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PubMed1990

Pulmonary endocrine cells in plexogenic pulmonary arteriopathy.

A study of the numbers of pulmonary endocrine cells per cm2 of section of lung obtained at combined heart-lung transplantation in 25 cases of plexogenic pulmonary arteriopathy demonstrated that the peptide which may become unduly prominent in pulmonary arterial disease is bombesin. The type of vascular disease in which bombesin becomes prominent is plexogenic pulmonary arteriopathy, be this primary or secondary to congenital heart disease. The increased prominence of bombesin appears to be related to the stage reached in the arteriopathy. Increased numbers of pulmonary endocrine cells are found in association with classic cellular plexiform lesions with narrow vascular channels. Their numbers are within normal limits when the plexiform lesions are mature with wide vascular channels and narrow intervening septa. The pulmonary endocrine cells are most prominent in the pre-plexiform stage when smooth muscle cells in the inner half of the media of the pulmonary artery show increased electron density, and migrate through gaps in the inner elastic lamina to reach the intima. Here they are transformed into myofibroblasts and proliferate. The migration of muscle cells may be related in some way to long-acting trophic factors released from the pulmonary endocrine cells into the surrounding tissues from which they reach the blood and hence the pulmonary arteries.

Adolescent↗

PubMed2006

HIP/PAP, a member of the reg family, is expressed in glucagon-producing enteropancreatic endocrine cells and tumors.

Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) protein, a member of the reg family, is constitutively expressed by some specialized epithelial cell subsets in the digestive tract and the pancreas. We performed a detailed analysis of the expression of HIP/PAP protein in normal digestive endocrine cells according to their localization, lineage, and differentiation stage, and in digestive endocrine tumors according to their site of origin and hormonal profile. In both adult and fetal normal tissues, HIP/PAP expression was detected only in endocrine cells of the small intestine, ascending colon, and pancreas. Two different expression patterns were identified: (a) a strong cytoplasmic labeling observed in the endocrine cells of the digestive mucosa and the outer rim of Langerhans islets specialized in the synthesis of glucagon and glucagon-like peptides; (b) a weak cytoplasmic immunoreactivity observed in the other pancreatic endocrine cell populations. HIP/PAP expression was detected in 36 of the 184 cases of digestive endocrine tumors examined; 32 of these cases (89%) were pancreatic. The 2 patterns observed in the normal state were retained: (a) a strong labeling was observed in 5% to 100% of tumor cells in 26 tumors, all expressing glucagon or glucagon-like peptides; (b) a weak labeling was present in 10 tumors, presenting various hormonal profiles. In conclusion, a strong expression of HIP/PAP is characteristic of glucagon-producing normal and neoplastic enteropancreatic endocrine cells. Our results lend further support to the concept that members of the reg family play regulatory roles in various endocrine cell populations and that their expression in endocrine cells is lineage-specific.

Adolescent↗

PubMed1987

Endocrine cells in ectocervical epithelium. An immunohistochemical and ultrastructural analysis.

A systematic study of endocrine cells in the ectocervix was carried out using histochemical, immunohistochemical and ultrastructural techniques. Serotonin and calcitonin immunoreactive cells were demonstrated in this site. Serotonin and calcitonin immunoreactivities were coexpressed in the same endocrine cell. These distinctive cells were encountered in two main morphological varieties of ectocervical epithelium. Normal-appearing stratified squamous epithelium contained only very rare serotonin and calcitonin cells. In contrast, endocrine cells were fairly abundant in a specific epithelium termed "transitional-like". This type of epithelium was not only confined to the transformation zone but could also extend onto the portio as far as the vaginal cut margin. In some cases, transitional-like epithelium bore morphological resemblance to urothelium. In other cases, it could be regarded as basal cell hyperplasia or immature squamous metaplasia. Of interest, serotonin and calcitonin cells have been well-documented as normal inhabitants of some other non-squamous epithelia, such as urothelium or pseudostratified columnar epithelium. Therefore, it is suggested that certain ectocervical epithelia show some similarities to urothelium, in respect of their morphological appearance and endocrine profile. Further investigations using more objective and specific markers of urothelial cells are needed to assess the exact degree of homology connecting all these types of epithelium.

