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PubMed1993

111In-octreotide scintigraphy in oncology.

Various tumors of neuroendocrine origin that have amine precursor and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous injection of the somatostatin analogue [123I-Tyr3]-octreotide. However, the relatively short effective half-life of this compound and the high background of radioactivity in the abdomen are drawbacks in its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]-octreotide) was developed. This analogue is excreted mainly via the kidneys, 90% of the dose being present in the urine 24 h after injection. Using 111In-octreotide scintigraphy, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1 glucagonoma, 3 out of 3 unclassified apudomas, but none out of 18 exocrine pancreatic carcinomas were visualized. Also, 19 out of 19 carcinoids, 15 out of 15 glomus tumors, 8 out of 12 medullary thyroid carcinomas, 6 out of 6 small cell lung carcinomas, 4 out of 4 growth hormone-producing and 6 out of 9 clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD-cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied to visualize breast cancer, lymphomas and granulomas. In 39 out of 50 patients with breast carcinoma, 10 out of 11 patients with non-Hodgkin lymphomas, 3 out of 3 patients with Hodgkin's disease, and 8 out of 8 patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, but also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy revealed more tumor sites than did conventional imaging techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Apudoma↗
PubMedDate not supplied

Physiology of the APUD system.

The characteristic biochemical pathway of the APUDoma cell, namely amine precursor uptake and decarboxylation, are illustrated by the examples of serotonin and catecholamine metabolism. Increasing understanding of the origins of APUDomas as well as the biochemistry and physiology of the hormones they produce, has led to improved methods of detection, imaging and treatment of afflicted patients.

APUD Cells↗
PubMed1991

Serotonin-containing epithelial cells in rat duodenum. II. Quantitative study of the effect of 5HTP administration.

The effect of 5-hydroxytryptophan (5HTP) administration on serotonin (5HT)-containing epithelial cells in rat duodenum was investigated quantitatively using three-dimensional morphometry to determine cell density and HPLC to measure 5HT and 5HTP concentrations. The results are interpreted in terms of the amine precursor uptake and decarboxylation (APUD) capacity of the cells. After administration of 5HTP, no significant change was observed in the density of 5HT-fluorescent epithelial cells in the duodenal region examined. Moreover, no evidence could be obtained that the concentration of 5HT in duodenal villi was increased after 5HTP administration, despite a highly significant increase in serum 5HTP and 5HT levels. These results indicate that no cells in the duodenal epithelium have the ability to decarboxylate exogenously administered 5HTP and convert it to 5HT under physiological conditions.

5-Hydroxytryptophan↗
PubMed1987

Somatostatinoma of Vater's papilla and of the minor papilla.

Two cases of somatostatinomas of the major and minor papilla are reported. The tumors were characterized by solid trabecular and tubular arrangements of tumor cells and in one case by the presence of microvilli and psammoma bodies. The tumor cells contain many amine precursor uptake and dicarboxylation (APUD)-granules with a diameter of 300 to 500 nm and low electron density. Immunoperoxidase stain showed intense staining only for somatostatin and low density of neuron-specific enolase. Those tumors either resulted from pluripotent endocrine cells or from D-cells of the mucosa or glands of the papilla.

APUD Cells↗
PubMed1982

Melanin production in a medullary thyroid carcinoma.

Melanin production by a medullary thyroid carcinoma (MTC) is reported and discussed. Immunohistochemically, the tumor cells contained calcitonin; by electron microscopy, they bore numerous, heterogeneous granules similar to those described previously in MTCs. One small focus of tumor was pigmented. Here, melanosomes in different stages of maturation were found in dendritic cells that ramified among granule-bearing cells. The remarkable phenotypic divergence in this solitary, nongerm cell neoplasm is unusual but not so surprising in light of the APUD nature and neural crest origin of both the melanocyte and the thyroid C cell, which gives rise to MTC. The authors view the calcitonin and melanosome phenotypes as closely related tumor clones evolving from a common precursor neoplastic cell. This unique "experiment of nature" adds to the set of rare human tumors that make melanin "ectopically."

