Science.gov

Sample records for histologically normal epithelium

  1. Gene expression profiles of estrogen receptor positive and estrogen receptor negative breast cancers are detectable in histologically normal breast epithelium

    PubMed Central

    Graham, Kelly; Ge, Xijin; de las Morenas, Antonio; Tripathi, Anusri; Rosenberg, Carol L.

    2010-01-01

    Purpose Previously, we found that gene expression in histologically normal breast epithelium (NlEpi) from women at high breast cancer risk can resemble gene expression in NlEpi from cancer-containing breasts. Therefore, we hypothesized that gene expression characteristic of a cancer subtype might be seen in NlEpi of breasts containing that subtype. Experimental Design We examined gene expression in 46 cases of microdissected NlEpi from untreated women undergoing breast cancer surgery. From 30 age-matched cases (15 estrogen receptor (ER)+, 15 ER-) we used Affymetryix U133A arrays. From 16 independent cases (9 ER+, 7 ER-), we validated selected genes using qPCR. We then compared gene expression between NlEpi and invasive breast cancer using 4 publicly available datasets. Results We identified 198 genes that are differentially expressed between NlEpi from breasts with ER+ (NlEpiER+) compared to ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers (e.g., ESR1, GATA3, and CX3CL1, FABP7). QPCR validated the microarray results in both the 30 original cases and the 16 independent cases. Gene expression in NlEpiER+ and NlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 25-53% of the genes or probes examined in 4 external datasets overlapped between NlEpi and the corresponding cancer subtype. Conclusions Gene expression differs in NlEpi of breasts containing ER+ compared to ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. NlEpi gene expression may help elucidate subtype-specific risk signatures, identify early genomic events in cancer development and locate targets for prevention and therapy. PMID:21059815

  2. Epithelium

    MedlinePlus

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Epithelium. In: Kierszenbaum AL, Tres LL. Histology and Cell Biology - An Introduction to Pathology , 3rd ed. Philadelphia, ...

  3. Transcriptomic profiles differentiate normal rectal epithelium and adenocarcinoma.

    PubMed

    Hogan, J; Dejulius, K; Liu, X; Coffey, J C; Kalady, M F

    2015-05-01

    Adenocarcinoma is a histologic diagnosis based on subjective findings. Transcriptional profiles have been used to differentiate normal tissue from disease and could provide a means of identifying malignancy. The goal of this study was to generate and test transcriptomic profiles that differentiate normal from adenocarcinomatous rectum. Comparisons were made between cDNA microarrays derived from normal epithelium and rectal adenocarcinoma. Results were filtered according to standard deviation to retain only highly dysregulated genes. Genes differentially expressed between cancer and normal tissue on two-groups t test (P < 0.05, Bonferroni P value adjustment) were further analyzed. Genes were rank ordered in terms of descending fold change. For each comparison (tumor versus normal epithelium), those 5 genes with the greatest positive fold change were grouped in a classifier. Five separate tests were applied to evaluate the discriminatory capacity of each classifier. Genetic classifiers derived comparing normal epithelium with malignant rectal epithelium from pooled stages had a mean sensitivity and specificity of 99.6% and 98.2%, respectively. The classifiers derived from comparing normal and stage I cancer had comparable mean sensitivities and specificities (97% and 98%, respectively). Areas under the summary receiver-operator characteristic curves for each classifier were 0.981 and 0.972, respectively. One gene was common to both classifiers. Classifiers were tested in an independent Gene Expression Omnibus-derived dataset. Both classifiers retained their predictive properties. Transcriptomic profiles comprising as few as 5 genes are highly accurate in differentiating normal from adenocarcinomatous rectal epithelium, including early-stage disease.

  4. Effects of formaldehyde on normal xenotransplanted human tracheobronchial epithelium.

    PubMed Central

    Ura, H.; Nowak, P.; Litwin, S.; Watts, P.; Bonfil, R. D.; Klein-Szanto, A. J.

    1989-01-01

    Epithelial cells obtained from autopsies of full-term fetuses or infants less than 1 year old were isolated, amplified in primary cultures and inoculated in deepithelialized rat tracheas. These tracheas were then sealed and transplanted subcutaneously into irradiated athymic nude mice. Four weeks after transplantation the tracheal lumen was completely covered by epithelium, most of which was of mucociliary respiratory type. At this stage, tracheal transplants containing tracheobronchial epithelium from 20 different donors were exposed to silastic devices containing 0, 0.5, 1 and 2 mg paraformaldehyde. The tracheal transplants were examined histologically at 2, 4, 8, and 16 weeks after transplantation. Before sacrifice, all animals were injected with a single pulse of tritiated thymidine. Important epithelial alterations could be seen in the formaldehyde treated transplants with a maximum effect visible at 2 weeks after exposure. The highest dose of 2 mg produced, in most cases, numerous areas of epithelial erosion and inflammation whereas this effect was not as evident with the lower doses. All doses produced areas of hyperplastic epithelium alternating with areas of pleomorphic-atrophic epithelium. Although the differences in predominance of different types of epithelium was not clearly dose-dependent, the labeling index (LI) showed dose dependence between 2 and 4 weeks after initiation of exposure. The maximum mean LI was three to four times higher than normal, although in some focal hyperplastic-metaplastic lesions the LI was increased up to 20 times. These studies show that formaldehyde, although toxic at higher doses, is able to elicit at lower doses a proliferative response of the human respiratory epithelium that is not preceded by a massive toxic effect. This response is similar, although less intense than that of the rat respiratory epithelium in which formaldehyde proved to be a carcinogen. Images Figure 2 Figure 5 PMID:2913828

  5. Anal anatomy and normal histology.

    PubMed

    Pandey, Priti

    2012-12-01

    The focus of this article is the anatomy and histology of the anal canal, and its clinical relevance to anal cancers. The article also highlights the recent histological and anatomical changes to the traditional terminology of the anal canal. The terminology has been adopted by the American Joint Committee on Cancer, separating the anal region into the anal canal, the perianal region and the skin. This paper describes the gross anatomy of the anal canal, along with its associated blood supply, venous and lymphatic drainage, and nerve supply. The new terminology referred to in this article may assist clinicians and health care providers to identify lesions more precisely through naked eye observation and without the need for instrumentation. Knowledge of the regional anatomy of the anus will also assist in management decisions.

  6. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

    PubMed

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L; Midkiff, Bentley; Troester, Melissa A

    2016-02-01

    Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P < 0.0001), with an approximate 0.7% change in area for each component, until age 55 years when these area measures reached a steady state. Although epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period.

  7. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma

    PubMed Central

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L.; Midkiff, Bentley; Troester, Melissa A.

    2015-01-01

    Complete age-related regression of mammary epithelium, often termed post-menopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study (NBS). High-resolution digital images of normal breast Hematoxylin & Eosin stained slides were partitioned into epithelium, adipose tissue, and non-fatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models Stromal area decreased (p=0.0002) and adipose tissue area increased (p<0.0001), with an approximate 0.7% change in area for each component, until age 55 when these area measures reached a steady state. While epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period. PMID:26772400

  8. Detection of human cytomegalovirus in normal and neoplastic breast epithelium

    PubMed Central

    2010-01-01

    Introduction Human cytomegalovirus (HCMV) establishes a persistent life-long infection, and can cause severe pathology in the fetus and the immunocompromised host[1]. Breast milk is the primary route of transmission in humans worldwide, and breast epithelium is thus a likely site of persistent infection and/or reactivation, though this phenomenon has not previously been demonstrated. Increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. We hypothesized that persistent HCMV infection occurs in normal adult breast epithelium and that persistent viral expression might be associated with normal and neoplastic ductal epithelium. Methods Surgical biopsy specimens of normal breast (n = 38) breast carcinoma (n = 39) and paired normal breast from breast cancer patients (n = 21) were obtained. Specimens were evaluated by immunohistochemistry, in situ hybridization, PCR and DNA sequencing for evidence of HCMV antigens and nucleic acids. Results We detected HCMV expression specifically in glandular epithelium in 17/27 (63%) of normal adult breast cases evaluated. In contrast, HCMV expression was evident in the neoplastic epithelium of 31/32 (97%) patients with ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) cases evaluated (p = 0.0009). Conclusions These findings are the first to demonstrate that persistent HCMV infection occurs in breast epithelium in a significant percentage of normal adult females. HCMV expression was also evident in neoplastic breast epithelium in a high percentage of normal and neoplastic breast tissues obtained from breast cancer patients, raising the possibility that viral infection may be involved in the neoplastic process. PMID:21429243

  9. Analysis of spatial heterogeneity in normal epithelium and preneoplastic alterations in mouse prostate tumor models

    PubMed Central

    Valkonen, Mira; Ruusuvuori, Pekka; Kartasalo, Kimmo; Nykter, Matti; Visakorpi, Tapio; Latonen, Leena

    2017-01-01

    Cancer involves histological changes in tissue, which is of primary importance in pathological diagnosis and research. Automated histological analysis requires ability to computationally separate pathological alterations from normal tissue with all its variables. On the other hand, understanding connections between genetic alterations and histological attributes requires development of enhanced analysis methods suitable also for small sample sizes. Here, we set out to develop computational methods for early detection and distinction of prostate cancer-related pathological alterations. We use analysis of features from HE stained histological images of normal mouse prostate epithelium, distinguishing the descriptors for variability between ventral, lateral, and dorsal lobes. In addition, we use two common prostate cancer models, Hi-Myc and Pten+/− mice, to build a feature-based machine learning model separating the early pathological lesions provoked by these genetic alterations. This work offers a set of computational methods for separation of early neoplastic lesions in the prostates of model mice, and provides proof-of-principle for linking specific tumor genotypes to quantitative histological characteristics. The results obtained show that separation between different spatial locations within the organ, as well as classification between histologies linked to different genetic backgrounds, can be performed with very high specificity and sensitivity. PMID:28317907

  10. Multi-resolution cell orientation congruence descriptors for epithelium segmentation in endometrial histology images.

    PubMed

    Li, Guannan; Raza, Shan E Ahmed; Rajpoot, Nasir M

    2017-04-01

    It has been recently shown that recurrent miscarriage can be caused by abnormally high ratio of number of uterine natural killer (UNK) cells to the number of stromal cells in human female uterus lining. Due to high workload, the counting of UNK and stromal cells needs to be automated using computer algorithms. However, stromal cells are very similar in appearance to epithelial cells which must be excluded in the counting process. To exclude the epithelial cells from the counting process it is necessary to identify epithelial regions. There are two types of epithelial layers that can be encountered in the endometrium: luminal epithelium and glandular epithelium. To the best of our knowledge, there is no existing method that addresses the segmentation of both types of epithelium simultaneously in endometrial histology images. In this paper, we propose a multi-resolution Cell Orientation Congruence (COCo) descriptor which exploits the fact that neighbouring epithelial cells exhibit similarity in terms of their orientations. Our experimental results show that the proposed descriptors yield accurate results in simultaneously segmenting both luminal and glandular epithelium.

  11. Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues

    DTIC Science & Technology

    2012-09-01

    undergoing reduction mammoplasty surgeries . (A) A normal breast TDLU with normal length telomeres in all cell types present. (B) A normal breast TDLU...to severe telomere shortening is highly prevalent within histologically normal TDLUs obtained from women undergoing reduction mammoplasty surgeries ...specialize in the research and treatment of breast cancer. The trainee has attended weekly journal clubs, Oncology translational research seminars , breast

  12. Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing.

    PubMed

    Radovich, Milan; Clare, Susan E; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A; Solzak, Jeffrey P; Kassem, Nawal; Mathieson, Theresa; Storniolo, Anna Maria V; Rufenbarger, Connie; Lillemoe, Heather A; Blosser, Rachel J; Choi, Mi Ran; Sauder, Candice A; Doxey, Diane; Henry, Jill E; Hilligoss, Eric E; Sakarya, Onur; Hyland, Fiona C; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W; Schneider, Bryan P

    2014-01-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.

  13. NORMAL GENE EXPRESSION IN MALE F344 RAT NASAL TRANSITIONAL/RESPIRATORY EPITHELIUM

    EPA Science Inventory

    Abstract

    The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity in rodents. Gene expression profiles were determined in order to provide normal baseline data for nasal transitional/respiratory epithelium from healthy rats. Ce...

  14. STUDIES OF NORMAL GENE EXPRESSION IN THE RAT NASAL EPITHELIUM USNG CDNA ARRAY TECHNOLOGY

    EPA Science Inventory


    Studies of Normal Gene Expression in the Rat Nasal Epithelium Using cDNA Array

    The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity .Gene expression data are being used increasingly for studies of such conditions. In or...

  15. Surfactant protein A expression in human normal and neoplastic breast epithelium.

    PubMed

    Braidotti, P; Cigala, C; Graziani, D; Del Curto, B; Dessy, E; Coggi, G; Bosari, S; Pietra, G G

    2001-11-01

    We studied the presence of surfactant protein A (Sp-A) immunoreactivity and messenger RNA in 62 normal and abnormal breast samples. Sections were immunostained with polyclonal anti-Sp-A antibody. The association between Sp-A immunoreactivity and histologic grade of 32 invasive ductal carcinomas was assessed by 3 pathologists who scored the intensity of Sp-A immunoreactivity times the percentage of tumor immunostained; individual scores were averaged, and the final scores were correlated with tumor grade, proliferative index, and expression of estrogen and progesterone receptors. Strong Sp-A immunoreactivity was present at the luminal surface of ductal epithelial cells in normal breast samples and in benign lesions; carcinomas displayed variable immunoreactivity, inversely proportional to the degree of differentiation. Sp-A messenger RNA was detected by reverse transcriptase-polymerase chain reaction in 3 of 3 normal breast samples and 9 of 9 carcinomas. The significance of Sp-A expression in breast epithelium requires further study; possibly it has a role in native host defense or epithelial differentiation.

  16. Multiphoton microscopic imaging of histological sections without hematoxylin and eosin staining differentiates carcinoma in situ lesion from normal oesophagus

    NASA Astrophysics Data System (ADS)

    Chen, Jianxin; Xu, Jian; Kang, Deyong; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Jiang, Xingshan

    2013-10-01

    Multiphoton microscopy (MPM) has become a powerful, important tool for tissues imaging at the molecular level. In this paper, this technique was extended to histological investigations, differentiating carcinoma in situ (CIS) lesion from normal oesophagus by imaging histological sections without hematoxylin and eosin (H&E) staining. The results show that the histology procedures of dehydration, paraffin embedding, and de-paraffinizing highlighted two photon excited fluorescence of cytoplasm and nucleolus of epithelial cell and collagen in stroma. MPM has the ability to identify the characteristics of CIS lesion including changes of squamous cells and full epithelium, identification of basement membrane, especially prominent nucleolus. The studies described here show that MPM has the potential for future retrospective studies of tumor staging by employing on histological section specimens without H&E staining.

  17. ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium.

    PubMed

    Nguyen-Ngoc, Kim-Vy; Cheung, Kevin J; Brenot, Audrey; Shamir, Eliah R; Gray, Ryan S; Hines, William C; Yaswen, Paul; Werb, Zena; Ewald, Andrew J

    2012-09-25

    Breast cancer progression involves genetic changes and changes in the extracellular matrix (ECM). To test the importance of the ECM in tumor cell dissemination, we cultured epithelium from primary human breast carcinomas in different ECM gels. We used basement membrane gels to model the normal microenvironment and collagen I to model the stromal ECM. In basement membrane gels, malignant epithelium either was indolent or grew collectively, without protrusions. In collagen I, epithelium from the same tumor invaded with protrusions and disseminated cells. Importantly, collagen I induced a similar initial response of protrusions and dissemination in both normal and malignant mammary epithelium. However, dissemination of normal cells into collagen I was transient and ceased as laminin 111 localized to the basal surface, whereas dissemination of carcinoma cells was sustained throughout culture, and laminin 111 was not detected. Despite the large impact of ECM on migration strategy, transcriptome analysis of our 3D cultures revealed few ECM-dependent changes in RNA expression. However, we observed many differences between normal and malignant epithelium, including reduced expression of cell-adhesion genes in tumors. Therefore, we tested whether deletion of an adhesion gene could induce sustained dissemination of nontransformed cells into collagen I. We found that deletion of P-cadherin was sufficient for sustained dissemination, but exclusively into collagen I. Our data reveal that metastatic tumors preferentially disseminate in specific ECM microenvironments. Furthermore, these data suggest that breaks in the basement membrane could induce invasion and dissemination via the resulting direct contact between cancer cells and collagen I.

  18. Normal anatomy and histology of the adult zebrafish.

    PubMed

    Menke, Aswin L; Spitsbergen, Jan M; Wolterbeek, Andre P M; Woutersen, Ruud A

    2011-08-01

    The zebrafish has been shown to be an excellent vertebrate model for studying the roles of specific genes and signaling pathways. The sequencing of its genome and the relative ease with which gene modifications can be performed have led to the creation of numerous human disease models that can be used for testing the potential and the toxicity of new pharmaceutical compounds. Many pharmaceutical companies already use the zebrafish for prescreening purposes. So far, the focus has been on ecotoxicity and the effects on embryonic development, but there is a trend to expand the use of the zebrafish with acute, subchronic, and chronic toxicity studies that are currently still carried out with the more conventional test animals such as rodents. However, before we can fully realize the potential of the zebrafish as an animal model for understanding human development, disease, and toxicology, we must first greatly advance our knowledge of normal zebrafish physiology, anatomy, and histology. To further this knowledge, we describe, in the present article, location and histology of the major zebrafish organ systems with a brief description of their function.

  19. Relative ion permeability of normal and cystic fibrosis nasal epithelium.

    PubMed Central

    Knowles, M; Gatzy, J; Boucher, R

    1983-01-01

    The raised transepithelial electric potential difference (PD) across respiratory epithelia in cystic fibrosis (CF) has suggested an abnormality in ion permeation. We characterized this abnormality further by measuring in the nasal epithelia of CF and normal subjects the concentration-PD relationship for amiloride, an inhibitor of cell Na+ permeability, and PD responses to superfusion with solutions of different composition. Amiloride was more efficacious in the CF subjects but the ED50 was not different from that of normals (approximately 2 X 10(-6) M). Na+ replacement by choline induced effects similar to those of amiloride, i.e. a greater depolarization in CF subjects. A 10-fold increase in the K+ concentration of the perfusate induced a small (less than 10 mV) depolarization in both subject populations. When Cl- in the perfusate was replaced by gluconate or SO2-(4) the nasal PD of normal subjects hyperpolarized (lumen became more negative) by approximately 35 mV. A significantly smaller response (less than 17 mV) was induced in CF homozygotes but not in heterozygotes (38 mV). The smaller response of CF subjects appears to reflect an absolute decrease in luminal surface Cl- permeability because pretreatment with amiloride did not increase the response to Cl- free solution (7 mV). Accordingly, three abnormalities (decreased Cl- permeability, raised PD, greater amiloride efficacy) have been identified in CF respiratory epithelia. Whereas "excessive" active Na+ transport can account for these abnormalities and the dessication of airway surface liquid, it is possible that a lower lumenal cell membrane Cl- permeability and inhibition of a potential path of Cl- secretion can also explain the observations. PMID:6853720

  20. Infrared spectroscopic characteristics of normal and malignant colonic epithelium

    NASA Astrophysics Data System (ADS)

    Krupnik, Eduardo; Jackson, Michael; Bird, Ranjana P.; Smith, Ian C. P.; Mantsch, Henry H.

    1998-04-01

    IR spectroscopy is being widely used to study the biochemical changes associated with cancer. In particular, based upon the hypothesis that biochemical changes associated with cancer precede morphological manifestations of the disease, IR spectroscopy is being evaluated as a potential early diagnostic and prognostic tool. In the current study, IR spectroscopy was applied to the study of colon tissue from rats treated with the specific colon carcinogen azoxymethane, to determine whether tumor induction was associated with identifiable spectroscopic changes in the colon. Characteristic spectra were found for each layer of the colon. Spectra of normal-appearing mucosa and tumors form treated animals then compared to spectra of control mucosa. Differences between tumors and control mucosa were apparent, indicating changes in cellular biochemistry associated with tumor development. In particular, differences in absorptions attributed to nucleic acids were seen, indicating alterations in the structure of cellular DNA in malignant and carcinogen treated tissues. Interestingly, spectra of carcinogen treated rates exhibit characteristics intermediate between those of normal mucosa and tumors. Application of multivariate analysis allowed non-subjective classification of the spectra into three distinct classes with and accuracy of 86.7 percent. The separate classification of control and treated mucosa suggests that IR spectroscopy, when combined with the appropriate classifier, can indeed detect biochemical changes in tissue before physical manifestation of the disease process.

  1. Histology, Immunohistochemistry and Ultrastructure of the Bovine Palatine Tonsil with Special Emphasis on Reticular Epithelium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The paired palatine tonsils are located at the junction of the nasopharynx and oropharynx; ideally positioned to sample antigens entering through either the nasal cavity or oral cavity. Entering antigens will first contact tonsilar epithelium. To better understand the cellular and functional composi...

  2. Detection of molecular signatures of oral squamous cell carcinoma and normal epithelium – application of a novel methodology for unsupervised segmentation of imaging mass spectrometry data

    PubMed Central

    Mrukwa, Grzegorz; Kalinowska, Magdalena; Pietrowska, Monika; Chekan, Mykola; Wierzgon, Janusz; Gawin, Marta; Drazek, Grzegorz; Polanska, Joanna

    2016-01-01

    Intra‐tumor heterogeneity is a vivid problem of molecular oncology that could be addressed by imaging mass spectrometry. Here we aimed to assess molecular heterogeneity of oral squamous cell carcinoma and to detect signatures discriminating normal and cancerous epithelium. Tryptic peptides were analyzed by MALDI‐IMS in tissue specimens from five patients with oral cancer. Novel algorithm of IMS data analysis was developed and implemented, which included Gaussian mixture modeling for detection of spectral components and iterative k‐means algorithm for unsupervised spectra clustering performed in domain reduced to a subset of the most dispersed components. About 4% of the detected peptides showed significantly different abundances between normal epithelium and tumor, and could be considered as a molecular signature of oral cancer. Moreover, unsupervised clustering revealed two major sub‐regions within expert‐defined tumor areas. One of them showed molecular similarity with histologically normal epithelium. The other one showed similarity with connective tissue, yet was markedly different from normal epithelium. Pathologist's re‐inspection of tissue specimens confirmed distinct features in both tumor sub‐regions: foci of actual cancer cells or cancer microenvironment‐related cells prevailed in corresponding areas. Hence, molecular differences detected during automated segmentation of IMS data had an apparent reflection in real structures present in tumor. PMID:27168173

  3. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

    PubMed

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella

    2014-01-01

    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

  4. Brain-derived neurotrophic factor (BDNF) expression in normal and regenerating olfactory epithelium of Xenopus laevis.

    PubMed

    Frontera, Jimena Laura; Cervino, Ailen Soledad; Jungblut, Lucas David; Paz, Dante Agustín

    2015-03-01

    Olfactory epithelium has the capability to continuously regenerate olfactory receptor neurons throughout life. Adult neurogenesis results from proliferation and differentiation of neural stem cells, and consequently, olfactory neuroepithelium offers an excellent opportunity to study neural regeneration and the factors involved in the maintenance and regeneration of all their cell types. We analyzed the expression of BDNF in the olfactory system under normal physiological conditions as well as during a massive regeneration induced by chemical destruction of the olfactory epithelium in Xenopus laevis larvae. We described the expression and presence of BDNF in the olfactory epithelium and bulb. In normal physiological conditions, sustentacular (glial) cells and a few scattered basal (stem) cells express BDNF in the olfactory epithelium as well as the granular cells in the olfactory bulb. Moreover, during massive regeneration, we demonstrated a drastic increase in basal cells expressing BDNF as well as an increase in BDNF in the olfactory bulb and nerve. Together these results suggest an important role of BDNF in the maintenance and regeneration of the olfactory system.

  5. The gastric shield and the underlying epithelium of Chlamys farreri: Morphological, histological and histochemical characterizations

    NASA Astrophysics Data System (ADS)

    Sheng, Xiuzhen; Zhan, Wenbin; Shi, Ping; Ren, Sulian

    2003-03-01

    The gastric shield and underlying stomach epithelium of Chlymas farreri were examined at the light and ultrastructural levels. The results showed that the gastric shield consisted of two different size lobes joined together by a narrow middle piece, the thicker lobe was shaped like a funnel, but unclosed at the lateral side; the other lobe was irregularly triangular-shaped. The transverse section of the thicker lobe was obviously laminated and gradually decreased in thickness from the peak to the margins of the shield. The underlying epithelium bore numerous about 3μm diameter spherical processes formed by the apical plasmalemma of the epithelial cells becoming blunt pseudopodia. Microvilli and some interspersed cilia were present in the areas among the spherical processes regions where only microvilli existed. Rough endoplasmic reticulum, Golgi apparatus, different-sized electron-dense secretory granules and electron-lucent vacuoles as well as abundant mitochondria were present in the underlying epithelial cells. Fused droplets of the secretion from the underlying epithelial cells formed the gastric shield.

  6. Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes.

    PubMed

    Desantis, Salvatore; Accogli, Gianluca; Silvestre, Fabio; Binetti, Francesco; Cox, Sharon Natasha; Roscino, Mariateresa; Caira, Michele; Lacalandra, Giovanni Michele

    2016-04-01

    Glycans of oviductal isthmus are implicated in sperm-isthmus interaction, sperm storage, survival, and capacitation. Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). In this study, the oviductal isthmus epithelium was evaluated in normal and in SE using morphologic and lectin histochemical analysis. The epithelium of normal isthmi was significantly taller in folds than in crypts, whereas it significantly decreased in the folds of SE. Nonciliated cells (NCs) from normal, showed apical blebs revealing apocrine secretory activity, which was missing in SE. The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. The NCs apical blebs showed terminal fucose (Fuc), N-acetylgalactosamine (GalNAc), galactose (Gal), lactosamine, and O- and N-sialoglycans. In normal isthmi, the luminal surface of NCs and ciliated cells expressed Fuc, highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc. Moreover, NCs microvilli contained Gal and α2-3-linked sialic acids. In SE, the luminal surface lacked Gal and GalNAcα1, 3(LFucα1,2)Galβ1,3/4GlcNAcβ1, whereas it was enriched with Fuc in the folds and with α2-3sialo-mucins both in crypts and in folds. The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. The cytoplasm of control NCs showed highly mannosilated N-glycans throughout the epithelium and GlcNAc in the folds. After superovulation treatment, NCs expressed cytoplasmic terminal Fuc, βGalNAc, lactosamine, α2-3-, and α2-6-linked sialic acids in the folds. The cytoplasm of normal

  7. The Project MACULA Retinal Pigment Epithelium Grading System for Histology and Optical Coherence Tomography in Age-Related Macular Degeneration

    PubMed Central

    Zanzottera, Emma C.; Messinger, Jeffrey D.; Ach, Thomas; Smith, R. Theodore; Freund, K. Bailey; Curcio, Christine A.

    2015-01-01

    Purpose. To seek pathways of retinal pigment epithelium (RPE) fate in age-related macular degeneration via a morphology grading system; provide nomenclature, visualization targets, and metrics for clinical imaging and model systems. Methods. Donor eyes with geographic atrophy (GA) or choroidal neovascularization (CNV) and one GA eye with previous clinical spectral-domain optical coherence tomography (SDOCT) imaging were processed for histology, photodocumented, and annotated at predefined locations. Retinal pigment epithelial cells contained spindle-shaped melanosomes, apposed a basal lamina or basal laminar deposit (BLamD), and exhibited recognizable morphologies. Thicknesses and unbiased estimates of frequencies were obtained. Results. In 13 GA eyes (449 locations), ‘Shedding,’ ‘Sloughed,’ and ‘Dissociated’ morphologies were abundant; 22.2% of atrophic locations had ‘Dissociated’ RPE. In 39 CNV eyes (1363 locations), 37.3% of locations with fibrovascular/fibrocellular scar had ‘Entombed’ RPE; ‘Sloughed,’ ‘Dissociated,’ and ‘Bilaminar’ morphologies were abundant. Of abnormal RPE, CNV and GA both had ∼35% ‘Sloughed’/‘Intraretinal,’ with more Intraretinal in CNV (9.5% vs. 1.8%). ‘Shedding’ cells associated with granule aggregations in BLamD. The RPE layer did not thin, and BLamD remained thick, with progression. Granule-containing material consistent with three morphologies correlated to SDOCT hyperreflective foci in the previously examined GA patient. Conclusions. Retinal pigment epithelium morphology indicates multiple pathways in GA and CNV. Atrophic/scarred areas have numerous cells capable of transcribing genes and generating imaging signals. Shed granule aggregates, possibly apoptotic, are visible in SDOCT, as are ‘Dissociated’ and ‘Sloughed’ cells. The significance of RPE phenotypes is addressable in longitudinal, high-resolution imaging in clinic populations. Data can motivate future molecular phenotyping

  8. TWIST and p-Akt immunoexpression in normal oral epithelium oral dysplasia and in oral squamous cell carcinoma

    PubMed Central

    Yamamoto, Fernanda-Paula; Corrêa Pontes, Flávia-Sirotheau; Cury, Sérgio-Elias; Fonseca, Felipe-Paiva; Rebelo-Pontes, Hélder; Pinto-Júnior, Décio-dos Santos

    2012-01-01

    Objectives: The aim of this study was to evaluate the immunoexpression of TWIST and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), correlating their expressions with the histological features of the lesions. Study design: Immunohistochemical studies were carried out on 10 normal oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on the specimens and the positivity of the reactions was calculated for 1000 epithelial cells. Results: Kruskal-Wallis and Dunn’s post tests revealed a significant difference in TWIST and p-Akt immunoexpression among normal oral mucosa, OL and OSCC. In addition, a significant positive correlation was found between TWIST and p-Akt expressions according to the Pearson’s correlation test. Conclusions: The results obtained in the current study suggest that TWIST and p-Akt may participate of the multi-step process of oral carcinogenesis since its early stages. Key words: Oral cancer, oral leukoplakia, dysplasia, immunohistochemistry. PMID:21743395

  9. Histological and electrophysiological properties of crypt cells from the olfactory epithelium of the marine teleost Trachurus symmetricus.

    PubMed

    Schmachtenberg, Oliver

    2006-03-01

    Crypt cells from the olfactory epithelium of the Pacific jack mackerel Trachurus symmetricus were characterized by light and electron microscopy and analyzed in dissociation with the patch-clamp technique in its cell-attached, perforated patch and normal whole-cell mode. Isolated crypt cells remained united with their supporting cells, and both were electrically coupled through gap junctions. Under voltage-clamp, depolarizing voltage steps triggered a transient sodium current, a sustained calcium current, and two types of potassium currents with fast and slow inactivation kinetics. No calcium-dependent potassium current could be observed. The sodium current was blocked by saxitoxin, the calcium current by cobalt and furnidipine, and the potassium currents by tetraethylammonium chloride. In the cell-attached configuration, crypt cells displayed spontaneous spike activity and responded to amino acid solutions with dose-dependent excitation, followed by a period of spike inhibition. These first recordings of individual crypt cells provide the basis for future studies of their odorant specificity, transduction mechanism, and overall function in the fish olfactory epithelium.

  10. Genes involved in epithelial differentiation and development are differentially expressed in oral and genital lichen planus epithelium compared to normal epithelium.

    PubMed

    Danielsson, Karin; Coates, Philip J; Ebrahimi, Majid; Nylander, Elisabet; Wahlin, Ylva Britt; Nylander, Karin

    2014-09-01

    Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

  11. Intracellular Fas ligand in normal and malignant breast epithelium does not induce apoptosis in Fas-sensitive cells

    PubMed Central

    Ragnarsson, G B; Mikaelsdottir, E K; Vidarsson, H; Jónasson, J G; Ólafsdóttir, K; Kristjánsdóttir, K; Kjartansson, J; Ögmundsdóttir, H M; Rafnar, T

    2000-01-01

    Fas ligand (FasL) is expressed on some cancers and may play a role in the immune evasion of the tumour. We used immuno-histochemistry to study the expression of Fas and FasL in tissue samples from breast cancer patients, as well as normal breast tissue. Our results show that Fas and FasL are co-expressed both in normal tissue and in breast tumours. Fas and FasL mRNA were expressed in fresh normal and malignant breast tissue, as well as cultured breast epithelium and breast cancer cell lines. Flow cytometry analysis of live cells failed to detect FasL on the surface of normal or malignant breast cells; however, both stained positive for FasL after permeabilization. Fas was detected on the surface of normal breast cells and T47D and MCF-10A cell lines but only intracellularly in other breast cell lines tested. Neither normal breast epithelium nor breast cell lines induced Fas-dependent apoptosis in Jurkat cells. Finally, 20 tumour samples were stained for apoptosis. Few apoptotic cells were detected and there was no increase in apoptotic cells on the borders between tumour cells and lymphocytes. We conclude that FasL is expressed intracellularly in both normal and malignant breast epithelium and unlikely to be important for the immune evasion of breast tumours. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11104571

  12. Regulation of transepithelial ion transport and intracellular calcium by extracellular ATP in human normal and cystic fibrosis airway epithelium.

    PubMed Central

    Mason, S. J.; Paradiso, A. M.; Boucher, R. C.

    1991-01-01

    1 The role of extracellular nucleotides in regulation of ion transport activities (short circuit current, Isc) of human respiratory epithelia was studied. 2 Application of nucleotides to the apical or basolateral membrane of human nasal epithelium induced a concentration-dependent increase in Isc. 3 The rank order of potency of purine- or pyrimidine-induced changes in Isc of normal human nasal epithelium when applied to the apical membrane (UTP greater than or equal to ATP greater than ATP gamma S greater than 2MeSATP greater than ADP beta S much greater than beta gamma MeATP greater than or equal to alpha beta MeATP) or basolateral membrane (2MeSATP greater than UTP greater than ATP greater than ATP gamma S greater than alpha beta MeATP greater than beta gamma MeATP) is consistent with involvement of a P2 purinoceptor. A similar rank order of potencies was observed for nucleotide effects on intracellular calcium measured by Fura-2 fluorescence using microspectrofluorimetry. 4 Similar nucleotide potency in the regulation of ion transport and intracellular calcium in cystic fibrosis (CF) airway epithelium (UTP greater than or equal to ATP) was observed, suggesting purinoceptors might be used to stimulate ion transport processes that would promote hydration of airway secretions and facilitate their clearance from CF lungs. 5 These data provide evidence for the regulation of ion transport by P2 purinoceptors in normal and cystic fibrosis human airway epithelium. PMID:1718521

  13. Differences in expression of retinal pigment epithelium mRNA between normal canines

    PubMed Central

    2004-01-01

    Abstract A reference database of differences in mRNA expression in normal healthy canine retinal pigment epithelium (RPE) has been established. This database identifies non-informative differences in mRNA expression that can be used in screening canine RPE for mutations associated with clinical effects on vision. Complementary DNA (cDNA) pools were prepared from mRNA harvested from RPE, amplified by PCR, and used in a subtractive hybridization protocol (representational differential analysis) to identify differences in RPE mRNA expression between canines. The effect of relatedness of the test canines on the frequency of occurrence of differences was evaluated by using 2 unrelated canines for comparison with 2 female sibling canines of blue heeler/bull terrier lineage. Differentially expressed cDNA species were cloned, sequenced, and identified by comparison to public database entries. The most frequently observed differentially expressed sequence from the unrelated canine comparison was cDNA with 21 base pairs (bp) identical to the human epithelial membrane protein 1 gene (present in 8 of 20 clones). Different clones from the same-sex sibling RPE contained repetitions of several short sequence motifs including the human epithelial membrane protein 1 (4 of 25 clones). Other prevalent differences between sibling RPE included sequences similar to a chicken genetic marker sequence motif (5 of 25), and 6 clones with homology to porcine major histocompatibility loci. In addition to identifying several repetitively occurring, noninformative, differentially expressed RPE mRNA species, the findings confirm that fewer differences occurred between siblings, highlighting the importance of using closely related subjects in representational difference analysis studies. PMID:15352545

  14. Anogenital Mammary-Like Glands: A Study of Their Normal Histology With Emphasis on Glandular Depth, Presence of Columnar Epithelial Cells, and Distribution of Elastic Fibers.

    PubMed

    Konstantinova, Anastasia M; Kyrpychova, Liubov; Belousova, Irena E; Spagnolo, Dominic V; Kacerovska, Denisa; Michal, Michal; Kerl, Katrin; Kazakov, Dmitry V

    2016-10-18

    The normal histology of anogenital mammary-like glands (AGMLG) has been studied previously, but some aspects, including glandular depth, presence of columnar epithelium resembling columnar cell change/hyperplasia as defined in mammary pathology, and distribution of elastic fibers, have not been previously investigated. To address these issues, we studied 148 AGMLG identified in 133 paraffin blocks sampled from 64 vulvar wide excision or vulvectomy specimens (64 patients, various indications for surgery). The depth of AGMLG ranged from 0.64 to 3.9 mm. Epithelial columnar cell change was noted in 33.1% of all AGMLG, whereas columnar cell hyperplasia was detected in 10.1%. Occasionally, combinations of cuboidal epithelium and columnar cell change were seen within 1 histological section. Of 22 specimens stained for elastic fibers, in only 6 (27.3%) cases were elastic fibers found around glands. Periductal elastic fibers were demonstrated around 3 of the only 5 ducts, which were available for analysis in slides stained for elastic fibers. The depth of AGMLG should be taken into account when planning topical and surgical therapies for lesions derived or evolving from AGMLG. Alterations identical to columnar cell change may represent a normal variation of AGMLG.

  15. Role of fucosyltransferases in the association between apomucin and Lewis antigen expression in normal and malignant gastric epithelium

    PubMed Central

    Lopez-Ferrer, A; de Bolos, C; Barranco, C; Garrido, M; Isern, J; Carlstedt, I; Reis, C; Torrado, J; Real, F

    2000-01-01

    BACKGROUND—In normal gastric epithelium, MUC5AC is detected in superficial epithelium associated with Lewis type 1 antigens and MUC6 is detected in antral glands with Lewis type 2. Therefore, the stomach constitutes an excellent model to examine the role of glycosyltransferases in determining the specificity of apomucin glycosylation.
AIMS—To determine the molecular basis of this association and to examine changes in expression of gastric and intestinal apomucins and their association with Lewis antigens during the gastric carcinogenesis process.
METHODS—Fucosyltransferase (FUT1, FUT2, FUT3) and mucin (MUC5AC, MUC6) transcripts were detected using reverse transcription-polymerase chain reaction. Apomucin (MUC2, MUC4, MUC5AC, MUC6) and Lewis antigen (types 1 and 2) expression were analysed using single and double immunohistochemistry and in situ hybridisation.
RESULTS—In the normal stomach, FUT1 is exclusively detected associated with MUC6; FUT2 is only detected when MUC5AC is present. This co-regulation is lost in gastric tumours, as is differential expression of MUC5AC and MUC6 in normal gastric epithelial cells. In gastric tumours, especially those with the intestinal phenotype, MUC2 and MUC4 genes are upregulated, and gastric-type and intestinal-type mucins are coexpressed. These changes are early events in the gastric carcinogenesis process, as they are detected in intestinal metaplasia.
CONCLUSIONS—The glycosylation pattern found in normal gastric epithelium is dictated by the specific set of fucosyltranferases expressed by the cells rather than by the apomucin sequence. The development of intestinal metaplasia and gastric cancer is associated with the appearance of cellular phenotypes that are absent from normal epithelium.


Keywords: fucosyltransferases; gastric carcinogenesis; gastric mucins; Lewis antigens PMID:10940270

  16. Anatomical and histological study of the dorsal and ventral nasal conchal bullae in normal horses.

    PubMed

    Froydenlund, T J; Dixon, P M; Smith, S H; Reardon, R J M

    2015-11-28

    The morphology of the dorsal conchal bulla (DCB) and ventral conchal bulla (VCB) are poorly described. The recent recognition that these bullae can become infected, causing chronic unilateral nasal discharge, has stimulated interest in these structures. Fourteen cadaveric horse heads were transected sagittally midline and dissected to expose the nasal conchal bullae. The dimensions of each bulla, the number and orientation of drainage apertures, and cellulae septae were recorded. Randomly selected samples were examined histologically. The mean DCB and VCB lengths were 78  and 57 mm, respectively; equivalent to 13.9 per cent and 10.2 per cent of skull length, respectively. The mean DCB and VCB heights were 29  and 28 mm, respectively; equivalent to 5.2 per cent and 5 per cent of skull length, respectively. The DCB was larger than the VCB, containing more septae, cellulae and drainage apertures. No communications were identified between the bullae and the immediately adjacent paranasal sinuses. Histology revealed that the bullae consist of ciliated, pseudostratified, columnar epithelium over glandular submucosa often overlying turbinate bone and, variably, hyaline cartilage. This more detailed description of equine DCB and VCB anatomy will hopefully facilitate successful treatment of their disorders.

  17. Detection of a novel stem cell probably involved in normal turnover of the lung airway epithelium.

    PubMed

    Ortega-Martínez, Marta; Rodríguez-Flores, Laura E; de-la-Garza-González, Carlos; Ancer-Rodríguez, Jesús; Jaramillo-Rangel, Gilberto

    2015-11-01

    Regeneration of the lung airway epithelium after injury has been extensively studied. In contrast, analysis of its turnover in healthy adulthood has received little attention. In the classical view, this epithelium is maintained in the steady-state by the infrequent proliferation of basal or Clara cells. The intermediate filament protein nestin was initially identified as a marker for neural stem cells, but its expression has also been detected in other stem cells. Lungs from CD1 mice at the age of 2, 6, 12, 18 or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Nestin expression was examined by an immunohistochemical peroxidase-based method. Nestin-positive cells were detected in perivascular areas and in connective tissue that were in close proximity of the airway epithelium. Also, nestin-positive cells were found among the cells lining the airway epithelium. These findings suggest that nestin-positive stem cells circulate in the bloodstream, transmigrate through blood vessels and localize in the lung airway epithelium to participate in its turnover. We previously reported the existence of similar cells able to differentiate into lung chondrocytes. Thus, the stem cell reported here might be a bone marrow-derived mesenchymal stem cell (BMDMSC) able to generate several types of lung tissues. In conclusion, our findings indicate that there exist a BMDMSC in healthy adulthood that participates in the turnover of the lung airway epithelium. These findings may improve our knowledge about the lung stem cell biology and also provide novel approaches to therapy for devastating pulmonary diseases.

  18. [The rabbit ear model as comedogenic test. 3. Histologic and enzyme histochemical studies of the follicle and sebaceous gland epithelium].

    PubMed

    Zimmermann, R

    1990-01-01

    A strongly comedogenic mineral oil induced histologically and enzyme-histochemically detectable changes in the follicles and sebaceous gland ducts in the skin of rabbit ears. These correlate to findings concerning acne vulgaris in humans. The rabbit ear model thus appears to be suitable for experimental studies into acne vulgaris.

  19. Nitric oxide synthase 2 (NOS2) expression in histologically normal margins of oral squamous cell carcinoma

    PubMed Central

    Itoiz, María E.; Guiñazú, Natalia; Piccini, Daniel; Gea, Susana; López-de Blanc, Silvia

    2014-01-01

    The activity of Nitric Oxide Synthase 2 (NOS2) was found in oral squamous cell carcinomas (OSCC) but not in normal mucosa. Molecular changes associated to early carcinogenesis have been found in mucosa near carcinomas, which is considered a model to study field cancerization. The aim of the present study is to analyze NOS2 expression at the histologically normal margins of OSCC. Study Design: Eleven biopsy specimens of OSCC containing histologically normal margins (HNM) were analyzed. Ten biopsies of normal oral mucosa were used as controls. The activity of NOS2 was determined by immunohistochemistry. Salivary nitrate and nitrite as well as tobacco and alcohol consumption were also analyzed. The Chi-squared test was applied. Results: Six out of the eleven HNM from carcinoma samples showed positive NOS2 activity whereas all the control group samples yielded negative (p=0.005). No statistically significant association between enzyme expression and tobacco and/or alcohol consumption and salivary nitrate and nitrite was found. Conclusions: NOS2 expression would be an additional evidence of alterations that may occur in a state of field cancerization before the appearance of potentially malignant morphological changes. Key words:Field cancerization, oral squamous cell carcinoma, Nitric Oxide Synthase 2 (NOS2), malignity markers. PMID:24316703

  20. Next-generation transcriptome sequencing of the premenopausal breast epithelium using specimens from a normal human breast tissue bank

    PubMed Central

    2014-01-01

    Introduction Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established. The KTB is, to our knowledge, the only biorepository in the world prospectively established to collect normal, healthy breast tissue from volunteer donors. As a first initiative toward a molecular understanding of the biology and developmental genetics of the normal mammary gland, the effect of the menstrual cycle and hormonal contraceptives on DNA expression in the normal breast epithelium was examined. Methods Using normal breast tissue from 20 premenopausal donors to KTB, the changes in the mRNA of the normal breast epithelium as a function of phase of the menstrual cycle and hormonal contraception were assayed using next-generation whole transcriptome sequencing (RNA-Seq). Results In total, 255 genes representing 1.4% of all genes were deemed to have statistically significant differential expression between the two phases of the menstrual cycle. The overwhelming majority (221; 87%) of the genes have higher expression during the luteal phase. These data provide important insights into the processes occurring during each phase of the menstrual cycle. There was only a single gene significantly differentially expressed when comparing the epithelium of women using hormonal contraception to those in the luteal phase. Conclusions We have taken advantage of a unique research resource, the KTB, to complete the first-ever next-generation transcriptome sequencing of the epithelial compartment of 20 normal human breast specimens. This work has produced a comprehensive catalog of the differences in the expression of protein-coding genes as a function of the phase of the menstrual cycle. These data constitute the beginning of

  1. The role of mast cells in histologically "normal" appendices following emergency appendectomy in pediatric patients.

    PubMed

    Yang, Zhongbo; Esebua, Magda; Layfield, Lester

    2016-10-01

    Fifteen percent to 25% of appendices resected for a preoperative diagnosis of acute appendicitis have no neutrophilic infiltration, thus histologically "normal." The discrepancy between clinical presentation and the lack of definite morphologic changes is confounding. It has been indicated that mast cells may play a role in the pathogenesis of the appendicitis-like pain in patients with histologically negative appendices (HNAs). To investigate whether mast cell density (MCD) is increased in pediatric HNAs, we retrieved 50 appendectomy cases (30 HNA and 20 control, ages 2 days-18 years) in our institute in the last 10 years. All cases were stained with mast cell tryptase by immunohistochemistry, and MCD (count/high-power field) was measured in mucosa, submucosa, muscularis, and serosa. Mast cells had the greatest density in the mucosa, followed by the submucosa, in all appendices. MCDs in all 4 layers were significantly higher in HNAs than in the normal controls (mucosa: 46±9 vs 26±11, P<.01; submucosa: 18±5 vs 11±5, P<.01; muscularis: 6±3 vs 4±2, P<.01; serosa: 6±2 vs 4±2, P<.01). This result suggests that mast cells play an important role in pathogenesis of HNA cases. In clinical practice, pathologists may order immunohistochemical stains for mast cells in cases with no classic histologic findings of acute appendicitis following emergency appendectomy. If increased MCD is noted, the case may be reported as "appendicitis with increased mast cells." This assures surgeons that the appendectomy is the correct treatment and it is not necessary to look for other causes of acute abdomen. This is especially important in children.

  2. Differences in MITF gene expression and histology between albino and normal sea cucumbers ( Apostichopus japonicus Selenka)

    NASA Astrophysics Data System (ADS)

    Zhao, Heling; Yang, Hongsheng; Zhao, Huan; Liu, Shilin; Wang, Tianming

    2012-01-01

    Albino Apostichopus japonicus occur both in the wild and in captivity. The offspring of albino A. japonicus also suffer from albinism. The formation of melanin in the melanocytes is dependant on microphthalmia-associated transcription factor (MITF). To investigate the role of MITF in controlling albinism, we cloned the full-length MITF cDNA from A. japonicus and compared MITF mRNA expression in albino and normal A. japonicus. In addition, we used light and electron microscopy to compare histological samples of normal and albino A. japonicus. The body wall of albino adults was characterized by significantly lower levels of MITF expression and lower numbers of epidermal melanocytes, which also contained less melanin. In albino juvenile offspring, MITF expression levels were significantly lower 32 d after fertilization and there were fewer, and less developed, epidermal melanocytes. Thus, we conclude that albino A. japonicus have fewer melanocytes and a reduced ability to synthesize melanin, likely because of lower expression of MITF.

  3. Comparison of the histological morphology between normal skin and scar tissue.

    PubMed

    Yang, Shao-wei; Geng, Zhi-jun; Ma, Kui; Sun, Xiao-yan; Fu, Xiao-bing

    2016-04-01

    Skin wound healing is a complex event, and interrupted wound healing process could lead to scar formation. The aim of this study was to examine the morphological changes of scar tissue. Pathological staining (HE staining, Masson's trichrome staining, methenamine silver staining) was used to evaluate the morphological changes of regenerating epidermis in normal skin and scar tissue, and immunofluorescence staining to detect the expression of collagen IV, a component of basement membrane (BM), and the expression of integrinβ4, a receptor for BM laminins. Additionally, the expression of CK14, CK5, and CK10 was measured to evaluate the proliferation and differentiation of keratinocytes in normal skin and scar tissue. The results showed that the structure of the skin was histologically changed in scar tissue. Collagen IV, expressed under the epidermis of normal skin, was reduced distinctly in scar tissue. Integrinβ4, expressed in the basal layer of normal skin, was found absent in the basal layer of scar tissue. Additionally, it was found that keratinocytes in scarring epidermis were more proliferative than in normal skin. These results indicate that during the skin wound healing, altered formation of BM may affect the proliferation of keratinocytes, reepithelial and tissue remodeling, and then result in scar formation. Thus, remodeling BM structure during wound repair may be beneficial for improving healing in cutaneous wounds during clinical practice.

  4. Variations of mitotic index in normal and dysplastic squamous epithelium of the uterine cervix as a function of endometrial maturation.

    PubMed

    Fadare, Oluwole; Yi, Xiaofang; Liang, Sharon X; Ma, Yanling; Zheng, Wenxin

    2007-09-01

    Cervical intraepithelial neoplasia is a premalignant (dysplastic) lesion that is characterized by abnormal cellular proliferation, maturation and nuclear atypia. The intraepithelial distribution, density, and nature (typical or atypical) of mitotic figures are routinely utilized diagnostic criteria to grade dysplasia and to distinguish high-grade dysplasia from potential histologic mimics such as transitional metaplasia, atrophy or immature squamous metaplasia. In this study, we evaluated the total mitotic indices of the cervical epithelia in hysterectomy specimens from patients with and without dysplastic lesions and investigated a possible relationship between mitotic index and hormonal status, using the endometrial maturation phase as a surrogate indicator of the latter. Two hundred seventy-four cervices from hysterectomy specimens (135 cases without dysplasia, 33, 35 and 71 cases with grades 1, 2 and 3 cervical intraepithelial neoplasia, respectively) were analyzed. A cervical mitotic index (total mitotic figures/10 high-power fields in the most proliferative area) was determined for each case. The endometrium in each case was classified into atrophic, early proliferative, late proliferative and secretory. For all three dysplasia grades, cases in the proliferative endometrium group always had a higher average mitotic index than those in the secretory and atrophic endometrium groups; this observation also held true for the benign cases. Furthermore, in all three dysplasia grades, the average mitotic index was always lowest in the atrophic endometrium group. Although the mitotic index showed expected patterns of increases with increasing dysplasia grades for most of the endometrial phases, this was not a universal finding. Notably, the average mitotic index for our cervical intraepithelial neoplasia 1 cases with late proliferative endometrium was higher than our cervical intraepithelial neoplasia 2 cases with secretory and atrophic endometrium. It is concluded

  5. Lesions of Copper Toxicosis in Captive Marine Invertebrates With Comparisons to Normal Histology.

    PubMed

    LaDouceur, E E B; Wynne, J; Garner, M M; Nyaoke, A; Keel, M K

    2016-05-01

    Despite increasing concern for coral reef ecosystem health within the last decade, there is scant literature concerning the histopathology of diseases affecting the major constituents of coral reef ecosystems, particularly marine invertebrates. This study describes histologic findings in 6 species of marine invertebrates (California sea hare [Aplysia californica], purple sea urchin [Strongylocentrotus purpuratus], sunburst anemone [Anthopleura sola], knobby star [Pisaster giganteus], bat star [Asterina miniata], and brittle star [Ophiopteris papillosa]) with spontaneous copper toxicosis, 4 purple sea urchins with experimentally induced copper toxicosis, and 1 unexposed control of each species listed. The primary lesions in the California sea hare with copper toxicosis were branchial and nephridial necrosis. Affected echinoderms shared several histologic lesions, including epidermal necrosis and ulceration and increased numbers of coelomocytes within the water-vascular system. The sunburst anemone with copper toxicosis had necrosis of both epidermis and gastrodermis, as well as expulsion of zooxanthellae from the gastrodermis. In addition to the lesions attributed to copper toxicosis, our results describe normal microscopic features of these animals that may be useful for histopathologic assessment of marine invertebrates.

  6. Histological and Clinical Characteristics of Patients with Chronic Hepatitis C and Persistently Normal Alanine Aminotransferase Levels

    PubMed Central

    Guzman, Grace

    2014-01-01

    Patients with chronic hepatitis C virus (HCV) infection and persistently normal alanine aminotransferase (PNALT) are generally described to have mild liver disease. The aim of this study was to compare clinical and histological features in HCV-infected patients with PNALT and elevated ALT. Patients presenting to the University of Illinois Medical Center, Chicago, who had biopsy proven HCV, an ALT measurement at the time of liver biopsy, at least one additional ALT measurement over the next 12 months, and liver biopsy slides available for review were identified. PNALT was defined as ALT ≤ 30 on at least 2 different occasions over 12 months. Of 1200 patients with HCV, 243 met the study criteria. 13% (32/243) of patients had PNALT while 87% (211/243) had elevated ALT. Significantly more patients with PNALT had advanced fibrosis (F3 and F4) compared to those with elevated ALT (P = 0.007). There was no significant difference in the histology activity index score as well as mean inflammatory score between the two groups. In conclusion, in a well-characterized cohort of patients at a tertiary medical center, PNALT did not distinguish patients with mild liver disease. PMID:24891947

  7. Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice.

    PubMed

    Xu, Z; Dong, Y; Peng, F; Yu, Z; Zuo, Y; Dai, Z; Chen, Y; Wang, J; Hu, X; Zhou, Q; Ma, H; Bao, Y; Gao, G; Chen, M

    2015-03-01

    This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.

  8. Infrared spectroscopy characterization of normal and lung cancer cells originated from epithelium

    PubMed Central

    Lee, So Yeong; Yoon, Kyong-Ah; Jang, Soo Hwa; Ganbold, Erdene Ochir; Uuriintuya, Dembereldorj; Shin, Sang-Mo; Ryu, Pan Dong

    2009-01-01

    The vibrational spectral differences of normal and lung cancer cells were studied for the development of effective cancer cell screening by means of attenuated total reflection infrared spectroscopy. The phosphate monoester symmetric stretching νs(PO32-) band intensity at ~970 cm-1 and the phosphodiester symmetric stretching νs(PO2-) band intensity at ~1,085 cm-1 in nucleic acids and phospholipids appeared to be significantly strengthened in lung cancer cells with respect to the other vibrational bands compared to normal cells. This finding suggests that more extensive phosphorylation occur in cancer cells. These results demonstrate that lung cancer cells may be prescreened using infrared spectroscopy tools. PMID:19934594

  9. Automatic segementation of histological structures in normal and neoplastic mammary gland tissue sections

    NASA Astrophysics Data System (ADS)

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam; Malladi, Ravikanth; Ortiz de Solorzano, Carlos

    2003-07-01

    In this paper we present a scheme for real time segmentation of histological structures in microscopic images of normal and neoplastic mammary gland sections. Paraffin embedded or frozen tissue blocks are sliced, and sections are stained with hematoxylin and eosin (H&E). The sections are then imaged using conventional bright field microscopy. The background of the images is corrected by arithmetic manipulation using a "phantom." Then we use the fast marching method with a speed function that depends on the brightness gradient of the image to obtain a preliminary approximation to the boundaries of the structures of interest within a region of interest (ROI) of the entire section manually selected by the user. We use the result of the fast marching method as the initial condition for the level set motion equation. We run this last method for a few steps and obtain the final result of the segmentation. These results can be connected from section to section to build a three-dimensional reconstruction of the entire tissue block that we are studying.

  10. Automatic segmentation of histological structures in normal and neoplastic mammary gland tissue sections

    SciTech Connect

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam K.; Malladi, Ravi; Ortiz de Solorzano, Carlos

    2003-01-18

    In this paper we present a scheme for real time segmentation of histological structures in microscopic images of normal and neoplastic mammary gland sections. Paraffin embedded or frozen tissue blocks are sliced, and sections are stained with hematoxylin and eosin (H&E). The sections are then imaged using conventional bright field microscopy. The background of the images is corrected by arithmetic manipulation using a ''phantom.'' Then we use the fast marching method with a speed function that depends on the brightness gradient of the image to obtain a preliminary approximation to the boundaries of the structures of interest within a region of interest (ROI) of the entire section manually selected by the user. We use the result of the fast marching method as the initial condition for the level set motion equation. We run this last method for a few steps and obtain the final result of the segmentation. These results can be connected from section to section to build a three-dimensional reconstruction of the entire tissue block that we are studying.

  11. Effect of hypoxia and TP53 mutation status and cytogenetics of normal and malignant mammary epithelium.

    PubMed

    Vidarsson, Hilmar; Steinarsdóttir, Margrét; Jónasson, Jón Gunnlaugur; Júlíusdóttir, Hildur; Hauksdóttir, Halla; Hilmarsdóttir, Hólmfrídur; Halldórsdóttir, Kristín; Ogmundsdóttir, Helga M

    2006-03-01

    It has been proposed that hypoxia favors the growth of tumor cells over normal cells, particularly tumor cells carrying TP53 mutations. Cytogenetic studies of breast cancer have shown that highly complex karyotypes seen in direct harvest preparations are rarely detected after short-term culture. In this study, 34 paired samples of breast carcinomas and grossly nontumorous tissue from the same breast were cultured at 20 and 5% (12 samples) or 20 and 0% oxygen (22 samples). Both carcinoma samples and nontumorous tissue survived at 0% oxygen. Recovery for 24 hours at 20% produced good yields for cytogenetic analysis. Lower oxygen levels did not specifically stimulate growth of tumor cells. Samples with TP53 mutations showed a consistently increased growth under anaerobic hypoxic conditions. Culture at 5% oxygen did not generally reveal more karyotypic abnormalities than found at 20%. In the samples cultured at 0 and 20%, karyotypic abnormalities were detected only in anaerobic hypoxic culture in two cases. Of the only four samples where more complex karyotypes were detected in the low-oxygen culture, two were TP53 mutated. Hypoxic treatment followed by recovery at 20% oxygen may thus increase the yield of complex karyotypes from a subset of breast carcinomas, particularly those with mutated TP53.

  12. Cellular Organization of Normal Mouse Liver: A Histological, Quantitative Immunocytochemical, and Fine Structural Analysis

    PubMed Central

    Baratta, Janie L.; Ngo, Anthony; Lopez, Bryan; Kasabwalla, Natasha; Longmuir, Kenneth J.; Robertson, Richard T.

    2009-01-01

    The cellular organization of normal mouse liver was studied using light and electron microscopy and quantitative immunocytochemical techniques. The general histological organization of the mouse liver is similar to livers of other mammalian species, with a lobular organization based on the distributions of portal areas and central venules. The parenchymal hepatocytes were detected with immunocytochemical techniques to recognize albumin or biotin containing cells. The macrophage Kupffer cells were identified with F4-80 immunocytochemistry, Ito stellate cells were identified with GFAP immunocytochemistry, and endothelial cells were labeled with the CD-34 antibody. Kupffer cells were labeled with intravascularly administered fluorescently labeled latex microspheres of both large (0.5 μm) and small (0.03 μm) diameters, while endothelial cells were labeled only with small diameter microspheres. Neither hepatocytes nor Ito stellate cells were labeled by intravascularly administered latex microspheres. The principal fine structural features of hepatocytes and non-parenchymal cells of mouse liver are similar to those reported for rat. Counts of immunocytochemically labeled cells with stained nuclei indicated that hepatocytes constituted approximately 52% of all labeled cells, Kupffer cells about 18%, Ito cells about 8%, and endothelial cells about 22% of all labeled cells. Approximately 35% of the hepatocytes contained two nuclei; none of the Kupffer or Ito cells were double nucleated. The presence of canaliculi and a bile duct system appear similar to that reported for other mammalian species. The cellular organization of the mouse liver is quite similar to that of other mammalian species, confirming that the mouse presents a useful animal model for studies of liver structure and function. PMID:19255771

  13. [Quantitative image analysis in pulmonary pathology - digitalization of preneoplastic lesions in human bronchial epithelium (author's transl)].

    PubMed

    Steinbach, T; Müller, K M; Kämper, H

    1979-01-01

    The report concerns the first phase of a quantitative study of normal and abnormal bronchial epithelium with the objective of establishing the digitalization of histologic patterns. Preparative methods, data collecting and handling, and further mathematical analysis are described. In cluster and discriminatory analysis the digitalized histologic features can be used to separate and classify the individual cases into the respective diagnostic groups.

  14. Effectiveness of an electronic histology tutorial for first-year dental students and improvement in "normalized" test scores.

    PubMed

    Rosenberg, Harold; Kermalli, Jaffer; Freeman, Eric; Tenenbaum, Howard; Locker, David; Cohen, Howard

    2006-12-01

    The effectiveness of an electronic histology tutorial (EHT) as a mode of learning was assessed by comparing performance on two term tests for an EHT class of sixty-nine students and five prior classes (n=347) who learned by traditional methods. The aims of this study were to 1) develop and introduce a self-instructional, computer-aided approach to guide student learning in the first-year histology course at the University of Toronto Faculty of Dentistry; 2) evaluate the effectiveness of the self-study electronic histology tutorial by comparing students' test scores for the EHT group to students' scores in previous years; and 3) evaluate students' acceptance of this novel mode of learning by means of a satisfaction questionnaire. The EHT group performed significantly better on both the general histology and oral histology term tests than the five prior control years (p<0.001), yet there were no significant differences in overall GPA between the groups, suggesting that the improvement was specific to the EHT/histology course grades (p=0.1 to 0.47). A statistically significant improvement in performance per unit overall GPA was noted in the test group, which demonstrated an increase in this test score normalized ratio (TSNR) of 3-18 percent in the general histology term test and 7-21 percent in the oral histology term test over the control groups. In addition to determining the effects of the EHT on grade performance, this study sought to evaluate students' acceptance of this alternative mode of learning in comparison to the standard teaching model by means of a satisfaction questionnaire. Overall, students' responses to the questionnaire were positive with an overall mean level of agreement for all ten responses of 4.5 out of 5 (90 percent).

  15. Normal Anatomy, Histology, and Spontaneous Pathology of the Nasal Cavity of the Cynomolgus Monkey (Macaca fascicularis).

    PubMed

    Chamanza, Ronnie; Taylor, Ian; Gregori, Michela; Hill, Colin; Swan, Mark; Goodchild, Joel; Goodchild, Kane; Schofield, Jane; Aldous, Mark; Mowat, Vasanthi

    2016-07-01

    The evaluation of inhalation studies in monkeys is often hampered by the scarcity of published information on the relevant nasal anatomy and pathology. We examined nasal cavities of 114 control cynomolgus monkeys from 11 inhalation studies evaluated 2008 to 2013, in order to characterize and document the anatomic features and spontaneous pathology. Compared to other laboratory animals, the cynomolgus monkey has a relatively simple nose with 2 unbranched, dorsoventrally stacked turbinates, large maxillary sinuses, and a nasal septum that continues into the nasopharynx. The vomeronasal organ is absent, but nasopalatine ducts are present. Microscopically, the nasal epithelium is thicker than that in rodents, and the respiratory (RE) and transitional epithelium (TE) rest on a thick basal lamina. Generally, squamous epithelia and TE line the vestibule, RE, the main chamber and nasopharynx, olfactory epithelium, a small caudodorsal region, while TE is observed intermittently along the passages. Relatively high incidences of spontaneous pathology findings, some resembling induced lesions, were observed and included inflammation, luminal exudate, scabs, squamous and respiratory metaplasia or hyperplasia, mucous cell hyperplasia/metaplasia, and olfactory degeneration. Regions of epithelial transition were the most affected. This information is considered helpful in the histopathology evaluation and interpretation of inhalation studies in monkeys.

  16. N-Ethylmaleimide–Sensitive Factor b (nsfb) Is Required for Normal Pigmentation of the Zebrafish Retinal Pigment Epithelium

    PubMed Central

    Hanovice, Nicholas J.; Daly, Christina M. S.; Gross, Jeffrey M.

    2015-01-01

    Purpose Despite the number of albinism-causing mutations identified in human patients and animal models, there remain a significant number of cases for which no mutation has been identified, suggesting that our understanding of melanogenesis is incomplete. Previously, we identified two oculocutaneous albinism mutations in zebrafish, au13 and au18. Here, we sought to identify the mutated loci and determine how the affected proteins contribute to normal pigmentation of the retinal pigment epithelium (RPE). Methods Complementation analyses revealed that au13 and au18 belonged to a single complementation group, suggesting that they affected the same locus. Whole-genome sequencing and single nucleotide polymorphism (SNP) analysis was performed to identify putative mutations, which were confirmed by cDNA sequencing and mRNA rescue. Transmission electron microscopy (TEM) and image quantification were used to identify the cellular basis of hypopigmentation. Results Whole-genome sequencing and SNP mapping identified a nonsense mutation in the N-ethylmaleimide–sensitive factor b (nsfb) gene in au18 mutants. Complementary DNA sequencing confirmed the presence of the mutation (C893T), which truncates the nsfb protein by roughly two-thirds (Y297X). No coding sequence mutations were identified in au13, but quantitative PCR revealed a significant decrease in nsfb expression, and nsfb mRNA injection rescued the hypopigmentation phenotype, suggesting a regulatory mutation. In situ hybridization revealed that nsfb is broadly expressed during embryonic development, including in the RPE. Transmission electron microscopy analyses indicated that average melanosome density and maturity were significantly decreased in nsfb mutants. Conclusions au18 and au13 contain mutations in nsfb, which encodes a protein that is required for the maturation of melanosomes in zebrafish RPE. PMID:26618645

  17. Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium

    NASA Technical Reports Server (NTRS)

    Shim, Veronica; Gauthier, Mona L.; Sudilovsky, Daniel; Mantei, Kristin; Chew, Karen L.; Moore, Dan H.; Cha, Imok; Tlsty, Thea D.; Esserman, Laura J.

    2003-01-01

    Cyclooxygenase-2 (COX-2) is emerging as an important cancer biomarker and is now an experimental target for solid tumor treatment.However, no study has exclusively focused on COX-2 expression in early lesions such as ductal carcinoma in situ (DCIS). We examined COX-2 expression by immunohistochemistry in 46 cases of women undergoing surgical resection for DCIS. We found that COX-2 expression was detected in 85% of all DCIS specimens, with increased COX-2 staining correlating with higher nuclear grade. Strikingly, COX-2 staining intensity in the normal adjacent epithelium was stronger than in the DCIS lesion itself. Our observations demonstrate that COX-2 is up-regulated in the normal adjacent epithelium and supports the hypothesis that the surrounding epithelial tissue is part of the disease process in DCIS.

