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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. Normal Vulvar Histology: Variation by Site.

    PubMed

    Day, Tania; Holland, Seán M; Scurry, James

    2016-01-01

    The aim of the study was to assess the histology of normal vulvar skin with attention to anatomic location and epithelium type. We performed a retrospective histologic review of 118 vulvar biopsies and excisions obtained between 2010 and 2014 with adjacent normal skin or mucosa. Exclusions included age younger than 18 years, vestibulectomy, labiaplasty, inflammatory dermatoses, and insufficient normal tissue for assessment. Stratum corneum morphology was assessed as basket weave, compact, or intermediate. Stratum granulosum cell layer number and epithelial thickness were recorded. Dermal lymphocytic infiltrate was described as nil, sparse, moderate, or dense. Fischer exact test, Pearson χ, and Student t test were used for statistical analysis. There were 7 cases from mons pubis, 11 from perineum, 83 from labia, and 17 from vestibule. In the skin, the stratum corneum morphology was basket weave in 31%, compact in 35%, and intermediate in 34%. Stratum corneum at the mons pubis was uniformly basket weave, whereas at perineum, it was either compact or intermediate (7/7 vs 0/11; p < .001); the labia demonstrated all 3 morphologies. Parakeratosis (PK) was identified at the specimen edge in 4 cases of hairless skin and 7 cases of squamous mucosa. Mean epithelial thickness and dermal lymphocytic infiltration were similar in specimens with and without PK. Compact stratum corneum of vulvar skin and a zone of PK at the mucocutaneous junction may be normal histological findings. Pathologists need to be aware of site-related differences of the vulvar epithelium to avoid overdiagnosis of pathological conditions.

  3. 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, ...

  4. 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.

  5. 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

  6. 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

  7. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Histology and ultrastructure of the gut epithelium of the neotenic cave salamander, Proteus anguinus (Amphibia, Caudata).

    PubMed

    Bizjak Mali, Lilijana; Bulog, Boris

    2004-01-01

    Histological, histochemical, and ultrastructural features of the gut of the European endemic cave salamander Proteus anguinus were studied. The gut is a relatively undifferentiated muscular tube lined with a simple columnar epithelium containing numerous goblet cells. The mucosa and underlying lamina propria/submucosa are elevated into a number of high longitudinal folds projecting into the lumen. The enterocytes are covered apically with uniform microvilli. Irregularity in the arrangement of microvilli was observed. Occasionally, irregular protrusions of the cytoplasm appear between groups of microvilli. Pinocytotic activity occurs at the bases of the intermicrovillous space. Mitochondria are numerous in the apical cytoplasm and basally beneath the nuclei. The supranuclear cytoplasm contains most of the cell organelles. The lateral plasma membranes of adjacent cells interdigitate and are joined by junctional complexes. The periodic acid-Schiff (PAS) reaction, indicating neutral mucosubstances, is positive only in the apical brush border of enterocytes and in goblet cells. The goblet cells also stained with Alcian blue (AB), at pH 2.5, thus revealing the presence of carboxylated glycosaminoglycans. Compact aggregations of AB- and PAS-negative cells are situated directly below the epithelium. Mitotic figures are present in individual clusters of cells. The fine structure of cells in these clusters indicated that these cells could be responsible for renewal of intestinal epithelium. Numerous endocrine-like cells could also be seen. The closely packed smooth muscle cells and amorphous extracellular material with collagen fibrils constitute a net-like structure under the basal lamina that is very closely associated with the epithelium. There are numerous acidophilic granular cells between epithelial cells, in the lamina propria/submucosa, and between cells aggregations. They seem to be associated with nematode infections and possibly constitute a humoral defense

  14. 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.

  15. Histological and scanning electron microscopical study of the olfactory epithelium of the Indian major carp, Catla catla (Hamilton).

    PubMed

    Chakrabarti, P; Ghosh, S K

    2010-02-01

    The histological and micro-architecture of different cells lining the olfactory epithelium in Catla catla (Hamilton) have been studied by means of light and scanning electron microscopes. The oval olfactory rosette of the fish consists of a rosette of 30 to 32 primary lamellae. Each lamella is provided with restricted area of sensory epithelium in the middle region while the apical and basal part of the lamella consists of non-sensory epithelium. The non-sensory epithelium is made up of patches of ciliated supporting cells, epidermal or stratified epithelial cells with concentrically arranged microridges and scattered mucous cells. The sensory epithelium contains two types of receptor cell (microvillar and flagellated) and mucous cells. The multilayer olfactory organ in C. catla provides an acute sense of smell, and various aspects of their existence are mediated through olfactory cues.

  16. Histological features of respiratory epithelium of calves held at differing temperature and humidity.

    PubMed Central

    Jericho, K W; Magwood, S E

    1977-01-01

    The effect of ambient temperature and humidity on the structure of respiratory epithelium of calves was studied. Four calves of each of three experiments were acclimatized to a nonoperational environmental chamber for six days and then exposed to constant extremes of temperatures and relative humidity of one of 30 degrees C --35%, or 27 degrees C--92%, or 5 degrees C--92% respectively in this chamber for eight days each. Five calves (3 and 2) were similarly acclimatized then exposed to 1 degrees C--40%. Nasal swabs were taken from all animals at regular intervals. Swabs of three animals yielded Mycoplasma spp. and one swab yielded the virus of infectious bovine rhinotracheitis. Detailed histological studies of respiratory epithelium of nose, trachea, major bronchus and terminal bronchioli were conducted at four sites. Goblet cells were least in calves held in hot and dry air; calves held in dry air had the least polymorphonuclear cells and the greatest prevalence of hypochromatic cell layers and vacuolation of epithelial cells. Differences between experiments were evident most for sites of trachea and major bronchus. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 1. Fig. 2. Fig. 3. PMID:922554

  17. 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...

  18. 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...

  19. 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...

  20. 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.

  1. 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.

  2. 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.

  3. Color normalization of histology slides using graph regularized sparse NMF

    NASA Astrophysics Data System (ADS)

    Sha, Lingdao; Schonfeld, Dan; Sethi, Amit

    2017-03-01

    Computer based automatic medical image processing and quantification are becoming popular in digital pathology. However, preparation of histology slides can vary widely due to differences in staining equipment, procedures and reagents, which can reduce the accuracy of algorithms that analyze their color and texture information. To re- duce the unwanted color variations, various supervised and unsupervised color normalization methods have been proposed. Compared with supervised color normalization methods, unsupervised color normalization methods have advantages of time and cost efficient and universal applicability. Most of the unsupervised color normaliza- tion methods for histology are based on stain separation. Based on the fact that stain concentration cannot be negative and different parts of the tissue absorb different stains, nonnegative matrix factorization (NMF), and particular its sparse version (SNMF), are good candidates for stain separation. However, most of the existing unsupervised color normalization method like PCA, ICA, NMF and SNMF fail to consider important information about sparse manifolds that its pixels occupy, which could potentially result in loss of texture information during color normalization. Manifold learning methods like Graph Laplacian have proven to be very effective in interpreting high-dimensional data. In this paper, we propose a novel unsupervised stain separation method called graph regularized sparse nonnegative matrix factorization (GSNMF). By considering the sparse prior of stain concentration together with manifold information from high-dimensional image data, our method shows better performance in stain color deconvolution than existing unsupervised color deconvolution methods, especially in keeping connected texture information. To utilized the texture information, we construct a nearest neighbor graph between pixels within a spatial area of an image based on their distances using heat kernal in lαβ space. The

  4. 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

  5. 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.

  6. Aspiration cytology of radiation-induced changes of normal breast epithelium

    SciTech Connect

    Bondeson, L.

    1987-05-01

    From a case illustrated, it appears that irradiation may induce changes in normal breast epithelium indistinguishable from malignancy by means of aspiration cytology. This fact must be considered in the choice of diagnostic methods for the evaluation of lesions in irradiated breast tissue.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  8. 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.

  9. Comparison of cytologic and histologic evaluations of the conjunctiva in the normal equine eye.

    PubMed

    Bourges-Abella, Nathalie; Raymond-Letron, Isabelle; Diquelou, Armelle; Guillot, Emilie; Regnier, Alain; Trumel, Catherine

    2007-01-01

    To describe the cells observed in conjunctival brush cytology (CBC) from normal horses and compare these findings with conjunctival structural histology so as to understand which cells are recovered from CBC. This study was divided into three parts. (1) Conjunctival brush smears were collected from 20 healthy horses on both eyes and a differential count on 300 cells was carried out on May Grünwald-Giemsa (MGG) smears. (2) A similar protocol was used for whole eyes from five horses obtained rapidly after death from a slaughterhouse. The eyes were then assessed for conjunctival histology. (3) Cytobrush smears were collected from five healthy horses. Smears were examined after MGG or periodic acid Schiff (PAS) staining. The differential cell count showed a majority of deep and intermediate epithelial cells with very few superficial and goblet cells in both eyes. A stratified columnar to cuboidal epithelium was observed on nearly the whole surface of the conjunctiva. A stratified squamous type was observed at the palpebral and bulbar edges. Areas with highest mucus cell indices were found from the nasal to the temporal edge of the equine inferior conjunctiva in the upper palpebral segment near the fornix and in a part of the nasal fornix. In MGG smears no mucus cells were identified; however, they were numerous in PAS smears (22.6% +/- 11) and were mostly cylindrical cells (42.5% +/- 14.4 PAS positive). Cytobrush smears in the healthy horse are characterized by a majority of polyhedral and cylindrical cells and a few squamous cells. The cylindrical cells may be mucous cells and probably originate from the main stratified columnar to cuboidal epithelium.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Bax and Bcl-2 are focally overexpressed in the normal epithelium of cancerous prostates.

    PubMed

    Tolonen, Teemu T; Tommola, Satu; Jokinen, Samuli; Parviainen, Tiina; Martikainen, Paula M

    2007-01-01

    Development of prostate cancer is connected with a disturbance of apoptosis. Prostate cancer is multifocal, suggesting that the control of apoptosis is impaired at multiple foci. We wanted to know whether apoptosis is generally disturbed in cancerous prostates and if changes in apoptotic control could be detected even in the absence of any morphologically visible changes. Therefore, we compared expression of two common apoptotic markers, Bax and Bcl-2, in normal epithelium of cancerous prostates and controls. We also evaluated the expression of these proteins in hyperplasia, prostatic intraepithelial neoplasia (PIN), carcinomas of different Gleason grades and capsular perineural invasion. The tissue material was obtained from radical prostatectomies, transurethral resection chips and autopsies. Individual tissue arrays were done for each patient. The intensity of Bax and Bcl-2 immunostaining was estimated semiquantitatively. The data were analyzed using a linear mixed-models analysis as well as dichotomized staining indices. Normal epithelium of cancerous prostates contained foci with high expression of Bax and Bcl-2. The expression of Bax in Gleason grades 3-5 carcinoma was significantly higher than that in Gleason grade 2, and was highest in foci with perineural invasion. The expression of Bcl-2 was strongest in PIN foci. Expression of Bax and Bcl-2 in normal epithelium of cancerous prostates suggests that increases in these indirect markers may reflect altered apoptotic control in these foci. Further studies are needed to show whether these changes represent the earliest step of the multifocal carcinogenetic process. Control of apoptosis seems to be involved and modulated during local progression of prostate cancer.

  16. Histologic effect of semiconductor diode laser transscleral cyclophotocoagulation on the normal equine eye.

    PubMed

    Morreale, Raymond J; Wilkie, David A; Gemensky-Metzler, Anne J; Weisbrode, Steven E; Willis, Michelle A

    2007-01-01

    To determine the acute histologic effects of semiconductor diode laser transscleral cyclophotocoagulation (TSCP) on the normal equine eye. Part 1: eight eyes of four horses. Part 2: 10 eyes of five horses. Part 1: TSCP was performed on four eyes at 4 mm and four eyes at 6 mm posterior to the limbus with 15 sites treated in four quadrants at 1800 mW for 1500 ms. The globes were sectioned transversely or sagitally to examine all quadrants and histologic sections were taken every 1 mm for the entire globe. Part 2: Based on the results from Part 1, TSCP was performed at 20 sites 4 mm posterior to the dorsotemporal limbus with a constant energy varying from 0.75 to 4 J/site. Histologic sections were taken every 1 mm for a total of 10 sections per eye and 20 sections per energy level group. Part 1: At 4 mm posterior to the limbus, coagulation of the nonpigmented epithelium (NPE) of the pars plicata was observed in the temporal (14%) and dorsal quadrants (12%). Retinal detachment was observed in the nasal quadrant (12%). Hemorrhage was common in the nasal (19%) and temporal (12%) quadrants. At 6 mm posterior to the limbus, coagulation of the NPE of the pars plicata was observed in the dorsal (14%), ventral (16%), nasal (2%), and temporal (2%) quadrants. Retinal detachment was observed in the dorsal (8%), ventral (18%), nasal (20%) and temporal (2%) quadrants. Part 2: Settings of 0.75 J/site were ineffective; 1.5, 2.25 and 3 J/site damaged the pars plicata without disruption of anatomy; and 4 J/site caused disruption of normal architecture. The most appropriate site for equine TSCP appears to be 4 mm posterior to the dorso- and ventrotemporal limbus avoiding the 3 and 9 o'clock positions and using an initial energy setting of 2.25 J/site. This results in effective damage to the pars plicata while minimizing surgical complications such as retinal detachment and hemorrhage.

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

    PubMed

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

    2015-05-01

    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. 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. 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. 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 studies.

  18. 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

  19. 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

  20. 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.

  1. Horizontal Basal Cells Are Multipotent Progenitors in Normal and Injured Adult Olfactory Epithelium

    PubMed Central

    Iwai, Naomi; Zhou, Zhijian; Roop, Dennis R.; Behringer, Richard R.

    2014-01-01

    The mammalian olfactory neuroepithelium provides a unique system for understanding the regulation of neurogenesis by adult neural stem cells. Recently, mouse horizontal basal cells (HBCs) were identified as stem cells that regenerate olfactory receptor neurons (ORNs) and non-neuronal cell types only after extensive injury of the olfactory epithelium (OE). Here we report a broader spectrum of action for these cells. We show that even during normal neuronal turnover, HBCs actively generate neuronal and non-neuronal cells throughout adulthood. This occurs in a temporally controlled manner: an initial wave of HBC-derived neurogenesis was observed soon after birth, and a second wave of neurogenesis was observed at 4 months of age. Moreover, upon selective depletion of mature ORNs by olfactory bulbectomy, HBCs give rise to more neurons. Our findings demonstrate a crucial role for HBCs as multipotent progenitors in the adult OE, acting during normal neuronal turnover as well as in acute regeneration upon injury. PMID:18308944

  2. 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.

  3. Human penile erection and organic impotence: normal histology and histopathology.

    PubMed

    Conti, G; Virag, R

    1989-01-01

    A very large amount of human material (7 embryos, 12 stillborns, 12 penes of males aged between 2 and 86 years, as well as bioptical material from 80 subjects affected by impotence problems) has been examined so as to study the penis arterial and venous walls, the blood flow regulation mechanisms and the intracavernal trabecular morphology. The amount of muscle tissue and of collagenous connective tissue has been numerically quantified by computer-assisted methods. This study enables the authors to underline three fundamental facts: (a) it confirms the normal penile erection mechanism, and the consequent theory, (b) it confirms that vascular sclerosis is a systemic phenomenon correlated to age, and that the penis is not exempt, and (c) in the case of impotence problems, the same sclerosis phenomenon may appear at an earlier age, and therefore induce pathological impotence.

  4. Expression of the apoptotic markers in normal breast epithelium, benign mammary dysplasia and in breast cancer.

    PubMed

    Koda, Mariusz; Kanczuga-Koda, Luiza; Reszec, Joanna; Sulkowska, Mariola; Famulski, Waldemar; Baltaziak, Marek; Kisielewski, Wojciech; Sulkowski, Stanislaw

    2004-08-01

    Apoptosis and proliferation are processes associated with the development and progression of breast cancer. The sensitivity of tumour cells to the induction of apoptosis depends on the balance between pro- and anti-apoptotic proteins. The expression of Bak and Bcl-2 was examined using an immunohistochemical method in 71 primary breast cancers. Furthermore, Bcl-2 and Bak were assessed in the normal mammary gland as well as in benign mammary dysplasia adjacent to breast cancer. Positive immunostaining for Bcl-2 was observed in 77.8% of cases of normal breast epithelium (NBE), 93% of benign dysplasia without intraductal proliferation (BBD) as well as in 94% of intraductal proliferative lesions of the breast (BIPL). Expression of Bak was detected in 39% of cases of NBE, 45% of BBD and in 67% of BIPL. In breast cancer Bcl-2 and Bak expression was found in 83% and 70% of the cases studied, respectively. Increased Bcl-2 expression in primary tumours significantly correlated with favourable prognostic factors, namely pT1, G2 and lack of metastases to the regional lymph nodes (p < 0.01, p < 0.03, p < 0.02, respectively). There were no relationships between Bak and the clinicopathological features studied, but our results indicate changes in the expression of Bak during breast cancer development and progression. It would appear to be important to assess and compare pro- and anti-apoptotic proteins between normal mammary gland, benign mammary dysplasia and the primary tumours of breast cancer. This knowledge should be helpful in understanding breast cancer development and progression.

  5. 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

  6. 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

  7. 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

  8. 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

  9. DNA synthesis, cell proliferation index in normal and abnormal gallbladder epithelium.

    PubMed

    Lamote, J; Willems, G

    1997-09-15

    The observation of mitotic figures in the epithelium of the normal gallbladder is exceptional because cell renewal is occurring at a very slow rate. It is only after using 3H-thymidine and autoradiography to observe the cells in DNA synthesis that evidence of a significant epithelial cell replication has been provided. Because numerous mitotic figures and increased 3H-thymidine uptake have been observed after intraluminal introduction of foreign bodies or after ligation of the common bile duct in animals, mechanical distension has been supposed to represent an important trigger factor of cell proliferation in this hollow organ. An increased epithelial cell renewal was also observed in human gallbladders of patients with a complete obstruction of the common bile duct causing the distension. However, the absence of correlation between the degree of gallbladder distension and the proliferative response was suggesting that factors other than distension could be involved. In studies on experimental lithiasis cell proliferation appeared to be enhanced in the gallbladder epithelium of mice fed on a cholesterol-cholic acid-rich lithogenic diet. The fact that the increase in proliferative activity was preceding the formation of gallstones was another indication that factors other than mechanical stimulation by stretching or by the stones may stimulate cell renewal in this organ. Factors in the bile of animals receiving a lithogenic diet could be involved which might cause cellular death and, hence, a regenerative reaction. Direct mitogenic effect of an unknown factor in the bile of these animals is an alternative possibility. On the other hand the stimulating effect of postprandial hormones on gallbladder cell renewal suggested by the observation of a DNA synthesis peak after feeding has been established. Synthetic cholecystokinin analogues have been shown to increase the proliferative activity and to induce epithelial hyperplasia in this organ. In one recent study using

  10. 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.

  11. The role of ovarian surface epithelium in folliculogenesis during fetal development of the bovine ovary: a histological and immunohistochemical study.

    PubMed

    Kenngott, R A M; Vermehren, M; Ebach, K; Sinowatz, F

    2013-01-01

    Although many aspects of ovarian differentiation have been established, comparatively little is known about prenatal follicle formation and differentiation of bovine ovaries. The objective of this investigation was to study the role of the surface epithelium during the development of germ cell nests, germ cell cords and follicle formation in the fetal bovine ovary. Associated important proliferation and apoptotic features were further investigated. Additionally, the expression pattern of the S100 protein was detected. A strong increase of mitotic figures was detected in the surface epithelium, germ cell nests and germ cell cords of ovaries with a crown-rump length (CRL) of 13.0-58.0 cm. Oocytes were positively stained with S100 in bovine ovaries from fetuses with a CRL of 21.0 cm. The staining intensity enhanced parallel to increasing oocyte and follicle sizes during the ovary development. In later stages, a strong staining for S100 was observed in healthy oocytes in contradistinction to atretic oocytes where no expression of the S100 protein could be found. In conclusion, increasing mitosis index of surface epithelium cells, as well as oogonia directly beneath the surface epithelium, in combination with open surface connection during stages from a CRL of 11.0-94.0 cm of bovine fetal ovaries could play an important role in the period of time of ongoing folliculogenesis and derivation of granulosa cells. Additionally, S100-positive oocytes in primordial and later follicle stages joined by a high rate of Ki67-positive index in surrounding granulosa cells indicate that in the oocytes the S100 protein can perhaps be a useful marker for intact oocytes in bovine ovaries. Copyright © 2013 S. Karger AG, Basel.

  12. 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.

  13. 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.

  14. Anatomy, histology, and ultrasonography of the normal adrenal gland in brown lemur: Eulemur fulvus.

    PubMed

    Raharison, Fidiniaina; Bourges Abella, Nathalie; Sautet, Jean; Deviers, Alexandra; Mogicato, Giovanni

    2017-04-01

    The medical care currently to brown lemurs (Eulemur fulvus) is limited by a lack of knowledge of their anatomy. The aim of this study was to describe the anatomy and histology and obtain ultrasonographic measurements of normal adrenal glands in these animals. The adrenal glands of four lemurs cadavers were used for the anatomical and histological studies, and those of 15 anesthetized lemurs were examined by ultrasonography. Anatomically, the adrenal glands of brown lemurs are comparable to those of other species. The histological findings showed that the cortex is organized into three distinct layers, whereas most domestic mammals have an additional zone. The surface area of the adrenal glands increased with body weight, and the area of the right adrenal was slightly larger than the left. We suggest using ultrasonography to aid the etiological diagnosis of behavioral abnormalities that might be due to dysfunctions of the adrenal gland. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Chronic hepatitis C with normal aminotransferase levels: a clinical histologic study.

    PubMed

    Gholson, C F; Morgan, K; Catinis, G; Favrot, D; Taylor, B; Gonzalez, E; Balart, L

    1997-10-01

    To define chronic hepatitis C virus (HCV) infection among patients with persistently normal aminotransferase levels (PNAL). Retrospective chart review of all patients encountered during 1-yr with positive hepatitis C antibody (anti-C100-3 ELISA), no alternative cause for their liver disease and PNAL for 6 or more consecutive months prebiopsy. Blinded review of liver histology. Outpatient hepatology clinics of two academic centers. Fifty patients with PNAL among 303 with hepatitis C. Epidemiologic profiles, reasons for seroscreening and confirmatory analyses were tabulated. Histology was reviewed and grading of inflammatory activity and stage of fibrosis was determined by protocol. Among 50 patients with PNAL, 35 (70%) were female, 34 (68%) had parenterally acquired HCV, 44 (88%) abstained (> 2 yr) from ethanol, all were HIV-negative and none pharmacologically immunosuppressed. HCV infection was uniformly confirmed by RIBA II or HCV-RNA assay. The mean level of HCV-RNA by quantitative PCR was 3.79 x 10(5) copies/ml (range, 500 to 1.8 x 10(6) copies/ ml) and by B-DNA, 53 x 10(5) copies/ml (range, 3.5-230 x 10(5) copies/ml). Traditional histoevaluation yielded chronic hepatitis ("active", n = 15; "persistent", n = 25), cirrhosis (n = 7), and normal histology (n = 3). Blinded protocol review of histology (inflammatory grade/fibrotic stage) revealed 0/0 (n = 4), 1/0 (n = 6), 2/0 (n = 17), 2/1 (n = 3), 2/4 (n = 1), 3/0 (n = 2), 3/1 (n = 6), 3/2 (n = 2), and 3/3 (n = 9). In chronic HCV infection, active inflammation, fibrosis, and variable circulating HCV-RNA levels may coexist with PNAL, particularly among female nondrinkers. Asymptomatic carriers with normal histology comprise 6 to 8% of chronic hepatitis C with PNAL. Management guidelines for this group of patients need to be developed.

  16. [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.

  17. EZH2 protein expression in normal breast epithelium and risk of breast cancer: results from the Nurses' Health Studies.

    PubMed

    Beca, Francisco; Kensler, Kevin; Glass, Benjamin; Schnitt, Stuart J; Tamimi, Rulla M; Beck, Andrew H

    2017-03-02

    Enhancer of zeste homolog 2 (EZH2) is a polycomb-group protein that is involved in stem cell renewal and carcinogenesis. In breast cancer, increased EZH2 expression is associated with aggressiveness and has been suggested to identify normal breast epithelium at increased risk of breast cancer development. However, the association between EZH2 expression in benign breast tissue and breast cancer risk has not previously been evaluated in a large prospective cohort. We examined the association between EZH2 protein expression and subsequent breast cancer risk using logistic regression in a nested case-control study of benign breast disease (BBD) and breast cancer within the Nurses' Health Studies. EZH2 immunohistochemical expression in normal breast epithelium and stroma was evaluated by computational image analysis and its association with breast cancer risk was analyzed after adjusting for matching factors between cases and controls, the concomitant BBD diagnosis, and the Ki67 proliferation index. Women with a breast biopsy in which more than 20% of normal epithelial cells expressed EZH2 had a significantly increased risk of developing breast cancer (odds ratio (OR) 2.95, 95% confidence interval (CI) 1.11-7.84) compared to women with less than 10% EZH2 epithelial expression. The risk of developing breast cancer increased for each 5% increase in EZH2 expression (OR 1.22, 95% CI 1.02-1.46, p value 0.026). Additionally, women with high EZH2 expression and low estrogen receptor (ER) expression had a 4-fold higher risk of breast cancer compared to women with low EZH2 and low ER expression (OR 4.02, 95% CI 1.29-12.59). These results provide further evidence that EZH2 expression in the normal breast epithelium is independently associated with breast cancer risk and might be used to assist in risk stratification for women with benign breast biopsies.

  18. 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

  19. Histologic studies on normal and persistent ductus arteriosus in the dog.

    PubMed

    Gittenberger-de Groot, A C; Strengers, J L; Mentink, M; Poelmann, R E; Patterson, D F

    1985-08-01

    The process of anatomic closure of the ductus arteriosus was studied at the ultrastructural level in 15 normal beagles (age 0 hour to 13 days) and in 18 specimens from a strain of dogs with hereditary persistent ductus arteriosus (age 4 hours to 27 days). Normal ductal closure takes place from the pulmonary artery to the aortic end. It is accompanied by a series of histologic changes: 1) separation of the endothelial cells from the internal elastic lamina resulting in a wide region of subendothelial edema; 2) ingrowth and infolding of endothelial cells and migration of undifferentiated smooth muscle cells from the inner media into the subendothelial region; 3) apposition of endothelial cells bordering the lumen; and 4) degenerative changes. In persistent ductus arteriosus, these changes do not occur. The endothelial cells remain closely adhered to the internal elastic lamina and the underlying media is abnormal in structure. In the case of partial persistent ductus arteriosus (ductus diverticulum), both the normal and the abnormal type of wall are found in a single ductus arteriosus. The histologic features of the normal and the persistent ductus arteriosus in the dog resemble those of the normal and the persistent ductus arteriosus in humans, suggesting a similar pathogenesis.

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

    PubMed

    Morelatto, Rosana; Itoiz, María-Elina; Guiñazú, Natalia; Piccini, Daniel; Gea, Susana; López-de Blanc, Silvia

    2014-05-01

    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. 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. 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. 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.

  1. 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

  2. A normal and biotransforming model of the human bronchial epithelium for the toxicity testing of aerosols and solubilised substances.

    PubMed

    Prytherch, Zoë C; BéruBé, Kelly A

    2014-12-01

    In this article, we provide an overview of the experimental workflow by the Lung and Particle Research Group at Cardiff University, that led to the development of the two in vitro lung models - the normal human bronchial epithelium (NHBE) model and the lung-liver model, Metabo-Lung™. This work was jointly awarded the 2013 Lush Science Prize. The NHBE model is a three-dimensional, in vitro, human tissue-based model of the normal human bronchial epithelium, and Metabo-Lung involves the co-culture of the NHBE model with primary human hepatocytes, thus permitting the biotransformation of inhaled toxicants in an in vivo-like manner. Both models can be used as alternative test systems that could replace the use of animals in research and development for safety and toxicity testing in a variety of industries (e.g. the pharmaceutical, environmental, cosmetics, and food industries). Metabo-Lung itself is a unique tool for the in vitro detection of toxins produced by reactive metabolites. This 21st century animal replacement model could yield representative in vitro predictions for in vivo toxicity. This advancement in in vitro toxicology relies on filter-well technology that will enable a wide-spectrum of researchers to create viable and economic alternatives for respiratory safety assessment and disease-focused research. 2014 FRAME.

