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At least 811 records · Page 45Linked to original sources
PubMed1986

The endocrine cells of the digestive system: amines, peptides, and modes of action.

The endocrine cells of the digestive system (entero-endocrine cells of gastro-intestinal epithelia and Langerhans' islets of the pancreas) and the chemical messengers produced by them constitute a complicated and complex system. The physiological function of this system is the regulation of all processes related to digestion and resorption, and to homeostasis of carbohydrate metabolism. Using morphological and histochemical features of this cellular community, the present review deals with amines and amine metabolism, polypeptides and their immunohistochemical identification, and with the modes of action of enteric and pancreatic hormones. Special attention is paid to the significance of amine precursor uptake and decarboxylation (APUD), to immunohistochemical methodology and the interpretation of immunohistochemical findings, and to local regulatory mechanisms, especially paracrinia. Finally, unifying concepts for the integration of these cells and similar endocrine cells of other organs into a common system are considered.

APUD Cells↗
PubMedDate not supplied

Embryologic concepts in the APUD system.

The amalgamation of the neural and endocrine physiologic mechanisms for functional homeostasis as a neuroendocrine system is brought into focus in this chapter on the embryologic concepts in the APUD system. The neuroendocrine system, now regarded as the third division of the nervous system, is a regulatory mechanism that links the functions of the autonomic nerves and the endocrine cells throughout the body. The current realization that both neural and endocrine actions are often involved in the clinical manifestations of many syndromes is clarified by the theories on the embryologic origin of the APUD system described here. Relevant historical developments, as well as cytochemical discoveries, have been gradually integrated into the evolving theories of the embryologic origin of the APUD system. These theories have not been without controversy, but new developments stimulate new concepts and, as new investigative tools have produced a plethora of new information that continues to push investigators, basic and clinical into new horizons, earlier theories have been modified and new theories have been developed. These theories are reviewed in chronological order in this chapter.

APUD Cells↗
PubMed1981

hCG and hCG subunits as tumour markers in patients with endocrine pancreatic tumours and carcinoids.

Serum levels of hCG, hCG-alpha- and hCG-beta-subunits were measured in 29 patients with APUD-tumours, 16 patients with endocrine pancreatic tumours (EPT) and 13 patients with carcinoids. Twenty out of 29 patients (69%) had elevated level of hCG and its subunits. Among patients with EPT, 11 out of 16 (69%) had raised levels of these peptides. Three patients with benign tumours had normal concentrations, thus giving a frequency of 85% in the group of malignant EPT. In patients with carcinoids 9 out of 13 (69%) had elevated serum levels of at least one of the components. A discordance in secretion pattern between the two types of APUD-tumours was noticed. Only one patient, a case with a carcinoid had raised levels of the complete hCG molecule. The levels of hCG-alpha were elevated in 23% of the patients with malignant EPT and 69% of the patients with carcinoids while the corresponding frequencies of raised hCG-beta levels were 69% and 8%, respectively. Three out of 4 patients with so-called non-functioning islet cell tumours had raised levels of the subunits. These results indicate that hCG subunits are valuable tumour markers in both of these APUD-tumours, and that malignant EPT predominantly secrete hCG-beta- and carcinoids hCG-alpha-subunits.

APUD Cells↗
PubMedDate not supplied

[Endocrine polyadenomatosis with carcinoid tumor].

The authors review 26 cases of multiple endocrine tumours with presence of a carcinoid tumour. In 44% the carcinoid was localised to the bronchus, in 20% of cases to the small intestine or duodenum. In 76% of cases during multiple endocrine tumours, the carcinoid appeared in embryological derivatives of the anterior part of the intestine. No carcinoid syndrome was reported. The difficulty of histological distinction has led to the description of carcinoid islet cell tumours. These facts fit in with the APUD concept.

Adenoma, Islet Cell↗
PubMed1995

Small cell carcinoma of the tonsil.

Extrapulmonary small cell carcinomas are rare tumors of the APUD system. They are most commonly seen in the esophagus with rare cases reported in the head and neck. We present the sixth reported case of primary small cell carcinoma of the tonsil. These tumors are usually widely disseminated initially. Aggressive locoregional treatment with radiation is the treatment of choice. Systemic treatment is needed for presumed metastatic disease. Surgery may be an adjunct treatment used for locoregional control.

Carcinoma, Small Cell↗
PubMed1992

111In-octreotide scintigraphy in oncology.

