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Sample records for normal oral epithelium

  1. Expression of Ki-67 in normal oral epithelium, leukoplakic oral epithelium and oral squamous cell carcinoma

    PubMed Central

    Birajdar, Smita Shrishail; Radhika, MB; Paremala, K; Sudhakara, M; Soumya, M; Gadivan, Mohsin

    2014-01-01

    Aims and Objective: To demonstrate the presence, location and pattern of cell proliferation in different histological grades of oral epithelial dysplasia (OED), oral squamous cell carcinoma (OSCC) and normal oral epithelium (NOE) using an antibody directed against the Ki-67 antigen and its intensity of staining evaluated respectively. Materials and Methods: A total number of 100 archival paraffin embedded blocks obtained from Department of Oral and Maxillofacial Pathology were studied. The case details were retrieved which consisted of histopathologically diagnosed cases of OSCC (n = 20), low risk OED (n = 30), high risk OED (n = 30) and normal appearing mucosa (n = 20) were taken as standard for comparison. Ki-67 immunostaining was detected. Ki-67 positive cells were counted in the five random high power fields in each case. Results: Ki-67 labeling Index (LI) was restricted to the basal and parabasal layers of the normal oral epithelium irrespective of age, sex and site whereas it was seen in the basal, suprabasal and spinous layers in OED. Ki-67 LI is increased in high risk cases than the low risk cases of OED. Ki-67 positive cells in OSCC were located in the periphery of the tumor nests than the center, where frequent mitoses were observed. Conclusion: The architectural alteration evaluated by Ki-67 antibody in proliferating cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of OED. Ki-67 LI increased in high risk cases than low risk cases of OED. This study showed that over expression of Ki-67 antigen between well-differentiated and poorly differentiated OSCC was in accordance with histologic grade of malignancy but not in accordance with moderately differentiated OSCC. PMID:25328294

  2. Caspase-3 expression in normal oral epithelium, oral submucous fibrosis and oral squamous cell carcinoma

    PubMed Central

    Veeravarmal, Veeran; Austin, Ravi David; Siddavaram, Nagini; Thiruneelakandan, Sambanthan; Nassar, Mohamed Hanifa Mohamed

    2016-01-01

    Context: The epithelium atrophy, as the oral submucous fibrosis (OSMF) progresses, is believed to be an after effect of stromal fibrosis, hyalinization, decrease in vascularity and cellularity and is considered as “ischemic atrophy.” Due to hypoxia, caspase-3 get activation and subsequent decrease in viable cell count can occur. Aims and Objectives: To determine caspase-3 expression in various grades of OSMF and oral squamous cell carcinoma (OSCC) to find out whether upregulation of apoptosis is responsible for the epithelial changes in OSMF. Subjects and Methods: The control tissue (15 samples from normal oral mucosa) and study group comprising 97 cases of OSMF of different grades and OSCC associated with OSMF were stained with caspase-3 antibody, and the percentage of positive cells was calculated using ImageJ software. Statistical Analysis: The results obtained were statistically analyzed using ANOVA and Tukey's honest significance difference test and Mann–Whitney U-test. Results: There was a nuclear expression of caspase-3 in basal and parabasal layers of normal epithelium. There was cytoplasmic expression of caspase-3 in OSMF without dysplasia, total absence of caspase-3 expression in dysplastic epithelium and in majority cases of OSCC. The caspase-3 percentage was increased in OSMF (0%–53%) when compared with OSCC (0%–8%). The statistical comparison of caspase-3 among normal, OSMF and OSCC patients revealed significant correlation (P < 0.00010). The comparison within different grades of OSMF and between dysplastic and nondysplastic epithelium OSMF also showed significance (P < 0.019). Conclusions: The decreased expression of caspase-3 in disease progression reflects its role in the malignant transformation. PMID:27721610

  3. 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

  4. 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

  5. The ionic components of normal human oesophageal epithelium.

    PubMed

    Hopwood, D; Milne, G; Curtis, M; Nicholson, G

    1979-11-01

    The distribution of cations and anions in normal human oesophageal epithelium has been investigated with the pyroantimonate and silver-osmium tetroxide techniques. There is a discontinuous distribution of both ions in the intercellular space. The ions are associated with various organelles, as has already been described in the literature. Specifically, in the oesophageal epithelium, there are a few deposits of pyroantimonate and occasional silver in the membrane coating granules, but here is no apparent relationship of either ion with the tonofilaments or glycogen particles. The superficial cells are leaky and contain fewer ions than the deeper functional layer cells.

  6. 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.

  7. Orthogonal arrays in normal and injured respiratory airway epithelium.

    PubMed

    Gordon, R E

    1985-02-01

    Orthogonal arrays are found on plasma membranes of glial cells, in the central nervous system, on muscle plasma membranes at neuromuscular junctions, and on a variety of epithelial cells. These structures have been correlated with ion flux. With the aid of freeze fracture technique, orthogonal particle arrays were found on plasma membranes on airway epithelial cells of rats and hamsters. They have been found in abundance at the base of secretory cells throughout normal airway epithelium. These structures were found to increase in number during regeneration in response to injury and they were found in great numbers on plasma membranes of all airway cells in response to acute and chronic NO2 exposure. The lateral and basal plasma membranes of the respiratory epithelium are a new source for studying orthogonal arrays. The normal number and distribution of these arrays can be perturbed in response to mechanical and chemical injury. PMID:3968185

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

    PubMed

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

    2016-04-01

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

  9. Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

    PubMed Central

    Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

    2014-01-01

    Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the

  10. Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma

    PubMed Central

    Gannot, G; Gannot, I; Vered, H; Buchner, A; Keisari, Y

    2002-01-01

    In the present study, epithelium derived lesions of various pathological manifestations were examined histologically and immunohistochemically for mononuclear cell infiltration. The infiltrate under the transformed epithelium of oral lesions, was examined for differences in the composition of immune mononuclear cells as the epithelium moves from hyperkeratosis through various degrees of dysplasia to squamous cell carcinoma. The study was performed on 53 human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19 cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases). Immunohistochemical analysis of various surface markers of the tumour infiltrating immune cells was performed and correlated with the transformation level as defined by morphology and the expression of p53 in the epithelium. The results revealed that, in the tongue lesions, the changes in the epithelium from normal appearance to transformed were accompanied by a corresponding increase in the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most significant change was an increase in B lymphocytes in tongue lesions, that was in accordance with the transformation level (P<0.001). In the salivary gland, a significant number of cases did not show an infiltrate. In cases where an infiltrate was present, a similar pattern was observed and the more malignant tissues exhibited a higher degree of immune cell infiltration. British Journal of Cancer (2002) 86, 1444–1448. DOI: 10.1038/sj/bjc/6600282 www.bjcancer.com © 2002 Cancer Research UK PMID:11986779

  11. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay

    PubMed Central

    Yilmaz, Özlem

    2009-01-01

    The microbiota of the human oral mucosa consists of a myriad of bacterial species that normally exist in commensal harmony with the host. Porphyromonas gingivalis, an aetiological agent in severe forms of periodontitis (a chronic inflammatory disease), is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. This Gram-negative anaerobe can also exist within the host epithelium without the existence of overt disease. Gingival epithelial cells, the outer lining of the gingival mucosa, which function as an important part of the innate immune system, are among the first host cells colonized by P. gingivalis. This review describes recent studies implicating the co-existence and intracellular adaptation of the organism in these target host cells. Specifically, recent findings on the putative mechanisms of persistence, intercellular dissemination and opportunism are highlighted. These new findings may also represent an original and valuable model for mechanistic characterization of other successful host-adapted, self-limiting, persistent intracellular bacteria in human epithelial tissues. PMID:18832296

  12. Epithelium

    MedlinePlus

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make up the outer surface of the body. Epithelial cells help to protect or enclose organs. Most produce mucus or other secretions. Certain ...

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

    EPA Science Inventory

    Abstract

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

  14. Cultivated Oral Mucosa Epithelium in Ocular Surface Reconstruction in Aniridia Patients

    PubMed Central

    Dobrowolski, Dariusz; Orzechowska-Wylegala, Boguslawa; Wowra, Bogumil; Wroblewska-Czajka, Ewa; Grolik, Maria; Szczubialka, Krzysztof; Nowakowska, Maria; Puzzolo, Domenico; Wylegala, Edward A.; Micali, Antonio; Aragona, Pasquale

    2015-01-01

    Purpose. Efficacy of cultivated oral mucosa epithelial transplantation (COMET) procedure in corneal epithelium restoration of aniridia patients. Methods. Study subjects were aniridia patients (13 patients; 17 eyes) with irregular, vascular conjunctival pannus involving visual axis who underwent autologous transplantation of cultivated epithelium. For the procedure oral mucosa epithelial cells were obtained from buccal mucosa with further enzymatic treatment. Suspension of single cells was seeded on previously prepared denuded amniotic membrane. Cultures were carried on culture dishes inserts in the presence of the inactivated with Mitomycin C monolayer of 3T3 fibroblasts. Cultures were carried for seven days. Stratified oral mucosa epithelium with its amniotic membrane carrier was transplanted on the surgically denuded corneal surface of aniridia patients with total or subtotal limbal stem cell deficiency. Outcome Measures. Corneal surface, epithelial regularity, and visual acuity improvement were evaluated. Results. At the end of the observation period, 76.4% of the eyes had regular transparent epithelium and 23.5% had developed epithelial defects or central corneal haze; in 88.2% of cases visual acuity had increased. VA range was from HM 0.05 before the surgery to HM up to 0.1 after surgery. Conclusion. Application of cultivated oral mucosa epithelium restores regular epithelium on the corneal surface with moderate improvement in quality of vision. PMID:26451366

  15. 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

  16. 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

  17. Desmosomal component expression in normal, dysplastic, and oral squamous cell carcinoma.

    PubMed

    Narayana, Nagamani; Gist, Julie; Smith, Tyler; Tylka, Daniel; Trogdon, Gavin; Wahl, James K

    2010-01-01

    Squamous cell carcinoma (oral SCC) is the most common oral cancer in the U.S., affecting nearly 30,000 Americans each year. Despite recent advances in detection and treatment, there has been little improvement in the five-year survival rate for this devastating disease. Oral cancer may be preceded by premalignant disease that appears histologically as dysplasia. Identification of molecular markers for cellular change would assist in determining the risk of dysplasia progressing to oral squamous cell carcinoma. The goal of this study was to determine if any correlation exists between histological diagnosed dysplasia and OSCC lesions and altered expression of desmosomal cell-cell adhesion molecules in the oral epithelium. Our data showed that oral SCC tissue samples showed decreased immunoreactivity of both desmoplakin and plakophilin-1 proteins compared to normal oral epithelium. Furthermore, significant decrease in desmoplakin immunoreactivity was observed in dysplastic tissue compared to normal oral epithelium. In contrast, the level of desmoglein-1 staining was unchanged between samples however desmoglein-1 was found localized to cell borders in oral SCC samples. These data suggest that changes in expression of desmoplakin and plakophilin-1 may prove to be a useful marker for changes in tissue morphology and provide a tool for identifying pre-neoplastic lesions of the oral cavity. PMID:20585603

  18. Substance P and NK-1R expression in oral precancerous epithelium.

    PubMed

    Gonzalez-Moles, Miguel A; Brener, S; Ruiz-Avila, I; Gil-Montoya, J A; Tostes, D; Bravo, M; Esteban, F

    2009-12-01

    The objectives of this study were to investigate the presence and distribution of substance P and neurokinin 1 receptor in oral premalignant epithelium and their relation with the presence of dysplasia, and to analyze whether the expression of substance P can be considered an early oncogenic event in oral carcinogenesis. substance P and neurokinin 1 receptor expression was immunohistochemically studied in 83 oral carcinomas and adjacent non-tumor epithelia. The presence and degree of epithelial dysplasia was assessed according to WHO criteria. The nuclear, cytoplasmic, and membrane expression of substance P and the cytoplasmic and membrane expression of neurokinin 1 receptor were assessed in tumor and adjacent non-tumor epithelium. Nuclear and cytoplasmic expression of substance P in non-tumor epithelium was significantly associated with the presence of epithelial dysplasia (p<0.001) and carcinoma in situ (p=0.021). Nuclear, cytoplasmic, and membrane expressions of substance P in non-tumor epithelium were significantly (p<0.001) associated with its expression in the corresponding tumor. These findings suggest that substance P plays a role in early oral carcinogenesis by promoting the proliferation and growth of premalignant fields.

  19. 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.

  20. Quantitative electron microscopic analysis of the epithelium of normal human alveolar mucosa.

    PubMed

    Bernimoulin, J P; Schroeder, H E

    1977-05-31

    The epithelium of normal human alveolar mucosa originating from the anterior vestibulum was subjected to stereologic analysis. Eight biopsies were collected half-way between the muco gingival junction and the vestibular fornix from 20 to 50 year-old females, and processed for light and electron microscopy. At two levels of magnification, electron micrographs were sampled from four artificially selected strata in regions of epithelial ridges. Stereologic point counting based on a computer-aided system for analyzing stratified epithelia served for examining a total of about 860 electron micrographs. The alveolar epithelium was 0.26 mm thick, occasionally interdigitated by short, slender connective tissue papillae, and consisted of (1) a narrow basal and suprabasal, and (2) a broad spinous and surface compartment. It displayed a differentiation pattern which, in most subjects studied, was similar to that of normal human buccal epithelium, however, on the average, produced less mature surface cells. This pattern was expressed mainly by a density increase of cytoplasmic filaments (98 A in diameter), a concomitant decrease of the cytoplasmic ground substance, the formation of dark-cored membrane coating granules, and invividually variable amounts of glycogen deposition. In some subjects, a mixed differentiation pattern was found. The structural organization of alveolar epithelium, in analogy to cheek epithelium, was compatible with the function of distensibility.

  1. Cavitary lung cancer lined with normal bronchial epithelium and cancer cells.

    PubMed

    Goto, Taichiro; Maeshima, Arafumi; Oyamada, Yoshitaka; Kato, Ryoichi

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells. PMID:21980325

  2. EDTA separation and recombination of epithelium and connective tissue of human oral mucosa. Studies of tissue transplants in nude mice.

    PubMed

    Holmstrup, P; Dabelsteen, E; Harder, F

    1985-01-01

    A possible epithelial-mesenchymal interaction in determining epithelial histologic features of human oral mucosa was examined. The study comprised 74 biopsies of normal buccal mucosa and 54 biopsies of normal palatal mucosa. Epithelium was separated from connective tissue by the use of 1 mM ethylenediamine tetraacetate dihydrate. Self-recombined and cross-recombined epithelial and connective tissues and connective tissue sheets alone were transplanted to subcutaneous sites of nude mice. Histologic examination of cross-recombined palatal epithelium/buccal connective tissue transplants showed a change in keratinization pattern but no major change in number of epithelial cell layers as the result of connective tissue influence. Transplanted sheets of connective tissue after growth for 14 days showed that complete separation of biopsies from buccal mucosa had been obtained. However, palatal mucosa had been incompletely separated as evidenced by re-epithelialization of most of the connective tissue transplants. The consequences of the incomplete palatal epithelium-connective tissue separation are discussed.

  3. Porphyromonas gingivalis infection of oral epithelium inhibits neutrophil transepithelial migration.

    PubMed Central

    Madianos, P N; Papapanou, P N; Sandros, J

    1997-01-01

    Periodontal diseases are inflammatory disorders caused by microorganisms of dental plaque that colonize the gingival sulcus and, subsequently, the periodontal pocket. As in other mucosal infections, the host response to plaque bacteria is characterized by an influx of polymorphonuclear leukocytes (PMNs) to the gingival crevice. Neutrophil migration through the epithelial lining of the gingival pocket is thought to be the first line of defense against plaque bacteria. In order to model this phenomenon in vitro, we used the oral epithelial cell line KB and human PMNs in the Transwell system and examined the impact of Porphyromonas gingivalis-epithelial cell interactions on subsequent PMN transepithelial migration. We demonstrate here that P. gingivalis infection of oral epithelial cells failed to trigger transmigration of PMNs. Furthermore, it significantly inhibited neutrophil transmigration actively induced by stimuli such as N-formylmethionyl leucyl phenylalanine, interleukin-8 (IL-8), and the intestinal pathogen enterotoxigenic Escherichia coli. The ability of P. gingivalis to block PMN transmigration was strongly positively correlated with the ability to adhere to and invade epithelial cells. In addition, P. gingivalis attenuated the production of IL-8 and the expression of intercellular adhesion molecule 1 by epithelial cells. The ability of P. gingivalis to block neutrophil migration across an intact epithelial barrier may critically impair the potential of the host to confront the bacterial challenge and thus may play an important role in the pathogenesis of periodontal disease. PMID:9316996

  4. Nicotine modulates gelatinase B (MMP-9) and epilysin (MMP-28) expression in reconstituted human oral epithelium.

    PubMed

    Renò, Filippo; Rocchetti, Vincenzo; Migliario, Mario; Cannas, Mario

    2011-01-01

    Oral epithelial keratinocytes express nicotinic cholinergic receptors which activation modulates keratinocytes differentiation and migration through different metabolic pathways. Matrix metalloproteinases (MMPs) are Zn-dependent enzyme involved in cell migration. Among them, gelatinase B (MMP-9) and epilysin (MMP-28) are two MMPs expressed by human keratinocytes during both wound healing and proliferation. Their expression has been investigated in a reconstituted human oral epithelium (HOE) exposed to nicotine (Nic, 1-50 μM) for 72 h both in the absence and presence of the nicotinic antagonist mecamylamine (Mec), H7, a PKC inhibitor and PD98059, a MAPK inhibitor (PD). At the end of treatment, MMP-28 expression has been analyzed in epithelium sections using an anti-MMP-28 antibody, whereas MMP-9 presence and activity has been measured in cell-conditioned medium analyzed by gelatine zymography. The expression of MMP-9 was reduced by Nic in a dose-dependent fashion and this effect was antagonized by Mec, H7 and PD. On the other hand, Nic increased the expression of MMP-28, and this effect was blocked both by H7 and PD, whereas Mec even enforced it. Nic effects on MMP-9 and MMP-28 expression by oral keratinocytes were not previously reported and these data suggest MMPs expression mediated by PKC and MAPK as a possible target for Nic toxicity in oral epithelium.

  5. 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.

  6. Overexpression of BMP-2/4, -5 and BMPR-IA associated with malignancy of oral epithelium.

    PubMed

    Jin, Y; Tipoe, G L; Liong, E C; Lau, T Y; Fung, P C; Leung, K M

    2001-04-01

    The aim of the present study was to determine the relationships between bone morphogenetic proteins (BMPs), BMP receptor type IA and carcinogenesis of oral epithelium. A retrospective study was performed on material obtained from oral mucosa, including nine cases of normal mucosa (NB), eight cases of nonspecific chronic inflammation (NCI), seven cases of hyperkeratosis (HK), five cases of squamous cell papilloma (SCP), 29 cases of squamous cell carcinoma (SCC) with various grades of differentiation and 10 cases of epithelium adjacent to carcinoma (EAC). Six cases of NB from hard palate (NHP) were chosen as a control group. The benign groups consisted of NCI, HK and SCP. The antibodies against BMP-2/4, -5, receptor BMPR-IA and purified bovine BMP (bBMP-McAb) were utilised using an immunocytochemical method. The results demonstrated that the immunostaining of BMP-2/4, BMP-5, BMPR-IA and bBMP-McAb was weak and not consistent in normal and benign groups. The immunoreactivity level was independent of the clinical and pathological grading of SCC. All cases of SCC showed positive staining for BMP-2/4, BMP-5, BMPR-IA and bBMP-McAb except for three cases and one case of SCC which negatively stained for BMP-2/4 and BMP-5, respectively. The staining intensity and proportion of the positively stained cells were markedly increased in SCC when compared with that of the normal and benign groups except for EAC. The metastatic carcinoma cells in lymph nodes were strongly and positively stained for BMP-2/4 and BMP-5 when compared with the primary lesions. Our results indicate that there was an overexpression of BMP-2/4, BMP-5, bBMP-McAb and BMPR-IA in the high-risk premalignant and malignant lesions of oral epithelium. Our findings suggest that BMP-2/4 and BMP-5 but not BMPR-IA might be involved in the metastasis of oral carcinoma cells.

  7. 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

  8. Histatin 5 inhibits adhesion of C. albicans to Reconstructed Human Oral Epithelium

    PubMed Central

    Moffa, Eduardo B.; Mussi, Maria C. M.; Xiao, Yizhi; Garrido, Saulo S.; Machado, Maria A. A. M.; Giampaolo, Eunice T.; Siqueira, Walter L.

    2015-01-01

    Candida albicans is the most pathogenic fungal species, commonly colonizing on human mucosal surfaces. As a polymorphic species, C. albicans is capable of switching between yeast and hyphal forms, causing an array of mucosal and disseminated infections with high mortality. While the yeast form is most commonly associated with systemic disease, the hyphae are more adept at adhering to and penetrating host tissue and are therefore frequently observed in mucosal fungal infections, most commonly oral candidiasis. The formation of a saliva-derived protein pellicle on the mucosa surface can provide protection against C. albicans on oral epithelial cells, and narrow information is available on the mucosal pellicle composition. Histatins are one of the most abundant salivary proteins and presents antifungal and antibacterial activities against many species of the oral microbiota, however, its presence has never been studied in oral mucosa pellicle. The objective of this study was to evaluate the potential of histatin 5 to protect the Human Oral Epithelium against C. albicans adhesion. Human Oral Epithelial Tissues (HOET) were incubated with PBS containing histatin 5 for 2 h, followed by incubation with C. albicans for 1 h at 37°C. The tissues were then washed several times in PBS, transferred to fresh RPMI and incubated for 16 h at 37°C at 5% CO2. HOET were then prepared for histopathological analysis using light microscopy. In addition, the TUNEL assay was employed to evaluate the apoptosis of epithelial cells using fluorescent microscopy. HOET pre-incubated with histatin 5 showed a lower rate of C. albicans growth and cell apoptosis when compared to the control groups (HOET alone and HOET incubated with C. albicans). The data suggest that the coating with histatin 5 is able to reduce C. albicans colonization on epithelial cell surfaces and also protect the basal cell layers from undergoing apoptosis. PMID:26379655

  9. Histatin 5 inhibits adhesion of C. albicans to Reconstructed Human Oral Epithelium.

    PubMed

    Moffa, Eduardo B; Mussi, Maria C M; Xiao, Yizhi; Garrido, Saulo S; Machado, Maria A A M; Giampaolo, Eunice T; Siqueira, Walter L

    2015-01-01

    Candida albicans is the most pathogenic fungal species, commonly colonizing on human mucosal surfaces. As a polymorphic species, C. albicans is capable of switching between yeast and hyphal forms, causing an array of mucosal and disseminated infections with high mortality. While the yeast form is most commonly associated with systemic disease, the hyphae are more adept at adhering to and penetrating host tissue and are therefore frequently observed in mucosal fungal infections, most commonly oral candidiasis. The formation of a saliva-derived protein pellicle on the mucosa surface can provide protection against C. albicans on oral epithelial cells, and narrow information is available on the mucosal pellicle composition. Histatins are one of the most abundant salivary proteins and presents antifungal and antibacterial activities against many species of the oral microbiota, however, its presence has never been studied in oral mucosa pellicle. The objective of this study was to evaluate the potential of histatin 5 to protect the Human Oral Epithelium against C. albicans adhesion. Human Oral Epithelial Tissues (HOET) were incubated with PBS containing histatin 5 for 2 h, followed by incubation with C. albicans for 1 h at 37°C. The tissues were then washed several times in PBS, transferred to fresh RPMI and incubated for 16 h at 37°C at 5% CO2. HOET were then prepared for histopathological analysis using light microscopy. In addition, the TUNEL assay was employed to evaluate the apoptosis of epithelial cells using fluorescent microscopy. HOET pre-incubated with histatin 5 showed a lower rate of C. albicans growth and cell apoptosis when compared to the control groups (HOET alone and HOET incubated with C. albicans). The data suggest that the coating with histatin 5 is able to reduce C. albicans colonization on epithelial cell surfaces and also protect the basal cell layers from undergoing apoptosis.

  10. The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol.

    PubMed

    Khan, S A; Sachdeva, A; Naim, S; Meguid, M M; Marx, W; Simon, H; Halverson, J D; Numann, P J

    1999-10-01

    Breast epithelial response to estradiol may play an important role in breast cancer etiology. We have examined the relationship between serum estradiol and progesterone levels and normal breast epithelial expression of estrogen receptor (ER) alpha, progesterone receptor (PgR), and epithelial proliferation (as reflected by the Ki-67 labeling index) in 121 women (50 newly diagnosed breast cancer cases and 71 benign breast disease controls). Simultaneous samples of grossly normal breast tissue and venous blood were obtained from women undergoing breast surgery. Serum estradiol and progesterone levels were measured by radioimmunoassay; breast epithelial ER, PgR, and Ki-67 expression was measured by immunohistochemistry. Linear regression, controlled for patient age and ductal and lobular composition of the tissue, showed that the breast epithelium of control women displayed an inverse correlation between serum estradiol and ER-alpha, which was not seen in case women (P for the difference in regression slopes = 0.001). PgR expression displayed a significant positive correlation with serum estradiol in cases, but not in controls. Epithelial proliferation had no relationship to either estradiol or progesterone in both cases and controls but showed an inverse relationship with ER in controls and a direct relationship in cases (P for the difference in regression slopes = 0.066). These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response.

  11. Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

    NASA Astrophysics Data System (ADS)

    Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

    2011-12-01

    Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

  12. Detection of aryl hydrocarbon hydroxylase activity in normal and neoplastic human breast epithelium

    SciTech Connect

    Greiner, J.W.; Malan-Shibley, L.B.; Janss, D.H.

    1980-01-28

    Studies were conducted to determine whether normal and/or neoplastic (MCF-7) human breast epithelial cells contain the microsomal aryl hydrocarbon hydroxylase (AHH) which catalyses the conversion of polycyclic aromatic hydrocarbons (PAH) to carcinogenic intermediates. Low constitutive levels of AHH activity were found in homogenates of both normal human breast epithelial and MCF-7 cells. The addition of 7,12-dimethylbenz(a)anthracene (DMBA) to the culture medium of either cell type significantly increased AHH activity. Peak induction of hydroxylase activity occurred following the in vitro addition of 10 ..mu..M DMBA. A time course of DMBA-induced AHH activity in both normal human breast epithelium and MCF-7 cells revealed maximal induction 16 hr after 10 ..mu..M DMBA was added to the culture medium. Benzo(a)pyrene (BP), 3-methylcholanthrene (MCA) and benz(a)anthracene (BA) also induced AHH activity in normal and MCF-7 cells. For example, the addition of 10 ..mu..M BP to the culture medium of either normal human breast epithelial or MCF-7 cells for 16 hr increased AHH activity 13.8 and 65.3-fold, respectively. For all PAH, the magnitude of AHH induction was substantially greater in MCF-7 than normal breast epithelial cells. Finally, ..cap alpha..-naphthoflavone inhibited BA-induced AHH activity in MCF-7 cells. The study demonstrates the presence of a PAH-inducible AHH enzyme(s) in normal human breast epithelial cells grown in primary culture and in the human breast tumor cell line, MCF-7.

  13. Histological features of oral epithelium in seven animal species: As a reference for selecting animal models.

    PubMed

    Sa, Guoliang; Xiong, Xuepeng; Wu, Tianfu; Yang, Jincheng; He, Sangang; Zhao, Yifang

    2016-01-01

    Several animals have been used as models for basic and clinical research on oral mucosa. Few studies have focused on the selection of an appropriate animal model. This study aimed to provide histological references for selecting a potential model. Histological features were assessed by exploring 6 morphological characteristics and 2 immunohistochemical markers. The morphological characteristics included keratinization, basal membrane appearance, epithelial thickness, rete ridge length, adjacent rete ridge distance, and regional variation; the immunohistochemical markers included Ki67 (a proliferative marker) and Cytokeratin 19 (CK19; a stemness marker). The histological similarity of each species compared to humans was calculated according to the designated scoring criteria. The results showed that the buccal mucosae from dog and pig were non-keratinized, with similar rete ridge length and distance, compared to that of humans. The dog, rat, and cavy mucosae had analogous gross appearances in the basal membrane. The dog oral mucosae shared similar epithelial thickness with human oral mucosae. Compared to the human mucosa, the dog, pig, rat, and rabbit mucosae exhibited corresponding regional variations. The Ki67-positive cells in human and canine mucosae were predominantly localized in the suprabasal layers, whereas most of the proliferative cells were in the basal layer in other species. CK19 immunoreactivities were detected only in human and canine mucosae. The canine mucosae gained the highest point value (14), whereas the scores for the pig, rat, rabbit, cavy, sheep, and buffalo mucosae were 8, 6, 5, 5, 5, and 2, respectively. The histological variations in the oral epithelium of diverse animal species are considerable; the mucosae from dogs are most similar to human mucosae, implicating its histological basis as an animal model.

  14. Corneal Epithelium Thickness Profile in 614 Normal Chinese Children Aged 7–15 Years Old

    PubMed Central

    Ma, Yingyan; He, Xiangui; Zhu, Xiaofeng; Lu, Lina; Zhu, Jianfeng; Zou, Haidong

    2016-01-01

    The purpose of the study is to describe the values and distribution of corneal epithelium thickness (CET) in normal Chinese school-aged children, and to explore associated factors with CET. CET maps were measured by Fourier-domain optical coherence tomography (FD-OCT) in normal Chinese children aged 7 to 15 years old from two randomly selected schools in Shanghai, China. Children with normal intraocular pressure were further examined for cycloplegic autorefraction, corneal curvature radius (CCR) and axial length. Central (2-mm diameter area), para-central (2- to 5-mm diameter area), and peripheral (5- to 6-mm diameter area) CET in the superior, superotemporal, temporal, inferotemporal, inferior, inferonasal, nasal, superonasal cornea; minimum, maximum, range, and standard deviation of CET within the 5-mm diameter area were recorded. The CET was thinner in the superior than in the inferior and was thinner in the temporal than in the nasal. The maximum CET was located in the inferior zone, and the minimum CET was in the superior zone. A thicker central CET was associated with male gender (p = 0.009) and older age (p = 0.037) but not with CCR (p = 0.061), axial length (p = 0.253), or refraction (p = 0.351) in the multiple regression analyses. CCR, age, and gender were correlated with para-central and peripheral CET. PMID:27004973

  15. Assessment of nuclear abnormalities in exfoliated cells from the oral epithelium of mobile phone users.

    PubMed

    Souza, Leonardo da Cunha Menezes; Cerqueira, Eneida de Moraes Marcílio; Meireles, José Roberto Cardoso

    2014-06-01

    Transmission and reception of mobile telephony signals take place through electromagnetic wave radiation, or electromagnetic radiofrequency fields, between the mobile terminal and the radio base station. Based on reports in the literature on adverse effects from exposure to this type of radiation, the objective of this study was to evaluate the genotoxic and cytotoxic potential of such exposure, by means of the micronucleus test on exfoliated cells from the oral epithelium. The sample included 45 individuals distributed in 3 groups according to the amount of time in hours per week (t) spent using mobile phones: group I, t > 5 h; group II, t > 1 h and ≤ 5 h; and group III, t ≤ 1 h. Cells from the oral mucosa were analyzed to assess the numbers of micronuclei, broken egg structures and degenerative nuclear abnormalities indicative of apoptosis (condensed chromatin, karyorrhexis and pyknosis) or necrosis (karyolysis in addition to these changes). The occurrences of micronuclei and degenerative nuclear abnormalities did not differ between the groups, but the number of broken egg (structures that may be associated with gene amplification) was significantly greater in the individuals in group I (p < 0.05).

  16. Tannic acid binding of cell surfaces in normal, premalignant, and malignant squamous epithelium of the human uterine cervix.

    PubMed

    Davina, J H; Lamers, G E; van Haelst, U J; Kenemans, P; Stadhouders, A M

    1984-01-01

    Alterations in tannic acid (TA) binding capacity of cell surface carbohydrates in normal, premalignant, and malignant squamous epithelium of the human uterine cervix have been studied using electron microscopic visualization in combination with microdensitometric evaluation. While in normal epithelium there is distinct binding in four to five cell layers of the deep intermediate zone, cells of carcinoma in situ and invasive cancer lesions lack TA binding. In moderate dysplasia an intermediate reacting pattern is found. Deep intermediate cells in areas bordering the carcinoma in situ lesions do not show any binding, although their ultrastructure cannot be distinguished from similar cells in normal tissue. The TA deposition within the deep intermediate zone is probably related to the presence here of glycoprotein-containing membrane-coating granules. The finding that TA binding discriminates between cells in normal squamous epithelium and morphologically normal cells in juxtaposition with lesional areas in premalignant and malignant epithelium opens the possibility for a more reliable cytologic diagnosis of cervical epithelial neoplasia.

  17. Metachronal activity of cultured mucociliary epithelium under normal and stimulated conditions.

    PubMed

    Gheber, L; Priel, Z

    1994-01-01

    In the present work we measured in real time the metachronism and degree of correlation between beating cilia from cultured mucociliary epithelium. The method is based on simultaneous measurement of ciliary beat frequency, phase shifts, and correlation factors in two directions: parallel and perpendicular to the effective stroke direction (ESD). From the phase shifts the lengths of wave components, and consequently the metachronal wavelength and direction, were evaluated. On active ciliary areas of cultured frog esophagus under normal conditions, a relatively high degree of correlation is observed, but cilia are more correlated in direction parallel to ESD which is also the direction of the mucus propulsion. The length of the wave component parallel to ESD is more than twice as large as that of the perpendicular component. The metachronal wavelength was found to be in the range of 5-9 microns, and the direction of the wave propagation was in the range of 90 degrees-125 degrees clockwise to the ESD. When ciliary beat frequency was rapidly increased by extracellular ATP or acetylcholine, only minor effects were observed on the degree of correlation between beating cilia. The length of the wave component parallel to ESD showed the most dramatic effect increasing up to tenfold. The perpendicular to ESD component was not affected by the stimulation. Consequently, the metachronism became more laeoplectic with the angle between the ESD and the wave directions decreasing by 10 degrees-30 degrees, and the metachronal wavelength remained unaltered.

  18. Different expression of calgizzarin (S100A11) in normal colonic epithelium, adenoma and colorectal carcinoma.

    PubMed

    Melle, Christian; Ernst, Günther; Schimmel, Bettina; Bleul, Annett; Mothes, Henning; Kaufmann, Roland; Settmacher, Utz; Von Eggeling, Ferdinand

    2006-01-01

    The aim of the study was to detect proteomic markers usable to distinguish colorectal carcinoma from colon adenoma for a better understanding of the molecular mechanisms in the process of tumourigenesis. Therefore, we microdissected colon carcinoma tissue, epithelial colon adenoma tissue as well as normal adjacent colon epithelium and determined protein profiles by SELDI-TOF MS. A multitude of significantly different signals was detected. For their identification colon biopsis were lysed and subjected to a two-dimensional gel electrophoresis for separation. Subsequently, we identified nearly 100 proteins by tryptic digestion, peptide fingerprint mapping and database search. Calgizzarin (S100A11; S100C) identified by peptide fingerprint mapping correlated very well with a significantly differentially expressed signal found in prior protein profiling. Using an immunodepletion assay we confirmed the identity of this signal as calgizzarin. To localise calgizzarin in tissues we performed immunohistochemistry. For further confirmation of the identity of calgizzarin we re-analysed IHC-positive as well as IHC-negative tissue sections on ProteinChip arrays. This work demonstrates that biomarkers in colorectal cancer can be detected, identified and assessed by a proteomic approach comprising tissue-microdissection, protein profiling and immunological techniques. PMID:16327996

  19. Polaprezinc protects normal intestinal epithelium against exposure to ionizing radiation in mice

    PubMed Central

    Odawara, Soichi; Doi, Hiroshi; Shikata, Toshiyuki; Kitajima, Kazuhiro; Suzuki, Hitomi; Niwa, Yasue; Kosaka, Kengo; Tarutani, Kazuo; Tsujimura, Tohru; Kamikonya, Norihiko; Hirota, Shozo

    2016-01-01

    Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant effects. The purpose of the present study was to assess the radioprotective effects of PZ in the normal intestine of C57BL/6J mice. PZ was orally administered at 100 mg/kg body weight in the drinking water. Firstly, the present study compared the survival of normal intestinal crypt epithelial cells with mice that received PZ prior to or following irradiation. Next, the present study examined the sequential changes of the incidence of apoptosis in the normal intestine of mice that received irradiation. The mice that received PZ prior to irradiation demonstrated a stronger protective effect on the normal intestine compared with those that received PZ after irradiation. The present study therefore administrated PZ 2 h before irradiation in the subsequent experiments. The mice receiving PZ developed fewer apoptotic cells in the duodenum, jejunum and ileum. Radiation-induced cell death occurred with a peak at position 10 or lower from the base of the crypt axis, and was subsequently reduced by PZ treatment. Pretreatment with PZ protected the normal intestinal tissues from radiation-induced apoptosis.

  20. Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation.

    PubMed

    Tran, Hai B; Lewis, Martin D; Tan, Lor Wai; Lester, Susan E; Baker, Leonie M; Ng, Jia; Hamilton-Bruce, Monica A; Hill, Catherine L; Koblar, Simon A; Rischmueller, Maureen; Ruffin, Richard E; Wormald, Peter J; Zalewski, Peter D; Lang, Carol J

    2012-01-01

    Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1β and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis. PMID:22523501

  1. Oral Diadochokinetic Rates for Normal Thai Children

    ERIC Educational Resources Information Center

    Prathanee, Benjamas; Thanaviratananich, Sangaunsak; Pongjanyakul, Amonrat

    2003-01-01

    Background: The diadochokinetic (DDK) rate represents an index for assessing motor skills. It is commonly used in routine clinical evaluation of diseases of the central nervous system, disturbances of the peripheral sensory motor formations and immaturity of the speech mechanism. "Oral" DDK rates are a popular guideline for the assessment,…

  2. Quantitative analysis of squamous epithelium of normal palatal mucosa in guinea pigs.

    PubMed

    Andersen, L; Schroeder, H E

    1978-07-01

    The epithelium of intact guinea pig palate was subjected to stereologic analysis in a study of structural alterations in the keratinizing epithelium in response to wounding. Point counting procedures were employed to analyse electron micrographs sampled from three epithelial strata in biopsies collected from five animals. The differentiation pattern of the guinea pig palate epithelium displayed the following structural density gradients from basal to granular layers: descending gradients of metabolically active organelles, ascending gradient of bundled filaments coupled with the appearance of membrane coating granules and keratohyalin granules, and a plateau-like gradient of cytoplasmic ground substance. This pattern of epithelial differentiation is basically identical to that of human hard palate epithelium and epidermis. Regional and species variations in structure of keratinizing epithelia are suggested based on interepithelial differences in morphometric parameters.

  3. Uniform expression of alcohol dehydrogenase 3 in epithelia regenerated with cultured normal, immortalised and malignant human oral keratinocytes.

    PubMed

    Hedberg, J J; Hansson, A; Nilsson, J A; Höög, J O; Grafström, R C

    2001-01-01

    The human oral epithelium is a target for damage from the inhalation of formaldehyde. However, most experimental studies on this chemical have relied on laboratory animals that are obligatory nose breathers, including rats and mice. Therefore, in vitro model systems that mimic the structure of the human oral epithelium and which retain normal tissue-specific metabolic competence are desirable. Based on the established role of alcohol dehydrogenase 3 (ADH3), also known as glutathione-dependent formaldehyde dehydrogenase, as the primary enzyme catalysing the detoxification of formaldehyde, the aim of this study was to investigate the expression of ADH3 in organotypic epithelia regenerated with normal (NOK), immortalised (SVpgC2a) and malignant (SqCC/Y1) human oral keratinocytes. Organotypic epithelia, usually consisting of 5-10 cell layers, were produced at the air-liquid interface of collagen gels containing human oral fibroblasts, after culture for 10 days in a standardised serum-free medium. Immunochemical staining demonstrated uniform expression of ADH3 in these organotypic epithelia, as well as in the epithelial cells of oral tissue. The specificity of the ADH3 antiserum was ascertained from the complete neutralisation of the immunochemical reaction with purified ADH3 protein. Assessment of the staining intensities indicated that the expression levels were similar among the regenerated epithelia. Furthermore, the regenerated epithelia showed similar ADH3 expression to the epithelium in oral tissue. Therefore, a tissue-like expression pattern for ADH3 can be generated from the culture of various oral keratinocyte lines in an organotypic state. Similar expression levels among the various cell lines indicate the preservation of ADH3 during malignant transformation, and therefore that NOK, SVpgC2a and SqCC/Y1 represent functional models for in vitro studies of formaldehyde metabolism in human oral mucosa.

  4. [Injury and reparative regeneration of the oral mucosal epithelium after cytostatic drugs administration (tissue, cell and molecular mechanisms)].

    PubMed

    Bykov, V L; Leont'eva, I V

    2011-01-01

    This paper presents the systematized summary of current literature data and the authors' own findings on the regularities of human and animal surface oral mucosal epithelium (OME) injury caused by cytostatic drugs (CSD) administration, and on the ways of its regeneration after the cytostatic chemotherapy (CSCT) discontinuation. Tissue, cell and molecular mechanisms of CSCT effects on OME, are described. The direct effects of CSD included the epithelial layer attenuation with the derangement of its architecture, epitheliocyte proliferation suppression, apoptosis activation, and differentiation disturbances (involving the broad spectrum of cytological, cytochemical, ultrastructural and molecular-biological changes). In severe cases, these processes resulted in the loss of the epithelial layer integrity with the development of ulceration. Complete epithelial regeneration requires a long period after the CSCT discontinuation. Indirect effects of CSD on OME are associated with the microbial invasion and the diffusion of microbial vital activity products into the epithelium with concurrent leukopenia, immunosuppression and decreased salivary secretion.

  5. Normalizing Oral Fluid Hydrocodone Data Using Calculated Blood Volume.

    PubMed

    Cummings, Oneka T; Morris, Ayodele A; Enders, Jeffrey R; McIntire, Gregory L

    2016-09-01

    Oral fluid testing to assist in the assessment of treatment adherence for chronic pain patients is attractive for a number of reasons. However, efforts focused on interpreting patient results have been modest when compared to urine drug testing. This work details a retrospective approach developed to transform and normalize oral fluid testing results to provide a historical picture of patient values in this important test fluid. Using this approach, a model was developed using data from 6,800 independent patients who were both prescribed hydrocodone and tested positive (with limitations: reporting cutoff < X < upper limit of quantitation) by liquid chromatography-mass spectrometry. Patient demographic data were used to calculate the relevant parameters (e.g., calculated blood volume (CBV)) used in the transformation and normalization of the oral fluid data. The crucial normalizing factor in oral fluids was found to be the CBV which parallels the use of creatinine to normalize drug concentration levels in urine and is consistent with the view that oral fluid samples reflect plasma concentrations of the respective drugs. The resulting near Gaussian distribution is dose independent and as such should be of value to physicians in quickly assessing whether their patient is consistent with this historical population in the broad terms of this model. While this comparison alone is not definitive for adherence with a treatment regimen, together with patient interviews, prescription history and other clinical criteria, it can add an idea of expected patient values from oral fluid testing. PMID:27405365

  6. Ion transport across CF and normal murine olfactory and ciliated epithelium

    PubMed Central

    Grubb, B. R.; Rogers, T. D.; Boucher, R. C.; Ostrowski, L. E.

    2009-01-01

    The nasal epithelium of the cystic fibrosis (CF) mouse has been used extensively in CF research because it exhibits ion transport defects similar to those of human CF airways. This tissue is composed of ∼50% olfactory (OE) and ∼50% ciliated epithelium (CE), and on the basis of previous observations, we hypothesized that a significant fraction of the bioelectric signals from murine nasal tissue may arise from OE rather than CE, while CE is the target tissue for CF gene therapy. We compared the bioelectric properties of isolated OE from the nasal cavity and CE from the nasopharynx in Ussing chamber studies. Hyperabsorption of Na+ [amiloride response; CF vs. wild type (WT)] was ∼7.5-fold greater in the OE compared with the CE. The forskolin response in native tissues did not reliably distinguish genotypes, likely due to a cyclic nucleotide-gated cation conductance in OE and a calcium-mediated Cl− conductance in CE. By potential difference assay, hyperabsorption of Na+ (CF vs. WT) and the difference in response to apical 0 Cl− buffer (CF vs. WT) were ∼2-fold greater in the nasal cavity compared with the nasopharynx. Our studies demonstrate that in the CF mouse, both the hyperabsorption of Na+ and the Cl− transport defect are of larger magnitude in the OE than in the CE. Thus, while the murine CF nasal epithelium is a valuable model for CF studies, the bioelectrics are likely dominated by the signals from the OE, and assays of the nasopharynx may be more specific for studying the ciliated epithelium. PMID:19321738

  7. 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

  8. Acquiring and maintaining a normal oral microbiome: current perspective.

    PubMed

    Zaura, Egija; Nicu, Elena A; Krom, Bastiaan P; Keijser, Bart J F

    2014-01-01

    The oral microbiota survives daily physical and chemical perturbations from the intake of food and personal hygiene measures, resulting in a long-term stable microbiome. Biological properties that confer stability in the microbiome are important for the prevention of dysbiosis-a microbial shift toward a disease, e.g., periodontitis or caries. Although processes that underlie oral diseases have been studied extensively, processes involved in maintaining of a normal, healthy microbiome are poorly understood. In this review we present our hypothesis on how a healthy oral microbiome is acquired and maintained. We introduce our view on the prenatal development of tolerance for the normal oral microbiome: we propose that development of fetal tolerance toward the microbiome of the mother during pregnancy is the major factor for a successful acquisition of a normal microbiome. We describe the processes that influence the establishment of such microbiome, followed by our perspective on the process of sustaining a healthy oral microbiome. We divide microbiome-maintenance factors into host-derived and microbe-derived, while focusing on the host. Finally, we highlight the need and directions for future research.

  9. The junction zone of human epithelium and foreign stroma. Ultrastructural observations in human oral mucosal transplants in nude mice.

    PubMed

    Holmstrup, P; Andersen, L; Harder, F

    1984-07-01

    This study describes ultrastructural features of epithelial-stromal junction of human buccal and palatal mucosal transplants and their outgrowths in nude mice. The investigation included transplant epithelium overlying human connective tissue in 27 cases, epithelial outgrowth formed over murine connective tissue in 33 cases, and over Millipore filter in 12 cases. The epithelial-stromal junction of the transplants differed from the normal state only in the presence of lamina densa loops projecting into the connective tissue and in lamina densa interruptions and duplications. In contrast the epithelial outgrowths demonstrated flattening of epithelial basal cells, lack of proximal epithelial cell projections, lack of complete hemidesmosome complexes, lack of distinct lamina densa, and lack of anchoring fibrils. It is suggested that these changes may be due to lack of necessary interaction between the human epithelium and the foreign stroma.

