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PubMed1985

[Neuroendocrine larynx cancer of the small cell (oat cell) type. Morphologic and immunohistochemical findings and their significance for therapy].

By combining immunohistochemical, biochemical, and light and electron microscopy techniques, the following original observations concerning the rare and highly malignant small cell ("oat cell") carcinoma of the larynx were made: The typical electron microscopic feature was the presence of neurosecretory granules in some cells. This indicates that this tumour was a carcinoma with endocrinal differentiation. The demonstration of cytokeratins as major cytoskeletal components, as well as the presence of desmosomes, confirmed the epithelial origin of the tumour cells. The detection of neuroendocrinal markers such as calcitonin and neuronspecific enolase (NSE) in some of the tumour cells, as well as the presence of neurosecretory granules allow us to classify this tumour as a neuroendocrinal carcinoma of the small-cell type. This is in accordance with the latest classification of neuroendocrine carcinomas of the lung. The rapid clinical evolution of the disease is typical for patients with anaplastic carcinomas. Laryngectomy followed by adjuvant chemotherapy and radiotherapy is indicated only in cases without metastases. The detection of regional metastases suggests haematogenous spread with distinct metastases, restricting treatment to chemotherapy and radiotherapy.

APUD Cells↗
PubMedDate not supplied

Role of biological markers and probes in lung carcinomas.

Bronchial carcinomas are frequently associated with ectopic secretion of hormones which may be responsible for paraneoplastic syndromes. In non small cells carcinomas, serum calcitonin levels may be raised. Hypercalcaemia can be found in squamous carcinomas and secretion of hCG (responsible for gynaecomastia) in large cells carcinomas. In small carcinomas, many hormones (ACTH, MSH, ADH, calcitonin) can be produced; however, their serial measurements as well as that of the carcino-embryonic antigen add nothing to the information available with standard staging investigations. More recent studies have identified three protein products: the BB-isoenzyme of creatine kinase, bombesin and neurone-specific enolase. The latter seems a promising marker to follow up the course of the disease.

APUD Cells↗
PubMed1990

[Endocrine cells of the small intestine in experimental strangulated intestinal obstruction].

In experiment on 25 cats reproducing small intestinal obstruction it has been established that the number of endocrine cells (EC) and the degree of their saturation with secretory granules increase in 3 and 6 h after the experiment. These indices decrease by 12 and 25 h after the experiment. The results obtained enable to reveal the EC participation in acute intestinal obstruction pathogenesis and to suppose the influence of released serotonin by paracrine way on mucous membrane as well as distant action on peristalsis and blood flow through intramural nerve plexus.

APUD Cells↗
PubMedDate not supplied

[Changes in the gastric mucosa in endocrine-cell cancer].

Mucous membrane from different parts of the stomach has been studied in 53 surgical cases of stomach carcinoma. All the tumours were subdivided into endocrine-cell (EC) and non-endocrine-cell. The background in all cases was chronic gastritis which was most pronounced at the border with tumour and in the pyloro-antral part of the stomach. Hyperplasia of the fundal glands with hyperfunction of the chief and lining cells, hypersecretion of foveal epithelium, pseudo-pyloric metaplasia and helicobacteriosis were more frequent in EC-carcinomas. Dysplastic epithelial changes in EC were found in the lower third of the necks and terminal regions of the intermediar and pseudo-pyloric glands and in some cases in the foveolar epithelium and intestinal crypts. These features of the background and precancerous lesions in EC should be taken into consideration in diagnosis.

APUD Cells↗
PubMed1980

Identification of paraneurons by labelling with quinacrine (Atebrin).