  18. Comparison of Histologic Characteristics of Chinese Chronic Hepatitis B Patients with Persistently Normal or Mildly Elevated ALT

    PubMed Central

    Wang, Hong; Xue, Li; Yan, Rong; Zhou, Yin; Wang, Ming-Shan; Cheng, Mei-Juan; Hai-Jun Huang

    2013-01-01

    Liver disease can develop in chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT) who seldom undergo liver biopsy. We aimed to determine histologic characteristics of a large cohort of Chinese CHB patients undergoing liver biopsy and to evaluate the utility of ALT and HBV DNA values at the time of biopsy in predicting liver disease in this population. This prospective study enrolled 230 treatment-naïve patients with persistently normal or mildly elevated ALT. All patients had a liver biopsy. ALT, aspartate aminotransferase (AST), and HBV DNA levels were some of the other parameters measured. Using Scheuer's classification, significant histology was defined as stage ≧2 fibrosis and/or stage 1 fibrosis plus≧ grade 2 inflammation. Liver disease was observed in 34.4% and 61.8% of patients with normal ALT and mildly elevated ALT, respectively. Patients with mildly elevated ALT levels had significantly more events, including liver disease, elevated AST, and moderate to severe inflammation and liver fibrosis, than patients with normal ALT (all P≤0.005). A total of 107 patients (46.5%) had liver disease and 123 (53.5%) did not. PLT and ALT were significantly associated with liver disease (both P<0.001). Patients with elevated ALT, lower platelet count and HBV DNA < 7 log10copies/mL may have histologically significant changes associated with liver disease. Multivariate analysis showed that PLT and HBV DNA levels were significantly associated with liver disease in patients with normal ALT while gender and HBV DNA levels were significantly associated with liver disease in patients with mildly elevated ALT. Assessing liver damage via biopsy in patients with normal or mildly elevated ALT may help to identify those who would benefit from antiviral therapy. PMID:24260428

  19. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

    PubMed Central

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

    2011-01-01

    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  20. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients

    PubMed Central

    Møller, Mia; Strand, Siri Hundtofte; Mundbjerg, Kamilla; Liang, Gangning; Gill, Inderbir; Haldrup, Christa; Borre, Michael; Høyer, Søren; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard

    2017-01-01

    Prostate cancer (PC) diagnosis is based on histological evaluation of prostate needle biopsies, which have high false negative rates. Here, we investigated if cancer-associated epigenetic field effects in histologically normal prostate tissue may be used to increase sensitivity for PC. We focused on nine genes (AOX1, CCDC181 (C1orf114), GABRE, GAS6, HAPLN3, KLF8, MOB3B, SLC18A2, and GSTP1) known to be hypermethylated in PC. Using quantitative methylation-specific PCR, we analysed 66 malignant and 134 non-malignant tissue samples from 107 patients, who underwent ultrasound-guided prostate biopsy (67 patients had at least one cancer-positive biopsy, 40 had exclusively cancer-negative biopsies). Hypermethylation was detectable for all genes in malignant needle biopsy samples (AUC: 0.80 to 0.98), confirming previous findings in prostatectomy specimens. Furthermore, we identified a four-gene methylation signature (AOX1xGSTP1xHAPLN3xSLC18A2) that distinguished histologically non-malignant biopsies from patients with vs. without PC in other biopsies (AUC = 0.65; sensitivity = 30.8%; specificity = 100%). This signature was validated in an independent patient set (59 PC, 36 adjacent non-malignant, and 9 normal prostate tissue samples) analysed on Illumina 450 K methylation arrays (AUC = 0.70; sensitivity = 40.6%; specificity = 100%). Our results suggest that a novel four-gene signature may be used to increase sensitivity for PC diagnosis through detection of epigenetic field effects in histologically non-malignant prostate tissue samples. PMID:28084441

  1. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients.

    PubMed

    Møller, Mia; Strand, Siri Hundtofte; Mundbjerg, Kamilla; Liang, Gangning; Gill, Inderbir; Haldrup, Christa; Borre, Michael; Høyer, Søren; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard

    2017-01-13

    Prostate cancer (PC) diagnosis is based on histological evaluation of prostate needle biopsies, which have high false negative rates. Here, we investigated if cancer-associated epigenetic field effects in histologically normal prostate tissue may be used to increase sensitivity for PC. We focused on nine genes (AOX1, CCDC181 (C1orf114), GABRE, GAS6, HAPLN3, KLF8, MOB3B, SLC18A2, and GSTP1) known to be hypermethylated in PC. Using quantitative methylation-specific PCR, we analysed 66 malignant and 134 non-malignant tissue samples from 107 patients, who underwent ultrasound-guided prostate biopsy (67 patients had at least one cancer-positive biopsy, 40 had exclusively cancer-negative biopsies). Hypermethylation was detectable for all genes in malignant needle biopsy samples (AUC: 0.80 to 0.98), confirming previous findings in prostatectomy specimens. Furthermore, we identified a four-gene methylation signature (AOX1xGSTP1xHAPLN3xSLC18A2) that distinguished histologically non-malignant biopsies from patients with vs. without PC in other biopsies (AUC = 0.65; sensitivity = 30.8%; specificity = 100%). This signature was validated in an independent patient set (59 PC, 36 adjacent non-malignant, and 9 normal prostate tissue samples) analysed on Illumina 450 K methylation arrays (AUC = 0.70; sensitivity = 40.6%; specificity = 100%). Our results suggest that a novel four-gene signature may be used to increase sensitivity for PC diagnosis through detection of epigenetic field effects in histologically non-malignant prostate tissue samples.

  2. Methylation of p16(INK4a) promoters occurs in vivo in histologically normal human mammary epithelia

    NASA Technical Reports Server (NTRS)

    Holst, Charles R.; Nuovo, Gerard J.; Esteller, Manel; Chew, Karen; Baylin, Stephen B.; Herman, James G.; Tlsty, Thea D.

    2003-01-01

    Cultures of human mammary epithelial cells (HMECs) contain a subpopulation of variant cells with the capacity to propagate beyond an in vitro proliferation barrier. These variant HMECs, which contain hypermethylated and silenced p16(INK4a) (p16) promoters, eventually accumulate multiple chromosomal changes, many of which are similar to those detected in premalignant and malignant lesions of breast cancer. To determine the origin of these variant HMECs in culture, we used Luria-Delbruck fluctuation analysis and found that variant HMECs exist within the population before the proliferation barrier, thereby raising the possibility that variant HMECs exist in vivo before cultivation. To test this hypothesis, we examined mammary tissue from normal women for evidence of p16 promoter hypermethylation. Here we show that epithelial cells with methylation of p16 promoter sequences occur in focal patches of histologically normal mammary tissue of a substantial fraction of healthy, cancer-free women.

  3. A histological and functional study on hippocampal formation of normal and diabetic rats

    PubMed Central

    Amin, Shaimaa N

    2013-01-01

    Background: The hippocampus is a key brain area for many forms of learning and memory and is particularly sensitive to changes in glucose homeostasis. Aim of the work: To investigate in experimentally induced type 1 and 2 diabetes mellitus in rat model the effect of  diabetes mellitus on cognitive functions and related markers of hippocampal synaptic plasticity, and the possible impact of blocking N-methyl-D-aspartic acid (NMDA) receptors by memantine. Materials and methods: Seven rat groups were included: non-diabetic control and non-diabetic receiving memantine; type-1 diabetic groups - untreated, treated with insulin alone and treated with insulin and memantine; and type 2 diabetic groups - untreated and memantine treated. Cognitive functions were assessed by the Morris Water Maze and passive avoidance test. Biochemical analysis was done for serum glucose, serum insulin and insulin resistance. Routine histological examination was done, together with immunohistochemistry for detection of the hippocampal learning and memory plasticity marker, namely activity regulated cytoskeletal-associated protein (Arc), and the astrocytes reactivity marker, namely glial fibrillary acidic protein (GFAP).  Results: Both type 1 and 2 untreated diabetic groups showed significantly impaired cognitive performance compared to the non-diabetic group. Treating the type 1 diabetic group with insulin alone significantly improved cognitive performance, but significantly decreased GFAP and Arc compared to the untreated type 1 group. In addition, the type 2 diabetic groups showed a significant decrease in hippocampus GFAP and Arc compared to the non-diabetic groups. Blocking NMDA receptors by memantine significantly increased cognitive performance, GFAP and Arc in the type 1 insulin-memantine group compared to the type 1-insulin group and significantly increased Arc in the type 2-memantine group compared to the untreated type 2 diabetic group. The non-diabetic group receiving memantine was

  4. Ultrasonography of histologically normal parathyroid glands and thyroid lobules in normocalcemic dogs.

    PubMed

    Liles, Sofija R; Linder, Keith E; Cain, Brandon; Pease, Anthony P

    2010-01-01

    The purpose of this study is to characterize the sonographic appearance of canine parathyroid glands using high-resolution ultrasonography. Ten cadaver dogs were studied after euthanasia for reasons not relating to the parathyroid. The cervical region was examined using a 13-5 MHz linear transducer in right and left recumbency. Ultrasonographic features of the parathyroid and thyroid glands were compared with the gross and histopathologic findings. Thirty-five structures were identified sonographically as parathyroid glands but only 26 of 35 glands (74% positive predictive value) were proven to be normal parathyroid glands histopathologically. Of the nine false positives, five (14%) were proven to be lobular thyroid tissue. The remaining four (11%) structures were visible grossly or found histopathologically. There were no statistical differences between ultrasonographic and gross measurements of the parathyroid glands. The average size as seen sonographically was 3.3 x 2.2 x 1.7 mm and the average gross size was 3.7 x 2.6 x 1.6 mm (length, width, height). The average size of the thyroid lobules assessed sonographically was 2.3 x1.6 x 0.8 mm (length, width, height). Normal parathyroid glands can be identified using high-resolution ultrasonography. But some thyroid lobules will be misinterpreted as parathyroid glands; this will result in false positives when identifying parathyroid glands with ultrasonography.

  5. Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

    PubMed

    Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

    2017-03-16

    We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

  6. Differentiating the two main histologic categories of fibroadenoma tissue from normal breast tissue by using multiphoton microscopy.

    PubMed

    Nie, Y T; Wu, Y; Fu, F M; Lian, Y E; Zhuo, S M; Wang, C; Chen, J X

    2015-04-01

    Multiphoton microscopy has become a novel biological imaging technique that allows cellular and subcellular microstructure imaging based on two-photon excited fluorescence and second harmonic generation. In this work, we used multiphoton microscopy to obtain the high-contrast images of human normal breast tissue and two main histologic types of fibroadenoma (intracanalicular, pericanalicular). Moreover, quantitative image analysis was performed to characterize the changes of collagen morphology (collagen content, collagen orientation). The results show that multiphoton microscopy combined with quantitative method has the ability to identify the characteristics of fibroadenoma including changes of the duct architecture and collagen morphology in stroma. With the advancement of multiphoton microscopy, we believe that the technique has great potential to be a real-time histopathological diagnostic tool for intraoperative detection of fibroadenoma in the future.

  7. Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues.

    PubMed

    Llanos, Adana A M; Marian, Catalin; Brasky, Theodore M; Dumitrescu, Ramona G; Liu, Zhenhua; Mason, Joel B; Makambi, Kepher H; Spear, Scott L; Kallakury, Bhaskar V S; Freudenheim, Jo L; Shields, Peter G

    2015-01-01

    Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed nucleotide element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for breast cancer. Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of carcinogenesis. In a cross-sectional study of 121 healthy women with no prior history of cancer who underwent reduction mammoplasty, we examined associations between plasma and breast folate, genetic variation in one-carbon metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and alcohol use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast folate and percent LINE-1 methylation. Variation in MTHFR, MTR, and MTRR were significantly associated with percent LINE-1 methylation. Variant allele carriers of MTHFR A1289C had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93-0.98), while variant allele carriers of MTR A2756G (Ratio 1.03, 95% CI 1.01-1.06) and MTRR A66G (Ratio 1.03, 95% CI 1.01-1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one-carbon metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on breast cancer susceptibility.

  8. Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues

    PubMed Central

    Llanos, Adana A M; Marian, Catalin; Brasky, Theodore M; Dumitrescu, Ramona G; Liu, Zhenhua; Mason, Joel B; Makambi, Kepher H; Spear, Scott L; Kallakury, Bhaskar V S; Freudenheim, Jo L; Shields, Peter G

    2015-01-01

    Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed nucleotide element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for breast cancer. Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of carcinogenesis. In a cross-sectional study of 121 healthy women with no prior history of cancer who underwent reduction mammoplasty, we examined associations between plasma and breast folate, genetic variation in one-carbon metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and alcohol use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast folate and percent LINE-1 methylation. Variation in MTHFR, MTR, and MTRR were significantly associated with percent LINE-1 methylation. Variant allele carriers of MTHFR A1289C had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93–0.98), while variant allele carriers of MTR A2756G (Ratio 1.03, 95% CI 1.01–1.06) and MTRR A66G (Ratio 1.03, 95% CI 1.01–1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one-carbon metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on breast cancer susceptibility. PMID:26090795

  9. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma

    SciTech Connect

    Howlett, Anthony R; Bailey, Nina; Damsky, Caroline; Petersen, Ole W; Bissell, Mina J

    1994-11-28

    We previously established a rapid three-dimensional assay for discrimination of normal and malignant human breast epithelial cells using a laminin-rich reconstituted basement membrane. In this assay, normal epithelial cells differentiate into well-organized acinar structures whereas tumor cells fail to recapitulate this process and produce large, disordered colonies. The data suggest that breast acinar morphogenesis and differentiation is regulated by cell-extracellular matrix (ECM) interactions and that these interactions are altered in malignancy. Here, we investigated the role of ECM receptors (integrins) in these processes and report on the expression and function of potential laminin receptors in normal and tumorigenic breast epithelial cells. Immmunocytochemical analysis showed that normal and carcinoma cells in a three-dimensional substratum express profiles of integrins similar to normal and malignant breast tissues in situ. Normal cells express {alpha}1, {alpha}2, {alpha}3, {alpha}6, {beta}1 and {beta}4 integrin subunits, whereas breast carcinoma cells show variable losses, disordered expression, or down regulation of these subunits. Function-blocking experiments using inhibitory antiintegrin subunit antibodies showed a >5-fold inhibition of the formation of acinar structures by normal cells in the presence of either anti-{beta}1 or anti-{alpha}3 antibodies, whereas anti-{alpha}2 or -{alpha}6 had little or no effect. In experiments where collagen type I gels were used instead of basement membrane, acinar morphogenesis was blocked by anti-{beta}1 and -{alpha}2 antibodies but not by anti-{alpha}3. These data suggest a specificity of integrin utilization dependent on the ECM ligands encountered by the cell. The interruption of normal acinar morphogenesis by anti-integrin antibodies was associated with an inhibition of cell growth and induction of apoptosis. Function-blocking antibodies had no inhibitory effect on the rate of tumor cell growth, survival or

  10. Quantitation of TGF-β proteins in mouse tissues shows reciprocal changes in TGF-β1 and TGF-β3 in normal vs neoplastic mammary epithelium.

    PubMed

    Flanders, Kathleen C; Yang, Yu-An; Herrmann, Michelle; Chen, JinQiu; Mendoza, Nerissa; Mirza, Amer M; Wakefield, Lalage M

    2016-06-21

    Transforming growth factor-βs (TGF-βs) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-β1, -β2, and -β3) have similar bioactivities in vitro but show distinct activities in vivo. Little quantitative information exists for expression of TGF-β isoform proteins in physiology or disease. We developed an optimized method to quantitate protein levels of the three isoforms, using a Luminex® xMAP®-based multianalyte assay following acid-ethanol extraction of tissues. Analysis of multiple tissues and plasma from four strains of adult mice showed that TGF-β1 is the predominant isoform with TGF-β2 being ~10-fold lower. There were no sex-specific differences in isoform expression, but some tissues showed inter-strain variation, particularly for TGF-β2. The only adult tissue expressing appreciable TGF-β3 was the mammary gland, where its levels were comparable to TGF-β1. In situ hybridization showed the luminal epithelium as the major source of all TGF-β isoforms in the normal mammary gland. TGF-β1 protein was 3-8-fold higher in three murine mammary tumor models than in normal mammary gland, while TGF-β3 protein was 2-3-fold lower in tumors than normal tissue, suggesting reciprocal regulation of these isoforms in mammary tumorigenesis.

  11. Quantitation of TGF-β proteins in mouse tissues shows reciprocal changes in TGF-β1 and TGF-β3 in normal vs neoplastic mammary epithelium

    PubMed Central

    Herrmann, Michelle; Chen, JinQiu; Mendoza, Nerissa; Mirza, Amer M.; Wakefield, Lalage M.

    2016-01-01

    Transforming growth factor-βs (TGF-βs) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-β1, -β2, and -β3) have similar bioactivities in vitro but show distinct activities in vivo. Little quantitative information exists for expression of TGF-β isoform proteins in physiology or disease. We developed an optimized method to quantitate protein levels of the three isoforms, using a Luminex® xMAP®-based multianalyte assay following acid-ethanol extraction of tissues. Analysis of multiple tissues and plasma from four strains of adult mice showed that TGF-β1 is the predominant isoform with TGF-β2 being ~10-fold lower. There were no sex-specific differences in isoform expression, but some tissues showed inter-strain variation, particularly for TGF-β2. The only adult tissue expressing appreciable TGF-β3 was the mammary gland, where its levels were comparable to TGF-β1. In situ hybridization showed the luminal epithelium as the major source of all TGF-β isoforms in the normal mammary gland. TGF-β1 protein was 3-8-fold higher in three murine mammary tumor models than in normal mammary gland, while TGF-β3 protein was 2-3-fold lower in tumors than normal tissue, suggesting reciprocal regulation of these isoforms in mammary tumorigenesis. PMID:27203217

  12. Breast Field Cancerization: Isolation and Comparison of Telomerase-Expressing Cells in Tumor and Tumor Adjacent, Histologically Normal Breast Tissue

    PubMed Central

    Trujillo, Kristina A.; Hines, William C.; Vargas, Keith M.; Jones, Anna C.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K.

    2011-01-01

    Telomerase stabilizes chromosomes by maintaining telomere length, immortalizes mammalian cells, and is expressed in more than 90% of human tumors. However, the expression of human telomerase reverse transcriptase (hTERT) is not restricted to tumor cells. We have previously shown that a subpopulation of human mammary epithelial cells (HMEC) in tumor-adjacent, histologically normal (TAHN) breast tissues expresses hTERT mRNA at levels comparable with levels in breast tumors. In the current study, we first validated a reporter for measuring levels of hTERT promoter activity in early-passage HMECs and then used this reporter to compare hTERT promoter activity in HMECs derived from tumor and paired TAHN tissues 1, 3, and 5 cm from the tumor (TAHN-1, TAHN-3, and TAHN-5, respectively). Cell sorting, quantitative real-time PCR, and microarray analyses showed that the 10% of HMECs with the highest hTERT promoter activity in both tumor and TAHN-1 tissues contain more than 95% of hTERT mRNA and overexpress many genes involved in cell cycle and mitosis. The percentage of HMECs within this subpopulation showing high hTERT promoter activity was significantly reduced or absent in TAHN-3 and TAHN-5 tissues. We conclude that the field of normal tissue proximal to the breast tumors contains a population of HMECs similar in hTERT expression levels and in gene expression to the HMECs within the tumor mass and that this population is significantly reduced in tissues more distal to the tumor. PMID:21775421

  13. Pigment epithelium-derived factor (PEDF) normalizes matrix defects in iPSCs derived from Osteogenesis imperfecta Type VI.

    PubMed

    Belinsky, Glenn S; Ward, Leanne; Chung, Chuhan

    2016-01-01

    Osteogenesis imperfecta (OI) Type VI is characterized by a defect in bone mineralization, which results in multiple fractures early in life. Null mutations in the PEDF gene, Serpinf1, are the cause of OI VI. Whether PEDF restoration in a murine model of OI Type VI could improve bone mass and function was previously unknown. In Belinsky et al, we provided evidence that PEDF delivery enhanced bone mass and improved parameters of bone function in vivo. Further, we demonstrated that PEDF temporally inhibits Wnt signaling to enhance osteoblast differentiation. Here, we demonstrate that generation of induced pluripotent stem cells (iPSCs) from a PEDF null patient provides additional evidence for PEDF's role in regulating extracellular matrix proteins secreted from osteoblasts. PEDF null iPSCs have marked abnormalities in secreted matrix proteins, capturing a key feature of human OI Type VI, which were normalized by exogenous PEDF. Lastly, we place our recent findings within the broader context of PEDF biology and the developmental signaling pathways that are implicated in its actions.

  14. Spatial differentiation of the intestinal epithelium: analysis of enteroendocrine cells containing immunoreactive serotonin, secretin, and substance P in normal and transgenic mice.

    PubMed Central

    Roth, K A; Gordon, J I

    1990-01-01

    The mammalian intestinal epithelium undergoes continuous and rapid renewal of its four principal terminally differentiated cell types. These cells arise from multipotent stem cells located at or near the base of the crypts of Lieberkühn. The differentiation process is precisely organized along two spatial dimensions (axes)--from the crypt to the villus tip and from the duodenum to the colon. The enteroendocrine cell population provides a sensitive marker of the intestine's topologic differentiation. At least 15 different regionally distributed subsets have been described based on their principal neuroendocrine products. We have used immunocytochemical methods to characterize the spatial relationships of the serotonin-, secretin-, and substance P-containing enteroendocrine cell subsets in normal adult C57BL/6J x LT/Sv mice as well as in transgenic littermates that contain rat liver fatty acid-binding protein-human growth hormone fusion genes. Our results reveal precise spatial interrelationships between these populations and suggest a differentiation pathway that may involve the sequential expression of substance P, serotonin, and secretin. Images PMID:1696730

  15. Selection of internal reference genes for normalization of reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis in the rumen epithelium

    PubMed Central

    Die, Jose V.; Rowland, Lisa J.; Li, Robert; Oh, Sunghee; Li, Congjun; Connor, Erin E.; Ranilla, Maria-Jose

    2017-01-01

    The rumen is lined on the luminal side by a stratified squamous epithelium that is responsible for not only absorption, but also transport, extensive short-chain fatty acid (SCFA) metabolism and protection. Butyrate has been demonstrated to initiate the differentiation of the tissue following introduction of solid feed to the weaning neonate as well as affecting the metabolism of other nutrients and absorption of nutrients in in vitro experiments. The objective of the present study was to validate expression stability of eight putative reference genes bovine rumen, considering the intrinsic heterogeneity of bovine rumen with regard to different luminal characteristics due to direct infusion of butyrate to double the intra-ruminal content of the rumen liquor. Our focus was on identifying stable reference genes which are suitable to normalize real-time RT-qPCR experiments from rumen samples collected from clinical assays, irrespective of localization within the organ and the across physiological state. The most stably expressed genes included: ACTB, UXT, DBNDD2, RPS9, DDX54 and HMBS. Their high stability values suggest these reference genes will facilitate better evaluation of variation of across an array of conditions including: localization within the rumen, differences among cattle fed an array of rations, as well as response to development in the weaning animal. Moreover, we anticipate these reference genes may be useful for expression studies in other ruminants. PMID:28234977

  16. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

    PubMed

    Thomas, Sushma S; Makar, Karen W; Li, Lin; Zheng, Yingye; Yang, Peiying; Levy, Lisa; Rudolph, Rebecca Y; Lampe, Paul D; Yan, Min; Markowitz, Sanford D; Bigler, Jeannette; Lampe, Johanna W; Potter, John D

    2015-12-01

    Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) - accession number GSE71571 - was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]).

  17. Airway epithelium stimulates smooth muscle proliferation.

    PubMed

    Malavia, Nikita K; Raub, Christopher B; Mahon, Sari B; Brenner, Matthew; Panettieri, Reynold A; George, Steven C

    2009-09-01

    Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that after injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air-liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (HASM) using commercially available Transwells. In some co-cultures, the NHBE were repeatedly (x4) scrape-injured. An in vivo model of tracheal injury consisted of gently denuding the tracheal epithelium (x3) of a rabbit over 5 days and then examining the trachea by histology 3 days after the last injury. Our results show that HASM cell number increases 2.5-fold in the presence of NHBE, and 4.3-fold in the presence of injured NHBE compared with HASM alone after 8 days of in vitro co-culture. In addition, IL-6, IL-8, monocyte chemotactic protein (MCP)-1 and, more markedly, matrix metalloproteinase (MMP)-9 concentration increased in co-culture correlating with enhanced HASM growth. Inhibiting MMP-9 release significantly attenuated the NHBE-dependent HASM proliferation in co-culture. In vivo, the injured rabbit trachea demonstrated proliferation in the smooth muscle (trachealis) region and significant MMP-9 staining, which was absent in the uninjured control. The airway epithelium modulates smooth muscle cell proliferation via a mechanism that involves secretion of soluble mediators including potential smooth muscle mitogens such as IL-6, IL-8, and MCP-1, but also through a novel MMP-9-dependent mechanism.

  18. A fusion-based approach for uterine cervical cancer histology image classification.

    PubMed

    De, Soumya; Stanley, R Joe; Lu, Cheng; Long, Rodney; Antani, Sameer; Thoma, George; Zuna, Rosemary

    2013-01-01

    Expert pathologists commonly perform visual interpretation of histology slides for cervix tissue abnormality diagnosis. We investigated an automated, localized, fusion-based approach for cervix histology image analysis for squamous epithelium classification into Normal, CIN1, CIN2, and CIN3 grades of cervical intraepithelial neoplasia (CIN). The epithelium image analysis approach includes medial axis determination, vertical segment partitioning as medial axis orthogonal cuts, individual vertical segment feature extraction and classification, and image-based classification using a voting scheme fusing the vertical segment CIN grades. Results using 61 images showed at least 15.5% CIN exact grade classification improvement using the localized vertical segment fusion versus global image features.

  19. The morphology and kinetics of spermatogonial degeneration in normal adult rats: an analysis using a simplified classification of the germinal epithelium.

    PubMed

    Huckins, C

    1978-04-01

    normal generminal epithelium remain obscure, it is proposed that the numerical ratio of A spermatogonia to Sertoli cells may be a significant limiting factor.

  20. [Morpho-functional characteristic of oral mucosal epithelium after treatment with a cytostatic drug].

    PubMed

    Leont'eva, I V; Bykov, V L

    2011-01-01

    The effect of cytostatic drug cyclophosphamide (CY) on lingual epithelium was studied in 90 female mice using histological, morphometric, quantitative histochemical and immunohistochemical methods. CY (400 mg/kg) was injected intraperitoneally three times with a 48 h interval. Material was obtained 2 days after injections and 10-20 days after their discontinuation. CY treatment was shown to result in the damage of both surface epithelium of the tongue and the epithelium of minor lingual salivary glands. Damage to the surface epithelium was more pronounced on the ventral surface of the tongue and was associated mainly with the disturbances of its proliferation. Changes were less severe on the dorsal surface and were seen as the disturbances of epithelial differentiation and desquamation. Glandular epithelium was damaged to a lesser extent than the surface one, with serocytes being more sensitive to the cytotoxic injury than mucocytes. After cytostatic drug discontinuation, the tendency for the normalization of the epithelial characteristics was noted. Most persistent changes in the surface epithelium were found on the dorsal surface of the tongue and in the glandular epithelium--in the serous secretory portions of the salivary glands.

  1. The significance of small intestinal epithelium in gastric antral biopsies in children.

    PubMed

    Weinberg, Arthur G

    2012-01-01

    Intestinal metaplasia of the gastric antrum is common in adults with chronic gastritis and occurs in Helicobacter -associated gastritis in children. This study examined the frequency and clinical correlates of intestinal epithelium in 1690 consecutive antral biopsies obtained from children over a 2-year period in a tertiary pediatric care facility. Intestinal epithelium in gastric glands not associated with overlying villi was present in 22 (1.3%) biopsies. These came from 20 patients, 2-17 years of age, none of whom had clinical or histologic evidence of Helicobacter infection or significant chronic gastritis. Eight (40%) had an antral pancreatic rest, 8 had some other localized antral abnormality, and 4 were endoscopically normal. Four additional patients with a pancreatic rest had no intestinal epithelium. Six surgically resected rests and 2 rests found at autopsy were also reviewed. Heterotopic intestinal epithelium was present in 1 of the 2 postmortem specimens but was absent from all 6 surgically resected lesions. No intestinal epithelium was present in 67 antral biopsies with Helicobacter gastritis observed during this same period. Although the intestinal epithelium in these patients could be metaplastic, it more likely represents inadvertent sampling of the gastroduodenal junction induced by a lesion in the distal antrum or a focus of heterotopic epithelium and might best be addressed in the surgical pathology report by a comment to this effect. The distinction from metaplasia is more than semantic, because a diagnosis of intestinal metaplasia can have adverse clinical implications and should be made with caution in a child.

  2. Role of Stroma-Derived Extracellular Matrix in Regulation of Growth and Hormonal Responsiveness of Normal and Cancerous Human Breast Epithelium.

    DTIC Science & Technology

    1998-09-01

    by residual estrogen or more likely by growth factor pathways ( Ignar -Trowbridge et al., 1996), have masked estrogen-induced proliferation in serum...an ERE- CAT construct independent of estrogen, but this was blocked by the anti-estrogen ICI 164,384 ( Ignar -Trowbridge et al., 1996). Again, these...modulates hormonal responsiveness of mammary epithelium in vivo in the mouse. Endocrinology, 129:2017-2023. Ignar -Trowbridge, D.M., M. Pimentel, M.G

  3. Normal sheep synovium has similar appearances and constitutive expression of inflammatory cytokines within and between knee joints: a baseline histological and molecular analysis.

    PubMed

    Solbak, Nathan; Achari, Yamini; Chung, May; Shrive, Nigel G; Hart, David A; Frank, Cyril B

    2014-04-01

    Abstract Clinical evidence suggests that synovium can add to adjacent articular cartilage damage, potentially contributing to the development of osteoarthritis (OA). Inflammation of the synovium (synovitis) is dependent on the type of injury sustained, the time after injury and concomitant changes in other joint tissues. To define the role of synovitis in OA development, there is a need for baseline measures that can reliably distinguish synovial inflammation from normal synovium both within and between joints. This study tested the hypothesis that normal synovium from distinct anatomical locations in young and adult sheep is homogeneous with respect to consistently low molecular expression of the inflammatory mediators - tumour necrosis factor alpha (TNF-α) and interleukins (IL) such as IL-1β, IL-1Ra, IL-6 and IL-8. Additionally, maturation will not influence the expression of these select inflammatory biomarkers. Samples of synovium from four anatomic locations (medial and lateral margins, suprapatellar pouch (patella region), posterior to the posterior cruciate ligament, from each joint of 5 adult and 4 immature animals were graded histologically or analyzed for mRNA expression of inflammatory cytokines. Histologically, no evidence of synovitis was noted although some variance in sub-intimal fibrosis was observed between sample locations in mature sheep. Molecular expression of all inflammatory mediators was low and homogeneously expressed at constitutive levels in all sample locations. These findings confirm the hypothesis that the normal sheep synovium is a homogeneous tissue throughout the joint and establishes the baseline expression levels for several pro-inflammatory mediators in both immature and mature sheep.

  4. Identification of a preneoplastic gene expression profile in tubal epithelium of BRCA1 mutation carriers.

    PubMed

    Press, Joshua Z; Wurz, Kaitlyn; Norquist, Barbara M; Lee, Ming K; Pennil, Christopher; Garcia, Rochelle; Welcsh, Piri; Goff, Barbara A; Swisher, Elizabeth M

    2010-12-01

    Microinvasive carcinomas and high-grade intraepithelial neoplasms are commonly discovered within the fallopian tube of BRCA1 mutation carriers at the time of risk-reducing salpingo-oophorectomy, suggesting that many BRCA1-mutated ovarian carcinomas originate in tubal epithelium. We hypothesized that changes in gene expression profiles within the histologically normal fallopian tube epithelium of BRCA1 mutation carriers would overlap with the expression profiles in BRCA1-mutated ovarian carcinomas and represent a BRCA1 preneoplastic signature. Laser capture microdissection of frozen sections was used to isolate neoplastic cells or histologically normal fallopian tube epithelium, and expression profiles were generated on Affymetrix U133 Plus 2.0 gene expression arrays. Normal-risk controls were 11 women wild type for BRCA1 and BRCA2 (WT-FT). WT-FT were compared with histologically normal fallopian tube epithelium from seven women with deleterious BRCA1 mutations who had foci of at least intraepithelial neoplasm within their fallopian tube (B1-FTocc). WT-FT samples were also compared with 12 BRCA1 ovarian carcinomas (B1-CA). The comparison of WT-FT versus B1-FTocc resulted in 152 differentially expressed probe sets, and the comparison of WT-FT versus B1-CA resulted in 4079 differentially expressed probe sets. The BRCA1 preneoplastic signature was composed of the overlap between these two lists, which included 41 concordant probe sets. Genes in the BRCA1 preneoplastic signature included several known tumor suppressor genes such as CDKN1C and EFEMP1 and several thought to be important in invasion and metastasis such as E2F3. The expression of a subset of genes was validated with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry.

  5. [Histology of keratoglobus (author's transl)].

    PubMed

    Knieper, P; Rochels, R; Nover, A

    1980-07-01

    The authors examined four cases of keratoglobus and report here on the histological changes found: degenerative alterations of the epithelium, characteristic changes of Bowman's membrane, such as thinning, detachment and wrinkling, alterations of the stroma and secondary alterations of the Descemet's membrane. These results indicate that keratoglobus is nearly an extreme variant of keratoconus.

  6. The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

    NASA Technical Reports Server (NTRS)

    Zerwekh, J. E.; Ruml, L. A.; Gottschalk, F.; Pak, C. Y.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal

  7. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

    The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

  8. Effect of carbonated drinks on wound healing of oral epithelium

    PubMed Central

    Fahim, Ayesha; Ilyas, Muhammad Sharjeel; Jafari, Fahim Haider; Farzana, Fauzia

    2015-01-01

    Background Carbonated drinks are the second most consumed non-alcoholic beverages in the world after tea. The effects of these drinks on hard tissues and vital organs of the body have been proved beyond doubt. This study, however, explains the effect of these drinks on wound healing of oral epithelium. Methods Thirty-six male Wistar rats were considered for the study. A circular wound of 3.0 mm was created on the buccal mucosa of all animals and they were divided into two groups. Animals in group 1 were fed with chow pellet and water, while those in group 2 were fed with a commercially available carbonated drink instead of water. Six animals from each group were euthanized at 0, 7, and 21 days. Wound site was histologically assessed for differences in thickness and characteristics of the regenerating epithelium between two groups. Results There was a marked difference in the healing pattern between the two groups. Animals in group 1 showed a normal healing pattern at the end of day 21. In the group 2, the regenerated epithelium showed hyperplasia and hyperkeratosis along with acanthosis at the end of the experiment with a subsequent delayed inflammatory reaction at day 21. Conclusion Consumption of carbonated drinks can disrupt oral wound healing. The contents in carbonated drinks have a proinflammatory action on the soft tissue. Results suggest that epithelial changes seen in experimental group 2 could be a result of constant irritation by the acidic and fizzy nature of carbonated drinks. PMID:26937370

  9. Clinico-histologic conferences: histology and disease.

    PubMed

    Shaw, Phyllis A; Friedman, Erica S

    2012-01-01

    Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical context, promote integration and application of science knowledge, and to foster peer teaching and learning: the Clinico-Histologic Conference (CHC) for the Mount Sinai School of Medicine Histology course. Teams of six students were each assigned specific disease processes and were charged with creating oral presentations and handouts that taught their classmates about the clinical manifestations, etiopathogeneses, diagnoses, and treatments of the assigned processes, along with comparisons of normal histology to the pathology of the disease. Each team also created four questions, some of which were used on Histology written examinations. The physician facilitator evaluated the presentation and handouts. About two-thirds of students agreed the CHC enhanced appreciation of the importance of histology, provided a context for integration and application of basic science to patient care and enhanced their ability to teach their peers. Student feedback demonstrated that the CHCs were successful in promoting teamwork, peer teaching, and the application of histology to diagnose diseases. The authors believe that teaching basic science content in this new format enhanced student learning and application of medical knowledge, and that this new teaching format can be adopted by other medical school courses.

  10. Genome-wide profiling of the human papillomavirus DNA integration in cervical intraepithelial neoplasia and normal cervical epithelium by HPV capture technology

    PubMed Central

    Liu, Ying; Zhang, Chaoting; Gao, Weijiao; Wang, Limin; Pan, Yaqi; Gao, Yunong; Lu, Zheming; Ke, Yang

    2016-01-01

    HPV integration plays an important role in cervical carcinogenesis. HPV genotypes and the exact integration sites were investigated using HPV capture technology combined with next generation sequencing in 166 women. Three, one and six integration sites were verified in 7 HPV-positive ‘normal cervical epithelium’, 6 HPV-positive CIN2 and 15 HPV-positive CIN 3 samples, respectively. Of the 10 integrations, one and nine were involved with HPV33 and HPV16, respectively. Our study accurately evaluated HPV integration level in CINs and normal cervical tissues using high-throughput viral integration detection method providing basic evidence for HPV integration-driven cervical carcinogenesis. PMID:27759101

  11. Ability of transplanted cultured epithelium to respond to dermal papillae.

    PubMed

    Xing, L; Kobayashi, K

    2001-10-01

    Cultured epithelium has been used successfully in the treatment of extensive burns. Regenerated epidermis, however, lacks such as hair follicles and sweat glands that are common in mammalian skin. We attempted to determine whether cultured epithelium could be induced to form hair follicles by dermal papillae, which are most important for the morphogenesis and growth of hair follicles. We cultivated adult rat sole keratinocytes, obtained the cultured epithelium, and prepared recombinants consisting of cultured epithelium and fresh dermal papillae with or without the sole dermis. These recombinants were then transplanted underneath the dermis of the dorsal skin of syngeneic rats or athymic mice. Histologic examination revealed that the transplanted cultured epithelium formed the follicular structures with sebaceous gland-like structure following induction of the dermal papillae, especially when supported by the dermis. We concluded that transplanted cultured epithelium of adult rat sole keratinocytes can respond to growth signals from adult dermal papillae.

  12. Specificity of Tumor Necrosis Factor Toxicity for Human Mammary Carcinomas Relative to Normal Mammary Epithelium and Correlation with Response to Doxorubicin

    NASA Astrophysics Data System (ADS)

    Dollbaum, Charles; Creasey, Abla A.; Dairkee, Shahnaz H.; Hiller, Alan J.; Rudolph, Alfred R.; Lin, Leo; Vitt, Charles; Smith, Helene S.

    1988-07-01

    By using a unique short-term culture system capable of growing both normal and malignant breast epithelial tissue, human recombinant tumor necrosis factor (TNF) showed preferential cytotoxicity to malignant cells as compared to the corresponding nonmalignant cells. Most of the malignant specimens were sensitive to TNF with 13 of 18 specimens showing 90% inhibition of clonal growth (ID90) by <500 units of TNF per ml of culture fluid. In contrast, all 13 nonmalignant specimens tested clustered at the resistant end of the TNF response spectrum, with ID90 values being >5000 units of TNF per ml of culture fluid. This differential sensitivity to TNF was seen in three cases in which malignant and nonmalignant breast epithelial tissues from the same patient were studied. To investigate the mechanism of resistance to TNF by normal cells, the presence of receptors for TNF was determined. Five of six cultures showed specific binding of 125I-labeled TNF and there was no relationship between the degree of resistance and the degree of specific binding. Simultaneous comparison of tumor responsiveness to doxorubicin and TNF revealed a positive correlation in ID90 values; these results may have important implications for the clinical use of TNF in cancer patients heavily pretreated with doxorubicin.

  13. Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.

    PubMed

    Hayakawa, Yoku; Ariyama, Hiroshi; Stancikova, Jitka; Sakitani, Kosuke; Asfaha, Samuel; Renz, Bernhard W; Dubeykovskaya, Zinaida A; Shibata, Wataru; Wang, Hongshan; Westphalen, Christoph B; Chen, Xiaowei; Takemoto, Yoshihiro; Kim, Woosook; Khurana, Shradha S; Tailor, Yagnesh; Nagar, Karan; Tomita, Hiroyuki; Hara, Akira; Sepulveda, Antonia R; Setlik, Wanda; Gershon, Michael D; Saha, Subhrajit; Ding, Lei; Shen, Zeli; Fox, James G; Friedman, Richard A; Konieczny, Stephen F; Worthley, Daniel L; Korinek, Vladimir; Wang, Timothy C

    2015-12-14

    The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1(+) stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12(+) endothelial cells and Cxcr4(+) gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.

  14. Cysts in the rat adenohypophysis: incidence and histology.

    PubMed

    Quintanar-Stephano, A; Muñoz Fernández, L; Quintanar, J L; Kovacs, K

    2001-01-01

    The incidence and histology of cysts in the adenohypophysis of adult male Wistar rats are reported. Of sixty pituitaries studied 13 of them (21.6%) presented a single cyst located in the pars distalis. The cysts varied in shape and size and were usually multilocular. Two of them were connected with the subdural space at the ventral surface of the adenohypophysis. Histology demonstrated that the cysts were filled with mucinous material and foamy macrophages and were lined by flat and cuboidal ciliated and nonciliated epithelial cells, goblet cells as well as several adenohypophysial endocrine cells such as somatotrophs, thyrotrophs, and gonadotrophs. The ciliated cells were the most numerous. Histologic and immunohistochemical studies of the uninvolved areas of the adenohypophysis showed no abnormalities and the weights and histology of the adenohypophyses and peripheral endocrine glands were within normal range, suggesting that the cysts did not impair the adenohypophysial endocrine activity. Although the morphogenesis of the cysts remained obscure, the histological and immunohistochemical findings support the hypothesis that during embryonic development, the future cysts coming from the pharyngeal epithelium is fused with the stomodeum before or during the formation of the Rathke's pouch.

  15. Morphological Alterations of the Palpebral Conjunctival Epithelium in a Dry Eye Model

    PubMed Central

    Henriksson, Johanna Tukler; De Paiva, Cintia S.; Farley, William; Pflugfelder, Stephen C.; Burns, Alan R.; Bergmanson, Jan P.G.

    2012-01-01

    Purpose To investigate the normal palpebral conjunctival histology in C57BL/6 mice, and the structural changes that occur in a dry eye model. Methods 24 male and female C57BL/6 mice, 8 untreated (UT) and 16 exposed to experimental ocular surface desiccating stress (DS). Ocular dryness was induced by administration of scopolamine hydrobromide (0.5 mg/0.2 ml) QID for 5 (DS5) or 10 (DS10) days. Counts and measurements were obtained using anatomical reference points and goblet cell density was investigated with a variety of stains. Results Near the junction between the lid margin and the normal palpebral conjunctiva, the epithelium had an average thickness of 45.6±10.5μm, 8.8±2.0 cell layers, versus 37.7±5.6μm, 7.4±1.3 layers in DS10 (P<0.05). In the goblet cell populated palpebral region the normal epithelium was thicker (P<0.05) than in DS5 and DS10. In the control, 43% of the goblet cells were covered by squamous epithelium, compared to 58% (DS5) and 63% (DS10) (P<0.05). A decreased number of Periodic Acid Schiff (PAS) and Alcian blue stained goblet cells was observed in the dry eye. Not all goblet cells stained with PAS and Alcian blue. Conclusions The mouse palpebral conjunctival epithelium was structurally similar to the human. After DS the palpebral conjunctival epithelium decreased in thickness and goblet cell access to the surface appeared to be inhibited by surrounding epithelial cells, potentially slowing down their migration to the surface. Differential staining with PAS and Alcian blue suggests there may be different subtypes of conjunctival goblet cells. PMID:23146932

  16. Lack of bronchial hyperresponsiveness to methacholine and to isocapnic dry air hyperventilation in heart/lung and double-lung transplant recipients with normal lung histology. The Paris-Sud Lung Transplant Group.

    PubMed

    Herve, P; Picard, N; Le Roy Ladurie, M; Silbert, D; Cerrina, J; Le Roy Ladurie, F; Chapelier, A; Dartevelle, P; Simonneau, G; Parquin, F

    1992-06-01

    To investigate whether survivors of heart/lung and double-lung transplantations have normal or increased nonspecific bronchial responsiveness, nine heart/lung and four double-lung transplant recipients with normal lung histology underwent methacholine challenge and voluntary isocapnic dry air hyperventilation (VIH) in a randomized order at a mean time of 14.8 +/- 12.1 months after surgery. Transplant recipients were compared with 10 normal subjects and 11 patients with mild asthma. Asthmatic patients had a mean provocative concentration of methacholine inducing a 20% fall (PC20) in FEV1 of 3.4 +/- 3.6 mg/ml (SD). Seventy seven percent of the transplant recipients and 70% of the normal subjects had PC20 superior to 32 mg/ml. The percentage fall from baseline FEV1 after VIH was 12.6 +/- 10.4% in asthmatic patients as compared with 1.9 +/- 2.9% in transplant recipients (p = 0.002) and 0.45 +/- 1.2% in normal subjects (p = 0.001). The decrease in FEV1 after VIH was similar in transplant recipients and normal subjects (p = 0.14). These results show that heart/lung or double-lung transplant recipients with normal lung histology have a normal response to nonspecific bronchial stimulation.

  17. Enhancements in localized classification for uterine cervical cancer digital histology image assessment

    PubMed Central

    Guo, Peng; Almubarak, Haidar; Banerjee, Koyel; Stanley, R. Joe; Long, Rodney; Antani, Sameer; Thoma, George; Zuna, Rosemary; Frazier, Shelliane R.; Moss, Randy H.; Stoecker, William V.

    2016-01-01

    Background: In previous research, we introduced an automated, localized, fusion-based approach for classifying uterine cervix squamous epithelium into Normal, CIN1, CIN2, and CIN3 grades of cervical intraepithelial neoplasia (CIN) based on digitized histology image analysis. As part of the CIN assessment process, acellular and atypical cell concentration features were computed from vertical segment partitions of the epithelium region to quantize the relative distribution of nuclei. Methods: Feature data was extracted from 610 individual segments from 61 images for epithelium classification into categories of Normal, CIN1, CIN2, and CIN3. The classification results were compared against CIN labels obtained from two pathologists who visually assessed abnormality in the digitized histology images. In this study, individual vertical segment CIN classification accuracy improvement is reported using the logistic regression classifier for an expanded data set of 118 histology images. Results: We analyzed the effects on classification using the same pathologist labels for training and testing versus using one pathologist labels for training and the other for testing. Based on a leave-one-out approach for classifier training and testing, exact grade CIN accuracies of 81.29% and 88.98% were achieved for individual vertical segment and epithelium whole-image classification, respectively. Conclusions: The Logistic and Random Tree classifiers outperformed the benchmark SVM and LDA classifiers from previous research. The Logistic Regression classifier yielded an improvement of 10.17% in CIN Exact grade classification results based on CIN labels for training-testing for the individual vertical segments and the whole image from the same single expert over the baseline approach using the reduced features. Overall, the CIN classification rates tended to be higher using the training-testing labels for the same expert than for training labels from one expert and testing labels from

  18. Effect of acetic acid on optical coherence tomography (OCT) images of cervical epithelium.

    PubMed

    Gallwas, Julia; Stanchi, Anna; Dannecker, Christian; Ditsch, Nina; Mueller, Susanna; Mortensen, Uwe; Stepp, Herbert

    2014-11-01

    Optical coherence tomography (OCT) can be used as an adjunct to colposcopy in the identification of precancerous and cancerous cervical lesions. The purpose of this study was to investigate the effect of acetic acid on OCT imaging. OCT images were taken from unsuspicious and suspicious areas of fresh conization specimens immediately after resection and 3 and 10 min after application of 6 % acetic acid. A corresponding histology was obtained from all sites. The images taken 3 and 10 min after application of acetic acid were compared to the initial images with respect to changes in brightness, contrast, and scanning depth employing a standard nonparametric test of differences of proportions. Further, mean intensity backscattering curves were calculated from all OCT images in the histological groups CIN3, inflammation, or normal epithelium. Mean difference profiles within each of these groups were determined, reflecting the mean differences between the condition before application of acetic acid and the exposure times 3 and 10 min, respectively. According to the null hypothesis, the difference profiles do not differ from profiles fluctuating around zero in a stationary way, which implies that the profiles do not differ significantly from each other. The null hypothesis was tested employing the KPSS test. The visual analysis of 137 OCT images from 46 sites of 10 conization specimens revealed a statistically significant increase in brightness for all three groups and a statistically significant decrease in contrast for normal epithelium after 10 min. Further, an increase in scanning depth was noted for normal epithelium after 10 min and for CIN3 after 3 min. The analysis of mean intensity profiles showed an increased backscattering intensity after application of acetic acid. Acetic acid significantly affects the quality of OCT images. Overall brightness and scanning depth increase with the opposite effect regarding the image contrast. Whether the observed changes

  19. Ductal barriers in mammary epithelium

    PubMed Central

    Owens, Mark B; Hill, Arnold DK; Hopkins, Ann M

    2013-01-01

    Tissue barriers play an integral role in the biology and pathobiology of mammary ductal epithelium. In normal breast physiology, tight and adherens junctions undergo dynamic changes in permeability in response to hormonal and other stimuli, while several of their proteins are directly involved in mammary tumorigenesis. This review describes first the structure of mammary ductal epithelial barriers and their role in normal mammary development, examining the cyclical changes in response to puberty, pregnancy, lactation and involution. It then examines the role of adherens and tight junctions and the participation of their constituent proteins in mammary tumorigenic functions such as migration, invasion and metastasis. Finally, it discusses the potential of these adhesion proteins as both prognostic biomarkers and potential therapeutic targets in breast cancer. PMID:24665412

  20. Cuboidal epithelium lining of the parietal layer of Bowman's capsule in Afghan pikas (Ochotona rufescens rufescens).

    PubMed

    Madarame, H; Kumagai, M; Motooka, N; Konno, S

    1991-01-01

    Kidneys of 64 Afghan pikas (Ochotona rufescens rufescens) were examined histologically. Seven of 21 males and two of 21 females over 6 months of age had a cuboidal epithelium lining of the parietal layer of Bowman's capsule.

  1. Relationship between histology, development and tumorigenesis of mammary gland in female rat

    PubMed Central

    LÍŠKA, Ján; BRTKO, Július; DUBOVICKÝ, Michal; MACEJOVÁ, Dana; KISSOVÁ, Viktória; POLÁK, Štefan; UJHÁZY, Eduard

    2015-01-01

    The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential. PMID:26424555

  2. Relationship between histology, development and tumorigenesis of mammary gland in female rat.

    PubMed

    Líška, Ján; Brtko, Július; Dubovický, Michal; Macejová, Dana; Kissová, Viktória; Polák, Štefan; Ujházy, Eduard

    2016-01-01

    The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential.

  3. Quantitative histology of cartilage vascular canals in the human rib. Findings in normal neonates and children and in achondrogenesis II-hypochondrogenesis.

    PubMed

    Gruber, H E; Lachman, R S; Rimoin, D L

    1990-12-01

    Knowledge of the structure of cartilage vascular canals is important for a more thorough understanding of the development of cartilage and the growth plate in the human neonate and growing child. We have studied the costochondral junction of 6 normal neonates and 12 normal children (age 4 months-16 years) and utilised quantitative histomorphometry to define the percentage tissue area occupied by canals and the number of canals/mm2. Both percentage canal area and the number of canals/mm2 were significantly greater in newborn vs. older children (percentage area: 0.42 +/- 0.15 (mean +/- S.E.M.) vs. 0.08 +/- 0.04, P = 0.003; number/mm2: 0.2 +/- 0.09 vs. 0.04 +/- 0.02, P = 0.02). Eight newborn patients with achondrogenesis II-hypochondrogenesis were also studied. Both percentage canal area and number were significantly elevated above normal (percentage area: 5.22 +/- 1.01, P less than 0.001; number/mm2: 1.45 +/- 0.26, P less than 0.001). Results presented here demonstrate that: (i) quantitative differences in vascular canal area and numbers occur during development; (ii) 10-fold increases in vascular canal area and number are present in achondrogenesis II-hypochondrogenesis. Data from normal subjects will provide normative values against which vascular abnormalities in other skeletal dysplasias can be compared.

  4. Analysis of the size variability of the human normal and cleft palate fetal nasal capsule by means of three-dimensional computer reconstruction of histologic preparations.

    PubMed

    Siegel, M I; Mooney, M P; Kimes, K R; Todhunter, J

    1987-07-01

    As part of an ongoing study of cleft palate fetal morphology, normal and dysmorphic development of the human fetal nasal capsule was studied in a cross-sectional sample of 29 human fetuses (20 "normal" and 9 cleft), ranging in age from 8 to 21 postmenstrual weeks. The specimens were celloidin embedded, sectioned at 20 microns, and every tenth section stained with hematoxylin and eosin. A computer reconstruction technique was applied to produce three-dimensional representations of the nasal capsule, nasal septal cartilage, and nasal airway. Qualitatively, the cleft palate nasal capsule exhibited gross abnormalities including cartilaginous nasal septum deformities, abnormal septal volume and hypertrophy, reduced nasal airway and capsule volumes, and abnormal spatial relationships between the nasal capsule components. These results suggest that the reduced nasal airways, noted clinically in cleft perinates, may be a function of an interaction of nasal capsule deficiency and nasal septum hypertrophy. However, when lengths and volumes were plotted against fetal postmenstrual age, producing fetal "growth" curves, no significant differences (p greater than 0.05) were noted for growth rates (slopes) or nasal capsule size between the normal and cleft palate fetal samples. Curvilinear regression analysis revealed that both normal and cleft palate nasal capsule and septum lengths changed in a sigmoidal fashion, with the steepest increases from 13 to 17 weeks. In contrast, nasal capsule, airway, and septum volumes changed curvilinearly, showing slow relative growth rates from 8 to 17 weeks, which increased sharply from 18 to 21 weeks. Results suggest that from 8 to 21 weeks prenatally, normal and cleft palate specimens exhibited a similar pattern of fetal nasal capsule development that was characterized by an initial anteroposterior elongation followed by circumferential (i.e., volumetric) growth.

  5. Expression of Prostanoid EP3 Receptors in Oral Squamous Epithelium and Oral Squamous Cell Carcinoma

    PubMed Central

    Ishfaq, Muhammad; Nagi, A. H.

    2015-01-01

    Objectives. To carry out a descriptive analysis of the expression of the EP3 receptors of PGE2 in different histological grades of OSCC and adjacent normal epithelium. Material and Methods. A total of 46 patients presenting with various histological subtypes and grades of OSCC were recruited from Maxillofacial Surgery Department of Nishtar Institute of Dentistry Multan. Microscopically tumour subtyping and histological grading according to Anneroth's grading system were carried out. Immunohistochemical staining with rabbit polyclonal EP3 receptor antibody was performed and sections were scored for intensity and proportion of positive adjacent squamous epithelial and tumour cells. Results. Out of 46 patients n = 28 (60.9%) were well differentiated, n = 15 (32.6%) were moderately differentiated, and only n = 3 (6.5%) were poorly differentiated. All n = 46 cases of OSCC were positive for EP3 receptor antibody, n = 14 (30.4%) cases had strong intensity of anti EP3 antibody staining in tumour tissue, n = 17 (37%) cases showed moderate intensity, and n = 15 (32.6%) cases showed weak intensity. Conclusion. Prostanoid EP3 receptors are widely but variably expressed in OSCC. Most of well differentiated OSCC cases show a moderate to strong expression of EP3 receptors. However, insignificant statistical relation to histological grades of OSCC has been observed. This might be due to small sample size of the study. PMID:25741449

  6. Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer

    PubMed Central

    Forsberg, Lars A.; Rasi, Chiara; Pekar, Gyula; Davies, Hanna; Piotrowski, Arkadiusz; Absher, Devin; Razzaghian, Hamid Reza; Ambicka, Aleksandra; Halaszka, Krzysztof; Przewoźnik, Marcin; Kruczak, Anna; Mandava, Geeta; Pasupulati, Saichand; Hacker, Julia; Prakash, K. Reddy; Dasari, Ravi Chandra; Lau, Joey; Penagos-Tafurt, Nelly; Olofsson, Helena M.; Hallberg, Gunilla; Skotnicki, Piotr; Mituś, Jerzy; Skokowski, Jaroslaw; Jankowski, Michal; Śrutek, Ewa; Zegarski, Wojciech; Tiensuu Janson, Eva; Ryś, Janusz; Tot, Tibor; Dumanski, Jan P.

    2015-01-01

    Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1–14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer. PMID:26430163

  7. Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer.

    PubMed

    Forsberg, Lars A; Rasi, Chiara; Pekar, Gyula; Davies, Hanna; Piotrowski, Arkadiusz; Absher, Devin; Razzaghian, Hamid Reza; Ambicka, Aleksandra; Halaszka, Krzysztof; Przewoźnik, Marcin; Kruczak, Anna; Mandava, Geeta; Pasupulati, Saichand; Hacker, Julia; Prakash, K Reddy; Dasari, Ravi Chandra; Lau, Joey; Penagos-Tafurt, Nelly; Olofsson, Helena M; Hallberg, Gunilla; Skotnicki, Piotr; Mituś, Jerzy; Skokowski, Jaroslaw; Jankowski, Michal; Śrutek, Ewa; Zegarski, Wojciech; Tiensuu Janson, Eva; Ryś, Janusz; Tot, Tibor; Dumanski, Jan P

    2015-10-01

    Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer.

  8. Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium.

    PubMed

    Madas, Balázs G

    2016-09-01

    There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

  9. Persistent disruption of ciliated epithelium following paediatric lung transplantation.

    PubMed

    Thomas, Biju; Aurora, Paul; Spencer, Helen; Elliott, Martin; Rutman, Andrew; Hirst, Robert A; O'Callaghan, Christopher

    2012-11-01

    It is unclear whether ciliary function following lung transplantation is normal or not. Our aim was to study the ciliary function and ultrastructure of epithelium above and below the airway anastomosis and the peripheral airway of children following lung transplantation. We studied the ciliary beat frequency (CBF) and beat pattern, using high speed digital video imaging and ultrastructure by transmission electron microscopy, of bronchial epithelium from above and below the airway anastomosis and the peripheral airway of 10 cystic fibrosis (CF) and 10 non-suppurative lung disease (NSLD) paediatric lung transplant recipients. Compared to epithelium below the anastomosis, the epithelium above the anastomosis in the CF group showed reduced CBF (median (interquartile range): 10.5 (9.0-11.4) Hz versus 7.4 (6.4-9.2) Hz; p<0.01) and increased dyskinesia (median (IQR): 16.5 (12.9-28.2)% versus 42.2 (32.6-56.4)%; p<0.01). In both CF and NSLD groups, compared with epithelium above the anastomosis, the epithelium below the anastomosis showed marked ultrastructural abnormalities (median duration post-transplant 7-12 months). Ciliary dysfunction is a feature of native airway epithelium in paediatric CF lung transplant recipients. The epithelium below the airway anastomosis shows profound ultrastructural abnormalities in both CF and NSLD lung transplant recipients, many months after transplantation.

  10. Immunohistochemistry of the cytoskeleton of human prostatic epithelium. Evidence for disturbed organization in neoplasia.

    PubMed Central

    Purnell, D. M.; Heatfield, B. M.; Anthony, R. L.; Trump, B. F.

    1987-01-01

    An indirect immunoperoxidase technique was used to evaluate keratin, actin, tubulin, and calmodulin immunoreactivity in histologic sections of normal, hyperplastic, and neoplastic human prostate. Polyclonal as well as monoclonal keratin antibodies produced equivalent and intense staining of normal epithelium. The immunoreactivity of normal prostate with keratin antibodies was more pronounced than with antibodies to the other components of the cytoskeleton. Variation in staining for components of the cytoskeleton was minimal. The same findings applied to hyperplastic prostate. The immunoreactivity of prostate tumors with antibodies to these cytoskeletal proteins differed markedly from normal prostate. Prostatic carcinomas showed reduced keratin immunoreactivity with a panepithelial antibody, but unaltered or enhanced immunoreactivity with tubulin, actin, and calmodulin antibodies. Many tumors were unreactive with a monoclonal keratin antibody that was strongly reactive with tissues that contained cytokeratin 18 (45-kd) and which intensely stained normal and hyperplastic prostate. In addition, prostate carcinomas often yielded heterogeneous patterns of staining with actin, tubulin, and calmodulin antibodies in contrast to normal and hyperplastic prostate, which showed uniform staining. The results suggest that a disturbance in the organization of the cytoskeleton may accompany neoplastic transformation of human prostate. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2435158

  11. Lung alveolar epithelium and interstitial lung disease.

    PubMed

    Corvol, Harriet; Flamein, Florence; Epaud, Ralph; Clement, Annick; Guillot, Loic

    2009-01-01

    Interstitial lung diseases (ILDs) comprise a group of lung disorders characterized by various levels of inflammation and fibrosis. The current understanding of the mechanisms underlying the development and progression of ILD strongly suggests a central role of the alveolar epithelium. Following injury, alveolar epithelial cells (AECs) may actively participate in the restoration of a normal alveolar architecture through a coordinated process of re-epithelialization, or in the development of fibrosis through a process known as epithelial-mesenchymal transition (EMT). Complex networks orchestrate EMT leading to changes in cell architecture and behaviour, loss of epithelial characteristics and gain of mesenchymal properties. In the lung, AECs themselves may serve as a source of fibroblasts and myofibroblasts by acquiring a mesenchymal phenotype. This review covers recent knowledge on the role of alveolar epithelium in the pathogenesis of ILD. The mechanisms underlying disease progression are discussed, with a main focus on the apoptotic pathway, the endoplasmic reticulum stress response and the developmental pathway.

  12. Keratoepithelioplasty in rat: development of a model and histological study.

    PubMed

    Amano, S; Sawa, M; Ishii, Y

    1992-01-01

    A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using this model. The entire corneal epithelium was removed mechanically and a 1.5-mm width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observations showed much less vascular invasion in the part of the cornea adjacent to the lenticule than in other parts of the cornea, and the cornea remained clear adjacent to the lenticule. Histologically, a few vessels were observed in the corneal stroma under the lenticule. Epithelial cells on the lenticule specimens showed histological characteristics of the corneal epithelium. These findings indicate that one of the functions of KEP is to block neovascularization in the newly developing corneal epithelium by transplanting the lenticule between the corneal epithelium and conjunctival vessels. The present study also confirmed that this model is useful in the research of the pathophysiological mechanism of KEP.

  13. A Rotating Bioreactor for Scalable Culture and Differentiation of Respiratory Epithelium.

    PubMed

    Raredon, Micha Sam Brickman; Ghaedi, Mahboobe; Calle, Elizabeth A; Niklason, Laura E

    2015-10-01

    Respiratory epithelium is difficult to grow in vitro, as it requires a well-maintained polarizing air-liquid interface (ALI) to maintain differentiation. Traditional methods rely on permeable membrane culture inserts, which are difficult to work with and are ill-suited for the production of large numbers of cells, such as the quantities required for cell-based clinical therapies. Herein, we investigate an alternative form of culture in which the cells are placed on a porous substrate that is continuously rolled, such that the monolayer of cells is alternately submerged in media or apically exposed to air. Our prototype bioreactor is reliable for up to 21 days of continuous culture and is designed for scale-up for large-scale cell culture with continuous medium and gas exchange. Normal human bronchial epithelial (NHBE) cells were cultured on an absorbent substrate in the reactor for periods of 7, 14, and 21 days and were compared to static controls that were submerged in media. Quantification by immunohistochemistry and quantitative PCR of markers specific to differentiated respiratory epithelium indicated increased cilia, mucous production, and tight junction formation in the rolled cultures, compared to static. Together with scanning electron microscopy and paraffin histology, the data indicate that the intermittent ALI provided by the rolling bioreactor promotes a polarized epithelial phenotype over a period of 21 days.

  14. Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

    NASA Astrophysics Data System (ADS)

    Knowles, M. R.; Stutts, M. J.; Spock, A.; Fischer, N.; Gatzy, J. T.; Boucher, R. C.

    1983-09-01

    The epithelium of nasal tissue excised from subjects with cystic fibrosis exhibited higher voltage and lower conductance than tissue from control subjects. Basal sodium ion absorption by cystic fibrosis and normal nasal epithelia equaled the short-circuit current and was amiloride-sensitive. Amiloride induced chloride ion secretion in normal but not cystic fibrosis tissue and consequently was more effective in inhibiting the short-circuit current in cystic fibrosis epithelia. Chloride ion-free solution induced a smaller hyperpolarization of cystic fibrosis tissue. The increased voltage and amiloride efficacy in cystic fibrosis reflect absorption of sodium ions across an epithelium that is relatively impermeable to chloride ions.

  15. [Effects of ischemia and revascularization on the epithelium of the small intestine: study on swine].

    PubMed

    Barthod, F

    1994-05-01

    Ischaemia of the small intestine leads to the destruction of the intestinal mucosa. The capacity of the epithelium to regenerate is proportional to the duration of revascularization. The aim of this work was to analyze the kinetic aspects of intestinal epithelial regeneration after destruction due to prolonged ischaemia. This study was conducted in 44 animals (swine) after development of an ischaemia-revascularization protocol of a jejunal loop and bipolar secondary cutaneous exteriorization. After a first series with ischaemia times of 1, 2, 3 and 4 hours, the 4 hour period of ischaemia was chosen for further analysis of the regeneration kinetics over a period of 21 days since it leads to regular and total destruction of the epithelium compatible with regeneration. This analysis included (1) a histological examination (semi-thin slices), (2) immunofluorescent detection of intestinal brush border proteins on frozen slices (villin, saccharase-isomaltase, aminopeptidase N, dipeptidylpeptidase-IV) and mucines, (3) measurement of specific intestinal hydrolase activities (saccharase, aminopeptidase N, dipeptidylpeptidase-IV and alkaline phosphatase) in enriched brush border fractions, and (4) an analysis of variations in intestinal flora. After the 4 hour ischaemia, total destruction of the epithelium with disappearance of the villin and intestinal hydrolases and disorganization of the mucosa invaded by mucosal lacks was observed. Epithelial regeneration was rapid and two days later the histological aspect of the mucosa showed apical expression (still discontinuous), villin and intestinal hydrolase activity. Luminal apical expression of the markers became continuous on day 4, demonstrating the total recovery of the intestinal barrier as confirmed by stable microbial flora. Mucine expression also returned to normal. This regeneration was however incomplete since the mucosa was seen to be flat, without villosities. Immunofluorescence showed the weak intensity of brush

  16. Scanning electron microscopic studies of the surface morphology of the vomeronasal epithelium and olfactory epithelium of garter snakes.

    PubMed

    Wang, R T; Halpern, M

    1980-04-01

    Fixed vomeronasal and olfactory epithelia from normal adult garter snakes were microdissected, fractured, and examined with a scanning electron microscope. The method permits a detailed comparative study of the structural organization and morphological characteristics of the constituent cells of the vomeronasal and olfactory epithelia. Despite similarities in the nomenclature of the constituent cells in both epithelia, significant differences exist in their surface morphology. A unique columnar structure composed of non-neuronal elements is present in the vomeronasal epithelium. These columns house the bioplar neurons and undifferentiated cells. Such a columnar organization is absent in the olfactory epithelium. In vomeronasal epithelium the bipolar neurons possess microvillous terminals at their dendritic tips, while the dendritic tips of the bipolar neurons of the olfactory epithelium possess cilia. Vomeronasal supporting cells are covered with microvilli, while olfactory supporting cells are covered with cytoplasmic protuberances in addition to the microvilli. In the vomeronasal epithelium the pear-shaped neurons have a grossly smooth surface and are organized into clusters, while in the olfactory epithelium the elliptical bipolar neurons are spinous, aligned side-by-side and interdigitate. The basal (undifferentiated) cell layer in the vomeronasal epithelium has a high packing density and is composed of several layers of irregularly shaped cells. In the olfactory epithelium the basal cell layer is loosely organized and composed of a single layer of oval cells. This information on the three-dimensional cell structure of both epithelia provides a basis for experimental observations on changes in morphology of the bipolar neurons during genesis, development, maturation, degeneration, and regeneration in postnatal, adult animals.

  17. Increased polysomy of chromosome 7 in bronchial epithelium from patients at high risk for lung cancer

    SciTech Connect

    Belinsky, S.A.; Neft, R.E.; Lechner, J.F.

    1995-12-01

    Current models of carcinogenesis suggest that tissues progress through multiple genetic and epigenetic changes which ultimately lead to development of invasive cancer. Epidemiologic studies of Peto, R.R. and J.A. Doll indicate that the accumulation of these genetic changes over time, rather than any single unique genetic change, is probably responsible for development of the malignant phenotype. The bronchial epithelium of cigarette smokers is diffusely exposed to a broad spectrum of carcinogens, toxicants, and tumor promoters contained in tobacco smoke. This exposure increases the risk of developing multiple, independent premalignant foci throughout the lower respiratory tract that may contain independent gene aberrations. This {open_quotes}field cancerization{close_quotes} theory is supported by studies that have demonstrated progressive histologic changes distributed throughout the lower respiratory tract of smokers. A series of autopsy studies demonstrated that cigarette smokers exhibit premalignant histologic changes ranging from hyperplasia and metaplasia to severe dysplasia and carcinoma in situ diffusely throughout the bronchial mucosa. The proximal bronchi appear to exhibit the greatest number of changes, particularly at bifurcations. The results described are the first to quantitate the frequency for a chromosome aberration in {open_quotes}normal{close_quotes} bronchial epithelial cells.