Various tumors of neuroendocrine origin that have amine precursor uptake and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous (IV) 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 to its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]- octreotide) was developed. This analogue is excreted mainly via the kidneys, with 90% of the dose being present in the urine 24 hours after injection. Using 111In-octreotide scintigraphy, seven of seven gastrinomas, four of seven insulinomas, one of one glucagonomas, three of three unclassified APUDomas, and none of 18 exocrine pancreatic carcinomas were visualized. Also, 19 of 19 carcinoids, 15 of 15 glomus tumors, eight of 12 medullary thyroid carcinomas, six of six small-cell lung carcinomas, four of four growth hormone-producing and six of nine clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied in visualizing breast cancer, lymphomas, and granulomas. In 39 of 50 patients with breast carcinoma, 10 of 11 patients with non-Hodgkin's lymphomas, three of three patients with Hodgkin's disease, and eight of eight patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, and also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy showed more tumor sites than did conventional imaging techniques. The results of imaging in vivo correlated with the somatostatin-receptor status on the tumors in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1979

Lysosomes in Brenner's tumor simulating secretory argentaffin granules.

Argentaffin cells were searched for in the epithelial nests of 30 Brenner's tumors, with the Fontana-Masson stain for the screening. Although these cells were found in five tumors, ultrastructural examination of one case, in which the argentaffin cells were multiple, identified the cytoplasmic granules as lysosomes and not as amine precursor uptake and decarboxylation (APUD)-type granules. We conclude that the epithelial component of Brenner's tumors consists of urothelium only and does not include the cells containing argentaffin APUD-type granules.

Brenner Tumor↗
PubMed1982

[Chemosensitive structures of the medulla oblongata participate in blood pressure regulation and belong to APUD-system].

It was shown in 25 experiments on anesthetized spontaneously breathing and immobilized artificially ventilated cats that the cooling of the intermediate chemosensitive area of the ventral surface of medulla oblongata to 20-22 degrees C is followed by depressor reaction that is more pronounced after preliminary occlusion of the sinocarotid and vagus nerves. Two types of apudocytes were revealed in this brain area with the use of the histochemical and immunohistochemical techniques. The first type cells are typically nervous and contain noradrenaline. The second type apudocytes adjacent to the microvascular wall showed melatonin and its precursors. It is assumed that the cells detected participate in the arterial pressure control.

APUD Cells↗
PubMed1987

A histochemical study of APUD ability in the taste buds of experimentally induced zinc-deficient mice.

To explore the relationship between taste acuity and zinc deficiency, a histochemical investigation was made into the taste buds of mice fed a zinc-deficient diet. Nine weeks after the start of the diet, the average serum zinc level of the mice was 45% lower than that of a control group of mice. Moreover, growth was arrested significantly. Two-bottle preference tests revealed that the intake ratio of 10(-5) M quinine hydrochloride solutions had increased markedly in the zinc-deficient mice compared with the controls. The circumvallate taste buds showed no morphological changes. Fluorescent histochemical examination showed an uptake of a monoamine precursor (5-HTP) by the gustatory cells in the zinc-deficient mice after the 5-HTP treatment. Upon immunohistological examination, however, no serotonin immunoreactivity appeared in the gustatory cells of the zinc-deficient mice after the 5-HTP treatment. These results suggest that zinc-deficiency may induce hypogeusia and decrease the ability to transform a monoamine precursor to monoamine in the gustatory cells, albeit the monoamine precursor uptake ability is not affected.

APUD Cells↗
PubMed1987

[Peptidergic innervation and the APUD system in normal conditions and in various pathological states].

The use of highly sensitive and selective methods (autoradiography, light and electron microscopy, radioimmunoassay) allowed identification of peptide hormones in both the specialized endocrine cells (apudocytes) of some internal organs and various structural elements of the central and peripheral nervous system. Current knowledge permits one to suggest the existence of a peptidergic innervation as one of the parts of the nervous system and to demonstrate the direct participation of these peptides in the pathogenesis of some diseases. Biological significance of these substances in supporting homeostasis determines the urgent need for a combined investigation of the structural-functional relationship between apudocytes and peripheral nerves under normal and pathologic conditions. This will promote new opportunities in the elucidation of the mechanisms of some pathologic processes.

APUD Cells↗
PubMedDate not supplied

Neuron-specific enolase-like immunoreactivity in human Leydig cells.