  3. Aldehyde dehydrogenase and estrogen receptor define a hierarchy of cellular differentiation in the normal human mammary epithelium

    PubMed Central

    2014-01-01

    Introduction Although estrogen and progesterone play a key role in normal mammary development and in breast cancer, the potential for proliferation and lineage differentiation as well as origin of cells that express the estrogen receptor (ER) in normal breast epithelium are not known. Some evidence suggests that normal human mammary stem/progenitor cells are ER–, but the identity of these cells and the cellular hierarchy of breast epithelium are still subjects of controversy. It is likely that elucidation of these aspects will bring insight into the cellular origin of breast cancer subtypes. Methods We used fluorescence-activated cell sorting of primary human mammary epithelial cells along with in vitro and in vivo functional assays to examine the hierarchic relation between cells with aldehyde dehydrogenase enzymatic activity (ALDH+ cells) and ER+ cells in the normal human breast epithelium. We assessed the proliferation and lineage differentiation potential of these cells in vitro and in vivo. A gene reporter assay was used to separate live ER+ and ER– mammary epithelial cells. With shRNA-mediated knockdown, we investigated the role of ALDH isoforms in the functionality of mammary epithelial progenitor cells. Results We describe a cellular hierarchy in the normal human mammary gland in which ER–/ALDH+ cells with functional properties of stem/progenitor cells generate ER+ progenitor cells, which in turn give rise to cells of luminal lineage. We show that the ALDH1A1 isoform, through its function in the retinoic acid metabolism, affects the proliferation and/or early differentiation of stem/progenitor cells and is important for branching morphogenesis. Conclusions This study presents direct evidence that ER+ cells are generated by ER–/ALDH+ stem/progenitor cells. We also show that ER+ cells are able to generate cell progeny of luminal lineage in vitro and in vivo. Loss of ALDH1A1 function impairs this process, as well as branching morphogenesis and

  4. Histological analysis of healthy epithelium of Wistar rats in vivo irradiated with different intensities of therapeutic ultrasound.

    PubMed

    De Bem, Daiane M; Maciel, Carlos D; Zuanon, José A; Neto, Carlos B; Parizotto, Nivaldo A

    2010-01-01

    Ultrasound (US) is a widely used and studied resource for physical therapy treatments. Given the scarcity of studies on the effects of US on healthy tissue, many physical therapy professionals make unfounded decisions regarding its methods and parameters of application. The possible histological and morphometric changes in the healthy tissue of Wistar rats in vivo irradiated with different intensities of US were evaluated. Thirty Wistar rats, randomly distributed among five groups of six animals each, were treated on the right side of the dorsal region, over an area of 4 cm(2). The left side served as a control. The treatment was applied over a four-day period, with two mins. of daily irradiation. The output intensity was checked using a precision dosimeter before the applications. Histological and morphometric analyses were performed using the Image Tool software. There were slight inflammatory infiltration and thinning of the dermis fibers, particularly in the groups irradiated with 1.5 and 2 W/cm(2). There was also thickening of the epidermis in the samples from the irradiated animals. To evaluate the quantitative results, the statistical analyses consisted of one-way ANOVAs with the post-hoc Tukey tests. There were significant differences in epidermis thicknesses between the control group and the groups irradiated with 1.0, 1.5 and 2.0 W/cm(2). Higher doses of US produced changes in the epidermis and dermis, i.e. increased thickness and collagen fiber thinning and proliferation, respectively. These results serve as a warning of the possible implications of therapeutic ultrasound use in esthetics.

  5. Phototoxic Action Spectrum on a Retinal Pigment Epithelium Model of Age-Related Macular Degeneration Exposed to Sunlight Normalized Conditions

    PubMed Central

    Arnault, Emilie; Barrau, Coralie; Nanteau, Céline; Gondouin, Pauline; Bigot, Karine; Viénot, Françoise; Gutman, Emmanuel; Fontaine, Valérie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, José-Alain; Picaud, Serge

    2013-01-01

    Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the

  6. Phototoxic action spectrum on a retinal pigment epithelium model of age-related macular degeneration exposed to sunlight normalized conditions.

    PubMed

    Arnault, Emilie; Barrau, Coralie; Nanteau, Céline; Gondouin, Pauline; Bigot, Karine; Viénot, Françoise; Gutman, Emmanuel; Fontaine, Valérie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, José-Alain; Picaud, Serge

    2013-01-01

    Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. A hardware approach for histological and histopathological digital image stain normalization.

    PubMed

    Şerbănescu, Mircea Sebastian; Pleşea, Iancu Emil

    2015-01-01

    Advances in technology made the migration of pathological diagnosis to digital slides possible. As the need for objectivity and automation emerged, new computer software algorithms were proposed. Computer algorithms demand accurate color and intensity values in order to provide reliable results. The tissue samples undergo several processing steps from histological preparation to digitalization, which cannot be completely standardized. Thus, non-standardized input data generates unreliable output data. In this article, we discuss a new computational normalization algorithm for histopathological stained slides that uses a hardware color marker. The marker is added to the glass slide together with the tissue section, exposed to all the processing steps and altered in the same manner as the biological material of interest, thus becoming a solid color marker for image normalization. The results of the proposed method are numerically and perceptually tested in order to prove the advantages of the method. We conclude that our combined hardware-software technique for staining normalization of digital slides is superior to the existing methods based on only software normalization, and that its implementation will tackle not only the acquisition errors but also the technical errors that may occur during the staining process.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. The fluorescence lifetime of lipofuscin granule fluorophores contained in the retinal pigment epithelium cells from human cadaver eyes in normal state and in the case of visualized pathology.

    PubMed

    Yakovleva, M A; Feldman, T B; Arbukhanova, P M; Borzenok, S A; Kuzmin, V A; Ostrovsky, M A

    2017-05-01

    A comparative analysis of fluorescence lifetime of lipofuscin granule fluorophores contained in the retinal pigment epithelium cells from human cadaver eyes in normal state and in the case of visualized pathology was carried out. Measurements of fluorescence lifetimes of bis-retinoids and their photooxidation and photodegradation products were carried out using the method of counting time-correlated photons. Comparative analysis showed that, in the case of visualized pathology, the contribution of photooxidation and photodegradation products of bis-retinoids to the total fluorescence of the retinal pigment epithelium cell suspension increases in comparison with the norm.

  18. Differential growth factor regulation of N-cadherin expression and motility in normal and malignant oral epithelium.

    PubMed

    Diamond, Michelle E; Sun, Limin; Ottaviano, Adam J; Joseph, Mathew J; Munshi, Hidayatullah G

    2008-07-01

    Aberrant expression of N-cadherin is associated with tumor progression in squamous cell carcinomas (SCCs). Consequently, we examined the regulation of N-cadherin by TGFbeta1, an important mediator of keratinocyte and SCC function. N-cadherin expression was increased in oral SCC (OSCC) cell lines, regulating motility and correlating with TGFbeta1 production. Moreover, in normal keratinocytes TGFbeta1 increased expression of N-cadherin to regulate motility. TGFbeta1-mediated N-cadherin expression in the oral keratinocytes was blocked using siRNA targeting Smads. Unexpectedly, we found that EGF blocked TGFbeta1-mediated N-cadherin expression in oral keratinocytes and not in OSCC cells. Mechanistically, EGF enhanced Smad phosphorylation in the linker region, and attenuated TGFbeta1-mediated phosphorylation of Smad at the C-terminus, localization of Smad to the nucleus as well as Smad-driven promoter activity exclusively in oral keratinocytes but not in OSCC cells. The effect of EGF on TGFbeta1-mediated Smad-driven promoter activity and N-cadherin expression was reversed when activation of ERK1/2 was blocked. Although EGF and TGFbeta1 independently promoted migration of both oral keratinocytes and OSCC cells, EGF decreased TGFbeta1-mediated migration of oral keratinocytes but enhanced migration of OSCC cells. Together, these data support a model wherein EGF signaling has an important negative regulatory role on TGFbeta1-mediated N-cadherin expression and motility in normal oral keratinocytes, and in which loss of this regulatory mechanism accompanies malignant transformation of the oral epithelium.

  19. 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.

  20. 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.

  1. [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.

  2. Role of Lynx1 and related Ly6 proteins as modulators of cholinergic signaling in normal and neoplastic bronchial epithelium.

    PubMed

    Fu, Xiao Wen; Song, Ping Fang; Spindel, Eliot R

    2015-11-01

    The ly-6 proteins are a large family of proteins that resemble the snake three finger alpha toxins such as α-bungarotoxin and are defined by their multiple cysteine residues. Multiple members of the ly-6 protein family can modulate nicotinic signaling including lynx1, lynx2, slurp-1, slurp-2 and prostate stem cell antigen (PSCA). Consistent with the expression of multiple nicotinic receptors in bronchial epithelium, multiple members of the nicotinic-modulatory ly-6 proteins are expressed in lung including lynx1 and lynx2. We studied the role of lynx1 as an exemplar of the role of ly-6 proteins in lung. Our data demonstrates that lynx1 acts as a negative modulator of nicotinic signaling in normal and neoplastic lung. In normal lung lynx1 serves to limit the ability of chronic nicotine exposure to increase levels of nicotinic receptors and also serves to limit the ability of nicotine to upregulate levels of GABAA receptors in lung. In turn this allows lynx1 to limit the ability of nicotine to upregulate levels of mucin which is mediated by GABAergic signaling. This suggests that lynx1-mimetics may have potential for treatment of asthma and COPD. In that most lung cancer cells also express nicotinic receptor and lynx1 we examined the role of lynx-1 in lung cancer. Lynx1 levels are decreased in lung cancers compared to adjacent normal lung. Knockdown of lynx1 by siRNAs increased growth of lung cancer cells while expression of lynx1 in lung cancer cell decreased cell proliferation. This suggests that lynx1 is an endogenous regulator of lung cancer growth. Given that multiple small molecule negative and positive allosteric modulators of nicotinic receptors have already been developed, this suggests that lynx1 is a highly druggable target both for development of drugs that may limit lung cancer growth as well as for drugs that may be effective for asthma or COPD treatment. Copyright © 2015. Published by Elsevier B.V.

  3. 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

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

    PubMed

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

    2015-11-01

    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). 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. 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. au18 and au13 contain mutations in nsfb, which encodes a protein that is required for the maturation of melanosomes in zebrafish RPE.

  5. 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

  6. 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.

  7. Magnetic resonance imaging, ultrasonography and histology of the suspensory ligament origin: a comparative study of normal anatomy of warmblood horses.

    PubMed

    Bischofberger, A S; Konar, M; Ohlerth, S; Geyer, H; Lang, J; Ueltschi, G; Lischer, C J

    2006-11-01

    The diagnosis of lameness caused by proximal metacarpal and metatarsal pain can be challenging. Magnetic resonance imaging (MRI) offers the possibility for further diagnosis but there have been no studies on the normal MRI appearance of the origin of the suspensory ligament (OSL) in conjunction with ultrasonography and histology. To describe the MRI appearance of the OSL in fore- and hindlimbs of sound horses and compare it to the ultrasonographic and histological appearance. The findings can be used as reference values to recognise pathology in the OSL. The OSL in the fore- and hindlimbs of 6 sound horses was examined by ultrasonography prior to death, and MRI and histology post mortem. Qualitative evaluation and morphometry of the OSL were performed and results of all modalities compared. Muscular tissue, artefacts, variable SL size and shape complicated ultrasonographic interpretation. In MRI and histology the forelimb OSL consisted of 2 portions, the lateral being significantly thicker than medial. The hindlimb SL had a single large area of origin. In fore- and hindlimbs, the amount of muscular tissue was significantly larger laterally than medially. Overall SL measurements using MRI were significantly higher than using histology and ultrasonography and histological higher than ultrasonographic measurements. Morphologically, there was a good correlation between MRI and histology. MRI provides more detailed information than ultrasonography regarding muscle fibre detection and OSL dimension and correlates morphologically well with histology. Therefore, ultrasonographic results should be regarded with caution. MRI may be a diagnostic aid when other modalities fail to identify clearly the cause of proximal metacarpal and metatarsal pain; and may improve selection of adequate therapy and prognosis for injuries in this region.

  8. 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).

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels.

    PubMed

    Renou, C; Halfon, P; Pol, S; Cacoub, P; Jouve, E; Bronowicki, J P; Arpurt, J P; Rifflet, H; Picon, M; Causse, X; Canva, V; Denis, J; Tran, A; Bourliére, M; Ouzan, D; Pariente, A; Dantin, S; Alric, L; Cartier, V; Reville, M; Caillat-Zucman, S

    2002-10-01

    A significant proportion of individuals with chronic hepatitis C virus (HCV) infection have persistently normal alanine aminotransferase (ALT) levels. Although data are controversial, such patients usually have weaker histological damage and a lower progression rate of fibrosis. The aims of this study were: (1) to compare demographic, virological, and histological parameters of HCV patients with normal ALT values with those of HCV patients with elevated ALT levels; and (2) to determine whether HLA class II alleles contribute to the persistence of normal ALT levels in HCV patients. Eighty three patients with chronic HCV infection and persistently normal ALT values (group 1) and 233 patients with chronic HCV infection and elevated ALT levels (group 2) were studied. Histological features were expressed using Knodell and Metavir scores. HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence specific oligonucleotides after genomic amplification. The kappa2 and Fisher's exact tests were used to compare discrete variables and phenotype frequencies between the two groups, and Wilcoxon's test was used for continuous variables. A multivariate logistic regression model was used to determine which variables predicted normal ALT values. ALT levels were correlated with the severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir index of fibrosis compared with 47% of patients in group 2 (p<0.001). A longer duration of infection (p<0.001) and increased DRB1*11 phenotype frequency (pc=0.03) were observed among patients with normal ALT. The two groups did not differ with regard to the mode of contamination or viral genotype. After logistic regression, young age (p=0.0008), female sex (p=0.01), long duration of infection (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with persistence of normal ALT. Our study confirms that patients with chronic hepatitis C and normal ALT levels have less severe liver disease than those

  16. Arterial spin-labeling assessment of normalized vascular intratumoral signal intensity as a predictor of histologic grade of astrocytic neoplasms.

    PubMed

    Furtner, J; Schöpf, V; Schewzow, K; Kasprian, G; Weber, M; Woitek, R; Asenbaum, U; Preusser, M; Marosi, C; Hainfellner, J A; Widhalm, G; Wolfsberger, S; Prayer, D

    2014-03-01

    Pulsed arterial spin-labeling is a noninvasive MR imaging perfusion method performed with the use of water in the arterial blood as an endogenous contrast agent. The purpose of this study was to determine the inversion time with the largest difference in normalized intratumoral signal intensity between high-grade and low-grade astrocytomas. Thirty-three patients with gliomas, histologically classified as low-grade (n = 7) or high-grade astrocytomas (n = 26) according to the World Health Organization brain tumor classification, were included. A 3T MR scanner was used to perform pulsed arterial spin-labeling measurements at 8 different inversion times (370 ms, 614 ms, 864 ms, 1114 ms, 1364 ms, 1614 ms, 1864 ms, and 2114 ms). Normalized intratumoral signal intensity was calculated, which was defined by the signal intensity ratio of the tumor and the contralateral normal brain tissue for all fixed inversion times. A 3-way mixed ANOVA was used to reveal potential differences in the normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas. The difference in normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas obtained the most statistically significant results at 370 ms (P = .003, other P values ranged from .012-.955). The inversion time by which to differentiate high-grade and low-grade astrocytomas by use of normalized vascular intratumoral signal intensity was 370 ms in our study. The normalized vascular intratumoral signal intensity values at this inversion time mainly reflect the labeled intra-arterial blood bolus and therefore could be referred to as normalized vascular intratumoral signal intensity. Our data indicate that the use of normalized vascular intratumoral signal intensity values allows differentiation between low-grade and high-grade astrocytomas and thus may serve as a new, noninvasive marker for astrocytoma grading.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Tumor-related markers in histologically normal margins correlate with locally recurrent oral squamous cell carcinoma: a retrospective study.

    PubMed

    Wang, Xinhong; Chen, Si; Chen, Xinming; Zhang, Cuicui; Liang, Xueyi

    2016-02-01

    Oral squamous cell carcinoma (OSCC) is characterized by a high rate of local recurrence (LR) even when the surgical margins are considered histopathologically 'normal'. The aim of our study was to determine the relationship between early tumor-related markers detected in histologically normal margins (HNM) and LR as well as disease-free survival in OSCC. The loss of heterozygosity (LOH) of markers on 9p21 (D9s1747, RPS6, D9s162) and 17p13 (TP53) and the immunostaining results of the corresponding mutant P53, P14, P15, and P16 proteins were assessed and correlated with LR and disease-free survival in 71 OSCC patients who had HNM. Fifteen of 71 patients with HNM developed LR. The presence of the following molecular markers in surgical margins was significantly correlated with the development of LR: LOH on chromosome 9p21 (D9s1747 + RPS6 + D9s162), any LOH, P16, and P53 (chi-square test, P < 0.05). The presence of TP53 LOH, 9p21 LOH, any LOH, P15, P16, P53, P16 + D9s1747, and P53 + TP53 had a significant effect on LR (Kaplan-Meier analysis, P < 0.05). P16 + D9s1747 was the most predictive factor using multivariate Cox analyses. Detection of tumor-related markers in histologically 'normal' resection margins may be a useful method for assessing LR in OSCC patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Histological and three dimensional organizations of lymphoid tubules in normal lymphoid organ of Penaeus monodon.

    PubMed

    Duangsuwan, Pornsawan; Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Wanichanon, Chaitip; Sobhon, Prasert

    2008-04-01

    The normal lymphoid organ of Penaeus monodon (which tested negative for WSSV and YHV) was composed of two parts: lymphoid tubules and interstitial spaces, which were permeated with haemal sinuses filled with large numbers of haemocytes. There were three permanent types of cells present in the wall of lymphoid tubules: endothelial, stromal and capsular cells. Haemocytes penetrated the endothelium of the lymphoid tubule's wall to reside among the fixed cells. The outermost layer of the lymphoid tubule was covered by a network of fibers embedded in a PAS-positive extracellular matrix, which corresponded to a basket-like network that covered all the lymphoid tubules as visualized by a scanning electron microscope (SEM). Argyrophilic reticular fibers surrounded haemal sinuses and lymphoid tubules. Together they formed the scaffold that supported the lymphoid tubule. Using vascular cast and SEM, the three dimensional structure of the subgastric artery that supplies each lobe of the lymphoid organ was reconstructed. This artery branched into highly convoluted and blind-ending terminal capillaries, each forming the lumen of a lymphoid tubule around which haemocytes and other cells aggregated to form a cuff-like wall. Stromal cells which form part of the tubular scaffold were immunostained for vimentin. Examination of the whole-mounted lymphoid organ, immunostained for vimentin, by confocal microscopy exhibited the highly branching and convoluted lymphoid tubules matching the pattern of the vascular cast observed in SEM.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Ultraviolet-induced autofluorescence characterization of normal and tumoral esophageal epithelium cells with quantitation of NAD(P)H.

    PubMed

    Villette, Sandrine; Pigaglio-Deshayes, Sophie; Vever-Bizet, Christine; Validire, Pierre; Bourg-Heckly, Geneviève

    2006-05-01

    Cellular autofluorescence was characterized in normal human esophageal cells and in malignant esophageal epithelial cells. The study was performed under excitation at 351 nm where the cell fluorescence is mainly due to the reduced pyridine nucleotides (NAD(P)H) with a very small contribution from the oxidized flavins (FMN, FAD) or lipopigments. The autofluorescence emission of squamous cell carcinoma, adenocarcinoma on Barrett's mucosa and normal cells was characterized by microspectrofluorimetry on monolayers and by spectrofluorimetry on cell suspensions. The relative contribution of each fluorophore to the fluorescence emission of the different cell types was evaluated by a curve-fitting analysis. A statistically highly significant difference was observed between the average intensity of the raw spectra of the different cell types. Tumoral cells had a fluorescence intensity approximately twice as high as that of normal cells. The results of the NAD(P)H quantitation analyzed by microspectrofluorimetry on single living cells and spectrofluorimetry on cell suspensions were consistent with those obtained by biochemical cycling assays, showing that the amount of intracellular NAD(P)H is higher in tumoral cells than in normal cells. Bound NAD(P)H concentration was found to be quite stable whatever the cell type while the amount of free NAD(P)H showed a very important increase in tumoral cells.

  9. 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.

  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 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

  11. A placebo controlled observer blind immunocytochemical and histologic study of epithelium adjacent to anogenital warts in patients treated with systemic interferon alpha in combination with cryotherapy or cryotherapy alone.

    PubMed Central

    Handley, J M; Maw, R D; Horner, T; Lawther, H; Walsh, M; Dinsmore, W W

    1992-01-01

    infiltrated into the upper dermis in 5/29 (17.2%). HLA DR was detected on the surface of dendritic cells throughout the epidermis in 22/29 (75.9%) of specimens, and on the surface of cells scattered both diffusely throughout the upper dermis and centred around dermal blood vessels in all specimens. Alpha one antitrypsin (A1AT) antigen was seen on the surface of cells in the upper dermis in 6/29 (20.7%) of biopsy specimens; no cells expressing CD22 surface antigen were seen. The nature of this local cellular immune response was not altered by treatment of nearby warts with either cryotherapy alone or cryotherapy plus systemic IFN alpha 2a, or related to the therapeutic outcome of these warts. CONCLUSIONS--(1) No convincing histological evidence of HPV infection was seen in epithelium surrounding AG warts. (2) A predominantly T cell-mediated immune response (the target of which is uncertain) was seen in this perilesional epithelium. (3) In the dosage regimens used in this study, treatment of AG warts with either systemic IFN alpha 2a plus cryotherapy or cryotherapy alone did not appear to augment localised cellular immune responses (against any presumed subclinical HPV infection) in epithelium surrounding AG warts. Images PMID:1316307

  12. The pattern of expression and role of triiodothyronine (T3) receptors and type I 5'-deiodinase in breast carcinomas, benign breast diseases, lactational change, and normal breast epithelium.

    PubMed

    Alyusuf, Raja H; Matouq, Jenan Al; Taha, Safa; Wazir, Javed F

    2014-08-01

    : To study the pattern of expression of triiodothyronine (T3) receptors and type I 5'-deiodinase in various breast pathologies comparing malignant and nonmalignant epithelia that include lactational change. A retrospective study was performed on formalin-fixed, paraffin-embedded archival material from 146 cases of carcinomas, normal breast tissue, breast tissue showing lactational change, and benign breast lesions. Archive tissue blocks were selected and sections were cut for immunohistochemistry to study the expression of thyroid hormone receptor α-1 (THR-α1) in the cytoplasm and nuclei of cells in tissues under study. Thick sections were cut for type I 5'-deiodinase evaluation using reverse transcriptional PCR.THR-α1 showed no nuclear expression in the carcinoma group. Combined nuclear and cytoplasmic expression was seen in 47.6%, 63.4%, 64.3%, and 58.3% in the benign, fibrocystic, fibroadenoma, and lactational change groups, respectively, compared with only 17.4% of cases in the carcinoma group. This suggests deregulation of the thyroid hormone in breast cancer. Theories for the possible role of thyroid hormone in the pathogenesis of breast cancer are discussed.Type I 5'-deiodinase was not shown to be differentially expressed in malignant versus nonmalignant groups. Our study revealed substantial reduction in the protein expression profile of THRs in malignant versus nonmalignant mammary epithelium suggesting a possible role in breast cancer development. The presence of THRs in mammary epithelium seems to be protective against the development of breast cancer. This could serve as a potential prognostic and therapeutic target for breast cancer.

  13. BMP-binding protein Twisted gastrulation is required in mammary gland epithelium for normal ductal elongation and myoepithelial compartmentalization

    PubMed Central

    Forsman, Cynthia L.; Ng, Brandon C.; Heinze, Rachel K.; Kuo, Claire; Sergi, Consolato; Gopalakrishnan, Rajaram; Yee, Douglas; Graf, Daniel; Schwertfeger, Kathryn L.; Petryk, Anna

    2012-01-01

    Bone morphogenetic proteins (BMPs) are involved in embryonic mammary gland (MG) development and can be dysregulated in breast cancer. However, the role BMPs play in the postnatal MG remains virtually unknown. BMPs are potent morphogens that are involved in cell fate determination, proliferation, apoptosis and adult tissue homeostasis. Twisted gastrulation (TWSG1) is a secreted BMP binding protein that modulates BMP ligand availability in the extracellular space. Here we investigate the consequences of TWSG1 deletion on development of the postnatal MG. At puberty, Twsg1 is expressed in the myoepithelium and in a subset of body cells of the terminal end buds. In the mature duct, Twsg1 expression is primarily restricted to the myoepithelial layer. Global deletion of Twsg1 leads to a delay in ductal elongation, reduced secondary branching, enlarged terminal end buds, and occluded lumens. This is associated with an increase in luminal epithelial cell number and a decrease in apoptosis. In the MG, pSMAD1/5/8 level and the expression of BMP target genes are reduced, consistent with a decrease in BMP signaling. GATA-3, which is required for luminal identity, is reduced in Twsg1−/− MGs, which may explain why K14 positive cells, which are normally restricted to the myoepithelial layer, are found within the luminal compartment and shed into the lumen. In summary, regulation of BMP signaling by TWSG1 is required for normal ductal elongation, branching of the ductal tree, lumen formation, and myoepithelial compartmentalization in the postnatal MG. PMID:23103586

  14. 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.

  15. 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

  16. 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

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

    PubMed

    Die, Jose V; Baldwin, Ransom L; 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.

  18. 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

  19. Four carcinoembryonic antigen subfamily members, CEA, NCA, BGP and CGM2, selectively expressed in the normal human colonic epithelium, are integral components of the fuzzy coat.

    PubMed

    Frängsmyr, L; Baranov, V; Hammarström, S

    1999-01-01

    To elucidate which of the seven transcriptionally active genes of the carcinoembryonic antigen (CEA) subfamily are expressed in human colon, we first examined mRNA expression using reverse transcriptase PCR. The result showed the CEA, nonspecific crossreacting antigen 50/90 (NCA), biliary glycoprotein (BGP), and carcinoembryonic antigen gene family member 2 (CGM2) mRNAs were expressed in the colon. To determine the cellular sources of these members within normal colonic mucosa, in situ hybridization and immunocytochemistry were then performed. CEA and NCA mRNAs were clearly detectable in the cytoplasm of columnar and goblet cells at the free luminal surface and the upper crypts with low hybridization in the mid crypt and the crypt base. In contrast, BGP and CGM2 mRNAs were restricted only to columnar cells at the upper third of the crypts and the luminal surface. Colon epithelium expression of CEA, NCA, BGP and CGM2 coincided with that of corresponding mRNAs. Ultrastructurally, CEA, NCA, BGP and CGM2 were localized mainly to the apical surface glycocalyx, the fuzzy coat, of columnar cells. Interestingly, these molecules were localized in different microdomains within the fuzzy coat. Furthermore, BGP was highly expressed in the fuzzy coat of cryptal caveolated cells. As integral components of the fuzzy coat, CEA, NCA, BGP and CGM2 can hardly function as intercellular adhesion molecules; they possibly play an important role in epithelial-microbial interactions.

  20. 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]).

  1. 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.

  2. 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.

  3. Histological and parasitological distinctive findings in clinically-lesioned and normal-looking skin of dogs with different clinical stages of leishmaniosis.

    PubMed

    Ordeix, Laura; Dalmau, Annabel; Osso, Montsant; Llull, Joan; Montserrat-Sangrà, Sara; Solano-Gallego, Laia

    2017-03-13

    Normal-looking skin of dogs with leishmaniosis frequently shows microscopic lesions along with the presence of Leishmania amastigotes. However, histological lesions with or without detection of amastigotes might not occur in less severe clinical cases. In addition, comparative studies between paired clinically-lesioned and normal-looking skin samples from dogs with different disease severity are lacking. The objective of this study was to compare histological and parasitological findings by Leishmania immunohistochemistry (IHC) and quantitative PCR (qPCR) on paired clinically-lesioned and normal-looking skin biopsies from 25 dogs with different clinical stages of leishmaniosis, 11 with stage I-mild disease (papular dermatitis) and 14 with stage II-III (ulcerative or exfoliative dermatitis). The study demonstrated microscopic lesions in 14 out of 25 (56%) samples from normal-looking skin biopsies. In those samples, perivascular to interstitial dermatitis composed by macrophages with lymphocytes and plasma cells was observed mainly in the superficial and mid-dermis. The intensity of the dermatitis was mild to moderate and always less prominent than in the clinically-lesioned skin. In normal-looking skin samples, the presence of parasites was detected by histology, IHC and qPCR in 5/25 (20%), 8/25 (32%) and 18/25 (72%), respectively. Leishmania was encountered in 11/25 (44%), 23/25 (92%) and 25/25 (100%) of clinically-lesioned skin samples by histology, IHC and qPCR, respectively. Normal-looking skin from dogs with stage I-mild disease was less frequently inflamed (P = 0.0172). Furthermore, Leishmania was more easily demonstrated by histology (P = 0.0464), IHC (P = 0.0421) or qPCR (P = 0.0068) in normal-looking skin of dogs with stage II-III-moderate to severe disease. In addition, in the latter group, there was a significantly higher parasite load studied by means of qPCR than in dogs with less severe disease (P = 0.043). Clinically-lesioned skin

  4. Differences in cellular glycoconjugates of quiescent, inflamed, and neoplastic colonic epithelium in colitis and cancer-prone tamarins.

    PubMed Central

    Moore, R.; King, N.; Alroy, J.