  18. Effluxing ABC Transporters in Human Corneal Epithelium

    PubMed Central

    Vellonen, Kati-Sisko; Mannermaa, Eliisa; Turner, Helen; Häkli, Marika; Wolosin, J. Mario; Tervo, Timo; Honkakoski, Paavo; Urtti, Arto

    2010-01-01

    ATP-binding cassette (ABC) transporters are able to efflux their substrate drugs from the cells. We compared expression of efflux proteins in normal human corneal epithelial tissue, primary human corneal epithelial cells (HCEpiC), and corneal epithelial cell culture model (HCE model) based on human immortal cell line. Expression of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1–6 (MRP1–6) and breast cancer resistance protein (BCRP) was studied using quantitative RT-PCR, Western blot, and immunohistochemistry. Only MRP1, MRP5, and BCRP were expressed in the freshly excised human corneal epithelial tissue. Expression of MRP1 and MRP5 was localized predominantly in the basal cells of the central cornea and limbus. Functional efflux activity was shown in the cell models, but they showed over-expression of most efflux transporters compared to that of normal corneal epithelium. In conclusion, MRP1, MRP5, and BCRP are expressed in the corneal epithelium, but MDR1, MRP2, MRP3, MRP4, and MRP6 are not significantly expressed. HCE cell model and commercially available primary cells deviate from this expression profile. PMID:19623615

  19. [Histological study of a model of keratoepithelioplasty in the rat].

    PubMed

    Amano, S; Sawa, M; Ishii, Y

    1992-11-01

    A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using the model. The entire corneal epithelium was removed using a spatula and a 1.5-mm-width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observation showed significantly less vascular invasion in the part of the cornea adjacent to the lenticule than in other part of cornea, and clear cornea was maintained in the cornea adjacent to the lenticule. Histologically only few vessels were recognized in the lenticule, and the epithelial cells on the lenticule showed histological characteristics of corneal epithelium. These results indicate that surgical function of KEP can be obtained because the lenticules keep distance between corneal epithelium and conjunctival vessels. And it is also confirmed that this model is useful in research on the pathophysiological mechanism of KEP.

  20. Structural changes in rabbit oral epithelium caused by zinc deficiency.

    PubMed

    Joseph, C E; Ashrafi, S H; Waterhouse, J P

    1981-01-01

    We report the successful establishment of zinc deficiency in rabbits by dietary means. The soybean protein of a standard rabbit diet was replaced by egg albumin. Weanling, New Zealand white rabbits, were fed a low zinc diet containing 1.5 microgram Zn/g of diet. Zinc-deficient rabbits showed stunted growth, weight loss, altered posture, partial alopecia and crusting of skin. Structural alterations in oral epithelium of the zinc-deficient rabbits included in the tongue flattened filiform papillae showing parakeratosis, in the cheek parakeratosis of the normally nonkeratinized epithelium and hyperplasia of the lip epidermis.

  1. Metabolic competence and susceptibility of intestinal epithelium to genotoxic injury during regeneration.

    PubMed

    Patel, H R; Hewer, A; Phillips, D H; Hayes, J D; Wolf, C R; Campbell, F C

    1997-11-01

    The carcinogenic potency of many mutagens is increased in conditions of tissue regeneration. This involves fundamental changes of cellular division and differentiation, in intestinal epithelium. However, effects on epithelial capacity for carcinogen metabolism and susceptibility to genotoxic injury are unknown. Using a novel rat model, this study assessed expression of cytochrome P450 mono-oxygenases (Cyps), glutathione S-transferases (GSTs) and uridine diphosphoglucuronosyl transferase (UGT) in intestinal epithelium during sequential stages of regeneration. Enzyme induction and DNA adduct formation were also assessed after benzo[a]pyrene (BaP) exposure. Control assays were carried out in normal intestinal epithelium. Fewer phase I and II xenobiotic metabolizing enzymes were expressed in regenerating intestinal epithelium than in normal control intestinal epithelium (GSTA3, UGT in regeneration vs Cyp2B, GSTA1/2, GSTA4, GSTP1, UGT in control). Benzo[a]pyrene induced GSTA3 and UGT in regeneration vs Cyp1A, Cyp2B, GSTA1/2, GSTA3, GSTA4, GSTP1 and UGT in control normal intestinal epithelium. Benzo[a]pyrene induced low levels of GSTA3 in early regenerating intestinal epithelium but induction increased by >2-fold at late stage regeneration. Higher levels of benzo[a]pyrene 7,8-diol-9,10-epoxide (BPDE) DNA adducts were formed at early stages of regeneration, than at later stages. Intestinal epithelium displayed reduced metabolic competence and differential susceptibility to genotoxic injury from BaP, during regeneration.

  2. Clinico-Histologic Conferences: Histology and Disease

    ERIC Educational Resources Information Center

    Shaw, Phyllis A.; Friedman, Erica S.

    2012-01-01

    Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical…

  3. Epigenetic Regulation of the Intestinal Epithelium

    PubMed Central

    Elliott, Ellen N.; Kaestner, Klaus H.

    2015-01-01

    The intestinal epithelium is an ideal model system for the study of normal and pathological differentiation processes. The mammalian intestinal epithelium is a single cell layer comprised of proliferative crypts and differentiated villi. The crypts contain both proliferating and quiescent stem cell populations that self-renew and produce all the differentiated cell types, which are replaced every 3 to 5 days. The genetics of intestinal development, homeostasis, and disease are well defined, but less is known about the contribution of epigenetics in modulating these processes. Epigenetics refers to heritable phenotypic traits, including gene expression, which are independent of mutations in the DNA sequence. We have known for several decades that human colorectal cancers contain hypomethylated DNA, but the causes and consequences of this phenomenon are not fully understood. In contrast, tumor suppressor gene promoters are often hypermethylated in colorectal cancer, resulting in decreased expression of the associated gene. In this review, we describe the role that epigenetics plays in intestinal homeostasis and disease, with an emphasis on results from mouse models. We highlight the importance of producing and analyzing next-generation sequencing data detailing the epigenome from intestinal stem cell to differentiated intestinal villus cell. PMID:26220502

  4. Neural regeneration dynamics of Xenopus laevis olfactory epithelium after zinc sulfate-induced damage.

    PubMed

    Frontera, J L; Raices, M; Cervino, A S; Pozzi, A G; Paz, D A

    2016-11-01

    Neural stem cells (NSCs) of the olfactory epithelium (OE) are responsible for tissue maintenance and the neural regeneration after severe damage of the tissue. In the normal OE, NSCs are located in the basal layer, olfactory receptor neurons (ORNs) mainly in the middle layer, and sustentacular (SUS) cells in the most apical olfactory layer. In this work, we induced severe damage of the OE through treatment with a zinc sulfate (ZnSO4) solution directly in the medium, which resulted in the loss of ORNs and SUS cells, but retention of the basal layer. During recovery following injury, the OE exhibited increased proliferation of NSCs and rapid neural regeneration. After 24h of recovery, new ORNs and SUS cells were observed. Normal morphology and olfactory function were reached after 168h (7 days) of recovery after ZnSO4 treatment. Taken together, these data support the hypothesis that NSCs in the basal layer activate after OE injury and that these are sufficient for complete neural regeneration and olfactory function restoration. Our analysis provides histological and functional insights into the dynamics between olfactory neurogenesis and the neuronal integration into the neuronal circuitry of the olfactory bulb that restores the function of the olfactory system.

  5. Increased expression of nestin in human pterygial epithelium

    PubMed Central

    Wen, Dan; Wang, Hua; Heng, Boon Chin; Liu, Hua

    2013-01-01

    AIM To investigate the distribution of nestin-positive cells in pterygium, as well as the relationship between nestin-positive cells and proliferative cells in the pathogenesis of pterygium. METHODS Nine pterygium specimens and 5 normal conjunctiva specimens were investigated. All explanted specimens were immediately immersed in 5-Ethynyl-2′-deoxyuridine, and were subjected to hematoxylin and eosin staining, as well as immunostaining to detect nestin. RESULTS Small sub-populations of nestin-expressing cells in both normal and pterygial conjunctiva epithelium were found. These were located at the superficial layer of the epithelium, and were significantly increased (P=0.007) and spread out in the pterygial conjunctiva epithelium, even though these cells were mitotically quiescent. CONCLUSION In pterygium, more nestin-positive cells were present at the superficial layer of the epithelium. With growing scientific evidence that nestin plays an important role in defining various specialized cell types, such as stem cells, cancer cells and angiogenic cells, further investigations on the roles of nestin-expressing cells in pterygium may help to uncover the mechanisms of initiation, development and the prognosis of this disease. PMID:23826515

  6. Gradual telomere shortening and increasing chromosomal instability among PanIN grades and normal ductal epithelia with and without cancer in the pancreas.

    PubMed

    Matsuda, Yoko; Ishiwata, Toshiyuki; Izumiyama-Shimomura, Naotaka; Hamayasu, Hideki; Fujiwara, Mutsunori; Tomita, Ken-Ichiro; Hiraishi, Naoki; Nakamura, Ken-Ichi; Ishikawa, Naoshi; Aida, Junko; Takubo, Kaiyo; Arai, Tomio

    2015-01-01

    A large body of evidence supports a key role for telomere dysfunction in carcinogenesis due to the induction of chromosomal instability. To study telomere shortening in precancerous pancreatic lesions, we measured telomere lengths using quantitative fluorescence in situ hybridization in the normal pancreatic duct epithelium, pancreatic intraepithelial neoplasias (PanINs), and cancers. The materials employed included surgically resected pancreatic specimens without cancer (n = 33) and with invasive ductal carcinoma (n = 36), as well as control autopsy cases (n = 150). In comparison with normal ducts, telomere length was decreased in PanIN-1, -2 and -3 and cancer. Furthermore, telomeres were shorter in cancer than in PanIN-1 and -2. Telomere length in cancer was not associated with histological type, lesion location, or cancer stage. PanINs with or without cancer showed similar telomere lengths. The incidences of atypical mitosis and anaphase bridges, which are morphological characteristics of chromosomal instability, were negatively correlated with telomere length. The telomeres in normal duct epithelium became shorter with aging, and those in PanINs or cancers were shorter than in age-matched controls, suggesting that telomere shortening occurs even when histological changes are absent. Our data strongly suggest that telomere shortening occurs in the early stages of pancreatic carcinogenesis and progresses with precancerous development. Telomere shortening and chromosomal instability in the duct epithelium might be associated with carcinogenesis of the pancreas. Determination of telomere length in pancreatic ductal lesions may be valuable for accurate detection and risk assessment of pancreatic cancer.

  7. Glucose metabolism in rat retinal pigment epithelium.

    PubMed

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2006-01-01

    The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress.

  8. Differential role of FGF9 on epithelium and mesenchyme in mouse embryonic lung.

    PubMed

    del Moral, Pierre-Marie; De Langhe, Stijn P; Sala, Frédéric G; Veltmaat, Jacqueline M; Tefft, Denise; Wang, Kasper; Warburton, David; Bellusci, Savério

    2006-05-01

    Mesothelial Fibroblast Growth Factor 9 (Fgf9) has been demonstrated by inactivation studies in mouse to be critical for the proliferation of the mesenchyme. We now show that Fgf9 is also expressed at significant levels in the distal epithelium from the mid-pseudoglandular stages. Using mesenchymal-free lung endoderm culture, we show that FGF9 triggers the proliferation of the distal epithelium leading to the formation of a cyst-like structure. On embryonic Fgfr2b-/- lungs, FGF9 induces proliferation of the mesenchyme but fails to trigger a similar effect on the epithelium, therefore involving the FGFR2b receptor in the proliferative response of the epithelium to FGF9. While FGF9 inhibits the differentiation of the mesenchyme, the epithelium appears to differentiate normally. At the molecular level, FGF9 up-regulates Fgf10 expression in the mesenchyme likely via increased expression of Tbx4 and 5 and controls the transcription of Hedgehog targets Ptc and Gli-1 in a Hedgehog-independent manner. We also show that FGF9 inhibits the activation of the canonical Wnt pathway in the epithelium by increasing Dkk1 expression, a canonical Wnt antagonist. Our work shows for the first time that FGF9 acts on the epithelium involving FGFR2b to control its proliferation but not its differentiation and contributes to the regulation of canonical Wnt signaling in the epithelium.

  9. Histologic effects of the high-energy pulsed CO2 laser on photoaged facial skin.

    PubMed

    Stuzin, J M; Baker, T J; Baker, T M; Kligman, A M

    1997-06-01

    To delineate the histologic effects of laser resurfacing at photoaged skin, a protocol was designed to biopsy laser test sites in conjunction with adjacent actinically damaged skin at the time of rhytidectomy. Five patients with photodamaged skin underwent resurfacing of the preauricular region to examine the effect of increasing pulse energy and increasing number of passes on depth of dermal penetration. Histologic examination of these specimens showed that the depth of laser injury was dose-dependent. Increasing pulse energy created a deeper wound, and increasing the number of passes similarly produced a larger band of necrosis. Ten patients with photodamaged skin underwent resurfacing of the preauricular region 15 days to 6 months prior to undergoing a rhytidectomy. A comparison of the laser-resurfaced test spot with the adjacent untreated photodamaged skin demonstrated consistent histologic changes to both epidermis and dermis in all specimens examined. Following laser resurfacing, epidermal atrophy and atypia were eliminated, and all specimens exhibited a regeneration of epithelium that was normal in its morphology. Melanocytic hypertrophy and hyperplasia were corrected following treatment, although density and function of epidermal melanocytes appeared normal. All specimens exhibited a substantial amount of neocollagen formation involving both the superficial and middermis following resurfacing. In association with new collagen development within the dermis, there was noted to be a similar degree of proliferation of elastic fibers, as well as a diminution of glycosaminoglycans, which are typically present in actinically damaged elastotic dermis. To determine the effect of laser resurfacing on-black skin, laser test spots were placed in the postauricular region of three black patients. Biopsy of these test sites showed that the histologic effects of laser resurfacing were similar to those observed in Caucasian patients, with complete repopulation of epidermal

  10. Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics.

    PubMed

    Sunil, Vasanthi R; Vayas, Kinal N; Massa, Christopher B; Gow, Andrew J; Laskin, Jeffrey D; Laskin, Debra L

    2013-06-01

    In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.

  11. Stages and duration of the cycle of the seminiferous epithelium in oncilla (Leopardus tigrinus, Schreber, 1775).

    PubMed

    Balarini, Maytê Koch; de Paula, Tarcízio Antônio Rego; da Matta, S L Pinto; Peixoto, J Vogas; Guião-Leite, F Lima; Rossi Júnior, J L; Czermak Junior, A C; Walker, N J

    2012-03-15

    Six adult Leopardus tigrinus (oncilla) were studied to characterize stages of the seminiferous epithelium cycle and its relative frequency and duration, as well as morphometric parameters of the testes. Testicular fragments were obtained (incisional biopsy), embedded (glycol methacrylate), and histologic sections examined with light microscopy. The cycle of the seminiferous epithelium was categorized into eight stages (based on the tubular morphology method). The duration of one seminiferous epithelium cycle was 9.19 d, and approximately 41.37 d were required for development of sperm from spermatogonia. On average, diameter of the seminiferous tubules was 228.29 μm, epithelium height was 78.86 μm, and there were 16.99 m of testicular tubules per gram of testis. Body weight averaged 2.589 kg, of which 0.06 and 0.04% were attributed to the testis and seminiferous tubules, respectively. In conclusion, there were eight distinct stages in the seminiferous epithelium, the length of the seminiferous epithelium cycle was close to that in domestic cats and cougars, and testicular and somatic indexes were similar to those of other carnivores of similar size.

  12. Identification of mammary epithelial cells subject to chronic oxidative stress in mammary epithelium of young women and teenagers living in USA: implication for breast carcinogenesis.

    PubMed

    Weisz, Judith; Shearer, Debra A; Murata, Erin; Patrick, Susan D; Han, Bing; Berg, Arthur; Clawson, Gary A

    2012-01-15

    Current knowledge of changes in the mammary epithelium relevant to breast carcinogenesis is limited to when histological changes are already present because of a lack of biomarkers needed to identify where such molecular changes might be ongoing at earlier during the of decades-long latent stages of breast carcinogenesis. Breast reduction tissues from young women and teenagers, representative of USA's high breast cancer incidence population, were studies using immunocytochemistry and targeted PCR arrays in order to learn whether a marker of chronic oxidative-stress [protein adducts of 4-hydroxy-2-nonenal (4HNE)] can identify where molecular changes relevant to carcinogenesis might be taking place prior to any histological changes. 4HNE-immunopositive (4HNE+) mammary epithelial cell-clusters were identified in breast tissue sections from most women and from many teenagers (ages 14-30 y) and, in tissues from women ages 17-27 y with many vs. few 4HNE+ cells, the expression of 30 of 84 oxidative-stress associated genes was decreased and only one was increased > 2-fold. This is in contrast to increased expression of many of these genes known to be elicited by acute oxidative-stress. The findings validate using 4HNE-adducts to identify where molecular changes of potential relevance to carcinogenesis are taking place in histologically normal mammary epithelium and highlight differences between responses to acute vs. chronic oxidative-stress. We posit that the altered gene expression in 4HNE+ tissues reflect adaptive responses to chronic oxidative-stress that enable some cells to evade mechanisms that have evolved to prevent propagation of cells with oxidatively-damaged DNA and to accrue heritable changes needed to establish a cancer.

  13. Quantitative Diagnosis of Tongue Cancer from Histological Images in an Animal Model

    PubMed Central

    Lu, Guolan; Qin, Xulei; Wang, Dongsheng; Muller, Susan; Zhang, Hongzheng; Chen, Amy; Chen, Zhuo Georgia; Fei, Baowei

    2016-01-01

    We developed a chemically-induced oral cancer animal model and a computer aided method for tongue cancer diagnosis. The animal model allows us to monitor the progress of the lesions over time. Tongue tissue dissected from mice was sent for histological processing. Representative areas of hematoxylin and eosin (H&E) stained tissue from tongue sections were captured for classifying tumor and non-tumor tissue. The image set used in this paper consisted of 214 color images (114 tumor and 100 normal tissue samples). A total of 738 color, texture, morphometry and topology features were extracted from the histological images. The combination of image features from epithelium tissue and its constituent nuclei and cytoplasm has been demonstrated to improve the classification results. With ten iteration nested cross validation, the method achieved an average sensitivity of 96.5% and a specificity of 99% for tongue cancer detection. The next step of this research is to apply this approach to human tissue for computer aided diagnosis of tongue cancer. PMID:27656036

  14. Quantitative diagnosis of tongue cancer from histological images in an animal model

    NASA Astrophysics Data System (ADS)

    Lu, Guolan; Qin, Xulei; Wang, Dongsheng; Muller, Susan; Zhang, Hongzheng; Chen, Amy; Chen, Zhuo G.; Fei, Baowei

    2016-03-01

    We developed a chemically-induced oral cancer animal model and a computer aided method for tongue cancer diagnosis. The animal model allows us to monitor the progress of the lesions over time. Tongue tissue dissected from mice was sent for histological processing. Representative areas of hematoxylin and eosin stained tissue from tongue sections were captured for classifying tumor and non-tumor tissue. The image set used in this paper consisted of 214 color images (114 tumor and 100 normal tissue samples). A total of 738 color, texture, morphometry and topology features were extracted from the histological images. The combination of image features from epithelium tissue and its constituent nuclei and cytoplasm has been demonstrated to improve the classification results. With ten iteration nested cross validation, the method achieved an average sensitivity of 96.5% and a specificity of 99% for tongue cancer detection. The next step of this research is to apply this approach to human tissue for computer aided diagnosis of tongue cancer.

  15. Salaries in histology.

    PubMed

    Buesa, René J

    2008-04-01

    An analysis of histology salaries from the last 4 national surveys conducted by the American Society of Clinical Pathologists is presented. The regional variations within and between years for histology salaries presented in the last 4 national surveys of medical laboratory specialties are not statistically significant. Local variations greater than the national variations reflect the preponderant effect of local supply and demand over regional characteristics. Salaries by hospitals are significantly different only between 2 size categories and the supervisors' salary. There is no correlation between the salary increase for any histology position in any one year and the vacancy level in the previous year. On the other hand, the correlation between histotechnicians' salaries and both the cost of living and the median income are significant, as well as between the latter and the supervisors' salary. The histotechnologists' salaries are significantly correlated with the consumer price index but not with the inflation rate. A survey of histology salaries in foreign countries was also undertaken and compared with salaries in the United States. National salaries rank close to the general average for 10 foreign countries when expressed as ratios with the personal gross domestic product or with the countries' minimum wage. For the midpoint salary ranges, the United States ranks fourth after Canada, the United Kingdom, and Australia, the latter 3 countries with structured pay rates adjusted to local costs of living in contrast with United States' salary characteristics. Histology salaries rest on negotiations within each employer's salary structure and fluctuate according to license level, documented studies, special training(s), years of experience, references, and the ability to negotiate, where each side tries to take advantage of the other. The result is a heterogeneous and chaotic salary situation driven by personal and local needs, where the histology worker usually

  16. Applying photoacoustics to quantification of melanin concentration in retinal pigment epithelium (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Shu, Xiao; Zhang, Hao F.; Liu, Wenzhong

    2016-03-01

    The melanin in the retinal pigment epithelium (RPE) protects retina and other ocular tissues by photo-screening and acting as antioxidant and free radical scavenger. It helps maintain normal visual functions since human eye is subjected to lifelong high oxygen stress and photon exposure. Loss of the RPE melanin weakens the protection mechanism and jeopardizes ocular health. Local decrease in the RPE melanin concentration is believed to be both a cause and a sign of early-stage age-related macular degeneration (AMD), the leading blinding disease in developed world. Current technology cannot quantitatively measure the RPE melanin concentration which might be a promising marker in early AMD screening. Photoacoustic ophthalmoscopy (PAOM), as an emerging optical absorption-based imaging technology, can potentially be applied to measure the RPE melanin concentration if the dependence of the detectable photoacoustic (PA) signal amplitudes on the RPE melanin concentrations is verified. In this study, we tested the feasibility of using PA signal ratio from RPE melanin and the nearby retinal blood vessels as an indicator of the RPE melanin variation. A novel whole eye optical model was designed and Monte Carlo modeling of light (MCML) was employed. We examined the influences on quantification from PAOM axial resolution, the depth and diameter of the retinal blood vessel, and the RPE thickness. The results show that the scheme is robust to individual histological and illumination variations. This study suggests that PAOM is capable of quantitatively measuring the RPE melanin concentration in vivo.

  17. Gastritis: the histology report.

    PubMed

    Rugge, Massimo; Pennelli, Gianmaria; Pilozzi, Emanuela; Fassan, Matteo; Ingravallo, Giuseppe; Russo, Valentina M; Di Mario, Francesco

    2011-03-01

    Gastritis is defined as inflammation of the gastric mucosa. In histological terms, it is distinguishable into two main categories, i.e. non-atrophic and atrophic. In the gastric mucosa, atrophy is defined as the loss of appropriate glands. There are several etiological types of gastritis, their different etiology being related to different clinical manifestations and pathological features. Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for the onset of (intestinal type) gastric cancer. The extent and site of the atrophic changes correlate significantly with the cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. Building on current knowledge of the biology of gastritis, an international group of pathologists [Operative Link for Gastritis Assessment (OLGA)] has proposed a system for reporting gastritis in terms of its stage (the OLGA Staging System): this system places the histological phenotypes of gastritis on a scale of progressively increasing gastric cancer risk, from the lowest (Stage 0) to the highest (Stage IV). The aim of this tutorial is to provide unequivocal information on how to standardize histology reports on gastritis in diagnostic practice.

  18. Histologic classification of gliomas.

    PubMed

    Perry, Arie; Wesseling, Pieter

    2016-01-01

    Gliomas form a heterogeneous group of tumors of the central nervous system (CNS) and are traditionally classified based on histologic type and malignancy grade. Most gliomas, the diffuse gliomas, show extensive infiltration in the CNS parenchyma. Diffuse gliomas can be further typed as astrocytic, oligodendroglial, or rare mixed oligodendroglial-astrocytic of World Health Organization (WHO) grade II (low grade), III (anaplastic), or IV (glioblastoma). Other gliomas generally have a more circumscribed growth pattern, with pilocytic astrocytomas (WHO grade I) and ependymal tumors (WHO grade I, II, or III) as the most frequent representatives. This chapter provides an overview of the histology of all glial neoplasms listed in the WHO 2016 classification, including the less frequent "nondiffuse" gliomas and mixed neuronal-glial tumors. For multiple decades the histologic diagnosis of these tumors formed a useful basis for assessment of prognosis and therapeutic management. However, it is now fully clear that information on the molecular underpinnings often allows for a more robust classification of (glial) neoplasms. Indeed, in the WHO 2016 classification, histologic and molecular findings are integrated in the definition of several gliomas. As such, this chapter and Chapter 6 are highly interrelated and neither should be considered in isolation.

  19. Microscopic esophagitis and Barrett's esophagus: the histology report.

    PubMed

    Fiocca, Roberto; Mastracci, Luca; Milione, Massimo; Parente, Paola; Savarino, Vincenzo

    2011-03-01

    Gastro-esophageal reflux disease (GERD) is the most common digestive disease in industrialized countries (Europe and North America) and is associated with microscopic changes in the squamous epithelium. However, biopsy is not presently included in the routine diagnostic flow chart of GERD. In contrast, esophageal biopsy is mandatory when diagnosing Barrett's esophagus. High quality histology reports are necessary to provide information on diagnosis and can also be important for research and epidemiological studies. It has been evident for decades that pathology reports vary between institutions and even within a single institution. Standardization of reporting is the best way to ensure that information necessary for patient management is included in pathology reports. This paper details the histological criteria for diagnosing GERD-associated microscopic esophagitis, other forms of esophagitis with specific features and columnar metaplasia in the lower esophagus (Barrett's esophagus). It provides a detailed description of appropriate sampling criteria, individual lesions and how they contribute to the histology report.

  20. Responses of the Rat Olfactory Epithelium to Retronasal Air Flow

    PubMed Central

    Scott, John W.; Acevedo, Humberto P.; Sherrill, Lisa; Phan, Maggie

    2008-01-01

    Responses of the rat olfactory epithelium were assessed with the electroolfactogram while odorants were presented to the external nares with an artificial sniff or to the internal nares by positive pressure. A series of seven odorants that varied from very polar, hydrophilic odorants to very non-polar, hydrophobic odorants were used. While the polar odorants activated the dorsal olfactory epithelium when presented by the external nares (orthonasal presentation), they were not effective when forced through the nasal cavity from the internal nares (retronasal presentation). However, the non-polar odorants were effective in both stimulus modes. These results were independent of stimulus concentration or of humidity of the carrier air. Similar results were obtained with multiunit recording from olfactory bulb. These results help to explain why human investigations often report differences in the sensation or ability to discriminate odorants presented orthonasally vs. retronasally. The results also strongly support the importance of odorant sorption in normal olfactory processes. PMID:17215498

  1. Biochemical studies of the tracheobronchial epithelium

    SciTech Connect

    Mass, M.J.; Kaufman, D.G.

    1984-06-01

    Tracheobronchial epithelium has been a focus of intense investigation in the field of chemical carcinogenesis. We have reviewed some biochemical investigations that have evolved through linkage with carcinogenesis research. These areas of investigation have included kinetics of carcinogen metabolism, identification of carcinogen metabolites, levels of carcinogen binding to DNA, and analysis of carcinogen-DNA adducts. Such studies appear to have provided a reasonable explanation for the susceptibilities of the respiratory tracts of rats and hamsters to carcinogenesis by benzo(a)pyrene. Coinciding with the attempts to understand the initiation of carcinogenesis in the respiratory tract has also been a major thrust aimed at effecting its prevention both in humans and in animal models for human bronchogenic carcinoma. These studies have concerned the effects of derivatives of vitamin A (retinoids) and their influence on normal cell biology and biochemistry of this tissue. Recent investigations have included the effects of retinoid deficiency on the synthesis of RNA and the identification of RNA species associated with this biological state, and also have included the effects of retinoids on the synthesis of mucus-related glycoproteins. Tracheal organ cultures from retinoid-deficient hamsters have been used successfully to indicate the potency of synthetic retinoids by monitoring the reversal of squamous metaplasia. Techniques applied to this tissue have also served to elucidate features of the metabolism of retinoic acid using high pressure liquid chromatography. 94 references, 9 figures, 2 tables.

  2. STUDIES ON SMALL INTESTINAL CRYPT EPITHELIUM

    PubMed Central

    Trier, Jerry S.

    1963-01-01

    Small intestinal crypt epithelium obtained from normal fasting humans by peroral biopsy of the mucosa was studied with the electron microscope. Paneth cells were identified at the base of the crypts by their elaborate highly organized endoplasmic reticulum, large secretory granules, and small lysosome-like dense bodies within the cytoplasm. Undifferentiated cells were characterized by smaller cytoplasmic membrane-bounded granules which were presumed to be secretory in nature, a less elaborate endoplasmic reticulum, many unattached ribosomes and, in some cells, the presence of glycogen. Some undifferentiated cells at the base of the crypts contained lobulated nuclei and striking paranuclear accumulations of mitochondria. Membrane-bounded cytoplasmic fragments, probably originating from undifferentiated and Paneth cells, were frequently apparent within crypt lumina. Of the goblet cells, some were seen actively secreting mucus. In these, apical mucus appeared to exude into the crypt lumen between gaps in the microvilli. The membrane formerly surrounding the apical mucus appeared to fuse with and become part of the plasma membrane of the cell, suggesting a merocrine secretory mechanism. Enterochromaffin cells were identified by their location between the basal regions of other crypt cells and by their unique intracytoplasmic granules. PMID:14064112

  3. Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations

    PubMed Central

    Morita, Ritsuko; Kihira, Miho; Nakatsu, Yousuke; Nomoto, Yohei; Ogawa, Miho; Ohashi, Kazumasa; Mizuno, Kensaku; Tachikawa, Tetsuhiko; Ishimoto, Yukitaka; Morishita, Yoshihiro; Tsuji, Takashi

    2016-01-01

    The morphologies of ectodermal organs are shaped by appropriate combinations of several deformation modes, such as invagination and anisotropic tissue elongation. However, how multicellular dynamics are coordinated during deformation processes remains to be elucidated. Here, we developed a four-dimensional (4D) analysis system for tracking cell movement and division at a single-cell resolution in developing tooth epithelium. The expression patterns of a Fucci probe clarified the region- and stage-specific cell cycle patterns within the tooth germ, which were in good agreement with the pattern of the volume growth rate estimated from tissue-level deformation analysis. Cellular motility was higher in the regions with higher growth rates, while the mitotic orientation was significantly biased along the direction of tissue elongation in the epithelium. Further, these spatio-temporal patterns of cellular dynamics and tissue-level deformation were highly correlated with that of the activity of cofilin, which is an actin depolymerization factor, suggesting that the coordination of cellular dynamics via actin remodeling plays an important role in tooth epithelial morphogenesis. Our system enhances the understanding of how cellular behaviors are coordinated during ectodermal organogenesis, which cannot be observed from histological analyses. PMID:27588418

  4. Activin Potentiates Proliferation in Mature Avian Auditory Sensory Epithelium

    PubMed Central

    McCullar, Jennifer S.; Ty, Sidya; Campbell, Sean; Oesterle, Elizabeth C.

    2010-01-01

    Humans and other mammals are highly susceptible to permanent hearing and balance deficits due to an inability to regenerate sensory hair cells lost to inner ear trauma. In contrast, nonmammalian vertebrates, such as birds, robustly regenerate replacement hair cells and restore hearing and balance functions to near-normal levels. There is considerable interest in understanding the cellular mechanisms responsible for this difference in regenerative capacity. Here we report on involvement of the TGFβ superfamily type II activin receptors, Acvr2a and Acvr2b, in regulating proliferation in mature avian auditory sensory epithelium. Cultured, posthatch avian auditory sensory epithelium treated with Acvr2a and Acvr2b inhibitors shows decreased proliferation of support cells, the cell type that gives rise to new hair cells. Conversely, addition of activin A, an Acvr2a/b ligand, potentiates support cell proliferation. Neither treatment (inhibitor or ligand) affected hair cell survival, suggesting a specific effect of Acvr2a/b signaling on support cell mitogenicity. Using immunocytochemistry, Acvr2a, Acvr2b, and downstream Smad effector proteins were differentially localized in avian and mammalian auditory sensory epithelia. Collectively, these data suggest that signaling through Acvr2a/b promotes support cell proliferation in mature avian auditory sensory epithelium and that this signaling pathway may be incomplete, or actively blocked, in the adult mammalian ear. PMID:20071511

  5. Empirical comparison of color normalization methods for epithelial-stromal classification in H and E images

    PubMed Central

    Sethi, Amit; Sha, Lingdao; Vahadane, Abhishek Ramnath; Deaton, Ryan J.; Kumar, Neeraj; Macias, Virgilia; Gann, Peter H.

    2016-01-01

    Context: Color normalization techniques for histology have not been empirically tested for their utility for computational pathology pipelines. Aims: We compared two contemporary techniques for achieving a common intermediate goal – epithelial-stromal classification. Settings and Design: Expert-annotated regions of epithelium and stroma were treated as ground truth for comparing classifiers on original and color-normalized images. Materials and Methods: Epithelial and stromal regions were annotated on thirty diverse-appearing H and E stained prostate cancer tissue microarray cores. Corresponding sets of thirty images each were generated using the two color normalization techniques. Color metrics were compared for original and color-normalized images. Separate epithelial-stromal classifiers were trained and compared on test images. Main analyses were conducted using a multiresolution segmentation (MRS) approach; comparative analyses using two other classification approaches (convolutional neural network [CNN], Wndchrm) were also performed. Statistical Analysis: For the main MRS method, which relied on classification of super-pixels, the number of variables used was reduced using backward elimination without compromising accuracy, and test - area under the curves (AUCs) were compared for original and normalized images. For CNN and Wndchrm, pixel classification test-AUCs were compared. Results: Khan method reduced color saturation while Vahadane reduced hue variance. Super-pixel-level test-AUC for MRS was 0.010–0.025 (95% confidence interval limits ± 0.004) higher for the two normalized image sets compared to the original in the 10–80 variable range. Improvement in pixel classification accuracy was also observed for CNN and Wndchrm for color-normalized images. Conclusions: Color normalization can give a small incremental benefit when a super-pixel-based classification method is used with features that perform implicit color normalization while the gain is

  6. The stem-cell profile of ovarian surface epithelium is reproduced in the oviductal fimbriae, with increased stem-cell marker density in distal parts of the fimbriae.

    PubMed

    Auersperg, Nelly

    2013-09-01

    High-grade serous ovarian carcinomas are the most common and most lethal ovarian cancers, but their histologic origin is still controversial. Current evidence suggests that they may originate in the ovarian surface epithelium (OSE) and/or epithelium of oviductal fimbriae (FE). To further investigate this question we compared the stem-cell profiles of these epithelia. Formalin-fixed sections of normal FE (N=21) and ovaries (N=21) were stained immunohistochemically for the stem-cell markers NANOG, SFRP1, LHX9, ALDH1A1, and ALDH1A2. All markers were detected in both OSE and FE. A total of 75% to 100% of surface OSE expressed all markers except ALDH1A1, which occurred in about 25% of cells. Among epithelial inclusion cysts with flat-to-cuboidal epithelium, resembling OSE, ALDH1A1 was significantly increased, whereas SFRP1 was reduced compared with surface OSE, suggesting an increased trend towards malignant transformation. Similarly, among cysts lined by columnar cells resembling FE, SFRP1 expression was low, whereas ALDH1A1 approached 100% of the cysts. FE exhibited considerable variation between and within specimens. In about half of the samples, SFRP1 and NANOG were detected in ≤25% FE. The most widespread markers were ALDH1A1 and ALDH1A2. The highest proportion of all markers occurred in the distal parts of the FE, the site of the putative ovarian cancer precursors. Marker expression in tubal ampullae was low or absent except for ALDH1A1 and ALDH1A2. The results provide an explanation for the characteristic distal location of fimbrial high-grade serous ovarian carcinoma precursor lesions, and indicate that both OSE and FE have the capacity to undergo neoplastic transformation.

  7. The junctional epithelium originates from the odontogenic epithelium of an erupted tooth.

    PubMed

    Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

    2014-05-02

    The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

  8. Mercuric chloride induced toxicity responses in the olfactory epithelium of Labeo rohita (Hamilton): a light and electron microscopy study.

    PubMed

    Ghosh, Debasree; Mandal, Dipak Kumar

    2014-02-01

    Bioaccumulation of mercury and histomorphological changes in the olfactory epithelium of Labeo rohita were investigated after exposing the fish to two sublethal concentrations of HgCl₂ (66 and 132 μg/L) for 15 and 30 days. Mercury deposition increased in the tissue significantly (p < 0.05) with dose- and duration-dependent manner. Severe damage to the olfactory epithelium was evident. When fish exposed to 66 μg/L for 15 days, the histology of olfactory epithelium exhibited that mucous cell proliferation was upregulated and cell size was significantly increased from the control. Similar trends were found in 30 days exposure in both treated groups. Histology showed that mercury induced degeneration of columnar sensory cells, supporting cells and ciliated non-sensory cells and induced basal cell proliferation. Basal cell hyperplasia led to form intraepithelial proliferative lesion, thickening of epithelium, basal lamina disruption and cyst formation. Scanning electron microscopy revealed that mercury exposure at 66 μg/L caused clumping and loss of cilia, erosion in microridges on the supporting cells and proliferation of mucous cell opening. Complete degeneration of ciliated cells and cyst formation was observed in the fish when exposed to 132 μg/L HgCl₂. This result suggests that prolonged exposure to mercury might cause irreversible damage to the olfactory epithelium and impair the olfactory function of fish.

  9. Comparative cytokeratin distribution patterns in cholesteatoma epithelium.

    PubMed

    Olszewska, E; Sudhoff, H

    2007-01-01

    Cytokeratins (CKs) are known as the intermediate filament proteins of epithelial origin. Their distribution in human epithelia is different according to the type of epithelium, state of growth and differentiation. We used monoclonal mouse antibodies against cytokeratins to study CK expression in the following human tissues: cholesteatoma, middle ear mucosa, glandular epithelium, and meatal ear canal epithelium. Immunohistochemical processing was performed using the labeled steptavidin peroxidase method to demonstrate the presence of CKs in cells of human epidermis. Positive reaction was obtained for CK4, CK34betaE12, CK10, CK14 in skin and cholesteatoma epithelium. However, a more extensive positive reaction with those CKs was observed in cholesteatoma epithelium. Positive immunoreactivity was seen with anti- CK19 in the glandular epithelium. Middle ear mucosa specimens revealed positive immunoreactivity with the antibodies against CK4. The expression of CK4 was definitely positive within the basal layers of the epidermis. The glandular epithelium showed no positive reaction with anti- CK4, anti- CK34betaE12, anti- CK14 and anti-CK10. Immunohistochemistry for CK18 showed no reaction in all examined tissues. Cholesteatoma is known as a proliferative disease in the middle ear which pathogenesis is not completely understood. Keratinocytes express hyperproliferation- associated CKs and after reaching the suprabasal layers they finally undergo apoptosis creating keratinous debris. Cytokeratin expression observed in the epithelium explains proliferative behavior of cholesteatoma which is associated with increased keratinocyte migration. Cytokeratins can be used as potential proliferative markers. It can also allow for searching the usefulness of inhibiting regulators in the treatment of hyperproliferative diseases.

  10. Pigmented ameloblastic fibro-odontoma: clinical, histological, and immunohistochemical profile.

    PubMed

    Martínez Martínez, Marisol; Romero, Celeste Sánchez; Piña, Alicia Rumayor; Palma Guzmán, José Mario; de Almeida, Oslei Paes

    2015-02-01

    Ameloblastic fibro-odontoma (AFO) is a slow-growing, expansive, benign odontogenic tumor, composed of ameloblastic epithelium embedded in an ectomesenchymal stroma resembling dental papilla, containing hard dental tissue in variable degrees of maturation, including enamel, dentin, and sometimes cementum. AFO typically affects the posterior mandible, causing bony expansion. We report a case of pigmented AFO in a 5-year-old boy, comprising clinical and histological features illustrated by immunohistochemistry using a large panel of antibodies, polarized light microscopy and scanning electron microscopy.

  11. Osmotic regulation of airway reactivity by epithelium.

    PubMed

    Fedan, J S; Yuan, L X; Chang, V C; Viola, J O; Cutler, D; Pettit, L L

    1999-05-01

    Inhalation of nonisotonic solutions can elicit pulmonary obstruction in asthmatic airways. We evaluated the hypothesis that the respiratory epithelium is involved in responses of the airways to nonisotonic solutions using the guinea pig isolated, perfused trachea preparation to restrict applied agents to the mucosal (intraluminal) or serosal (extraluminal) surface of the airway. In methacholine-contracted tracheae, intraluminally applied NaCl or KCl equipotently caused relaxation that was unaffected by the cyclo-oxygenase inhibitor, indomethacin, but was attenuated by removal of the epithelium and Na+ and Cl- channel blockers. Na+-K+-2Cl- cotransporter and nitric oxide synthase blockers caused a slight inhibition of relaxation, whereas Na+,K+-pump inhibition produced a small potentiation. Intraluminal hyperosmolar KCl and NaCl inhibited contractions in response to intra- or extraluminally applied methacholine, as well as neurogenic cholinergic contractions elicited with electric field stimulation (+/- indomethacin). Extraluminally applied NaCl and KCl elicited epithelium-dependent relaxation (which for KCl was followed by contraction). In contrast to the effects of hyperosmolarity, intraluminal hypo-osmolarity caused papaverine-inhibitable contractions (+/- epithelium). These findings suggest that the epithelium is an osmotic sensor which, through the release of epithelium-derived relaxing factor, can regulate airway diameter by modulating smooth muscle responsiveness and excitatory neurotransmission.

  12. Validation of histology image registration

    NASA Astrophysics Data System (ADS)

    Shojaii, Rushin; Karavardanyan, Tigran; Yaffe, Martin; Martel, Anne L.

    2011-03-01

    The aim of this paper is to validate an image registration pipeline used for histology image alignment. In this work a set of histology images are registered to their correspondent optical blockface images to make a histology volume. Then multi-modality fiducial markers are used to validate the alignment of histology images. The fiducial markers are catheters perfused with a mixture of cuttlefish ink and flour. Based on our previous investigations this fiducial marker is visible in medical images, optical blockface images and it can also be localized in histology images. The properties of this fiducial marker make it suitable for validation of the registration techniques used for histology image alignment. This paper reports on the accuracy of a histology image registration approach by calculation of target registration error using these fiducial markers.

  13. Intestinal epithelium is more susceptible to cytopathic injury and altered permeability than the lung epithelium in the context of acute sepsis.

    PubMed

    Julian, Mark W; Bao, Shengying; Knoell, Daren L; Fahy, Ruairi J; Shao, Guohong; Crouser, Elliott D

    2011-10-01

    Mitochondrial morphology and function are altered in intestinal epithelia during endotoxemia. However, it is unclear whether mitochondrial abnormalities occur in lung epithelial cells during acute sepsis or whether mitochondrial dysfunction corresponds with altered epithelial barrier function. Thus, we hypothesized that the intestinal epithelium is more susceptible to mitochondrial injury than the lung epithelium during acute sepsis and that mitochondrial dysfunction precedes impaired barrier function. Using a resuscitated feline model of Escherichia coli-induced sepsis, lung and ileal tissues were harvested after 6 h for histological and mitochondrial ultrastructural analyses in septic (n = 6) and time-matched controls (n = 6). Human lung epithelial cells (HLEC) and Caco-2 monolayers (n = 5) were exposed to 'cytomix' (TNFα: 40 ng/ml, IL-1β: 20 ng/ml, IFNγ: 10 ng/ml) for 24-72 h, and measurements of transepithelial electrical resistance (TER), epithelial permeability and mitochondrial membrane potential (ΔΨ) were taken. Lung epithelial morphology, mitochondrial ultrastructure and pulmonary gas exchange were unaltered in septic animals compared to matching controls. While histologically intact, ileal epithelia demonstrated marked mitochondrial ultrastructural damage during sepsis. Caco-2 monolayers treated with cytomix showed a significant decrease in mitochondrial ΔΨ within 24 h, which was associated with a progressive reduction in TER and increased epithelial permeability over the subsequent 48 h. In contrast, mitochondrial ΔΨ and epithelial barrier functions were preserved in HLEC following cytomix. These findings indicate that intestinal epithelium is more susceptible to mitochondrial damage and dysfunction than the lung epithelium in the context of sepsis. Early alterations in mitochondrial function portend subsequent epithelial barrier dysfunction.

  14. The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium.

    PubMed

    Grego-Bessa, Joaquim; Bloomekatz, Joshua; Castel, Pau; Omelchenko, Tatiana; Baselga, José; Anderson, Kathryn V

    2016-01-26

    Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical-basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis.

  15. Histology without xylene.

    PubMed

    Buesa, René J; Peshkov, Maxim V

    2009-08-01

    After the hazardous effects of xylene became indisputable in the 1970s, many potential substitutes became available, some with as many if not more hazards. This article discusses the inadequacy of 5 vegetable oils as substitutes, as well as the characteristics of 22 D-limonene-based substitutes, all less effective in their chemical role, some capable of inducing health problems, and costing more than twice as much as xylene. Some of the 35 alkane-based substitutes discussed are effective for tissue processing, less toxic, with a cost about the same as xylene, but are not very effective for dewaxing and other staining tasks. Isopropanol (2-propanol) alone or mixed with molten paraffin is a technically acceptable and cost-effective substitute for xylene for tissue processing, but in this study, we demonstrate that the best clearing agents from the sectioning quality and diagnostic value point of view, with automated or manual protocols, are mixtures of 5:1 and 2:1 isopropanol and mineral oil, followed by undiluted mineral oil, all at 50 degrees C, making them a safer and cheaper substitute than xylene. Using a 1.7% dishwasher soap aqueous solution at 90 degrees C to dewax before staining and oven drying the stained sections before coverslipping will eliminate xylene from the staining tasks. Tissue processors retorts and conduits can be dewaxed with a 2% solution of a strong glassware laboratory detergent. These 4 methodologies will make the histology laboratory xylene-free but, due to the natural resistance to change, many histotechs will be reluctant to adopt them if they think that their technical expertise could be jeopardized, and the only way these changes will succeed is if the pathologists, as stewards of the histology laboratory, commit to their implementation.

  16. Multilayered epithelium at the gastroesophageal junction is a marker of gastroesophageal reflux disease: data from a prospective Central European multicenter study (histoGERD trial).

    PubMed

    Langner, Cord; Wolf, Eva-Maria; Plieschnegger, Wolfgang; Geppert, Michael; Wigginghaus, Bernd; Höss, Gabriele M; Eherer, Andreas; Schneider, Nora I; Rehak, Peter; Vieth, Michael

    2014-04-01

    Multilayered epithelium is defined as hybrid epithelium with characteristics of both squamous and columnar epithelia. Our aim was to evaluate the clinicopathological significance of the lesion by relating its presence to various histological and clinical and/or endoscopic features indicating gastroesophageal reflux disease (GERD). A total of 1,071 individuals participated in a prospective cross-sectional study (576 females and 495 males; median age 53 years). Biopsy material was systematically sampled from the gastroesophageal junction. The histological diagnosis of esophagitis was made according to the Esohisto consensus guidelines. The endoscopic diagnosis of esophagitis was made according to the modified Los Angeles classification and the diagnosis of Barrett's esophagus according to Prague's C & M criteria, respectively. Multilayered epithelium was identified in 103 (9.6 %) individuals, frequently within or adjacent to the ducts of esophageal glands. Its presence was associated with increasing age (p < 0.001), high BMI (p = 0.026), hiatal hernia (p < 0.001), and the endoscopic diagnoses of esophagitis (p = 0.002) and Barrett's esophagus (p < 0.001). Upon histology, multilayered epithelium was associated with features of the squamous epithelium indicating GERD, particularly intercellular space dilation (p = 0.005), and presence of cardiac mucosa (<0.001). For intestinal metaplasia, a trend was noted (p = 0.094). In conclusion, multilayered epithelium was observed in about every tenth individual undergoing upper gastrointestinal endoscopy. The association with histological and clinical features indicating GERD advocates the lesion as a promising new marker for reflux esophagitis. The association with cardiac mucosa and Barrett's esophagus suggests multilayered epithelium to be an intermediate step in the development of columnar metaplasia and, ultimately, Barrett's esophagus.

  17. Morphologic changes in basal cells during repair of tracheal epithelium.

    PubMed Central

    Wang, C. Z.; Evans, M. J.; Cox, R. A.; Burke, A. S.; Zhu, Q.; Herndon, D. N.; Barrow, R. E.

    1992-01-01

    Basal cells are differentiated with respect to junctional adhesion mechanisms and play a role in attachment of columnar epithelium to the basal lamina. Although much is known about nonciliated and ciliated cell differentiation during the repair process after injury, little is known about the basal cell. We studied the morphology of basal cells and quantitated junctional adhesion structures during repair of tracheal epithelium exposed to toxic cotton smoke. Ten adult ewes were given a smoke injury to a portion of the upper cervical trachea and were killed at 4, 6, 8, 10, and 18 days after injury for morphometric studies. At 4 days, there was a stratified reparative epithelium over the basal lamina, which was two to four cells in depth. The basal cells were identified by their hemidesmosome (HD) attachment to the basal lamina. Basal cells were about 69% larger than controls and flattened rather than columnar. The amount of HD attachment was 192% greater than controls. In contrast, volume density of cytokeratin filaments had decreased about 47%. Basal cells had returned to normal numbers and size and a columnar shape by day 18. The amount of desmosome (D) and HD attachment and volume density of cytokeratins had also reached control levels by day 18. These data indicate that morphology of basal cells changes during the initial stages of reparative regeneration but returns to normal by 18 days. Morphologic changes appear to reflect changes in size of the cell associated with cell division rather than differentiation of recently divided basal cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1381564

  18. LM and TEM study of the orthokeratinized and parakeratinized epithelium of the tongue in the domestic duck (Anas platyrhynchos f. domestica).

    PubMed

    Skieresz-Szewczyk, Kinga; Jackowiak, Hanna; Ratajczak, Marlena

    2014-12-01

    The previous histological studies of the lingual mucosa in birds characterized two types of keratinized epithelium, i.e. orthokeratinized and parakeratinized. These epithelia are composed of three layers: basal, intermediate and keratinized. The present study showed detailed ultrastructural features of cells in particular layers of two types of keratinized epithelia on the tongue in the domestic duck and defined structural differences. TEM observations showed a gradual reduction in cell organelles in the following layers, at increasing amounts of keratin fibers. The characteristic feature of the ortho- and parakeratinized epithelium is the presence of sub-layers in the intermediate layer, i.e. the upper and lower part, which results from the different shape of cell nuclei and dye affinity of the cytoplasm. The keratinized layer of ortho- and parakeratinized epithelium is built of two types of cells such as electron dark and light cells, which undergo exfoliation. The basic difference between the keratinized epithelia is the presence of flattened cell nuclei in the keratinized layer of the parakeratinized epithelium. The differentiating feature is also an arrangement of keratin fibers in the cell cytoplasm of the keratinized layer. The analysis of the thickness of the epithelium and the keratinized layer, indicated differences between keratinized epithelia, which result from two variants of performing protective functions, either through a thick keratinized layer or by a higher epithelium. Differences in the ultrastructure of the ortho- and parakeratinized epithelium are associated with mechanical functions of the epithelium resulting from different forces acting on the tongue during feeding activities.

  19. Olfactory epithelium changes in germfree mice

    PubMed Central

    François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

    2016-01-01

    Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

  20. Dicer function is essential for lung epithelium morphogenesis.

    PubMed

    Harris, Kelley S; Zhang, Zhen; McManus, Michael T; Harfe, Brian D; Sun, Xin

    2006-02-14

    DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their short mature forms, enabling them to regulate gene expression. Only a single Dicer gene exists in the mouse genome, and it is broadly expressed in developing tissues. Dicer-null mutants die before gastrulation. Therefore, to study Dicer function in the later event of lung formation, we inactivated it in the mouse lung epithelium using a Dicer conditional allele and the Sonic Hedgehogcre (Shhcre) allele. Branching arrests in these mutant lungs, although epithelial growth continues in distal domains that are expanded compared with normal samples. These defects result in a few large epithelial pouches in the mutant lung instead of numerous fine branches present in a normal lung. Significantly, the initial phenotypes are apparent before an increase in epithelial cell death is observed, leading us to propose that Dicer plays a specific role in regulating lung epithelial morphogenesis independent of its requirement in cell survival. In addition, we found that the expression of Fgf10, a key gene involved in lung development, is up-regulated and expanded in the mesenchyme of Dicer mutant lungs. Previous studies support the hypothesis that precise localization of FGF10 in discrete sites of the lung mesenchyme serves as a chemoattractant for the outgrowth of epithelial branches. The aberrant Fgf10 expression may contribute to the Dicer morphological defects. However, the mechanism by which DICER functions in the epithelium to influence Fgf10 expression in the mesenchyme remains unknown.

  1. [Regulatory elements in the skin epithelium of Saccoglossus mereschkowskii (Enteropneusta, Hemichordata): electron microscopic and immunocytochemical study].

    PubMed

    Stoliarova, M V; Val'kovich, E I

    2013-01-01

    The aim of this investigation was to demonstrate the regulatory elements in the skin epithelium of Enteropneusta which are supposed to be related to the chordate ancestors. Using electron microscopy, it was found that in the skin epithelium of a representative of enteropneusts Saccoglossus mereschkowskii, the basal parts of some epitheliocytes took part in formation of a nerve layer. These cells were considered as receptor ciliated cells. The granular epithelial cells were shown to release secretion according to both exocrine and endocrine mechanism; these cells were characterized as endocrine-like regulatory cells. Fine granular cells possibly represent special receptor-endocrine-like cell type. The immunocytochemical detection of FMRFamid neuropeptide localization in histological sections confirmed the electron microscopic data on the presence of receptor and endocrine-like cells in the epithelium. It is suggested that the skin epithelium of Enteropneusta contains a peculiar neuro-endocrine regulatory system that is represented by receptor cells, receptor-endocrine-like cells of an open type and nerve elements of the nerve layer.

  2. Repeated intranasal exposure to microcystin-LR affects lungs but not nasal epithelium in mice.

    PubMed

    Oliveira, Vinícius R; Mancin, Viviane G L; Pinto, Eliete F; Soares, Raquel M; Azevedo, Sandra M F O; Macchione, Mariangela; Carvalho, Alysson R; Zin, Walter A

    2015-09-15

    Microcystin-LR (MC-LR) is a harmful cyanotoxin able to induce adverse outcomes in the respiratory system. We aimed to examine the lungs and nasal epithelium of mice following a sub-chronic exposure to MC-LR. Swiss mice were intranasally instilled with 10 μL of distilled water (CTRL, n = 10) or 6.7 ng/kg of MC-LR diluted in 10 μL of distilled water (TOX, n = 8) during 30 consecutive days. Respiratory mechanics was measured in vivo and histology measurements (morphology and inflammation) were assessed in lungs and nasal epithelium samples 24 h after the last intranasal instillation. Despite the lack of changes in the nasal epithelium, TOX mice displayed an increased amount of PMN cells in the lungs (× 10(-3)/μm(2)), higher lung static elastance (cmH2O/mL), resistive and viscoelastic/inhomogeneous pressures (cmH2O) (7.87 ± 3.78, 33.96 ± 2.64, 1.03 ± 0.12, 1.01 ± 0.08, respectively) than CTRL (5.37 ± 4.02, 26.65 ± 1.24, 0.78 ± 0.06, 0.72 ± 0.05, respectively). Overall, our findings suggest that the nasal epithelium appears more resistant than lungs in this model of MC-LR intoxication.

  3. Interferon-gamma-secreting T cells localize to the epithelium in coeliac disease.

    PubMed

    Olaussen, R W; Johansen, F E; Lundin, K E A; Jahnsen, J; Brandtzaeg, P; Farstad, I N

    2002-12-01

    Increased levels of interferon-gamma (IFN-gamma) transcripts have previously been found in duodenal biopsy specimens from patients with untreated coeliac disease (CD). Such samples and duodenal control mucosa were therefore studied to locate and phenotype cells spontaneously secreting IFN-gamma. Specimens were collected from consecutively recruited patients with untreated (seven), treated (four) or refractory (three) CD and from five histologically normal controls. Morphological and immunohistochemical examinations were performed, and epithelial and lamina propria cell suspensions were prepared from parallel samples. Unstimulated viable cells secreting IFN-gamma were identified and phenotyped with a new fluorescence-activated cell sorter-based assay, and IFN-gamma messenger RNA (mRNA) was analysed in snap-frozen aliquots of the same suspensions. Untreated CD cases had the highest fraction of IFN-gamma+ cells in the epithelial compartment (median 2.6%, range 1.6-6.2%) and, less strikingly, in the lamina propria compartment (1.6%, range 0.3-3.6%), followed by refractory (1.4%, 1.0-1.9%; and 0.3%, 0.0-1.2%) and treated (0.8%, 0.5-0.9%; and 0.7%, 0.2-1.1%) disease and finally the controls (0.5%, 0.3-0.9%; and 0.2%, 0.1-0.7%). IFN-gamma mRNA data supported these findings. IFN-gamma+ intraepithelial lymphocytes were mostly CD3+ and CD8+, whereas many positive lamina propria cells were CD8-. We conclude that isolated T cells spontaneously secreting IFN-gamma localize preferentially in the epithelium of patients with classical and refractory CD.

  4. Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium

    PubMed Central

    Ach, Thomas; Huisingh, Carrie; McGwin, Gerald; Messinger, Jeffrey D.; Zhang, Tianjiao; Bentley, Mark J.; Gutierrez, Danielle B.; Ablonczy, Zsolt; Smith, R. Theodore; Sloan, Kenneth R.; Curcio, Christine A.

    2014-01-01

    Purpose. Lipofuscin (LF) accumulation within RPE cells is considered pathogenic in AMD. To test whether LF contributes to RPE cell loss in aging and to provide a cellular basis for fundus autofluorescence (AF) we created maps of human RPE cell number and histologic AF. Methods. Retinal pigment epithelium–Bruch's membrane flat mounts were prepared from 20 donor eyes (10 ≤ 51 and 10 > 80 years; postmortem: ≤4.2 hours; no retinal pathologies), preserving foveal position. Phalloidin-binding RPE cytoskeleton and LF-AF (488-nm excitation) were imaged at up to 90 predefined positions. Maps were assembled from 83,330 cells in 1470 locations. From Voronoi regions representing each cell, the number of neighbors, cell area, and total AF intensity normalized to an AF standard was determined. Results. Highly variable between individuals, RPE-AF increases significantly with age. A perifoveal ring of high AF mirrors rod photoreceptor topography and fundus-AF. Retinal pigment epithelium cell density peaks at the fovea, independent of age, yet no net RPE cell loss is detectable. The RPE monolayer undergoes considerable lifelong re-modeling. The relationship of cell size and AF, a surrogate for LF concentration, is orderly and linear in both groups. Autofluorescence topography differs distinctly from the topography of age-related rod loss. Conclusions. Digital maps of quantitative AF, cell density, and packing geometry provide metrics for cellular-resolution clinical imaging and model systems. The uncoupling of RPE LF content, cell number, and photoreceptor topography in aging challenges LF's role in AMD. PMID:25034602

  5. [Histologic studies on otomycosis].

    PubMed

    Vennewald, Irina; Schönlebe, J; Klemm, E

    2002-01-01

    Fungal infections of the ear are mostly described as mycoses of the auditory canal. The aim of our investigations was to find out how fungi colonize the ear in immunocompetent patients. In the years from 1993 to 2000, 128 patients suspected of having otomycosis were examined. Of these 115 patients suffered from chronic otitis media with persisting tympanum perforation and otorrhea. A further 13 patients had clinical signs of otitis externa only. In 54 out of 139 samples, fungi were found in the auditory canal, in five on the tympanic membrane, and in five in the middle ear. Two-thirds were isolated as moulds and one-third as yeasts. Dominating species were Aspergillus niger and Candida parapsilosis. Samples of 15 patients suspected of having mastoiditis or cholesteatoma were examined histologically. Fungal hyphae were observed in the middle ear cavity and/or between horny lamellae of cholesteatoma in 4 patients. In the middle ear of immunocompetent patients chronic-hyperplastic (polypous) inflammation was detected with increased production of mucus, which probably promotes the colonization with pathogenic fungi as in the middle ear just like in the auditory canal.

  6. Two neutrophilic dermatoses captured simultaneously on histology

    PubMed Central

    Wlodek, Christina; Bhatt, Nidhi; Kennedy, Cameron

    2016-01-01

    A number of neutrophilic dermatoses are associated with malignancies and their treatment. These rarely occur together in the same patient. A Caucasian 72-year-old male was treated for acute myeloid leukemia (AML) with chemotherapy including daunorubicin and cytarabine. Within 48 hours of commencing treatment, he developed pyrexia and, two days later, disseminated non-tender pink plaques on the limbs and trunk. A skin biopsy showed a dermal interstitial infiltrate of lymphocytes, histiocytoid cells and predominantly neutrophils. This extended into the subcutis, where a neutrophilic lobular panniculitis was seen. These findings are consistent with Sweet’s syndrome. In addition, a neutrophilic and lymphocytic infiltrate was also present around eccrine coils and lower ducts. The eccrine epithelium showed squamous metaplasia with dyskeratosis and sloughing into the lumen. These latter findings are consistent with neutrophilic eccrine hidradenitis (NEH). These two histologically distinct entities form part of the neutrophilic dermatoses that have been described in oncology patients with reports of concurrent or sequential occurrence of various neutrophilic dermatoses in the same patient. Ours, however, is only the second reported case of simultaneously captured Sweet’s and NEH in the setting of AML. The most likely explanation is that of an epiphenomenon, whereby the neutrophilic infiltrate extended around the sweat glands in the context of the neutrophilic dermatosis. PMID:27648385

  7. Effects of vocal fold epithelium removal on vibration in an excised human larynx model

    PubMed Central

    Tse, Justin R.; Zhang, Zhaoyan; Long, Jennifer L.

    2015-01-01

    This study investigated the impact of selective epithelial injury on phonation in an excised human larynx apparatus. With intact epithelium, the vocal folds exhibited a symmetrical vibration pattern with complete glottal closure during vibration. The epithelium was then enzymatically removed from one, then both vocal folds, which led to left-right asymmetric vibration and a decreased closed quotient. Although the mechanisms underlying these vibratory changes are unclear, these results demonstrate that some component of an intact surface layer may play an important role in achieving normal symmetric vibration and glottal closure. PMID:26233062

  8. Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues

    DTIC Science & Technology

    2010-09-01

    right) yes 12 19 63% 0 1 0 0 4 0% 9 (left) Fibroadenoma 9 (right) Fibrocystic changes 10 (left) yes 3 22 14% 0 3 0 0 5 0% 10 (right) yes 6 18 33...E, Kanada N, Jibiki K, et al. Reduction of telomeric length and c-erbB-2 gene amplification in human breast cancer, fibroadenoma , and gynecomastia

  9. Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues

    DTIC Science & Technology

    2011-09-01

    nucleotide polymorphism or a panel of single nucleotide polymorphisms , may provide useful diagnostic information and may identify a subset of people at...Mutat Res. 1995; 338: 25–34. 11. von Zglinicki T, Pilger R, Sitte N. Accumulation of single - strand breaks is the major cause of telomere shortening...Background: Telomeres, nucleoprotein complexes located at the extreme ends of eukaryotic chromosomes, function to mask double strand break DNA damage

  10. Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues

    DTIC Science & Technology

    2013-09-01

    prognostic and/or risk biomarker [2]. Dysfunctional telomeres cause genomic instability via chromosomal breakage-fusion-bridge cycles. In the...invited to write a review article describing “The potential utility of telomere-related markers for cancer diagnosis” [7]. In alignment with his...De Marzo, E.A. Platz, and A.K. Meeker. Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for

  11. Antibodies against Escherichia coli O24 and O56 O-Specific Polysaccharides Recognize Epitopes in Human Glandular Epithelium and Nervous Tissue.

    PubMed

    Korzeniowska-Kowal, Agnieszka; Kochman, Agata; Gamian, Elżbieta; Lis-Nawara, Anna; Lipiński, Tomasz; Seweryn, Ewa; Ziółkowski, Piotr; Gamian, Andrzej

    2015-01-01

    Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, contains the O-polysaccharide, which is important to classify bacteria into different O-serological types within species. The O-polysaccharides of serotypes O24 and O56 of E. coli contain sialic acid in their structures, already established in our previous studies. Here, we report the isolation of specific antibodies with affinity chromatography using immobilized lipopolysaccharides. Next, we evaluated the reactivity of anti-O24 and anti-O56 antibody on human tissues histologically. The study was conducted under the assumption that the sialic acid based molecular identity of bacterial and tissue structures provides not only an understanding of the mimicry-based bacterial pathogenicity. Cross-reacting antibodies could be used to recognize specific human tissues depending on their histogenesis and differentiation, which might be useful for diagnostic purposes. The results indicate that various human tissues are recognized by anti-O24 and anti-O56 antibodies. Interestingly, only a single specific reactivity could be found in the anti-O56 antibody preparation. Several tissues studied were not reactive with either antibody, thus proving that the presence of cross-reactive antigens was tissue specific. In general, O56 antibody performed better than O24 in staining epithelial and nervous tissues. Positive staining was observed for both normal (ganglia) and tumor tissue (ganglioneuroma). Epithelial tissue showed positive staining, but an epitope recognized by O56 antibody should be considered as a marker of glandular epithelium. The reason is that malignant glandular tumor and its metastasis are stained, and also epithelium of renal tubules and glandular structures of the thyroid gland are stained. Stratified epithelium such as that of skin is definitely not stained. Therefore, the most relevant observation is that the epitope recognized by anti-O56 antibodies is a new marker

  12. Structural Development, Cellular Differentiation and Proliferation of the Respiratory Epithelium in the Bovine Fetal Lung.

    PubMed

    Drozdowska, J; Cousens, C; Finlayson, J; Collie, D; Dagleish, M P

    2016-01-01

    Fetal bovine lung samples of 11 different gestational ages were assigned to a classical developmental stage based on histological morphology. Immunohistochemistry was used to characterize the morphology of forming airways, proliferation rate of airway epithelium and the presence of epithelial cell types (i.e. ciliated cells, club cells, neuroepithelial cells (NECs) and type II pneumocytes). Typical structural organization of pseudoglandular (84-98 days gestational age [DGA]), canalicular (154-168 DGA) and alveolar (224-266 DGA) stages was recognized. In addition, transitional pseudoglandular-canalicular (112-126 DGA) and canalicular-saccular (182 DGA) morphologies were present. The embryonic stage was not observed. A significantly (P <0.05) higher proliferation rate of pulmonary epithelium, on average 5.5% and 4.4% in bronchi and bronchioles, respectively, was present in the transitional pseudoglandular-canalicular phase (112-126 DGA) compared with all other phases, while from 8 weeks before term (224-266 DGA) proliferation had almost ceased. The first epithelial cells identified by specific marker proteins in the earliest samples available for study (84 DGA) were ciliated cells and NECs. Club cells were present initially at 112 DGA and type II pneumocytes at 224 DGA. At the latest time points (224-226 DGA) these latter cell types were still present at a much lower percentage compared with adult cattle. This study characterized bovine fetal lung development by histological morphology and cellular composition of the respiratory epithelium and suggests that the apparent structural anatomical maturity of the bovine lung at term is not matched by functional maturity of the respiratory epithelium.

