Electronic Structure of Ce-Doped and -Undoped Nd_{2}CuO_{4} Superconducting Thin Films Studied by Hard X-Ray Photoemission and Soft X-Ray Absorption Spectroscopy.

In order to realize superconductivity in cuprates with the T^{'}-type structure, not only chemical substitution (Ce doping) but also postgrowth reduction annealing is necessary. In the case of thin films, however, well-designed reduction annealing alone without Ce doping can induce superconductivity in the T^{'}-type cuprates. In order to unveil the origin of superconductivity in the Ce-undoped T^{'}-type cuprates, we have performed bulk-sensitive hard x-ray photoemission and soft x-ray absorption spectroscopy on superconducting and nonsuperconducting Nd_{2-x}Ce_{x}CuO_{4} (x=0, 0.15, and 0.19) thin films. By postgrowth annealing, core-level spectra exhibited dramatic changes, which we attributed to the enhancement of core-hole screening in the CuO_{2} plane and the shift of chemical potential along with changes in the band filling. The result suggests that the superconducting Nd_{2}CuO_{4} film is doped with electrons despite the absence of the Ce substitution.

Tensile-Strain-Dependent Spin States in Epitaxial LaCoO_{3} Thin Films.

The spin states of Co^{3+} ions in perovskite-type LaCoO_{3}, governed by the complex interplay between the electron-lattice interactions and the strong electron correlations, still remain controversial due to the lack of experimental techniques which can directly detect them. In this Letter, we revealed the tensile-strain dependence of spin states, i.e., the ratio of the high- and low-spin states, in epitaxial thin films and a bulk crystal of LaCoO_{3} via resonant inelastic soft x-ray scattering. A tensile strain as small as 1.0% was found to realize different spin states from that in the bulk.

Telomere length determined by the fluorescence in situ hybridisation distinguishes malignant and benign cells in cytological specimens.

BACKGROUND: Telomeres are tandem repeats of TTAGGG at the end of eukaryotic chromosomes that play a key role in preventing chromosomal instability. The aim of the present study is to determine telomere length using fluorescence in situ hybridisation (FISH) on cytological specimens. METHODS: Aspiration samples (n = 41) were smeared on glass slides and used for FISH. RESULTS: Telomere signal intensity was significantly lower in positive cases (cases with malignancy, n = 25) as compared to negative cases (cases without malignancy, n = 16), and the same was observed for centromere intensity. The difference in DAPI intensity was not statistically significant. The ratio of telomere to centromere intensity did not show a significant difference between positive and negative cases. There was no statistical difference in the signal intensities of aspiration samples from ascites or pleural effusion (n = 23) and endoscopic ultrasound-guided FNA samples from the pancreas (n = 18). CONCLUSIONS: The present study revealed that telomere length can be used as an indicator to distinguish malignant and benign cells in cytological specimens. This novel approach may help improve diagnosis for cancer patients.

Endocytoscopic observation of various esophageal lesions at ×600: can nuclear abnormality be recognized?

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.

Secreted factor R-Spondin 2 is involved in refinement of patterning of the mammalian cochlea.

BACKGROUND: In the cochlea, patterning of the organ of Corti is tightly regulated to produce a single row of sound-detecting inner hair cells and three rows of outer hair cells, which amplify and refine the signal. The recently identified R-Spondin family of signaling molecules usually act as co-activators of Wnt signaling; it is thought that they regulate turnover of Wnt receptors at the membrane. We sought to test whether R-Spondins function in the developing cochlea. RESULTS: Expression analysis of all four members of the R-Spondin family showed that only R-Spondin2 (Rspo2) is expressed in the cochlea during development of the sensory epithelium. Examination of an Rspo2(-/-) mouse showed that loss of Rspo2 results in an additional single row of outer hair cells and disruption of peripheral innervation pattern. Addition of Rspo2 recombinant protein to organotypic cochlear cultures resulted in a small but significant decrease in the number of outer hair cells. CONCLUSIONS: Rspo2 is required to limit the number of outer hair cells to three rows and for optimal arrangement of peripheral nerve fibers. The Rspo2 gain- and loss-of-function studies show that in the ear, Rspo2 function is not consistent with its assigned role as a Wnt potentiator.

