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Mesonephric adenocarcinoma of the uterine cervix with focal endocrine cell differentiation.

A case of cervical adenocarcinoma arising in diffuse mesonephric hyperplasia is presented. The hyperplastic and neoplastic tubules showed focal endocrine cell differentiation. Endocrine cells stained with the Grimelius technique, and were immunoreactive for chromogranin and serotonin. Antisera to additional specific hormones were negative. The natural history of this rare tumor is uncertain; the patient presented in this report is free of disease at 10-year follow-up.

Adult↗

Collagen matrix promotes reorganization of pancreatic endocrine cell monolayers into islet-like organoids.

To evaluate the capacity of pancreatic endocrine cells to reassociate in vitro according to the characteristic topographical pattern observed in the islets of Langerhans in situ, we cultured cells dissociated from neonatal rat pancreas within a three-dimensional collagen matrix. Cell monolayers grown on the surface of collagen gels were covered with a second layer of collagen. This induced the monolayers of endocrine cells to reorganize into smooth-contoured, three-dimensional aggregates, in which non-B cells (identified by electron microscopy and immunofluorescence) had a preferential distribution at the periphery, whereas B cells were concentrated in a central position. These results show that cultured pancreatic endocrine cells have the capacity to reassociate into islet-like organoids in vitro, and that collagen matrices may have a permissive effect on the expression of this potential.

Animals↗

Ontogeny of endocrine cells in the gut of the insect Periplaneta americana.

The ontogeny of the endocrine cells of the gut of the cockroach Periplaneta americana was studied by immunohistochemistry. During embryogenesis, the midgut begins to be formed as an outgrowth of the foregut and hindgut invaginations. Gut endocrine cells with pancreatic polypeptide (PP)-like immunoreactivity begin to appear at the anterior and posterior ends of the forming midgut. These cells are restricted to the midgut epithelium, and no mitotic cells with PP-like immunoreactivity are observed. These results strongly suggest that the gut endocrine cells, at least those with PP-like immunoreactivity, are derived from precursor cells they have in common with other epithelial cells of the midgut.

Age Factors↗

[Development and function of endocrine cells in the proventriculus of the chicken (author's transl)].

An argyrophil endocrine cell type with typical intraepithelial development is seen initially on the 8th day of incubation in the epithelium of the main lumen of the chicken-proventriculus. During the embryonic period, rapid development of these cells can be observed with a quantitative maximum on the 13th day of incubation. At this time increased digestive efficiency is necessary for the chicken embryo with the start of gastric secretion combined with the first swallowing of albumen. There is a subsequent decrease in the number of endocrine cells in the main lumen epithelium, their function in hatched or adult specimens is largely taken over by cells which appear in the epithelium of the glands of the proventriculus on the 16th and later days of incubation. On the 2nd day after hatching the adult distribution pattern of endocrine cells in the proventriculus is attained.

Age Factors↗

An immunohistochemical study of endocrine cells in the alimentary tract of the red-bellied frog, Bombina orientalis.

The regional distribution and relative frequency of endocrine cells was studied immunohistochemically (PAP method) in the alimentary tract of the red-bellied frog, Bombina orientalis, using antisera against serotonin, somatostatin, chromogranin (CG), cholecystokinin (CCK)-8, bombesin, secretin, glucagon and pancreatic polypeptide (PP). Eight kinds of endocrine cells were identified in this study. These immunoreactive cells were located in the gastric glands of the stomach regions and in the intestinal or esophageal epithelium with variable frequencies. They were spherical or spindle-shaped. Serotonin- and somatostatin-immunoreactive cells were demonstrated in the whole alimentary tract including esophagus. CG-immunoreactive cells were restricted to the stomach. CCK-8-immunoreactive cells were observed from the antrum to the ileum. Bombesin-immunoreactive cells were restricted to the stomach. Secretin-immunoreactive cells were demonstrated in the pylorus, duodenum and ileum. Glucagon-immunoreactive cells were found in the antrum and duodenum. PP-immunoreactive cells were detected from the antrum to the rectum. In conclusion, throughout the alimentary tract of the red-bellied frog, the different regional distribution and relative frequency of endocrine cells were demonstrated. The regional distributions and relative frequencies of the endocrine cells in the alimentary tract of the red-bellied frog were resembled to those of the other anuran species except for esophagus.