  13. Connexins form functional hemichannels in porcine ciliary epithelium.

    PubMed

    Shahidullah, Mohammad; Delamere, Nicholas A

    2014-01-01

    The expression of connexins in the ciliary epithelium is consistent with gap junctions between the pigmented (PE) and nonpigmented ciliary epithelium (NPE) that form when connexon hemichannels from adjacent cells pair to form a channel. Here we present evidence that suggests undocked connexons may form functional hemichannels that permit exchange of substances between NPE and the aqueous humor. Intact porcine eyes were perfused via the ciliary artery and propidium iodide (PI) (MW 668) was added to the aqueous humor compartment as a tracer. After calcium-free solution containing PI was introduced into the aqueous humor compartment for 30 min, fluorescence microscopy revealed PI in the NPE cell layer. PI entry into the NPE was inhibited by calcium and by the connexin antagonist 18α-glycyrrhetinic acid (18-AGA). Studies also were carried out with cultured porcine NPE. Under normal conditions, little PI entered the cultured cells but calcium-free medium stimulated PI accumulation and the entry was inhibited by 18-AGA. In cells loaded with calcein (MW 622), calcium-free solution stimulated calcein exit. 18-AGA partially suppressed calcein exit in calcium-free medium. Connexin 43 and connexin 50 proteins were detected by western blot analysis in both native and cultured NPE. In the intact eye, immunolocalization studies revealed connexin 50 at the basolateral, aqueous humor-facing, margin of the NPE. In contrast, connexin 43 was observed at the junction of the PE and NPE layer and on the basolateral membrane of PE. The results point to functional hemichannels at the NPE basolateral surface. It is feasible that hemichannels might contribute to the transfer of substances between the ciliary epithelium cytoplasm and aqueous humor.

  14. Cell cycle of globose basal cells in rat olfactory epithelium.

    PubMed

    Huard, J M; Schwob, J E

    1995-05-01

    The olfactory epithelium of adult mammals has the unique property of generating olfactory sensory neurons throughout life. Cells of the basal compartment, which include horizontal and globose basal cells, are responsible for the ongoing process of neurogenesis in this system. We report here that the globose basal cells in olfactory epithelium of rats, as in mice, are the predominant type of proliferating cell, and account for 97.6% of the actively dividing cells in the basal compartment of the normal epithelium. Globose basal cells have not been fully characterized in terms of their proliferative properties, and the dynamic aspects of neurogenesis are not well understood. As a consequence, it is uncertain whether cell kinetic properties are under any regulation that could affect the rate of neurogenesis. To address this gap in our knowledge, we have determined the duration of both the synthesis phase (S-phase) and the full cell cycle of globose basal cells in adult rats. The duration of the S-phase was found to be 9 hr in experiments utilizing sequential injections of either IdU followed by BrdU or 3H-thy followed by BrdU. The duration of the cell cycle was determined by varying the time interval between the injections of 3H-thy and BrdU and tracking the set of cells that exit S shortly after the first injection. With this paradigm, the interval required for these cells to traverse G2, M, G1, and a second S-phase, is equivalent to the duration of one mitotic cycle and equals 17 hr. These observations serve as the foundation to assess whether the cell cycle duration is subject to regulation in response to experimental injury, and whether such regulation is partly responsible for changes in the rate of neurogenesis in such settings.

  15. Expression of semaphorin 3A in the rat corneal epithelium during wound healing

    SciTech Connect

    Morishige, Naoyuki; Ko, Ji-Ae; Morita, Yukiko; Nishida, Teruo

    2010-05-14

    The neural guidance protein semaphorin 3A (Sema3A) is expressed in corneal epithelial cells of the adult rat. We have now further investigated the localization of Sema3A in the normal rat corneal epithelium as well as changes in its expression pattern during wound healing after central corneal epithelial debridement. The expression pattern of Sema3A was compared with that of the tight-junction protein zonula occludens-1 (ZO-1), the gap-junction protein connexin43 (Cx43), or the cell proliferation marker Ki67. Immunofluorescence analysis revealed that Sema3A was present predominantly in the membrane of basal and wing cells of the intact corneal epithelium. The expression of Sema3A at the basal side of basal cells was increased in the peripheral epithelium compared with that in the central region. Sema3A was detected in all layers at the leading edge of the migrating corneal epithelium at 6 h after central epithelial debridement. The expression of Sema3A was markedly up-regulated in the basal and lateral membranes of columnar basal cells apparent in the thickened, newly healed epithelium at 1 day after debridement, but it had largely returned to the normal pattern at 3 days after debridement. The expression of ZO-1 was restricted to superficial epithelial cells and remained mostly unchanged during the wound healing process. The expression of Cx43 in basal cells was down-regulated at the leading edge of the migrating epithelium but was stable in the remaining portion of the epithelium. Ki67 was not detected in basal cells of the central epithelium at 1 day after epithelial debridement, when Sema3A was prominently expressed. Immunoblot analysis showed that the abundance of Sema3A in the central cornea was increased 1 day after epithelial debridement, whereas that of ZO-1 or Cx43 remained largely unchanged. This increase in Sema3A expression was accompanied by up-regulation of the Sema3A coreceptor neuropilin-1. Our observations have thus shown that the expression of

  16. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium

    PubMed Central

    Walker, Nancy M.; Liu, Jinghua; Stein, Sydney R.; Stefanski, Casey D.; Strubberg, Ashlee M.

    2015-01-01

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl− and HCO3− efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3−)-loading proteins and upregulation of the basolateral membrane HCO3−-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl−/HCO3− exchange with maximized gradients, it also had increased intracellular Cl− concentration relative to wild-type. Pharmacological reduction of intracellular Cl− concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl− and HCO3− efflux, which impairs pHi regulation by Ae2. Retention of Cl− and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. PMID:26542396

  17. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.

    PubMed

    Walker, Nancy M; Liu, Jinghua; Stein, Sydney R; Stefanski, Casey D; Strubberg, Ashlee M; Clarke, Lane L

    2016-01-15

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine.

  18. Effect of Atmospheric-Pressure Cold Plasma on Pathogenic Oral Biofilms and In Vitro Reconstituted Oral Epithelium

    PubMed Central

    Zago, Chaiene Evelin; Tyhovych, Natalia

    2016-01-01

    Considering the ability of atmospheric-pressure cold plasma (ACP) to disrupt the biofilm matrix and rupture cell structure, it can be an efficient tool against virulent oral biofilms. However, it is fundamental that ACP does not cause damage to oral tissue. So, this study evaluated (1) the antimicrobial effect of ACP on single- and dual-species biofilms of Candida albicans and Staphylococcus aureus as well as (2) the biological safety of ACP on in vitro reconstituted oral epithelium. Standardized cell suspensions of each microorganism were prepared for biofilm culture on acrylic resin discs at 37°C for 48 hours. The biofilms were submitted to ACP treatment at 10 mm of plasma tip-to-sample distance during 60 seconds. Positive controls were penicillin G and fluconazole for S. aureus and C. albicans, respectively. The biofilms were analyzed through counting of viable colonies, confocal laser scanning microscopy, scanning electron microscopy and fluorescence microscopy for detection of reactive oxygen species. The in vitro reconstituted oral epithelium was submitted to similar ACP treatment and analyzed through histology, cytotoxocity test (LDH release), viability test (MTT assay) and imunnohistochemistry (Ki67 expression). All plasma-treated biofilms presented significant log10 CFU/mL reduction, alteration in microorganism/biofilm morphology, and reduced viability in comparison to negative and positive controls. In addition, fluorescence microscopy revealed presence of reactive oxygen species in all plasma-treated biofilms. Low cytotoxicity and high viability were observed in oral epithelium of negative control and plasma group. Histology showed neither sign of necrosis nor significant alteration in plasma-treated epithelium. Ki67-positive cells revealed maintenance of cell proliferation in plasma-treated epithelium. Atmospheric-pressure cold plasma is a promissing approach to eliminate single- and dual-species biofilms of C. albicans and S. aureus without having

  19. Histological process and dynamics of germ cell degeneration in pejerrey Odontesthes bonariensis larvae and juveniles during exposure to warm water.

    PubMed

    Ito, Lauro Satoru; Yamashita, Michiaki; Strüssmann, Carlos Augusto

    2003-06-01

    Elevated temperature causes degeneration and disappearance of the germ cells in the males of scrotal mammals. It was recently shown that heat-induced germ cell degeneration occurs also in fish but, unlike in mammals, it occurs not only in males but also in females. The purpose of this study was to clarify the histological process and dynamics of heat-induced germ cell disappearance in pejerrey Odontesthes bonariensis larvae and juveniles. Monosex and mixed-sex fish produced by thermal manipulation of sex (temperature-dependent sex determination) were subjected to 29 degrees C for periods between 1 and 12 weeks, and used to analyze, by histological methods, the changes in gonadal size and the number of normal and degenerating germ cells. Groups exposed to 29 degrees C for 8-12 weeks were subsequently transferred to 24 degrees C to verify if any gonadal damage would be permanent. Germ cell degeneration, histologically characterized by nuclear pyknosis or eosinophilia and cytoplasmic eosinophilia, was observed with increasing frequency at higher temperatures (29>24> 17 degrees C) and more in males than in females. Clear degenerative changes in the germinal epithelium usually began within one week of exposure to 29 degrees C and appeared clearer in females than in males. Complete loss of germ cells was observed only in individuals exposed for periods of 8-12 weeks to 29 degrees C but no treatment produced 100% sterile fish. Germ cells that remained in the gonads after exposure to 29 degrees C retained the capacity to rapidly recolonize germ cell-depleted areas, suggesting that the associated somatic cells in the gonads are little or not affected by this temperature.

  20. Reproductive Tract Histology in South American Fur Seal Pups (Arctophoca australis).

    PubMed

    Katz, Helena; Johansson, Olle

    2017-03-01

    In the present study, a detailed histological description of the female reproductive tract of South American fur seal (Arctophoca australis) pups has been conducted. The uterine tube was covered by cuboidal to columnar epithelium; nerve fibers were present in the mesosalpinx and beneath the muscular layer. The uterus was bipartitus; the endometrial surface of the horns was lined by a simple cuboidal or columnar epithelium with deep tubular glands; caudally ("the transition area"), the epithelium changed to pseudostratified columnar, few tubular glands were present and the myometrium increased in width. A bistratified epithelium internally coated the uterine body, whereas it changed to cylindrical stratified epithelium with a highly vascularized lamina propria and a strong muscular layer in the cervix; no endometrial glands were observed in this region. From the transition area of the uterus to the vagina there were several nerve fibers and ganglia belonging to the uterovaginalis plexus. In the vestibule, hymenal folds were poorly developed; adnexa structures included the major vestibular glands and a neurovascular structure similar to the vestibular bulb. Minor vestibular glands were associated with the clitoris. The skin of the perineum was lined by a keratinized stratified epithelium, pigmented, with sebaceous glands, sweat glands and hair follicles. This is the first detailed histological description of the reproductive tract of South American fur seal pups, including the glandular adnexa and nerve structures. These results contribute to the reproductive biology in Pinniped species, and give a better understanding of the utero-placental perfusion mechanism during diving. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:600-613, 2017. © 2016 Wiley Periodicals, Inc.

  1. Differential Expression Patterns of EGF, EGFR, and ERBB4 in Nasal Polyp Epithelium

    PubMed Central

    Zhao, Li; Subramaniam, Somasundaram; Yu, Xue Min; Li, Ying Ying; Chen, De Hua; Li, Tian Ying; Shen, Liang; Shi, Li; Wang, De Yun

    2016-01-01

    Epidermal growth factor receptors play an important role in airway epithelial cell growth and differentiation. The current study investigates the expression profiles of EGF, EGFR and ERBB4 in patients with nasal polyps (NP), and their response to glucocorticosteroid (GC) treatment. Fifty patients with NP (40 without GC treatment and 10 with oral GC) and 20 control subjects with septal deviation were recruited into the study. Protein levels of EGF, EGFR, and ERBB4 were evaluated by immune-staining. In healthy nasal epithelium, EGF and EGFR localized within p63+ basal cells, while ERBB4 localized within ciliated cells. GC-naïve NP epithelium showed weak expression of EGF in 90% of samples versus 5% of controls. EGFR was significantly increased in the epithelium with basal cell hyperplasia from GC-naïve NPs (78%, 31/40) compared to controls (23%, 4/17). EGFR was also found in some degranulating goblet cells. ERBB4 expression was significantly higher in hyperplastic epithelium from GC-naïve NPs (65%, 26/40) than in controls (6%, 1/17). GC treatment restored the EGF expression and normalized the EGFR and ERBB4 expression in NPs. Differential expression patterns of EGF, EGFR, and ERBB4 are essential in epithelial restitution and remodeling in nasal epithelium. PMID:27285994

  2. Immunohistochemical characteristics of normal canine eyes.

    PubMed

    Labelle, P; Reilly, C M; Naydan, D K; Labelle, A L

    2012-09-01

    Immunohistochemistry is widely utilized in diagnostic laboratories to study neoplastic and nonneoplastic diseases. Knowledge of the immunohistochemical characteristics of normal tissue is essential for interpretation of immunoreactivity in pathologic conditions. In this study, immunohistochemistry was performed with a broad panel of diagnostically relevant antibodies on 4 normal canine globes--namely, vimentin, pan-cytokeratin (AE1/AE3), cytokeratin 7, cytokeratin 8/18, cytokeratin 20, α-smooth muscle actin, muscle specific actin, desmin, Melan-A, microphthalmia transcription factor, S-100, glial fibrillary acidic protein, triple neurofilaments, neuron-specific enolase, chromogranin A, synaptophysin, laminin and CD31. Results include cytokeratin immunoreactivity limited to the conjunctival epithelium, corneal epithelium, and retinal pigment epithelium; distinct patterns of immunopositivity of muscle markers; and widespread immunoreactivity for vimentin and most neural/neuroendocrine markers. These findings in normal eyes provide the basis for interpretation of ocular immunohistochemistry in dogs. Published immunophenotypes of primary ocular neoplasms are also reviewed.

  3. Normal osteoid tissue

    PubMed Central

    Raina, Vinita

    1972-01-01

    The results of a histological study of normal osteoid tissue in man, the monkey, the dog, and the rat, using thin microtome sections of plastic-embedded undecalcified bone, are described. Osteoid tissue covers the entire bone surface, except for areas of active resorption, although the thickness of the layer of osteoid tissue varies at different sites and in different species of animals. The histological features of osteoid tissue, apart from its amount, are the same in the different species studied. Distinct bands or zones are recognizable in some layers of osteoid tissue, particularly those of greatest thickness, and their significance is discussed. Some of the histological features of the calcification front are described. Images PMID:4111820

  4. Effect of nitrogen dioxide on human nasal epithelium

    SciTech Connect

    Carson, J.L.; Collier, A.M.; Hu, S.C.; Delvin, R.B. )

    1993-09-01

    The nasal epithelium of young adult white men in good health was evaluated by electron microscopy in a condition blind fashion relative to exposures of 2 ppm nitrogen dioxide (NO2) or clean air for 4 h. The exposure protocol involved two separate exposures of the same individuals to NO2 or clean air approximately 3 wk apart. We found qualitative and quantitative evidence that luminal border membranes of ciliated cells were ultrastructurally altered in six of seven samples of nasal epithelium obtained following NO2 exposures, although subsequent morphometric statistical analyses were not significant. This alteration was characterized by cilia containing excess matrix in which individual or, more commonly, multiple ciliary axonemes were embedded, and by vesiculations of luminal border ciliary membranes, a pattern less common in clean air-exposed control specimens. Although these patterns were not widespread, their morphology was consistent with findings of previous animal studies involving acute and chronic exposure to NO2. Our findings suggest that adverse effects on mucociliary function in normal humans due to acute exposure to low levels of NO2 are most likely minimal. However, in view of other reports of NO2 exposure in laboratory animals documenting ciliary injury, our observations support a view that similar patterns might appear more prominently with higher NO2 levels and/or more extended exposure intervals.

  5. An Apical-Membrane Chloride Channel in Human Tracheal Epithelium

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.

    1986-06-01

    The mechanism of chloride transport by airway epithelia has been of substantial interest because airway and sweat gland-duct epithelia are chloride-impermeable in cystic fibrosis. The decreased chloride permeability prevents normal secretion by the airway epithelium, thereby interfering with mucociliary clearance and contributing to the morbidity and mortality of the disease. Because chloride secretion depends on and is regulated by chloride conductance in the apical cell membrane, the patch-clamp technique was used to directly examine single-channel currents in primary cultures of human tracheal epithelium. The cells contained an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches. The channel was also blocked by analogs of carboxylic acid that decrease apical chloride conductance in intact epithelia. When attached to the cell, the channel was activated by isoproterenol, although the channel was also observed to open spontaneously. However, in some cases, the channel was only observed after the patch was excised from the cell. These results suggest that this channel is responsible for the apical chloride conductance in airway epithelia.

  6. Unicystic Ameloblastoma: A Perception for the Cautious Interpretation of Radiographic and Histological Findings.

    PubMed

    Arora, Shelly

    2015-10-01

    The term Unicystic Ameloblastoma (UA) refers to those cystic lesions that show clinical and radiological characteristics of an odontogenic cyst but on histological examination show a typical ameloblastomatous epithelium lining part of the cyst cavity, with or without luminal and/or mural tumor growth. Till date, lot of controversies exist among oral surgeons and oral pathologists regarding this entity. An attempt is being made here to discuss all the diagnostic dilemmas associated with UA.

  7. Colorectal tumors: the histology report.

    PubMed

    Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

    2011-03-01

    Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed.

  8. Machine learning approaches to analyze histological images of tissues from radical prostatectomies.

    PubMed

    Gertych, Arkadiusz; Ing, Nathan; Ma, Zhaoxuan; Fuchs, Thomas J; Salman, Sadri; Mohanty, Sambit; Bhele, Sanica; Velásquez-Vacca, Adriana; Amin, Mahul B; Knudsen, Beatrice S

    2015-12-01

    Computerized evaluation of histological preparations of prostate tissues involves identification of tissue components such as stroma (ST), benign/normal epithelium (BN) and prostate cancer (PCa). Image classification approaches have been developed to identify and classify glandular regions in digital images of prostate tissues; however their success has been limited by difficulties in cellular segmentation and tissue heterogeneity. We hypothesized that utilizing image pixels to generate intensity histograms of hematoxylin (H) and eosin (E) stains deconvoluted from H&E images numerically captures the architectural difference between glands and stroma. In addition, we postulated that joint histograms of local binary patterns and local variance (LBPxVAR) can be used as sensitive textural features to differentiate benign/normal tissue from cancer. Here we utilized a machine learning approach comprising of a support vector machine (SVM) followed by a random forest (RF) classifier to digitally stratify prostate tissue into ST, BN and PCa areas. Two pathologists manually annotated 210 images of low- and high-grade tumors from slides that were selected from 20 radical prostatectomies and digitized at high-resolution. The 210 images were split into the training (n=19) and test (n=191) sets. Local intensity histograms of H and E were used to train a SVM classifier to separate ST from epithelium (BN+PCa). The performance of SVM prediction was evaluated by measuring the accuracy of delineating epithelial areas. The Jaccard J=59.5 ± 14.6 and Rand Ri=62.0 ± 7.5 indices reported a significantly better prediction when compared to a reference method (Chen et al., Clinical Proteomics 2013, 10:18) based on the averaged values from the test set. To distinguish BN from PCa we trained a RF classifier with LBPxVAR and local intensity histograms and obtained separate performance values for BN and PCa: JBN=35.2 ± 24.9, OBN=49.6 ± 32, JPCa=49.5 ± 18.5, OPCa=72.7 ± 14.8 and Ri=60.6

  9. Donkey dental anatomy. Part 2: Histological and scanning electron microscopic examinations.

    PubMed

    Du Toit, N; Kempson, S A; Dixon, P M

    2008-06-01

    Ten normal cheek teeth (CT) were extracted at post mortem from donkeys that died or were euthanased for humane reasons. Decalcified histology was performed on three sections (sub-occlusal, mid-tooth and pre-apical) of each tooth, and undecalcified histology undertaken on sub-occlusal sections of the same teeth. The normal histological anatomy of primary, regular and irregular secondary dentine was found to be similar to that of the horse, with no tertiary dentine present. Undecalcified histology demonstrated the normal enamel histology, including the presence of enamel spindles. Scanning electron microscopy was performed on mid-tooth sections of five maxillary CT, five mandibular CT and two incisors. The ultrastructural anatomy of primary and secondary dentine, and equine enamel types-1, -2 and -3 (as described in horses) were identified in donkey teeth. Histological and ultrastructural donkey dental anatomy was found to be very similar to equine dental anatomy with only a few quantitative differences observed.

  10. Immunoglobulin deposits in labial mucosal epithelium of patients suspected of Sjögren's syndrome.

    PubMed

    Oxholm, P; Manthorpe, R; Oxholm, A; Schiødt, M

    1986-02-01

    Lower lip biopsies from twenty-three consecutive patients under evaluation for Sjögren's syndrome, and from six normal controls, were investigated for deposits of immunoglobulins, fibrinogen and C3, using a direct immunofluorescence technique. Deposits of both IgG and IgA were demonstrated in the mucosal epithelium in three of six patients with primary Sjögren's syndrome. Similar IgG deposits were found in two of three patients with xerostomia and in one of three patients with Sjögren's syndrome secondary to rheumatoid arthritis. Immunoglobulins were located in close relation to cell surfaces in the basal and suprabasal layers of the epithelium. Double labelling experiments indicated a partial topographic concordance between the immunoglobulin deposits and OKT6 positive Langerhans cells in the epithelium. No deposits of immunoglobulins, fibrinogen or C3 were found in the remaining eleven patients and six normal controls. We conclude that deposits of IgG and IgA in the labial mucosal epithelium seem to be a characteristic finding in patients with primary Sjögren's syndrome as well as in patients with xerostomia. The diagnostic value of this new observation needs to be clarified in future studies.

  11. Retinal pigment epithelium engineering using synthetic biodegradable polymers.

    PubMed

    Lu, L; Yaszemski, M J; Mikos, A G

    2001-12-01

    Retinal pigment epithelium (RPE) plays a key role in the maintenance of the normal functions of the retina, especially photoreceptors. Alteration in RPE structure and function is implicated in a variety of ocular disorders. Tissue engineering strategies using synthetic biodegradable polymers as temporary substrates for RPE cell culture and subsequent transplantation may provide a promising new therapy. In this review article, the manufacture of thin biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) films and their degradation behavior in vitro are discussed. RPE cell proliferation and differentiation on these PLGA films are reviewed. The fabrication of model substrates with desired chemical micropatterns in the micrometer scale is discussed and the effects of surface patterning on RPE morphology and function are assessed. Finally. the preparation of biodegradable micropatterns with adhesive PLGA and non-adhesive poly(ethylene glycol)/PLA domains to modulate RPE cell adhesion is presented.

  12. X-ray microanalysis of hamster tracheal epithelium

    SciTech Connect

    Spencer, A.J.; Roomans, G.M. )

    1989-06-01

    Studies of ion transport across respiratory epithelia are of great interest if we are to understand the pathophysiology of diseases such as cystic fibrosis in which ion transport is abnormal. Concentrations of elements were determined in various subcellular regions of normal or isoproterenol-treated hamster tracheal epithelium, using X-ray microanalysis of freeze-dried cryosections. Samples of trachea were taken from animals under anesthesia and either frozen in situ or dissected and plunge frozen. Concentrations of Mg, P, S, Cl, K and Ca were higher in cytoplasm and nuclei of control epithelial cells in dissected samples than in cryoneedle samples. Following treatment with isoproterenol, a large decrease in the concentration of Cl was observed. The results confirm that cyclic AMP-regulated chloride secretion is unaffected by anesthesia.

  13. Mechanically patterning the embryonic airway epithelium.

    PubMed

    Varner, Victor D; Gleghorn, Jason P; Miller, Erin; Radisky, Derek C; Nelson, Celeste M

    2015-07-28

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo.

  14. Odors Discrimination by Olfactory Epithelium Biosensor

    NASA Astrophysics Data System (ADS)

    Liu, Qingjun; Hu, Ning; Ye, Weiwei; Zhang, Fenni; Wang, Hua; Wang, Ping

    2011-09-01

    Humans are exploring the bionic biological olfaction to sense the various trace components of gas or liquid in many fields. For achieving the goal, we endeavor to establish a bioelectronic nose system for odor detection by combining intact bioactive function units with sensors. The bioelectronic nose is based on the olfactory epithelium of rat and microelectrode array (MEA). The olfactory epithelium biosensor generates extracellular potentials in presence of odor, and presents obvious specificity under different odors condition. The odor response signals can be distinguished with each other effectively by signal sorting. On basis of bioactive MEA hybrid system and the improved signal processing analysis, the bioelectronic nose will realize odor discrimination by the specific feature of signals response to various odors.

  15. [Neutrophils and monocytes in gingival epithelium

    PubMed

    Meng, H X; Zheng, L P

    1994-06-01

    Neutrophils and monocytes of gingival epithellium in health gingiva(H),marginal gingivitis(MG),juvenile periodontitis(JP),adult periodontitis(AP) and subgingival bacteria were quantitated and analyzed,The results showed that the numbers of PMN within either pocket epithelium or oral gingival epithelium in JP were significantly lower than in AP and G.The amounts of PMN in AP were much larger than other three groups.Positive correlation between the number of PMN in sulcular pocket epitelium and the motile bacteri of subgingival plaque was demonstrated by correlation analysis.Monocytes mainly presented in deep pocket and junctional epithelum which were stained by NAE method,however very few Langhans cells were seen in these areas.

  16. Mechanically patterning the embryonic airway epithelium

    PubMed Central

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  17. Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6

    PubMed Central

    Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

    2017-01-01

    AIM To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. METHODS Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. RESULTS After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age (P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P < 0.05). CONCLUSION Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation. PMID:28293090

  18. Neurogenesis in the vomeronasal epithelium of adult garter snakes: 3. Use of /sup 3/H-thymidine autoradiography to trace the genesis and migration of bipolar neurons

    SciTech Connect

    Wang, R.T.; Halpern, M.

    1988-10-01

    Use of 3H-thymidine autoradiography and unilateral vomeronasal (VN) axotomy has permitted us to demonstrate directly the existence of VN stem cells in the adult garter snake and to trace continuous bipolar neuron development and migration in the normal VN and deafferentated VN epithelium in the same animal. The vomeronasal epithelium and olfactory epithelium of adult garter snakes are both capable of incorporating 3H-thymidine. In the sensory epithelium of the vomeronasal organ, 3H-thymidine-labeled cells were initially restricted to the base of the undifferentiated cell layer in animals surviving 1 day following 3H-thymidine injection. With increasing survival time, labeled cells progressively migrated vertically within the receptor cell column toward the apex of the bipolar neuron layer. In both the normal and denervated VN epithelium, labeled cells were observed through the 56 days of postoperative survival. In the normal epithelium, labeled cells were always located within the matrix of the intact receptor cell columns. However, labeled cells of the denervated epithelium were always located at the apical front of the newly formed cell mass following depletion of the original neuronal cell population. In addition, at postoperative days 28 and 56, labeled cells of the denervated VN epithelium achieved neuronal differentiation and maturation by migrating much farther away from the base of the receptor cell column than the labeled cells on the normal, unoperated contralateral side. This study directly demonstrates that basal cells initially incorporating 3H-thymidine are indeed stem cells of the VN epithelium in adult garter snakes.

  19. [Morpho-functional characteristics of the lingual epithelium after administration of hydra peptide morphogen].

    PubMed

    Kulaeva, V V; Bykov, V L

    2007-01-01

    Using histological, morphometric and quantitative histoenzymological methods, the changes of lingual epithelium were studied in 40 outbred albino mice after 5 intraperitoneal injections of 100 micrograms of hydra peptide morphogen (HPM) per 1 kg of body weight. Administration of HPM was found to increase the total thickness of epithelial layer on the dorsal tongue surface in the interpapillary regions, while in the area of filiform papillae these changes were not significant. On the ventral tongue surface HPM induced a marked increase of total thickness of the epithelial layer as compared to that in control animals. Mitotic activity was increased in the epithelium covering the ventral surface and in the interpapillary regions on the dorsal tongue surface. Histoenzymologic study which involved the demonstration of NADH-diaphorase, succinate- and lactate-dehydrogenase (LDH) activities, followed by a cytophotometric evaluation of enzyme activity, has shown a stimulatory effect of HPM on the activity of all the enzymes studied, which was most pronounced in respect to LDH and was maximally expressed on the dorsal tongue surface. These findings collectively suggest that HPM exerts a stimulatory effect on proliferation activity and metabolism of lingual epithelium, which is differentially expressed in its variuoe topographical zones.

  20. Annexin A2 Acts as an Adhesion Molecule on the Endometrial Epithelium during Implantation in Mice.

    PubMed

    Wang, Bing; Ye, Tian-Min; Lee, Kai-Fai; Chiu, Philip C N; Pang, Ronald T K; Ng, Ernest H Y; Yeung, William S B

    2015-01-01

    To determine the function of Annexin A2 (Axna2) in mouse embryo implantation in vivo, experimental manipulation of Axna2 activities was performed in mouse endometrial tissue in vivo and in vitro. Histological examination of endometrial tissues was performed throughout the reproduction cycle and after steroid treatment. Embryo implantation was determined after blockage of the Axna2 activities by siRNA or anti-Axna2 antibody. The expression of Axna2 immunoreactivies in the endometrial luminal epithelium changed cyclically in the estrus cycle and was upregulated by estrogen. After nidatory estrogen surge, there was a concentration of Axna2 immunoreactivities at the interface between the implanting embryo and the luminal epithelium. The phenomenon was likely to be induced by the implanting embryos as no such concentration of signal was observed in the inter-implantation sites and in pseudopregnancy. Knockdown of Axna2 by siRNA reduced attachment of mouse blastocysts onto endometrial tissues in vitro. Consistently, the number of implantation sites was significantly reduced after infusion of anti-Axna2 antibody into the uterine cavity. Steroids and embryos modulate the expression of Axna2 in the endometrial epithelium. Axna2 may function as an adhesion molecule during embryo implantation in mice.

  1. Epithelium-stroma classification via convolutional neural networks and unsupervised domain adaptation in histopathological images.

    PubMed

    Huang, Yue; Zheng, Han; Liu, Chi; Ding, Xinghao; Rohde, Gustavo

    2017-04-06

    Epithelium-stroma classification is a necessary preprocessing step in histopathological image analysis. Current deep learning based recognition methods for histology data require collection of large volumes of labeled data in order to train a new neural network when there are changes to the image acquisition procedure. However, it is extremely expensive for pathologists to manually label sufficient volumes of data for each pathology study in a professional manner, which results in limitations in real-world applications. A very simple but effective deep learning method, that introduces the concept of unsupervised domain adaptation to a simple convolutional neural network (CNN), has been proposed in this paper. Inspired by transfer learning, our work assumes that the training data and testing data follow different distributions, and there is an adaptation operation to more accurately estimate the kernels in CNN in feature extraction, in order to enhance performance by transferring knowledge from labeled data in source domain to unlabeled data in target domain. The model has been evaluated using three independent public epithelium-stroma datasets by cross-dataset validations. The experimental results demonstrate that for epithelium-stroma classification, the proposed framework outperforms the state-of-the-art deep neural network model, and it also achieves better performance than other existing deep domain adaptation methods. The proposed model can be considered to be a better option for real-world applications in histopathological image analysis, since there is no longer a requirement for large-scale labeled data in each specified domain.

  2. Killifish opercular skin: a flat epithelium with a high density of chloride cells.

    PubMed

    Karnaky, K G; Kinter, W B

    1977-03-01

    In teleosts the head region, particularly the gills, plays the key role in osmoregulatory NaCl transport, presumably by mechanisms located in the chloride cell. As interest has focused on specific mechanisms of chloride cell function, two classical preparations, the intact fish and the isolated, perfused gill, have continued to serve as the only available model systems. However, both of these preparations have severe limitations, e.g., as they are not flat sheets, they cannot be studied readily under the ideal thermodynamic conditions achieved with the short-circuit current technique. The present sutdy describes the histology and ultrastructure of a particular area of skin in the head region of both killifish (Fundulus heteroclitus) and sea raven (Hemitripterus americanus). This skin lies on the inside of the operculum and possesses a flat epithelium containing chloride cells. In the present study the identity of the chloride cell in this epithelium was definitively established with the electron microscope. Although the opercular epithelium from the marine sea raven contains few chloride cells, that from the euryhaline killifish adapted to pond water, 100%-, and 200% artificial seawater is predominately chloride cells. Significantly, the teleost gill has never been reported to contain more than 10% chloride cells. Thus the opercular skin of the killifish can serve as a model to study the adaptive role of chloride cells in euryhaline teleosts. A separate electrophysiological study has deminstrated that the short-circuit current technique can be applied to this skin.

  3. Development of an electrode for the artificial cochlear sensory epithelium.

    PubMed

    Tona, Yosuke; Inaoka, Takatoshi; Ito, Juichi; Kawano, Satoyuki; Nakagawa, Takayuki

    2015-12-01

    An artificial cochlear sensory epithelium has been developed on the basis of a new concept that the piezoelectric membrane, which converts mechanical distortion into electricity, can mimic the function of the inner hair cell and basilar membrane of the mammalian cochlea. Our previous research demonstrated that the piezoelectric membrane generated electrical outputs in response to the sound stimulation after implantation into the guinea pig cochlea, whereas electrodes for the stimulation of spiral ganglion neurons have not been fabricated, and a method to fix the device in the cochlea is also required to show proof-of-concept. In the present study, to achieve proof-of-concept of hearing recovery by implantation of the artificial cochlear sensory epithelium, we fabricated new electrodes that stick into the cochlear modiolus, which also play a role in the fixation of the device in the cochlea. The efficacy of new electrodes for fixation of the device in the cochlea and for the stimulation of spiral ganglion neurons was estimated in guinea pigs. Four weeks after implantation, we confirmed that the devices were in place. Histological analysis of the implanted cochleae revealed inconspicuous fibrosis and scar formation compared with the sham-operated specimens (n = 5 for each). The terminal deoxynucleotidyl transferase dUTP nick end labeling method was used to assess cell death due to surgical procedures in the cochleae that were harvested after 1 day (n = 6) and 7 days (n = 6) of implantation; there was no significant increase in apoptotic cell death in the implanted cochleae compared with sham-operated cochleae. In seven animals, serial measurements of electrically evoked auditory brainstem responses were obtained, with the electrode positioned in the scala tympani and with the electrode inserted into the cochlear modiolus. With the insertion of electrodes into the cochlear modiolus, significant reduction was achieved in the thresholds of electrically evoked auditory

  4. Modulating Effect of Peptide Therapy on the Morphofunctional State of Bronchial Epithelium in Rats with Obstructive Lung Pathology.

    PubMed

    Kuzubova, N A; Lebedeva, E S; Dvorakovskaya, I V; Surkova, E A; Platonova, I S; Titova, O N

    2015-09-01

    On the model of chronic obstructive pulmonary disease, the effect of therapy with low-molecular-weight peptides on restructuring and functional activity of bronchial epithelium for restoring the immune and barrier function of the lungs and prevention of inflammatory process progression was studied. Chronic obstructive pulmonary disease was modeled in rats by 60-day intermittent exposure to NO2. Administration of tetrapeptide Bronchogen for 1 month eliminates symptoms of remodeling of the bronchial epithelium and lung tissue typical of chronic obstructive pulmonary disease (goblet cell hyperplasia, squamous metaplasia, lymphocytic infiltration and emphysema, and restoration of ciliated cells). Enhanced production of secretory IgA, a local immunity marker, attested to normalization of functional activity of bronchial epithelium, while normalization of cell composition and profile of proinflammatory cytokines in the bronchoalveolar space reflected reduction of neutrophilic inflammation.

  5. Remote Histology Learning from Static versus Dynamic Microscopic Images

    ERIC Educational Resources Information Center

    Mione, Sylvia; Valcke, Martin; Cornelissen, Maria

    2016-01-01

    Histology is the study of microscopic structures in normal tissue sections. Curriculum redesign in medicine has led to a decrease in the use of optical microscopes during practical classes. Other imaging solutions have been implemented to facilitate remote learning. With advancements in imaging technologies, learning material can now be digitized.…

  6. Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

    PubMed Central

    Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

    2011-01-01

    Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute

  7. Lgr5 regulates the regeneration of lesioned nasal respiratory epithelium.

    PubMed

    Zhang, Yan-Qiang; Li, Peng; Zhang, Feng-Qin; Sun, Shao-Jun; Cao, Yin-Guang

    2016-12-09

    Nasal respiratory epithelium is a ciliated pseudostratified columnar epithelium. The cellular components of nasal respiratory epithelium include ciliated cells, goblet cells, and basal cells. Until now, our knowledge in the development of nasal respiratory epithelium is still limited and the cellular mechanism of regeneration is still elusive. In this study, we found that adult stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is expressed in the mice nasal respiratory epithelium. Both immunostaining and lineage tracing analysis indicated Lgr5 positive cells in the nasal respiratory epithelium are proliferative stem/progenitor cells. Using the Rosa-Tdtomato and Rosa26-DTR mice, we elucidated that Lgr5(+) cells participate in the regeneration of lesioned nasal respiratory epithelium, and this group of cells is necessary in the process of epithelium recovery. Using the in vitro culture system, we observed the formation of spheres from Lgr5(+) cells and these spheres have the capacity to generate other types of cells. Above all, this study reported a group of previously unidentified progenitor/stem cells in nasal respiratory epithelium, unveiling the potential cellular mechanism in nasal respiratory epithelium regeneration.

  8. Reordering Histology to Enhance Engagement

    ERIC Educational Resources Information Center

    Amerongen, Helen

    2011-01-01

    In redesigning the preclinical curriculum and shifting from a discipline-based approach to an organ system-based approach, faculty at the University of Arizona College of Medicine in Tucson took the opportunity to restructure the sequence of introductory histology content to make it more engaging and relevant. In this article, the author describes…

  9. Histology and scanning electron microscopy of the tubal tonsil of goats

    PubMed Central

    Indu, V. R.; Lucy, K. M.; Chungath, J. J.; Ashok, N.; Maya, S.

    2015-01-01

    Aim: To observe the light and scanning electron microscopy (SEM) of the caprine tubal tonsil. Materials and Methods: The study was conducted on six crossbred male goats of 6 months of age. From the median sections of the head, tissue pieces from the nasopharynx around the auditory tube were collected and fixed for histology and SEM. Results: Tonsillar lymphoid tissue was located in the nasopharynx ventral to the auditory tube opening in the lateral wall of the pharynx. The height of the surface epithelium of the tubal tonsil measured 80.17±1.08 µm and was a pseudostratified ciliated columnar type with basal, supporting, and goblet cells. Above the dome of lymphoid nodules, the epithelium was modified into a follicle associated epithelium (FAE), also called lympho-epithelium or reticular epithelium and was characterized by the absence of goblet cells and cilia, reduced number of cell layers, and a large number of lymphoid cells due to interrupted basement membrane. The height of FAE was smaller than that of the surface epithelium and measured 34.33±0.92 µm. The surface of tubal tonsil showed folds and invaginations, which formed crypts. The lamina propria-submucosa underneath the epithelium was formed by the meshwork of reticular and, thin and loose collagen fibers with dome-like accumulation of lymphoid nodules. In the secondary lymphoid nodules, a corona, parafollicular area, and interfnodular area were observed. The average number of lymphoid nodules counted per field under low power magnification of microscope was 1.17±0.17, and the internodular distance was 34.00±4.37 µm. The mean diameter of lymphoid nodules was 566.67±11.45 µm and the lymphocyte count per nodule was 14741.67±174.36. The number of plasma cells counted per field under low power was 44.38±2.90 below the surface epithelium. The tubal tonsil was not encapsulated. In SEM, the surface epithelium of the tubal tonsils presented ciliated cells, microvillus (MV) cells, and goblet cells. The

  10. Deletion of JAM-A causes morphological defects in the corneal epithelium.

    PubMed

    Kang, Liang I; Wang, Yan; Suckow, Arthur T; Czymmek, Kirk J; Cooke, Vesselina G; Naik, Ulhas P; Duncan, Melinda K

    2007-01-01

    Junctional adhesion molecule-A (JAM-A, JAM-1, F11R) is an Ig domain containing transmembrane protein that has been proposed to function in diverse processes including platelet activation and adhesion, leukocyte transmigration, angiogenesis, epithelial cell shape and endothelial cell migration although its function in vivo is less well established. In the mouse eye, JAM-A protein expression is first detected at 12.5 dpc in the blood vessels of the tunica vasculosa, while it is first detected in both the corneal epithelium and lens between 13.5 and 14.5 dpc. In the corneal epithelium, JAM-A levels remain appreciable throughout life, while JAM-A immunostaining becomes stronger in the lens as the animals age. Both the cornea and lens of mice lacking an intact JAM-A gene are transparent until at least a year of age, although the cells of the JAM-A null corneal epithelium are irregularly shaped. In wild-type mice, JAM-A protein is found at the leading edge of repairing corneal epithelial wounds, however, corneal epithelial wound repair was qualitatively normal in JAM-A null animals. In summary, JAM-A is expressed in the corneal epithelium where it appears to regulate cell shape.

  11. Morphological and Functional Features of Hepatic Cyst Epithelium in Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Alvaro, Domenico; Onori, Paolo; Alpini, Gianfranco; Franchitto, Antonio; Jefferson, Douglas M.; Torrice, Alessia; Cardinale, Vincenzo; Stefanelli, Fabrizio; Mancino, Maria Grazia; Strazzabosco, Mario; Angelico, Mario; Attili, Adolfo; Gaudio, Eugenio

    2008-01-01

    We evaluated the morphological and functional features of hepatic cyst epithelium in adult autosomal dominant polycystic kidney disease (ADPKD). In six ADPKD patients, we investigated the morphology of cyst epithelium apical surface by scanning electron microscopy and the expression of estrogen receptors (ERs), insulin-like growth factor 1 (IGF1), IGF1 receptors (IGF1-R), growth hormone receptor, the proliferation marker proliferating cell nuclear antigen, and pAKT by immunohistochemistry and immunofluorescence. Proliferation of liver cyst-derived epithelial cells was evaluated by both MTS proliferation assay and [3H]thymidine incorporation into DNA. The hepatic cyst epithelium displayed heterogeneous features, being normal in small cysts (<1 cm), characterized by rare or shortened cilia in 1- to 3-cm cysts, and exhibiting the absence of both primary cilia and microvilli in large cysts (>3 cm). Cyst epithelium showed marked immunohistochemical expression of ER, growth hormone receptor, IGF1, IGF1-R, proliferating cell nuclear antigen, and pAKT. IGF1 was 10-fold more enriched in the hepatic cyst fluid than in serum. Serum-deprived liver cyst-derived epithelial cells proliferated when exposed to 17β-estradiol and IGF1 and when exposed to human cyst fluid. ER or IGF1-R antagonists inhibited the proliferative effect of serum readmission, cyst fluid, 17β-estradiol, and IGF1. Our findings could explain the role of estrogens in accelerating the progression of ADPKD and may suggest a potential benefit of therapeutic strategies based on estrogen antagonism. PMID:18202196

  12. Activation of the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway in human cholesteatoma epithelium.

    PubMed

    Liu, Wei; Yin, Tuanfang; Ren, Jihao; Li, Lihua; Xiao, Zian; Chen, Xing; Xie, Dinghua

    2014-02-01

    Cholesteatoma is a benign keratinizing squamous epithelial lesion characterized by the hyper-proliferation of keratinocytes with abundant production of keratin debris in the middle ear. The epidermal growth factor receptor (EGFR)/Akt/nuclear factor-kappa B (NF-κB)/cyclinD1 signaling pathway is one of the most important pathways in regulating cell survival and proliferation. We hypothesized that the EGFR/Akt/NF-κB/cyclinD1 signaling pathway may be activated and involved in the cellular hyperplasia mechanism in acquired cholesteatoma epithelium. Immunohistochemical staining of phosphorylated EGFR (p-EGFR), phosphorylated Akt (p-Akt), activated NF-κB and cyclinD1 protein was performed in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium. Protein expression of p-EGFR, p-Akt, activated NF-κB and cyclinD1 in cholesteatoma epithelium was significantly increased when compared with normal EAC epithelium (p < 0.01). In cholesteatoma epithelium, a significant positive association was observed between p-EGFR and p-Akt expression and between the expressions of p-Akt and NF-κB, NF-κB and cyclinD1, respectively (p < 0.01). No significant relationships were observed between the levels of investigated proteins and the degree of bone destruction (p > 0.05). The increased protein expression of p-EGFR, p-Akt, NF-κB and cyclinD1 and their associations in cholesteatoma epithelium suggest that the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway is active and may be involved in the regulatory mechanisms of cellular hyperplasia in cholesteatoma epithelium.

  13. Reduced expression of cytokeratin 4 and 13 is a valuable marker for histologic grading of esophageal squamous intraepithelial neoplasia.

    PubMed

    Takashima, Masaki; Kawachi, Hiroshi; Yamaguchi, Tsukasa; Nakajima, Yutaka; Kitagaki, Keisuke; Sekine, Masaki; Iida, Tadatsune; Takemura, Kosuke; Kawano, Tatsuyuki; Eishi, Yoshinobu

    2012-03-13

    Histologic evaluation of low-grade or high-grade intraepithelial neoplasia (LG-IN or HG-IN) of the esophagus is important for estimating the risk of progression to invasive carcinoma. Discrimination between LG-IN and HG-IN, or neoplasia and non-neoplastic lesion (NNL), however, is occasionally difficult. This study was designed to evaluate whether cytokeratin expression can be used for discrimination of these lesions. Esophageal Iodine-unstained lesions (n=154), less than 10 mm, were classified into HG-IN, LG-IN, and NNL. These lesions together with 154 foci of normal esophageal epithelium (NEE) were examined by immunohistochemistry for cytokeratins (CK4 and CK13), p53 overexpression, and the MIB-1 labeling index. The ratios of CK4- and CK13-positive staining were scored from 1 to 3. The CK4- and CK13-positive staining ratios were decreased in NNL (73% and 78%), LG-IN (55% and 69%), and HG-IN (33% and 48%), compared to NEE (91% and 95%). The differences between LG-IN and HG-IN, neoplasia and NNL, and among these three lesions and NEE were statistically significant (p < 0.005). The cytokeratin scores correlated with the MIB-1 labeling index (both: p < 0.0001), but not with p53 overexpression. CK4 and CK13 immunohistochemistry could be an objective method for evaluating the risk for progression to invasive carcinoma.

  14. Classification of Tumor Histology via Morphometric Context.

    PubMed

    Chang, Hang; Borowsky, Alexander; Spellman, Paul; Parvin, Bahram

    2013-06-23

    Image-based classification of tissue histology, in terms of different components (e.g., normal signature, categories of aberrant signatures), provides a series of indices for tumor composition. Subsequently, aggregation of these indices in each whole slide image (WSI) from a large cohort can provide predictive models of clinical outcome. However, the performance of the existing techniques is hindered as a result of large technical and biological variations that are always present in a large cohort. In this paper, we propose two algorithms for classification of tissue histology based on robust representations of morphometric context, which are built upon nuclear level morphometric features at various locations and scales within the spatial pyramid matching (SPM) framework. These methods have been evaluated on two distinct datasets of different tumor types collected from The Cancer Genome Atlas (TCGA), and the experimental results indicate that our methods are (i) extensible to different tumor types; (ii) robust in the presence of wide technical and biological variations; (iii) invariant to different nuclear segmentation strategies; and (iv) scalable with varying training sample size. In addition, our experiments suggest that enforcing sparsity, during the construction of morphometric context, further improves the performance of the system.

  15. Gross anatomy and histology of the olfactory rosette of the shark Heptranchias perlo.

    PubMed

    Ferrando, Sara; Gallus, Lorenzo; Amaroli, Andrea; Gambardella, Chiara; Waryani, Baradi; Di Blasi, Davide; Vacchi, Marino

    2017-02-17

    Sharks belonging to the family Hexanchidae have six or seven gill slits, unlike all other elasmobranchs, which have five gill slits. Their olfactory organs have a round shape, which is common for holocephalans, but not for elasmobranchs. Thus, the shape of the olfactory organ represents a further, less striking, peculiarity of this family among elasmobranchs. Despite that, the microscopic anatomy and histology of the olfactory organ have not yet been studied in any species of this family. Here, an anatomical and histological description of the olfactory organ of the sharpnose sevengill shark Heptranchias perlo is given. The organ is a rosette, with a central raphe and 31-34 primary lamellae, which bear secondary lamellae with a more or less branched shape. The elastic connective capsule which envelops the olfactory rosette possibly changes its shape along with water influx. In the olfactory epithelium, the supporting cells also have a secretory function, while no specialized mucous cells are visible; regarding this feature the olfactory epithelium of H. perlo differs from that of other chondrichthyan species. The immunohistochemical investigation of the sensory epithelium shows the absence of immunoreactivity for Gαolf in receptor neurons, which confirms previous observations in Chondrichthyes.

  16. Acid phosphatase and lipid peroxidation in human cataractous lens epithelium.

    PubMed

    Vasavada, A R; Thampi, P; Yadav, S; Rawal, U M

    1993-12-01

    The anterior lens epithelial cells undergo a variety of degenerative and proliferative changes during cataract formation. Acid phosphatase is primarily responsible for tissue regeneration and tissue repair. The lipid hydroperoxides that are obtained by lipid peroxidation of polysaturated or unsaturated fatty acids bring about deterioration of biological membranes at cellular and tissue levels. Acid phosphatase and lipid peroxidation activities were studied on the lens epithelial cells of nuclear cataract, posterior subcapsular cataract, mature cataract, and mixed cataract. Of these, mature cataractous lens epithelium showed maximum activity for acid phosphatase (516.83 moles of p-nitrophenol released/g lens epithelium) and maximum levels of lipid peroxidation (86.29 O.D./min/g lens epithelium). In contrast, mixed cataractous lens epithelium showed minimum activity of acid phosphatase (222.61 moles of p-nitrophenol released/g lens epithelium) and minimum levels of lipid peroxidation (54.23 O.D./min/g lens epithelium). From our study, we correlated the maximum activity of acid phosphatase in mature cataractous lens epithelium with the increased areas of superimposed cells associated with the formation of mature cataract. Likewise, the maximum levels of lipid peroxidation in mature cataractous lens epithelium was correlated with increased permeability of the plasma membrane. Conversely, the minimum levels of lipid peroxidation in mixed cataractous lens epithelium makes us presume that factors other than lipid peroxidation may also account for the formation of mixed type of cataract.

  17. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia

    PubMed Central

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E.; Ablonczy, Zsolt

    2016-01-01

    In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA), suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro) and fluid transport (in vivo). Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina. PMID:27617745

  18. Immunolocalization of NGF and its Receptors in Ovarian Surface Epithelium of the Wild Ground Squirrel during the Breeding and Nonbreeding Seasons

    PubMed Central

    Bao, L.; Li, Q.; Liu, Y.; Li, B.; Sheng, X.; Han, Y.; Weng, Q.

    2014-01-01

    The ovarian surface epithelium (OSE) plays an important role in normal ovarian physiology. During each reproductive cycle, the OSE takes part in the cyclical ovulatory ruptures and repair. The aim of this study was to investigate the immunolocalization of nerve growth factor (NGF) and its receptors, tyrosine kinase A (TrkA) and p75, in the OSE cells of the wild ground squirrels during the breeding and nonbreeding seasons. There were marked variations in ovarian weight and size between the breeding and the nonbreeding seasons. Histologically, cuboidal cells and squamous cells were identified in the OSE of both seasons. Yet, stronger immunostaining of NGF, TrkA and p75 were observed in cuboidal cells and squamous cells in the breeding season as compared to the nonbreeding season. In addition, plasma gonadotropin concentrations were higher in the breeding season than in the nonbreeding season, suggesting that the expression patterns of NGF, TrkA and p75 in the OSE were correlated with changes in plasma gonadotropins. These findings suggested that NGF and its receptor TrkA and p75 may be involved in the regulation of seasonal changes in the OSE of wild ground squirrel. PMID:24998925

  19. Immunolocalization of NGF and its receptors in ovarian surface epithelium of the wild ground squirrel during the breeding and nonbreeding seasons.

    PubMed

    Bao, L; Li, Q; Liu, Y; Li, B; Sheng, X; Han, Y; Weng, Q

    2014-05-09

    The ovarian surface epithelium (OSE) plays an important role in normal ovarian physiology. During each reproductive cycle, the OSE takes part in the cyclical ovulatory ruptures and repair. The aim of this study was to investigate the immunolocalization of nerve growth factor (NGF) and its receptors, tyrosine kinase A (TrkA) and p75, in the OSE cells of the wild ground squirrels during the breeding and nonbreeding seasons. There were marked variations in ovarian weight and size between the breeding and the nonbreeding seasons. Histologically, cuboidal cells and squamous cells were identified in the OSE of both seasons. Yet, stronger immunostaining of NGF, TrkA and p75 were observed in cuboidal cells and squamous cells in the breeding season as compared to the nonbreeding season. In addition, plasma gonadotropin concentrations were higher in the breeding season than in the nonbreeding season, suggesting that the expression patterns of NGF, TrkA and p75 in the OSE were correlated with changes in plasma gonadotropins. These findings suggested that NGF and its receptor TrkA and p75 may be involved in the regulation of seasonal changes in the OSE of wild ground squirrel.in the OSE of wild ground squirrel.

  20. Adapting lean to histology laboratories.

    PubMed

    Buesa, René J

    2009-10-01

    Histology laboratories (histolabs) can increase productivity and reduce turnaround time and errors by using any one of several available management tools. After a few years of operation, all histolabs develop workflow problems. Histology laboratories handling more than 20,000 cases per year benefit the most from implementing management tools, as occurred in the 25 facilities summarized in this article. Discontinuous workflow, lack of "pulling" between steps, accepting unavoidable waiting times while working with small batches within work cells, and a workflow with an uneven rate of completion, are some of the adaptations required by the Lean system when it is used in histology because 70% of the tasks are manual and the flow has to be interrupted to add value to the pieces of tissue during tissue processing, no matter how short that step is. After all these adaptations are incorporated, the histolab becomes as "Lean" as it can be, and the qualifier is also a recognition of the effort and personnel involvement in the implementation. Given its service nature, productivity increments do not expand the histolab customer base and could lead to staffing reductions. This is one of the causes of reluctance by some employees for implementing these techniques which are mostly driven by cost reductions sought by insurance companies and administrators, and not necessarily because of a real medical need to reduce the turnaround time. Finally, any histolab wanting to improve its workflow can follow some easy steps presented here as a guide to accomplish that objective. These steps stress the need for the supervisors to insure that the personnel in the histology laboratory are being paid at a comparable rate as other histolabs in the area.

  1. Effect of Pregnancy on Vocal Cord Histology: An Animal Experiment

    PubMed Central

    Köybaşı Şanal, Serap; Biçer, Yusuf Özgür; Kükner, Aysel; Tezcan, Erkan

    2016-01-01

    Background: Voice may be affected during the period of pregnancy, especially in the third trimester. However, the exact mechanisms leading to the phonatory changes have not yet uncovered. Aims: The aim of this study is to investigate the possible histological changes in the vocal cords of the pregnant rats in three separate trimesters. Study Design: Animal experiment. Methods: Twenty-five Wistar-Albino female rats were divided into four groups: control group, pregnancy day 7 (Group 1), pregnancy day 14 (Group 2) and pregnancy day 20 (Group 3). The laryngeal specimens were obtained under general anesthesia. Histological assessment was performed using Hematoxylin-eosin and toluidine blue. A stereological analysis of vocal cord tissue was performed using a NIS-Elements D32 Imaging Software. Results: Lamina propria was observed to be edematous, and the lamina propria area was thickened starting from the second trimester. Glycosaminoglycans were observed to increase in the second trimester. Although none was encountered in the control, mast cells were observed in the lamina propria layer of the vocal cord starting in the muscular layer in the first trimester proceed to the subepithelial region as degranulated just before term. The covering epithelium remained unchanged throughout pregnancy. Conclusion: Lamina propria thickening may be attributed to both edema and increased glycosaminoglycans. The presence of mast cells in the cordal tissue may induce edema during pregnancy in rats. PMID:27606142

  2. Impact of fine needle aspiration (FNA) and of the number of punctures on the feline testis: clinical, gross anatomy and histological assessment.

    PubMed

    Gouletsou, Pagona G; Galatos, Apostolos D; Sideri, Aikaterini I; Kostoulas, Polychronis

    2012-07-01

    The safety of testicular fine needle aspiration (FNA) has been proven in dogs but has not been fully established in men, while studies in rats have given contradictory results. Furthermore, the extent of damage inflicted by multiple punctures is unknown. The aim of this study was to determine the impact of FNA and of the number of punctures on the feline testis with clinical, gross anatomy and histological examinations. Twenty-seven sexually mature healthy laboratory Domestic Shorthair cats were randomly assigned to two groups: 5 cats in which no FNA was performed (control group), and 22 cats which had their left and right testis punctured with a 26 ga needle towards 3 and 8 directions, respectively (experimental group). Two cats at a time were orchiectomized 5 or 30 min, 1, 2, 4, 7 or 14 days or 1, 2, 3 or 4 mo post-aspiration. The cats of the control group were also orchiectomized. During the first week post-aspiration clinical examination revealed vaginal cavity hematoma (8/44 testes), while the histological findings were focal hemorrhagic areas (20/24 testes), erythrocytes inside the seminiferous tubules' lumen (9/24 testes), and germinal cell degeneration in <1.94% of the seminiferous tubules (15/24 testes). After the first week the histological findings were germinal cell degeneration in <2.14% of the seminiferous tubules (19/20 testes) and enlargement of the lumen of <5.16% of the seminiferous tubules (7/20 testes). The germinal epithelium and interstitium had an overall normal appearance. No significant differences were observed between the left and right testis. The results of the study indicate that testicular FNA should be considered a safe procedure in the cat when up to 8 punctures are performed.

  3. Histochemical profiles of mucins in the tracheal epithelium during the posthatching period of Japanese quail.

    PubMed

    Alan, Emel; Liman, Narin

    2010-01-01

    Mucus normally protects the airway epithelium from dehydration and inhaled infectious agents and possibly toxic substances. Two components of mucus, mucin and water play major roles in the elimination of inhaled foreign material. Mucins are large carbohydrates rich glycoprotein. The objective of the present study was to determine the histochemical changes in mucin pattern of the goblet cells and intraepithelial glands of the trachea in quails during the post-hatching period using specific various staining procedures for complex carbohydrates (Periodic acid Schiff, Alcian blue-Periodic acid Schiff (pH 2.5), Aldehyde fuchsin-Alcian blue (pH 2.5), High-iron diamine-Alcian blue (pH 2.5), Periodic acid-Phenylhydrazine-Schiff). The intraepithelial alveolar glands were present at hatching and their numbers increased with the advance of age. In quail of all ages, the histochemical reactions revealed that the goblet cells and mucous cells of intraepithelial glands contained the mucins with vicinal diol groups, neutral mucin, sialomucin and sulphomucin. In all ages studied, the tracheal epithelium contained three distinct types of goblet or mucous cells producing neutral-, acid- and mixture of neutral- and acid mucins. In 1 day old, the majority of the goblet cells and gland cells contained neutral mucin or a mixture of neutral- and acid mucins, while the proportion of only acid mucin-producing cells was few. The majority of acidic mucins consisted of sulphomucin. The sialomucin-containing cells were only a few. After day 14, it was seen that the content of sialomucin in the epithelium became more diffuse toward adulthood. In conclusion, the content of mucin of tracheal epithelium was variable depending on the ages during the post-hatching period. These changes in mucin dynamics could affect the protective functions against pathogens and toxins of the tracheal epithelium.

  4. Cytological evaluation of spermatogenesis and organization of the germinal epithelium in the male slider turtle, Trachemys scripta.

    PubMed

    Gribbins, Kevin M; Gist, Daniel H; Congdon, Justin D

    2003-03-01

    The germ cell development in the slider turtle (Trachemys scripta) testis was investigated by viewing the histology of the seminiferous epithelium in plastic sections with a light microscope. Germ cell morphologies in the slider turtle testis were similar to the morphologies of other vertebrate germ cell types. However, the slider turtle seminiferous epithelium contained germ cells that progress through spermatogenesis in a temporal rather than a spatial pattern, resulting in a single spermatogenic event that climaxed with one massive sperm release in November. Mature sperm then are stored within the epididymis until breeding commences in the following spring. The germ cell development strategy in the slider turtle is different from that of other amniotes and is more reminiscent of the developmental strategy found in the anamniotic testis. This temporal progression of germ cells through spermatogenesis within a tubular testis represents a transitional model that may be evolutionarily significant.

  5. Forensic value of the Lugol's staining method: further studies on glycogenated epithelium in the male urinary tract.

    PubMed

    Hausmann, R; Schellmann, B

    1994-01-01

    This study presents findings from a series of investigations on the presence of glycogenated epithelium in the male urinary tract and on the penile surface in order to assess the forensic value of the Lugol's method for the identification of vaginal cells. Direct smears obtained from the urethral opening, glans penis, and penile shaft, along with post-mortem samples of the fossa navicularis, and histological sections of the penis were examined. The presence of polygonal, glycogenated, Lugol-positive epithelium cells in the male urinary tract was found to be common. Our results suggest that these cells originate from the fossa navicularis. Because of the possibility of exfoliation of glycogenated male cells and transfer to the penile surface a Lugol-positive reaction in epithelial cells on penile swabs can no longer be assumed to prove the presence of vaginal cells.

  6. Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision

    NASA Astrophysics Data System (ADS)

    Cursiefen, Claus; Chen, Lu; Saint-Geniez, Magali; Hamrah, Pedram; Jin, Yiping; Rashid, Saadia; Pytowski, Bronislaw; Persaud, Kris; Wu, Yan; Streilein, J. Wayne; Dana, Reza

    2006-07-01

    Transparency of the cornea, the window of the eye, is a prerequisite for vision. Angiogenesis into the normally avascular cornea is incompatible with good vision and, therefore, the cornea is one of the few tissues in the human body where avascularity is actively maintained. Here, we provide evidence for a critical mechanism contributing to corneal avascularity. VEGF receptor 3, normally present on lymphatic and proliferating blood vascular endothelium, is strongly constitutively expressed by corneal epithelium and is mechanistically responsible for suppressing inflammatory corneal angiogenesis. angiogenesis | cornea | lymphatics | inflammation

  7. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma

    PubMed Central

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R.; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A.; Bielenberg, Diane R.

    2017-01-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. PMID:26877262

  8. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    PubMed

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.

  9. Histology of the mucosa of the oesophagogastric junction and the stomach in adult Rana perezi.

    PubMed Central

    Gallego-Huidobro, J; Pastor, L M

    1996-01-01

    The histological structure of the frog digestive mucosa changes at the oesophagogastric junction. The pseudostratified ciliated mucosal epithelium of oesophageal type changes to a simple mucus-secreting epithelium of gastric type. The glands straighten and the muscularis mucosae develops as a complete layer. The muscularis increases in thickness. Unlike the mammalian stomach, in the frog the surface of the plicae forms convoluted ridges that delimit furrow-shaped pits. Two types of gastric glands are distinguished, fundal and pyloric. The former consist of mucous, oxynticopeptic and endocrine cells. The pyloric glandular cells are mainly of mucus-secreting type with scattered endocrine cells. Scattered endocrine cells of P, D, G, A, EC, and EC-L-like types are found in the glands along the stomach. It is concluded that the mucosal structure of the anuran oesophagogastric junction and stomach is less complicated than that of mammals, including man. Images Fig. 1 Fig. 2 PMID:8621343

  10. Localization and expression of zonula occludins-1 in the rabbit corneal epithelium following exposure to benzalkonium chloride.

    PubMed

    Chen, Wensheng; Hu, Jiaoyue; Zhang, Zhenhao; Chen, Lelei; Xie, Hui; Dong, Nuo; Chen, Yongxiong; Liu, Zuguo

    2012-01-01

    Preservatives are a major component of the ophthalmic preparations in multi-dose bottles. The purpose of this study was to investigate the acute effect of benzalkonium chloride (BAC), a common preservative used in ophthalmic preparations, on the localization and expression of zonula occludens (ZO)-1 in the rabbit corneal epithelium in vivo. BAC at 0.005%, 0.01%, or 0.02% was topically applied to one eye each of albino rabbits at 5 min intervals for a total of 3 times. The contralateral untreated eyes served as controls. The following clinical indications were evaluated: Schirmer test, tear break-up time (BUT), fluorescein and rose Bengal staining. The structure of central cornea was examined by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance and permeability to carboxy fluorescein. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of ZO-1, 2, occludin, claudin-1, Ki67 and cell apoptosis in the epithelium. The expression of ZO-1 in the corneal epithelium was also examined by western blot and reverse transcription-polymerase chain reaction analyses. Exposure to BAC resulted in higher rose Bengal staining scores while no significant changes in BUT, Schirmer and corneal florescein scores. It also induced corneal epithelial cell damage, dispersion of ZO-1 and ZO-2 from their normal locus at the superficial layer and disruption of epithelial barrier function. However, the amounts of ZO-1 mRNA and protein in the corneal epithelium were not affected by BAC treatment. Exposure to BAC can quickly impair the corneal epithelium without tear deficiency. BAC disrupts the tight junctions of corneal epithelium between superficial cells in the rabbit corneal epithelium in vivo.

  11. Localization and Expression of Zonula Occludins-1 in the Rabbit Corneal Epithelium following Exposure to Benzalkonium Chloride

    PubMed Central

    Zhang, Zhenhao; Chen, Lelei; Xie, Hui; Dong, Nuo; Chen, Yongxiong; Liu, Zuguo

    2012-01-01

    Preservatives are a major component of the ophthalmic preparations in multi-dose bottles. The purpose of this study was to investigate the acute effect of benzalkonium chloride (BAC), a common preservative used in ophthalmic preparations, on the localization and expression of zonula occludens (ZO)-1 in the rabbit corneal epithelium in vivo. BAC at 0.005%, 0.01%, or 0.02% was topically applied to one eye each of albino rabbits at 5 min intervals for a total of 3 times. The contralateral untreated eyes served as controls. The following clinical indications were evaluated: Schirmer test, tear break-up time (BUT), fluorescein and rose Bengal staining. The structure of central cornea was examined by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance and permeability to carboxy fluorescein. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of ZO-1, 2, occludin, claudin-1, Ki67 and cell apoptosis in the epithelium. The expression of ZO-1 in the corneal epithelium was also examined by western blot and reverse transcription-polymerase chain reaction analyses. Exposure to BAC resulted in higher rose Bengal staining scores while no significant changes in BUT, Schirmer and corneal florescein scores. It also induced corneal epithelial cell damage, dispersion of ZO-1 and ZO-2 from their normal locus at the superficial layer and disruption of epithelial barrier function. However, the amounts of ZO-1 mRNA and protein in the corneal epithelium were not affected by BAC treatment. Exposure to BAC can quickly impair the corneal epithelium without tear deficiency. BAC disrupts the tight junctions of corneal epithelium between superficial cells in the rabbit corneal epithelium in vivo. PMID:22815857

  12. Morphological and histological characterization of production structures, storage and distribution of venom in the parasitic wasp Bracon vulgaris.

    PubMed

    Alves, Thiago J S; Wanderley-Teixeira, Valéria; Teixeira, Álvaro A C; Alves, Luiz C; Araújo, Breno C; Barros, Eduardo M; Cunha, Franklin M

    2015-12-15

    It was described the morphology and histological composition of the structures related to production, storage and distribution of Bracon vulgaris venom, a wasp that parasite their hosts after the inoculation of a venom which causes irreversible paralysis. Were found 22 glandular filaments, coated with secretory epithelium associated with a reservoir coated internally by a chitin layer and externally by striated muscular fibers. A valve mediates the passage of the toxin to venom duct towards the parasitoids sting.

  13. Challenges and opportunities for tissue-engineering polarized epithelium.

    PubMed

    Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

    2014-02-01

    The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

  14. Histologic evaluation of an Nd:YAG laser-assisted new attachment procedure in humans.

    PubMed

    Yukna, Raymond A; Carr, Ronald L; Evans, Gerald H

    2007-12-01

    This report presents histologic results in humans following a laser-assisted new attachment procedure (LANAP) for the treatment of periodontal pockets. Six pairs of single-rooted teeth with moderate to advanced chronic periodontitis associated with subgingival calculus deposits were treated. A bur notch was placed within the pocket at the clinically and radiographically measured apical extent of calculus. All teeth were scaled and root planed with ultrasonic and hand scalers. One of each pair of teeth received treatment of the inner pocket wall with a free-running pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to remove the pocket epithelium, and the test pockets were lased a second time to seal the pocket. After 3 months, all treated teeth were removed en bloc for histologic processing. LANAP-treated teeth exhibited greater probing depth reductions and clinical probing attachment level gains than the control teeth. All LANAP-treated specimens showed new cementum and new connective tissue attachment in and occasionally coronal to the notch, whereas five of the six control teeth had a long junctional epithelium with no evidence of new attachment or regeneration. There was no evidence of any adverse histologic changes around the LANAP specimens. These cases support the concept that LANAP can be associated with cementum-mediated new connective tissue attachment and apparent periodontal regeneration of diseased root surfaces in humans.