    1988-01-01

    In the preceding paper the authors demonstrated that the lectin staining patterns of normal colonic epithelium obtained from colitis and carcinoma-prone cotton top tamarins (CTTs), Saguinus oedipus, a New World primate, differs from colitis- and carcinoma-resistant primate species. In this study they determined the usefulness of cytochemical features in inflamed epithelium as indicators for malignant change. They compared the lectin staining pattern in inflamed mucosa and adjacent mucosa with colonic carcinoma from 8 CTTs with that of 9 clinically healthy CTTs with no histologic evidence of colitis. Deparaffinized sections were labeled with ten biotinylated lectins and stained by the avidin-biotin peroxidase complex method. Numerous significant differences were demonstrated in the lectin staining pattern between normal epithelium and colonic carcinoma; fewer between normal and chronic inflamed epithelium. However, between chronic inflamed epithelium and colonic carcinoma significant staining differences were observed with only two lectins, peanut agglutinin (PNA) and Ulex europaeus agglutinin-I (UEA-I). These findings suggest that there is a progression in alteration of lectin staining pattern from normal epithelium, via chronic colitis, to colonic carcinoma. Furthermore, the differences between chronic colitis and colonic carcinoma are expressed only with those lectins that are associated with malignant transformation of human colonic epithelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3132858

  5. Exposure to a commercial glyphosate formulation (Roundup®) alters normal gill and liver histology and affects male sexual activity of Jenynsia multidentata (Anablepidae, Cyprinodontiformes).

    PubMed

    Hued, Andrea Cecilia; Oberhofer, Sabrina; de los Ángeles Bistoni, María

    2012-01-01

    Roundup is the most popular commercial glyphosate formulation applied in the cultivation of genetically modified glyphosate-resistant crops. The aim of this study was to evaluate the histological lesions of the neotropical native fish, Jenynsia multidentata, in response to acute and subchronic exposure to Roundup and to determine if subchronic exposure to the herbicide causes changes in male sexual activity of individuals exposed to a sublethal concentration (0.5 mg/l) for 7 and 28 days. The estimated 96-h LC50 was 19.02 mg/l for both male and female fish. Gill and liver histological lesions were evaluated through histopathological indices allowing quantification of the histological damages in fish exposed to different concentrations of the herbicide. Roundup induced different histological alterations in a concentration-dependent manner. In subchronic-exposure tests, Roundup also altered normal histology of the studied organs and caused a significant decrease in the number of copulations and mating success in male fish exposed to the herbicide. It is expected that in natural environments contaminated with Roundup, both general health condition and reproductive success of J. multidenatata could be seriously affected.

  6. 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.

  7. [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.

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

    USDA-ARS?s Scientific Manuscript database

    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 intro...

  9. Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold.

    PubMed

    Dowdall, Jayme R; Sadow, Peter M; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C; Franco, Ramon A; Rajagopal, Jayaraj

    2015-09-01

    A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Qualitative study with adult human larynges. Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Treatment of congenital melanocytic nevi using the combined (normal-mode plus Q-switched) ruby laser in Asians: clinical response in relation to histological type.

    PubMed

    Kono, Taro; Erçöçen, Ali Rza; Nozaki, Motohiro

    2005-05-01

    Clinical response of congenital melanocytic nevus (CMN) to the combined normal-mode ruby laser (NMRL) and Q-switched ruby laser (QSRL) treatment method (ie, NM plus QS) was correlated with the histologic depth of nevomelanocytic nests to predict the efficacy rate and therapeutic outcome of the laser treatment. Thirty-four patients with CMN were treated using the combined (NM plus QS) ruby laser method. The clinical results of the laser treatment demonstrated that 20 had excellent response, 11 had good response, 3 had fair response, and there was no poor response. When correlated with the histologic type, the efficacy rate of the combined ruby laser was significantly higher in the superficial intradermal type than in the others. We conclude that combining the NMRL and QSRL with appropriate parameters to target both superficial and deep nevomelanocytic components provides a greater degree of penetration of laser light.

  11. Defective barrier function in neosquamous epithelium.

    PubMed

    Jovov, Biljana; Shaheen, Nicholas J; Orlando, Geraldine S; Djukic, Zorka; Orlando, Roy C

    2013-03-01

    Radiofrequency ablation (RFA) of Barrett's esophagus (BE) is a common strategy for the prevention of esophageal adenocarcinoma (EAC). After RFA, the ablated esophagus heals on acid suppressive therapy, and is re-populated with a stratified squamous epithelium, referred to as "neosquamous epithelium (NSE)." Because the ability of the NSE to protect the underlying tissue from recurrent insult by reflux is unclear, we assessed the barrier function of NSE by comparing it to that of the native upper squamous epithelium (USE) in subjects having undergone RFA. At varying intervals following RFA, the barrier function of NSE and USE were assessed in endoscopic biopsies by light and electron microscopy, and by measurement of electrical resistance (R) and fluorescein flux in mini-Ussing chambers. Chamber results were further compared with results from control biopsies (healthy distal esophagus). A claudin expression profile in the tight junctions (TJs) of NSE and USE was determined using Quantitative reverse transcriptase PCR. Differential expression of claudin-4 between NSE and USE was assayed by immunoblots. USE was histologically normal whereas NSE showed dilated intercellular spaces and marked eosinophilia. NSE was also more permeable than USE and healthy controls, having lower mean R and higher fluorescein fluxes. Abnormally low R values for NSE were unrelated to the time period following RFA (or number of prior RFA sessions), being abnormal even 26 months after RFA. Abnormal permeability in NSE was associated with significantly lower values for claudin-4 and claudin-10 than in USE. NSE commonly exhibits defective barrier function. As this defect will make it vulnerable to injury, inflammation, and destruction by acidic and weakly acidic refluxates, it may in part explain incidences of recurrence of BE following ablation.

  12. 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.

  13. 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.

  14. 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

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

    PubMed

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

    2016-01-01

    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. 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. 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. 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.

  16. 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

  17. PKC iota in the intestinal epithelium protects against DSS-induced colitis

    PubMed Central

    Calcagno, Shelly R.; Li, Shuhua; Shahid, Muhammad W.; Wallace, Michael B.; Leitges, Michael; Fields, Alan P.; Murray, Nicole R.

    2010-01-01

    Background The integrity of the intestinal epithelium is critical for the absorption and retention of fluid and nutrients. The intestinal epithelium also provides a barrier between the intestinal bacteria and the body's immune surveillance. Therefore, intestinal epithelial barrier function is critically important, and disruption of the intestinal epithelium results in rapid repair of the damaged area. Methods We evaluated the requirement for protein kinase C iota (PKCι) in intestinal epithelial homeostasis and response to epithelial damage using a well-characterized mouse model of colitis. Mice were analyzed for the clinical, histological and cellular effects of dextran sodium sulfate (DSS) treatment. Results Knock out of the mouse PKCι gene (Prkci) in the intestinal epithelium (Prkci KO mice) had no effect on normal colonic homeostasis, however, Prkci KO mice were significantly more sensitive to DSS-induced colitis and death. After withdrawal of DSS, Prkci KO mice exhibited a continued increase in apoptosis, inflammation and damage to the intestinal microvasculature, and a progressive loss of trefoil factor 3 (TFF3) expression, a regulatory peptide important for intestinal wound healing. Knockdown of PKCι expression in HT-29 cells reduced wound healing and TFF3 expression, while addition of exogenous TFF3 restored wound healing in PKCι-depleted cells. Conclusions Expression of PKCι in the intestinal epithelium protects against DSS-induced colitis. Our data suggest that PKCι reduces DSS-induced damage by promoting intestinal epithelial wound healing through the control of TFF3 expression. PMID:21744423

  18. [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.

  19. 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

  20. 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

  1. Enhancement by tetragastrin of experimental induction of gastric epithelium in the duodenum.

    PubMed Central

    Tatsuta, M; Iishi, H; Yamamura, H; Yamamoto, R; Taniguchi, H

    1989-01-01

    The effects of tetragastrin and truncal vagotomy on the incidence of gastric type epithelium in the duodenum by intraduodenal instillation of 5% NaOH solution were investigated in Wistar rats. Prolonged administration of 1 mg tetragastrin/kg body weight in depot form starting one week after NaOH treatment resulted in a significant increase in gastric acid secretion and the incidence and number of villi with gastric epithelium in the duodenum in experimental week 10. Villi with gastric epithelium were found in five (23%) of 22 rats in control group, whereas abnormal villi were found in 13 (59%) of 22 rats in the tetragastrin treated group (p less than 0.05). The average number of villi with gastric epithelium rose from 0.6 (0.4) per 100 villi in control rats to 2.4 (0.6) per 100 villi in tetragastrin treated rats (p less than 0.01). On histological examination, gastric type epithelium was most often found on stunted or flattened villi, and was always within the boundaries of the area of Brunner's glands. These mucosal changes reverted toward normal with time. In week 35, the incidence of gastric epithelium was significantly less than at week 10 (p less than 0.05). In contrast, no villi with gastric epithelium were found in vagotomised rats in week 10 (p less than 0.05). Vagotomy also caused a significant decrease in gastric acid secretion. These results show that exposure of the duodenal mucosa to high levels of gastric acid enhance the induction of gastric eithelium in the duodenum. Images Figure PMID:2707631

  2. 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

  3. p16 INK4a and Ki67 expression in normal, dysplastic and neoplastic uterine cervical epithelium and human papillomavirus (HPV) infection.

    PubMed

    Calil, L N; Edelweiss, M I A; Meurer, L; Igansi, C N; Bozzetti, M C

    2014-08-01

    Cellular cycle proteins like the p16(INK4a) and the Ki67 proliferation nuclear antigen have been used as oncogenicity cellular markers. The E6 and E7 oncoproteins interact with tumor suppressor genes p53 and pRb, culminating with the p16(INK4a) overexpression. The objective of this study was to evaluate the presence of HPV-DNA in 174 cervical biopsies and correlate the different histological grades with the p16(INK4a) and Ki67 immunohistochemical expression (IHC). A cross-sectional study that enrolled a total of 174 women who underwent uterine cervical biopsies between February 2003 and December 2006, in southern Brazil, was performed. Cervical smear samples were analyzed for the presence of HPV-DNA through polymerase chain reaction (PCR), and biopsy samples were examined for p16(INK4A) and Ki67 expression through IHC techniques. The presence of HPV-DNA was observed in 89% of the tested patients, among which 52% were positive for high-risk (HR) viral types [16, 18 and 31]. Regarding p16(INK4a), an expression of 69% was observed, being expressed in 100% of the high-grade squamous lesions (HSIL) and HR-HPV-DNA positives. Ki67 expression was associated with the lesion grade, being more expressive in the most severe lesions (p<0.001). p16(INK4A) and Ki67 markers coexpression was present in 86% of the samples (p<0.001), being 100% among those positive to HR-HPV-DNA with HSIL (p<0.001). The results suggest an association between the presence of HR-HPV infection and the p16(INK4a) and Ki67 expression and which is even stronger among women with HSIL. Copyright © 2014 Elsevier GmbH. All rights reserved.

  4. 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.

  5. 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

    mammary glands. HGF was of estrogen and IGF-I (36). Studies of cultured normal reportedly secreted by 3T3 - L1 adipocytes, raising the and cancerous...charcoal stripped fetal bovine serum. White bars=control treatment, black bars=10 nM estrogen. Cells were plated on plastic (Plas), collagen I (Col 1...free media was determined. Serum-free media contained 5 ng/ml EGF and 25 ng/ml IGF-I. White bars=control treatment, black bars=10 nM estrogen. Cells

  6. Nuclear receptor co-repressor is required to maintain proliferation of normal intestinal epithelial cells in culture and down-modulates the expression of pigment epithelium-derived factor.

    PubMed

    Doyon, Geneviève; St-Jean, Stéphanie; Darsigny, Mathieu; Asselin, Claude; Boudreau, Francois

    2009-09-11

    Stem cells of the gut epithelium constantly produce precursors that progressively undergo a succession of molecular changes resulting in growth arrest and commitment to a specific differentiation program. Few transcriptional repressors have been identified that maintain the normal intestinal epithelial cell (IEC) proliferation state. Herein, we show that the nuclear receptor co-repressor (NCoR1) is differentially expressed during the proliferation-to-differentiation IEC transition. Silencing of NCoR1 expression in proliferating cells of crypt origin resulted in a rapid growth arrest without associated cell death. A genechip profiling analysis identified several candidate genes to be up-regulated in NCoR1-deficient IEC. Pigment epithelium-derived factor (PEDF, also known as serpinf1), a suspected tumor suppressor gene that plays a key role in the inhibition of epithelial tissue growth, was significantly up-regulated in these cells. Chromatin immunoprecipitation experiments showed that the PEDF gene promoter was occupied by NCoR1 in proliferating epithelial cells. Multiple retinoid X receptor (RXR) heterodimers interacting sites of the PEDF promoter were confirmed to interact with RXR and retinoid acid receptor (RAR). Cotransfection assays showed that RXR and RAR were able to transactivate the PEDF promoter and that NCoR1 was repressing this effect. Finally, forced expression of PEDF in IEC resulted in a slower rate of proliferation. These observations suggest that NCoR1 expression is required to maintain IEC in a proliferative state and identify PEDF as a novel transcriptional target for NCoR1 repressive action.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Nuclei-Based Features for Uterine Cervical Cancer Histology Image Analysis With Fusion-Based Classification.

    PubMed

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

    2016-11-01

    Cervical cancer, which has been affecting women worldwide as the second most common cancer, can be cured if detected early and treated well. Routinely, expert pathologists visually examine histology slides for cervix tissue abnormality assessment. In previous research, we investigated an automated, localized, fusion-based approach for classifying squamous epithelium into Normal, CIN1, CIN2, and CIN3 grades of cervical intraepithelial neoplasia (CIN) based on image analysis of 61 digitized histology images. This paper introduces novel acellular and atypical cell concentration features computed from vertical segment partitions of the epithelium region within digitized histology images to quantize the relative increase in nuclei numbers as the CIN grade increases. Based on the CIN grade assessments from two expert pathologists, image-based epithelium classification is investigated with voting fusion of vertical segments using support vector machine and linear discriminant analysis approaches. Leave-one-out is used for the training and testing for CIN classification, achieving an exact grade labeling accuracy as high as 88.5%.

  14. Revisiting the human seminiferous epithelium cycle.

    PubMed

    Nihi, F; Gomes, M L M; Carvalho, F A R; Reis, A B; Martello, R; Melo, R C N; Almeida, F R C L; Chiarini-Garcia, H

    2017-06-01

    Can all types of testicular germ cells be accurately identified by microscopy techniques and unambiguously distributed in stages of the human seminiferous epithelium cycle (SEC)? By using a high-resolution light microscopy (HRLM) method, which enables an improved visualization of germ cell morphological features, we identified all testicular germ cells in the seminiferous epithelium and precisely grouped them in six well-delimitated SEC stages, thus providing a reliable reference source for staging in man. Morphological characterization of germ cells in human has been done decades ago with the use of conventional histological methods (formaldehyde-based fixative -Zenker-formal- and paraffin embedding). These early studies proposed a classification of the SEC in six stages. However, the use of stages as baseline for morphofunctional evaluations of testicular parenchyma has been difficult because of incomplete morphological identification of germ cells and their random distribution in the human SEC. Testicular tissue from adult and elderly donors with normal spermatogenesis according to Levin's, Johnsen's and Bergmann's scores were used to evaluate germ cell morphology and validate their distribution and frequency in stages throughout human spermatogenesis. Testicular tissue from patients diagnosed with congenital bilateral agenesis of vas deferens (n = 3 adults) or prostate cancer (n = 3 elderly) were fixed in glutaraldehyde and embedded in araldite epoxy resin. Morphological analyses were performed by both light and transmission electron microscopy. HRLM method enabled a reliable morphological identification of all germ cells (spermatogonia, spermatocytes and spermatids) based on high-resolution aspects of euchromatin, heterochromatin and nucleolus. Moreover, acrosomal development of spermatids was clearly revealed. Altogether, our data redefined the limits of each stage leading to a more reliable determination of the SEC in man. Occasionally, germ cells can be

  15. 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

  16. 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

  17. 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

  18. 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.

  19. Brain histology.

    PubMed

    Jeans, Alexander; Esiri, Margaret

    2008-10-01

    In this article we summarise nervous system histology in health and disease and acquaint the reader with developments in the staining techniques that are in current use, particularly immunostains. Although clinicians do not need to know the details of stain appearances, some familiarity with these aspects of neuropathology is invaluable in interpreting the reports they receive from the laboratory, as well as reminding them of the amazing beauty of the central nervous system's microscopic structure.

  20. Comparative characterization of the canine normal prostate in intact and castrated animals.

    PubMed

    Lai, Chen-Li; van den Ham, René; van Leenders, Geert; van der Lugt, Jaco; Teske, Erik

    2008-04-01

    Prostate diseases in the dog are generally regarded as representative for their human counterparts. We characterized the normal canine prostate in comparison to the normal human prostate. Prostates of dogs were examined histomorphologically and by immunohistochemical detection of the markers CK14, HMWCK, CK5, CK18, CK7, UPIII, PSA, and PSMA. Histomorphologically, the canine prostate lacks the human zonal differentiation, has much more prominent acini, while comprising less stromal tissue. In general, the canine prostate epithelium displayed a highly differentiated character, with no cells expressing CK14, minimal amounts of cells expressing HMWCK/CK5 and the vast majority of cells expressing CK18 and PSA. After castration, the prostate epithelium regressed, and the remaining tubules were largely populated by cells showing a ductal phenotype (HMWCK+/CK5+/CK18+/CK7+). The human and canine prostate are histologically differently organized. The general scheme of cellular differentiation of the prostate epithelium may however be applicable to both species.

  1. Histological and immunohistological investigation of the lymphoid tissue in normal and mycobacteria-affected specimens of the Rufous Hare-wallaby (Lagorchestes hirsutus)

    PubMed Central

    Young, LJ; McFarlane, R; Slender, AL; Deane, EM

    2003-01-01

    The histology of the spleen, lymph nodes, Gut-associated lymphoid tissue (GALT) and Bronchus-associated lymphoid tissue (BALT) are described for samples collected opportunistically from healthy and mycobacteria-affected specimens of the endangered marsupial Lagorchestes hirsutus, the Rufous Hare-wallaby. The structural elements, organization and distribution of T and B lymphocytes determined by immunohistological techniques using species cross-reactive antibodies in the lymph nodes, spleen and GALT of this species demonstrated lymphoid cell distributions that were consistent with other marsupial and eutherian mammals. The tissues of animals identified as acid-fast positive displayed immunopathology consistent with the responses to intracellular bacteria displayed in some eutherian mammals and included the presence of focal lesions, giant cells in the lung and lymphoid aggregations situated adjacent to blood and airway vessels. This is the first study to describe the lymphoid tissue of this rare macropod species and the first to document the tissue bed response to mycobacteria. PMID:12713272

  2. Thermosensitive chitosan-based hydrogels releasing stromal cell derived factor-1 alpha recruit MSC for corneal epithelium regeneration.

    PubMed

    Tang, Qiaomei; Luo, Chenqi; Lu, Bing; Fu, Qiuli; Yin, Houfa; Qin, Zhenwei; Lyu, Danni; Zhang, Lifang; Fang, Zhi; Zhu, Yanan; Yao, Ke

    2017-10-01

    Corneal epithelium integrity depends on continuous self-renewing of epithelium and connections between adjacent cells or between the cells and the basement membrane. Self-renewing epithelium cells mainly arise from the continuous proliferation and differentiation of the basal layer and limbal stem cells. The aim of the present study was to generate a bioactive, thermosensitive chitosan-gelatin hydrogel (CHI hydrogel) by incorporating exogenous recombinant human stromal cell-derived factor-1 alpha (SDF-1 alpha) for corneal epithelium regeneration. The exogenous SDF-1 alpha could enhance the stem cells proliferation, chemotaxis and migration, and the expression levels of related genes were significantly elevated in LESCs and mesenchymal stem cells (MSCs) in vitro. Moreover, the MSCs promoted the proliferation and maintained the corneal fate of the LESCs. The rat alkali injury model was used for in vivo study. The injured eyes were covered with CHI hydrogel alone or rhSDF-1 alpha-loaded CHI hydrogel. All rats were followed for 13days. Histological examination showed that the SDF-1 alpha/CHI hydrogel complex group had a nearly normal thickness; moreover, it was also found that this group could upregulate the expression of some genes and had more ΔNp63-positive cells. The SDF-1 alpha/CHI hydrogel complex group had a more tightly arranged epithelium compared with the control group using transmission electron microscopy (TEM). The mechanism for this may have involved the activation of stem cell homing and the secretion of growth factors via the SDF-1/CXCR4 chemokine axis. Therefore, SDF-1 alpha/CHI hydrogel complexes could provide a new idea for the clinical application. The clarity of cornea is important for normal vision. The loss or dysfunction of LESCs leads to the impairment of corneal epithelium. The complete regeneration of corneal epithelium has not been achieved. Our study demonstrated that the incorporation of rhSDF-1 alpha with CHI hydrogel accelerated corneal

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  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. 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.

  10. 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

  11. HISTOLOGICAL FEATURES OF EOSINOPHILIC ESOPHAGITIS IN CHILDREN AND ADOLESCENTS.

    PubMed

    Carrasco, Adriana Elisabeth Aguiar Benavides; Machado, Rodrigo Strehl; Patrício, Francy Reis da Silva; Kawakami, Elisabete

    2017-09-21

    Eosinophilic esophagitis is an emerging disease featured by eosinophilic esophageal infiltrate not responsive to proton pump inhibitors. To characterize histological features of children and adolescents with eosinophilic esophagitis. Cross-sectional study in a tertiary hospital. Biopsies from each esophageal third from 14 patients (median age 7 years) with eosinophilic esophagitis were evaluated. Histological features evaluated included morphometry of esophageal epithelium, esophageal density (per high power field), extracellular eosinophilic granules, eosinophilic microabscesses, surface disposition of eosinophils, epithelial desquamation, peripapillary eosinophilia, basal layer hyperplasia and papillary elongation. Several patients presented a normal esophageal macroscopy in the upper digestive endoscopy (6, 42.8%), and the most common abnormality were vertical lines (7, 50%) and whitish spots over esophageal mucosa (7, 50%). Basal layer hyperplasia was observed in 88.8%, 100% e 80% of biopsies from proximal, middle and lower esophagus, respectively (P=0.22). Esophageal density ranges from 0 to more than 50 per hpf. Extracellular eosinophilic granules (70%-100%), surface disposition of eosinophils (60%-93%), epithelial desquamation (60%-100%), peripapillary eosinophilia (70%-80%) were common, but evenly distributed among each esophageal third. Just one patient did not present eosinophils in the lower third, four in the middle third and four in the upper esophageal third. In the absence of hypereosinophilia, other histological features are present in eosinophilic esophagitis and may contribute to diagnosis. Eosinophilic infiltrate is focal, therefore multiple biopsies are needed for diagnosis.

  12. 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.

  13. [Regeneration of airway epithelium].

    PubMed

    Adam, D; Perotin, J-M; Lebargy, F; Birembaut, P; Deslée, G; Coraux, C

    2014-04-01

    Epithelial regeneration is a complex process. It can lead to the remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis. The development of in vivo and in vitro models has allowed the analysis of remodeling mechanisms and showed the role of components of extracellular matrix, proteases, cytokines and growth factors. Airway epithelial progenitors and stems cells have been studied in these models. However, their identification remains difficult. Identification and characterization of airway epithelial progenitor/stem-cells, and a better knowledge of the regeneration process may allow the development of new therapeutic strategies for airway epithelial reconstitution. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  14. Expressions of TRPVs in the cholesteatoma epithelium.

    PubMed

    Do, Ba Hung; Koizumi, Hiroki; Ohbuchi, Toyoaki; Kawaguchi, Rintaro; Suzuki, Hideaki

    2017-10-01

    We have recently proposed a hypothesis that acid leakage through the cholesteatoma epithelium mediates bone resorption in middle ear cholesteatoma. In the present study, we investigated the expressions of transient receptor potential vanilloid (TRPV) channels, which have been shown to play roles in the regulation of epidermal barrier function, in the cholesteatoma epithelium in comparison with the normal skin. Cholesteatoma epithelium and postauricular skin were collected from 17 patients with primary acquired middle ear cholesteatoma who underwent tympanomastoidectomy. Expressions of TRPV1, TRPV3, TRPV4, and TRPV6 were explored by fluorescence immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). TRPV1, TRPV3, TRPV4, and TRPV6 mRNAs were all detected by qRT-PCR both in the skin and cholesteatoma tissue. Immunohistochemical staining showed that TRPV1 and TRPV3 were positive in the viable cell layers of the epidermis of the skin, and only TRPV3 was positive in those of the cholesteatoma epithelium. The immunoreactivity for TRPV3 was significantly weaker in cholesteatoma than in the skin. The lower expression of TRPV3 in cholesteatoma may be one of the mechanisms underlying the increased permeability of this tissue. On the other hand, TRPV1, TRPV4, and TRPV6 are unlikely to be involved in the regulation of epithelial permeability in cholesteatoma.

  15. [Influence of cancer chemotherapy on conjunctival epithelium and goblet cells].

    PubMed

    Wojciechowska, Katarzyna; Jesionek-Kupnicka, Dorota; Jurowski, Piotr

    2013-01-01

    Evaluation of different types of chemotherapy schemes administered in lung, breast and bowel cancer on conjunctival epithelium and goblet cells morphology. 36 patients (72 eyes) were enrolled to the study. Patients were divided into three groups depending on type of cancer and chemotherapy: group I - patients diagnosed with non- small cells lung cancer treated with PE schema (cisplatin, etoposide), group II - with breast cancer treated with FAC schema (fluorouracil, doxorubicin, cyclophosphamide), group Ill - bowel cancer treated with FU/LV schema (fluorouracil, leucovorin). Examinations were performed before chemotherapy and after Il'th, IV'th, VI'th chemotherapy cycle. Conjuntival specimen were obtained with exfoliative cytology, stained with PAS and hematoxyline. Statistically significant deterioration of conjunctival epithelium and goblet cells in all the groups in each time of examination (p<0.001) was observed. Alterations were aggravated with duration of chemotherapy. Before chemotherapy all the patients had normal epithelium and goblet cells (grade 0 or 1 according to the Nelson's scale). Conjunctival cells status gradually deteriorated and altered from the normal glandular epithelium to the squamous cells epithelium through the process of squamous metaplasia. In further chemotherapy cycles each patient (1,0 fraction) had abnormal morphology of epithelium and goblet cells (grade 2 or 3 of Nelson's scale). Chemotherapy induces squamous metaplasia of epithelium and the reduction of number of conjunctival goblet cells. This abnormalities were time dependent and increased with duration of chemotherapy and were not depended on type of chemotherapy scheme.

  16. Effects of intratesticular zinc gluconate treatment on testicular dimensions, echodensity, histology, sperm production, and testosterone secretion in American black bears (Ursus americanus).

    PubMed

    Brito, Leonardo F C; Sertich, Patricia L; Rives, William; Knobbe, Marc; Del Piero, Fabio; Stull, Gordon B

    2011-05-01

    Eight adult American black bears were used to evaluate the effects of chemical castration by intratesticular zinc gluconate treatment on testicular dimensions, echodensity, histology, sperm production, and testosterone secretion. Treatment did not affect testicular dimensions and did not result in decreased resting or GnRH-stimulated testosterone secretion. Multifocal hyperchoic areas in the testicular parenchyma were observed on ultrasound examination, and white foci were observed on gross pathology examination after zinc gluconate treatment. Histologically, there were normal seminiferous tubules containing either round or elongated spermatids, along with abnormal tubules in all bears after treatment. Vacuolation of the seminiferous epithelium, sloughing of germ cells into the tubules' lumen, presence of multinuclear giant cells, and reduced height of the seminiferous epithelium with missing generations of germ cells were commonly observed. The most severe testicular changes were multifocal and included fibrosis, complete degeneration of the seminiferous epithelium with shrinkage of the tubule, and sperm stasis. Epididymal sperm reserve was 982.74 ± 654.16 × 10(6) sperm (mean ± SEM) and motile sperm were observed in the epididymis of all but one of the bears. In conclusion, although intratesticular zinc gluconate treatment in black bears resulted in testicular degenerative changes detected by ultrasound and histology examinations, sperm production was not completely ablated. We inferred that normal fertility might have been compromised, but treatment unlikely resulted in sterility. Copyright © 2011. Published by Elsevier Inc.

  17. Molecular Damage in the Bronchial Epithelium of Current and Former Smokers

    PubMed Central

    Wistuba, Ignacio I.; Lam, Stephen; Behrens, Carmen; Virmani, Arvind K.; Fong, Kwun M.; LeRiche, Jean; Samet, Jonathan M.; Srivastava, Sudhir; Minna, John D.; Gazdar, Adi F.

