than to the membrane. Tissues were fixed in an aqueous mixture containing glutaraldehyde (6 25% v/v), picric acid (three-quarters saturation) and sodium acetate (I% W/V)adjusted to PH 7 with sodium hydroxide. This was found to be a very satisfactory fixative for electron microscopy Some morphological details of C cells were noted, such as the richness of desmosomes between C cells in this species, and frequent direct contact with the colloid.

Animals↗

Carcinoid tumour arising in a recurrent intradural spinal teratoma.

We report the case of a recurrent intradural spinal teratoma in a 44-year-old woman. Histological examination showed the lesion to be composed entirely of mature elements including an argyrophil carcinoid tumour. Electron microscopy showed the neoplastic cells to possess the ultrastructural features of a foregut type APUDoma. Gamma enolase, a marker of APUD cells, was demonstrated in the neoplasm by the peroxidase-antiperoxidase technique. This method was also used to demonstrate the presence of cytokeratins in the neoplastic cells and the squamous and columnar epithelia within the teratoma. These results are consistent with the suggestion that APUD cells of foregut type may be of endodermal rather than neuroectodermal origin.

Adult↗

Effect of veratrine and 50 mM K on ileal transport and electrically induced secretion.

To obtain additional evidence that the Cl secretion caused by electrical field stimulation (EFS) in rabbit ileum in vitro is mediated by nerves or amine precursor uptake and decarboxylation (APUD) cells, we determined whether the response could be prevented by agents that depolarize nerves, veratrine or 50 mM K. EFS 1) increased transmural electrical potential difference (PD) and the short-circuit current (Isc) and reduced total ion conductivity (G), 2) caused Cl secretion by reducing the mucosal-to-serosal flow of chloride (JClm leads to s) alone or in combination with an increase in the serosal-to-mucosal flux of chloride (JCls leads to m), and 3) reduced Na absorption or caused secretion by increasing JCls leads to m alone or in association with a reduction in JNam leads to s. At 10(-5) g/ml, veratrine prevented the changes in ionic fluxes caused by EFS and reduced the PD and Isc. It did not reduce the Isc response to 5 mM aminophylline, however. Fifty millimolar K decreased PD and Isc and increased G. JNam leads to s and JNas leads to m diminished in proportion to the reduction in bath Na concentration, so the net flux of sodium (JNanet) was not affected. JClnet did not change, although both JClm leads to s and JCls leads to m increased. Fifty millimolar K prevented the changes in ionic fluxes caused by EFS and reduced the Isc response to aminophylline by half. The study provides additional evidence that the effects of EFS are mediated by nerves or electrically excitable APUD cells, but the contribution of each is uncertain.

APUD Cells↗

Grimelius' silver method for all types of malignant melanomas.

Various cytologic appearances of malignant melanomas represent a great diagnostic problem in the pathologist's everyday work. The new Pearse concept that the melanoblast/cyte is the APUD cell led the authors to the idea of using Grimelius' silver method, characteristic of APUD cells, in the diagnostic pathologic work of both melanotic and amelanotic malignant melanomas. The results are based on the examination of 20 tumours. All types of malignant melanomas were Grimelius reactive. The blanching by hydrogen peroxidase of Grimelius reactive cells makes this silver reaction specific in the study of melanomas.

Histocytochemistry↗

Light and electron microscopic characteristics of the various lung endocrine cell types.

Morphological and histochemical studies on APUD-cells in the lung epithelium are reviewed. Common features of these cells are their capacity to produce and store amine, their argyrophilia and their characteristic cytoplasmic secretory granules. Based on the fine structural morphology of the secretory granules three types of cells were observed in human foetal lung. In the human adult lung, endocrine cells were few in number and widely scattered. Contact between endocrine cells and nerves was never seen. One 'function' of endocrine cells in the human adult lung may be to act as precursor cells for carcinoid tumours and small cell anaplastic carcinomas (the APUDomas of the lung).

APUD Cells↗

[Changes in the neuromediator system of the thymus in rats after splenectomy].