  15. Expression of Ia antigens by murine kidney epithelium after exposure to streptozotocin.

    PubMed Central

    Farr, A. G.; Mannschreck, J. W.; Anderson, S. K.

    1987-01-01

    In the normal murine kidney, Ia antigens are expressed by dendritic cells located within the interstitial connective tissue and scattered cells within the glomerulus. After receiving multiple low doses of streptozotocin, a nitrosourea derivative of glucose, kidney epithelium labeled intensely with anti-Ia antibodies. Ultrastructural immunohistochemistry indicated that the epithelial cells of the proximal convoluted tubules expressed Ia antigens on their basolateral surfaces while remaining Ia- on their luminal surfaces. This response to streptozotocin does not appear to be related to the diabetogenic potential of the drug, because BALB/cJ mice, which remain normoglycemic after treatment with streptozotocin, also exhibited strongly Ia+ tubular epithelium after treatment with streptozotocin. Images Figure 1 Figure 2 Figure 3 PMID:2950766

  16. Testosterone-induced "Virilization" of Mesonephric Duct Remnants and Cervical Squamous Epithelium in Female-to-Male Transgenders: A Report of 3 Cases.

    PubMed

    Singh, Kamaljeet; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

    2016-08-26

    Mesonephric ducts regress in genotypic females, leaving behind few remnants. These vestigial structures are often recognized in the mesosalpinx and paracervical regions. We report here 3 cases of female-to-male transgenders who underwent hysterectomy following testosterone treatment. Both female and male genital structures were identified on histologic examination. Although the morphologic appearances of the specimens were unremarkable, histologically 1 case revealed a well-formed fallopian tube as well as an epididymis and 2 cases showed prostate glands to be present in the cervical squamous epithelium.

  17. Bronchial epithelium in children: a key player in asthma.

    PubMed

    Carsin, Ania; Mazenq, Julie; Ilstad, Alexandra; Dubus, Jean-Christophe; Chanez, Pascal; Gras, Delphine

    2016-06-01

    Bronchial epithelium is a key element of the respiratory airways. It constitutes the interface between the environment and the host. It is a physical barrier with many chemical and immunological properties. The bronchial epithelium is abnormal in asthma, even in children. It represents a key component promoting airway inflammation and remodelling that can lead to chronic symptoms. In this review, we present an overview of bronchial epithelium and how to study it, with a specific focus on children. We report physical, chemical and immunological properties from ex vivo and in vitro studies. The responses to various deleterious agents, such as viruses or allergens, may lead to persistent abnormalities orchestrated by bronchial epithelial cells. As epithelium dysfunctions occur early in asthma, reprogramming the epithelium may represent an ambitious goal to induce asthma remission in children.

  18. [The new era of epithelium-targeted drug development].

    PubMed

    Shimizu, Yoshimi; Nagase, Shotaro; Yagi, Kiyohito; Kondoh, Masuo

    2014-01-01

    Epithelium plays pivotal roles in biological barrier separating the inside of body and the outside environment. Ninety percent of malignant tumors are derived from epithelium. Most pathological microorganisms invade into the body from mucosal epithelium. Thus, epithelium is potential targets for drug development. Claudins (CLs), a family of tetra-transmembrane protein consisting of over 20 members, are structural and functional components of tight junction-seals in epithelium. Modulation of CL-seals enhanced mucosal absorption of drugs. CLs are often over-expressed in malignant tumors. CL-4 expression is increased in the epithelial cells covering the mucosal immune tissues. Very recently, CLs are also expected to be targets for traumatic brain injury and regenerative therapy. In this review, we overview the past, the present and the future of CLs-targeted drug development.

  19. A three-dimensional study of human fetal endocervix with special reference to its epithelium.

    PubMed

    Barberini, F; Makabe, S; Motta, P M

    1998-07-01

    The development of human fetal cervix has been systematically studied by SEM, obtaining a detailed map of its fine structure, particularly concerning the differentiation and maturation of the endocervical epithelium, including its "eversion" and "squamous metaplasia", normally occurring in postnatal life, but not yet observed in detail by electron microscopy in the fetus. Cervices from spontaneous abortion at 12, 15, 18, 20, 21 and 22 weeks and from intrauterine fetal death (hydrocephalus) at 31 weeks of development have been examined. At 12-15 weeks, as the canalization of the cervix proceeded, the endocervical epithelium consisted of high polyhedral cells, with regularly flattened or concave apices exhibiting scarce microvilli and often single primary cilia. Some narrow intercellular infoldings probably corresponded to primordial tubular glands. At the 18th week the epithelium was made up of a mosaic of flat or slightly raised polygonal cells, whose apical surface showed thin microplicae. At the 20th week a pseudostratified epithelium with many apically convex cells lined the cervical canal and the tubular glands. At 21 and 22 weeks "plicae palmatae" developed, covered by cells, often showing a smooth central area surrounded by microvilli, provided with a primary cilium and swollen by secretory material. This also formed rounded masses on the epithelium. In the lower part of the endocervix some very elongated cells showed short microplicae resulting from fusion of microvilli. At the 31st week secretion increased and its products spreading from the bottom of the glands contacted isolated ciliated cells at their openings and diffusely covered the surface epithelium. Most of the ectocervix exhibited squamous elements, with well-developed labyrinthine microplicae. These cells could overlap each other and also desquamate. The zone of the portio vaginalis around the os of the cervical canal appeared infolded and hypertrophic. Here, an indented squamo-columnar junction

  20. Vasopressin regulates the growth of the biliary epithelium in polycystic liver disease.

    PubMed

    Mancinelli, Romina; Franchitto, Antonio; Glaser, Shannon; Vetuschi, Antonella; Venter, Julie; Sferra, Roberta; Pannarale, Luigi; Olivero, Francesca; Carpino, Guido; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

    2016-11-01

    The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium.

  1. An immunohistological study of cytokeratin 20 in human and mammalian oral epithelium.

    PubMed

    Barrett, A W; Cort, E M; Patel, P; Berkovitz, B K

    2000-10-01

    Cytokeratin (CK) 20 is a low molecular-weight intermediate filament reportedly expressed only by benign and malignant gastrointestinal epithelium, urothelium and Merkel cells. The main aims here were to map its expression in normal oral mucosa of humans and other mammals, and to determine whether it was expressed by abnormal human oral epithelium. Salivary and odontogenic epithelium were also analysed. An immunoperoxidase method was used on wax-embedded and cryostat sections. In addition, double-labelling experiments were undertaken to determine the association between CK 20 expression and that of CK 8/18 or S100 protein. Normal human oral mucosa from four sites, together with abdominal skin, was studied in autopsy samples from 32 individuals. CK 20-positive, basally situated, round or angular cells, consistent with Merkel cells, were recorded in 24/32 (75.0%) samples of mandibular gingiva, 25/32 (78.1%) samples of hard palate, 7/32 (21.9%) samples of buccal mucosa, 0/32 samples of lateral border of tongue, and 2/32 (6.3%) samples of abdominal skin. Double-labelling showed that all CK 20-positive Merkel cells also expressed CK 8/18 and S100. The only other cells to express CK 20 were human taste buds. There was no expression by dysplastic or invasive oral epithelium from biopsy samples. Colonic mucosa showed luminal-cell positivity in man, marmoset, ferret, rabbit and guinea-pig, but oral mucosa was universally negative in non-human species. It is concluded that in oral mucosa CK 20 is a specific marker of Merkel cells and taste buds, that Merkel cells are more frequently present in keratinized than non-keratinized oral mucosa, that CK 20-positive Merkel cells are also S100-positive, that there may be interspecies variations in CK 20 polypeptide composition and that, by contrast to urothelium, CK 20 has no value in the diagnosis of oral epithelial dysplasia.

  2. Coeliac disease: the histology report.

    PubMed

    Villanacci, Vincenzo; Ceppa, Paola; Tavani, Enrico; Vindigni, Carla; Volta, Umberto

    2011-03-01

    To this day intestinal biopsy is justly considered the "gold standard" for the diagnosis of coeliac disease (CD). The aim of the authors in setting up these guidelines was to assist pathologists in formulating a more precise morphological evaluation of a duodenal biopsy in the light of clinical and laboratory data, to prepare histological samples with correctly oriented biopsies and in the differential diagnosis with other pathological entities and complications of the disease. A further intention was to promote the conviction for the need of a close collaborative relationship between different specialists namely the concept of a "multidisciplinary team".

  3. Gastric lymphoma: the histology report.

    PubMed

    Doglioni, Claudio; Ponzoni, Maurilio; Ferreri, Andrés J M; Savio, Antonella

    2011-03-01

    The diagnosis of gastric MALT lymphoma is frequently difficult for the general histopathologist. During recent years there have been relevant changes in the therapeutic approach to gastric MALT lymphoma and our knowledge about its pathogenesis has greatly improved. The management of this disease actually requires a close cooperation between the histopathologist and the clinicians. The histology report of biopsies of a newly diagnosed or of an already treated case implies information of clinical and therapeutical relevance. This paper aims at giving the histopathologist a general knowledge about the state of art of this disease and its management. The diagnostic process leading to a complete and competent report is then described step by step.

  4. Sox9 drives columnar differentiation of esophageal squamous epithelium: a possible role in the pathogenesis of Barrett's esophagus.

    PubMed

    Clemons, Nicholas J; Wang, David H; Croagh, Daniel; Tikoo, Anjali; Fennell, Christina M; Murone, Carmel; Scott, Andrew M; Watkins, D Neil; Phillips, Wayne A

    2012-12-15

    The molecular mechanism underlying the development of Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma, remains unknown. Our previous work implicated sonic hedgehog (Shh) signaling as a possible driver of BE and suggested that bone morphogenetic protein 4 (Bmp4) and Sox9 were downstream mediators. We have utilized a novel in vivo tissue reconstitution model to investigate the relative roles of Bmp4 and Sox9 in driving metaplasia. Epithelia reconstituted from squamous epithelial cells or empty vector-transduced cells had a stratified squamous phenotype, reminiscent of normal esophagus. Expression of Bmp4 in the stromal compartment activated signaling in the epithelium but did not alter the squamous phenotype. In contrast, expression of Sox9 in squamous epithelial cells induced formation of columnar-like epithelium with expression of the columnar differentiation marker cytokeratin 8 and the intestinal-specific glycoprotein A33. In patient tissue, A33 protein was expressed specifically in BE, but not in normal esophagus. Expression of Cdx2, another putative driver of BE, alone had no effect on reconstitution of a squamous epithelium. Furthermore, epithelium coexpressing Cdx2 and Sox9 had a phenotype similar to epithelium expressing Sox9 alone. Our results demonstrate that Sox9 is sufficient to drive columnar differentiation of squamous epithelium and expression of an intestinal differentiation marker, reminiscent of BE. These data suggest that Shh-mediated expression of Sox9 may be an important early event in the development of BE and that the potential for inhibitors of the hedgehog pathway to be used in the treatment of BE and/or esophageal adenocarcinoma could be tested in the near future.

  5. Trachea Epithelium as a “Canary” for Cigarette Smoking-induced Biologic Phenotype of the Small Airway Epithelium*

    PubMed Central

    Turetz, Meredith L.; O’Connor, Timothy P.; Tilley, Ann E.; Strulovici-Barel, Yael; Salit, Jacqueline; Dang, David; Teater, Matthew; Mezey, Jason; Clark, Andrew G.; Crystal, Ronald G.

    2013-01-01

    The initial site of smoking-induced lung disease is the small airway epithelium, which is difficult and time consuming to sample by fiberoptic bronchoscopy. We developed a rapid, office-based procedure to obtain trachea epithelium without conscious sedation from healthy nonsmokers (n=26) and healthy smokers (n=19, 27 ± 15 pack-yr). Gene expression differences (fold-change >1.5, p<0.01, Benjamini-Hochberg correction) were assessed with Affymetrix microarrays. 1,057 probe sets were differentially expressed in healthy smokers vs nonsmokers, representing >500 genes. Trachea gene expression was compared to an independent group of small airway epithelial samples (n=23 healthy nonsmokers, n=19 healthy smokers, 25 ± 12 pack-yr). The trachea epithelium is more sensitive to smoking, responding with 3-fold more differentially-expressed genes than small airway epithelium. The trachea transcriptome paralleled the small airway epithelium, with 156 of 167 (93%) genes that are significantly upand down-regulated by smoking in the small airway epithelium showing similar direction and magnitude of response to smoking in the trachea. Trachea epithelium can be obtained without conscious sedation, representing a less invasive surrogate “canary” for smoking-induced changes in the small airway epithelium. This should prove useful in epidemiologic studies correlating gene expression with clinical outcome in assessing smoking-induced lung disease. PMID:20443905

  6. Histology of the central nervous system.

    PubMed

    Garman, Robert H

    2011-01-01

    The intent of this article is to assist pathologists inexperienced in examining central nervous system (CNS) sections to recognize normal and abnormal cell types as well as some common artifacts. Dark neurons are the most common histologic artifact but, with experience, can readily be distinguished from degenerating (eosinophilic) neurons. Neuron degeneration stains can be useful in lowering the threshold for detecting neuron degeneration as well as for revealing degeneration within populations of neurons that are too small to show the associated eosinophilic cytoplasmic alteration within H&E-stained sections. Neuron degeneration may also be identified by the presence of associated macroglial and microglial reactions. Knowledge of the distribution of astrocyte cytoplasmic processes is helpful in determining that certain patterns of treatment-related neuropil vacuolation (as well as some artifacts) represent swelling of these processes. On the other hand, vacuoles with different distribution patterns may represent alterations of the myelin sheath. Because brains are typically undersampled for microscopic evaluation, many pathologists are unfamiliar with the circumventricuar organs (CVOs) that represent normal brain structures but are often mistaken for lesions. Therefore, the six CVOs found in the brain are also illustrated in this article.

  7. Tonic and Phasic Receptor Neurons in the Vertebrate Olfactory Epithelium

    PubMed Central

    Madrid, Rodolfo; Sanhueza, Magdalena; Alvarez, Osvaldo; Bacigalupo, Juan

    2003-01-01

    Olfactory receptor neurons (ORNs) respond to odorants with characteristic patterns of action potentials that are relevant for odor coding. Prolonged odorant exposures revealed three populations of dissociated toad ORNs, which were mimicked by depolarizing currents: tonic (TN, displaying sustained firing, 49% of 102 cells), phasic (PN, exhibiting brief action potential trains, 36%) and intermediate neurons (IN, generating trains longer than PN, 15%). We studied the biophysical properties underlying the differences between TNs and PNs, the most extreme cases among ORNs. TNs and PNs possessed similar membrane capacitances (∼4 pF), but they differed in resting potential (−82 versus −64 mV), input resistance (4.2 versus 2.9 GΩ) and unspecific current, Iu (TNs: 0 < Iu ≤ 1 pA/pF; and PNs: Iu > 1 pA/pF). Firing behavior did not correlate with differences in voltage-gated conductances. We developed a mathematical model that accurately simulates tonic and phasic patterns. Whole cell recordings from rat ORNs in fragments (∼4 mm2) of olfactory epithelium showed that such a tissue normally contains tonic and phasic receptor neurons, suggesting that this feature is common across a wide range of vertebrates. Our findings show that the individual passive electrical properties can govern the firing patterns of ORNs. PMID:12770919

  8. The multiple antibacterial activities of the bladder epithelium

    PubMed Central

    Wu, Jianxuan; Miao, Yuxuan

    2017-01-01

    The urinary tract is subject to frequent challenges from the gut microflora. Indeed, up to 40% of women will experience at least one urinary tract infection (UTI) during their lifetime. Uropathogenic Escherichia coli (UPEC) contribute to an overwhelming majority of these cases and they typically initiate UTIs by invading the superficial epithelium that lines the bladder lumen. In addition to serving as an effective barrier to noxious agents found in urine, bladder epithelial cells (BECs) play a key physiological role in regulating bladder volume to accommodate urine flow. UPEC appear to coopt this latter property to circumvent this normally impregnable epithelial barrier. However, in spite of this shortcoming, recent studies suggest that BECs possess several immune mechanisms to combat bacterial invasion including expulsion of invading bacteria back into the bladder lumen following infection. These antibacterial activities of BECs are triggered and coordinated by sensory molecules located on the epithelial cell membrane and within the cells. Although, they are the primary targets of microbial attack, BECs appear to be equipped with a diverse repertoire of defense schemes to fend off many of these microbial challenges. PMID:28217700

  9. Roles of lung epithelium in neutrophil recruitment during pneumococcal pneumonia.

    PubMed

    Yamamoto, Kazuko; Ahyi, Ayele-Nati N; Pepper-Cunningham, Zachary A; Ferrari, Joseph D; Wilson, Andrew A; Jones, Matthew R; Quinton, Lee J; Mizgerd, Joseph P

    2014-02-01

    Epithelial cells line the respiratory tract and interface with the external world. Epithelial cells contribute to pulmonary inflammation, but specific epithelial roles have proven difficult to define. To discover unique epithelial activities that influence immunity during infection, we generated mice with nuclear factor-κB RelA mutated throughout all epithelial cells of the lung and coupled this approach with epithelial cell isolation from infected and uninfected lungs for cell-specific analyses of gene induction. The RelA mutant mice appeared normal basally, but in response to pneumococcus in the lungs they were unable to rapidly recruit neutrophils to the air spaces. Epithelial cells expressed multiple neutrophil-stimulating cytokines during pneumonia, all of which depended on RelA. Cytokine expression by nonepithelial cells was unaltered by the epithelial mutation of RelA. Epithelial cells were the predominant sources of CXCL5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), whereas nonepithelial cells were major sources for other neutrophil-activating cytokines. Epithelial RelA mutation decreased whole lung levels of CXCL5 and GM-CSF during pneumococcal pneumonia, whereas lung levels of other neutrophil-recruiting factors were unaffected. Defective neutrophil recruitment in epithelial mutant mice could be rescued by administration of CXCL5 or GM-CSF. These results reveal a specialized immune function for the pulmonary epithelium, the induction of CXCL5 and GM-CSF, to accelerate neutrophil recruitment in the infected lung.

  10. The Role of the Papillary Epithelium in Stone Growth

    NASA Astrophysics Data System (ADS)

    Bergsland, Kristin J.

    2007-04-01

    The papillary surface epithelium (PSE) covers the renal papilla in mammalian kidneys and serves as a diffusion barrier between the urine on the apical surface and the interstitium on the basolateral surface. The PSE also plays a physiological role in transport of solutes between the urine and interstitium both by active transport and paracellular pathways. Permeability of the PSE may be affected by alterations in specific transporters, components of intercellular tight junctions, cell surface glycosaminoglycans and urine composition. In idiopathic calcium oxalate (CaOx) stone formers, apatite deposits known as Randall's plaque form in the papillary interstitium and lodge beneath the PSE. The presence of plaque may perturb the normal function of the PSE, possibly by provoking the up-regulation of pro-inflammatory cytokines such as TNFα in the interstitium. Disruption of the epithelial barrier may lead to increased permeability and exposure of the plaque matrix to urine constituents, followed by loss of the PSE and growth of CaOx stone over the plaque. To investigate the role of the PSE in stone development, new experimental systems are needed, including animal models of plaque formation as well as cell culture systems for papillary epithelial cells.

  11. Histology of the first fish

    USGS Publications Warehouse

    Smith, M.P.; Sansom, I.J.; Repetski, J.E.

    1996-01-01

    THE first description of Anatolepis Bockelie & Fortey was from early Ordovician sediments of Ny Friesland, Spitsbergen1,2, but the genus is now known from many localities in North America and Greenland, ranging in age from the Late Cambrian period to the Early Ordovician3-6. Although initially interpreted as an agnathan fish2,3 that predated other representatives7, this has been widely disputed because the available histological data were unconvincing6,8-10 and the scales fell outside the known morphological range of other accepted early vertebrates9-11. Further doubt was cast upon the vertebrate affinity of Anatolepis when specimens from East Greenland were interpreted as the cuticular fragments of aglaspid arthropods6, although this interpretation has also been refuted12. Here we report on the morphology and histology of large collections of Anatolepis, and demonstrate the presence of dentine, a tissue unique to vertebrates, confirming that the taxon is both a vertebrate and the oldest known fish.

  12. Phenotyping the claudin 11 deficiency in testis: from histology to immunohistochemistry.

    PubMed

    Mazaud-Guittot, Séverine; Gow, Alexander; Le Magueresse-Battistoni, Brigitte

    2011-01-01

    The testis is a heterogeneous organ that comprises a number of cell types, including germ cells at -different stages in their maturation, differentiated neighbor nursing cells, and endocrine somatic cells. Despite such cellular heterogeneity the testis is highly organized, with germ cell development and differentiation being compartmentalized into the interconnected tubular network of the seminiferous epithelium. Intratesticular scaffolds rely heavily on the basement membrane of the seminiferous tubules while germ cell development inside the seminiferous epithelium is critically dependent on the Blood Testis Barrier (BTB). The BTB is a macromolecular tight junction complex generated by somatic Sertoli cells within the seminiferous epithelium. The BTB divides the seminiferous epithelium into two compartments: the basal compartment, which delineates a niche for the proliferation and renewal of spermatogonia; and the adluminal compartment, where differentiating germ cells undergo meiosis and spermiogenesis. The BTB is unique in mammalian tissues because it is cyclically reconstructed during the spermatogenic cycle as preleptotene spermatocytes migrate from the basal compartment to the adluminal compartment and enter meiosis. In mouse, the loss of the BTB in the absence of the claudin 11 protein causes azoospermia and leads to infertility. Specifically, cldn11 deficiency results in sloughing of the cells of the seminiferous epithelium into the lumen. Understanding this pathophysiology has involved histological examination of the tissue defects as well as immunohistological characterization. Here, we present a comparative study of several modifications to the classical Hematoxylin-Eosin stain that may improve the diagnostic usefulness of this technique, as well as the use of several selective markers to identify testicular cell types.

  13. Effects of chronic 137Cs ingestion on barrier properties of jejunal epithelium in rats.

    PubMed

    Dublineau, I; Grison, S; Grandcolas, L; Baudelin, C; Paquet, F; Voisin, P; Aigueperse, J; Gourmelon, P

    2007-05-15

    Environmental contamination by 137Cs is of particular public health interest because of the various sources of fallout originating from nuclear weapons, radiological source disruptions, and the Chernobyl disaster. This dispersion may lead to a chronic ecosystem contamination and subsequent ingestion of contaminated foodstuffs. The aim of this study was to thus determine the impact of a chronic ingestion of low-dose 137Cs on small intestine functions in rats. The animals received 150 Bq per day in drinking water over 3 mo. At these environmental doses, 137Cs contamination did not modify the crypt and villus architecture. In addition, epithelial integrity was maintained following the chronic ingestion of 137Cs, as demonstrated by histological analyses (no breakdown of the surface mucosa) and electrical transepithelial parameters (no change in potential difference and tissue conductance). Furthermore, cesium contamination seemed to induce contradictory effects on the apoptosis pathway, with an increase in the gene expression of Fas/FasL and a decrease in the apoptotic cell number present in intestinal mucosa. No marked inflammation was observed following chronic ingestion of 137Cs, as indicated by neutrophil infiltration and gene expression of cytokines and chemokines. Results indicated no imbalance in the Th1/Th2 response induced by cesium at low doses. Finally, evaluation of the functionality of the jejunal epithelium in rats contaminated chronically with 137Cs did not demonstrate changes in the maximal response to carbachol, nor in the cholinergic sensitivity of rat jejunal epithelium. In conclusion, this study shows that chronic ingestion of 137Cs over 3 mo at postaccidental doses exerts few biological effects on the epithelium of rat jejunum with regard to morphology, inflammation status, apoptosis/proliferation processes, and secretory functions.

  14. Intestinal Bacterial Infection Diagnosed by Histological Examination of Endoscopic Biopsy Specimens

    PubMed Central

    Yuki, Michiko; Emoto, Yuko; Yoshizawa, Katsuhiko; Yuri, Takashi; Tsubura, Airo

    2016-01-01

    Intestinal spirochetosis (IS) in humans is characterized by spirochetal microorganisms attached to the luminal surface of the colonic epithelium. In the present case, attached organisms appeared as 3- to 4 μm-thick (average thickness, 3.4 μm) basophilic fringes or haze in HE-stained endoscopic biopsy specimens. The basophilic fringes were clearly labeled by Treponema pallidum antiserum. Because IS is relatively rare in developed countries, thin basophilic fringes characteristic of IS are readily overlooked. Thus, the recognition of histological characteristics of this disease is important for its diagnosis. PMID:27920653

  15. Effects of aging on mouse tongue epithelium focusing on cell proliferation rate and morphological aspects.

    PubMed

    Carrard, Vinicius Coelho; Pires, Aline Segatto; Badauy, Cristiano Macabu; Rados, Pantelis Varvaki; Lauxen, Isabel Silva; Sant'Ana Filho, Manoel

    2008-11-01

    The aim of this study was to investigate cell proliferation rate and certain morphological features of mouse epithelium as aging progresses. Tongue biopsies were performed on female mice (Mus domesticus domesticus) at 2, 8, 14 and 20 months of age as indicative of adolescence, adulthood, early senescence and senescence, respectively. Histological sections of tongue were stained with hematoxylin-eosin and subjected to silver staining for active nucleolar organizer region counting. Cell proliferation rate and epithelial thickness analysis were carried out. Analysis of variance detected no differences between the groups in terms of numbers of silver-stained dots associated with nucleolar proteins. There was an increase in mean epithelial thickness in adult animals, followed by a gradual reduction until senescence. Mean keratin thickness presented an increase at 8 and 20 months of age. This difference is probably related to puberty, growth or dietary habits. Aging has no influence on oral epithelial proliferation rate in mice. A gradual reduction in epithelial thickness is a feature of aging in mammals. A conspicuous increase in the keratin layer was observed in senescence as an adaptative response to the reduction in epithelial thickness. These results suggest that aging affects the oral epithelium maturation process through a mechanism that is not related to cell proliferation.

  16. Glandular Epithelium as a Possible Source of a Fertility Signal in Ectatomma tuberculatum (Hymenoptera: Formicidae) Queens

    PubMed Central

    da Hora, Riviane Rodigues; Delabie, Jacques Hubert Charles; dos Santos, Carolina Gonçalves; Serrão, José Eduardo

    2010-01-01

    The wax layer covering the insect's cuticle plays an important protective role, as for example, uncontrolled water loss. In social insects, wax production is well-known in some bees that use it for nest building. Curiously, mated-fertile queens of the ant Ectatomma tuberculatum produce an uncommon extra-wax coat and, consequently queens (mated-fertile females) are matte due to such extra cuticular hydrocarbon (CHC) coat that covers the cuticle and masks the brightness of the queens' cuticle while gynes (virgin-infertile queens) are shiny. In this study, histological analysis showed differences in the epidermis between fertile (i.e., queens or gynes with highly ovarian activity) and infertile females (gynes or workers with non developed ovaries). In fertile females the epidermis is a single layer of cubic cells found in all body segments whereas in infertile females it is a thin layer of flattened cells. Ultrastructural features showed active secretory tissue from fertile females similar to the glandular epithelium of wax-producing bees (type I gland). Different hypotheses related to the functions of the glandular epithelium exclusive to the E. tuberculatum fertile queens are discussed. PMID:20419093

  17. Glandular epithelium as a possible source of a fertility signal in Ectatomma tuberculatum (Hymenoptera: Formicidae) queens.

    PubMed

    da Hora, Riviane Rodigues; Delabie, Jacques Hubert Charles; dos Santos, Carolina Gonçalves; Serrão, José Eduardo

    2010-04-19

    The wax layer covering the insect's cuticle plays an important protective role, as for example, uncontrolled water loss. In social insects, wax production is well-known in some bees that use it for nest building. Curiously, mated-fertile queens of the ant Ectatomma tuberculatum produce an uncommon extra-wax coat and, consequently queens (mated-fertile females) are matte due to such extra cuticular hydrocarbon (CHC) coat that covers the cuticle and masks the brightness of the queens' cuticle while gynes (virgin-infertile queens) are shiny. In this study, histological analysis showed differences in the epidermis between fertile (i.e., queens or gynes with highly ovarian activity) and infertile females (gynes or workers with non developed ovaries). In fertile females the epidermis is a single layer of cubic cells found in all body segments whereas in infertile females it is a thin layer of flattened cells. Ultrastructural features showed active secretory tissue from fertile females similar to the glandular epithelium of wax-producing bees (type I gland). Different hypotheses related to the functions of the glandular epithelium exclusive to the E. tuberculatum fertile queens are discussed.

  18. Morphologic responses of the mouse ovarian surface epithelium to ovulation and steroid hormonal milieu.

    PubMed

    Gotfredson, Garry S; Murdoch, William J

    2007-02-01

    Ovarian cancer of surface epithelial origin is an ovulation- and endocrine-related disease. It appears that a cell transformed by genotoxins generated at follicular rupture is propagated during postovulatory wound repair. A consequent steroid hormonal imbalance favoring the mitogenic estrogens is a prospective predisposing factor in ovarian neoplasia. Protection against epithelial ovarian cancer is conferred by progesterone. The objective of this study was to characterize the acute effects of ovulation and steroid hormonal exposure on morphologic responses of surface epithelial cells of mouse ovaries. Follicular development and ovulation were induced in immature animals with equine and human (=Day 0) choriogonadotropins, respectively. On Day 2 (approximately 36 hrs after ovulation), surface epithelial classifications presented in histologic sections were altered from simple (single-layered) squamous and cuboidal toward stratification; this trend was reversed (i.e., reverted to the control status) on Days 4-8. Shifts in the ovarian epithelium from simple to stratified were accentuated following postovulatory (Days 1-8) treatment with estradiol. Surface epithelia of ovaries obtained after 1 week of progesterone administration were exclusively of a simple phenotype. We conclude that the proliferative/procarcinogenic reaction of the ovarian surface epithelium to ovulation is exacerbated by estrogen and counteracted by progesterone.

  19. Influence of histological degree of seminiferous tubular degeneration and stage of seminiferous cycle on the proliferation of spermatogonia in aged Syrian hamster (Mesocricetus auratus).

    PubMed

    Bernal-Mañas, C M; Cortes, S; Morales, E; Horn, R; Seco-Rovira, V; Beltran-Frutos, E; Ferrer, C; Canteras, M; Pastor, L M

    2014-08-01

    The ageing testis is associated with germ loss in the seminiferous epithelium and a decrease in spermatogonia proliferation. In this work, we study whether the stages of the seminiferous epithelium cycle and/or the degree of histological tubular degeneration resulting from ageing is related with this decrease in spermatogonia proliferation. Eleven hamsters were used, five aged 6 months and six aged 24 months. In both groups, the proliferative activity was studied by BrdU immunostaining. The number of BrdU-positive and BrdU-negative cells was measured, providing the overall proliferation index in adult and aged testes. The mean number of BrdU-positive cells was also determined for each degree of histological degeneration of seminiferous epithelium, and a spermatogonia proliferation index was obtained for each stage of the seminiferous cycle. Ageing caused an overall decrease in the BrdU-positive cell percentage and a decrease in the number of BrdU-positive cells in the tubular sections with hypospermatogenesis, the sloughing of germ cells and maturation arrest, these changes being similar in both young and old animals. The spermatogonia proliferation index was only seen to be significantly lower in ageing hamster in stages VII-VIII of the seminiferous epithelium cycle. In conclusion, the overall decrease in proliferation observed in aged seminiferous epithelium is correlated with an increase in the number of degenerated sections of the seminiferous tubules, and this decrease is a phenomenon which occurs in specific stages of the seminiferous cycle.

  20. Human vomeronasal epithelium development: An immunohistochemical overview.

    PubMed

    Dénes, Lóránd; Pap, Zsuzsanna; Szántó, Annamária; Gergely, István; Pop, Tudor Sorin

    2015-06-01

    The vomeronasal organ (VNO) is the receptor structure of the vomeronasal system (VNS) in vertebrates. It is found bilaterally in the submucosa of the inferior part of the nasal septum. There are ongoing controversies regarding the functionality of this organ in humans. In this study we propose the immunohistochemical evaluation of changes in components of the human vomeronasal epithelium during foetal development. We used 45 foetuses of different age, which were included in three age groups. After VNO identification immunohistochemical reactions were performed using primary antibodies against the following: neuron specific enolase, calretinin, neurofilament, chromogranin, synaptophysin, cytokeratin 7, pan-cytokeratin and S100 protein. Digital slides were obtained and following colorimetric segmentation, surface area measurements were performed. The VNO was found in less than half of the studied specimens (42.2%). Neuron specific enolase and calretinin immunoexpression showed a decreasing trend with foetal age, while the other neural/neuroendocrine markers were negative in all specimens. Cytokeratin 7 expression increased with age, while Pan-Ctk had no significant variations. S100 protein immunoexpression also decreased around the VNO. The results of the present work uphold the theory of regression of the neuroepithelium that is present during initial stages of foetal development.

  1. Stem cells of the skin epithelium

    PubMed Central

    Alonso, Laura; Fuchs, Elaine

    2003-01-01

    Tissue stem cells form the cellular base for organ homeostasis and repair. Stem cells have the unusual ability to renew themselves over the lifetime of the organ while producing daughter cells that differentiate into one or multiple lineages. Difficult to identify and characterize in any tissue, these cells are nonetheless hotly pursued because they hold the potential promise of therapeutic reprogramming to grow human tissue in vitro, for the treatment of human disease. The mammalian skin epithelium exhibits remarkable turnover, punctuated by periods of even more rapid production after injury due to burn or wounding. The stem cells responsible for supplying this tissue with cellular substrate are not yet easily distinguishable from neighboring cells. However, in recent years a significant body of work has begun to characterize the skin epithelial stem cells, both in tissue culture and in mouse and human skin. Some epithelial cells cultured from skin exhibit prodigious proliferative potential; in fact, for >20 years now, cultured human skin has been used as a source of new skin to engraft onto damaged areas of burn patients, representing one of the first therapeutic uses of stem cells. Cell fate choices, including both self-renewal and differentiation, are crucial biological features of stem cells that are still poorly understood. Skin epithelial stem cells represent a ripe target for research into the fundamental mechanisms underlying these important processes. PMID:12913119

  2. Building and maintaining the epithelium of the lung.

    PubMed

    Rackley, Craig R; Stripp, Barry R

    2012-08-01

    Airspaces of the lung are lined by an epithelium whose cellular composition changes along the proximal-to-distal axis to meet local functional needs for mucociliary clearance, hydration, host defense, and gas exchange. Advances in cell isolation, in vitro culture techniques, and genetic manipulation of animal models have increased our understanding of the development and maintenance of the pulmonary epithelium. This review discusses basic cellular mechanisms that regulate establishment of the conducting airway and gas exchange systems as well as the functional maintenance of the epithelium during postnatal life.

  3. Histologic effects of resurfacing lasers.

    PubMed

    Freedman, Joshua R; Greene, Ryan M; Green, Jeremy B

    2014-02-01

    By utilizing resurfacing lasers, physicians can significantly improve the appearance of sun-damaged skin, scars, and more. The carbon dioxide and erbium:yttrium-aluminum-garnet lasers were the first ablative resurfacing lasers to offer impressive results although these earlier treatments were associated with significant downtime. Later, nonablative resurfacing lasers such as the neodymium:yttrium-aluminum-garnet laser proved effective, after a series of treatments with less downtime, but with more modest results. The theory of fractional photothermolysis has revolutionized resurfacing laser technology by increasing the safety profile of the devices while delivering clinical efficacy. A review of the histologic and molecular consequences of the resurfacing laser-tissue interaction allows for a better understanding of the devices and their clinical effects.

  4. An integrated model supporting histological and biometric responses as predictive biomarkers of fish health status

    NASA Astrophysics Data System (ADS)

    Torres Junior, Audalio Rebelo; Sousa, Débora Batista Pinheiro; Neta, Raimunda Nonata Fortes Carvalho

    2014-10-01

    In this work, an experimental system of histological (branchial lesions) biomarkers and biometric data in catfish (Sciades herzbergii) was modeled. The fish were sampled along known pollution areas (S1) and from environmental protect areas (S2) in São Marcos' Bay, Brazil. Gills were fixed in 10% formalin and usual histological techniques were used in the first gill arch right. The lesions were observed by light microscopy. There were no histopathological changes in animals captured at reference site (S1). However, in the catfish collected in the potentially contaminated area (S2) was observed several branchial lesions, such as lifting of the lamellar epithelium, fusion of some secondary lamellae, hypertrophy of epithelial cells and lamellar aneurysm. The analysis using the biometric data showed significant differences, being highest in fish analyzed in the reference area. This approach revealed spatial differences related with biometric patterns and morphological modifications of catfish.

  5. An integrated model supporting histological and biometric responses as predictive biomarkers of fish health status

    SciTech Connect

    Torres Junior, Audalio Rebelo; Sousa, Débora Batista Pinheiro; Neta, Raimunda Nonata Fortes Carvalho

    2014-10-06

    In this work, an experimental system of histological (branchial lesions) biomarkers and biometric data in catfish (Sciades herzbergii) was modeled. The fish were sampled along known pollution areas (S1) and from environmental protect areas (S2) in São Marcos' Bay, Brazil. Gills were fixed in 10% formalin and usual histological techniques were used in the first gill arch right. The lesions were observed by light microscopy. There were no histopathological changes in animals captured at reference site (S1). However, in the catfish collected in the potentially contaminated area (S2) was observed several branchial lesions, such as lifting of the lamellar epithelium, fusion of some secondary lamellae, hypertrophy of epithelial cells and lamellar aneurysm. The analysis using the biometric data showed significant differences, being highest in fish analyzed in the reference area. This approach revealed spatial differences related with biometric patterns and morphological modifications of catfish.

  6. Stress preconditioning attenuates oxidative injury to the alveolar epithelium of the lung following haemorrhage in rats

    PubMed Central

    Pittet, J F; Lu, L N; Geiser, T; Lee, H; Matthay, M A; Welch, W J

    2002-01-01

    Inhibition of cAMP-dependent stimulation of vectorial fluid transport across the alveolar epithelium following haemorrhagic shock is mediated by reactive nitrogen species released within the airspaces of the lung. We tested here the hypothesis that the prior activation of the cellular heat shock or stress response, via exposure to either heat or geldanamycin, would attenuate the release of airspace nitric oxide (NO) responsible for the shock-mediated failure of the alveolar epithelium to respond to catecholamines in rats. Rats were haemorrhaged to a mean arterial pressure of 30–35 mmHg for 60 min, and then resuscitated with a 4 % albumin solution. Alveolar fluid clearance was measured by change in concentration of a protein solution instilled into the airspaces 5 h after the onset of haemorrhage. Stress preconditioning restored the cAMP-mediated upregulation of alveolar liquid clearance after haemorrhage. The protective effect of stress preconditioning was mediated in part by a decrease in the expression of iNOS in the lung. Specifically, stress preconditioning decreased the production of nitrite by endotoxin-stimulated alveolar macrophages removed from haemorrhaged rats or by A549 and rat alveolar epithelial type II cell monolayers stimulated with cytomix (a mixture of TNF-α, IL-1β and IFN-γ) for 24 h. In summary, these results provide the first in vivo evidence that stress preconditioning restores a normal fluid transport capacity of the alveolar epithelium in the early phase following haemorrhagic shock by attenuating NO-mediated oxidative stress to the lung epithelium. PMID:11790821

  7. Virtual tissue alignment and cutting plane definition – a new method to obtain optimal longitudinal histological sections

    PubMed Central

    Danz, J C; Habegger, M; Bosshardt, D D; Katsaros, C; Stavropoulos, A

    2014-01-01

    Histomorphometric evaluation of the buccal aspects of periodontal tissues in rodents requires reproducible alignment of maxillae and highly precise sections containing central sections of buccal roots; this is a cumbersome and technically sensitive process due to the small specimen size. The aim of the present report is to describe and analyze a method to transfer virtual sections of micro-computer tomographic (CT)-generated image stacks to the microtome for undecalcified histological processing and to describe the anatomy of the periodontium in rat molars. A total of 84 undecalcified sections of all buccal roots of seven untreated rats was analyzed. The accuracy of section coordinate transfer from virtual micro-CT slice to the histological slice, right–left side differences and the measurement error for linear and angular measurements on micro-CT and on histological micrographs were calculated using the Bland–Altman method, interclass correlation coefficient and the method of moments estimator. Also, manual alignment of the micro-CT-scanned rat maxilla was compared with multiplanar computer-reconstructed alignment. The supra alveolar rat anatomy is rather similar to human anatomy, whereas the alveolar bone is of compact type and the keratinized gingival epithelium bends apical to join the junctional epithelium. The high methodological standardization presented herein ensures retrieval of histological slices with excellent display of anatomical microstructures, in a reproducible manner, minimizes random errors, and thereby may contribute to the reduction of number of animals needed. PMID:24266502

  8. Virtual tissue alignment and cutting plane definition--a new method to obtain optimal longitudinal histological sections.

    PubMed

    Danz, J C; Habegger, M; Bosshardt, D D; Katsaros, C; Stavropoulos, A

    2014-02-01

    Histomorphometric evaluation of the buccal aspects of periodontal tissues in rodents requires reproducible alignment of maxillae and highly precise sections containing central sections of buccal roots; this is a cumbersome and technically sensitive process due to the small specimen size. The aim of the present report is to describe and analyze a method to transfer virtual sections of micro-computer tomographic (CT)-generated image stacks to the microtome for undecalcified histological processing and to describe the anatomy of the periodontium in rat molars. A total of 84 undecalcified sections of all buccal roots of seven untreated rats was analyzed. The accuracy of section coordinate transfer from virtual micro-CT slice to the histological slice, right-left side differences and the measurement error for linear and angular measurements on micro-CT and on histological micrographs were calculated using the Bland-Altman method, interclass correlation coefficient and the method of moments estimator. Also, manual alignment of the micro-CT-scanned rat maxilla was compared with multiplanar computer-reconstructed alignment. The supra alveolar rat anatomy is rather similar to human anatomy, whereas the alveolar bone is of compact type and the keratinized gingival epithelium bends apical to join the junctional epithelium. The high methodological standardization presented herein ensures retrieval of histological slices with excellent display of anatomical microstructures, in a reproducible manner, minimizes random errors, and thereby may contribute to the reduction of number of animals needed.

  9. Morphology of the tongue of the emu (Dromaius novaehollandiae). II. Histological features.

    PubMed

    Crole, M R; Soley, J T

    2009-12-01

    Although a number of brief, fragmented descriptions have been provided on the gross morphology of the ratite tongue, very few studies have documented the histological structure of this organ. This paper presents the first definitive histological description of the emu tongue and reviews, consolidates and compares the scattered information on the histology of the ratite tongue available in the literature. Five tongues were removed from heads obtained from birds at slaughter and fixed in 10% neutral buffered formalin. Appropriate longitudinal and transverse segments were removed, routinely processed for light microscopy, and sections examined after staining with H & E and PAS. The entire tongue (body and root) is invested by a non-keratinized stratified squamous epithelium. The supporting connective tissue of the tongue dorsum displays only large, simple branched tubular mucus-secreting glands, whereas the caudal tongue body ventrum and tongue root, in addition to these glands, also exhibits small, simple tubular mucus-secreting glands. Herbst corpuscles are associated with the large, simple branched glands. Lymphoid tissue is restricted to the tongue ventrum and is particularly obvious at the junction of the ventral tongue body and frenulum where a large aggregation of diffuse lymphoid tissue, with nodular tissue proximally, was consistently observed. A structure resembling a taste bud was located in the epithelium on the caudal extremity of the tongue root of one bird. This is the first reported observation of taste buds in ratites. Forming the core of the tongue body is the cartilaginous paraglossum lying dorsal to the partially ossified rostral projection of the basihyale. The histological features of the emu tongue are generally similar to those described for the greater rhea and ostrich, except that taste buds were not identified in these species. The results would suggest that the emu tongue functions as a sensory organ, both for taste and touch (by virtue of

  10. Immunohistochemical characterization of FHIT expression in normal human tissues

    PubMed Central

    Kujan, Omar; Abuderman, Abdulwahab; Al-Shawaf, Ahmad Zahi

    2016-01-01

    Background Fragile histidine triad (FHIT) is a tumor suppressor gene that is commonly inactivated in human tumors. Interestingly, the normal pattern of FHIT expression is largely unknown. Aim This study is aimed to characterize the expression of FHIT protein in normal human tissues. Materials and methods A total of 119 normal human tissue specimens were analyzed for the FHIT expression using immunohistochemistry technique. The inclusion criteria included: normal/inflammatory tissue with no evidence of cellular atypia. Results All studied specimens were stained positively with FHIT and showed either nuclear or cytoplasmic expression. Interestingly, the pattern of FHIT staining was similar among different specimens from each organ. FHIT is located predominantly in the nucleus, although cytoplasmic staining is also present in some cell types. Oral squamous epithelium, breast ductal epithelium, squamous and tubal metaplastic epithelium of the uterine cervix, esophageal squamous epithelium, salivary glands, and bronchial epithelia all strongly expressed the nuclear protein. In connective tissue, FHIT has shown strong cytoplasmic expression in histocytes including macrophages and dendritic cells, fibroblasts, and myofibroblasts. Conclusion Documentation of the pattern of FHIT expression in normal tissues will contribute to our understanding of the normal function of this protein and to interpretation of potentially altered FHIT expression in human tumors. PMID:28250975

  11. Detachments of the retinal pigment epithelium at the posterior pole.

    PubMed

    Noble, K G; Levitzky, M J; Carr, R E

    1976-08-01

    Multiple vitelliform cysts of the retina, a disorder of unknown cause in which there are multiple detachments of the retinal pigment epithelium at the posterior pole, occurred in five patients. In four patients all lesions were located outside the parafoveal area while one patient showed bilateral foveal elevations associated with more eccentric detachments. Several patients showed slow resolution of some of the detachments with mild disturbances of the pigment epithelium.

  12. Stacked Predictive Sparse Decomposition for Classification of Histology Sections.

    PubMed

    Chang, Hang; Zhou, Yin; Borowsky, Alexander; Barner, Kenneth; Spellman, Paul; Parvin, Bahram

    2015-05-01

    Image-based classification of histology sections, in terms of distinct components (e.g., tumor, stroma, normal), provides a series of indices for histology composition (e.g., the percentage of each distinct components in histology sections), and enables the study of nuclear properties within each component. Furthermore, the study of these indices, constructed from each whole slide image in a large cohort, has the potential to provide predictive models of clinical outcome. For example, correlations can be established between the constructed indices and the patients' survival information at cohort level, which is a fundamental step towards personalized medicine. However, performance of the existing techniques is hindered as a result of large technical variations (e.g., variations of color/textures in tissue images due to non-standard experimental protocols) and biological heterogeneities (e.g., cell type, cell state) that are always present in a large cohort. We propose a system that automatically learns a series of dictionary elements for representing the underlying spatial distribution using stacked predictive sparse decomposition. The learned representation is then fed into the spatial pyramid matching framework with a linear support vector machine classifier. The system has been evaluated for classification of distinct histological components for two cohorts of tumor types. Throughput has been increased by using of graphical processing unit (GPU), and evaluation indicates a superior performance results, compared with previous research.

  13. Stacked Predictive Sparse Decomposition for Classification of Histology Sections

    PubMed Central

    Zhou, Yin; Borowsky, Alexander; Barner, Kenneth; Spellman, Paul

    2016-01-01

    Image-based classification of histology sections, in terms of distinct components (e.g., tumor, stroma, normal), provides a series of indices for histology composition (e.g., the percentage of each distinct components in histology sections), and enables the study of nuclear properties within each component. Furthermore, the study of these indices, constructed from each whole slide image in a large cohort, has the potential to provide predictive models of clinical outcome. For example, correlations can be established between the constructed indices and the patients’ survival information at cohort level, which is a fundamental step towards personalized medicine. However, performance of the existing techniques is hindered as a result of large technical variations (e.g., variations of color/textures in tissue images due to non-standard experimental protocols) and biological heterogeneities (e.g., cell type, cell state) that are always present in a large cohort. We propose a system that automatically learns a series of dictionary elements for representing the underlying spatial distribution using stacked predictive sparse decomposition. The learned representation is then fed into the spatial pyramid matching framework with a linear support vector machine classifier. The system has been evaluated for classification of distinct histological components for two cohorts of tumor types. Throughput has been increased by using of graphical processing unit (GPU), and evaluation indicates a superior performance results, compared with previous research. PMID:27721567

  14. Histological alterations in the intestinal epithelium caused by the inclusion of full-fat sunflower kernels in broiler chicken diets.

    PubMed

    Arija, I; Viveros, A; Brenes, A; Canales, R; Pizarro, M; Castaño, M

    2000-09-01

    Changes in small intestinal morphology (jejunum) were examined at 28 d of age in chicks fed with full-fat sunflower kernels (FFSK)-based diets. Jejunal mucosa of chicks (six chicks per treatment) were embedded in Epon-812 for examination by a conventional electron microscope procedure. A portion of the tissues was also sectioned and embedded in paraffin for examination by light microscopy. Brush border, goblet cells, and intraepithelial lymphocytes, on the one hand, and fibroblast and mononuclear cells (lymphocytes, plasma cells, macrophages) were observed in the enterocytes and lamina propria, respectively. The results showed that the birds fed 150 g kg(-1) of FFSK showed a shortening and thickening of the villi, hyperplasia and vacuolar degeneration of enterocytes, and hypertrophy and hyperplasia of goblet cells. Likewise, an increment of intraepithelial lymphoid cells and hypercellularity of the lamina propria was observed. In addition, electron microscopy showed large vacuoles in the enterocytes, which could be dilations of agranular and granular endoplasmic reticulum or Golgi. There were many dark granules within the vacuoles that could be triglyceride-rich lipoproteins (portomicrons). These lesions could have been due to the presence of chlorogenic acid or to the greater concentration of oil in the FFSK diet. Our observations demonstrated that addition of 150 g kg(-1) FFSK to broiler chicken diets caused alterations in jejunal mucosa that could explain the decrease in fat digestibility observed in a previous experiment in which we incorporated FFSK into broiler diets.

  15. Cell polarity and spindle orientation in the distal epithelium of embryonic lung.

    PubMed

    El-Hashash, Ahmed H; Warburton, David

    2011-02-01

    A proper balance between self-renewal and differentiation of lung-specific progenitors at the distal epithelial tips is absolutely required for normal lung morphogenesis. Cell polarity and mitotic spindle orientation play a critical role in the self-renewal/differentiation of epithelial cells and can impact normal physiological processes, including epithelial tissue branching and differentiation. Therefore, understanding the behavior of lung distal epithelial progenitors could identify innovative solutions to restoring normal lung morphogenesis. Yet little is known about cell polarity, spindle orientation, and segregation of cell fate determinant in the embryonic lung epithelium, which contains progenitor cells. Herein, we provide the first evidence that embryonic lung distal epithelium is polarized and highly mitotic with characteristic perpendicular cell divisions. Consistent with these findings, mInsc, LGN, and NuMA polarity proteins, which control spindle orientation, are asymmetrically localized in mitotic distal epithelial progenitors of embryonic lungs. Furthermore, the cell fate determinant Numb is asymmetrically distributed at the apical side of distal epithelial progenitors and segregated to one daughter cell in most mitotic cells. These findings provide evidence for polarity in distal epithelial progenitors of embryonic lungs and provide a framework for future translationally oriented studies in this area.

  16. Abnormal apical cell membrane in cystic fibrosis respiratory epithelium. An in vitro electrophysiologic analysis.

    PubMed Central

    Cotton, C U; Stutts, M J; Knowles, M R; Gatzy, J T; Boucher, R C

    1987-01-01

    The transepithelial chloride permeability of airway and sweat ductal epithelium has been reported to be decreased in patients with cystic fibrosis (CF). In the present study, we investigated whether the airway epithelial defect was in the cell path by characterizing the relative ion permeabilities of the apical membrane of respiratory epithelial cells from CF and normal subjects. Membrane electric potential difference (PD) and the responses to luminal Cl- replacement, isoproterenol, and amiloride were measured with intracellular microelectrodes. The PD across the apical barrier was smaller for CF (-11 mV) than normal (-29 mV) epithelia whereas the PD across the basolateral barrier was similar, (-26 and -34 mV respectively). In contrast to normal nasal epithelium, the apical membrane in CF epithelia was not Cl- permselective and was not responsive to isoproterenol. Amiloride, a selective Na+ channel blocker, induced a larger apical membrane hyperpolarization and a greater increase in transepithelial resistance in CF epithelia. Both reduced apical cell membrane Cl- conductance and increased Na+ conductance appear to contribute to the abnormal function of respiratory epithelia of CF patients. PMID:3793933

  17. Actual drawing of histological images improves knowledge retention.

    PubMed

    Balemans, Monique C M; Kooloos, Jan G M; Donders, A Rogier T; Van der Zee, Catharina E E M

    2016-01-01

    Medical students have to process a large amount of information during the first years of their study, which has to be retained over long periods of nonuse. Therefore, it would be beneficial when knowledge is gained in a way that promotes long-term retention. Paper-and-pencil drawings for the uptake of form-function relationships of basic tissues has been a teaching tool for a long time, but now seems to be redundant with virtual microscopy on computer-screens and printers everywhere. Several studies claimed that, apart from learning from pictures, actual drawing of images significantly improved knowledge retention. However, these studies applied only immediate post-tests. We investigated the effects of actual drawing of histological images, using randomized cross-over design and different retention periods. The first part of the study concerned esophageal and tracheal epithelium, with 384 medical and biomedical sciences students randomly assigned to either the drawing or the nondrawing group. For the second part of the study, concerning heart muscle cells, students from the previous drawing group were now assigned to the nondrawing group and vice versa. One, four, and six weeks after the experimental intervention, the students were given a free recall test and a questionnaire or drawing exercise, to determine the amount of knowledge retention. The data from this study showed that knowledge retention was significantly improved in the drawing groups compared with the nondrawing groups, even after four or six weeks. This suggests that actual drawing of histological images can be used as a tool to improve long-term knowledge retention.

  18. Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium

    NASA Astrophysics Data System (ADS)

    Chaudhuri, Ovijit; Koshy, Sandeep T.; Branco da Cunha, Cristiana; Shin, Jae-Won; Verbeke, Catia S.; Allison, Kimberly H.; Mooney, David J.

    2014-10-01

    In vitro models of normal mammary epithelium have correlated increased extracellular matrix (ECM) stiffness with malignant phenotypes. However, the role of increased stiffness in this transformation remains unclear because of difficulties in controlling ECM stiffness, composition and architecture independently. Here we demonstrate that interpenetrating networks of reconstituted basement membrane matrix and alginate can be used to modulate ECM stiffness independently of composition and architecture. We find that, in normal mammary epithelial cells, increasing ECM stiffness alone induces malignant phenotypes but that the effect is completely abrogated when accompanied by an increase in basement-membrane ligands. We also find that the combination of stiffness and composition is sensed through β4 integrin, Rac1, and the PI3K pathway, and suggest a mechanism in which an increase in ECM stiffness, without an increase in basement membrane ligands, prevents normal α6β4 integrin clustering into hemidesmosomes.

  19. Histological and Ultrastructural Studies on the Conjunctiva of the Barred Owl (Strix varia)

    PubMed Central

    Jochems, Brian; Phillips, Thomas E.

    2015-01-01

    This report is the first characterization of the histology and ultrastructure of the barred owl conjunctiva. The inferior eyelid was dominated by a large disk-shaped plate covered by a non-keratinized stratified squamous or cuboidal epithelium of variable thickness. The apical surface of the plate epithelium varied from flat to long microvilli or even short cytoplasmic extensions similar to those seen in the third eyelid. All specimens had a few goblet cells filled with mucous secretory granules in the plate region. The underlying connective tissue was a dense fibroelastic stroma. Eosinophils were surprisingly common in the epithelial layer and underlying connective tissue in the plate and more distal orbital mucosal region. The orbital mucosa contained goblet cells with heterogeneous glycosylation patterns. The leading edge and marginal plait of the third eyelid are designed to collect fluid and particulate matter as they sweep across the surface of the eye. The palpebral conjunctival surface of the third eyelid was covered by an approximately five-cell-deep stratified squamous epithelium without goblet cells. The bulbar surface of the third eyelid was a bilayer of epithelial cells whose superficial cells have elaborate cytoplasmic tapering extensions reaching out 25 μm. Narrow cytofilia radiated outwards up to an additional 15–20 μm from the cytoplasmic extensions. Lectin labeling demonstrated heterogeneous glycosylation of the apical membrane specializations but only small amounts of glycoprotein-filled secretory granules in the third eyelid. PMID:26562834

  20. Histologic analysis of postmeniscectomy osteonecrosis.

    PubMed

    Higuchi, Hiroshi; Kobayashi, Yasukazu; Kobayashi, Atsushi; Hatayama, Kazuhisa; Kimura, Masashi

    2013-05-01

    Bone marrow signal changes on magnetic resonance imaging (MRI) after meniscectomy have been reported as evidence of postmeniscectomy osteonecrosis, but this pathology is unclear. We conducted a study to follow-up cases with bone marrow signal changes on MRI after meniscectomy and investigate the pathology of underlying lesions. Of 136 patients with no presurgical evidence of osteonecrosis, 29 had juxta-articular bone marrow signal changes on MRI after arthroscopic meniscectomy and subsequently underwent conservative therapy. In 6 of these 29 patients, clinical symptoms and radiographic changes began deteriorating. Based on the Koshino classification, 4 of the 6 patients had Stage-2 knee osteonecrosis and 2 had Stage-3. Arthroscopic and pathologic examinations were performed. Arthroscopic findings were fibrillation (all 6 cases), fissuring (4), ulceration (2), and eburnation (2). Histologic analysis confirmed subchondral bone fractures in all 6 cases, but osteonecrotic lesions were detected only in 2 cases with obvious radiologic deterioration. Postmeniscectomy osteonecrosis might result from subchondral bone fractures. Fracture healing is worse in patients with comorbidities than in those without it; comorbidities might be a risk factor for osteonecrosis.

  1. Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema.

    PubMed

    Woods, Jason C; Choong, Cliff K; Yablonskiy, Dmitriy A; Bentley, John; Wong, Jonathan; Pierce, John A; Cooper, Joel D; Macklem, Peter T; Conradi, Mark S; Hogg, James C

    2006-12-01

    Diffusion MRI of hyperpolarized (3)He shows that the apparent diffusion coefficient (ADC) of (3)He gas is highly restricted in the normal lung and becomes nearly unrestricted in severe emphysema. The nature of this restricted diffusion provides information about lung structure; however, no direct comparison with histology in human lungs has been reported. The purpose of this study is to provide information about (3)He gas diffusivity in explanted human lungs, and describe the relationship between (3)He diffusivity and the surface area to lung volume ratio (SA/V) and mean linear intercept (L(m)) measurements--the gold standard for diagnosis of emphysema. Explanted lungs from patients who were undergoing lung transplantation for advanced COPD, and donor lungs that were not used for transplantation were imaged via (3)He diffusion MRI. Histological measurements were made on the same specimens after they were frozen in the position of study. There is an inverse correlation between diffusivity and SA/V (and a positive correlation between diffusivity and L(m)). An important result is that restricted (3)He diffusivity separated normal from emphysematous lung tissue more clearly than the morphometric analyses. This effect may be due to the smaller histologic sampling size compared to the MRI voxel sizes.

  2. Endometrial biopsy in Holstein-Friesian dairy cows. II. Correlations between histological criteria.

    PubMed Central

    Bonnett, B N; Miller, R B; Martin, S W; Etherington, W G; Buckrell, B C

    1991-01-01

    Endometrial biopsies were taken for histological assessment from 97 cows which calved in a commercial dairy herd between April and August 1984. The main objectives of this study were to analyze the interrelationships among histological criteria and to identify a shortlist of histological parameters to be included in subsequent analysis of associations with results of bacteriological culture, clinical findings and reproductive performance. Epithelial height and segmented cell counts were highly correlated within biopsy, between horns and between days. Subjective assessment of inflammation in the epithelium and/or stratum compactum generally identified biopsies which had any inflammation present. Cows which had inflammation in a biopsy from day 26 were likely to show inflammatory changes at day 40. Quantitative and subjective assessments of gland number, dilation and fibrosis were highly correlated. There was a positive association between the number of cross sections and the diameter of glands, and both of these criteria were negatively correlated with fibrosis and inflammatory changes. There may be different functional significance of the same histological finding at a different number of days postpartum. PMID:1884296

  3. Granular cell ameloblastoma: case report of a particular ameloblastoma histologically resembling oncocytoma.

    PubMed

    Matsushita, Yuki; Fujita, Shuichi; Kawasaki, Goro; Hirota, Yoshinosuke; Rokutanda, Satoshi; Yamashita, Kentaro; Yanamoto, Souichi; Ikeda, Tohru; Umeda, Masahiro

    2015-01-01

    Granular cell ameloblastoma is classified as a histological subtype of solid/multicystic ameloblastoma. Usual granular cell ameloblastoma is histologically characterized by granular changes of stellate-like cells located in the inner portion of the epithelial follicles. Here we report a case of another type of granular cell ameloblastoma, showing predominant anastomosing double-stranded trabeculae of granular cells. This type of granular cell ameloblastoma is extremely rare, and the World Health Organization classification does not contain the entity. We tentatively termed it 'anastomosing granular cell ameloblastoma' in this report. The present case suggests the importance of differential diagnosis because the histology of 'anastomosing granular cell ameloblastoma' resembles that of salivary gland oncocytoma rather than that of usual granular cell ameloblastoma. The trabeculae observed in our case continued to the peripheral cells of a small amount of epithelial sheets of plexiform ameloblastoma, and the tumor cells were positive for CK19, which is regarded as an immunohistochemical marker of odontogenic epithelium. Similar to usual granular cell ameloblastoma, the tumor cells had CD68-positive granules. For precise diagnosis of this condition, immunohistochemistry using CK19 and CD68, as well as detailed histological observation, are recommended.

  4. Histological and lectin histochemical studies on the olfactory mucosae of the Korean roe deer, Capreolus pygargus.

    PubMed

    Park, Changnam; Ahn, Meejung; Kim, Jeongtae; Kim, Seungjoon; Moon, Changjong; Shin, Taekyun

    2015-04-01

    The morphological features of the olfactory mucosae of Korean roe deer, Capreolus pygargus, were histologically studied using the ethmoid turbinates containing the olfactory mucosae from six roe deer (male, 2-3 years old). The ethmoid turbinates were embedded in paraffin, and histochemically evaluated in terms of the mucosal characteristics. Lectin histochemistry was performed to investigate the carbohydrate-binding specificity on the olfactory mucosa. Lectins, including Triticum vulgaris wheat germ agglutinin (WGA), Ulex europaeus agglutinin I (UEA-I), and soybean agglutinin (SBA) were used for the N-acetylglucosamine, fucose and N-acetylgalactosamine carbohydrate groups, respectively. Histologically, the olfactory mucosa, positioned mainly in the caudal roof of the nasal cavity, consisted of the olfactory epithelium and the lamina propria. The olfactory epithelium consisted of protein gene product (PGP) 9.5-positive olfactory receptor cells, galectin-3-positive supporting cells and basal cells. Bowman's glands in the lamina propria were stained by both the periodic acid Schiff reagent and alcian blue (pH 2.5). Two types of lectin, WGA and SBA, were labeled in free border, receptor cells, supporting cells and Bowman's glands, with the exception of basal cells, while UEA-I was labeled in free border, supporting cells and Bowman's glands, but not in receptor cells and basal cells, suggesting that carbohydrate terminals on the olfactory mucosae of roe deer vary depending on cell type. This is the first morphological study of the olfactory mucosa of the Korean roe deer to evaluate carbohydrate terminals in the olfactory mucosae.

  5. Solvent/Detergent Virally Inactivated Serum Eye Drops Restore Healthy Ocular Epithelium in a Rabbit Model of Dry-Eye Syndrome

    PubMed Central

    Tseng, Ching-Li; Chen, Zhi-Yu; Renn, Ting-Yi; Hsiao, Shun-Hung; Burnouf, Thierry

    2016-01-01

    Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer’s test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S

  6. Solvent/Detergent Virally Inactivated Serum Eye Drops Restore Healthy Ocular Epithelium in a Rabbit Model of Dry-Eye Syndrome.

    PubMed

    Tseng, Ching-Li; Chen, Zhi-Yu; Renn, Ting-Yi; Hsiao, Shun-Hung; Burnouf, Thierry

    2016-01-01

    Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer's test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S

  7. Macroscopic and histological variations in the cellular tapetum in dogs.

    PubMed

    Yamaue, Yasuhiro; Hosaka, Yoshinao Z; Uehara, Masato

    2014-08-01

    We aimed to document macroscopic variations in the cellular tapetum in the dog, to provide a histologic description of the macroscopic results and to evaluate the correlation between the macroscopic appearance and aging. Fifty three dogs including 5 beagles, 1 Chihuahua and 47 mixed breeds of each gender were used. For a macroscopic study, the fresh tapetal fundi were photographed using digital camera. For a histological study, the glutaraldehyde-formalin fixed eyes were embedded in nitrocellulose and stained with hematoxylin-eosin or thionine. The normal tapetum was triangular with the rounded angles and the smooth contour. The atypical tapetum was smaller and more variable in shape, contour and color than the normal one. In severe cases, the fundus was devoid of the tapetum. The atypical tapetum tended to increase in frequency with aging. Retinal pigment epithelial cells on the normal tapetum were unpigmented. In the eye with the atypical tapetum, regardless of tapetal size and shape, unpigmented retinal pigment epithelial cells showed a similar distribution to that on the normal tapetum, even in a dog without a tapetum. Although there is a congenitally hypoplastic tapetum, the atypical tapetum tends to increase in incidence and severity with aging.

  8. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice.

    PubMed

    Feng, Dilu; Menger, Michael D; Wang, Hongbo; Laschke, Matthias W

    2014-02-01

    In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE(+)) and without luminal epithelium (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE(-) fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE(+) fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE(+) lesions compared with LE(-) lesions. In addition, we found that many GFP(+) microvessels grew outside the LE(-) lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  9. Inframammary fold: a histologic reappraisal.

    PubMed

    Muntan, C D; Sundine, M J; Rink, R D; Acland, R D

    2000-02-01

    The inframammary fold is a defining element in the shape and structure of the female breast. It should be preserved whenever possible in ablative procedures and recreated accurately when the breast is reconstructed after mastectomy. To date, no accurate anatomic description of this essential structure exists. Previous studies have suggested that the fold is produced by a supporting ligament running from the dermis in the fold region to a variety of locations on the rib cage. This clinic's experience with mastectomy, augmentation mammaplasty, and breast reconstruction does not support the existence of a ligamentous structure. To define the structure of the inframammary fold, 10 female and 2 male cadavers were studied. The anterior chest wall was removed en bloc and frozen in orthostatic position. Parasagittal sections were made of the inframammary fold with the chest wall intact. After decalcification of the ribs and routine histologic preparation, thin sections were stained with Gomori's trichrome. On light microscopic examination, no demonstrable ligamentous structure of dense regular connective tissue could be identified in the fold region in any of the 12 specimens. Superficial and deep fascial layers were uniformly observed anterior to the pectoralis major and serratus anterior muscles. The superficial fascia was connected to the dermis in the fold region in a variety of configurations. In some cases, the deep fascia fused with the superficial fascia and dermis at the fold level. In other cases, bundles of collagen fibers arising from the superficial fascial layer were found to insert into the dermis at the inframammary fold, slightly inferior to it, or both. These bundles were observed consistently in sections from the sternum to the middle axillary line. They were distinct from Cooper's suspensory ligaments, which are seen more superiorly in the glandular tissue.

  10. Latent heat loss and sweat gland histology of male goats in an equatorial semi-arid environment

    NASA Astrophysics Data System (ADS)

    de Melo Costa, Cíntia Carol; Maia, Alex Sandro Campos; Neto, José Domingues Fontenele; Oliveira, Steffan Edward Octávio; de Queiroz, João Paulo Araújo Fernandes

    2014-03-01

    The objective of this work was to quantify the heat loss by cutaneous evaporation of goats in an equatorial semi-arid environment. The latent heat loss from the body surfaces of these ten undefined breed goats was measured using a ventilated capsule in sun and shade and in the three body regions (neck, flank and hindquarters). Skin samples from these three regions were histologically analyzed to relate the quantity of sweat glands, the area of sweat glands and the epithelium thickness of each of these regions to the heat loss by cutaneous evaporation of the examined goats. The epithelium thickness that was measured varied significantly for body regions with different quantities and areas of sweat glands ( P < 0.01). Among the body regions that were examined, the samples from the neck demonstrated the highest epithelium thickness (16.23 ± 0.13 μm). However, the samples of sweat glands from the flank had the biggest area (43330.51 ± 778.71 μm2) and quantity per square centimeter (390 ± 9 cm-2). After the animals were exposed to sun, the flanks lost the greatest amount of heat by cutaneous evaporation (73.03 ± 1.75 W m-2) and possessed the highest surface temperatures (39.47 ± 0.18 °C). The histological characteristics may have influenced the heat loss by cutaneous evaporation that was observed in the flank region after the animals were exposed to sun.