APUD Cells↗
PubMed1983

[Cutaneous apudoma. Apropos of a case and review of the literature].

It has been suggested that Merkel Ranvier cells, generally considered as belonging to the Apud system, may be the origin of extremely rare skin tumors. The authors analyse the characteristics of an apudoma in connexion with a case, and compare their findings with those of 58 other cases reported in the literature. With light microscopy techniques, the differential diagnosis is essentially one of a non-differentiated primary or secondary carcinoma, or of a lymphosarcoma. Detection by electron microscopy of neurosecretory granules in the cell cytoplasm, the neuron-specific enolase activity, when this is detectable, the possibility of ectopic polypeptide secretions, and the evolution potential of the tumor, are all features warranting inclusion of this type of tumor in the category of apudomas.

APUD Cells↗
PubMed2006

Evolution of the diffuse neuroendocrine system--clear cells and cloudy origins.

As early as the 2nd century, Galen proposed that 'vital spirits' in the blood regulated human bodily functions. However, the concept of hormonal activity required a further 18 centuries to develop and relied upon the identification of 'ductless glands', Schwann's cell and the recognition by Bayliss and Starling of chemical messengers. Bernard's introduction of 'internal secretion' and its role in homeostasis laid a physiological basis for the development of endocrinology. Kocher and Addison recognized the consequences of ablation of glands by disease or surgery and identified their necessary role in life. Detailed descriptions of the endocrine cells of the gut and pancreas and their putative function were provided by Heidenhain, Langerhans, Laguesse and Sharpey-Schafer. Despite the dominant 19th century concept of nervism (Pavlov), in 1902, Starling and Bayliss using Hardy's term 'hormonos' described secretin and in so doing, established the gut as an endocrine organ. Thus, nervism was supplanted by hormonal regulation of function and thereafter numerous bioactive gut peptides and amines were identified. At virtually the same time (1892), Ramón y Cajal of Madrid reported the existence of a group of specialized intestinal cells that he referred to as 'interstitial cells'. Cajal postulated that they might function as an interface between the neural system and the smooth muscles of the gut. Some 22 years later, Keith suggested that their function might be analogous to the electroconductive system of the heart and proposed their role as components of an intestinal pacemaker system. This prescient hypothesis was subsequently confirmed in 1982 by Thuneberg and a decade later Maede identified c-Kit as a critical molecular regulator in the development and function of the interstitial cells of Cajal and further confirmed the commonality of neural and endocrine cells. The additional characterization of the endocrine regulatory system of the GI tract was implemented when Feyrter (1938) using Masson's staining techniques, identified 'helle Zellen' within the pancreatic ductal system and the intestinal epithelium and proposed the concept of a diffuse neuroendocrine system. Pearse subsequently grouped the various cells belonging to that system under the rubric of a unifying APUD series. Currently, the gut neuroendocrine system is viewed as a syncytium of neural and endocrine cells sharing a common cell lineage whose phenotypic regulation is as yet unclear. Their key role in the regulation of gastrointestinal function is, however, indubitable.

APUD Cells↗
PubMedDate not supplied

The dynamic histopathologic spectrum of lung cancer.

The APUD concept has postulated that pulmonary carcinoids and small cell carcinomas arise from the neural crest. In development from hypothesis to tautology is traced, and evidence is presented that all pulmonary epithelial tumors arise from the primitive endoderm. Morphologic studies show that a dynamic spectrum exists. Not only do various cell types appear within a single section, but cell types may change from biopsy to autopsy with or without chemotherapy. The spectrum is sustained at the ultramicroscopic level in regard to organelles such as desmosomes, tonofibrils, and dense core granules. Secretory products such as ACTH and L-dopa decarboxylase also show that all lung cancers are related. Epidemiologic evidence indicates that small cell carcinomas in uranium miners occur after prolonged squamous cell dysplasia, and that carcinoids occur independently of external carcinogens, but show transitions to other tumors. Finally, experimental evidence indicates that the K cells, to which carcinoids are most closely related, are of local origin.

