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Background: Pigeons (Columba livia) are mainly raised as a source of animal protein, racing, leisure and as an experimental animal. The present study investigated the morphology of the esophagus in the young and adult domestic pigeon, Columba livia domestica., Methods: Ten young and ten adult, normal, and healthy pigeons were collected from the local breeders. Samples from different parts of esophagus and crop were examined grossly, by stereomicroscopy, scanning and light microscopy., Results: The esophagus consisted of a long cervical part, a crop, and a short thoracic part. The crop was represented by a thin-walled outpouching with two lateral diverticula. The mucosa presented wavy fine folds in the cervical esophagus, irregular folds in the lateral diverticula giving it a corrugated appearance, and prominent longitudinal folds with several gland openings in the middle and lower parts of the crop, as well as in the thoracic esophagus. The density of gland openings was higher in adult pigeons than that in young pigeons. The mucosa of the esophagus was lined by non-keratinized stratified squamous epithelium. The shape, height, and branching of the mucosal folds differed between young and adult pigeons. Mucous-secreting alveoli were detected in the middle part of the crop as well as in the thoracic esophagus, but not in the cervical esophagus or lateral diverticula of the crop., Conclusion: The variations between the young and adult pigeons suggest a functional adaptation of adult pigeons to their diet compared to young pigeons., (© 2024. The Author(s).)

Several morphogenetic sequences occur during esophageal development and birth defects occur due to defects in foregut morphogenesis. This work aimed to record the cellular events in the morphogenesis of rabbits' esophageal epithelium. On the 16th day of gestation, the esophageal epithelium varied from stratified ciliated columnar to stratified squamous type. The surface epithelium presented mucous cells with mucigen granules of various sizes occupying their supranuclear cytoplasm. Cytoplasmic vacuolation was evident in all layers of the esophageal epithelium at this age. On the 18th gestational day, some light cells could be detected in the middle portion of the epithelium, while others occupied the whole epithelial length. On the 21st day, mucous cells are more frequently observed at the apical esophageal part as well as at the surface epithelium. Numerous elongated dark cells could be distinguished embedded between the basal cells. On the 24th gestational day the number of the mucous cells reached its peak. Reaching the 30th gestational day, several lamellar bodies, a keratinized layer and mitotic divisions could be demonstrated, and the number of both mucous and dark cells was greatly decreased. Collectively, detection of surface mucous and dark cells together with the non-cornified surface in some regions of the rabbit esophageal epithelium at the end of gestation ensure a postnatal development to reach the adult epithelium essential to sustain the passage of the harsh raw food. Future immunohistochemical studies are recommended to investigate the components of secretions in mucous cells and functional studies to highlight the dark cells significance. RESEARCH HIGHLIGHTS: Esophageal epithelium of fetal rabbit was analyzed by light and transmission microscopy. Surface epithelium presented mucous cells with mucigen granules of various sizes. They reached their maximum number on 24th day then decreased. On the 16th day, cytoplasmic vacuolation was evident in all epithelial layers. On the 21st day, numerous elongated dark cells could be distinguished embedded between the basal cells. Before birth, several lamellar bodies, a keratinized layer and mitotic divisions could be demonstrated, and the number of both mucous and dark cells was greatly decreased., (© 2023 Wiley Periodicals LLC.)

The current study investigated epithelial modification of embryonic quail esophagus using gross examination, light microscopy, transmission and scanning electron microscopy. By semithin sections, the pre-gastric modified region had unfolded mucosa, formed epithelial flabs and pockets, and had reduced muscularis mucosae, thin muscular layer, less glandular tissue, and outer esophageal groove. Conversely, the normal esophageal mucosa was folded, had abundant glandular tissue and prominent muscularis mucosae, with two muscular layers; the outer and the inner. The modified epithelium resembled stratified squamous type that had a high affinity for PAS, methylene blue, and PAP stains. Ultra-structural features of the modified esophageal epithelium resembled stratified squamous epithelium and contained hypertrophic Keratinocytes; dark and light. Hypertrophic keratinocytes had RER organized, few ribosomes, and developed loose bundle of cytokeratin compared with squamous keratinocytes. Hypertrophic Keratinocytes synthesize two types of granules; peripherally located small electron-dense granules and large electron-lucent granules. Hypertrophic keratinocytes had peroxisomes that were identified by the crystalline core of the urate oxidase. In conclusion, epithelia modification may have secretory function. Further studies should be carried out to explain the exact function of this type of modified epithelium., (© 2022 Wiley Periodicals LLC.)

The American horseshoe crab (Limulus polyphemus) is one of four extant species in the Order Xiphosura, subphylum Chelicerata, and are evolutionarily more closely related to scorpions and spiders, than crabs. The basic structure, function, and physiology of these invertebrates and their internal organs are not well documented in the literature. In this study, the gastrointestinal system, with a focus on the stomach, of adult L. polyphemus were assessed by gross and histologic methods to further characterize the pyloric valve, the lining of the ventricular lumen, and the muscular tunics of the stomach. Determination of normal anatomical structure of this organ system, along with characterization of the esophagus and intestinal tract, will set a standard against which tissue abnormalities, such as those seen with disease or pathology were to arise, would allow for better interpretation.

The esophageal pouches of Chaetopleura angulata and Acanthochitona fascicularis were investigated using light and transmission electron microscopy. These pouches linked to the posterior region of the esophagus are known as sugar glands as they contain a fluid rich in polysaccharide digesting enzymes. They are the second largest glands in the digestive system of chitons, just after the digestive gland. In both species, the pouches contain a dense array of finger-shaped villi. The villi epithelium includes absorptive cells, basophilic secretory cells, mucus-secreting cells, and basal cells. Some absorptive cells were bordered by a dense cover of long microvilli, whereas other absorptive cells had short and sparse microvilli. Absorptive cells contain several lysosomes, mitochondria, peroxisomes, a few small Golgi stacks, some lipid droplets, and large amounts of glycogen. The basophilic secretory cells are characterized by the presence of many electron-dense vesicles, with a glycoprotein content, a large number of rough endoplasmic reticulum cisternae, and a highly developed Golgi apparatus. Mucus-secreting cells are characterized by large vesicles containing acid polysaccharides and wide Golgi stacks. Basal cells that were found at the base of the epithelium in contact with the basal lamina exhibit histological and ultrastructural features of enteroendocrine cells. We suggest that these glandular pouches are involved in extracellular and intracellular digestion, and accumulate lipid and glycogen reserves., (© 2020 Wiley Periodicals LLC.)

The TFF peptides xP1 and xP4 from Xenopus laevis are orthologs of TFF1 and TFF2, respectively. xP1 is secreted as a monomer from gastric surface mucous cells and is generally not associated with mucins, whereas xP4 is a typical secretory peptide from esophageal goblet cells, and gastric mucous neck and antral gland cells tightly associated as a lectin with the ortholog of mucin MUC6. Both TFF peptides have diverse protective functions, xP1 as a scavenger for reactive oxygen species preventing oxidative damage and xP4 as a constituent of the water-insoluble adherent inner mucus barrier. Here, we present localization studies using immunofluorescence and immunoelectron microscopy. xP1 is concentrated in dense cores of secretory granules of surface mucous cells, whereas xP4 mixes with MUC6 in esophageal goblet cells. Of note, we observe two different types of goblet cells, which differ in their xP4 synthesis, and this is even visible morphologically at the electron microscopic level. xP4-negative granules are recognized by their halo, which is probably the result of shrinkage during the processing of samples for electron microscopy. Probably, the tight lectin binding of xP4 and MUC6 creates a crosslinked mucous network forming a stabile granule matrix, which prevents shrinkage., Competing Interests: The authors declare no conflict of interest.