Animals↗

The measurement of mucosal non-myelinated nerve fibre area and endocrine cell area in coeliac disease using morphometric analysis.

A preliminary morphometric analysis of non-myelinated nerve fibres and endocrine cells in the mucosa of normal and coeliac jejunal biopsies has been performed at the ultrastructural level. Biopsies from 5 children with histologically normal mucosa and 5 children with coeliac disease have been analysed. The percentage of endocrine cells per unit of crypt epithelial area, the percentage nerve area per unit area of lamina propria and the lamina propria area per unit length of mucosa in the crypt base region has been measured in ultrathin sections. A significantly higher percentage of nerves could be demonstrated in the lamina propria of the crypt base region in coeliac biopsies compared to normal biopsies. The lamina propria area/mucosal length ratio was similar in normal and coeliac disease. The endocrine cell area as a percentage of the crypt epithelial area was also similar in both normal and coeliac biopsies. There was no correlation between the increase in nerve fibre area and the endocrine cell area in coeliac disease.

Adolescent↗

Immunocytochemical studies on endocrine cells of alimentary tract of the pig in the embryonic and fetal period of life.

The study aimed at immunocytochemical analysis of alimentary tract endocrine cells between 20th day of embryonal life and 105th day of fetal life of domestic pig. In the pancreas, presence of endocrine cells was detected already in 20th day and, at the time, the cells comprised around 3/4 all cells in primordia of the organ. Starting at that time, numerous endocrine cells produced insulin and glucagon and individual cells synthesized somatostatin and pancreatic polypeptide. In the 20th day, stomach and duodenum contained single endocrine cells but hormone production was not detected until days 27 and 30. Beginning from this days, both organs manifested rapid increase in the number of gastrin-producing cells. In each of the three organs, the number of somatostatin-producing cells exhibited most extensive changes.

Animals↗

Diethylnitrosamine-induced pulmonary endocrine cell hyperplasia and its association with adenomatosis and adenocarcinoma in rabbits.

Pulmonary endocrine cells are suspected of being the precursors for small cell carcinoma of the lung (SCCL). The purpose of this study was to determine whether Diethylnitrosamine (DEN) can induce SCCL in rabbits. New Zealand white rabbits were injected subcutaneously with 20 mg/kg body weight of DEN, twice per week, starting when they were 1 week old. Controls received saline vehicle only. The animals were sacrificed 6 to 8.5 months after the first injection and lung tissues were processed for light microscopy. Using serotonin (5-HT) as a marker for the endocrine cells, tissue sections were stained immunohistochemically by the avidin-biotin complex method. In both control and DEN-treated animals, serotonin-immunoreactive cells organized into neuroepithelial bodies (NEBs). There was an apparent increase in the size, number, and stainability of NEB in DEN-injected animals. A majority of these NEBs were localized in the alveolar duct region. Small foci of adenomatosis and well-differentiated adenocarcinomas, which sometimes coexisted with hyperplastic pulmonary endocrine cells, were also found in the DEN-treated rabbits.

Adenocarcinoma↗

Localisation of mRNA and co-expression and molecular forms of GRP gene products in endocrine cells of fetal human lung.

The presence of bombesin (gastrin-releasing peptide, GRP)-like immunoreactivity in mucosal endocrine cells of human fetal lung is well established. In this study we have investigated the localisation of pro-GRP mRNA and GRP gene products and compared the distribution and levels of extractable GRP- and C-terminal flanking peptide of human pro-GRP-like immunoreactivity in order to verify synthesis and to investigate their coexistence and molecular forms. Human fetal lungs (14 to 23 weeks gestation) were immunostained, and extracts were assayed using region-specific antisera to pro-GRP. Additional antisera to chromogranin and protein gene product 9.5 (PGP 9.5) were used for immunostaining by the peroxidase anti-peroxidase technique and for double immunofluorescence staining using antisera raised in two species. Immunoreactivity for both bombesin (GRP) and flanking peptide was seen mainly in the same endocrine cells, but more cells were stained with antisera to flanking peptide than with antiserum to bombesin (GRP). In situ hybridisation showed that pro-GRP mRNA was present and thus synthesis of the peptides was taking place. Endocrine cells and nerve fibres were PGP 9.5-immunoreactive, and a subset of cells was immunoreactive for bombesin gene products. Radioimmunoassay and chromatography show that pro-GRP is present in both the uncleaved and cleaved forms, and, in agreement with immunocytochemistry results, that an excess of C-terminal peptide of pro-GRP is detectable. It is therefore concluded that GRP-like peptides and flanking peptide are co-localised in human pulmonary endocrine cells, but the latter is found in larger concentrations than free GRP. Thus GRP-like peptides may be secreted separately from the flanking peptide(s) of pro-GRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Gel↗

