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PubMed1980

Enkephalin-, VIP- and substance P-like immunoreactivity in the carotid body.

The carotid body type I cell contains amines and has features, both morphological and cytochemical, which indicate that it may also produce a peptide. Many regulatory peptides are now known to be present in both central and peripheral tissues. In the periphery these neuropeptides occur in both classical endocrine (APUD) cells and the neurones of the autonomic nervous system. We have now investigated the possible presence of neuropeptides in the cat carotid body using both immunocytochemistry and radioimmunoassay. Met- and Leu-enkephalin-like material occurred in considerable quantities in carotid body extracts and enkephalin-like immunoreactivity was localised in type I cells. Both vasoactive intestinal polypeptide (VIP)- and substance P-like immunoreactivity was also present but was localised in nerve fibres distributed throughout the organ. These active neuropeptides are widely distributed in mammalian tissues, forming a diffuse regulatory system which now seems to include the carotid body.

Animals↗

PubMed1990

Atrial natriuretic polypeptide in human adrenal pheochromocytoma: immunohistochemical and immunoelectron microscopical localization.

Using the immunoperoxidase and immunogold methods with specific antibody, we studied the atrial natriuretic polypeptide (ANP) in seven tumor tissues of six patients with adrenal pheochromocytoma. Light microscopically, the reaction product for ANP was observed in all seven tumor tissues. Intracytoplasmic immunoreaction product for ANP was finely granular. In four cases studied with the electron microscope, the immunogold stain for ANP was demonstrated in secretory granules of the tumor cells. A considerable amount of alpha-hANP immunoreactive substance was also extracted from two tumor tissues (67.2 and 28.7 pg/mg wet tissue). This is the first report of the human adrenal pheochromocytoma that contains immunoreactive ANP. These findings provide additional evidence for the multisecretory APUD cells of neural crest origin.

Adrenal Gland Neoplasms↗

PubMedDate not supplied

[Morphofunctional characteristics of the cells of the APUD system of the adrenal glands and the duodenum in the cerebral form of acute radiation sickness].

Changes of a phase nature develop in the APVD system cells of rats, dogs, and monkeys exposed to electron radiation of doses inducing a cerebral form of radiation sickness. These changes in the morphofunctional status of APVD system cells may be considered as a syndrome displaying acute radiation apudopathies.

APUD Cells↗

PubMedDate not supplied

In vitro study of the biology of small cell carcinoma of the lung.

WE HAVE DEVELOPED THREE TYPES OF EXPERIMENTAL SYSTEMS FOR THE STUDY OF SCCL: (1) serially heterotransplanted tumors in athymic nude mice; (2) continuous, clonable cell cultures; and (3) direct clonogenic assays for tumor specimens. These systems have their own individual advantages, applications, and limitations, but these are interrelated and complementary. The study of these systems has greatly aided our understanding of the biology of SCCL, and its relationship to other lung cancers and the APUD cell system. In addition, new markers for SCCL have been identified, such as a creatine kinase and its BB isoenzyme (CK-BB). These cellular markers may have clinical applications, as serum levels of CK-BB are an indicator of tumor burden. Assays for clonogenic tumor cells may permit selection of optimal drug combinations for the treatment of individual tumors. Variant cultures having the morphology of SCCL, but lacking some or all of the other features, have been identified. While our systems have been used primarily for biological studies, they have clinical applications for both diagnostic and therapeutic purposes.

Animals↗

PubMed1976

Formaldehyde induced catecholamine fluoroscence in the mouse inferior laryngeal paraganglion.

The presence of high concentrations of catecholamines is shown in the mouse's inferior laryngeal paraganglion by means of fluorescence histochemistry. In mice, the entire organ is composed of 20 to 25 small, intensely fluorescent cells of oval shape (about 15 mum in diameter). The paraganglion is well provided with capillaries. The identification of catecholamines in the inferior laryngeal paraganglion, originally described as nonchromaffin (parasympathetic) paraganglion, presents additional evidence that all paraganglia store biogenic amines, are related to the sympathetic nervous system, and belong to the APUD cell series.