Telocytes (TCs) are CD34 and Vimentin positive (+) immunoreactive stromal cells with a small-sized body and several extremely long telopodes. TCs have been described to provide a mechanical support throughout the tissue by making cellular connections (homo- or hetero) to form a 3D network. Such network can transmit the intercellular signaling. Recently, TCs have been described in the esophageal wall. However, information concerning the role of these cells in esophageal organization and development is rare. Thus, we aimed to record the temporo-spatial localization pattern of TCs during esophageal morphogenesis in rabbit. Embryos and fetuses of New Zealand White rabbits (10th-30th gestational days) were collected. Using CD34 immunostaining, TCs have not been demonstrated in the wall of the developing esophagus till the end of the second third of pregnancy. On 24th gestational day, CD34+ TCs were organized in the adventitia of the esophageal wall specifically in close association with the endothelial cells lining the micro vessels. Later on 26th gestational day, CD34+TCs were additionally expressed in the sub-mucosa and in lamina propria (sub-epithelial). On 28th gestational day, additional CD34 + TCs were detected among the smooth muscle bundles of the muscular layer. Reaching the last gestational day, CD34 + TCs formed several sheaths in the esophageal wall namely sub epithelial sheath, sub-mucosal, muscular (circular and longitudinal) and inter-muscular sheaths and an outer adventitial one. On the other hand, vimentin immunohistochemistry revealed wider spread TCs positivity in all developmental ages. Presumptively, arrangement of CD34 and vimentin positive TCs in all layers of the developing esophageal wall hypothesizes that TC may play a potential role as a progenitor cell initially in differentiation of the epithelial and muscular precursors and finally in shaping of the various layers of the rabbit esophageal wall during its morphogenesis. TCs are also proposed to be involved in the angiogenesis of the esophageal blood capillaries., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Esophagogastroduodenoscopy (EGD) is a widely used procedure, posing significant financial burden on both healthcare systems and patients. Moreover, EGD is time consuming, sometimes difficult to tolerate, and suffers from an imperfect diagnostic yield as the limited number of collected biopsies does not represent the whole organ. In this paper, we report on technological and clinical feasibility of a swallowable tethered endomicroscopy capsule, which is administered without sedation, to image large regions of esophageal and gastric mucosa at the cellular level. To demonstrate imaging capabilities, we conducted a human pilot study (n = 17) on Eosinophilic Esophagitis (EoE) patients and healthy volunteers from which representative cases are presented and discussed. Results indicate that, compared to endoscopic biopsy, unsedated tethered capsule endomicroscopy obtains orders of magnitude more cellular information while successfully resolving characteristic tissue microscopic features such as stratified squamous epithelium, lamina propria papillae, intraepithelial eosinophils, and gastric cardia and body/fundic mucosa epithelia. Based on the major import of whole organ, cellular-level microscopy to obviate sampling error and the clear cost and convenience advantages of unsedated procedure, we believe that this tool has the potential to become a simpler and more effective device for diagnosing and monitoring the therapeutic response of EoE and other esophageal diseases.

Competing Interests: There are no conflicts of interest

The organization of the coelomic system and the ultrastructure of the coelomic lining are used in phylogenetic analysis to establish the relationships between major taxa. Investigation of the anatomy and ultrastructure of the coelomic system in brachiopods, which are poorly studied, can provide answers to fundamental questions about the evolution of the coelom in coelomic bilaterians. In the current study, the organization of the coelom of the lophophore in the brachiopod Lingula anatina was investigated using semithin sectioning, 3D reconstruction, and transmission electron microscopy. The lophophore of L. anatina contains two main compartments: the preoral coelom and the lophophoral coelom. The lining of the preoral coelom consists of ciliated cells. The lophophoral coelom is subdivided into paired coelomic sacs: the large and small sinuses (= canals). The lining of the lophophoral coelom varies in structure and includes monociliate myoepithelium, alternating epithelial and myoepithelial cells, specialized peritoneum and muscle cells, and podocyte-like cells. Connections between cells of the coelomic lining are provided by adherens junctions, tight-like junctions, septate junctions, adhesive junctions, and direct cytoplasmic bridges. The structure of the coelomic lining varies greatly in both of the main stems of the Bilateria, that is, in the Protostomia and Deuterostomia. Because of this great variety, the structure of the coelomic lining cannot by itself be used in phylogenetic analysis. At the same time, the ciliated myoepithelium can be considered as the ancestral type of coelomic lining. The many different kinds of junctions between cells of the coelomic lining may help coordinate the functioning of epithelial cells and muscle cells., (© 2017 Wiley Periodicals, Inc.)

The regeneration of the anterior portion of the body after fission was studied in the holothurian Cladolabes schmeltzii using electron microscopy methods. Following fission, the posterior portion of the digestive tube, cloaca, and respiratory trees remain in the posterior fragment of the body. The regeneration comprises five stages. In the first stage, connective-tissue thickening (an anlage of the aquapharyngeal bulb) occurs on the anterior end between the torn-off ends of the ambulacra. Most of the lost anterior organs developed in the second and third stages. The structures of water-vascular system and nerve ring form through dedifferentiation, proliferation, and migration of cells of the radial water-vascular canals and the radial nerve cords, correspondently. The lost digestive system portion is restored through the formation and merging of two anlagen. The digestive epithelium of the esophagus and pharynx develops from lining cells of microcavities near the central portion of the connective-tissue thickening, which probably migrate from the epidermis. The second gut anlage develops through transformation of the anterior gut remnant portion. The enterocytes partly dedifferentiate, but the epithelium retains integrity. The gut anlage grows down the mesentery and joins the regenerating aquapharyngeal bulb. In the fourth and fifth stages, all lost organs are formed and have nearly normal structure. The regeneration was concluded to occur through morphallactic rearrangements of the remaining parts of organs. Epithelial morphogenesis is the key development mechanism of the digestive, water-vascular, and nervous systems., (© 2016 Wiley Periodicals, Inc.)

Introduction: Nowadays the level of early and late complications after the operations for esophageal corrosive strictures such as esophago-organ anastomotic leak, development of infections, pneumonia, pleural empyema, mediastinitis, peritonitis, postoperative corrosive stricture development etc. remains rather high. Besides, postoperative mortality rate is high as well - 3.5-30 %. For that reason, an experimental model of esophageal stricture was suggested and ultrastructural mucosal changes in the stricture itself were studied to elaborate the unified pathogenic approach in treatment of esophageal stricture and improvement of its results. The aim of our work was to study the dynamics of ultrastructural changes both in normal esophageal walls and in third degree esophageal stricture Materials and Methods: The experiment was carried out on white male rats weighting 250-300 grams, to whom the third degree esophageal stricture model was created. After layer-by-layer incision of anterior abdominal wall abdominal portion of the esophagus was completely ligated (10 rats). In the control group (6 rats) anterior abdominal wall was opened with its subsequent layered closure. The animals were withdrawn from the experiment on the third day by ketamine overdose, and the samples were taken for ultrastructural study., Results: Electron microscopic study of submicroscopic organization of basal, prickle, superficial epithelial cells in stratified non-squamous epithelium, smooth myocytes of muscle plate and contractile elements in esophageal muscular layer was carried out. Nuclear membrane, membranes of mitochondria, endoplasmic reticulum and cytoplasmic Golgi complex were found to be subjected to focal lysis. The third degree esophageal stricture caused destructive lesions in ultrastructural architectonics of stratified non-squamous epithelium cells, smooth myocytes of muscle plate and contractile elements in esophageal muscular layer of rats., Conclusion: Thus, catabolic processes leading to organelle disintegration develop in esophageal cells of rats with third degree stricture.