  10. Quantification of telomerase activity in normal oral mucosal tissue and oral squamous cell carcinoma

    PubMed Central

    Rai, Arpita; Naikmasur, Venkatesh G.; Sattur, Atul

    2016-01-01

    Background and Objective: The role of telomeres and telomerase in oral cancer is an area of much recent interest. The understanding of the role of telomere biology, the end replication problem leading to genomic instability and the reactivation of telomerase, is absolutely critical to our understanding of oral cancer, and more so, to our ability of early diagnosis and developing novel therapies and cancer prevention approaches. The aim of the present study was to quantify telomerase activity (TA) in oral squamous cell carcinoma (OSCC) and normal oral mucosa and assess the role of telomerase as diagnostic and prognostic marker of oral malignancy. Materials and Methods: We quantified TA in 45 patients with OSCC and 20 normal oral mucosal specimens using polymerase chain reaction-based telomeric repeat amplification protocol assay and compared it with the clinical status and grade of malignancy. Results: TA was detected in 89% of malignant and 5% of normal oral mucosal tissue. The TA levels ranged from 0.28 to 6.91 (mean 2.05, standard deviation [SD] 1.33) in OSCC and 0.21 to 1.09 (mean 0.54, SD 0.27) in normal oral mucosa. There was no relationship between TA levels and clinical stages, site of the lesion, history of adverse habits, or sex of the patient. However, under the WHO classification, there were significant differences (P < 0.00) between Grades I, II, and III. Furthermore, increasing age of the patient significantly correlated with TA. Interpretation and Conclusion: The results of the present study indicate that activation of TA is frequent in OSCC. Statistically significant difference in quantified telomerase levels of OSCC and normal oral mucosa (P < 0.00) demonstrates the significant clinical usefulness of telomerase activation as a valuable marker for diagnosis while significant correlation of TA with grades of malignancy indicates its effectiveness as marker for prognosis of OSCC.

  11. Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast.

    PubMed Central

    Battersby, S.; Robertson, B. J.; Anderson, T. J.; King, R. J.; McPherson, K.

    1992-01-01

    Steroid receptor was assessed immunohistochemically in 158 samples of normal breast for variation through the menstrual cycle. Patterns and intensity of reaction were used in a semi-quantitative scoring system to examine the influence of cycle phase, cycle type, parity and age. The changes in oestrogen receptor for natural cycle and oral contraceptive (OC) cycles indicated down-regulation by progestins. Progesterone receptor did not vary significantly in natural cycles, but increased steadily through OC cycles. This study provides strong evidence that both oestrogen and progesterone influence breast epithelium, but dissimilarities from the endometrium are apparent. The interval since pregnancy had a significant negative effect on frequency and score of oestrogen receptor and score of progesterone receptor. Multivariate analysis established the phase of cycle and OC use as independent significant influences on oestrogen receptor. The interval since pregnancy was an independent significant factor for both oestrogen and progesterone receptor presence. Images Figure 1 Figure 2 PMID:1562470

  12. 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. PMID:25635646

  13. 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.

  14. Carbamazepine transbuccal delivery: the histo-morphological features of reconstituted human oral epithelium and buccal porcine mucosae in the transmucosal permeation.

    PubMed

    Campisi, G; Paderni, C; Saccone, R; Siragusa, M G; Lo Muzio, L; Tripodo, C; Giannola, L I; Florena, A M

    2008-01-01

    Transbuccal drug delivery is an attractive way of administration since several well-known advantages are provided, especially with respect to peroral management. Carbamazepine (CBZ) is an anticonvulsant which is useful in controlling neuropathic pain, and it is currently administered by peroral route, although its absorption and bioavailability is limited due to various factors. The oral cavity could be an interesting site for transbuccal CBZ delivery due to two properties: slow administration of constant low drug doses and less dose-related side effects. However, in transbuccal absorption a major limitation could be the low permeability of the mucosa which results in low drug bioavailability; thus the aptitude of the drug to penetrate the buccal mucosa has to be assessed by using tissue models resembling human normal mucosa. In our experience, CBZ well permeates mucosal membranes. In order to assess the efficacy of CBZ transbuccal delivery and to verify the reliability of these tissues in permeability testing before and after the passage of CBZ, the histo-morphological features of reconstituted human oral (RHO) epithelium (E) and buccal porcine mucosae were investigated. Significant histological changes due to CBZ passage were observed both in RHO-E and porcine mucosa. The main findings detected in RHO samples were cellular swellings with a signet ring-like appearance, nuclear swelling, prominent nucleoli lined against the nuclear membrane and the presence of keratohyalin granules. The most striking finding regarding porcine buccal mucosa was a cytoplasmic vacuolization, mainly involving the basal layer. PMID:19144275

  15. Skp2 Is Necessary for Myc-Induced Keratinocyte Proliferation but Dispensable for Myc Oncogenic Activity in the Oral Epithelium

    PubMed Central

    Sistrunk, Christopher; Macias, Everardo; Nakayama, Keiichi; Kim, Yongbaek; Rodriguez-Puebla, Marcelo L.

    2011-01-01

    The proto-oncogene c-Myc encodes a transcription factor that is implicated in the regulation of cellular proliferation, differentiation, and apoptosis. Myc accelerates the rate of cell proliferation, at least in part, through its ability to down-regulate the expression of the cell cycle inhibitor p27Kip1. Moreover, p27Kip1 protein levels are regulated by ubiquitin-mediated turnover, leading to destruction by the E3 ubiquitin ligase SCFSkp2. Therefore, we hypothesize that a lack of Skp2 expression should lead to increased p27Kip1 levels and further inhibition of Myc-mediated proliferation and tumorigenesis. Myc expression in epithelial tissues of transgenic mice (K5-Myc) led to increased keratinocyte proliferation and the development of spontaneous tumors within the oral cavity. We generated K5-Myc–transgenic mice in an Skp2-null background. Consistent with our hypothesis, we found that Myc-mediated keratinocyte hyperproliferation was abolished by the loss of Skp2. However, Skp2 ablation did not affect Myc-driven tumorigenesis because the incidence, latency, and degree of differentiation of oral tumors were identical between K5-Myc/Skp2+/+ and K5-Myc/Skp2−/− mice. Altogether, these findings suggest that Skp2 and p27Kip1 are critical for Myc-driven keratinocyte proliferation; however, Myc-mediated tumorigenesis in the oral epithelium is independent of the Skp2-p27Kip1 axis. PMID:21641375

  16. Zinc iodide-osmium staining of membrane-coating granules in keratinized and non-keratinized mammalian oral epithelium.

    PubMed

    Squier, C A

    1982-01-01

    Specimens of keratinized and non-keratinized oral epithelium were examined in the electron microscope after being stained with zinc iodide-osmium. In both types of tissue, reaction was seen in unmyelinated nerves, in the specific granules of epithelial Langerhans cells and within lysosome-like organelles and small vesicles associated with Golgi systems. In keratinized epithelia, the reaction was also present in the membrane-coating granules and between the deepest cells of the keratinized layer. In contrast, the membrane-coating granules of non-keratinized epithelia lacked Zn iodide-osmium staining despite the presence of reaction in adjacent Golgi systems. It is suggested that Zn iodide-osmium stains glycolipid or glycoprotein material in the cell. This material is elaborated in the Golgi systems from which lysosomes and the membrane-coating granules of keratinized tissues are probably derived.

  17. Proto-oncogenes and p53 protein expression in normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia.

    PubMed

    Ngan, H Y; Liu, S S; Yu, H; Liu, K L; Cheung, A N

    1999-10-01

    The aim of this study was to study the protein expression of six proto-oncogenes (epidermal growth factor receptor (EGFR), c-fms, c-myc, c-kit, c-erbB-2 and pan-ras) and one tumour suppressor gene (TP53), by immunohistochemical staining of normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia (CIN). Paraffin sections of 45 normal cervical specimens, 38 CIN grade one (CIN1), 37 CIN2 and 43 CIN3 were studied. An immunohistochemical (IHC) score was derived from the intensity of staining and the percentages of cells stained. In normal cervical specimens, a higher IHC score was found with EGFR and c-fms in superficial (S), intermediate (I) and parabasal (PB) cells compared with basal cells. In contrast, a higher IHC score was found with c-erbB-2 in basal cells in normal cervical specimens. Dysplastic cells in CIN had a higher IHC score with c-myc and c-erbB-2 than normal S/I and PB cells. Dysplastic cells had a higher score with EGFR than normal basal cells. However, a higher IHC score with EGFR and c-fms was found in normal S/I cells than dysplastic cells. These findings suggested that EGFR and c-fms were activated in more differentiated normal cells but were less active in less differentiated normal basal cells. However, EGFR was reactivated in dysplastic cells. Meanwhile, c-erbB-2 was activated in less differentiated normal basal cells and dysplastic cells, and was less active in differentiated normal cells. c-myc was activated in dysplastic cells. c-fms was more active in more differentiated normal cells and was not activated in less differentiated or dysplastic cells. c-kit, pan-ras and TP53 were not activated in normal nor dysplastic cervical cells. These results suggest EGFR, c-erbB-2 and c-myc may be important proto-oncogenes in CIN and that antibodies or anti-genes targeted against them may alter the progress of CIN to invasive cancer.

  18. Transcriptional regulation by normal epithelium of premalignant to malignant progression in Barrett’s esophagus

    PubMed Central

    Zeng, Jia; Kelbauskas, Laimonas; Rezaie, Aida; Lee, Kristen; Ueberroth, Benjamin; Gao, Weimin; Derkach, Dmitry; Tran, Thai; Smith, Dean; Bussey, Kimberly J.; Meldrum, Deirdre R.

    2016-01-01

    In carcinogenesis, intercellular interactions within and between cell types are critical but remain poorly understood. We present a study on intercellular interactions between normal and premalignant epithelial cells and their functional relevance in the context of premalignant to malignant progression in Barrett’s esophagus. Using whole transcriptome profiling we found that in the presence of normal epithelial cells, dysplastic cells but not normal cells, exhibit marked down-regulation of a number of key signaling pathways, including the transforming growth factor beta (TGFβ) and epithelial growth factor (EGF). Functional assays revealed both cell types showed repressed proliferation and significant changes in motility (speed, displacement and directionality) as a result of interactions between the two cell types. Cellular interactions appear to be mediated through both direct cell-cell contact and secreted ligands. The findings of this study are important in that they reveal, for the first time, the effects of cellular communication on gene expression and cellular function between premalignant (dysplastic) epithelial cells and their normal counterparts. PMID:27731371

  19. Apical Secretion of FSTL1 in the Respiratory Epithelium for Normal Lung Development

    PubMed Central

    Li, Xue; Liang, Jiurong; Jiang, Dianhua; Geng, Yan; Ning, Wen

    2016-01-01

    Follistatin-like 1 (FSTL1) is a secreted bone morphogenetic protein (BMP) antagonist, and it plays a crucial role in normal lung development. Deletion of Fstl1 leads to postnatal death in mice due to respiratory failure. To further explore the role of FSTL1 in mouse lung development, we created a transgene SFTPC-Fstl1 allele mouse displaying significant epithelial overexpression of Fstl1 in all stages of lung development. However, epithelial overexpression of Fstl1 did not alter lung morphogenesis, epithelial differentiation and lung function. Moreover, we found that FSTL1 function was blocked by the epithelial polarization, which was reflected by the remarkable apical secretion of FSTL1 and the basolateral BMP signaling. Taken together, this study demonstrates that tightly spatial interaction of FSTL1 and BMP signaling plays an essential role in lung development. PMID:27355685

  20. Comparative gene expression analysis of ovarian carcinoma and normal ovarian epithelium by serial analysis of gene expression.

    PubMed

    Peters, David G; Kudla, Donna M; Deloia, Julie A; Chu, Tian Jiao; Fairfull, Liane; Edwards, Robert P; Ferrell, Robert E

    2005-07-01

    Despite the poor prognosis of ovarian cancer and the importance of early diagnosis, there are no reliable noninvasive biomarkers for detection in the early stages of disease. Therefore, to identify novel ovarian cancer markers with potential utility in early-stage screening protocols, we have undertaken an unbiased and comprehensive analysis of gene expression in primary ovarian tumors and normal human ovarian surface epithelium (HOSE) using Serial Analysis of Gene Expression (SAGE). Specifically, we have generated SAGE libraries from three serous adenocarcinomas of the ovary and, using novel statistical tools, have compared these to SAGE data derived from two pools of normal HOSE. Significantly, in contrast to previous SAGE-based studies, our normal SAGE libraries are not derived from cultured cell lines. We have also compared our data with publicly available SAGE data obtained from primary tumors and "normal" HOSE-derived cell lines. We have thus identified several known and novel genes whose expressions are elevated in ovarian cancer. These include but are not limited to CLDN3, WFDC2, FOLR1, COL18A1, CCND1, and FLJ12988. Furthermore, we found marked differences in gene expression patterns in primary HOSE tissue compared with cultured HOSE. The use of HOSE tissue as a control for these experiments, along with hierarchical clustering analysis, identified several potentially novel biomarkers of ovarian cancer, including TACC3, CD9, GNAI2, AHCY, CCT3, and HMGA1. In summary, these data identify several genes whose elevated expressions have not been observed previously in ovarian cancer, confirm the validity of several existing markers, and provide a foundation for future studies in the understanding and management of this disease. PMID:16030107

  1. [The study of HPV prevalence in normal oral mucosa and oral squamous cell carcinoma].

    PubMed

    Jiang, Qian; Zhang, Zhi-yuan

    2007-10-01

    Mucosal infection with high-risk human papiloma virus(HPV) types 16 and 18 is the cause of cervical cancer and might be a subset of oral squamous cell carcinoma (OSCC), yet the prevalence and type distribution of HPV in oral SCC remained unclear. We systematically reviewed published studies of OSCC biopsies, which were employed to detect and genotype HPV through different methods. The aim of this investigation is to carry out a bibliographic review on the prevalence of HPV in OSCC and normal oral mucosa. Supported by Key Project of National Natural Science Foundation of China (Grant No.30630065), Key Lab Project of Science and Technology Committee of Shanghai Municipality (Grant No.06DZ22026) and Shanghai Leading Academic Discipline Project (Grant No. Y0203).

  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. PMID:26025503

  3. Expression of Cell Competition Markers at the Interface between p53 Signature and Normal Epithelium in the Human Fallopian Tube

    PubMed Central

    Kito, Masahiko; Maeda, Daichi; Kudo-Asabe, Yukitsugu; Sato, Naoki; Shih, Ie-Ming; Wang, Tian-Li; Tanaka, Masamitsu; Terada, Yukihiro; Goto, Akiteru

    2016-01-01

    There is a growing body of evidence regarding cell competition between normal and mutant mammalian cells, which suggest that it may play a defensive role in the early phase of carcinogenesis. In vitro study in the past has shown that overexpression of vimentin in normal epithelial cells at the contact surface with transformed cells is essential for the cell competition involved in epithelial defense against cancer. In this study, we attempted to examine cell competition in human tissue in vivo by investigating surgically resected human fallopian tubes that contain p53 signatures and serous tubal intraepithelial lesions (STILs), a linear expansion of p53-immunopositive/TP53 mutant tubal epithelial cells that are considered as precursors of pelvic high grade serous carcinoma. Immunofluorescence double staining for p53 and the cell competition marker vimentin was performed in 21 sections of human fallopian tube tissue containing 17 p53 signatures and 4 STILs. The intensities of vimentin expression at the interface between p53-positive cells at the end of the p53 signature/STIL and adjacent p53-negative normal tubal epithelial cells were compared with the background tubal epithelium. As a result, the average vimentin intensity at the interfaces relative to the background intensity was 1.076 (95% CI, 0.9412 – 1.211 for p53 signature and 0.9790 (95% CI, 0.7206 – 1.237) for STIL. Thus, it can be concluded that overexpression of the cell competition marker vimentin are not observed in human tissue with TP53 alterations. PMID:27258067

  4. Zinc-rich inhibitor of apoptosis proteins (IAPs) as regulatory factors in the epithelium of normal and inflamed airways.

    PubMed

    Roscioli, Eugene; Hamon, Rhys; Lester, Susan; Murgia, Chiara; Grant, Janet; Zalewski, Peter

    2013-04-01

    Integrity of the airway epithelium (AE) is important in the context of inhaled allergens and noxious substances, particularly during asthma-related airway inflammation where there is increased vulnerability of the AE to cell death. Apoptosis involves a number of signaling pathways which activate procaspases leading to cleavage of critical substrates. Understanding the factors which regulate AE caspases is important for development of strategies to minimize AE damage and airway inflammation, and therefore to better control asthma. One such factor is the essential dietary metal zinc. Zinc deficiency results in enhanced AE apoptosis, and worsened airway inflammation. This has implications for asthma, where abnormalities in zinc homeostasis have been observed. Zinc is thought to suppress the steps involved in caspase-3 activation. One target of zinc is the family of inhibitor of apoptosis proteins (IAPs) which are endogenous regulators of caspases. More studies are needed to identify the roles of IAPs in regulating apoptosis in normal and inflamed airways and to study their interaction with labile zinc ions. This new information will provide a framework for future clinical studies aimed at monitoring and management of airway zinc levels as well as minimising airway damage and inflammation in asthma.

  5. High-risk human papilloma virus in archival tissues of oral pathosis and normal oral mucosa

    PubMed Central

    Dhanapal, Raghu; Ranganathan, K.; Kondaiah, Paturu; Devi, R. Uma; Joshua, Elizabeth; Saraswathi, T. R.

    2015-01-01

    Objectives: Oral cancer ranks third among all cancers in the Indian population. Human papilloma virus (HPV) plays a significant role in oral carcinogenesis. Population-based subtype variations are present in the HPV prevalence. This study gives an emphasis on the parameters to be considered in formalin fixed paraffin embedded tissues for polymerase chain reaction (PCR)-based research work. Materials and Methods: Cross-sectional study on archival paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC), epithelial dysplasia, and normal oral mucosa surrounding impacted tooth was amplified by PCR for the E6 gene of HPV type 16 and E1 gene of HPV type 18. Results: HPV 18 was positive in three OSCC cases. There was no statistically significant association of the positivity of HPV with the age, gender or habit. The HPV positive patients had a tobacco habit and were of a younger age group. Conclusion: The presence of HPV in carcinomatous tissue highlights the possible role of HPV in carcinogenesis and archival paraffin embedded tissue specimen can be used for this analysis. Recent studies on genomic analyses have highlighted that the HPV positive tumors are a separate subgroup based on genomic sequencing. The results of a larger retrospective study will help further in our understanding of the role of HPV in carcinogenesis, this study could form the baseline for such follow-up studies. PMID:26097346

  6. 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

  7. 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.

  8. Overcoming the diffusion barrier of mucus and absorption barrier of epithelium by self-assembled nanoparticles for oral delivery of insulin.

    PubMed

    Shan, Wei; Zhu, Xi; Liu, Min; Li, Lian; Zhong, Jiaju; Sun, Wei; Zhang, Zhirong; Huang, Yuan

    2015-03-24

    Nanoparticles (NPs) have demonstrated great potential for the oral delivery of protein drugs that have very limited oral bioavailability. Orally administered NPs could be absorbed by the epithelial tissue only if they successfully permeate through the mucus that covers the epithelium. However, efficient epithelial absorption and mucus permeation require very different surface properties of a nanocarrier. We herein report self-assembled NPs for efficient oral delivery of insulin by facilitating both of these two processes. The NPs possess a nanocomplex core composed of insulin and cell penetrating peptide (CPP), and a dissociable hydrophilic coating of N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) derivatives. After systematic screening using mucus-secreting epithelial cells, NPs exhibit excellent permeation in mucus due to the "mucus-inert" pHPMA coating, as well as high epithelial absorption mediated by CPP. The investigation of NP behavior shows that the pHPMA molecules gradually dissociate from the NP surface as it permeates through mucus, and the CPP-rich core is revealed in time for subsequent transepithelial transport through the secretory endoplasmic reticulum/Golgi pathway and endocytic recycling pathway. The NPs exhibit 20-fold higher absorption than free insulin on mucus-secreting epithelium cells, and orally administered NPs generate a prominent hypoglycemic response and an increase of the serum insulin concentration in diabetic rats. Our study provides the evidence of using pHPMA as dissociable "mucus-inert" agent to enhance mucus permeation of NPs, and validates a strategy to overcome the multiple absorption barriers using NP platform with dissociable hydrophilic coating and drug-loaded CPP-rich core.

  9. Expression of the carcinoma markers: the sialylated Lewis A and X carbohydrate antigens in normal laryngeal surface epithelium and submucosal glands from old humans.

    PubMed

    Kirkeby, Svend; Moe, Dennis

    2013-03-01

    Aberrant surface expression of the carbohydrate ABH and Lewis antigens are often used as markers for the diagnosis of cancer, but while the distribution of these histo-blood group antigens is relatively well-described in tissues and organs from young and middle-aged humans little is known of their expression in old age. The objective for this study was to estimate if the Lewis A and X antigens together with their sialylated modifications, are expressed in sections of normal laryngeal tissue from old humans. Antibodies directed against the tumor markers Sialyl Lewis A and Sialyl Lewis X showed positive reaction in the surface epithelia from normal larynx autopsies obtained from people aged 77-90 years. The sialylated and non-sialylated Lewis A antigens were more frequently expressed in the pseudostratified epithelium than in squamous surface epithelium. Both the sialylated and the non-sialylated carbohydrates were stained in the submucosal glands in all the autopsies. In conclusion, visualization of Lewis tumor markers in the larynx should be interpreted with great care, as they may be present in normal laryngeal epithelial cells from old humans.

  10. Carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) for corneal epithelium reconstruction: a histological study.

    PubMed

    Bardag-Gorce, Fawzia; Oliva, Joan; Wood, Andrew; Hoft, Richard; Pan, Derek; Thropay, Jacquelyn; Makalinao, Andrew; French, Samuel W; Niihara, Yutaka

    2015-04-01

    This study investigates the therapeutic effects of carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) transplantation for experimentally induced severe rabbit limbal stem cell deficiency (LSCD). Buccal biopsies were performed and CAOMECS were cultured and transplanted onto diseased corneas. Six-month follow-up examinations indicated that three out of four corneas with CAOMECS grafts showed a decrease in superficial vascularization, while almost all the sham corneas did not show a similar decrease. H&E staining of corneas showed that CAOMECS transplantation reduced blood vessel invasion of central cornea, reduced lymphocyte infiltration and fibrotic tissue formation. DeltaNp63 stained markedly in the grafted cornea and to a lesser extent in the sham corneas. PCNA and Ki-67 staining were much greater in the sham corneas than in the grafted and normal corneas. K3 and K13 staining demonstrated that CAOMECS transplanted corneas had much more K3- and less K13- positive cells compared to the sham corneas. Muc5AC was decreased in the central region of grafted corneas. Very little alpha-smooth muscle actin (aSMA) staining was detected in grafted corneas, while there was a greater amount of aSMA staining in sham corneas. Staining for anti-angiogenic factor TIMP -3 was also increased, and pro-angiogenic factor MMP-3 was decreased in grafted corneas compared to sham corneas. Our results indicate that CAOMECS grafts resulted in improved epithelialization of the corneal surface and decreased vascularization and fibrosis of the diseased corneas.

  11. Carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) for corneal epithelium reconstruction: a histological study.

    PubMed

    Bardag-Gorce, Fawzia; Oliva, Joan; Wood, Andrew; Hoft, Richard; Pan, Derek; Thropay, Jacquelyn; Makalinao, Andrew; French, Samuel W; Niihara, Yutaka

    2015-04-01

    This study investigates the therapeutic effects of carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) transplantation for experimentally induced severe rabbit limbal stem cell deficiency (LSCD). Buccal biopsies were performed and CAOMECS were cultured and transplanted onto diseased corneas. Six-month follow-up examinations indicated that three out of four corneas with CAOMECS grafts showed a decrease in superficial vascularization, while almost all the sham corneas did not show a similar decrease. H&E staining of corneas showed that CAOMECS transplantation reduced blood vessel invasion of central cornea, reduced lymphocyte infiltration and fibrotic tissue formation. DeltaNp63 stained markedly in the grafted cornea and to a lesser extent in the sham corneas. PCNA and Ki-67 staining were much greater in the sham corneas than in the grafted and normal corneas. K3 and K13 staining demonstrated that CAOMECS transplanted corneas had much more K3- and less K13- positive cells compared to the sham corneas. Muc5AC was decreased in the central region of grafted corneas. Very little alpha-smooth muscle actin (aSMA) staining was detected in grafted corneas, while there was a greater amount of aSMA staining in sham corneas. Staining for anti-angiogenic factor TIMP -3 was also increased, and pro-angiogenic factor MMP-3 was decreased in grafted corneas compared to sham corneas. Our results indicate that CAOMECS grafts resulted in improved epithelialization of the corneal surface and decreased vascularization and fibrosis of the diseased corneas. PMID:25881998

  12. Different production of interleukin-1alpha, interleukin-1beta and interleukin-8 from cholesteatomatous and normal epithelium.

    PubMed

    Chung, J W; Yoon, T H

    1998-06-01

    Cholesteatomatous bone destruction is caused by an increase in collagenase activity and activation of the osteoclasts. Cytokines. such as interleukins (IL), are important in intercellular communication in the mechanism of bone destruction. Middle ear cholesteatomas and external auditory canal skins (EACS) can be surgically obtained and cultured. The quantities of IL-1alpha, IL-1beta and IL-8 secretions were measured in the supernatant of each culture series. On the 2nd day of culture, the level of IL-1alpha was 0.60+/-0.13 (pg/microg of total protein) in cholesteatoma, and 0.25+/-0.02 in EACS. The levels of IL-1beta in cholesteatoma and EACS were 0.41+/-0.06 and 0.24+/-0.02, respectively. The levels of IL-8 in cholesteatoma and EACS were 146.50+/-32.37 and 50.40+/-6.24, respectively. After 2 days, the levels of IL-1alpha and IL-8 of each tissue decreased. The value from fibroblasts did not show a significant difference between cholesteatoma and EACS, and the values did not change as time passed. We can conclude that the IL-1alpha and IL-8 from the cholesteatomatous epithelium are responsible for the cholesteatomatous bone destruction and certain substances from the subepithelial granulation tissue can stimulate the cholesteatoma to produce IL-1alpha and IL-8.

  13. 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

  14. Growth hormone is secreted by normal breast epithelium upon progesterone stimulation and increases proliferation of stem/progenitor cells.

    PubMed

    Lombardi, Sara; Honeth, Gabriella; Ginestier, Christophe; Shinomiya, Ireneusz; Marlow, Rebecca; Buchupalli, Bharath; Gazinska, Patrycja; Brown, John; Catchpole, Steven; Liu, Suling; Barkan, Ariel; Wicha, Max; Purushotham, Anand; Burchell, Joy; Pinder, Sarah; Dontu, Gabriela

    2014-06-01

    Using in vitro and in vivo experimental systems and in situ analysis, we show that growth hormone (GH) is secreted locally by normal human mammary epithelial cells upon progesterone stimulation. GH increases proliferation of a subset of cells that express growth hormone receptor (GHR) and have functional properties of stem and early progenitor cells. In 72% of ductal carcinoma in situ lesions, an expansion of the cell population that expresses GHR was observed, suggesting that GH signaling may contribute to breast cancer development.

  15. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

    SciTech Connect

    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

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

    PubMed Central

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

    2016-01-01

    ABSTRACT 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. PMID:27579219

  17. 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. PMID:27579219

  18. The Role of E-Cadherin in Maintaining the Barrier Function of Corneal Epithelium after Treatment with Cultured Autologous Oral Mucosa Epithelial Cell Sheet Grafts for Limbal Stem Deficiency

    PubMed Central

    Hoft, Richard H.; Wood, Andrew; Oliva, Joan; Niihara, Hope; Makalinao, Andrew; Thropay, Jacquelyn; Pan, Derek; Tiger, Kumar; Garcia, Julio; Laporte, Amanda; French, Samuel W.; Niihara, Yutaka

    2016-01-01

    The role of E-cadherin in epithelial barrier function of cultured autologous oral mucosa epithelial cell sheet (CAOMECS) grafts was examined. CAOMECS were cultured on a temperature-responsive surface and grafted onto rabbit corneas with Limbal Stem Cell Deficiency (LSCD). E-cadherin levels were significantly higher in CAOMECS compared to normal and LSCD epithelium. Beta-catenin colocalized with E-cadherin in CAOMECS cell membranes while phosphorylated beta-catenin was significantly increased. ZO-1, occludin, and Cnx43 were also strongly expressed in CAOMECS. E-cadherin and beta-catenin localization at the cell membrane was reduced in LSCD corneas, while CAOMECS-grafted corneas showed a restoration of E-cadherin and beta-catenin expression. LSCD corneas did not show continuous staining for ZO-1 or for Cnx43, while CAOMECS-grafted corneas showed a positive expression of ZO-1 and Cnx43. Cascade Blue® hydrazide did not pass through CAOMECS. Because E-cadherin interactions are calcium-dependent, EGTA was used to chelate calcium and disrupt cell adhesion. EGTA-treated CAOMECS completely detached from cell culture surface, and E-cadherin levels were significantly decreased. In conclusion, E cadherin high expression contributed to CAOMECS tight and gap junction protein recruitment at the cell membrane, thus promoting cellular adhesion and a functional barrier to protect the ocular surface. PMID:27777792

  19. Early transformative changes in normal ovarian surface epithelium induced by oxidative stress require Akt upregulation, DNA damage and epithelial-stromal interaction.

    PubMed

    King, Shelby M; Quartuccio, Suzanne M; Vanderhyden, Barbara C; Burdette, Joanna E

    2013-05-01

    Ovarian cancer is the deadliest gynecological malignancy due to detection of cancer at a late stage when the disease has metastasized. One likely progenitor cell type of ovarian cancer is the ovarian surface epithelium (OSE), which proliferates rapidly in the presence of inflammatory cytokines and oxidative stress following ovulation. To determine whether oxidative stress induces DNA damage leading to spontaneous transformative changes in normal OSE, an immortalized mouse OSE cell line (MOSE cells) or normal mouse ovarian organoids were treated with hydrogen peroxide (H2O2) and loss of contact inhibition was assessed by soft agar assay. In response to H2O2, OSE cells grown in 3D exhibited growth in soft agar but MOSE cells grown on 2D plastic did not, indicating a critical role for epithelial-stromal interactions in neoplastic initiation. Loss of contact inhibition in response to H2O2 correlated with an increase in proliferation, DNA damage and upregulation of the oncogene Akt1. Use of a reactive oxygen species scavenger or Akt inhibitor blocked H2O2-induced proliferation and growth in soft agar. Although parental MOSE cells did not undergo transformation by H2O2, MOSE cells stably overexpressing constitutively active myristoylated Akt or knockdown of phosphatase and tensin homolog (PTEN) exhibited loss of contact inhibition and increased proliferation. This study indicates that normal OSE undergo transformative changes induced by oxidative stress and that this process requires Akt upregulation and activation. A 3D model that retains tissue architecture is critical for studying this process and may lead to development of new intervention strategies directed at early stages of ovarian cancer.

  20. Nano-hydroxyapatite and nano-titanium dioxide exhibit different subcellular distribution and apoptotic profile in human oral epithelium.

    PubMed

    Tay, Chor Yong; Fang, Wanru; Setyawati, Magdiel Inggrid; Chia, Sing Ling; Tan, Kai Soo; Hong, Catherine Hsu Ling; Leong, David Tai

    2014-05-14

    Nanomaterials (NMs) such as titanium dioxide (nano-TiO2) and hydroxyapatite (nano-HA) are widely used in food, personal care, and many household products. Due to their extensive usage, the risk of human exposure is increased and may trigger NMs specific biological outcomes as the NMs interface with the cells. However, the interaction of nano-TiO2 and nano-HA with cells, their uptake and subcellular distribution, and the cytotoxic effects are poorly understood. Herein, we characterized and examined the cellular internalization, inflammatory response and cytotoxic effects of nano-TiO2 and nano-HA using TR146 human oral buccal epithelial cells as an in vitro model. We showed both types of NMs were able to bind to the cellular membrane and passage into the cells in a dose dependent manner. Strikingly, both types of NMs exhibited distinct subcellular distribution profile with nano-HA displaying a higher preference to accumulate near the cell membrane compared to nano-TiO2. Exposure to both types of NMs caused an elevated reactive oxygen species (ROS) level and expression of inflammatory transcripts with increasing NMs concentration. Although cells treated with nano-HA induces minimal apoptosis, nano-TiO2 treated samples displayed approximately 28% early apoptosis after 24 h of NMs exposure. We further showed that nano-TiO2 mediated cell death is independent of the classical p53-Bax apoptosis pathway. Our findings provided insights into the potential cellular fates of human oral epithelial cells as they interface with industrial grade nano-HA and nano-TiO2.

  1. Nano-hydroxyapatite and nano-titanium dioxide exhibit different subcellular distribution and apoptotic profile in human oral epithelium.

    PubMed

    Tay, Chor Yong; Fang, Wanru; Setyawati, Magdiel Inggrid; Chia, Sing Ling; Tan, Kai Soo; Hong, Catherine Hsu Ling; Leong, David Tai

    2014-05-14

    Nanomaterials (NMs) such as titanium dioxide (nano-TiO2) and hydroxyapatite (nano-HA) are widely used in food, personal care, and many household products. Due to their extensive usage, the risk of human exposure is increased and may trigger NMs specific biological outcomes as the NMs interface with the cells. However, the interaction of nano-TiO2 and nano-HA with cells, their uptake and subcellular distribution, and the cytotoxic effects are poorly understood. Herein, we characterized and examined the cellular internalization, inflammatory response and cytotoxic effects of nano-TiO2 and nano-HA using TR146 human oral buccal epithelial cells as an in vitro model. We showed both types of NMs were able to bind to the cellular membrane and passage into the cells in a dose dependent manner. Strikingly, both types of NMs exhibited distinct subcellular distribution profile with nano-HA displaying a higher preference to accumulate near the cell membrane compared to nano-TiO2. Exposure to both types of NMs caused an elevated reactive oxygen species (ROS) level and expression of inflammatory transcripts with increasing NMs concentration. Although cells treated with nano-HA induces minimal apoptosis, nano-TiO2 treated samples displayed approximately 28% early apoptosis after 24 h of NMs exposure. We further showed that nano-TiO2 mediated cell death is independent of the classical p53-Bax apoptosis pathway. Our findings provided insights into the potential cellular fates of human oral epithelial cells as they interface with industrial grade nano-HA and nano-TiO2. PMID:24734929

  2. A single nucleotide polymorphism associated with isolated cleft lip and palate, thyroid cancer and hypothyroidism alters the activity of an oral epithelium and thyroid enhancer near FOXE1.

    PubMed

    Lidral, Andrew C; Liu, Huan; Bullard, Steven A; Bonde, Greg; Machida, Junichiro; Visel, Axel; Uribe, Lina M Moreno; Li, Xiao; Amendt, Brad; Cornell, Robert A

    2015-07-15

    Three common diseases, isolated cleft lip and cleft palate (CLP), hypothyroidism and thyroid cancer all map to the FOXE1 locus, but causative variants have yet to be identified. In patients with CLP, the frequency of coding mutations in FOXE1 fails to account for the risk attributable to this locus, suggesting that the common risk alleles reside in nearby regulatory elements. Using a combination of zebrafish and mouse transgenesis, we screened 15 conserved non-coding sequences for enhancer activity, identifying three that regulate expression in a tissue specific pattern consistent with endogenous foxe1 expression. These three, located -82.4, -67.7 and +22.6 kb from the FOXE1 start codon, are all active in the oral epithelium or branchial arches. The -67.7 and +22.6 kb elements are also active in the developing heart, and the -67.7 kb element uniquely directs expression in the developing thyroid. Within the -67.7 kb element is the SNP rs7850258 that is associated with all three diseases. Quantitative reporter assays in oral epithelial and thyroid cell lines show that the rs7850258 allele (G) associated with CLP and hypothyroidism has significantly greater enhancer activity than the allele associated with thyroid cancer (A). Moreover, consistent with predicted transcription factor binding differences, the -67.7 kb element containing rs7850258 allele G is significantly more responsive to both MYC and ARNT than allele A. By demonstrating that this common non-coding variant alters FOXE1 expression, we have identified at least in part the functional basis for the genetic risk of these seemingly disparate disorders.

  3. A single nucleotide polymorphism associated with isolated cleft lip and palate, thyroid cancer and hypothyroidism alters the activity of an oral epithelium and thyroid enhancer near FOXE1

    PubMed Central

    Lidral, Andrew C.; Liu, Huan; Bullard, Steven A.; Bonde, Greg; Machida, Junichiro; Visel, Axel; Uribe, Lina M. Moreno; Li, Xiao; Amendt, Brad; Cornell, Robert A.

    2015-01-01

    Three common diseases, isolated cleft lip and cleft palate (CLP), hypothyroidism and thyroid cancer all map to the FOXE1 locus, but causative variants have yet to be identified. In patients with CLP, the frequency of coding mutations in FOXE1 fails to account for the risk attributable to this locus, suggesting that the common risk alleles reside in nearby regulatory elements. Using a combination of zebrafish and mouse transgenesis, we screened 15 conserved non-coding sequences for enhancer activity, identifying three that regulate expression in a tissue specific pattern consistent with endogenous foxe1 expression. These three, located −82.4, −67.7 and +22.6 kb from the FOXE1 start codon, are all active in the oral epithelium or branchial arches. The −67.7 and +22.6 kb elements are also active in the developing heart, and the −67.7 kb element uniquely directs expression in the developing thyroid. Within the −67.7 kb element is the SNP rs7850258 that is associated with all three diseases. Quantitative reporter assays in oral epithelial and thyroid cell lines show that the rs7850258 allele (G) associated with CLP and hypothyroidism has significantly greater enhancer activity than the allele associated with thyroid cancer (A). Moreover, consistent with predicted transcription factor binding differences, the −67.7 kb element containing rs7850258 allele G is significantly more responsive to both MYC and ARNT than allele A. By demonstrating that this common non-coding variant alters FOXE1 expression, we have identified at least in part the functional basis for the genetic risk of these seemingly disparate disorders. PMID:25652407

  4. 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]).

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

    PubMed Central

    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.

    2015-01-01

    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]). PMID:26697360

  6. 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.

  7. 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

  8. Progenitor Epithelium

    PubMed Central

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

  9. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    PubMed

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines.

  10. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    PubMed

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines. PMID:26102179

  11. Hypermethylation of the p16 gene in normal oral mucosa of smokers.

    PubMed

    von Zeidler, S Ventorin; Miracca, E C; Nagai, M A; Birman, E G

    2004-11-01

    The oral cavity is the sixth most common anatomical localization of head and neck carcinoma in men. Detection of oral carcinomas in the early asymptomatic stages improves cure rates and the quality of life. Tobacco smoking and alcohol drinking are the most important known risk factors for the development of head and neck tumors, suggesting that the exposure to these risk factors may increase the predisposition for genetic and epigenetic alterations, such as DNA methylation. The presence of methylated CpG islands in the promoter region of human genes can suppress their expression due to the presence of 5-methylcytosine that interferes with the binding of transcription factors or other DNA-binding proteins repressing transcription activity. Hypermethylation leading to the inactivation of some tumor suppressor genes, such as p16, has been pointed out as an initial event in head and neck cancer. Our aim was to evaluate an early diagnostic method of oral pre-cancerous lesions through the analysis of methylation of the p16 gene. DNA samples from normal oral mucosa and posterior tongue border from 258 smokers, without oral cancer, were investigated for the occurrence of p16 promoter hypermethylation. The methylation status of the p16 gene was analyzed using MS-PCR (methylation-sensitive restriction enzymes and PCR amplification), MSP (Methylation-specific PCR) or direct DNA sequence of bisulfite modified DNA. Hyper-methylation was detected in 9.7% (25/258) of the cases analyzed. These findings provide further evidence that epigenetic alteration, leading to the inactivation of the p16 tumor suppressor gene is an early event that might confer cell growth advantages contributing to the tumorigenic process. Thus, the detection of abnormal p16 methylation pattern may be a valuable tool for early oral cancer detection. PMID:15492849

  12. Hypermethylation of the p16 gene in normal oral mucosa of smokers.

    PubMed

    von Zeidler, S Ventorin; Miracca, E C; Nagai, M A; Birman, E G

    2004-11-01

    The oral cavity is the sixth most common anatomical localization of head and neck carcinoma in men. Detection of oral carcinomas in the early asymptomatic stages improves cure rates and the quality of life. Tobacco smoking and alcohol drinking are the most important known risk factors for the development of head and neck tumors, suggesting that the exposure to these risk factors may increase the predisposition for genetic and epigenetic alterations, such as DNA methylation. The presence of methylated CpG islands in the promoter region of human genes can suppress their expression due to the presence of 5-methylcytosine that interferes with the binding of transcription factors or other DNA-binding proteins repressing transcription activity. Hypermethylation leading to the inactivation of some tumor suppressor genes, such as p16, has been pointed out as an initial event in head and neck cancer. Our aim was to evaluate an early diagnostic method of oral pre-cancerous lesions through the analysis of methylation of the p16 gene. DNA samples from normal oral mucosa and posterior tongue border from 258 smokers, without oral cancer, were investigated for the occurrence of p16 promoter hypermethylation. The methylation status of the p16 gene was analyzed using MS-PCR (methylation-sensitive restriction enzymes and PCR amplification), MSP (Methylation-specific PCR) or direct DNA sequence of bisulfite modified DNA. Hyper-methylation was detected in 9.7% (25/258) of the cases analyzed. These findings provide further evidence that epigenetic alteration, leading to the inactivation of the p16 tumor suppressor gene is an early event that might confer cell growth advantages contributing to the tumorigenic process. Thus, the detection of abnormal p16 methylation pattern may be a valuable tool for early oral cancer detection.

  13. Expression of MUC1 mucin in potentially malignant disorders, oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study

    PubMed Central

    Kumar, M Harish; Sanjai, Karpagaselvi; Kumarswamy, Jayalakshmi; Keshavaiah, Roopavathi; Papaiah, Lokesh; Divya, S

    2016-01-01

    Background: Mucins alteration in glycosylation is associated with the development and progression of malignant diseases. Therefore, mucins are used as valuable markers to distinguish normal and disease conditions. Many studies on MUC1 expression have been conducted on variety of neoplastic lesions other than head and neck region. None of the study has made an attempt to show its significance in potentially malignant disorders (PMDs) and oral squamous cell carcinoma (OSCC). Hence, ours is one of the pioneer studies done to assess and evaluate the same. Aims: This study aims to compare and correlate the expression of MUC1 mucin protein in normal oral mucosa (NOM), PMD's and OSCC by immunohistochemical method. Materials and Methods: Institutional study, archived tissue sections of OSCC (n = 20), PMD's (n = 20) and NOM (n = 20) were immunostained for MUC1 mucin and percentage of positive cells evaluated. Results obtained were statistically analyzed using Kruskal–Wallis test, Mann–Whitney test and Student's t-test. Results: The mean MUC1 mucin positive cells in the study groups were as follows, 40% in OSCC, 28% in PMD's and 0.75% in NOM. Higher mean immunohistochemical score was observed in OSCC group followed by PMD's group and NOM group. The difference in immunohistochemical score among the groups was found to be statistically significant (P < 0.001). Conclusion: The result of the current study suggests that determination of MUC1 mucin expression may be a parameter in the diagnosis of malignant behavior of PMD's to OSCC. MUC1 mucin expression may be a useful diagnostic marker for prediction of the invasive/metastatic potential of OSCC. PMID:27601811

  14. Expression of keratins in normal, immortalized and malignant oral epithelia in organotypic culture.

    PubMed

    Hansson, A; Bloor, B K; Haig, Y; Morgan, P R; Ekstrand, J; Grafström, R C

    2001-07-01

    Keratins have been extensively studied in tissues and cultured keratinocytes but limited information is available on epithelia reconstructed in vitro. The aim of this study was to examine keratin expression in organotypic epithelia with normal (NOK), immortalized (SVpgC2a) and malignant (SqCC/Y1) human buccal cells. Organotypic epithelia were derived from 10 days of culture at the air-liquid interface of collagen gels containing human oral fibroblasts using a standardized serum-free medium. Sections were stained immunohistochemically with selected mono-specific antibodies to a range of keratins. Organotypic epithelia showed sharp differences in keratin expression and distribution. K4/K13, K1/K10, K6/K16 were variably expressed in NOK and SqCC/Y1 but were not detected in SVpgC2a. K5 was expressed in all organotypic epithelia but K14 was absent in SVpgC2a. K7 and K8 showed variable expression while K18 was expressed uniformly in all epithelia. K19 was expressed consistently in NOK and K20 was distributed heterogeneously in SVpgC2a. Overall, organotypic cultures of normal keratinocytes express many of the same keratins as buccal mucosa. Further, the loss of keratins in SVpgC2a and their retention in SqCC/Y1 have several features in common with the respective keratin profile of oral epithelial dysplasia and well-differentiated oral squamous cell carcinoma. Although qualitative and quantitative differences exist compared to keratin expression in vivo, these cell lines in organotypic culture may serve in studies of the multi-step progression of oral cancer.

  15. Oral health conditions and behaviors among hearing impaired and normal hearing college students at Ratchasuda College, Nakhon Pathom, Thailand.

    PubMed

    Vichayanrat, Tippanart; Kositpumivate, Waritorn

    2014-09-01

    This study aimed to explore oral health and oral health related behaviors among hearing impaired and normal hearing students at Rachasuda College. The association between socioeconomic factors, hearing status, oral health behaviors, oral hygiene levels and dental caries status were also examined. The students filled out a self-administered questionnaire with assistance of a sign language video to obtain personal and behavior information. A total of 180 students, 83 normal hearing and 97 hearing impaired students completed the questionnaire and underwent an oral examination. The prevalences of caries were 53.6% and 50.6% among students with hearing impairment and normal hearing, respectively (p=0.354). After age stratification, the hearing impaired students aged 18-21 years had significantly less filled teeth (p=0.012), and those older than 21 years had less missing teeth due to caries than normal-hearing students (p=0.023). Poor oral hygiene was found in 51.8% and 42.2% of normal and hearing-impaired students, respectively (p=0.365). Caries status was significantly associated with maternal education level (OR 3.56; 95% CI: 1.52-8.32) and oral hygiene (OR 3.26; 95% CI: 1.64-6.45). The high prevalence of dental caries and poor oral hygiene among college students is alarming. Hearing impairment did not appear to affect the prevalences of these conditions compared to those with normal hearing. Oral health education tools need to be developed and utilized for both normal hearing and hearing impaired college students in Thailand.

  16. 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.

  17. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

    SciTech Connect

    Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, d.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.

    2010-09-21

    Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

  18. Oral and parenteral therapy with saperconazole (R 66905) of invasive aspergillosis in normal and immunocompromised animals.