Animals↗

PubMed1990

Small cell carcinoma of the esophagus. Report of three cases and review of the literature.

Small cell carcinoma has been described in the lung, stomach, pancreas, small intestine, larynx, hypopharynx, thymus, kidney, prostate, breast, cervix, skin, and esophagus. Our three cases and review of the literature confirm that the clinical presentation and eventual evolution of small cell carcinomas of the esophagus appear to be basically similar to those of the far more frequently occurring squamous and glandular carcinomas. However, certain differences in age and sex distribution of cases should be noted. Although squamous cell carcinomas occur three to four times more commonly in males, the male-to-female ratio in SCC in 1.6. Squamous cell carcinomas of the esophagus reach a peak in the fifth and sixth decades of life; SCC cases occur a decade later. All of our patients had history of heavy smoking more than 50 pack-years, a factor that has also been implicated in predisposition to squamous cell carcinoma of the esophagus. History of smoking to this extent was also mentioned in three other patients. There are also some differences in the location of the tumor. SCC rarely occurs in the upper third of the esophagus. The most common location of this tumor is the lower third where APUD cells are most abundant. On the other hand, a majority of squamous cell carcinomas of the esophagus are localized to the middle third, the upper and lower third being involved in equal proportions of the cases. Despite the above reported differences in clinical symptoms and course of these two tumors, their gross appearance is similar. Mean survival of both diseases also seems to be similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1976

Carboxylic ester hydrolases in the thyroid gland of the guinea-pig. A light microscopic study.

The location of cholinesterase and non-specific esterase in the thyroid gland of the guniea-pig was studied with the light microscope. It was found that the idoxyl method for non-specific esterase activity under special conditions is superior to the cholinesterase method in a number of respects for the demonstration of the intra-, inter- and parafollicular cells. When using the indoxyl method the incubation period can be reduced from 2.5-3 hr to 40-50 min. Further, the reaction can be followed during the incubation. False localization of the reaction products is avoided,and nerves and erythrocytes are not stained. By varying the fixation time and the time of storage in gum arabic-sucrose, it was found that the miscellaneous activity of non-specific esterase in APUD cells (C-cells) and follicle cells may be due to both factors. In fresh tissue the activity of the enzyme was equal in follicle and C cells. Special cyst-like structures containing an esterase which is NaF-resistanct when alpha-naphthyl acetate is employed as a substrate and which gives a strong reaction at low pH values when 5-bromo indoxyl acetate is the substrate, are described, and their nature and possible origin are discussed.

Animals↗

PubMed1986

Neuroendocrine heart and hypothalamus.

Data on the endocrine heart--neurosecretory cells of heart, producing coronary-dilatory, metabolically active glycopeptides with physico-chemical and biological properties similar to those of previously discovered cardioactive hypothalamic neurohormones--are summarized. Heart hormones participate in both local and distant regulation of heart metabolism and function. Formation and action of these heart hormones is closely related to hypothalamic cardioactive neurohormones K, C, and G and their protein precursors. Neurohormones from heart and hypothalamus comprise a system of neurohumoral connections between these two organs. A possible role of APUD cells in the generation of a number of heart peptides and glycopeptides exerting hormonal activity is discussed.

Animals↗

PubMedDate not supplied

Regulatory peptides and the lung.

