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Abnormal patterns of pulmonary neuroendocrine cells in victims of sudden infant death syndrome.

Ventilatory dysfunction has become the main focus of current research in sudden infant death syndrome (SIDS). This has been correlated with structural abnormalities in the carotid body and respiratory nuclei of the brainstem. In recent studies, the denervating effect of asphyxial brainstem dysfunction on the pulmonary neuroendocrine cells, which probably function as chemoreceptors, was demonstrated and prompted the following study. The pulmonary neuroendocrine system was evaluated in 25 victims of SIDS and 20 control infants, ranging in age from 3 weeks to 7 months and 1 to 12 months, respectively. The pulmonary neuroendocrine cells were stained by the Churukian-Schenk method and the neuroendocrine cell-positive airway values expressed as a percentage of the total number of airways. The range of positive airway values for victims of SIDS was 2% to 97% with a median of 73%. In contrast, the range for the control infants was 1% to 44% with a median of 25.5%. The SIDS victims' percentage was significantly greater than the control infants' percentage (P less than .0001). The number of pulmonary neuroendocrine cells in positive airway was also increased among SIDS victims compared with control infants. The altered pulmonary neuroendocrine cell pattern could be attributable to either brainstem dysfunction or chronic hypoxia. These explanations are not, however, mutually exclusive of one another; in fact, it is possible that both mechanisms may be operative.

APUD Cells↗

[Gastrointestinal endocrine cells in metaplasia of the gastric mucosa and duodenum].

Grimelius reaction and immunohistochemical PAP method were used to study endocrine cells producing gastrin (G-cells), somatostatin (D-cells) and gamma-endorphin (GER-cells) in gastric and duodenal mucosa of 95 males with atrophic gastritis with intestinal and pyloric metaplasia. The number of cells was counted per 1 mm2 of the mucosa. In the cases of marked intestinal metaplasia the number of G-, GER- and especially D-cells in the pyloric region non-metaplastic epithelium decreases and is approaching to its number in the duodenum of the control group. In the foci of marked pyloric metaplasia of gastric corpus the number of G- and GER-cells is almost the same as in the zones of gastric metaplasia of duodenum, and is approximating their number in the pyloric region of controls, thus allowing the designation of pyloric metaplasia as a complete one.

APUD Cells↗

Endometrial argyrophil cell adenocarcinoma with indole- or catecholamine precursor uptake and decarboxylation.

The capacity for indole- or catecholamine precursor uptake and decarboxylation of the argyrophil cell adenocarcinoma of the endometrium was examined by fluorescence microscopy, microspectrofluorometry, and biochemical analyses. Both argyrophil and nonargyrophil cell adenocarcinomas of the human endometrium have been grown serially in nude mice. With the use of the formaldehyde-induced wet-histofluorescence method, yellowish green fluorescence was demonstrated in the cytoplasm of some cells of the argyrophil cell adenocarcinomas after exposure in vitro and in vivo to L-dopa. When 5-hydroxytrytophan was administered in vitro and in vivo to these tumors, an intense yellow fluorescence was also obtained in the cytoplasm. These fluorescent products were located in the argyrophil cells and corresponded to argyrophil granules. Microspectrofluorometrical and biochemical analyses strongly suggested that the yellowish green fluorescent products were dopamine and the yellow ones were serotonin, produced by decarboxylation of each amine precursor.

APUD Cells↗

[Effect of pineal peptides on neuroendocrine system after pinealectomy].

Removal of the pineal gland leads to structural and functional rearrangement of gastric endocrine cells and thyroid C-cells in albino rats, as was shown by immunohistological methods and morphometry. Injection of pineal peptides epithalone and epithalamine eliminated these changes. Biological activity of epithalone is believed to be higher than that of epithalamine.

APUD Cells↗

Neuroendocrine components of the bronchopulmonary tract: hyperplasias, dysplasias, and neoplasms.