Using the peroxidase anti-peroxidase immunocytochemical technique, neuron-specific enolase (NSE)-like immunoreactivity (NSE-LI) was revealed in Leydig cells of adult human testes at the light microscopic level. Differences in the NSE staining intensity were observed between the individual Leydig cells, separate cell groups within a testis and between the testes of individual patients. Together with the already established substance P-like immunoreactivity (SP-LI), the results obtained provided further evidence for the possible neuroectodermal origin of human Leydig cells and their presumable relation to the APUD- or the Diffuse Neuroendocrine System (DNES).

Adult↗
PubMed1982

Expression of receptors for tetanus toxin and monoclonal antibody A2B5 by pancreatic islet cells.

Studies of the reaction of antibody A2B5 and tetanus toxin with pancreatic islet cells, islet cell tumors, and other human amine precursor uptake and decarboxylation (APUD) tumors are described. By indirect immunofluorescence, antibody A2B5 and tetanus toxin were shown to specifically bind to the plasma membrane of human, rat, chicken, and mouse islet cells. The binding of antibody A2B5 to the cell surface of living islet cells has allowed isolation of these cells from a suspension of pancreatic cells by using a fluorescence-activated cell sorter. In studies designed to determine whether tetanus toxin and antibody A2B5 bound to the same surface antigen, A2B5 and tetanus toxin did not compete for binding to normal islet cells, a human islet cell tumor, or a rat islet cell tumor. In addition to binding to islet cell tumors, antibody A2B5 reacts with frozen sections, isolated cells, and cell lines of neural, neural crest, and APUD origin.

Animals↗
PubMed1981

Neuron-specific enolase is produced by neuroendocrine tumours.

Neuron-specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase, which was first found in extracts of brain tissue, and was later shown to be present in APUD (amine precursor uptake and decarboxylation) cells and neurons of the diffuse neuroendocrine system but not in other peripheral cells. 90 neuroendocrine neoplasias (APUDomas) (including islet-cell tumours, phaeochromocytomas, medullary thyroid carcinomas, oat-cell tumours, and APUDomas of the gut, pancreas, and lung) reacted strongly with antisera to NSE. In addition, large amounts of the enzyme were found by radioimmunoassay in the tumours (mean 1626 +/- 479 SEM ng of NSE/mg protein), whereas control non-endocrine neoplasias contained less than 15 ng NSE/mg protein. Thus NSE, a specific enzyme produced in the neural and endocrine systems, was found to be produced in considerable quantities by all types of APUDomas but not in any non-endocrine tumours. NSE seems to be a useful and easily detected marker which may be used to distinguish endocrine from nonendocrine neoplasias. Clinical detection of endocrine tumours is difficult and such tumours are often missed. Use of NSE as a marker may avoid this.

Apudoma↗
PubMed1977

Attempted treatment of inoperable pheochromocytoma with streptozocin.

Currently the only treatment available for inoperable pheochromocytoma is symptomatic and palliative with alpha- and beta- adrenergic blockade. Pheochromocytoma is a tumor of chromaffin tissue derived from the neural crest and closely related to other APUD (amine precursor uptake and decarboxylation) cell tumors, including those of the pancreatic islets. Streptozocin has been used with varying success in some of these tumors and therefore merited a trial in pheochromocytoma. We used streptozocin to treat two patients with inoperable pheochromocytoma; the drug failed to have any effect, either on catecholamine excretion or tumor growth.

Adult↗
PubMed1984

Anti-ulcer drugs and hypergastrinism: utilization in surgery.

The peptic ulcer disease associated with hypergastrinemia is very often a challenging problem of diagnosis and therapy. In absolute surgical emergency (haemorrhagic and perforative complications), the utilization of the most recently discovered anti-ulcer drugs appears to be extremely helpful; the prevention of incumbent complications can be accomplished, in fact, during the post-operative treatment and the "free time" so obtained can be used for an adequate differential diagnosis (gastrinoma-induced Zollinger-Ellison syndrome: antrum retained, G cells of the antrum hyperplastic, apud-tumours with hypersecretion). The "anti-H2 and anti-muscarinic" drugs (often in association) give the surgeon the possibility of an accurate diagnosis and the choice of the best surgical procedure (tumorectomy, DCP, gastrectomy). Even in elective surgery the prevention with anti-H2 drugs permits greater "safety margins" and an optimal follow-up study. The results of the surgical experience in the General Surgical Clinic of Pisa (18 cases of Z.E.'s) confirm the validity of the associated anti-ulcer therapy.