Powerful regulatory peptides have been found in nerves and cells of peripheral tissues. The lung has been found to contain almost all the active peptides previously described. The respiratory tracts of three mammalian species--rat, guinea pig, and cat--were examined, and significant quantities of vasoactive intestinal peptide (VIP), bombesin, substance P, somatostatin, and cholecystokinin were found. The VIP nerves were most numerous in the upper respiratory tract, particularly the nasal mucosa. A close association with seromucous glands, blood vessels, and bronchial smooth muscle was particularly noteworthy and paralleled the pharmacologic actions of VIP, i.e., secretomotor, vasodilatory, and smooth muscle relaxation. In contrast, bombesin was localized to epithelial amine precursor uptake and decarboxylation (APUD) cells, which were particularly numerous in the fetus, suggesting a possible role in control of pulmonary growth. Substance P, a peptide thought to subserve a sensory role, was localized to fine nerve fibers, with a particularly close association with bronchial epithelium. The quantities of somatostatin and cholecystokinin were very low and, therefore, difficult to localize. In the human, bombesin and VIP were present in considerable quantities. Bombesin cells were again most numerous in the fetal and neonatal small bronchi and bronchiolar epithelium. During development VIP-ergic nerves showed little change in number but demonstrated a gradient of distribution, with the largest quantities located in the extrapulmonary airways. In preliminary investigations of pulmonary disease, bombesin levels were found to be very greatly reduced with acute hyaline membrane disease in the newborn.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1980

Immunoreactive nervous system of specific enolase (14-3-2 protein) in human serum and cerebrospinal fluid.

Nervous system-specific 14-3-2 protein is an acidic enolase (EC 4.2.1.11) isoenzyme which is found in high concentrations in nervous tissue and which is also considered to be a molecular marker for amine precursor uptake and decarboxylation (APUD) cells. A radioimmunoassay for this protein shows levels of immunoreactivity of 10 ng/ml and 5 ng/ml in human cerebrospinal fluid and serum respectively. The immunoreactivity in concentrated cerebrospinal fluid dilutes out in parallel with the standard curve in the assay, has a similar molecular weight to the immunoreactivity in soluble protein extracts of whole human brain, and on polyacrylamide gel electrophoresis migrates as two forms representing the homodimer and probably the heterodimer species of the enzyme. The protein also occurs at relatively high levels in erythrocytes and an approximately 1% haemolysis would be sufficient to account for the normal serum level of immunoreactivity. Clinical measurements of 14-3-2 protein in neurological disorders or APUD-system disease could be potentially useful in cerebrospinal fluid but are unlikely to be of value in serum.

Brain↗

PubMed1984

5-HT immunoreactive hypothalamic neurons in rat and cat after 5-HTP administration.

Using immunohistochemistry for serotonin (5-HT) after administration of 5-hydroxytryptophan (5-HTP), we have demonstrated the existence of a particular group of 5-HT accumulating neurons in the posterior hypothalamus of the rat and cat. This cluster of neurons, which we termed "5-HT immunoreactive (IR) posterior hypothalamic magnocellular neurons," was characterized by: (1) diffuse 5-HT-IR staining; (2) rather large-sized cell bodies; (3) a marked activity of monoamine oxydase (MAO); (4) capacity of uptake and decarboxylation of 5-HTP; and (5) the absence of capacity of uptake and hydroxylation of tryptophan. These 5-HT-IR magnocellular neurons extended from the suprachiasmatic nucleus area to the caudal end of the hypothalamus. In the rat, the majority of these neurons was found in the tuberal and caudal magnocellular nuclei, whereas in the cat, it was found more widespread in the ventrolateral part of the posterior hypothalamus including the tuberomamillary nucleus. The characteristics of the 5-HT-IR magnocellular neurons which project directly both to the cerebral cortex and the pontine tegmentum are discussed in comparison with those of "APUD" cell series or "paraneurons," as well as with those of other 5-HT-IR neurons demonstrated in the hypothalamus after administration of 5-HTP or tryptophan.

5-Hydroxytryptophan↗

PubMed2000

Multiple familial cutaneous glomangioma: a pedigree of 4 generations and critical analysis of histologic and genetic differences of glomus tumors.