Calcitonin↗

PubMed1988

Clonal origin of columnar, mucous, and endocrine cell lineages in human colorectal epithelium.

Human colorectal epithelium is composed mainly of columnar, mucous and endocrine cells; origin of these cell lineages from a multi-potential stem cell at the base of the crypt (the Unitarian hypothesis) has been proposed but not yet demonstrated. Gut endocrine cells have variously been considered of neural crest or endodermal origin, but conclusive evidence, particularly in humans, is lacking. It has been shown that in mouse gastrointestinal tract, a single progenitor cell gives rise to both columnar and mucous cells, but it has yet to be demonstrated that such a progenitor cell can also give rise to endocrine cells. Here, a single human rectal adenocarcinoma cell has been shown to differentiate into columnar, mucous and endocrine cells; therefore all epithelial lineages are of clonal origin. Additionally, these results show that human colorectal enteroendocrine cells, at least in neoplastic epithelium, have an endodermal origin.

Adenocarcinoma↗

PubMed1998

Identification of glycine-extended CCK peptides in endocrine cells and modulation of CCK amide and CCK Gly content and secretion from endocrine tumor cells by an inhibitor of amidation.

Immunoreactive glycine-extended CCK peptides are found in normal mouse cerebral cortex and are very abundant in some CCK expressing endocrine tumor cells in culture. The glycine-extended forms in mouse cortex and in cell lines mirror their respective amidated forms. Mouse cerebral cortex, mouse AtT20 and rat WE cells produce mainly CCK 8 amide and CCK 8 Gly. In contrast, mouse intestinal STC-1 cells produce CCK 22 and CCK 8 amide along with forms of CCK Gly which are slightly larger than their respective amidated forms. The CCK 8 Gly-like peptide from AtT20 cells, after desulfation, co-eluted on HPLC with unsulfated CCK 8 Gly. Addition of copper and ascorbate to culture medium of WE cells caused a small increase in secretion of amidated CCK, without changing cellular levels of this peptide. Treatment with the amidation inhibitor diethyldithiocarbamate greatly decreased cellular content and secretion of CCK amide while it increased cellular content and secretion of CCK Gly. These results provide further evidence that glycine-extended CCK peptides are the immediate precursors of amidated CCK peptides.

Amides↗

PubMed1975

The relationship of gastrointestinal endocrine cells to gastric epithelial changes with special reference to gastric cancer.

Using advanced gastric adenocarcinoma and carcinoid as human material and gastric adenocarcinoma in rats induced by MNNG and in mice by localized X-irradiation of the stomach as experimental material, a pathological study was made on the relationship of gastric endocrine cells to gastric cancer. The results of the present study suggest that most of the endocrine cells in the cancer tissue are derived from the differentiation of cancer cells. Therefore, the following three may be given as the aformentioned relationship, that is, 1) carcinoid of endocrine cell origin, 2) endocrine cell carcinoma showing undifferentiated adenocarcinoma, and 3) endocrine cell cloning developed from the differentiation of cancer cell of adenocarcinoma. There is the possibility that most of 2) are of 3) origin and thus 2) and 3) should be discriminated from 1), having a functioning tumor in rare cases. The significance of reactive hyperplasia of endocrine cells in the non-metaplastic mucosa of the stomach around cancer and atypical epithelium is not yet determined, but that of EC cell seems at least to be related with the development of intestinal metaplasia in the gastric mucosa.

Adenocarcinoma↗

PubMed1987

Endocrine cells of gastric aberrant pancreas by PAP staining method.

Histopathological classification of gastric aberrant pancreas has been done by Heinrich's criteria. However in some case it was difficult to detect incomplete Langerhans' island consisting of several endocrine cells or a single endocrine cell by usual H-E staining. To identify the distribution of incomplete Langerhans' islands and endocrine cells, we applied an enzyme antibody method utilizing PAP method for 7 cases of gastric aberrant pancreas. It became easy to identify the endocrine cells such as single cell and islet cells by using the PAP method. In all 3 cases of aberrant pancreas classified as Heinrich type II and one of 2 case of type III, Langerhans' islands or endocrine small cell groups and single cells were found. The PAP staining method was useful to determine the Heinrich's classification of the aberrant pancreas.