    2016-01-01

    Background Most lung cancers are attributed to smoking. These cancers have been associated with multiple genetic alterations and with the presence of preneoplastic bronchial lesions. In view of such associations, we evaluated the status of specific chromosomal loci in histologically normal and abnormal bronchial biopsy specimens from current and former smokers and specimens from nonsmokers. Methods Multiple biopsy specimens were obtained from 18 current smokers, 24 former smokers, and 21 nonsmokers. Polymerase chain reaction-based assays involving 15 polymorphic microsatellite DNA markers were used to examine eight chromosomal regions for genetic changes (loss of heterozygosity [LOH] and microsatellite alterations). Results LOH and microsatellite alterations were observed in biopsy specimens from both current and former smokers, but no statistically significant differences were observed between the two groups. Among individuals with a history of smoking, 86% demonstrated LOH in one or more biopsy specimens, and 24% showed LOH in all biopsy specimens. About half of the histologically normal specimens from smokers showed LOH, but the frequency of LOH and the severity of histologic change did not correspond until the carcinoma in situ stage. A subset of biopsy specimens from smokers that exhibited either normal or preneoplastic histology showed LOH at multiple chromosomal sites, a phenomenon frequently observed in carcinoma in situ and invasive cancer. LOH on chromosomes 3p and 9p was more frequent than LOH on chromosomes 5q, 17p (17p13; TP53 gene), and 13q (13q14; retinoblastoma gene). Microsatellite alterations were detected in 64% of the smokers. No genetic alterations were detected in nonsmokers. Conclusions Genetic changes similar to those found in lung cancers can be detected in the nonmalignant bronchial epithelium of current and former smokers and may persist for many years after smoking cessation. PMID:9308707

  18. Chronic tonsillitis: histological and immunohistochemical aspects.

    PubMed

    Mogoantă, Carmen Aurelia; Ioniţă, Elena; Pirici, D; Mitroi, Mihaela; Anghelina, Fl; Ciolofan, S; Pătru, Emilia

    2008-01-01

    Chronic tonsillitis represents the most common inflammatory lesions of the pharynx determining numerous local or distant evolutive complications. We decided to study the histological and especially immunohistochemical expression of this pathology. We have studied 112 surgical samples representing tonsils resected from 56 patients with chronic tonsillitis. The tonsillectomies were performed in the ENT Clinic of the Emergency County Hospital of Craiova, between 01.01.2007--31.12.2007. The processed histological samples were stained using Hematoxylin-Eosin, light green trichromic and argental impregnation. For the immunohistochemical study, we used LSAB method with CD20, CD45 RO, CD68 antibodies in order to reveal and differentiate T- and B-lymphocytes and also the macrophages. In all samples, we found hyperplasia and hypertrophy of the lymphoid follicle with excessive developing of the clear germinal center as a normal reaction to antigens presence. In some cases, we remarked micro hemorrhages and hematic extravasations inside the follicles, probably due to the excessive virulence of the pathogens causing endothelial lesions. The conjunctive stroma was enriched in collagen fibbers, in some cases organized in strong fascicles with an obvious tendency to divide the tonsils in lobules. The young fibroblastic type cells were numerous. The specific reticulin fibbers had a low representation being disorganized. The immunohistochemical study proved that the clear center of the lymphoid follicles was occupied by B-lymphocytes, but the T-lymphocytes were present in the cortical region of the follicles, perifollicles and in the surface epithelium. In some pathological cases, the predominant cellular population of the clear center was formed by T-lymphocytes.

  19. Retinol binding protein-4 circulating levels were higher in nonalcoholic fatty liver disease vs. histologically normal liver from morbidly obese women.

    PubMed

    Terra, Ximena; Auguet, Teresa; Broch, Montserrat; Sabench, Fàtima; Hernández, Mercè; Pastor, Rosa M; Quesada, Isabel M; Luna, Anna; Aguilar, Carmen; del Castillo, Daniel; Richart, Cristóbal

    2013-01-01

    We aimed to analyze the retinol binding protein-4 (RBP4) messenger RNA (mRNA) expression profiles in adipose tissues and liver of morbidly obese (MO) women with or without nonalcoholic fatty liver disease (NAFLD), and to study the relationships with other pro- and anti-inflammatory adipokines in vivo and in vitro. We performed a cross-sectional analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and liver samples from four lean and 45 MO women with or without NAFLD by enzyme-linked immunosorbent assay and real-time reverse transcription-PCR. We also studied RBP4 expression in HepG2 hepatocytes under various inflammatory stimuli. Circulating RBP4 levels were higher in MO women, and specifically, in MO subjects with NAFLD compared with normal liver controls (lean and MO). RBP4 liver expression was higher in nonalcoholic steatohepatitis (NASH)-moderate/severe than in NASHmild. Overall RBP4 gene expression was higher in liver than in adipose tissues. Among them, the higher expression corresponded to SAT. VAT expression was lower in the MO cohort. In HepG2, RBP4 mRNA expression was reduced by tumor necrosis factor (TNF)-α and increased by adiponectin treatment. The results obtained in MO women with NAFLD, brings up the use of RBP4 and other adipokines as a panel of noninvasive molecular biomarkers when NAFLD is suspected. Further studies are needed with other obesity groups. Copyright © 2012 The Obesity Society.

  20. Biochemical, histologic, and biomechanical characterization of native and decellularized flexor tendon specimens harvested from the pelvic limbs of orthopedically normal dogs.

    PubMed

    Balogh, Daniel G; Biskup, Jeffery J; O'Sullivan, M Gerard; Scott, Ruth M; Groschen, Donna; Evans, Richard B; Conzemius, Michael G

    2016-04-01

    To evaluate the biochemical and biomechanical properties of native and decellularized superficial digital flexor tendons (SDFTs) and deep digital flexor tendons (DDFTs) harvested from the pelvic limbs of orthopedically normal dogs. 22 commercially supplied tendon specimens (10 SDFT and 12 DDFT) harvested from the pelvic limbs of 13 canine cadavers. DNA, glycosaminoglycan, collagen, and protein content were measured to biochemically compare native and decellularized SDFT and DDFT specimens. Mechanical testing was performed on 4 groups consisting of native tendons (5 SDFTs and 6 DDFTs) and decellularized tendons (5 SDFTs and 6 DDFTs). All tendons were preconditioned, and tension was applied to failure at 0.5 mm/s. Failure mode was video recorded for each tendon. Load-deformation and stress-strain curves were generated; calculations were performed to determine the Young modulus and stiffness. Biochemical and biomechanical data were statistically compared by use of the Wilcoxon rank sum test. Decellularized SDFT and DDFT specimens had significantly less DNA content than did native tendons. No significant differences were identified between native and decellularized specimens with respect to glycosaminoglycan, collagen, or protein content. Biomechanical comparison yielded no significant intra- or intergroup differences. All DDFT constructs failed at the tendon-clamp interface, whereas nearly half (4/10) of the SDFT constructs failed at midsubstance. Decellularized commercial canine SDFT and DDFT specimens had similar biomechanical properties, compared with each other and with native tendons. The decellularization process significantly decreased DNA content while minimizing loss of extracellular matrix components. Decellularized canine flexor tendons may provide suitable, biocompatible graft scaffolds for bioengineering applications such as tendon or ligament repair.

  1. Immunohistochemical expression of p53 and its clinicopathological correlation with modified Anneroth's histological grading system

    PubMed Central

    Dave, Kajal V; Chalishazar, Monali; Dave, Vishal R; Panja, Pritam; Singh, Manisha; Modi, Tapan G

    2016-01-01

    Introduction and Objectives: Oral squamous cell carcinoma (OSCC) is an epithelial neoplasm generally beginning as focal overgrowth of altered stem cells near the basement membrane, moving upward and laterally, replacing the normal epithelium. Histopathological grading has been used for many decades in an attempt to predict the clinical behavior of oral squamous cell carcinoma. In the present study, Forty biopsies were studied for histological grading and p53 expression. The p53 expression was studied in relation to clinical parameters such as age, sex of patient and site of tumors. Relation between histological grade of malignancy and p53 protein expression was analysed. All cases were classified according to Anneroth's histological malignancy grading system (1987). Materials and Methods: 40 cases of OSCC were assessed for clinical parameters, Anneroth's histological grading and immunohistochemically stained with p53 protien. Statistical Analysis: The results obtained were analyzed using Spearman's Co-relation. Observations and Results: The positive expression of p53 was found in 62% of carcinomas studied. Positivity of p53 showed correlation with histological grade of malignancy and with individual parameters like degree of keratinization, nuclear polymorphism, number of mitoses and lymphoplasmacytic infiltration while showed a negative correlation with pattern of invasion. Conclusion: Our study showed a significant correlation between parameters of tumor cell population, lymphoplasmacytic infiltration and p53 expression. A significant association between high grade of malignancy and p53 overexpression and insignificant correlation of p53 with age, sex of the patient and site of the tumor was found. PMID:27194859

  2. 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

  3. 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.

  4. Thoracoabdominal foregut duplication cyst with respiratory epithelium and alimentary epithelium.

    PubMed

    Zhang, Juan; Zhang, Ke Ren; Bai, Yu Zuo; Song, Dan; Wang, Weilin

    2010-05-01

    Thoracoabdominal foregut duplication is a rare congenital abnormality. The authors report a case of thoracoabdominal foregut duplication cyst in a 13-year-old male patient. The pathologic report revealed that a thoracic mass with a pseudostratified, ciliated, columnar epithelial lining (respiratory tract epithelium), an abdominal mass with gastric mucosa (alimentary tract epithelium), and the cyst originated from the foregut. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Ovariectomy increases the phenotypic plasticity of the female prostate epithelium in the Mongolian gerbil (Meriones unguiculatus).

    PubMed

    Zanatelli, Marianna; Custodio, Ana M G; Biancardi, Manoel F; Santos, Fernanda C A; Góes, Rejane M; Falleiros-Jr, Luiz R; Vilamaior, Patricia S L; Taboga, Sebastião R

    2016-10-14

    The female prostate is a reproductive gland that typically presents a morphology similar to that of the male gland and is highly developed in female Mongolian gerbils. Two main cell populations compose the epithelium gland: basal and secretory luminal cells. However, during postnatal development, diverse secretory cell phenotypes are distributed among the typical ones. Prostate homeostasis is under the control of sexual hormones, such as oestrogen and progesterone. After hormonal deprivation the female gland undergoes several morphophysiological changes. The objective of this study was to identify and characterise, structurally and ultrastructurally, the cellular heterogeneity of the female prostate epithelium in normal conditions and after ovariectomy. Histological routine stains, such as haematoxylin-eosin, periodic acid-Schiff and silver impregnation, as well as immunocytochemical techniques were used to enable identification of the different cell types. Some secretory cells types were identified and characterised as mucinous, basophil, clear, ciliated, droplet, spumous and neuroendocrine cells. Population tally data showed that the hormonal suppression caused by ovariectomy resulted in a decrease in the proportions of basophil and clear cells and an increase in spumous cells. Thus, the secretory epithelial cells of the female gerbil prostate are not morphologically and functionally uniform, presenting a phenotypical plasticity according to the hormonal environment in which they operate.

  6. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26858899

  8. Lingual cyst lined by respiratory epithelium: a case report and review of literature.

    PubMed

    Juneja, Manish; Boaz, Karen; Srikant, N; Nandita, K P; Vidya, M

    2011-01-01

    The present report describes a case of a lingual cyst lined by a respiratory epithelium occurring in a 1-year-old girl. The article also reviews the cases published in the literature under the heading of lingual cysts and segregates all the cases having predominant respiratory epithelium as the cystic lining. Reclassification, with more descriptive histologic terminology to name the lingual cysts, has been proposed.

  9. 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.

  10. [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

  11. 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.

  12. 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.

  13. 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

  14. Generation of tooth-periodontium complex structures using high-odontogenic potential dental epithelium derived from mouse embryonic stem cells.

    PubMed

    Zhang, Yancong; Li, Yongliang; Shi, Ruirui; Zhang, Siqi; Liu, Hao; Zheng, Yunfei; Li, Yan; Cai, Jinglei; Pei, Duanqing; Wei, Shicheng

    2017-06-08

    A number of studies have shown that tooth-like structures can be regenerated using induced pluripotent stem cells and mouse embryonic stem (mES) cells. However, few studies have reported the regeneration of tooth-periodontium complex structures, which are more suitable for clinical tooth transplantation. We established an optimized approach to induce high-odontogenic potential dental epithelium derived from mES cells by temporally controlling bone morphogenic protein 4 (BMP4) function and regenerated tooth-periodontium complex structures in vivo. First, immunofluorescence and quantitative reverse transcription-polymerase chain reaction were used to identify the watershed of skin and the oral ectoderm. LDN193189 was then used to inhibit the BMP4 receptor around the watershed, followed by the addition of exogenous BMP4 to promote BMP4 function. The generated dental epithelium was confirmed by western blot analysis and immunofluorescence. The generated epithelium was ultimately combined with embryonic day 14.5 mouse mesenchyme and transplanted into the renal capsules of nude mice. After 4 weeks, the tooth-periodontium complex structure was examined by micro-computed tomography (CT) and hematoxylin and eosin (H&E) staining. Our study found that the turning point of oral ectoderm differentiation occurred around day 3 after the embryoid body was transferred to a common culture plate. Ameloblastin-positive dental epithelial cells were detected following the temporal regulation of BMP4. Tooth-periodontium complex structures, which included teeth, a periodontal membrane, and alveolar bone, were formed when this epithelium was combined with mouse dental mesenchyme and transplanted into the renal capsules of nude mice. Micro-CT and H&E staining revealed that the generated tooth-periodontium complex structures shared a similar histological structure with normal mouse teeth. An optimized induction method was established to promote the differentiation of mES cells into dental

  15. 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.

  16. On the origin of cardiac mucosa: a histological and immunohistochemical study of cytokeratin expression patterns in the developing esophagogastric junction region and stomach.

    PubMed

    De Hertogh, Gert; Van Eyken, Peter; Ectors, Nadine; Geboes, Karel

    2005-08-07

    To examine the fetal and neonatal esophagogastric junction region (EGJ) histologically for the presence of an equivalent to adult cardiac mucosa (CM); to study the expression patterns of all cytokeratins (CK) relevant to the EGJ during gestation; to compare the CK profile of the gestational and the adult EGJ; and to determine the degree of development in the adult EGJ histology and CK profile during gestation. Forty-eight fetal autopsy specimens of the EGJ were step-sectioned and stained with hematoxylin and eosin (H and E) to select sections showing the mucosal lining. Immunohistochemistry for CK5, 7, 8, 13, 18, 19, and 20 was performed. Antibody staining was then graded for location, intensity, and degree. The distal esophagus was lined by simple columnar epithelium from 12-wk gestational age (GA). The proximal part of this segment consisted of mucus-producing epithelium, devoid of parietal cells. CK5 and 13 were present exclusively in multilayered epithelia and CK8, 18, and 19 predominantly in simple columnar epithelium. There were no differences in the frequencies of the co-ordinate CK7+/20+ and the CK7-/20- immunophenotypes between different locations. The prevalence of the CK7+/20- immunophenotype decreased, and that of the CK7-/20+ immunophenotype increased significantly from the distal esophagus to the distal stomach. Fetal columnar-lined lower esophagus (fetal CLE) may be the equivalent and precursor of the short segments of columnar epithelium found in the distal esophagus of some normal adult subjects. Esophageal simple columnar epithelium without parietal cells (ESN) may be the precursor of adult CM. The similarities between the fetal and adult EGJ and stomach CK expression patterns support the conclusion that adult CM has an identifiable precursor in the fetus. This would then indicate that at least a part of the adult CM has a congenital origin.

  17. 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.

  18. 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.

  19. Characterization of Side Population Cells from Human Airway Epithelium

    PubMed Central

    Hackett, Tillie-Louise; Shaheen, Furquan; Johnson, Andrew; Wadsworth, Samuel; Pechkovsky, Dmitri V.; Jacoby, David B.; Kicic, Anthony; Stick, Stephen M.; Knight, Darryl A.

    2010-01-01

    The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelial cells were obtained from seven nontransplantable healthy lungs and four asthmatic lungs by pronase digestion. SP cells were identified by verapamil-sensitive efflux of the DNA-binding dye Hoechst 33342. Using flow cytometry, CD45− SP, CD45+ SP, and non-SP cells were isolated and sorted. CD45− SP cells made up 0.12% ± 0.01% of the total epithelial cell population in normal airway but 4.1% ± 0.06% of the epithelium in asthmatic airways. All CD45− SP cells showed positive staining for epithelial-specific markers cytokeratin-5, E-cadherin, ZO-1, and p63. CD45− SP cells exhibited stable telomere length and increased colony-forming and proliferative potential, undergoing population expansion for at least 16 consecutive passages. In contrast with non-SP cells, fewer than 100 CD45− SP cells were able to generate a multilayered and differentiated epithelium in air-liquid interface culture. SP cells are present in human tracheobronchial epithelium, exhibit both short- and longterm proliferative potential, and are capable of generation of differentiated epithelium in vitro. The number of SP cells is significantly greater in asthmatic airways, providing evidence of dysregulated resident SP cells in the asthmatic epithelium. PMID:18653771

  20. 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

  1. [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.

  2. Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co-expressed in normal, hyperplastic, and neoplastic human breast epithelium.

    PubMed

    Poulsom, R; Hanby, A M; Lalani, E N; Hauser, F; Hoffmann, W; Stamp, G W

    1997-09-01

    pS2-TFF 1 is expressed in breast cancers and has been investigated as a potential prognostic factor reflecting oestrogen dependence. The relationship to the expression of other trefoil peptides, human spasmolytic polypeptide (hSP-TFF 2) and intestinal trefoil factor (hITF/hPI.B-TFF 3) is documented here. Fifty-seven breast specimens were selected from surgical pathology archives and included five normal breasts (two lactating), seven benign proliferative lesions, 11 ductal carcinomas in situ (DCIS), three lobular carcinomas in situ (LCIS), 24 invasive ductal carcinomas (IDC), and seven invasive lobular carcinomas (ILC). The comparative distribution of trefoil mRNAs was assessed by in situ hybridization using 35S-labelled riboprobes and immunohistochemical staining for pS2-TFF 1 and hSP-TFF 2. pS2-TFF 1 and hITF/hPI.B-TFF 3 mRNA were focally present at low signal intensity in normal and benign breast. Both pS2-TFF 1 and hITF/hPI.B-TFF 3 were expressed in all DCIS, LCIS and ILC, and 21/24 IDC. Overall, expression patterns of pS2-TFF 1 and hITF/hPI.B-TFF 3 coincided, but hITF/hPI.B-TFF 3 mRNA was usually found in a greater proportion of cells. Expression of hSP-TFF 2 peptide or mRNA was not detected in any of these cases. MCF 7 breast carcinoma cells also expressed hITF/hPI.B-TFF 3 and pS2-TFF 1 mRNAs but not hSP-TFF 2. hITF/hPI.B-TFF 3 co-expression with pS2-TFF 1 may act as a prognostic factor, but also raises questions about the regulatory pathway for pS2-TFF 1 hITF/hPI.B-TFF 3. Trefoil factors have effects on cell motility and spreading in vitro, and co-expression of hITF/hPI.B-TFF 3 with pS2-TFF 1 could be functionally significant if they form a heterodimer or compete for receptor binding. Absence of hSP-TFF 2 expression may be of equal relevance to tumour cell biology.

  3. Stimulation of mucus secretion, ciliary activity, and transport in frog palate epithelium.

    PubMed

    Spungin, B; Silberberg, A

    1984-11-01

    Particle transport velocity and ciliary beat frequency, at the level of a single cell of the epithelium, were measured simultaneously. The preparation used keeps the mucociliated epithelium of the frog palate functionally intact but is thin enough for light to be transmitted. The observations confirm that there exists a resting, or unstimulated, state of the epithelium in which the cilia do not beat. It is shown that tactile stimulation (contact with a small 50- to 75-microns foreign particle or with a fine wire probe) restarts ciliary beat. If the epithelium has not been depleted of its mucus, normal ciliary beat frequency is restored, and there is particle transport at the normal velocity. Only the cilia surrounding the moving particle in a patch about 10 times larger are beating at one time. Beat frequency is highest in the center of the patch, near the particle, and tapers to zero toward the edge. Mucus has to be present for particle transport to occur. Particles impacted on a depleted epithelium are not moved. The placement of previously collected endogenous mucus onto a depleted epithelium produces full ciliary activity and normal particle transport. The moving patch of beating cilia corresponds to a plaque of mucus surrounding the particle being transported. This plaque was produced upon first impact of the particle, presumably by mucus secretion, from the epithelial region which then surrounds it. Stimulation of a quiescent nondepleted epithelium with a wire probe induces a normal ciliary beat frequency that gradually decreases to zero. Stimulation by a wire probe of a mucus-depleted epithelium produces a level of initial beat frequency much below normal. Depletion of the epithelial preparation is by an episode of "creeping" over a glass surface. Depletion of the epithelium could be demonstrated histochemically. Analysis of the data of particle velocity and beat frequency is consistent with a wave-length of 45 microns for the metachronous wave.

  4. 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

  5. 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.

  6. Submucosal glands in the columnar-lined oesophagus: evidence of an association with metaplasia and neosquamous epithelium.

    PubMed

    Lörinc, Ester; Öberg, Stefan

    2012-07-01

    A multipotential stem cell, possibly located in the submucosal gland ducts, has been suggested as the origin of metaplastic mucosa in the oesophagus. The topographic distribution of these glands and their excretory ducts (SMG) within the columnar lined oesophagus (CLO) is largely unknown. The aim of this study was to examine the distribution of SMG in relation to the type of overlying epithelium in patients with CLO. Seven oesophageal resection specimens were examined histologically in toto. The median frequency of SMG was similar in the metaplastic segments (0.12 SMG/mm) and the normal squamous segments (0.10 SMG/mm). Within the metaplastic segments, the median frequency of SMG beneath the squamous islands was significantly higher than that observed under the columnar lined parts (0.22 versus 0.08 SMG/mm, P = 0.046), There was a strong accumulation of SMG at the squamo-columnar transition zones (0.53 SMG/mm), which was significantly greater than that found in the columnar and squamous parts (P = 0.001 and 0.002, respectively). The relative accumulation of SMG beneath squamous islands and the squamo-columnar junctions within the metaplastic segment supports the hypothesis that both metaplastic columnar mucosa and neosquamous epithelium originate from a progenitor in the SMG. © 2012 Blackwell Publishing Ltd.

  7. Histological Effect of Certain Pickles on the Human Gastric Mucos

    PubMed Central

    MacDonald, W. C.; Anderson, F. H.; Hashimoto, S.

    1967-01-01

    The histological effects of several types of pickles and control substances were assessed by repeated suction (per os) biopsies of the gastric antrum in three healthy men. The ingestion of 30 ounces of fukujinzuke (assorted vegetables pickled in soy sauce) or of vinegared gherkins over a three-day period caused marked changes in the surface epithelium and gastric pits in all three subjects. The abnormalities consisted of loss of cellular mucus, nuclear enlargement, prominent nuclear chromatin and an increased number of mitotic figures. All control biopsies were normal, as were biopsies after the ingestion of 30 ounces of raw carrots or cucumbers over a three-day period. This study shows that eating a sufficient quantity of certain types of pickles causes marked changes in the human stomach. Peroral suction biopsy of the gastric antrum appears to be a practical method for testing the effect of various foods on the human gastric mucosa. ImagesFig. 1Fig. 2aFig. 2bFig. 3aFig. 3bFig. 4Fig. 5aFig. 5b PMID:6026337

  8. 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…

  9. 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…

  10. Restoration of the normal squamous lining in Barrett's esophagus by argon beam plasma coagulation.

    PubMed

    Byrne, J P; Armstrong, G R; Attwood, S E

    1998-10-01

    Barrett's esophagus is associated with significantly increased risk of development of esophageal adenocarcinoma. Replacing columnar epithelium with the normal squamous lining in this condition offers the possibility of decreasing the risk of degeneration to invasive adenocarcinoma. This study aimed to establish the feasibility of argon beam plasma coagulation (ABPC), in conjunction with control of gastroesophageal reflux, to restore the squamous lining. Thirty patients with Barrett's esophagus (four low-grade dysplasia, three high-grade) were recruited from our surveillance program, and underwent endoscopic ABPC. Twenty-seven patients completed treatment, with macroscopic replacement of their columnar lining by squamous epithelium, histologically confirmed in all 27, and followed up for a median of 9 months (range, 6-18 months). Two patterns of squamous replacement were identified: 70% of patients showed squamous epithelium with no persistent intestinal metaplasia, and in 30% the new squamous epithelium covered areas of underlying intestinal metaplasia. One patient has withdrawn from the study. Two esophageal perforations, with one death, occurred early in the study. ABPC, in conjunction with control of gastroesophageal reflux, allows squamous regrowth in both benign and dysplastic Barrett's esophagus. Despite the theoretical safety advantages of ABPC over techniques such as laser, esophageal perforation may occur with this technique. It is too soon to recommend ABPC for dysplastic or nondysplastic Barrett's because follow-up is too short to show a decreased incidence of and mortality from adenocarcinoma.

  11. 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.

  12. 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.

  13. [Histological findings in an irradiated choroidal melanoma].

    PubMed

    Koinzer, S; Hasselbach, H; Bräsen, J H; Leuschner, I; Roider, J

    2011-06-01

    Histological findings of choroidal melanomas after proton beam irradiation have been reported for complicated cases after enucleation. We present specimens of a tumor after transretinal probe excision. One year after irradiation, the biopsy was examined histologically. The specimens showed pigmented, spindle-shaped cells staining positively for Melan-A and HMB-45. Ki-67 showed low proliferation. Caspase-3 staining was normal. The melanoma still contained vital and even single proliferating cells, but regressed afterwards without additional therapy.

  14. 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.

  15. Pigmentation of the Lacrimal Sac Epithelium.

    PubMed

    Jakobiec, Frederick A; Stagner, Anna M; Sutula, Francis C; Freitag, Suzanne K; Yoon, Michael K

    To describe the patterns of the melanocytic populations of 3 cases of lacrimal sac benign melanosis and 1 of atypical primary-acquired sac melanosis with a melanomatous nodule secondary to spread of atypical conjunctival primary-acquired melanosis to the sac. Clinical records, photographs, and paraffin sections stained with hematoxylin and eosin and the Fontana reaction were critically reviewed. Additional sections were immunoreacted for melanoma antigen recognized by T cells and microphthalmia-associated transcription factor. Five nonpigmented pterygia and 4 nonpigmented lacrimal sacs served as controls. Three patients with obstructive dacryocystitis and benign melanosis were African-Americans whose sacs disclosed the presence of nonclustering, melanoma antigen recognized by T cells, and microphthalmia-associated transcription factor-positive intraepithelial dendritic melanocytes at all levels of the epithelium. The transferred melanin granules were concentrated in the adlumenal apical region of the epithelial cells. No fusiform melanocytes were found in the lamina propria. The fourth patient, a white, had atypical conjunctival and sac primary-acquired melanosis and conjunctival and sac melanomas. The intraepithelial sac melanocytes in this case were strikingly atypical and profusely distributed in a back to back fashion at all levels of a thickened epithelial layer focally approximating the appearance of a melanoma in situ. Five nonpigmented pterygia and 4 nonpigmented lacrimal sacs served as controls. Each displayed nonnesting dendritic melanocytes of various densities without back to back contact. Low densities of intraepithelial melanocytes were discovered in all controls and therefore represent a normal subpopulation within the conjunctival and lacrimal sacs. Due to the pseudostratification of the sac epithelium, melanocytes can move to higher levels without implying atypia. Benign melanosis is produced by small diffusely distributed individual

  16. 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.

  17. 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.

  18. Ozone-Induced Injury and Oxidative Stress in Bronchiolar Epithelium Are Associated with Altered Pulmonary Mechanics

    PubMed Central

    Sunil, Vasanthi R.

    2013-01-01

    In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3h) resulted in rapid (within 3h) and persistent (up to 72h) 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 24h 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 (3–24h), 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. PMID:23492811

  19. Interactive Atlas of Histology

    PubMed Central

    Goubran, Emile Z.; Vinjamury, Sivarama P.

    2007-01-01

    Purpose: An interactive atlas of histology was developed for online use by chiropractic students to enable them to practice and self-assess their ability to identify various histological structures. This article discusses the steps in the development, implementation, and usefulness of an interactive atlas of histology for students who take histology examinations. Methods: The atlas was developed by digitizing images imported through a video-microscope using actual microscope slides. Leica EWS 2100 and PowerPoint software were used to construct the atlas. The usefulness of the atlas was assessed through a comparison of histology exam scores between four classes before and four classes after the use of the atlas. Analysis of admissions data, including overall grade point average (GPA), science and nonscience GPA, and a number of course units, was done initially to avoid any identifiable differences in the academic competency between the two being compared. A survey of the students was also done to assess atlas usefulness and students' satisfaction with the atlas. Results: Analysis of histology exam scores showed that the average scores in the lab exam were significantly higher for the classes that used the atlas. Survey results showed a high level of student satisfaction with the atlas. Conclusion: The development and use of an online interactive atlas of histology for chiropractic students helped to improve lab exams scores. In addition, students were satisfied with the features and usefulness of this atlas. PMID:18483638

  20. 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.

  1. The effects of coronavirus on human nasal ciliated respiratory epithelium.

    PubMed

    Chilvers, M A; McKean, M; Rutman, A; Myint, B S; Silverman, M; O'Callaghan, C

    2001-12-01

    Human coronavirus (HCoV) accounts for 15-30% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium. The authors examined the effects of infection with HCoV on ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immediately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by transmission electron microscopy. Symptom diaries were kept for the duration of the study. All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6-14.0) and day 3 (9.4 Hz (95% CI 7.2-11.6)), there was a significant increase (p<0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0-0.5)) and day 3 (1.1 (95% CI 0.5-1.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary structure and function were found between day 0 and day 3. Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infection, may occur without overt clinical symptoms.