Coexistence of gastric- and intestinal-type endocrine cells in gastric and intestinal mixed intestinal metaplasia of the human stomach.

Intestinal metaplasia (IM) in the human stomach has previously been classified into a gastric and intestinal mixed (GI-IM) and a solely intestinal phenotype (I-IM). The phenotypes of mucous and endocrine cells were evaluated in 3034 glandular ducts associated with chronic gastritis. In the pyloric region, the relative expression of gastric endocrine cell markers, such as gastrin and somatostatin, decreased gradually from glandular ducts with only gastric mucous cell phenotype (G type) to GI-IM toward I-IM, while that of the intestinal endocrine cell markers, glicentin, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) was inversely correlated. In the fundic region, gastrin-positive cells emerged in the pseudo-pyloric and GI-IM glands, whereas I-IM glands did not possess any gastrin-positive cells, suggesting the presence of a distinct pathway of intestinalization. Double staining revealed coexistence of gastrin- and GLP-1-positive cells in the same gland and occasionally in the same cell in GI-IM glands. These results suggest that the phenotypes of endocrine cells are in line with those for mucous counterparts and support the concept that all of the different types of mucous and endocrine cells in normal and IM glands might be derived from a single progenitor cell in each gland.

Aged↗

Co-localisation of substance P-, bombesin- and peptide histidine isoleucine (PHI)-like peptides in gut endocrine cells of the dogfish Scyliorhinus stellaris.

The gastrointestinal tract of cartilaginous fishes, like that of higher vertebrates, is known to contain endocrine cells and nerves immunoreactive for a wide variety of peptides, some of which have been structurally characterised. Since we have found that substance P-, bombesin- and peptide histidine isoleucine-like immunoreactivities are similarly distributed in the endocrine cells of the dogfish pyloric stomach, we have tried to establish whether any of these peptides are co-localised. The cells were compared in thin serial sections with both light- and electron microscopical immunocytochemistry. Double immunolabelling was also used to show two immunoreactive peptides in the same tissue section. Further characterisation of the immunoreactivity was attempted by preabsorbing the antibodies with various peptides or synthetic fragments of peptide molecules. Immunoreactivity for all three peptides was frequently present in the same cells, whereas antibodies to other peptides such as gastrin and somatostatin marked different cells. Electron microscopy indicated that all the secretory granules in three morphologically different cell types reacted with antibodies to all three peptides. Dual localisation of unrelated peptides in endocrine cells or nerves is established in many cases, but triple localisation is as yet unusual. The immunoreaction for bombesin-like peptides is different in endocrine cells and nerves, indicating that dogfish bombesin may be present in two forms, in agreement with biochemical evidence.

Animals↗

High avidity antibodies to fetal pig pancreas endocrine cells transfer rejection but are not normally generated to fetal pig pancreas xenografts.