Quinacrine (Atebrin), an antimalarial drug that binds to adenine nucleotides, was used to label paraneurons. The drug was dissolved in physiological saline and intraperitoneally injected (rats, mice, guinea pigs) in concentrations of 120 or 200 mg/kg body weight. The animals were killed three days later and paraneurons were studied in the fluorescence microscope aftre freeze drying. Bright fluorescence is observed in adrenomedullary cells, SIF cells, carotid body chief cells, pancreatic islet cells, anterior pituitary cells, pinealocytes, and mast cells. Weak fluorescence occurs in thyroid parafollicular Merkel cells, and a few entero-endocrine cells. It is suggested that quinacrine binds to ATP or related adenine nucleotides which are stored in secretory granules of paraneurons. Varying fluorescence intensity seems to depend on different concentrations of adenine nucleotides within the storage granules, as well as on the different size and number of these granules in various paraneurons. Besides formaldehyde-induced fluorescence of biogenic amines, HCl-basic dye staining methods and electron microscopy, the method is useful to identify and define paraneurons.

APUD Cells↗
PubMed1991

[Endocrine cells of the duodenal glands in various representatives of Primates].

The duodenum of four species of monkeys, belonging to the genera Macaca and Papio, has been investigated. In order to reveal argyrophil and argentaffin Ec-cells, Grimelius and Masson-Hamperl methods have been used, respectively. In all the species studied in the terminal parts and in the ducts of the duodenal glands presence of endocrine cells is noted; their amount, however, is considerably less than in crypts. Open and close types of endocrine cells++ have been revealed in the glands. A part of the endocrine cells population is argentaffin Ec-cells (about 40% in Papio and 80% in Macaca). This demonstrates participation of serotonin they produce in regulation of the duodenal glands functional activity. Dependence between taxonomic position of the species and degree of endocrine cells++ development in the duodenal glands has been followed. In particular, in representatives of Macaca amount of argyrophil and argentaffin in the glands is greater than in Papio. Possible reasons of the differences are discussed. Comparing the results on investigation of the glands in the primates with those previously obtained for representatives of Carnivora, a suggestion is made concerning some general principles in organization of the proper endocrinic apparatus of the mammalian duodenal glands.

APUD Cells↗
PubMed1986

Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies.

Antibodies to histamine were used to examine the localization of the amine in cells of the stomach and upper small intestine of a great variety of species, including cartilaginous and bony fish, amphibia, reptiles (lizard), birds (chicken) and a large number of mammals. In all species gastric histamine was localized in endocrine cells (invariably found in the epithelium) and mast cells (usually with an extra-epithelial localization). The endocrine cells were identified as such by immunostaining with antibodies to chromogranin A and the mast cells were identified by toluidine blue staining. Histamine-immunoreactive endocrine cells were found almost exclusively in the acid-producing part of the stomach; only rarely were such cells observed in the pyloric gland area. They were fairly numerous in the gastric mucosa of the two subclasses of fish as well as in the amphibia and reptile species studied. Here, the majority of the histamine-immunoreactive endocrine cells seemed to have contact with the gastric lumen (open type cells) and were located in the surface epithelium (certain fish only) or together with mucous neck cells at the bottom of the pits. In the chicken, histamine-immunoreactive endocrine cells were numerous and located peripherally in the deep compound glands. They were without contact with the lumen (closed type) and had long basal extensions ("paracrine" appearance), running close to the base of the oxyntic-peptic cells. In mammals, the number of histamine-immunoreactive endocrine cells in the stomach varied greatly. They were particularly numerous in the rat and notably few in the dog, monkey and man. In all mammals, the histamine-immunoreactive endocrine cells were of the closed type and located basally in the oxyntic glands. They often had a "paracrine" appearance with long basal processes. Histamine-storing mast cells, finally, were few in both subclasses of fish as well as in the amphibian species and in the lizard. They were fairly numerous in chicken proventriculus (beneath the surface epithelium), few in the oxyntic mucosa of mouse, rat and hamster, moderate in number in hedgehog, guinea-pig, rabbit, pig and monkey, and numerous in cat, dog and man.(ABSTRACT TRUNCATED AT 400 WORDS)

APUD Cells↗
PubMed1988

[Morphology of the apudocytes and neuroepithelial bodies in the lungs of rats].