BACKGROUND: Glomangiomas are benign tumors arising from neuromyoarterial cells surrounding cutaneous arteriovenous anastomoses that serve as temperature regulators. They exist as solitary or multiple types, occurring sporadically or in a familial pattern, the latter of which is rare. OBJECTIVE: We describe a 4-generation pedigree of familial cutaneous glomangioma, in addition to the 3 other well-documented pedigrees reported in the literature to date, and we clarify ways in which to distinguish the different types of glomus tumors. METHODS: Nodular skin lesions of 4 affected family members were analyzed by histologic, immunohistologic, and electron microscopic methods. To elucidate the gene defect in this family, we searched for a linkage to a candidate locus on chromosome 11q23 previously identified in paragangliomas, one form of glomus tumor, in 16 family members of 4 generations by using polymorphic markers. RESULTS: The diagnosis of disseminated cutaneous glomangiomas was confirmed histologically in 4 family members of 3 different generations. Glomangiomas were transmitted in an autosomal dominant pattern via the paternal line. Genetic linkage analysis of the affected family members excluded linkage to chromosome 11q23. CONCLUSION: An autosomal dominant pattern of inheritance has been described for glomus tumors of the paraganglioma type originating from the APUD cell system, the underlying genetic defect of which has been mapped to chromosome 11q23. In contrast, we show that the genetic defect in disseminated cutaneous glomus tumors of the glomangioma type deriving from smooth muscle cells or pericytes is not linked to chromosome 11. Thus we suggest that the common term glomus tumor, used for both paragangliomas and glomangiomas in the current literature, is misleading and should be avoided because these tumors have different histologic derivation and genetic origin.

Adult↗

PubMed1995

Use of an isotopic somatostatin receptor probe to image gut endocrine tumors.

OBJECTIVES: To evaluate the effectiveness of indium In 111 pentetate (diethylenetriaminepentaacetic acid [DTPA]-D-Phe-labeled octreotide scintigraphy in the localization of gastroenteropancreatic neuroendocrine lesions, and to identify covert lesions, determine multicentricity, define the distribution of metastases, confirm complete removal of tumor postoperatively, and evaluate the efficacy of therapeutic embolization. DESIGN: Unmasked comparison. SETTING: Tertiary care referral center. PATIENTS: We studied 28 patients over a 12-month period. Biochemical evidence of a gastroenteropancreatic tumor was present in 13 patients. Octreoscan 111 was employed in four patients with an ambiguous biochemical diagnosis of gastroenteropancreatic tumor. Postoperative examination to document complete tumor removal was undertaken in seven patients. In one patient, Octreoscan 111 was used to evaluate the efficacy of therapeutic embolization. INTERVENTION: [111In]DTPA-D-Phe-octreotide scintigraphy. MAIN OUTCOME MEASURE: Identification of somatostatin receptor-bearing neuroendocrine tumors. RESULTS: Intravenous administration of [111In]DTPA-D-Phe-octreotide followed by whole-body gamma camera scintigraphy resulted in the localization of gastroenteropancreatic neuroendocrine tumors with 75% sensitivity, 100% specificity, 100% positive predictive value, 63% negative predictive value, and 82% overall accuracy. CONCLUSIONS: While Octreoscan 111 has been shown to localize the majority of amine precursor uptake and decarboxylation system (APUD) cell tumors as well as various other somatostatin-positive tumors, this technique may also be useful in a number of other circumstances. These include prediction of tumors that will respond to octreotide therapy, identification of covert metastases, intraoperative identification of tumors, and postoperative surveillance. Use of an alternative isotope may provide a vehicle for the administration of local therapeutic radiation to tumor cells. The precise efficacy of Octreoscan 111 in the identification of lesions smaller than 3 cm with low-density somatostatin-2 receptor expression remains to be determined.

Adult↗

PubMed1980

Successful therapy of an ACTH-producing gastric carcinoid APUD tumor: report of a case and review of the literature.

