Fig 1 - uploaded by Mark Kidd
Content may be subject to copyright.
The legacy of the enterochromaffin (EC) cell. Rudolf Peter Heidenhain (1834– 1897) (top) was the first to identify EC cells in the gastric mucosa of rabbits and dogs in 1868. Nikolai Kulchitsky (1856–1925) (center) noted similar cells in the crypts of Lie berkühn in the intestinal mucosa of cats and dogs in 1897. The EC cell origin of appendiceal 'carcinoid' tumor was proposed in 1914 by A. Gosset (1872–1944) and P. Masson (1880–1859) (center left and right) utilizing silver impregnation techniques . In 1906, C. Ciacco (1877–1956) (bottom right) suggested that the term 'Enterochromaffin Cell' be adopted to reflect the special staining properties and anatomical location of the cell. Finally, in 1938, Friederich Feyrter (1895–1973) (bottom left) introduced the concept of a diffuse endocrine system and proposed that this novel entity was the source of 'carcinoid' tumors.
Source publication
By the end of the 19th century, the subject of internal secretion and the consequences of its perturbations had been explored in considerable depth but with little clear understanding. Despite the anatomic delineation of the majority of the glands and tissues that comprised the gross endocrine system, the cellular basis and the interactions between...
Citations
... The journey toward understanding neuroendocrine tumors (NETs) commenced in 1868 with Rudolf Heidenhain's discovery of neuroendocrine cells, later noted by Nikolai Kulchitsky in 1897 [1]. However, it wasn't until 1907 that Siegfried Oberdorfer differentiated between carcinomas and less aggressive ileal lesions, termed "karzinoide" [2]. ...
Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, with the gastric (stomach) subtype (G-NETs) representing a significant clinical focus. Type 1 G-NETs are particularly noteworthy due to their relationship with autoimmune atrophic gastritis (AAG) and pernicious anemia (PA), conditions that impact vitamin B12 absorption. This report presents the case of a patient with a type 1 G-NET identified at the initial diagnosis of PA, demonstrating the connection between these conditions. In the literature review, we discuss the general mechanisms underlying PA, including its etiology, pathogenesis, clinical presentations, and diagnostic approaches. Emphasis is placed on the importance of recognizing and diagnosing this condition early, given the treatable nature of the associated gastric neuroendocrine dysregulation. Additionally, the report examines the broad spectrum of G-NETs, with a special emphasis on the characteristics of type 1 tumors. By considering recent developments in the field, we provide an overview of the current understanding of G-NET epidemiology, classification, clinical features, diagnosis, and management strategies.
... Немецкий физиолог Рудольф Петер Гейденгайн (Rudolf Peter Heinrich Heidenhain, 1834-1897) первым идентифицировал энтерохромаффинные клетки в слизистой оболочке желудка кролика и собаки, описав окрашенные в желтый цвет (хромовой кислотой) клетки в 1868 году, а в 1870 году также идентифицировали небольшие гранулированные желто-окрашенные клетки на поверхности желудочных желез [18]. ...
... Адольф Николя (Adolphe Nicolas, 1861-1939) в 1891 году сообщил о распространении энтерохромаффинных клеток желудочно-кишечного тракта у ящериц и тем самым заложил основу для последующего развития концепции диффузной нейроэндокринной системы (ДНС) [18]. ...
... Ученый описал лейкоциты эпителия миндалин и кишечника. Однако больше всего его помнят за идентификацию энтерохромаффинной клетки в 1897 году, поскольку это наблюдение легло в основу последующего описания ДНС и обеспечило клеточную основу, на которой стала основана нейроэндокринология [18]. ...
Статья посвящена истории развития физиологии эндокринной системы начиная с предпосылок в эпоху Древнего мира и до настоящего времени. При подготовке текста данной публикации использовались статьи в изданиях, включенных в РИНЦ и PubMed. Глубина поиска публикаций составила 20 лет, также в обзор был включен ряд более ранних работ, соответствующих теме исследования. Были обобщены результаты о развитии представлений о физиологии эндокринной системы. Первые представления начали формироваться еще в эпоху античности. В период Нового времени эмпирические знания продолжали накапливаться в результате проведения различных экспериментов. Знаковым событием развития данного направления физиологии стало открытие инсулина. Показан вклад отечественных физиологов в развитие физиологии эндокринной системы (Кульчицкий Н.К., Соболев Л.В., Чебоксаров М.Н., Завадовский М.М., Павлов И.П., Немилов А.В., Колесов Д.В., Бабичев В.Н.). История развитии физиологии эндокринной системы может рассматриваться при изучении специальных вопросов в рамках вузовских дисциплин «Нормальная физиология», «Эндокринология», «История медицины», «История биологии».