    PubMed Central

    Van Cutsem, J; Van Gerven, F; Janssen, P A

    1989-01-01

    Saperconazole (R 66905) is a broad-spectrum antifungal triazole with potent in vitro activity against Aspergillus spp. A total of 279 strains were tested in brain heart infusion broth. Development of the Aspergillus spp. was completely inhibited at 0.1 and 1 microgram of saperconazole per ml for 80.3 and 99.6% of the strains, respectively. Normal and immunocompromised guinea pigs were infected intravenously with Aspergillus fumigatus and treated orally, intravenously, or intraperitoneally with saperconazole or intraperitoneally with amphotericin B. Leukopenia, neutropenia, lymphocytosis, and monocytosis were obtained with mechlorethamine hydrochloride; leukopenia, neutrophilia, and lymphopenia were obtained with cyclophosphamide. Saperconazole was dissolved for oral treatment in polyethylene glycol and for parenteral treatment in cyclodextrins. Amphotericin B was given parenterally as Fungizone (E.R. Squibb & Sons). Treatment was given once daily for 14 days. An early starting treatment was efficacious, but the activity of saperconazole was maintained even when the onset of the treatment was delayed to the moribund state. The activity of saperconazole was not altered in immunocompromised animals. Saperconazole was clearly superior to amphotericin B and free of side effects. The oral and parenteral formulations of saperconazole were equipotent. The systemic activity of saperconazole in guinea pigs was confirmed in invasive aspergillosis in pigeons. PMID:2619273

  19. Antimicrobial effects of herbal extracts on Streptococcus mutans and normal oral streptococci.

    PubMed

    Lee, Sung-Hoon

    2013-08-01

    Streptococcus mutans is associated with dental caries. A cariogenic biofilm, in particular, has been studied extensively for its role in the formation of dental caries. Herbal extracts such as Cudrania tricuspidata, Sophora flavescens, Ginkgo biloba, and Betula Schmidtii have been used as a folk remedy for treating diseases. The purpose of this study was to evaluate and compare the antibacterial activity of herbal extracts against normal oral streptococci, planktonic and biofilm of S. mutans. Streptococcus gordonii, Streptococcus oralis, Streptococcus salivarius, Streptococcus sanguinis, and S. mutans were cultivated with brain heart infusion broth and susceptibility assay for the herbal extracts was performed according to the protocol of Clinical and Laboratory Standard Institute. Also, S. mutans biofilm was formed on a polystyrene 12-well plate and 8-well chamber glass slip using BHI broth containing 2% sucrose and 1% mannose after conditioning the plate and the glass slip with unstimulated saliva. The biofilm was treated with the herbal extracts in various concentrations and inoculated on Mitis-Salivarius bacitracin agar plate for enumeration of viable S. mutans by counting colony forming units. Planktonic S. mutans showed susceptibility to all of the extracts and S. mutans biofilm exhibited the highest level of sensitivity for the extracts of S. flavescens. The normal oral streptococci exhibited a weak susceptibility in comparison to S. mutans. S. oralis, however, was resistant to all of the extracts. In conclusion, the extract of S. flavescens may be a potential candidate for prevention and management of dental caries.

  20. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    SciTech Connect

    D. W. Nigg

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  1. PCR based detection of HPV 16 and 18 genotypes in normal oral mucosa of tobacco users and non-users.

    PubMed

    Pattanshetty, S; Kotrashetti, V S; Nayak, R; Bhat, K; Somannavar, P; Babji, D

    2014-08-01

    There is increasing evidence of a causal association between human papillomavirus (HPV) and oral squamous cell carcinoma (OSCC). Several studies have shown that HPV is associated with increased risk of oral cancer independent of exposure to tobacco and alcohol. The association is valid for HPVs 16 and 18, which generally are considered high risk types, because they have been detected in oral dysplastic lesions and cancers. We determined the baseline prevalence of HPVs 16 and 18 in normal oral mucosa of individuals with and without tobacco habit. PCR was used for DNA collected by oral smears to detect HPV 16/18 DNA in normal oral mucosa of 60 healthy individuals who were assigned to two groups of 30 subjects each. One group had a tobacco habit, the other did not. The tobacco user group comprised individuals who were tobacco chewers only. Sixty-five percent of individuals were positive for HPV 16/18 DNA, but HPV 16/18 positivity was less in individuals with tobacco habit than in those without tobacco habit. No significant association was found between the presence of HPVs and gender, age or duration of chewing habit, or between groups with and without a tobacco habit. We propose that HPVs16 and 18 commonly are present in normal oral mucosa and emphasize the importance of distinguishing clinical, subclinical and latent HPV infections when investigating HPVs and OSCC.

  2. Tear film concentrations of doxycycline following oral administration in ophthalmologically normal dogs.

    PubMed

    Collins, Sean P; Labelle, Amber L; Dirikolu, Levent; Li, Zhong; Mitchell, Mark A; Hamor, Ralph E

    2016-09-01

    OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration. DESIGN Crossover study. ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease. PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography-mass spectrometry and compared between the 2 doxycycline doses. RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22). CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug. PMID:27556265

  3. A histochemical comparison of methyl green-pyronin, and hematoxylin and eosin for detecting apoptotic cells in oral squamous cell carcinoma, oral leukoplakia, oral submucous fibrosis and normal oral mucosa.

    PubMed

    Sumedha, S; Kotrashetti, V S; Somannavar, P; Nayak, R; Babji, D

    2015-05-01

    Analysis of apoptotic cells in oral pathological states could be useful for determining the rates of tissue turnover, which would help determine prognosis. The use of histochemical stains such as hematoxylin and eosin (H & E) and methyl green-pyronin (MGP) can provide a simple and cost-effective method for detecting apoptotic cells. We compared the efficacy of MGP and H & E for detecting apoptotic cells in oral squamous cell carcinoma (OSCC), oral leukoplakia (OL), oral submucous fibrosis (OSMF) and normal oral mucosa (NOM). Ten cases each of OSCC, OSMF, OL and NOM were retrieved from the archives and two serial sections were stained, one with H & E and the other with MGP. Apoptotic cells were identified at 100 x magnification and the apoptotic index was calculated. Apoptotic cells were distinguished more readily in MGP stained sections than in those stained with H & E. Also, the apoptotic cell count was greater in OSCC compared to OL, OSMF and NOM. We concluded that MGP staining can be used as a routine, cost-effective method for detecting apoptotic cells.

  4. Intracellular transport of nanocarriers across the intestinal epithelium.

    PubMed

    Fan, Weiwei; Xia, Dengning; Zhu, Quanlei; Hu, Lei; Gan, Yong

    2016-05-01

    The intestinal epithelium is the main barrier restricting the oral delivery of low-permeability drugs. Over recent years, numerous nanocarriers have been designed to improve the efficiency of oral drug delivery. However, the intracellular processes determining the transport of nanocarriers across the intestinal epithelium remain elusive, and only limited enhancement of the oral bioavailability of drugs has been achieved. Here, we review the processes involved in nanocarrier trafficking across the intestinal epithelium, including apical endocytosis, intracellular transport, and basolateral exocytosis. Understanding the complex intracellular processes of nanocarrier trafficking is particularly essential for the rational design of oral drug delivery systems. PMID:27094490

  5. Nasal and oral flow-volume loops in normal subjects and patients with obstructive sleep apnea.

    PubMed

    Shepard, J W; Burger, C D

    1990-12-01

    Because flow-volume loops (FVLs) are clinically useful in evaluating upper airway (UA) obstruction and the fact that patency of the nasopharyngeal ventilatory pathway is important to the prevention of obstructive sleep apnea (OSA), the present study examined the role of nasal compared with oral FVLs in evaluating patients with OSA. Fourteen obese male patients 56 +/- 3 yr of age with a mean apnea plus hypopnea index (AHI) of 51 +/- 9/h were studied along with 14 nonobese, healthy, age- and sex-matched control subjects whose mean AHI was 6 +/- 1/h. Nasal and oral FVLs obtained in the normal subjects indicated the nose behaved like a variable resistor, with flow limitation during inspiration but not during expiration. In the patient group, flow limitation was observed during expiration as well as inspiration indicating nondistensibility of the nasopharyngeal ventilatory pathway in the patients compared to the control subjects. A change in body position from upright to supine in the OSA group was associated with small reductions in expiratory but not inspiratory flow rates. The area under the nasal supine flow-volume loop (FVLANaSup) was found to be highly correlated with awake resting PaO2 (r = 0.80) and PaCO2 (r = -0.83) in the patient group. In addition, multiple linear regression analysis revealed that PaO2 and the area under the nasal FVLs independently contributed to the prediction of AHI with a multiple R of 0.89. These results suggest that limitations to ventilation via the nasopharynx may significantly influence both gas exchange and the frequency of sleep-disordered breathing in patients with OSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2252246

  6. 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

  7. Do rhythms exist in elbow flexor torque, oral temperature and muscle thickness during normal waking hours?

    PubMed

    Buckner, Samuel L; Dankel, Scott J; Counts, Brittany R; Barnett, Brian E; Jessee, Matthew B; Mouser, J Grant; Halliday, Tanya M; Loenneke, Jeremy P

    2016-06-01

    The purpose of the current study was to examine the influence of "time" on isometric elbow flexion torque, body temperature and muscle size without interrupting the sleep wake cycle in college aged males. Two hours following the participants normal wake time, oral temperature was measured, followed by muscle thickness of the upper and lower body using ultrasound, as well as elbow flexor torque via a maximal voluntary contraction (MVC). Measurements were repeated every 2h for 12h (Time points 1-7). To examine the repeatability of the rhythm, participants returned and completed the same procedures as before within 14days of their first circadian visit (Circadian visit 2). There was no time×day interaction for body temperature (p=0.29), nor were there main effects for time (p=0.15) or day (p=0.74). For MVC, there was no time×day interaction (p=0.93) or main effect for day (p=0.50), however, there was a main effect for time (p=0.01). MVC at time points 1 (86.4±6.4Nm) and 2 (87.1±6.2Nm) was greater than time points 4 (84.2±6.6Nm) and 6 (83.4±6.8Nm, p<0.05). Additionally, time point 5 MVC was greater than time point 4. For upper body muscle thickness, there was no time×day interaction (p=0.34), nor was there a main effect for day (p=0.38), or time (p=0.06). For lower body muscle thickness, there was no time×day interaction (p=0.57), nor was there a main effect for day (p=0.75), or time (p=0.13). Cosinor analyses revealed no group level rhythms for oral temperature, muscle thickness or strength (p>0.05), however, there were some individual rhythms noted for muscle thickness and strength. Results suggest that, when accounting for an individuals normal wake time, circadian rhythms of strength, temperature and muscle thickness are not apparent in most individuals.

  8. Normalization.

    ERIC Educational Resources Information Center

    Cuevas, Eduardo J.

    1997-01-01

    Discusses cornerstone of Montessori theory, normalization, which asserts that if a child is placed in an optimum prepared environment where inner impulses match external opportunities, the undeviated self emerges, a being totally in harmony with its surroundings. Makes distinctions regarding normalization, normalized, and normality, indicating how…

  9. Syntactic Development in the Oral Language of Learning Disabled and Normal Students at the Intermediate and Secondary Level.

    ERIC Educational Resources Information Center

    Simms, Rochelle B.; Crump, W. Donald

    1983-01-01

    Syntactic development in the oral language of learning disabled and normal students at two intermediate and two secondary-school age levels was compared using two indices, the T-unit and the Syntactic Density Score. It was concluded that no single, sensitive, numerical index exists to quantify syntactic development. (SW)

  10. DNA damage in oral cancer and normal cells induced by nitrogen atmospheric pressure plasma jets

    NASA Astrophysics Data System (ADS)

    Han, Xu; Kapaldo, James; Liu, Yueying; Stack, M. Sharon; Ptasinska, Sylwia

    2015-09-01

    Nitrogen atmospheric pressure plasma jets (APPJs) have been shown to effectively induce DNA double strand breaks in SCC25 oral cancer cells. The APPJ source constructed in our laboratory operates based on dielectric barrier discharge. It consists of two copper electrodes alternatively wrapping around a fused silica tube with nitrogen as a feed gas. It is generally more challenging to ignite plasma in N2 atmosphere than in noble gases. However, N2 provides additional advantages such as lower costs compared to noble gases, thus this design can be beneficial for the future long-term clinical use. To compare the effects of plasma on cancer cells (SCC25) and normal cells (OKF), the cells from both types were treated at the same experimental condition for various treatment times. The effective area with different damage levels after the treatment was visualized as 3D maps. The delayed damage effects were also explored by varying the incubation times after the treatment. All of these studies are critical for a better understanding of the damage responses of cellular systems exposed to the plasma radiation, thus are useful for the development of the advanced plasma cancer therapy. The research described herein was supported by the Division of Chemical Sciences, Geosciences and Biosciences, Basic Energy Sciences, Office of Science, United States Department of Energy through Grant No. DE-FC02-04ER15533.

  11. Irf6 directly regulates Klf17 in zebrafish periderm and Klf4 in murine oral epithelium, and dominant-negative KLF4 variants are present in patients with cleft lip and palate

    PubMed Central

    Liu, Huan; Leslie, Elizabeth J.; Jia, Zhonglin; Smith, Tiffany; Eshete, Mekonen; Butali, Azeez; Dunnwald, Martine; Murray, Jeffrey; Cornell, Robert A.

    2016-01-01

    Non-syndromic (NS) cleft lip with or without cleft palate (CL/P) is a common disorder with a strong genetic underpinning. Genome-wide association studies have detected common variants associated with this disorder, but a large portion of the genetic risk for NSCL/P is conferred by unidentified rare sequence variants. Mutations in IRF6 (Interferon Regulatory Factor 6) and GRHL3 (Grainyhead-like 3) cause Van der Woude syndrome, which includes CL/P. Both genes encode members of a regulatory network governing periderm differentiation in model organisms. Here, we report that Krüppel-like factor 17 (Klf17), like Grhl3, acts downstream of Irf6 in this network in zebrafish periderm. Although Klf17 expression is absent from mammalian oral epithelium, a close homologue, Klf4, is expressed in this tissue and is required for the differentiation of epidermis. Chromosome configuration capture and reporter assays indicated that IRF6 directly regulates an oral-epithelium enhancer of KLF4. To test whether rare missense variants of KLF4 contribute risk for NSCL/P, we sequenced KLF4 in approximately 1000 NSCL/P cases and 300 controls. By one statistical test, missense variants of KLF4 as a group were enriched in cases versus controls. Moreover, two patient-derived KLF4 variants disrupted periderm differentiation upon forced expression in zebrafish embryos, suggesting that they have dominant-negative effect. These results indicate that rare NSCL/P risk variants can be found in members of the gene regulatory network governing periderm differentiation. PMID:26692521

  12. Detection of human papillomavirus in normal oral cavity in a group of Pakistani subjects using real-time PCR.

    PubMed

    Gichki, Abdul Samad; Buajeeb, Waranun; Doungudomdacha, Sombhun; Khovidhunkit, Siribang-on Pibooniyom

    2012-01-01

    Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the β-globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1 μg of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p=0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients.

  13. Engineering Airway Epithelium

    PubMed Central

    Soleas, John P.; Paz, Ana; Marcus, Paula; McGuigan, Alison; Waddell, Thomas K.

    2012-01-01

    Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990). In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium. PMID:22523471

  14. Assessment of Oral Conditions and Quality of Life in Morbid Obese and Normal Weight Individuals: A Cross-Sectional Study.

    PubMed

    Yamashita, Joselene Martinelli; Moura-Grec, Patrícia Garcia de; Freitas, Adriana Rodrigues de; Sales-Peres, Arsênio; Groppo, Francisco Carlos; Ceneviva, Reginaldo; Sales-Peres, Sílvia Helena de Carvalho

    2015-01-01

    The aim of this study was to identify the impact of oral disease on the quality of life of morbid obese and normal weight individuals. Cohort was composed of 100 morbid-obese and 50 normal-weight subjects. Dental caries, community periodontal index, gingival bleeding on probing (BOP), calculus, probing pocket depth, clinical attachment level, dental wear, stimulated salivary flow, and salivary pH were used to evaluate oral diseases. Socioeconomic and the oral impacts on daily performances (OIDP) questionnaires showed the quality of life in both groups. Unpaired Student, Fisher's Exact, Chi-Square, Mann-Whitney, and Multiple Regression tests were used (p<0.05). Obese showed lower socio-economic level than control group, but no differences were found considering OIDP. No significant differences were observed between groups considering the number of absent teeth, bruxism, difficult mastication, calculus, initial caries lesion, and caries. However, saliva flow was low, and the salivary pH was changed in the obese group. Enamel wear was lower and dentine wear was higher in obese. More BOP, insertion loss, and periodontal pocket, especially the deeper ones, were found in obese subjects. The regression model showed gender, smoking, salivary pH, socio-economic level, periodontal pocket, and periodontal insertion loss significantly associated to obesity. However, both OIDP and BOP did not show significant contribution to the model. The quality of life of morbid obese was more negatively influenced by oral disease and socio-economic factors than in normal weight subjects. PMID:26177268

  15. Cell lineage-specific and differentiation-dependent patterns of CCAAT/enhancer binding protein alpha expression in the gut epithelium of normal and transgenic mice.

    PubMed Central

    Chandrasekaran, C; Gordon, J I

    1993-01-01

    The proliferation and differentiation programs of gut epithelial cells are expressed rapidly and perpetually along an anatomically well defined pathway. The mouse intestine thus provides an excellent in vivo model system to define the contributions of CCAAT enhancer binding protein alpha (C/EBP alpha) and related bZIP proteins to these processes. Immunocytochemical studies revealed that C/EBP alpha is produced in villus-associated enterocytes located in the duodenum and jejunum of adult mice. The protein is located in the cytoplasmic and nuclear compartments of these cells. C/EBP alpha is not detectable in proliferating and nonproliferating epithelial cells situated in small intestinal crypts nor is it evident in any gut epithelial cell lineage located in the ileum and colon. The related C/EBP beta and C/EBP delta proteins are not detectable by sensitive immunocytochemical methods in epithelial cells distributed along the duodenal-to-colonic axis. Developmental surveys indicate that C/EBP alpha is confined to postmitotic, villus-associated epithelial cells during conversion of the polyclonal intervillus epithelium to monoclonal crypts. Analyses of intestinal isografts reveal that these developmental stage-specific, lineage-specific, differentiation-dependent, and regional patterns of C/EBP alpha expression can be established and maintained in the absence of exposure to luminal contents. Transgenic mice containing nucleotides -1178 to +28 of the rat intestinal fatty acid binding protein gene (I-FABP-1178 to +28) linked to the simian virus 40 large tumor antigen (T antigen) gene express T antigen in villus-associated enterocytes. This results in reentry of enterocytes into the cell cycle and a silencing of C/EBP alpha expression without an apparent effect on the accumulation of several markers of this lineage's terminal differentiation program or on gut morphogenesis. These findings indicate that there is a relationship between expression of C/EBP alpha in

  16. E-cadherin in non-tumor epithelium adjacent to oral cancer as risk marker for the development of multiple tumors.

    PubMed

    González-Moles, M A; Bravo, M; Ruiz-Avila, I; Gil-Montoya, J A; Acebal, F; Esteban, F

    2013-03-01

    Our aim was to find out whether the loss of E-cadherin is a risk factor for the development of multiple tumours in the oral cavity and whether it could serve as a diagnostic marker for oral premalignant fields. We studied 77 oral squamous cell carcinomas (SCC) with associated non-tumour epithelia from 61 patients. Immunohistochemical studies (antibody NHC-38) were used to investigate E-cadherin expression, which was completely lost in basal (48% of cases) and parabasal (43%) layers of non-tumour epithelia close to the tumour and in basal (47%) and parabasal (38%) layers of non-tumour epithelia distant from the tumour. In multiple tumours E-cadherin expression was significantly lower than in single tumours in the basal, parabasal layers, and the middle third of close (p=0.002, <0.001, <0.001) and distant (p=0.041, p<0.001, p=0.005) non-tumour epithelia, respectively. Downregulation of E-cadherin may be valuable as a risk marker for the development of multiple tumours in the oral cavity and for the diagnosis of premalignant fields.

  17. 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

  18. Fluorine-18-labeled boronophenylalanine positron emission tomography for oral cancers: Qualitative and quantitative analyses of malignant tumors and normal structures in oral and maxillofacial regions

    PubMed Central

    ARIYOSHI, YASUNORI; SHIMAHARA, MASASHI; KIMURA, YOSHIHIRO; ITO, YUICHI; SHIMAHARA, TAKESHI; MIYATAKE, SHIN-ICHI; KAWABATA, SHINJI

    2011-01-01

    The present study aimed to demonstrate the features of fluorine-18-labeled boronophenylalanine positron emission tomography (18F-BPA-PET) to reveal oral cancer, as well as normal structures in the oral and maxillofacial regions. We analyzed 18F-BPA-PET findings from 8 patients with histologically confirmed recurrent and/or advanced oral cancer scheduled for boron neutron capture therapy. The capacity of 18F-BPA-PET to delineate tumor and normal structures was assessed qualitatively and quantitatively. Tumors were easily identified as high uptake areas in all cases. Although the eyes, which were depicted as a low uptake area, and tongue musculature were readily identified, major vessels were not noted in any of the cases. Areas corresponding to the surface of the dorsum tongue to middle pharynx were expressed as high uptake areas in all of the cases. Quantitatively, tumors were expressed as the highest uptake area in 6 of the 8 cases, while the dorsum tongue had the highest uptake area in the remaining 2 cases. 18F-BPA-PET is useful in demonstrating the presence of a tumor. Thus, it is crucial to note the presence of a high uptake area corresponding to the dorsum area of the tongue when diagnosing a tumor using this technique. PMID:22866098

  19. Expression of transient receptor potential channel vanilloid (TRPV) 1–4, melastin (TRPM) 5 and 8, and ankyrin (TRPA1) in the normal and methimazole-treated mouse olfactory epithelium

    PubMed Central

    Nakashimo, Yousuke; Takumida, Masaya; Fukuiri, Takashi; Anniko, Matti; Hirakawa, Katsuhiro

    2010-01-01

    Conclusion: It is suggested that TRPV1, 2, 3, and 4, TRPM5 and 8, and TRPA1 may play several roles in the olfactory epithelium (OE), contributing to olfactory chemosensation, olfactory adaptation, olfactory-trigeminal interaction, and OE fluid homeostasis. In patients with olfactory disturbance, TRPV1 and TRPM8 may be closely related to a high rate of recognition of curry and menthol odors, while TRPV2 may also play a crucial role in the regeneration of olfactory receptor neurons. Objective: Expression of TRPV1–4, TRPM5 and 8, and TRPA1 in the normal and methimazole-treated mouse OE was analyzed. Methods: The localization of TRPV1–4, TRPM5 and 8, and TRPA1 in the OE of normal and methimazole-treated CBA/J mice was investigated by immunohistochemistry. Results: Normal OE showed a positive immunofluorescent reaction to TRPV1–4, TRPM5 and 8, and TRPA1. In lamina propria, the nerve fibers displayed TRPV 1, 2, and 3, TRPM8 and TRPA1. In the pathological condition, the expression of TRPV3, TRPV4, TRPM5, and TRPA1 was markedly reduced and took a long time to recover. In contrast, expression of TRPM8 was scarcely affected, even in the pathological condition, while TRPV1 and TRPV2 showed early recovery following methimazole treatment. PMID:20586674

  20. Comparison of oral health status between children with cerebral palsy and normal children in India: A case–control study

    PubMed Central

    Sinha, Nidhi; Singh, Bijay; Chhabra, Kumar Gaurav; Patil, Santosh

    2015-01-01

    Background: The aim of the present research was to describe and compare the oral health of children with cerebral palsy (CP) with the normal children in India. Materials and Methods: Fifty children with CP of the age range 7-17 years and fifty normal children were selected for the study. An oral examination was carried out and decayed, missing, and filled teeth (dmft/DMFT) index, oral hygiene index-simplified (OHI-S) index, Angles malocclusion were charted along with other significant dental findings. Data were analyzed using Student's t-test and Kruskal–Wallis one-way ANOVA test. Results: The mean dmft/DMFT of the CP group was 4.11 ± 2.62, while that of controls was 2.95 ± 2.75, which showed higher caries prevalence in the CP group. There was a significant association between the dmft/DMFT (P = 0.03), OHI-S (P = 0.001), and Angles Class 2 malocclusion and CP. Conclusions: Cerebral palsy group had higher caries, poor oral hygiene and Class 2 malocclusion when compared to controls primarily because of their compromised general health condition and also less dental awareness. Effort should be made for better organization of preventive dental care and promoting dental health of this challenged population. PMID:25810598

  1. Effect of oral administration of mutagens found in food on the frequency of sister chromatid exchanges in the colonic epithelium of mice

    SciTech Connect

    Couch, D.B.; Stuart, E.; Heddle, J.A.

    1987-01-01

    Epidemiological studies indicate there is a link between dietary factors and the incidence of colon cancer, and it has been suggested mutagens in foods might be responsible for initiating the carcinogenic process. Some food mutagens are formed during the cooking process. For example, certain heterocyclic amines, including Trp-P-2 (3-amino-1-methyl-5H-pyrido(4,3-n) indole) and MeIQ (2-amino-3,4-dimethylimidazo(4,5-f)quinoline), which have been isolated from broiled meat and fish at low (ng/g) levels, are extremely potent mutagens in the Ames Salmonella/microsome test and can induce mutation in cultured mammalian cells as well. Other mutagens in foods are natural products; quercetin, a flavanoid widely distributed in plant products, is mutagenic to Salmonella and cultured mammalian cells. As most of the evidence implicating substance in food as mutagenic carcinogens comes from in vitro studies, it is of interest to determine whether these compounds can also exert genotoxic effects in vivo, particularly in colonic tissue. The ability to induce nuclear aberrations in vivo in murine colonic epithelial tissue has been suggested to be a property of colon carcinogens specifically, and several mutagens found in cooked food, including MeIQ and Trp-P-2, have been found to produce such nucleotoxicity. The authors report here tests of the ability of MeIQ, Trp-P-2, and quercetin to induce sister chromatid exchanges (SCEs) in the colonic epithelium of mice.

  2. 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

  3. Oral exposure to environmental pollutant benzo[a]pyrene impacts the intestinal epithelium and induces gut microbial shifts in murine model

    PubMed Central

    Ribière, Céline; Peyret, Pierre; Parisot, Nicolas; Darcha, Claude; Déchelotte, Pierre J.; Barnich, Nicolas; Peyretaillade, Eric; Boucher, Delphine

    2016-01-01

    Gut microbiota dysbiosis are associated with a wide range of human diseases, including inflammatory bowel diseases. The physiopathology of these diseases has multifactorial aetiology in which environmental factors, particularly pollution could play a crucial role. Among the different pollutants listed, Polycyclic Aromatic Hydrocarbons (PAHs) are subject to increased monitoring due to their wide distribution and high toxicity on Humans. Here, we used 16S rRNA gene sequencing to investigate the impact of benzo[a]pyrene (BaP, most toxic PAH) oral exposure on the faecal and intestinal mucosa-associated bacteria in C57BL/6 mice. Intestinal inflammation was also evaluated by histological observations. BaP oral exposure significantly altered the composition and the abundance of the gut microbiota and led to moderate inflammation in ileal and colonic mucosa. More severe lesions were observed in ileal segment. Shifts in gut microbiota associated with moderate inflammatory signs in intestinal mucosa would suggest the establishment of a pro-inflammatory intestinal environment following BaP oral exposure. Therefore, under conditions of genetic susceptibility and in association with other environmental factors, exposure to this pollutant could trigger and/or accelerate the development of inflammatory pathologies. PMID:27503127

  4. Oral exposure to environmental pollutant benzo[a]pyrene impacts the intestinal epithelium and induces gut microbial shifts in murine model.

    PubMed

    Ribière, Céline; Peyret, Pierre; Parisot, Nicolas; Darcha, Claude; Déchelotte, Pierre J; Barnich, Nicolas; Peyretaillade, Eric; Boucher, Delphine

    2016-01-01

    Gut microbiota dysbiosis are associated with a wide range of human diseases, including inflammatory bowel diseases. The physiopathology of these diseases has multifactorial aetiology in which environmental factors, particularly pollution could play a crucial role. Among the different pollutants listed, Polycyclic Aromatic Hydrocarbons (PAHs) are subject to increased monitoring due to their wide distribution and high toxicity on Humans. Here, we used 16S rRNA gene sequencing to investigate the impact of benzo[a]pyrene (BaP, most toxic PAH) oral exposure on the faecal and intestinal mucosa-associated bacteria in C57BL/6 mice. Intestinal inflammation was also evaluated by histological observations. BaP oral exposure significantly altered the composition and the abundance of the gut microbiota and led to moderate inflammation in ileal and colonic mucosa. More severe lesions were observed in ileal segment. Shifts in gut microbiota associated with moderate inflammatory signs in intestinal mucosa would suggest the establishment of a pro-inflammatory intestinal environment following BaP oral exposure. Therefore, under conditions of genetic susceptibility and in association with other environmental factors, exposure to this pollutant could trigger and/or accelerate the development of inflammatory pathologies. PMID:27503127

  5. 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.

  6. Assessment of Oral Conditions and Quality of Life in Morbid Obese and Normal Weight Individuals: A Cross-Sectional Study

    PubMed Central

    de Freitas, Adriana Rodrigues; Sales-Peres, Arsênio; Ceneviva, Reginaldo

    2015-01-01

    The aim of this study was to identify the impact of oral disease on the quality of life of morbid obese and normal weight individuals. Cohort was composed of 100 morbid-obese and 50 normal-weight subjects. Dental caries, community periodontal index, gingival bleeding on probing (BOP), calculus, probing pocket depth, clinical attachment level, dental wear, stimulated salivary flow, and salivary pH were used to evaluate oral diseases. Socioeconomic and the oral impacts on daily performances (OIDP) questionnaires showed the quality of life in both groups. Unpaired Student, Fisher’s Exact, Chi-Square, Mann-Whitney, and Multiple Regression tests were used (p<0.05). Obese showed lower socio-economic level than control group, but no differences were found considering OIDP. No significant differences were observed between groups considering the number of absent teeth, bruxism, difficult mastication, calculus, initial caries lesion, and caries. However, saliva flow was low, and the salivary pH was changed in the obese group. Enamel wear was lower and dentine wear was higher in obese. More BOP, insertion loss, and periodontal pocket, especially the deeper ones, were found in obese subjects. The regression model showed gender, smoking, salivary pH, socio-economic level, periodontal pocket, and periodontal insertion loss significantly associated to obesity. However, both OIDP and BOP did not show significant contribution to the model. The quality of life of morbid obese was more negatively influenced by oral disease and socio-economic factors than in normal weight subjects. PMID:26177268

  7. 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.

  8. Obtaining Normal Tissue Constraints Using Intensity Modulated Radiotherapy (IMRT) in Patients with Oral Cavity, Oropharnygeal, and Laryngeal Carcinoma

    SciTech Connect

    Skinner, William K.J.

    2009-01-01

    The purpose of this study was to evaluate normal tissue dose constraints while maintaining planning target volume (PTV) prescription without reducing PTV margins. Sixteen patients with oral cavity carcinoma (group I), 27 patients with oropharyngeal carcinoma (group II), and 28 patients with laryngeal carcinoma (group III) were reviewed. Parotid constraints were a mean dose to either parotid < 26 Gy (PP1), 50% of either parotid < 30 Gy (PP2), or 20 cc of total parotid < 20 Gy (PP3). Treatment was intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB). All patients met constraints for cord and brain stem. The mandibular constraints were met in 66%, 29%, and 57% of patients with oral, oropharyngeal, and laryngeal cancers, respectively. Mean dose of 26 Gy (PP1) was achieved in 44%, 41%, and 38% of oral, oropharyngeal, and laryngeal patients. PP2 (parotid constraint of 30 Gy to less than 50% of one parotid) was the easiest to achieve (group I, II, and III: 82%, 76%, and 78%, respectively). PP3 (20 cc of total parotid < 20 Gy) was difficult, and was achieved in 25%, 17%, and 35% of oral, oropharyngeal, and laryngeal patients, respectively. Mean parotid dose of 26 Gy was met 40% of the time. However, a combination of constraints allowed for sparing of the parotid based on different criteria and was met in high numbers. This was accomplished without reducing PTV-parotid overlap. What dose constraint best correlates with subjective and objective functional outcomes remains a focus for future study.

  9. Comparative study of frequency of micronuclei in normal, potentially malignant diseases and oral squamous cell carcinoma

    PubMed Central

    Sangle, Varsha Ajit; Bijjaragi, Shobha; Shah, Nishat; Kangane, Suresh; Ghule, Hrishikesh M.; Rani, SR Ashwini

    2016-01-01

    Context: The assessment of micronuclei (MN) in exfoliated oral epithelial cells is a promising tool for the study of epithelial carcinogens and can be used to detect chromosome breakage or mitotic interference, thought to be relevant to carcinogenesis. Aims: To detect MN in exfoliated oral mucosal cells in individuals using various tobacco forms and also to detect frequency of MN in premalignant lesions and conditions (potentially malignant diseases [PMD's]) and oral squamous cell carcinoma (OSCC). To correlate frequency of MN in oral exfoliated cells in clinically diagnosed cases of OSCC followed by a histopathological grading. Materials and Methods: A total of 90 subjects (30 smokeless tobacco users, 30 smokers and 30 nontobacco users) consisted of clinically diagnosed cases of PMD's and OSCC were selected for the study. Cytosmears from the groups were stained with rapid Papanicolaou stain. MN was identified according to the Tolbert et al. criteria. Results: MN cells were found to be significantly higher in smokeless tobacco users than in smokers. The frequency of MN was three to four times higher in patients with OSCC as compared to patients in PMD's (P < 0.0001). The frequency of MN correlated with the histopathological grade was statistically significant. Conclusion: MN index can be used as a biomarker/screening test among the high-risk groups particularly the smokeless tobacco users and PMD's. MN can be a candidate to serve as a biomarker for prediction of the grade of OSCC. PMID:27003966

  10. Quantification of PCNA+ cells within odontogenic jaw cyst epithelium.

    PubMed

    Li, T J; Browne, R M; Matthews, J B

    1994-04-01

    The aim of this study was to investigate the reactivity of the epithelial linings of the three major types of odontogenic cyst with a monoclonal antibody to proliferating cell nuclear antigen (PCNA; clone PC10). PCNA expression was studied in odontogenic cysts (n = 31) and normal oral epithelium (n = 10) using a biotin-streptavidin method on routinely processed paraffin sections. PCNA+ cells were counted manually and related to the length of basement membrane (mm) and the epithelial area (mm2) as determined by TV image analysis. The epithelial linings of odontogenic keratocysts (OKC; n = 11) contained the highest number of PCNA+ cells, most of which were located in the suprabasal layers. The mean value of PCNA+ cells in OKC linings (94.4 +/- 22.7 cells/mm) was similar to that of oral epithelia (80.8 +/- 20.6 cells/mm), but both were significantly higher than that of dentigerous (n = 10, 5.1 +/- 3.0 cells/mm) and radicular (n = 10, 11.0 +/- 4.1 cells/mm) cyst linings (P < 0.005). The epithelial distribution of PCNA+ cells differed between groups with the basal/suprabasal PCNA+ cell ratio in OKC linings (0.05 +/- 0.02) being significantly lower than that of normal oral epithelium (0.5 +/- 0.14), dentigerous (1.6 +/- 1.23) and radicular (1.9 +/- 1.09) cyst linings respectively (P < 0.005). These results demonstrate differences in PCNA expression between the epithelial linings of the major odontogenic cyst types, indicating differences in proliferative and differentiation processes within these lesions.

  11. Can MMP-9 be a Prognosticator Marker for Oral Squamous Cell Carcinoma?

    PubMed Central

    Basu, Shiva Kumar; Kumar, Manish

    2016-01-01

    Introduction Invasion and metastasis of malignant tumours severely endanger the life of cancer patients. Squamous cell carcinoma is one of the commonly found malignancies in the oral cavity and its survival rate has not improved from past few decades. Since an important risk factor for oral squamous cell carcinoma is the presence of epithelial dysplasia, it is necessary to check the presence of a prognosticator marker in both of them. As matrix metalloproteinase’s (MMP’s) are involved in degradation of type IV collagen, which are one of the important components of extracellular matrix components which play a relevant role in several steps of tumour progression such as invasion and metastasis. We have studied MMP-9 expression to evaluate its prognostic potential in oral cancers as well as oral epithelial dysplasia along with tissues of normal oral epithelium. Materials and Methods The expression was examined using immunohistochemistry procedure with MMP-9 in 100 samples including cases of epithelium from normal oral mucosa, oral dysplastic lesions and oral squamous cell carcinoma. One set of formalin fixed, paraffin embedded sections of the three categories were stained by haematoxylin and eosin. The sections were then evaluated under microscope. Data was examined for statistical significance using SPSS 13.0 by Mann-Whitney Test and Kruskal-Wallis Test. Results With MMP-9 gain of expression was noted from Control group to oral squamous cell carcinoma. Cytoplasmic staining was seen with MMP-9. Statistically highly significant differences were seen between oral epithelial dysplasia and oral squamous cell carcinoma and statistically significant differences were found between the control group and the oral squamous cell carcinoma group. Conclusion This study suggested that oral squamous cell carcinoma shows higher MMP-9 expression as compared to oral epithelial dysplasia followed by epithelium from normal oral mucosa. However, no correlation was found among the

  12. Oral stereognostic ability among tongue thrusters with interdental lisp, tongue thrusters without interdental lisp and normal children.

    PubMed

    Colletti, E A; Geffner, D; Schlanger, P

    1976-02-01

    30 children, i.e., 10 children per group, 8 yr. of age, were given an oral stereognostic test. This test of 10 geometric forms varying in shape were developed by NIDR. 47 stimuli pairs were used and 10 pairs were repeated to measure test reliability. Subjects were blindfolded and asked to respond whether Items 1 and 2, presented consecutively, were the same or different. Results indicated that both groups of tongue thrusters with and without interdental lisp scored significantly more poorly than did normal children (t = 4.68, P less than .001; t = 5.00, P less than .001), respectively. There were no significant differences, however, between tongue thrusters with and without interdental lisp (t = .33, P greater than .05). Observations indicated that normal children used the tongue tip more frequently and accurately when discriminating the geometric forms than did the other groups. PMID:943761

  13. Comparison of the cardiovascular and pulmonary effects of oral celiprolol, propranolol and placebo in normal volunteers.

    PubMed Central

    Busst, C M; Bush, A

    1989-01-01

    1. The effects on heart rate, blood pressure and pulmonary function of single oral doses of celiprolol hydrochloride (400 mg), and propranolol (40 mg) were compared with placebo in 12 healthy volunteers, in a double-blind three-period crossover study. 2. Celiprolol had no effect on heart rate while propranolol caused a significant reduction compared with placebo. Systolic blood pressure was reduced by propranolol but not celiprolol, whereas standing diastolic blood pressure was lowered by both drugs. 3. The maximal expiratory flow at 50% vital capacity (MEF.50), was significantly lower after propranolol compared with placebo and celiprolol. Celiprolol had no effect on the flow-volume loop parameters. 4. Effective pulmonary blood flow was significantly increased by celiprolol, but reduced by propranolol. 5. A high incidence of subjective side-effects were experienced on celiprolol (10/12; particularly unpleasant in 5). Side-effects were experienced to a lesser extent on placebo (8/12). Only one volunteer experienced a side-effect on propranolol. 6. Oral celiprolol exerts its hypotensive effect by vasodilatation without reflex tachycardia. It does not cause airways obstruction in healthy subjects. PMID:2566321

  14. A quantitative electron microscopic analysis of the keratinizing epithelium of noral human hard palate.

    PubMed

    Meyer, M; Schroeder, H E

    1975-01-01

    The epithelium of normal human hard palate was subjected to sterologic analysis. Ten biosies were selected from a total of twenty specimens collected from 9 to 16 year old females, and processed for light- and electron microscopy. At two levels of magnification, electron micrographs were sampled from three strata (basale, spinosum, granulosum) in two locations (epithelial ridges and portions over connective tissue papillae). Stereologic point counting procedures were employed to analyse a total 1560 electron micrographs. In general, the thickness of the palate epithelium was 0.12 mm (over papillae) and 0.31 mm (in ridges), the epithelium is distinctly stratified, and homogeneously ortho-keratinized. From basal to granular layers, the composition of strata revealed decreasing densities of nuclei, mitochondria, membrane-bound organelles and aggregates of free ribosomes. Keratohyalin bodies and membrane coating granules increased, and cytoplasmic filaments with a constant diameter of about 85 A increased from 14 to 30% of cytoplasmic unit volume. The cytoplasmic ground substance occupied a stable 50% of the epithelial cytoplasm in all strata. The composition of basal layers in ridges differed from that over connective tissue papillae. The data are discussed in relation to the observations that (1) an increasing gradient of filament density is not the most characteristic feature of ortho-keratinizing oral epithelium and (2) differences in the degree of differentiation in cells of the stratum basale coincided with the comparable frequency distribution pattern of dividing cells.

  15. [Autocrine growth mechanisms of cholesteatoma epithelium].

    PubMed

    Schilling, V; Holly, A; Bujía, J; Schulz, P

    1993-07-01

    Transforming growth factor alpha (TGF alpha) and interleukin 1 alpha (IL-1 alpha) are known to be produced by normal human keratinocytes stimulating their proliferation. The distribution and expression of TGF alpha and IL-1 alpha were examined in specimens of middle ear cholesteatoma by means of immunohistochemical methods using a monoclonal antibody against TGF alpha and a polyclonal one against IL-1 alpha. Normal retroauricular skin was stained for comparison. Staining for TGF alpha was consistently stronger in cholesteatoma epithelium than in normal epidermis, and encompassed all epithelial cell layers. Immune cells occurring in the stroma of cholesteatoma also reacted positively for TGF alpha. The intensity of staining for IL-1 alpha was markedly stronger in cholesteatoma tissue than in normal epidermis. All cellular layers of the squamous epithelium of cholesteatoma stained strongly and uniformly for IL-1 alpha, whereas the keratin layer was negative for IL-1 alpha. In the connective tissue beneath the cholesteatoma epithelium intensely positive cells were scattered between negative stromal cells. These data are consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF alpha and IL-1 alpha as well as with a paracrine stimulation by immune cells. Both factors contribute to the unrestrained growth of cholesteatoma in the middle ear cavity.

  16. Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes

    PubMed Central

    Nanjappa, Vishalakshi; Renuse, Santosh; Sathe, Gajanan J; Raja, Remya; Syed, Nazia; Radhakrishnan, Aneesha; Subbannayya, Tejaswini; Patil, Arun; Marimuthu, Arivusudar; Sahasrabuddhe, Nandini A; Guerrero-Preston, Rafael; Somani, Babu L; Nair, Bipin; Kundu, Gopal C; Prasad, T Keshava; Califano, Joseph A; Gowda, Harsha; Sidransky, David; Pandey, Akhilesh; Chatterjee, Aditi

    2015-01-01

    Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies, short-term exposure to tobacco has been evaluated. From a biological perspective, however, long-term (chronic) exposure to tobacco mimics the pathogenesis of oral cancer more closely. We developed a cell line model to investigate the chronic effects of chewing tobacco. Chronic exposure to tobacco resulted in higher cellular proliferation and invasive ability of the normal oral keratinocytes (OKF6/TERT1). We carried out quantitative proteomic analysis of OKF6/TERT1 cells chronically treated with chewing tobacco compared to the untreated cells. We identified a total of 3,636 proteins among which expression of 408 proteins were found to be significantly altered. Among the overexpressed proteins, stearoyl-CoA desaturase (SCD) was found to be 2.6-fold overexpressed in the tobacco treated cells. Silencing/inhibition of SCD using its specific siRNA or inhibitor led to a decrease in cellular proliferation, invasion and colony forming ability of not only the tobacco treated cells but also in a panel of head and neck cancer cell lines. These findings suggest that chronic exposure to chewing tobacco induced carcinogenesis in non-malignant oral epithelial cells and SCD plays an essential role in this process. The current study provides evidence that SCD can act as a potential therapeutic target in head and neck squamous cell carcinoma, especially in patients who are users of tobacco. PMID:26391970

  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. Oral Administration of Collagen Hydrolysates Improves Glucose Tolerance in Normal Mice Through GLP-1-Dependent and GLP-1-Independent Mechanisms.

    PubMed

    Iba, Yoshinori; Yokoi, Koji; Eitoku, Itsuka; Goto, Masaki; Koizumi, Seiko; Sugihara, Fumihito; Oyama, Hiroshi; Yoshimoto, Tadashi

    2016-09-01

    The aim of this study was to evaluate the antidiabetic properties of collagen hydrolysates (CHs). CHs exhibited dipeptidyl peptidase-IV inhibitory activity and stimulated glucagon-like-peptide-1 (GLP-1) secretion in vitro. We also determined whether CHs improve glucose tolerance in normal mice. Oral administration of CHs suppressed the glycemic response during the oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT), but the effects were weaker in IPGTT than in OGTT. CHs had no effect on the gastric emptying rate. A pretreatment with the GLP-1 receptor antagonist, exendin 9-39 (Ex9), partially reversed the glucose-lowering effects of CHs, but only when coadministered with glucose. CHs administered 45 min before the glucose load potentiated the glucose-stimulated insulin secretion. This potentiating effect on insulin secretion was not reversed by the pretreatment with Ex9, it appeared to be enhanced. These results suggest that CHs improve glucose tolerance by inhibiting intestinal glucose uptake and enhancing insulin secretion, and also demonstrated that GLP-1 was partially involved in the inhibition of glucose uptake, but not essential for the enhancement of insulin secretion. PMID:27540823

  19. [Immunomorphology of oral lichen planus].

    PubMed

    Rabinovich, O F; Ivina, A A; Guseva, A V; Babichenko, I I

    2016-01-01

    The article is devoted to immunohistochemical study of reticular and erosive forms of oral lichen planus. Morphological examination of the reticular form revealed the increased number of Langerhans cells (CD1a), mast cells (CD25) and T lymphocytes (CD4, CD8, CD16) in the oral epithelium. Activation of these cells leads to the secretion of TNF-α and destruction of basal keratinocytes, which manifests as a focal reduction of intercellular protein expression of E-cadherin. Destruction of basal keratinocytes in a reticular form of oral lichen planus is accompanied by a significant decrease in proliferative activity of the basal cell layer (21.7±10.2%) compared with normal mucosa (33.6±7.0%), p=0.0045. In erosive form along with the above changes IgG and C3d complement's elements are revealed, which confirms the activation of immune complex mechanisms in the erosion area.

  20. More men than women make mucosal IgA antibodies to Human papillomavirus type 16 (HPV-16) and HPV-18: a study of oral HPV and oral HPV antibodies in a normal healthy population

    PubMed Central

    Marais, Dianne J; Sampson, Candice; Jeftha, Anthea; Dhaya, Dherendra; Passmore, Jo-Ann S; Denny, Lynette; Rybicki, Edward P; Van Der Walt, Eric; Stephen, Lawrence XG; Williamson, Anna-Lise

    2006-01-01

    Background We have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with HPV-associated cervical neoplasia. It was postulated that the HPV antibodies were initiated after HPV antigenic stimulation at the cervix via the common mucosal immune system. The present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to HPV infection and to advance our limited understanding of the immune response to HPV. Methods The prevalence of oral HPV infection and oral antibodies to HPV types 16, 18 and 11 was determined in a normal, healthy population of children, adolescents and adults, both male and female, attending a dental clinic. HPV types in buccal cells were determined by DNA sequencing. Oral fluid was collected from the gingival crevice of the mouth by the OraSure method. HPV-16, HPV-18 and HPV-11 antibodies in oral fluid were detected by virus-like particle-based enzyme-linked immunosorbent assay. As a reference group 44 women with cervical neoplasia were included in the study. Results Oral HPV infection was highest in children (9/114, 7.9%), followed by adolescents (4/78, 5.1%), and lowest in normal adults (4/116, 3.5%). The predominant HPV type found was HPV-13 (7/22, 31.8%) followed by HPV-32 (5/22, 22.7%). The prevalence of oral antibodies to HPV-16, HPV-18 and HPV-11 was low in children and increased substantially in adolescents and normal adults. Oral HPV-16 IgA was significantly more prevalent in women with cervical neoplasia (30/44, 68.2%) than the women from the dental clinic (18/69, 26.1% P = 0.0001). Significantly more adult men than women displayed oral HPV-16 IgA (30/47 compared with 18/69, OR 5.0, 95% CI 2.09–12.1, P < 0.001) and HPV-18 IgA (17/47 compared with 13/69, OR 2.4, 95% CI 0.97–6.2, P = 0.04). Conclusion The increased prevalence of oral HPV antibodies in adolescent individuals compared with children was attributed to the

  1. Immunohistochemical expression of EGFR in oral leukoplakia: Association with clinicopathological features and cellular proliferation

    PubMed Central

    Ribeiro, Daniela C.; Gleber-Netto, Frederico O.; Sousa, Sílvia F.; Bernardes, Vanessa F.; Guimarães-Abreu, Mauro H.N.