  2. Abhraka Bhasma treatment ameliorates proliferation of germinal epithelium after heat exposure in rats

    PubMed Central

    Bhatia, Babita S.; Kale, Purushottam G.; Daoo, Jayashree V.; Panchal, Pranali P.

    2012-01-01

    This study was conducted to evaluate the protective effect of Abhraka Bhasma on spermatogenesis in heat-damaged testis. A histological analysis over the sukravaha srotomula (testes) of male albino Wistar rat was carried out in order to examine the potency of the test drug in preventing the organ from heat damage. The current experiment was carried out on 32 healthy adult male albino Wistar rats divided into four groups. Sahastraputi Abhraka Bhasma, subjected to 1000 putas, was used as the test drug. On sacrificing the animals after 30 days, it was observed that control animals (G1) had normal spermatogenesis and drug-induced animals (G2) showed hyperactive tubules. Testicular hyperthermia occurred in few (G3) animals, who were subjected to 43°C for 1 h daily for four consecutive weeks, resulting in degeneration of tubules with inspissated spermatozoa (25%) leading to atrophy of the organ. 3% tubules showed disintegration, 23% were in the recovery stage while 71% tubules exhibited enhanced proliferation of germinal epithelium leading to hypertrophy and hyperplasia. The present study reveals that the test drug can correct heat-induced male infertility and provides us with the possibility of treatment of human heat-induced oligozoospermia and azoospermia. Hence, this ayurvedic maharasa (primary mineral) can be a promising formulation as an anti-impotency fecundity drug. PMID:23661864

  3. Abhraka Bhasma treatment ameliorates proliferation of germinal epithelium after heat exposure in rats.

    PubMed

    Bhatia, Babita S; Kale, Purushottam G; Daoo, Jayashree V; Panchal, Pranali P

    2012-04-01

    This study was conducted to evaluate the protective effect of Abhraka Bhasma on spermatogenesis in heat-damaged testis. A histological analysis over the sukravaha srotomula (testes) of male albino Wistar rat was carried out in order to examine the potency of the test drug in preventing the organ from heat damage. The current experiment was carried out on 32 healthy adult male albino Wistar rats divided into four groups. Sahastraputi Abhraka Bhasma, subjected to 1000 putas, was used as the test drug. On sacrificing the animals after 30 days, it was observed that control animals (G1) had normal spermatogenesis and drug-induced animals (G2) showed hyperactive tubules. Testicular hyperthermia occurred in few (G3) animals, who were subjected to 43°C for 1 h daily for four consecutive weeks, resulting in degeneration of tubules with inspissated spermatozoa (25%) leading to atrophy of the organ. 3% tubules showed disintegration, 23% were in the recovery stage while 71% tubules exhibited enhanced proliferation of germinal epithelium leading to hypertrophy and hyperplasia. The present study reveals that the test drug can correct heat-induced male infertility and provides us with the possibility of treatment of human heat-induced oligozoospermia and azoospermia. Hence, this ayurvedic maharasa (primary mineral) can be a promising formulation as an anti-impotency fecundity drug.

  4. 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.

  5. Notch signaling promotes the corneal epithelium wound healing.

    PubMed

    Lu, Huayi; Lu, Qingxian; Zheng, Yajuan; Li, Qiutang

    2012-01-01

    The Notch signaling pathway plays crucial roles in regulation of cell proliferation, differentiation and cell fate decision in multiple tissues and cell types. This study was designed to test the effects of enhanced Notch activity on corneal epithelium homeostasis and wound healing using the transgenic mice that overexpressed an activated Notch1 (NICD) in cornea epithelium. The studies were performed on R26(fN1-ICD) transgenic mice that carry a NICD cDNA (cDNA) whose expression is prevented by a "Lox-STOP-Lox" cassette. When this transgenic mouse is bred to a mouse strain carrying a Cre recombinase expression cassette driven by a tissue-specific keratin 14 (K14) promoter, the floxed "STOP" cassette is excised and NICD is expressed in the cornea epithelium. The expression level of NICD and its downstream target genes, hairy and enhancer of split 1 (Hes1) and hairy/enhancer-of-split related with YRPW motif 1 (Hey1), in the transgenic corneal epithelium was examined by quantitative PCR (qPCR). The phenotypes and morphology of the transgenic corneal epithelium were compared with that of wild type (WT) controls. The proliferation rate of the epithelial cells was assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation and the differentiation statues were examined by K14, tumor protein p63 (p63), K12, and zona occludens 1 (ZO-1) immunoreactivity at either normal developmental condition or after corneal epithelial debridement. The corneal epithelial response to wound healing was studied by fluorescent staining and Richardson's staining macroscopically and by H&E staining at microscope level at 0, 6, 12, 18, and 24 h post injury. Although overexpression of NICD in cornea epithelium led to upregulation of its downstream targets, i.e., Hes1 and Hey1, this did not alter corneal epithelial cell proliferation and differentiation. However, wound healing induced Notch activity and overexpression of NICD promoted corneal epithelial wound healing, which was in agreement with more

  6. 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

  7. Cell proliferation is not required for the initiation of early cleft formation in mouse embryonic submandibular epithelium in vitro.

    PubMed

    Nakanishi, Y; Morita, T; Nogawa, H

    1987-03-01

    An X-ray irradiation method was employed to analyse the role of cell proliferation in vitro in the cleft formation of mouse embryonic submandibular epithelium at early stages. When the mid 12-day gland was exposed to 200 rad of X-rays, the growth was severely retarded. In contrast, late 12-day and early 13-day glands grew apparently in a normal fashion, as did the control gland, for up to 40 h. In either case, they formed shallow clefts within 10 h of culture. With 1000 rad irradiation, the mid 12-day gland did not grow at all, but formed clefts within 20 h of culture followed by a rapid degeneration. Under the same conditions, the growth of the late 12-day gland, which was at the stage just before branching, was retarded until 10 h of culture, followed by a slight increase in epithelial size, but cleft formation was also observed within 6-10 h, as in the control gland. When exposed to a dose of 1000 rad of X-rays, the early 13-day and the late 12-day glands exhibited similar radiosensitivity; the initial narrow clefts in the epithelium deepened and new clefts began to form within 6-10 h of culture. [3H]thymidine incorporation studies revealed that a dose of 1000 rad reduced DNA synthesis of mid and late 12-day glands by 72 and 65%, respectively. Histological examination of X-irradiated late 12-day gland showed that mitotic figures were rarely seen in the epithelium at 6 h of culture. Aphidicolin, a specific inhibitor of DNA synthesis, could not halt the cleft formation of the late 12-day gland. In this experiment 89% of DNA synthesis was inhibited. Treatment of an X-ray irradiated late 12-day gland with aphidicolin blocked 92% of the DNA synthesis, but did not prevent cleft formation taking place. These results indicate that neither cell division nor DNA synthesis, is required for the initiation process of the cleft formation of the mouse embryonic submandibular epithelium at early morphogenetic stages in vitro.

  8. 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

  9. Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

    PubMed

    Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

    2016-01-01

    In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. 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

  11. 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.

  12. Histology of periapical lesions obtained during apical surgery.

    PubMed

    Schulz, Malte; von Arx, Thomas; Altermatt, Hans Jörg; Bosshardt, Dieter

    2009-05-01

    The aim of this was to evaluate the histology of periapical lesions in teeth treated with periapical surgery. After root-end resection, the root tip was removed together with the periapical pathological tissue. Histologic sectioning was performed on calcified specimens embedded in methylmethacrylate (MMA) and on demineralized specimens embedded in LR White (Fluka, Buchs, Switzerland). The samples were evaluated with light and transmission electron microscopy (TEM). The histologic findings were classified into periapical abscesses, granulomas, or cystic lesions (true or pocket cysts). The final material comprised 70% granulomas, 23% cysts and 5% abscesses, 1% scar tissues, and 1% keratocysts. Six of 125 samples could not be used. The cystic lesions could not be subdivided into pocket or true cysts. All cysts had an epithelium-lined cavity, two of them with cilia-lined epithelium. These results show the high incidence of periapical granulomas among periapical lesions obtained during apical surgery. Periapical abscesses were a rare occasion. The histologic findings from samples obtained during apical surgery may differ from findings obtained by teeth extractions. A determination between pocket and true apical cysts is hardly possible when collecting samples by apical surgery.

  13. 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

  14. 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.

  15. Neuropilins: expression and roles in the epithelium

    PubMed Central

    Wild, Jonathan R L; Staton, Carolyn A; Chapple, Keith; Corfe, Bernard M

    2012-01-01

    Summary Initially found expressed in neuronal and then later in endothelial cells, it is well established that the transmembrane glycoproteins neuropilin-1 (NRP1) and neuropilin-2 (NRP2) play essential roles in axonal growth and guidance and in physiological and pathological angiogenesis. Neuropilin expression and function in epithelial cells has received little attention when compared with neuronal and endothelial cells. Overexpression of NRPs is shown to enhance growth, correlate with invasion and is associated with poor prognosis in various tumour types, especially those of epithelial origin. The contribution of NRP and its ligands to tumour growth and metastasis has spurred a strong interest in NRPs as novel chemotherapy drug targets. Given NRP’s role as a multifunctional co-receptor with an ability to bind with disparate ligand families, this has sparked new areas of research implicating NRPs in diverse biological functions. Here, we review the growing body of research demonstrating NRP expression and role in the normal and neoplastic epithelium. PMID:22414290

  16. [Precancerous changes in the epithelium of the cervix uteri: terminology and principles of differential diagnosis].

    PubMed

    Danilova, N V; Andreeva, Iu Iu; Mal'kov, P G

    2010-01-01

    Three most popular classifications of precancerous changes in the epithelium of the cervix uteri, their merits and demerits, morphological criteria, and principles of differential diagnosis are considered. The advantage of the SIL classification is the more accurate reflection of the biology of the process and a common terminological base proposed for histological and cytological classifications, which is particularly important to overcome difficulties in clinical interpretation. LGSIL provides a high rate of diagnostic errors; therefore elaboration of unique criteria for histological evaluation is a problem of great importance. HGSIL should be differentiated with regenerative and atrophic processes in the cervix uteri with a special accuracy.

  17. 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

  18. Diode laser endoscopic cyclophotocoagulation in the normal equine eye.

    PubMed

    Harrington, Jay T; McMullen, Richard J; Cullen, John M; Campbell, Nigel B; Gilger, Brian C

    2013-03-01

    To determine the clinical and histologic effects of diode endoscopic cyclophotocoagulation (ECP) in the phakic equine eye. Phase I: 10 equine cadaver eyes. Phase II: four normal adult horses. Phase I: ECP probe angle of reach (AR) was determined. Multiple ECP energy levels: 0.75, 0.90, 1.05, 1.20, 1.35, 1.50 J, and the resulting visible and histologic ciliary process changes were evaluated. Phase II: Ocular quadrants were treated with ECP at 0.90, 1.14, 1.38 J, and a control. The contralateral eye underwent a sham operation. Tissue changes (clinical and histologic) were evaluated. Phase I: Mean combined AR was 162 ± 29 degrees. Mean visible tissue scores: 2.60 ± 0.58 (0.75 J) to 5.04 ± 0.30 (1.50 J) from possible total of 6. Tissue 'popping' was observed at 1.50 J. Histologic ciliary tissue damage was present at all settings. Phase II: Mean visible tissue scores: 2.90 ± 0.48 (0.90 J), 3.61 ± 0.57 (1.14 J), and 4.52 ± 0.56 (1.38 J). Tissue 'popping' was observed at 1.38 J. Histologic ciliary tissue damage was present at all settings. Clinical effects included acute inflammation, intraocular pressure reduction, cataract formation, corneal edema, corneal ulceration, and postoperative ocular hypertension. Diode ECP between 0.90 and 1.14 J is a potential treatment option for glaucoma in horses based on visible tissue effects and target ciliary epithelium damage. Iatrogenic cataract development may limit the use of an anterior chamber approach in phakic horses. Supported in part by an ACVO VAF grant. © 2012 American College of Veterinary Ophthalmologists.

  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. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24785116

  6. 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.

  7. 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.

  8. 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.

  9. Histological Organization in Hepatocyte Organoid Cultures

    PubMed Central

    Michalopoulos, George K.; Bowen, William C.; Mulè, Karen; Stolz, Donna Beer

    2001-01-01

    Hepatocytes and other cellular elements isolated by collagenase perfusion of the liver and maintained in defined culture conditions undergo a series of complex changes, including apoptosis and cell proliferation, to reconstruct tissue with specific architecture. Cultures in collagen-coated pleated surface roller bottles, with hepatocyte growth medium medium and in the presence of hepatocyte growth factor (HGF) and epidermal growth factor (EGF), form characteristic and reproducible tissue architecture composed of a superficial layer of biliary epithelial cells, an intermediate layer of connective tissue and hepatocytes, and a basal layer of endothelial cells. Dexamethasone, EGF, and HGF are required for the complete histological organization. Analysis of the structures formed demonstrates that the receptor tyrosine kinase ligands HGF and EGF are required for the presence, growth, and phenotypic maturation of the biliary epithelium on the surface of the cultures and for the formation of connective tissue in the cultures. Dexamethasone, in the presence of HGF and EGF, was required for the phenotypic maturation of hepatocytes. The results demonstrate the role of these molecules for the formation and phenotypic maturation of specific histological elements of the liver and suggest roles for these signaling molecules in the formation and structure of the in vivo hepatic architecture. PMID:11696448

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Decreased expression of intelectin 1 in the human airway epithelium of smokers compared to nonsmokers.

    PubMed

    Carolan, Brendan J; Harvey, Ben-Gary; De, Bishnu P; Vanni, Holly; Crystal, Ronald G

    2008-10-15

    Lectins are innate immune defense proteins that recognize bacterial cell wall components. Based on the knowledge that cigarette smoking is associated with an increased risk of infections, we hypothesized that cigarette smoking may modulate the expression of lectin genes in airway epithelium. Affymetrix microarrays were used to survey the expression of lectin genes in large airway epithelium from nine nonsmokers and 20 healthy smokers and in small airway epithelium from 13 nonsmokers and 20 healthy smokers. There were no changes (>2-fold change; p < 0.05) in lectin gene expression among healthy smokers compared with nonsmokers except for down-regulation of intelectin 1, a lectin that binds to galactofuranosyl residues in bacterial cell walls (large airway epithelium, p < 0.01; small airway epithelium, p < 0.01). This was confirmed by TaqMan RT-PCR in both large (p < 0.05) and small airway epithelium (p < 0.02). Immunohistochemistry assessment of airway biopsies demonstrated that intelectin 1 was expressed in secretory cells, while Western analysis confirmed the decreased expression of intelectin 1 in airway epithelium of healthy smokers compared with healthy nonsmokers (p < 0.02). Finally, compared with healthy nonsmokers, intelectin 1 expression was also decreased in small airway epithelium of smokers with lone emphysema and normal spirometry (n = 13, p < 0.01) and smokers with established chronic obstructive pulmonary disease (n = 14, p < 0.01). In the context that intelectin 1 plays a role in defense against bacteria, its down-regulation in response to cigarette smoking is another example of the immunomodulatory effects of smoking on the immune system and may contribute to the increase in susceptibility to infections observed in smokers.

  15. Decreased Expression of Intelectin 1 in the Human Airway Epithelium of Smokers Compared to Nonsmokers*

    PubMed Central

    Carolan, Brendan J.; Harvey, Ben-Gary; De, Bishnu P.; Vanni, Holly; Crystal, Ronald G.

    2009-01-01

    Summary Lectins are innate immune defense proteins that recognize specific bacterial cell wall components. Based on the knowledge that cigarette smoking is associated with increased risk of bacterial infections, we hypothesized that cigarette smoking may modulate the expression of lectin genes in airway epithelium. Affymetrix microarrays were used to survey expression of lectin genes in large airway epithelium from 9 nonsmokers and 20 healthy smokers and in small airway epithelium from 13 nonsmokers and 20 healthy smokers. There were no changes (>2-fold change, p<0.05) in lectin gene expression among healthy smokers compared to nonsmokers except for a striking down regulation of intelectin 1, a lectin that binds to galactofuranosyl residues in the cell walls of bacteria (large airway epithelium, p<0.01; small airway epithelium, p<0.01). This was confirmed by TaqMan RT-PCR in both large (p<0.05) and small airway epithelium (p<0.02). Immunohistochemistry assessment of airway biopsies demonstrated that intelectin 1 was expressed in secretory cells, while Western analysis confirmed the decreased expression of intelectin 1 in airway epithelium of healthy smokers compared to healthy nonsmokers (p<0.02). Finally, compared to healthy nonsmokers, intelectin 1 expression was also decreased in small airway epithelium of smokers with lone emphysema with normal spirometry (n= 13, p<0.01) and smokers with established COPD (n= 14, p<0.01). In the context that intelectin 1 is an epithelial molecule that likely plays a role in defense against bacteria, its down regulation in response to cigarette smoking is another example of the immunomodulatory effects of smoking on the immune system and may contribute to the increase in susceptibility to infections observed in smokers, including those with COPD. PMID:18832735

  16. 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

  17. Bone marrow histology in monoclonal macroglobulinemia.

    PubMed

    Rywlin, A M; Civantos, F; Ortega, R S; Dominguez, C J

    1975-06-01

    Rywlin, Arkadi, M., Civantos, Francisco, Ortega, Rolando S., and Dominguez, Carlos J.: Bone marrow histology in monoclonal macroglobulinemiamam J Clin Pathol 63. 769-778, 1975. Histologic sections and smears of aspirated bone marrow particles in 26 cases of monoclonal macroglobulinemia were studied. The bone marrows did not show uniform histologic features. Twenty-two patients had various degrees of lymphoid infiltration of the marrow, including nodules of malignant lymphoma, diffuse lymphocytic infiltration, nodular lymphoid hyperplasia, and normal lymphoid nodules. Four patients had no demonstrable lymphoid collections in the marrow. Additional histologic features of the marrows are summarized. A variant of a Dutcher body consisting of multiple PAS-positive inclusions that by light microscopy appear intranuclear is described. Even though the average macroglobulin levels were higher in patients with abnormal lymphoid infiltrates than in patients with noraml or no lymphoid collections, there was considerable overlap between individual patients values in the different groups. Similarly, no correlation between macroglobulin levels and other histologic features could be established. Patients with monoclonal macroglobulinemia represent a spectrum including benign monoclonal gammopathy, lymphoproliferative disorders of the marrow, nodal or extranodal lymphomas. The separation of Waldenström's macroglobulinemia by arbitrary criteria does not appear justified. (key words: Bone marrow; Monoclonal macroglobulinemia.

  18. Effects of formaldehyde on xenotransplanted human respiratory epithelium. Research report, August 1986-April 1991

    SciTech Connect

    Klein-Szanto, A.J.P.; Ura, H.; Momiki, S.; Bonfil, D.; Litwin, S.

    1992-07-01

    A laboratory animal model that permits the exposure of xenotransplanted human respiratory epithelium to formaldehyde was used to study the effects of formaldehyde alone or in combination with a carcinogenic metabolite of benzo(a)pyrene, benzo(a)pyrene diol epoxide. Epithelial cells obtained from autopsies of 20 full-term human fetuses or infants less than one year old were isolated, amplified in vitro, inoculated into rat tracheas from which the epithelial layer had been removed, and then transplanted subcutaneously into irradiated athymic nude mice. Four weeks after transplantation, the tracheal transplants were implanted with silastic devices containing 0, 0.5, 1, or 2 mg of powdered formaldehyde (Study 1). The tracheal transplants were examined histologically 2, 4, 8, or 16 weeks after transplantation. Before killing, all animals were injected with a single pulse of tritiated thymidine. A maximum effect was visible two weeks after exposure; 2 mg of formaldehyde produced numerous areas of epithelial erosion and inflammation. All doses produced areas of hyperplastic epithelium and areas of atrophic epithelium. The labeling indices showed dose dependence between two and four weeks after the initiation of exposure. These studies show that low doses of formaldehyde can elicit a proliferative response in human infant tracheobronchial epithelium that is not preceded by a massive toxic effect. Similar studies using xenotransplanted human adult nasal respiratory epithelium (Study 2) showed a response pattern similar to that of Study 1. In Study 3, using cells from 11 human infants, formaldehyde applied simultaneously or sequentially with benzo(a)pyrene diol epoxide did not induce epithelial alterations different from those observed with formaldehyde alone. This indicated that, under the doses and exposure conditions used, it was not possible to observe any cocarcinogenic or promoting effects of formaldehyde on the human infant tracheobronchial epithelium.

  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. THE PERMEABILITY OF RAT TRANSITIONAL EPITHELIUM

    PubMed Central

    Hicks, R. M.

    1966-01-01

    Permeability barriers must exist in transitional epithelium to prevent the free flow of water from underlying blood capillaries through the epithelium into the hypertonic urine, and such a barrier has now been demonstrated in isolated bladders. This barrier is passive in function and can be destroyed by damaging the luminal surface of the transitional epithelium with sodium hydroxide and 8 M urea solutions, by digesting it with trypsin, lecithinase C, and lecithinase D, or by treating it with lipid solvents such as Triton x 100 and saponin. From this it is concluded that the barrier depends on the integrity of lipoprotein cell membranes. The barrier function is also destroyed by sodium thioglycollate solutions, and electron microscope investigations show that sodium thioglycollate damages the thick asymmetric membrane which limits the luminal face of the superficial squamous cell. Cytochemical staining shows the epithelium to contain disulfide and thiol groups and to have a concentration of these groups at the luminal margin of the superficial cells. It thus appears that the permeability barrier also depends on the presence of disulfide bridges in the epithelium, and it is presumed that these links are located in keratin. Because of the effect of thioglycollates, both on the barrier function and on the morphology of the membrane, it is suggested that keratin may be incorporated in the thick barrier membrane. It is proposed that the cells lining the urinary bladder and ureters should be regarded as a keratinizing epitheluim. PMID:5901498

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. [In vivo imaging of the conjunctival epithelium using confocal laser scanning microscopy].

    PubMed

    Rath, R; Stave, J; Guthoff, R; Giebel, J; Tost, F

    2006-05-01

    In various ocular diseases, cytomorphological findings of the ocular surface are an essential component of clinical diagnostics. When evaluating the conjunctival epithelium, minimally invasive acquisition of biomaterial is necessary for lab and technical processing and in vitro histological examination. To examine corneal structures in vivo, confocal laser scanning microscopy is a successful standard method. Our aim was to employ in vivo confocal laser scanning microscopy also for examining the conjunctival epithelium. Results were analyzed and compared with cytomorphological findings of impression cytology. Accordingly, the basic features of conjunctival in vivo examination using RLSM were described and defined. In vivo images were analyzed and compared with impression cytological slide preparations (n=110) of 23 healthy test persons. Examination was standardized. Finally, the confocal laser scan images were compared to the impression cytological patterns. Due to the distribution of reflectors (pixel brightness), diagnostic analysis of important morphological structures (cell nucleus, cytoplasm, nucleus/plasma relation) of the conjunctiva is possible. Secretory cells of the epithelium (goblet cells) can be easily recognized by their size. Highly reflective pixels depict cell walls or wide intercellular spaces with high contrast. The in vivo investigation of important anatomical and morphological structures of the conjunctival epithelium is possible using RLSM. The distribution pattern of goblet cell pixel brightness may correlate with various secretion contents or suggest distinct, recognizable, functional conditions (hypo- or hypersecretion).

  6. [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.

  7. 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.

  8. 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

  9. 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.

  10. Transcriptome of the human retina, retinal pigmented epithelium and choroid

    PubMed Central

    Tian, Lifeng; Kazmierkiewicz, Krista L; Bowman, Anita S; Li, Mingyao; Curcio, Christine A; Stambolian, Dwight E

    2015-01-01

    The retina and its adjacent supporting tissues -- retinal pigmented epithelium (RPE) and choroid -- are critical structures in human eyes required for normal visual perception. Abnormal changes in these layers have been implicated in diseases such as age-related macular degeneration and glaucoma. With the advent of high-throughput methods, such as serial analysis of gene expression, cDNA microarray, and RNA sequencing, there is unprecedented opportunity to facilitate our understanding of the normal retina, RPE, and choroid. This information can be used to identify dysfunction in age-related macular degeneration and glaucoma. In this review, we describe the current status in our understanding of these transcriptomes through the use of high throughput techniques. PMID:25645700

  11. Proliferation of the Superficial Epithelium of Ovaries in Senile Female Rats Following Oral Administration of Conjugated Equine Estrogens

    PubMed Central

    Perniconi, Sergio Eduardo; de Jesus Simões, Manuel; dos Santos Simões, Ricardo; Haidar, Mauro Abi; Baracat, Edmund C; Soares, Jose Maria

    2008-01-01

    OBJECTIVE To evaluate the effect of different concentrations of estrogen on the ovarian superficial epithelium in senile female rats. Design: Fifty female rats at 15 months of age and with irregular estrous cycles were selected and randomly divided into five experimental groups containing equal numbers of animals in each: GPROP, control group receiving vehicle only; GE0.05mg, group receiving conjugated equine estrogens (CEE) at a dose of 50 μg/kg; GE0.5mg, group receiving CEE at 500 μg/kg; GE1mg, group receiving CEE at 1 mg/kg; and GE2mg, receiving CEE at 2 mg/kg. The length of treatment was 21 days. After this period, the animals were anesthetized and the ovaries were fixed in 10% formaldehyde and processed for routine histology. Histomorphology was analyzed by light microscopy, and histomorphometrics were evaluated using the Imagelab program. RESULTS In the GPROP and GE0.05mg groups, the superficial epithelium of the ovary had a simple cuboidal shape, and as the estrogen dose increased, the epithelium thickened, with pseudo-stratified or stratified epithelium appearing in the GE2mg group. The animals in the group given the highest estrogen dose (GE2mg) showed the thickest ovarian epithelium and the largest perimeter and surface area of the surface ovarian epithelium (P < 0.01). However, the difference in epithelium thickness between the GE0.5mg and GE1mg groups was only slight. CONCLUSION Our data suggest that CEE at a dose of 2 mg/kg may induce marked proliferation of rat ovarian epithelium. PMID:18568250

  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. 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

  14. Histological and ultrastructural studies on the toxic effect of pan masala and its amelioration by Elettaria cardamomum.

    PubMed

    Kumari, Sweety; Dutta, Abhijit

    2014-03-01

    To investigate the histological and ultrastructural changes observed in pan masala intoxicated mammalian testes under the effect of cardamom. Male Swiss mice were given pan masala orally at a dose of 2% of the feed and cardamom at a dose of 0.2% of the feed. They were divided into three groups, control (Group I), pan masala-treated (Group II), and a combination of pan masala and cardamom-treated group (Group III). Histologically, the testes of Group II mice displayed degeneration of tubular epithelium, disruption of spermatogenesis, and a marked reduction in germ cells. When cardamom was given, damage was less with fewer distorted cells and also improvement with normal tubules and spermatid differentiation in Group III. Ultrastructurally, pan masala-treated testes showed cytoplasmic vacuolation, shrinkage and pyknotic nuclei of spermatogonia, and abnormal acrosomal granules. When cardamom was given, the amelioration process was more evident showing a comparable morphology with control. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  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. Glycoconjugate secretion in human airways in vitro: effects of epithelium removal.

    PubMed Central

    Sossé-Alaoui, H; Labat, C; Gorenne, I; Thomas de Montpreville, V; Bara, J; Brink, C

    1998-01-01

    The aim of this study was to examine glycoconjugate secretion in human airways with and without an epithelium. Glycoconjugate release in supernatants derived from human airways in vitro was determined using an ELISA assay with an anti-human mucin monoclonal antibody (MAb 3D3). This monoclonal antibody reacted strongly with Le(b) antigen but also recognized in vitro Le(a) and Le(y) determinants. In 11 of the 34 different lung samples (32%) studied the glycoconjugate levels were below the threshhold of detection for this assay. The mean basal secretion of glycoconjugates in human airways in vitro was 100+/-28 microg/g tissue (Period I; n = 23 different lung samples). The amount of glycoconjugate measured in the medium derived from human isolated bronchial ring preparations did not change under control conditions during the course of the experimental procedure (Period I; 128+/-46 microg/g tissue and Period II; 159 +/-48 microg/g tissue; n = 13 paired lung samples). In the supernatants of airway preparations with an intact epithelium the amount of glycoconjugates detected was 90+/-38 microg/g tissue (Period I; n = 12 different lung samples) and removal of the epithelium did not alter this basal glycoconjugate release (94+/-60 microg/g tissue: Period I, n = 8 different lung samples). The absence of the epithelial layer was confirmed by histological evaluation. Methacholine (100 microM) induced a 10- and four-fold increase in glycoconjugate release from airways with and without an epithelium, respectively. In contrast, in preparations with an epithelium, LTD4 (10 microM) and anti-IgE (dilution: 1/1000) did not cause an increase of glycoconjugate release. The methacholine difference between airways with and without an epithelium was not significantly different (P > 0.10). However, a treatment with atropine (100 microM) prevented the increase of glycoconjugate release in preparations with an epithelium. These data derived from a limited number of experiments suggest that

  17. 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.

  18. 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.

  19. [Regeneration of corneal epithelium using keratin modified chitosan membranes].