[Lymph node metastasis in superficial squamous carcinoma of the esophagus]. / Lymphknotenmetastasen bei Plattenepithelfrühkarzinomen des Ösophagus.

The definition of early carcinoma of the esophagus has changed with time on the basis of new data. As from 2007 an early carcinoma is defined as an intramucosal carcinoma with or without metastasis. In the subclassification based on invasion depth, m1 and m2 squamous cell carcinomas have no metastasis and are considered curable by endoscopic resection alone, whereas less than 10% of m3 carcinomas and some 20% of sm1 squamous cell carcinomas have lymph node metastasis. In this article the relationship between various histopathological findings and the incidence of lymph node metastasis is reviewed. The m3 and sm1 superficial squamous cell carcinomas showing 0-I and 0-III types, large tumors over 50 mm in size or those showing vessel permeation have higher incidences of lymph node metastasis. In the field of gastrointestinal surgical pathology pathologists are now expected to not only diagnose the presence or absence of malignancy but also to investigate in detail many of the histological factors related to the prevalence of lymph node metastasis.

Detailed features of palisade vessels as a marker of the esophageal mucosa revealed by magnifying endoscopy with narrow band imaging.

The palisade vessels present at the distal end of the esophagus are considered to be a landmark of the esophagogastric junction and indispensable for diagnosis of columnar-lined esophagus on the basis of the Japanese criteria. Here we clarified the features of normal palisade vessels at the esophagogastric junction using magnifying endoscopy. We prospectively studied palisade vessels in 15 patients undergoing upper gastrointestinal endoscopy using a GIF-H260Z instrument (Olympus Medical Systems Co., Tokyo, Japan). All views of the palisade vessels were obtained at the maximum magnification power in the narrow band imaging mode. We divided the area in which palisade vessels were present into three sections: the area from the squamocolumnar junction (SCJ) to about 1 cm orad within the esophagus (Section 1); the area between sections 1 and 3 (Section 2); and the area from the upper limit of the palisade vessels to about 1 cm distal within the esophagus (Section 3). In each section, we analyzed the vessel density, caliber of the palisade vessels, and their branching pattern. The vessel density in Sections 1, 2, and 3 was 9.1 ± 2.1, 8.0 ± 2.6, and 3.3 ± 1.3 per high-power field (mean ± standard deviation [SD]), respectively, and the differences were significant between Sections 1 and 2 (P= 0.0086) and between Sections 2 and 3 (P < 0.0001). The palisade vessel caliber in Sections 1, 2, and 3 was 127.6 ± 52.4 µm, 149.6 ± 58.6 µm, and 199.5 ± 75.1 µm (mean ± SD), respectively, and the differences between Sections 1 and 2, and between Sections 2 and 3, were significant (P < 0.0001). With regard to branching form, the frequency of branching was highest in Section 1, and the 'normal Y' shape was observed more frequently than in Sections 2 and 3. Toward the oral side, the frequency of branching diminished, and the frequency of the 'upside down Y' shape increased. The differences in branching form were significant among the three sections (P < 0.0001). These results indicate that the density of palisade vessels is highest near the SCJ, and that towards their upper limit they gradually become more confluent and show an increase of thickness. Within a limited area near the SCJ, observations of branching form suggest that palisade vessels merge abruptly on the distal side. We have demonstrated that palisade vessels are a useful marker for endoscopic recognition of the lower esophagus.

Band structure of the heavily-electron-doped FeAs-based Ba(Fe,Co)2As2 superconductor suppresses antiferromagnetic correlations.

In the heavily-electron-doped regime of the Ba(Fe,Co)2As2 superconductor, three hole bands at the zone center are observed and two of them reach the Fermi level. The larger hole pocket at the zone center is apparently nested with the smaller electron pocket around the zone corner. However, the (pi,0) Fermi surface reconstruction reported for the hole-doped case is absent in the heavily-electron-doped case. This observation shows that the apparent Fermi surface nesting alone is not enough to enhance the antiferromagnetic correlation as well as the superconducting transition temperature.