APUD Cells↗
PubMed1984

[Value of immunohistochemistry in the study of medullary cancer of the thyroid. Implications of the results for the concept of the APUD system and of apudomas].

Immunohistochemical studies in medullary thyroid carcinoma demonstrate the presence of C cells secreting calcitonin but also of other cells secreting other peptides or proteins. These different cells exist in the tumor as well as in metastases. These results and other reported in the literature suggest a common ultimobranchial and endodermal origin for these cells.

APUD Cells↗
PubMed1989

[Paraneoblastic endocrinne syndromes--mechanisms of paraneoblastic hormone production].

The author deals with mechanisms of paraneoblastic hormone production. Paraneoblastic production of protein hormones is closely linked with processes of malignant transformation of cells which takes place as a result of dysregulation of hyperactive c-oncogens. Products of these oncogens either directly code growth factors or form their receptors or the receptors of dijerent hormones. The product of the family of c-ras-oncogens creates by excessive formation of G-proteins an excessively long activation of adenyl cyclase by hormones which act via cAMP. Under the influence of c-oncogens proliferating and differentiating stem cells reach in larger amounts the APUD stage of differentiation, where they express their genes for the formation of the entire range of protein hormones. Their ectopic formation may acquire biological or clinical significance, as relatively many cells remain in the APUD stage of differentiation, if the process of postscriptional adjustment of the formed hormones is not impaired.

Cell Transformation, Neoplastic↗
PubMed1977

Neuro-epithelial bodies in the lung of the rat and the mouse.

Histochemical and ultrastructural examinations were performed on neuroepithelial bodies (N. E. B.) in the lung of the mouse and rat. The N. E. B. were identified as specialized groups of pale, columnar cells. They were located throughout the intrapulmonary airway. These cells displayed some special cytochemical properties also seen in the APUD (Amine Precursors Uptake and Decarboxylation) endocrine system, such as cytoplasmic argyrophilia and the capability of selective uptake of amine precursors. Ultrastructrally the N. E. B. were composed of a kind of granulated cell which had concentrations of specific cored vesicles in the basal cytoplasm. It seemed likely that the cells released the contents of the cored vesicles into the extracellular space by exocytosis. These cells made extensive and intimate contact with the mitochondria-rich nerve terminals which occurred mainly at the level of the supranuclear portions of the granulated cells. In this contact area, the membrane of the nerve terminals were apposed to that of the granulated cells with a consistent gap of about 20 nm. Among these membrane appositions, some membrane thickenings were observed in which cored vesicles were closely associated in the granulated cell cytoplasm. From these observations, it was conceived that the lung N. E. B. function both as receptor and endocrine organs and that their specific cored vesicles may have an intimate correlation with these dual functions.

APUD Cells↗
PubMed1982

Ultrastructural and histochemical observations of neuroendocrine granules in nonneoplastic ovaries.

Argyrophil and argentaffin cells are rarely seen in female genital tract structures. Their presence in normal, apparently healthy ovaries has not been reported until the present observation. Histochemical and ultrastructural studies demonstrated cells within the ovaries of two nonpregnant patients in the reproductive age that belong to the neuroendocrine or amine precursor uptake and decarboxylation (APUD) system. The lack of other discernible pathologic conditions suggests that these cells may be normal cellular constituents within the ovaries and lends support to the belief of a neural crest origin for primary ovarian carcinoid not associated with teratomatous or mucinous elements.

APUD Cells↗
PubMed1980

Neuroendocrine skin carcinoma associated with calcitonin production: a Merkel cell carcinoma?