    2012-01-01

    Objectives: to investigate the immunoexpression of epidermal growth factor receptor (EGFR) in a sample of oral leukoplakias (OL) and to determine the receptor’s association with dysplasia, tobacco consumption, lesion site, and proliferation rate. Although EGFR should be overexpressed in some oral leukoplakias, the factors that may interfere with this expression and the influence of this receptor on epithelial proliferation have yet to be investigated. Study Design: Samples of oral leukoplakias (48) and of normal oral epithelium (10) were immunohistologically examined for expression of EGFR. Immunohistochemistry for Ki-67, and p27 were also performed in leukoplakias. EGFR expression was associated with clinical and pathological features. Results: EGFR was positive in 62.5% of the leukoplakias and 50% of normal oral epithelium. The number of EGFR positive OL located in high-risk sites was significantly higher than EGFR positive OL located in low-risk sites. Most of the p27 negative leukoplakias were EGFR positive, and the p27 index in the parabasal layer was diminished in the presence of dysplasia. Positivity for EGFR was not associated with dysplasia, tobacco exposure, or Ki-67. Conclusion: EGFR is expressed in leukoplakia regardless of dysplasia, but EGFR positivity should be more frequent in lesions sited in areas of high cancer risk. The association between EGFR and p27 may represent an important mechanism in the control of cellular proliferation and malignant progression of oral epithelium and therefore warrants further investigation. Key words:Oral leukoplakia, EGFR, p27, Ki-67, epithelial dysplasia. PMID:22322523

  2. Raman microspectroscopic study of oral buccal mucosa

    NASA Astrophysics Data System (ADS)

    Behl, Isha; Mamgain, Hitesh; Deshmukh, Atul; Kukreja, Lekha; Hole, Arti R.; Krishna, C. Murali

    2014-03-01

    Oral cancer is the most common cancer among Indian males, with 5-year- survival-rates of less than 50%. Efficacy of Raman spectroscopic methods in non-invasive and objective diagnosis of oral cancers and confounding factors has already been demonstrated. The present Raman microspectroscopic study was undertaken for in-depth and site-specific analysis of normal and tumor tissues. 10 normal and 10 tumors unstained sections from 20 tissues were accrued. Raman data of 160 x 60 μm and 140 x 140 μm in normal and tumor sections, respectively, were acquired using WITec alpha 300R equipped with 532 nm laser, 50X objective and 600 gr/mm grating. Spectral data were corrected for CCDresponse, background. First-derivitized and vector-normalized data were then subjected to K-mean cluster analysis to generate Raman maps and correlated with their respective histopathology. In normal sections, stratification among epithelial layers i.e. basal, intermediate, superficial was observed. Tumor, stromal and inflammatory regions were identified in case of tumor section. Extracted spectra of the pathologically annotated regions were subjected to Principal component analysis. Findings suggest that all three layers of normal epithelium can be differentiated against tumor cells. In epithelium, basal and superficial layers can be separated while intermediate layer show misclassifications. In tumors, discrimination of inflammatory regions from tumor cells and tumor-stroma regions were observed. Finding of the study indicate Raman mapping can lead to molecular level insights of normal and pathological states.

  3. Extraction of RNA from archival tissues and measurement of thrombospondin-1 mRNA in normal, dysplastic, and malignant oral tissues.

    PubMed

    Macluskey, M; Baillie, R; Morrow, H; Schor, S L; Schor, A M

    2006-04-01

    Thrombospondin-1 (TSP-1) is an extracellular matrix glycoprotein implicated in the regulation of angiogenesis and tumour development. Our objectives were to ascertain the quantity and quality of RNA extracted from archival, formalin-fixed, paraffin embedded, oral tissues and their application in measuring the concentrations of TSP-1 mRNA in these tissues. We compared three techniques of isolation of RNA as well as related experimental variables. TSP-1 mRNA was measured in specimens of normal, dysplastic, and malignant oral tissues by real-time reverse transcriptase polymerase chain reaction (RT-PCR). RNA suitable for analysis by real-time RT-PCR was obtained by the three techniques tested, although the yield varied depending on the protocol used (range 0.2-3.6 microg/mm(3)). The mean (S.D.) concentrations of TSP-1 mRNA relative to 18S were 21.1 (7.2) in normal oral tissues (n=9), 11.0 (8.2) in dysplastic tissue (n=8) and 7.3 (5.3) in carcinomatous tissue (n=17). The difference between normal and carcinomatous specimens was significant (p=0.01). This reduction in expression of TSP-1 mRNA from normal to dysplasia to carcinoma may favour the angiogenic drive that accompanies the development of oral tumours.

  4. Bmi-1 extends the life span of normal human oral keratinocytes by inhibiting the TGF-{beta} signaling

    SciTech Connect

    Kim, Reuben H.; Lieberman, Mark B.; Lee, Rachel; Shin, Ki-Hyuk; Mehrazarin, Shebli; Oh, Ju-Eun; Park, No-Hee; Kang, Mo K.

    2010-10-01

    We previously demonstrated that Bmi-1 extended the in vitro life span of normal human oral keratinocytes (NHOK). We now report that the prolonged life span of NHOK by Bmi-1 is, in part, due to inhibition of the TGF-{beta} signaling pathway. Serial subculture of NHOK resulted in replicative senescence and terminal differentiation and activation of TGF-{beta} signaling pathway. This was accompanied with enhanced intracellular and secreted TGF-{beta}1 levels, phosphorylation of Smad2/3, and increased expression of p15{sup INK4B} and p57{sup KIP2}. An ectopic expression of Bmi-1 in NHOK (HOK/Bmi-1) decreased the level of intracellular and secreted TGF-{beta}1 induced dephosphorylation of Smad2/3, and diminished the level of p15{sup INK4B} and p57{sup KIP2}. Moreover, Bmi-1 expression led to the inhibition of TGF-{beta}-responsive promoter activity in a dose-specific manner. Knockdown of Bmi-1 in rapidly proliferating HOK/Bmi-1 and cancer cells increased the level of phosphorylated Smad2/3, p15{sup INK4B}, and p57{sup KIP2}. In addition, an exposure of senescent NHOK to TGF-{beta} receptor I kinase inhibitor or anti-TGF-{beta} antibody resulted in enhanced replicative potential of cells. Taken together, these data suggest that Bmi-1 suppresses senescence of cells by inhibiting the TGF-{beta} signaling pathway in NHOK.

  5. Phospholipase C-gamma1 is required for subculture-induced terminal differentiation of normal human oral keratinocytes.

    PubMed

    Oh, Ju-Eun; Kook, Joong-Ki; Park, Kyung-Hee; Lee, Gene; Seo, Byoung-Moo; Min, Byung-Moo

    2003-04-01

    Serial subculture of primary normal human oral keratinocytes (NHOKs) to the post-mitotic stage induces terminal differentiation, which is in part linked to elevated levels of phospholipase C (PLC)-gamma1. Therefore, PLC-gamma1 may be involved in the signal transduction system that leads to the calcium regulation of subculture-induced keratinocyte differentiation. To test this hypothesis, the expression of PLC-gamma1 in primary NHOKs was blocked by transfecting cells with the antisense PLC-gamma1 cDNA construct. These cells demonstrated dramatic reductions in PLC-gamma1 protein and in the differentiation markers involucrin and transglutaminase following calcium exposure and an increase (15-20%) in in vitro life span versus empty vector-transfected cells. In addition, we established the ability of antisense PLC-gamma1 to block the serial subculture-induced rise in intracellular calcium. Similar observations were made following treatment with the specific PLC inhibitor U73122. These results indicate that the terminal differentiation of NHOKs by serial subculture is associated with PLC-gamma1, which mediates calcium regulation by mobilizing intracellular calcium.

  6. Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation

    PubMed Central

    2014-01-01

    The presence of melanocytes in the oral epithelium is a well-established fact, but their physiological functions are not well defined. Melanin provides protection from environmental stressors such as ultraviolet radiation and reactive oxygen species; and melanocytes function as stress-sensors having the capacity both to react to and to produce a variety of microenvironmental cytokines and growth factors, modulating immune, inflammatory and antibacterial responses. Melanocytes also act as neuroendocrine cells producing local neurotransmitters including acetylcholine, catecholamines and opioids, and hormones of the melanocortin system such as proopiomelanocortin, adrenocorticotropic hormone and α-melanocyte stimulating hormone, that participate in intracellular and in intercellular signalling pathways, thus contributing to tissue homeostasis. There is a wide range of normal variation in melanin pigmentation of the oral mucosa. In general, darker skinned persons more frequently have oral melanin pigmentation than light-skinned persons. Variations in oral physiological pigmentation are genetically determined unless associated with some underlying disease. In this article, we discuss some aspects of the biophysiology of oral melanocytes, of the functions of melanin, and of physiological oral pigmentation. PMID:24661309

  7. Quantification of the global and local complexity of the epithelial-connective tissue interface of normal, dysplastic, and neoplastic oral mucosae using digital imaging.

    PubMed

    Abu Eid, Rasha; Landini, Gabriel

    2003-01-01

    This study aimed at quantifying the complexity of the epithelial-connective tissue interface (ECTI) in human normal mucosa, premalignant, and malignant lesions using fractal geometry. Two approaches were used to describe the complexity of 377 oral mucosa ECTI profiles. The box counting method was used to estimate their global fractal dimension, while local fractal dimensions were estimated using the mass radius relation at various local scales. The ECTI complexity significantly increased from normal through premalignant to malignant profiles in both global and local (over 283 microm) scales. Normal mucosa samples from different sites of the oral cavity also had different degrees of global complexity. Fractal geometry is a useful morphological marker of tissue complexity changes taking place during epithelial malignancy and premalignancy, and we propose it as a quantitative marker of epithelial complexity. PMID:14521264

  8. Characterization of different tissue changes in normal, betel chewers, potentially malignant lesions, conditions and oral squamous cell carcinoma using reflectance confocal microscopy: correlation with routine histopathology.

    PubMed

    Anuthama, Krishnamurthy; Sherlin, Herald J; Anuja, N; Ramani, Pratibha; Premkumar, Priya; Chandrasekar, T

    2010-04-01

    The goal of this study was to characterize the features of normal mucosa, mucosa in betel chewers and smokers, potentially malignant lesions and squamous cell carcinoma of oral mucosa using reflectance confocal microscopy. Oral cavity biopsies were acquired from 25 patients from College of Dental Surgery, Saveetha University who underwent screening for suspected lesions of Oral precancer and Oral cancer along with normal patients who underwent impaction. Biopsies were acquired from the clinically suspicious area and immediately placed in Dulbecco modified eagles growth medium (DMEM). Reflectance confocal images were obtained at multiple image plane depths from biopsies within 6h of excision. After imaging, biopsies were fixed in 10% formalin and submitted for routine histopathological examination by an experienced oral and maxillofacial pathologist. Reflectance confocal images were compared with histological images from the same sample to determine the tissue features which contribute to early cellular changes, image contrast and early diagnosis. The confocal images were obtained to a depth of up to 150 microns on intact biopsy specimens and subsequent 3-dimensional images, keratin thickness measurements, cell measurements, cell density analysis and graphical representations were performed using Leica image analysis software. In normal mucosa keratin deposition were seen as alternating dark and bright stacks and in different cell layers the nuclei were seen as disks of varying intensities. In pre-cancerous lesions the keratin thickness and cell nuclear density were found to be increased when compared to normal controls. In OSMF cases confocal images of fibrosis show scattering from individual fibres as hyperdense areas. Oral squamous cell carcinoma cases demonstrated extensive variations in cell size, nuclear size and nuclear morphology. At cellular level, dysplastic features like increased nuclear density, increased nuclear cytoplasmic ratio, nuclear and cellular

  9. Raman mapping of oral buccal mucosa: a spectral histopathology approach

    NASA Astrophysics Data System (ADS)

    Behl, Isha; Kukreja, Lekha; Deshmukh, Atul; Singh, S. P.; Mamgain, Hitesh; Hole, Arti R.; Krishna, C. Murali

    2014-12-01

    Oral cancer is one of the most common cancers worldwide. One-fifth of the world's oral cancer subjects are from India and other South Asian countries. The present Raman mapping study was carried out to understand biochemical variations in normal and malignant oral buccal mucosa. Data were acquired using WITec alpha 300R instrument from 10 normal and 10 tumors unstained tissue sections. Raman maps of normal sections could resolve the layers of epithelium, i.e. basal, intermediate, and superficial. Inflammatory, tumor, and stromal regions are distinctly depicted on Raman maps of tumor sections. Mean and difference spectra of basal and inflammatory cells suggest abundance of DNA and carotenoids features. Strong cytochrome bands are observed in intermediate layers of normal and stromal regions of tumor. Epithelium and stromal regions of normal cells are classified by principal component analysis. Classification among cellular components of normal and tumor sections is also observed. Thus, the findings of the study further support the applicability of Raman mapping for providing molecular level insights in normal and malignant conditions.

  10. Examination of the reticular epithelium of the bovine pharyngeal tonsil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The nasopharyngeal tonsil (adenoid), located at the posterior of the nasopharynx is ideally positioned to sample antigens entering through the nasal cavity or oral cavity. Entering antigens will first contact tonsilar epithelium. To better understand the cellular composition of this important epithe...

  11. Ultrastructural study of grafted autologous cultured human epithelium.

    PubMed

    Aihara, M

    1989-01-01

    An electron microscopical study of grafted autologous cultured human epithelium is presented. Biopsy samples were collected from four patients with full thickness burns at 9 days, 6 weeks and 5-21 months after grafting of the cultured epithelium. By the sixth week after transplantation, grafted cultured epithelial sheets had developed to consist of 10 to 20 layers of cells and the epithelium showed distinct basal, spinous, granular and horny layers, and a patchy basement membrane had formed. Langerhans cells and melanocytes were identifiable. From 5 months onwards flat basal cells became oval, and oval keratohyalin granules in the keratinocytes also assumed a normal irregular shape. Membrane-coating granules in the keratinocytes increased in number. The fine structures of desmosomes also showed a normal mature appearance. Furthermore, complete extension of the basement membrane could be observed. The maturation of cultured human epithelium is complete by 5 months after grafting.

  12. Comparative evaluation of eosinophils in normal mucosa, dysplastic mucosa and oral squamous cell carcinoma with hematoxylin-eosin, Congo red, and EMR1 immunohistochemical staining techniques

    PubMed Central

    kargahi, Neda; Razavi, Sayyed Mohammad; Deyhimi, Parviz; Homayouni, Solmaz

    2015-01-01

    Background: Oral squamous cell carcinoma is the most common malignant lesion of the oral cavity, and it involves various molecular mechanisms. The development of oral squamous cell carcinoma is influenced by the host immune cells, such as eosinophils. The present study was conducted to compare the presence of eosinophils in normal mucosa, dysplastic mucosa, and oral squamous cell carcinoma by -hematoxylin- eosin staining, Congo red staining, and epidermal growth factor-like (EGF-like) module containing a mucin–like hormone receptor1 (EMR1) immunohistochemical marker. Methods: In this cross-sectional study, 60 paraffinized samples were selected, consisting of 20 normal mucosae, 20 dysplastic mucosae, and 20 squamous cell carcinoma samples. After confirmation of the diagnosis, the mean number of eosinophils was evaluated by hematoxylin-eosin, Congo red, and immunohystochemical staining techniques. The data were analyzed by SPSS-10 software using the Kruskal-Wallis and Friedman tests. Results: The results showed that the number of eosinophils in dysplastic mucosa was significantly higher than the number in normal mucosa, and the number of eosinophils in squamous cell carcinoma was significantly higher than the number in dysplastic mucosa in all staining techniques (p<0.001). Moreover, the comparison of staining techniques showed a significantly higher number of eosinophils in EMR1immunohistochemicalmarker than were observed when Congo red and hematoxylin - eosin (H&E) staining techniques were used (p<0.001). Conclusion: It can be argued that eosinophil contributes to the identification of lesions that have a higher potential of malignant transformation. Moreover, eosinophil can be suggested as an indicator in the differentiation of oral lesions in cases with borderline diagnosis and in targeted molecular therapy. PMID:26120409

  13. Expression of CD1a by Langerhan’s Cells in Oral Lichen Planus - A Retrospective Analysis

    PubMed Central

    Sakki, Esther Priyadarshini; Kumar, Yennavaram Vijay; Kolimi, Sadananda; Perika, Ravi; Karthik, Kalepu Venkata; Kumar, Kandukuri Mahesh; Kalyan, Venumbaka Siva

    2016-01-01

    Introduction Langerhan’s Cells (LCs) are dendritic cells of the oral epithelium which play a role in a series of oral lesions from gingivitis to oral cancer. Oral Lichen Planus (OLP) is an oral mucosal T-lymphocyte mediated immunologic reaction to an unidentified putative antigen or allergen. Aim The aim of this study was to quantify the presence of immature LCs in OLP comparing them with normal epithelium. Materials and Methods A retrospective study using 30 of OLP cases were conducted. Immunohistochemistry was performed using polyclonal anti-CD1a antibodies to identify LCs in 10 cases of normal tissue and 30 samples of OLP. The distribution of LCs among lesional tissue and normal mucosa was analysed using Mann-Whitney U test. Results LC population in OLP was significantly higher when compared to the normal epithelium (p<0.001). Conclusion The increase in LCs indicates the active role played during the antigen detection in OLP and subsequent presentation to T-lymphocytes. PMID:27504405

  14. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    PubMed

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P < 0.05 or 0.001). These results suggested that RRDY and yam dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models. PMID:27499387

  15. Development of tissue-engineered models of oral dysplasia and early invasive oral squamous cell carcinoma

    PubMed Central

    Colley, H E; Hearnden, V; Jones, A V; Weinreb, P H; Violette, S M; MacNeil, S; Thornhill, M H; Murdoch, C

    2011-01-01

    Background: Current organotypic models of dysplasia and oral squamous cell carcinoma (OSCC) lack the complexity that mimics in vivo tissue. Here we describe a three-dimensional in vitro model of the oral epithelium that replicates tumour progression from dysplasia to an invasive phenotype. Methods: The OSCC cell lines were seeded as a cell suspension (D20, Cal27) or as multicellular tumour spheroids (FaDu) with oral fibroblasts on to a de-epidermised acellular dermis to generate tissue-engineered models and compared with patient biopsies. Results: The D20 and Cal27 cells generated a model of epithelial dysplasia. Overtime Cal27 cells traversed the basement membrane and invaded the connective tissue to reproduce features of early invasive OSCC. When seeded onto a model of the normal oral mucosa, FaDu spheroids produced a histological picture mimicking carcinoma in situ with severe cellular atypia juxtaposed to normal epithelium. Conclusion: It is possible to culture in vitro models with the morphological appearance and histological characteristics of dysplasia and tumour cell invasion seen in vivo using native dermis. Such models could facilitate study of the molecular processes involved in malignant transformation, invasion and tumour growth as well as in vitro testing of new treatments, diagnostic tests and drug delivery systems for OSCC. PMID:21989184

  16. Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

    PubMed

    Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

    2015-10-10

    Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. PMID:26048667

  17. Downregulation of Keratin 76 Expression during Oral Carcinogenesis of Human, Hamster and Mouse

    PubMed Central

    Heath, Emma; Pandey, Manishkumar; Kumar, Gaurav; Kane, Shubhada; Patil, Asawari; Maru, Girish B.; Desai, Rajiv S.; Watt, Fiona M.; Mahimkar, Manoj B.

    2013-01-01

    Background Keratins are structural marker proteins with tissue specific expression; however, recent reports indicate their involvement in cancer progression. Previous study from our lab revealed deregulation of many genes related to structural molecular integrity including KRT76. Here we evaluate the role of KRT76 downregulation in oral precancer and cancer development. Methods We evaluated KRT76 expression by qRT-PCR in normal and tumor tissues of the oral cavity. We also analyzed K76 expression by immunohistochemistry in normal, oral precancerous lesion (OPL), oral squamous cell carcinoma (OSCC) and in hamster model of oral carcinogenesis. Further, functional implication of KRT76 loss was confirmed using KRT76-knockout (KO) mice. Results We observed a strong association of reduced K76 expression with increased risk of OPL and OSCC development. The buccal epithelium of DMBA treated hamsters showed a similar trend. Oral cavity of KRT76-KO mice showed preneoplastic changes in the gingivobuccal epithelium while no pathological changes were observed in KRT76 negative tissues such as tongue. Conclusion The present study demonstrates loss of KRT76 in oral carcinogenesis. The KRT76-KO mice data underlines the potential of KRT76 being an early event although this loss is not sufficient to drive the development of oral cancers. Thus, future studies to investigate the contributing role of KRT76 in light of other tumor driving events are warranted. PMID:23936238

  18. The permeability of a keratinizing squamous epithelium in culture.

    PubMed

    Squier, C A; Fejerskov, O; Jepsen, A

    1978-05-01

    Horseradish peroxidase or lanthanum was applied to the surface of keratinized oral epithelium growing in tissue culture and the extent of penetration of these substances examined with the electron microscope. Both tracer substances penetrated between the superficial keratinized squames of the tissue, the lanthanum reaching the basal cell layer and the peroxidase diffusing to within 3--8 cells of the basal layer. The permeability of the keratinized layer in this epithelium is in contrast to the situation in vivo where an intercellular barrier is found in the superficial layer. This difference might be related to the absence of membrane-coating granules from the tissue maintained in culture.

  19. Confocal fluorescence microendoscopy of bronchial epithelium

    NASA Astrophysics Data System (ADS)

    Lane, Pierre M.; Lam, Stephen; McWilliams, Annette; Leriche, Jean C.; Anderson, Marshall W.; Macaulay, Calum E.

    2009-03-01

    Confocal microendoscopy permits the acquisition of high-resolution real-time confocal images of bronchial mucosa via the instrument channel of an endoscope. We report here on the construction and validation of a confocal fluorescence microendoscope and its use to acquire images of bronchial epithelium in vivo. Our objective is to develop an imaging method that can distinguish preneoplastic lesions from normal epithelium to enable us to study the natural history of these lesions and the efficacy of chemopreventive agents without biopsy removal of the lesion that can introduce a spontaneous regression bias. The instrument employs a laser-scanning engine and bronchoscope-compatible confocal probe consisting of a fiber-optic image guide and a graded-index objective lens. We assessed the potential of topical application of physiological pH cresyl violet (CV) as a fluorescence contrast-enhancing agent for the visualization of tissue morphology. Images acquired ex vivo with the confocal microendoscope were first compared with a bench-top confocal fluorescence microscope and conventional histology. Confocal images from five sites topically stained with CV were then acquired in vivo from high-risk smokers and compared to hematoxylin and eosin stained sections of biopsies taken from the same site. Sufficient contrast in the confocal imagery was obtained to identify cells in the bronchial epithelium. However, further improvements in the miniature objective lens are required to provide sufficient axial resolution for accurate classification of preneoplastic lesions.

  20. Oral insulin--a perspective.

    PubMed

    Raj, N K Kavitha; Sharma, Chandra P

    2003-01-01

    Diabetes mellitus is generally controlled quite well with the administration of oral medications or by the use of insulin injections. The current practice is the use of one or more doses, intermediate or long acting insulin per day. Oral insulin is a promising yet experimental method providing tight glycemic control for patients with diabetes. A biologically adhesive delivery systems offer important advantage over conventional drug delivery systems. The engineered polymer microspheres made of erodable polymer display strong adhesive interactions with gastrointestinal mucus and cellular lining can traverse both the mucosal epithelium and the follicle associated epithelium covering the lymphoid tissue of Peyer's patches. Alginate, a natural polymer recovered from seaweed is being developed as a nanoparticle for the delivery of insulin without being destroyed in the stomach. Alginate is in fact finding application in biotechnology industry as thickening agent, a gelling agent and a colloid stabilizer. Alginate has in addition, several other properties that have enabled it to be used as a matrix for entrapment and for the delivery of a variety of proteins such as insulin and cells. These properties include: a relatively inert aqueous environment within the matrix; a mild room temperature encapsulation process free of organic solvents; a high gel porosity which allows for high diffusion rates of macromolecules; the ability to control this porosity with simple coating procedures and dissolution and biodegradation of the system under normal physiological conditions.

  1. Survivin expression in oral lichen planus: Role in malignant transformation

    PubMed Central

    Suganya, G; Bavle, Radhika M; Paremala, K; Makarla, Soumya; Sudhakar, M; Reshma, V

    2016-01-01

    Context: Oral lichen planus (OLP) is a potentially malignant disease with a prevalence rate of 0.5–2.2%. It is a T-cell-mediated autoimmune disease, in which cytotoxic CD8+ T-cells trigger apoptosis of the basal cells of oral epithelium. The reported progression of OLP to oral squamous cell carcinoma (OSCC) ranges from 0.4% to 6.5%. Apoptosis plays a major role in the maintenance of tissue homeostasis. The evasion of apoptosis in the form of dysregulation of inhibitors of apoptosis proteins (IAPs) may lead to malignant transformation. Survivin belongs to the second gene family of IAPs, which is overexpressed in many tumors such as OSCC and gastric carcinomas, and its expression is widely involved in apoptosis as well as in tumor metastasis. Materials and Methods: Sections were obtained from the paraffin-embedded archival blocks of patients diagnosed histologically as OLP, and cases with normal epithelium were used for comparison whereas cases with OSCC were used as positive control. Results: We analyzed the expression of survivin in OLP and normal epithelium. Survivin expression with moderate intensity was seen in the cells of basal layer with nuclear positivity in cases of OLP, whereas mild to nil expression was seen in normal epithelium with nuclear and cytoplasmic positivity in different layers. Conclusions: Survivin positivity was seen predominantly in the basal cells of OLP suggesting increased longevity of these cells which in turn might acquire dysplastic changes leading to increased risk of malignant transformation of this premalignant condition. Although the conversion rate may be low, the potential exists in the indolent course of the disease. PMID:27601815

  2. Study on discrimination of oral cancer from normal using blood plasma based on fluorescence steady and excited state at excitation wavelength 280 nm

    NASA Astrophysics Data System (ADS)

    Rekha, Pachaiappan; Aruna, Prakasa Rao; Ganesan, Singaravelu

    2016-03-01

    Many research works based on fluorescence spectroscopy have proven its potential in the diagnosis of various diseases using the spectral signatures of the native key fluorophores such as tryptophan, tyrosine, collagen, NADH, FAD and porphyrin. These fluorophores distribution, concentration and their conformation may be changed depending upon the pathological and metabolic conditions of cells and tissues. In this study, we have made an attempt to characterize the blood plasma of normal subject and oral cancer patients by native fluorescence spectroscopy at 280 nm excitation. Further, the fluorescence data were analyzed by employing the multivariate statistical method - linear discriminant analyses (LDA) using leaves one out cross validation method. The results illustrate the potential of fluorescence spectroscopy technique in the diagnosis of oral cancer using blood plasma.

  3. Performance evaluation of on-site oral fluid drug screening devices in normal police procedure in Germany.

    PubMed

    Musshoff, Frank; Hokamp, Eva Große; Bott, Ulrich; Madea, Burkhard

    2014-05-01

    There is a need for quick and reliable methods for rapid screening of drug-influenced drivers on the roadside by police. Because the window of detection in oral fluid is more similar to blood than to urine, this matrix should therefore be appropriate for screening procedures. The performance of the Rapid STAT(®) (Mavand Solution GmbH, Mössingen, Germany), DrugWipe5/5+(®) (Securetec Detektions-Systeme AG, Brunnthal, Germany) and Dräger DrugTest(®) 5000 (Draeger Safety AG & Co. KGaA, Luebeck, Germany) on-site oral fluid devices was evaluated with random oral fluid specimens from car drivers in North Rhine-Westphalia (Germany). Additionally, some drivers were checked using an on-site urine device (DrugScreen(®), NAL von Minden, Regensburg, Germany). During a 11-month period, 1.212 drivers were tested. Both OF and urine on-site tests were compared to serum results. The following sensitivities were obtained by the oral fluid devices: THC 71% (DrugWipe(®)), 87% (Dräger), 91% (RapidSTAT); opiates 95% (Dräger), 100% (DrugWipe(®), RapidSTAT(®)); amphetamine 84% (DrugTest(®) 5000), 90% (RapidSTAT(®)), 100% (DrugTest(®) 5000); methamphetamine 50% (DrugTest(®) 5000), 100% (RapidSTAT(®)); cocaine 76% (DrugTest(®) 5000), 100% (DrugWipe(®), RapidSTAT(®)); methadone 33-63%, and benzodiazepines 0-33% (both with a low number of positives). THC specificity was especially low (29% [DrugWipe(®)] and 47% [DrugTest(®) 5000]) due to low cut-off concentrations. These data were similar to those obtained from the literature (e.g., DRUID project). The urine screening device showed a good sensitivity (THC 93%, opiate 94%, amphetamine 94%, methamphetamine 75% (low number of positives), cocaine 100%) and also an acceptable specificity (39%, 86%, 63%, 77%, 47%, respectively). Although oral fluid may be a useful matrix for on-site testing of drugged drivers, it is evident that oral fluid devices still show a lack of sensitivity (methamphetamine, benzodiazepines) and

  4. Flow cytometric DNA analysis of corneal epithelium.

    PubMed

    Burns, E R; Roberson, M C; Brown, M F; Shock, J P; Pipkin, J L; Hinson, W G; Anson, J F

    1990-03-01

    We have modified an existing technique in order to perform DNA analysis by flow cytometry (FCM) of corneal epithelium from the mouse, rat, chicken, rabbit, and human. This protocol permitted an investigation of human corneal scrapings from several categories: normal, aphakic bullous keratopathy (ABK), keratoconus (KC), Fuch's dystrophy, edema, epithelial dysplasia, and lipid degeneration. No abnormal characteristic cell-kinetic profile was detected when averaged DNA histograms were compared statistically between the normal and either ABK, KC, edema, or Fuch's dystrophy groups. Abnormal DNA histograms were recorded for cell samples that were taken 1) from three individuals who had epithelial dysplasia and 2) from one individual diagnosed with lipid degeneration. The former condition was characterized by histograms that had a subpopulation of cells with an aneuploid amount of DNA or had higher than normal percentages of cells in the S and G2 + M phases of the cell cycle. Corneal cells from the patient who had lipid degeneration had an abnormally high percentage of cells in the G2 + M phases of the cell cycle. The availability of accurate DNA flow cytometric analysis of corneal epithelium allows further studies on this issue from both experimental and clinical situations.

  5. Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier

    PubMed Central

    Wijnholds, Jan; de Lange, Elizabeth C.M.; Scheffer, George L.; van den Berg, Dirk-Jan; Mol, Carla A.A.M.; van der Valk, Martin; Schinkel, Alfred H.; Scheper, Rik J.; Breimer, Douwe D.; Borst, Piet

    2000-01-01

    Multidrug resistance protein 1 (MRP1) is a transporter protein that helps to protect normal cells and tumor cells against the influx of certain xenobiotics. We previously showed that Mrp1 protects against cytotoxic drugs at the testis-blood barrier, the oral epithelium, and the kidney urinary collecting duct tubules. Here, we generated Mrp1/Mdr1a/Mdr1b triple-knockout (TKO) mice, and used them together with Mdr1a/Mdr1b double-knockout (DKO) mice to study the contribution of Mrp1 to the tissue distribution and pharmacokinetics of etoposide. We observed increased toxicity in the TKO mice, which accumulated etoposide in brown adipose tissue, colon, salivary gland, heart, and the female urogenital system. Immunohistochemical staining revealed the presence of Mrp1 in the oviduct, uterus, salivary gland, and choroid plexus (CP) epithelium. To explore the transport function of Mrp1 in the CP epithelium, we used TKO and DKO mice cannulated for cerebrospinal fluid (CSF). We show here that the lack of Mrp1 protein causes etoposide levels to increase about 10-fold in the CSF after intravenous administration of the drug. Our results indicate that Mrp1 helps to limit tissue distribution of certain drugs and contributes to the blood-CSF drug-permeability barrier. PMID:10675353

  6. Salivary trefoil factor 3 enhances migration of oral keratinocytes.

    PubMed

    Storesund, Trond; Hayashi, Katsuhiko; Kolltveit, Kristin M; Bryne, Magne; Schenck, Karl

    2008-04-01

    Trefoil factor 3 (TFF3) is a member of the mammalian TFF family. Trefoil factors are secreted onto mucosal surfaces of the entire body and exert different effects according to tissue location. Trefoil factors may enhance mucosal healing by modulating motogenic activity, inhibiting apoptosis, and promoting angiogenesis. Trefoil factor 3 is secreted from the submandibular gland and is present in whole saliva. The aim of this study was to assess the migratory and proliferative effects of TFF3 on primary oral human keratinocytes and oral cancer cell lines. The addition of TFF3 increased the migration of both normal oral keratinocytes and the cancer cell line D12, as evaluated by a two-dimensional scratch assay. By contrast, no increase in proliferation or energy metabolism was observed after stimulation with TFF3. Trefoil factor 3-enhanced migration was found to be driven partly by the extracellular signal-related kinase (Erk1/2) pathway, as shown by addition of the mitogen-activated protein kinase (MAPK) inhibitor PD 98059. Previous functional studies on trefoil peptides have all been based on cells from monolayered epithelium like the intestinal mucosa; this is the first report to show that normal and cancerous keratinocytes from stratified epithelium respond to TFF stimuli. Taken together, salivary TFF3 is likely to contribute to oral wound healing. PMID:18353006

  7. Salivary trefoil factor 3 enhances migration of oral keratinocytes.

    PubMed

    Storesund, Trond; Hayashi, Katsuhiko; Kolltveit, Kristin M; Bryne, Magne; Schenck, Karl

    2008-04-01

    Trefoil factor 3 (TFF3) is a member of the mammalian TFF family. Trefoil factors are secreted onto mucosal surfaces of the entire body and exert different effects according to tissue location. Trefoil factors may enhance mucosal healing by modulating motogenic activity, inhibiting apoptosis, and promoting angiogenesis. Trefoil factor 3 is secreted from the submandibular gland and is present in whole saliva. The aim of this study was to assess the migratory and proliferative effects of TFF3 on primary oral human keratinocytes and oral cancer cell lines. The addition of TFF3 increased the migration of both normal oral keratinocytes and the cancer cell line D12, as evaluated by a two-dimensional scratch assay. By contrast, no increase in proliferation or energy metabolism was observed after stimulation with TFF3. Trefoil factor 3-enhanced migration was found to be driven partly by the extracellular signal-related kinase (Erk1/2) pathway, as shown by addition of the mitogen-activated protein kinase (MAPK) inhibitor PD 98059. Previous functional studies on trefoil peptides have all been based on cells from monolayered epithelium like the intestinal mucosa; this is the first report to show that normal and cancerous keratinocytes from stratified epithelium respond to TFF stimuli. Taken together, salivary TFF3 is likely to contribute to oral wound healing.

  8. Evaluation of Various Nuclear Cytological Changes in Normal Buccal Mucosa and Peritumoural Area in Patients with Oral Squamous Cell Carcinoma Receiving Concomitant Chemoradiotherapy

    PubMed Central

    Minhas, Sadia; Kashif, Muhammad; Nagi, A. H.

    2016-01-01

    Objectives. To evaluate the role of serial cytological assay in calculating the nuclear response of contralateral normal buccal mucosa and peritumoural area of squamous cell carcinoma of oral cavity in patients receiving fractionated radiotherapy (RT) and chemotherapy. Materials and Methods. This prospective, nonrandomized study was comprised of 76 histologically confirmed cases of oral squamous cell carcinoma on cyclical chemoradiation treatment. Chemoradiosensitivity was evaluated using serial scrape smears taken before and after immediate exposure to CCRT, at 17th day of CCRT (mid of treatment), and at the end of treatment. The nuclear changes, such as multinucleation, micronucleation, karyorrhexis, karyolysis, nuclear budding, prominent nucleoli, and binucleation occurring in both irradiated cancer cells and contralateral normal buccal mucosa, had a statistically significant dose related increase with concomitant chemoradiotherapy (p < 0.05). Conclusion. We recommend regular use of serial cytological assay during CCRT as it may prove to be a valuable tool for assessment of chemoradiosensitivity and persistence of tumour/dysplastic cells after radiotherapy. PMID:27148467

  9. Influence of the mesenchymal cell source on oral epithelial development.

    PubMed

    Kinikoglu, Beste; Rovere, Marie Rose; Haftek, Marek; Hasirci, Vasif; Damour, Odile

    2012-03-01

    The extent of the influence of mesenchymal tissue on epithelial development is still debated, and elucidation of epithelial-mesenchymal interactions should be of relevance for controlling normal as well as pathological growth and development. The aim of the present study was to elucidate the influence of the mesenchymal cell type on oral mucosa epithelial development in vitro, using tissue-engineering principles, by including three different sources for mesenchymal cell type, viz. oral mucosa, skin and cornea, each of them presenting a distinct type of epithelium in situ. We investigated epithelial-mesenchymal interactions, considering both morphological criteria and protein expression (filaggrin, keratin 10, keratin 12, keratin 13 and laminin 5). The results of the histology, immunohistochemistry and transmission electron microscopy of the three types of tissue-engineered constructs composed of mesenchymal cells of different sources (oral, dermal and corneal fibroblasts) and of the same oral epithelial cells showed that the mesenchymal cell source had a significant influence on the thickness and ultrastructure of the epithelium, but not on the differentiation of oral epithelial cells, which might be an intrinsic property of these cells due to their genetic programming. PMID:21548135

  10. Evaluation of myofibroblasts in oral squamous cell carcinoma using H1 calponin: An immunohistochemical study

    PubMed Central

    Ganesan, Kesavan; Nirmal, R Madhavan; Nassar, M Mohamed; Veeravarmal, V; Amsaveni, R; Kumar, Arul

    2015-01-01

    Background: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. The purpose of this study was to evaluate and compare the presence of myofibroblasts in normal mucosa, early invasive carcinoma and different grades of OSCC. Materials and Methods: The study included the archival tissues of 18 OSCC of well, moderate and poorly differentiated grades, three early invasive carcinomas and five normal mucosa. Myofibroblasts were identified by immunohistochemical detection of h1 calponin. Results: The percentage and intensity of h1 calponin were examined and positive immunostaining was observed in the myofibroblasts of all SCCs and early invasive carcinomas; however, these cells did not stain in the normal epithelium specimens. The presence of myofibroblasts was significantly higher in invasive pattern of OSCCs compared to normal mucosa cases (P < 0.070). A significant difference was not observed between the different grades of OSCC (P ≤ 0.812). Conclusion: These findings show the presence of myofibroblasts in OSCC but not in normal mucosa, suggesting that the genetically altered epithelium (carcinomatous epithelium) may have an inductive effect on the adjacent stroma to produce myofibroblasts. Also transdifferentiation of myofibroblasts is induced somewhere in the invasive stage of SCC irrespective of the epithelial cell differentiation. PMID:26097306

  11. Point-of-Care International Normalized Ratio (INR) Monitoring Devices for Patients on Long-term Oral Anticoagulation Therapy

    PubMed Central

    2009-01-01

    Executive Summary Subject of the Evidence-Based Analysis The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care (POC) international normalized ratio (INR) monitoring devices for patients on long-term oral anticoagulation therapy (OAT). Clinical Need: Target Population and Condition Long-term OAT is typically required by patients with mechanical heart valves, chronic atrial fibrillation, venous thromboembolism, myocardial infarction, stroke, and/or peripheral arterial occlusion. It is estimated that approximately 1% of the population receives anticoagulation treatment and, by applying this value to Ontario, there are an estimated 132,000 patients on OAT in the province, a figure that is expected to increase with the aging population. Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range. This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses. Optimal INR scores depend on the underlying indication for treatment and patient level characteristics, but for most patients the therapeutic range is an INR score of between 2.0 and 3.0. The current standard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics (ACCs). Patients also regularly visit a hospital or community-based facility to provide a venous blood samples (venipuncture) that are then sent to a laboratory for INR analysis. Experts, however, have commented that there may be under-utilization of OAT due to patient factors, physician factors, or regional practice variations and that sub-optimal patient management may also occur. There is currently no population-based Ontario data to permit the assessment of patient care, but recent systematic reviews have estimated that less that 50% of patients receive OAT on a

  12. Aerobic bacterial oral flora of garter snakes: development of normal flora and pathogenic potential for snakes and humans.

    PubMed Central

    Goldstein, E J; Agyare, E O; Vagvolgyi, A E; Halpern, M

    1981-01-01

    Garter snakes that are used for scientific laboratory studies or kept as exotic pets often become ill and die early in captivity. They may also act as reservoirs of potential human pathogens or transmit infection to man. A total of 126 strains of aerobic and facultative bacteria, most potential human and snake pathogens, were isolated from 82 garter snake oropharyngeal cultures. Coagulase-negative Staphylococcus species were the most common species isolated. Acinetobacter calcoaceticus var. anitratus, Hafnia alvei, Arizona hinshawii, Salmonella species, Shigella species, Klebsiella oxytoca, and Pseudomonas aeruginosa were among the potential pathogens isolated. The spectrum of bacteria with potential for causing oral and pulmonary infections in garter snakes is greater than has been previously appreciated. Garter snakes should also be considered reservoirs of human pathogens, and appropriate precautions should be taken by laboratory personnel and pet owners. PMID:7240404

  13. Defective Barrier Function in Neosquamous Epithelium

    PubMed Central

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

    2013-01-01

    BACKGROUND 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. METHODS 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 (RT) 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 (TJ) of NSE and USE was determined using qRT-PCR. Differential expression of claudin 4 between NSE and USE was assayed by immunoblots. RESULTS USE was histologically normal while NSE showed dilated intercellular spaces and marked eosinophilia. NSE was also more permeable than USE and healthy controls, having lower mean RT and higher fluorescein fluxes. Abnormally low RT 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. CONCLUSIONS NSE commonly exhibits defective barrier function. Since 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. PMID:23318477

  14. [Normalization of hypercholesterolemia in a female stroke patient after switching from enteral tube feeding to oral feeding].

    PubMed

    Takahashi, R; Kanemaru, A; Yamanaka, T; Sakurai, Y; Mochizuki, N; Matsukura, T; Fujitomi, A; Ashikawa, S

    1996-02-01

    A 70-year-old female was admitted to a general hospital in a rural area due to left putamenal cerebral hemorrhage in December 1994. She had right hemiplegia and was totally aphasic. In May 1995, she was moved to Tokyo where her son lives, and she was admitted to Tokyo Metropolitan Geriatric Hospital in order to prepare a home care system. her family's support (serving her favorite dishes) allowed enteral tube feeding to be halted. After one month she could absorb enough energy to maintain her serum albumin level. The total calories ingested orally was comparable to that of enteral feeding but the fat composition was 62% of that of enteral feeding (fat was 19.6% and 31.7% of the total calories in the two diets, respectively). Her cholesterol level decreased from 286 mg/dl to 197 mg/dl. Nutrient-balanced tube feeding is useful, but may disturb lipid metabolism in patients used to having vegetable-rich diets. PMID:8656578

  15. Acute D-psicose administration decreases the glycemic responses to an oral maltodextrin tolerance test in normal adults.

    PubMed

    Iida, Tetsuo; Kishimoto, Yuka; Yoshikawa, Yuko; Hayashi, Noriko; Okuma, Kazuhiro; Tohi, Mikiko; Yagi, Kanako; Matsuo, Tatsuhiro; Izumori, Ken

    2008-12-01

    An examination was conducted to verify D-psicose suppressed the elevation of blood glucose and insulin concentration in a dose-dependent manner under the concurrent administration of maltodextrin and D-psicose to healthy humans. Twenty subjects aged 20-39 y, 11 males and 9 females were recruited. A load test of oral maltodextrin was conducted as a randomized single blind study. The subjects took one of five test beverages (7.5 g D-psicose alone, 75 g maltodextrin alone, 75 g maltodextrin +2.5, 5 or 7.5 g D-psicose). Blood was collected before an intake and at 30, 60, 90 and 120 min after an intake. Intervals of administration were at least 1 wk. The load test with 75 g maltodextrin showed significant suppressions of the elevation of blood glucose and insulin concentration under the doses of 5 g or more D-psicose with dose dependency. An independent administration of 7.5 g D-psicose had no influence on blood glucose or insulin concentration. D-Psicose is considered efficacious in the suppression of the elevation of blood glucose concentration after eating in humans.

  16. Intramuscular testosterone enanthate plus very low dosage oral levonorgestrel suppresses spermatogenesis without causing weight gain in normal young men: a randomized clinical trial.

    PubMed

    Anawalt, Bradley D; Amory, John K; Herbst, Karen L; Coviello, Andrea D; Page, Stephanie T; Bremner, William J; Matsumoto, Alvin M

    2005-01-01

    The development of a safe, well-tolerated, effective, and reversible male hormonal contraceptive would be a major clinical advance for couples planning their family size and for control of population growth. High-dosage parenteral testosterone (T) esters alone or in combination with a progestogen (eg, depot medroxyprogesterone) have been shown to confer effective and reversible male contraception in clinical trials, but these regimens are associated with weight gain and suppression of serum high-density lipoprotein cholesterol (HDL) levels. We have previously demonstrated that intramuscular T enanthate 100 mg weekly plus oral levonorgestrel (LNG) 125, 250, or 500 microg daily suppresses spermatogenesis to levels associated with effective contraception, but there is a LNG-dosage-dependent effect of weight gain and HDL suppression. We hypothesized that intramuscular T enanthate 100 mg weekly plus a very low dosage of oral LNG would effectively suppress spermatogenesis in normal men without inducing weight gain or HDL suppression. We conducted a randomized trial comparing 6 months of intramuscular T enanthate (100 mg weekly) plus 31.25 microg of oral LNG daily (T+LNG 31; n = 20) or 62.5 microg of oral LNG daily (T+LNG 62; n = 21). The 2 regimens were equally effective in suppressing spermatogenesis to azoospermia, fewer than 1 million sperm/mL and fewer than 3 million sperm/mL (T+LNG 31 [60%, 85%, and 90%] vs T+LNG 62 [62%, 91%, and 95%] for azoospermia, fewer than 1 million and fewer than 3 million, respectively; P = NS). The T+LNG 31 group did not gain weight (0.25 +/- 1.08 kg; P = NS compared with baseline), but the T+LNG 62 group gained 2.5 +/- 0.77 kg (P < .05 compared with baseline). Serum HDL cholesterol levels declined significantly in both groups (percentage decline month 6 of treatment vs baseline: 12.0% +/- 2.6% and 15.1% +/- 3.0%; P < .05 for T+LNG 31 and 62 respectively). Serum low-density lipoprotein cholesterol levels also declined in both groups

  17. [Generation of a substitute for human oral mucosa and verification of its viability by tissue-engineering].

    PubMed

    Marañés Gálvez, C; Liceras Liceras, E; Alaminos, M; Fernández Valadés, R; Ruiz Montes, A M; Garzón, I; Sánchez-Quevedo, M C; Campos, A

    2011-01-01

    Reconstruction of large oral mucosa defects is often challenging, since the shortage of healthy oral mucosa to replace the excised tissues. This way, tissue ingineering techniques may provide a source of autologous tissues available for transplant in these patients. In this work, we have developed a new model for artificial oral mucosa generated by tissue engineering using a fibrin-agarosa scaffold. For that purpose, we have generated primary cultures of human oral mucosa fibroblasts and keratinocytes from small biopsies of normal mucosa oral using enzymatic treatments. Then, we have determined the viability of cultured cells by electron probe quantitative X-ray microanalysis, and we have demonstrated that most of the cells in the primary cultures were alive and hd high K/Na ratios. Once cell viability was determined, we used cultured fibroblasts and keratinocytes to develop an artificial oral mucosa construct by using a fibrin-agarosa extracellular matrix and a sequential culture technique using porous culture inserts. Histological analysis of the artificial tissues showed high similarities with normal oral mucosa controls. The epithelium of the oral substitutes had several layers, with desmosomes and apical microvilli and microplicae. Both the controls and de oral mucosa substitutes showed high suprabasal expression of cytokeratin 13 and low expression of cytokeratin 10. All these results suggest that our model of oral mucosa using fibrin-agarose scaffolds show several similarities with native human oral mucosa.