Previous studies on the contribution of T cell-dependent antibody (Ab) to non-vascular xenograft rejection have yielded conflicting results, being confounded by the presence of recipient T cells and the use of different tissues and immunizing regimens to generate Ab. In the present study, the effect of adoptive transfer of Ab on fetal pig pancreas (FPP) and pig PK15 cell xenografts was examined in T cell-deficient severe combined immune deficiency (SCID) mice. T cell-dependent Abs raised by hyperimmunization with different cell types and by FPP transplantation were compared. Ab raised by hyperimmunization with pig thymocytes exhibited strong binding to pig thymocytes and PK15 cells but did not transfer FPP rejection. IgG1 and IgM, but not IgG3, Abs bound strongly to FPP exocrine and connective tissue, whereas binding to endocrine cells in vitro and in vivo was weak or absent. This pattern of Ab binding was similar to that observed after transplanting FPP into BALB/c mice. Furthermore, serum recovered from BALB/c mice 20 days after FPP transplantation bound strongly to non-endocrine but not endocrine cells and did not transfer FPP rejection. In contrast, serum from mice hyperimmunized with PK15 cells bound strongly to PK15 cells and transferred rejection of intraperitoneal PK15 cells. Furthermore, this serum contained IgG1 and IgM Abs that bound strongly, and IgG3 Abs that bound weakly, to endocrine cells in FPP, and also transferred rejection of FPP in SCID mice. These results indicate that endocrine cells express low concentrations of xenoreactive Ab epitopes and that high Ab concentrations and/or high avidity Abs are required for sufficient endocrine cell binding to cause damage and rejection in the immunodeficient mouse model. Such Abs are not elicited by transplanting FPP into immunocompetent mice. Nevertheless, a contribution of Ab to rejection in immunocompetent mice cannot be excluded.

3T3 Cells↗

Endocrine cells in tumour-bearing lungs.

BACKGROUND: When hormones are detected in the serum of patients with bronchial carcinoma they are generally considered to originate from the tumour, but this may be not the only explanation. Pulmonary endocrine cells proliferate in lungs affected by non-neoplastic disease and their products are often demonstrable in the serum. The aim of this study was to examine the pulmonary endocrine systems of a series of tumour-bearing lungs to see whether any changes in them could possibly account for raised levels of pulmonary peptides in the blood. METHODS: The morphology, number, distribution, and content of pulmonary endocrine cells in 30 pairs of tumour-bearing lungs from patients coming to necropsy with bronchial carcinoma were examined. These features were related to the pathology of the tumour and to other pathological changes present in the lungs, and compared with pulmonary endocrine cells in 10 pairs of control lungs from patients without pulmonary disease. RESULTS: Increased numbers of endocrine cells, often in the form of large abnormal aggregates, were present in 17 pairs of tumour-bearing lungs where they were associated not with the tumour but with non-tumoral pathology, especially inflammation and changes associated with cardiac failure. Appropriate and inappropriate peptides were identified within them. CONCLUSION: The possibility is raised that, in some subjects with bronchial carcinoma who have raised serum hormone levels, the source of these substances might be the endocrine cells in the diseased lung around the tumour.

Aged↗

The prevalence, prognostic significance and hormonal content of endocrine cells in gastric cancer.

Twenty-six of 100 cases of gastric adenocarcinoma contained argyrophil cells. All these tumours were carcino-embryonic antigen positive and 13 contained variable amounts of gastro-enteropancreatic peptides and amines. There was no significant difference in mucin type, extent or incidence of intestinal metaplasia between tumours with and those without endocrine cells. The prognosis for both groups was similarly poor, contrasting with that for carcinoid and atypical carcinoid. Endocrine cell hyperplasia was evident in the adjacent mucosa in some of the cases of endocrine positive tumours. There was no association between achlorhydria and the presence of endocrine cells in the tumours. The origin of the neoplastic endocrine cells remains speculative, occurring either as a mutation of a single stem cell or as a synchronous malignant transformation of two epithelial cell types exposed to a particular carcinogenic factor(s). Adenocarcinomas containing endocrine cells appear to be as biologically aggressive as the usual adenocarcinomas of the stomach and therefore should be treated in a like manner.

APUD Cells↗

Development of pancreatic endocrine cells in the rat fetus.