Background/aim: Lymphocytic oesophagitis (LyE) is a newly described entity characterized by a high number of intraepithelial lymphocytes/ high power field (≥40 CD3+IELs/HPF) in the oesophageal epithelium. The aim of the study was to investigate possible ultrastructural changes taking place in LyE at the transmission electron microscopic (TEM) level., Materials and Methods: Oesopageal biopsies from seven patients were investigated: four were consecutive patients with LyE, one with reflux oesopagitis, one with eosinophilic oesopagitis (EoE) and one with histologically normal squamous epithelium., Results: In LyE, marked intercellular oedema (spongiosis) and a gamut of regressive changes were found in squamous cells, ranging from cytoplasmic oedema and vacuolization, to total cell disintegration. IELs also showed regressive changes ranging from ballooned, oedematous cytoplasm to signs of intracytoplasmatic disintegration., Conclusion: Besides hampered cell nutrition conveyed by spongiosis, putative noxious molecules contained in the intercellular spongiotic oedema might account for the dramatic TEM alterations found in LyE. The present findings provide, for the first time, "inside information" on the ultrastructural alterations taking place in LyE, both in squamous cells and in IELs., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

This study was embarked upon to evaluate the effects of pantoprazole and palonosetron on experimental esophagitis in albino wistar rats. Groups of rats, fasted for 36 h, were subjected to pylorus and forestomach ligation, supervened by treatment with normal saline (3 ml/kg, po, sham control), esophagitis control (3 ml/kg, po), pantoprazole (30 mg/kg, po), palonosetron (0.5 mg/kg, po), and their combination. Animals were sacrificed after 12 h and appraised for the volume of gastric juices, total acidity, free acidity, and esophagitis index. Esophageal tissues were further figured out biochemically for markers of oxidative stress and inflammatory mediators. The combination therapy comparably inhibited the esophagitis index (52.86%), gastric volume (66.04%), free acidity (43.76%), and total acidity (42.60%) in comparison with toxic control. The combination therapy also subsidized the biochemical and inflammatory markers to the purview less than toxic control. The morphological changes were scrutinized by scanning electron microscopy and were observed to demonstrate momentous protection by the amalgamation therapy. Combination therapy with pantoprazole and palonosetron flaunted sententious protection against experimental esophagitis., (© The Author(s) 2015.)

Purpose: To analyze value of the computed tomography (CT) perfusion imaging in response evaluation of the esophageal carcinoma to neoadjuvant chemoradiotherapy (nCRT) using the histopathology as reference standard., Methods: Forty patients with the squamous cell esophageal carcinoma were re-evaluated after the nCRT by CT examination, which included low-dose CT perfusion study that was analyzed using the deconvolution-based CT perfusion software (Perfusion 3.0, GE). Histopathologic assessment of tumor regression grade (TRG) according to Mandard's criteria served as reference standard of response evaluation. Statistical analysis was performed using Spearman's rank correlation coefficient (r(S)) and Kruskal-Wallis's test., Results: The perfusion CT parameter values, measured after the nCRT in the segment of the esophagus that had been affected by neoplasm prior to therapy, significantly correlated with the TRG: blood flow (BF) (r(S)=0.851; p<0.001), blood volume (BV) (r(S)=0.732; p<0.001) and mean transit time (MTT) (r(S)=-0.386; p=0.014). Median values of BF and BV significantly differed among TRG 1-4 groups (p<0.001), while maximal esophageal wall thickness did not (p=0.102). Median BF and BV were gradually rose and MTT decreased as TRG increased, from 21.4 ml/min/100 g (BF), 1.6 ml/100 g (BV) and 8.6 s (MTT) in TRG 1 group, to 37.3 ml/min/100 g, 3.5 ml/100 g and 7.5 s in TRG 2 group, 81.4 ml/min/100 g, 4.1 ml/100 g and 3.8 s in TRG 3 group, and 121.1 ml/min/100 g, 4.9 ml/100 g and 3.7 s in TRG 4 group. In all 15 patients who achieved complete histopathologic regression (TRG 1), BF was <30.0 ml/min/100 g., Conclusions: CT perfusion could improve the accuracy in response evaluation of the esophageal carcinoma to nCRT., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

High levels of intracellular reactive oxygen species (ROS) in cells is recognized as one of the major causes of cancer cell apoptosis and has been developed into a promising therapeutic strategy for cancer therapy. However, whether apoptosis associated biophysical properties of cancer cells are related to intracellular ROS functions is still unclear. Here, for the first time, we determined the changes of biophysical properties associated with the ROS-mediated oesophageal cancer KYSE-150 cell apoptosis using high resolution atomic force microscopy (AFM). Oridonin was proved to induce ROS-mediated KYSE-150 cell apoptosis in a dose dependent manner, which could be reversed by N-acetylcysteine (NAC) pretreatment. Based on AFM imaging, the morphological damage and ultrastructural changes of KYSE-150 cells were found to be closely associated with ROS-mediated oridonin-induced KYSE-150 cell apoptosis. The changes of cell stiffness determined by AFM force measurement also demonstrated ROS-dependent changes in oridonin induced KYSE-150 cell apoptosis. Our findings not only provided new insights into the anticancer effects of oridonin, but also highlighted the use of AFM as a qualitative and quantitative nanotool to detect ROS-mediated cancer cell apoptosis based on cell biophysical properties, providing novel information of the roles of ROS in cancer cell apoptosis at nanoscale.

The Chinese giant salamander belongs to an old lineage of salamanders and endangered species. Many studies of breeding and disease regarding this amphibian had been implemented. However, the studies on the ultrastructure of this amphibian are rare. In this work, we provide a histological and ultrastructural investigation on posterior esophagus of Chinese giant salamander. The sections of amphibian esophagus were stained by hematoxylin & eosin (H&E). Moreover, the esophageal epithelium was observed by transmission electron microscopy (TEM). The results showed that esophageal epithelium was a single layer epithelium, which consisted of mucous cells and columnar cells. The esophageal glands were present in submucosa. The columnar cells were ciliated. According to the diverging ultrastructure of mucous vesicles, three types of mucous cells could be identified in the esophageal mucosa: i) electron-lucent vesicles mucous cell (ELV-MC); ii) electron-dense vesicles mucous cell (EDV-MC); and iii) mixed vesicles mucous cell (MV-MC).

Endocytoscopy (ECS) is a novel endoscopic technique that allows detailed diagnostic examination of the gastrointestinal tract at the cellular level. We previously reported that use of ECS at ×380 magnification (GIF-Y0002) allowed a pathologist to diagnose esophageal squamous cell carcinoma (ESCC) with high sensitivity (94.9%) but considerably low specificity (46.7%) because this low magnification did not reveal information about nuclear abnormality. In the present study, we used the same magnifying endoscope to observe various esophageal lesions, but employed digital 1.6-fold magnification to achieve an effective magnification of ×600, and evaluated whether this improved the diagnostic accuracy in distinguishing neoplastic from non-neoplastic lesions.We examined the morphology of surface cells using vital staining with toluidine blue and compared the histological features of 40 cases, including 19 case of ESCC and 21 non-neoplastic esophageal lesions (18 cases of esophagitis, 1 case of glycogenic acanthosis, 1 case of leiomyoma, and 1 case of normal squamous epithelium). One endoscopist classified the lesions using the type classification, and we consulted one pathologist for judgment of the ECS images as 'neoplastic', 'borderline', or 'non-neoplastic'. At ×600 magnification, the pathologist confirmed that nuclear abnormality became evident, in addition to the information about nuclear density provided by observation at ×380. The overall sensitivity and specificity with which the endoscopist was able to predict neoplastic lesions using the type classification was 100% (19/19) and 90.5% (19/21), respectively, in comparison with values of 94.7% (18/19 cases) and 76.2% (16/21), respectively, for the pathologist using a magnification of ×600. The pathologist diagnosed two non-neoplastic lesions and one case of ESCC showing an apparent increase of nuclear density with weak nuclear abnormality as 'borderline'. Among the 21 non-cancerous lesions, two cases of esophagitis that were misdiagnosed by the endoscopist were also misinterpreted as 'neoplastic' by the pathologist. We have shown, by consultation with a pathologist, that an ECS magnification of ×600 (on a 19-inch monitor) is adequate for recognition of nuclear abnormality. We consider that it is feasible to diagnose esophageal neoplasms on the basis of ECS images, and that biopsy histology can be omitted if a combination of increased nuclear density and nuclear abnormality is observed., (© 2014 International Society for Diseases of the Esophagus.)