  11. Latent heat loss and sweat gland histology of male goats in an equatorial semi-arid environment

    NASA Astrophysics Data System (ADS)

    de Melo Costa, Cíntia Carol; Maia, Alex Sandro Campos; Neto, José Domingues Fontenele; Oliveira, Steffan Edward Octávio; de Queiroz, João Paulo Araújo Fernandes

    2013-03-01

    The objective of this work was to quantify the heat loss by cutaneous evaporation of goats in an equatorial semi-arid environment. The latent heat loss from the body surfaces of these ten undefined breed goats was measured using a ventilated capsule in sun and shade and in the three body regions (neck, flank and hindquarters). Skin samples from these three regions were histologically analyzed to relate the quantity of sweat glands, the area of sweat glands and the epithelium thickness of each of these regions to the heat loss by cutaneous evaporation of the examined goats. The epithelium thickness that was measured varied significantly for body regions with different quantities and areas of sweat glands (P < 0.01). Among the body regions that were examined, the samples from the neck demonstrated the highest epithelium thickness (16.23 ± 0.13 μm). However, the samples of sweat glands from the flank had the biggest area (43330.51 ± 778.71 μm2) and quantity per square centimeter (390 ± 9 cm-2). After the animals were exposed to sun, the flanks lost the greatest amount of heat by cutaneous evaporation (73.03 ± 1.75 W m-2) and possessed the highest surface temperatures (39.47 ± 0.18 °C). The histological characteristics may have influenced the heat loss by cutaneous evaporation that was observed in the flank region after the animals were exposed to sun.

  12. Signature microRNAs in human cornea limbal epithelium.

    PubMed

    Teng, Yufei; Wong, Hoi Kin; Jhanji, Vishal; Chen, Jian Huan; Young, Alvin Lerrmann; Zhang, Mingzhi; Choy, Kwong Wai; Mehta, Jodhbir Singh; Pang, Chi Pui; Yam, Gary Hin-Fai

    2015-05-01

    This study was aimed to identify the signature microRNAs, which regulate the biological processes of corneal epithelial progenitor cell (CEPC) homeostasis and regulation through characterizing the differential expression profile of microRNAs in human limbal epithelium containing adult CEPC versus central corneal epithelium without CEPC. MicroRNA microarray had identified 37 microRNAs enriched in human corneal epithelium. Among them, nine were significantly upregulated in limbal epithelium and one in central corneal epithelium after validation by TaqMan® real-time polymerase chain reaction. In addition to our previous finding of miR-143 and 145, the expression of miR-10b, 126, and 155 was localized in limbal epithelium (LE) (predominantly basal layers) by using locked nucleic acid-based in situ hybridization. Potential target genes were predicted by TargetScan Human v6.0 and compared to the reported human cornea epithelial gene profile GSE5543. Analyzed by web-based Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and DAVID Functional Annotation Bioinformatics Resources v6.7, the downregulated genes were involved in pathways of immune response and cellular protection, apoptosis, and cell movement whereas upregulated genes with cell survival, cell-matrix interaction, and cell-cell adhesion. We found a constant occurrence of miR-143, 145, and 155 in all KEGG pathways regulating limbal epithelial events. By Ingenuity Systems (IPA®) analysis, these microRNAs could cooperatively regulate cell growth and apoptosis via tumor necrosis factor activation and MYC repression. Our findings thus suggest a unique microRNA signature existing in human limbal epithelium and participating in CEPC homeostasis.

  13. Modulation of extracellular conditions prevents the multilayering of the simple epithelium.

    PubMed

    Mizutani, Takeomi; Takeda, Kazuki; Haga, Hisashi; Todo, Mitsugu; Kawabata, Kazushige

    2014-05-01

    Simple epitheliums in normal glandular systems are regulated not to stratify even though the constituent cells proliferate and will rise from the epithelium. Since epithelial cells have the potential to establish cell-cell adhesions, the avoidance of stratification must be related to the intracellular signal cascades and the extracellular conditions. The contributions of the former are becoming clarified, but the influence of the latter is poorly understood. In the present study, we examined whether the frequency of cell-on-cell adhesion, which mimics the early stage of multilayering, is dependent on the type of the extracellular scaffold protein. Wild-type epithelial cells were cultured on E-cadherin-Fc (a cell-cell adhesion protein) or collagen (an extracellular matrix protein), and then, green fluorescent protein (GFP)-positive cells were seeded onto these wild-type cells. We observed that the cell-on-cell adhesion (adhesion of the GFP-positive cell to the wild-type cells) was more frequent in the E-cadherin-Fc treatment than the collagen treatment. The cell-on-cell adhesions that were observed in the E-cadherin treatment were transient and decreased in frequency to that of the collagen treatment after the 12 h of cell culture. We observed the disappearance of E-cadherin-Fc but not collagen during cell culture. These results suggest that transient multilayering in simple epithelium is possible, depending on the types of extracellular scaffold protein, and they imply that cells can modify the extracellular conditions to meet normal cellular conditions.

  14. Global Expression Profiling of Globose Basal Cells and Neurogenic Progression Within the Olfactory Epithelium

    PubMed Central

    Krolewski, Richard C.; Packard, Adam; Schwob, James E.

    2013-01-01

    Ongoing, lifelong neurogenesis maintains the neuronal population of the olfactory epithelium in the face of piecemeal neuronal turnover and restores it following wholesale loss. The molecular phenotypes corresponding to different stages along the progression from multipotent globose basal cell (GBC) progenitor to differentiated olfactory sensory neuron are poorly characterized. We used the transgenic expression of enhanced green fluorescent protein (eGFP) and cell surface markers to FACS-isolate ΔSox2-eGFP(+) GBCs, Neurog1-eGFP(+) GBCs and immature neurons, and ΔOMP-eGFP(+) mature neurons from normal adult mice. In addition, the latter two populations were also collected 3 weeks after olfactory bulb ablation, a lesion that results in persistently elevated neurogenesis. Global profiling of mRNA from the populations indicates that all stages of neurogenesis share a cohort of >2,100 genes that are upregulated compared to sustentacular cells. A further cohort of >1,200 genes are specifically upregulated in GBCs as compared to sustentacular cells and differentiated neurons. The increased rate of neurogenesis caused by olfactory bulbectomy had little effect on the transcriptional profile of the Neurog1-eGFP(+) population. In contrast, the abbreviated lifespan of ΔOMP-eGFP(+) neurons born in the absence of the bulb correlated with substantial differences in gene expression as compared to the mature neurons of the normal epithelium. Detailed examination of the specific genes upregulated in the different progenitor populations revealed that the chromatin modifying complex proteins LSD1 and coREST were expressed sequentially in upstream ΔSox2-eGFP(+) GBCs and Neurog1-eGFP(+) GBCs/immature neurons. The expression patterns of these proteins are dynamically regulated after activation of the epithelium by methyl bromide lesion. PMID:22847514

  15. Histological Changes in Gills of Two Fish Species as Indicators of Water Quality in Jansen Lagoon (São Luís, Maranhão State, Brazil)

    PubMed Central

    Santos, Débora M. S.; Melo, Mércia Regina S.; Mendes, Denise Carla S.; Rocha, Iolanda Karoline B. S.; Silva, Jakeline Priscila L.; Cantanhêde, Sildiane M.; Meletti, Paulo C.

    2014-01-01

    Water quality of the Jansen Lagoon (São Luís, Maranhão State, Brazil) was assessed through histological biomarkers and microbiological parameters. To this end, 29 fish specimens (11 Centropomus undecimalis and 18 Sardinella sp) and eight water samples were collected during the rainy and dry periods of 2013. The lagoon water showed thermotolerant coliform indices above the limit set forth in CONAMA Resolution 357/2005. Histological changes observed in the gills were: lifting of the respiratory epithelium, hyperplasia of the lamellar epithelium, incomplete and complete fusion of several lamellae, disorganization of the lamellae, congestion of blood vessels, aneurysms, hypertrophy of the respiratory epithelium, hemorrhage and rupture of the lamellar epithelium and parasite. The histological alteration index (HAI) average value to Sardinella sp was 31.8 and to C. undecimalis was 22.2. The average HAI value in both species corresponds to category 21–50, with tissue injuries being classified from moderate to severe. The presence of histological injuries and the HAI values indicate that the fish sampled from the Jansen Lagoon are reacting to non-specific xenobiotics present at the site. PMID:25514148

  16. Model-based recovery of histological parameters from multispectral images of the colon

    NASA Astrophysics Data System (ADS)

    Hidovic-Rowe, Dzena; Claridge, Ela

    2005-04-01

    Colon cancer alters the macroarchitecture of the colon tissue. Common changes include angiogenesis and the distortion of the tissue collagen matrix. Such changes affect the colon colouration. This paper presents the principles of a novel optical imaging method capable of extracting parameters depicting histological quantities of the colon. The method is based on a computational, physics-based model of light interaction with tissue. The colon structure is represented by three layers: mucosa, submucosa and muscle layer. Optical properties of the layers are defined by molar concentration and absorption coefficients of haemoglobins; the size and density of collagen fibres; the thickness of the layer and the refractive indexes of collagen and the medium. Using the entire histologically plausible ranges for these parameters, a cross-reference is created computationally between the histological quantities and the associated spectra. The output of the model was compared to experimental data acquired in vivo from 57 histologically confirmed normal and abnormal tissue samples and histological parameters were extracted. The model produced spectra which match well the measured data, with the corresponding spectral parameters being well within histologically plausible ranges. Parameters extracted for the abnormal spectra showed the increase in blood volume fraction and changes in collagen pattern characteristic of the colon cancer. The spectra extracted from multi-spectral images of ex-vivo colon including adenocarcinoma show the characteristic features associated with normal and abnormal colon tissue. These findings suggest that it should be possible to compute histological quantities for the colon from the multi-spectral images.

  17. Characterization of the global profile of genes expressed in cervical epithelium by Serial Analysis of Gene Expression (SAGE)

    PubMed Central

    Pérez-Plasencia, Carlos; Riggins, Gregory; Vázquez-Ortiz, Guelaguetza; Moreno, José; Arreola, Hugo; Hidalgo, Alfredo; Piña-Sanchez, Patricia; Salcedo, Mauricio

    2005-01-01

    Background Serial Analysis of Gene Expression (SAGE) is a new technique that allows a detailed and profound quantitative and qualitative knowledge of gene expression profile, without previous knowledge of sequence of analyzed genes. We carried out a modification of SAGE methodology (microSAGE), useful for the analysis of limited quantities of tissue samples, on normal human cervical tissue obtained from a donor without histopathological lesions. Cervical epithelium is constituted mainly by cervical keratinocytes which are the targets of human papilloma virus (HPV), where persistent HPV infection of cervical epithelium is associated with an increase risk for developing cervical carcinomas (CC). Results We report here a transcriptome analysis of cervical tissue by SAGE, derived from 30,418 sequenced tags that provide a wealth of information about the gene products involved in normal cervical epithelium physiology, as well as genes not previously found in uterine cervix tissue involved in the process of epidermal differentiation. Conclusion This first comprehensive and profound analysis of uterine cervix transcriptome, should be useful for the identification of genes involved in normal cervix uterine function, and candidate genes associated with cervical carcinoma. PMID:16171524

  18. Anatomy, histology, histochemistry and fine structure of the Harderian gland in the South American armadillo Chaetophractus villosus (Xenarthra, Mammalia).

    PubMed

    Aldana Marcos, Hernán Javier; Affanni, Jorge Mario

    2005-06-01

    The anatomical, histological, histochemical and ultrastructural characteristics of the Harderian gland of the armadillo Chaetophractus villosus were described. The gland is the largest structure in the bony orbit. It is situated in the anteroventral region of the orbit. Obvious structural differences are not observed between males and females. The gland is compound-branched tubulo-alveolar, being characterized by a single layer of columnar cells surrounded by myoepithelial cells. It possesses a single excretory duct opened into the inner canthus. All glandular cells show yellow-green autofluorescence and additionally some glandular lumen may contain dense autofluorescent solid accretions. There are two peculiar and outstanding cytoplasmic features. One is represented by the smooth endoplasmic reticulum (SER), forming a closely woven meshwork. The other one is represented by "membranous bodies" apparently derived from the SER, RER and cytoskeleton with a "Star of David" configuration situated in the supranuclear region. Three types of vesicles are detected in the cytoplasm. Histochemical staining methods reveal lipids, proteins, neutral and acidic containing glycoconjugates in secretory vesicles. The mechanism of secretion appears either merocrine or apocrine. The epithelium of the intra- and inter-lobular excretory ducts suggests secretory activity. Tubulo-acinar glands similar to those seen in the lacrimal gland and nictitans glands are found related to the intralobular and main excretory ducts. The capillary network is characterized by fenestrated endothelium. The stroma possesses unmyelinated axons and plasma cells. The normal secretion of the secretory endpieces, particularly lipids, proteins and glycoconjugates, is complemented by mucous and serous secretions released by ductal cells and glands associated to the ducts.

  19. Developmental origin of the posterior pigmented epithelium of iris.

    PubMed

    Wang, Xiaobing; Xiong, Kai; Lu, Lei; Gu, Dandan; Wang, Songtao; Chen, Jing; Xiao, Honglei; Zhou, Guomin

    2015-03-01

    Iris epithelium is a double-layered pigmented cuboidal epithelium. According to the current model, the neural retina and the posterior iris pigment epithelium (IPE) are derived from the inner wall of the optic cup, while the retinal pigment epithelium (RPE) and the anterior IPE are derived from the outer wall of the optic cup during development. Our current study shows evidence, contradicting this model of fetal iris development. We demonstrate that human fetal iris expression patterns of Otx2 and Mitf transcription factors are similar, while the expressions of Otx2 and Sox2 are complementary. Furthermore, IPE and RPE exhibit identical morphologic development during the early embryonic period. Our results suggest that the outer layer of the optic cup forms two layers of the iris epithelium, and the posterior IPE is the inward-curling anterior rim of the outer layer of the optic cup. These findings provide a reasonable explanation of how IPE cells can be used as an appropriate substitute for RPE cells.

  20. Multivariate normality

    NASA Technical Reports Server (NTRS)

    Crutcher, H. L.; Falls, L. W.

    1976-01-01

    Sets of experimentally determined or routinely observed data provide information about the past, present and, hopefully, future sets of similarly produced data. An infinite set of statistical models exists which may be used to describe the data sets. The normal distribution is one model. If it serves at all, it serves well. If a data set, or a transformation of the set, representative of a larger population can be described by the normal distribution, then valid statistical inferences can be drawn. There are several tests which may be applied to a data set to determine whether the univariate normal model adequately describes the set. The chi-square test based on Pearson's work in the late nineteenth and early twentieth centuries is often used. Like all tests, it has some weaknesses which are discussed in elementary texts. Extension of the chi-square test to the multivariate normal model is provided. Tables and graphs permit easier application of the test in the higher dimensions. Several examples, using recorded data, illustrate the procedures. Tests of maximum absolute differences, mean sum of squares of residuals, runs and changes of sign are included in these tests. Dimensions one through five with selected sample sizes 11 to 101 are used to illustrate the statistical tests developed.

  1. Quantitative proteomic analysis of microdissected oral epithelium for cancer biomarker discovery.

    PubMed

    Xiao, Hua; Langerman, Alexander; Zhang, Yan; Khalid, Omar; Hu, Shen; Cao, Cheng-Xi; Lingen, Mark W; Wong, David T W

    2015-11-01

    Specific biomarkers are urgently needed for the detection and progression of oral cancer. The objective of this study was to discover cancer biomarkers from oral epithelium through utilizing high throughput quantitative proteomics approaches. Morphologically malignant, epithelial dysplasia, and adjacent normal epithelial tissues were laser capture microdissected (LCM) from 19 patients and used for proteomics analysis. Total proteins from each group were extracted, digested and then labelled with corresponding isobaric tags for relative and absolute quantitation (iTRAQ). Labelled peptides from each sample were combined and analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) for protein identification and quantification. In total, 500 proteins were identified and 425 of them were quantified. When compared with adjacent normal oral epithelium, 17 and 15 proteins were consistently up-regulated or down-regulated in malignant and epithelial dysplasia, respectively. Half of these candidate biomarkers were discovered for oral cancer for the first time. Cornulin was initially confirmed in tissue protein extracts and was further validated in tissue microarray. Its presence in the saliva of oral cancer patients was also explored. Myoglobin and S100A8 were pre-validated by tissue microarray. These data demonstrated that the proteomic biomarkers discovered through this strategy are potential targets for oral cancer detection and salivary diagnostics.

  2. Development and Characterization of Uterine Glandular Epithelium Specific Androgen Receptor Knockout Mouse Model.

    PubMed

    Choi, Jaesung Peter; Zheng, Yu; Skulte, Katherine A; Handelsman, David J; Simanainen, Ulla

    2015-11-01

    While estrogen action is the major driver of uterine development, androgens acting via the androgen receptor (AR) may also promote uterine growth as suggested by uterine phenotypes in global AR knockout (ARKO) female mice. Because AR is expressed in uterine endometrial glands, we generated (Cre/loxP) uterine gland epithelium-specific ARKO (ugeARKO) to determine the role of endometrial gland-specific androgen actions. However, AR in uterine gland epithelium may not be required for normal uterine development and function because ugeARKO females had normal uterine development and fertility. To determine if exogenous androgens acting via AR can fully support uterine growth in the absence of estrogens, the ARKO and ugeARKO females were ovariectomized and treated with supraphysiological doses of testosterone or dihydrotestosterone (nonaromatizable androgen). Both dihydrotestosterone and testosterone supported full uterine regrowth in wild-type females while ARKO females had no regrowth (comparable to ovariectomized only). These findings suggest that androgens acting via AR can promote full uterine regrowth in the absence of estrogens. The ugeARKO had 50% regrowth when compared to intact uterine glands, and histomorphologically, both the endometrial and myometrial areas were significantly (P < 0.05) reduced, suggesting glandular epithelial AR located in the endometrium may indirectly modify myometrial development. Additionally, to confirm Cre function in endometrial glands, we generated uge-specific PTEN knockout mouse model. The ugePTEN knockout females developed severe endometrial hyperplasia and therefore present a novel model for future research.

  3. FOXJ1 prevents cilia growth inhibition by cigarette smoke in human airway epithelium in vitro.

    PubMed

    Brekman, Angelika; Walters, Matthew S; Tilley, Ann E; Crystal, Ronald G

    2014-11-01

    Airway epithelium ciliated cells play a central role in clearing the lung of inhaled pathogens and xenobiotics, and cilia length and coordinated beating are important for airway clearance. Based on in vivo studies showing that the airway epithelium of healthy smokers has shorter cilia than that of healthy nonsmokers, we investigated the mechanisms involved in cigarette smoke-mediated inhibition of ciliogenesis by assessing normal human airway basal cell differentiation in air-liquid interface (ALI) cultures in the presence of nontoxic concentrations of cigarette smoke extract (CSE). Measurements of cilia length from Day 28 ALI cultures demonstrated that CSE exposure was associated with shorter cilia (P < 0.05), reproducing the effect of cigarette smoking on cilia length observed in vivo. This phenotype correlated with a broad CSE-mediated suppression of genes involved in cilia-related transcriptional regulation, intraflagellar transport, cilia motility, structural integrity, and basal body development but not of control genes or epithelial barrier integrity. The CSE-mediated inhibition of cilia growth could be prevented by lentivirus-mediated overexpression of FOXJ1, the major cilia-related transcription factor, which led to partial reversal of expression of cilia-related genes suppressed by CSE. Together, the data suggest that components of cigarette smoke are responsible for a broad suppression of genes involved in cilia growth, but, by stimulating ciliogenesis with the transcription factor FOXJ1, it may be possible to maintain close to normal cilia length despite the stress of cigarette smoking.

  4. The Role of NF-kB in Normal and Transformed Mammary Epithelium.

    DTIC Science & Technology

    1998-08-01

    aAN has been constructed by standard molecular cloning techniques. The plasmid is called pBLG-AN. The avian IiB- aAN has been used successfully in...Mercurio, F., DiDonato, J., Rosette, C., and Karin, M. 1992. Molecular cloning and characterization of a novel Rel/NF-id3 family member displaying...reaching a peak during lactation. Using Dr. Clark’s pBJ41 construct, a transgene bearing the human NFKB2 cDNA has been constructed by standard molecular

  5. Haploinsufficiency in tumor predisposition syndromes: altered genomic transcription in morphologically normal cells heterozygous for VHL or TSC mutation.

    PubMed

    Peri, Suraj; Caretti, Elena; Tricarico, Rossella; Devarajan, Karthik; Cheung, Mitchell; Sementino, Eleonora; Menges, Craig W; Nicolas, Emmanuelle; Vanderveer, Lisa A; Howard, Sharon; Conrad, Peggy; Crowell, James A; Campbell, Kerry S; Ross, Eric A; Godwin, Andrew K; Yeung, Anthony T; Clapper, Margie L; Uzzo, Robert G; Henske, Elizabeth P; Ricketts, Christopher J; Vocke, Cathy D; Linehan, W Marston; Testa, Joseph R; Bellacosa, Alfonso; Kopelovich, Levy; Knudson, Alfred G

    2016-09-22

    Tumor suppressor genes and their effector pathways have been identified for many dominantly heritable cancers, enabling efforts to intervene early in the course of disease. Our approach on the subject of early intervention was to investigate gene expression patterns of morphologically normal "one-hit" cells before they become hemizygous or homozygous for the inherited mutant gene which is usually required for tumor formation. Here, we studied histologically non-transformed renal epithelial cells from patients with inherited disorders that predispose to renal tumors, including von Hippel-Lindau (VHL) disease and Tuberous Sclerosis (TSC). As controls, we studied histologically normal cells from non-cancerous renal epithelium of patients with sporadic clear cell renal cell carcinoma (ccRCC). Gene expression analyses of VHLmut/wt or TSC1/2mut/wt versus wild-type (WT) cells revealed transcriptomic alterations previously implicated in the transition to precancerous renal lesions. For example, the gene expression changes in VHLmut/wt cells were consistent with activation of the hypoxia response, associated, in part, with the "Warburg effect". Knockdown of any remaining VHL mRNA using shRNA induced secondary expression changes, such as activation of NFκB and interferon pathways, that are fundamentally important in the development of RCC. We posit that this is a general pattern of hereditary cancer predisposition, wherein haploinsufficiency for VHL or TSC1/2, or potentially other tumor susceptibility genes, is sufficient to promote development of early lesions, while cancer results from inactivation of the remaining normal allele. The gene expression changes identified here are related to the metabolic basis of renal cancer and may constitute suitable targets for early intervention.

  6. Keratocyte loss in corneal infection through apoptosis: a histologic study of 59 cases

    PubMed Central

    Vemuganti, Geeta K; Reddy, Kishore; Iftekhar, Ghazala; Garg, Prashant; Sharma, Savitri

    2004-01-01

    Background Keratocyte loss by apoptosis following epithelial debridement is a well-recognized entity. In a study of corneal buttons obtained from patients of corneal ulcer undergoing therapeutic keratoplasty, we observed loss of keratocytes in the normal appearing corneal stroma, surrounding the zone of inflammation. Based on these observations, we hypothesized that the cell loss in the inflammatory free zone of corneal stroma is by apoptosis that could possibly be a non-specific host response, independent of the nature of infectious agent. Methods To test our hypothesis, in this study, we performed Terminal deoxyribonucleotidyl transferase-mediated d-Uridine 5" triphosphate Nick End Labelling (TUNEL) staining on 59 corneal buttons from patients diagnosed as bacterial, fungal, viral and Acanthamoeba keratitis. The corneal sections were reviewed for morphologic changes in the epithelium, stroma, type, degree and depth of inflammation, loss of keratocytes in the surrounding stroma (posterior or peripheral). TUNEL positivity was evaluated in the corneal sections, both in the zone of inflammation as well as the surrounding stroma. A correlation was attempted between the keratocyte loss, histologic, microbiologic and clinical features. Results The corneal tissues were from 59 patients aged between 16 years and 85 years (mean 46 years) and included fungal (22), viral (15), bacterial (14) and Acanthamoeba (8) keratitis. The morphological changes in corneal tissues noted were: epithelial ulceration (52, 88.1%), destruction of Bowman's layer (58, 99%), mild to moderate (28; 47.5%) to severe inflammation (31; 52.5%). Morphologic evidence of disappearance or reduced number of keratocytic nuclei in the corneal stroma was noted in 49 (83%) cases; while the TUNEL positive brown cells were identified in all cases 53/54 (98%), including cases of fungal (19), bacterial (14), viral (13), and Acanthamoeba keratitis. TUNEL staining was located mostly in the deeper stroma and in few

  7. Could magnetic resonance provide in vivo histology?

    PubMed

    Dominietto, Marco; Rudin, Markus

    2014-01-13

    THE DIAGNOSIS OF A SUSPECTED TUMOR LESION FACES TWO BASIC PROBLEMS: detection and identification of the specific type of tumor. Radiological techniques are commonly used for the detection and localization of solid tumors. Prerequisite is a high intrinsic or enhanced contrast between normal and neoplastic tissue. Identification of the tumor type is still based on histological analysis. The result depends critically on the sampling sites, which given the inherent heterogeneity of tumors, constitutes a major limitation. Non-invasive in vivo imaging might overcome this limitation providing comprehensive three-dimensional morphological, physiological, and metabolic information as well as the possibility for longitudinal studies. In this context, magnetic resonance based techniques are quite attractive since offer at the same time high spatial resolution, unique soft tissue contrast, good temporal resolution to study dynamic processes and high chemical specificity. The goal of this paper is to review the role of magnetic resonance techniques in characterizing tumor tissue in vivo both at morphological and physiological levels. The first part of this review covers methods, which provide information on specific aspects of tumor phenotypes, considered as indicators of malignancy. These comprise measurements of the inflammatory status, neo-vascular physiology, acidosis, tumor oxygenation, and metabolism together with tissue morphology. Even if the spatial resolution is not sufficient to characterize the tumor phenotype at a cellular level, this multiparametric information might potentially be used for classification of tumors. The second part discusses mathematical tools, which allow characterizing tissue based on the acquired three-dimensional data set. In particular, methods addressing tumor heterogeneity will be highlighted. Finally, we address the potential and limitation of using MRI as a tool to provide in vivo tissue characterization.

  8. NORMAL NASAL GENE EXPRESSION LEVELS USING CDNA ARRAY TECHNOLOGY

    EPA Science Inventory

    Normal Nasal Gene Expression Levels Using cDNA Array Technology.

    The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...

  9. Variation in testicular histology of the spiny tailed lizard Uromastyx aegyptius microlepis during hibernation and active periods.

    PubMed

    Abu-Zinadah, Osama A

    2008-06-15

    The testicular histology of the lizard, Uromastyx aegyptius microlepis were varied considerably during hibernation and activity periods, reaching maximum values in summer. The onset of winter induces testicular regression, reduced testis size, testis diameter, diameter and epithelial height of the seminiferous tubules and epididymal epithelial height. Animals exhibit testicular recrudescence during late winter (February and March) and maximum testicular volume occurred during June. The period of maximal testicular volume was positively correlated with increasing ambient temperature. The summer season induces the testicular activity in contrast with the winter season in which the activity decreased and the testes were collapsed. Spermatocytogenesis is active in early spring and the major portion of the seminiferous epithelium comprises spermatids in various stages of maturation and their luminae were filled with spermatozoa. The size of the interstitial cells is direct correlated with changes occurring in epididymis and seminiferous epithelium. Most interstitial cell nuclei show clear regression when spermatocytogenesis were diminishes.

  10. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    PubMed

    Brune, Kieran A; Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R; D'Alessio, Franco R; Lambert, Allison A; Kirk, Gregory; Blankson, Joel; Drummond, M Bradley; Tsibris, Athe M; Sidhaye, Venkataramana K

    2016-01-01

    Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE) cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI) to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1) and activated extracellular signal-regulated kinase (ERK). We demonstrate that HIV can enter airway

  11. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation

    PubMed Central

    Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R.; D’Alessio, Franco R.; Lambert, Allison A.; Kirk, Gregory; Blankson, Joel; Drummond, M. Bradley; Tsibris, Athe M.

    2016-01-01

    Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE) cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI) to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1) and activated extracellular signal-regulated kinase (ERK). We demonstrate that HIV can enter airway

  12. Assessment of oestrogen and progestin effects on epithelium and stroma from pre- and postmenopausal endometria.

    PubMed

    King, R J; Lane, G; Siddle, N; Taylor, R W; Townsend, P T; Whitehead, M I

    1981-12-01

    The efficacy of commercially available progestin preparations were investigated with a view toward determining the optimum type, dose, duration, and route of administration required to protect the endometrium. Biochemical indices of estrogen and progestin action in endometria from postmenopausal women receiving various hormone therapies were monitored. The premenopausal samples obtained during the proliferative and secretory phases of the cycle can be compared with physiologically normal activities. Estrogen effects were monitored by nuclear estradiol receptor (REN) and soluble progesterone receptor (RP) content and DNA synthesis by autoradiography after [3-H]-thymidine labelling. Progestin action was assayed by inhibition of estrogen-induced REN and DNA synthesis by induction of isocritic and estradiol dehydrogenases and by morphological criteria. Postmenopausal patients were attending the menopause clinics at King's College Hospital or the Chelsea Hospital for Women in London for symptoms associated with the climacteric. Premenopausal samples were obtained from women attending the above hospitals as well as St. Thomas Hospital in London. There are no differences in REN or estradiol receptor content (RET) between epithelium and stroma for any of the groups. Progestins, regardless of whether they are derived from exogenous (postmenopausal) or endogenous (premenopausal sources, decrease REN and RET in both fractions. Progestins also decreased DNA synthesis in both cell types and this suppression correlates with the fall in REN. The RP content of epithelium is greater than stroma, but the 2 enzymes are markedly stimulated by progestins in epithelium but not stroma. The lower RP content of the stromal fraction could be because of cellular heterogeneity, differential loss of receptor during processing, or to genuine differences between epithelium and stroma. Estrogen induced DNA synthesis is inhibited by progestins in both epithelium ans stroma but the induction of

  13. Morphology of the epithelium of the lower rectum and the anal canal in the adult human.

    PubMed

    Tanaka, Eiichi; Noguchi, Tsuyoshi; Nagai, Kaoruko; Akashi, Yuichi; Kawahara, Katsunobu; Shimada, Tatsuo

    2012-06-01

    The anal canal is an important body part clinically. However, there is no agreement about the epithelium of the anal canal, the anal transitional zone (ATZ) epithelium in particular. The aim of this study is to clarify the structure of the epithelium of the human lower rectum and anal canal. Intact rectum and anus obtained from patients who underwent surgery for rectal carcinoma were examined by light and scanning electron microscopy (LM and SEM). By LM, three types of epithelium were observed in the anal canal: simple columnar epithelium, stratified squamous epithelium, and stratified columnar epithelium. The lower rectum was composed of simple columnar epithelium. SEM findings showed stratified squamous epithelium that consisted of squamous cells with microridges, changing to simple columnar epithelium consisting of columnar cells with short microvilli at the anorectal line. LM and SEM observations in a one-to-one ratio revealed that the area of stratified columnar epithelium based on LM corresponded to the anal crypt and sinus. In conclusion, the epithelium of the human anal canal was fundamentally composed of simple columnar epithelium and stratified squamous epithelium. We found no evidence of the ATZ.

  14. Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium

    PubMed Central

    Sridhar, Sriram; Schembri, Frank; Zeskind, Julie; Shah, Vishal; Gustafson, Adam M; Steiling, Katrina; Liu, Gang; Dumas, Yves-Martine; Zhang, Xiaohui; Brody, Jerome S; Lenburg, Marc E; Spira, Avrum

    2008-01-01

    Background Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal) and intrathoracic (bronchial) epithelium in healthy current and never smokers. Results Using genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome"), we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure. Conclusion Our findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for tobacco exposure as well as a

  15. The seminiferous epithelium cycle and its duration in different breeds of dog (Canis familiaris)

    PubMed Central

    Soares, Jaqueline M; Avelar, Gleide F; França, Luiz R

    2009-01-01

    Testis structure and function in dogs are relatively poorly investigated. The aim of the present study was to carry out a comparative investigation of the stages of the seminiferous epithelium cycle and its duration in different breeds of dog. Fifty-six sexually mature dogs (mongrel, n = 12; pinscher, n = 12; beagle, n = 5; American pit bull, n = 9; poodle, n = 12; and Labrador retriever, n = 6) were analysed. Intratesticular injections of tritiated thymidine were given to determine the duration of spermatogenesis. Orchiectomy was performed at different time periods following injection (1 h, 2 and 4 weeks). Testis fragments were embedded in plastic and routinely prepared for histological and autoradiographic evaluations. Eight stages were characterized based on the acrosome system. Significant (P < 0.05) differences were found for the frequencies of the different stages characterized (except Stages V, VI and VIII), particularly for the mongrel. Stage IV (when spermiation occurs) was the most frequent in all six breeds (∼25%), whereas Stages II and VIII were the least frequent (< 8%). Each spermatogenic cycle and the total duration of spermatogenesis lasted 13.73 ± 0.03 and 61.9 ± 0.14 days, respectively, for the mongrel, poodle, pinscher, beagle, and Labrador retriever. These values were ∼10% lower (P < 0.03) for the American pit bull (12.55 ± 0.26 and 56.5 ± 1.17 days, respectively). To our knowledge, this is the first comprehensive study to perform a careful investigation of stage frequencies and seminiferous epithelium cycle duration in this very important domestic species. PMID:19627387

  16. Morphology of non-sensory epithelium during post-natal development of the rabbit vomeronasal organ.

    PubMed

    Elgayar, S A M; Eltony, S A; Othman, M A

    2014-08-01

    The vomeronasal organ (VNO), because of its ability to detect pheromones, has an important role in many social and sexual behaviours in mammals. It also mediates defensive behaviours through detection of protein pheromone homologues. A detailed morphological description of the post-natal development of the 'non-sensory' epithelium (NSE) of the female rabbit is recorded. Histological techniques were used to study the NSE of the VNO in post-natal development of female rabbits. The study focused on the following post-natal ages: newborn, 1 week, 2 weeks and 1 month (five animals each) beside to two adult animals. The rabbit VNO was surrounded externally by bony capsule and internally by cartilaginous capsule. NSE was pseudostratified columnar partially ciliated epithelium without goblet cells. In addition to basal cells, NSE contained ciliated and three types of non-ciliated columnar cells (dark, pale and light). At birth, dark cells may have primary cilia. By 1 month, the cytoplasm became lighter with less free ribosomes. The pale cells had electron-lucent cytoplasm, which contained a few organelles. Mitotic figures were observed in basal and columnar cells, particularly during the first 2 weeks of post-natal development. Light columnar cells were common during the first week. Numerous leucocytes and a few nerve endings were detected intra-epithelial. Scanning electron microscope revealed a gradual increase in height of microvilli of non-ciliated cells. Ciliated cells had cilia and microvilli. Cells were arranged singly, in clumps or in a dense population of cells. The rabbit VNO-NSE had a unique morphological structure.

  17. Metaplastic changes in the epithelium of radicular cysts: A series of 711 cases

    PubMed Central

    Rosen, Eyal; Dubinsky, Liz; Buchner, Amos; Vered, Marilena

    2016-01-01

    Background This study was aimed to evaluate the prevalence of metaplastic changes in the epithelium of radicular cysts and to investigate how they relate to the clinical and radiographic characteristics of the cysts, based on a large series of radicular cysts. Material and Methods Biopsies of cysts of endodontic origin that were examined at the Department of Oral Pathology between 2004 and 2011 have been re-evaluated for this study. Only cases that were re-confirmed with clinical and histological diagnoses of a radicular or residual radicular cyst were included. The included cases were evaluated for the prevalence of metaplastic changes in the form of mucous secreting cells (MSC) or ciliated cells (CC). The relations between the metaplastic changes and the cyst type (radicular or residual radicular), as well as demographic, clinical and radiographic parameters, were statistically evaluated using Fischer and chi-square tests. Significance was set at p<0.05. Results A total of 711 cysts were included: 677 were radicular cysts (95%) and 34 (5%) were residual radicular cysts. 23 cases had histopathological diagnoses other than radicular or residual radicular cysts and were excluded from the study. MSC were present in 47 (6.6%) cysts. MSC were significantly more common in residual radicular cysts than in radicular cysts [8 (23.5%) and 39 (5.8%), respectively; p<0.001]. MSC-containing cysts were commonly found in asymptomatic patients (10.5%, p<0.001), and usually presented with well-defined radiographic borders (7.2%, p<0.05). CC were present in 34 (4.8%) cysts, with a markedly high prevalence in the maxillary molar sextant (15%, p<0.001). Conclusions In the epithelium of radicular and residual radicular cysts the presence of specific metaplastic changes may be related to cyst type, symptomatology, radiographic findings and tooth location. Key words:Radicular cyst, metaplasia, mucous secreting cells, ciliated cells. PMID:27957265

  18. Expression of S100B during the innate immune of corneal epithelium against fungi invasion

    PubMed Central

    Zhang, Jie; Zhao, Gui-Qiu; Qu, Jing; Che, Cheng-Ye; Lin, Jing; Jiang, Nan; Zhao, Han; Wang, Xue-Jun

    2016-01-01

    AIM To explore the expression of S100B in corneal epithelial cells under Aspergillus stimulation both in vivo and in vitro. METHODS Immortalized human corneal epithelial cells (HCECs) were exposed to inactive Aspergillus fumigatus (A. fumigatus) conidia at 0, 4, 8, 12, 16, and 24h respectively. The corneas of Wistar rats were exposed to active A. fumigatus at 0, 12, 24, 48h and the normal rat corneas were used for normal control. The mRNA level of S100B was evaluated by real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). S100B protein expression in cornea epithelium was detected by immunohistochemical/immunocytochemical staining (IHC/ICC). RESULTS Histopathology revealed a significant inflammatory cell infiltration in fungal keratitis human and rat cornea. Corneal epithelial cells didn't express or rarely express S100B at baseline. A. fumigatus significantly induced S100B mRNA expression in cultured corneal epithelial cells in a time depended manner in vitro, the mRNA began to rise significantly at 8h in vitro (P<0.05) and continue to rise as time prolonged (P<0.01). In vivo, S100B mRNA level was low in the normal corneas. However, it was increased in keratitis corneas from 12h after infection (P<0.05) and reached to a peak at 24h (P<0.001). Immunochemistry revealed an obvious staining in fungal keratitis corneas as well as immortalized HCECs compared to the normal ones respectively, indicating an increased expression of S100B protein. CONCLUSION S100B exists in corneal epithelial cells and is over-expressed under A. fumigatus stimulation. S100B may play an important role in the innate immune response of the corneal epithelium during A. fumigatus infection. PMID:26949634

  19. Morphology of the pancreatic ductal epithelium after traumatization of the papilla of Vater or endoscopic retrograde pancreatography with various contrast media in cats.

    PubMed

    Bub, H; Bürner, W; Riemann, J F; Stolte, M

    1983-07-01

    The epithelium of the pancreatic duct in cats was examined histologically, in the scanning electron and in the transmission electron microscope, after traumatization of the papilla of Vater or after pancreatography (ERP) with various contrast media. Ten minutes after traumatizing the papilla by repeated cannulation, we found lesions of the surface membrane of the epithelial cells. After ERP with the contrast media metrizamide and sodium meglumine ioxaglate, in the acute experiments, the least damage was observed when the low-osmolar, non-ionic metrizamide was used. In our chronic experiments the epithelial changes did not correlate with the contrast medium used. The degree of papillary stenoses and, probably, the initial injection pressure are more important. A mixture of the antiseptic polyvinyl pyrrolidone iodine to the contrast medium, which would prevent a bacterial contamination of the pancreatic duct after ERP, is morphologically justifiable but entails a risk of latent hyperthyroidism. Parenchymography with this mixture damaged the epithelium more than pancreatography.

  20. Histological preparation of developing vestibular otoconia for scanning electron microscopy

    NASA Technical Reports Server (NTRS)

    Huss, D.; Dickman, J. D.

    2003-01-01

    The unique nature of vestibular otoconia as calcium carbonate biominerals makes them particularly susceptible to chemical deformation during histological processing. We fixed and stored otoconia from all three otolith endorgans of embryonic, hatchling and adult Japanese quail in glutaraldehyde containing either phosphate or non-phosphate buffers for varying lengths of time and processed them for scanning electron microscopy. Otoconia from all age groups and otolith endorgans processed in 0.1 M phosphate buffer (pH 7.4) showed abnormal surface morphology when compared to acetone fixed controls. Otoconia processed in 0.1 M sodium cacodylate or HEPES buffered artificial endolymph (pH 7.4) showed normal morphology that was similar to controls. The degree of otoconial deformation was directly related to the time exposed to phosphate buffer. Short duration exposure produced particulate deformations while longer exposures resulted in fused otoconia that formed solid sheets. Otoconial surface deformation and fusing was independent of the glutaraldehyde component of the histological processing. These findings should help vestibular researchers to develop appropriate histological processing protocols in future studies of otoconia.

  1. The human sunburn reaction: histologic and biochemical studies

    SciTech Connect

    Gilchrest, B.A.; Soter, N.A.; Stoff, J.S.; Mihm, M.C. Jr.

    1981-01-01

    The ultraviolet-induced erythema reaction was investigated histologically and biochemically in four subjects, utilizing suction blister aspirates, analyzed for histamine and prostaglandin E2 (PGE2), and Epon-embedded 1-mu skin biopsy sections from control skin and from irradiated skin at intervals for 72 hours after exposure to a Hanovia lamp. Major histologic alterations in the epidermis included dyskeratotic and vacuolated keratinocytes (sunburn cells), and disappearance of Langerhans cells. In the dermis the major changes were vascular, involving both the superficial and deep venular plexuses. Endothelial cell enlargement was first apparent within 30 minutes of irradiation, peaked at 24 hours, and persisted throughout the 72-hour study period. Mast cell degranulation and associated perivenular edema were first apparent at 1 hour and striking at the onset of erythema, 3 to 4 hours postirradiation; edema was absent and mast cells were again normal in number and granule content at 24 hours. Histamine levels rose approximately fourfold above control values immediately after the onset of erythema and returned to baseline within 24 hours. PGE2 levels were statistically elevated even before the onset of erythema and reached approximately 150% of the control value at 24 hours. These data provide the first evidence that histamine may mediate the early phase of the human sunburn reaction and increase our understanding of its complex histologic and biochemical sequelae.

  2. Histologic progression in non-hodgkin's lymphoma

    SciTech Connect

    Hubbard, S.M.; Chabner, B.A.; DeVita, V.T., Jr.; Simon, R.; Berard, C.W.; Jones, R.B.; Garvin, A.J.; Canellos, G.P.; Osborne, C.K.; Young, R.C.

    1982-02-01

    The clinical course and biopsy specimens from 515 consecutive non-Hodgkin's lymphoma patients was evaluated retrospectively in an attempt to determine the clinical importance of documented changes in histology over time. Two-hundred and five of these patients has an initial diagnosis of nodular lymphoma and were reviewed for this anaysis. Sixty-three underwent a repeat biopsy greater than 6 mo after initial diagnosis. In 23 patients, these repeat biopsies revealed a change in histology to a diffuse pattern and/or a change to a larger ''histiocytic'' cell type, while repeat biopsies for the other 40 (63%) disclosd persistence of a nodular pattern and no clear change in basic cell type. Progression from nodular lymphoma to diffuse histiocytic, mixed, or undifferentiated types of lymphomas of Rappaport was found in repeate biopsies obtained from 19 patients (30%). Prognosis for survival following a biopsy that demonstrated histologic change was related to the histology demonstrated at the most recent biopsy and to the response to subsequent drug treatment. Survival following repeat biopsy for these 19 patients was significantly shorter than for the 40 patients whose histology remained nodular (p < 0.001). However, attainment of a complete remission with intensive combination chemotherapy was associated with prolonged survival in eight patients and prolonged disease-free survival in one patient. Since prior treatment may compromise the ability to achieve a complete response to chemotherapy in patients with nodular lymphoma who develop an aggressive diffuse histology, the likelihood of histologic progression must be considered in the design of future clinical trials in nodular lymphoma. Histologic progression does not preclude attainment of a complete response to intensive chemotherapy.

  3. Graphs and Grammars for Histology: An Introduction

    PubMed Central

    Prewitt, Judith M. S.

    1979-01-01

    The invention of the microscope disclosed a whole new world, that of the hitherto invisibly small. Histologic evidence as revealed by the microscope has become a cornerstone of medical diagnosis, and efforts are now being made to lay foundations so that the medical visual information processing burden can be alleviated significantly by cost-effective automation. This paper lays image processing foundations by presenting a graph-theoretic and syntactic model for the analysis of histologic patterns, and presents results to date.

  4. Epithelium-dependent extracellular matrix synthesis in transforming growth factor-beta 1-growth-inhibited mouse mammary gland.

    PubMed

    Silberstein, G B; Strickland, P; Coleman, S; Daniel, C W

    1990-06-01

    Exogenous transforming growth factor beta (TGF-beta 1) was shown in earlier studies to reversibly inhibit mouse mammary ductal growth. Using small plastic implants to treat regions of developing mammary glands in situ, we now report that TGF-beta 1 growth inhibition is associated with an ectopic accumulation of type I collagen messenger RNA and protein, as well as the glycosaminoglycan, chondroitin sulfate. Both macromolecules are normal components of the ductal extracellular matrix, which, under the influence of exogenous TGF-beta 1, became unusually concentrated immediately adjacent to the epithelial cells at the tip of the ductal growth points, the end buds. Stimulation of extracellular matrix was confined to aggregations of connective tissue cells around affected end buds and was not present around the TGF-beta 1 implants themselves, indicating that the matrix effect was epithelium dependent. Ectopic matrix synthesis was specific for TGF-beta 1 insofar as it was absent at ducts treated with other growth inhibitors, or at ducts undergoing normal involution in response to endogenous regulatory processes. These findings are consistent with the matrix-stimulating properties of TGF-beta 1 reported for other systems, but differ in their strict dependence upon epithelium. A possible role for endogenous TGF-beta 1 in modulating a mammary epithelium-stroma interaction is suggested.

  5. Diagnostic dry bone histology in human paleopathology.

    PubMed

    de Boer, H H Hans; Van der Merwe, A E Lida

    2016-10-01

    Paleopathology is the study of trauma and disease as may be observed in ancient (human) remains. In contrast to its central role in current medical practice, microscopy plays a rather modest role in paleopathology. This is at least partially due to the differences between fresh and decomposed (i.e., skeletonized or "dry bone") tissue samples. This review discusses these differences and describes how they affect the histological analysis of paleopathological specimens. First, we provide a summary of some general challenges related to the histological analysis of palaeopathological specimens. Second, the reader is introduced in bone tissue histology and bone tissue dynamics. The remainder of the paper is dedicated to the diagnostic value of dry bone histology. Its value and limitations are illustrated by comparing several well-studied paleopathological cases with similar contemporary, clinical cases. This review illustrates that due to post-mortem loss of soft tissue, a limited number of disorders display pathognomonic features during histological analysis of skeletonized human remains. In the remainder of cases, histology may help to narrow down the differential diagnosis or is diagnostically unspecific. A comprehensive, multidisciplinary diagnostic approach therefore remains essential. Clin. Anat. 29:831-843, 2016. © 2016 Wiley Periodicals, Inc.

  6. Stem and progenitor cells of the mammalian olfactory epithelium: Taking poietic license.

    PubMed

    Schwob, James E; Jang, Woochan; Holbrook, Eric H; Lin, Brian; Herrick, Daniel B; Peterson, Jesse N; Hewitt Coleman, Julie

    2017-03-01

    The capacity of the olfactory epithelium (OE) for lifelong neurogenesis and regeneration depends on the persistence of neurocompetent stem cells, which self-renew as well as generating all of the cell types found within the nasal epithelium. This Review focuses on the types of stem and progenitor cells in the epithelium and their regulation. Both horizontal basal cells (HBCs) and some among the population of globose basal cells (GBCs) are stem cells, but the two types plays vastly different roles. The GBC population includes the basal cells that proliferate in the uninjured OE and is heterogeneous with respect to transcription factor expression. From upstream in the hierarchy to downstream, GBCs encompass 1) Sox2(+) /Pax6(+) stem-like cells that are totipotent and self-renew over the long term, 2) Ascl1(+) transit-amplifying progenitors with a limited capacity for expansive proliferation, and 3) Neurog1(+) /NeuroD1(+) immediate precursor cells that make neurons directly. In contrast, the normally quiescent HBCs are activated to multipotency and proliferate when sustentacular cells are killed, but not when only OSNs die, indicating that HBCs are reserve stem cells that respond to severe epithelial injury. The master regulator of HBC activation is the ΔN isoform of the transcription factor p63; eliminating ΔNp63 unleashes HBC multipotency. Notch signaling, via Jagged1 ligand on Sus cells and Notch1 and Notch2 receptors on HBCs, is likely to play a major role in setting the level of p63 expression. Thus, ΔNp63 becomes a potential therapeutic target for reversing the neurogenic exhaustion characteristic of the aged OE. J. Comp. Neurol. 525:1034-1054, 2017. © 2016 Wiley Periodicals, Inc.

  7. Dual roles of hemidesmosomal proteins in the pancreatic epithelium: the phosphoinositide 3-kinase decides.

    PubMed

    Laval, S; Laklai, H; Fanjul, M; Pucelle, M; Laurell, H; Billon-Galés, A; Le Guellec, S; Delisle, M-B; Sonnenberg, A; Susini, C; Pyronnet, S; Bousquet, C

    2014-04-10

    Given the failure of chemo- and biotherapies to fight advanced pancreatic cancer, one major challenge is to identify critical events that initiate invasion. One priming step in epithelia carcinogenesis is the disruption of epithelial cell anchorage to the basement membrane which can be provided by hemidesmosomes (HDs). However, the existence of HDs in pancreatic ductal epithelium and their role in carcinogenesis remain unexplored. HDs have been explored in normal and cancer pancreatic cells, and patient samples. Unique cancer cell models where HD assembly can be pharmacologically manipulated by somatostatin/sst2 signaling have been then used to investigate the role and molecular mechanisms of dynamic HD during pancreatic carcinogenesis. We surprisingly report the presence of mature type-1 HDs comprising the integrin α6β4 and bullous pemphigoid antigen BP180 in the human pancreatic ductal epithelium. Importantly, HDs are shown to disassemble during pancreatic carcinogenesis. HD breakdown requires phosphoinositide 3-kinase (PI3K)-dependent induction of the matrix-metalloprotease MMP-9, which cleaves BP180. Consequently, integrin α6β4 delocalizes to the cell-leading edges where it paradoxically promotes cell migration and invasion through S100A4 activation. As S100A4 in turn stimulates MMP-9 expression, a vicious cycle maintains BP180 cleavage. Inactivation of this PI3K-MMP-9-S100A4 signaling loop conversely blocks BP180 cleavage, induces HD reassembly and inhibits cell invasion. We conclude that mature type-1 HDs are critical anchoring structures for the pancreatic ductal epithelium whose disruption, upon PI3K activation during carcinogenesis, provokes pancreatic cancer cell migration and invasion.

  8. Quality control in microarray assessment of gene expression in human airway epithelium

    PubMed Central

    Raman, Tina; O'Connor, Timothy P; Hackett, Neil R; Wang, Wei; Harvey, Ben-Gary; Attiyeh, Marc A; Dang, David T; Teater, Matthew; Crystal, Ronald G

    2009-01-01

    Background Microarray technology provides a powerful tool for defining gene expression profiles of airway epithelium that lend insight into the pathogenesis of human airway disorders. The focus of this study was to establish rigorous quality control parameters to ensure that microarray assessment of the airway epithelium is not confounded by experimental artifact. Samples (total n = 223) of trachea, large and small airway epithelium were collected by fiberoptic bronchoscopy of 144 individuals and hybridized to Affymetrix microarrays. The pre- and post-chip quality control (QC) criteria established, included: (1) RNA quality, assessed by RNA Integrity Number (RIN) ≥ 7.0; (2) cRNA transcript integrity, assessed by signal intensity ratio of GAPDH 3' to 5' probe sets ≤ 3.0; and (3) the multi-chip normalization scaling factor ≤ 10.0. Results Of the 223 samples, all three criteria were assessed in 191; of these 184 (96.3%) passed all three criteria. For the remaining 32 samples, the RIN was not available, and only the other two criteria were used; of these 29 (90.6%) passed these two criteria. Correlation coefficients for pairwise comparisons of expression levels for 100 maintenance genes in which at least one array failed the QC criteria (average Pearson r = 0.90 ± 0.04) were significantly lower (p < 0.0001) than correlation coefficients for pairwise comparisons between arrays that passed the QC criteria (average Pearson r = 0.97 ± 0.01). Inter-array variability was significantly decreased (p < 0.0001) among samples passing the QC criteria compared with samples failing the QC criteria. Conclusion Based on the aberrant maintenance gene data generated from samples failing the established QC criteria, we propose that the QC criteria outlined in this study can accurately distinguish high quality from low quality data, and can be used to delete poor quality microarray samples before proceeding to higher-order biological analyses and interpretation. PMID:19852842

  9. Remote histology learning from static versus dynamic microscopic images.

    PubMed

    Mione, Sylvia; Valcke, Martin; Cornelissen, Maria

    2016-05-06

    Histology is the study of microscopic structures in normal tissue sections. Curriculum redesign in medicine has led to a decrease in the use of optical microscopes during practical classes. Other imaging solutions have been implemented to facilitate remote learning. With advancements in imaging technologies, learning material can now be digitized. Digitized microscopy images can be presented in either a static or dynamic format. This study of remote histology education identifies whether dynamic pictures are superior to static images for the acquisition of histological knowledge. Test results of two cohorts of second-year Bachelor in Medicine students at Ghent University were analyzed in two consecutive academic years: Cohort 1 (n = 190) and Cohort 2 (n = 174). Students in Cohort 1 worked with static images whereas students in Cohort 2 were presented with dynamic images. ANCOVA was applied to study differences in microscopy performance scores between the two cohorts, taking into account any possible initial differences in prior knowledge. The results show that practical histology scores are significantly higher with dynamic images as compared to static images (F (1,361) = 15.14, P < 0.01), regardless of student's gender and performance level. Several reasons for this finding can be explained in accordance with cognitivist learning theory. Since the findings suggest that knowledge construction with dynamic pictures is stronger as compared to static images, dynamic images should be introduced in a remote setting for microscopy education. Further implementation within a larger electronic learning management system needs to be explored in future research. Anat Sci Educ 9: 222-230. © 2015 American Association of Anatomists.

  10. Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

    NASA Astrophysics Data System (ADS)

    Garzotto, D.; De Marchis, S.

    2010-10-01

    Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

  11. Cigarette smoke inhibition of ion transport in canine tracheal epithelium

    SciTech Connect

    Welsh, M.J.

    1983-06-01

    To determine the effect of cigarette smoke on airway epithelial ion transport, the electrical properties and transepithelial Na and Cl fluxes were measured in canine tracheal epithelium. In vivo, the inhalation of the smoke from one cigarette acutely and reversibly decreased the electrical potential difference across the tracheal epithelium. In vitro, exposure of the mucosal surface of the epithelium to cigarette smoke decreased the short circuit current and transepithelial resistance. The decrease in short circuit current was due to an inhibition of the rate of Cl secretion with minimal effect on the rate of Na absorption. The effect of cigarette smoke was reversible, was not observed upon exposure of the submucosal surface to smoke, and was most pronounced when secretion was stimulated. The particulate phase of smoke was largely responsible for the inhibitory effect, since filtering the smoke minimized the effect. The effect of cigarette smoke was not prevented by addition of antioxidants to the bathing solutions, suggesting that the inhibition of Cl secretion cannot be entirely attributed to an oxidant mechanism. These results indicate that cigarette smoke acutely inhibits active ion transport by tracheal epithelium, both in vivo and in vitro. This effect may explain, in part, both the abnormal mucociliary clearance and the airway disease observed in cigarette smokers.

  12. Examination of the reticular epithelium of the bovine pharyngeal tonsil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The nasopharyngeal tonsil (adenoid), located at the posterior of the nasopharynx is ideally positioned to sample antigens entering through the nasal cavity or oral cavity. Entering antigens will first contact tonsilar epithelium. To better understand the cellular composition of this important epithe...

  13. Coelomic epithelium-derived cells in visceral morphogenesis.

    PubMed

    Ariza, Laura; Carmona, Rita; Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón

    2016-03-01

    Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans.

  14. The multi-tasking gut epithelium of insects.

    PubMed

    Huang, Jia-Hsin; Jing, Xiangfeng; Douglas, Angela E

    2015-12-01

    The insect gut epithelium plays a vital role in multiple processes, including nutrition, immunity and osmoregulation. Recent research is revealing the molecular and biochemical basis of these functions. For example, the pattern of nutrient acquisition by the gut epithelium is integrated into the overall regulation of nutrient allocation, as illustrated by evidence for systemic controls over expression of key genes coding digestive enzymes and transporters in carbohydrate acquisition; and the abundance and diversity of microorganisms in the gut lumen is regulated by multiple molecular properties of the gut epithelial cells, including the synthesis of enzymes that produce reactive oxygen species and anti-microbial peptides. These traits are underpinned by the function of the gut epithelium as a selective barrier which mediates the controlled movement of water, ions, metabolites and macromolecules between the gut lumen and insect tissues. Breakdown of the gut epithelial barrier has been implicated in muscle paralysis of insects at low temperatures (chill coma) and in aging. The key challenge for future research is to understand how the multiple functions of the insect gut epithelium are integrated by signaling interactions among epithelial cells, the gut microbiota and other insect organs.

  15. The Olfactory Neural Epithelium As a Tool in Neuroscience.

    PubMed

    Lavoie, Joëlle; Gassó Astorga, Patricia; Segal-Gavish, Hadar; Wu, YeeWen Candace; Chung, Youjin; Cascella, Nicola G; Sawa, Akira; Ishizuka, Koko

    2017-02-01

    Capturing both dynamic changes (state) and persistent signatures (trait) directly associated with disease at the molecular level is crucial in modern medicine. The olfactory neural epithelium, easily accessible in clinical settings, is a promising surrogate model in translational brain medicine, complementing the limitations in current engineered cell models.

  16. Histological and morphometric study of the epididymus of Chinchilla lanigera Grey under controlled conditions in captivity.

    PubMed

    Gramajo-Bühler, M C; Pucci, F J; Sanchez-Toranzo, G

    2016-06-01

    Chinchilla lanigera, native to the Andean Mountains of Perú, Chile, Bolivia and Argentina, is a specimen of great economic importance because of its fur. In mammals, spermatozoa originate in testes and are transported to the epididymis, where they undergo morphological and biochemical modifications known as sperm maturation, a basic step in the acquisition of their fertilizing ability. The aim of this work is the macroscopic and microscopic analysis of the epididymis of Chinchilla lanigera Grey and its sectorization based on a histomorphological study. The epididymis presents a clear segmentation into four regions: initial segment, caput, corpus and cauda. The epithelium lining the seminiferous tubules is pseudostratified, with principal cells with stereocilia and basal, clear, apical, narrow and halo cells. The histological analysis showed that principal and basal cells are the prevailing populations in all regions, also revealing narrow cells and the absence of clear cells in the initial segment. Each segment presents its different histological and morphometric characteristics, which supports the idea of the specific behaviour of each region, giving a segment-specific character to the process of sperm maturation in this species. No significant differences were found in the morphometric measurements or in the histological evaluation of the epididymis of samples collected in April and October. The fact that no differences were found between the samples collected during the two periods when the reproductive ability in nature is different suggests the importance of external factors in the control of the reproductive cycle of Chinchilla lanigera.

  17. Physiological COX-2 expression in breast epithelium associates with COX-2 levels in ductal carcinoma in situ and invasive breast cancer in young women.

    PubMed

    Fornetti, Jaime; Jindal, Sonali; Middleton, Kara A; Borges, Virginia F; Schedin, Pepper

    2014-04-01

    Cyclooxygenase-2 (COX-2) overexpression is implicated in increased risk and poorer outcomes in breast cancer in young women. We investigated COX-2 regulation in normal premenopausal breast tissue and its relationship to malignancy in young women. Quantitative COX-2 immunohistochemistry was performed on adjacent normal and breast cancer tissues from 96 premenopausal women with known clinical reproductive histories, and on rat mammary glands with distinct ovarian hormone exposures. COX-2 expression in the normal breast epithelium varied more than 40-fold between women and was associated with COX-2 expression levels in ductal carcinoma in situ and invasive cancer. Normal breast COX-2 expression was independent of known breast cancer prognostic indicators, including tumor stage and clinical subtype, indicating that factors regulating physiological COX-2 expression may be the primary drivers of COX-2 expression in breast cancer. Ovarian hormones, particularly at pregnancy levels, were identified as modulators of COX-2 in normal mammary epithelium. However, serial breast biopsy analysis in nonpregnant premenopausal women suggested relatively stable baseline levels of COX-2 expression, which persisted independent of menstrual cycling. These data provide impetus to investigate how baseline COX-2 expression is regulated in premenopausal breast tissue because COX-2 levels in normal breast epithelium may prove to be an indicator of breast cancer risk in young women, and predict the chemopreventive and therapeutic efficacy of COX-2 inhibitors in this population.

  18. Maintenance of the corneal epithelium is carried out by germinative cells of its basal stratum and not by presumed stem cells of the limbus.

    PubMed

    Haddad, A; Faria-e-Sousa, S J

    2014-06-01

    The purpose of this investigation was to analyze the proliferative behavior of rabbit corneal epithelium and establish if any particular region was preferentially involved in epithelial maintenance. [3H]-thymidine was injected intravitreally into both normal eyes and eyes with partially scraped corneal epithelium. Semithin sections of the anterior segment were evaluated by quantitative autoradiography. Segments with active replication (on) and those with no cell division (off) were intermingled in all regions of the tissue, suggesting that the renewal of the epithelial surface of the cornea followed an on/off alternating pattern. In the limbus, heavy labeling of the outermost layers was observed, coupled with a few or no labeled nuclei in the basal stratum. This suggests that this region is a site of rapid cell differentiation and does not contain many slow-cycling cells. The conspicuous and protracted labeling of the basal layer of the corneal epithelium suggests that its cells undergo repeated cycles of replication before being sent to the suprabasal strata. This replication model is prone to generate label-retaining cells. Thus, if these are adult stem cells, one must conclude that they reside in the corneal basal layer and not the limbal basal layer. One may also infer that the basal cells of the cornea and not of the limbus are the ones with the main burden of renewing the corneal epithelium. No particular role in this process could be assigned to the cells of the basal layer of the limbal epithelium.

  19. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    PubMed

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

  20. Prediction of esophageal and gastric histology by macroscopic diagnosis during upper endoscopy in pediatric celiac disease

    PubMed Central

    Boschee, Erin D; Yap, Jason Y K; Turner, Justine M

    2017-01-01

    AIM To determine the sensitivity of macroscopic appearance for predicting histological diagnosis at sites other than duodenum in pediatric celiac disease (CD). METHODS Endoscopic and histologic findings in pediatric patients undergoing upper endoscopy for first-time diagnosis of CD at Stollery Children’s Hospital from 2010-2012 were retrospectively reviewed. RESULTS Clinical charts from 140 patients were reviewed. Esophageal and gastric biopsies were taken in 54.3% and 77.9% of patients, respectively. Endoscopic appearance was normal in the esophagus and stomach in 75% and 86.2%. Endoscopic esophageal diagnoses were eosinophilic esophagitis (EE) (11.8%), esophagitis (7.9%), glycogenic acanthosis (1.3%) and non-specific abnormalities (3.9%). Endoscopic gastric diagnoses were gastritis (8.3%), pancreatic rest (0.9%), and non-specific abnormalities (4.6%). Histology was normal in 76.3% of esophageal and 87.2% of gastric specimens. Abnormal esophageal histology was EE (10.5%), esophagitis (10.5%), glycogenic acanthosis (1.3%) and non-specific (1.3%). Gastritis was reported in 12.8% of specimens. Sensitivity and specificity of normal endoscopy for predicting normal esophageal histology was 86.2% and 61.1%, and for normal gastric histology was 87.4% and 21.4%. CONCLUSION In the absence of macroscopic abnormalities, routine esophageal and gastric biopsy during endoscopy for pediatric CD does not identify major pathologies. These findings have cost and time saving implications for clinical practice. PMID:28216971

  1. A study on the differences between oral squamous cell carcinomas and normal oral mucosas measured by Fourier transform infrared spectroscopy.

    PubMed

    Fukuyama, Y; Yoshida, S; Yanagisawa, S; Shimizu, M

    1999-01-01

    We investigated the differences of Fourier transform infrared (FTIR) spectra between oral squamous cell carcinoma (OSCC) and normal gingival epithelium (NGE) or normal subgingival tissue (NST). We used 15 specimens of OSCC which had not been treated before measurement and 10 of NGE or NST. We also used cultured oral squamous cell carcinoma (COSCC) and the tissue (MSCC) which massed for 3 months after the cultured oral squamous cell carcinoma was transplanted into the lower back of a rat. Those tissue spectra were compared with the purified human collagens and human keratin. One half of every tissue specimen was measured with FTIR and the other half was investigated histologically. The differences of FTIR spectra between OSCC and NGE were observed in the bands between 1431 and 1482 cm(-1) and between 1183 and 1274 cm(-1). The shoulder at 1368 cm(-1) tended to disappear in OSCC, and the peaks at 1246 and 1083 cm(-1) found in NGE tended to shift to those at 1242 and 1086 cm(-1) in OSCC, respectively. The infrared spectrum of NST was noticed to be strongly influenced by the presence of collagen. Significant differences were also observed in the second derivative FTIR spectra between OSCC and NGE. Our data suggested that this infrared technique is applicable to clinical diagnostics.

  2. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay.

    PubMed

    Yilmaz, Ozlem

    2008-10-01

    The microbiota of the human oral mucosa consists of a myriad of bacterial species that normally exist in commensal harmony with the host. Porphyromonas gingivalis, an aetiological agent in severe forms of periodontitis (a chronic inflammatory disease), is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. This Gram-negative anaerobe can also exist within the host epithelium without the existence of overt disease. Gingival epithelial cells, the outer lining of the gingival mucosa, which function as an important part of the innate immune system, are among the first host cells colonized by P. gingivalis. This review describes recent studies implicating the co-existence and intracellular adaptation of the organism in these target host cells. Specifically, recent findings on the putative mechanisms of persistence, intercellular dissemination and opportunism are highlighted. These new findings may also represent an original and valuable model for mechanistic characterization of other successful host-adapted, self-limiting, persistent intracellular bacteria in human epithelial tissues.

  3. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.

    PubMed

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J; Klein, Ophir D; Barlow, Linda A

    2014-08-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation.

  4. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium

    PubMed Central

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J.; Klein, Ophir D.; Barlow, Linda A.

    2014-01-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation. PMID:24993944

  5. Age and disease-related structural changes in the retinal pigment epithelium

    PubMed Central

    Bonilha, Vera L

    2008-01-01

    As the retinal pigment epithelium (RPE) ages, a number of structural changes occur, including loss of melanin granules, increase in the density of residual bodies, accumulation of lipofuscin, accumulation of basal deposits on or within Bruch’s membrane, formation of drusen (between the basal lamina of the RPE and the inner collagenous layer of Bruch’s membrane), thickening of Bruch’s membrane, microvilli atrophy and disorganization of the basal infoldings. Although these changes are well known, the basic mechanisms involved in them are frequently poorly understood. These age-related changes progress slowly and vary in severity in different individuals. These changes are also found in age-related macular degeneration (AMD), a late onset disease that severely impacts the RPE, but they are much more pronounced than during normal aging. However, the changes in AMD lead to severe loss of vision. Given the many supporting functions which the RPE serves for the retina, it is important to decipher the age-related changes in this epithelium in order to understand age-related changes in vision. PMID:19668732

  6. Distribution and ultrastructural characteristics of dark cells in squamous metaplasias of the respiratory tract epithelium. [Rats

    SciTech Connect

    Klein-Szanto, A.J.P.; Nettesheim, P.; Pine, A.; Martin, D.