    PubMed

    Grolik, Maria; Kopeć, Maciej; Szczubiałka, Krzysztof; Wowra, Bogumił; Dobrowolski, Dariusz; Wylegała, Edward; Nowakowska, Maria

    2012-01-01

    The cornea is a transparent front layer of the eye. It functions like a window that controls and focuses the light entering into the eye. The cornea contributes to 65-75% of the eye's total focusing power and it acts as a physical barrier against pathogenic microorganisms, dirt and other noxious physical factors. The corneal tissue is arranged in five basic layers. The outermost layer (epithelium) is made up of highly regenerative cells that allow for quick healing of superficial injuries. Eye infections, diseases, or mechanical injury can harm corneal epithelium and cause blindness. Under certain circumstances, to prevent that, it is recommended to perform complete corneal transplantation. However, due to lack of sufficient number of donors, researchers are searching for alternative solutions.. Regeneration of epidermal tissue can restore and ensure normal functioning of cornea. For that purpose proper grafts are needed. The goal of current research was to develop the material for scaffold preparation providing optimal conditions for the epithelium cornea cell culturing and to determine its chemical, physical, and biological properties. The scaffolds, which could be applied in ophthalmology should fulfill a lot of requirements, among them such as biocompatibility, biodegradability, restorability, non-toxicity. They should also have adequate mechanical strength, flexibility and porosity. The aim of this work was to synthesize and to determine the properties of polymeric material for ophthalmic surgery applications. A hydrogel scaffold in the form of membrane was obtained from chitosan - natural, biocompatible, biologically inert, stable in the natural environmental and antibacterial polysaccharide derived from chitin. Biodegradable chitosan films containing keratin were crosslinked with genipin - a naturally occurring and nontoxic agent. In this study we present physicochemical characterization of the scaffolds. Porosity, contact angle and swelling ratio (at

  20. [Experimental hypervitaminosis A in the rat. 14. Morphological and morphometric study of changes in the esophageal epithelium].

    PubMed

    Oliveira, J A; Silva-Netto, C R; Sala, M A; Lopes, R A; Maia Campos, G

    1990-01-01

    Male rats were subjected to hypervitamin A treatment by daily intraperitoneal injections of 150 UI Arovit per g body weight. Another group of rats were injected intraperitoneally with saline solution for ten days and were used as controls. The results indicated that: 1) the body weight of animals treated with excess vitamin A was decreased; 2) histological analysis of the esophageal epithelium in treated animals showed increased thickness, characterizing a picture of hyperplasia and hypertrophy. On the basis of the results obtained, we suggest that excess vitamin A may act on the esophageal epithelium by direct action on the epithelial structures, stimulating and increase of the mitosis, and on the epithelium (mediated by the adrenals), resulting in increased thickness due to the concentration of a larger number of more immature cells. These alterations were more evident in the lower esophageal third.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

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

    PubMed

    Delben, Juliana Aparecida; Zago, Chaiene Evelin; Tyhovych, Natalia; Duarte, Simone; Vergani, Carlos Eduardo

    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

  8. 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

  9. Rhinovirus Delays Cell Repolarization in a Model of Injured/Regenerating Human Airway Epithelium

    PubMed Central

    Faris, Andrea N.; Ganesan, Shyamala; Chattoraj, Asamanja; Chattoraj, Sangbrita S.; Comstock, Adam T.; Unger, Benjamin L.; Hershenson, Marc B.

    2016-01-01

    Rhinovirus (RV), which causes exacerbation in patients with chronic airway diseases, readily infects injured airway epithelium and has been reported to delay wound closure. In this study, we examined the effects of RV on cell repolarization and differentiation in a model of injured/regenerating airway epithelium (polarized, undifferentiated cells). RV causes only a transient barrier disruption in a model of normal (mucociliary-differentiated) airway epithelium. However, in the injury/regeneration model, RV prolongs barrier dysfunction and alters the differentiation of cells. The prolonged barrier dysfunction caused by RV was not a result of excessive cell death but was instead associated with epithelial-to-mesenchymal transition (EMT)-like features, such as reduced expression of the apicolateral junction and polarity complex proteins, E-cadherin, occludin, ZO-1, claudins 1 and 4, and Crumbs3 and increased expression of vimentin, a mesenchymal cell marker. The expression of Snail, a transcriptional repressor of tight and adherence junctions, was also up-regulated in RV-infected injured/regenerating airway epithelium, and inhibition of Snail reversed RV-induced EMT-like features. In addition, compared with sham-infected cells, the RV-infected injured/regenerating airway epithelium showed more goblet cells and fewer ciliated cells. Inhibition of epithelial growth factor receptor promoted repolarization of cells by inhibiting Snail and enhancing expression of E-cadherin, occludin, and Crumbs3 proteins, reduced the number of goblet cells, and increased the number of ciliated cells. Together, these results suggest that RV not only disrupts barrier function, but also interferes with normal renewal of injured/regenerating airway epithelium by inducing EMT-like features and subsequent goblet cell hyperplasia. PMID:27119973

  10. Cell Lineage metastability in Gfi1-deficient mouse intestinal epithelium.

    PubMed

    Bjerknes, Matthew; Cheng, Hazel

    2010-09-01

    Elucidating the mechanisms determining multipotent progenitor cell fate remains a fundamental project of contemporary biology. Various tissues of mice and men with defects in the zinc-finger transcriptional repressor Gfi1 have dramatic perturbations in the proportions of their differentiated cell types. In Gfi1-deficient intestinal epithelium there is a shift from mucous and Paneth towards enteroendocrine cells, leading to the proposal that Gfi1 functions in the allocation of the progeny derived from a hypothetical common granulocytic progenitor. However, studies of clones have yielded no evidence of such a common progenitor prompting us to investigate alternate mechanisms explaining the Gfi1-deficient phenotype. We report that mucous and Paneth but not enteroendocrine lineage cells normally express Gfi1. Sporadic mucous and Paneth lineage cells in the crypts of Gfi1-deficient mice aberrantly express the pro-enteroendocrine transcription factor Neurog3, indicating that stable repression of Neurog3 in these lineages requires Gfi1. Importantly, we also find mucous and Paneth lineage cells in various stages of cellular reprogramming into the enteroendocrine lineage in Gfi1-deficient mice. We propose that mucous and Paneth cell lineage metastability, rather than reallocation at the level of a hypothetical common granulocytic progenitor, is responsible for the shifts in cell type proportions observed in Gfi1-deficient intestinal epithelium. Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.

  11. 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.

  12. 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.

  13. [Anatomy and histology of salivary glands of Triatominae].

    PubMed

    Lacombe, D

    1999-01-01

    Histological studies upon the salivary glands of ten species of triatomine bugs were performed looking for their number and structural organization in different genera. It was possible to evaluate the celular epithelium type of each gland, as well as the merocrine and apocrine secretions of the glands. Secretion run until the hilo and after to salivary pump and hypofaringe. The glandular components, D1, D2 and D3 are always present in the Triatoma, Panstrongylus and Diptelogaster but in Rhodnius there are only the first two pairs of glands. The salivary channels and the hilo are analyzed by histology. The whole pair D3 has a clear valve that regularizes the exit of the secretions to the hilo. According to the genus the valves appear in different locations. They have low and dense epithelium, and their nucleus are rich in chromatin. The secondary channels leaving these valves, are very different, with clear chitinous ringer, low level of chromatin in the nucleus and homogeneous cytoplasm.

  14. Visualization of ex vivo human ciliated epithelium and induced flow using optical coherence tomography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Ling, Yuye; Gamm, Uta A.; Yao, Xinwen; Arteaga-Solis, Emilio; Emala, Charles W.; Choma, Michael A.; Hendon, Christine P.

    2017-04-01

    The ciliated epithelium is important to the human respiratory system because it clears mucus that contains harmful microorganisms and particulate matter. We report the ex vivo visualization of human trachea/bronchi ciliated epithelium and induced flow characterized by using spectral-domain optical coherence tomography (SD-OCT). A total number of 17 samples from 7 patients were imaged. Samples were obtained from Columbia University Department of Anesthesiology's tissue bank. After excision, the samples were placed in Gibco Medium 199 solution with oxygen at 4°C until imaging. The samples were maintained at 36.7°C throughout the experiment. The imaging protocol included obtaining 3D volumes and 200 consecutive B-scans parallel to the head-to-feet direction (superior-inferior axis) of the airway, using Thorlabs Telesto system at 1300 nm at 28 kHz A-line rate and a custom built high resolution SDOCT system at 800nm at 32 kHz A-line rate. After imaging, samples were processed with H and E histology. Speckle variance of the time resolved datasets demonstrate significant contrast at the ciliated epithelium sites. Flow images were also obtained after injecting 10μm polyester beads into the solution, which shows beads traveling trajectories near the ciliated epithelium areas. In contrary, flow images taken in the orthogonal plane show no beads traveling trajectories. This observation is in line with our expectation that cilia drive flow predominantly along the superior-inferior axis. We also observed the protective function of the mucus, shielding the epithelium from the invasion of foreign objects such as microspheres. Further studies will be focused on the cilia's physiological response to environmental changes such as drug administration and physical injury.

  15. [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.

  16. [Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures].

    PubMed

    Rojas, Luz-Marina; Mata, Claunis; Oliveros, Aridays; Salazar-Lugo, Raquel

    2013-06-01

    Abstract: Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures. Water temperature is an important factor that affects growth and antioxidant enzyme activities in fish, and when adverse, it may trigger diseases in fish populations. C. macropomum is a freshwater neotropical fish widely distributed in South America and abundant in river basins as the Amazon and Orinoco. It is highly used for intensive aquaculture development and is a very important product for the local riverside economy in Venezuela. The purpose of our study was to examine the water temperature effect on gills, liver and kidneys of juvenile fishes of C macropomum. Eighteen juveniles with biometrical index of 17.87 +/- 7.88 cm and 87.69 +/- 34.23 g were respectively exposed to three culture temperatures (T18, T29 and T35 degrees C) during a period of 21 days. Histological analyses on gills, liver and kidney were made according to standard methodologies. Our results showed that these tissues exhibited normal citoarchitecture at T29. On the contrary, T18-gills displayed brachiallipid droplets inside brachial epithelium; and disorganization in the brachial tissue was observed at T35. Furthermore, we observed two kinds of hepatocytes (dark and light) on T180 degrees C-liver. The T35-liver samples showed cytoplasmatic granulation and damages in cytoplasmatic membrane. Kidney samples from T18 observed alterations in the cellular distribution of the hematopoietic tissue; while, at T35, the most important feature observed was the disorganization of the glomerular structure. We concluded that T18 and T35 are respectively critical and severe temperatures to C. macropomum; besides, the most sensible tissues to changes induced by temperature in this species were the liver and gills.

  17. 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

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

    DTIC Science & Technology

    2011-09-01

    0893-3952/11 $32.00 www.modernpathology.org length, correlates with aneuploidy and lymph node metastasis ,9 and shorter telomeres were associated with... metastasis in invasive human breast carcinoma. Breast Cancer Res Treat 1999;54:59–64. 10 Radpour R, Barekati Z, Haghighi MM, et al. Correlation of...axillary node metastasis , and histopathologic grading. Cancer 1984;54:2237–2242. 26 Anderson WF, Chu KC, Chatterjee N, et al. Tumor variants by hormone

  19. 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

  20. 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.

  1. 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

  2. Biomechanical and Histopathologic Effects of Pulsed-Light Accelerated Epithelium-On/-Off Corneal Collagen Cross-Linking.

    PubMed

    Zhang, Xiaoyu; Sun, Ling; Shen, Yang; Tian, Mi; Zhao, Jing; Zhao, Yu; Li, Meiyan; Zhou, Xingtao

    2017-07-01

    This study aimed to compare the biomechanical and histopathologic effects of transepithelial and accelerated epithelium-off pulsed-light accelerated corneal collagen cross-linking (CXL). A total of 24 New Zealand rabbits were analyzed after sham operation (control) or transepithelial or epithelium-off operation (45 mW/cm for both). The transepithelial group was treated with pulsed-light ultraviolet A for 5 minutes 20 seconds, and the epithelium-off group was treated for 90 seconds. Biomechanical testing, including ultimate stress, Young modulus, and the physiological modulus, was analyzed. Histological changes were evaluated by light microscopy and transmission electron microscopy. The stress-strain curve was nonlinear in both accelerated transepithelial and epithelium-off CXL groups. The stress and elastic moduli were all significantly higher in both experimental groups compared with the control group (P < 0.05), whereas there were no significant differences between the 2 treatment groups (P > 0.05). Six months after the operation, hematoxylin and eosin staining and transmission electron microscopy showed that the subcutaneous collagen fibers were arranged in a regular pattern, and the fiber density was higher in the experimental groups. Both transepithelial and accelerated epithelium-off CXL produced biomechanical and histopathologic improvements, which were not significantly different between the 2 pulsed-light accelerated CXL treatments.

  3. The anatomy of the dog soft palate. II. Histological evaluation of the caudal soft palate in brachycephalic breeds with grade I brachycephalic airway obstructive syndrome.

    PubMed

    Pichetto, Michela; Arrighi, Silvana; Roccabianca, Paola; Romussi, Stefano

    2011-07-01

    In brachycephalic dogs, the skull bone shortening is not paralleled by a decreased development of soft tissues. Relatively longer soft palate is one of the main factors contributing to pharyngeal narrowing during normal respiratory activity of these dog breeds, which are frequent carriers of the brachycephalic airway obstructive syndrome (BAOS), which affects most part of them during their postnatal life. No histological studies assessing the morphology and the normal tissue composition of the soft palate in brachycephalic dogs are available, neither has ever been determined whether the elongated soft palate is a primary or secondary event. Aim of this study was to describe the morphology of the caudal soft palate in brachycephalic dogs with Grade I BAOS to identify potential features possibly favoring the pathogenesis of BAOS. Specimens from brachycephalic dogs (N = 11) that underwent preventive surgery were collected from surgery, processed for histology, and examined at six transversal levels. The brachycephalic soft palates showed peculiar features such as thickened superficial epithelium, extensive oedema of the connective tissue, and mucous gland hyperplasia. Several muscular alterations were evidenced in addition. The results of this investigation add to the general knowledge of the anatomy of soft palate in the canine species and establish baseline information on the morphological basis of the soft palate thickening in brachycephalic dogs. Copyright © 2011 Wiley-Liss, Inc.

  4. 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

  5. Intrinsic Defense Mechanisms of the Intestinal Epithelium.

    PubMed

    Ramanan, Deepshika; Cadwell, Ken

    2016-04-13

    The intestinal epithelium is a single cell layer that facilitates the absorption of nutrients but also provides a tight barrier to prevent pathogen invasion and dissemination of commensal microbes. Specialized epithelial cells of the gastrointestinal tract achieve this frontline defense by working in concert with lymphoid, myeloid, and stromal cells to secrete an array of factors that limit direct contact between the epithelium and infectious agents. The importance of these mechanisms is underscored by the ability of enteric pathogens to target these mechanisms to achieve invasion and dissemination. This review highlights recent advances in our understanding of these intricate molecular and cellular mechanisms adopted by these cells to promote spatial segregation and barrier maintenance. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Intrinsic Defense Mechanisms of the Intestinal Epithelium

    PubMed Central

    Ramanan, Deepshika; Cadwell, Ken

    2016-01-01

    SUMMARY The intestinal epithelium is a single cell layer that facilitates the absorption of nutrients but also provides a tight barrier to prevent pathogen invasion and dissemination of commensal microbes. Specialized epithelial cells of the gastrointestinal tract achieve this front-line defense by working in concert with lymphoid, myeloid, and stromal cells to secrete an array of factors that limit direct contact between the epithelium and infectious agents. The importance of these mechanisms is underscored by the ability of enteric pathogens to target these mechanisms to achieve invasion and dissemination. This review highlights recent advances in our understanding of these intricate molecular and cellular mechanisms adopted by these cells to promote spatial segregation and barrier maintenance. PMID:27049583

  7. 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.

  8. 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

  9. 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.

  10. [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.

  11. Electrically assisted delivery of macromolecules into the corneal epithelium.

    PubMed

    Hao, Jinsong; Li, S Kevin; Liu, Chia-Yang; Kao, Winston W Y

    2009-12-01

    Electrically assisted delivery is noninvasive and has been investigated in a number of ocular drug delivery studies. The objectives of this study were to examine the feasibility of electrically assisted delivery of macromolecules such as small interfering RNA (siRNA) into the corneal epithelium, to optimize the iontophoresis and electroporation methods, and to study the mechanisms of corneal iontophoresis for macromolecules. Anodal and cathodal iontophoresis, electroporation and their combinations were the methods examined with mice in vivo. Cyanine 3 (Cy3)-labeled glyceraldehyde-3-phosphate dehydrogenase (GAPDH) siRNA and fluorescein isothiocyanate (FITC)-labeled dextran of different molecular weights (4-70 kDa) were the macromolecules studied. Microscopy and histology after cryostat sectioning were used to analyze and compare the delivery of the macromolecules to the cornea. Iontophoresis was effective in delivering siRNA and dextran up to 70 kDa into the cornea. The electroporation method studied was less effective than that of iontophoresis. Although both iontophoresis and electroporation alone can deliver the macromolecules into the cornea, these methods alone were not as effective as the combination of iontophoresis and electroporation (iontophoresis followed by electroporation). The significant enhancement of dextran delivery in anodal iontophoresis suggests that electroosmosis can be a significant flux-enhancing mechanism during corneal iontophoresis. These results illustrate the feasibility of electrically assisted delivery of macromolecules such as siRNA into the cornea.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Endoscopic and histological features of gastric cancers after successful Helicobacter pylori eradication therapy.

    PubMed

    Saka, Akiko; Yagi, Kazuyoshi; Nimura, Satoshi

    2016-04-01

    Gastric cancer after successful Helicobacter pylori eradication therapy is often difficult to diagnose by endoscopy because of its indistinct borderline or lack of obviously cancerous characteristics. Furthermore, it has become evident that non-neoplastic epithelium covers cancerous areas in gastric cancer after eradication. Here, we investigated these endoscopic features and their relationship to histological findings. We studied 24 and 47 gastric cancers in patients who had (eradication group) and had not (control group) undergone H. pylori eradication, respectively. A gastritis-like appearance revealed by conventional endoscopy was defined as a mucosal pattern with no marked difference from the surrounding non-cancerous area and that revealed by narrow-band imaging (NBI)-magnifying endoscopy (ME) as the mucosal pattern observed in H. pylori-associated atrophic gastritis. We investigated a gastritis-like appearance revealed by conventional endoscopy (A), a gastritis-like appearance at the margin (B) and within (C) the cancerous area revealed by NBI-ME, and the histological characteristics of the overlying non-neoplastic epithelium. We also evaluated the relationship between endoscopic and histological findings in the eradication group. Endoscopy showed that features A, B and C were significantly more frequent in the eradication group (P = 0.031, P < 0.001, P < 0.001, respectively). Non-neoplastic epithelium covered more than 10 % of the cancerous area more frequently in the eradication group. In the eradication group, more than 90 % of cancers showing a gastritis-like appearance had non-neoplastic epithelium extending over 10 % of the cancerous area. Gastric cancer after successful H. pylori eradication tends to have gastritis-like features due to non-neoplastic epithelium covering the cancerous tissue.

  17. 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.

  18. 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

  19. Novel organelles in primate retinal epithelium.

    PubMed

    Biesemeier, A; Gouras, P

    2016-10-01

    We are investigating age-related changes in organelles in monkey retinal epithelium using transmission and analytic electron microscopy. We previously described a circular organelle in retinal epithelium with a diameter of about 0.5μm. The organelle is unique in containing a single, round vacuole within an otherwise electron dense interior. We suggested that the organelle might be a melanosome with lysosomal properties. We now find that there are two similar organelles with such a single vacuole but which differ in their chemical composition, electron density, cell location and according to age. Epon embedded sections from the macular epithelium of seven monkeys, ranging from 1 to 35 years of age, were examined by transmission electron microscopy. A seven year old monkey was processed for analytic electron microscopy to determine the chemical composition of the organelles. The number and location of the organelles in the retinal epithelium were determined. The chemical composition of these two organelles was different. One of the organelles contained high mole fractions of oxygen and nitrogen and little phosphorous characteristic of melanin; the other had little oxygen and nitrogen and higher mole fractions of phosphorous uncharacteristic of melanin, but more common with lysosomal organelles. The latter had an electron dense rim around the vacuole, a less electron dense interior than the melanin containing organelle and also contained iron. The melanin containing organelle was more common in young monkeys and in the middle third of the cell. The organelle without melanin was more common in old monkeys and localized in the basal third of the cell. Two similarly vacuolated organelles, not identified before in retinal epithelium, differ in their chemical composition. One contains melanin; the other does not. The former is more common in young and the latter more common in old monkeys. This suggests reorganization and or degradation of melanin-containing organelles

  20. 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.

  1. 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.

  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. [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.

  4. 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.

  5. 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.

  6. 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

  7. EXPRESSION OF PAX6 AND SOX2 IN ADULT OLFACTORY EPITHELIUM

    PubMed Central

    Guo, Zhen; Packard, Adam; Krolewski, Richard C.; Harris, Margaret T.; Manglapus, Glen L.; Schwob, James E.

    2010-01-01

    The olfactory epithelium maintains stem and progenitor cells that support the neuroepithelium’s life-long capacity to reconstitute after injury. However, the identity of the stem cells – and their regulation – remain poorly defined. The transcription factors Pax6 and Sox2 are characteristic of stem cells in many tissues, including the brain. Therefore, we assessed the expression of Pax6 and Sox2 in normal olfactory epithelium and during epithelial regeneration after methyl bromide lesion or olfactory bulbectomy. Sox2 is found in multiple kinds of cells in normal epithelium, including sustentacular cells, horizontal basal cells, and some globose basal cells. Pax6 is co-expressed with Sox2 in all these, but is also found in duct/gland cells as well as olfactory neurons that innervate necklace glomeruli. Most of the Sox2/Pax6-positive globose basal cells are actively cycling, but some express the cyclin-dependent kinase inhibitor p27Kip1, and are presumably mitotically quiescent. Among globose basal cells, Sox2 and Pax6 are co-expressed by putatively multipotent progenitors (labeled by neither anti-Mash1 nor anti-Neurog1) and neuron-committed transit amplifying cells (which express Mash1). However, Sox2 and Pax6 are expressed by only a minority of immediate neuronal precursors (Neurog1- and NeuroD1-expressing). The assignment of Sox2 and Pax6 to these categories of globose basal cells is confirmed by a temporal analysis of transcription factor expression during the recovery of the epithelium from methyl bromide-induced injury. Each of the Sox2/Pax6-colabeled cell types is at a remove from the birth of neurons; thus, suppressing their differentiation may be among the roles of Sox2/Pax6 in the olfactory epithelium. PMID:20852734

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Asymmetric ( UC)albumin transport across bullfrog alveolar epithelium

    SciTech Connect

    Kim, K.J.; LeBon, T.R.; Shinbane, J.S.; Crandall, E.D.

    1985-10-01

    Bullfrog lungs were prepared as planar sheets and bathed with Ringer solution in Ussing chambers. In the presence of a constant electrical gradient (20, 0, or -20 mV) across the tissue, UC-labeled bovine serum albumin or inulin was instilled into the upstream reservoir and the rate of appearance of the tracer in the downstream reservoir was monitored. Two lungs from the same animal were used to determine any directional difference in tracer fluxes. An apparent permeability coefficient was estimated from a relationship between normalized downstream radioactivities and time. Results showed that the apparent permeability of albumin in the alveolar to pleural direction across the alveolar epithelial barrier is 2.3 X 10(-7) cm/s, significantly greater (P less than 0.0005) than that in the pleural to alveolar direction (5.3 X 10(-8) cm/s) when the tissue was short circuited. Permeability of inulin, on the other hand, did not show any directional dependence and averaged 3.1 X 10(-8) cm/s in both directions. There was no effect on radiotracer fluxes permeabilities of different electrical gradients across the tissue. Gel electrophoretograms and corresponding radiochromatograms suggest that the large and asymmetric isotope fluxes are not primarily due to digestion or degradation of labeled molecules. Inulin appears to traverse the alveolar epithelial barrier by simple diffusion through hydrated paracellular pathways. On the other hand, ( UC)albumin crosses the alveolar epithelium more rapidly than would be expected by simple diffusion. These asymmetric and large tracer fluxes suggest that a specialized mechanism is present in alveolar epithelium that may be capable of helping to remove albumin from the alveolar space.

  15. 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

  16. 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.

  17. Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori-infected human gastric epithelium.

    PubMed

    Mihara, Hiroshi; Suzuki, Nobuhiro; Muhammad, Jibran Sualeh; Nanjo, Sohachi; Ando, Takayuki; Fujinami, Haruka; Kajiura, Shinya; Hosokawa, Ayumu; Sugiyama, Toshiro

    2017-04-01

    Helicobacter pylori (HP) infection induces methylation silencing of specific genes in gastric epithelium. Various stimuli activate the nonselective cation channel TRPV4, which is expressed in gastric epithelium where it detects mechanical stimuli and promotes ATP release. As CpG islands in TRPV4 are methylated in HP-infected gastric epithelium, we evaluated HP infection-dependent changes in TRPV4 expression in gastric epithelium. Human gastric biopsy samples, a human gastric cancer cell line (AGS), and a normal gastric epithelial cell line (GES-1) were used to detect TRPV4 mRNA and protein expression by RT-PCR and Western blotting, respectively. Ca(2+) imaging was used to evaluate TRPV4 ion channel activity. TRPV4 methylation status was assessed by methylation-specific PCR (MSP). ATP release was measured by a luciferin-luciferase assay. TRPV4 mRNA and protein were detected in human gastric biopsy samples and in GES-1 cells. MSP and demethylation assays showed TRPV4 methylation silencing in AGS cells. HP coculture directly induced methylation silencing of TRPV4 in GES-1 cells. In human samples, HP infection was associated with TRPV4 methylation silencing that recovered after HP eradication in a time-dependent manner. HP infection-dependent DNA methylation suppressed TRPV4 expression in human gastric epithelia, suggesting that TRPV4 methylation may be involved in HP-associated dyspepsia. © 2016 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

  18. 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.

  19. Demonstration of an antibody to tubular epithelium in glomerulonephritis associated with obstructive uropathy.

    PubMed

    Pascal, R R; Sian, C S; Brensilver, J M; Kahn, M; Lefavour, G S

    1980-12-01

    It has been postulated that in some patients with obstructive and reflux uropathy proteinuria develops through an intermediate mechanism of immune complex glomerulonephritis involving antigenic material of renal tubular epithelium. A patient with a unilateral ureterocele and nephrotic syndrome underwent bilateral renal biopsies during surgical correction of the obstruction. The obstructed kidney showed mild pyelonephritis, but both kidneys showed a glomerulopathy with electron-dense deposits in the mesangial and paramesangial regions associated with positive immunofluorescence for immunoglobulin M (IgM) and the third component of complement (C3). An IgM antibody was eluted from the biopsy specimens and it reacted by indirect immunofluorescence with normal renal tubular epithelium and with the patient's renal tubular epithelium. The eluate also reacted with pre-eluted glomeruli of the patient, but not with normal glomeruli. All antibody activity could be removed from the eluate by pre-incubation with normal kidney. It is concluded that the unilateral renal obstruction produced tubular injury so that as yet unidentified antigens were recognized by the immune system. The resultant antibody response gave rise to circulating immune complexes which were then deposited in glomeruli with subsequent glomerular damage and nephrotic syndrome.

  20. Odontogenic potential of post-natal oral mucosal epithelium.

    PubMed

    Nakagawa, E; Itoh, T; Yoshie, H; Satokata, I

    2009-03-01

    A bioengineered tooth would provide a powerful alternative to currently available clinical treatments. Previous experiments have succeeded in bioengineering teeth using tooth germs from animal embryos. However, the ultimate goal is to develop a technology which enables teeth to be regenerated with the use of autologous cells. To pursue this goal, we re-associated the palatal epithelium from young mice with the odontogenic dental mesenchyme and transplanted the re-associated tissues into mouse kidney capsules. Morphologically defined teeth were formed from the re-associated cultured palatal epithelial cell sheets from mice aged up to 4 wks, but no tooth was formed when the palatal epithelium from mice after 2 days of age was directly re-associated. Our results demonstrated that post-natal non-dental oral mucosal epithelium can be used as a substitute for dental epithelium, and that epithelial cell sheet improves the ability of the oral epithelium of older mice to differentiate into dental epithelium.

  1. [Effect of cryotherapy over the expression of vascular endothelial growth factor and pigment epithelium-derived factor].