Adult↗

PubMed1983

Gut endocrine cells in rat intestinal-tract carcinoma induced by 1,2-dimethylhydrazine.

Gut endocrine cells in a total of 122 intestinal-tract adenocarcinomas induced in inbred Wistar rats by 1,2-dimethylhydrazine dihydrochloride were examined histologically, ultrastructurally, and immunohistochemically for gastrin, somatostatin, vasoactive-intestinal polypeptide (VIP), and glicentin (enteroglucagon). Of the 122 tumors, argyrophil cells were detected in 42 tumors (34.3%) comprising 15 tumors of the well differentiated type and 27 tumors of the poorly differentiated type, including signet-ring-cell carcinomas. Of the 27 tumors of the poorly differentiated type, 12 were regarded as endocrine-cell carcinomas composed of numerous argyrophil or argentaffin cells and mucus-containing cells. Immunohistochemically, 7 of the 12 tumors had glicentin and two of these seven tumors also had gastrin and argentaffin cells synchronously. None of the tumors showed immunoreactivity for somatostatin and VIP. Nine of the 12 tumors metastasized to the lung, pancreas, liver, mesenterium, omentum, and lymph nodes. The metastatic foci of these tumors were also shown to have glicentin and argentaffin cells. Ultrastructurally, four types of endocrine granule were found in the tumor cells and amphicrine cells containing endocrine granules and mucous granules were noted. These endocrine-cell tumors were assumed to develop from totipotent immature cells of endodermal origin.

1,2-Dimethylhydrazine↗

PubMed1984

Intracerebral allotransplantation of purified pancreatic endocrine cells and pancreatic islets in diabetic rats.

Allogeneic pancreatic endocrine cells (PEC) and whole islets from inbred Lewis (AgB 1/1) and outbred Wistar rats were implanted intracerebrally (i.c.) into two designated areas of streptozotocin-induced diabetic ACI (AgB 4/4) rats across the major histocompatibility barrier. All the transplants of PEC from Lewis (n = 12) and Wistar (n = 7) donors remained functional for an observation period in excess of 200 days. In contrast, only 3/6 Lewis and 3/9 Wistar whole-islet transplants were able to maintain function for a prolonged period. Recipients with functional PEC or islet allografts had normalized nonfasting blood glucose (BG) in the 24-hr. BG profile, and they maintained a steady body weight gain. ACI recipients of PEC from Lewis rats had glucose disappearance K rates of 1.3 +/- 0.3 (mean +/- SE) and a normal basal BG level in 4 hr following the i.v. glucose load. Histological section of the brain tissues with successful i.c. islet or PEC grafts up to a duration of 5 1/2 months revealed healthy endocrine cells in the cortex and the subarachnoid space. These grafts were permeated with capillaries but devoid of exocrine tissues or lymphoid cell infiltration. These observations suggest that the brain is an immunologically privileged site, and that it is a hospitable site for the pancreatic endocrine cell suspension. However, the immunological protection offered to allogeneic transplants by the brain is incomplete, and purified PEC must be employed to ensure consistent long-term allograft survival.

Animals↗

PubMed1987

[Malignant mixed mesodermal tumor with endocrine cells of the corpus uteri].

A case of uterine malignant mixed mesodermal tumor harboring endocrine cells is reported. Endocrine cells were immunocharacterized as serotonin, somatostatin and pancreatic polypeptide cells. This variety of mixed müllerian tumor is added to other endocrine cells-containing neoplasms of the uterus.

Adenocarcinoma↗

PubMed1985

Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract.