Prenatal development of rat pancreatic endocrine cells was investigated by the immunoperoxidase technique and the following results were obtained: 1) Glucagon immunoreactive cells are first endocrine element of the pancreas appearing already on day 11 of gestation, when the dorsal pancreatic bud is still quite small and the ventral pancreatic primordium is hardly swollen out. Most of the glucagon reactive cells are located in the epithelium of the foregut and the dorsal pancreatic bud but a few of them are attached to the base of the epithelium from the outside. 2) Insulin and pancreatic polypeptide (PP) immunoreactive cells are first demonstrable in small cell clusters budding from the exocrine tubules on day 14, whereas somatostatin and gastrin reactive cells on day 17 and 18, respectively. These findings support the hypothesis that the majority of pancreatic endocrine cells is derived from the epithelium of the foregut. 3) PP reactive cells, appearing first on day 14, assume gradually a peripheral position in the growing islet of Langerhans. Immediately before birth they attain the population and flattened cell shape comparable to those in adult pancreas. Their counterpart in the duodenum is found as open type basal-granulated cells in the rat fetus. 4) Noteworthily, glucagon-like immunoreactivity is found in some neuron-like cells of the Auerbach's plexus between the muscle layers of the duodenum on day 19.

Animals↗

Pulmonary endocrine cells in native Peruvian guinea-pigs at low and high altitude.

The role of pulmonary endocrine cells is unclear, but those which are aggregated into innervated clusters are probably chemoreceptors, responding to hypoxia in the airways, whereas solitary endocrine cells are probably quite different in their function. There were significantly more clusters of endocrine cells in the lungs of a group of 10 indigenous Peruvian guinea-pigs considered to be adapted to high altitude, in comparison with controls from sea-level, whereas there was no difference in the number of solitary cells. It is concluded that, whereas the clusters are indeed responding to and affected by hypoxia, the solitary cells are not, and play a distinct and possibly trophic role in the lung.

Altitude↗

[Immunocytochemical studies on the pancreatic endocrine cells in the Japanese newt (Cynopus pyrrhogaster)].

Pancreatic endocrine cells were examined by light and electron microscopic immunocytochemistry to discuss the co-localization of peptides in one cell type. A cells were irregular in shape with an occasional long cytoplasmic process, and contained glucagon-immunoreactive granules with various contours. These granules were 160-300nm in diameter with various density, and also immunoreactive to anti-human pancreatic polypeptide (PP) serum. A part of them were further immunoreactive to anti-somatostatin serum. B cells were round to elliptical in shape, and often aggregated around the capillaries. Granules of B cells were round to irregular in shape, 270-410 nm in diameter, and immunoreactive to anti-insulin serum. D cells were irregular in shape with meager cytoplasm, and contained somatostatin-immunoreactive granules. These granules were ovoid or teardrop in shape, 140-250nm in longitudinal diameter, and immunoreactive to both anti-somatostatin and anti-human PP sera. PP cells were round to spindle-shaped, and contained human PP-immunoreactive round granules 150-35nm in diameter. These findings reveal the existence of at least 4 types of endocrine cells secreting glucagon, insulin, somatostatin, and PP, respectively, in the newt pancreas, and suggest the co-localization of some of these peptides in one cell type.

Animals↗

Immunohistochemical survey of the gut endocrine cells in the common tree shrew (Tupaia belangeri).

Regional distribution and relative frequency of endocrine cells in the gastrointestinal tract of the common tree shrew (Tupaia belangeri) were studied immunohistochemically. Ten types of immunoreactive endocrine cells were localized in the gastric mucosa, i.e., chromogranin-, serotonin-, gastrin-, somatostatin-, bovine pancreatic polypeptide (BPP)-, enteroglucagon-, pancreatic glucagon-, peptide tyrosine tyrosine (PYY)-, motilin-, and substance P (SP)-immunoreactive (IR) cells. In the intestine, 13 types of immunoreactive cells were observed, i.e., chromogranin-, serotonin-, somatostatin-, gastrin-, BPP-, enteroglucagon-, PYY-, secretin-, cholecystokinin (CCK)-, gastric inhibitory peptide (GIP)-, motilin-, neurotensin-, and SP-IR cells. The regional distribution and relative frequency of the cell types varied along the gastrointestinal tract. Basically, the types, distribution, and relative frequency of the gut endocrine cells were similar to those reported in other mammalian species. However, some characteristic findings were noted in the present study: (1) the considerably large number of gastrin-IR cells in the pyloric region; (2) numerous serotonin-IR cells in the stomach; (3) appreciable number of BPP-IR cells in the transitional region of the stomach; and (4) wide distribution of PYY- and motilin-IR cells in the gut.

Animals↗