An elderly woman presented with an ulcerating skin carcinoma located over the right parietal area. It healed after local radiotherapy but recurred locally and metastasized to the subcutaneous tissue and one regional lymph node. Neurosecretory granules were demonstrated ultrastructurally, and blood levels of calcitonin were repeatedly elevated. A metastasizing medullary carcinoma of the thyroid was suspected, and a total thyroidectomy was performed; however, no medullary carcinoma or C cell hyperplasia could be identified. Furthermore, the calcitonin levels remained unchanged following thyroidectomy, whereas they decreased twice after the skin tumor or its metastases were ablated. Clinical follow-up for over seven years revealed no other lesion that could have been responsible for the overproduction of calcitonin. The ultrastructural features of this skin carcinoma and its metastases, particularly the neurosecretory granules, were reminiscent of those of the so-called Merkel cell. We conclude that this skin carcinoma might indeed produce calcitonin, that this tumor may be derived from Merkel cells, and that Merkel cells may belong within the APUD system.

Aged↗
PubMed1977

Catecholamine accumulation in neural crest cells and the primary sympathetic chain.

Catecholamine accumulation in chick embryos of stages 16 to 24 was investigated using formaldehyde-induced fluorescence. Fluorescence first appeared at stage 21 in the anterior sympathetic chain. After L-DOPA treatment, this fluorescence appeared at stage 18. Noradrenaline could not advance the onset of fluorescence or reconstitute fluorescence after its depletion by reserpine at stages 22 to 24. Under no conditions could fluorescence be identified in neural crest cells prior to their aggregation to form the primary sympathetic chain. Noradrenaline induced fluorescence in the neural tube, notochord, myotome, sclerotome, gut mesenchyme and suprarenal cortical cells. In addition to these structures, the dorsal pancreas and some blood cells were fluorescent after l-DOPA treatment. The implication of the results for the neural crest origin of APUD (Amine Precursor Uptake Decaboxylase) cells is considered.

Animals↗
PubMed2007

Immunohistochemical localization of aromatic L-amino acid decarboxylase in mouse taste buds and developing taste papillae.

Aromatic L-amino acid decarboxylase (AADC) catalyses the decarboxylation of all aromatic L-amino acids. In mammals, AADC is expressed in many tissues besides the nervous system, and is associated with additional regulatory roles of dopamine and serotonin in a wide range of tissues. We examined the expression of AADC by using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR analysis showed that mRNA of AADC was detected in the taste bud-containing epithelium of the circumvallate papilla of mice. By immunohistochemical analyses, AADC was detected in a subset of taste bud cells of fungiform, foliate, and circumvallate papillae. Double-label studies showed that AADC colocalized with serotonin, NCAM, PLCbeta2, and PGP9.5. On the other hand, AADC never colocalized with alpha-gustducin. Our results of double staining with AADC and taste cell markers indicate that only the type III cells could convert 5-hydroxytryptophan (5-HTP) to serotonin within taste buds. Taken together with previous studies, the properties of the type III cell of taste buds exactly fit into the APUD (amine and amine precursor uptake and decarboxylation) cell scheme. Furthermore, in the developing circumvallate papilla, AADC are first detected in a small number of papillary epithelial cells at E14.5. By E18.5, AADC-positive epithelial cells also express PGP9.5, which is one of marker of taste cells, and these cells have been contacted by developing nerve fibers. These results suggest that AADC expression begins at early stages of taste bud cell differentiation, and biogenic amines may act on taste bud differentiation of tongue epithelial cells, and further may regulate innervation of taste bud progenitor cells.

Animals↗
PubMed1977

[APUD system and neuroendocrine tumors ("apudomas")].

Current concepts of the APUD-system combining neuroendocrinal cells located in different organs are presented. The main feature of these cells is the capacity to accumulate precursors of biogenic amines, to decarboxylate them and to produce biogenic amines or polypeptide hormones. The problem of the development of tumours of these cells is discussed, and their morphological, histochemical and clinical features are described.

Biogenic Amines↗