    1981-05-01

    Dark epithelial basal cells were found in both carcinogen-induced and non-carcinogen-induced squamous metaplasias of the tracheal epithelium. Formaldehyde-induced squamous metaplasias exhibited 4% dark cells in the basal layer. Metaplasias induced by vitamin A deficiency and those induced by dimethylbenz(a)anthracene (DMBA) without atypia showed 18-20% basal dark cells. DMBA-induced metaplasias with moderate to severe atypia exhibited 50% basal dark cells. The labeling index of basal cells in metaplastic epithelia, regardless of the inducing agent, was 16-18%, ie, the same as that of the normal esophageal stratified squamous epithelium. The percentage of labeled dark basal cells per total dark cell population was approximately 19% in the non-carcinogen-induced metaplasias and in the DMBA-induced metaplasias without atypia. In the atypical metaplasias induced by DMA this percentage increased to 26. On the basis of ultrastructural observations, five types of dark epithelial cells could be distinguished in the metaplastic epithelia. Each type of squamous metaplasia could thus be recognized by a determined numerical distribution of dark cells in the basal layer and a specific pattern of distribution of the ultrastructurally defined dark cell categories.

  7. Extremely elongated Mitochondria in Ioncytes of the saccular Epithelium of a Teleost, Oreochromis mossambiscus (Cichlidae)

    NASA Astrophysics Data System (ADS)

    Muders, K.; Anken, R.; Ibsch, M.; Rahmann, H.

    Earlier investigations have clearly shown that altered gravity affects the calcium incorporation of fish inner ear otoliths. The incorporation of such inorganic components requires a particular composition of the endolymph, which is maintained by specialized cells in the inner ear epithelium, which are responsible for ion exchange. These so-called ionocytes therefore may play an important role in altered gravity affected ion deposition on otoliths. In order to clarify the ultrastructure of ionocytes, respective cells within the saccular epithelium of the cichlid fish Oreochromis mossamb cus were analyzed byi imaging of thick sections with energy -filtering transmission electron microscopy. It was found that ionocytes do not contain numerous mitochondria of litte size as has been suggested earlier but rather few, extremely elongated megamitochondria. Such worm-like mitochondria seemed hitherto to be restricted to some higher plants and fungi. Since the particular mitochondrial structure is important for normal cell function, such megamitochondria possibly reflect a functional advantage in the context of the presumed role of teleostean ionocytes in regulating the electrolyte composition of the endolymph. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

  8. Mitosis in the oesophageal epithelium of rats during chronic antithyroid treatment with carbimazole.

    PubMed

    Tuffery, A R; Mobarak, M

    1990-11-01

    The mitotic activity of the oesophageal epithelium of male rats maintained under carefully controlled conditions was studied, using the metaphase-arrest agent, vincristine sulphate. The accumulation of metaphases was linear (r = 0.97). In untreated rats there was a clear mitotic rhythm with a peak metaphase index (expressed as a percentage) of 12.4 +/- 0.86 (S.E.M.) at 12.00-15.00 h and a trough of 1.3 +/- 0.35 at 24.00 h. The overall mean metaphase index was 5.4 +/- 0.76. The effect of treatment with the antithyroid agent, carbimazole (0.1 g/100 ml in the drinking water), for 3 weeks was to depress the higher values at 12.00-18.00 h (P less than 0.01), while leaving the overall index unchanged. Carbimazole caused a significant (P less than 0.01), transient 40% increase in the metaphase index after 2 days; thereafter the metaphase index remained at control levels until 12 weeks of treatment when a steady decline occurred until 24 weeks. The results are in contrast to those in previously described experiments on thyroid follicular cells which show a large increase in the first few days of treatment, followed by a steady decline towards control levels at 12 weeks. The metabolic activity of the animals is about 50% of normal at 12 weeks when both the oesophageal epithelium and the thyroid follicular cells begin to show a reduction in proliferative activity.

  9. The crypt cycle. Crypt and villus production in the adult intestinal epithelium.

    PubMed Central

    Totafurno, J; Bjerknes, M; Cheng, H

    1987-01-01

    We propose a model for the growth of individual crypts that is able to account for the observed changes in the number of cells in crypts under normal conditions, after irradiation, and after 30% resection. Parameter values for this model are estimated both for mouse and man, and detailed predictions of crypt growth rates are made. This model does not predict a steady-state crypt size; rather it suggests that crypts grow until they bifurcate. We therefore propose a crypt cycle (analogous to the cell cycle) and present evidence that most if not all crypts in the adult mouse are cycling asynchronously and independently. This evidence consists of four experiments that indicate that branching crypts are randomly distributed over the intestinal epithelium, that the plane of bifurcation of branching crypts is randomly oriented with respect to the villus base, and that the size distribution of crypts is consistent with an expanding crypt population. We also report for the first time evidence of villus production in the adult mouse intestinal epithelium. We conclude that the crypt and villus populations in the adult mouse are not in a steady state. Images FIGURE 4 PMID:3663832

  10. Collagenase-3 (matrix metalloproteinase-13) expression is induced in oral mucosal epithelium during chronic inflammation.

    PubMed Central

    Uitto, V. J.; Airola, K.; Vaalamo, M.; Johansson, N.; Putnins, E. E.; Firth, J. D.; Salonen, J.; López-Otín, C.; Saarialho-Kere, U.; Kähäri, V. M.

    1998-01-01

    Increased proliferation of mucosal epithelium during inflammation is associated with degradation of subepithelial connective tissue matrix and local invasion of the epithelial cells. Here we have studied, whether collagenase-3 (MMP-13), a collagenolytic matrix metalloproteinase with an exceptionally wide substrate specificity, is expressed in the epithelium of chronically inflamed mucosa. Examination of human gingival tissue sections from subjects with chronic adult periodontitis with in situ hybridization revealed marked expression of MMP-13 in basal cells of some epithelial rete ridges expanding into connective tissue. Immunohistochemical staining demonstrated that these cells also expressed strongly laminin-5, suggesting that they are actively migrating cells. A strong signal for MMP-13 mRNA was occasionally also noted in the suprabasal epithelial cells facing the gingival pocket, whereas no collagenase-1 (MMP-1) mRNA was detected in any areas of the epithelium. MMP-13 expression was also detected in fibroblast-like cells associated with collagen fibers of the inflamed subepithelial connective tissue. In organ culture of human oral mucosa, MMP-13 mRNA expression was observed in epithelial cells growing into connective tissue of the specimens. Regulation of MMP-13 expression was examined in cultured normal nonkeratinizing epithelial cells isolated from porcine periodontal ligament. In these cells, MMP-13 expression at the mRNA and protein level was potently enhanced (up to sixfold) by tumor necrosis factor-alpha, transforming growth factor-beta(1), and transforming growth factor-alpha and by keratinocyte growth factor in the presence of heparin. In addition, plating periodontal ligament epithelial cells on type I collagen stimulated MMP-13 expression (sevenfold) as compared with cells grown on tissue culture plastic. The results of this study show, that expression of MMP-13 is specifically induced in undifferentiated epithelial cells during chronic inflammation

  11. [The rabbit ear model as an acnegenicity test. 2. Effect of coal tar on follicle and sebaceous gland epithelium tumor induction].

    PubMed

    Zimmermann, R

    1989-01-01

    Tar produced from hard coal was found to be acanthogenic to the interfollicular epiderm of rabbit ear skin and comedogenic to follicular epithelium in short-term (two weeks) and long-term (12 weeks) tests. Histological and autoradiographic experiments revealed a hyperproliferative effect in all cases in long-term tests. This contrasts with the atrophying effects reported by other authors. Tar application reduced the sebaceous gland area per follicle. Benignant epidermal tumours consisting of papillomas with a striking degree of sebaceous gland proliferation appeared on the rabbit ear skin after 8 weeks at the earliest.

  12. Expression of keratin 14 in the basal cells of the lingual epithelium of mice during the morphogenesis of filiform papillae: visualization by fluorescent immunostaining and confocal laser-scanning microscopy in the transmission mode.

    PubMed

    Iwasaki, Shin-Ichi; Aoyagi, Hidekazu

    2007-07-01

    We examined the expression of keratin 14 (K14) on the lingual epithelium by immunofluorescent staining while monitoring morphological changes in the filiform papillae of mice by confocal laser-scanning microscopy in the transmission mode of the same sections to define both the histology and the morphology of cells. It is difficult to visualize histological details of the fetal lingual epithelium of the mouse on semi-ultrathin sections by light microscopy after immunohistochemical staining because the histological structures in such sections cannot be distinguished by standard counterstaining. To solve this problem and to visualize the immunoreactivity specific for K14, we analyzed the results of immunofluorescent staining of semi-ultrathin sections in combination with an examination of the corresponding images by laser-scanning microscopy in the transmission mode after staining of specimens with toluidine blue. No immunoreactivity specific for K14 was detected on the lingual epithelium of fetuses on embryonic day 15 (E15), but immunoreactivity was distinct at all postnatal stages from postnatal day 0 (P0) to P21.

  13. Pigment Epithelium Derived Factor Peptide Protects Murine Hepatocytes from Carbon Tetrachloride-Induced Injury

    PubMed Central

    Shih, Shou-Chuan; Ho, Tsung-Chuan; Chen, Show-Li; Tsao, Yeou-Ping

    2016-01-01

    Fibrogenesis is induced by repeated injury to the liver and reactive regeneration and leads eventually to liver cirrhosis. Pigment epithelium derived factor (PEDF) has been shown to prevent liver fibrosis induced by carbon tetrachloride (CCl4). A 44 amino acid domain of PEDF (44-mer) was found to have a protective effect against various insults to several cell types. In this study, we investigated the capability of synthetic 44-mer to protect against liver injury in mice and in primary cultured hepatocytes. Acute liver injury, induced by CCl4, was evident from histological changes, such as cell necrosis, inflammation and apoptosis, and a concomitant reduction of glutathione (GSH) and GSH redox enzyme activities in the liver. Intraperitoneal injection of the 44-mer into CCl4-treated mice abolished the induction of AST and ALT and markedly reduced histological signs of liver injury. The 44-mer treatment can reduce hepatic oxidative stress as evident from lower levels of lipid hydroperoxide, and higher levels of GSH. CCl4 caused a reduction of Bcl-xL, PEDF and PPARγ, which was markedly restored by the 44-mer treatment. Consequently, the 44-mer suppressed liver fibrosis induced by repeated CCl4 injury. Furthermore, our observations in primary culture of rat hepatocytes showed that PEDF and the 44-mer protected primary rat hepatocytes against apoptosis induced by serum deprivation and TGF-β1. PEDF/44-mer induced cell protective STAT3 phosphorylation. Pharmacological STAT3 inhibition prevented the antiapoptotic action of PEDF/44-mer. Among several PEDF receptor candidates that may be responsible for hepatocyte protection, we demonstrated that PNPLA2 was essential for PEDF/44-mer-mediated STAT3 phosphorylation and antiapoptotic activity by using siRNA to selectively knockdown PNPLA2. In conclusion, the PEDF 44-mer protects hepatocytes from single and repeated CCl4 injury. This protective effect may stem from strengthening the counter oxidative stress capacity and

  14. Echocardiographic versus histologic findings in Marfan syndrome.

    PubMed

    Gu, Xiaoyan; He, Yihua; Li, Zhian; Han, Jiancheng; Chen, Jian; Nixon, J V Ian

    2015-02-01

    This retrospective study attempted to establish the prevalence of multiple-valve involvement in Marfan syndrome and to compare echocardiographic with histopathologic findings in Marfan patients undergoing valvular or aortic surgery. We reviewed echocardiograms of 73 Marfan patients who underwent cardiovascular surgery from January 2004 through October 2009. Tissue histology was available for comparison in 29 patients. Among the 73 patients, 66 underwent aortic valve replacement or the Bentall procedure. Histologic findings were available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients with moderate or severe aortic regurgitation as determined by echocardiography, 4 had thickened aortic valves. The echocardiographic findings in 18 patients with mitral involvement included mitral prolapse in 15. Of 11 patients with moderate or severe mitral regurgitation as determined by echocardiography, 4 underwent mitral valve repair and 7 mitral valve replacement. Histologic findings among mitral valve replacement patients showed thickened valve tissue and myxomatous degeneration. Tricuspid involvement was seen echocardiographically in 8 patients, all of whom had tricuspid prolapse. Two patients had severe tricuspid regurgitation, and both underwent repair. Both mitral and tricuspid involvement were seen echocardiographically in 7 patients. Among the 73 patients undergoing cardiac surgery for Marfan syndrome, 66 had moderate or severe aortic regurgitation, although their valves manifested few histologic changes. Eighteen patients had mitral involvement (moderate or severe mitral regurgitation, prolapse, or both), and 8 had tricuspid involvement. Mitral valves were most frequently found to have histologic changes, but the tricuspid valve was invariably involved.

  15. Association of Escherichia coli with the Small Intestinal Epithelium I. Comparison of Enteropathogenic and Nonenteropathogenic Porcine Strains in Pigs

    PubMed Central

    Bertschinger, Hans U.; Moon, Harley W.; Whipp, Shannon C.

    1972-01-01

    Two enteropathogenic strains of Escherichia coli (EEC) differed from a nonenteropathogenic strain of E. coli (NEEC) in their association with porcine small intestinal epithelium. The EEC characteristically were found along villi from tip to base and contiguous to the brush border. They were not in crypts. In contrast, the NEEC characteristically remained in the central lumen near the tips of villi and was only occasionally contiguous to the brush border. No organisms were detected within epithelial cells. The difference in distribution between EEC and NEEC was apparent in ligated jejunal loops 45 min postexposure. The association between host and bacterial cells was most consistently demonstrated on frozen sections of intestine, as other histological techniques removed many bacteria. However, cellular details of the association were best demonstrated in chemically fixed tissues. Images PMID:4564680

  16. Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway epithelium ameliorates allergic lung inflammation.

    PubMed

    Bacsi, Attila; Aguilera-Aguirre, Leopoldo; Szczesny, Bartosz; Radak, Zsolt; Hazra, Tapas K; Sur, Sanjiv; Ba, Xueqing; Boldogh, Istvan

    2013-01-01

    Allergic airway inflammation is characterized by increased expression of pro-inflammatory mediators, inflammatory cell infiltration, mucus hypersecretion, and airway hyperresponsiveness, in parallel with oxidative DNA base and strand damage, whose etiological role is not understood. Our goal was to establish the role of 8-oxoguanine (8-oxoG), a common oxidatively damaged base, and its repair by 8-oxoguanine DNA glycosylase 1 (Ogg1) in allergic airway inflammatory processes. Airway inflammation was induced by intranasally administered ragweed (Ambrosia artemisiifolia) pollen grain extract (RWPE) in sensitized BALB/c mice. We utilized siRNA technology to deplete Ogg1 from airway epithelium; 8-oxoG and DNA strand break levels were quantified by Comet assays. Inflammatory cell infiltration and epithelial methaplasia were determined histologically, mucus and cytokines levels biochemically and enhanced pause was used as the main index of airway hyperresponsiveness. Decreased Ogg1 expression and thereby 8-oxoG repair in the airway epithelium conveyed a lower inflammatory response after RWPE challenge of sensitized mice, as determined by expression of Th2 cytokines, eosinophilia, epithelial methaplasia, and airway hyperresponsiveness. In contrast, 8-oxoG repair in Ogg1-proficient airway epithelium was coupled to an increase in DNA single-strand break (SSB) levels and exacerbation of allergen challenge-dependent inflammation. Decreased expression of the Nei-like glycosylases Neil1 and Neil2 that preferentially excise ring-opened purines and 5-hydroxyuracil, respectively, did not alter the above parameters of allergic immune responses to RWPE. These results show that DNA SSBs formed during Ogg1-mediated repair of 8-oxoG augment antigen-driven allergic immune responses. A transient modulation of OGG1 expression/activity in airway epithelial cells could have clinical benefits.

  17. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    PubMed

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC.

  18. Histology image search using multimodal fusion.

    PubMed

    Caicedo, Juan C; Vanegas, Jorge A; Páez, Fabian; González, Fabio A

    2014-10-01

    This work proposes a histology image indexing strategy based on multimodal representations obtained from the combination of visual features and associated semantic annotations. Both data modalities are complementary information sources for an image retrieval system, since visual features lack explicit semantic information and semantic terms do not usually describe the visual appearance of images. The paper proposes a novel strategy to build a fused image representation using matrix factorization algorithms and data reconstruction principles to generate a set of multimodal features. The methodology can seamlessly recover the multimodal representation of images without semantic annotations, allowing us to index new images using visual features only, and also accepting single example images as queries. Experimental evaluations on three different histology image data sets show that our strategy is a simple, yet effective approach to building multimodal representations for histology image search, and outperforms the response of the popular late fusion approach to combine information.

  19. Establishment of a novel lingual organoid culture system: generation of organoids having mature keratinized epithelium from adult epithelial stem cells.

    PubMed

    Hisha, Hiroko; Tanaka, Toshihiro; Kanno, Shohei; Tokuyama, Yoko; Komai, Yoshihiro; Ohe, Shuichi; Yanai, Hirotsugu; Omachi, Taichi; Ueno, Hiroo

    2013-11-15

    Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.

  20. Wound healing of true vocal cord squamous epithelium after CO2 laser ablation and cup forceps stripping.

    PubMed

    Durkin, G E; Duncavage, J A; Toohill, R J; Tieu, T M; Caya, J G

    1986-10-01

    A study was conducted on the effect of deepithelization of the true vocal cords; microcup forceps were used, as opposed to CO2 laser ablation. A CO2 laser, coupled to an operating microscope, was used to ablate the surface epithelium of the right true vocal cords in eight canines, while conventional microlaryngeal stripping was performed on the left true cords in the same animals. Photographs were taken immediately after injury and again before the animals were killed. Histologically, the series of true vocal cords ablated by the CO2 laser revealed granulation formation at day 5, whereas those treated with conventional stripping developed granulation at day 3, thus indicating delayed healing. Charred carbonaceous debris of CO2 laser ablation was found to cause a giant cell reaction that persisted after reepithelization. Despite the precise control offered by the laser, many of the laser-injured true vocal cords revealed vocalis muscle edema and muscle destruction. After healing occurred, dense fibrosis was found in the vocal muscle injured during CO2 laser ablation of the overlying squamous epithelium.

  1. Establishment of a Novel Lingual Organoid Culture System: Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells

    NASA Astrophysics Data System (ADS)

    Hisha, Hiroko; Tanaka, Toshihiro; Kanno, Shohei; Tokuyama, Yoko; Komai, Yoshihiro; Ohe, Shuichi; Yanai, Hirotsugu; Omachi, Taichi; Ueno, Hiroo

    2013-11-01

    Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.

  2. Subchondral bone histology and grading in osteoarthritis

    PubMed Central

    Aho, Olli-Matti; Finnilä, Mikko; Thevenot, Jerome; Saarakkala, Simo; Lehenkari, Petri

    2017-01-01

    Objective Osteoarthritis (OA) has often regarded as a disease of articular cartilage only. New evidence has shifted the paradigm towards a system biology approach, where also the surrounding tissue, especially bone is studied more vigorously. However, the histological features of subchondral bone are only poorly characterized in current histological grading scales of OA. The aim of this study is to specifically characterize histological changes occurring in subchondral bone at different stages of OA and propose a simple grading system for them. Design 20 patients undergoing total knee replacement surgery were randomly selected for the study and series of osteochondral samples were harvested from the tibial plateaus for histological analysis. Cartilage degeneration was assessed using the standardized OARSI grading system, while a novel four-stage grading system was developed to illustrate the changes in subchondral bone. Subchondral bone histology was further quantitatively analyzed by measuring the thickness of uncalcified and calcified cartilage as well as subchondral bone plate. Furthermore, internal structure of calcified cartilage-bone interface was characterized utilizing local binary patterns (LBP) based method. Results The histological appearance of subchondral bone changed drastically in correlation with the OARSI grading of cartilage degeneration. As the cartilage layer thickness decreases the subchondral plate thickness and disorientation, as measured with LBP, increases. Calcified cartilage thickness was highest in samples with moderate OA. Conclusion The proposed grading system for subchondral bone has significant relationship with the corresponding OARSI grading for cartilage. Our results suggest that subchondral bone remodeling is a fundamental factor already in early stages of cartilage degeneration. PMID:28319157

  3. Protective role of small pigment epithelium-derived factor (PEDF) peptide in diabetic renal injury.

    PubMed

    Awad, Alaa S; Gao, Ting; Gvritishvili, Anzor; You, Hanning; Liu, Yanling; Cooper, Timothy K; Reeves, W Brian; Tombran-Tink, Joyce

    2013-09-15

    Pigment epithelium-derived factor (PEDF) is a multifunctional protein with antiangiogenic, antioxidative, and anti-inflammatory properties. PEDF is involved in the pathogenesis of diabetic retinopathy, but its direct role in the kidneys remains unclear. We hypothesize that a PEDF fragment (P78-PEDF) confers kidney protection in diabetic nephropathy (DN). The localization of the full-length PEDF protein were determined in DBA mice following multiple low doses of streptozotocin. Using immunohistochemistry, PEDF was localized in the kidney vasculature, interstitial space, glomeruli, tubules, and renal medulla. Kidney PEDF protein and mRNA expression were significantly reduced in diabetic mice. Continuous infusion of P78-PEDF for 6 wk resulted in protection from diabetic neuropathy as indicated by reduced albuminuria and blood urea nitrogen, increased nephrin expression, decreased kidney macrophage recruitment and inflammatory cytokines, and reduced histological changes compared with vehicle-treated diabetic mice. In vitro, P78-PEDF blocked the increase in podocyte permeability to albumin and disruption of the actin cytoskeleton induced by puromycin aminonucleoside treatment. These findings highlight the importance of P78-PEDF peptide as a potential therapeutic modality in early phase diabetic renal injury.

  4. Modelling the porcine oviduct epithelium: a polarized in vitro system suitable for long-term cultivation.

    PubMed

    Miessen, K; Sharbati, S; Einspanier, R; Schoen, J

    2011-09-15

    For exploring the processes leading to successful reproduction, differentiated long-term in vitro systems modelling the mammalian oviduct are needed. Therefore, in the present study culture conditions for primary porcine oviductal epithelial cells were optimized with regard to morphological differentiation and usability for extended cultivation periods. To evaluate different growth media for the primary cells, we used morphological criteria as well as real-time impedance measurement. After an initial media testing, the cells were grown on hanging membranes and the culture settings (conventionally cultured, serum gradient over the membrane and air-liquid interface) were assessed by histology and electron microscopy. We proved long-term expression of an oviduct specific marker (oviductal glycoprotein 1) and showed a hormone responsiveness of the culture system by means of quantitative reverse transcription-PCR. Differentiated epithelial cells could reproducibly be cultured up to 6 weeks in an air-liquid interface. After 3 weeks of culturing, the cells were clearly polarized and exhibited cilia. The model maintains physiological properties such as morphological features (mixed cell population of ciliated and secretory cells, apical cell-cell contacts typical for columnar epithelial cells) and oviduct-specific markers showing hormone responsiveness. We established a polarized long-term in vitro-system of the porcine oviductal epithelium preserving detailed features of the porcine oviduct. Therefore, we provide a useful tool to elucidate unsolved scientific questions concerning reproductive physiology.

  5. Spermidine Oxidation-Mediated Degeneration of Retinal Pigment Epithelium in Rats

    PubMed Central

    Kageyama, Masaaki; Shinomiya, Katsuhiko; Fujita-Koyama, Yukie; Hirai, Shin-ichiro; Katsuta, Osamu; Nakamura, Masatsugu

    2017-01-01

    Retinal pigment epithelium (RPE) degeneration is a crucial event in dry age-related macular degeneration and gyrate atrophy. The polyamine spermidine has been shown to induce RPE cell death in vitro. The present study aimed to establish a novel in vivo model of spermidine-induced RPE degeneration and to determine whether spermidine-induced RPE cell death involves oxidative mechanisms. In this study, spermidine caused ARPE-19 cell death in a concentration-dependent manner. This effect was prevented by removal of serum from the culture medium or treatment with amine oxidase inhibitors, N-acetylcysteine (NAC), or aldehyde dehydrogenase (ALDH). Intravitreal injection of spermidine into rats significantly increased the permeability of the blood-retinal barrier and decreased the amplitudes of scotopic electroretinogram a- and b-waves. Histological analysis revealed that spermidine induced vacuolation, atrophy, and dropout of RPE cells, leading to the disruption of photoreceptor outer segments. Simultaneous intravitreal administration of NAC and ALDH with spermidine prominently inhibited the functional and morphological changes induced by spermidine. In conclusion, this study demonstrated that the intravitreal administration of spermidine induced RPE cell dysfunction and death followed by photoreceptor degeneration in rats. These effects of spermidine are thought to be mediated by oxidative stress and a toxic aldehyde generated during spermidine oxidation. PMID:28367269

  6. Age-Dependent TLR3 Expression of the Intestinal Epithelium Contributes to Rotavirus Susceptibility

    PubMed Central

    Pott, Johanna; Stockinger, Silvia; Torow, Natalia; Smoczek, Anna; Lindner, Cornelia; McInerney, Gerald; Bäckhed, Fredrik; Baumann, Ulrich; Pabst, Oliver; Bleich, André; Hornef, Mathias W.

    2012-01-01

    Rotavirus is a major cause of diarrhea worldwide and exhibits a pronounced small intestinal epithelial cell (IEC) tropism. Both human infants and neonatal mice are highly susceptible, whereas adult individuals remain asymptomatic and shed only low numbers of viral particles. Here we investigated age-dependent mechanisms of the intestinal epithelial innate immune response to rotavirus infection in an oral mouse infection model. Expression of the innate immune receptor for viral dsRNA, Toll-like receptor (Tlr) 3 was low in the epithelium of suckling mice but strongly increased during the postnatal period inversely correlating with rotavirus susceptibility, viral shedding and histological damage. Adult mice deficient in Tlr3 (Tlr3−/−) or the adaptor molecule Trif (TrifLps2/Lps2) exerted significantly higher viral shedding and decreased epithelial expression of proinflammatory and antiviral genes as compared to wild-type animals. In contrast, neonatal mice deficient in Tlr3 or Trif did not display impaired cell stimulation or enhanced rotavirus susceptibility. Using chimeric mice, a major contribution of the non-hematopoietic cell compartment in the Trif-mediated antiviral host response was detected in adult animals. Finally, a significant age-dependent increase of TLR3 expression was also detected in human small intestinal biopsies. Thus, upregulation of epithelial TLR3 expression during infancy might contribute to the age-dependent susceptibility to rotavirus infection. PMID:22570612

  7. Otx but not Mitf transcription factors are required for zebrafish retinal pigment epithelium development.

    PubMed

    Lane, Brandon M; Lister, James A

    2012-01-01

    Otx and Mitf transcription factors have been implicated in the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific roles in the development of the RPE have not been fully defined. The role of the three Otx transcription factors (Otx1a, Otx1b, and Otx2) and two Mitf transcription factors (Mitfa and Mitfb) in the development of the zebrafish RPE was explored in these experiments. The loss of Otx activity through morpholino knockdown produced variable eye defects, ranging from delayed RPE pigmentation to severe coloboma, depending on the combination of Otx factors that were targeted. Expression analysis through in situ hybridization demonstrates that otx transcription factors are necessary for the proper expression of mitfa and mitfb while Mitf transcription factors are not required for the expression of otx genes. Surprisingly, the loss of Mitf activity in mitfa, mitfb, or double mitf mutant zebrafish had no effect on RPE pigmentation or development. Moreover, histological analysis revealed that retinal lamination is unaffected in mitf mutants, as well as in otx morphants, even in regions lacking RPE. Otx and Mitf combined loss of function experiments suggest that mitfa and mitfb may still influence zebrafish RPE development. This is further supported by the ability of mitfa to induce pigmentation in the zebrafish retina when misexpressed. These findings suggest that one or more Otx targets in addition to mitfa and mitfb, possibly another mitf family member, are necessary for development of the RPE in zebrafish.

  8. Histology of the kidney and urinary bladder of Siphonops annulatus (Amphibia-Gymnophiona).

    PubMed

    Carvalho, E T; Junqueira, L C

    1999-03-01

    The histology of the kidney and urinary bladder of Siphonops annulatus was studied by light microscopy in semithin sections of tissue embedded in hydrophilic resin. The kidney's nephron comprises the renal corpuscle, neck segment, proximal tubule, intermediate segment, distal tubule and collecting tubule. Nephrostomes are present. This structure, the neck segment, and intermediate tubules present long cilia, and probably play important roles in the propulsion of the peritoneal fluid and glomerular filtrate. The proximal tubule cells possess loosely packed microvilli and contain abundant polymorphic granules and vesicles that assume the aspect of lysosomes in different stages of intracellular digestion. The distal tubules are characterized by large, vertically disposed mitochondria assuming the aspect of ions transporting cells. The urinary bladder is lined with a transitional epithelium, whose aspect varies according to the quantity of urine.

  9. Histological assessment of ovaries and uterus of rats subjected to nandrolone decanoate treatment.

    PubMed

    Gerez, Juliana Rubira; Frei, Fernando; Camargo, Isabel Cristina Cherici

    2005-07-01

    This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats.

  10. Characterization of human papillomavirus in airway papillomas by histologic and biochemical analysis.

    PubMed

    Glynn, M; Sanford, T; Hoover, L; Kinsey, W; Dobbs, L; Bruegger, D

    1999-11-01

    The role of human papillomavirus (HPV) in airway papillomas has been well defined in recent literature. The chronicity and recurrence of papillomas has been postulated to be a result of residual viral genome in tissue treated with standard laser techniques. Thirteen patients with airway papillomas were selected for study with polymerase chain reaction (PCR) methods to detect viral DNA. Specimens taken prior to laser therapy and specimens taken at laser margins were consistently positive for HPV DNA by PCR. The HPV DNA is apparently present in tissues after macroscopic disease has been ablated by laser techniques. Histologic analysis of laser biopsies demonstrated fragments of squamous epithelium with cytologic features of HPV infection. Laser treatment is ineffective in eradicating HPV-infected tissues from airway papillomas, and this finding supports the notion that recurrence is a product of HPV incorporated into tissue not ablated by laser irradiation. Specific methods, results, and clinical correlation will be discussed.

  11. Histological study of the thyroid gland following 904-nm laser radiation

    NASA Astrophysics Data System (ADS)

    Perez de Vargas, I.; Parrado, C.; Gonzalez, V.; Vidal, Lourdes; Rius, F.

    1993-06-01

    The present histological and stereological studies are on thyroid glands of Wistar rats irradiated with an IR laser. The animals were exposed to total doses of 46,80 J/cm2, and sacrificed at 1, 40, and 180 days after the last treatment. A morphological and stereological study was made on follicular epithelium, follicle, stroma, and capillary. The laser beam produced an increase of follicular epithelial volume and hyperplasia of follicular cells in the animals sacrificed at 1, 40, and 180 days after the last treatment. Capillary dilation underwent a progressive decrease as time passed. It was higher in the animals sacrificed after 24 hours, then it decreased after 40 days and finally disappeared after 180 days.

  12. Histological and histochemical analyses of the cuttlebone sac of the golden cuttlefish Sepia esculenta

    NASA Astrophysics Data System (ADS)

    Zheng, Xiaodong; Xiao, Shu; Wang, Zhaoping; Wang, Rucai

    2007-10-01

    The secretion function of mantle is closely related to shell formation in some bivalves and gastropods. Up to now, few researches have been reported for cuttlebone formation in the class Cephalopoda. In this study, the structure and secretion function of cuttlebone sac of the golden cuttlefish Sepia esculenta was analyzed using the histological and histochemical methods. The results showed that high and columnar cells located in sac epithelium, and flat cells existed near the base membrane. A lot of fibroblasts were found in the lateral mantle collective tissue. Some mucus, mucopolysaccharide and alkaline phosphatase (ALP) were found in the sac. The ultrastructural characteristics of Quasi-connective-tissue-calcium cells (QCTCC) were observed using a transmission electron microscope (TEM). The relationship between cuttlebone sac secretion function and shell formation was discussed.

  13. Cytologic features of the normal pineal gland of adults.

    PubMed

    Jiménez-Heffernan, José A; Bárcena, Carmen; Agra, Carolina; Asunción, Alfonso

    2015-08-01

    It is well known that the histology of normal pineal gland may resemble not only pineal tumors but also gliomas, owing to its cellularity which is much greater than that of normal white or gray matter. Our recent experience with a case in which part of a normal gland was submitted for intraoperative consultation, together with the scarcity of cytologic descriptions, led us to perform a cyto-histologic correlation study. In addition to the intraoperative case, we collected five pineal glands from consecutive adult autopsies. During the squash procedure, we often noted the presence of calcified grains. Smears were hypercellular, distributed in tissue fibrillary fragments and as numerous single cells, with crystalline structures. Pineal gland cells (pineocytes) were large, round, epithelioid with ill-defined cytoplasms and moderate nuclear pleomorphism. Spindle cells with greater fibrillary quality were less common. One of the most remarkable findings seen in all cases was the presence of cytoplasmic pigment. Histological evaluation and immunohistochemical staining confirmed that the tissue was normal pineal gland. The histology showed a characteristic lobular aspect and frequent corpora arenacea. The pigment seen cytologically was also encountered in histology and corresponded to lipofuscin. Cytologic features of the pineal gland are peculiar when compared to other normal structures of the central nervous system. These features correlate closely with what is seen on histology. In an adequate clinical context, and in combination with frozen sections, cytology allows a specific recognition of the pineal gland during intraoperative pathologic consultations.

  14. Optical diagnosis of gallbladder cancers via two-photon excited fluorescence imaging of unstained histological sections.

    PubMed

    Hong, Zhipeng; Chen, Youting; Chen, Jing; Chen, Hong; Xu, Yahao; Zhu, Xiaoqin; Zhuo, Shuangmu; Shi, Zheng; Chen, Jianxin

    2015-01-01

    Two-photon excited fluorescence (TPEF) microscopy, based on signal from cells, can provide detailed information on tissue architecture and cellular morphology in unstained histological sections to generate subcellular-resolution images from tissue directly. In this paper, we used TPEF microscopy to image microstructure of human normal gallbladder and three types of differentiated carcinomas in order to investigate the morphological changes of tissue structure, cell, cytoplasm, and nucleus without hematoxylin and eosin (H&E) staining. It displayed that TPEF microscopy can well image the stratified normal gallbladder tissue, including the mucosa, the muscularis, and the serosa. The typical cancer cell, characterized by cellular and nuclear pleomorphism, enlarged nuclei, and augmented nucleolus, can be identified in histological sections without H-E staining as well. The quantitative results showed that the areas of the nucleus and the nucleolus in three types of cancerous cells were all significantly greater than those in normal gallbladder columnar epithelial cells derived from TPEF microscopic images. The studies demonstrated that TPEF microscopy has the ability to characterize tissue structures and cell morphology of gallbladder cancers differentiated from a normal gallbladder in a manner similar to traditional histological analysis. As a novel tool, it has the potential for future retrospective studies of tumor staging and migration by utilizing histological section specimens without H-E staining.

  15. Using Color and Grayscale Images to Teach Histology to Color-Deficient Medical Students

    ERIC Educational Resources Information Center

    Rubin, Lindsay R.; Lackey, Wendy L.; Kennedy, Frances A.; Stephenson, Robert B.

    2009-01-01

    Examination of histologic and histopathologic microscopic sections relies upon differential colors provided by staining techniques, such as hematoxylin and eosin, to delineate normal tissue components and to identify pathologic alterations in these components. Given the prevalence of color deficiency (commonly called "color blindness")…

  16. Female reproductive tract of the lesser anteater (Tamandua tetradactyla, myrmecophagidae, Xenarthra). Anatomy and histology.

    PubMed

    Rossi, L F; Luaces, J P; Marcos, H J Aldana; Cetica, P D; Gachen, G; Jimeno, G Pérez; Merani, M S

    2011-11-01

    The morphological and histological features of the unusual reproductive tract of the female lesser anteater, Tamandua tetradactyla (Myrmecophagidae, Xenarthra), are described for the first time. The present study aimed to establish the main similarities and differences between this species and other xenarthrans. The populations of this species are declining rapidly for a number of reasons and our study is relevant to diverse programs related to its conservation. Studies were carried out on five female genital tracts of adult specimens. Ovaries were ovoid, presenting a medulla completely surrounded by the cortex, differently from that described in other xenarthans. Like in Dasypus but different from all other armadillos studied, single oocyte follicles were observed and a simple the uterus. The uterovaginal canal connects the uterus with the urogenital sinus. The simple columnar epithelium of the uterovaginal canal ends abruptly at a septum which resembles a hymen, where the transitional epithelium of the urogenital sinus appears. This ancestral feature is shared with that of other armadillos, except Tolypeutes matacus, which has a true vagina. Characteristics of the reproductive tract and sperm morphology of other Xenarthra are comparatively discussed. These observations suggest that important reproductive features are shared between the family Myrmecophagidae and the genus Dasypus, a basal group in the phylogeny of Xenarthra.

  17. Identification of striatin, a desmosomal protein, in the canine corneal epithelium.

    PubMed

    Stern, Joshua A; Lahmers, Sunshine; Meurs, Kathryn M

    2015-10-01

    Striatin is a scaffolding protein expressed in brain and cardiac tissues. In the heart, striatin has been localized to the region of the cardiac desmosome. A causal mutation within the gene encoding for this scaffolding protein has been described as the etiology for arrhythmogenic right ventricular cardiomyopathy, a disease of the cardiac desmosome, in a canine model. Hemidesmosomes are cell adhesion complexes located within the cornea where they anchor the corneal epithelium to the stroma at the basement membrane and participate in cell-signaling processes. Traditional cell adhesion desmosomes are also known to link the corneal epithelial cells together. We hypothesized that striatin may be found in the cornea localized to regions of either hemidesmosomes and/or desmosomes. Immunohistochemical evaluation was performed to evaluate for striatin labeling in normal canine cornea. Striatin was localized to the cytoplasmic region of corneal epithelial cells. The role of striatin in corneal disease warrants investigation.

  18. Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme.

    PubMed

    Rajagopal, Jayaraj; Carroll, Thomas J; Guseh, J Sawalla; Bores, Sam A; Blank, Leah J; Anderson, William J; Yu, Jing; Zhou, Qiao; McMahon, Andrew P; Melton, Douglas A

    2008-05-01

    The effects of Wnt7b on lung development were examined using a conditional Wnt7b-null mouse. Wnt7b-null lungs are markedly hypoplastic, yet display largely normal patterning and cell differentiation. In contrast to findings in prior hypomorphic Wnt7b models, we find decreased replication of both developing epithelium and mesenchyme, without abnormalities of vascular smooth muscle development. We further demonstrate that Wnt7b signals to neighboring cells to activate both autocrine and paracrine canonical Wnt signaling cascades. In contrast to results from hypomorphic models, we show that Wnt7b modulates several important signaling pathways in the lung. Together, these cascades result in the coordinated proliferation of adjacent epithelial and mesenchymal cells to stimulate organ growth with few alterations in differentiation and patterning.

  19. Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium.

    PubMed

    Ferrari, S; Kitson, C; Farley, R; Steel, R; Marriott, C; Parkins, D A; Scarpa, M; Wainwright, B; Evans, M J; Colledge, W H; Geddes, D M; Alton, E W

    2001-09-01

    Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier can, in part, be overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine using either a cationic lipid or a cationic polymer as the gene transfer agent. Further, in vivo application of either Nacystelyn or the anticholinergic glycopyrrolate, both clinically used agents, resulted in increased reporter gene expression in the mouse lung, but no significant correction of the bioelectric defect in CF null mice. These results, whilst unlikely to be sufficient in themselves to achieve clinically relevant gene therapy, may be a further useful step in the attainment of this goal.

  20. Histological structure of duodenum in gilts receiving low doses of zearalenone and deoxynivalenol in feed.

    PubMed

    Lewczuk, Bogdan; Przybylska-Gornowicz, Barbara; Gajęcka, Magdalena; Targońska, Krystyna; Ziółkowska, Natalia; Prusik, Magdalena; Gajęcki, Maciej

    2016-01-01

    Deoxynivalenol (DON) and zearalenone (ZEN), produced by microfungi of the Fusarium family, are among the most commonly occurring mycotoxins. They are considered important factors affecting human and animal health as well as livestock productivity. The aim of this study was to determine the effect of low doses of these mycotoxins on the histological structure of the pig duodenum. The study was performed on 72 gilts, with initial weights of approximately 25kg, divided into 4 equal groups. Group I received per os ZEN (40μg/kg BW), group II-DON (12μg/kg BW), group III-ZEN (40μg/kg BW) and DON (12μg/kg BW), and group IV-vehicle. The pigs were killed after 1, 2, 3, 4, 5 and 6 weeks of the treatment, and the duodenum samples were prepared for histological investigations. The slides were digitalized and subjected to morphometrical analysis. The treatment with DON and ZEN did not change the architecture of the mucosa or the ratio between goblet and adsorptive cells in the epithelium. The administration of DON induced an increase in the number of lymphocytes in the mucosal epithelium. Both mycotoxins, administered alone or together, increased the quantity of lymphocytes, plasma cells and macrophages with black-brown granules in the lamina propria. The time-courses of changes in the number of defense system cells evoked by DON and ZEN were different. In conclusion, dietary exposure to low doses of Fusarium mycotoxins should be considered an important risk factor for subclinical inflammation in the small intestine.

  1. Hydrodynamics of stratified epithelium: Steady state and linearized dynamics

    NASA Astrophysics Data System (ADS)

    Yeh, Wei-Ting; Chen, Hsuan-Yi

    2016-05-01

    A theoretical model for stratified epithelium is presented. The viscoelastic properties of the tissue are assumed to be dependent on the spatial distribution of proliferative and differentiated cells. Based on this assumption, a hydrodynamic description of tissue dynamics at the long-wavelength, long-time limit is developed, and the analysis reveals important insights into the dynamics of an epithelium close to its steady state. When the proliferative cells occupy a thin region close to the basal membrane, the relaxation rate towards the steady state is enhanced by cell division and cell apoptosis. On the other hand, when the region where proliferative cells reside becomes sufficiently thick, a flow induced by cell apoptosis close to the apical surface enhances small perturbations. This destabilizing mechanism is general for continuous self-renewal multilayered tissues; it could be related to the origin of certain tissue morphology, tumor growth, and the development pattern.

  2. Nanoparticle incorporation of melittin reduces sperm and vaginal epithelium cytotoxicity.

    PubMed

    Jallouk, Andrew P; Moley, Kelle H; Omurtag, Kenan; Hu, Grace; Lanza, Gregory M; Wickline, Samuel A; Hood, Joshua L

    2014-01-01

    Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro. In the current study, we assessed the impact of blank and melittin-containing perfluorocarbon nanoparticles on sperm motility and the viability of both sperm and vaginal epithelial cells. We found that free melittin was toxic to sperm and vaginal epithelium at concentrations greater than 2 µM (p<0.001). However, melittin nanoparticles were not cytotoxic to sperm (p = 0.42) or vaginal epithelium (p = 0.48) at an equivalent melittin concentration of 10 µM. Thus, nanoparticle formulation of melittin reduced melittin cytotoxicity fivefold and prevented melittin toxicity at concentrations previously shown to inhibit HIV infectivity. Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin concentrations ≥20 µM (p<0.001) and were toxic to sperm at equivalent melittin concentrations ≥40 µM (p<0.001). Sperm cytotoxicity was enhanced by targeting of the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While further testing is needed to determine the extent of cytotoxicity in a more physiologically relevant model system, these results suggest that melittin-containing nanoparticles could form the basis of a virucide that is not toxic to sperm and vaginal epithelium. This virucide would be beneficial for HIV serodiscordant couples seeking to achieve natural pregnancy.

  3. Gallbladder epithelium as a niche for chronic Salmonella carriage.

    PubMed

    Gonzalez-Escobedo, Geoffrey; Gunn, John S

    2013-08-01

    Although typhoid fever has been intensively studied, chronic typhoid carriage still represents a problem for the transmission and persistence of the disease in areas of endemicity. This chronic state is highly associated with the presence of gallstones in the gallbladder of infected carriers upon which Salmonella can form robust biofilms. However, we hypothesize that in addition to gallstones, the gallbladder epithelium aids in the establishment/maintenance of chronic carriage. In this work, we present evidence of the role of the gallbladder epithelium in chronic carriage by a mechanism involving invasion, intracellular persistence, and biofilm formation. Salmonella was able to adhere to and invade polarized gallbladder epithelial cells apically in the absence and presence of bile in a Salmonella pathogenicity island 1 (SPI-1)-dependent manner. Intracellular replication of Salmonella was also evident at 12 and 24 h postinvasion. A flowthrough system revealed that Salmonella is able to adhere to and form extensive bacterial foci on gallbladder epithelial cells as early as 12 h postinoculation. In vivo experiments using a chronic mouse model of typhoid carriage showed invasion and damage of the gallbladder epithelium and lamina propria up to 2 months after Salmonella infection, with an abundant presence of macrophages, a relative absence of neutrophils, and extrusion of infected epithelial cells. Additionally, microcolonies of Salmonella cells were evident on the surface of the mouse gallbladder epithelia up to 21 days postinfection. These data reveal a second potential mechanism, intracellular persistence and/or bacterial aggregation in/on the gallbladder epithelium with luminal cell extrusion, for Salmonella maintenance in the gallbladder.

  4. Reptilian spermatogenesis: A histological and ultrastructural perspective.

    PubMed

    Gribbins, Kevin M

    2011-07-01

    Until recently, the histology and ultrastructural events of spermatogenesis in reptiles were relatively unknown. Most of the available morphological information focuses on specific stages of spermatogenesis, spermiogenesis, and/or of the mature spermatozoa. No study to date has provided complete ultrastructural information on the early events of spermatogenesis, proliferation and meiosis in class Reptilia. Furthermore, no comprehensive data set exists that describes the ultrastructure of the entire ontogenic progression of germ cells through the phases of reptilian spermatogenesis (mitosis, meiosis and spermiogenesis). The purpose of this review is to provide an ultrastructural and histological atlas of spermatogenesis in reptiles. The morphological details provided here are the first of their kind and can hopefully provide histological information on spermatogenesis that can be compared to that already known for anamniotes (fish and amphibians), birds and mammals. The data supplied in this review will provide a basic model that can be utilized for the study of sperm development in other reptiles. The use of such an atlas will hopefully stimulate more interest in collecting histological and ultrastructural data sets on spermatogenesis that may play important roles in future nontraditional phylogenetic analyses and histopathological studies in reptiles.

  5. Histology. Notes for Students of Animal Husbandry.

    ERIC Educational Resources Information Center

    Price, Charles J.; Reed, Josephine E.

    This document approaches the subject of Histology by way of simple independent unicellular organisms through the lower levels of cell organization and specialization to a detailed study of the highly complex tissues of vertebrate animals. Emphasis is placed on structure, but function is explained in some detail. The relationships between tissues…

  6. Developing the eHistology Atlas.

    PubMed

    Richardson, Lorna; Graham, Liz; Moss, Julie; Burton, Nick; Roochun, Yogmatee; Armit, Chris; Baldock, Richard A

    2015-01-01

    The eMouseAtlas project has undertaken to generate a new resource providing access to high-resolution colour images of the slides used in the renowned textbook 'The Atlas of Mouse Development' by Matthew H. Kaufman. The original histology slides were digitized, and the associated anatomy annotations captured for display in the new resource. These annotations were assigned to objects in the standard reference anatomy ontology, allowing the eHistology resource to be linked to other data resources including the Edinburgh Mouse Atlas Gene-Expression database (EMAGE) an the Mouse Genome Informatics (MGI) gene-expression database (GXD). The provision of the eHistology Atlas resource was assisted greatly by the expertise of the eMouseAtlas project in delivering large image datasets within a web environment, using IIP3D technology. This technology also permits future extensions to the resource through the addition of further layers of data and annotations to the resource. Database URL: www.emouseatlas.org/emap/eHistology/index.php.

  7. Segmentation of histological structures for fractal analysis

    NASA Astrophysics Data System (ADS)

    Dixon, Vanessa; Kouznetsov, Alexei; Tambasco, Mauro

    2009-02-01

    Pathologists examine histology sections to make diagnostic and prognostic assessments regarding cancer based on deviations in cellular and/or glandular structures. However, these assessments are subjective and exhibit some degree of observer variability. Recent studies have shown that fractal dimension (a quantitative measure of structural complexity) has proven useful for characterizing structural deviations and exhibits great potential for automated cancer diagnosis and prognosis. Computing fractal dimension relies on accurate image segmentation to capture the architectural complexity of the histology specimen. For this purpose, previous studies have used techniques such as intensity histogram analysis and edge detection algorithms. However, care must be taken when segmenting pathologically relevant structures since improper edge detection can result in an inaccurate estimation of fractal dimension. In this study, we established a reliable method for segmenting edges from grayscale images. We used a Koch snowflake, an object of known fractal dimension, to investigate the accuracy of various edge detection algorithms and selected the most appropriate algorithm to extract the outline structures. Next, we created validation objects ranging in fractal dimension from 1.3 to 1.9 imitating the size, structural complexity, and spatial pixel intensity distribution of stained histology section images. We applied increasing intensity thresholds to the validation objects to extract the outline structures and observe the effects on the corresponding segmentation and fractal dimension. The intensity threshold yielding the maximum fractal dimension provided the most accurate fractal dimension and segmentation, indicating that this quantitative method could be used in an automated classification system for histology specimens.

  8. Biomechanics of liquid-epithelium interactions in pulmonary airways

    PubMed Central

    Ghadiali, Samir N.; Gaver, Donald P.

    2008-01-01

    The delicate structure of the lung epithelium makes it susceptible to surface tension induced injury. For example, the cyclic reopening of collapsed and/or fluid-filled airways during the ventilation of injured lungs generates hydrodynamic forces that further damage the epithelium and exacerbate lung injury. The interactions responsible for epithelial injury during airway reopening are fundamentally multiscale, since air-liquid interfacial dynamics affect global lung mechanics, while surface tension forces operate at the molecular and cellular scales. This article will review the current state-of-knowledge regarding the effect of surface tension forces on a) the mechanics of airway reopening and b) epithelial cell injury. Due to the complex nature of the liquid-epithelium system, a combination of computational and experimental techniques are being used to elucidate the mechanisms of surface-tension induced lung injury. Continued research is leading to an integrated understanding of the biomechanical and biological interactions responsible for cellular injury during airway reopening. This information may lead to novel therapies that minimize ventilation induced lung injury. PMID:18511356

  9. Mucosal adenosine stimulates chloride secretion in canine tracheal epithelium

    SciTech Connect

    Pratt, A.D.; Clancy, G.; Welsh, M.J.

    1986-08-01

    Adenosine is a local regulator of a variety of physiological functions in many tissues and has been observed to stimulate secretion in several Cl-secreting epithelia. In canine tracheal epithelium the authors found that adenosine stimulates Cl secretion from both the mucosal and submucosal surfaces. Addition of adenosine, or its analogue 2-chloroadenosine, to the mucosal surface potently stimulated Cl secretion with no effect on the rate of Na absorption. Stimulation resulted from an interaction of adenosine with adenosine receptors, because it was blocked by the adenosine receptor blocker, 8-phenyltheophylline. The adenosine receptor was a stimulatory receptor as judged by the rank-order potency of adenosine and its analogues and by the increase in cellular adenosine 3',5'-cyclic monophosphate levels produced by 2-chloroadenosine. Adenosine also stimulated Cl secretion when it was added to the submucosal surface, although the maximal increase in secretion was less and it was much less potent. The observation that mucosal 8-phenyletheophylline blocked the effect of submucosal 2-chloroadenosine, whereas submucosal 8-phenyltheophylline did not prevent a response to mucosal or submucosal 2-chloroadenosine, suggests that adenosine receptors are located on the mucosal surface. Thus submucosal adenosine may stimulate secretion by crossing the epithelium and interacting with receptors located on the mucosal surface. Because adenosine can be released from mast cells located in the airway lumen in response to inhaled material, and because adenosine stimulated secretion from the mucosal surface, it may be in a unique position to control the epithelium on a regional level.

  10. Olfactory receptor gene expression in tiger salamander olfactory epithelium.

    PubMed

    Marchand, James E; Yang, Xinhai; Chikaraishi, Dona; Krieger, Jurgen; Breer, Heinz; Kauer, John S

    2004-06-28

    Physiological studies of odor-elicited responses from the olfactory epithelium and bulb in the tiger salamander, Ambystoma tigrinum, have elucidated a number of features of olfactory coding that appear to be conserved across several vertebrate species. This animal model has provided an accessible in vivo system for observing individual and ensemble olfactory responses to odorant stimulation using biochemical, neurophysiological, and behavioral assays. In this paper we have complemented these studies by characterizing 35 candidate odorant receptor genes. These receptor sequences are similar to those of the large families of olfactory receptors found in mammals and fish. In situ hybridization, using RNA probes to 20 of these sequences, demonstrates differential distributions of labeled cells across the extent and within the depth of the olfactory epithelium. The distributions of cells labeled with probes to different receptors show spatially restricted patterns that are generally localized to different degrees in medial-lateral and anterior-posterior directions. The patterns of receptor expression in the ventral olfactory epithelium (OE) are mirrored in the dorsal OE. We present a hypothesis as to how the sensory neuron populations expressing different receptor types responding to a particular odorant may relate to the distribution patterns of epithelial and bulbar responses previously characterized using single-unit and voltage-sensitive dye recording methods.

  11. Passive Electrical Properties of Toad Urinary Bladder Epithelium

    PubMed Central

    Reuss, Luis; Finn, Arthur L.

    1974-01-01

    The electrical resistances of the transcellular and paracellular pathways across the toad urinary bladder epithelium (a typical "tight" sodium-transporting epithelium) were determined by two independent sets of electrophysiological measurements: (a) the measurement of the total transepithelial resistance, the ratio of resistance of the apical to the basal cell membrane, and cable analysis of the voltage spread into the epithelium; (b) the measurement of the total transepithelial resistance and the ratio of resistances of both cell membranes before and after replacing all mucosal sodium with potassium (thus, increasing selectively the resistance of the apical membrane). The results obtained with both methods indicate the presence of a finite transepithelial shunt pathway, whose resistance is about 1.8 times the resistance of the transcellular pathway. Appropriate calculations show that the resistance of the shunt pathway is almost exclusively determined by the zonula occludens section of the limiting junctions. The mean resistance of the apical cell membrane is 1.7 times that of the basal cell membrane. The use of nonconducting materials on the mucosal side allowed us to demonstrate that apparently all epithelial cells are electrically coupled, with a mean space constant of 460 µm, and a voltage spread consistent with a thin sheet model. PMID:4209766

  12. Expression of interleukin-18 by porcine airway and intestinal epithelium.

    PubMed

    Muneta, Yoshihiro; Goji, Noriko; Tsuji, Noriko M; Mikami, Osamu; Shimoji, Yoshihiro; Nakajima, Yasuyuki; Yokomizo, Yuichi; Mori, Yasuyuki

    2002-08-01

    In this study, we investigated the expression of interleukin-18 (IL-18) in porcine airway and intestinal epithelium. We found constitutive protein expression of precursor IL-18 in primary culture of porcine airway epithelium. Immunohistochemical staining revealed that porcine IL-18 was localized in the porcine airway epithelium and that it was significantly upregulated with experimental endotoxemia induced by Escherichia coli lipopolysaccharide (LPS) inoculation. We also confirmed by immunohistochemical staining that IL-18 was expressed in porcine intestinal epithelial cells. Moreover, the concentration of IL-18 in intestinal cell lysates of 1-day-old piglets was about 3-fold and 6-fold less than that in those of 1-month-old and 6-month-old piglets, respectively. Exogenous IL-18 was able to induce interferon-gamma (IFN-gamma) in the peripheral blood of 1-day-old piglets, whereas concanavalin A (ConA) was not able to induce IFN-gamma in the same condition. These results suggest that mucosal epithelial cells are among the major sources of IL-18 in pig and that IL-18 may be useful as a therapeutic agent for the enhancement of immune responses and as a vaccine adjuvant, especially in neonatal piglets.

  13. Candida albicans Ultrastructure: Colonization and Invasion of Oral Epithelium

    PubMed Central

    Howlett, Julie A.; Squier, Christopher A.

    1980-01-01

    The colonization and invasion of various animal oral mucosae by Candida albicans were examined in an organ culture model. Scanning and transmission electron microscopy of the oral epithelium between 12 and 30 h after inoculation with the fungus revealed the morphological relationships between host and parasite. Examination of the fungi in thin sections showed five distinct layers in the cell wall of C. albicans within the epithelium, but changes were evident in the organization and definition of the outer cell wall layers in budding hyphae and in hyphae participating in colonization and invasion of the epithelial cells. Adherence of the fungus to the superficial cells of the oral mucosa appeared to involve intimate contact between the epithelial cell surface and the deeper layers of the fungal cell wall. During invasion a close seal was maintained between the invading hyphae and the surrounding epithelial cell envelope, there being no other evidence of damage to the host cell surface except at the site of entry. Within the epithelial cells there was only occasional loss of cytoplasmic components in the vicinity of the invading hyphae. These findings would suggest that enzymatic lysis associated with the invasive process is localized and that the mechanical support provided by surface adherence and the intimate association between the fungus and the epithelial cell envelope may permit growth of Candida on through the epithelium. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:6995338

  14. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.

  15. Pax9 is required for filiform papilla development and suppresses skin-specific differentiation of the mammalian tongue epithelium.

    PubMed

    Jonker, Leon; Kist, Ralf; Aw, Andrew; Wappler, Ilka; Peters, Heiko

    2004-11-01

    The epidermis is a derivative of the surface ectoderm. It forms a protective barrier and specific appendages including hair, nails, and different eccrine glands. The surface ectoderm also forms the epithelium of the oral cavity and tongue, which develop a slightly different barrier and form different appendages such as teeth, filiform papillae, taste papillae, and salivary glands. How this region-specific differentiation is genetically controlled is largely unknown. We show here that Pax9, which is expressed in the epithelium of the tongue but not in skin, regulates several aspects of tongue-specific epithelial differentiation. In Pax9-deficient mice filiform papillae lack the anterior-posterior polarity, a defect that is associated with temporal-spatial changes in Hoxc13 expression. Barrier formation is disturbed in the mutant tongue and genome-wide expression profiling revealed that the expression of specific keratins (Krt), keratin-associated proteins, and members of the epidermal differentiation complex is significantly down-regulated. In situ hybridization demonstrated that several 'hard' keratins, Krt1-5, Krt1-24, and Krt2-16, are not expressed in the absence of Pax9. Notably, specific 'soft' keratins, Krt2-1 and Krt2-17, normally weakly expressed in the tongue but present at high levels in skin and in orthokeratinized oral dysplasia are up-regulated in the mutant tongue epithelium. This result indicates a partial trans-differentiation to an epithelium with skin-specific characteristics. Together, our findings show that Pax9 regulates appendage formation in the mammalian tongue and identify Pax9 as an important factor for the region-specific differentiation of the surface ectoderm.

  16. T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium.

    PubMed

    Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

    2016-01-01

    An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an "inverse" configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this

  17. New Colors for Histology: Optimized Bivariate Color Maps Increase Perceptual Contrast in Histological Images

    PubMed Central

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Marx, Alexander; Schuster, Alexander K.; Schad, Lothar R.; Zöllner, Frank Gerrit

    2015-01-01

    Background Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions. Methods and Results In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin—3,3’-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images. Validation To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images. Context Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics. PMID:26717571

  18. Correlation between Histological Status of the Pulp and Its Response to Sensibility Tests

    PubMed Central

    Naseri, Mandana; Khayat, Akbar; Zamaheni, Sara; Shojaeian, Shiva

    2017-01-01

    Introduction: The purpose of this study was to assess the accuracy of sensibility tests by correlating it with histologic pulp condition. Methods and Materials: Assessment of clinical signs and symptoms were performed on 65 permanent teeth that were scheduled to be extracted for periodontal, prosthodontic or orthodontic reasons. The normal pulp and reversible pulpitis were considered as treatable tooth conditions while irreversible pulpitis and necrosis were considered as untreatable conditions. The teeth were then extracted and sectioned for histological analysis of dental pulp. Histologic status and classification corresponded to the treatable or untreatable pulp condition. Comparisons between histological treatable and untreatable pulp condition were performed with chi-square analysis for sensibility test responses. The positive predictive value (PPV), negative predictive value (NPV) and accuracy to detect untreatable from treatable pulp condition were calculated for each test. Results: A significant difference was detected in the normal and a sharp lingered response to heat and cold tests. There was significant difference in the negative response to EPT between histological groups. The kappa agreement coefficient between clinical and histological diagnosis of pulp condition was about 0.843 (P<0.001). The accuracy of cold and heat tests and EPT to detect treatable pulp or untreatable pulp states were 78, 74 and 62%, respectively. The sensibility tests diagnosed untreatable pulpitis with a higher probability (NPV=63%-67% -54%, PPV=83%-91% -95% for heat, cold and EPT, respectively). Conclusion: Sensibility test results were more likely to diagnose pulpal disease or untreatable pulp conditions. However, to increase the diagnostic accuracy patient history, clinical signs and symptoms and also radiographic findings in conjunction with sensibility tests must be used. The result of this small study demonstrated a good agreement between clinical and histological pulp

  19. Histological examination of the human obliquus capitis inferior myodural bridge.

    PubMed

    Pontell, Matthew E; Scali, Frank; Enix, Dennis E; Battaglia, Patrick J; Marshall, Ewarld

    2013-12-01

    This study was designed to examine the anatomical relationship between the obliquus capitis inferior (OCI) muscle and the cervical dura mater at the histological level. Eight human cadavers, with an average age of 65 ± 7.9 years were selected from a convenience sample for suboccipital dissection. Twelve OCI muscle specimens were excised, 100% of which emitted grossly visible soft tissue tracts that inserted into the posterolateral aspect of the cervical dura. These 12 myodural specimens were excised as single, continuous structures and sent for H&E staining. One sample also underwent immuno-peroxidase staining. Microscopic evaluation confirmed a connective tissue bridge emanating from the OCI muscular body and attaching to the posterolateral aspect of the cervical dura mater in 75% of the specimens. Microtome slices of the remaining 25% were not able to capture muscle, connective tissue and dura within the same plane and were therefore unable to be properly analyzed. The sample sent for neuro-analysis stained positively for several neuronal fascicles traveling within, and passing through the OCI myodural bridge. This study histologically confirms the presence of a connective tissue bridge that links the OCI muscle to the dura mater and the presence of neuronal tissue within this connection warrants further examination. This structure may represent a component of normal human anatomy. In addition to its hypothetical role in human homeostasis, it may contribute to certain neuropathological conditions, as well.

  20. Bone welding--a histological evaluation in the jaw.

    PubMed

    Mai, Ronald; Lauer, Günter; Pilling, Eckart; Jung, Roland; Leonhardt, Henry; Proff, Peter; Stadlinger, Bernd; Pradel, Winnie; Eckelt, Uwe; Fanghänel, Jochen; Gedrange, Tomas

    2007-01-01

    The expansion of biodegradable osteosynthesis systems in clinical application correlates well to the progress in development of new materials as to the improvement of application methods. One of those new application methods is the ultrasound-aided insertion of Resorb-X pins. The aim of this study was the histological evaluation of possible thermal damage to bone due to the ultrasound insertion. For this purpose, condylar neck fractures in 12 sheep were produced, repositioned and fixed by Resorb-X plates and pins. The animals were sacrificed in two groups, one after 2 weeks and one after 9 weeks. The bone-pin interlinkage and the structure of the bone were histologically evaluated. After 2 weeks a tight bone-polymer interlinkage was seen. Neither a pronounced foreign body reaction nor an interposition of fibrous tissue at the interface or a thermally induced necrosis was observed. The late phase of wound healing after 9 weeks showed pathomorphological characteristics within the normal range of bone healing. The bone seemed to be free of any alteration caused by process engineering. We conclude that thermal stress caused by ultrasound-aided pin insertion does not lead to cellular reaction in the bone. The fast and easy application of this improved biodegradable osteosynthesis system will bring a clear advantage in clinical use.

  1. Thermoacoustic imaging of prostate cancer: comparison to histology

    NASA Astrophysics Data System (ADS)

    Patch, S. K.; Griep, S. K.; Jacobsohn, K.; See, W. A.; Hull, D.

    2014-03-01

    Ex vivo imaging of fresh prostate specimens was performed to test the hypothesis that the thermoacoustic (TA) contrast mechanism generated with very high frequency electromagnetic (EM) irradiation is sensitive to prostate cancer. Ex vivo imaging was performed immediately after radical prostatectomy, performed as part of normal care. Irradiation pulsewidth was 700 ns and duty cycle was extremely low. Typical specific absorption rate (SAR) throughout the prostate was 70-90 kW/kg during pulsing, but time-averaged SAR was below 2 W/kg. TA pressure pulses generated by rapid heating due to EM energy deposition were detected using single element transducers. 15g/L glycine powder mixed into DI water served as acoustic couplant, which was chilled to prevent autolysis. Spatial encoding was performed by scanning in tomographic "step-and-shoot" mode, with 3 mm translation between slices and 1.8-degree rotation between tomographic views. Histology slides for 3 cases scanned with 2.25 MHz transducers were marked for comparison to TA reconstructions. These three cases showed little, moderate, and severe involvement in the histology levels surrounding the verumontanum. TA signal strength decreased with percent cancerous involvement. When VHF is used for tissue heating, the TA contrast mechanism is driven by ionic content and we observed suppressed TA signal from diseased prostate tissue in the peripheral zone. For the 45 regions of interest analyzed, a reconstruction value of 0.4 mV provides 100% sensitivity but only 29% specificity.

  2. In vivo effect of the lipido-sterolic extract of Serenoa repens (Permixon) on mast cell accumulation and glandular epithelium trophism in the rat prostate.

    PubMed

    Mitropoulos, Dionisios; Kyroudi, Aspasia; Zervas, Anastasios; Papadoukakis, Stefanos; Giannopoulos, Aris; Kittas, Christos; Karayannacos, Panagiotis

    2002-04-01

    The Serenoa repens lipido-sterolic extract (SRLSE, Permixon, Pierre Fabre Medicament, Castres, France) is used to treat benign prostate hyperplasia. We studied the in vivo effect of SRLSE on mast cell accumulation and the histological characteristics of the rat ventral prostate. Adult Wistar rats received either tocopherol or SRLSE (50 and 100 mg/kg body weight, respectively) every second day for 90 days. Histological features were studied in hematoxylin-eosin stained tissue sections while mean mast cell numbers were determined in Giemsa-stained sections. The central region of the ventral prostate in treated animals showed significant changes with acinar epithelium becoming flat or low cuboidal. In the same region, mean mast cell number per optical field in the control, low-dose and high-dose groups were, respectively, 4.7+/-0.7, 3.4+/-1.0 and 2.4+/-0.6, showing a dose-dependent, statistically significant decrease. Administering SRLSE significantly reduces mast cell accumulation and provokes epithelium atrophy within the central area of the rat ventral prostate. These phenomena may participate in the clinical activity of the drug.

  3. Microvillus inclusion disease: a genetic defect affecting apical membrane protein traffic in intestinal epithelium.

    PubMed

    Ameen, N A; Salas, P J

    2000-01-01

    The striking similarities between microvillus inclusions (MIs) in enterocytes in microvillus inclusion disease (MID) and vacuolar apical compartment in tissue culture epithelial cells, led us to analyze endoscopic biopsies of duodenal mucosa of a patient after the samples were used for diagnostic procedures. Samples from another patient with an unrelated disease were used as controls. The MID enterocytes showed a decrease in the thickness of the apical F-actin layer, and normal microtubules. The immunofluorescence analysis of the distribution of five apical membrane markers (sucrase isomaltase, alkaline phosphatase, NHE-3 Na+/H+ exchanger, cGMP-dependent protein kinase, and cystic fibrosis trans-membrane conductance regulator), showed low levels of these proteins in their standard localization at the apical membrane as compared with normal duodenal epithelium processed in parallel. Instead, four of these markers were found in a diffuse distribution in the apical cytoplasm, below the terminal web (as indicated by co-localization with F-actin and cytokeratin 19), and in MIs as well. The basolateral protein Na(+)-K+ATPase, in contrast, was normally localized. These results support the hypothesis that MID may represent the first genetic defect affecting apical membrane traffic, possibly in a late step of apical exocytosis.

