The Origin of a New Progenitor Stem Cell Group in Human Development.

The observation of two precursor groups of the early stem cells (Groups I and II) leads to the realization that a first amount of fetal stem cells (Group I) migrate from the AMG (Aortal-Mesonephric-Gonadal)-region into the aorta and its branching vessels. A second group (Group II) gains quite a new significance during human development. This group presents a specific developmental step which is found only in the human. This continuation of the early development along a different way indicates a general alteration of the stem cell biology. This changed process in the stem cell scene dominates the further development of the human stem cells. It remains unclear where this phylogenetic step first appears. By far not all advanced mammals show this second group of stem cells and their axonal migration. Essentially only primates seem to be involved in this special development.

[Disperse endocrine system and APUD concept].

This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

Distribution and morphology of argyrophilic cells in the digestive tract of the African ostrich.

We used light microscopy to elucidate the morphological features of argyrophilic cells in the digestive tract of the African ostrich (Struthio camelus). The results indicated that argyrophilic cells were found to be distributed among the epithelial cells of the mucosa or glands throughout the digestive tract, except for the esophagus; two types of argyrophilic cells were found; i.e., closed-type cells and cells with triangular or elongated shapes and with their apical cytoplasmic process in contact with the lumen (open-type cells); the greatest number of argyrophilic cells was found in the proventriculus, and the argyrophilic cell density gradually decreased from the proventriculus to the rectum; Furthermore, the number of argyrophilic cells in the duodenum and ileum was higher than that in the jejunum. This text still combined the characteristics that the argyrophilic cells in digestive tract of ostrich maybe related to different digestive function of different region and the basis of their morphology to carry on a discussion. It was speculated that argyrophilic cells in the digestive tract may have both endocrine and exocrine functions.

[Effect of pineal peptides on neuroendocrine system after pinealectomy]. / Vliianie peptidov pineal'noi zhelezy na neiroéndokrinnye vzaimosviazi posle pinealéktomii.

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.

Gut endocrine cells in birds: an overview, with particular reference to the chemistry of gut peptides and the distribution, ontogeny, embryonic origin and differentiation of the endocrine cells.

This review deals with gut endocrine cells in birds. It focuses on both morphological and developmental aspects of these cells, which were included members of Pearse's APUD series. They comprise many cell types, which, in birds as in mammals, produce serotonin and a range of regulatory peptides. The chemical structure of most avian gut peptides has been established. These peptides and their functions are outlined here. The types and distribution of avian gut endocrine cells are detailed and compared with the situation in mammals. In birds, ultrastructural work has been limited to certain types of gut endocrine cell and not as widely applied as in mammals. However, immunocytochemistry has found widespread application in studies on birds: the hatching chick and also the adult chicken and certain other species such as the quail and duck have been studied. Gut endocrine cells showing immunoreactivity for the following peptides/serotonin have been identified: somatostatin, pancreatic polypeptide (PP), peptide YY, glucagon, secretin, vasoactive intestinal peptide, gastrin, cholecystokinin (CCK), neurotensin, motilin, gastrin-releasing peptide, substance P, enkephalin and serotonin. The colocalization of different peptides (including chromogranins) and of peptides and serotonin in the same gut endocrine cells is reviewed: notable amongst such associations are glucagon with PP and gastrin/CCK with neurotensin in the same cells. On morphological grounds cells have been identified as endocrine in avian gut from at least 9 days of incubation. Immunocytochemical studies show the majority of the various types first to appear between 12 to 14 days of incubation, with substantial numbers being recorded from 17 days onwards. Experimental studies on chicken and quail embryos have determined the embryonic origin of gut endocrine cells: evidence is unequivocal that such cells arise from the endoderm, not the neural crest, other ectoderm or the mesoderm. Studies on avian embryos have also contributed to our knowledge of mechanisms controlling the differentiation of gut endocrine cells: evidence shows that gut mesenchyme plays an important role in provoking (or inhibiting) the development of gut endocrine cells and there are indications that the endocrine cell pattern in gut is established early and that an axially-derived factor may be important in this process. The kinds of genetic mechanism possibly involved are mentioned but full elucidation of the processes concerned is awaited. A better understanding of the formation of endocrine tumours of the gut should result from the findings.