Cimetidine↗
PubMed1995

[Gamma-enolase (gamma-eno)].

Enolase catalyzes the interconversion of 2-phosphoglycelate and phosphoenolpyruvate in the glycolytic pathway. Enolase isozymes are dimers formed from three subunits (alpha, beta, and gamma). The gamma subunit, containing enolase (gamma-enolase) in serum, is important in the diagnosis of tumors originating from APUD (amine precursor uptake and decarboxylation) cells, like neuroblastoma, small cell carcinoma for the lung and certain carcinomas of the thyroid, the pancreas and the gut. Therefore, the determination of serum gamma-enolase levels is useful as a tumor marker of these neoplasms. On the other hand, raised gamma-enolase levels in cerebrospinal fluid have been demonstrated in patients suffering from various neurological disorders. In this paper, the author reviews the results of some of many studies related to gamma-enolase, up to now.

Animals↗
PubMedDate not supplied

[Immunohistochemistry of biomolecular markers of early thyroid cancer].

Surgery material from 28 cases was studied. Thyroid adenoma differs from thyroid carcinoma by a lower level of expression of Ki-67 and bcl-2, while the mutated p53 expression is lacking. These indices may be used for early and differential diagnosis of thyroid carcinoma. Medullary carcinoma is a tumor with the highest malignant potential and p53 and bcl-2 may serve as markers of a higher degree of malignancy. Ki-67 may serve a marker of proliferative activity of tumors belonging to the same histological type. Thus, its high expression in follicular carcinoma is an index of a high proliferative activity of its cells, correlates with its rapid growth and should be taken into consideration in therapy and prognosis. Expression of bcl-2 clearly correlates with neuroendocrine differentiation of carcinoma and its highest expression was found in the medullary carcinoma as well as in the chromogranin positive cells of the papillary thyroid carcinoma. APUD amyloid deposits in medullary carcinoma and high levels of c-myc in adenomas indicate some genetic restructurizations in malignant and benign thyroid tumors.

Acute Disease↗
PubMed1982

Morphological and cytochemical characterization of neuroepithelial bodies in fetal rabbit lung. I. Studies of isolated neuroepithelial bodies.

Neuroepithelial bodies (NEB) in 29-day fetal rabbit lung were examined by light microscopy and cytochemistry to demonstrate their structural and biochemical properties in situ. Longitudinal sections of NEB at airway bifurcations demonstrated their chemoreceptor-like appearance. Furthermore, the cytochemical presence of serotonin, acetylcholinesterase, formaldehyde-induced fluorescence, and silver-staining properties demonstrated the neural-like biochemical properties of NEB cells. Forty-one NEB and eight single neuroendocrine cells from whole fetal lungs were examined ultrastructurally. Juxtaluminal junctional complexes composed of tight and intermediate junctions, desmosomes, and cytoplasmic filaments were demonstrated in the corpuscular-shaped NEB. Basal bodies were apparent in NEB cell cytoplasm; cilia extended from NEB cells. Dense-core vesicles (DCV) were of at least three types: type 1, type 2, and enterochromaffin type. The majority of epithelial cells adjacent to NEB in near-term airway epithelium were undifferentiated, with large amounts of glycogen. However, ciliated cells were adjacent to some small NEB and single neuroendocrine cells; mucus or Clara-type cells were not observed. NEB isolated by collagenase treatment revealed an intact organoid structure, DCV, and desmosomes and retained their argyrophilia and formaldehyde-induced fluorescence. NEB were recovered in cell fractions separated by unit gravity that had cells in clumps of four or more. One to five NEB stained with silver in cytocentrifuge preparations of control, mixed cells, whereas up to 20 intact NEB were demonstrated in the clump-containing, separated fractions. We propose that isolated NEB retain certain biochemical and metabolic properties similar to those of their counterparts in situ. Serotonin and 5-hydroxyindole acetic acid were found by high-performance liquid chromatography analysis in the fractions containing NEB, and amine precursor uptake and decarboxylation (APUD) activity were demonstrated. Moreover, muscarinic cholinergic receptors were detected, consistent with the occurrence of acetylcholinesterase in NEB. The elution profile of bombesin radioimmunoactivity substantiated that isolated fetal rabbit NEB contained this neuropeptide and that NEB were enriched by unit gravity sedimentation. These studies suggest that NEB are structurally and functionally developed before other cell types in immature airway epithelium and can be isolated as intact organoids, which retain some of their structural and metabolic integrity.

APUD Cells↗