The dispersed neuroendocrine (NE) system is represented in the bronchopulmonary tract by the solitary neuroendocrine cells and the neuroepithelial bodies (NEBs). Immunohistochemically, neuron-specific enolase, serotonin, bombesin, and calcitonin are demonstrable in both components, whereas leu-enkephalin is demonstrable only in solitary NE cells. The precise function of and interplay between these two components under physiologic and pathologic conditions are not entirely clear. Current indications are that NEBs act as intrapulmonary chemoreceptors sensitive to hypoxia and hypercapnia, whereas solitary NE cells may have a paracrine, regulatory function. Even less clear is the possible role of solitary NE cells and NEBs in the processes associated with intrauterine and neonatal pulmonary growth and maturation. Various experimental manipulations have resulted in proliferation of solitary NE cells and NEBs. Of particular interest is the apparently selective proliferative effect on NEBs shown by several nitroso compounds. Diethylnitrosamine administration to hamsters for several weeks results in an increase in the number of NEBs and an increase in the number of cells per NEB. These hyperplastic NEBs express the same immunoreactive hormones as their normal counterparts. However, when NEB cells from diethylnitrosamine-treated hamsters are cultured in vitro a notable proportion of the resulting endocrine cells express ACTH immunoreactivity. Interestingly, the neoplasms that eventually develop in these hamsters are not comprised of NE cells. Studies on human bronchi from specimens resected for various types of neoplasms and for bronchiectasis with and without associated chronic obstructive pulmonary disease have revealed frequent hyperplasias of solitary NE cells and NEBs. In about 10% of the specimens, dysplastic aggregates of solitary NE cells and NEBs are found. Unexpected "microcarcinoids" and tumorlets are also seen. The mildly and moderately hyperplastic solitary NE cells and NEBs tend to express the hormones indigenous to the bronchi, whereas in the severely hyperplastic and dysplastic cells, "ectopic" hormones may also be expressed; the latter include predominantly ACTH and vasoactive intestinal polypeptide. A distinct hyperplasia of NEBs has been found in the lungs from individuals living at altitudes ranging from 3400 to 4300 meters; these changes may represent an adaptive response to chronic hypoxia parallel to the hyperplastic carotid paraganglia that may be found in the same type of population. Bronchopulmonary NE neoplasms comprise a spectrum that includes typical carcinoids, well-differentiated NE carcinomas, and NE carcinomas of intermediate and small cell types. Typical carcinoids are predominantly central, display little if any pleomorphism, are richly granulated by electron microscopy, and by immunohistochemistry express predominantly, although not exclusively, hormones indigenous to their site of origin.(ABSTRACT TRUNCATED AT 400 WORDS)

APUD Cells↗

Bodian's silver impregnation of endocrine cells. A tentative explanation to the staining mechanism.

We have recently shown that a variety of proteins, including albumin and immunoglobulins conjugated to colloidal gold, strongly binds to certain basic peptide sequences, and neurohormonal peptides. Silver proteinate, used in the classical Bodian's neurohistological procedure, is now shown to bind to the same peptide sequences in cytochemical model systems. In tissue, gastrin cells and glucagon cells have been reported to show strong unspecific immunocytochemical staining and these cell types also stain in the Bodian's procedure. These results suggest that certain types of unspecific immunocytochemical staining and the Bodian's silver staining method may depend upon a common mechanism, involving binding of labelled or aggregated protein to basic and hydrophobic sequences in tissue.

APUD Cells↗

Hyperplastic lesions of the gastrointestinal endocrine cells.

A substantial body of knowledge is presently available on the morphologic, histochemical, ultrastructural, and functional characteristics of both the normal endocrine cell population of the gut and their related endocrine tumors. In contrast to this, we have only recently begun to recognize the existence of hyperplastic proliferations of various endocrine cell types, and information is therefore steadily accumulating on the morphologic criteria for their recognition, their clinicopathologic correlates and the clinical relevance of this morphologic finding. Hyperplastic proliferations of various endocrine cell types most often develop as a secondary phenomenon in a variety of clinical situations, and may modify the clinical course of the associated condition in a manner that underscores the functional interrelationships these endocrine cells have not only with each other but with other cell types as well. However, similar proliferations may also occur as a primary event (e.g. primary antral G-cell hyperplasia) and give rise to clinical and biochemical features attributable to the overproduction of their specific hormonal product (e.g. Zollinger-Ellison Syndrome, type I). This communication provides a broad overview of the current state of our knowledge of hyperplastic lesions of a variety of gut endocrine cell types in humans, their pathophysiologic significance, their relationship (if any) to the subsequent development of endocrine tumors (i.e. the hyperplasia-neoplasia sequence), and the utility of certain experimental models for the study of such proliferations in a variety of animal species.

APUD Cells↗

Pulmonary neuroendocrine cells: decreased serotonin fluorescence and stable argyrophil-cell numbers in acute hypoxia.

We recorded serotonin-emission intensity using formalin induced fluorescence and counted the number of neuroendocrine cells (NEC's) and neuroepithelial bodies (NEB's) containing argyrophil granules. Comparison of serotonin-emission intensity of NEB's of acutely hypoxic neonates (520 mmHg for 2-2 1/2 h) and normoxic controls showed significantly lower fluorescence in hypoxic animals. Neuroendocrine cell numbers as shown wit Grimelius silver-nitrate stain did not change. This suggests either that the Grimelius stain reacts with compounds other than serotonin, or that the decrease in serotonin in acutely hypoxic rabbits is not sufficient to alter argyrophil stainability.