    PubMed

    Toscano-Garibay, Julia Dolores; Quiroz-Mercado, Hugo; Espitia-Pinzón, Clara; Gil-Carrasco, Félix; Flores-Estrada, José Javier

    2014-01-01

    Cryotherapy is a no invasive technique that uses intense cold to freeze and destroy cancer tissues. There are no descriptions of its effects over the expression of vascular endothelial growth factor and pigment epithelium-derived factor. Experimental study in cryogenic spot were applied in the right sclera of twelve pigs for ten minutes. Other 3 pigs were used as normal controls. Animals were sacrificed at 7, 14 and 21 and the tissues of choriodes and retina were dissected in areas of approximately 1 cm2 surrounding cryogenic spots. Expression levels of vascular endothelial growth factor and pigment epithelium-derived factor were determined analyzed using polymerase chain reaction coupled to reverse-transcription. Vascular endothelial growth factor was significantly downregulated (24%, p< 0.05) seven days post-treatment meanwhile pigment epithelium-derived factor levels increased 44.8% (p< 0.05) as compared to normal controls (untreated). Both vascular endothelial growth factor and pigment epithelium-derived factor levels remain the same until day 14 but returned to basal expression at day 21. This work expose the relation of cryotherapy with the expression of two factors related to angiogenesis. RESULTS showed significant changes on the expression of vascular endothelial growth factor and pigment epithelium-derived factor illustrating that both proteins are regulated in response to cryogenic treatment in relatively short periods (21 days).

  2. Tooth ankylosis. Clinical, radiographic and histological assessments.

    PubMed

    Andersson, L; Blomlöf, L; Lindskog, S; Feiglin, B; Hammarström, L

    1984-10-01

    Ankylosis is a serious condition for the affected teeth as such teeth form part of the remodelling process of the alveolar bone and are therefore progressively resorbed. There are, however, very few clinical studies on tooth ankylosis and the reason for this may be due to the difficulties that are encountered in the diagnosis of minor areas of ankylosis. In the present study, the radiographs, percussion sound and mobility of experimentally extracted and replanted monkey incisors were compared with a morphometric histological study of ankylosis. Ankylotic areas were evident radiographically when the ankylosis was located on the proximal surfaces of the root, but were not evident when the ankylosis occurred on the lingual and labial surfaces. The percussion sound was dull and the mobility normal in all non-ankylotic teeth as well as in those teeth which histologically demonstrated ankylosis on less than 10% of the root surface. When the ankylosis affected 10-20% of the root surface, 2 out of 4 teeth changed their percussion sound from dull to high and these teeth no longer possessed normal mobility. When more than 20% of the root surface was affected with ankylosis, the percussion sound was characteristically high in all teeth and no mobility was present.

  3. Transport pathways in rat lingual epithelium.

    PubMed

    Simon, S A; Robb, R; Schiffman, S S

    1988-02-01

    Measurements of ion transport across isolated lingual epithelium of rat were correlated with electrophysiological recordings from taste nerves. At hyperosmotic concentrations of NaCl, sodium ions enter the mucosal membrane of the isolated epithelium partially through an amiloride-inhibitable pathway and exit the serosal membrane through a Na+-K+-ATPase. At hyposmotic concentrations of KCl, potassium ions enter the mucosal membrane through a K+ pathway that is inhibited by 4-aminopyridine and exit at the serosal membrane through a K+ pathway that is inhibited by BaCl2. The inhibition of sodium transport by amiloride and potassium transport by 4-aminopyridine is consistent with previously published electrophysiological recordings from the chorda tympani nerve bundle (CT) and recordings from nucleus of the solitary tract (NST) obtained here. The responses to NaCl are greater than the responses to KCl at equimolar concentrations over the entire concentration range both in epithelial and neural measurements. At hyposmotic concentrations of NaCl the epithelial responses include inward sodium and outward chloride components. Isolated rat tongue is only slightly stimulated by D-glucose or sucrose as are the CT and NTS responses. These data suggest that events in taste transduction can be understood, in part, by measuring the epithelial responses of isolated rat tongue.

  4. [Histological alterations in the submandibular glands and testicles in rats induced by soy and zinc deficient diet].

    PubMed

    Vanderlei, L C; Arruda Veiga, M C; Reis, N S; Tambeli, C H

    1995-09-01

    The purpose of this study was to examine in rats the histologic alterations of the submandibular glands and testicles induced by soy diets and zinc deficient diet. The zinc deficiency produced testicles alterations including seminiferous tubulus atrophy, germinative epithelium degeneration, spermatogenesis alterations and a significant atrophy of the submandibular glands which presented no much delimitated acines. The soy diet without complementations also compromised the spermatogenesis by showing seminiferous tubulus atrophied and a reduction of the germinative epithelium. The soy diet complemented by saline and vitaminic mixtures didn't produced testicles alterations but its induced in the submandibular glands a hypertrophy of the ductal component mainly in relation to the granular component.

  5. 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.

  6. Regulation of Tight Junctions in Upper Airway Epithelium

    PubMed Central

    Kojima, Takashi; Go, Mitsuru; Takano, Ken-ichi; Kurose, Makoto; Ohkuni, Tsuyoshi; Koizumi, Jun-ichi; Kamekura, Ryuta; Ogasawara, Noriko; Masaki, Tomoyuki; Fuchimoto, Jun; Obata, Kazufumi; Hirakawa, Satoshi; Nomura, Kazuaki; Keira, Takashi; Miyata, Ryou; Fujii, Nobuhiro; Tsutsumi, Hiroyuki; Himi, Tetsuo; Sawada, Norimasa

    2013-01-01

    The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs) are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP), which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECs in vitro induces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release. This paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions. PMID:23509817

  7. 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

  8. Histological features of localized scleroderma 'en coup de sabre': a study of 16 cases.

    PubMed

    Taniguchi, T; Asano, Y; Tamaki, Z; Akamata, K; Aozasa, N; Noda, S; Takahashi, T; Ichimura, Y; Toyama, T; Sugita, M; Sumida, H; Kuwano, Y; Miyazaki, M; Yanaba, K; Sato, S

    2014-12-01

    Early lesions of localized scleroderma are histologically characterized by perivascular lymphocytic infiltrate in the reticular dermis and swollen endothelial cells. However, there have been few information regarding histological features other than these findings in localized scleroderma. Since en coup de sabre (ECDS) is a certain subset of localized scleroderma with a relatively uniform clinical manifestation, we focused on this disease subset and evaluated its histopathological features. A total of 16 patients with ECDS were retrospectively evaluated on the basis of clinical and histological findings. Regardless of clinical manifestations, vacuolar degeneration was found in all of the ECDS patients. Importantly, keratinocyte necroses were restricted to early and active ECDS lesions. In early ECDS patients (disease duration of <3 years), moderate to severe perivascular and/or periappendageal lymphocytic infiltrate and vacuolar changes in follicular epithelium were more prominent, whereas epidermal atrophy was less frequently observed, than in late ECDS patients (disease duration of ≥6 years). Vacuolar degeneration at the dermoepidermal junction is a common histological feature in ECDS and perivascular and/or periappendageal lymphocytic infiltrate and vacuolar degeneration of follicular epithelium are characteristic especially in early ECDS, further supporting a canonical idea that the elimination of mutated epidermal cells by immune surveillance contributes to tissue damage and resultant fibrosis in localized scleroderma. © 2013 European Academy of Dermatology and Venereology.

  9. Transgenic Overexpression of cdx1b Induces Metaplastic Changes of Gene Expression in Zebrafish Esophageal Squamous Epithelium

    PubMed Central

    Hu, Bo; Chen, Hao; Liu, Xiuping; Zhang, Chengjin; Cole, Gregory J.

    2013-01-01

    Abstract Cdx2 has been suggested to play an important role in Barrett's esophagus or intestinal metaplasia (IM) in the esophagus. To investigate whether transgenic overexpression of cdx1b, the functional equivalent of mammalian Cdx2 in zebrafish, may lead to IM of zebrafish esophageal squamous epithelium, a transgenic zebrafish system was developed by expressing cdx1b gene under the control of zebrafish keratin 5 promoter (krt5p). Gene expression in the esophageal squamous epithelium of wild-type and transgenic zebrafish was analyzed by Affymetrix microarray and confirmed by in situ hybridization. Morphology, mucin expression, cell proliferation, and apoptosis were analyzed by hematoxylin & eosin (HE) staining, Periodic acid Schiff (PAS) Alcian blue staining, proliferating cell nuclear antigen (PCNA) immunohistochemical staining, and TUNEL assay as well. cdx1b was found to be overexpressed in the nuclei of esophageal squamous epithelial cells of the transgenic zebrafish. Ectopic expression of cdx1b disturbed the development of this epithelium in larval zebrafish and induced metaplastic changes in gene expression in the esophageal squamous epithelial cells of adult zebrafish, that is, up-regulation of intestinal differentiation markers and down-regulation of squamous differentiation markers. However, cdx1b failed to induce histological IM, or to modulate cell proliferation and apoptosis in the squamous epithelium of adult transgenic zebrafish. PMID:23672288

  10. Transgenic overexpression of cdx1b induces metaplastic changes of gene expression in zebrafish esophageal squamous epithelium.

    PubMed

    Hu, Bo; Chen, Hao; Liu, Xiuping; Zhang, Chengjin; Cole, Gregory J; Lee, Ju-Ahng; Chen, Xiaoxin

    2013-06-01

    Cdx2 has been suggested to play an important role in Barrett's esophagus or intestinal metaplasia (IM) in the esophagus. To investigate whether transgenic overexpression of cdx1b, the functional equivalent of mammalian Cdx2 in zebrafish, may lead to IM of zebrafish esophageal squamous epithelium, a transgenic zebrafish system was developed by expressing cdx1b gene under the control of zebrafish keratin 5 promoter (krt5p). Gene expression in the esophageal squamous epithelium of wild-type and transgenic zebrafish was analyzed by Affymetrix microarray and confirmed by in situ hybridization. Morphology, mucin expression, cell proliferation, and apoptosis were analyzed by hematoxylin & eosin (HE) staining, Periodic acid Schiff (PAS) Alcian blue staining, proliferating cell nuclear antigen (PCNA) immunohistochemical staining, and TUNEL assay as well. cdx1b was found to be overexpressed in the nuclei of esophageal squamous epithelial cells of the transgenic zebrafish. Ectopic expression of cdx1b disturbed the development of this epithelium in larval zebrafish and induced metaplastic changes in gene expression in the esophageal squamous epithelial cells of adult zebrafish, that is, up-regulation of intestinal differentiation markers and down-regulation of squamous differentiation markers. However, cdx1b failed to induce histological IM, or to modulate cell proliferation and apoptosis in the squamous epithelium of adult transgenic zebrafish.

  11. Histologic chorioamnionitis: different histologic features at different gestational ages.

    PubMed

    Torricelli, Michela; Voltolini, Chiara; Toti, Paolo; Vellucci, Francesca Letizia; Conti, Nathalie; Cannoni, Alice; Moncini, Irene; Occhini, Rossella; Severi, Filiberto Maria; Petraglia, Felice

    2014-06-01

    The aim of this study was to investigate the rate of the different histological chorioamnionitis (HCA) grade in relation to the gestational age in term and preterm delivery. Three hundred and ninety-two women with singleton pregnancy with spontaneous onset of labor either prematurely or at term, with histologic diagnosis of HCA, were enrolled. Placentas were classified as: deciduitis and/or histologic chorioamnionitis within the membranes (HCA1); amnionitis or inflammation of the chorionic plate without funisitis (HCA2); and histologic chorioamnionitis with funisitis (HCA3). Microbiological culture was performed on both placental and fetal membrane samples. HCA1 was more frequent in women delivering at term than in preterm (p < 0.001). HCA2 was more represented in women delivering between 32 and 36 weeks (p < 0.001) and HCA3 occurred more frequently in those delivering within 32 weeks (p < 0.001). The positive bacterial culture was higher (p = 0.008) in presence of HCA3 in comparison with HCA1 and HCA2. This study showed a significantly different distribution of HCA grades in relation to gestational age at delivery. HCA may represent the expression of different subtending etiologies and may also reflect specific immune competence of gestational tissues at different gestational ages, strengthening as pregnancy advances.

  12. The electrical potential profile of gallbladder epithelium.

    PubMed

    van Os, C H; Slegers, J F

    1975-12-04

    In this study the relative ionic permeabilities of the cell membranes of Necturus gallbladder epithelium have been determined by means of simultaneous measurement of transmural and transmucosal membrane potential differences (PD) and by ionic substitution experiments with sodium, potassium and chloride ions. It is shown that the mucosal membrane is permeable to sodium and to potassium ions. The baso-lateral membrane PD is only sensitive to potassium ions. In both membranes chloride conductance is negligible or absent. The ratio of the resistances of the mucosal and baso-lateral membranes, RM/RS, increases upon reducing the sodium concentration in the mucosal solution. The same ratio decreases when sodium is replaced by potassium which implies a greater potassium than sodium conductance in the mucosal membrane. The relative permeability of the shunt for potassium, sodium and chloride ions is: PK/PNa/PCl=1.81:1.00:0.32. From the results obtained in this study a value for the PK/PNa ratio of the mucosal membrane could be evaluated. This ratio is 2.7. From the same data the magnitude of the electromotive forces generated across the cell membranes could be calculated. The EMF's are -15mV across the mucosal membrane and -81mV across the baso-lateral one. Due to the presence of the low resistance shunt the transmucosal membrane PD is -53.2mV (cell inside negative) and the transmural PD is +2.6mV (serosal side positive). The change in potential profile brought about by the low resistance shunt favors passive entry of Na ions into the cell across the mucosal membrane. Calculations show that this passive Na influx is maximally 64% of the net Na flux estimated from fluid transport measurements. The C-1 conductive of the baso-lateral membrane is too small to allow electrogenic coupling of C1 with Na transport across this membrane. Experiments with rabbit gallbladder epithelium indicate that the membrane properties in this tissue are qualitatively similar to those of Necturus

  13. 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.

  14. Gene expression based evidence of innate immune response activation in the epithelium with oral lichen planus

    PubMed Central

    Adami, Guy R.; Yeung, Alexander C.F.; Stucki, Grant; Kolokythas, Antonia; Sroussi, Herve Y.; Cabay, Robert J.; Kuzin, Igor; Schwartz, Joel L.

    2014-01-01

    Objective Oral lichen planus (OLP) is a disease of the oral mucosa of unknown cause producing lesions with an intense band-like inflammatory infiltrate of T cells to the subepithelium and keratinocyte cell death. We performed gene expression analysis of the oral epithelium of lesions in subjects with OLP and its sister disease, oral lichenoid reaction (OLR), in order to better understand the role of the keratinocytes in these diseases. Design Fourteen patients with OLP or OLR were included in the study, along with a control group of 23 subjects with a variety of oral diseases and a normal group of 17 subjects with no clinically visible mucosal abnormalities. Various proteins have been associated with OLP, based on detection of secreted proteins or changes in RNA levels in tissue samples consisting of epithelium, stroma, and immune cells. The mRNA level of twelve of these genes expressed in the epithelium was tested in the three groups. Results Four genes showed increased expression in the epithelium of OLP patients: CD14, CXCL1, IL8, and TLR1, and at least two of these proteins, TLR1 and CXCL1, were expressed at substantial levels in oral keratinocytes. Conclusions Because of the large accumulation of T cells in lesions of OLP it has long been thought to be an adaptive immunity malfunction. We provide evidence that there is increased expression of innate immune genes in the epithelium with this illness, suggesting a role for this process in the disease and a possible target for treatment. PMID:24581860

  15. 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

  16. 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.…

  17. 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.…

  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. Comparative mutational analysis of pulmonary scar epithelium, bronchioloalveolar carcinomas, and invasive well-differentiated pulmonary adenocarcinomas: a molecular approach to diagnostically challenging cases.

    PubMed

    Sheikh, Hina A; Sasatomi, Eizaburo; Finkelstein, Sydney; Yousem, Samuel A

    2005-10-01

    Discrimination of invasive well-differentiated adenocarcinoma (IAD) from reactive bronchioloalveolar epithelium entrapped in pulmonary scars (PSE) may be difficult on routine histology, especially on small biopsies. Ancillary studies to help in this regard are desirable. Whereas IADs have been shown to harbor cumulative mutational damage of tumor suppressor genes, little is known about molecular changes in PSEs. In this study, we compared cumulative loss of heterozygosity (LOH) of tumor suppressor genes in PSEs (N = 12), bronchioloalveolar carcinomas (BACs, N = 15) and stage 1 IADs (N = 7). Unstained serial sections were microdissected to obtain lesional and normal tissue DNA. PCR was performed for up to 16 polymorphic markers. An allelic ratio of < 0.5 or >2.0 was designated as LOH. Fractional allelic loss (FAL) was calculated for each case as the number of markers with LOH divided by the total number of informative markers. Mean percentage of informative markers was 76.8%. PSEs showed significantly lower mean FAL compared with BACs and IADs (3.0% vs. 20.4% and 28.5%, respectively; P < 0.003). Only 1 case of PSE showed LOH of one marker in two different areas, whereas the majority of allelic losses in the neoplasms were present in two or more microdissected foci. Our study shows that PSEs harbor LOH of tumor suppressor genes at relatively low rates and in a random distribution compared with BACs and IADs, which show consistent allelic losses, and high FALs. These molecular differences may serve as an adjunct to histology in challenging glandular lesions of the lung.

  1. Repair of tracheal epithelium by basal cells after chlorine-induced injury

    PubMed Central

    2012-01-01

    Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU) to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5) and keratin 14 (K14) for basal cells, Clara cell secretory protein (CCSP) for Clara cells, and acetylated tubulin (AcTub) for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10), but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion The data are

  2. 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

  3. The pineal gland does not control rod outer segment shedding and phagocytosis in the rat retina and pigment epithelium.

    PubMed

    Tamai, M; Teirstein, P; Goldman, A; O'Brien, P; Chader, G

    1978-06-01

    Diurnal patterns of retinal outer segment shedding and phagocytosis by the pigment epithelium were examined in pinealectomized, superior-cervical-ganglionectomized, and sham-operated rats. Phagocytosis was quantitatively similar in all groups. Sharp increases in the number of large phagosomes were observed soon after lights were turned on in the tree sets of animals. Pinealectomized animals kept in constant darkness over a 24 hr period also exhibited normal shedding patterns. Our results suggest that the pineal does not exert a major influence on the daily rhythms of shedding and phagocytosis observed in the retina-pigment epithelium unit.

  4. Barrier function of airway tract epithelium

    PubMed Central

    Ganesan, Shyamala; Comstock, Adam T; Sajjan, Uma S

    2013-01-01

    Airway epithelium contributes significantly to the barrier function of airway tract. Mucociliary escalator, intercellular apical junctional complexes which regulate paracellular permeability and antimicrobial peptides secreted by the airway epithelial cells are the three primary components of barrier function of airway tract. These three components act cooperatively to clear inhaled pathogens, allergens and particulate matter without inducing inflammation and maintain tissue homeostasis. Therefore impairment of one or more of these essential components of barrier function may increase susceptibility to infection and promote exaggerated and prolonged innate immune responses to environmental factors including allergens and pathogens resulting in chronic inflammation. Here we review the regulation of components of barrier function with respect to chronic airways diseases. PMID:24665407

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

    PubMed Central

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

    2016-01-01

    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. DOI: http://dx.doi.org/10.7554/eLife.12034.001 PMID:26809587

  6. 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

  7. 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.

  8. 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.

  9. Histochemical and morpho-metrical study of mouse intestine epithelium after a long term diet containing genetically modified soybean

    PubMed Central

    Battistelli, S.; Citterio, B.; Baldelli, B.; Parlani, C.; Malatesta, M.

    2010-01-01

    Diet can influence the structural characteristics of both small and large intestine. In this study, we investigated the duodenum and colon of mice fed on genetically modified (GM) soybean during their whole life span (1–24 months) by focusing our attention on the histological and ultrastructural characteristics of the epithelium, the histochemical pattern of goblet cell mucins, and the growth profile of the coliform population. Our results demonstrate that controls and GM-soybean fed mice are similarly affected by ageing. Moreover, the GM soybean-containing diet does not induce structural alterations in duodenal and colonic epithelium or in coliform population, even after a long term intake. On the other hand, the histochemical approach revealed significant diet-related changes in mucin amounts in the duodenum. In particular, the percentage of villous area occupied by acidic and sulpho-mucin granules decreased from controls to GM-fed animals, whereas neutral mucins did not change. PMID:20819774

  10. 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.

  11. 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…

  12. 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…

  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. 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

  15. 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.

  16. 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.

  17. Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer.

    PubMed

    Henry, C E; Emmanuel, C; Lambie, N; Loo, C; Kan, B; Kennedy, C J; de Fazio, A; Hacker, N F; Ford, C E

    2017-06-01

    The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n=178). Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Epithelium-derived chemokines induce airway smooth muscle cell migration.

    PubMed

    Takeda, N; Sumi, Y; Préfontaine, D; Al Abri, J; Al Heialy, N; Al-Ramli, W; Michoud, M-C; Martin, J G; Hamid, Q

    2009-07-01

    The remodelling of airway smooth muscle (ASM) associated with asthma severity may involve the migration of ASM cells towards the epithelium. However, little is known about the mechanisms of cell migration and the effect of epithelial-derived mediators on this process. The main objective of the current study is to assess the effects of epithelial-derived chemokines on ASM cell migration. Normal human ASM cells were incubated with supernatants from cells of the bronchial epithelial cell line BEAS-2B and normal human bronchial epithelial (NHBE) cells. To induce chemokine production, epithelial cells were treated with TNF-alpha. Chemokine expression by epithelial cells was evaluated by quantitative real-time PCR, ELISA and membrane antibody array. To identify the role of individual chemokines in ASM cell migration, we performed migration assays with a modified Boyden chamber using specific neutralizing antibodies to block chemokine effects. Supernatants from BEAS-2B cells treated with TNF-alpha increased ASM cell migration; migration was increased 1.6 and 2.5-fold by supernatant from BEAS-2B cells treated with 10 and 100 ng/mL TNF-alpha, respectively. Protein levels in supernatants and mRNA expression by BEAS-2B cells of regulated on activation, normal T cell expressed and secreted (RANTES) and IL-8 were significantly increased by 100 ng/mL TNF-alpha treatment. The incubation of supernatant with antibodies to RANTES or IL-8 significantly reduced ASM cell migration, and the combined antibodies further inhibited the cell migration. The migratory effects of supernatants and inhibiting effects of RANTES and/or IL-8 were confirmed also using NHBE cells. The results show that chemokines from airway epithelial cells cause ASM cell migration and might potentially play a role in the process of airway remodelling in asthma.

  19. Histology and ultrastructure of the chorioallantoic membrane of the mallard duck (Anas platyrhynchos).

    PubMed

    Lusimbo, W S; Leighton, F A; Wobeser, G A

    2000-05-01

    The histology and fine structure of the chorioallantoic membrane of the mallard duck (Anas platyrhynchos), and the density of vessels per millimeter of membrane were assessed between days 12 and 24 of incubation. Light and transmission electron microscopy of the chorioallantoic membrane of the mallard duck after various days of incubation was carried out. Blood vessels within the mesoderm were counted per millimeter of membrane by light microscopy (40x). The chorioallantoic membrane had three distinct layers from day 12 to 24 of incubation, the chorionic epithelium, the mesoderm, and the allantoic epithelium. After day 12, chorionic epithelium consisted of two layers of flattened, elongated epithelial cells interfaced by numerous desmosomes, and separated from the underlying mesoderm by a basement membrane. At this stage, the allantoic epithelium consisted of a single layer of flattened, overlapping cells. Blood capillaries were observed in the mesoderm close to the chorionic epithelium on days 12 and 13; by day 14, these capillaries were located within the chorionic epithelium, forming a capillary sinus. Between days 14 and 16, the chorion underwent cellular and cytological differentiation into three cell types: capillary covering cells, villus cavity cells, and less differentiated basal cells. The mesoderm was composed of a loose matrix of mesenchymal cells and collagen fibrils through which coursed blood and lymphatic vessels. The vascular density in the mesoderm increased rapidly from 4.2+/-0.6 vessels per mm (n = 12) on day 12 to a maximum of 9.4+/-0.3 vessels per mm (n = 15) by day 16. From day 16, the allantoic epithelium had two to three layers of elongated and overlapping cells. The luminal layer of allantoic epithelial cells had microvillus projections and varying numbers of membrane-bound dense vesicles at all stages from day 12 onward. The histologic and ultrastructural features of mallard duck chorioallantoic membrane from day 12 to 24 of incubation

  20. A comparison of three Peyer's patch "M-like" cell culture models: particle uptake, bacterial interaction, and epithelial histology.

    PubMed

    Ahmad, Tauseef; Gogarty, Martina; Walsh, Edwin G; Brayden, David J

    2017-10-01

    Intestinal Peyer's patch (PP) microfold (M) cells transport microbes and particulates across the follicle-associated epithelium (FAE) as part of the mucosal immune surveillance system. In vitro human M-like cell co-culture models are used as screens to investigate uptake of antigens-in-nanoparticles, but the models are labour-intensive and there is inter-laboratory variability. We compared the three most established filter-grown Caco-2/Raji B cell co-culture systems. These were Model A (Kernéis et al., 1997), Model B (Gullberg et al., 2000), and Model C (Des Rieux et al. 2007). The criteria used were transepithelial resistance (TEER), the apparent permeability coefficient (Papp) of [(14)C]-mannitol, M cell-like histology, as well as latex particle and Salmonella typhimurium translocation. Each co-culture model displayed substantial increases in particle translocation. Truncated microvilli compared to mono-cultures was their most consistent feature. The inverted model developed by des Rieux et al. (2007) displayed reductions in TEER and an increased (Papp), accompanied by the largest increase in particle translocation compared to the other two models. The normally-oriented model developed by Gullberg et al. (2000) was the only one to consistently display an increased translocation of Salmonella typhimurium. By applying a double Matrigel™ coating on filters, altering the medium feeding regime for Raji B cells, and restricting the passage number of B cells, improvements to the Gullberg model B were achieved, as reflected by increased particle translocation and improved histology. In conclusion, this is the first time all three designs have been compared in one study and each displays phenotypic features of M-like cells. While Model C was the most robust co-culture, the Model B protocol could be improved by optimizing several variables and is less complicated to establish than the two inverted models. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. The nanomechanical role of melanin granules in the retinal pigment epithelium.

    PubMed

    Sarna, Michal; Olchawa, Magdalena; Zadlo, Andrzej; Wnuk, Dawid; Sarna, Tadeusz

    2017-04-01

    Nanomechanical properties of cells and tissues, in particular their elasticity, play an important role in different physiological and pathological processes. Recently, we have demonstrated that melanin granules dramatically modify nanomechanical properties of melanoma cells making them very stiff and, as a result, less aggressive. Although the mechanical effect of melanin granules was demonstrated in pathological cells, it was never studied in the case of normal cells. In this work, we analyzed the impact of melanin granules on nanomechanical properties of primary retinal pigment epithelium tissue fragments isolated from porcine eyes. The obtained results clearly show that melanin granules are responsible for the exceptional nanomechanical properties of the tissue. Our findings suggest that melanin granules in the retinal pigment epithelium may play an important role in sustaining the stiffness of this single cell layer, which functions as a natural mechanical barrier separating the retina from the choroid. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. 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

  3. 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.

  4. [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.

  5. Conductive keratoplasty: histological study of human corneas.

    PubMed

    Naoumidi, Tatiana L; Pallikaris, Ioannis G; Naoumidi, Irini I; Astyrakakis, Nikolaos I

    2005-12-01

    To determine the morphologic changes in human corneas over time following radiofrequency-based conductive keratoplasty (CK) treatment. Prospective, observational case series. In a single-center study six human corneas of six patients with localized peripheral keratoconus underwent CK treatment followed by penetrating keratoplasty. Three spots were applied in the periphery of each cornea (6 mm optical zone). Corneal buttons were examined with light and electron microscopy at different postoperative intervals up to 6 months post-CK. In samples assessed on day one post-CK, small areas of detachment between the basal layer of epithelial cells and Bowman's layer were observed. At 1 week after the CK procedure, the epithelium appeared almost normal. Endothelium and Descemet's membrane had no alterations. In all samples, thermally induced misconfiguration of collagen fibers, described as "crumpled" changes of collagen layers, was observed reaching 75% to 80% of the stromal depth. The area of alterations had a cylindrical shape with a diameter of 120 mum. The conductive keratoplasty procedure produced collagen "crumpling and splitting" changes in human corneas, which were observed during the follow-up of 6 months. Areas adjacent to treatment site were minimally damaged.

  6. The effect of the corneal epithelium on the intraocular penetration of fluoroquinolone ophthalmic solution.

    PubMed

    Fukuda, Masamichi; Inoue, Amane; Sasaki, Kazuyuki; Takahashi, Nobuo

    2004-01-01

    Pharmacokinetic studies of antibacterial agents for infectious eye diseases have usually been performed on normal rabbit eyes. In this study, the intraocular penetration of fluoroquinolone ophthalmic solutions was determined in normal rabbit eyes and in rabbit eyes that had the corneal epithelium intentionally removed. We determined the intraocular penetration of ofloxacin (OFLX), levofloxacin (LVFX), and norfloxacin (NFLX), fluoroquinolone ophthalmic solutions that are already on the market and undergoing clinical studies, by injecting 50 microl of each solution into the cul-de-sacs of rabbit eyes three times at 15-min intervals. The drug concentration at 10, 30, 60, 120, and 240 min after final instillation was determined by high-performance liquid chromatography. The maximum concentration in the aqueous humor of normal rabbit eyes was 2.09 +/- 1.56 microg/ml (60 min, OFLX), 2.57 +/- 1.00 microg/ml (30 min, LVFX), and 0.42 +/- 0.12 microg/ml (120 min, NFLX). The drug concentration in the aqueous humor of eyes with intentionally removed corneal epithelium was 12.50 +/- 5.62 microg/ml (30 min, OFLX), 9.02 +/- 2.45 microg/ml (60 min, LVFX), and 8.54 +/- 5.17 microg/ml (30 min, NFLX). The drug penetration of the eye drops into eyes with removed corneal epithelium was around 6 times (OFLX), 3.5 times (LVFX), and 20 times (NFLX) higher than the penetration into the eye with normal cornea. Among the pharmacokinetic parameters of the three ophthalmic solutions according to the one-compartment model, the maximum concentration in the aqueous and the area under the concentration-time curve in the aqueous tended to be higher in the eyes with intentionally removed corneal epithelia than in those with normal corneas.