Periplakin (PPL), a member of the plakin family of proteins that localizes to desmosomes and intermediate filaments, is downregulated in human esophageal squamous cell carcinoma (ESCC). Little is known, however, about the molecular mechanism underlying the regulation of PPL expression and the contribution of PPL loss to the malignant property of the cancer is unclear. We demonstrated that PPL mRNA expression was significantly reduced in ESCC tissues compared with that in normal tissues. Therefore, we hypothesized that CpG hypermethylation is the cause of the downregulation of PPL. Bisulfite-pyrosequencing of 17 cases demonstrated that the frequency of PPL methylation was higher in ESCC tissues than in normal tissues. When human ESCC cell lines were treated with 5-aza-2'-deoxycytidine (5-aza-dC), a DNA-methyltransferase inhibitor, PPL transcription was induced. Human KYSE270 ESCC cells do not stratify under ordinary culture conditions and rarely produce desmosomes; however, the forced expression of PPL promoted cell stratification. PPL induction also promoted adhesion to extracellular matrix but delayed cell migration. The abundance of desmosome-like structures was greatly increased in PPL transfectant as determined by transmission electron microscopy. Very low expression of another desmosome protein EVPL in ESCC, even in PPL transfectant, also supported the significant role of PPL in desmosome formation and cell stratification. Our results first indicate that the downregulation of PPL mediated by DNA hypermethylation, which may play an important role in the loss of ESCC stratification and likely in metastatic phenotype., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Mast cells (MCs) were studied quantitatively and qualitatively in the wall of the esophagus (upper, middle and lower portions) of the individuals in the I period of mature age (22-35 years, n = 6) as well as in old and senile persons (61-82 years, n = 10). In all the individuals, the total number of MCs was found to increase from the upper portion of the esophagus towards the lower one. Within the esophageal wall, the total number of MCs decreased in the direction from tunica mucosa towards adventitia. During I period of mature age, the resting MCs filled with granules predominated, while the degranulating MCs were located in the lower esophageal segment. In the individuals of old and senile age, the degranulating MCs were more frequently observed in the upper and lower esophageal segments.

Background: The esophagus of blood-feeding schistosomes has been largely neglected although its posterior portion was designated as a gland decades ago. However, we recently showed it plays a pivotal role in blood processing. It is clearly demarcated into anterior and posterior compartments, both surrounded by a mass of cell bodies. Feeding movies revealed that erythrocytes accumulate in the anterior compartment before entering the posterior, indicating that a distinct process is executed there. We therefore investigated ultrastructural aspects and possible functions of the anterior region., Methods: The heads of adult Schistosoma japonicum were detached and prepared for both transmission and scanning electron microscopy to define the detailed ultrastructure of the anterior esophagus. Cryosections of heads were also prepared for immunocytochemistry and confocal microscopy to define the pattern of intrinsic host antibody binding in the anterior esophageal lining., Results: The anterior syncytial lining of the esophagus is highly extended by long, thin corrugations of cytoplasm projecting towards the lumen. Strikingly in the male worm, the tips of the corrugations are further expanded by numerous threads of cytoplasm, producing a spaghetti-like appearance in the central lumen. Flattened, pitted cytoplasmic plates are interspersed in the tangled mass of threads. Abundant, morphologically distinct light vesicles of varied size and contents are manufactured in the cell bodies, from where they traffic through cytoplasmic connections to the corrugations and out to the tips. Clusters of vesicles accumulate in expanded tips in males, together with occasional mitochondria whilst females have more mitochondria but fewer vesicles. The membranous contents of light vesicles are secreted mainly from the tips, but also from the sides of the corrugations. They coat the surfaces and then form organised self-adherent membrane figures when shed into the lumen. Host antibody binds strongly in a characteristic pattern to the anterior esophageal lining indicating that the secretions are highly immunogenic., Conclusions: We suggest that the anterior esophageal region is an independent secretory organ. The contents of light vesicles are released into the esophageal lumen via the tips of corrugation to interact with incoming blood. Our immediate task is to establish their composition and role in blood processing.

Megaesophagus is defined as the abnormal enlargement or dilatation of the esophagus, characterized by a lack of normal contraction of the esophageal walls. This is called achalasia when associated with reduced or no relaxation of the lower esophageal sphincter (LES). To date, there are few naturally occurring models for this disease. A colony of transgenic (Pvrl3-Cre) rats presented with megaesophagus at 3 to 4 months of age; further breeding studies revealed a prevalence of 90% of transgene-positive animals having megaesophagus. Affected rats could be maintained on a total liquid diet long term and were shown to display the classic features of dilated esophagus, closed lower esophageal sphincter, and abnormal contractions on contrast radiography and fluoroscopy. Histologically, the findings of muscle degeneration, inflammation, and a reduced number of myenteric ganglia in the esophagus combined with ultrastructural lesions of muscle fiber disarray and mitochondrial changes in the striated muscle of these animals closely mimic that seen in the human condition. Muscle contractile studies looking at the response of the lower esophageal sphincter and fundus to electrical field stimulation, sodium nitroprusside, and L-nitro-L-arginine methyl ester also demonstrate the similarity between megaesophagus in the transgenic rats and patients with achalasia. No primary cause for megaesophagus was found, but the close parallel to the human form of the disease, as well as ease of care and manipulation of these rats, makes this a suitable model to better understand the etiology of achalasia as well as study new management and treatment options for this incurable condition., (© The Author(s) 2014.)

Ontogenesis comprises a series of events including cell proliferation and apoptosis and resulting in the normal development of the embryo. Protein p53 has been described as being involved in the development of several animal species. The aim of this study was to analyze the expression of protein p53 during the morphogenesis of the gastroesophageal mucosa of Gallus gallus domesticus and to correlate it with the histogenesis of structures present in this tissue. We used 24 embryos (at 12-20 days of incubation) and the thymus of two chickens. Immunohistochemical analysis was performed with the ABC indirect method. The expression of p53 in the gastroesophageal mucosa increased during the formation of the organ, mainly at the stages during which tissue remodeling and cell differentiation began. In the esophagus at stages 42 and 45, we observed immunoreactive (IR) cells in the surface epithelium and in early esophageal glands. In the proventriculus at stages 39-45, IR cells were present in the epithelial mucosa and rarely in the proventricular glands. In the gizzard after stage 42, we found IR cells mainly in the medial and basal epithelial layers of the mucosa and especially within the intercellular spaces that appeared at this phase and formed the tubular gland ducts. Thus, protein p53 occurs at key stages of development: in the esophagus during the remodeling of esophageal glands, in the proventriculus during the differentiation of the epithelium of the mucosa and in the gizzard during the formation of tubular glands.

Background and Study Aims: Esophageal adenocarcinoma (EAC) has a dismal prognosis unless treated early or prevented at the precursor stage of Barrett's esophagus-associated dysplasia. However, some patients with cancer or dysplastic Barrett's esophagus (DBE) may not be captured by current screening and surveillance programs. Additional screening techniques are needed to determine who would benefit from endoscopic screening or surveillance. Partial wave spectroscopy (PWS) microscopy (also known as nanocytology) measures the disorder strength (Ld ), a statistic that characterizes the spatial distribution of the intracellular mass at the nanoscale level and thus provides insights into the cell nanoscale architecture beyond that which is revealed by conventional microscopy. The aim of the present study was to compare the disorder strength measured by PWS in normal squamous epithelium in the proximal esophagus to determine whether nanoscale architectural differences are detectable in the field area of EAC and Barrett's esophagus., Methods: During endoscopy, proximal esophageal squamous cells were obtained by brushings and were fixed in alcohol and stained with standard hematoxylin and Cyto-Stain. The disorder strength of these sampled squamous cells was determined by PWS., Results: A total of 75 patient samples were analyzed, 15 of which were pathologically confirmed as EAC, 13 were DBE, and 15 were non-dysplastic Barrett's esophagus; 32 of the patients, most of whom had reflux symptoms, acted as controls. The mean disorder strength per patient in cytologically normal squamous cells in the proximal esophagus of patients with EAC was 1.79-times higher than that of controls (P<0.01). Patients with DBE also had a disorder strength 1.63-times higher than controls (P<0.01)., Conclusion: Intracellular nanoarchitectural changes were found in the proximal squamous epithelium in patients harboring distal EAC and DBE using PWS. Advances in this technology and the biological phenomenon of the field effect of carcinogenesis revealed in this study may lead to a useful tool in non-invasive screening practices in DBE and EAC., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: IGLEs represent the only low-threshold vagal mechanosensory terminals in the tunica muscularis of the esophagus. Previously, close relationships of vesicular glutamate transporter 2 (VGLUT2) immunopositive IGLEs and cholinergic varicosities suggestive for direct contacts were described in almost all mouse esophageal myenteric ganglia. Possible cholinergic influence on IGLEs requires specific acetylcholine receptors. In particular, the occurrence and location of neuronal muscarinic acetylcholine receptors (mAChR) in the esophagus were not yet characterized., Methods: This study aimed at specifying relationships of VGLUT2 immunopositive IGLEs and vesicular acetylcholine transporter (VAChT)-immunopositive varicosities using pre-embedding electron microscopy and the location of mAChR1-3 (M1-3) within esophagus and nodose ganglia using multilabel immunofluorescence and retrograde tracing., Key Results: Electron microscopy confirmed synaptic contacts between cholinergic varicosities and IGLEs. M1- and M2-immunoreactivities (-iry; -iries) were colocalized with VGLUT2-iry in subpopulations of IGLEs. Retrograde Fast Blue tracing from the esophagus showed nodose ganglion neurons colocalizing tracer and M2-iry. M1-3-iries were detected in about 80% of myenteric ganglia and in about 67% of myenteric neurons. M1- and M2-iry were present in many fibers and varicosities within myenteric ganglia. Presynaptic M2-iry was detected in all, presynaptic M3-iry in one-fifth of motor endplates of striated esophageal muscles. M1-iry could not be detected in motor endplates of the esophagus, but in sternomastoid muscle., Conclusions & Inferences: Acetylcholine probably released from varicosities of both extrinsic and intrinsic origin may influence a subpopulation of esophageal IGLEs via M2 and M1-receptors., (© 2013 John Wiley & Sons Ltd.)