Chronic administration of DSP-7238, a novel, potent, specific and substrate-selective DPP IV inhibitor, improves glycaemic control and beta-cell damage in diabetic mice.

AIMS: The purpose of this study is to assess the in vitro enzyme inhibition profile of DSP-7238, a novel non-cyanopyrrolidine dipeptidyl peptidase (DPP) IV inhibitor and to evaluate the acute and chronic effects of this compound on glucose metabolism in two different mouse models of type 2 diabetes. METHODS: The in vitro enzyme inhibition profile of DSP-7238 was assessed using plasma and recombinant enzymes including DPP IV, DPP II, DPP8, DPP9 and fibroblast activation protein alpha (FAPalpha) with fluorogenic substrates. The inhibition type was evaluated based on the Lineweaver-Burk plot. Substrate selectivity of DSP-7238 and comparator DPP IV inhibitors (vildagliptin, sitagliptin, saxagliptin and linagliptin) was evaluated by mass spectrometry based on the changes in molecular weight of peptide substrates caused by release of N-terminal dipeptides. In the in vivo experiments, high-fat diet-induced obese (DIO) mice were subjected to oral glucose tolerance test (OGTT) following a single oral administration of DSP-7238. To assess the chronic effects of DSP-7238 on glycaemic control and pancreatic beta-cell damage, DSP-7238 was administered for 11 weeks to mice made diabetic by a combination of high-fat diet (HFD) and a low-dose of streptozotocin (STZ). After the dosing period, HbA1c was measured and pancreatic damage was evaluated by biological and histological analyses. RESULTS: DSP-7238 and sitagliptin both competitively inhibited recombinant human DPP IV (rhDPP IV) with K(i) values of 0.60 and 2.1 nM respectively. Neither vildagliptin nor saxagliptin exhibited competitive inhibition of rhDPP IV. DSP-7238 did not inhibit DPP IV-related enzymes including DPP8, DPP9, DPP II and FAPalpha, whereas vildagliptin and saxagliptin showed inhibition of DPP8 and DPP9. Inhibition of glucagon-like peptide-1 (GLP-1) degradation by DSP-7238 was apparently more potent than its inhibition of chemokine (C-X-C motif) ligand 10 (IP-10) or chemokine (C-X-C motif) ligand 12 (SDF-1alpha) degradation. In contrast, vildagliptin and saxagliptin showed similar degree of inhibition of degradation for all the substrates tested. Compared to treatment with the vehicle, single oral administration of DSP-7238 dose-dependently decreased plasma DPP IV activity and improved glucose tolerance in DIO mice. In addition, DSP-7238 significantly decreased HbA1c and ameliorated pancreatic damage following 11 weeks of chronic treatment in HFD/STZ mice. CONCLUSIONS: We have shown in this study that DSP-7238 is a potent DPP IV inhibitor that has high specificity for DPP IV and substrate selectivity against GLP-1. We have also found that chronic treatment with DSP-7238 improves glycaemic control and ameliorates beta-cell damage in a mouse model with impaired insulin sensitivity and secretion. These findings indicate that DSP-7238 may be a new therapeutic agent for the treatment of type 2 diabetes.

Prospective replacement of magnifying endoscopy by a newly developed endocytoscope, the 'GIF-Y0002'.

Endocytoscopy has the potential to reduce the need for histologic examination of biopsy specimens in cases of esophageal squamous cell carcinoma. Up to now, two types of endocytoscope have been used: the probe type and the integrated type. In this study we examined the utility of a newly developed endocytoscope, the 'GIF-Y0002,' which has a single lens allowing consecutive magnification from the conventional endoscopy level up to ×380. Using the GIF-Y0002, we examined 24 examples of normal esophageal mucosa to clarify the appearance of the microvasculature of the normal squamous epithelium in vivo. We also examined 11 cases of esophageal cancer in the same way, employing methylene blue as a vital dye to stain the surface cells. In normal squamous epithelium, we clarified the relationship between the subepithelial capillary network, IPCLs and subepithelial venules. With methylene blue staining, we observed typical squamous cells (low nuclear density and low N/C ratio without nuclear abnormality). When cancerous lesions were observed using lower-power magnification, we were able to visualize their microvascular architecture to the same extent as when conventional magnifying endoscopy was used. Furthermore, at higher magnification, we were able to visualize the features of blood flow in both superficial and advanced cancer. Methylene blue staining revealed an increase of nuclear density in all cases of cancer. The pathologist agreed to omit biopsy histology in 81.8% (9/11) of cancer cases considering the nuclear density and nuclear abnormality. The GIF-Y0002 provides information on cell abnormality in addition to the features revealed by currently available magnifying endoscopy.