The origin of gut and pancreatic neuroendocrine (APUD) cells--the last word?

The evidence that gut and pancreatic endocrine cells are not derivatives of the neural crest is overwhelming: yet this conclusion is still not universally accepted. In this editorial attention is drawn to the body of experimental evidence which points conclusively to gut and pancreatic endocrine cells arising from endoderm, not the neural crest, the neurectoderm or neuroendocrine programmed epiblast.

Ontogeny, distribution and amine/peptide content of chromogranin A- and B-immunoreactive endocrine cells in the small and large intestine of the chicken.

Chromogranin A-(CgA-) and chromogranin B-(CgB-)-immunoreactive endocrine cells were investigated in the chicken intestine during embryonic and post-hatching life. CgA- and CgB-immunoreactive cells first appeared in the intestinal tract at various embryonic ages from day 10 in the cloaca to day 16 in the distal ileum and colon. To identify the CgA- and CgB-immunoreactive cells, each tissue section was double-immunostained using a panel of polyclonal antibodies raised against gut amine/peptides. Almost all the serotonin-immunoreactive cells co-localised CgA and CgB along the entire intestinal mucosa and at all ages examined. In contrast, substance P-, peptide tyrosine tyrosine-, neurotensin- and secretin-immunoreactive cells displayed heterogeneous co-localisation patterns. For example, either all or only some cells of a given endocrine type co-stored Cg; they did so variously - only in the embryo, only after hatching, or at both stages, and co-localizing cells were sometimes located within the mucosa only in the villi and not in the glands, and sometimes vice versa. All the CgA/CgB-immunoreactive cells also displayed argyrophilia.

Células endócrinas gastrointestinais: breve histórico e principais métodos de identificaçäo à microscopia óptica / Gastrointestinal endocrine cells: brief history and main identification methods under light microscopy

O trato gastrointestinal apresenta um amplo espectro de células endócrinas distribuídas difusamente ao longo da mucosa, intercaladas com as células exócrinas. Essas células compartilham diversas características como a capacidade de produzir vários peptídios. Apesar do grande desenvolvimento da endocrinologia digestiva, especialmente na última década e no que tange ao conhecimento bioquímica e localizaçao celular dos peptídios reguladores gastrointestinais, seu significado funcional e papel na fisiopatologia digestiva permanecem em parte desconhecidos. É apresentado um resumo das principais informaçoes sobre características morfológicas, histoquímicas, origem embriológica, dados históricos e métodos de identificaçao das células endócrinas do trato gastrointestinal.

[Gastrointestinal endocrine cells: brief history and main identification methods under light microscopy]. / Células endócrinas gastrointestinais: breve histórico e principais métodos de identificação à microscopia óptica.

The gastrointestinal tract shows a wide spectrum of endocrine cells diffusely distributed along the mucosa, interspersed among the exocrine cells. These cells share several features such as the capacity to produce a series of peptides. Despite the development of digestive endocrinology, especially in the last decade and with respect to the biochemical knowledge and cellular localization of gastrointestinal regulatory peptides, their functional significance and their role in digestive phisiopathology remain partially unknown. This review represents a summary of the principal information about morphological and histochemical features, embryologic origin, historical data, methods of identification and types of endocrine cells, of gastrointestinal tract.

Neuroendocrine differentiation in the precursors of prostate cancer.

OBJECTIVES: To review neuroendocrine differentiation in the precursors of prostatic carcinoma (prostatic intraepithelial neoplasia). METHODS: Background information is given on the prostatic neuroendocrine cell and neuroendocrine differentiation in prostatic carcinoma. Neuroendocrine differentiation in prostatic intraepithelial neoplasia is reviewed. RESULTS: Neuroendocrine differentiation occurs in prostatic intraepithelial neoplasia and is intermediate in degree between normal (which has the most cells with neuroendocrine differentiation) and carcinoma. CONCLUSION: Neuroendocrine differentiation in the precursors of prostatic carcinoma may play a role in the pathogenesis of cancer but is speculative at this time. Methods to better assess neuroendocrine differentiation are needed.