Removal of spleen leads to compensatory activation of the function of central immunogenetic organ and increase of hyperplastic processes in it on d 3 postoperatively which is accompanied by growth of biogenic amine concentration, appearance of bioaminergic areas and lobules-satellites as well as formation of new cloe correlative links. Transitory inhibition of immunogenesis occurs on d 15 and d 30 peaking on d 45 following splenectomy. At this period glycosaminoglycan composition of mast cells and their functional activity changes which is manifested by appearance of juvenile T-0 forms and new metachromatic types of mast cells. In 2 months decrease of APUD cells number and their mono- and diamine content and weakening of correlative interconnections is accompanied by true significant disturbance in T lymphocytes differentiation, their release in peripheral blood and further insufficiency of cellular immunity.

APUD Cells↗

[The endocrine cells of the digestive system (author's transl)].

Endocrine cells occur in the digestive system as micro-organs (islets of Langerhans) or scattered throughout the epithelium of the gastrointestinal tract ("diffuse endocrine epithelial organ" of Feyrter). These gastro-entero-pancreatic (GEP) endocrine cells synthesize--in addition to serotonin--a great variety of polypeptide hormones, which regulate both carbohydrate metabolism and digestive processes. The present review deals mainly with cytology and cytochemistry of GEP endocrine cells. A synopsis is presented of the 19 endocrine cell types identified to date, which includes their update nomenclature and their anatomical distribution pattern. Morphological-functional aspects of cell biology, pathology, and cytogenesis of theses cells and their position within superimposed systems (APUD cells, paraneurons) are discussed.

APUD Cells↗

Immunocytochemical localization of aromatic L-amino acid decarboxylase in human, rat, and mouse bronchopulmonary and gastrointestinal endocrine cells.

Aromatic L-amino acid decarboxylase (AADC) catalyzes the cellular decarboxylation of L-aromatic amino acids and is therefore involved in the synthesis of several biogenic amines. Application of the indirect immunoperoxidase method on human, rat, and mouse tissues using specific antibodies to AADC revealed all AADC-containing cells. Besides mast cells and adrenergic nerve fibers, the following cells were immunostained: neuroendocrine cells in the tracheobronchial epithelium; neuroepithelial bodies in the bronchopulmonary epithelium; Kultschitzky cells in the small intestine and appendix as well as adrenal chromaffin cells. All the latter cells belong to the so-called APUD system, the "D" in the acronym standing for the activity of the enzyme aromatic L-amino acid decarboxylase. Immunocytochemistry for AADC may become an additional tool not only to highlight APUD cells in tissue sections but also to differentiate the sites of cellular amine synthesis from those of amine storage.

APUD Cells↗

The ultrastructure of focal islet cell adenomatosis in the newborn with hypoglycemia and hyperinsulinism.

In a newborn severe persistent hypoglycemia due to an insulin-producing tumorous proliferation of pancreatic islet cells (insulinoma) was observed. The insulinoma showed the histologic pattern of focal adenomatosis of islet cells. According to the present literature the focal proliferation of islet cell complexes seems to be a frequent and particular feature of insulinomas in the newborn. Differential islet cell staining identified 80%-90% of the proliferated islet cells as B cells. 10%-20% of the cells were found to be A or D cells. Ultrastructurally the majority of the proliferated islet cells were well differentiated B cells. The remaining cells represented either A or D cells or a fourth islet cell type with small spheric granules. Electronmicrscopic evidence of transitions between differentiated islet cells, particularly B cells, and the fourth islet cell type suggests that the fourth islet cell type might represent a precursor cell within the APUD-cell system.

Adenoma, Islet Cell↗

Radioautographic study of uptake and storage of indoleamines in the rabbit enterochromaffin cells.

After in vitro intra-arterial injection of tritium-labeled 5-hydroxytryptamine or -hydroxytryptophan ([3H]5-HT or [3H]5-HTP) (5 x 10(-7) M) in the presence of cold noradrenaline (5 x 10(-6) M) into rabbit colon, a clear-cut labeling pattern was observed by radioautography. Labelled cells were observed within the mucosa. The labeling was less important after [3H]5-HTP than after [3H]5-HT injection. Ultrastructural study indicates that labeling is confined to the cytoplasm and coincides with polymorphic secretory granules. Hence these labeled cells display not only APUD cells characteristics but also true neuronal properties.

5-Hydroxytryptophan↗

Iodine-131 MIBG scintigraphy in small cell lung cancer.