APUD Cells↗

[Metachronous cancer of the gastro-intestinal tract with signs of endocrine-cell differentiation].

A case of metachronous cancer of gastrointestinal tract is reported. Three poorly differentiated malignant epithelial tumours developed in a 27-year-old patient within three years. They located in the stomach, small and large intestine. Light-microscopically, the tumours were formed mainly of non-differentiated rounded cells with occasional signet ring cells. At electron microscopic examination the presence of mucin granules was confirmed. Moreover, a variable amount of electron-dense endocrine-like granules was found in tumour cells. According to some publications, endocrine differentiation of gastrointestinal cancers is considered to be a poor prognostic feature, hence electron microscopy or special staining when possible can be important in the evaluation of prognosis.

APUD Cells↗

[The functional morphology of the intestines in escherichiosis].

Inflammatory, degenerative and neurocirculatory disturbances in the intestine of children suffering from colibacillosis was followed by pronounced immune reactions: the number of IgG-, IgM- and IgE-containing cells increased and that of IgA-containing cells decreased, the number of enteroendocrinocytes and labrocytes changed. Progressing disturbances of blood circulation enhanced trophic changes of the mucosa, resulting in various complications. The data obtained allowed us to distinguish the syndrome of capillary-trophic insufficiency in the patho- and morphogenesis of colibacillosis.

APUD Cells↗

High activity of mitochondrial glycerol phosphate dehydrogenase in insulinomas and carcinoid and other tumors of the amine precursor uptake decarboxylation system.

The activity of the mitochondrial glycerol phosphate dehydrogenase (EC 1.1.99.5), the enzyme unique to the glycerol phosphate hydrogen shuttle, was measured in normal human tissues and tumors and compared with the activity of succinate dehydrogenase, another enzyme that transfers electrons to ubiquinone at site II of the electron transport chain. Six of 7 insulinomas and 10 of 12 carcinoid tumors showed high glycerol phosphate dehydrogenase activity. The activity was also increased in 3 of 4 gastrinomas, 2 paraganglionomas, 1 of 4 thyroid nodules, and 1 parathyroid tumor. These tissues belong to the amine precursor uptake decarboxylation system. The activity of glycerol phosphate dehydrogenase was generally unremarkable in non-amine precursor uptake decarboxylation system tumors and in normal tissues studied. However, 1 of 2 breast carcinomas, 1 submandibular tumor, and 2 of 3 melanomas were enriched in glycerol phosphate dehydrogenase activity. In general, succinate dehydrogenase activity exceeded that of glycerol phosphate dehydrogenase in all tissues except some of the tissues in which glycerol phosphate dehydrogenase activity was high. Normal tissues, such as the pancreatic beta-cell, which aerobically metabolize glucose rapidly utilize the glycerol phosphate shuttle to oxidize the large amount of NADH formed from glucose metabolism in the cytosol. Whether this is the reason for the enriched activity of the glycerol phosphate dehydrogenase in certain amine precursor uptake decarboxylation system tumors is unknown.

APUD Cells↗

Immunohistochemical study of HNK-1 (Leu-7) antigen in prostate cancer and its clinical significance.

Anti-HNK-1 monoclonal antibody (MAb) was reactive with non-cancerous and cancerous prostatic epithelia, as well as natural killer cells, myelinated nerves and cells from APUD systems. The expression of HNK-1 antigen on prostate cancer was investigated immunohistochemically by avidinbiotin-peroxidase complex (ABC) method with anti-HNK-1 MAb to clarify the relationship between anti-HNK-1 immunostaining of the cancerous tissue and the tumor differentiation, and that between the former and the survival rate of patients. Of 52 patients with prostate cancer, 49 were reactive with anti-HNK-1 MAb, the positive rate being 94%. The well differentiated cancer showed the highest percentage of positive cancer cells and the strongest staining, while the poorly differentiated cancer had the lowest percentage of positive cancer cells and the weakest staining. HNK-1 antigen was highly expressed on prostate cancer, and the better differentiated the cancer, the more HNK-1 antigen expressed. We also analyzed the total 5-year survival rate of the 52 patients, and the average 5-year survival rate and non-progression rate of 32 patients in stage D2 who had received only endocrinotherapy. Significantly higher survival rate and non-progression rate were observed in the group with more than two-thirds positive cancer cells as compared with the group with less than two-thirds positive cancer cells. The results suggest that the expression of HNK-1 antigen on prostate cancer may be a useful prognostic factor for patients with prostate cancer.