  18. Regular black tea habit could reduce tobacco associated ROS generation and DNA damage in oral mucosa of normal population.

    PubMed

    Pal, Debolina; Sur, Subhayan; Mandal, Shyamsundar; Das, Sukta; Panda, Chinmay Kumar

    2012-09-01

    Tobacco and tea habit are very common in world wide. In the present study, an attempt was made to evaluate the effect of regular drinking of black tea on reactive oxygen species (ROS) generation and DNA damage in buccal cells of normal subjects with or without tobacco habit. Expression of ROS associated proteins IκB, NF-κB as well as DNA repair associated proteins p53, MLH1 were also analyzed. Exfoliated buccal cells were collected from 308 healthy individuals and classified according to age, tobacco and tea habits. In all age groups, comparatively high ROS level and significantly high DNA damage frequency were seen in individuals with tobacco habit than the subjects without tea and tobacco habits. Tea habit effectively lowered ROS level and restrict DNA damage in tobacco users irrespective of ages. The DNA damage seen in the subjects was not associated with apoptosis. Moreover, tea habit effectively lowered the expression of IκB, NF-κB, p53 and MLH1 in tobacco users in all age groups. It seems that regular black tea habit could have anti-genotoxic effect as revealed by reduced tobacco associated ROS generation and DNA damage in buccal cells.

  19. Regionalisation of early head ectoderm is regulated by endoderm and prepatterns the orofacial epithelium.

    PubMed

    Haworth, Kim E; Healy, Christopher; Morgan, Pamela; Sharpe, Paul T

    2004-10-01

    The oral epithelium becomes regionalised proximodistally early in development, and this is reflected by the spatial expression of signalling molecules such as Fgf8 and Bmp4. This regionalisation is responsible for regulating the spatial expression of genes in the underlying mesenchyme. These genes are required for the spatial patterning of bone, cartilage orofacial development and, in mammals, teeth. The mechanism and timing of this important regionalisation during head epithelium development are not known. Using lipophilic dyes to fate map the oral epithelium in chick embryos, we show that the cells that will occupy the epithelium of the distal and the proximal mandible primordium already occupy different spatial locations in the developing head ectoderm prior to the formation of the first pharyngeal arch and neural crest migration. Moreover, the ectoderm cells fated to become proximal oral epithelium express Fgf8 and this expression requires the presence of endoderm. Thus, the first fundamental patterning process in jaw morphogenesis is controlled by the early separation of specific areas of ectoderm that are regulated by ectoderm-endoderm interactions, and does not involve neural crest cells.

  20. 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. PMID:16475003

  1. Thrush (Oral Candidiasis) in Children

    MedlinePlus

    ... A A A In oral candidiasis, normal mouth yeast overgrows, causing white, slightly elevated lesions. Overview Thrush ( ... candidiasis), also known as oral moniliasis, is a yeast infection of the mouth or throat (the oral ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. A review of the clinical efficacy of the Oral-B oscillating/rotating power toothbrush and the Philips Sonicare toothbrush in normal subject populations.

    PubMed

    Warren, P R; Cugini, M A; Chater, B V; Strate, J

    2004-12-01

    Plaque removal by a toothbrush results from a physical scrubbing of bristles on the tooth surface that removes adherent plaque bacteria. Because of the frequency of brush head motion, some power toothbrushes generally remove plaque more effectively than a manual brush. One power toothbrush, Philips Sonicare, claims also to remove plaque as a result of dynamic fluid activity. This effect has been shown in laboratory studies but clinical evidence is currently lacking. This review evaluated the data from well-controlled clinical studies carried out in normal subjects from a general population comparing the Sonicare toothbrushes with the Oral-B oscillating/rotating power toothbrush technology. It focuses on plaque removal from approximal surfaces where it is difficult for toothbrush bristles to reach, as it is here that any dynamic fluid effect should be most apparent. Results from the review found no evidence to support a greater efficacy for the Sonicare toothbrushes either generally or at approximal surfaces. Data revealed that the oscillating/rotating toothbrush was more effective than the Sonicare toothbrushes with respect to plaque removal. It is possible that factors associated with the clinical situation such as damping resulting from bristle contact with the tooth surface and the high viscosity of saliva and dentifrice may counteract dynamic fluid activity in vivo. This review indicates that dynamic fluid activity beyond the reach of bristles as demonstrated in the laboratory is yet unproven in the clinical situation.

  4. Effect of the tongue rotation exercise training on the oral functions in normal adults - Part 1 investigation of tongue pressure and labial closure strength.

    PubMed

    Arakawa, I; Koide, K; Takahashi, M; Mizuhashi, F

    2015-06-01

    The aim of this study was to investigate the effect of the tongue rotation exercise training on the oral functions using the measurement of maximum tongue pressure (MTP) and labial closure strength (LCS) in normal adults. In experiment 1, the differences in MTP and LCS at the measurement point for both groups with and without tongue rotation exercise training were examined. We instructed subjects to perform the tongue rotation exercise for 2 months. We measured MTP and LCS at the point before training and at the points of 1 and 2 months after the beginning of training. In experiment 2, the changes of MTP and LCS based on the sex differences and the measurement points in training were examined. We instructed subjects to perform the tongue rotation exercise for 3 months, and measured MTP and LCS at the point before training and at the points of 2 weeks and 1, 2 and 3 months after the beginning of training. The results of experiment 1 showed MTP and LCS increased with the progress of continuous training. The results of experiment 2 showed MTP and LCS were always higher in men than in women and increased significantly at 2 weeks of training in both sexes (P < 0.01). These results might be suggested that the tongue rotation exercise training was effective for the recovery of the activity of the stomatognathic system.

  5. Oral Health in Pregnancy.

    PubMed

    Hartnett, Erin; Haber, Judith; Krainovich-Miller, Barbara; Bella, Abigail; Vasilyeva, Anna; Lange Kessler, Julia

    2016-01-01

    Oral health is crucial to overall health. Because of normal physiologic changes, pregnancy is a time of particular vulnerability in terms of oral health. Pregnant women and their providers need more knowledge about the many changes that occur in the oral cavity during pregnancy. In this article we describe the importance of the recognition, prevention, and treatment of oral health problems in pregnant women. We offer educational strategies that integrate interprofessional oral health competencies. PMID:27281467

  6. [Epithelium and anal glands in rectal pouches and fistula. Histologic studies of swine with congenital anal atresia].

    PubMed

    Lambrecht, W; Kluth, D; Lierse, W

    1989-02-01

    The epithelial coating of the rectal pouch and fistula was studied morphologically in 33 newborn piglets with high and low forms of anal atresia and was found to be similar to the epithelial coating of the anal canal in normal piglets: the typical epithelium of the rectum changed its character into transitional epithelium at the region of the internal sphincter which surrounded the fistulae in all animals. In the caudal part of the fistula the transitional epithelium was followed by squamous epithelium. Only in male piglets with deformities and recto-urethral fistulae no squamous epithelium was found. In these cases transitional epithelium covered all parts of the fistula and the region of the internal sphincter. Anal glands were found in all animals, with or without anorectal malformations. They always invaded the internal sphincter. According to our morphological studies the fistula in anorectal malformations represents an ectopic anal canal.

  7. Quantitative dimensions of histopathological attributes and status of GSTM1-GSTT1 in oral submucous fibrosis.

    PubMed

    Pal, Mousumi; Chaudhuri, Susri Ray; Jadav, Abhijeet; Banerjee, Swapna; Paul, Ranjan Rashmi; Dutta, Pranab Kumar; Ghosh, Bhaskar; Chatterjee, Jyotirmoy; Chaudhuri, Keya

    2008-12-01

    Oral submucous fibrosis (OSF) is a precancerous condition of the oral cavity and oropharynx and a significant number of such cases transform into oral squamous cell carcinoma (OSCC). Presently, diagnosis of OSF is done mainly through qualitative histopathological techniques and in the level of diagnostic molecular biology no specific genetic marker is evident. Keeping these facts in mind this study evaluates histopathological changes in the epithelium and subepithelial connective tissue of OSF through quantitative digital image analysis in respect to specific candidate features and analyses null mutations in the GSTM1 and GSTT1 by PCR amplification. The analysis revealed that there are subtle quantitative differences in the histological images of OSF compared to NOM. The thickness of the epithelium and cell population in its different zones, radius of curvature of rete-ridges and connective tissue papillae were decreased but length of rete-ridges and connective tissue papillae, fibrocity and the number of cellular components (predominantly inflammatory cells) in the subepithelial connective tissue were increased in OSF. The PCR study revealed that there is no significant difference in the allelic variants in GSTM1 between OSF and normal, while GSTT1 null gene showed significantly higher frequencies in this precancerous condition. This study establishes a distinct quantitative difference between normal oral mucosa (NOM) and OSF in respect to their histological features and GST null gene frequencies. PMID:18573513

  8. Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune/epithelial cell interaction

    SciTech Connect

    Pellegrina, Chiara Dalla; Perbellini, Omar; Scupoli, Maria Teresa; Tomelleri, Carlo; Zanetti, Chiara; Zoccatelli, Gianni; Fusi, Marina; Peruffo, Angelo; Rizzi, Corrado; Chignola, Roberto

    2009-06-01

    Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed, among many others, by human gastrointestinal epithelial and immune cells. WGA is a toxic compound and an anti-nutritional factor, but recent works have shown that it may have potential as an anti-tumor drug and as a carrier for oral drugs. To quantitate the toxicity threshold for WGA on normal epithelial cells we previously investigated the effects of the lectin on differentiated Caco2 cells, and showed that in the micromolar range of concentrations WGA could alter the integrity of the epithelium layer and increase its permeability to both mannitol and dextran. WGA was shown to be uptaken by Caco2 cells and only {approx} 0.1% molecules were observed to cross the epithelium layer by transcytosis. Here we show that at nanomolar concentrations WGA is unexpectedly bioactive on immune cells. The supernatants of WGA-stimulated peripheral blood mononuclear cells (PBMC) can alter the integrity of the epithelium layer when administered to the basolateral side of differentiated Caco2 cells and the effects can be partially inhibited by monoclonal antibodies against IL1, IL6 and IL8. At nanomolar concentrations WGA stimulates the synthesis of pro-inflammatory cytokines and thus the biological activity of WGA should be reconsidered by taking into account the effects of WGA on the immune system at the gastrointestinal interface. These results shed new light onto the molecular mechanisms underlying the onset of gastrointestinal disorders observed in vivo upon dietary intake of wheat-based foods.

  9. Validation of the international normalized ratio (INR) in a new point-of-care system designed for home monitoring of oral anticoagulation therapy.

    PubMed

    Plesch, W; van den Besselaar, A M H P

    2009-02-01

    The new CoaguChek XS system is designed for use in patient self testing with a measuring range from 0.8 INR up to 8.0 INR, which has been calibrated against the mean INR of rTF/95 and ERM-AD149. This study was performed to confirm the correct INR results received from two routinely manufactured lots of test strips when compared with the international reference preparations (IRP) rTF/95 and ERM-AD149. At one study site capillary and noncitrated venous whole blood samples from 20 normal donors and 62 anticoagulated patients were applied to two test strip lots of the new system in duplicate. Additionally blood was collected in citrate tubes, processed to plasma, and PT results were obtained using rTF/95 and ERM-AD149 by the manual tilt tube method. Method comparisons of the INR results of the CoaguChek XS system vs. the mean INR of the IRP demonstrated a mean relative bias of -0.02% to -0.4%, mean absolute relative deviations of 6.4-9.6%, and accuracy observing >95% of CoaguChek XS INR within limits of +/-14% to +/-21.5% to the mean INR of the IRP. The results of the study confirm the successful calibration of two lots of the new CoaguChek XS system, demonstrate the validity of the calibration concept and prove the accuracy of the new system in comparison with the IRP. Clinical decisions in oral anticoagulation therapy may be reliably made upon the INR results of the new system.

  10. Concurrence of replicative senescence and elevated expression of p16(INK4A) with subculture-induced but not calcium-induced differentiation in normal human oral keratinocytes.

    PubMed

    Lee, G; Park, B S; Han, S E; Oh, J E; You, Y O; Baek, J H; Kim, G S; Min, B M

    2000-10-01

    Primary normal human oral keratinocytes (NHOKs) undergo differentiation in the presence of calcium concentrations higher than 0.15 mM in vitro, which is useful in investigating the mechanisms involved in the differentiation of epithelial cells. Serial subculture of NHOKs to the postmitotic stage also induces terminal differentiation. However, the detailed mechanisms of both differentiation processes remain substantially unknown. To investigate the molecular differences in these processes, NHOKs were induced to differentiate by exposure to 1.2 mM of calcium and by serial subculture to the postmitotic stage. To study whether the cells were induced to differentiate and to undergo replicative senescence, the amount of cellular involucrin and the expression of senescence-associated beta-galactosidase (SA-beta-gal) were measured respectively. The expression of replicative senescence-associated genes and the activity of telomerase from the differentiated cells were also determined. Both calcium treatment and serial subculture to the postmitotic stage notably elevated the cellular involucrin. The percentage of SA-beta-gal-positive cells was significantly elevated by the continued subculture, but such changes were not observed in keratinocytes exposed to calcium. The concentration of cellular p16(INK4A) protein was progressively increased by the continued subculture but was not changed by calcium treatment. On the other hand, the concentrations of cellular p53 were similar in both differentiation processes. However, telomerase activity was lost in NHOKs that had undergone differentiation by both calcium treatment and serial subculture. The results indicate that calcium-induced differentiation of NHOKs has similar characteristics to their serial subculture-induced differentiation, but that the differentiation processes are not identical, because calcium-induced differentiation does not concur with either replicative senescence or the gradually increased concentration of p16

  11. [Hormone-mediated reactions in the endosalpinx epithelium].

    PubMed

    Glukhovets, B I; Ukhov, Iu I; Lebedev, S S; Plastun, G A; Bulaeva, V P

    1983-07-01

    The epithelium of normal uterine tubes resected in 38 young women of the child-bearing age during the periods of the maximal physiological fluctuations of the ovarian steroid hormones levels has been studied. The correlative dependence between the morphometrical data and the results of quanitative biochemical analysis of the estrogen excretion has been investigated. The morphometric method reliably reflects the hormone-dependent variabilities of the oviduct epithelium and makes it possible to perform an objective morphological evaluation of the ovarian functional activity. The height and specific density of cells in the epithelial layer, portion of the aciliary cells and nuclear volume of the ciliary cells are the most important for diagnosis as compared to the excretory level of the estrogenic hormones. PMID:6625907

  12. Airway responsiveness: role of inflammation, epithelium damage and smooth muscle tension.

    PubMed

    Gourgoulianis, K I; Domali, A; Molyvdas, P A

    1999-01-01

    The purpose of this study was the effect of epithelium damage on mechanical responses of airway smooth muscles under different resting tension. We performed acetylcholine (ACh) (10(-5) M)-induced contraction on tracheal strips from 30 rabbits in five groups (0.5, 1, 1.5, 2 and 2.5 g) before and after epithelium removal. At low resting tension (0.5-1.5 g), the epithelium removal decreased the ACh-induced contractions. At 2 g resting tension, the epithelium removal increased the ACh-induced contractions of airways with intact epithelium about 20%. At 2.5 g resting tension, the elevation of contraction is about 25% (P<0.01). Consequently, after epithelium loss, the resting tension determines the airway smooth muscles responsiveness. In asthma, mediators such as ACh act on already contracted inflammatory airways, which results in additional increase of contraction. In contrast, low resting tension, a condition that simulates normal tidal breathing, protects from bronchoconstriction even when the epithelium is damaged. PMID:10704081

  13. 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.

  14. Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

    PubMed Central

    Chen, Jichao; Krasnow, Mark A.

    2012-01-01

    Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered). Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1) in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program. PMID:23285215

  15. Thymus epithelium induces tissue-specific tolerance

    PubMed Central

    1993-01-01

    Most current models of T cell development include a positive selection step in the thymus that occurs when T cells interact with thymic epithelium and a negative selection step after encounters with bone marrow-derived cells. We show here that developing T cells are tolerized when they recognize antigens expressed by thymic epithelium, that the tolerance is tissue specific, and that it can occur by deletion of the reactive T cells. PMID:8459209

  16. Teaching normal birth, normally.

    PubMed

    Hotelling, Barbara A

    2009-01-01

    Teaching normal-birth Lamaze classes normally involves considering the qualities that make birth normal and structuring classes to embrace those qualities. In this column, teaching strategies are suggested for classes that unfold naturally, free from unnecessary interventions. PMID:19436595

  17. Reflectance confocal microscopy of oral epithelial tissue using an electrically tunable lens

    NASA Astrophysics Data System (ADS)

    Jabbour, Joey M.; Malik, Bilal H.; Cuenca, Rodrigo; Cheng, Shuna; Jo, Javier A.; Cheng, Yi-Shing L.; Wright, John M.; Maitland, Kristen C.

    2014-02-01

    We present the use of a commercially available electrically tunable lens to achieve axial scanning in a reflectance confocal microscope. Over a 255 μm axial scan range, the lateral and axial resolutions varied from 1-2 μm and 4-14 μm, respectively, dependent on the variable focal length of the tunable lens. Confocal imaging was performed on normal human biopsies from the oral cavity ex vivo. Sub-cellular morphologic features were seen throughout the depth of the epithelium while axially scanning using the focus tunable lens.

  18. Optimizing modulation frequency for structured illumination in a fiber-optic microendoscope to image nuclear morphometry in columnar epithelium.

    PubMed

    Keahey, P A; Tkaczyk, T S; Schmeler, K M; Richards-Kortum, R R

    2015-03-01

    Fiber-optic microendoscopes have shown promise to image the changes in nuclear morphometry that accompany the development of precancerous lesions in tissue with squamous epithelium such as in the oral mucosa and cervix. However, fiber-optic microendoscopy image contrast is limited by out-of-focus light generated by scattering within tissue. The scattering coefficient of tissues with columnar epithelium can be greater than that of squamous epithelium resulting in decreased image quality. To address this challenge, we present a small and portable microendoscope system capable of performing optical sectioning using structured illumination (SI) in real-time. Several optical phantoms were developed and used to quantify the sectioning capabilities of the system. Columnar epithelium from cervical tissue specimens was then imaged ex vivo, and we demonstrate that the addition of SI achieves higher image contrast, enabling visualization of nuclear morphology.

  19. Nonlinear optical microscopy and microspectroscopy of oral precancers and early cancer

    NASA Astrophysics Data System (ADS)

    Vargas, Gracie; Edward, Kert

    2013-02-01

    Multiphoton autofluorescence microscopy (MPAM) offers the ability to assess morphometry similar to that of pathologic evaluation as well as biochemical information from endogenous fluorophores which are altered with neoplastic transformation. In this study the spectroscopic properties of normal and neoplastic oral epithelium were evaluated toward the goal of identifying image/spectroscopic based indicators of neoplastic transformation using nonlinear optical microscopy. Results indicated measureable differences between normal, dysplasia, and SCC that could be helpful in delineating between the three conditions. In particular, a blue shift in autofluorescence emission was experienced for dysplasia relative to normal. However, in the case of SCC the epithelial emission experienced a significant red shift relative to both dysplasia and normal and displayed in an additional red peak that was not present in either normal or dysplastic mucosa. Results were consistent with published results for SCC in the single-photon literature. The study demonstrates that multiphoton autofluorescence spectroscopy may reveal features of oral mucosa that can be useful for differentiating normal and neoplastic mucosa. When combined with morphometry provided by MPAM, a potentially powerful technique for imaging of the oral cavity could be developed which provides both morphometric and spectroscopic information.

  20. Cytological response of palatal epithelium to TiN-coated CoCr alloy denture.

    PubMed

    Lukomska-Szymańska, Monika; Brzeziński, Piotr M; Zieliński, Andrzej; Sokołowski, Jerzy

    2012-04-24

    The aim of this study was to assess the impact of titanium nitride coatings on CoCr alloy metal parts in framework dentures on human palatal epithelium cytology compared to framework dentures made with the same alloy but without titanium nitride coating, and to acrylic dentures. Every prosthetic restoration introduced into the oral cavity and remaining in direct contact with the palate exhibits a varied and harmful effect on the state of the palatal epithelium by disturbing its keratinization. CoCr alloy dentures produce a significantly greater perturbation of keratinization compared to acrylic dentures. There is no evidence showing that a titanium nitride coating of the CoCr alloy plays a protective role in the environment of the oral cavity.

  1. 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

  2. Expression of keratins in mouse vaginal epithelium.

    PubMed

    Gimenez-Conti, I B; Lynch, M; Roop, D; Bhowmik, S; Majeski, P; Conti, C J

    1994-05-01

    In the epithelium of the rodent vagina proliferation and differentiation are tightly regulated by ovarian hormones. Estrogens stimulate proliferation and squamous differentiation, whereas progesterone redirects differentiation to a mucus-secreting epithelium formed by goblet-like cells. In the present study, we used monospecific keratin antibodies to show the expression and distribution of keratins in SENCAR mouse vaginal epithelium in different stages of the estral cycle and in ovariectomized animals. In ovariectomized animals, the vaginal epithelium expressed K6, K8, K13 and K14, but not K1. After estrogen treatment, K1 was expressed. During proestrus and estrus, the keratin pattern was essentially identical to that observed in 17 beta-estradiol-stimulated animals. In contrast, during the progestational stages (metaestrus and diestrus) or after progesterone treatment of ovariectomized mice, the most relevant change was the loss of K1. Together, these results show that K1 expression is induced by estrogens in the vaginal epithelium. In contrast, K6, K8, K13 and K14 are constitutively expressed even when squamous differentiation is not observed.

  3. 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

  4. Fungal infections of the oral cavity.

    PubMed

    Zegarelli, D J

    1993-12-01

    Although several strains of Candida can infect the oral mucosa, the most commonly encountered oral fungal infection is Candida albicans, which may be highly infective because of its greater level of pathogenicity and adherence properties. C. albicans is an oral commensal in as many as 40% to 65% of healthy adult mouths. The papillated dorsal surface of the tongue and palatal mucosa beneath a maxillary denture are favored reservoir sites. Oral candidal infection almost always involves a compromised host. The compromise may be local or systemic. Local factors include decreased salivation and the weaning of dentures. Systemic factors include diabetes mellitus, pernicious anemia, and AIDS. Some have even implicated advanced age and the female gender as being mild predisposing factors. Furthermore, the C. albicans infection itself can depress a host's immune system. A patient with oral candidiasis can present with one or more of the following clinical forms: pseudomembranous, erythematous, hyperplastic, and denture erythematous. Many investigators accept median rhomboid glossitis as a form of chronic oral candidiasis. In some patients with angular cheilitis, genesis of the lesions is secondary to monilial infestation. Because C. albicans is a normal inhabitant in many mouths, diagnostic confirmation of infection often rests with successful response (i.e., resolution of lesions) to antifungal medications. This form of diagnostic confirmation can be further enhanced by culturing the offending microbe, preparing a fungal smear, or even incisional biopsy. The microscopic demonstration of fungal hyphae is highly diagnostic of the candidal infection, whether the hyphae are demonstrated on a PAS smear or on a biopsy within surface stratified squamous epithelium. Numerous medications exist for the treatment of oral candidiasis. They include the antibiotic nystatin as well as clotrimazole, ketoconazole, and fluconazole. Nystatin is safe and is used as a topical agent in rinse or

  5. Simultaneous determination of senkyunolide I and senkyunolide H in rat plasma by LC-MS: application to a comparative pharmacokinetic study in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract.

    PubMed

    Zhao, Xu; Ma, Tiancheng; Zhang, Chenning; Shi, Shaohuai; Cui, Sijiao; Bi, Kaishun; Jia, Ying

    2015-09-01

    A selective liquid chromatographic-mass spectrometric method has been developed and validated for simultaneous determination of senkyunolide I (SEI) and senkyunolide H (SEH) from Chuanxiong Rhizoma in rat plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Kromasil C18 column (250 × 4.6 mm, 5 µm), with methanol-water (55:45, v/v) as mobile phase. The linear range was 0.05-25 µg/mL for SEI and 0.01-5.0 µg/mL for SEH, with lower limits of quantitation of 0.05 and 0.01 µg/mL, respectively. Intra- and inter-day precision were within 10.0 and 9.8%, and the accuracies (relative errors) were <9.6 and 5.9%, with the mean extraction recoveries 81.0-86.6 and 80.5-85.0% for the two anayltes, respectively. The validated method was successfully applied to a comparative pharmacokinetic study of SEI and SEH in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract. The results indicated that there were obvious differences between normal and migrainous rats in the pharmacokinetic behavior after oral administration of Chuanxiong Rhizoma extract. The absorption of SEI and SEH were significantly increased in migrainous rats compared with normal rats. PMID:25620053

  6. Simultaneous determination of senkyunolide I and senkyunolide H in rat plasma by LC-MS: application to a comparative pharmacokinetic study in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract.

    PubMed

    Zhao, Xu; Ma, Tiancheng; Zhang, Chenning; Shi, Shaohuai; Cui, Sijiao; Bi, Kaishun; Jia, Ying

    2015-09-01

    A selective liquid chromatographic-mass spectrometric method has been developed and validated for simultaneous determination of senkyunolide I (SEI) and senkyunolide H (SEH) from Chuanxiong Rhizoma in rat plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Kromasil C18 column (250 × 4.6 mm, 5 µm), with methanol-water (55:45, v/v) as mobile phase. The linear range was 0.05-25 µg/mL for SEI and 0.01-5.0 µg/mL for SEH, with lower limits of quantitation of 0.05 and 0.01 µg/mL, respectively. Intra- and inter-day precision were within 10.0 and 9.8%, and the accuracies (relative errors) were <9.6 and 5.9%, with the mean extraction recoveries 81.0-86.6 and 80.5-85.0% for the two anayltes, respectively. The validated method was successfully applied to a comparative pharmacokinetic study of SEI and SEH in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract. The results indicated that there were obvious differences between normal and migrainous rats in the pharmacokinetic behavior after oral administration of Chuanxiong Rhizoma extract. The absorption of SEI and SEH were significantly increased in migrainous rats compared with normal rats.

  7. Comparative tissue distribution profiles of five major bio-active components in normal and blood deficiency rats after oral administration of Danggui Buxue Decoction by UPLC-TQ/MS.

    PubMed

    Shi, Xuqin; Tang, Yuping; Zhu, Huaxu; Li, Weixia; Li, Zhenhao; Li, Wei; Duan, Jin-ao

    2014-01-01

    Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) were frequently combined and used in China as herbal pair called as Danggui Buxue Decoction (DBD) for treatment of blood deficiency syndrome, such as women's ailments. This study is to investigate the tissue distribution profiles of five major bio-active constituents (ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV) in DBD after oral administration of DBD in blood deficiency rats, and to compare the difference between normal and blood deficiency rats. The blood deficiency rats were induced by bleeding from orbit at the dosages of 5.0mLkg(-1) every day, and the experimental period was 12 days. At the finally day of experimental period, both normal and blood deficiency rats were orally administrated with DBD, and then the tissues samples were collected at different time points. Ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV in different tissues were detected simultaneously by UPLC-TQ/MS, and the histograms were drawn. The results showed that the overall trend was CLiver>CKidney>CHeart>CSpleen>CLung, CC-30min>CM-30min>CM-60min>CC-5min>CM-5min>CC-60min>CM-240min>CC-240min. The contents of the detected compounds in liver were more than that in other tissues no matter in normal or blood deficiency rats. Compared to normal rats, partial contents of the compounds in blood deficiency rats' tissues at different time points had significant difference (P<0.05). This study was the first report about tissue distribution investigation in blood deficiency animals which is conducted by bleeding. And the results demonstrated that the five DBD components in normal and blood deficiency rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in blood deficiency animals. PMID:24076576

  8. Effects of the GABA(B) receptor agonist baclofen administered orally on normal food intake and intraperitoneally on fat intake in non-deprived rats.

    PubMed

    Bains, Rasneer S; Ebenezer, Ivor S

    2013-01-01

    It has been previously reported that the GABA(B) receptor agonist baclofen decreases food intake after oral administration and fat intake after intraperitoneal administration. The aim of the study was to investigate the effects of baclofen (1-4 mg/ kg) administered orally (Experiment 1) on food intake in non-deprived rats (n=6) and intraperitoneally (Experiment 2) on fat intake in non-deprived rats (n=8) that were naïve to baclofen (1st set of trials) and in the same group of rats after they were sub-chronically exposed to baclofen (2nd set of trials). The results from Experiment 1 show that baclofen had no effects on food intake during the 1st set of trials, but the 2 and 4 mg/kg doses significantly increased food consumption during the 2nd set of trials. Baclofen produced sedation during the 1st set of trials, but tolerance occurred to this effect and was not apparent during the 2nd set of trials. These observations suggest that the motor effects may have competed with the hyperphagic effects of baclofen during the 1st set of trials. The data from Experiment 2 show that baclofen had no effects on fat intake during either the 1st or 2nd set of trials. The results of the study thus indicate that orally administrated baclofen increases food intake and intraperitoneal administration has no effect on fat intake in non-deprived rats under the conditions used in this study. These findings may have important implications for research on the use of baclofen in studies concerned with ingestive behaviours.

  9. The Epithelial-Mesenchymal Interactions: Insights into Physiological and Pathological Aspects of Oral Tissues

    PubMed Central

    Santosh, Arvind Babu Rajendra; Jones, Thaon Jon

    2014-01-01

    In the human biological system, the individual cells divide and form tissues and organs. These tissues are hetero-cellular. Basically any tissue consists of an epithelium and the connective tissue. The latter contains mainly mesenchymally-derived tissues with a diversified cell population. The cell continues to grow and differentiate in a pre-programmed manner using a messenger system. The epithelium and the mesenchymal portion of each tissue have two different origins and perform specific functions, but there is a well-defined interaction mechanism, which mediates between them. Epithelial mesenchymal interactions (EMIs) are part of this mechanism, which can be regarded as a biological conversation between epithelial and mesenchymal cell populations involved in the cellular differentiation of one or both cell populations. EMIs represent a process that is essential for cell growth, cell differentiation and cell multiplication. EMIs are associated with normal physiological processes in the oral cavity, such as odontogenesis, dentino-enamel junction formation, salivary gland development, palatogenesis, and also pathological processes, such as oral cancer. This paper focuses the role EMIs in odontogenesis, salivary gland development, palatogenesis and oral cancer. PMID:25992230

  10. Inhibition of 4NQO-Induced Oral Carcinogenesis by Dietary Oyster Shell Calcium.

    PubMed

    Chen, Ying; Jiang, Yi; Liao, Liyan; Zhu, Xiaoxin; Tang, Shengan; Yang, Qing; Sun, Lihua; Li, Yujie; Gao, Shuangrong; Xie, Zhongjian

    2016-03-01

    Oyster has gained much attention recently for its anticancer activity but it is unclear whether calcium, the major antitumor ingredient in oyster shell, is responsible for the anticarcinogenic role of the oyster. To address this issue, C57BL/6 mice were fed with the carcinogen 4-nitroquinoline-1-oxide (4NQO, 50 µg/mL) and normal diet or a diet containing oyster powder, oyster calcium, or calcium depleted oyster powder. The tongue tissue specimens isolated from these mice were histologically evaluated for hyperplasia, dysplasia, and papillary lesions, and then analyzed for proliferation and differentiation markers by immunohistochemistry. The results showed that mice on the diet containing oyster calcium significantly reduced rates of tumors in the tongue and proliferation and enhanced differentiation in the oral epithelium compared with the diet containing calcium depleted oyster powder. These results suggest that calcium in oyster plays a critical role in suppressing formation of oral squamous cell carcinoma and proliferation and promoting differentiation of the oral epithelium.

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

    PubMed

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

    2015-07-01

    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.

  12. Role of human papillomavirus and tumor suppressor genes in oral cancer

    PubMed Central

    Manvikar, Vardendra; Kulkarni, Rama; Koneru, Anila; Vanishree, M

    2016-01-01

    The incidence of oral cancer remains high and is associated with many deaths in both Western and Asian countries. Several risk factors for the development of oral cancer are now well known, including smoking, drinking and consumption of smokeless tobacco products. Genetic predisposition to oral cancer has been found in certain cases, but its components are not yet entirely clear. In accordance with the multi-step theory of carcinogenesis, the natural history of oral cancer seems to gradually evolve through transitional precursor lesions from normal epithelium to a full-blown metastatic phenotype. A number of genomic lesions accompany this transformation and a wealth of related results has appeared in recent literature and is being summarized here. Furthermore, several key genes have been implicated, especially well-known tumor suppressors such as the cyclin-dependent kinase inhibitors, TP53 and RB1 and oncogenes such as the cyclin family, epidermal growth factor receptor and RAS. Viral infections, particularly oncogenic human papillomavirus subtypes and Epstein–Barr virus, can have a tumorigenic effect on oral epithelia and their role is discussed, along with potential therapeutic interventions. A brief explanatory theoretical model of oral carcinogenesis is provided and potential avenues for further research are highlighted. PMID:27194871

  13. Role of human papillomavirus and tumor suppressor genes in oral cancer.

    PubMed

    Manvikar, Vardendra; Kulkarni, Rama; Koneru, Anila; Vanishree, M

    2016-01-01

    The incidence of oral cancer remains high and is associated with many deaths in both Western and Asian countries. Several risk factors for the development of oral cancer are now well known, including smoking, drinking and consumption of smokeless tobacco products. Genetic predisposition to oral cancer has been found in certain cases, but its components are not yet entirely clear. In accordance with the multi-step theory of carcinogenesis, the natural history of oral cancer seems to gradually evolve through transitional precursor lesions from normal epithelium to a full-blown metastatic phenotype. A number of genomic lesions accompany this transformation and a wealth of related results has appeared in recent literature and is being summarized here. Furthermore, several key genes have been implicated, especially well-known tumor suppressors such as the cyclin-dependent kinase inhibitors, TP53 and RB1 and oncogenes such as the cyclin family, epidermal growth factor receptor and RAS. Viral infections, particularly oncogenic human papillomavirus subtypes and Epstein-Barr virus, can have a tumorigenic effect on oral epithelia and their role is discussed, along with potential therapeutic interventions. A brief explanatory theoretical model of oral carcinogenesis is provided and potential avenues for further research are highlighted. PMID:27194871

  14. In vitro reconstruction of human junctional and sulcular epithelium

    PubMed Central

    Dabija-Wolter, G; Bakken, V; Cimpan, M R; Johannessen, A C; Costea, D E

    2013-01-01

    BACKGROUND The aim of this study was to develop and characterize standardized in vitro three-dimensional organotypic models of human junctional epithelium (JE) and sulcular epithelium (SE). METHODS Organotypic models were constructed by growing human normal gingival keratinocytes on top of collagen matrices populated with gingival fibroblasts (GF) or periodontal ligament fibroblasts (PLF). Tissues obtained were harvested at different time points and assessed for epithelial morphology, proliferation (Ki67), expression of JE-specific markers (ODAM and FDC-SP), cytokeratins (CK), transglutaminase, filaggrin, and basement membrane proteins (collagen IV and laminin1). RESULTS The epithelial component in 3- and 5-day organotypics showed limited differentiation and expressed Ki-67, ODAM, FDC-SP, CK 8, 13, 16, 19, and transglutaminase in a similar fashion to control JE samples. PLF supported better than GF expression of CK19 and suprabasal proliferation, although statistically significant only at day 5. Basement membrane proteins started to be deposited only from day 5. The rate of proliferating cells as well as the percentage of CK19-expressing cells decreased significantly in 7- and 9-day cultures. Day 7 organotypics presented higher number of epithelial cell layers, proliferating cells in suprabasal layers, and CK expression pattern similar to SE. CONCLUSION Both time in culture and fibroblast type had impact on epithelial phenotype. Five-day cultures with PLF are suggested as JE models, 7-day cultures with PLF or GF as SE models, while 9-day cultures with GF as gingival epithelium (GE) models. Such standard, reproducible models represent useful tools to study periodontal bacteria–host interactions in vitro. PMID:22947066

  15. Connexins form functional hemichannels in porcine ciliary epithelium

    PubMed Central

    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. PMID:24262135

  16. 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.

  17. Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapy

    PubMed Central

    Dean, Jamie A; Wong, Kee H; Welsh, Liam C; Jones, Ann-Britt; Schick, Ulrike; Newbold, Kate L; Bhide, Shreerang A; Harrington, Kevin J; Nutting, Christopher M; Gulliford, Sarah L

    2016-01-01

    Background and Purpose Severe acute mucositis commonly results from head and neck (chemo)radiotherapy. A predictive model of mucositis could guide clinical decision-making and inform treatment planning. We aimed to generate such a model using spatial dose metrics and machine learning. Material and Methods Predictive models of severe acute mucositis were generated using radiotherapy dose (dose-volume and spatial dose metrics) and clinical data. Penalised logistic regression, support vector classification and random forest classification (RFC) models were generated and compared. Internal validation was performed (with 100-iteration cross-validation), using multiple metrics, including area under the receiver operating characteristic curve (AUC) and calibration slope, to assess performance. Associations between covariates and severe mucositis were explored using the models. Results The dose-volume-based models (standard) performed equally to those incorporating spatial information. Discrimination was similar between models, but the RFCstandard had the best calibration. The mean AUC and calibration slope for this model were 0.71 (s.d.=0.09) and 3.9 (s.d.=2.2), respectively. The volumes of oral cavity receiving intermediate and high doses were associated with severe mucositis. Conclusions The RFCstandard model performance is modest-to-good, but should be improved, and requires external validation. Reducing the volumes of oral cavity receiving intermediate and high doses may reduce mucositis incidence. PMID:27240717

  18. A novel male contraceptive pill-patch combination: oral desogestrel and transdermal testosterone in the suppression of spermatogenesis in normal men.

    PubMed

    Hair, W M; Kitteridge, K; O'Connor, D B; Wu, F C

    2001-11-01

    This study investigated the effect of transdermal T and oral desogestrel on the reproductive axis of healthy men. Twenty-three men were randomized to 1 of 3 treatment groups and received a daily transdermal T patch plus oral desogestrel at a dose of 75, 150, or 300 microg/d for 24 wk. Baseline blood and semen samples were obtained and then every 4 wk thereafter for 32 wk. The outcome measures were sperm density and plasma levels of FSH, LH, total and free T. The results show a dose-dependent suppression of spermatogenesis and gonadotropins. Seven of the 17 subjects became azoospermic. Desogestrel (300 microg daily) in combination with 5 mg daily transdermal T was the most effective (57% azoospermic), whereas a dose of 75 microg was ineffective (0% azoospermic). Total and free plasma T were reduced by approximately 30%. High density lipoprotein cholesterol was significantly reduced. No serious side-effects were encountered. We conclude that daily self-administered desogestrel with transdermal T is capable of suppressing the male reproductive axis, although the efficacy was less marked and less consistent than injectable regimens. The lower efficacy is likely to be due to failure of the transdermal T system to maintain circulating T levels consistently in the required range.

  19. 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

  20. 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.

  1. Mechanisms of Acid and Base Secretion by the Airway Epithelium

    PubMed Central

    Fischer, Horst; Widdicombe, Jonathan H.

    2010-01-01

    SUMMARY One of the main functions of the airway epithelium is to inactivate and remove infectious particles from inhaled air and thereby prevent infection of the distal lung. This function is achieved by mucociliary and cough clearance and by antimicrobial factors present in the airway surface liquid (ASL). There are indications that airway defenses are affected by the pH of the ASL and historically, acidification of the airway surfaces has been suggested as a measure of airway disease. However, even in health, the ASL is slightly acidic, and this acidity might be part of normal airway defense. Only recently research has focused on the mechanisms responsible for acid and base secretion into the ASL. Advances resulted from research into the airway disease associated with cystic fibrosis (CF) after it was found that the CFTR C1- channel conducts HCO3- and, therefore, may contribute to ASL pH. However, the acidity of the ASL indicated parallel mechanisms for H+ secretion. Recent investigations identified several H+ transporters in the apical membrane of the airway epithelium. These include H+ channels and ATP-driven H+ pumps, including a non-gastric isoform of the H+-K+ ATPase and a vacuolar-type H+ ATPase. Current knowledge of acid and base transporters and their potential roles in airway mucosal pH regulation is reviewed here. PMID:17091214

  2. 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.

  3. Epithelial-connective tissue boundary in the oral part of the human soft palate

    PubMed Central

    PAULSEN, FRIEDRICH; THALE, ANDREAS

    1998-01-01

    The papillary layer of the oral part of the human soft palate was studied in 31 subjects of different age by means of histological, immunohistochemical and scanning electron microscopical methods. For scanning electron microscopy a new maceration method was introduced. Results determine epithelial thickness, height and density of connective tissue papillae and their 3-dimensional architecture inside the lining epithelium as well as the collagenous arrangement of the openings of the glandular ducts. The individual connective tissue papillae of the soft palate are compared with the connective tissue boundary on the other side of the oral cavity. The connective tissue plateaux carrying a variable number of connective tissue papillae were found to be the basic structural units of the papillary body. The function of the epithelial-connective tissue interface and the extracellular matrix arrangement in the lamina propria are discussed in order to promote the comparability of normal with pathologically altered human soft palates. PMID:9877301

  4. Trefoil factor family 3 expression in the oral cavity.

    PubMed

    Storesund, T; Schreurs, O; Messelt, E B; Kolltveit, K M; Schenck, K

    2009-12-01

    This study examined the expression, in oral keratinocytes and in the major and minor salivary glands, of Trefoil factor family 3 (TFF3) peptide. Trefoil factor family 3 messenger RNA (mRNA) and peptide were detected in cultures of normal oral keratinocytes by quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. Trefoil factor family 3 was found, by immunohistochemical analyses, to be expressed in the basal layers of the oral mucosal epithelium. In salivary glands, immunohistochemical staining showed that TFF3 peptide expression was strongest in the mucous acini of the submandibular and the small salivary glands. Serous cells in the same glands showed weak staining. In the parotid gland, many serous acini showed weak positive staining, while other areas did not. In all glands examined, the intercalated, striated, and collecting ducts were moderately TFF3-positive. Double immunostaining confirmed that mucous (MUC5B positive) cells were moderately or strongly positive for TFF3 and that some serous (MUC7 positive) cells showed restricted TFF3 expression, mostly in a granular pattern. The prevalence of the TFF3 peptide in the salivary secretions of healthy volunteers was detected by western blotting of saliva from minor salivary glands (four of five) and the parotid gland (one of five) and of mixed submandibular/sublingual saliva (five of five). In conclusion, the submandibular and small salivary glands appear to be the major producers of oral TFF3, but duct cells of all glands and keratinocytes of the oral mucosa may also contribute as sources of TFF3 in the oral cavity.

  5. DNA damage in normal and choline deficient male B6C3F1 mice treated by oral gavage with fly ash

    SciTech Connect

    Andrews, P.W.; Tice, R.R.; Schmitt, M.T.; Yager, J.W.

    1994-12-31

    This study evaluated the ability of fly ash containing 199 mg/kg total arsenic to induce DNA damage in tissues of male B6C3F1 mice maintained on a choline sufficient (CS) or a choline deficient (CD) diet. DNA damage was assessed using the Single Cell Gel (SCG) assay in cells sampled from the blood, bladder, liver, lung, and skin; and micronuclei (MN) induction in bone marrow polychromatic erythrocytes (PCE). Sodium arsenite was given by oral gavage in water once or on 4 consecutive days at doses of 12.5, 25.0, and 50.0 mg/kg. Cell samples were collected at 3, 6, 24 and 48 hrs after the single treatment and at 4 hrs after the last of 4 treatments. In addition, urine was collected at 24, 48, and 72 hours after treatment to evaluate arsenic excretion kinetics. A significant depression in DNA migration (indicative of DNA crosslinking) was detected in blood cells of both CS and CD mice, and in bladder and liver cells of CS mice. Levels of MN-PCE or %PCE were not affected by a single treatment with fly ash. These preliminary data demonstrate indicate that fly ash may exhibit in vivo genotoxicity and the ability of hepatic methylation status to modulate the pattern and magnitude of the response.

  6. 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

  7. 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.

  8. Comparison of the effects of different menstrual tampons on the vaginal epithelium: a randomised clinical trial.

    PubMed

    Raudrant, D; Landrivon, G; Frappart, L; De Haas, P; Champion, F; Ecochard, R

    1995-01-01

    The effects on the vaginal epithelium of three different menstrual tampons in normal conditions of use were studied in 41 women during the menstrual period. The vaginal epithelium was studied in a total of 123 cycles at a structural and ultra-structural level with colposcopy, vaginal smear and biopsy on TEM and SEM. One of the three tampons studied showed a lower level of abnormalities on colposcopy (36.6% vs. 56.1% vs. 68.3%), with an inverse correlation between the severity of the dryness and the quantity of blood absorbed by the tampon (4.2 g when the colposcopy was normal vs. 1.8 g in case of severe dryness). Cytology is not a good test for assessing the effects of tampons because of the high rate of acellular and uninterpretable samplings. The biopsy effects were defined according to their depth in the epithelium. The same tampon showed the lowest level in biopsy abnormalities. No correlation was found between severity of the colposcopy and biopsy results. Colposcopy can demonstrate the degree of severity of dryness or any other effect, but biopsy only confirms the effect and does not correlate the degree of severity. Materials and designs of tampons can play a role in reducing the drying effects to the vaginal epithelium.

  9. 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.

  10. Periluminal Distribution of HIV-Binding Target Cells and Gp340 in the Oral, Cervical and Sigmoid/Rectal Mucosae: A Mapping Study.

    PubMed

    Patyka, Mariia; Malamud, Daniel; Weissman, Drew; Abrams, William R; Kurago, Zoya

    2015-01-01

    Studies have shown that the transmission of HIV is most likely to occur via rectal or vaginal routes, and rarely through oral exposure. However, the mechanisms of virus entry at mucosal surfaces remain incompletely understood. Prophylactic strategies against HIV infection may be attainable once gaps in current knowledge are filled. To address these gaps, we evaluated essentially normal epithelial surfaces and mapped the periluminal distribution of CD4+ HIV target cells, including T cells and antigen-presenting cells, and an HIV-binding molecule gp340 that can be expressed by epithelial cells in secreted and cell-associated forms. Immunohistochemistry for CD4, CD16, CD3, CD1a and gp340 in human oral, rectal/sigmoid and cervical mucosal samples from HIV-negative subjects demonstrated that periluminal HIV target cells were more prevalent at rectal/sigmoid and endocervical surfaces lined by simple columnar epithelium, than at oral and ectocervical surfaces covered by multilayered stratified squamous epithelium (p<0.001). gp340 expression patterns at these sites were also distinct and strong in oral minor salivary gland acini and ducts, including ductal saliva, in individual rectum/sigmoid and endocervix periluminar columnar cells, and in ectocervix squamous cells. Only weak expression was noted in the oral non-ductal squamous epithelium. We conclude that periluminal HIV target cells, together with periluminal epithelial cell-associated gp340 appear to be most accessible for HIV transmission at rectal/sigmoid and endocervical surfaces. Our data help define vulnerable structural features of mucosal sites exposed to HIV.

  11. Periluminal Distribution of HIV-Binding Target Cells and Gp340 in the Oral, Cervical and Sigmoid/Rectal Mucosae: A Mapping Study.