There is a well documented relationship between small cell carcinoma of the lung and the amine precursor uptake and decarboxylation system of endocrine cells (APUD). We attempted to exploit this association by employing the unique radiopharmaceutical, 131I-MIBG, which is recognized and taken up by the APUD system to monitor disease activity in patients with small cell carcinoma of the lung. A total of eight patients with biopsy proven, metastatic small cell carcinoma of the lung were studied. 131I-MIBG was synthesized in our laboratory by reacting metaiodobenzylamine hydrochloride with cyanamide with subsequent solid phase radioiodination. A dose of 0.5 mCi radiopharmaceutical was injected and images obtained on a large field of view gamma camera with a high energy parallel hole collimator at 2, 24, and either 48 or 72 h. Images were compared with known focal areas of metastatic disease demonstrable on computed tomographic scan, chest roentgenogram or bone scan. We were unable to detect reproducible correlations between the images produced by conventional radiographic techniques and the images produced by our radiopharmaceutical. We conclude that this agent will probably not be useful for localization of metastatic small cell lung carcinoma.

3-Iodobenzylguanidine↗

Endocrine tumors of the pancreas.

The identification and description of a widely dispersed group of cells of common origin and biochemical characteristics, APUD cells, has allowed a better understanding and classification of endocrine tumors of the pancreas. Similarly, it has enabled the relationships between the endocrine tumors of the multiple endocrine neoplasia type I syndrome and the endocrine tumors of the pancreas to be better appreciated. This has facilitated both diagnosis and management of these conditions. The pluripotentiality of the cells of the APUD system combined with the certain existence of many unidentified peptides suggests the likelihood of other undescribed pancreatic endocrine tumors. Many of these are probably part of the heterogenous group of neoplasms currently designated as carcinoids, since their secretory products and exact cell types are not known. The recognition of the physiologic characteristics and cells of origin of these peptides, amines or other bioactive agents will allow delineation of the symptom complex and the identification of further functional tumors of the pancreas. The development of plasma radioimmunoassays for the various hormones and the appreciation of the specific clinical syndromes related to each tumor have enabled earlier diagnosis. The understanding of the hormonal physiopathologic functions has led to the evolution of specific therapeutic maneuvers. Provocative tests have allowed increased precision of the differential diagnosis, while selective arteriography and pancreatic venous sampling have greatly enhanced the accuracy of topical localization. The role of operation in tumor removal is still prominent, but malignant and recurrent tumors may now also be controlled with specific pharmacotherapy or appropriate endocrine cytotoxic agents. The use of peptides with antagonistic actions or the administration of specific antibodies to the active tumor products are areas of therapy that require further exploration.

Adult↗

Presence of cells with argyrophil granules in normal, hyperplastic, and neoplastic endometrium.

Cells with argyrophil granules were searched for in 131 consecutive specimens obtained from endometrial curettage. Particular care was taken with the fixation methods to avoid a false positivity to the silver impregnation according to Grimelius. We did not consider the grossly argyrophilic positivity on the cellular apex or of the whole cytoplasm, which was partially reduced by diastase digestion and probably due to the presence of glycogen and secretory mucoproteins. Cells with thin argyrophilic granules similar to those observed in endocrine APUD cells were present among glandular cells and/or among stromal cells in 15 of 131 examined specimens. They concerned 5 cases of proliferative endometrium, 3 of secretive endometrium, 5 of hyperplasia, and 2 of carcinoma. In 8 of the 15 cases with argyrophilic cells, immunohistochemical studies with the PAP method showed cells with the presence of FSH, S-100 protein, somatostatin, vasoactive intestinal peptide (VIP), gastrin, and neuron-specific enolase (NSE). The significance and origin of these cells in normal and neoplastic endometrium are discussed.

APUD Cells↗

[APUD and mast cells of the gastrointestinal system: immunohistochemical and ultrastructural identification].

A rationale for sequential immunohistochemical studies of the endocrine function of APUD cells is described, as exemplified by a study of serotonin-containing cells in rat small intestine, involving preparation of paraffin and semithin sections of epoxide resin-embedded tissue, followed by electron-microscopic examination of cells detected by the immunoperoxidase technique. With the approach described, it has been shown that a positive immunohistochemical reaction to antiserotonin antiserum is given, along with EC cells, by those mast cells disposed in groups near the EC cells as well as among connective-tissue cells of villi under the basement membrane. It is suggested that by collecting and accumulating the serotonin synthesized by specialized EC cells, mast cells transport it to sites of utilization as required by the specific arrangement.

APUD Cells↗