Objective: In this study, we investigated histological and electron microscopic changes of the laryngeal and esophageal epithelium in an animal model of reflux to demonstrate: (1) the association between laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD) and (2) the value of dilated intercellular space (DIS) as a marker of LPR., Methods: Eight New Zealand albino rabbits were utilized. Four rabbits underwent total cardiomyectomy to induce reflux. The remains underwent a sham operation as controls. The animals were sacrificed 12 weeks after surgery to obtain histological and electron microscopic results., Results: There were significant differences in the histological results between the study group and the control group in both the esophagus and the larynx (P=0.041 and 0.014). Significant changes in the intercellular space (IS) were observed between the study group and the control group in the esophageal and laryngeal samples (P<0.001)., Conclusion: The results of this study suggest that LPR and GERD have a common mechanism and DIS is a morphologic marker of LPR in rabbits., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Eosinophilic esophagitis (EoE) is a food allergy-associated inflammatory disease characterized by esophageal eosinophilia. Current management strategies for EoE are nonspecific, and thus there is a need to identify specific immunological pathways that could be targeted to treat this disease. EoE is associated with polymorphisms in the gene that encodes thymic stromal lymphopoietin (TSLP), a cytokine that promotes allergic inflammation, but how TSLP might contribute to EoE disease pathogenesis has been unclear. Here, we describe a new mouse model of EoE-like disease that developed independently of IgE, but was dependent on TSLP and basophils, as targeting TSLP or basophils during the sensitization phase limited disease. Notably, therapeutic TSLP neutralization or basophil depletion also ameliorated established EoE-like disease. In human subjects with EoE, we observed elevated TSLP expression and exaggerated basophil responses in esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with increased basophil responses in patients with EoE. Together, these data suggest that the TSLP-basophil axis contributes to the pathogenesis of EoE and could be therapeutically targeted to treat this disease.

Background: Patients with gastroesophageal reflux disease (GERD) have impaired esophageal mucosal integrity. Measurement of the mucosal integrity is complex and time-consuming. Electrical tissue impedance spectroscopy (ETIS) is a device that measures impedance of tissue in vivo during endoscopy. In this study, we aimed to validate ETIS as a measure of esophageal mucosal integrity., Methods: Electrical tissue impedance spectroscopy measurements were performed during upper endoscopy in 12 GERD patients and 11 healthy controls after cessation of proton pump inhibition. During endoscopy biopsies of the distal esophagus were obtained for transmission electron microscopy to determine dilation of intercellular spaces (DIS) and for Ussing chamber experiments to determine transepithelial permeability and transepithelial electrical resistance., Key Results: Extracellular impedance measured in vivo by ETIS was significantly lower in GERD patients compared to controls [mean (SD) 5621 (3299) Ω.m and 8834 (2542) Ω.m, respectively, P < 0.05]. We found a strong inverse relation between extracellular impedance determined by ETIS and DIS (r = -0.76, P < 0.05), and between extracellular resistance in vivo and transepithelial permeability of esophageal biopsies (r = -0.65, P < 0.01)., Conclusions & Inferences: Electrical tissue impedance spectroscopy is a new tool that can be used to evaluate esophageal mucosal integrity changes during endoscopy., (© 2013 John Wiley & Sons Ltd.)

The microanatomy of the digestive and respiratory systems of the holothurian Cladolabes schmeltzii was studied. The digestive tube of C. schmeltzii is divided into seven parts. The pharynx, esophagus, and stomach are lined with cuticular immersed epithelium. In these regions, the epithelial cells are connected via desmosomes, septate junctions, and rivet-like structures. The presence of the cuticle and rivet-like structures suggests an ectodermal origin for these parts of the digestive tube. The luminal intestinal epithelium is formed by vesicular enterocytes, which have different structures in different intestinal regions. Moreover, the epithelium of the first descending part of the intestine contains the granular enterocytes. The respiratory system consists of paired respiratory trees lined by a luminal epithelium that is formed by cells of irregular shape. The apical surface of these epithelial cells has few lamellae. The cells are connected to each other through a system of intercellular junctions, consisting of both desmosomes and well-developed septate junctions. The coelomic epithelium of the intestine and the respiratory trees consists of peritoneal and myoepithelial cells., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The morphology of the digestive tract of the peppered moray eel, Gymnothorax pictus (G. pictus) (Elopomorpha: Anguilliformes) was examined using both light and scanning electron microscopy. The digestive tract is composed of the esophagus, the stomach, and the intestines; pyloric caeca were absent. The stomach was divided into a cardiac region that was continuous with the esophagus, a body which terminated in a long blind sac, and a pyloric region that was continuous with the intestine. The short intestine possessed several partitions that were created by the mucosal folds within the posterior region. The terminal region of the stomach was characterized by the thick longitudinal muscularis and subserosa, and the gastric glands and microvilli were absent. Ciliary tufts of ciliated cells were observed on the surface of the partition-like mucosal folds within the intestinal wall. Acidic mucus was secreted throughout the digestive tract. It was suggested that the terminal region of the stomach is specialized for storage of large food items. In addition, it is possible that the partition-like mucosal folds within the intestine perform a function similar to that of the spiral valve and, and along with ciliated cells, facilitated digestion and absorption. The acidic mucus likely maintained surface epithelium pH and protease activity. Within a phylogenetic context, the absence of a pyloric caeca in G. pictus while possessing an intestine implies that this species is affiliated to groups that had branched off earlier than basal teleosts. Inc., (Copyright © 2013 Wiley Periodicals, Inc.)

We studied morphological and cell characteristics of stenosis of esophagogastric and esophagocolonic anastomosis. It was demonstrated that sclerogenesis in the gastric transplants is associated with hypertrophy of leiomyocytes, hyperelastosis foci, degenerative and atrophic modifications of the glands, and foveolar cell hypersecretion. In colonic transplant, collagen synthesis predominates in the esophageal anastomosis and can be associated with proliferation of blood capillaries; hyperplastic reactions of leiomyocytes and elastic fibers are minor, colonocytes exhibit high secretory activity. Differences in the cell reactions of the transplants reflect complex character of the formation of esophageal anastomosis stenosis.