Endocytoscopic observation for esophageal squamous cell carcinoma: can biopsy histology be omitted?

We examined whether endocytoscopic observation of esophageal squamous cell carcinoma can replace the histologic examination of biopsy specimens. In a basic investigation, we examined 57 iodine-unstained areas in the resected specimens of the esophagus from 28 individuals. The endocytoscopic findings were graded from 0 to 3 in tandem with observations of the iodine staining. For endocytoscopic observation, we sprayed 1% methylene blue or toluidine blue as a vital dye on the surface of the esophageal mucosa, allowing 15-20 s for sufficient staining. One endoscopist observed the target lesions and decided their endocytoscopic type classification. Histological diagnoses were made by two pathologists who were unaware of the endoscopic findings. We then compared the endocytoscopic diagnosis and conventional histological diagnosis. In an in vivo investigation, we examined 71 lesions of esophageal squamous cell carcinoma. Two endoscopists diagnosed the type classification in consultation with a pathologist with regard to 'nuclear density,''nuclear abnormality,' and 'whether biopsy histology could have been omitted on the basis of endocytoscopic findings.' For the in vivo observation, we utilized XEC120U (higher magnification type [x1100]), XEC300F (lower magnification type [x450]), and XGIF-Q260EC1 (lower magnification type [x450]) instruments. In the basic investigation, among the 11 areas classified as Type 1, 10 (91%) were category 1 by the Vienna classification. Among the 39 lesions classified as Type 3, 36 (92%) were category 4 or 5. The sensitivity of endocytoscopy for malignant lesions (Vienna classification categories 4 and 5) was 94.7%, if Type 3 was considered malignant. The specificity was 84.2% according to the same criteria. In the in vivo observation, two endoscopists diagnosed more than 90% of esophageal squamous cell carcinomas as neoplasms using each type of endocytoscope. With regard to nuclear density, the pathologist considered it to be increased in 98% of cases with the XEC120U, in 94% with the XEC300F, and in 93% with the XGIF-Q260EC1. With regard to nuclear abnormality, the positivity rate was 90% with the XEC120U, 78% with the XEC300F, and 80% with the XGIF-Q260EC1. As to whether or not biopsy histology examination was considered necessary, the pathologist made a 'Yes' judgment for 84% of cases observed with the XEC120U, 66% with the XEC300F, and 67% with the XGIF-Q260EC1. Cancerous lesions diagnosed as Type 3 by both endoscopists using the XEC120U accounted for 46 (90.2%) of the 51 cases. Among these 46 cases, biopsy histology was considered unnecessary by the pathologist in 43 (93.5%). We believe that endocytoscopic observation has the potential to reduce the extent of histologic examination of biopsy specimens in cases corresponding to Types 1 and 3 of our classification.

Detailed comparison between endocytoscopy and horizontal histology of an esophageal intraepithelial squamous cell carcinoma.

Endocytoscopy allows the real-time microscopic observation of living cells. Unlike the cross-sectional images obtained by conventional histology, endocytoscopy provides cellular images in a plane parallel to the surface of the mucosa. However, there is little knowledge about the endocytoscopic diagnosis of carcinomas. Using a specimen obtained by the endoscopic submucosal dissection of an intraepithelial esophageal squamous cell carcinoma, a detailed comparison between endocytoscopic and horizontal histological images was made, revealing the similarity between the images. Sharp lateral borders between atypical and normal epithelium and differences in cellularity and the sizes and shapes of the nuclei were clearly identified by endocytoscopy. Further horizontal histological investigations of this case also showed the variety of endocytoscopic images in non-cancerous and cancerous epithelia.