  4. Liposoluble vitamins in Crustacean feed: Metabolic and Histological responses.

    PubMed

    Fernández-Gimenez, Analía Verónica

    2016-05-01

    Vitamins are vital for normal growth and survival of living organisms and they are distributed in feedstuffs in small quantities. This review is focused on the liposoluble vitamins (A, D, E and K) in the diets and metabolic responses of the Argentine penaeoid shrimps Pleoticus muelleri and Artemesia longinaris, distributed along the South American coast line. Growth, survival and histological analyses serve as indicators of the nutritional value derived from vitamin deficiency. Liposoluble vitamins are also related to stress, antioxidant defense and immune response of shrimps. Effective diet for shrimp culture that provide not only macronutrients including protein and lipid but also micronutrients such as vitamins for optimal growth is an ever improving subject. This review may help formulating suitable feeds for shrimps.

  5. A histological study of cerebral aqueduct.

    PubMed

    Stanković, Gordana; Nikolić, Valentina; Puskas, Laslo; Filipović, Branislav; Stojsić-Dzunja, Ljubica; Krivokuća, Dragan

    2005-01-01

    Cerebral (sylvian) aqueduct is a narrow channel in the mesencephalon. It lies between the tectum and the tegmentum of the mesencephalon and is surrounded by the periaqueductal gray matter. The aim of this study was to determine the shape of the aqueduct of sylvius and the structure of its walls in a series of transverse histological sections. Serial transverse sections of the mesencephalon were examined in twenty adult brains of both sexes. Six sections were stained by the hematoxylin-eosin method. The rostral part of the the aqueduct has a triangular shape with dorsal concavity caused by retrocommissural fossae. In the middle, its shape is oval to irregular, the rostral part has a T shape due to isthmic recess on the floor. Walls of the aqueduct are coated with a layer of prismatic cells. Determination of the morphological and histological features of the mesencephalic aqueduct is important for differentiation between physiological and pathological processes in this region.

  6. Histologic changes in previously irradiated thyroid glands

    SciTech Connect

    Valdiserri, R.O.; Borochovitz, D.

    1980-03-01

    Thyroid tissue from 90 patients with a history of therapeutic irradiation to the head and neck in childhood and adolescence was examined microscopically. In addition to the well-known observation that these individuals have an increased incidence of primary thyroid carcinoma, it was also demonstrated that they have an increased incidence of benign histologic changes. These changes represent a spectrum from nonspecific hyperplastic lesions to benign neoplasis and thyroidltis.

  7. Histological and hormonal changes in the European eel (Anguilla anguilla) after exposure to environmental cocaine concentration.

    PubMed

    Gay, F; Ferrandino, I; Monaco, A; Cerulo, M; Capasso, G; Capaldo, A

    2016-03-01

    The aim of this study was the assessment of histological and hormonal changes induced in the European eel from environmental concentrations of cocaine. Silver eels were exposed to 20 ng L(-1) of cocaine during 50 days; at the same time, control, vehicle control and two post-exposure recovery groups (3 and 10 days) were made. The general morphology of the skin and the intestine, and the plasma levels of prolactin, cortisol and dopamine were evaluated. In the skin, cocaine decreased the number and size of mucous cells, increased the thickness of the epidermis and altered the club cells and the basal lamina. In the intestine, cocaine increased the thickness of the epithelium and the number of mucous cells and reactivated the structure of the intestine and of the intestinal musculature. Moreover, cocaine increased plasma prolactin, cortisol and dopamine levels. These results suggest that cocaine induced histological changes, directly and/or through the hormonal changes observed. Considering the complex life cycle of the eel, the changes induced by cocaine in the skin, the intestine and the endocrine system could threaten the ability of the eel to successfully migrate and reproduce.

  8. Olfactory Neuroblastoma with Divergent Differentiation: An Unusual Histologic Finding in a Rare Tumor.

    PubMed

    Meyer, Charles; Hamersley, Erin R S; Manosalva, Rodolfo E; Torske, Kevin; McIntyre, Nicole; Mitchell, Allen

    2017-02-06

    Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the sinonasal tract that arises from olfactory epithelium. There have been reports, mainly in tumors treated with chemoradiation or with distant metastases, describing focal histologic changes of divergent cell populations within archetypal ONB. Only three cases have been reported of ONB coexisting with non-neuroendocrine tumors. We describe our experience with a 35-year-old male with a nasal cavity mass extending into the anterior cranial fossa. Pathology revealed this to be a high grade malignant neoplasm with features of olfactory neuroblastoma and a significant divergent population of pancytokeratin and epithelial membrane antigen-reactive cells. The patient underwent combined endoscopic and open craniofacial resection followed by adjuvant chemoradiation. We describe the clinical presentation, treatment, and outcome followed by a review of the literature. Surgical pathology clearly demonstrated two cell populations evenly distributed and displaying classic histologic and immunohistochemical markers of ONB, as well as poorly differentiated cells with an epithelial immunophenotype. The patient is now 16 months status post completion of treatment with no evidence of recurrence. Our patient's presentation is unique and unusual in that the tumor demonstrated a high grade olfactory neuroblastoma and a divergent, epithelial-marker reactive cell population in the same tumor. This combined appearance is unusual and may represent an "olfactory carcinoma". Only one previous case has reported carcinomatous involvement of an ONB. There is insufficient information in the literature to draw conclusions on the impact these divergent cell populations have on prognosis or treatment.

  9. Morphological and histological characteristics of mammary dysplasias occurring in cell dissociation-derived murine mammary outgrowths

    SciTech Connect

    Ethier, S.P.; Adams, L.M.; Ullrich, R.L.

    1984-10-01

    The morphological and histological characteristics of ductal dysplasias that were observed in mammary outgrowths derived from monodispersed mammary cells of carcinogen-treated mice are described. Mammary outgrowths were derived by injecting either 10(4) or 10(5) enzymatically dissociated mammary cells, obtained from control or carcinogen-treated BALB/c mice, into gland-free mammary fat pads of syngeneic hosts. The mammary dysplasias observed varied considerably in morphological and histological characteristics. The majority of the lesions were ductal in origin and were associated with epithelial hyperplasia which ranged from mild hyperplasia, in which only a few extra layers of epithelium were present, to severe hyperplasia, in which the ducts and end buds were occluded and distended with epithelial cells. In addition, papillary and lobular lesions were observed which were also associated with varying degrees of hyperplasia. The range of mammary dysplasias observed in these outgrowths closely resembles that of lesions associated with the pathogenesis of mammary carcinoma in mice, rats, and humans.

  10. Histological and morphological alterations induced by copper exposure in Laeonereis acuta (Polychaeta, Nereididae).

    PubMed

    Geracitano, L A; Luquet, C; Monserrat, J M; Bianchini, A

    2004-01-01

    Laeonereis acuta (Polychaeta, Nereididae) was collected in an unpolluted (UP) and an polluted (P) site at the Patos Lagoon estuary (Southern Brazil) and maintained under control conditions (UPC and PC, respectively) or exposed to waterborne copper (UPCu and PCu; 500 microg Cu/l), for 48 h. Four groups (aaUPC, aaPC, aaUPCu, and aaPCu) were also pre-exposed for 48 h to ascorbic acid (aa; 0.1 mM) before copper exposure. Histological and morphological alterations, as well as oxygen consumption changes were evaluated. Independently of the sampling site and the pre-exposure to the ascorbic acid, morphological abnormalities were evident in more than 80% of worms exposed to copper. Conspicuous histological changes (coeloma obliteration, cuticle separation from the epidermis, and absence of dorsal vessel) were also observed. In addition, PCu worms showed loss of the digestive epithelium and coiling behavior. Similar oxygen consumption values were observed in control and copper exposed worms.

  11. Anatomy and histology of Virchow's node.

    PubMed

    Mizutani, Masaomi; Nawata, Shin-ichi; Hirai, Ichiro; Murakami, Gen; Kimura, Wataru

    2005-12-01

    A regional lymphatic system is composed of the first, second, third and even fourth or much more intercalated nodes along the lymptatic route from the periphery to the venous angle or the thoracic duct. The third or fourth node is usually termed the last-intercalated node or end node along the route. Similarly, one of the supraclavicular nodes is known to correspond to the end node along the thoracic duct. It is generally called 'Virchow's node', in which the famous 'Virchow's metastasis' of advanced gastric cancer occurs. The histology of this node has not been investigated, although region-specific differences in histology are evident in human lymph nodes. We found macroscopically the end node in five of 30 donated cadavers. Serial sections were prepared for these five nodes and sections stained with hematoxylin and eosin. Histological investigation revealed that, on the inferior or distal side of the end node, the thoracic duct divided into three to 10 collateral ducts and these ducts surrounded the node. The node communicated with the thoracic duct and its collaterals at multiple sites in two to three hilus-like portions, as well as along the subcapsular sinus. Thus, the end node was aligned parallel to the thoracic duct. Moreover, the superficial and deep cortex areas of the end node were fragmented to make an island-like arrangement, which may cause the short-cut intranodal shunt. Consequenly, the filtration function of most of Virchow's node seemed to be quite limited.

  12. Histological changes of kidney in diabetic nephropathy

    PubMed Central

    Pourghasem, Mohsen; Shafi, Hamid; Babazadeh, Zahra

    2015-01-01

    Diabetes mellitus is the most common cause of chronic renal disorders and end-stage kidney disease in developed countries. It is the major cause of dialysis and transplantation. Failure in renal function causes wide disorders in the body. Diabetes results in wide range of alterations in the renal tissue. It is believed that early histological changes in diabetic nephropathy are detectable 2 years after diabetes is diagnosed. The glomerular alterations are the most important lesions in the diabetic nephropathy (DN). The Renal Pathology Society provides a new pathological classification for the detection of histopathology of DN. It divides diabetic nephropathy into four hierarchical glomerular lesions. Alloxan or streptozotocin induced diabetic rat is the one most widely used specie to study DN. Histological changes in the rat DN closely resemble the human disease and the most information of this review was obtained through the study of rat DN. All cell types of the kidney such as mesangial cells, podocytes and tubulointerstitial cells are liable to be affected in the event of DN. Severity of renal lesions is associated to the clinical aspect of renal outcome, but the aim of this article was only to review the histological changes of kidney in diabetes mellitus. PMID:26644877

  13. Validation of Normal Human Bronchial Epithelial Cells as a Model for Influenza A Infections in Human Distal Trachea

    PubMed Central

    Davis, A. Sally; Chertow, Daniel S.; Moyer, Jenna E.; Suzich, Jon; Sandouk, Aline; Dorward, David W.; Logun, Carolea; Shelhamer, James H.

    2015-01-01

    Primary normal human bronchial/tracheal epithelial (NHBE) cells, derived from the distal-most aspect of the trachea at the bifurcation, have been used for a number of studies in respiratory disease research. Differences between the source tissue and the differentiated primary cells may impact infection studies based on this model. Therefore, we examined how well-differentiated NHBE cells compared with their source tissue, the human distal trachea, as well as the ramifications of these differences on influenza A viral pathogenesis research using this model. We employed a histological analysis including morphological measurements, electron microscopy, multi-label immunofluorescence confocal microscopy, lectin histochemistry, and microarray expression analysis to compare differentiated NHBEs to human distal tracheal epithelium. Pseudostratified epithelial height, cell type variety and distribution varied significantly. Electron microscopy confirmed differences in cellular attachment and paracellular junctions. Influenza receptor lectin histochemistry revealed that α2,3 sialic acids were rarely present on the apical aspect of the differentiated NHBE cells, but were present in low numbers in the distal trachea. We bound fluorochrome bioconjugated virus to respiratory tissue and NHBE cells and infected NHBE cells with human influenza A viruses. Both indicated that the pattern of infection progression in these cells correlated with autopsy studies of fatal cases from the 2009 pandemic. PMID:25604814

  14. Changes of the lingual epithelium in Ambystoma mexicanum.

    PubMed

    Wistuba, J; Clemen, G

    1998-12-01

    Changes in the lingual epithelium during ontogenesis and after induced metamorphosis in Ambystoma mexicanum are described as observed by light microscopy and scanning electron microscopy. The epithelium of the tongue is always multilayered in the larva as well as in the adult. It consists of a stratum germinativum with little differentiated basal cells and a stratum superficiale (superficial layer) with specialized superficial cells and goblet cells. Usually, there are more than two layers because of a stratum intermedium consisting of replacement cells. The apical cell membrane of the superficial cells is perforated by fine pores. Its most typical feature are microridges. Maturing superficial cells possess microvilli. Goblet cells occur in early larvae primarily in the centre of the tongue. They spread throughout the dorsal face of the tongue as their numbers increase during ontogenesis. The small apices of the goblet cells are intercalated in the wedges between the superficial cells. Leydig cells are not found on the larval tongue but on that of adults. Due to metamorphosis, the epithelium of the tongue changes. It is furrowed in its anterior part. The furrows house the openings of the lingual glands. The surface is further modulated by ridges which are densely coated by microvilli and which bear the taste buds. The villi of the tongue which lack extrusion pores show cilia and microvilli but lack microridges. The Leydig cells disappear during metamorphosis. In addition to the two types of goblet cells found in different regions of the glandular tubules, goblet cells occur in the caudal part. They secrete directly into the cavity of the mouth. The posterior part is characterised by a dense coat of cilia.

  15. Megalin and cubilin in the human gallbladder epithelium.

    PubMed

    Tsaroucha, Alexandra K; Chatzaki, Ekaterini; Lambropoulou, Maria; Despoudi, Kaliopi; Laftsidis, Prodromos; Charsou, Chara; Polychronidis, Alexandros; Papadopoulos, Nikolaos; Simopoulos, Constantinos E

    2008-09-01

    Although the role of cholesterol absorption by the gallbladder epithelium in gallstone formation is well established, the exact process is poorly understood. Potential candidates for regulation of transepithelial cholesterol transport are suggested to be two large membrane multiple ligand receptors, megalin and cubilin. We studied the expression of these two proteins in both acalculous and calculous human gallbladder epithelia. Adult human gallbladder tissues were received from 21 patients (9 men, 12 women) who had undergone cholecystectomy. The patients were divided into two groups: group A (calculous gallbladder group; 5 men, 6 women; mean age 64.4 +/- 11.1 years) with cholelithiasis, and group B (acalculous gallbladder group; 4 men, 6 women; mean age 55.3 +/- 16.1 years). In the gallbladder tissues megalin and cubilin expression was studied by immunohistochemistry and conventional RT-PCR, and gene expression levels were estimated by real-time RT-PCR. Both megalin and cubilin gene transcripts were found in total RNA preparations from acalculous gallbladder. In contrast, in preparations from calculous gallbladder, none or only one of the proteins was detected. Immunoreactive proteins were detected in the simple columnar acalculous gallbladder epithelium but not in the calculous gallbladder epithelium. Our results show different expression patterns of the two proteins in calculous gallbladders and acalculous gallbladders. In the latter both proteins are expressed, suggesting an association with gallstone formation and implying a putative role of the two proteins in cholesterol endocytosis. In other words, the presence of both proteins may be essential for the prevention of stone formation.

  16. The Ciona intestinalis immune-related galectin genes (CiLgals-a and CiLgals-b) are expressed by the gastric epithelium.

    PubMed

    Parrinello, Daniela; Sanfratello, Maria Antonietta; Vizzini, Aiti; Testasecca, Lelia; Parrinello, Nicolò; Cammarata, Matteo

    2017-03-01

    The transcription of two Ciona intestinalis galectin genes (CiLgals-a and CiLgals-b) is uparegulated by LPS in the pharynxis (hemocytes, vessel epithelium, endostilar zones) which is retained the main organ of the immunity. In this ascidian, for the first time we show, by immunohistochemistry and in situ hybridization methods, that these two immune-related genes are expressed in the gastric epithelium of naïve ascidians, whereas the galectins appear to be only contained in the intestine columnar epithelium. In addition, according to previous results on the pharynx, the genes are also expressed and galectins produced by hemocytes scattered in the connective tissue surrounding the gut. The genes expression and galectin localization in several tissues, including the previous findings on the transcription upregulation, the constitutive expression of these genes by endostylar zones and by the gastric epithelium suggest a potential multifunctional role of these galectins. In this respect, it is of interest to define where the CiLgals are normally found as related to the tissue functions. Such an approach should be a starting point for further investigations.

  17. Spatial pattern of receptor expression in the olfactory epithelium.

    PubMed Central

    Nef, P; Hermans-Borgmeyer, I; Artières-Pin, H; Beasley, L; Dionne, V E; Heinemann, S F

    1992-01-01

    A PCR-based strategy for amplifying putative receptors involved in murine olfaction was employed to isolate a member (OR3) of the seven-transmembrane-domain receptor superfamily. During development, the first cells that express OR3 appear adjacent to the wall of the telencephalic vesicle at embryonic day 10. The OR3 receptor is uniquely expressed in a subset of olfactory cells that have a characteristic bilateral symmetry in the adult olfactory epithelium. This receptor and its specific pattern of expression may serve a functional role in odor coding or, alternatively, may play a role in the development of the olfactory system. Images PMID:1384038

  18. Diet, Microbiome, and the Intestinal Epithelium: An Essential Triumvirate?

    PubMed Central

    Guzman, Javier Rivera; Conlin, Victoria Susan; Jobin, Christian

    2013-01-01

    The intestinal epithelium represents a critical barrier protecting the host against diverse luminal noxious agents, as well as preventing the uncontrolled uptake of bacteria that could activate an immune response in a susceptible host. The epithelial monolayer that constitutes this barrier is regulated by a meshwork of proteins that orchestrate complex biological function such as permeability, transepithelial electrical resistance, and movement of various macromolecules. Because of its key role in maintaining host homeostasis, factors regulating barrier function have attracted sustained attention from the research community. This paper will address the role of bacteria, bacterial-derived metabolism, and the interplay of dietary factors in controlling intestinal barrier function. PMID:23586037

  19. Are pheromones detected through the main olfactory epithelium?

    PubMed

    Wang, Zhenshan; Nudelman, Aaron; Storm, Daniel R

    2007-06-01

    A major sensory organ for the detection of pheromones by animals is the vomeronasal organ (VNO). Although pheromones control the behaviors of various species, the effect of pheromones on human behavior has been controversial because the VNO is not functional in adults. However, recent genetic, biochemical, and electrophysiological data suggest that some pheromone-based behaviors, including male sexual behavior in mice, are mediated through the main olfactory epithelium (MOE) and are coupled to the type 3 adenylyl cyclase (AC3) and a cyclic nucleotide-gated (CNG) ion channel. These recent discoveries suggest the provocative hypothesis that human pheromones may signal through the MOE.

  20. Regulation and expression of multidrug resistance (MDR) transcripts in the intestinal epithelium

    PubMed Central

    Li, M; Hurren, R; Zastawny, R L; Ling, V; Buick, R N

    1999-01-01

    A paucity of information exists on the regulation of gene expression in the undifferentiated intestine. The intestinal epithelium is one of the few normal tissues expressing the multidrug resistance (MDR) genes that confer the multidrug resistant phenotype to a variety of tumours. Expression of mdr1a has been observed in the primitive rat intestinal epithelial cell line, IEC-18. It is hypothesized that characterization of MDR gene expression in IEC-18 cells will provide insight into gene regulation in undifferentiated intestinal cells. A series of hamster mdr1a promoter deletion constructs was studied in IEC-18 and a region with 12–13-fold enhancer activity was identified. This region was shown to function in an orientation- and promoter context-independent manner, specifically in IEC-18 cells. Unexpectedly, Northern probing revealed a greater expression of mdr1b than mdr1a in IEC-18 cells. A quantitative reverse transcription polymerase chain reaction assay was used to compare the relative expression of MDR genes in IEC cells, fetal intestine, and in the undifferentiated and differentiated components of adult intestinal epithelium. MDR transcript levels in IEC cells were found to resemble those of fetal intestine and small intestinal crypts, where a conversion from mixed mdr1a/mdr1b to predominantly mdr1a expression occurs as cells mature. This work describes two contributions to the field of gene regulation in the undifferentiated intestine – first, the initial characterization of a putative mdr1a enhancer region with specificity for primitive intestinal cells and secondly, the first report of mdr1b detection in the intestine and its expression in primitive cell types. © 1999 Cancer Research Campaign PMID:10376961

  1. Formation of pancreatic duct epithelium from bone marrow during neonatal development.

    PubMed

    Wang, Xiuli; Ge, Shundi; Gonzalez, Ignacio; McNamara, George; Rountree, C Barth; Xi, Kenny Kezhe; Huang, Grace; Bhushan, Anil; Crooks, Gay M

    2006-02-01

    Recent reports suggest that bone marrow-derived cells engraft and differentiate into pancreatic tissue at very low frequency after pancreatic injury. All such studies have used adult recipients. The aim of our studies was to investigate the potential of bone marrow to contribute to the exocrine and endocrine components of the pancreas during the normal rapid growth of the organ that occurs during the neonatal period. Five to ten million bone marrow cells from adult, male, transgenic, green fluorescent protein (GFP) mice were injected into neonatal nonobese diabetic/severely compromised immunodeficient/beta2microglobulin-null mice 24 hours after birth. Two months after bone marrow transplantation, pancreas tissue was analyzed with fluorescence immunohistochemistry and fluorescence in situ hybridization (FISH). Co-staining of GFP, with anticytokeratin antibody, and with FISH for the presence of donor Y chromosome indicated that up to 40% of ducts (median 4.6%) contained epithelial cells derived from donor bone marrow. In some of these donor-derived ducts, there were clusters of large and small ducts, all comprised of GFP+ epithelium, suggesting that whole branching structures were derived from donor bone marrow. In addition, rare cells that coexpressed GFP and insulin were found within islets. Unlike pancreatic damage models, no bone marrow-derived vascular endothelial cells were found. In contrast to the neonatal recipients, bone marrow transplanted into adult mice rarely generated ductal epithelium or islet cells (p<.05 difference between adult and neonate transplants). These findings demonstrate the existence in bone marrow of pluripotent stem cells or epithelial precursors that can migrate to the pancreas and differentiate into complex organ-specific structures during the neonatal period.

  2. Expression of the apoptotic calcium channel P2X7 in the glandular epithelium.

    PubMed

    Slater, Michael; Danieletto, Suzanne; Barden, Julian A

    2005-03-01

    In the current study, expression of the apoptotic calcium channel receptor P2X(7) and prostate-specific antigen (PSA) levels were studied in biopsy cores from 174 patients as well as 20 radical prostatectomy cases. In clinical biopsies, we have previously demonstrated that P2X(1 )and P2X(2) calcium channel receptors are absent from normal prostate epithelium that does not progress to prostate cancer within 5 years. In cases that did progress to prostate cancer however, P2X(1 )and P2X(2) labeling was observed in a stage-specific manner first in the nucleus, then the cytoplasm and finally on the apical epithelium, as prostate cancer developed. These markers were present up to 5 years before cancer was detectable by the usual morphological criteria (Gleason grading) as determined by H and E staining. In the current study, the apoptotic calcium channel receptor P2X(7) yielded similar results to that of P2X(1) and P2X(2). Using radical prostatectomy tissue sections as well as biopsies, these changes in calcium channel metabolism were noted throughout the prostate, indicating a field effect. This finding suggests that the presence of a prostate tumor could be detected without the need for direct sampling of tumor tissue, leading to detection of false negative cases missed by H or E stain. The reliability of PSA levels as a prognostic indicator has been questioned in recent years. In the current study, PSA levels were correlated with the P2X(7) labeling results. All patients who exhibited no P2X(7) labeling had a prostatic serum antigen (PSA) level of <2. Patients who exhibited stage-specific P2X(7) expression, and who later developed obvious prostate cancer as diagnosed by H and E stain, all had a PSA > 2. This finding suggests that increasing PSA may be an accurate indicator of cancer development.

  3. Stage specific requirement of Gfrα1 in the ureteric epithelium during kidney development.

    PubMed

    Keefe Davis, T; Hoshi, Masato; Jain, Sanjay

    2013-01-01

    Glial cell line-derived neurotrophic factor (GDNF) binds a coreceptor GDNF family receptor α1 (GFRα1) and forms a signaling complex with the receptor tyrosine kinase RET. GDNF-GFRα1-RET signaling activates cellular pathways that are required for normal induction of the ureteric bud (UB) from the Wolffian duct (WD). Failure of UB formation results in bilateral renal agenesis and perinatal lethality. Gfrα1 is expressed in both the epithelial and mesenchymal compartments of the developing kidney while Ret expression is specific to the epithelium. The biological importance of Gfrα1's wider tissue expression and its role in later kidney development are unclear. We discovered that conditional loss of Gfrα1 in the WD epithelium prior to UB branching is sufficient to cause renal agenesis. This finding indicates that Gfrα1 expressed in the nonepithelial structures cannot compensate for this loss. To determine Gfrα1's role in branching morphogenesis after UB induction we used an inducible Gfrα1-specific Cre-deletor strain and deleted Gfrα1 from the majority of UB tip cells post UB induction in vivo and in explant kidney cultures. We report that Gfrα1 excision from the epithelia compartment after UB induction caused a modest reduction in branching morphogenesis. The loss of Gfrα1 from UB-tip cells resulted in reduced cell proliferation and decreased activated ERK (pERK). Further, cells without Gfrα1 expression are able to populate the branching UB tips. These findings delineate previously unclear biological roles of Gfrα1 in the urinary tract and demonstrate its cell-type and stage-specific requirements in kidney development.

  4. Topographical organization of TRPV1-immunoreactive epithelium and CGRP-immunoreactive nerve terminals in rodent tongue.

    PubMed

    Kawashima, M; Imura, K; Sato, I

    2012-05-10

    Transient receptor potential vanilloid subfamily member 1 (TRPV1) is activated by capsaicin, acid, and heat and mediates pain through peripheral nerves. In the tongue, TRPV1 expression has been reported also in the epithelium. This indicates a possibility that sensation is first received by the epithelium. However, how nerves receive sensations from the epithelium remains unclear. To clarify the anatomical basis of this interaction, we performed immunohistochemical studies in the rodent tongue to detect TRPV1 and calcitonin gene-related peptide (CGRP), a neural marker. Strong expression of TRPV1 in the epithelium was observed and was restricted to the apex of the tongue. Double immunohistochemical staining revealed that CGRP-expressing nerve terminals were in close apposition to the strongly TRPV1-expressing epithelium of fungiform papilla in the apex of rodent tongues. These results suggest that the TRPV1-expressing epithelium monitors the oral environment and acquired information may then be conducted to the adjacent CGRP-expressing terminals.

  5. Expression of Human β-Defensins in Conjunctival Epithelium: Relevance to Dry Eye Disease

    PubMed Central

    Narayanan, Srihari; Miller, William L.; McDermott, Alison M.

    2006-01-01

    Purpose. The goals of this study were to investigate whether β-defensins are differentially expressed in the conjunctival epithelium of patients with moderate dry eye when compared with normal subjects and whether proinflammatory cytokines or bacteria can modulate the expression of human β-defensins (hBDs)-1, -2, and -3 by conjunctival epithelial cells. Methods. RNA extracted from conjunctival impression cytology specimens of eight normal subjects and nine patients with moderate dry eye was used in RT-PCR to detect mRNA for hBDs-1, -2, and -3. Two conjunctival epithelial cell lines and primary cultured conjunctival epithelial cells were treated with proinflammatory cytokines or heat-killed Pseudomonas aeruginosa. RT-PCR and immunoblot analysis were used to detect mRNA for hBD-1, -2, and -3 and protein secretion of hBD-2, respectively. Results. hBD-2 message was detected in RNA samples of eight of nine patients with dry eye, but not in any of the normal subjects’ samples, whereas hBD-1 and -3 were detected in all subjects tested. RT-PCR revealed an upregulation of hBD-2 but no difference in expression of hBD-1 and -3 in cultured conjunctival cells after a 24-hour treatment with 10 ng/mL interleukin (IL)-1β, IL-1β and tumor necrosis factor-α (10 ng/mL) or heat-killed Pseudomonas aeruginosa (1 million colony-forming units; n = 3). hBD-2 expression was upregulated from 4 hours of treatment with IL-1β (at 10 ng/mL; (n = 2–3) and at a concentration of 0.1 ng/mL IL-1β (24-hour treatment; n = 2–3). Immunoblots demonstrated protein secretion results corresponding to the RT-PCR data. Conclusions. hBD-2 was expressed only in the conjunctival epithelium of patients with moderate dry eye. Because cytokines such as IL-1β and TNF-α induced the expression of hBD-2 by conjunctival epithelial cells and because increased proinflammatory cytokine activity is a feature of dry eye disease, it can be speculated that the hBD-2 upregulation observed in subjects with moderate

  6. The Phototoxicity of ’Blue Light’ on the Functional Properties of the Retinal Pigment Epithelium

    DTIC Science & Technology

    1990-10-15

    RETINAL PIGMENT P - AF EPITHELIUM PE - 61102F IL PR - 2312 S. AUTNOIS) ITA - A5 Dr Pautler 7. PIRIPORMING ORGANIATION NAMIES) ANO AOOR!SS(ES) L...SUEMENTARY NOTES E C7 D2 E 26 99 12a. OISTRJSUTJTOAVAILAUIT STATEMENT Mr L 0ISTRIBUjTMO cow Irradiation of the isolated bovine retinal pigment epithelium...light filter.- Blue light depolarized the transepithelial potential of pigment epithelium, an action spectrum established that a hemoprotein(s) is one

  7. Collagen scaffold meniscus implant integration in a canine model: a histological analysis.

    PubMed

    Hansen, Robert; Bryk, Eli; Vigorita, Vincent

    2013-12-01

    In the situation of an irreparable meniscus tear, an implant comparable to a normal meniscus is an attractive option. Using a canine model, we assessed the early and late histologic response to a tissue engineered meniscal collagen scaffold (CS). All animals received bilateral arthrotomies, and all joints receiving the CS had an 80% resection of the meniscus. Animals were sacrificed at 3 and 6 weeks, and 12, 13, and 17 months. The CS/tissue complex and host meniscal rim were sectioned for histologic examination with specific focus on the extracellular matrix, angiogenesis, cellular resorption of the scaffold, scaffold appearance, and CS/Host integration. Early histologic samples (3-6 weeks) revealed active angiogenesis and fibrin clots evolving into cellular granulation type tissue. At 12 months, a mature fibrochondrocytic matrix was depositing with gradations of dissolution and integration of the CS implant. Maturing CS/host integration was observed at 18 months. Active cellular resorption of the implant decreased over time. Four cases showed a mild non-specific chronic inflammation and one additional case showed inflammatory engulfment of the scaffold with giant cells at 3 weeks. No evidence of infection either clinically or histologically was observed at any time point. Overall, this histologic analysis demonstrated the active integration of a meniscal like cartilage into a tissue engineered biological scaffold in a canine model.

  8. Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro.

    PubMed

    Steinfort, C; Wilson, R; Mitchell, T; Feldman, C; Rutman, A; Todd, H; Sykes, D; Walker, J; Saunders, K; Andrew, P W

    1989-07-01

    A total of 11 of 15 Streptococcus pneumoniae culture filtrates and all five bacterial autolysates produced by cell death in the stationary phase caused slowed ciliary beating and disruption of the surface integrity of human respiratory epithelium in organ culture. This effect was inhibited by cholesterol and was heat labile and reduced by standing at room temperature but was stable at -40 degrees C. The activity was detected at the late stationary phase of culture and was associated with the presence of hemolytic activity. Gel filtration of a concentrated culture filtrate and autolysate both yielded a single fraction of approximately 50 kilodaltons which slowed ciliary beating and were the only fractions with hemolytic activity. Rabbit antiserum to pneumolysin, a sulfhydryl-activated hemolytic cytotoxin released by S. pneumoniae during autolysis, neutralized the effect of the culture filtrate on respiratory epithelium. Both native and recombinant pneumolysin caused ciliary slowing and epithelial disruption. Electron microscopy showed a toxic effect of pneumolysin on epithelial cells: cytoplasmic blebs, mitochondrial swelling, cellular extrusion, and cell death, but no change in ciliary ultrastructure. Recombinant pneumolysin (10 micrograms/ml) caused ciliary slowing in the absence of changes in cell ultrastructure. Release of pneumolysin in the respiratory tract during infection may perturb host defenses, allowing bacterial proliferation and spread.

  9. The skin of fish as a transport epithelium: a review.

    PubMed

    Glover, Chris N; Bucking, Carol; Wood, Chris M

    2013-10-01

    The primary function of fish skin is to act as a barrier. It provides protection against physical damage and assists with the maintenance of homoeostasis by minimising exchange between the animal and the environment. However in some fish, the skin may play a more active physiological role. This is particularly true in species that inhabit specialised environmental niches (e.g. amphibious and air-breathing fish such as the lungfish), those with physiological characteristics that may subvert the need for the integument as a barrier (e.g. the osmoconforming hagfish), and/or fish with anatomical modifications of the epidermis (e.g. reduced epithelial thickness). Using examples from different fish groups (e.g. hagfishes, elasmobranchs and teleosts), the importance of fish skin as a transport epithelium for gases, ions, nitrogenous waste products, and nutrients was reviewed. The role of the skin in larval fish was also examined, with early life stages often utilising the skin as a surrogate gill, prior to the development of a functional branchial epithelium.

  10. An in vitro model of murine middle ear epithelium

    PubMed Central

    Mulay, Apoorva; Akram, Khondoker M.; Williams, Debbie; Armes, Hannah; Russell, Catherine; Hood, Derek; Armstrong, Stuart; Stewart, James P.; Brown, Steve D. M.; Bingle, Lynne

    2016-01-01

    ABSTRACT Otitis media (OM), or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well-characterised in vitro model of the middle ear (ME) epithelium that replicates the complex cellular composition of the middle ear. Here, we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs) at an air–liquid interface (ALI) that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We showed that the mMECs supported the growth of the otopathogen, nontypeable Haemophilus influenzae (NTHi), suggesting that the model can be successfully utilised to study host–pathogen interactions in the middle ear. Overall, our mMEC culture system can help to better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling that underpin OM development. PMID:27660200

  11. Attack and defence in the gastric epithelium - a delicate balance.

    PubMed

    Dimaline, Rod; Varro, Andrea

    2007-07-01

    The gastric epithelium is a complex structure formed into tubular branched gastric glands. The glands contain a wide variety of cell types concerned with the secretion of hydrochloric acid, proteases, mucus and a range of signalling molecules. All cell types originate from stem cells in the neck region of the gland, before migrating and differentiating to assume their characteristic positions and functions. Endocrine and local paracrine mediators are of crucial importance for maintaining structural and functional integrity of the epithelium, in the face of a hostile luminal environment. The first such mediator to be recognized, the hormone gastrin, was identified over a century ago and is now established as the major physiological stimulant of gastric acid secretion. Recent studies, including those using mice that overexpress or lack the gastrin gene, suggest a number of previously unrecognized roles for this hormone in the regulation of cellular proliferation, migration and differentiation. This review focuses on the identification of hitherto unsuspected gastrin-regulated genes and discusses the paracrine cascades that contribute to the maintenance of gastric epithelial architecture and secretory function. Helicobacter infection is also considered in cases where it shares targets and signalling mechanisms with gastrin.

  12. Selective gene expression by rat gastric corpus epithelium

    PubMed Central

    Goebel, M.; Stengel, A.; Sachs, G.

    2011-01-01

    The gastrointestinal (GI) tract is divided into several segments that have distinct functional properties, largely absorptive. The gastric corpus is the only segment thought of as largely secretory. Microarray hybridization of the gastric corpus mucosal epithelial cells was used to compare gene expression with other segments of the columnar GI tract followed by statistical data subtraction to identify genes selectively expressed by the rat gastric corpus mucosa. This provides a means of identifying less obvious specific functions of the corpus in addition to its secretion-related genes. For example, important properties found by this GI tract comparative transcriptome reflect the energy demand of acid secretion, a role in lipid metabolism, the large variety of resident neuroendocrine cells, responses to damaging agents and transcription factors defining differentiation of its epithelium. In terms of overlap of gastric corpus genes with the rest of the GI tract, the distal small bowel appears to express many of the gastric corpus genes in contrast to proximal small and large bowel. This differential map of gene expression by the gastric corpus epithelium will allow a more detailed description of major properties of the gastric corpus and may lead to the discovery of gastric corpus cell differentiation genes and those mis-regulated in gastric carcinomas. PMID:21177383

  13. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    NASA Astrophysics Data System (ADS)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  14. Mucous granule exocytosis and CFTR expression in gallbladder epithelium.

    PubMed

    Kuver, R; Klinkspoor, J H; Osborne, W R; Lee, S P

    2000-02-01

    A mechanistic model of mucous granule exocytosis by columnar epithelial cells must take into account the unique physical-chemical properties of mucin glycoproteins and the resultant mucus gel. In particular, any model must explain the intracellular packaging and the kinetics of release of these large, heavily charged species. We studied mucous granule exocytosis in gallbladder epithelium, a model system for mucus secretion by columnar epithelial cells. Mucous granules released mucus by merocrine exocytosis in mouse gallbladder epithelium when examined by transmission electron microscopy. Spherules of secreted mucus larger than intracellular granules were noted on scanning electron microscopy. Electron probe microanalysis demonstrated increased calcium concentrations within mucous granules. Immunofluorescence microscopic studies revealed intracellular colocalization of mucins and the cystic fibrosis transmembrane conductance regulator (CFTR). Confocal laser immunofluorescence microscopy confirmed colocalization. These observations suggest that calcium in mucous secretory granules provides cationic shielding to keep mucus tightly packed. The data also suggests CFTR chloride channels are present in granule membranes. These observations support a model in which influx of chloride ions into the granule disrupts cationic shielding, leading to rapid swelling, exocytosis and hydration of mucus. Such a model explains the physical-chemical mechanisms involved in mucous granule exocytosis.

  15. Re-epithelialization: advancing epithelium frontier during wound healing.

    PubMed

    Ben Amar, M; Wu, M

    2014-04-06

    The first function of the skin is to serve as a protective barrier against the environment. Its loss of integrity as a result of injury or illness may lead to a major disability and the first goal of healing is wound closure involving many biological processes for repair and tissue regeneration. In vivo wound healing has four phases, one of them being the migration of the healthy epithelium surrounding the wound in the direction of the injury in order to cover it. Here, we present a theoretical model of the re-epithelialization phase driven by chemotaxis for a circular wound. This model takes into account the diffusion of chemoattractants both in the wound and the neighbouring tissue, the uptake of these molecules by the surface receptors of epithelial cells, the migration of the neighbour epithelium, the tension and proliferation at the wound border. Using a simple Darcy's law for cell migration transforms our biological model into a free-boundary problem, which is analysed in the simplified circular geometry leading to explicit solutions for the closure and making stability analysis possible. It turns out that for realistic wound sizes of the order of centimetres and from experimental data, the re-epithelialization is always an unstable process and the perfect circle cannot be observed, a result confirmed by fully nonlinear simulations and in agreement with experimental observations.

  16. Nanotopography follows force in TGF-β1 stimulated epithelium

    NASA Astrophysics Data System (ADS)

    Thoelking, Gerold; Reiss, Bjoern; Wegener, Joachim; Oberleithner, Hans; Pavenstaedt, Hermann; Riethmuller, Christoph

    2010-07-01

    Inflammation and cellular fibrosis often imply an involvement of the cytokine TGF-β1. TGF-β1 induces epithelial-to-mesenchymal transdifferentiation (EMT), a term describing the loss of epithelium-specific function. Indicative for this process are an elongated cell shape parallel to stress fibre formation. Many signalling pathways of TGF-β1 have been discovered, but mechanical aspects have not yet been investigated. In this study, atomic force microscopy (AFM) was used to analyse surface topography and mechanical properties of EMT in proximal kidney tubule epithelium (NRK52E). Elongated cells, an increase of stress fibre formation and a loss of microvillus compatible structures were observed as characteristic signs of EMT. Furthermore, AFM could identify an increase in stiffness by 71% after six days of stimulation with TGF-β1. As a novel topographical phenomenon, nodular protrusions emerged at the cell-cell junctions. They occurred preferentially at sites where stress fibres cross the border. Since these nodular protrusions were sensitive to inhibitors of force generation, they can indicate intracellular tension. The results demonstrate a manifest impact of elevated tension on the cellular topography.

  17. Accumulation of Topical Naproxen by Cultured Oral Epithelium

    PubMed Central

    Fitzgerald, R.R.; Walters, J.D.

    2008-01-01

    Topically administered non-steroidal anti-inflammatory drugs (NSAIDs) inhibit periodontal bone loss, but little is known about the mechanism by which they penetrate oral epithelium. Active transporters could potentially play a role in this process. In this study, we used a cell line derived from oral epithelium to investigate a role for transporters and to characterize conditions that enhance epithelial penetration. Using fluorescence to monitor uptake, we demonstrated that SCC-25 cell monolayers transport naproxen with a Michaelis constant (Km) and maximum velocity (Vmax) of 164 μg/mL and 0.94 ng/min/μg protein, respectively. At steady state, the intracellular/extracellular concentration ratio was 3.4. Naproxen accumulation was more efficient at acidic pH than under neutral or alkaline conditions. Small proportions of glycerol, Pluronic F-127, and glucosylceramide enhanced naproxen entry. The individual and combined effects of glycerol and Pluronic F-127 were of lesser magnitude than those obtained with glucosylceramide or at pH 6.3. Thus, SCC-25 cells possess transporters for naproxen. PMID:17652209

  18. Ex vivo culture of the intestinal epithelium: strategies and applications.

    PubMed

    Leushacke, Marc; Barker, Nick

    2014-08-01

    Limited pools of resident adult stem cells are critical effectors of epithelial renewal in the intestine throughout life. Recently, significant progress has been made regarding the isolation and in vitro propagation of fetal and adult intestinal stem cells in mammals. It is now possible to generate ever-expanding, three-dimensional epithelial structures in culture that closely parallel the in vivo epithelium of the intestine. Growing such organotypic epithelium ex vivo facilitates a detailed description of endogenous niche factors or stem-cell characteristics, as they can be monitored in real time. Accordingly, this technology has already greatly contributed to our understanding of intestinal adult stem-cell renewal and differentiation. Transplanted organoids have also been proven to readily integrate into, and effect the long-term repair of, mouse colonic epithelia in vivo, establishing the organoid culture as a promising tool for adult stem cell/gene therapy. In another exciting development, novel genome-editing techniques have been successfully employed to functionally repair disease loci in cultured intestinal stem cells from human patients with a hereditary defect. It is anticipated that this technology will be instrumental in exploiting the regenerative medicine potential of human intestinal stem cells for treating human disorders in the intestinal tract and for creating near-physiological ex vivo models of human gastrointestinal disease.

  19. Hematological and serum biochemical parameters of blood in adolescent rats and histomorphological changes in the jejunal epithelium and liver after chronic exposure to cadmium and lead in the case of supplementation with green tea vs black, red or white tea.

    PubMed

    Tomaszewska, Ewa; Winiarska-Mieczan, Anna; Dobrowolski, Piotr

    2015-01-01

    Rats were used to check whether regular consumption of black, red, or white tea would have a protective effect similar to the action of green tea on the intestine and liver in the case of exposure to Cd and Pb within the limits of human environmental exposure to these elements. Rats at the age of 6 weeks were divided into the control and four groups supplemented with green (GT), black (BT), red (RT), or white (WT) tea extracts. Their diet (except the control) was mixed with 7 mg Cd/kg and 50mg Pb/kg. The experiment lasted 12 weeks. The effects of administration of tea in Cd- and Pb-poisoned rats on plasma biochemical parameters and the jejunal epithelium and liver were determined. The highest body mass was found in the GT group. The highest hemoglobin and Fe concentrations were in the control and GT groups. The highest activity of AST was in groups poisoned with Cd and Pb independently on supplementation. The highest ALT activity was in BT and RT groups with lower content of polifenoles. Pb and Cd disturbed the liver leading to necrosis and fatty degenerative changes, and a loss of normal architecture of the hepatocytes. Rats from the GT group had the highest cell proliferation rate in intestinal glands and the largest absorptive surface. Black, red, and white tea exerted a varied impact on the histological structure and innervation of the small intestine wall as well as on the absorptive function of small intestine mucosa in rats poisoned with Pb and Cd than green tea. On the other hand, taking into account the number of apoptotic cells, the effect of the teas was the same. Moreover, it is clear that long term exposure to Cd and Pb contamination causes toxic effect in the liver.

  20. Histologic evaluation of probe penetration during clinical assessment of periodontal attachment levels. An investigation of experimentally induced periodontal lesions in beagle dogs.

    PubMed

    Jansen, J; Pilot, T; Corba, N

    1981-04-01

    The purpose of this study was to evaluate histologically the extent and characteristics of the penetration of a periodontal probe during clinical assessment of loss of periodontal attachment in three different situations: (1) experimental mild gingivitis, (2) experimental severe periodontal inflammation and (3) experimental moderate periodontal inflammation. Mild gingivitis was obtained by merely allowing plaque to accumulate on the teeth. Severe periodontal inflammation was created using copper bands for a period of 3 weeks followed by placement of cotton ligatures for another 11 weeks. Moderate periodontal inflammation group was obtained by allowing the experimental defects to recover for a period of 3 to 31 weeks. At different times gutta percha imitations of a thin periodontal probe were inserted into the pockets using a gentle but unknown force. Histologic observation in 30 specimens showed that epithelium was always present around the probe tip, in most instances forming a continuous layer of epithelial cells. Histometrical analysis showed that in mild gingivitis the probe tip failed to reach the apical termination of the junctional epithelium (mean = -0.84 mm). In severe periodontal inflammation the tip of the probe went past this point (mean = +0.50 mm), while in moderate periodontal inflammation the probe tip came closest to the apical termination of the junctional epithelium (mean = -0.05 mm). It is concluded that the epithelial lining of a pocket stays intact, even in severe periodontal inflammation where the probe tip is situated apical to the apical termination of the junctional epithelium, indicating that during clinical probing the periodontal tissues are compressed and displaced but not perforated. It is also concluded that in beagle dogs the extent of probe penetration in experimentally inflamed periodontal tissues is dependent upon the degree of inflammation.

  1. Ultrastructural Analysis of in vivo Expanded Corneal Epithelium on Amniotic Membrane

    PubMed Central

    Ha, Hyo Shin; Song, Kye Yong

    2006-01-01

    The purpose of this study is to characterize and compare the ultrastructural changes occurring during the in vivo cultivation of corneal epithelium on amniotic membrane (AM) at several different time points. Corneal burn patients (n=7) with a corneal epithelial defect and severe limbal damage were selected. Initially, AM transplantation with limbal autograft was performed at the acute stage of corneal burn to reconstruct the damaged ocular surface. One to six (mean interval; 3.3±1.2) months later, the central part of AM containing an in vivo expanded corneal epithelium was excised and retransplanted in adjacent lesions. The excised epithelium with AM was examined by electron microscopy and immunohistochemical study. By electron microscopy, one and two months after expansion, cultivated epithelium on AM showed an undifferentiated epithelium and an incomplete basement membrane (BM). But, after three months, the cultivated epithelium began to differentiate into a multilayered epithelium with a continuous BM with increased hemidesmosomes. These findings were further confirmed by immunohistochemical study, that cytokeratin K3 was expressed in the cultivated corneal epithelium and newly formed BM was partially positive of collagen IV at three months. At least 3 months may be needed for the proliferation and differentiation of in vivo cultivated corneal epithelium on AM. PMID:16778403

  2. Diacylglycerol O-Acyltransferase Type-1 Synthesizes Retinyl Esters in the Retina and Retinal Pigment Epithelium

    PubMed Central

    Kaylor, Joanna J.; Radu, Roxana A.; Bischoff, Nicholas; Makshanoff, Jacob; Hu, Jane; Lloyd, Marcia; Eddington, Shannan; Bianconi, Tran; Bok, Dean; Travis, Gabriel H.

    2015-01-01

    Retinyl esters represent an insoluble storage form of vitamin A and are substrates for the retinoid isomerase (Rpe65) in cells of the retinal pigment epithelium (RPE). The major retinyl-ester synthase in RPE cells is lecithin:retinol acyl-transferase (LRAT). A second palmitoyl coenzyme A-dependent retinyl-ester synthase activity has been observed in RPE homogenates but the protein responsible has not been identified. Here we show that diacylglycerol O-acyltransferase-1 (DGAT1) is expressed in multiple cells of the retina including RPE and Müller glial cells. DGAT1 catalyzes the synthesis of retinyl esters from multiple retinol isomers with similar catalytic efficiencies. Loss of DGAT1 in dgat1 -/- mice has no effect on retinal anatomy or the ultrastructure of photoreceptor outer-segments (OS) and RPE cells. Levels of visual chromophore in dgat1 -/- mice were also normal. However, the normal build-up of all-trans-retinyl esters (all-trans-RE’s) in the RPE during the first hour after a deep photobleach of visual pigments in the retina was not seen in dgat1 -/- mice. Further, total retinyl-ester synthase activity was reduced in both dgat1 -/- retina and RPE. PMID:25974161

  3. Imaging human retinal pigment epithelium cells using adaptive optics optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Liu, Zhuolin; Kocaoglu, Omer P.; Turner, Timothy L.; Miller, Donald T.

    2016-03-01

    Retinal pigment epithelium (RPE) cells are vital to health of the outer retina, but are often compromised in ageing and major ocular diseases that lead to blindness. Early manifestation of RPE disruption occurs at the cellular level, and while biomarkers at this scale hold considerable promise, RPE cells have proven extremely challenging to image in the living human eye. We present a novel method based on optical coherence tomography (OCT) equipped with adaptive optics (AO) that overcomes the associated technical obstacles. The method takes advantage of the 3D resolution of AO-OCT, but more critically sub-cellular segmentation and registration that permit organelle motility to be used as a novel contrast mechanism. With this method, we successfully visualized RPE cells and characterized their 3D reflectance profile in every subject and retinal location (3° and 7° temporal to the fovea) imaged to date. We have quantified RPE packing geometry in terms of cell density, cone-to-RPE ratio, and number of nearest neighbors using Voronoi and power spectra analyses. RPE cell density (cells/mm2) showed no significant difference between 3° (4,892+/-691) and 7° (4,780+/-354). In contrast, cone-to- RPE ratio was significantly higher at 3° (3.88+/-0.52:1) than 7° (2.31+/- 0.23:1). Voronoi analysis also showed most RPE cells have six nearest neighbors, which was significantly larger than the next two most prevalent associations: five and seven. Averaged across the five subjects, prevalence of cells with six neighbors was 51.4+/-3.58% at 3°, and 54.58+/-3.01% at 7°. These results are consistent with histology and in vivo studies using other imaging modalities.

  4. Understanding the molecular basis of histologic grade.

    PubMed

    Ignatiadis, M; Sotiriou, C

    2008-01-01

    Histologic grading in breast cancer is based on the evaluation of 3 morphologic features (tubule formation, nuclear pleomorphism and mitotic count), is essentially describing proliferation and differentiation in breast cancer, and is considered an important prognostic factor for this disease. It has been suggested that histologic grade 1 and 3 breast tumors are 2 different diseases that may have distinct molecular origins, pathogenesis and natural history. Different single markers like Ki-67, thymidine labeling index and S phase fraction/flow cytometry have been studied as markers of proliferation, but none of them, with the possible exception of Ki-67, is currently employed routinely in clinical practice. The advent of the powerful microarray technology has enabled scientists to comprehensively study proliferation in breast cancer on a genome-wide scale. A gene expression grade index (GGI) was developed that challenges the existence and clinical relevance of an intermediate grade 2 classification. The GGI could reclassify patients with histologic grade 2 tumors into 2 groups with high versus low risks of recurrence. GGI has also been used to define 2 clinically relevant subgroups in estrogen receptor-positive breast carcinomas. Finally, in the largest meta-analysis of publicly available gene expression and clinical data, 4 stable molecular subgroups of breast cancer have been identified, namely ER-/HER-, HER2+ and ER+/HER2-, which was divided into 2 subgroups (ER+/low proliferation and ER+/high proliferation). In this same meta-analysis, proliferation was shown to be the common driving force responsible for the performance of various breast cancer prognostic signatures.

  5. Histological characteristics of diffuse idiopathic skeletal hyperostosis.

    PubMed

    Kuperus, Jonneke S; Westerveld, L Anneloes; Rutges, Joost P H J; Alblas, Jacqueline; van Rijen, Mattie H P; Bleys, Ronald L A W; Öner, F Cumhur; Verlaan, Jorrit-Jan

    2017-01-01

    Diffuse idiopathic skeletal hyperostosis (DISH) is a predominantly radiographic diagnosis and histological knowledge of DISH is limited. The aim of this study was to describe the histological characteristics of DISH in the spinal column and to study the relation between DISH and intervertebral disc (IVD) degeneration. Therefore, 10 human cadaveric spines with fluoroscopic evidence of DISH were compared with 10 controls. Plain radiographs and computed tomography (CT) scans were obtained and tissue blocks were resected from three predefined levels of all specimens. The microscopic sections were scored by two blinded observers using a newly developed scoring system specific for characteristics of DISH and a validated scoring system for IVD degeneration. Maximum IVD height was measured on the CT scans. Analyses were performed using Fisher's exact test and Student's t-test. When compared to controls, the right sided sections from DISH specimens showed partial or complete bone bridges, consisting of cortical woven bone, accompanied by morphological changes in the adjoining part of the IVD. Using the histological scoring system for DISH, all parameters were significantly different between the DISH and control group (p < 0.01). The contralateral location did not show differences between the groups. The overall degree of IVD degeneration and height of IVD was comparable for the two groups. The histopathological changes observed in spines with DISH corresponded to the fluoroscopic images and CT scans. The degree of IVD degeneration and IVD height was comparable for both groups, suggesting a limited role for IVD degeneration in the pathogenesis of DISH. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:140-146, 2017.

  6. Integration of Histology Lectures and Practical Teaching in China

    ERIC Educational Resources Information Center

    Lu, Xiaoye; Cheng, Xin; Li, Ke; Lee, Kenneth Ka Ho; Yang, Xuesong

    2016-01-01

    Objectives: Human histology is a discipline concerning the study of microscopic structures of human tissues and organs--with the aid of light or electron microscopes. Traditional teaching of histology is composed of two separated components, theory and practice. The main disadvantage with traditional histology teaching is the detachment of theory…

  7. Mouse redox histology using genetically encoded probes.

    PubMed

    Fujikawa, Yuuta; Roma, Leticia P; Sobotta, Mirko C; Rose, Adam J; Diaz, Mauricio Berriel; Locatelli, Giuseppe; Breckwoldt, Michael O; Misgeld, Thomas; Kerschensteiner, Martin; Herzig, Stephan; Müller-Decker, Karin; Dick, Tobias P

    2016-03-15

    Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation.

  8. [Histological and molecular classification of gliomas].

    PubMed

    Figarella-Branger, D; Colin, C; Coulibaly, B; Quilichini, B; Maues De Paula, A; Fernandez, C; Bouvier, C

    2008-01-01

    Gliomas are the most frequent tumors of the central nervous system. The WHO classification, based on the presumed cell origin, distinguishes astrocytic, oligodendrocytic and mixed gliomas. A grading system is based on the presence of the following criteria: increased cellular density, nuclear atypias, mitosis, vascular proliferation and necrosis. The main histological subtype of grade I gliomas are pilocytic astrocytomas, which are benign. Diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas are low-grade (II) or high-grade (III and IV) tumors. Glioblastomas correspond to grade IV astrocytomas. C. Daumas-Duport et al. have proposed another classification based on histology and imaging data, which distinguishes oligodendrogliomas and mixed gliomas of grade A (without endothelial proliferation and/or contrast enhancement), oligodendrogliomas and mixed gliomas of grade B (with endothelial proliferation or contrast enhancement), glioblastomas and glioneuronal malignant tumors. Both classifications lack reproducibility. Many studies have searched for a molecular classification. Recurrent abnormalities in gliomas have been found. They encompassed recurrent chromosomal alterations, such as lost of chromosome 10, gain of chromosome 7, deletion of chromosome 1p and 19q, but also activation of the Akt pathway (amplification of EGFR), dysregulation of the cell cycle (deletion of p16, p53). These studies have enabled the description of two molecular subtypes for glioblastomas. De novo glioblastomas, which occur in young patients without of a prior history of brain tumor and harbor frequent amplification of EGFR, deletion of p16 and mutation of PTEN while mutation of p53 is infrequent. Secondary glioblastomas occur in the context of a preexisting low-grade glioma and are characterized by more frequent mutation of p53. On the other side, combined complete deletion of 1p and 19q as the result of the translocation t(1;19)(q10;p10) is highly specific of oligodendrogliomas

  9. Human bronchial epithelial cells exposed in vitro to cigarette smoke at the air-liquid interface resemble bronchial epithelium from human smokers.

    PubMed

    Mathis, Carole; Poussin, Carine; Weisensee, Dirk; Gebel, Stephan; Hengstermann, Arnd; Sewer, Alain; Belcastro, Vincenzo; Xiang, Yang; Ansari, Sam; Wagner, Sandra; Hoeng, Julia; Peitsch, Manuel C

    2013-04-01

    Organotypic culture of human primary bronchial epithelial cells is a useful in vitro system to study normal biological processes and lung disease mechanisms, to develop new therapies, and to assess the biological perturbations induced by environmental pollutants. Herein, we investigate whether the perturbations induced by cigarette smoke (CS) and observed in the epithelium of smokers' airways are reproducible in this in vitro system (AIR-100 tissue), which has been shown to recapitulate most of the characteristics of the human bronchial epithelium. Human AIR-100 tissues were exposed to mainstream CS for 7, 14, 21, or 28 min at the air-liquid interface, and we investigated various biological endpoints [e.g., gene expression and microRNA profiles, matrix metalloproteinase 1 (MMP-1) release] at multiple postexposure time points (0.5, 2, 4, 24, 48 h). By performing a Gene Set Enrichment Analysis, we observed a significant enrichment of human smokers' bronchial epithelium gene signatures derived from different public transcriptomics datasets in CS-exposed AIR-100 tissue. Comparison of in vitro microRNA profiles with microRNA data from healthy smokers highlighted various highly translatable microRNAs associated with inflammation or with cell cycle processes that are known to be perturbed by CS in lung tissue. We also found a dose-dependent increase of MMP-1 release by AIR-100 tissue 48 h after CS exposure in agreement with the known effect of CS on this collagenase expression in smokers' tissues. In conclusion, a similar biological perturbation than the one observed in vivo in smokers' airway epithelium could be induced after a single CS exposure of a human organotypic bronchial epithelium-like tissue culture.

  10. Histologic classification of penile intraepithelial neoplasia.

    PubMed

    Velazquez, Elsa F; Chaux, Alcides; Cubilla, Antonio L

    2012-05-01

    Penile squamous cell carcinomas (SCCs) and their corresponding precancerous lesions can be classified in 2 major groups: human papillomavirus (HPV) related and HPV unrelated. In the former (warty and basaloid SCC), there is a predominance of undifferentiated basaloid cells. In the latter (eg, usual, papillary, and verrucous SCC), the predominant cell is larger with abundant eosinophilic cytoplasm. Based on these morphologic features, a new term, "penile intraepithelial neoplasia" (PeIN), was proposed. PeIN was further subclassified into differentiated and undifferentiated, with the latter being subdivided into basaloid, warty, and warty-basaloid subtypes. Macroscopically, PeIN subtypes are indistinguishable. Microscopically, differentiated PeIN is characterized by acanthosis, parakeratosis, enlarged keratinocytes with abundant "pink" cytoplasm (abnormal maturation), and hyperchromatic cells in the basal layer. In basaloid PeIN the epithelium is replaced by a monotonous population of uniform, small, round, and basophilic cells. Warty PeIN is characterized by a spiky surface, prominent atypical parakeratosis, and pleomorphic koilocytosis. Warty-basaloid PeIN show features of both warty and basaloid PeIN. There is a significant association of subtypes of PeIN with specific variants of invasive SCCs. This is a simple and reproducible nomenclature for penile precancerous lesions based on cell type and differentiation. It takes into account the similarities between vulvar and penile pathology and the hypothesis of a bimodal pathway of penile cancer progression.

  11. Cell- and developmental stage-specific Dicer1 ablation in the lung epithelium models cystic pleuropulmonary blastoma.

    PubMed

    Wagh, Purnima K; Gardner, Margaret A; Ma, Xiaolan; Callahan, Melissa; Shannon, John M; Wert, Susan E; Messinger, Yoav H; Dehner, Louis P; Hill, D Ashley; Wikenheiser-Brokamp, Kathryn A

    2015-05-01

    Inherited syndromes provide unique opportunities to identify key regulatory mechanisms governing human disease. We previously identified germline loss-of-function DICER1 mutations in a human syndrome defined by the childhood lung neoplasm pleuropulmonary blastoma (PPB), which arises during lung development. DICER1 regulates many biological processes critical in development and disease pathogenesis. Significant challenges in defining the role of DICER1 in human disease are identifying cause-effect relationships and generating manipulatable systems that model the complexity of organ development and disease pathogenesis. Here we report the generation of a murine model for PPB and demonstrate that precise temporal and cell type-specific Dicer1 ablation is necessary and sufficient for the development of cystic lungs that histologically and phenotypically model PPB. Dicer1 ablation in the distal airway epithelium during early stages of lung development resulted in a cystic lung phenotype indistinguishable from PPB, whereas DICER1 function was not required for development of the proximal airway epithelium or during later stages of organogenesis. Mechanistic studies demonstrate that Dicer1 loss results in epithelial cell death, followed by cystic airway dilatation accompanied by epithelial and mesenchymal proliferation. These studies define precise temporal and epithelial cell type-specific DICER1 functions in the developing lung and demonstrate that loss of these DICER1 functions is sufficient for the development of cystic PPB. These results also provide evidence that PPB arise through a novel mechanism of non-cell-autonomous tumour initiation, in which the genetic abnormality initiating the neoplasm does not occur in the cells that ultimately transform, but rather occurs in a benign-appearing epithelial cell component that predisposes underlying mesenchymal cells to malignant transformation.

  12. Morpho-histological characterisation of the alimentary canal of an important food fish, Asian seabass (Lates calcarifer)

    PubMed Central

    Purushothaman, Kathiresan; Lau, Doreen; Saju, Jolly M.; Musthaq SK, Syed; Lunny, Declan Patrick

    2016-01-01

    Asian seabass (Lates calcarifer) is a food fish of increasing aquaculture importance. In order to improve our understanding on the digestive system and feeding of this species, morphological and histological features of the gut were studied. Morphologically, the Asian seabass gut is defined by a short and muscular esophagus, well-developed stomach and comparatively short intestine. Mucous secreting goblet cells reactive to PAS (Periodic Acid Schiff) and AB (Alcian Blue) stain were present throughout the esophagus. The stomach was sac-like and could be distinguished into the cardiac, fundic and pyloric regions. Gastric glands and mucus cells were predominately present in the cardiac and fundic regions. Five finger-like pyloric caeca were present between the stomach and intestine. The intestine was a short, tubular structure with no morphological differences between the various regions. Histologically, the intestinal regions were similar, the main difference being in the number of goblet cells that increased from anterior to posterior intestine, with 114 ± 9, 153 ± 7 and 317 ± 21 goblet cells in the anterior, mid and posterior regions, respectively. The intestinal epithelium stained positively for PAS, but the staining was stronger for acidic glycoproteins. The rectum was similar to intestine, except for increased goblet cell numbers (anterior rectum: 529 ± 26; posterior rectum: 745 ± 29). Gut morpho-histology did not respond to salinity changes, however, there was a significant reduction of mucosal height, goblet cell numbers and muscularis thickness upon food deprivation. PMID:27635341

  13. Nose-to-Brain Delivery: Investigation of the Transport of Nanoparticles with Different Surface Characteristics and Sizes in Excised Porcine Olfactory Epithelium.

    PubMed

    Mistry, Alpesh; Stolnik, Snjezana; Illum, Lisbeth

    2015-08-03

    The ability to deliver therapeutically relevant amounts of drugs directly from the nasal cavity to the central nervous system to treat neurological diseases is dependent on the availability of efficient drug delivery systems. Increased delivery and/or therapeutic effect has been shown for drugs encapsulated in nanoparticles; however, the factors governing the transport of the drugs and/or the nanoparticles from the nasal cavity to the brain are not clear. The present study evaluates the potential transport of nanoparticles across the olfactory epithelium in relation to nanoparticle characteristics. Model systems, 20, 100, and 200 nm fluorescent carboxylated polystyrene (PS) nanoparticles that were nonmodified or surface modified with polysorbate 80 (P80-PS) or chitosan (C-PS), were assessed for transport across excised porcine olfactory epithelium mounted in a vertical Franz diffusion cell. Assessment of the nanoparticle content in the donor chamber of the diffusion cell, accompanied by fluorescence microscopy of dismounted tissues, revealed a loss of nanoparticle content from the donor suspension and their association with the excised tissue, depending on the surface properties and particle size. Chitosan surface modification of PS nanoparticles resulted in the highest tissue association among the tested systems, with the associated nanoparticles primarily located in the mucus, whereas the polysorbate 80-modified nanoparticles showed some penetration into the epithelial cell layer. Assessment of the bioelectrical properties, metabolic activity, and histology of the excised olfactory epithelium showed that C-PS nanoparticles applied in pH 6.0 buffer produced a damaging effect on the epithelial cell layer in a size-dependent manner, with fine 20 nm sized nanoparticles causing substantial tissue damage relative to that with the 100 and 200 nm counterparts. Although histology showed that the olfactory tissue was affected by the application of citrate buffer that was

  14. Rat mandibular distraction osteogenesis: Part I. Histologic and radiographic analysis.

    PubMed

    Rowe, N M; Mehrara, B J; Dudziak, M E; Steinbreck, D S; Mackool, R J; Gittes, G K; McCarthy, J G; Longaker, M T

    1998-11-01

    The application of distraction osteogenesis to craniofacial surgery has altered the approach and treatment of congenital and acquired craniofacial defects. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been described extensively, relatively little is known about the molecular regulation of this process. The elucidation of the molecular mechanisms of distraction osteogenesis has important clinical implications because it may facilitate the use of recombinant proteins or gene therapy to accelerate bone regeneration. Molecular analysis of distraction osteogenesis has been hindered by the use of large animal models in which only limited genetic information is available. In this study, a rat model of mandibular distraction osteogenesis is described. This report includes a pilot study (n = 50) to develop an appropriate distraction device and to determine the optimal placement of the osteotomy. The study subsequently included 80 animals, 35 of which were distracted at a rate of 0.25 mm per day for 6 days (1.5 mm total) and 35 that were distracted at a rate of 0.25 mm twice per day (3.0 mm total). These animals were killed at various time points (after latency and during the distraction and consolidation periods) and displayed histologic and radiographic findings of membranous bone distraction osteogenesis that were consistent with those in large ,animal and clinical models. In addition, five animals each were acutely lengthened 1.5 mm and 3.0 mm and demonstrated a fibrous nonunion. Furthermore, the utility of this model is demonstrated in the analysis of the molecular mechanisms of distraction osteogenesis by applying the polymerase chain reaction to total cellular RNA isolated from normal and distracted rat mandibles. In conclusion, it is believed that the rat model of distraction osteogenesis has significant advantages over traditional models, including decreased costs and facilitation of molecular analysis.

  15. Osteoprotegerin expression and sensitivity in otosclerosis with different histological activity.

    PubMed

    Karosi, Tamás; Csomor, Péter; Szalmás, Anita; Kónya, József; Petkó, Mihály; Sziklai, István

    2011-03-01

    Otosclerosis is a complex bone dystrophy of the human otic capsule leading to conductive and sensorineural hearing loss. Since otosclerosis may, at least in part, be considered as an autoimmune-inflammatory disease, disturbed balance of TNF-alpha and osteoprotegerin (OPG) expression has been implicated in the pathological bone remodeling. It has been supposed that active otosclerosis is characterized by decreased or missing local OPG production with invariable OPG sensitivity of the otosclerotic foci. Ankylotic stapes footplates (n = 41) removed by stapedectomy were processed to histological examination, OPG-specific RT-PCR, tissue culturing and alkaline-phosphatase (AP) activity assessment, respectively. OPG concentration of serum specimens (n = 41) was measured by ELISA. Cortical bone fragments harvested from the external ear canal were used as negative controls of otosclerosis. Among 41 ankylotic stapes footplates, 22 active and 19 inactive otosclerosis cases were histologically diagnosed. OPG expression was significantly lower (p < 0.001) in active otosclerosis compared to inactive cases. Osteoclast cultures originated from active otosclerotic foci showed a