Existing methods for the histochemical demonstration of gastrointestinal cells are somewhat limited. Chromogranin represents a family of proteins that coexist with catecholamines in the secretory vesicles of adrenal medulla cells. In the present study, immunocytochemistry was used to test whether chromogranin is a marker for gut endocrine cells. Serial sections of each area of human gut were immunostained for chromogranin and for the amine and each of the peptides known to be present in mucosal endocrine cells. Chromogranin was immunostained in large numbers of endocrine cells in all tissues examined. All identified endocrine cell types were found, in serial sections or by sequential silver impregnations, to be chromogranin immunoreactive. However, the possibility exists that some chromogranin-immunoreactive cells contain a yet to be discovered endocrine substance. Immunostaining of chromogranin thus appears to provide a means for demonstrating all gastrointestinal mucosal endocrine cells identifiable by the methods described in this study.

Chromogranins↗

PubMed1985

[Nephroblastoma with endocrine cells. Immunohistochemical study].

A case of a nephroblastoma harbouring numerous endocrine cells is reported. Endocrine cells were immuno-characterized as serotonin and somatostatin cells. In addition, a small group of pigmented cells, probably melanin-containing, was observed. This tumor could belong to the teratoid variety of nephroblastoma.

Child, Preschool↗

PubMed1994

Prevalence and prognostic significance of endocrine cells in colorectal adenocarcinomas.

Sporadic differentiation of endocrine cells inside adenocarcinomas of the gut (combined tumors) has been observed mainly in the stomach and less frequently in the colon. Since one or more lines of endocrine cells could be present, a wide-spectrum marker of neuroendocrine cells seems to be useful in defining the prevalence of an endocrine component in colorectal carcinomas. One hundred and fifty-eight cases of unselected colorectal adenocarcinomas were immunohistochemically evaluated on formalin fixed and paraffin embedded material, employing streptavidin-biotin-peroxidase-complex (SABC) with anti chromogranin antibodies. All samples were obtained in peripheral areas of neoplastic proliferation without necrosis or haemorrhage. Semiserial sections from each block were cut and stained with H.E., Grimelius, Masson Fontana and SABC anti chromogranin. Chromogranin positive cells were found in 22 of 158 cases (14%). In 18 cases (11.39%), scattered cells (one single cell or a few cells in each section) were located between neoplastic epithelial cells; in 4 cases (2.53%), clusters of chromogranin positive cells were found. Twelve tumors were located in the sigma-rectum, eight in the right colon and two in the left colon. According to tumor grading, five were G1 and seventeen were G2. According to tumor staging following Dukes' classification, eleven were stage B, and eleven stage C. In conclusion, no statistically significant correlations resulted between the adenocarcinoma with endocrine component and tumor location (p = 0.1 n.s.), tumor grading (p = 0.2 n.s.), and tumor staging (p = 0.1 n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1985

The first appearance of endocrine cells in the splenic lobe of the embryonic chick pancreas.

In seeking a source of a pure population of a single type of endocrine cell, the splenic lobe of the chick pancreas was investigated. This was because, in adult life, this lobe contains an abundance of glucagon cells and only a few endocrine cells of other types. The presence of cells containing insulin, glucagon, somatostatin, and pancreatic polypeptide was sought by immunocytochemical means in splenic lobes of normal chicks of 6, 7, and 8 days incubation as well as in splenic lobes which had been removed from donors of the same ages and cultured in isolation from the rest of the pancreas as chorioallantoic grafts. Insulin and glucagon cells were present in all specimens. Somatostatin cells were found in all splenic lobes except one from a normal 6-day embryo. Avian pancreatic polypeptide (APP)-immunoreactive cells were detected in all grafts from donors of 6 or more days incubation and, in normal splenic lobes, were first found at 7 days of incubation. In all grafted and normal splenic lobes older than 7 days on original isolation, glucagon- and APP-immunoreactivities were occasionally present in the same cells. Thus, although the splenic lobe cannot be used as a pure endocrine cell source, this study has demonstrated APP immunoreactivity in the chick pancreas at an earlier stage than has previously been reported, and has also revealed "double staining" of some pancreatic endocrine cells with antisera raised to glucagon and APP.

Animals↗

PubMed1988

Gut endocrine cells in the snail Helix aspersa.