  7. 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

    2017-06-01

    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. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. 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

  9. HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients.

    PubMed

    Dunne, Margaret R; Michielsen, Adriana J; O'Sullivan, Katie E; Cathcart, Mary Clare; Feighery, Ronan; Doyle, Brendan; Watson, Jenny A; O'Farrell, Naoimh J; Ravi, Narayanasamy; Kay, Elaine; Reynolds, John V; Ryan, Elizabeth J; O'Sullivan, Jacintha

    2017-07-01

    Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett's esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC. HLA-DR expression in tissue epithelium and stroma was assessed by immunohistochemistry. HLA-DR expression increased early in the inflammation to cancer progression sequence; with higher expression detected in esophagitis and BE compared to normal tissue. Patients with low (<50%) HLA-DR expression in the EAC tumor epithelium had significantly worse survival outcomes, compared to those with high expression, in both the tumor core (hazard ratio, HR = 2.178, p = 0.024, n = 70) and leading edge (HR = 2.86, p = 0.013, n = 41). Multivariate analysis demonstrated that low HLA-DR expression in leading edge tumor epithelium was an independent predictor of poor survival, associated with a 2.8-fold increase in disease-associated death (p = 0.023). This study shows that HLA-DR is an independent prognostic marker in EAC tumor epithelium. This may have implications for patient stratification strategies as well as EAC tumor immunology.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Light microscopic histology of supraspinatus tendon ruptures.

    PubMed

    Longo, Umile Giuseppe; Franceschi, Francesco; Ruzzini, Laura; Rabitti, Carla; Morini, Sergio; Maffulli, Nicola; Forriol, Francisco; Denaro, Vincenzo

    2007-11-01

    We analysed the morphological features of the human surgical specimens of supraspinatus tendon from patients with rotator cuff tears. Tendon samples were harvested from 31 subjects (21 men and 10 women; mean age 51 years, range 38-64) who underwent arthroscopic repair of a rotator cuff tear, and from five male patients who died of cardiovascular events (mean age, 69.6 years). Histological examination was performed using Haematoxylin and Eosin, Masson's Trichrome and Van Gieson's connective tissue stain. The specimens were examined twice by the same examiner under white light and polarized light microscopy. Particular effort was made to assess any evidence of the changes associated with tendinopathy. Within each specific category of tendon abnormalities, the chi-square test showed significant differences between the control and ruptured tendons (P < 0.05). Using the kappa statistics, the agreement between the two readings ranged from 0.57 to 0.84. We found thinning and disorientation of collagen fibres and chondroid metaplasia to be more pronounced on the articular side of the specimens from patients with rotator cuff tear (P < 0.05). The present study provides a description of the histological architecture of human surgical specimens of normal supraspinatus tendon from patients with rotator cuff tears and demonstrates more frequent tendon changes on the articular side of the rotator cuff.

  15. 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.

  16. Change of morphological and functional characteristics of retinal pigment epithelium cells during cultivation of retinal pigment epithelium-choroid perfusion tissue culture.

    PubMed

    Miura, Yoko; Klettner, Alexa; Noelle, Bernhard; Hasselbach, Heike; Roider, Johann

    2010-01-01

    To evaluate the changes of morphological and functional characteristics of the retinal pigment epithelium (RPE)-choroid perfusion culture during cultivation. PorcineRPE-choroid tissue was cultivated in a perfusion tissue culture system. After the indicated times, histology, immunolocalization of collagen IV and von Willebrand factor, RPE cell viability with calcein-AM, TUNEL assay and occludin immunolocalization of RPE cells were examined. The tissue was treated with selective RPE treatment laser after different time periods and the wound healing response was characterized. Vascular endothelial growth factor secretion was measured by enzyme-linked immunosorbent assay. On day 8, prominent morphological degenerative changes of RPE cells were observed in histology. According to the immunohistochemistry for collagen IV, the Bruch's membrane did not display any obvious decomposition until day 8. Von Willebrand factor staining decreased during cultivation, especially at the choriocapillaris. Calcein-AM staining and TUNEL assay displayed the increase of apoptotic changes in only a minority of the cells on day 4, but in many cells on day 8. Occludin delocalization was observed on day 8. Selective RPE treatment laser-produced wounds were completely closed by monolayer RPE when wounded on fresh and 3-day-old cultures, but not when wounded on 6-day-old cultures. Vascular endothelial growth factor secretion was stable between days 2 and 5, but increased after that. Under the stated culture perfusion conditions, porcine RPE-choroid tissue was suitable for experimentation up to 5 days of maintenance. Copyright 2009 S. Karger AG, Basel.

  17. 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

  18. 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

  19. 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.

  20. Surface characteristics of isopod digestive gland epithelium studied by SEM.

    PubMed

    Millaku, Agron; Leser, Vladka; Drobne, Damjana; Godec, Matjaz; Torkar, Matjaz; Jenko, Monika; Milani, Marziale; Tatti, Francesco

    2010-05-01

    The structure of the digestive gland epithelium of a terrestrial isopod Porcellio scaber has been investigated by conventional scanning electron microscopy (SEM), focused ion beam-scanning electron microscopy (FIB/SEM), and light microscopy in order to provide evidence on morphology of the gland epithelial surface in animals from a stock culture. We investigated the shape of cells, extrusion of lipid droplets, shape and distribution of microvilli, and the presence of bacteria on the cell surface. A total of 22 animals were investigated and we found some variability in the appearance of the gland epithelial surface. Seventeen of the animals had dome-shaped digestive gland "normal" epithelial cells, which were densely and homogeneously covered by microvilli and varying proportions of which extruded lipid droplets. On the surface of microvilli we routinely observed sparsely distributed bacteria of different shapes. Five of the 22 animals had "abnormal" epithelial cells with a significantly altered shape. In three of these animals, the cells were much smaller, partly or completely flat or sometimes pyramid-like. A thick layer of bacteria was detected on the microvillous border, and in places, the shape and size of microvilli were altered. In two animals, hypertrophic cells containing large vacuoles were observed indicating a characteristic intracellular infection. The potential of SEM in morphological investigations of epithelial surfaces is discussed.

  1. Melatonin Modulates Prohibitin and Cytoskeleton in the Retinal Pigment Epithelium.

    PubMed

    Sripathi, Srinivas R; Prigge, Cameron L; Elledge, Beth; He, Weilue; Offor, Johnpaul; Gutsaeva, Diana R; Jahng, Wan Jin

    2017-07-01

    The retinal pigment epithelium (RPE) plays imperative roles in normal retinal function by photoreceptor protection from light and phagocytosis of rod and cone outer segments during disc shedding. Melatonin is the free radical scavenger and circadian determinant to protect the RPE and retina from oxidative stress and regulate the circadian clock. The current study tested the hypothesis whether melatonin could affect cytoskeletal structure within RPE. Our Western blot analysis demonstrated that melatonin treatment up-regulated prohibitin 3-fold compared to control. β-tubulin levels were also up-regulated by melatonin but to a lesser extent. Initial cell shape of ARPE-19 is epitheloid, however, after 30-minute treatment with melatonin, RPE cells undergo a morphological change to a fusiform shape with spindle outgrowth. Cells return to epitheloid shape after 12 hours in untreated medium. Melatonin treated cells showed increased and dissimilar distribution of prohibitin and β-tubulin compared to non-treated cells, thus altered cytoskeletal and mitochondrial structure in the RPE. Our data implies that melatonin may play a protective role under oxidative stress, which is shown by the marker prohibitin in terms of increased expression and nuclear distribution. During the protective process, cells change their morphology. Our results suggest that melatonin treatment could be beneficial to protect mitochondria under oxidative stress and treat certain ocular diseases, including age-related macular degeneration.

  2. 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.

  3. 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.

  4. 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.

  5. 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

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

    PubMed

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

    2016-07-01

    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. The aim of this study is to investigate the possible histological changes in the vocal cords of the pregnant rats in three separate trimesters. Animal experiment. 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. 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. 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.

  7. 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.

  8. 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

  9. Cell dynamics in the olfactory epithelium of the tiger salamander: a morphometric analysis.

    PubMed

    Mackay-Sim, A; Breipohl, W; Kremer, M

    1988-01-01

    The factors controlling neurogenesis and differentiation of olfactory receptor cells in adults are poorly understood, although it is often stated that these cells undergo continual turnover after a predetermined lifespan. An interesting model in which to study mechanisms which control olfactory receptor neurogenesis and cell turnover is the tiger salamander, since basal cell mitosis varies with epithelial thickness and location in the nasal cavity. This paper presents a quantitative light-microscopic study of the different cell types within the ventral olfactory epithelium of the tiger salamander using a computer-assisted morphometric analysis of 2 micron sections. The results show that the surface density of olfactory vesicles remained constant throughout most of the epithelium and was independent of nasal cavity location, epithelial thickness and the total number of nuclei per unit epithelial surface area. Histological classification of nuclei into different cell types indicated that the increase in total cell number with epithelial thickness was mainly due to an increase in the number of immature receptor cells since the number of supporting cells varied only slightly and the numbers of basal cells and mature receptor cells remained constant except in the thinnest, most caudally located epithelium. It is concluded that the rate of maturation of receptor cells may be limited by an optimal surface density of olfactory vesicles. That is, when this density reaches 4.5 x 10(4) vesicles per mm2 there is a physical or chemical mechanism which prevents the final maturation of newly developing receptor cells, leading to their accumulation. This mechanism may also account for the variations in basal cell mitosis in this species.

  10. 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.

  11. 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

  12. Culturing of retinal pigment epithelium cells.

    PubMed

    Valtink, Monika; Engelmann, Katrin

    2009-01-01

    The retinal pigment epithelium (RPE) is a monolayer of cells adjacent to the photoreceptors of the retina. It plays a crucial role in maintaining photoreceptor health and survival. Degeneration or dysfunction of the RPE can lead to photoreceptor degeneration and as a consequence to visual impairment. The most common diseased state of the RPE becomes manifest in age-related macular degeneration, an increasing cause of blindness in the elderly. RPE cells are therefore of great interest to researchers working in the field of tissue engineering and cell transplantation. In fact, studies in animal models have proven that the transplantation of RPE cells can delay the course of photoreceptor degenerative diseases. Although first attempts to transplant RPE cells into the subretinal space in human individuals suffering from age-related macular degeneration were less successful, RPE cell transplantation is still favored as a future therapeutic option, and much work is done to develop and design cell transplants. Cell banking is a prerequisite to have well-differentiated and characterized cells at hand when needed for research purposes, but also for therapeutic approaches. In this chapter the authors will describe methods to isolate, culture and preserve adult human RPE cells for the purpose of RPE cell banking. Copyright 2009 S. Karger AG, Basel.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  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. Histological and morphometric studies on the dromedary camel epididymis in relation to reproductive activity.

    PubMed

    Ibrahim, Zarroug Hassan; Singh, Shio Kumar

    2014-10-01

    The reproductive efficiency of male dromedary camels under natural conditions is regarded to be low due to a relatively short breeding season and a long prepubertal period. This study was carried out to investigate the histological and morphometric changes in the Sudanese dromedary camel epididymis in relation to the breeding (rutting) and non-breeding (non-rutting) seasons at monthly intervals up to one year. Specimens were collected from different regions of the epididymis of 48 mature and healthy Sudanese male camels slaughtered at Tambul slaughter house in central Sudan. Paraffin sections of the caput, corpus and cauda regions of the epididymis were stained conventionally for general histology and morphometry. The epididymal stereociliated epithelium showed five types of cells: principal, basal, apical, halo and dark cells and the epithelium was surrounded by a thin layer of lamina propria and a circumtubular smooth muscle coat. No significant seasonal histological or morphometric changes were observed in the caput and corpus epididymides. However, a remarkable decrease in epididymal epithelial thickness and length of stereocilia with consequent increase in luminal diameter was observed in the cauda epididymidis during the rutting season; there was also an increase in the smooth muscle coat thickness. Thus, the results suggest that the epididymis of Sudanese dromedary camel is active throughout the year, but the activity remains low during winter and increases to its maximum during summer, especially during the rainy months. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. 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.

  1. Histomorphometric analysis of nuclear and cellular volumetric alterations in oral lichen planus, lichenoid lesions and normal oral mucosa using image analysis software.

    PubMed

    Venkatesiah, Sowmya S; Kale, Alka D; Hallikeremath, Seema R; Kotrashetti, Vijayalakshmi S

    2013-01-01

    Lichen planus is a chronic inflammatory mucocutaneous disease that clinically and histologically resembles lichenoid lesions, although the latter has a different etiology. Though criteria have been suggested for differentiating oral lichen planus from lichenoid lesions, confusion still prevails. To study the cellular and nuclear volumetric features in the epithelium of normal mucosa, lichen planus, and lichenoid lesions to determine variations if any. A retrospective study was done on 25 histologically diagnosed cases each of oral lichen planus, oral lichenoid lesions, and normal oral mucosa. Cellular and nuclear morphometric measurements were assessed on hematoxylin and eosin sections using image analysis software. Analysis of variance test (ANOVA) and Tukey's post-hoc test. The basal cells of oral lichen planus showed a significant increase in the mean nuclear and cellular areas, and in nuclear volume; there was a significant decrease in the nuclear-cytoplasmic ratio as compared to normal mucosa. The suprabasal cells showed a significant increase in nuclear and cellular areas, nuclear diameter, and nuclear and cellular volumes as compared to normal mucosa. The basal cells of oral lichenoid lesions showed significant difference in the mean cellular area and the mean nuclear-cytoplasmic ratio as compared to normal mucosa, whereas the suprabasal cells differed significantly from normal mucosa in the mean nuclear area and the nuclear and cellular volumes. Morphometry can differentiate lesions of oral lichen planus and oral lichenoid lesions from normal oral mucosa. Thus, morphometry may serve to discriminate between normal and premalignant lichen planus and lichenoid lesions. These lesions might have a high risk for malignant transformation and may behave in a similar manner with respect to malignant transformation.

  2. Generation of Human Female Reproductive Tract Epithelium from Human Embryonic Stem Cells

    PubMed Central

    Ye, Louie; Mayberry, Robyn; Lo, Camden Y.; Britt, Kara L.; Stanley, Edouard G.; Elefanty, Andrew G.; Gargett, Caroline E.

    2011-01-01

    Background Recent studies have identified stem/progenitor cells in human and mouse uterine epithelium, which are postulated to be responsible for tissue regeneration and proliferative disorders of human endometrium. These progenitor cells are thought to be derived from Müllerian duct (MD), the primordial female reproductive tract (FRT). Methodology/Principal Findings We have developed a model of human reproductive tract development in which inductive neonatal mouse uterine mesenchyme (nMUM) is recombined with green fluorescent protein (GFP)-tagged human embryonic stem cells (hESCs); GFP-hESC (ENVY). We demonstrate for the first time that hESCs can be differentiated into cells with a human FRT epithelial cell phenotype. hESC derived FRT epithelial cells emerged from cultures containing MIXL1+ mesendodermal precursors, paralleling events occurring during normal organogenesis. Following transplantation, nMUM treated embryoid bodies (EBs) generated epithelial structures with a typical MD phenotype that expressed the MD markers PAX2, HOXA10. Functionally, the hESCs derived FRT epithelium responded to exogenous estrogen by proliferating and secreting uterine-specific glycodelin A (GdA). Conclusions/Significance These data show nMUM can induce differentiation of hESC to form the FRT epithelium. This may provide a model to study early developmental events of the human FRT. PMID:21698266

  3. Tissue specific loss of A-type lamins in the gastrointestinal epithelium can enhance polyp size.

    PubMed

    Wang, Audrey S; Kozlov, Serguei V; Stewart, Colin L; Horn, Henning F

    2015-01-01

    The nuclear lamina, comprised of the A and B-type lamins, is important in maintaining nuclear shape and in regulating key nuclear functions such as chromatin organization and transcription. Deletion of the A-type lamins results in genome instability and many cancers show altered levels of A-type lamin expression. Loss of function mutations in the mouse Lmna gene result in early postnatal lethality, usually within 3-5 weeks of birth making an analysis of the role of lamins in carcinogenesis difficult. To circumvent early lethality, and determine the role of the A-type lamins in specific tissues in older mice we derived a conditional allele of Lmna(FL/FL) (floxed). Lmna(FL/FL) was specifically deleted in the gastrointestinal (GI) epithelium by crossing the Lmna(FL/FL) mice with Villin-Cre mice. Mice lacking Lmna in the GI are overtly normal with no effects on overall growth, longevity or GI morphology. On a GI specific sensitized (Apc(Min/+)) background, polyp numbers are unchanged, but polyp size is slightly increased, and only in the duodenum. Our findings reveal that although A-type lamins are dispensable in the postnatal GI epithelium, loss of Lmna under malignant conditions may, to a limited extent, enhance polyp size indicating that A-type lamins may regulate cell proliferation in the transformed GI epithelium. Published by Elsevier B.V.

  4. Assessment of tissue-engineered stomach derived from isolated epithelium organoid units.

    PubMed

    Maemura, T; Ogawa, K; Shin, M; Mochizuki, H; Vacanti, J P

    2004-06-01

    Isolated stomach epithelial organoid units developed on biodegradable polymers were transplanted to assess the feasibility of a tissue-engineered stomach. Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. An alternative treatment would be a tissue-engineered stomach, which replaces the mechanical and metabolic functions of a normal stomach. Stomach epithelial organoid units isolated from neonatal rats were seeded onto biodegradable polymers. The constructs implanted into the omenta of adult rats were harvested for examination at designated times. Nine rats underwent a second operation for anastomosis. The constructs resulted in cyst-like formations showing vascularized tissue with neomucosa lining the lumen. The surface morphology as assessed using scanning electron microscopy was similar to that of a native stomach. Immunohistochemical staining for alpha-actin smooth muscle and gastric mucin indicated the presence of a smooth muscle layer and a well-developed gastric epithelium, respectively. The luminal surface of the anastomosed tissue-engineered stomach was well-covered with epithelium. Epithelium-derived stomach organoid units seeded on biodegradable polymers and transplanted into donor rats were shown to vascularize, survive, and regenerate into complex tissue resembling native stomach. Anastomosis between the units and native small intestine may have the potential to stimulate epithelial growth. This research may provide insight into new approaches to alleviate complications following total gastrectomy. Copyright 2004 Elsevier Inc.

  5. HistoLogical, a computer atlas and drill of histology.

    PubMed

    Alper, E J; Cardasis, C

    1991-01-01

    An educational program has been developed to aid the instruction of Histology, a required course for the first year medical student. The program was developed using SuperCard on an Apple Macintosh IIci computer. It incorporates high quality color images with a hypermedia format, i.e. the student can jump from topic to topic as he/she wishes. The program has an "atlas," which provides information about each image and topic being discussed, and a "drill," which presents to the student a question about an image and provides feedback tailored to the student's answer. In the drill, the student is asked to type in responses to the questions; the answer is judged by text recognition. For each question, feedback is written for the correct answer, incorrect answer, and up to 10 "accessory answers" (answers which might be expected although they are not correct). The faculty of the UMMS Histology course has encouraged the use of this program in this years' course, and evaluation received from faculty and students has been quite positive.

  6. Nuclear changes in colo-rectal epithelium with special reference to nuclear inclusions in carcinoma, dysplasia, adenoma and Peutz-Jeghers polyps.

    PubMed

    Sato, E; Goto, M; Saku, T

    1985-05-01

    The incidence and types of unusual nuclear structures (UNS) were examined based on the observation of randomly photographed 1,919 nuclei in total from the normal epithelium, dysplasia, Peutz-Jeghers type polyp, adenoma and carcinoma of the large bowel. These nuclear structures were classified as filamentous, granular and vesicular inclusions, and invaginated structures were also taken into consideration. Although all types of UNS were found in the normal epithelium, carcinoma cells had the most numerous UNS, especially of the invaginated type. The possible process of nuclear inclusion (NI) formation was discussed in connection with malignant transformation of colo-rectal epithelial cells.

  7. 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

  8. Airway epithelium-derived relaxing factor: myth, reality, or naivety?

    PubMed

    Vanhoutte, Paul M

    2013-05-01

    The presence of a healthy epithelium can moderate the contraction of the underlying airway smooth muscle. This is, in part, because epithelial cells generate inhibitory messages, whether diffusible substances, electrophysiological signals, or both. The epithelium-dependent inhibitory effect can be tonic (basal), synergistic, or evoked. Rather than a unique epithelium-derived relaxing factor (EpDRF), several known endogenous bronchoactive mediators, including nitric oxide and prostaglandin E2, contribute. The early concept that EpDRF diffuses all the way through the subepithelial layers to directly relax the airway smooth muscle appears unlikely. It is more plausible that the epithelial cells release true messenger molecules, which alter the production of endogenous substances (nitric oxide and/or metabolites of arachidonic acid) by the subepithelial layers. These substances then diffuse to the airway smooth muscle cells, conveying epithelium dependency.

  9. Staffing benchmarks for histology laboratories.

    PubMed

    Buesa, René J

    2010-06-01

    This article summarizes annual workloads for staff positions and work flow productivity (WFP) values from 247 human pathology, 31 veterinary, and 35 forensic histology laboratories (histolabs). There are single summaries for veterinary and forensic histolabs, but the data from human pathology are divided into 2 groups because of statistically significant differences between those from Spain and 6 Hispano American countries (SpHA) and the rest from the United States and 17 other countries. The differences reflect the way the work is organized, but the histotechnicians and histotechnologists (histotechs) from SpHA have the same task productivity levels as those from any other country (Buesa RJ. Productivity standards for histology laboratories. [YADPA 50,552]). The information is also segregated by groups of histolabs with increasing workloads; this aspect also showed statistical differences. The information from human pathology histolabs other than those from SpHA were used to calculate staffing annual benchmarks for pathologists (from 3700 to 6500 cases depending on the histolab annual workload), pathology assistants (20,000 cases), staff histotechs (9900 blocks), cutting histotechs (15,000 blocks), histotechs doing special procedures (9500 slides if done manually or 15,000 slides with autostainers), dieners (100 autopsies), laboratory aides and transcriptionists (15,000 cases each), and secretaries (20,000 cases). There are also recommendations about workload limits for supervisory staff (lead techs and supervisors) and when neither is required. Each benchmark was related with the productivity of the different tasks they include (Buesa RJ. Productivity standards for histology laboratories. [YADPA 50,552]) to calculate the hours per year required to complete them. The relationship between workload and benchmarks allows the director of pathology to determine the staff needed for the efficient operation of the histolab.

  10. 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.

  11. 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".

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Enhanced proliferation in colorectal epithelium of patients with type 2 diabetes correlates with β-catenin accumulation.

    PubMed

    Li, Jie-Yao; Yu, Tao; Xia, Zhong-Sheng; Chen, Guang-Cheng; Yuan, Yu-Hong; Zhong, Wa; Zhao, Li-Na; Chen, Qi-Kui

    2014-01-01

    β-Catenin accumulation promotes proliferation. However, the correlation between proliferation of colorectal epithelium and β-catenin in type 2 diabetes mellitus (DM) patients remains unclear. Colorectal epithelium samples from distal ends of colorectal adenocarcinomas without histological aberrances were divided into two groups: DM patients with type 2 DM for more than 1year (n=27) and non-DM patients without hyperglycemia (n=20). Samples from patients without colorectal epithelial disease or hyperglycemia served as a control group (n=6). Proliferative index was calculated as the percentage of proliferating cell nuclear antigen positive cells. Wnt/β-catenin signaling was assessed immunohistochemically and phosphorylation of β-catenin was assessed by immunofluorescence. Compared with the non-DM or control group, the proliferative index and expression of lactate dehydrogenase A and Wnt/β-catenin signaling were significantly higher in the DM group (all p<0.01). The proliferative index correlated positively with β-catenin expression (Spearman correlation coefficient=0.55; p<0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of β-catenin were detected in the DM group (all p<0.01). Enhanced proliferation, accompanied by increased aerobic glycolysis, was detected in colorectal epithelium of patients with diabetes. β-Catenin accumulation with altered phosphorylation correlated with the proliferative changes. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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

  3. 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.

  4. Diagnosing oesophagitis in children: how discriminative is histology?

    PubMed

    Karabulut, Y Y; Savaş, B; Kansu, A; Kurşun, N; Ensari, A

    2013-09-01

    We set out to evaluate the discriminatory value of currently available histologic criteria in the differential diagnosis of reflux oesophagitis and eosinophilic oesophagitis in children. We evaluated the oesophageal biopsies of 145 children and selected 28 demonstrative cases of clinically confirmed eosinophilic oesophagitis (n = 7), and reflux oesophagitis (n = 11) with a control group with normal histology (n = 10). Histological assessment was performed for the presence of papillary elongation, dilatation of intercellular spaces, basal cell hyperplasia and the number of intraepithelial eosinophils, lymphocytes and neutrophils. Among 28 children, there were 3 boys and 4 girls in eosinophilic oesophagitis group, 8 boys and 3 girls in reflux group, and 5 boys and 5 girls in normal group. The mean age was 10,4 years. Basal cell hyperplasia was observed in 12 cases while papillary elongation was found in 25, and dilated intercellular spaces were present in 20 cases. Lymphocyte and neutrophil counts were significantly higher in reflux group when compared to eosinophilic oesophagitis and normal group. Eosinophil counts were significantly higher in eosinophilic group. Results of the present study suggest that, basal cell hyperplasia, papillary elongation, and dilated intercellular spaces all seem to be markers of oesophagitis regardless of the underlying pathology and etiology, thereby, highlighting their rather nonspecific nature in the differential diagnosis of various types of oesophagitis. The additional information on inflammatory cell counts may help to distinguish reflux oesophagitis from other causes of oesophagitis including EoO.

  5. The long-term effects of semiconductor diode laser transscleral cyclophotocoagulation on the normal equine eye and intraocular pressure(a).

    PubMed

    Cavens, Vanessa J Kuonen; Gemensky-Metzler, Anne J; Wilkie, David A; Weisbrode, Steven E; Lehman, Amy M

    2012-11-01

    To describe the long-term histologic and intraocular pressure (IOP) lowering effects of diode laser transscleral cyclophotocoagulation (TSCP) on the normal equine eye. Eight normal adult horses. TSCP was performed in one randomly assigned eye. Sixty spots were treated at settings of 1500 ms and 1500 mW. Two horses were randomly selected for euthanasia at 2, 4, 12, or 24 weeks post-TSCP. Both eyes were enucleated and histologically evaluated. Intraocular pressure was measured by applanation tonometry prior to TSCP, immediately post-TSCP, twice daily for 7 days post-TSCP and then monthly until study conclusion. A longitudinal model estimated the average IOP values for the treated and untreated eyes at 1 week, 1, 3, and 6 months post-TSCP. All treated eyes at all time periods exhibited four characteristic histologic lesions: scleral collagen hyalinization, ciliary body pigment dispersion and clumping, focal disruption of the ciliary body epithelium, and focal ciliary process atrophy. After TSCP, there were no significant changes in IOP from baseline for the control eyes, while the IOP in treated eyes was significantly decreased from baseline (P < 0.05) at all time periods. The estimated decrease in IOP in the treated eyes compared to baseline IOP at 6 months was -3.76 mmHg for an average decrease in IOP of 20% from baseline. Diode laser TSCP produces histologic lesions in the equine ciliary body that result in a significant and sustained decrease in IOP. TSCP may be an effective management for equine glaucoma. © 2012 American College of Veterinary Ophthalmologists.

  6. Normal clotting.

    PubMed

    Moran, Theresa A; Viele, Carol S

    2005-11-01

    To review the normal coagulation process and the mechanisms that lead to abnormal clotting. Primary and tertiary literature and the authors' clinical experience. The process of coagulation is complex and can be easily misunderstood. It is important to be familiar with normal coagulation before one can comprehend the coagulopathies associated with malignancies. A thorough understanding of the coagulation process is a critical prerequisite to caring for patients with clotting disorders. Once the normal clotting process is understood, the abnormal becomes easier to recognize and the cancer-associated dysfunctions more readily identified.

  7. Prediction of esophageal and gastric histology by macroscopic diagnosis during upper endoscopy in pediatric celiac disease.

    PubMed

    Boschee, Erin D; Yap, Jason Y K; Turner, Justine M

    2017-01-28

    To determine the sensitivity of macroscopic appearance for predicting histological diagnosis at sites other than duodenum in pediatric celiac disease (CD). Endoscopic and histologic findings in pediatric patients undergoing upper endoscopy for first-time diagnosis of CD at Stollery Children's Hospital from 2010