Endocrine cells (apudocytes) and neuroepithelial bodies (NEBs) were revealed in the lungs of rats of different ages by Grimelius' argyrophilic method. Solitary apudocytes were found among the bronchial epitheliocytes, they had the oval, columnar or triangular shape. NEBs comprise groups of argyrophilic cells, in some cases the penetration of neural fibers into the bodies and their branching in the terminals are observed. Apudocytes and NEBs in 1-, 7-, and 15-day-old rats are more numerous in the epithelium of small than big bronchi. In 21- and 30-day-old and in adult animals apudocytes and NEBs are very scarce. The elements under study are likely to take part in the early postnatal development of the rat lungs.

APUD Cells↗
PubMed1985

Medullary thyroid carcinoma and calcitonin.

Medullary carcinoma of the thyroid (MCT) develops from the thyroid C-cells. Thyroid C-cells and MCTs secrete calcitonin (CT), a 32 amino acid polypeptide hormone. The author has described a sensitive direct sequential radioimmunoassay of CT in human serum. The vast majority of healthy subjects had detectable values of serum immunoreactive calcitonin (iCT) and elevated levels were found in patients with MCT. Besides CT, several higher molecular weight substances contribute to CT-immunoreactivity. These substances may represent metabolic products in the processing of a glycosylated procalcitonin to CT. Calcium, several gastrointestinal hormones and ethanol increases CT secretion from normal and neoplastic C-cells, but the physiological regulation of CT secretion has not been firmly established. The author has shown that the levels of serum iCT vary little during day and nighttime. CT acutely reduces bone resorption and, in pharmacological doses, increases urinary electrolyte excretions. A lowering in serum calcium, magnesium and phosphorus levels result but the effect is pronounced only in disease states with a high bone turnover. The physiological role for CT may be preservation of the skeleton at times of increased need for calcium. A causal relationship between postmenopausal osteoporosis and CT deficiency has been proposed. The author has described increased serum 1,25-dihydroxyvitamin D levels and increased trabecular bone remodeling in patients with MCT and normalization of these parameters following surgical cure for MCT. These results were interpreted to indicate that chronic endogenous CT excess directly enhances the renal production of 1,25-dihydroxyvitamin D which, acting synergistically with parathyroid hormone, increases trabecular bone remodeling. Elevated serum iCT is almost invariably found in patients with clinically manifest MCT as well as in several patients with clinically occult MCT. An exaggerated increase in serum iCT levels after provocative testing with pentagastrin and/or calcium can disclose early C-cell neoplasia. Elevated serum iCT may be encountered in non-C-cell neoplasias and in renal insufficiency. Compared to MCT, circulating iCT may show a different immunochemical profile and the response to provocative testing is blunted in these conditions. MCT occurs in a sporadic variety, and in a familial variety as part of two related multiple endocrine neoplasia (MEN) syndromes. MEN IIa consists of MCT and often phaeochromocytomas and/or hyperparathyroidism and invariably exhibits an autosomal dominant mode of inheritance but a variable age of expression.(ABSTRACT TRUNCATED AT 400 WORDS)

APUD Cells↗
PubMed1979

[Double paraneoplastic syndrome and anaplastic carcinoma of the lung. ADH and ACTH levels in the tumoral tissue (author's transl)].

A double paraneoplasic syndrome with hypersecretion of ADH and ACTH revealed the presence of a small cell bronchial cancer in a man aged 62 years. Water and electrolyte anomalies due to the hypersecretions were of such a degree that an occlusive syndrome occurred. Very high levels of ADH and ACTH were found in the tumoral tissue. The measurement of these levels is rarely conducted at the present time but was able to define the mechanism of abnormal secretion of these two hormones in this case.

APUD Cells↗
PubMed1981

[Pathogenetic problems of goiter].

The extrafollicular growth (hyperplasia) of the thyroid parenchyma resulting in the development of epithelial goiter begins with proliferation of thyrocytes of the follicular wall (sometimes called "clear cells" and erroneously identified with the parafollicular cells or C-cells). An important role in the pathogenesis of goiter disease belongs to the transition of the thyroid parenchyma hyperplasia from the initial adaptative (compensatory) reaction which arises under conditions of thyroid hormone production deficiency into the irreversible pathological process of indefinite duration after restoration of the euthyroid state of the patient. It may be assumed that this transition results from stabilization of gradually increasing shift of protein biosynthesis in the thyrocytes towards preferential thyroalbumin formation at the expense of thyroglobulin.