    PubMed

    Patyka, Mariia; Malamud, Daniel; Weissman, Drew; Abrams, William R; Kurago, Zoya

    2015-01-01

    Studies have shown that the transmission of HIV is most likely to occur via rectal or vaginal routes, and rarely through oral exposure. However, the mechanisms of virus entry at mucosal surfaces remain incompletely understood. Prophylactic strategies against HIV infection may be attainable once gaps in current knowledge are filled. To address these gaps, we evaluated essentially normal epithelial surfaces and mapped the periluminal distribution of CD4+ HIV target cells, including T cells and antigen-presenting cells, and an HIV-binding molecule gp340 that can be expressed by epithelial cells in secreted and cell-associated forms. Immunohistochemistry for CD4, CD16, CD3, CD1a and gp340 in human oral, rectal/sigmoid and cervical mucosal samples from HIV-negative subjects demonstrated that periluminal HIV target cells were more prevalent at rectal/sigmoid and endocervical surfaces lined by simple columnar epithelium, than at oral and ectocervical surfaces covered by multilayered stratified squamous epithelium (p<0.001). gp340 expression patterns at these sites were also distinct and strong in oral minor salivary gland acini and ducts, including ductal saliva, in individual rectum/sigmoid and endocervix periluminar columnar cells, and in ectocervix squamous cells. Only weak expression was noted in the oral non-ductal squamous epithelium. We conclude that periluminal HIV target cells, together with periluminal epithelial cell-associated gp340 appear to be most accessible for HIV transmission at rectal/sigmoid and endocervical surfaces. Our data help define vulnerable structural features of mucosal sites exposed to HIV. PMID:26172445

  12. 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

  13. UFLC-Q-TOF/MS based screening and identification of the metabolites in plasma, bile, urine and feces of normal and blood stasis rats after oral administration of hydroxysafflor yellow A.

    PubMed

    Jin, Yi; Wu, Liang; Tang, Yuping; Cao, Yujie; Li, Shujiao; Shen, Juan; Yue, Shijun; Qu, Cheng; Shan, Chenxiao; Cui, Xiaobing; Zhang, Li; Duan, Jin-ao

    2016-02-15

    The dried flower of Carthamus tinctorius L. (honghua) is a widely used traditional Chinese medicine in clinics to treat coronary heart disease, hypertension, and cerebrovascular disease due to its functions of ameliorating circulation and removing blood stasis. Hydroxysafflor yellow A (HSYA) is an active marker component of honghua. In this paper, ultra-flow liquid chromatography coupled with quadrupole-time-of-flight mass-spectrometry (UFLC-Q-TOF/MS) was established and successfully applied to the detection and identification of the metabolites in bile, urine, plasma and feces samples of normal and model rats with orally administrated HSYA. A total of 8 metabolites were observed in normal rats, while 7 metabolites were detected in model rats. The distribution of metabolites in the plasma, bile, urine and feces of normal and model rats had obvious differences. The major in vivo metabolic pathways for HSYA included hydroxylation, hydroxylation+methylation, acetylation and glucuronidation, and there were also dehydration, hydrogenation, hydration, and hydroxylation+glucuronidation. All of these metabolites were reported for the first time, and these results are valuable and important for the understanding of the metabolic process and therapeutic mechanism of HSYA and some other pigments in honghua.

  14. UFLC-Q-TOF/MS based screening and identification of the metabolites in plasma, bile, urine and feces of normal and blood stasis rats after oral administration of hydroxysafflor yellow A.

    PubMed

    Jin, Yi; Wu, Liang; Tang, Yuping; Cao, Yujie; Li, Shujiao; Shen, Juan; Yue, Shijun; Qu, Cheng; Shan, Chenxiao; Cui, Xiaobing; Zhang, Li; Duan, Jin-ao

    2016-02-15

    The dried flower of Carthamus tinctorius L. (honghua) is a widely used traditional Chinese medicine in clinics to treat coronary heart disease, hypertension, and cerebrovascular disease due to its functions of ameliorating circulation and removing blood stasis. Hydroxysafflor yellow A (HSYA) is an active marker component of honghua. In this paper, ultra-flow liquid chromatography coupled with quadrupole-time-of-flight mass-spectrometry (UFLC-Q-TOF/MS) was established and successfully applied to the detection and identification of the metabolites in bile, urine, plasma and feces samples of normal and model rats with orally administrated HSYA. A total of 8 metabolites were observed in normal rats, while 7 metabolites were detected in model rats. The distribution of metabolites in the plasma, bile, urine and feces of normal and model rats had obvious differences. The major in vivo metabolic pathways for HSYA included hydroxylation, hydroxylation+methylation, acetylation and glucuronidation, and there were also dehydration, hydrogenation, hydration, and hydroxylation+glucuronidation. All of these metabolites were reported for the first time, and these results are valuable and important for the understanding of the metabolic process and therapeutic mechanism of HSYA and some other pigments in honghua. PMID:26827279

  15. Development of the ovarian follicular epithelium.

    PubMed

    Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

    1999-05-25

    A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women. PMID:10411332

  16. The role of lens epithelium in sugar cataract formation.

    PubMed

    Robison, W G; Houlder, N; Kinoshita, J H

    1990-06-01

    Previous evidence has shown clearly that sugar cataract formation results from unusually high intracellular levels of polyol. Documentation of polyol-related histological changes in the cortical fiber cells of the equatorial zone has been extensive. However, little attention has been given to the early changes in the lens epithelial cells, in spite of the fact that the highest level of aldose reductase is found in this layer of the lens. Also, cultured lens epithelial cells exposed to high sugar levels exhibit rapid accumulation of polyol and show ultrastructural alterations. Therefore, a study was designed to evaluate the role of the lens epithelium in sugar cataract formation. Specifically, an attempt was made to localize the earliest fine structural lesions in intact lenses of galactose-fed rats and to test their relation to aldose reductase. Rats were fed either a normal diet or a 50% galactose diet with or without sorbinil, an aldose reductase inhibitor. Rats were killed at varying periods of time ranging from 6 to 96 hr, and the eyes were processed for light and electron microscopy. The first detectable abnormalities occurred after 36 hr of galactose feeding, and were limited to the central lens epithelium. Cell edema, apparent dilution of cytoplasm, rounding of nuclei, aberrant intracellular vacuoles, and loss of normal tortuosity of cell boundaries were the salient lesions. No changes were detectable in the equatorial zone until 48 hr, and no deviation from the control structure was found in any of the rats treated with an aldose reductase inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Chromosomal Damage and Apoptosis in Exfoliated Buccal Cells from Individuals with Oral Cancer

    PubMed Central

    Dórea, Lavínia Tércia Magalhães; Meireles, José Roberto Cardoso; Lessa, Júlia Paula Ramos; Oliveira, Márcio Campos; de Bragança Pereira, Carlos Alberto; Polpo de Campos, Adriano; Cerqueira, Eneida de Moraes Macílio

    2012-01-01

    This study aimed to investigate cytological abnormalities indicative of chromosome damage (micronuclei) and apoptosis (karyorrhexis, pyknosis, and condensed chromatin) in exfoliated cells from the buccal mucosa of patients with oral cancer and control subjects. The sample included twenty individuals with oral cancer and forty individuals with normal buccal mucosa. Material was collected from the cheek epithelium in areas with lesions and areas without abnormalities. A minimum of one thousand cells was analyzed. Micronuclei were found significantly more frequently in cells collected from lesions than in cells from normal areas, independent of the presence/absence of cancer (P < 0.0001). They were also significantly more frequent in smokers and in mouthwash users (P < 0.0001). Apoptosis occurred significantly less frequently in individuals with oral cancer (P < 0.0001). These results show that oral cancer is associated with higher frequency of chromosomal damage and suggest that apoptosis is compromised in the buccal cells of individuals with this kind of neoplasia. PMID:22315605

  18. Methylglyoxal (MG) and cerebro-renal interaction: does long-term orally administered MG cause cognitive impairment in normal Sprague-Dawley rats?

    PubMed

    Watanabe, Kimio; Okada, Kana; Fukabori, Ryoji; Hayashi, Yoshimitsu; Asahi, Koichi; Terawaki, Hiroyuki; Kobayashi, Kazuto; Watanabe, Tsuyoshi; Nakayama, Masaaki

    2014-01-07

    Methylglyoxal (MG), one of the uremic toxins, is a highly reactive alpha-dicarbonyl compound. Recent clinical studies have demonstrated the close associations of cognitive impairment (CI) with plasma MG levels and presence of kidney dysfunction. Therefore, the present study aims to examine whether MG is a direct causative substance for CI development. Eight-week-old male Sprague-Dawley (SD) rats were divided into two groups: control (n = 9) and MG group (n = 10; 0.5% MG in drinking water), and fed a normal diet for 12 months. Cognitive function was evaluated by two behavioral tests (object exploration test and radial-arm maze test) in early (4-6 months of age) and late phase (7-12 months of age). Serum MG was significantly elevated in the MG group (495.8 ± 38.1 vs. 244.8 ± 28.2 nM; p < 0.001) at the end of study. The groups did not differ in cognitive function during the course of study. No time-course differences were found in oxidative stress markers between the two groups, while, antioxidants such as glutathione peroxidase and superoxide dismutase activities were significantly increased in the MG group compared to the control. Long-term MG administration to rats with normal kidney function did not cause CI. A counter-balanced activation of the systemic anti-oxidant system may offset the toxicity of MG in this model. Pathogenetic significance of MG for CI requires further investigation.

  19. Expression of E-cadherin and vimentin in oral squamous cell carcinoma

    PubMed Central

    Zhou, Jingping; Tao, Detao; Xu, Qing; Gao, Zhenlin; Tang, Daofang

    2015-01-01

    The aim of the study is to determine the levels of E-cadherin, vimentin expression in tumor tissues from patients with oral squamous cell carcinoma (OSCC), and the relationship between the expression of E-cadherin, vimentin and epithelial-mesenchymal transition, in order to explore its values for predicting the invasion and metastasis of oral squamous cell carcinoma, short survival of patients in many types of cancer. E-cadherin and vimentin expression of 10 benign and 42 OSCC tumor tissues was examined by immunohistochemical staining. E-cadherin is positively expressed in normal oral mucosa epithelium, but vimentin expression is not found in normal oral mucosa epithelia; the E-cadherin and vimentin were expressed in 26 of 42 (61.9%) and 16 of 42 (38.1%), respectively. No statistically difference was found for E-cadherin and vimentin expression in patients with different age, gender and tumor location, E-cadherin and vimentin expression was significantly associated with lymph node metastasis and tissue location (P < 0.05); E-cadherin expression was also significantly associated with tumor stage (P < 0.05); there are significantly difference between infiltrative margin and central area in patients with oral squamous cell carcinoma for E-cadherin and vimentin positive expression (P < 0.05). E-cadherin and vimentin positive expression was associated with tumor metastasis of oral squamous cell carcinoma. Our study preliminarily confirmed that EMT phenomenon is existed during the development of oral squamous cell carcinoma. Co-evaluation of E-cadherin and vimentin might be a valuable tool for predicting OSCC patient outcome. PMID:26045832

  20. 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

  1. 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

  2. Pharmacokinetic comparison of ferulic acid in normal and blood deficiency rats after oral administration of Angelica sinensis, Ligusticum chuanxiong and their combination.

    PubMed

    Li, Weixia; Guo, Jianming; Tang, Yuping; Wang, Huan; Huang, Meiyan; Qian, Dawei; Duan, Jin-Ao

    2012-01-01

    Radix Angelica Sinensis (RAS) and Rhizome Ligusticum (RLC) combination is a popular herb pair commonly used in clinics for treatment of blood deficiency syndrome in China. The aim of this study is to compare the pharmacokinetic properties of ferulic acid (FA), a main bioactive constituent in both RAS and RLC, between normal and blood deficiency syndrome animals, and to investigate the influence of compatibility of RAS and RLC on the pharmacokinetic of FA. The blood deficiency rats were induced by injecting 2% Acetyl phenylhydrazine (APH) on the first day, every other day, to a total of five times, at the dosage of 100, 50, 50, 30, 30 mg/kg body mass, respectively. Quantification of FA in rat plasma was achieved by using a simple and rapid HPLC method. Plasma samples were collected at different time points to construct pharmacokinetic profiles by plotting drug concentration versus time, and estimate pharmacokinetic parameters. Between normal and blood deficiency model groups, both AUC((0-) (t) ()) and C(max) of FA in blood deficiency rats after RAS-RLC extract administration increased significantly (P < 0.05), while clearance (CL) decreased significantly. Among three blood deficiency model groups, t(1/2α), V(d), AUC((0-) (t) ()) and AUC((0-∞)) all increased significantly in the RAS-RLC extract group compared with the RAS group. The results indicated that FA was absorbed better and eliminated slower in blood deficiency rats; RLC could significantly prolong the half-life of distribution, increase the volume of distribution and the absorption amount of FA of RAS in blood deficiency rats, which may be due to the synergic action when RAS and RLC were used together to treat blood deficiency syndrome. PMID:22489169

  3. Effect of tobacco and alcohol consumption on the Langerhans cell population of human lingual epithelium determined using a monoclonal antibody against HLADR.

    PubMed

    Barrett, A W; Williams, D M; Scott, J

    1991-02-01

    Tobacco and alcohol consumption are known predisposing factors to the development of oral cancer, though the mechanism by which they act is unclear. The density of Langerhans cells (LC) has been shown to decrease in the uterine cervix of smokers, possibly indicating reduced immune surveillance and increased risk of malignant change. This study examined biopsies of normal human lateral border of tongue taken from 41 necropsies whose histories of tobacco and alcohol consumption were known. LC were identified in fixed, wax-embedded sections using a monoclonal antibody to HLADR and an immunoperoxidase technique. The mean density of LC in smokers of the equivalent of 11 or more cigarettes daily was significantly higher than moderate and non-smokers when counts were expressed per mm epithelial surface and basement membrane length. There were no significant differences in LC numbers in relation to alcohol consumption, age or sex, but there was a significant interaction between tobacco and alcohol. The results suggest that either human oral LC respond to external toxins, or that physical changes in the epithelial barrier induced by such toxins necessitate the presence of more LC to maintain the integrity of the epithelium.

  4. Ontogeny of the mouse vocal fold epithelium

    PubMed Central

    Lungova, Vlasta; Verheyden, Jamie M.; Herriges, John; Sun, Xin; Thibeault, Susan L.

    2015-01-01

    This investigation provides the first systematic determination of the cellular and molecular progression of vocal fold (VF) epithelium development in a murine model. We define five principal developmental events that constitute the progression from VF initiation in the embryonic anterior foregut tube to fully differentiated and functional adult tissue. These developmental events include (1) the initiation of the larynx and vocal folds with apposition of the lateral walls of the primitive laryngopharynx (embryonic (E) day 10.5); (2) the establishment of the epithelial lamina with fusion of the lateral walls of the primitive laryngopharynx (E11.5); (3) the epithelial lamina recanalization and separation of VFs (E13.5–18.5); (4) the stratification of the vocal folds (E13.5–18.5); and (5) the maturation of vocal fold epithelium (postnatal stages). The illustration of these morphogenetic events is substantiated by dynamic changes in cell proliferation and apoptosis, as well as the expression pattern of key transcription factors, FOXA2, SOX2 and NKX2-1 that specify and pattern the foregut endoderm. Furthermore, we documented the gradual conversion of VF epithelial cells from simple precursors expressing cytokeratins 8 and 18 in the embryo into mature stratified epithelial cells also expressing cytokeratins 5 and 14 in the adult. Interestingly, in the adult, cytokeratins 5 and 14 appear to be expressed in all cell layers in the VF, in contrast to their preferential localization to the basal cell layer in surrounding epithelium. To begin investigating the role of signaling molecules in vocal fold development, we characterized the expression pattern of SHH pathway genes, and how loss of Shh affects vocal fold development in the mutant. This study defines the cellular and molecular context and serves as the necessary foundation for future functional investigations of VF formation. PMID:25601450

  5. Uptake of inert microparticles in normal and immune deficient mice.

    PubMed

    Smyth, S H; Feldhaus, S; Schumacher, U; Carr, K E

    2008-01-01

    Intestinal microparticle uptake is important for drug delivery, environmental pollution and multiple organ dysfunction syndrome. This paper explores further whether uptake occurs at mucosa associated lymphoid tissue (MALT) via the microfold (M) cells of Peyer's patch domes or through villous epithelium. It does this by comparing the results of exposure of either severe combined immunodeficient (SCID) mice (lacking MALT) or normal BALBc mice, to oral gavage with 2 microm fluorescent latex microparticles. At 5 and 30 min after gavage, full circumference samples along the small intestine were processed for fluorescence microscopy and microparticle numbers were collected for surface and tissue sites. Uptake occurred in both BALBc and SCID mice within 5 min of particle administration and increased further in the following 25 min. In BALBc mice, almost all particles (96%) are in non-MALT sites in MALT circumference samples, with very few at the domes: uptake was also substantial in entirely villous samples. In SCID mice, particle numbers were only slightly lower than those of the BALBc mice, and occurred exclusively by the villous route. These findings confirm that the villous uptake route must be considered when assessing the extent of the dose delivered following pharmaceutical or toxicological oral exposure to microparticles. PMID:17723283

  6. Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium

    PubMed Central

    Horvay, Katja; Jardé, Thierry; Casagranda, Franca; Perreau, Victoria M; Haigh, Katharina; Nefzger, Christian M; Akhtar, Reyhan; Gridley, Thomas; Berx, Geert; Haigh, Jody J; Barker, Nick; Polo, Jose M; Hime, Gary R; Abud, Helen E

    2015-01-01

    Snail family members regulate epithelial-to-mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote an undifferentiated state. Here, we demonstrate that conditional knockout of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snai1 conditional knockout mice also undergo apoptosis when Snai1 is deleted. Conversely, ectopic expression of Snai1 in the intestinal epithelium in vivo results in the expansion of the crypt base columnar cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following conditional deletion of Snai1, the intestinal epithelium fails to produce a proliferative response following radiation-induced damage indicating a fundamental requirement for Snai1 in epithelial regeneration. These results demonstrate that Snai1 is required for regulation of lineage choice, maintenance of CBC stem cells and regeneration of the intestinal epithelium following damage. PMID:25759216

  7. Effect of bisphosphonates on the mandibular bone and gingival epithelium of rats without tooth extraction

    PubMed Central

    DE PONTE, FRANCESCO SAVERIO; CATALFAMO, LUCIANO; MICALI, GREGORIO; RUNCI, MICHELE; CUTRONEO, GIUSEPPINA; VERMIGLIO, GIOVANNA; CENTOFANTI, ANTONIO; RIZZO, GIUSEPPINA

    2016-01-01

    Osteonecrosis of the jaw (ONJ) is an adverse effect of bisphosphonate treatment that has become the subject of increasing investigations, in particular due to its poorly understood pathogenesis. Several experimental studies on animal models have been conducted; however, the majority of these replicate human ONJ following tooth extraction, and describe alterations in the bone and gingival epithelium when necrosis is manifested. The aim of the present study was to analyze the rat mandibular bone and gingival epithelium during 45 days of zoledronate treatment (which is a bisphosphonate agent), without tooth extraction. Intraperitoneal injections of zoledronate acid (0.1 mg/kg) were performed three times a week in normal male Wistar rats (n=20), while a control group of rats (n=20) was treated with saline solution for 45 days. After 7, 15, 30 and 45 days of drug treatment, all rats were sacrificed and hematoxilin and eosin staining, immunofluorescence and scanning electron microscopy analyses were performed. The results of the analyses after 7 and 15 days of treatment were similar in the treatment and control group. After 30 and 45 days of treatment, structural alterations were observed in the bone. No structural alterations to the gingival epithelium were observed. Based on these results, it was hypothesized that low doses of zoledronate act directly on the bone tissues to induce morphological alterations from bone to necrotic tissue following surgical procedures, although no cytotoxic effects were detected in the gingival epithelium. PMID:27168789

  8. In vitro absorption of gamma-globulin by neonatal intestinal epithelium of the pig.

    PubMed

    Lecce, J G

    1966-06-01

    1. An in vitro method, using fluorescent gamma-globulin and everted neonatal pig's intestinal slices, for the study of the active transport of large molecules is described.2. Uptake of gamma-globulin occurred within 15 min and required no exogenous substrates.3. In vitro absorption of gamma-globulin by intestinal epithelium was limited to the neonatal pig and 5-day-old mouse. No uptake was seen in intestines from a mature mouse, a pig with diarrhoea, a normal pig, a mature rabbit, a guinea-pig, a chick, and a chick embryo. Chick embryo yolk sac readily took up gamma-globulin.4. Rings of everted intestinal epithelium remained active (still absorbed gamma-globulin) after incubating for 4-6 hr in balanced salt solution (BSS).5. Uptake of gamma-globulin required oxygen and sodium and was reversibly inhibited by metabolic antagonists such as iodoacetate, arsenate, fluoride, 4,6-dinitro-varphi-cresol, phlorrhizin, anaerobiosis and cold. Under the conditions of the test, large colloidal molecules did not inhibit uptake of gamma-globulin.6. Similar results (although not as clear-cut) with metabolic inhibitors were obtained with preparations of chick embryo yolk sacs.7. Injuring mature pig's intestinal epithelium with surface-active agents did not produce non-specific absorption artifacts that resembled the specific absorption found in immature pig's intestinal epithelium.

  9. Ultrastructural observations on experimentally produced melanin pigmentation of the corneal epithelium.

    PubMed Central

    McCracken, J. S.; Klintworth, G. K.

    1976-01-01

    Melanin pigmentation of the corneal epithelium was induced in pigmented guinea pigs by the topical application of colchicine to their eyes or by corneal cauterization with silver nitrate. With colchicine the pigmentation was preceded by the development of an abnormal corneal epithelium in which numerous cells became arrested in cell division. The corneal melanosis resulted largely from the migration of melanocytes into the corneal epithelium from the normally pigmented contiguous conjunctiva and to a lesser extent from the presence of melanin granules within corneal epithelial cells. In both models a leukocytic and vascular invasion of the cornea proceded and accompanied the migration of melanocytes into the corneal epithelium. Electron microscopy disclosed cells with the same morphology as conjunctival melanocytes between the epithelial cells of the cornea. Mature melanin granules were also present within some squamous epithelial cells as individual granules or as clusters. The ultrastructural findings are viewed in relation to how melanin granules are transferred from melanocytes to epithelial cells. Evidence is presented which suggests that malanin granule transfer may follow the fusion of the membranes of the melanocytes and epithelial cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 PMID:970438

  10. A light, transmission and scanning electron microscope study of snuff-treated hamster cheek pouch epithelium.

    PubMed

    Ashrafi, S H; Das, A; Worowongvasu, R; Mehdinejad, B; Waterhouse, J P

    1992-03-01

    The effects of smokeless tobacco (snuff) on hamster cheek mucosa were studied by light microscopy, transmission (TEM) and scanning electron microscopy (SEM). Two grams of commercially available smokeless tobacco were placed into the blind end of the right cheek pouch of each experimental animal, once a day and five days a week for 24 months. The control animals did not receive smokeless tobacco. After 24 months treatment with smokeless tobacco, hamster cheek mucosal epithelium lost its translucency and had become whitish in color. By light microscopy hyperorthokeratosis, prominent granular cell layers with increased keratohyalin granules and hyperplasia were seen. At the ultrastructural level, wider intercellular spaces filled with microvilli, numerous shorter desmosomes, many thin tonofilament bundles, increased number of mitochondria, membrane coating granules and keratohyalin granules were seen in snuff-treated epithelium. The changes in the surface of the epithelium as seen by SEM were the development of an irregular arrangement of the microridges and the disappearance of the normal honeycomb pattern. The microridges were irregular, widened and surrounded the irregular elongated pits. Some smooth areas without microridges and pits were also seen. The long-term histological, TEM and SEM changes induced by smokeless tobacco treatment of the epithelium are well correlated with each other and were similar to those reported in human leukoplakia without dyskeratosis. They imply changes of pathological response resulting from topically applied snuff.

  11. 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.

  12. Alterations in phenotypic biochemical markers in bladder epithelium during tumorigenesis.

    PubMed

    Rao, J Y; Hemstreet, G P; Hurst, R E; Bonner, R B; Jones, P L; Min, K W; Fradet, Y

    1993-09-01

    Phenotypic biochemical markers of oncogenesis and differentiation were mapped in bladder biopsies to investigate changes that occur in bladder tumorigenesis and to identify markers for increased bladder cancer risk. Touch preparations from biopsy specimens from 30 patients were obtained from tumors, the adjacent bladder epithelium, and random distant bladder epithelium. Markers, including DNA ploidy, epidermal growth factor receptor (EGFR), and oncoproteins, were quantified in individual cells by using quantitative fluorescence image analysis. Cluster analysis revealed the markers fell into three independent groups: (i) G-actin and EGFR; (ii) ploidy, cytology, and p185 (HER-2/neu oncoprotein) (ERBB2); and (iii) p300, a low-grade tumor antigen. Each marker displayed a gradient of abnormality from distant field to adjacent field to tumor. Different patterns for each marker suggested a developmental sequence of bladder cancer oncogenesis; G-actin was altered in 58% of distant biopsies (vs. 0/6 normals, P < 0.001), ploidy and cytology were altered in < 20% of distant fields and approximately 80% of tumors, and the other markers were intermediate. Patterns of EGFR and p185 suggest low-and high-grade tracks diverge early (P < 0.05 by Mann-Whitney U test for EGFR and ANOVA for p185). In conclusion, this study shows that a sequence of phenotypic changes accompanies development and progression of bladder cancers. Biochemical alterations in cells of the bladder field are often detectable before abnormal pathology, and markers previously thought to be limited to tumors were found in the field. The hierarchy of expression may be useful in identifying high-risk patients, assessing completeness of response to therapy, and monitoring and predicting recurrence. PMID:8367495

  13. Aggressive Calcifying Epithelial Odontogenic Tumor of the Maxillary Sinus with Extraosseous Oral Mucosal Involvement: A Case Report

    PubMed Central

    Rani, Vidya; Masthan, Mahaboob Kadar; Aravindha, Babu; Leena, Sankari

    2016-01-01

    Calcifying epithelial odontogenic tumors are benign odontogenic neoplasms whose occurrence in the maxillary sinus is rare. Maxillary tumors tend to be locally aggressive and may rapidly involve the surrounding vital structures. We report a case of a large calcifying epithelial odontogenic tumor of the maxilla, involving the maxillary sinus in a 48-year-old woman. The tumor was largely intraosseous. In the canine and first premolar regions, the loss of bone could be palpated but the oral mucosa appeared normal. Histologically, the tumor tissue could be seen in the connective tissue below the oral epithelium. The most significant finding was the presence of an intraosseous tumor with an extraosseous involvement in a single tumor, indicating aggressive behavior and warranting aggressive treatment. In this article, we discuss the rare presentation of the tumor and its radiological appearance and histological features. We also highlight the importance of a detailed histopathological examination of the excised specimen. PMID:26989286

  14. Objectivity in the classification of tumours of the nasal epithelium

    PubMed Central

    Michaels, L.; Hyams, V. J.

    1975-01-01

    A survey of tumours derived from each of the four cell types of nasal epithelium is presented. Criticism is levelled at the adoption of additional terms for tissue types such as lympho-epithelium and transitional cell epithelium and tumours said to be derived from them. Electron microscopy is of assistance in classification particularly in the detection of evidence of keratin synthesis. The proposed classification of tumours of the nasal epithelium is: (1) Pseudostratified columnar epithelium: (a) papillary adenoma, (b) papillary carcinoma. (2) Squamous epithelium: (a) everted squamous papilloma, (b) inverted papilloma, (c) squamous carcinoma of any grade of differentiation from well differentiated to undifferentiated. (3) Melanocyte: malignant melanoma. (4) Olfactory neuroepithelium: olfactory neuroblastoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16Fig. 17Fig. 18Fig. 19Fig. 21Fig. 20 PMID:1197175

  15. Activation of the IL-6/JAK/STAT3 signaling pathway in human middle ear cholesteatoma epithelium

    PubMed Central

    Liu, Wei; Xie, Shumin; Chen, Xing; Rao, Xingwang; Ren, Hongmiao; Hu, Bing; Yin, Tuanfang; Xiang, Yuyan; Ren, Jihao

    2014-01-01

    Interleukin-6 (IL-6) is one of the most important cytokines which has been shown to play a critical role in the pathogenesis of cholesteatoma. In this study, we aimed to investigate the expression of interleukin-6 (IL-6) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in middle ear cholesteatoma epithelium in an effort to determine the role of IL-6/JAK/STAT3 signaling pathway in the pathogenesis of cholesteatoma. Immunohistochemistry was used to examine the expression of IL-6 and p-STAT3 in 25 human middle ear cholesteatoma samples and 15 normal external auditory canal (EAC) epithelium specimens. We also analyzed the relation of IL-6 and p-STAT3 expression levels to the degree of bone destruction in cholesteatoma. We found that the expression of IL-6 and p-STAT3 were significantly higher in cholesteatoma epithelium than in normal EAC epithelium (p<0.05). In cholesteatoma epithelium, a significant positive association was observed between IL-6 and p-STAT3 expression (p<0.05). However, no significant relationships were observed between the degree of bone destruction and the levels of IL-6 and p-STAT3 expression (p>0.05). To conclude, our results support the concept that IL-6/JAK/STAT3 signaling pathway is active and may play an important role in the mechanisms of epithelial hyper-proliferation responsible for cholesteatoma. PMID:24551293

  16. Ultra structural study of the rat cheek epithelium treated with Neem extract.

    PubMed

    Azmi, Muhammad Arshad; Khatoon, Nasira; Ghaffar, Rizwana Abdul

    2015-11-01

    The purpose of this study was to investigate the effects of neem extract (Azadirachta indica A. Juss) on the ultrastructure of the rat oral epithelium, because neem extract has been added in the tooth paste as an anti-plaque-forming substance in Asian countries. The non-toxic dose of 2000 mg/kg body weight of Neem extract (NBE) was applied daily to the surface of buccal epithelium for four weeks and controls did not receive Neem extract. After four weeks cheek epithelial tissues were excised and processed for light microscopy, scanning and transmission electron microscopy. Light microscopy did not show significant differences between NBE-treated and control epithelium. Difference between control and treated rats weight was non-significant. Moreover, time period was also non-significant. Irregular cell surfaces were noticed when compared to control specimens when examined by scanning electron microscopy. Under transmission electron microscopy, wider intercellular spaces were observed in the treated epithelial spinous cellular layers when compared to control. Further, more keratohyalin granules were present in experimental granular cells. It was concluded that present study showed differences between Neem-treated and control in epithelial tissues but these structural differences may not be related to adverse side effects of the Neem extract.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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

  19. Immunohistochemical expression of p16 protein in oral squamous cell carcinoma and lichen planus.

    PubMed

    Salehinejad, Jahanshah; Sharifi, Nourieh; Amirchaghmaghi, Maryam; Ghazi, Narges; Shakeri, Mohammad Taghi; Ghazi, Ala

    2014-08-01

    Epithelial carcinogenesis is a multistep process. Specific genetic events lead to malignant transformation of oral epithelium. Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant lesions such as oral lichen planus (OLP). The p16 protein functions as a negative regulator of the cell cycle progression. Altered pattern of p16 serves as a biomarker for oral mucosal dysplasia and malignant growth. The purpose of this study was to evaluate p16 expression in OSCC and OLP to determine whether it can be a useful marker for early detection of carcinogenesis. We examined p16 expression in 45 OSCCs (15 grade I, 15 grade II, and 15 grade III), 15 OLPs without dysplasia, and 8 normal mucosal specimens with immunohistochemistry. p16 was interpreted as positive if more than 70% of tumor cells showed brown nuclear and cytoplasmic staining. All of the OSCC and control group samples showed negative immunoreactivity, whereas 26.7% of OLP samples were positive for p16. Our findings suggest that p16 expression could not be used as a helpful marker for detection of development toward malignancy in OLP samples. PMID:24850170

  20. CD44 expression in intraoral salivary ductal papillomas and oral papillary squamous cell carcinoma.

    PubMed

    Fitzpatrick, Sarah G; Montague, Lindsay J; Cohen, Donald M; Bhattacharyya, Indraneel

    2013-06-01

    CD44 is a transmembrane adhesion molecule which has been previously shown to be useful in the differentiation of benign papillary lesions from invasive carcinoma in several different areas including sinonasal mucosa and breast tissue. CD44 expression has previously been shown to be lost in invasive carcinoma and retained in benign papillary lesions in both of the above locations. In addition, studies have evaluated oral mucosal lesions for CD44 expression and found a loss with invasive squamous cell carcinoma when compared to normal epithelium, hyperplasia, and squamous papillomas, which stained particularly strongly. To the best of our knowledge, no study has evaluated CD44 expression when comparing salivary ductal papillomas in comparison to oral papillary SCCA. In this study 18 cases of intraductal papilloma were compared to 19 cases of oral papillary SCCA. Within the ductal papilloma group, all cases stained either absent (6%), weakly (33%), or moderately (61%) with 76% expressing the stain diffusely and 24% focally. In comparison, the papillary squamous cell carcinoma cases expressed the CD44 moderately (26%) or strongly (74%) with 100 % showing diffuse staining. Thus, the CD44 expression was contrary to expectation based on previous studies, which we hypothesize is due to the extremely well differentiated nature of papillary SCCA which expressed CD44 staining compatible with levels previously reported with oral squamous papillomas than invasive carcinoma.

  1. Bisphenol A Promotes Human Prostate Stem-Progenitor Cell Self-Renewal and Increases In Vivo Carcinogenesis in Human Prostate Epithelium

    PubMed Central

    Hu, Wen-Yang; Shi, Guang-Bin; Hu, Dan-Ping; Majumdar, Shyama; Li, Guannan; Huang, Ke; Nelles, Jason L.; Ho, Shuk-Mei; Walker, Cheryl Lyn; Kajdacsy-Balla, Andre; van Breemen, Richard B.

    2014-01-01

    Previous studies in rodent models have shown that early-life exposure to bisphenol A (BPA) reprograms the prostate and enhances its susceptibility to hormonal carcinogenesis with aging. To determine whether the human prostate is similarly sensitive to BPA, the current study used human prostate epithelial stem-like cells cultured from prostates of young, disease-free donors. Similar to estradiol-17β (E2), BPA increased stem-progenitor cell self-renewal and expression of stem-related genes in a dose-dependent manner. Further, 10 nM BPA and E2 possessed equimolar membrane-initiated signaling with robust induction of p-Akt and p-Erk at 15 minutes. To assess in vivo carcinogenicity, human prostate stem-progenitor cells combined with rat mesenchyme were grown as renal grafts in nude mice, forming normal human prostate epithelium at 1 month. Developmental BPA exposure was achieved through oral administration of 100 or 250 μg BPA/kg body weight to hosts for 2 weeks after grafting, producing free BPA levels of 0.39 and 1.35 ng/mL serum, respectively. Carcinogenesis was driven by testosterone plus E2 treatment for 2 to 4 months to model rising E2 levels in aging men. The incidence of high-grade prostate intraepithelial neoplasia and adenocarcinoma markedly increased from 13% in oil-fed controls to 33% to 36% in grafts exposed in vivo to BPA (P < .05). Continuous developmental BPA exposure through in vitro (200 nM) plus in vivo (250 μg/kg body weight) treatments increased high-grade prostate intraepithelial neoplasia/cancer incidence to 45% (P < .01). Together, the present findings demonstrate that human prostate stem-progenitor cells are direct BPA targets and that developmental exposure to BPA at low doses increases hormone-dependent cancer risk in the human prostate epithelium. PMID:24424067

  2. Computer vision approach to morphometric feature analysis of basal cell nuclei for evaluating malignant potentiality of oral submucous fibrosis.

    PubMed

    Muthu Rama Krishnan, M; Pal, Mousumi; Paul, Ranjan Rashmi; Chakraborty, Chandan; Chatterjee, Jyotirmoy; Ray, Ajoy K

    2012-06-01

    This research work presents a quantitative approach for analysis of histomorphometric features of the basal cell nuclei in respect to their size, shape and intensity of staining, from surface epithelium of Oral Submucous Fibrosis showing dysplasia (OSFD) to that of the Normal Oral Mucosa (NOM). For all biological activity, the basal cells of the surface epithelium form the proliferative compartment and therefore their morphometric changes will spell the intricate biological behavior pertaining to normal cellular functions as well as in premalignant and malignant status. In view of this, the changes in shape, size and intensity of staining of the nuclei in the basal cell layer of the NOM and OSFD have been studied. Geometric, Zernike moments and Fourier descriptor (FD) based as well as intensity based features are extracted for histomorphometric pattern analysis of the nuclei. All these features are statistically analyzed along with 3D visualization in order to discriminate the groups. Results showed increase in the dimensions (area and perimeter), shape parameters and decreasing mean nuclei intensity of the nuclei in OSFD in respect to NOM. Further, the selected features are fed to the Bayesian classifier to discriminate normal and OSFD. The morphometric and intensity features provide a good sensitivity of 100%, specificity of 98.53% and positive predicative accuracy of 97.35%. This comparative quantitative characterization of basal cell nuclei will be of immense help for oral onco-pathologists, researchers and clinicians to assess the biological behavior of OSFD, specially relating to their premalignant and malignant potentiality. As a future direction more extensive study involving more number of disease subjects is observed.

  3. Spatially limited growth of an epithelium

    NASA Astrophysics Data System (ADS)

    Deforet, Maxime; Cochet, Olivier; Buguin, Axel; Silberzan, Pascal

    2012-02-01

    We present a study dealing with the growth of an epithelium on a spatially limited adhesive substrate. Adhesive patterns (typical size: 50μm to 500μm) are created by micro-fabrication techniques: A protein repellent polymeric gel homogeneously grafted on a coverslip is selectively ablated by plasma treatment through a thin layer of photoresist. The technique achieves a high resolution of patterning (around 2μm). After seeding cells (MDCK) on circular adhesive patterns, we let the monolayer grow for 30 hours after reaching the confluence. We use physical descriptors to describe migration and compaction. Two days after the confluence, we observe and characterize by confocal microscopy, the appearance of a tridimensionnal assembly of cells in the peripherical zone of the adhesive pattern (a ``rim''). Moreover using other patterns, the existence of a tissue line tension and internal pressure is investigated.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Do Airway Epithelium Air–Liquid Cultures Represent the In Vivo Airway Epithelium Transcriptome?

    PubMed Central

    Dvorak, Anna; Tilley, Ann E.; Shaykhiev, Renat; Wang, Rui; Crystal, Ronald G.

    2011-01-01

    Human airway epithelial cells cultured in vitro at the air–liquid interface (ALI) form a pseudostratified epithelium that forms tight junctions and cilia, and produces mucin. These cells are widely used in models of differentiation, injury, and repair. To assess how closely the transcriptome of ALI epithelium matches that of in vivo airway epithelial cells, we used microarrays to compare the transcriptome of human large airway epithelial cells cultured at the ALI with the transcriptome of large airway epithelium obtained via bronchoscopy and brushing. Gene expression profiling showed that global gene expression correlated well between ALI cells and brushed cells, but with some differences. Gene expression patterns mirrored differences in proportions of cell types (ALIs have higher percentages of basal cells, whereas brushed cells have higher percentages of ciliated cells), that is, ALI cells expressed higher levels of basal cell–related genes, and brushed cells expressed higher levels of cilia-related genes. Pathway analysis showed that ALI cells had increased expression of cell cycle and proliferation genes, whereas brushed cells had increased expression of cytoskeletal organization and humoral immune response genes. Overall, ALI cells provide a good representation of the in vivo airway epithelial transcriptome, but for some biologic questions, the differences between in vitro and in vivo environments need to be considered. PMID:20525805

  9. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology. PMID:16277953

  10. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology.

  11. Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond

    PubMed Central

    Washio, Jumpei; Takahashi, Nobuhiro

    2016-01-01

    Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the ‘Warburg effect’. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases. PMID:27271597

  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. Human milk hyaluronan enhances innate defense of the intestinal epithelium.

    PubMed

    Hill, David R; Rho, Hyunjin K; Kessler, Sean P; Amin, Ripal; Homer, Craig R; McDonald, Christine; Cowman, Mary K; de la Motte, Carol A

    2013-10-01

    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn.

  14. Mesenchymal signaling in dorsoventral differentiation of palatal epithelium.

    PubMed

    Sohn, Wern-Joo; Gwon, Gi-Jeong; Kim, Hyeng-Soo; Neupane, Sanjiv; Cho, Sung-Jin; Lee, Jae-Hyung; Yamamoto, Hitoshi; Choi, Je-Yong; An, Chang-Hyeon; Lee, Youngkyun; Shin, Hong-In; Lee, Sanggyu; Kim, Jae-Young

    2015-12-01

    After palatal fusion, the dorsal and ventral epithelia of the palatal shelf differentiate into the nasal and oral mucosa, respectively. The tissue-specific differentiation of palatal epithelia along the dorsal-ventral axis is regulated by the signaling molecules expressed in the underlying mesenchyme. Thus, as in many other epithelial organs, differentiation relies on epithelial-mesenchymal interactions. To screen for region-specific mesenchymal signaling molecules that determine the fate of the palatal epithelia, we employed a laser microdissection (LMD) method. LMD allowed us to collect region-specific mesenchymal tissues at E13, prior to palatal fusion and the development of distinct dorsal and ventral epithelial morphology. Genome-wide screening was performed on the tissues collected using LMD to identify candidate mesenchymal signaling molecules. The microarray results were validated using real-time quantitative (qPCR) and in situ hybridization methods. The developmental role and interactions of the candidate genes were evaluated in in vitro-cultivated E13 palates using an anti-sense oligodeoxynucleotide (AS-ODN)-based loss-of-function approach. Apparent changes in the expression patterns of Runt-related transcription factor 2 (Runx2) and LIM homeobox 8 (Lhx8) were observed after knocking down each gene. Knock-down of Runx2 and Lhx8 also altered the immunolocalization pattern of cytokeratin18 (CK18), an established marker for nasal epithelium. These results were confirmed using Runx2 heterozygote mice. The mesenchymal signaling molecules Runx2 and Lhx8, which possess region-specific expression patterns along the dorsoventral axis, functionally interact to regulate the cellular and molecular characteristics of dorsal and ventral epithelia, suggesting that mesenchymal signaling molecules determine the dorsoventral fate of epithelial structures in the developing palate. PMID:26123167

  15. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

  16. Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells

    PubMed Central

    Fukahori, Mioko; Chitose, Shun-ichi; Sato, Kiminori; Sueyoshi, Shintaro; Kurita, Takashi; Umeno, Hirohito; Monden, Yu; Yamakawa, Ryoji

    2016-01-01

    Objectives Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells. Study Design Animal experiment using eight beagles (including three controls). Methods A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed. Results A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site. Conclusion The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds. PMID:26730600

  17. Simple epithelium keratins are required for maintenance of hepatocyte integrity.

    PubMed Central

    Loranger, A.; Duclos, S.; Grenier, A.; Price, J.; Wilson-Heiner, M.; Baribault, H.; Marceau, N.

    1997-01-01

    Keratin 8 (K8)-deficient adult mice develop a severe disease of the gastrointestinal tract characterized mainly by colorectal hyperplasia and inflammation. Given that hepatocytes contain K8/K18 heteropolymers only, this animal model was used to assess the contribution of these simple epithelium keratins to hepatocyte structural and functional integrity. Homozygous mutant (HMZ), heterozygous, and wild-type (WT) mice were examined for hepatocyte structural and metabolic features and their survival to partial hepatectomy. Except for the presence of few necrotic foci, no other tissular or cellular alterations were observed in nonhepatectomized HMZ mouse livers; glycogen and lipid peroxidation levels were essentially normal, but a small reduction in bile flow was observed. In response to a single pentobarbital injection, HMZ mice had longer sleeping times than heterozygous and WT mice. After a two-thirds partial hepatectomy under pentobarbital anesthesia, all HMZ mice died within a few hours, whereas those anesthetized with ether survived for 1 to 2 days. One hour after hepatectomy after pentobarbital anesthesia, many hepatocytes contained erythrocytes and large vacuoles in the cytoplasm, which suggests damage at the plasma membrane level in response to a sudden increase in portal blood flow. In line with these findings, an uptake of trypan blue by HMZ but not WT mouse hepatocytes was observed during a 10 ml/minute perfusion via the portal vein with a dye-supplemented buffer. Subsequent cellular dispersion led to viable WT mouse hepatocytes but largely nonviable HMZ mouse hepatocytes. Better viability was obtained at lower perfusion rates. Partially hepatectomized heterozygous mice developed liver steatosis, a condition that was not associated with a change in K8 content but perhaps linked to the presence of the neo gene. Transgenic HMZ mouse rescue experiments with a full-length K8 gene confirmed that the phenotypic alterations observed in partially hepatectomized HMZ

  18. 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

  19. 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.

  20. Cell Jamming in the Airway Epithelium.

    PubMed

    Park, Jin-Ah; Fredberg, Jeffrey J

    2016-03-01

    Hallmarks of asthma include chronic airway inflammation, progressive airway remodeling, and airway hyperresponsiveness. The initiation and perpetuation of these processes are attributable at least in part to critical events within the airway epithelium, but the underlying mechanisms remain poorly understood. New evidence now suggests that epithelial cells derived from donors without asthma versus donors with asthma, even in the absence of inflammatory cells or mediators, express modes of collective migration that innately differ not only in the amount of migration but also in the kind of migration. The maturing cell layer tends to undergo a transition from a hypermobile, fluid-like, unjammed phase in which cells readily rearrange, exchange places, and flow, to a quiescent, solid-like, jammed phase in which cells become virtually frozen in place. Moreover, the unjammed phase defines a phenotype that can be perpetuated by the compressive stresses caused by bronchospasm. Importantly, in cells derived from donors with asthma versus donors without asthma, this jamming transition becomes substantially delayed, thus suggesting an immature or dysmature epithelial phenotype in asthma. PMID:27027955

  1. Oral Insulin Delivery: How Far Are We?

    PubMed Central

    Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

    2013-01-01

    Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

  2. In-Vivo Nonlinear Optical Microscopy (NLOM) of Epithelial-Connective Tissue Interface (ECTI) Reveals Quantitative Measures of Neoplasia in Hamster Oral Mucosa

    PubMed Central

    Pal, Rahul; Yang, Jinping; Ortiz, Daniel; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2015-01-01

    The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (ΔLinearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ΔLinearity was significantly (p < 0.01) higher in dysplasia (0.41±0.24) than normal (0.11±0.04) as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ΔLinearity. Increase in ΔLinearity was also statistically significant for different grades of dysplasia. In-vivo ΔLinearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in

  3. Changes in the adult vertebrate auditory sensory epithelium after trauma.

    PubMed

    Oesterle, Elizabeth C

    2013-03-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes.

  4. [Ovarian surface epithelium and its histogenic relation to ovarian cancer].

    PubMed

    Dietl, J; Buchholz, F; Stoll, P

    1986-09-01

    Approximately 80 to 90 per cent of adult ovarian cancers are assumed to originate from ovarian surface cells. A series of morphological and biochemical studies has been recently conducted to test this. The ovarian surface epithelium shows permanent morphological changes such as crypts, inclusion cysts, villous processes and different forms of müllerian epithelium. The unique nature of ovarian surface changes and their abrupt disappearance in immediately adjacent mesothelia suggest that local factors may play an important part in modifying the growth and morphogenesis of the epithelium of the ovarian surface. Whether these endogenous and/or exogenous factors may also induce surface neoplasia is a moot point.