The article is devoted to the history of the development of the physiology of the endocrine system, from the prerequisites in the era of the Ancient World to the present day. In preparing this article, publications included in the RSCI and PubMed were used. The depth of the search for publications was 20 years, and a number of earlier works relevant to the research topic were also included in the review. The results on the development of ideas about the physiology of the endocrine system were summarized. The first ideas began to form in the era of antiquity. During the modern period, empirical knowledge continued to accumulate as a result of various experiments. A landmark event in the development of this area of physiology was the discovery of insulin. The contribution of domestic physiologists to the development of the physiology of the endocrine system is shown (Kulchitsky N.K., Sobolev L.V., Cheboksarov M.N., Zavadovsky M.M., Pavlov I.P., Nemilov A.V., Kolesov D.V., Babichev V.N.). The history of the development of the physiology of the endocrine system can be considered when studying special issues within the university disciplines “Normal Physiology”, “Endocrinology”, “History of Medicine”, “History of Biology”.
... First described by Kultchinsky in 1897 (Drozdov et al. 2009), EC-cells are mainly found interspersed among intestinal epithelial lining and are most numerous in the deep half of the crypts. In the stomach, they are rarer than in the intestine and are scattered along the whole mucosa. ...
... Nikolai Kulchitsky first identified the enterochromaffin cell in 1897 in the intestinal mucosa of cats and dogs, nevertheless lung neuroendocrine cells (LNC) were first discovered by Feyrter in 1938 1,2 . Normal lung tissue contains neuroendocrine cells along the bronchial and bronchiolar epitelium. ...
Lung tumorlets are rare neuroendocrine neoplasms of 0.5 cm or less in diameter that extend beyond the basement membrane. Although they are associated with bronchiectasis and fibrosis they tend to be asymptomatic and behave in a benign way, usually being diagnosed as incidental microscopic nests of neuroendocrine cells in lung tissue. We present a case of a pulmonary tumorlet finding after right upper lobectomy for lung cancer.
... In 1868, Heidenhain (1834-1897) was the first scientist to stain ECs in the gastric mucosa of a rabbit and a dog describing their yellow cytoplasmic granules [24]. In particular, the name was chosen because of their specificity to bind chromium-salt to form a colored deposit [25,26]. ...
... The Figure is obtained from Drozdov et al., (2008). Reprinted by permission from Springer Nature Customer Service Centre GmbH: Springer Nature, Cell and Tissue Research (License Number 5232431160386, 19 January 2022)[24]. ...
The intestinal epithelium plays a key role in managing the relationship with the environment, the internal and external inputs, and their changes. One percent of the gut epithelium is represented by the enteroendocrine cells. Among the enteroendocrine cells, a group of specific cells characterized by the presence of yellow granules, the enterochromaffin cells, has been identified. These granules contain many secretion products. Studies showed that these cells are involved in gastrointestinal inflammatory conditions and hyperalgesia; their number increases in these conditions both in affected and not-affected zones of the gut. Moreover, they are involved in the preservation and modulation of the intestinal function and motility, and they sense metabolic–nutritional alterations. Sometimes, they are confused or mixed with other enteroendocrine cells, and it is difficult to define their activity. However, it is known that they change their functions during diseases; they increased in number, but their involvement is related mainly to some secretion products (serotonin, melatonin, substance P). The mechanisms linked to these alterations are not well investigated. Herein, we provide an up-to-date highlight of the main findings about these cells, from their discovery to today. We emphasized their origin, morphology, and their link with diet to better evaluate their role for preventing or treating metabolic disorders considering that these diseases are currently a public health burden.
... One of the anatomy demonstrators to join Elliot Smith's department in 1919 was a young doctor, Raymond Dart (1893-1988, Fig. 4) later to become professor of anatomy at the University of the Witwatersrand, South Africa. At the same time, Elliot Smith had learned that the brilliant Russian neurohistologist, and by then Imperial Minister of Education for all of Russia, Nikolai Kulchitsky (1856-1925) had fled the Bolshevik armies with his family and was now penniless in London and so Elliot Smith assigned him to Dart as an assistant to pass on his knowledge of neuroanatomy, histology and staining techniques 18 . Not long after leaving UCL in 1923 Dart boldly published a paper in Nature 19 describing the first juvenile fossil hominin to be found in Africa. ...
Many primates are now listed as endangered species and so historical museum collections that contain primate remains have become an invaluable research resource that can never be replaced. Consequently, it is increasingly important that we document what is known about the origins and the age of specimens in our museums. The Elliot Smith Primate Collection at UCL originated at a time of change immediately after the First World War and while primarily a research collection it was used to teach aspects of comparative anatomy to generations of medical and dental students until the late 1980s. The lives of the people involved in acquiring and using the collection at the turn of the twentieth century provide us with a fascinating insight into their attitudes and ambitions and on what, sadly, was once considered acceptable collecting practise at the time.