[The cytogenesis and differentiation of the epithelial endocrinocytes of the large intestine in hens and rats in ontogeny]. / Tsitogenez i differentsirovka éndokrinotsitov épiteliia tolstoi kishki kur i krys v ontogeneze.

Cytogenesis and differentiation of epithelial endocrinocytes were studied by methods of histochemistry and electron microscopy in large intestine of hen and rat in the course of their individual development. In the embryogenesis processes of cellular and organospecific differentiation occur in epithelium of these animals large intestine, which is proved by early revealing of endocrinocytes, when epithelial plast is yet undifferentiated. Growth of differentiation in hen and rats is marked on day 19-21 of postnatal embryonal development. In postnatal ontogenesis endocrine apparatus achieves definitive state by day 5 in hen and day 20 in rats. Argentaffin cells are the leading sub-population, which reflects the importance of serotonine they produce in realizing regulatory reactions of the organism. Slightly differentiated cells are the source of endocrinocyte cytogenesis.

[The histotopography of the endocrinocytes in the rectal epithelium of hens in ontogeny]. / Gistotopografiia éndokrinotsitov v épitelii priamoi kishki kur v ontogeneze.

Histotopography and content of argyrophilic and argentaffin endocrinocytes per 1 mm2 of section of the hen rectal mucosa in ontogenesis were studied by method of light microscopy. Endocrinocytes were demonstrated in a part of epithelial layer from 12 day of embryogenesis. By 21 day their number increased 23 times. By the 3rd day of postnatal development endocrinocyte number reaches definitive values. Endocrinocytes are evenly distributed in the rectal epithelium, their shape varies. Forming of the endocrine apparatus structural organization in the hen rectum deals with the processes of the early endocrinocyte differentiation in a part of the epithelial layer during embryogenesis.

Carcinoma de células de Merkel / Merkel cell carcinoma

El carcinoma de células de Merkel es un tumor maligno de la piel poco frecuente, descrito en los últimos años como una nueva entidad. Probablemente se origina en las células de Merkel, únicas células de la piel con gránulos neuroendócrinos citoplasmáticos. Afecta predominantemente a mujeres añosas y su localización más frecuente es en zonas expuestas. Puede manifestarse clínicamente como un tumor solitario eritematoso; múltiples tumores en un área (remedando satelitosis de melanoma) o múltiples tumores generalizados (merkeliomatosis cutánea). Existen tres patrones histopatológicos, que en orden de frecuencia son sólido o nodular, difuso (tipo linfomatoso) y trabecular. La microscopía electrónica revela dos estructuras citoplasmáticas típicas: gránulos revestidos de membrana y espirales perinucleares de filamentos intermedios (cuerpos fibrosos). Pueden reconocerse tres grupos de marcadores inmunohistoquímicos:filamentos intermedios (citoqueratinas y neurofilamentos); neuropéptidos pan-neuroendócrinos (enolosa, cromogranina y sinaptofisina) y marcadores de diferenciación epitelial (citoqueratina, EMA y desmoplaquina). Pero la coexpresión de citoqueratinas y neurofilamentos es considerada como la de mayor valor diagnóstico. El diagnóstico se basa en la clínica, la histopatología e inmunohistoquímica, siendo la microscopía electrónica una técnica opcional. El tratamiento de elección es la cirugía con amplios márgenes a la que puede agregarse vaciamiento ganglionar. El tumor es radiosensible y responde a la quimioterapia