Ex vivo pilot study using computed analysis of endo-cytoscopic images to differentiate normal and malignant squamous cell epithelia in the oesophagus.

BACKGROUND AND STUDY AIMS: An endo-cytoscopy system allows acquisition of optical biopsies that are quite similar to conventional histology. To simplify discrimination between normal and malignant tissue in the oesophagus using endo-cytoscopy system, we analysed the nuclear (dark staining) area in the obtained images with the goal of an accurate, automatic diagnosis. PATIENTS AND METHODS: Ex vivo endo-cytoscopic observation was performed using endoscopically or surgically resected oesophagus from 10 enrolled patients. Oesophageal tissues were stained using 1% methylene blue, and endo-cytoscopic images were obtained at normal and malignant areas (two areas of each) in each oesophagus. The centre of each image (4x10(-2) mm(2)) was processed by computer, and the area occupied by the total nuclei in each selected field and its ratio to the entire field were calculated. RESULTS: The mean area of the total nuclei was 0.10x10(-2)+/-0.03x10(-2) mm(2) (range 0.05x10(-2) to 0.18x10(-2) mm(2)) in the normal group and 0.40x10(-2)+/-0.06x10(-2) mm(2) (range 0.33x10(-2) to 0.55x10(-2) mm(2)) in the malignant group (P<0.001). The mean ratio of total nuclei to the entire selected field was 6.4+/-1.9% (range 3.1-11.3%) in the normal tissues and 25.3+/-3.8% (range 20.5-34.5%) in the malignant samples (P<0.001). CONCLUSIONS: Endo-cytoscopy system allowed automatic differentiation of normal and malignant tissues in the oesophagus, which could simplify endo-cytoscopic diagnosis. Further study will elucidate whether such analysis is applicable to inflammatory or pre-malignant epithelia in the oesophagus or other gastrointestinal organs.

Light and electron microscopic studies of perineural invasion by esophageal carcinoma.

Light and electron microscopic findings on perineural invasion by human esophageal squamous cell carcinoma are reported. Perineural invasion was observed histologically in 30 of a total of 129 cases (23%) of esophageal squamous cell carcinoma and in 11 of the 24 cases (46%) in which tumors infiltrated other organs by passing through the esophageal adventitial layer. Electron microscopic observation showed that the perineurium of peripheral nerves was completely surrounded by carcinoma cells and that marked degeneration and loss of perineural cells occurred. Irregularly thickened basal laminae were detected in the perineurium. For nerves incompletely surrounded by carcinoma tissue, the free portion of the perineurium revealed degenerative findings similar to those for completely surrounded nerves. Cytoplasmic projections of the leading margin of the invading cancer tissue were located in the degenerated perineurium, contained many lysosomes, and were not always surrounded by basal laminae. These observations suggest that invading carcinoma tissue actively contributes to the degeneration of the perineural sheath and that the special pattern of carcinoma tissue surrounding the peripheral nerves results from infiltration along the degenerated sheath of the perineurium.

Increased expression of ornithine decarboxylase messenger RNA in human esophageal carcinoma.

Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines, which are essential for cell proliferation. The purpose of this study was to evaluate ODC expression in human esophageal cancer at the mRNA level. Sixty-four pairs of primary esophageal cancers and normal esophageal epithelia were examined by reverse transcription-PCR for ODC mRNA expression. The ODC mRNA levels were higher in primary esophageal carcinoma than in adjacent normal esophageal epithelium in 58 (90.6%) of 64 cases. The tumor:normal (T:N) ratio of ODC mRNA expression in esophageal specimens has a significant correlation with tumor-node-metastasis staging (P = 0.043), lymph node metastasis (P = 0.039), vascular vessel invasion (P = 0.035), and histology (P = 0.034) of the tumor. In well- and moderately differentiated squamous cell carcinoma, the patients with a higher T:N ratio showed a significantly poorer prognosis (P = 0.027), and multivariate analysis also confirmed that the T:N ratio has a significant correlation with poor prognosis (P = 0.043). The steady-state of ODC mRNA overexpression in esophageal carcinoma implies that the ODC gene may play an important role in tumorgenesis in squamous epithelium. Furthermore, ODC mRNA expression may be used as a prognostic marker, especially for well- and moderately differentiated squamous cell carcinoma.