Adenocarcinoma↗

Amyloid-containing renal interstitial cell nodules (RICNs) associated with chronic arterial hypertension in older age groups.

A highly significant correlation is demonstrated between the presence in older persons of medullary renal interstitial cell nodules (RICNs) containing amyloid and increased heart weight indicative of chronic arterial hypertension. By contrast, the population with amyloid-free RICNs 1) showed heart weights comparable to those of controls and 2) had a mean age about 11 years less (56.7 +/- 9.6 vs 68 +/- 12 years) than the group with amyloid-containing RICNs. In a series of 55 autopsy cases presenting with RICNs, no individual was younger than 30 years. In two cases, in which fresh material was available, histochemical reactions suggested that the RICNs contained APUD amyloid. It is speculated that fully functional RICNs may evolve on a compensatory base counteracting an increase in mean arterial blood pressure and that the deposition of amyloid within RICNs could be associated with, or be an expression of, a reduced endocrine function of these structures, finally resulting in the development of arterial hypertension.

APUD Cells↗

Neuroendocrine and metabolic factors in pulmonary circulatory control.

New approaches to elucidating control mechanisms of the pulmonary circulation are presented. The relationship of inspired oxygen, pulmonary arterial medial thickness, numbers, and serotonin fluorescence intensity of pulmonary neuroendocrine cells is described. Neuroendocrine cells appear to react to changes in O2 level by a decrease in serotonin emission intensity acutely and chronically. The response of the cell numbers is different between acute hypoxic and hyperoxic exposure but similar under chronic exposure conditions. The roles of neither serotonin nor the regulatory peptides localized in the lung are defined; however, a possible relationship between these elements is described. Although Weir's hypothesis of normoxic pulmonary vasodilatation is compatible with these concepts, evidence for its proof is still lacking.

APUD Cells↗

Endocrine pancreatic tumors.

The pathology and cell biology of endocrine pancreatic tumors are reviewed. It is probable that all these tumors are "functioning" in the sense that they elaborate hormones that cause more or less conspicuous clinical syndromes. Identification of such secretory products is essential for an optimal diagnosis, localization, treatment, and follow-up. Recent data indicate that endocrine pancreatic tumors evolve from progenitor cells of ducts. This histogenetic mechanism may explain the occurrence not only of mixed or multihormonal tumors but also of tumors producing hormones that are absent from the adult human pancreas. In addition to their clinically apparent effects, many endocrine pancreatic tumors affect the surrounding endocrine pancreas in a characteristic way. The mechanisms behind and the potential diagnostic usefulness of these changes are discussed.

APUD Cells↗

[Prostatic type papillary tumor of the urethra with endocrine cells. Immunohistochemical study].

A peculiar variety of prostatic neoplasm harbouring a constellation of endocrine cells is reported. The tumor had a papillary growth projecting into the lumen of the prostatic urethra. The histological appearances were somewhat unusual. One fragment showed a typical feature of a prostatic-type polyp. However, much of the tissue were covered by a dysplastic epithelium. Adenomatous transformation of prostate-type polyp or "endometrial" adenocarcinoma could be considered.

APUD Cells↗

[Melatonin and serotonin in inflammatory colon diseases and colorectal neoplasms].

Patients with inflammatory intestinal diseases and colorectal adenocarcinoma in sigmoid mucosa were examined using light and electron microscopy, immunohistochemical tests, radioimmunoassay and morphometry. Functional morphology of the general population of the endocrine cells and apudocytes producing melatonin and serotonin as well as urine excretion of 6-sulfatoxymelatonin changed in quality and quantity. The parameters showed specificity depending on clinicomorphological variant of colorectal pathology. The findings provide additional criteria in diagnosis and prediction of the course of different types of inflammatory and tumor affections of the colon.

APUD Cells↗

[Distribution of argyrophilic cells in the lungs of human fetuses].

Lungs of the human fetuses have been investigated at the age of 11, 18, 22 and 25 weeks. General histological staining methods and silver nitrate impregnation of the sections after Grimelius have been applied. Single argyrophile endocrinic cells (apudocytes) are revealed in the fetal lungs during all the time investigated. Groups of the argyrophilic cells--neuroepithelial bodies (NEB)--appear later and in small quantity. The quantity of the apudocytes and NEB gradually increases, especially noticeably in the distal parts of the bronchial tree. The number of the apudocytes increases during the canalicular stage of the pulmonary development. The endocrinic apparatus of the human lungs is forming in connection with development of the airy pathways, respiratory part and intraorganic vascular system.

APUD Cells↗