A microscopic study of the endocrine cells present in the gut of the snail Helix aspersa is made. Electron microscopy is necessary in most cases to identify the enteroendocrine cells, since neither silver impregnations nor immunocytochemical staining have rendered positive results. Endocrine cells are scarce and rest on the basement membrane. They display a clear cytoplasm and variable amounts of small (143 nm) secretory granules of diverse electron-density. They are ovoid or rounded and possess apical processes which extend into the lumen of the gut. The nucleus, located in the basal region of the cell, presents characteristic cytoplasmic indentations. Intraepithelial nerve bundles in contact with endocrine cells are present.

Animals↗

PubMed1999

Changes in intestinal endocrine cells in the mouse after unilateral cervical vagotomy.

The effect of right or left unilateral cervical vagotomy on the intestinal endocrine cells was studied in 23 mice at 2 and 8 weeks after operation, respectively. The results were compared with that from 10 sham operated mice. Various types of endocrine cells in duodenum and proximal colon were detected by immunohistochemistry and quantified by computerized image analysis. In mouse duodenum, chromogranin-, CCK/gastrin-, GIP- and somatostatin-cells were significantly decreased at 2 weeks after right vagotomy, but returned to the control levels at 8 weeks. Serotonin-cells were reduced at both 2 and 8 weeks after right vagotomy. The amount of the duodenal endocrine cells did not change after left vagotomy with the exception of secretin-cells, which were diminished at 8 weeks after both right and left vagotomy. In the proximal colon, chromogranin-cells were also decreased at 2 weeks after right vagotomy. Serotonin-cells were reduced at 8 weeks after left vagotomy but not right vagotomy. There was no significant difference between the unilaterally vagotomized and the sham operated mice with regard to PYY- and glucagon-cells. It was concluded that vagotomy affected the intestinal endocrine cells in mouse. The influence was more pronounced in the small intestine than the proximal colon. The right vagus nerves seemed to exert more effect on the intestinal endocrine cells than the left ones.

Animals↗

PubMed1977

Ontogeny of peptide-producing nerves and endocrine cells of the gastro-duodeno-pancreatic region.

The ontogeny of different types of endocrine cells and nerves producing different hormonal peptides was studied by immunocytochemistry. The data indicate that several endocrine cell types are more frequent in the foetal than in the adult gastro-duodeno-pancreatic region. Some cell types were found to show an over-lapping distribution. Such distributional over-laps were more frequent in foetuses and neonates than in adults. Both parallel and non-parallel patterns of development of endocrine cells and peptide-producing nerves were detected. Together with available information on the trophic effects of the gastrointestinal hormonal peptides these findings indicate that foetal and neonatal endocrine cells may participate in the regulation of growth and morphogenesis in the gastrointestinal tract.

Animals↗

PubMed1999

Gastrointestinal endocrine cells in an animal model for human type 2 diabetes.

Endocrine cells were investigated in various parts of the gastrointestinal tract in an animal model for human type 2 diabetes, namely the homozygous obese mouse. As controls, age- and sex-matched homozygous lean mice were used. The different endocrine cell types were stained by using immunocytochemistry and quantified by computerized image analysis. The numbers of PYY- and enteroglucagon-immunoreactive (IR) cells were decreased in the colon of obese diabetic mice vis-à-vis controls. Serotonin-IR cells were significantly decreased in numbers in the duodenum and colon. Furthermore, colonic serotonin cells had a high cell secretory index (CSI), but an unchanged nuclear area, indicating an impaired cellular release of this amine. There was no statistical difference between obese diabetic mice and lean controls regarding the numbers and CSI of antral gastrin/CCK-, somatostatin- and serotonin-; and duodenal secretin-, gastric inhibitory peptide (GIP)-, CCK/gastrin-, and somatostatin-IR cells; nor was there any difference regarding nuclear area, with the exception of the antral somatostatin- and duodenal GIP-IR cells. It is concluded that the abnormalities in gut endocrine cells observed in the present study might explain the gut dysmotility reported in animal models for human diabetes. They may also be of importance in gastrointestinal dysfunction occurring in diabetes patients.

Animals↗