  5. Effects of irradiation on canine tracheal epithelium: a physiological and morphological correlate

    SciTech Connect

    Man, S.F.; Logus, J.W.; Mok, K.; Yamamoto, H.; Ahmed, I.H.; Man, G.C.; Hulbert, W.C.

    1987-01-01

    We delivered 20 Gy irradiation in one fraction to a 6 cm segment of trachea in 11 dogs. Tracheal mucous transport was studied before and whenever possible at weekly intervals after irradiation using a gamma camera system and /sup 99m/technetium labeled sulfur colloid. Ten of the eleven animals were sacrificed at three different time intervals (1-2, 15-16 and 30-34 weeks) post-irradiation, and the tracheal epithelium removed for studies using Ussing chambers followed by preparation for microscopic analysis. Mucous transport along the length of the trachea was normal before irradiation, but following irradiation it became abnormal in the irradiated zone. Compared to the epithelium from the cranial and caudal segments, the irradiated epithelium had similar bioelectric measurements (potential difference, short-circuit current and resistance) and mannitol permeability. Also, the changes in the bioelectric measurements following indomethacin (10(-6) M) and epinephrine (10(-6) M) used sequentially, were similar in both the control and irradiated tissues. Scanning electron microscopic analysis of the irradiated zone revealed patches of nonciliated epithelial cells among the ciliates. We conclude that irradiation caused a persistent replacement of ciliated cells with nonciliates throughout the entire study period and that this alteration impaired mucous transport but did not affect epithelial ion secretion or barrier function.

  6. DICER Regulates the Formation and Maintenance of Cell-Cell Junctions in the Mouse Seminiferous Epithelium.

    PubMed

    Korhonen, Hanna Maria; Yadav, Ram Prakash; Da Ros, Matteo; Chalmel, Frédéric; Zimmermann, Céline; Toppari, Jorma; Nef, Serge; Kotaja, Noora

    2015-12-01

    The endonuclease DICER that processes micro-RNAs and small interfering RNAs is essential for normal spermatogenesis and male fertility. We previously showed that the deletion of Dicer1 gene in postnatal spermatogonia in mice using Ngn3 promoter-driven Cre expression caused severe defects in the morphogenesis of haploid spermatid to mature spermatozoon, including problems in cell polarization and nuclear elongation. In this study, we further analyzed the same mouse model and revealed that absence of functional DICER in differentiating male germ cells induces disorganization of the cell-cell junctions in the seminiferous epithelium. We detected discontinuous and irregular apical ectoplasmic specializations between elongating spermatids and Sertoli cells. The defective anchoring of spermatids to Sertoli cells caused a premature release of spermatids into the lumen. Our findings may help also explain the abnormal elongation process of remaining spermatids because these junctions and the correct positioning of germ cells in the epithelium are critically important for the progression of spermiogenesis. Interestingly, cell adhesion-related genes were generally upregulated in Dicer1 knockout germ cells. Claudin 5 ( Cldn5 ) was among the most upregulated genes and we show that the polarized localization of CLAUDIN5 in the apical ectoplasmic specializations was lost in Dicer1 knockout spermatids. Our results suggest that DICER-dependent pathways control the formation and organization of cell-cell junctions in the seminiferous epithelium via the regulation of cell adhesion-related genes. PMID:26510868

  7. Lipoma in oral mucosa: two case reports.

    PubMed

    Hoseini, Ali Tavakoli; Razavi, Seyed Mohammad; Khabazian, Arezu

    2010-01-01

    Lipoma is a common tumor of soft tissue. Its location on the oral mucosa is rare, representing 1% to 5% of benign oral tumors although it is the most mesenchymal tumor of the trunk and proximal por-tions of extremities. Lipoma of the oral cavity may occur in any region. The buccal mucosa, tongue, and floor of the mouth are among the common locations. The clinical presentation is typically as an asymptomatic yellowish mass. The overlying epithelium is intact, and superficial blood vessels are usually evident over the tumor. Other benign connective tissue lesions such as granular cell tumor, neurofibroma, traumatic fibroma and salivary gland lesions (mucocele and mixed tumor) might be included in differential diagnosis. We present two cases of oral lipoma in unusual locations: one in junction of soft and hard palate and the other in tongue. Both were rare in the literature.

  8. Degeneration and recovery of rat olfactory epithelium following inhalation of dibasic esters.

    PubMed

    Keenan, C M; Kelly, D P; Bogdanffy, M S

    1990-08-01

    Dibasic esters (DBE) are solvent mixtures used in the paint and coating industry. To evaluate the potential subchronic toxicity of DBE, groups of male and female rats were exposed for periods of up to 13 weeks to DBE concentrations of 0, 20, 76, or 390 mg/m3. After approximately 7 and 13 weeks of exposure, 10 rats per sex per group were subjected to clinical chemical, hematological, and urine analyses. Following 7 or 13 weeks of exposure, 10 or 20 rats per sex per group, respectively, were euthanized. An additional 10 rats were euthanized following a 6-week recovery period. A standard profile of tissues, including four levels of nasal cavity, was evaluated histopathologically. After 7 weeks of exposure, slight degeneration of the olfactory epithelium was observed in both male and female rats at 76 and 390 mg/m3. After 13 weeks, degeneration of the olfactory epithelium was present at all DBE concentrations in female rats, but only at the mid and high concentrations in male rats. The severity and incidence of the lesions were concentration related for both sexes with female rats being more sensitive than males. Following the recovery period, histological changes compatible with repair in the olfactory mucosa included an absence of degeneration, focal disorganization of the olfactory epithelium, and respiratory metaplasia. All other tissues were macroscopically normal. No other signs of toxicity were indicated by the other parameters evaluated. Inhalation studies of other esters demonstrate similar pathology in the olfactory epithelium. Since olfactory mucosa is rich in carboxylesterase activity, acids may be the toxic metabolites of these compounds. This hypothetical mechanism may explain the sensitivity of olfactory tissue to the effects of DBE.

  9. 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

  10. Melanocyte biology and function with reference to oral melanin hyperpigmentation in HIV-seropositive subjects.

    PubMed

    Feller, Liviu; Chandran, Rakesh; Kramer, Beverley; Khammissa, Razia A G; Altini, Mario; Lemmer, Johan

    2014-09-01

    The color of normal skin and of oral mucosa is not determined by the number of melanocytes in the epithelium but rather by their melanogenic activity. Pigmented biopolymers or melanins are synthesized in melanosomes. Tyrosinase is the critical enzyme in the biosynthesis of both brown/black eumelanin and yellow/red pheomelanin. The number of the melanosomes within the melanocytes, the type of melanin within the melanosomes, and the efficacy of the transfer of melanosomes from the melanocytes to the neighboring keratinocytes all play an important role in tissue pigmentation. Melanin production is regulated by locally produced factors including proopiomelanocortin and its derivative peptides, particularly alpha-melanocyte-stimulating hormone (α-MSH), melanocortin 1 receptor (MC1R), adrenergic and cholinergic agents, growth factors, cytokines, and nitric oxide. Both eumelanin and pheomelanin can be produced by the same melanocytes, and the proportion of the two melanin types is influenced by the degree of functional activity of the α-MSH/MC1R intracellular pathway. The cause of HIV oral melanosis is not fully understood but may be associated with HIV-induced cytokine dysregulation, with the medications commonly prescribed to HIV-seropositive persons, and with adrenocortical dysfunction, which is not uncommon in HIV-seropositive subjects with AIDS. The purpose of this article is to discuss some aspects of melanocyte biology and HIV-associated oral melanin hyperpigmentation.

  11. The presence of bacteria within tissue provides insights into the pathogenesis of oral lichen planus

    PubMed Central

    Choi, Yun Sik; Kim, Yunji; Yoon, Hye-Jung; Baek, Keum Jin; Alam, Jehan; Park, Hee Kyung; Choi, Youngnim

    2016-01-01

    Oral lichen planus (OLP) is a chronic T cell-mediated mucocutaneous disease of unknown etiopathogenesis. Although various antigens have been considered, what actually triggers the inflammatory response of T cells is unknown. In the present study, we propose that intracellular bacteria present within tissues trigger T cell infiltration and provide target antigens. Sections of OLP (n = 36) and normal (n = 10) oral mucosal tissues were subjected to in situ hybridization using a universal probe targeting the bacterial 16S rRNA gene and immunohistochemistry with anti-CD3, anti-CD4, anti-CD8, and anti-macrophage-specific antibodies. Bacteria were abundant throughout the epithelium and the lamina propria of OLP tissues, which exhibited positive correlations with the levels of infiltrated CD3+, CD4+, and CD8+ cells. Furthermore, bacteria were detected within the infiltrated T cells. Pyrosequencing analysis of the mucosal microbiota from OLP patients (n = 13) and control subjects (n = 11) revealed a decrease in Streptococcus and increases in gingivitis/periodontitis-associated bacteria in OLP lesions. Using the selected bacterial species, we demonstrated that certain oral bacteria damage the epithelial physical barrier, are internalized into epithelial cells or T cells, and induce production of T cell chemokines CXCL10 and CCL5. Our findings provide insights into the pathogenesis of OLP. PMID:27383402

  12. The presence of bacteria within tissue provides insights into the pathogenesis of oral lichen planus.

    PubMed

    Choi, Yun Sik; Kim, Yunji; Yoon, Hye-Jung; Baek, Keum Jin; Alam, Jehan; Park, Hee Kyung; Choi, Youngnim

    2016-01-01

    Oral lichen planus (OLP) is a chronic T cell-mediated mucocutaneous disease of unknown etiopathogenesis. Although various antigens have been considered, what actually triggers the inflammatory response of T cells is unknown. In the present study, we propose that intracellular bacteria present within tissues trigger T cell infiltration and provide target antigens. Sections of OLP (n = 36) and normal (n = 10) oral mucosal tissues were subjected to in situ hybridization using a universal probe targeting the bacterial 16S rRNA gene and immunohistochemistry with anti-CD3, anti-CD4, anti-CD8, and anti-macrophage-specific antibodies. Bacteria were abundant throughout the epithelium and the lamina propria of OLP tissues, which exhibited positive correlations with the levels of infiltrated CD3(+), CD4(+), and CD8(+) cells. Furthermore, bacteria were detected within the infiltrated T cells. Pyrosequencing analysis of the mucosal microbiota from OLP patients (n = 13) and control subjects (n = 11) revealed a decrease in Streptococcus and increases in gingivitis/periodontitis-associated bacteria in OLP lesions. Using the selected bacterial species, we demonstrated that certain oral bacteria damage the epithelial physical barrier, are internalized into epithelial cells or T cells, and induce production of T cell chemokines CXCL10 and CCL5. Our findings provide insights into the pathogenesis of OLP. PMID:27383402

  13. Progress in reflectance confocal microscopy for imaging oral tissues in vivo

    NASA Astrophysics Data System (ADS)

    Peterson, Gary; Zanoni, Daniella K.; Migliacci, Jocelyn; Cordova, Miguel; Rajadhyaksha, Milind; Patel, Snehal

    2016-02-01

    We report progress in development and feasibility testing of reflectance confocal microscopy (RCM) for imaging in the oral cavity of humans. We adapted a small rigid relay telescope (120mm long x 14mm diameter) and a small water immersion objective lens (12mm diameter, NA 0.7) to a commercial handheld RCM scanner (Vivascope 3000, Caliber ID, Rochester NY). This scanner is designed for imaging skin but we adapted the front end (the objective lens and the stepper motor that axially translates) for intra-oral use. This adaption required a new approach to address the loss of the automated stepper motor for acquisition of images in depth. A helical spring-like cap (with a coverslip to contact tissue) was designed for approximately 150 um of travel. Additionally other methods for focusing optics were designed and evaluated. The relay telescope optics is being tested in a clinical setting. With the capture of video and "video-mosaicing", extended areas can be imaged. The feasibility of imaging oral tissues was initially investigated in volunteers. RCM imaging in buccal mucosa in vivo shows nuclear and cellular detail in the epithelium and epithelial junction, and connective tissue and blood flow in the underlying lamina propria. Similar detail, including filiform and fungiform papillae, can be seen on the tongue in vivo. Clinical testing during head and neck surgery is now in progress and patients are being imaged for both normal tissue and cancerous margins in lip and tongue mucosa.

  14. Rapid disappearance of the medial epithelial seam during palatal fusion occurs by multifocal breakdown that is preceded by expression of alpha smooth muscle actin in the epithelium.

    PubMed

    Gibbins, J R; Brent, S; Srivastava, M; Garibotto, N; Tazawa, Y M; Cameron, A; Hunter, N

    2000-02-01

    Breakdown of the medial epithelial seam (MES) is essential to allow bridging of the mesenchyme during palatal fusion. Evidence exists for three mechanisms for this breakdown that are incompatible at the level of individual cells in the seam. To determine if breakdown of the seam was regionally restricted, 3-dimensional reconstructions were generated using volume rendering software from 1 micron serial sections in the sagittal plane of rat palates fixed during the process of fusion. The earliest break detected in electron micrographs was cell separation and in reconstructions was a discrete defect, with a rounded outline, nearer to the nasal than to the oral margin of the seam. Further breakdown produced a pattern of rounded defects along the nasal margin of the seam resulting in interconnected columns of cells preferentially attached to the oral epithelium. Computer generated slicing of reconstructed seams showed that groups of cells evident in cross-sections as islands at this stage of breakdown of the MES could be artifacts. Unequivocal islands of epithelial cells formed later in fusion had a rounded outline, an incomplete basal lamina and a halo of cells containing phagocytosed apoptotic debris. The pattern of breakdown indicated that the MES breaks down under tension. Laser confocal microscopy of sections and whole-mounts of palates demonstrated alpha-smooth muscle actin preferentially localized in the epithelial cells of the palatal shelves immediately before and during formation of the seam. Expression in epithelial cells of the isoform of actin normally restricted to smooth muscle cells engaged in tonic contraction supported an interpretation that the epithelial cells of the seam may be capable of generating tension during the palatal fusion event. PMID:10794080

  15. Human papillomavirus infections and oral tumors.

    PubMed

    Syrjänen, Stina

    2003-08-01

    In the past 20 years, there has been an increasing interest in human papillomaviruses (HPV) because of their potential role in the pathogenesis of malignant tumors. In 1983, we published the first evidence that HPV might be involved in oral squamous cell carcinomas. The identification of morphological similarities between oral and cervical mucosa lead us to this original proposal. In a recent meta-analysis, HPV was indeed confirmed as an independent risk factor for oral carcinoma. To date, totally more than 100 types of HPV have been identified. As in anogenital cancers, HPV type 16 is the most prevalent type in oral carcinomas. The benign oral lesions, associated with HPV infection, include squamous cell papilloma, condyloma acuminatum, verrucca vulgaris and focal epithelial hyperplasia (FEH). Papillomas and condylomas are mostly caused by HPV type 6 or 11, while oral verrucas are associated with the skin types 2 or 4. A family history of FEH has been suggested. The FEH lesions are caused by HPV types 13 and 32, only detected in oral epithelium. In immunocompromised patients, benign HPV-induced lesions are characterized by atypical morphology and the simultaneous detection of multiple HPV types. Oral benign HPV lesions are mostly asymptomatic, and may persist or regress spontaneously.

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

    PubMed

    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.

  17. 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.

  18. Tonsillar crypt epithelium is an important extra-central nervous system site for viral replication in EV71 encephalomyelitis.

    PubMed

    He, Yaoxin; Ong, Kien Chai; Gao, Zifen; Zhao, Xishun; Anderson, Virginia M; McNutt, Michael A; Wong, Kum Thong; Lu, Min

    2014-03-01

    Enterovirus 71 (EV71; family Picornaviridae, species human Enterovirus A) usually causes hand, foot, and mouth disease, which may rarely be complicated by fatal encephalomyelitis. We investigated extra-central nervous system (extra-CNS) tissues capable of supporting EV71 infection and replication, and have correlated tissue infection with expression of putative viral entry receptors, scavenger receptor B2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL-1). Formalin-fixed, paraffin-embedded CNS and extra-CNS tissues from seven autopsy cases were examined by IHC and in situ hybridization to evaluate viral antigens and RNA. Viral receptors were identified with IHC. In all seven cases, the CNS showed stereotypical distribution of inflammation and neuronal localization of viral antigens and RNA, confirming the clinical diagnosis of EV71 encephalomyelitis. In six cases in which tonsillar tissues were available, viral antigens and/or RNA were localized to squamous epithelium lining the tonsillar crypts. Tissues from the gastrointestinal tract, pancreas, mesenteric nodes, spleen, and skin were all negative for viral antigens/RNA. Our novel findings strongly suggest that tonsillar crypt squamous epithelium supports active viral replication and represents an important source of viral shedding that facilitates person-to-person transmission by both the fecal-oral or oral-oral routes. It may also be a portal for viral entry. A correlation between viral infection and SCARB2 expression appears to be more significant than for PSGL-1 expression.

  19. Live imaging of baculovirus infection of midgut epithelium cells: a functional assay of per os infectivity factors.

    PubMed

    Mu, Jingfang; van Lent, Jan W M; Smagghe, Guy; Wang, Yun; Chen, Xinwen; Vlak, Just M; van Oers, Monique M

    2014-11-01

    The occlusion-derived viruses (ODVs) of baculoviruses are responsible for oral infection of insect hosts, whereas budded viruses (BVs) are responsible for systemic infection within the host. The ODV membrane proteins play crucial roles in mediating virus entry into midgut epithelium cells to initiate infection and are important factors in host-range determination. For Autographa californica multiple nucleopolyhedrovirus (AcMNPV), seven conserved ODV membrane proteins have been shown to be essential for oral infectivity and are called per os infectivity factors (PIFs). Information on the function of the individual PIF proteins in virus entry is limited, partly due to the lack of a good in vitro system for monitoring ODV entry. Here, we constructed a baculovirus with EGFP fused to the nucleocapsid to monitor virus entry into primary midgut epithelium cells ex vivo using confocal fluorescence microscopy. The EGFP-labelled virus showed similar BV virulence and ODV infectivity as WT virus. The ability to bind and enter host cells was then visualized for WT AcMNPV and viruses with mutations in P74 (PIF0), PIF1 or PIF2, showing that P74 is required for ODV binding, whilst PIF1 and PIF2 play important roles in the entry of ODV after binding to midgut cells. This is the first live imaging of ODV entry into midgut cells and complements the genetic and biochemical evidence for the role of PIFs in the oral infection process. PMID:25006078

  20. Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium.

    PubMed

    Nickell, William T; Kleene, Nancy K; Kleene, Steven J

    2007-09-15

    When olfactory receptor neurons respond to odours, a depolarizing Cl(-) efflux is a substantial part of the response. This requires that the resting neuron accumulate Cl(-) against an electrochemical gradient. In isolated olfactory receptor neurons, the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 is essential for Cl(-) accumulation. However, in intact epithelium, a robust electrical olfactory response persists in mice lacking NKCC1. This response is largely due to a neuronal Cl(-) efflux. It thus appears that NKCC1 is an important part of a more complex system of Cl(-) accumulation. To identify the remaining transport proteins, we first screened by RT-PCR for 21 Cl(-) transporters in mouse nasal tissue containing olfactory mucosa. For most of the Cl(-) transporters, the presence of mRNA was demonstrated. We also investigated the effects of pharmacological block or genetic ablation of Cl(-) transporters on the olfactory field potential, the electroolfactogram (EOG). Mice lacking the common Cl(-)/HCO(3)(-) exchanger AE2 had normal EOGs. Block of NKCC cotransport with bumetanide reduced the EOG in epithelia from wild-type mice but had no effect in mice lacking NKCC1. Hydrochlorothiazide, a blocker of the Na(+)-Cl(-) cotransporter, had only a small effect. DIDS, a blocker of some KCC cotransporters and Cl(-)/HCO(3)(-) exchangers, reduced the EOG in epithelia from both wild-type and NKCC1 knockout mice. A combination of bumetanide and DIDS decreased the response more than either drug alone. However, no combination of drugs completely abolished the Cl(-) component of the response. These results support the involvement of both NKCC1 and one or more DIDS-sensitive transporters in Cl(-) accumulation in olfactory receptor neurons.

  1. Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium

    PubMed Central

    Nickell, William T; Kleene, Nancy K; Kleene, Steven J

    2007-01-01

    When olfactory receptor neurons respond to odours, a depolarizing Cl− efflux is a substantial part of the response. This requires that the resting neuron accumulate Cl− against an electrochemical gradient. In isolated olfactory receptor neurons, the Na+–K+–2Cl− cotransporter NKCC1 is essential for Cl− accumulation. However, in intact epithelium, a robust electrical olfactory response persists in mice lacking NKCC1. This response is largely due to a neuronal Cl− efflux. It thus appears that NKCC1 is an important part of a more complex system of Cl− accumulation. To identify the remaining transport proteins, we first screened by RT-PCR for 21 Cl− transporters in mouse nasal tissue containing olfactory mucosa. For most of the Cl− transporters, the presence of mRNA was demonstrated. We also investigated the effects of pharmacological block or genetic ablation of Cl− transporters on the olfactory field potential, the electroolfactogram (EOG). Mice lacking the common Cl−/HCO3− exchanger AE2 had normal EOGs. Block of NKCC cotransport with bumetanide reduced the EOG in epithelia from wild-type mice but had no effect in mice lacking NKCC1. Hydrochlorothiazide, a blocker of the Na+–Cl− cotransporter, had only a small effect. DIDS, a blocker of some KCC cotransporters and Cl−/HCO3− exchangers, reduced the EOG in epithelia from both wild-type and NKCC1 knockout mice. A combination of bumetanide and DIDS decreased the response more than either drug alone. However, no combination of drugs completely abolished the Cl− component of the response. These results support the involvement of both NKCC1 and one or more DIDS-sensitive transporters in Cl− accumulation in olfactory receptor neurons. PMID:17656441

  2. Injurious effects of lysophosphatidylcholine on barrier properties of alveolar epithelium.

    PubMed

    Niewoehner, D E; Rice, K; Sinha, A A; Wangensteen, D

    1987-11-01

    We studied the effects of lysophosphatidylcholine (lysoPC) on the barrier properties and the morphology of the alveolar-capillary membrane in isolated, fluid-filled hamster lungs continuously perfused. When instilled into the airspace at initial concentrations of 8-128 micrograms/ml, lysoPC causes dose-dependent increases in the permeability-surface area product of the alveolar epithelium for small (14C-sucrose, 342) and large (125I-neutral dextran, 70,000) solutes, with maximal values for each solute approximately 15 times control. Rapid whole-lung weight gains are caused by 128 micrograms lysoPC per milliliter, but each of the lower concentrations has no effect on net lung water balance. Electron-microscopic studies demonstrate that type I pneumonocytes are the lung cells most susceptible to lysoPC exposure, with cell swelling being the most prominent feature from low-dose exposure with more severe disruptive changes at the highest concentration tested. The effects of lysoPC are relatively specific, as several structurally related lipids have little or no effect at equivalent concentrations. Instillation of phospholipase A2 causes functional changes similar to those seen with lysoPC, presumably by generation of lysoPC from endogenous phospholipids. Studies employing a 14C-radiolabeled compound show that instilled lysoPC rapidly partitions into the lung lipid fraction where a major portion of the acyl group becomes incorporated into phosphatidylcholine. The amount of instilled lysoPC required to produce functional and morphological effects comprises only a few percent of total lung phospholipids. Since lysoPC is a normal component of lung phospholipids, severe lung dysfunction might result from minor abnormalities in the formation or degradation of this compound.

  3. Optical Coherence Tomography for Quantitative Assessment of Microstructural and Microvascular Alterations in Late Oral Radiation Toxicity

    NASA Astrophysics Data System (ADS)

    Davoudi, Bahar

    More than half of head-and-neck cancer patients undergo radiotherapy at some point during their treatment. Even though the use of conformed therapeutic beams has increased radiation dose localization to the tumor, resulting in more normal tissue sparing, still, in many head-and-neck cancer patients, the healthy tissue of the oral cavity still receives a sizeable amount of radiation. This causes acute and / or late complications in these patients. The latter occur as late as several months or even years after the completion of treatment and are typically associated with severe symptoms. Currently, the clinical method for diagnosing these complications is visual examination of the oral tissue surface. However, it has been well established that such complications originate in subsurface oral tissue layers including its microvasculature. Therefore, to better understand the mechanism of these complications and to be able to diagnose them earlier, there exists a need for subsurface monitoring of the irradiated oral tissue. Histology has been used as such a tool for research purposes; however, its use in clinical diagnosis is limited due to its invasive and hazardous nature. Therefore, in this thesis, I propose to use optical coherence tomography (OCT) as a subsurface, micron-scale resolution optical imaging tool that can provide images of oral tissue subsurface layers down to a depth of 1-2 mm (structural OCT), as well as images demonstrating vessel morphology (speckle variance OCT) and blood flow information (Doppler OCT). This thesis explains the development of an OCT setup and an oral probe to acquire images in-vivo. Moreover, it introduces a software-based quantification platform for extracting specific biologically-meaningful metrics from the structural and vascular OCT images. It then describes the application of the developed imaging and quantification platform in a feasibility clinical study that was performed on 15 late oral radiation toxicity patients and 5 age

  4. Oral cysticercosis.

    PubMed

    Chunduri, Nagendra S; Goteki, Venkateswarulu; Gelli, Vamsi; Madasu, Krishnaveni

    2013-03-01

    Cysticercosis is a common disease in developing countries, but oral lesions caused by this parasitic infestation are rare. We report here a rare case of oral cysticercosis in a 17 year old male who sought treatment for an asymptomatic nodule of the lower lip that had previously been diagnosed as a mucocele. PMID:23691623

  5. Global expression profiling of globose basal cells and neurogenic progression within the olfactory epithelium.

    PubMed

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

    2013-03-01

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

  6. Global expression profiling of globose basal cells and neurogenic progression within the olfactory epithelium.

    PubMed

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

    2013-03-01

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

  7. Nrf2 deficiency impairs the barrier function of mouse esophageal epithelium

    PubMed Central

    Chen, Hao; Hu, Yuhui; Fang, Yu; Djukic, Zorka; Yamamoto, Masayuki; Shaheen, Nicholas J.; Orlando, Roy C.; Chen, Xiaoxin

    2013-01-01

    Objective As a major cellular defense mechanism, the Nrf2/Keap1 pathway regulates expression of genes involved in detoxification and stress response. Our previous study revealed activation of the Nrf2/Keap1 pathway at the maturation phase during mouse esophageal development, suggesting a potential function in epithelial defense. Here we hypothesize that Nrf2 is involved in the barrier function of esophageal epithelium, and plays a protective role against gastroesophageal reflux disease (GERD). Design Human esophageal biopsy samples, mouse surgical models and Nrf2-/- mice were used to assess the role of the Nrf2/Keap1 pathway in esophageal mucosal barrier function. Trans-epithelial electrical resistance (TEER) was measured with mini-Ussing chambers. Hematoxylin and eosin (HE) staining and transmission electron microscopy were used to examine cell morphology, while gene microarray, immunohistochemistry, Western blotting and ChIP analysis were used to assess the expression of pathway genes. Results Nrf2 was expressed in normal esophageal epithelium and activated in GERD of both humans and mice. Nrf2 deficiency and gastroesophageal reflux in mice, either alone or in combination, reduced TEER and increased intercellular space diameter in esophageal epithelium. Nrf2 target genes and gene sets associated with oxidoreductase activity, mitochondrial biogenesis and energy production were down-regulated in the esophageal epithelium of Nrf2-/- mice. Consistent with the antioxidative function of Nrf2, a DNA oxidative damage marker (8OHdG) dramatically increased in esophageal epithelial cells of Nrf2-/- mice compared with those of wild-type mice. Interestingly, ATP biogenesis, Cox IV (a mitochondrial protein) and Claudin-4 (Cldn4) expression were down-regulated in the esophageal epithelium of Nrf2-/- mice, suggesting that energy-dependent tight junction integrity was subject to Nrf2 regulation. ChIP analysis confirmed the binding of Nrf2 to Cldn4 promoter. Conclusion Nrf2

  8. Examination of Oral Cancer Biomarkers by Tissue Microarray Analysis

    PubMed Central

    Choi, Peter; Jordan, C. Diana; Mendez, Eduardo; Houck, John; Yueh, Bevan; Farwell, D. Gregory; Futran, Neal; Chen, Chu

    2008-01-01

    Background Oral squamous cell carcinoma (OSCC) is a major healthcare problem worldwide. Efforts in our laboratory and others focusing on the molecular characterization of OSCC tumors with the use of DNA microarrays have yielded heterogeneous results. To validate the DNA microarray results on a subset of genes from these studies that could potentially serve as biomarkers of OSCC, we elected to examine their expression by an alternate quantitative method and by assessing their protein levels. Design Based on DNA microarray data from our lab and data reported in the literature, we identified six potential biomarkers of OSCC to investigate further. We employed quantitative, real-time polymerase chain reaction (qRT-PCR) to examine expression changes of CDH11, MMP3, SPARC, POSTN, TNC, TGM3 in OSCC and normal control tissues. We further examined validated markers on the protein level by immunohistochemistry (IHC) analysis of OSCC tissue microarray (TMA) sections. Results qRT-PCR analysis revealed up-regulation of CDH11, SPARC, POSTN, and TNC gene expression, and decreased TGM3 expression in OSCC compared to normal controls. MMP3 was not found to be differentially expressed. In TMA IHC analyses, SPARC, periostin, and tenascin C exhibited increased protein expression in cancer compared to normal tissues, and their expression was primarily localized within tumor-associated stroma rather than tumor epithelium. Conversely, transglutaminase-3 protein expression was found only within keratinocytes in normal controls, and was significantly down-regulated in cancer cells. Conclusions Of six potential gene markers of OSCC, initially identified by DNA microarray analyses, differential expression of CDH11, SPARC, POSTN, TNC, and TGM3 were validated by qRT-PCR. Differential expression and localization of proteins encoded by SPARC, POSTN, TNC, and TGM3 were clearly shown by TMA IHC. PMID:18490578

  9. Oral cenesthopathy.

    PubMed

    Umezaki, Yojiro; Miura, Anna; Watanabe, Motoko; Takenoshita, Miho; Uezato, Akihito; Toriihara, Akira; Nishikawa, Toru; Toyofuku, Akira

    2016-01-01

    Cenesthopathy is characterized by abnormal and strange bodily sensations and is classified as a 'delusional disorder, somatic type' or 'somatoform disorder' according to the DSM 5. The oral cavity is one of the frequent sites of cenesthopathy, thus the term 'oral cenesthopathy.' Patients with oral cenesthopathy complain of unusual sensations without corresponding abnormal findings in the oral area, such as excessive mucus secretion, a slimy sensation, or a feeling of coils or wires being present within the oral region. They usually visit multiple dentists rather than psychiatrists. Without a proper diagnosis, they repeatedly pursue unnecessary surgical procedures to remove their 'foreign body'. This sometimes creates a dilemma between the dentists and patients. The nosography of oral cenesthopathy has been discussed in some case reports and reviews but is overlooked in mainstream medicine. This review focuses on the various aspects of oral cenesthopathy. The estimated prevalence of cenesthopathy was 0.2 to 1.9 % in a study done at a Japanese university psychiatry clinic and 27 % in a study done at a Japanese psychosomatic dentistry clinic. Oral cenesthopathy do not have clear disposition, while some studies reported that elderly women were most commonly affected. Its pathophysiology has not been fully elucidated. However, recent studies have suggested a right > left asymmetrical pattern of the cerebral blood flow of patients with oral cenesthopathy. Antidepressants, antipsychotic drugs, electroconvulsive therapy, and psychotherapy might be effective in some cases, though it is known to be intractable. To date, the epidemiology, pathophysiology, etiology, classification and treatment of oral cenesthopathy are unknown due to the few reports on the disorder, though there are a few case reports. To overcome this difficult medical condition, clinico-statistical and case-control studies done under rigorous criteria and with a large sample size are required. PMID

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

    PubMed

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

    2015-03-01

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

  11. FOXJ1 Prevents Cilia Growth Inhibition by Cigarette Smoke in Human Airway Epithelium In Vitro

    PubMed Central

    Brekman, Angelika; Walters, Matthew S.; Tilley, Ann E.

    2014-01-01

    Airway epithelium ciliated cells play a central role in clearing the lung of inhaled pathogens and xenobiotics, and cilia length and coordinated beating are important for airway clearance. Based on in vivo studies showing that the airway epithelium of healthy smokers has shorter cilia than that of healthy nonsmokers, we investigated the mechanisms involved in cigarette smoke–mediated inhibition of ciliogenesis by assessing normal human airway basal cell differentiation in air–liquid interface (ALI) cultures in the presence of nontoxic concentrations of cigarette smoke extract (CSE). Measurements of cilia length from Day 28 ALI cultures demonstrated that CSE exposure was associated with shorter cilia (P < 0.05), reproducing the effect of cigarette smoking on cilia length observed in vivo. This phenotype correlated with a broad CSE-mediated suppression of genes involved in cilia-related transcriptional regulation, intraflagellar transport, cilia motility, structural integrity, and basal body development but not of control genes or epithelial barrier integrity. The CSE-mediated inhibition of cilia growth could be prevented by lentivirus-mediated overexpression of FOXJ1, the major cilia-related transcription factor, which led to partial reversal of expression of cilia-related genes suppressed by CSE. Together, the data suggest that components of cigarette smoke are responsible for a broad suppression of genes involved in cilia growth, but, by stimulating ciliogenesis with the transcription factor FOXJ1, it may be possible to maintain close to normal cilia length despite the stress of cigarette smoking. PMID:24828273

  12. BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors

    PubMed Central

    Tadokoro, Tomomi; Gao, Xia; Hong, Charles C.; Hotten, Danielle; Hogan, Brigid L. M.

    2016-01-01

    The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this brake is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair, the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal crucial roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium. PMID:26811382

  13. BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors.

    PubMed

    Tadokoro, Tomomi; Gao, Xia; Hong, Charles C; Hotten, Danielle; Hogan, Brigid L M

    2016-03-01

    The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this brake is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair, the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal crucial roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium. PMID:26811382

  14. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention.

    PubMed

    Holpuch, Andrew S; Phelps, Maynard P; Desai, Kashappa-Goud H; Chen, Wei; Koutras, George M; Han, Byungdo B; Warner, Blake M; Pei, Ping; Seghi, Garrett A; Tong, Meng; Border, Michael B; Fields, Henry W; Stoner, Gary D; Larsen, Peter E; Liu, Zhongfa; Schwendeman, Steven P; Mallery, Susan R

    2012-05-01

    Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels. Local drug delivery, however, provides site-specific therapeutically relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal mucosa. Fenretinide and blank-control patches were placed on right/left buccal mucosa, respectively, in eight rabbits (30 min, q.d., 10 days). No clinical or histological deleterious effects occurred. LC-MS/MS analyses of post-treatment samples revealed a delivery gradient with highest fenretinide levels achieved at the patch-mucosal interface (no metabolites), pharmacologically active levels in fenretinide-treated oral mucosa (mean: 5.65 μM; trace amounts of 4-oxo-4-HPR) and undetectable sera levels. Epithelial markers for cell proliferation (Ki-67), terminal differentiation (transglutaminase 1-TGase1) and glucuronidation (UDP-glucuronosyltransferase1A1-UGT1A1) exhibited fenretinide concentration-specific relationships (elevated TGase1 and UGT1A1 levels <5 μM, reduced Ki-67 indices >5 μM) relative to blank-treated epithelium. All fenretinide-treated tissues showed significantly increased intraepithelial apoptosis (TUNEL) positivity, implying activation of intersecting apoptotic and differentiation pathways. Human oral mucosal correlative studies showed substantial interdonor variations in levels of the enzyme (cytochrome P450 3A4-CYP3A4) responsible for conversion of fenretinide to its highly active metabolite, 4-oxo-4-HPR. Complementary in vitro assays in human oral keratinocytes revealed fenretinide and 4-oxo-4-HPR's preferential suppression of DNA synthesis in dysplastic as opposed to normal oral keratinocytes. Collectively, these data showed that mucoadhesive patch-mediated fenretinide delivery is a viable strategy to reintroduce

  15. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention.

    PubMed

    Holpuch, Andrew S; Phelps, Maynard P; Desai, Kashappa-Goud H; Chen, Wei; Koutras, George M; Han, Byungdo B; Warner, Blake M; Pei, Ping; Seghi, Garrett A; Tong, Meng; Border, Michael B; Fields, Henry W; Stoner, Gary D; Larsen, Peter E; Liu, Zhongfa; Schwendeman, Steven P; Mallery, Susan R

    2012-05-01

    Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels. Local drug delivery, however, provides site-specific therapeutically relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal mucosa. Fenretinide and blank-control patches were placed on right/left buccal mucosa, respectively, in eight rabbits (30 min, q.d., 10 days). No clinical or histological deleterious effects occurred. LC-MS/MS analyses of post-treatment samples revealed a delivery gradient with highest fenretinide levels achieved at the patch-mucosal interface (no metabolites), pharmacologically active levels in fenretinide-treated oral mucosa (mean: 5.65 μM; trace amounts of 4-oxo-4-HPR) and undetectable sera levels. Epithelial markers for cell proliferation (Ki-67), terminal differentiation (transglutaminase 1-TGase1) and glucuronidation (UDP-glucuronosyltransferase1A1-UGT1A1) exhibited fenretinide concentration-specific relationships (elevated TGase1 and UGT1A1 levels <5 μM, reduced Ki-67 indices >5 μM) relative to blank-treated epithelium. All fenretinide-treated tissues showed significantly increased intraepithelial apoptosis (TUNEL) positivity, implying activation of intersecting apoptotic and differentiation pathways. Human oral mucosal correlative studies showed substantial interdonor variations in levels of the enzyme (cytochrome P450 3A4-CYP3A4) responsible for conversion of fenretinide to its highly active metabolite, 4-oxo-4-HPR. Complementary in vitro assays in human oral keratinocytes revealed fenretinide and 4-oxo-4-HPR's preferential suppression of DNA synthesis in dysplastic as opposed to normal oral keratinocytes. Collectively, these data showed that mucoadhesive patch-mediated fenretinide delivery is a viable strategy to reintroduce

  16. Oral and neck examination for early detection of oral cancer--a practical guide.

    PubMed

    MacCarthy, Denise; Flint, Stephen R; Healy, Claire; Stassen, Leo F A

    2011-01-01

    Cancer of the head and neck region presents a challenge since, unlike other areas of the body, the boundaries are not always easy to delineate. The functional morbidity associated with head and neck cancer and its treatment are considerable. Head and neck cancer is described as cancer of the lip, mouth, tongue, tonsil, pharynx (unspecified), salivary gland, hypopharynx, larynx and other. Oral cancer refers to cancers of the lip, tongue, gingivae, floor of the mouth, palate (hard and soft), maxilla, vestibule and retromolar area up to the anterior pillar of the fauces (tonsil). When patients present with oral cancer, over 60% of them have regional (lymph node) and sometimes distant (metastatic) spread. The overall five-year survival rates for oral cancer average at between 50 and 80%, depending on the stage of the disease, varying from 86% for stage I to 12-16% for stage IV. The incidence of 'field cancerisation'/unstable oral epithelium is high (17%), and even after successful treatment our patients need to be monitored for dental care and further disease. Unlike other areas in the body, the oral epithelium is readily accessible for examination and even self-examination. Dentists and dental hygienists are effective clinicians in the examination of the oral cavity for mouth cancer. An oral and neck examination must be part of every dental examination. An examination protocol is suggested here, which is similar to, but more detailed than, the standardised oral examination method recommended by the World Health Organisation, and consistent with those protocols followed by the Centres for Disease Control and Prevention and the National Institutes of Health.

  17. The Oral Microbiota.

    PubMed

    Arweiler, Nicole B; Netuschil, Lutz

    2016-01-01

    The oral microbiota represents an important part of the human microbiota, and includes several hundred to several thousand diverse species. It is a normal part of the oral cavity and has an important function to protect against colonization of extrinsic bacteria which could affect systemic health. On the other hand, the most common oral diseases caries, gingivitis and periodontitis are based on microorganisms. While (medical) research focused on the planktonic phase of bacteria over the last 100 years, it is nowadays generally known, that oral microorganisms are organised as biofilms. On any non-shedding surfaces of the oral cavity dental plaque starts to form, which meets all criteria for a microbial biofilm and is subject to the so-called succession. When the sensitive ecosystem turns out of balance - either by overload or weak immune system - it becomes a challenge for local or systemic health. Therefore, the most common strategy and the golden standard for the prevention of caries, gingivitis and periodontitis is the mechanical removal of this biofilms from teeth, restorations or dental prosthesis by regular toothbrushing. PMID:27161350

  18. The Oral Microbiota.

    PubMed

    Arweiler, Nicole B; Netuschil, Lutz

    2016-01-01

    The oral microbiota represents an important part of the human microbiota, and includes several hundred to several thousand diverse species. It is a normal part of the oral cavity and has an important function to protect against colonization of extrinsic bacteria which could affect systemic health. On the other hand, the most common oral diseases caries, gingivitis and periodontitis are based on microorganisms. While (medical) research focused on the planktonic phase of bacteria over the last 100 years, it is nowadays generally known, that oral microorganisms are organised as biofilms. On any non-shedding surfaces of the oral cavity dental plaque starts to form, which meets all criteria for a microbial biofilm and is subject to the so-called succession. When the sensitive ecosystem turns out of balance - either by overload or weak immune system - it becomes a challenge for local or systemic health. Therefore, the most common strategy and the golden standard for the prevention of caries, gingivitis and periodontitis is the mechanical removal of this biofilms from teeth, restorations or dental prosthesis by regular toothbrushing.

  19. Orally administered grass pollen.

    PubMed

    Taudorf, E; Weeke, B

    1983-11-01

    In 1900 it was claimed that oral administration of ragweed could be used for the hyposensitization of hay fever patients. Several uncontrolled trials have been published, all showing an effect of oral hyposensitization. Only one study was controlled and showed no effect of oral hyposensitization. It was decided to undertake controlled clinical trials to determine the safety and effectiveness of orally administered enteric-coated grass pollen tablets in patients with hay fever. The actual grass pollen dose in the first trial was 30 times the dose that is normally recommended for preseasonal oral pollen hyposensitization using pollen aqueous solution or pollen powder. The safety study will be described here. Twelve young adults with a history of grass pollen hay fever positive skin prick test and positive nasal provocation test with extracts of timothy grass pollen were randomly allocated to one of the treatment groups with four patients in each group taking enteric-coated Conjuvac Timothy tablets or enteric-coated Whole Timothy pollen tablets or enteric-coated placebo tablets. The study was double blind. Preseasonally, the patients received 342,500 PNU and in total they received 4,500,000 PNU during 6 months. The patients receiving active treatment did not have any side effects. No significant changes were shown in the skin and nasal reactivity to grass pollen during the study. Neither were there any changes in timothy-specific IgE, IgG, total IgE nor histamine liberation from basophils.

  20. Ultrastructural localization of acid phosphatase in nonhuman primate vaginal epithelium.

    PubMed

    King, B F

    1985-01-01

    The vagina of the rhesus monkey is lined by a stratified squamous epithelium. However, little is known regarding the cytochemical composition of its cell organelles and the substances found in the intercellular spaces. In this study we have examined the ultrastructural distribution of acid phosphatase in the vaginal epithelium. In basal and parabasal cells reaction product was found in some Golgi cisternae and vesicles and in a variety of cytoplasmic granules. Reaction product was also found in some, but not all, membrane-coating granules. In the upper layers of the epithelium, the membrane-coating granules extruded their contents and acid phosphatase was localized in the intercellular spaces. The possible roles of acid phosphatase in keratinization, desquamation, or modification of substances in the intercellular compartment are discussed.

  1. Bisphosphonates Inhibit Expression of p63 by Oral Keratinocytes

    PubMed Central

    Scheller, E.L.; Baldwin, C.M.; Kuo, S.; D’Silva, N.J.; Feinberg, S.E.; Krebsbach, P.H.; Edwards, P.C.

    2011-01-01

    Osteonecrosis of the jaw (ONJ), a side-effect of bisphosphonate therapy, is characterized by exposed bone that fails to heal within eight weeks. Healing time of oral epithelial wounds is decreased in the presence of amino-bisphosphonates; however, the mechanism remains unknown. We examined human tissue from individuals with ONJ and non-bisphosphonate-treated controlindividuals to identify changes in oral epithelium and connective tissue. Oral and intravenous bisphosphonate-treated ONJ sites had reduced numbers of basal epithelial progenitor cells, as demonstrated by a 13.8 ± 1.1% and 31.9 ± 5.8% reduction of p63 expression, respectively. No significant differences in proliferation rates, vessel density, or macrophage number were noted. In vitro treatment of clonal and primary oral keratinocytes with zoledronic acid (ZA) inhibited p63, and expression was rescued by the addition of mevalonate pathway intermediates. In addition, both ZA treatment and p63 shRNA knock-down impaired formation of 3D Ex Vivo Produced Oral Mucosa Equivalents (EVPOME) and closure of an in vitro scratch assay. Analysis of our data suggests that bisphosphonate treatment may delay oral epithelial healing by interfering with p63-positive progenitor cells in the basal layer of the oral epithelium in a mevalonate-pathway-dependent manner. This delay in healing may increase the likelihood of osteonecrosis developing in already-compromised bone. PMID:21551338

  2. Minor Salivary Gland Changes in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma - A Histopathological Study

    PubMed Central

    Chitturi, Ravi Teja; Ragunathan, Yoithapprabhunath Thukanayakanpalayam; Lakshmi, Suman Jhansi; Nallusamy, Jaisanghar; Joseph, Isaac

    2016-01-01

    Introduction The most common etiology for Oral Squamous Cell Carcinoma (OSCC) is tobacco and tobacco related products which cause nuclear damage to the keratinocytes. The chemical carcinogens not only affect the lining of oral epithelium but also affect the lining epithelium of the excretory ducts of the salivary glands. Thus, there is a possibility of epithelial dysplasia of the salivary duct epithelium which may lead to potential malignant transformation. Aim The study was performed to see the changes in the minor salivary glands and excretory ducts in cases of oral epithelial dysplasia and OSCC. Materials and Methods A total of 278 archival cases of mild, moderate and severe epithelial dysplasia, carcinoma in situ, OSCC including verrucous carcinoma were histopathologically evaluated to observe changes in the excretory ducts and the minor salivary glands. Results In the study there were 56.5% males and 43.5% females. The age group that was most commonly affected in both the sexes was 50-60 yr old. Buccal mucosa was the most common site of involvement. Ductal changes observed in the excretory duct include simple hyperplasia, metaplastic changes such as mucous, oncocytic & squamous, and infiltration of inflammatory cells and malignant cells. Acinar changes observed were degeneration, squamous metaplasia, myoepithelial cell proliferation and inflammatory cell infiltration. Both the excretory ducts and ducts within the gland showed dysplasia. Conclusion According to observations in our study it is suggested that histopathological interpretation for oral mucosal lesions especially oral epithelial dysplasias and OSCC should also include changes related to salivary gland tissue to provide a better treatment plan and prevent recurrence of the malignant tumours. PMID:27630945

  3. Minor Salivary Gland Changes in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma - A Histopathological Study

    PubMed Central

    Chitturi, Ravi Teja; Ragunathan, Yoithapprabhunath Thukanayakanpalayam; Lakshmi, Suman Jhansi; Nallusamy, Jaisanghar; Joseph, Isaac

    2016-01-01

    Introduction The most common etiology for Oral Squamous Cell Carcinoma (OSCC) is tobacco and tobacco related products which cause nuclear damage to the keratinocytes. The chemical carcinogens not only affect the lining of oral epithelium but also affect the lining epithelium of the excretory ducts of the salivary glands. Thus, there is a possibility of epithelial dysplasia of the salivary duct epithelium which may lead to potential malignant transformation. Aim The study was performed to see the changes in the minor salivary glands and excretory ducts in cases of oral epithelial dysplasia and OSCC. Materials and Methods A total of 278 archival cases of mild, moderate and severe epithelial dysplasia, carcinoma in situ, OSCC including verrucous carcinoma were histopathologically evaluated to observe changes in the excretory ducts and the minor salivary glands. Results In the study there were 56.5% males and 43.5% females. The age group that was most commonly affected in both the sexes was 50-60 yr old. Buccal mucosa was the most common site of involvement. Ductal changes observed in the excretory duct include simple hyperplasia, metaplastic changes such as mucous, oncocytic & squamous, and infiltration of inflammatory cells and malignant cells. Acinar changes observed were degeneration, squamous metaplasia, myoepithelial cell proliferation and inflammatory cell infiltration. Both the excretory ducts and ducts within the gland showed dysplasia. Conclusion According to observations in our study it is suggested that histopathological interpretation for oral mucosal lesions especially oral epithelial dysplasias and OSCC should also include changes related to salivary gland tissue to provide a better treatment plan and prevent recurrence of the malignant tumours.