Carcinoma de células de Merkel / Merkel cell carcinoma

El carcinoma de células de Merkel es un tumor maligno de la piel poco frecuente, descrito en los últimos años como una nueva entidad. Probablemente se origina en las células de Merkel, únicas células de la piel con gránulos neuroendócrinos citoplasmáticos. Afecta predominantemente a mujeres añosas y su localización más frecuente es en zonas expuestas. Puede manifestarse clínicamente como un tumor solitario eritematoso; múltiples tumores en un área (remedando satelitosis de melanoma) o múltiples tumores generalizados (merkeliomatosis cutánea). Existen tres patrones histopatológicos, que en orden de frecuencia son sólido o nodular, difuso (tipo linfomatoso) y trabecular. La microscopía electrónica revela dos estructuras citoplasmáticas típicas: gránulos revestidos de membrana y espirales perinucleares de filamentos intermedios (cuerpos fibrosos). Pueden reconocerse tres grupos de marcadores inmunohistoquímicos:filamentos intermedios (citoqueratinas y neurofilamentos); neuropéptidos pan-neuroendócrinos (enolosa, cromogranina y sinaptofisina) y marcadores de diferenciación epitelial (citoqueratina, EMA y desmoplaquina). Pero la coexpresión de citoqueratinas y neurofilamentos es considerada como la de mayor valor diagnóstico. El diagnóstico se basa en la clínica, la histopatología e inmunohistoquímica, siendo la microscopía electrónica una técnica opcional. El tratamiento de elección es la cirugía con amplios márgenes a la que puede agregarse vaciamiento ganglionar. El tumor es radiosensible y responde a la quimioterapia

[The distribution of mucosal endocrinocytes in the normal human appendix and in inflammation]. / Raspredelenie éndokrinotsitov slizistoi obolochki cherveobraznogo otrostka u cheloveka v norme i pri vospalenii.

The method of light microscopy was used for studying the histotopography of endocrinocytes of the vermiform process mucosa of man. The direction of their distribution was found in distal, medial and proximal parts of the vermiform process mucosa. The greatest amount of endocrinocytes in normal conditions per 1 mm2 of the mucous membrane was found in the proximal part and it was getting less towards the distal one. In inflammation there occurs an increase of the amount of endocrinocytes (in acute ordinary appendicitis, it is 1.5 times higher, in the phlegmonous form--2 times). With the development of deep destructive processes in the mucous membrane the content of endocrinocytes is sharply decreased.

[Neuroendocrine system and its tumors]. / Neuroendokrines System mit seinen Tumoren.

The original classification of neuroendocrine tumours proposed by Pearse was based on a common embryologic origin in the neuroectoderm. The term, carcinoid, literally means carcinoma-like, was coined in 1907 to describe the histologic similarity of these tumors to carcinomas on the one hand and their generally indolent biologic behaviour on the other hand. Neuroendocrine tumours represent a group with complex biological, histological, ultrastructural and immunocytochemical properties. This concept was replaced by another classification based on results of modern techniques (electron microscopy, immunocytochemistry, molecular and DNA analyses). This permits a more reliable classification of tumours, that can be used to determine their biological behaviour and prognosis.

Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic, prognostic, and therapeutic implications.

Endocrine-paracrine cells of the prostate (also known as APUD or neuroendocrine cells) constitute, in addition to the basal and exocrine secretory cells, a third population of highly specialized epithelial cells in the prostate gland. These endocrine-paracrine cells contain, and most likely secrete, serotonin and calcitonin, as well as variety of other peptides. Little is known of the functional role of these cells, but they probably subserve a paracrine or local regulatory role. They may also regulate via endocrine, lumencrine, or neurocrine mechanisms. These endocrine-paracrine cells probably play a significant role during prostatic growth and differentiation as well as regulating the secretory process of the mature gland. Neuroendocrine differentiation in prostatic carcinoma occurs in the form of the relatively rare small cell carcinoma and carcinoid or carcinoid-like tumor, but most commonly as focal neuroendocrine differentiation in a conventional prostatic adenocarcinoma that is a very frequent, if not ubiquitous phenomenon, and reflects tumor cell heterogeneity mimicking the normal differentiation process. The world's literature on neuroendocrine differentiation in prostatic carcinoma is reviewed. Neuroendocrine differentiation in all types of prostatic carcinoma appears to correlate with a poor prognosis. This correlation is probably multifactorial and may relate to a positive correlation with grade, a direct resistance to hormonal manipulation, and/or autocrine/paracrine growth factor activity due to the secretion of neuroendocrine products. Neuron-specific enolase and chromogranin, as well as other neuroendocrine products, may be useful as serum markers in patients with prostatic carcinoma with neuroendocrine differentiation. New therapeutic strategies need to be developed to treat these tumors. This includes the use of specialized protocols that have been effective against neuroendocrine carcinomas arising in other organ systems.