APUD Cells↗
PubMed1994

Immunocytochemical study of intestinal endocrine cells in germ-free mice.

Morphological and functional modifications have been described in the gastrointestinal tract of germ-free rodents in comparison to their conventional counterparts. These differences have been related to the absence of normal flora, but peptides and biogenic amines may also be involved. Enteroglucagon-, peptide YY-, somatostatin-, serotonin-, neurotensin-, chole-cystokinin-, and secretin-producing cells were studied by immunocytochemistry in the ileum, cecum and colon of 10 germ-free, 10 conventional and 5 conventionalized CFW adult male mice. In the cecum and colon of germfree mice, enteroglucagon- and peptide YY-positive cells appeared enlarged, were globular in shape and strongly immunostained. Enlarged and strongly immunostained serotonin- and neurotensin-positive cells were also seen in some germ-free mice. Somatostatin-positive cells and all the endocrine cells of the ileum were similar in the 3 groups, and no cholecystokinin- or secretin-positive cells were observed. Our results are consistent with higher enteroglucagon and peptide YY production in germ-free mice that may be related to the lower cellular renewal rates and slower gastrointestinal transit reported in these animals. Locally produced biogenic amines and peptides may be important factors in the mediation of the effect of the intestinal flora on gastrointestinal structure and function and germ-free mice seem to be a good model for the study of the mechanisms involved.

APUD Cells↗
PubMed1989

Pulmonary neuroendocrine cells. Their secretory products and their potential roles in health and chronic lung disease in infancy.

Pulmonary neuroendocrine cells (PNEC) are granulated epithelial cells distributed throughout conducting airways. Among the bioactive products identified within the secretory granules of these cells are potent mitogens and bronchoactive and vasoactive agents. The secretory status of these cells, which are in greatest number in the fetus and newborn, is modulated by neural reflexes and by changes in airway gas composition. The aggregate data suggest roles for PNEC in airway "chemoception" and/or regulation of airway epithelial differentiation. Marked increases in PNEC are observed in bronchopulmonary dysplasia, where airway and alveolar fibrosis, epithelial metaplasia, and airway and vascular smooth muscle hypertrophy contribute to marked pathophysiologic changes in lung function. Considering the biologic effects of PNEC secretory products, particularly gastrin-releasing peptide on airway epithelial cell and fibroblast proliferation, we propose that an increase in PNEC secretory products in the regenerating airway epithelium may contribute to the development of the pathologic alterations in lung structure seen in bronchopulmonary dysplasia. In this proposed scheme, secretion of abnormally large amounts of bronchoactive and vasoactive agents from PNEC (e.g., serotonin, gastrin-releasing peptide) in response to airway hypoxia and hypercapnia may be partially responsible in the genesis of reactive airway disease and pulmonary hypertension seen in this disease.

APUD Cells↗
PubMedDate not supplied

[Changes in the endocrine apparatus of the gastric mucosa in forms of cancer of varying origin].

The authors studied endocrine apparatus of the mucous membrane of 53 stomachs in various forms of carcinoma. Silver impregnation and electron microscopy were used as well as routine histology and histochemistry. All the tumors were divided into endocrine-cell and non-endocrine-cell tumors (ET and NET). Cells of the diffuse endocrine system take an important part in the development of the background and pretumorous processes in the stomach mucous membrane. Endocrinocyte hyperplasia, degree I and II, of the mucous membrane of the antrum and enterolysation foci was the background for all NET. Endocrinocyte hyperplasia was more pronounced (degree II and III) in ET and spread to the fundal glands being combined with endocrinocyte dysplasia and metaplasia. These changes are assessed as precancerous for tumors with high content of endocrinocytes.

APUD Cells↗
PubMed1981

A scanning and transmission electron-microscopic study on neuro-epithelial bodies in the neonatal mouse lung.