Background and Aim: Accumulating evidence suggests that the extracellular matrix play important roles in intercellular communications and contribute to the development of a number of diseases, including diseases of the gastrointestinal tract. The present study examined the structural characteristics and alterations of the extracellular matrix of the mucosa stroma in the Barrett's esophagus metaplasia-dysplasia-adenocarcinoma sequence., Methods: A total of 41 esophageal tissue specimens (15 esophageal adenocarcinoma, 10 Barrett's esophagus intestinal metaplasia, seven dysplasia and nine normal esophagus) were studied. The present study used transmission electron microscopy and computerized quantitative electron-microscopic analysis in order to investigate the characteristics of the extracellular matrix of the mucosa., Results: The study revealed that marked structural alterations of the mucosa stroma, relating to changes in the distribution and appearance of collagen fibers as well as to changes in numbers of matrix microvesicles, occur in Barrett's esophagus and esophageal adenocarcinoma. It was found that there were 3.1 times more microvesicles in the stroma in Barrett's esophagus than in the stroma of the normal esophagus (P<0.0001) and that there were 5.8 times more microvesicles in esophageal adenocarcinoma than in the normal esophagus (P<0.0001). There were 1.9 times more microvesicles in esophageal adenocarcinoma than in Barrett's esophagus (P=0.0043)., Conclusions: The study demonstrates distinctive alterations of the mucosa stroma extracellular matrix in the metaplasia-dysplasia-adenocarcinoma sequence. The findings suggest that the redistribution of collagen fibers and increases in numbers of matrix microvesicles may play roles in the formation of specialized intestinal metaplasia and the development of adenocarcinoma., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

We studied ultrastructural reorganization of the colon transplant in delayed period after esophagoplasty. It was found that during functioning of the artificial esophagus, a complex of adaptive and pathologic processes occurs in the mucosa. Focal sclerosis of the mucosa and slight epithelial degeneration with hyperplasia and hypersecretion of goblet cells were found in biopsy specimens with stenosis of the anastomosis. In case of colonopathy of the transplant, more pronounced epithelial degeneration and proliferation accompanied by abundant polymorphocellular stromal infiltration were seen. Deformation of the transplant was characterized by progressive atrophic and sclerotic reorganization of the mucosa. Goblet cells with ultrastructural signs of hypersecretion predominated in the population of epithelial cells of the colon transplant; oligomucus and poorly differentiated cell and colonocytes with signs of alteration and degenerative changes in cytoplasmic organelles were also found.

Background: The success of a tissue engineered construct is greatly influenced by the choice of scaffold material. Decellularized esophageal matrix is a promising material for esophageal tissue engineering. The aim of this study was to develop a decellularized ovine esophageal mucosa and to investigate the effect of decellularization on the appearance of the resulting tissue., Methods: Ovine esophagi were decellularized by combination of agitation, enzymatic digestion and treatment with 1 and 5% sodium dodecyl sulphate (SDS). Efficiency of decellularization was assessed by histological examination and DNA quantification. Finally, the effect of decellularization on tissue morphology was investigated by scanning electron microscopy., Results: Decellularization resulted in a highly efficient removal of cells and DNA content. Electron microscopic investigation revealed a denuded, rough, undulating surface with preserved papillary structures. Individual papillae had a length of approximately 55 μm and were present at a density of 1332 μm/mm(2). Closer examination revealed a tightly packed sponge-like appearance with pores in the region of 300 nm. Numerous, intact collagen fibres were also visible., Conclusion: Ovine esophagus can be successfully decellularized through treatment with SDS. The resulting decellularized mucosal surface possesses a rough, 2D surface with a well preserved extracellular matrix. Such a material may be of advantage in tissue engineering of the esophagus. Characterisation of the papillary layer gives important insight into the suitability of decellularized esophageal mucosa for use in esophageal reconstruction and also provides morphological information which may help in the design of synthetic, biomimetic materials.

Basement membrane (BM) has been investigated widely and applied in the field of bio-synthesized scaffold design in tissue engineering. However, this respect of investigation has seen scarcely in the field of esophageal tissue engineering. This study reports BM's basic topographic characters and quantification of structural and major proteins involving collagen IV, laminin, entactin, proteoglycans of porcine esophagus. Several methods were adopted to strip epithelium from mucosa tissue. For example, ethylene diamine tetraacetic acid, sonication, dithiothreitol, cold sodium chloride (NaCl), mechanical force of glass coverslip, and cold trypsin and so forth. Assessed experimental results under different conditions, the optimal condition to isolate epithelium from BM was established. After the reaction of cold trypsin at 4°C for 15 h, the BM was isolated from epithelium and exposed integratedly. Hematoxylin and eosin staining and immunohistochemical staining verified the effectiveness of epithelium removal and the integrity of BM. The topographic features of the exposed BM were observed under transmission electron microscopy and scanning electron microscopy. It displayed a rugged surface and 3-D topography consisting of pores and fibers with sub-100 nm range via ImageJ software. The major proteins existing in BM were quantitatively analyzed by enzyme-linked immune sorbent assay. All these results will provide references for the design of synthesized scaffolds and protein modification in esophageal tissue-engineering research., (Copyright © 2011 Wiley Periodicals, Inc.)

TCs (telocytes) are actually defined as stromal cells with specific long and thin prolongations, called Tp (telopodes). They have been positively identified in various tissues and we now report their presence in the esophagus. These cells were identified by TEM (transmission electron microscopy) in esophageal samples of Wistar rats (n = 5) occurring beneath the basal epithelial layer, in submucosa, closely related to smooth and striated muscular fibres, as also in the adventitia. They are closely related to mast cells, macrophages and microvessels. Hybrid morphologies of stromal cells processes were found: cytoplasmic processes continued distally in a telopodial fashion. Telopodes alone may not be sufficient, however, for a safe diagnosis of TCs in TEM. A larger set of specific standards (such as the telopodial emergence, and the size of the cell body and telopodes) should be considered to differentiate TCs from various species of fibroblasts. The morphological and ultrastructural features should distinguish between TCs and interstitial cells of Cajal in the digestive tract.

A new nematode species, Philometra terapontis n. sp. (Philometridae), is described from male and female specimens found in the ovary of the jarbua terapon Terapon jarbua (Forsskål) (Terapontidae, Perciformes) from the Bay of Bengal off the eastern coast of India. Based on light and scanning electron microscopical examination, the new species differs from most other gonad-infecting Philometra spp. in the length of the spicules (105-114 μm), a gubernaculum with dorsal, lamella-like structures and a distinct protuberance on its distal end, and a U-shaped, dorsally uninterrupted caudal mound in the male. From a few congeneric, gonad-infecting species with unknown males, it can be distinguished by morphological and biometrical features found in gravid females (i.e. length of body, length of first-stage larvae or oesophagus, and caudal structure), by the host type (fish family) and by the geographical distribution. Philometra terapontis is the first philometrid species reported from a fish belonging to the family Terapontidae. Philometra sawara Quiazon, Yoshinaga & Ogawa, 2008 is considered a junior synonym of P. scomberomori (Yamaguti, 1935). A key to gonad-infecting species of Philometra parasitising marine and brackish-water fishes is provided.

Background: Oesophageal intraluminal impedance is currently used for assessment of reflux in gastro-oesophageal reflux disease (GORD). Oesophageal mucosa integrity may have a key role in heartburn perception in non-erosive reflux disease (NERD). Severe erosive oesophagitis is associated with low impedance baseline. We hypothesised that impedance baseline measurements could be used to evaluate changes in oesophageal mucosa integrity in man., Methods: We measured oesophageal impedance baseline before, during and after acid perfusion in rabbits and healthy subjects. Transepithelial resistance (TER) was determined and dilated intercellular spaces (DIS) were assessed in isolated rabbit oesophageal mucosa. Impedance baseline was measured retrospectively at different levels of the oesophagus in impedance-pH recordings from asymptomatic volunteers and patients with GORD., Results: In healthy subjects and rabbits, impedance baseline dropped dramatically during perfusion of control solution (pH 7.2) but after perfusion, impedance recovered. In rabbits, after perfusion with saline pH 1.5 and 1.0 impedance values remained a 39.1 ± 7.0% and 63.9 ± 6.5% (p < 0.05) lower respectively. There was a positive correlation between in vivo basal impedance and in vitro TER values (r = 0.72, p = 0.0021). Tissue showed no erosions but both acidic solutions induced DIS. In healthy subjects, after perfusion with saline pH 2.0 and 1.0 the impedance baseline remained lower a 21.9 ± 6.5% and 52.7 ± 5.0%, (p < 0.0001) respectively. Patients with GORD have a lower impedance baseline than healthy volunteers at the distal oesophagus., Conclusions: Impedance baseline measurements might be used to evaluate the status of the oesophageal mucosa and to study the role of the impaired mucosal integrity in acid-induced heartburn in healthy volunteers and in patients with GORD.