Telomerase activity and telomere length in benign and malignant human thyroid tissues.

Several studies have demonstrated that telomerase is activated and telomere length is altered in various types of tumors. In this study, we investigated telomerase activities and telomere length in 21 thyroid tumors. Telomerase activity was detected in 11 of 12 thyroid cancers and three of nine follicular adenomas. The mean telomere lengths in the cancers tissue and follicular adenomas were lower than in the respective background tissues, the differences being significant (P=0.0055 and P<0.006), respectively. Our findings suggest that change in telomerase activity and telomere length may be important for development of thyroid tumors.

Correlation of telomere lengths in normal and cancers tissue in the large bowel.

The hypothesis that telomeres in colorectal cancer cells exhibit age-related shortening, as in normal cells of the colorectal epithelium, was tested with samples of non-cancerous mucosa and cancer tissue from 124 patients (aged 29-97 years). Shortening with aging could be demonstrated for both normal and cancer tissues; regression analysis showed rates for length reduction of 44 and 50 base pair/year, respectively. Straight, essentially parallel, lines were obtained for the two cases, normal tissue values being about 2 kilobase pairs (kbp) higher, with a significant correlation between data at the individual patient level.

alpha6 integrin expression in esophageal carcinoma.

One of the genes that the authors have isolated by a differential display of hepatocellular carcinoma compared to adjacent liver is the alpha6 integrin. alpha6 integrin is the major adhesion receptor for laminin and is suggested to be involved in tumor cell invasion and metastasis. To our knowledge, however, there are no reports on alpha6 integrin expression in esophageal carcinoma. We thus conducted a study to determine its clinicopathologic significance in human esophageal carcinoma. The tumor/normal (T/N) ratio of alpha6 integrin expression was calculated by Northern hybridization in 45 cases of esophageal carcinoma. In selected cases the expression of the alpha6 integrin variants A and B was also investigated by reverse transcriptase-polymerase chain reaction, and immunostaining for alpha6 integrin was performed. The expression levels of alpha6 integrin mRNA in the tumor tissue were greater than those of the corresponding normal tissue in 39 of 45 cases (87%). The overexpression of alpha6 integrin was also recognized by immunostaining. Fifteen cases with a high T/N ratio demonstrated a deeper invasion into the esophageal wall than the 30 cases with a low T/N ratio. Although there was no significant difference, the 15 cases with a high T/N ratio had a tendency for a worse prognosis. The ratio of the two variants (alpha6A/alpha6B) did not show any relationship to survival. The findings imply that alpha6 integrin is overexpressed in human esophageal carcinomas and that alpha6 integrin may play an important role in esophageal tumor invasion.

Double muscularis mucosae in Barrett's esophagus.

To clarify the histology and morphogenesis of the double muscularis mucosae in Barrett's esophagus, eight specimens resected from patients with Barrett's esophagus were compared histopathologically with 352 specimens resected from patients without Barrett's esophagus. A double muscularis mucosae was observed in seven (87.5%) of the eight cases with Barrett's esophagus, but in none of the 352 cases without Barrett's esophagus. The mucosa in the segment of Barrett's esophagus consisted of columnar epithelium, a superficial lamina propria, a superficial muscularis mucosae, a deep lamina propria, and a deep muscularis mucosae. The distal end of the superficial muscularis mucosae was connected to the deep muscularis mucosae at the esophagogastric junction, and its proximal end was located in fibrous tissue below the squamocolumnar junction of the mucosal epithelium or the distal edge of the erosive lesion. The deep muscularis mucosae in the portion with Barrett's esophagus was continuous with the original muscularis mucosae of the proximal esophagus and muscularis mucosae of the stomach. Barrett's esophagus is considered to be not merely a metaplastic lesion within the epithelium, but a newly developed lesion containing columnar epithelium, lamina propria, and a superficial muscularis mucosae on the lamina propria of the esophageal mucosa.