Neuro-epithelial bodies (NEBs) in the neonatal mouse lung have been studied by transmission (TEM) and scanning (SEM) electron microscopy. The TEM appearance of mouse NEBs are easily identified as island-like, half-spherical epithelial protrusions whose surface structure is obviously different from that of the surrounding ordinary respiratory epithelium. Their surfaces are devoid of ciliated cells and are covered by flattened, irregular contoured Clara cells and the apical surfaces of NEB cells. The latter are singly dispersed among the modified Clara cells, and the apical structure consists of characteristic microvillous projections. The SEM also reveals that most of the NEBs (86%) are preferentially located at the branching points of the intrapulmonary airways. The unique surface structure of NEBs, as well as their strategic location at the branching points of airways, gives support to the suggestion that NEBs might function not only as an intrapulmonary chemoreceptor, but also as a local endocrine organ regulating the air-flow and/or blood-flow dynamics in the specific peripheral region of the lung.

APUD Cells↗
PubMed1995

I-45 islet cell antigen is a 68kD neuroendocrine protein.

A monoclonal antibody approach was used to characterize islet cell differentiation antigens involved in autoimmunity related diabetes mellitus. This procedure yielded islet cell monoclonal antibodies (ICMAbs) that demonstrated varying tissue/cellular distribution. The ICMAb I-45 showed a pan-islet reactivity similar to the reactivity of islet cell autoantibodies. The target antigen of the ICMAb I-45 demonstrated a neuroendocrine distribution. Single step immunoaffinity purification of I-45 antigen using I-45 monoclonal antibody immunoaffinity matrix yielded a 68kD protein. The specificity of the immunoaffinity purified 68kD protein was further demonstrated by the lack of binding of this protein to immunoaffinity columns of irrelevant monoclonal antibodies. The neuroendocrine distribution of the I-45 antigen, like that of other differentiation molecules like HISL-19, neuron specific enolase and chromogranin A strengthens the hypothesis of neuroectodermal origin of the islets of Langerhans.

APUD Cells↗
PubMed2000

Divergent neuroendocrine differentiation in prostatic carcinoma.

A rich variety of neuroendocrine cells are present in the normal prostate gland. Prostatic carcinoma may show divergent differentiation towards a neuroendocrine phenotype in the form of neuroendocrine small cell carcinoma or carcinoid-like tumors. Much more common is focal neuroendocrine differentiation in prostatic adenocarcinoma which may be pronounced in approximately 10% of adenocarcinomas. The prognostic significance of focal neuroendocrine differentiation in prostatic carcinoma is controversial but current evidence suggests an influence on prognosis related to hormone resistant tumors and/or a role in the conversion to a hormonal resistant phenotype. Chromogranin A appears to be the best overall tissue and serum marker of neuroendocrine differentiation. Chromogranin A serum levels may be useful in the assessment of the emergence of and/or progression of hormone resistant cancer.

APUD Cells↗
PubMed1990

[Changes in the prostanoid content and the population of endocrine cells in jejunal biopsies from celiac children].

Prostanoid content prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) and endocrine cells population were evaluated in jejunal biopsies from celiac children; findings were compared to active celiac patients on a challenge diet. Patients were divided as follows: Group A: 14 children with active untreated celiac disease; Group B: 7 celiac children on gluten challenge who had received diet therapy for the past 2 years; Group C: 8 normal control children. Jejunal biopsies were used for endocrine cell population measurement by immunocytochemistry, using a specific marker (chromogranin), and for prostanoid radioimmunological evaluation. The quantitative assessment of the endocrine cell population in Groups A and B revealed a significantly higher number of endocrine cells (20 +/- 11.5; 18.4 +/- 9.8 n. cell/visual field respectively) compared to Group C (8.44 +/- 2.3 n. cell/visual field) (p less than 0.05). In the jejunal extract the PGE2 content (341.8 +/- 82.3) ng/g) for Group A biopsies was significantly higher than that of Group C biopsies (93 +/- 23 ng/g) (p less than 0.05. The PGE2 content (69.4 +/- +13.2 ng/g) for Group B did not show any statistically significant change. In contrast, TxB2 content in jejunal biopsies from all three groups was not significantly different.

APUD Cells↗