Type VII collagen (COL7) is a major constituent of the cutaneous basement membrane. Loss of tolerance to COL7 leads to the blistering skin disease epidermolysis bullosa acquisita (EBA). Antibodies to COL7 have also been detected in patients with inflammatory bowel disease (IBD), yet reports on the expression of COL7 in the gut are controversial and a pathogenic relevance of anti-COL7 autoantibodies in IBD has not been demonstrated. We therefore characterized the expression patterns of COL7 in murine gastrointestinal organs and investigated if anti-COL7 antibodies induce an inflammatory response in the gut. COL7 expression was analysed on the mRNA and protein levels. Mice were injected with rabbit anti-murine COL7 IgG (passive EBA) or immunized with a fragment of murine COL7 (active EBA). COL7 was found to be expressed in buccal mucosa, oesophagus, stomach, small intestine, and colon. In addition to skin blistering, in both passive and active EBA, autoantibodies bound to the gastrointestinal basement membrane, fixed complement, and led to recruitment of leukocytes. Furthermore, blister formation was observed in the oesophagus (40%/38% of mice in passive/active model), stomach (40%/63%), small intestine (20%/13%), and colon (20%/13%). Compared to control animals, we found a significantly reduced body weight in diseased mice, suggesting that autoantibody-induced gastrointestinal inflammation is clinically relevant. Those observations may help us to understand the co-incidence of IBD with EBA, and vice versa: The inflammatory response in IBD might expose novel antigens (COL7), which leads to the formation of anti-COL7 antibodies. On the contrary, anti-COL7 antibody-induced gastrointestinal inflammation might pave the way for IBD pathogenesis. In summary, our results provide strong evidence that COL7 is expressed in different portions of the gut and that anti-COL7 antibodies induce distinct gastrointestinal tissue damage., (Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background/aims: At present, the dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. Nevertheless, previous electron microscopic (EM) studies had focused only on the suprabasal layer of squamous epithelium or did not nearly specify which layer of squamous epithelium was studied. Therefore, we aimed to assess the volumetric amount of the ICS in all layers of SE in patients with GERD., Methods: In this study, 48 patients were prospectively included (NERD = 18, ERD = 17; Barrett's esophagus = 5, controls = 8). All patients with ERD and NERD had typical reflux symptoms, as assessed by a valid GERD questionnaire. ICS volume was assessed by electron microscopy in the superficial, prickle cell, and basal layers of esophageal squamous epithelium using the method of Weibel., Results: ERD was associated with increased ICS volume in the basal layer (LA-A, p = 0.038; LA-B, p = 0.005) and prickle cell layer (LA-A, p = 0.006; LA-B, p = 0.007) as compared to controls. Comparisons between NERD and ERD patients revealed more dilated ICS in the basal layer (LA-B, p = 0.007), prickle cell layer (LA-A, p = 0.008; LA-B, p = 0.001) and superficial layer (LA-B, p = 0.018) in patients with ERD., Conclusions: Not only the diameter but also the volume of the ICS is increased in patients with GERD. Furthermore, the dilation of ICS is present in all three layers of the SE, being more pronounced in the basal layer. These findings support the concept that the impairment of the esophagus begins in the deeper parts of the esophageal epithelium.

Objectives: Refractory heartburn despite acid suppression may be explained by ongoing gastroesophageal reflux disease (GERD) or functional heartburn (FH), i.e., symptoms without evidence of GERD. Impedance-pH monitoring (impedance-pH) detects acid and nonacid reflux and is useful for evaluating acid-suppressed, refractory patients. Intercellular space diameter (ISD) of esophageal epithelium measured by transmission electron microscopy (TEM) is a marker of epithelial damage present in both erosive and nonerosive reflux disease. ISD has not been used to study refractory heartburn or FH. Our aim was to compare ISD in healthy controls and refractory heartburn patients with GERD and FH., Methods: In refractory heartburn patients (heartburn more than twice/week for at least 2 months despite proton pump inhibitor (PPI) b.i.d.), erosive esophagitis and/or abnormal impedance-pH (increased acid exposure or positive symptom index) defined GERD; normal esophagogastroduodenoscopy (EGD)/impedance-pH defined FH. Asymptomatic, healthy controls had normal EGD and pH-metry. Mean ISD in each subject, determined by blinded TEM of esophageal biopsies, was the average of 100 measurements (10 measurements in each of 10 micrographs)., Results: In all, 11 healthy controls, 11 FH, and 15 GERD patients were studied. Mean ISD was significantly higher in GERD compared with controls (0.87 vs. 0.32 μm, P=0.003) and FH (0.87 vs. 0.42 μm, P=0.012). Mean ISD was similar in FH and controls (0.42 vs. 0.32 μm, P=0.1). The proportion of patients with abnormal ISD was significantly higher for GERD compared with FH (60 vs. 9%, P=0.014)., Conclusions: ISD is increased in refractory heartburn patients with GERD but not those with FH. Our findings suggest that measurement of ISD by TEM might be a useful tool to distinguish GERD from FH in patients with refractory heartburn.

Barrett's esophagus (BE) is an intestinal metaplasia that occurs in the setting of chronic acid and bile reflux and is associated with a risk for adenocarcinoma. Expression of intestine-specific transcription factors in the esophagus likely contributes to metaplasia development. Our objective was to explore the effects of an intestine-specific transcription factor when expressed in the mouse esophageal epithelium. Transgenic mice were derived in which the transcription factor Cdx2 is expressed in squamous epithelium using the murine Keratin-14 gene promoter. Effects of the transgene upon cell proliferation and differentiation, gene expression, and barrier integrity were explored. K14-Cdx2 mice express the Cdx2 transgene in esophageal squamous tissues. Cdx2 expression was associated with reduced basal epithelial cell proliferation and altered cell morphology. Ultrastructurally two changes were noted. Cdx2 expression was associated with dilated space between the basal cells and diminished cell-cell adhesion caused by reduced Desmocollin-3 mRNA and protein expression. This compromised epithelial barrier function, as the measured trans-epithelial electrical resistance (TEER) of the K14-Cdx2 epithelium was significantly reduced compared to controls (1189 Ohm*cm(2) ±343.5 to 508 Ohm*cm(2)±92.48, p = 0.0532). Secondly, basal cells with features of a transitional cell type, intermediate between keratinocytes and columnar Barrett's epithelial cells, were observed. These cells had reduced keratin bundles and increased endoplasmic reticulum levels, suggesting the adoption of secretory-cell features. Moreover, at the ultrastructural level they resembled "Distinctive" cells associated with multilayered epithelium. Treatment of the K14-Cdx2 mice with 5'-Azacytidine elicited expression of BE-associated genes including Cdx1, Krt18, and Slc26a3/Dra, suggesting the phenotype could be advanced under certain conditions. We conclude that ectopic Cdx2 expression in keratinocytes alters cell proliferation, barrier function, and differentiation. These altered cells represent a transitional cell type between normal squamous and columnar BE cells. The K14-Cdx2 mice represent a useful model to study progression from squamous epithelium to BE.

The celomic system of the articulate brachiopod Hemithyris psittacea is composed of the perivisceral cavity, the canal system of the lophophore, and the periesophageal celom. We study the microscopic anatomy and ultrastructure of the periesophageal celom using scanning and transmission electron microscopy. The periesophageal celom surrounds the esophagus, is isolated from the perivisceral cavity, and is divided by septa. The lining of the periesophageal celom includes two types of cells, epithelial cells and myoepithelial cells, both are monociliary. Some epithelial cells have long processes extending along the basal lamina, suggesting that these cells might function as podocytes. The myoepithelial cells have basal myofilaments and may be overlapped by the apical processes of the adjacent epithelial cells. The periesophageal celom forms protrusions that penetrate the extracellular matrix (ECM) of the body wall above the mouth and the ECM that surrounds the esophagus. The canals of the esophageal ECM form a complicated system. The celomic lining of the external circumferential canals consists of the epithelial cells and the podocyte-like cells. The deepest canals lack a lumen; they are filled with the muscle cells surrounded by basal lamina. These branched canals might perform dual functions. First, they increase the surface area and might therefore facilitate ultrafiltration through the podocyte-like cells. Second, the deepest canals form the thickened muscle wall of the esophagus and could be necessary for antiperistalsis of the gut., (Copyright © 2010 Wiley-Liss, Inc.)