... Although GEP-NENs represent a heterogeneous group of neoplasms, they each derive from neuroendocrine cells which share a common genotype and are dispersed throughout the digestive system [21,22]. GNENs are a component of GEP-NENs [2] and previous reports have suggested that the NETest signature may be valid for GNETs. ...
Abstract Background NETest, a novel multi-gene liquid biopsy has utility in neuroendocrine tumor (NET) diagnosis and identification of residual disease. We independently assessed utility of the NETest to diagnose gastric neuroendocrine neoplasms (GNENs) and identify micro- and macroscopic residual disease. Methods Cohorts comprised histologically confirmed GNENs at biopsy, n = 46; GNETs Type 1: 42 (32 NET G1, 10 NET G2), a GNET Type 3: 1 well-differentiated NET G3, neuroendocrine carcinomas (NECs) (n = 3), and controls (n = 63). Disease status at sampling was assessed by gastroscopy, histology (resection margin [R] positivity of polypectomy or biopsy), EUS, CT or MRI, and/or 68Ga-DOTA-TATE PET/CT. Groups included image- (gastroscopy, EUS, and anatomical and/or functional imaging) positive or image negative disease. NETest assay by PCR (spotted plates, normal cut-off: 20). Data: mean ± SD. Results Disease extent: Image-negative (n = 30) (21 R0, 9 R1); Image-positive, n = 16. Diagnosis: NETest was increased in GNETs (23 ± 11) vs. controls (7 ± 4, p
... 14,15 Its incidence has increased 4-fold between 1973 and 2004 (from 2.1 to 9.3 cases per million), and it has transcended adenocarcinoma as the most common cancer type of the small bowel in 2000. 15 The neuroendocrine cell giving rise to small bowel carcinoids of the jejunum and ileum is the Kulchitsky-enterochromaffin (EC) cell, 16 which is a gut epithelial cell that contains secretory granules that store and release Maxwell et al. Page 2 Surg Oncol Clin N Am. ...
... 14,15 Its incidence has increased 4-fold between 1973 and 2004 (from 2.1 to 9.3 cases per million), and it has transcended adenocarcinoma as the most common cancer type of the small bowel in 2000. 15 The neuroendocrine cell giving rise to small bowel carcinoids of the jejunum and ileum is the Kulchitsky-enterochromaffin (EC) cell, 16 which is a gut epithelial cell that contains secretory granules that store and release serotonin (5-hydroxytryptamine) and other peptides (such as CgA, synaptophysin, and substance P). 4 They are actually derived from enterocyte stem cells, rather than from neural crest cells, as first proposed by Pearse. 17 The majority of serotonin in the body (>90%) is produced in the GI tract, which is metabolized by monoamine oxidase (MAO) into its breakdown product 5-hydroxyindole acetic acid (5-HIAA) in the liver and lung, and then excreted into the urine. ...
Neuroendocrine tumors are a group of neoplasms that can arise in a variety of locations throughout the body and often metastasize early. A patient's only chance for cure is surgical removal of the primary tumor and all associated metastases, although even when surgical cure is unlikely, patients can benefit from surgical debulking. A thorough preoperative workup will often require multiple clinical tests and imaging studies to locate the primary tumor, delineate the extent of the disease, and assess tumor functionality. This review discusses the biomarkers important for the diagnosis of these tumors and the imaging modalities needed.
... During these studies he identified the "small homogeneous islands of clear cells lying throughout the gland." After his death at the early age of 41 years (from tuberculosis), subsequent researchers magnanimously named these cells as "The islets of Langerhans" 4,5 (Fig. 1). ...
... The EC cell is thought to respond to chemical or mechanical stimuli by releasing 5-HT and other potential mediators that act on afferent nerve terminals to initiate GI reflexes and modulate visceral perception [26][27][28]. The EC cell was discovered in the early 1900's, when silver and chromium histological methods showed a population of intestinal epithelial cells that could be stained in a manner similar to the chromaffin cells in the adrenal gland [well reviewed in 29,30,31]. The great Italian pharmacologist and biochemist Vittrio Erspamer published a comprehensive and highly cited review of gut serotonin (previously called 'enteramine') and the EC cell in the mid-1950's [32]. ...
The role of melatonin in the gastrointestinal (GI) tract had previously been limited to its well-described anti-oxidant properties. Recent studies have, however, expanded the role of melatonin in the intestine, showing that it acts as a hormone with local paracrine actions to modulate GI function and the release of other hormones. The GI epithelium produces melatonin from the active precursor serotonin, which is thought to come from the serotonin synthesising enterochromaffin cells (EC). The receptors for melatonin, the membrane bound melatonin receptors 1 and 2, are present on some smooth muscles, neurons, and epithelium. Endogenous release of melatonin has been linked with secretory reflexes and the ileal brake reflex, while exogenous application of melatonin in pharmacological doses has been associated with reduced inflammation in a variety of animal models.