A case of a patient with a metastatic ACTH (adrenocorticotrophic hormone)-producing gastric carcinoid APUD (amine precursor uptake and decarboxylation) tumor is presented. The patient presented with Cushing's syndrome and very high levels of ACTH. The Cushing's syndrome was controlled medically, and when the patient deteriorated clinically she received treatment with a combination of BCNU, adriamycin, and ftorafur. She responded dramatically with marked clinical improvement and normalization of plasma ACTH levels. The current status of the APUD cell concept is discussed, with its overall implications for treatment of this group of malignancies.

Adrenocorticotropic Hormone↗

PubMed1982

An original hypercalcemic infantile renal tum or without bone metastasis: heterotransplantation to nude mice: report of two cases.

Two cases of hypercalcemic infantile renal tumor without macroscopic bone metastases are reported. Optical and ultrastructural characteristics as well as biological and clinical data are sufficiently different from those of other infantile renal tumors to justify the individualization of an original tumor entity. The hypercalcemia is not clearly understood but may be related, in one case, with a high N terminal PTH serum level. Ultrastructural elements (secretory granules) and polypeptide hormone products (glucagon) are discussed in relation with APUD cells characteristics.

Animals↗

PubMed1988

Thyroid uptake of MIBG in Sipple's syndrome.

The use of the adrenomedullary tracer metaiodobenzylguanidine (MIBG) in the localization of medullary carcinoma of the thyroid (MCT) is based on the embryologic relationship of the APUD cell series. The authors report the results obtained in six patients with MCT: two had Sipple's syndrome and four sporadic forms of the disease. MIBG uptake by the CMT was observed in both cases of Sipple's syndrome and in only one of the other cases. Scintigraphic detection seems to depend on the clinical features, the size of the tumour and also on the part played by its secretory function. MCT would thus appear to be more frequently visualized by MIBG in cases of Sipple's syndrome than in sporadic cases. The procedure therefore seems useful in the diagnosis, follow up and even in the treatment of MCT.

3-Iodobenzylguanidine↗

PubMed1976

[Thymic carcinoid. Case report and review of the literature (author's transl)].

A case of a primary thymic carcinoid tumour of a 32 year old male is reported, and the previously published 25 cases are reviewed. The neoplasms occur in adults, predominantly in males: they are located in the anterior or antero-superior mediastinum. The only sufficient treatment is the surgical excision; through radiotherapy may be indicated in some cases, too. The tumour is characterized by the formation of rosettes, ribbons and garlands; sheet-like or medullary areas, and large clusters with central necrosis. The tumour is positive for the Grimelius argyrophil silver stain. Ultrastructurally numerous dense-core "neurosecretory" granules are observed. The formal pathogenesis is similar to that of carcinoid tumours of other locations; particularly of those arriving from derivates of the foregut, respectively from the APUD cell system. At present it cannot be decided whether this particular tumour of the thymus represents an autochthonic thymic carcinoid or simply a teratoma with a differentiation in one direction in the sence of a simplified teratoma.

Adrenocorticotropic Hormone↗

PubMed1979

Release of vasoactive intestinal peptide in the central nervous system in man.

Recent work has shown that vasoactive intestinal peptide (VIP), one of the many candidate hormones of the gut, also occurs widely in neurones. To determine whether the neuronal peptide may have a neurotransmitter function, we studied changes in immunoreactive VIP in dog plasma and human cerebrospinal fluid after the infusion of choline esterase inhibitors (neostigmine and physostigmine, respectively). Immunoreactive VIP was released in both situations. The systemic changes (in VIP levels) were enhanced five weeks after portacaval shunting in dogs. Our results demonstrate that the immunoreactive VIP level increases as a result of choline esterase inhibitors. The plasma "release" may originate either from peripheral peptidinergic nerve terminals or from APUD cells of the gastroenteropancreatic system. The increase in immunoreactive cerebrospinal fluid VIP may very well originate from central neurons, since the peptide does not apparently cross the blood-brain barrier.

Animals↗