The organization of the oesophagus in the budding styelid ascidian, Polyandrocarpa misakiensis, is described. The oesophagus consists of external and internal epithelium, and there are loose connective tissue, blood sinuses, and a muscular layer between them. The internal epithelium is simple columnar, except for the bottom of three folds. The external epithelium is simple squamous. The internal epithelium contains four cell types, i.e., ciliated mucous cells, band cells, endocrine cells, and undifferentiated cells. The ciliated mucous cells have apical cilia and microvilli, and two types of mucous vesicle. The band cells also have apical cilia and electron-dense granules in the apical cytoplasm. The endocrine cells are bottle-shaped, and have electron-dense granules both above and below the nucleus. The undifferentiated cells form pseudostratified epithelium at the bottom of each fold, and they have nuclei with prominent nucleoli. One type of coelomic cell, which has retractile cytoplasm, often migrates in the internal epithelium. Near the stomach, there are many darkly stained round cells clustered around the posterior end of the oesophagus. These two types of coelomic cells may be involved in the defense mechanism against the invasion of foreign organisms. The basic organization of the oesophagus of P. misakiensis is similar to those of other ascidians. However, the presence of three folds is a characteristic of a solitary species, rather than of a colonial species. Although ascidians are chordate invertebrates, the organization of their oesophagus is not very complex, which might reflect their life style.

Purpose: To investigate the use and subsequent healing of a silicone stented small intestinal submucosa (SIS) tube as a full-circumference replacement following surgical resection of the esophagus in piglets., Material and Methods: Three centimeters of the intrathoracic esophagus was replaced with a silicone stented SIS tube (Cook Medical) in 6 growing piglets. The esophageal stent was retained for 4 weeks. Esophageal dilations were performed, if needed, after stent removal., Results: The piglets were sacrificed 1-17 weeks after surgery. Recurrent dilations were needed after stent removal. Histology showed that the gap between the resection margins was filled with new loose connective tissue consisting of fibroblasts and few inflammatory cells. In this tissue, intense angiogenesis was seen at the early time points, which then gave way to the proliferation of immature-looking smooth-muscle-like cells in the submucosa, which appeared to stem from the pericytes of the ingrowing capillaries., Conclusions: Through using a stented SIS tube as a circumferential esophageal replacement in a piglet model, this study suggests that pericytes from ingrowing capillaries may play a role in the remodeling of the SIS mesh. It remains to be seen if this process gives a favorable end result because stricture formation after stent removal remains a problem., (Copyright © 2011 S. Karger AG, Basel.)

The study aims to determine whether light microscopy can be used to accurately measure the diameters of intercellular spaces between squamous epithelial cells in the lower esophagus, and whether changes in this outcome measure can be used as a diagnostic marker for gastroesophageal reflux disease (GERD). The study has two parts. Part 1 involves 42 asymptomatic controls and 119 patients with typical symptoms of GERD, including 58 with erosive esophagitis (EE), and 61 patients with nonerosive gastroesophageal reflux disease (NERD). All biopsies were taken from the lower esophagus. All samples were observed using an immersion objective, after which diameters were measured by computer-assisted morphometry. Part 2 involves 61 individuals who were randomly selected from part 1, including 19 controls, 13 with NERD and 29 with EE. Diameter measurements using both light microscopy and transmission electron microscopy (TEM) were performed for samples of 61 individuals. Samples from a total of 61 individuals (31 male, 30 female, mean age 44.3 ± 16.0 years) were observed using both light microscopy and TEM. Both methods showed significant differences between control and disease groups; the outcomes from the two methods had a certain correlation (r = 0.605, P = 0.000). Morphometric analysis of all 161 individuals (83 males, 78 females, mean age 41.4 ± 15.7) showed mean diameters from light microscopy to be 0.58 ± 0.16 µm for controls, 1.07 ± 0.30 µm for NERD, and 1.29 ± 0.20 µm for EE; differences between control and disease groups were significant (P<0.05). The optimal cut-off value from receiver operator characteristic analysis was 0.85 µm. Diagnoses were validated using the combination of symptoms of GERD, endoscopy, and 24 h ambulatory pH monitoring as the gold standard. At the optimal cutoff, sensitivity was 93.3% and specificity was 100%. The diameters of the intercellular spaces in squamous epithelium of lower esophagus from controls and in patients with GERD can be quantitatively measured using light microscopy. Dilated diameters can serve as a sensitive, specific, and objective indicator for diagnosis of GERD., (© 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Background and Aims: Bronchial asthma (BA) is considered an extra-esophageal syndrome of gastroesophageal reflux disease (GERD) with poor pathophysiological background. We analyzed the correlation between GERD and BA, examining esophageal epithelium with transmission electron microscopy (TEM), along with clinical findings., Methods: BA patients of controlled and partly-controlled levels were enrolled in the study. A pulmonary and gastrointestinal (GI) questionnaire was given. Patients with no symptoms joined the control group. Esophageal mucosal tissue was taken by esophagogastroduodenoscopy from both groups and processed for TEM. Intercellular space (IS) was measured with an image analyzing program, 100 times for each patient., Results: The control (n=20) and BA (n=20) groups revealed no significant differences in baseline characteristics. All BA patients were using corticosteroid inhalers, with seven patients having a recent history of acute exacerbation. Patients with at least one GI symptom made up 70% (14/20) of the BA group, and heartburn and/or regurgitation were detected in 40% of patients. Endoscopic findings of GERD were mucosal breaks (n=3). The IS of the control group was 0.389±0.297 um, while the BA group was 0.806±0.556 um (P=0.001). The presence of GERD symptoms (P=0.306) and a history of recent asthma attacks (P=0.710) did not show significant differences., Conclusions: The BA group showed a significant difference in the dilatation of IS compared to the control group, suggesting a higher prevalence of GERD in BA patients and a close pathophysiological correlation., (© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Purpose: To investigate the optimal concentration of sodium hydroxide (NaOH) on esophageal stricture formation in rats to establish an animal model of benign esophageal stricture (BES)., Methods: Corrosive esophageal burn was produced by internal application of different concentrations of NaOH to the distal esophagus in rats. As much as 66 male rats were randomly divided into eight groups: Group A (control, n = 6), Group B (sham-operated group, n = 6), Group C (5% NaOH, n = 8), Group D (10% NaOH, n = 8), Group E (20% NaOH, n = 8), Group F (30% NaOH, n = 10), Group G (40% NaOH, n = 14), and Group H (50% NaOH, n = 6). Surviving rats were killed at 28 days. The survival rate, body weight gain, symptoms, and histopathological changes were assessed., Results: The mortality rate was high in Groups G and H (73 and 67%). The prevalence of symptoms of BES was 43% in Groups D and E, 50% in Group F, 75% in Group G, and 100% in Group H. Statistically significant stricture formation of the esophagus was observed in Groups F and G. The degree of tissue damage was significantly higher in Groups E, F, and G., Conclusion: A high concentration of NaOH of 30% was required to establish a survivable BES model in rats.

The posterior esophagus of Bulla striata, running from the gizzard to the stomach, was investigated with light and electron microscopy to obtain new data for a comparative analysis of the digestive system in cephalaspidean opisthobranchs. In this species, the posterior esophagus can be divided into two regions. In the first, the epithelium is formed by columnar cells with apical microvilli embedded in a cuticle. Many epithelial and subepithelial secretory cells are present in this region. In both, electron-lucent secretory vesicles containing filaments and a peripheral round mass of secretory material fill the cytoplasm. These acid mucus-secreting cells may also contain a few dense secretory vesicles. In the second part of the posterior esophagus, the cuticle is absent and the epithelium is ciliated. In this region, epithelial cells may contain larger lipid droplets and glycogen reserves. Subepithelial secretory cells are not present, and in epithelial secretory cells the number of dense vesicles increases, but most secretory cells still contain some electron-lucent vesicles. These cells secrete a mixture of proteins and acid polysaccharides and should be considered seromucous. The secretory cells of the posterior esophagus are significantly different from those previously reported in the anterior esophagus of this herbivorous species.