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

    PubMed

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

    2016-01-01

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

  5. Evaluation and Comparison of the Biopathology of Collagen and Inflammation in the Extracellular Matrix of Oral Epithelial Dysplasias and Inflammatory Fibrous Hyperplasia Using Picrosirius Red Stain and Polarising Microscopy: A Preliminary Study

    PubMed Central

    Varghese, Soma Susan; Sarojini, Sreenivasan Bargavan; George, Giju Baby; Vinod, Sankar; Mathew, Philips; Babu, Anulekh; Sebastian, Joseph

    2015-01-01

    Background: The role of tumour inflammation and the dysplastic epithelial-stromal interactions on the nature of collagen fibres in the extracellular matrix of dysplastic epithelium is not fully understood. The present study was aimed to evaluate and compare the inflammation and pathological stromal collagen (loosely packed thin disorganized collagen) present in mild, moderate and severe epithelial dysplasias with that of inflammatory fibrous hyperplasias. The basement membrane intactness of epithelial dysplasias was also evaluated to determine if dysplastic epithelial mesenchymal interaction has any role in the integrity of stromal collagen in epithelial dysplasia. Methods: Oral epithelial dysplasias, inflammatory fibrous hyperplasia and normal oral mucosal samples were used for the study. Packing, thickness and orientation of collagen fibres in mild, moderate and severe grades of oral epithelial dysplasias (n = 24), inflammatory fibrous hyperplasia (n = 8) and normal oral mucosal samples (n = 8) were analysed based on the polarisation of collagen fibres in picrosirius red polarising stain under polarising microscope. Results: All the grades of epithelial dysplasias showed greenish yellow birefringence confirming the presence of loosely arranged pathological collagen in the presence of moderate inflammation. All the cases of inflammatory fibrous hyperplasia showed red polarisation hue and moderate inflammation. A statistically significant difference was found in the packing and orientation of collagen when epithelial dysplasias and inflammatory fibrous hyperplasia were compared (P < 0.01). When the intactness of basement membrane integrity was compared in all the groups of epithelial dysplasia, a statistically significant result was obtained (P < 0.05). Conclusions: Presence of significant amount of loosely packed thin disoriented collagen even in mild epithelial dysplasia suggests that tumourigenic factors are released to connective tissue stroma much earlier than

  6. Ultrastructure of free-ending nerve fibres in oesophageal epithelium.

    PubMed Central

    Robles-Chillida, E M; Rodrigo, J; Mayo, I; Arnedo, A; Gómez, A

    1981-01-01

    For the first time, at the ultrastructural level, the existence of free-ending, intraepithelial nerve fibres has been demonstrated in the oesophagus wall of adult cats and monkeys. Their form, the way they penetrate the epithelium, their location within the epithelium and their relationships with neighbouring cells have been established. A sensory function is suggested for this type of ending. Images Figs. 1-4 Figs. 5-6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Figs. 14-15 Figs. 16-17 PMID:7333951

  7. Extremely elongated mitochondria in ionocytes of the saccular epithelium of a teleost, Oreochromis mossambicus (Cichlidae)

    NASA Astrophysics Data System (ADS)

    Muders, K.; Anken, R.; Ibsch, M.; Rahmann, H.

    2004-01-01

    Unusually large mitochondria are a rather scarce feature in normal biological tissue and string-like giant mitochondria have hitherto not been reported in animals. Investigating the role of inner ear ionocytes for otolith growth, large ionocytes of the saccular epithelium of the cichlid fish Oreochromis mossambicus were analyzed by imaging of thick sections with energy-filtering transmission electron microscopy. We report here that ionocytes do not contain numerous small-sized mitochondria as has been suggested earlier but rather few, extremely elongated megamitochondria. Since the particular mitochondrial structure is important for normal cell function, such megamitochondria possibly reflect a functional advantage in the context of the presumed role of teleostean ionocytes in regulating the composition of the endolymphatic fluid.

  8. Ampicillin Oral

    MedlinePlus

    ... capsule, liquid, and pediatric drops to take by mouth. It is usually taken every 6 hours (four ... blood thinners') such as warfarin (Coumadin), atenolol (Tenormin), oral contraceptives, probenecid (Benemid), rifampin, sulfasalazine, and vitamins.tell ...

  9. Oral pathology.

    PubMed

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  10. Oral Cancer

    MedlinePlus

    ... swallowing A lump in your neck An earache Oral cancer treatments may include surgery, radiation therapy or chemotherapy. Some patients have a combination of treatments. NIH: National Cancer Institute

  11. Oral Health

    MedlinePlus

    ... its box has the American Dental Association's (ADA) seal of acceptance, it is good for your oral ... dispensed solutions have the American Dental Association (ADA) seal. Other over-the-counter whitening products include whitening ...

  12. Oral Cancer

    MedlinePlus

    ... use. Some oral cancers are linked to human papilloma virus (HPV) infections of the mouth and throat. ... The number of oropharyngeal cancers linked to human papilloma virus (HPV) has risen dramatically over the past ...

  13. Spontaneous oral chytridiomycosis in wild bullfrog tadpoles in Japan

    PubMed Central

    KADEKARU, Sho; TAMUKAI, Ken-ichi; TOMINAGA, Atsushi; GOKA, Koichi; UNE, Yumi

    2015-01-01

    Batrachochytrium dendrobatidis (Bd) infects Anuran larvae (tadpole) mouthparts and causes oral chytridiomycosis, which can be diagnosed in tadpoles by detecting mouthparts deformities. However, oral chytridiomycosis may or may not be observable, depending on species, tadpole stage and season, and has never been reported in Japan. We aimed to observe oral chytridiomycosis characteristics in bullfrog (Lithobates catesbeiana) tadpoles, determine associated pathologic features and investigate the usability of bullfrog tadpoles in Japanese Bd field surveys. Wild-captured bullfrog tadpole mouthparts were examined macroscopically, histopathologically and by molecular biological examination. Macroscopic lesions were observed in 21 of 59 tadpole mouthparts. Lesions were most frequently located in the lower jaw sheaths and were mainly recognized by partial depigmentation (11 tadpoles; some were completely depigmented) and thinning of the pigmented layer (10 tadpoles). Partial defects of the tips and blunt cutting edges of the jaw sheaths were observed with severe jaw sheath depigmentation. Whitened tooth rows were observed in 7 tadpoles. Histologically, the stratified epithelium (pigmented epithelium) showed partial or diffuse hypopigmentation or pigment loss. Irregular stratified epithelium thickening with hyperkeratosis or parakeratosis was observed in the jaw sheaths. Bd infection was confirmed in 20 of 21 tadpoles presenting jaw sheath deformities, by histopathological examination and/or nested polymerase chain reaction. Depigmentation and thinning of the pigmented layers of jaw sheaths were associated with Bd infection. Thus, diagnosis of Bd infection by macroscopic observation of bullfrog tadpole mouthparts is feasible. This is the first report of oral chytridiomycosis in wild bullfrog tadpoles in Japan. PMID:26685882

  14. Vascular Biology of the Biliary Epithelium

    PubMed Central

    Morell, Carola M.; Fabris, Luca; Strazzabosco, Mario

    2012-01-01

    Cholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are nourished by an own arterial supply, the peribiliary plexus. This capillary network originates from the hepatic artery and is strictly arranged around the intrahepatic bile ducts. Biliary and vascular structures are linked by a close anatomic and functional association necessary for liver development, normal organ physiology and liver repair. This strong association is finely regulated by a range of angiogenic signals, enabling the crosstalk between cholangiocytes and the different vascular cell types. This review will briefly illustrate the “vascular” properties of cholangiocytes, their underlying molecular mechanisms and the relevant pathophysiological settings. PMID:23855292

  15. NORMAL NASAL GENE EXPRESSION LEVELS USING CDNA ARRAY TECHNOLOGY

    EPA Science Inventory

    Normal Nasal Gene Expression Levels Using cDNA Array Technology.

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

  16. Multivariate normality

    NASA Technical Reports Server (NTRS)

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

    1976-01-01

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

  17. Quality control in microarray assessment of gene expression in human airway epithelium

    PubMed Central

    Raman, Tina; O'Connor, Timothy P; Hackett, Neil R; Wang, Wei; Harvey, Ben-Gary; Attiyeh, Marc A; Dang, David T; Teater, Matthew; Crystal, Ronald G

    2009-01-01

    Background Microarray technology provides a powerful tool for defining gene expression profiles of airway epithelium that lend insight into the pathogenesis of human airway disorders. The focus of this study was to establish rigorous quality control parameters to ensure that microarray assessment of the airway epithelium is not confounded by experimental artifact. Samples (total n = 223) of trachea, large and small airway epithelium were collected by fiberoptic bronchoscopy of 144 individuals and hybridized to Affymetrix microarrays. The pre- and post-chip quality control (QC) criteria established, included: (1) RNA quality, assessed by RNA Integrity Number (RIN) ≥ 7.0; (2) cRNA transcript integrity, assessed by signal intensity ratio of GAPDH 3' to 5' probe sets ≤ 3.0; and (3) the multi-chip normalization scaling factor ≤ 10.0. Results Of the 223 samples, all three criteria were assessed in 191; of these 184 (96.3%) passed all three criteria. For the remaining 32 samples, the RIN was not available, and only the other two criteria were used; of these 29 (90.6%) passed these two criteria. Correlation coefficients for pairwise comparisons of expression levels for 100 maintenance genes in which at least one array failed the QC criteria (average Pearson r = 0.90 ± 0.04) were significantly lower (p < 0.0001) than correlation coefficients for pairwise comparisons between arrays that passed the QC criteria (average Pearson r = 0.97 ± 0.01). Inter-array variability was significantly decreased (p < 0.0001) among samples passing the QC criteria compared with samples failing the QC criteria. Conclusion Based on the aberrant maintenance gene data generated from samples failing the established QC criteria, we propose that the QC criteria outlined in this study can accurately distinguish high quality from low quality data, and can be used to delete poor quality microarray samples before proceeding to higher-order biological analyses and interpretation. PMID:19852842

  18. Oral biopsy: oral pathologist's perspective.

    PubMed

    Kumaraswamy, K L; Vidhya, M; Rao, Prasanna Kumar; Mukunda, Archana

    2012-01-01

    Many oral lesions may need to be diagnosed by removing a sample of tissue from the oral cavity. Biopsy is widely used in the medical field, but the practice is not quite widespread in dental practice. As oral pathologists, we have found many artifacts in the tissue specimen because of poor biopsy technique or handling, which has led to diagnostic pitfalls and misery to both the patient and the clinician. This article aims at alerting the clinicians about the clinical faults arising preoperatively, intraoperatively and postoperatively while dealing with oral biopsy that may affect the histological assessment of the tissue and, therefore, the diagnosis. It also reviews the different techniques, precautions and special considerations necessary for specific lesions.

  19. Analysis of the goldfish Carassius auratus olfactory epithelium transcriptome reveals the presence of numerous non-olfactory GPCR and putative receptors for progestin pheromones

    PubMed Central

    Kolmakov, Nikolay N; Kube, Michael; Reinhardt, Richard; Canario, Adelino VM

    2008-01-01

    Background The goldfish (Carassius auratus) uses steroids and prostaglandins as pheromone cues at different stages of the reproductive cycle to facilitate spawning synchronization. Steroid progestin pheromone binding has been detected in goldfish olfactory membranes but the receptors responsible for this specific binding remain unknown. In order to shed some light on the olfactory epithelium transcriptome and search for possible receptor candidates a large set of EST from this tissue were analysed and compared to and combined with a similar zebrafish (Danio rerio) resource. Results We generated 4,797 high quality sequences from a normalized cDNA library of the goldfish olfactory epithelium, which were clustered in 3,879 unique sequences, grouped in 668 contigs and 3,211 singletons. BLASTX searches produced 3,243 significant (E-value < e-10) hits and Gene Ontology (GO) analysis annotated a further 1,223 of these genes (37.7%). Comparative analysis with zebrafish olfactory epithelium ESTs revealed 1,088 identical unigenes. The transcriptome size of both species was estimated at about 16,400 unigenes, based on the proportion of genes identified involved in Glucose Metabolic Process. Of 124 G-protein coupled receptors identified in the olfactory epithelium of both species, 56 were olfactory receptors. Beta and gamma membrane progestin receptors were also isolated by subcloning of RT-PCR products from both species and an olfactory epithelium specific splice form identified. Conclusion The high similarity between the goldfish and zebrafish olfactory systems allowed the creation of a 'cyprinid' olfactory epithelium library estimated to represent circa 70% of the transcriptome. These results are an important resource for the identification of components of signalling pathways involved in olfaction as well as putative targets for pharmacological and histochemical studies. The possible function of the receptors identified in the olfactory system is described. Moreover, the

  20. Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis.

    PubMed

    Yadev, Nishant P; Murdoch, Craig; Saville, Stephen P; Thornhill, Martin H

    2011-06-01

    Candida albicans is a commensal organism that can be isolated from the majority of healthy individuals. However, in certain susceptible individuals C. albicans can become pathogenic leading to the mucocutaneous infection; oral candidiasis. Murine models and in vitro monolayer cultures have generated some data on the likely virulence and host factors that contribute to oral candidiasis but these models have limitations. Recently, tissue engineered oral mucosal models have been developed to mimic the normal oral mucosa but little information is available on their true representation. In this study, we assessed the histological features of three different tissue engineered oral mucosal models compared to the normal oral mucosa and analysed both cell damage and cytokine release following infection with C. albicans. Models comprised of normal oral keratinocytes and a fibroblast-containing matrix displayed more similar immunohistological and proliferation characteristics to normal mucosa, compared to models composed of an oral carcinoma cell line. Although all models were invaded and damaged by C. albicans in a similar manner, the cytokine response was much more pronounced in models containing normal keratinocytes. These data suggest that models based on normal keratinocytes atop a fibroblast-containing connective tissue will significantly aid in dissecting the molecular pathogenesis of oral candidiasis.

  1. Cigarette smoke inhibition of ion transport in canine tracheal epithelium

    SciTech Connect

    Welsh, M.J.

    1983-06-01

    To determine the effect of cigarette smoke on airway epithelial ion transport, the electrical properties and transepithelial Na and Cl fluxes were measured in canine tracheal epithelium. In vivo, the inhalation of the smoke from one cigarette acutely and reversibly decreased the electrical potential difference across the tracheal epithelium. In vitro, exposure of the mucosal surface of the epithelium to cigarette smoke decreased the short circuit current and transepithelial resistance. The decrease in short circuit current was due to an inhibition of the rate of Cl secretion with minimal effect on the rate of Na absorption. The effect of cigarette smoke was reversible, was not observed upon exposure of the submucosal surface to smoke, and was most pronounced when secretion was stimulated. The particulate phase of smoke was largely responsible for the inhibitory effect, since filtering the smoke minimized the effect. The effect of cigarette smoke was not prevented by addition of antioxidants to the bathing solutions, suggesting that the inhibition of Cl secretion cannot be entirely attributed to an oxidant mechanism. These results indicate that cigarette smoke acutely inhibits active ion transport by tracheal epithelium, both in vivo and in vitro. This effect may explain, in part, both the abnormal mucociliary clearance and the airway disease observed in cigarette smokers.

  2. Effects of CO2 inhalation exposure on mice vomeronasal epithelium.

    PubMed

    Hacquemand, Romain; Buron, Gaelle; Pourié, Gregory; Karrer, Melanie; Jacquot, Laurence; Brand, Gerard

    2010-08-01

    Nasal epitheliums are the first sites of the respiratory tract in contact with the external environment and may therefore be susceptible to damage from exposure to many toxic volatile substances (i.e., volatile organic components, vapors, and gases). In the field of inhalation toxicology, a number of studies have considered the main olfactory epithelium, but few have dealt with the epithelium of the vomeronasal organ (VNO). However, in several species such as in rodents, the VNO (an organ of pheromone detection) plays an important role in social interactions, and alterations of this organ are known to induce adaptative behavioral disturbances. Among volatile toxicants, health effects of inhaled gases have been thoroughly investigated, especially during CO(2) inhalation because of its increasing atmospheric concentration. Therefore, this work was designed to examine the effects of 3% CO(2) inhalation on VNO in two different exposure conditions (5 h/day and 12 h/day) in mice. Behavioral sensitivity tests to urine of congener and histological measurements of VNO were conducted before, during (weeks 1-4), and after (weeks 5-8) CO(2) inhalation exposures. Results showed no significant modifications of behavioral responses to urine, but there were significant changes of both cell number and thickness of the VNO epithelium. Moreover, the findings indicated a selectively dose-dependent effect of CO(2), and further research could use other gases in the same manner for comparison.

  3. Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

    NASA Astrophysics Data System (ADS)

    Garzotto, D.; De Marchis, S.

    2010-10-01

    Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

  4. Effects of CO2 inhalation exposure on mice vomeronasal epithelium.

    PubMed

    Hacquemand, Romain; Buron, Gaelle; Pourié, Gregory; Karrer, Melanie; Jacquot, Laurence; Brand, Gerard

    2010-08-01

    Nasal epitheliums are the first sites of the respiratory tract in contact with the external environment and may therefore be susceptible to damage from exposure to many toxic volatile substances (i.e., volatile organic components, vapors, and gases). In the field of inhalation toxicology, a number of studies have considered the main olfactory epithelium, but few have dealt with the epithelium of the vomeronasal organ (VNO). However, in several species such as in rodents, the VNO (an organ of pheromone detection) plays an important role in social interactions, and alterations of this organ are known to induce adaptative behavioral disturbances. Among volatile toxicants, health effects of inhaled gases have been thoroughly investigated, especially during CO(2) inhalation because of its increasing atmospheric concentration. Therefore, this work was designed to examine the effects of 3% CO(2) inhalation on VNO in two different exposure conditions (5 h/day and 12 h/day) in mice. Behavioral sensitivity tests to urine of congener and histological measurements of VNO were conducted before, during (weeks 1-4), and after (weeks 5-8) CO(2) inhalation exposures. Results showed no significant modifications of behavioral responses to urine, but there were significant changes of both cell number and thickness of the VNO epithelium. Moreover, the findings indicated a selectively dose-dependent effect of CO(2), and further research could use other gases in the same manner for comparison. PMID:19924548

  5. Histology and Ultrastructure of Metaplasia of Alveolar Epithelium Following Infection of Mice and Hamsters with Influenza Virus

    PubMed Central

    Baskerville, A.; Thomas, G.; Wood, M.; Harris, W. J.

    1974-01-01

    Mice and hamsters were infected with the NWS strain of influenza virus and metaplastic changes which developed in the lungs during the healing phase were studied by histology and electron microscopy. Transformation of alveolar epithelium occurred in many animals, producing alveolar epithelialization. This was due to replacement of the normal alveolar epithelium by ciliated columnar and cuboidal cells of bronchiolar type. Squamous changes also developed in healing lungs during the 11-22 day period after infection. Since these lesions regressed later and the cells did not metastasize they were considered to be metaplastic rather than neoplastic in nature. ImagesFigs. 4-7Figs. 1-3Figs. 8-9 PMID:4835801

  6. [Selected aspects of oral contraception side effects].

    PubMed

    Wolski, Hubert

    2014-12-01

    The first hormonal pill was approved in the 60s of the twentieth century Since that time, oral contraception has been used worldwide by dozens of women due to its high availability as well as relative ease and safety of taking. The main side effects of oral contraception include elevated risk for venous thromboembolism (VTE). Estrogens increase the probability of VTE development, depending on the dose in medication, and third-generation progestins increase the risk of VTE development more than older-generation progestins. Also, the coexistence of hereditary thrombophilia increases the risk of VTE development in women using oral contraceptives. Other side effects include changes in the carbohydrate and lipid economy Progestins in oral contraceptives decrease HDL cholesterol levels but increase LDL cholesterol and total cholesterol levels. Additionally estrogens are a recognized mitogenic factor for the epithelium of the mammary gland, acting proliferative on the glandular tissue and in the same way influence on the increased risk of breast cancer development. Patients sometimes complain about some subjective side symptoms such as headache, mood changes, nausea, back pain, breast pain and swelling, as well as decreased libido. Some patients discontinue oral contraception due to fear of side effects or temporary ailments before con- sulting their doctor what may result in unintended pregnancy The aim of the following paper was to present most frequent side effects of oral contraception, ways of their moni- toring and diagnosis. PMID:25669065

  7. Maintenance of the corneal epithelium is carried out by germinative cells of its basal stratum and not by presumed stem cells of the limbus.

    PubMed

    Haddad, A; Faria-e-Sousa, S J

    2014-06-01

    The purpose of this investigation was to analyze the proliferative behavior of rabbit corneal epithelium and establish if any particular region was preferentially involved in epithelial maintenance. [3H]-thymidine was injected intravitreally into both normal eyes and eyes with partially scraped corneal epithelium. Semithin sections of the anterior segment were evaluated by quantitative autoradiography. Segments with active replication (on) and those with no cell division (off) were intermingled in all regions of the tissue, suggesting that the renewal of the epithelial surface of the cornea followed an on/off alternating pattern. In the limbus, heavy labeling of the outermost layers was observed, coupled with a few or no labeled nuclei in the basal stratum. This suggests that this region is a site of rapid cell differentiation and does not contain many slow-cycling cells. The conspicuous and protracted labeling of the basal layer of the corneal epithelium suggests that its cells undergo repeated cycles of replication before being sent to the suprabasal strata. This replication model is prone to generate label-retaining cells. Thus, if these are adult stem cells, one must conclude that they reside in the corneal basal layer and not the limbal basal layer. One may also infer that the basal cells of the cornea and not of the limbus are the ones with the main burden of renewing the corneal epithelium. No particular role in this process could be assigned to the cells of the basal layer of the limbal epithelium. PMID:24820068

  8. Maintenance of the corneal epithelium is carried out by germinative cells of its basal stratum and not by presumed stem cells of the limbus.

    PubMed

    Haddad, A; Faria-e-Sousa, S J

    2014-06-01

    The purpose of this investigation was to analyze the proliferative behavior of rabbit corneal epithelium and establish if any particular region was preferentially involved in epithelial maintenance. [3H]-thymidine was injected intravitreally into both normal eyes and eyes with partially scraped corneal epithelium. Semithin sections of the anterior segment were evaluated by quantitative autoradiography. Segments with active replication (on) and those with no cell division (off) were intermingled in all regions of the tissue, suggesting that the renewal of the epithelial surface of the cornea followed an on/off alternating pattern. In the limbus, heavy labeling of the outermost layers was observed, coupled with a few or no labeled nuclei in the basal stratum. This suggests that this region is a site of rapid cell differentiation and does not contain many slow-cycling cells. The conspicuous and protracted labeling of the basal layer of the corneal epithelium suggests that its cells undergo repeated cycles of replication before being sent to the suprabasal strata. This replication model is prone to generate label-retaining cells. Thus, if these are adult stem cells, one must conclude that they reside in the corneal basal layer and not the limbal basal layer. One may also infer that the basal cells of the cornea and not of the limbus are the ones with the main burden of renewing the corneal epithelium. No particular role in this process could be assigned to the cells of the basal layer of the limbal epithelium.

  9. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    PubMed

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

  10. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    PubMed

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD. PMID:26956365

  11. Epithelial expression of keratinocytes growth factor in oral precancer lesions

    PubMed Central

    Jimson, Sudha; Murali, S.; Zunt, Susan L.; Goldblatt, Lawrence I.; Srinivasan, Mythily

    2016-01-01

    Background: Keratinocyte growth factor (KGF) is a potent epithelial mitogen that acts by binding the KGF receptors (KGFRs) expressed on epithelial cells and regulates proliferation and differentiation. The objective of this study was to investigate the expression of KGF in the epithelium in oral precancer. Materials and Methods: Archival tissues of oral submucous fibrosis (SMF) and leukoplakia were assessed for epithelial KGF expression by immunohistochemistry and real-time quantitative polymerase chain reaction. Results: KGF was predominantly expressed in the basal and parabasal cells in the epithelium of SMF tissues. KGF transcript in the epithelial cells increased with increasing severity of epithelial dysplasia in oral leukoplakia. Conclusion: Although widely reported as a product secreted by the mesenchymal cells, our data suggest that the KGF is also expressed in oral epithelial cells much like the expression in ovarian epithelial cells. Based on the localization of KGF in cells at the epithelial mesenchymal junction and that of the reported presence of KGFR in oral keratinocytes, a potential mechanism involving paracrine and autocrine interactions of KGF and KGFR in early stages of oral precancer is postulated. PMID:27274338

  12. Tight junction alterations of respiratory epithelium following long-term NO2 exposure and recovery.

    PubMed

    Gordon, R E; Solano, D; Kleinerman, J

    1986-01-01

    Acute exposure to NO2 is reported to disrupt tight junctions in lung epithelium. We have studied the effects of chronic NO2 exposure and recovery breathing clean air to tight junctions of distal airway and alveolar epithelium. Syrian Golden hamsters were exposed to NO2 (30 PPM) for 5 or 9 months and a group of those animals for 9 months were allowed to recover breathing clean air for 3 or 9 months. Animals were sacrificed after 5 and 9 months of NO2 exposure and after 3, and 9 mos. recovery breathing clean air. The lungs were carefully removed, inflation fixed with glutaraldehyde and then processed for freeze fracture and transmission electron microscopy of ultra-thin epon sections. Evaluation of tight junctions of bronchioles and alveoli were disrupted in ultrathin sections and freeze fracture replicas during the period of NO2 exposure. Fibril number, length, degree of fragmentation and orientation were different from age matched controls. The bronchiolar tight junctional fibrils were quantitatively reduced in number and fragmented into much smaller fibril lengths. Alveolar tight junctions were qualitatively disrupted in a similar fashion, however, the sites of damage were focal. During recovery tight junctions in bronchioles did not regain normal fibril number, orientation and continuity, based on quantitative assessment, observed in age matched controls. Alveolar tight junctions remained focally altered. This data indicated that chronic NO2 altered morphologic characteristics of epithelial tight junctions of the lung throughout the period of exposure. The repair process during recovery did not restore the normal tight junction ultrastructural organization observed in age controls. This persistent deviation from the normal is likely to alter and compromise airway epithelial barrier function in the lungs of these hamsters. PMID:3780600

  13. Human vaginal epithelium and the epithelial lining of a cyst model constructed from it: a comparative light microscopic and electron microscopic study.

    PubMed

    Thompson, I O; van Wyk, C W; Darling, M R

    2001-11-01

    The light microscopic features and keratin filament distribution of human vaginal epithelium resemble those of buccal mucosa. We used vaginal epithelium to establish a human cyst model in immunodeficient mice. To strengthen the view that this experimental cyst is a suitable model to study mucosal diseases, we compared specific light microscopic and ultra-structural features of vaginal epithelium and the epithelial lining of the cyst. Nineteen cyst walls and 6 specimens of vaginal mucosa, which had been used to establish the cysts, were examined. We counted the number of cell layers of 17 cyst linings and the 6 vaginal specimens. Surface keratinisation was evaluated on sections stained with the Picro-Mallory method. To demonstrate intercellular lamellae and membrane coating granules 2 cyst linings were examined ultra-structurally. The epithelium lining of the cyst wall was thinner than that of vaginal mucosa but the surface keratinisation and ultra-structural features of the intercellular lamellae and membrane coating granules were similar. We concluded that vaginal mucosa is a useful substitute for oral mucosa in the cyst model.

  14. Distribution and ultrastructural characteristics of dark cells in squamous metaplasias of the respiratory tract epithelium. [Rats

    SciTech Connect

    Klein-Szanto, A.J.P.; Nettesheim, P.; Pine, A.; Martin, D.

    1981-05-01

    Dark epithelial basal cells were found in both carcinogen-induced and non-carcinogen-induced squamous metaplasias of the tracheal epithelium. Formaldehyde-induced squamous metaplasias exhibited 4% dark cells in the basal layer. Metaplasias induced by vitamin A deficiency and those induced by dimethylbenz(a)anthracene (DMBA) without atypia showed 18-20% basal dark cells. DMBA-induced metaplasias with moderate to severe atypia exhibited 50% basal dark cells. The labeling index of basal cells in metaplastic epithelia, regardless of the inducing agent, was 16-18%, ie, the same as that of the normal esophageal stratified squamous epithelium. The percentage of labeled dark basal cells per total dark cell population was approximately 19% in the non-carcinogen-induced metaplasias and in the DMBA-induced metaplasias without atypia. In the atypical metaplasias induced by DMA this percentage increased to 26. On the basis of ultrastructural observations, five types of dark epithelial cells could be distinguished in the metaplastic epithelia. Each type of squamous metaplasia could thus be recognized by a determined numerical distribution of dark cells in the basal layer and a specific pattern of distribution of the ultrastructurally defined dark cell categories.

  15. 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

  16. Age and disease-related structural changes in the retinal pigment epithelium

    PubMed Central

    Bonilha, Vera L

    2008-01-01

    As the retinal pigment epithelium (RPE) ages, a number of structural changes occur, including loss of melanin granules, increase in the density of residual bodies, accumulation of lipofuscin, accumulation of basal deposits on or within Bruch’s membrane, formation of drusen (between the basal lamina of the RPE and the inner collagenous layer of Bruch’s membrane), thickening of Bruch’s membrane, microvilli atrophy and disorganization of the basal infoldings. Although these changes are well known, the basic mechanisms involved in them are frequently poorly understood. These age-related changes progress slowly and vary in severity in different individuals. These changes are also found in age-related macular degeneration (AMD), a late onset disease that severely impacts the RPE, but they are much more pronounced than during normal aging. However, the changes in AMD lead to severe loss of vision. Given the many supporting functions which the RPE serves for the retina, it is important to decipher the age-related changes in this epithelium in order to understand age-related changes in vision. PMID:19668732

  17. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.

    PubMed

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J; Klein, Ophir D; Barlow, Linda A

    2014-08-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation. PMID:24993944

  18. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.

    PubMed

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J; Klein, Ophir D; Barlow, Linda A

    2014-08-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation.

  19. Extremely elongated Mitochondria in Ioncytes of the saccular Epithelium of a Teleost, Oreochromis mossambiscus (Cichlidae)

    NASA Astrophysics Data System (ADS)

    Muders, K.; Anken, R.; Ibsch, M.; Rahmann, H.

    Earlier investigations have clearly shown that altered gravity affects the calcium incorporation of fish inner ear otoliths. The incorporation of such inorganic components requires a particular composition of the endolymph, which is maintained by specialized cells in the inner ear epithelium, which are responsible for ion exchange. These so-called ionocytes therefore may play an important role in altered gravity affected ion deposition on otoliths. In order to clarify the ultrastructure of ionocytes, respective cells within the saccular epithelium of the cichlid fish Oreochromis mossamb cus were analyzed byi imaging of thick sections with energy -filtering transmission electron microscopy. It was found that ionocytes do not contain numerous mitochondria of litte size as has been suggested earlier but rather few, extremely elongated megamitochondria. Such worm-like mitochondria seemed hitherto to be restricted to some higher plants and fungi. Since the particular mitochondrial structure is important for normal cell function, such megamitochondria possibly reflect a functional advantage in the context of the presumed role of teleostean ionocytes in regulating the electrolyte composition of the endolymph. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

  20. Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

    PubMed Central

    Pavlov, Tengis S.; Ilatovskaya, Daria V.; Palygin, Oleg; Levchenko, Vladislav; Pochynyuk, Oleh; Staruschenko, Alexander

    2015-01-01

    Cyst initiation and expansion during polycystic kidney disease is a complex process characterized by abnormalities in tubular cell proliferation, luminal fluid accumulation and extracellular matrix formation. Activity of ion channels and intracellular calcium signaling are key physiologic parameters which determine functions of tubular epithelium. We developed a method suitable for real-time observation of ion channels activity with patch-clamp technique and registration of intracellular Ca2+ level in epithelial monolayers freshly isolated from renal cysts. PCK rats, a genetic model of autosomal recessive polycystic kidney disease (ARPKD), were used here for ex vivo analysis of ion channels and calcium flux. Described here is a detailed step-by-step procedure designed to isolate cystic monolayers and non-dilated tubules from PCK or normal Sprague Dawley (SD) rats, and monitor single channel activity and intracellular Ca2+ dynamics. This method does not require enzymatic processing and allows analysis in a native setting of freshly isolated epithelial monolayer. Moreover, this technique is very sensitive to intracellular calcium changes and generates high resolution images for precise measurements. Finally, isolated cystic epithelium can be further used for staining with antibodies or dyes, preparation of primary cultures and purification for various biochemical assays. PMID:26381526

  1. Respiratory syncytial virus alters electrophysiologic properties in cotton rat airway epithelium.

    PubMed

    Cloutier, M M; Wong, D; Ogra, P L

    1989-01-01

    The effect of respiratory syncytial virus (RSV) infection on the electrophysiologic properties of the airway epithelium was studied in tracheas obtained from cotton rats, after in vivo exposure to the virus. RSV infection was documented by tissue culture infectivity and immunofluorescent antibody techniques. Light microscopic studies of the tracheas 72 hours after exposure to RSV revealed normal epithelial morphology. RSV infection produced a 28% decrease in short-circuit current (Isc) and an almost 100% increase in tissue resistance. The decrease in Isc was partially attributed to a decrease in Cl secretion, while the increase in tissue resistance was associated with significant restriction to sodium and chloride movement through the paracellular pathway in RSV-infected tracheas. We conclude from these studies that RSV infection in the cotton rat trachea produces significant changes in active and passive ion flows. Alterations in ion transport across the airway epithelium may result in changes in secondary water transport across the airways and may contribute to the pathophysiology of RSV bronchiolitis and other locally invasive mucosal viral infections in children.

  2. Collagenous spherulosis in an oral mucous cyst.

    PubMed

    Henry, Cathy Renee; Nace, Mindy; Helm, Klaus F

    2008-04-01

    Collagenous spherulosis is a histological pattern that has been described in both benign and malignant salivary gland tumors, proliferative lesions of breast ductal epithelium, chondroid syringomas and schwannomas. Histologic structures of similar appearance have also been reported in oral extravasation mucoceles as questionable myxoglobulosis or myxoglobulosis-like change. We report collagenous spherulosis within a mucocele removed from the lower lip of a 17-year-old female. Based upon histologic appearance, immunophenotypic data and review of the literature, we hypothesize that collagenous spherulosis and myxoglobulosis are morphologically related reaction patterns. PMID:18333906

  3. Collagenous spherulosis in an oral mucous cyst.

    PubMed

    Henry, Cathy Renee; Nace, Mindy; Helm, Klaus F

    2008-04-01

    Collagenous spherulosis is a histological pattern that has been described in both benign and malignant salivary gland tumors, proliferative lesions of breast ductal epithelium, chondroid syringomas and schwannomas. Histologic structures of similar appearance have also been reported in oral extravasation mucoceles as questionable myxoglobulosis or myxoglobulosis-like change. We report collagenous spherulosis within a mucocele removed from the lower lip of a 17-year-old female. Based upon histologic appearance, immunophenotypic data and review of the literature, we hypothesize that collagenous spherulosis and myxoglobulosis are morphologically related reaction patterns.

  4. Oral candidiasis.

    PubMed

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options.

  5. Reconstruction of a full-thickness collagen-based human oral mucosal equivalent.

    PubMed

    Kinikoglu, Beste; Auxenfans, Céline; Pierrillas, Pascal; Justin, Virginie; Breton, Pierre; Burillon, Carole; Hasirci, Vasif; Damour, Odile

    2009-11-01

    Tissue engineered human oral mucosa has the potential to be applied to the closure of surgical wounds after tissue deficits due to facial trauma, malignant lesion surgery or preposthetic procedure. It can also be used to elucidate the biology and pathology of oral mucosa and as a model alternative to animals for safety testing of oral care products. Using the technology previously developed in our laboratory for the production of a skin equivalent, we were able to reconstruct a nonkeratinized full-thickness human oral mucosal equivalent closely mimicking human native oral mucosa. The successive coculture of human lamina propria fibroblasts and human oral epithelial cells isolated from the nonkeratinized region of oral cavity in a porous collagen-glycosaminoglycan (GAG)-chitosan scaffold gave rise to a lamina propria equivalent (LPE) and then to an oral mucosa equivalent (OME). The results of the histology, immunohistology and transmission electron microscopy of this OME demonstrated the presence of a nonkeratinized pluristratified and differentiated epithelium as in native nonkeratinized human oral mucosa expressing both K13 and K3/76. This epithelium was firmly anchored to the LPE by a continuous and ultrastructurally well-organized basement membrane. In the LPE, fibroblasts synthesized new extracellular matrix where the average collagen fibre diameter was 28.4 nm, close to that of native oral mucosa. The proliferative capacity of the basal cells was demonstrated by the expression of Ki67. PMID:19698987

  6. Oral exposure to polystyrene nanoparticles affects iron absorption

    NASA Astrophysics Data System (ADS)

    Mahler, Gretchen J.; Esch, Mandy B.; Tako, Elad; Southard, Teresa L.; Archer, Shivaun D.; Glahn, Raymond P.; Shuler, Michael L.

    2012-04-01

    The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron transport in an in vitro model of the intestinal epithelium and an in vivo chicken intestinal loop model. Intestinal cells that are exposed to high doses of nanoparticles showed increased iron transport due to nanoparticle disruption of the cell membrane. Chickens acutely exposed to carboxylated particles (50 nm in diameter) had a lower iron absorption than unexposed or chronically exposed birds. Chronic exposure caused remodelling of the intestinal villi, which increased the surface area available for iron absorption. The agreement between the in vitro and in vivo results suggests that our in vitro intestinal epithelium model is potentially useful for toxicology studies.

  7. Normalizing Rejection.

    PubMed

    Conn, Vicki S; Zerwic, Julie; Jefferson, Urmeka; Anderson, Cindy M; Killion, Cheryl M; Smith, Carol E; Cohen, Marlene Z; Fahrenwald, Nancy L; Herrick, Linda; Topp, Robert; Benefield, Lazelle E; Loya, Julio

    2016-02-01

    Getting turned down for grant funding or having a manuscript rejected is an uncomfortable but not unusual occurrence during the course of a nurse researcher's professional life. Rejection can evoke an emotional response akin to the grieving process that can slow or even undermine productivity. Only by "normalizing" rejection, that is, by accepting it as an integral part of the scientific process, can researchers more quickly overcome negative emotions and instead use rejection to refine and advance their scientific programs. This article provides practical advice for coming to emotional terms with rejection and delineates methods for working constructively to address reviewer comments. PMID:26041785

  8. Fasting Increases Tobramycin Oral Absorption in Mice▿

    PubMed Central

    De Leo, Luigina; Di Toro, Nicola; Decorti, Giuliana; Malusà, Noelia; Ventura, Alessandro; Not, Tarcisio

    2010-01-01

    The pharmacokinetics of the aminoglycoside tobramycin was evaluated after oral administration to fed or fasting (15 h) mice. As expected, under normal feeding conditions, oral absorption was negligible; however, fasting induced a dramatic increase in tobramycin bioavailability. The dual-sugar test with lactulose and l-rhamnose confirmed increased small bowel permeability via the paracellular route in fasting animals. When experiments aimed at increasing the oral bioavailability of hydrophilic compounds are performed, timing of fasting should be extremely accurate. PMID:20086144

  9. Oral Cancer

    MedlinePlus

    ... What are the effects of oral cancer on speech and swallowing? The effects of cancer on speech and swallowing depend on the location and size ... movement. This could result in unclear production of speech sounds made with the lips such as /p/, / ...

  10. Oral Warts

    MedlinePlus

    ... Title: Oral Warts Description: Warts are small, white, gray, or pinkish rough bumps that look like cauliflower. They can appear inside the lips and on other parts of the mouth. Credit: NIDCR publication: Mouth Problems + HIV Download: Low-Resolution Image High- ...

  11. Changes in Abundance of Oral Microbiota Associated with Oral Cancer

    PubMed Central

    Schmidt, Brian L.; Kuczynski, Justin; Bhattacharya, Aditi; Huey, Bing; Corby, Patricia M.; Queiroz, Erica L. S.; Nightingale, Kira; Kerr, A. Ross; DeLacure, Mark D.; Veeramachaneni, Ratna; Olshen, Adam B.; Albertson, Donna G.

    2014-01-01

    Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence. PMID:24887397

  12. Oral care.

    PubMed

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable. PMID:21325845

  13. Oral care.

    PubMed

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable.

  14. [Tissue and cell interactions in the oral mucosa after cytostatic drugs administration].

    PubMed

    Bykov, V L; Leont'eva, I V

    2011-01-01

    In the preceding work ("Morphology", 2011, issue 2), the regularities of oral mucosal (OM) epithelium injury after the cytostatic drug (CSD) treatment and its further regeneration, were reviewed. This paper presents the systematized summary of current literature data and the authors' own findings on the regularities of CSD effect on non-epithelial OM cell populations and their interactions with each other and the epithelium. The changes of intraepithelial tissue homeostasis, associated with CSD effect on intraepithelial lymphocytes, granulocytes, dendritic antigen presenting cells and melanocytes, interacting with epitheliocytes, are described. The data are presented, indicating that along with the epithelium, the cell populations of lamina propria and submucosal connective tissue, as well as the small blood vessels, are important targets of CSD in the OM tissues. The concept of a unifying model, describing tissue, cellular and molecular mechanisms of the oral mucositis development after CSD treatment, is reviewed.

  15. Oral Cancer Screening

    MedlinePlus

    ... Prevention Oral Cavity and Oropharyngeal Cancer Screening Research Oral Cavity and Oropharyngeal Cancer Screening (PDQ®)–Patient Version What ... These are called diagnostic tests . General Information About Oral Cavity and Oropharyngeal Cancer Key Points Oral cavity and ...

  16. The MYC oncogene in breast cancer progression: from benign epithelium to invasive carcinoma.

    PubMed

    Corzo, Cristina; Corominas, Josep M; Tusquets, Ignacio; Salido, Marta; Bellet, Meritxell; Fabregat, Xavier; Serrano, Sergio; Solé, Francesc

    2006-03-01

    One hypothesis for breast cancer development suggests that breast carcinogenesis involves a progression of events leading from benign epithelium to hyperplasia (with or without atypia) to carcinoma in situ and then invasive carcinoma. The MYC gene (alias c-Myc) is a transcriptional regulator whose expression is strongly associated with cell proliferation and cell differentiation. The present study is a descriptive analysis of MYC status throughout the hypothesized stages of invasive ductal carcinoma progression. A tissue microarray (TMA) was constructed including representative selected areas (normal cells, hyperplasia, in situ carcinoma, and invasive carcinoma) from each of 15 patients. Fluorescence in situ hybridization (FISH) with the LSI c-MYC/CEN8/IgH probe was performed. Two cases displayed MYC amplification (13%), showing this amplification only in the invasive carcinoma zones selected. Five cases displayed polysomy of chromosome 8 (33%), detected only in ductal in situ and invasive zones selected. Benign lesions and normal adjacent cells were classified as normal. None of the hyperplasia specimens and normal specimens analyzed showed any alterations in MYC status or any aneusomies of chromosome 8. The presence of MYC amplification only in invasive cells suggests that the finding of MYC amplification could reflect an advanced tumor progression.

  17. Degeneration and regeneration of the olfactory epithelium following inhalation exposure to methyl bromide: pathology, cell kinetics, and olfactory function.

    PubMed

    Hurtt, M E; Thomas, D A; Working, P K; Monticello, T M; Morgan, K T

    1988-06-30

    The effects of acute inhalation exposure to methyl bromide (MeBr) on the olfactory epithelium of male F-344 rats was investigated by morphologic examination of animals killed at varying timepoints during and following exposure to 200 ppm MeBr 6 hr/day for 5 days. Cell replication rate and histopathology were used to assess the kinetics of repair. In addition, olfactory function, using the buried food pellet test, was assessed and the result compared with morphological recovery. Extensive destruction of the olfactory epithelium was evident in animals killed directly after a single 6-hr exposure to MeBr. Histologic features of these lesions indicate that the primary, or most severe, effect of MeBr exposure was on the sustentacular cells and mature sensory cells; basal cells were generally unaffected. By Day 3, despite continued exposure, there was replacement of the olfactory epithelium by a squamous cell layer that increased in thickness and basophilic cytoplasmic staining over the next 2 days of exposure. One week postexposure, the epithelial region was covered by a layer of polyhedral, basophilic cells, and from 2 to 10 weeks postexposure, the epithelium exhibited progressive reorganization to reform the original olfactory epithelium pattern. By Week 10, 75-80% of the olfactory epithelium appeared morphologically normal. Cell replication showed a single peak of olfactory epithelial cell proliferation at Day 3 of exposure, with a labeling index of 14.5% compared to 0.7% in controls. Cell replication rates returned gradually to control levels by Week 10 postexposure. Behavioral tests of olfactory function in animals after a single 6-hr exposure to 200 ppm MeBr demonstrated a loss of the sense of smell, with recovery of this function by Day 6. Exposure to 90 ppm caused no observable effect on olfactory function or morphology. These findings demonstrate that the olfactory mucosa is highly sensitive to the toxic effects of MeBr and that olfactory epithelial cell

  18. Normal development.

    PubMed

    Girard, Nadine; Koob, Meriam; Brunel, Herv

    2016-01-01

    Numerous events are involved in brain development, some of which are detected by neuroimaging. Major changes in brain morphology are depicted by brain imaging during the fetal period while changes in brain composition can be demonstrated in both pre- and postnatal periods. Although ultrasonography and computed tomography can show changes in brain morphology, these techniques are insensitive to myelination that is one of the most important events occurring during brain maturation. Magnetic resonance imaging (MRI) is therefore the method of choice to evaluate brain maturation. MRI also gives insight into the microstructure of brain tissue through diffusion-weighted imaging and diffusion tensor imaging. Metabolic changes are also part of brain maturation and are assessed by proton magnetic resonance spectroscopy. Understanding and knowledge of the different steps in brain development are required to be able to detect morphologic and structural changes on neuroimaging. Consequently alterations in normal development can be depicted. PMID:27430460

  19. Hydrodynamics of stratified epithelium: Steady state and linearized dynamics

    NASA Astrophysics Data System (ADS)

    Yeh, Wei-Ting; Chen, Hsuan-Yi

    2016-05-01

    A theoretical model for stratified epithelium is presented. The viscoelastic properties of the tissue are assumed to be dependent on the spatial distribution of proliferative and differentiated cells. Based on this assumption, a hydrodynamic description of tissue dynamics at the long-wavelength, long-time limit is developed, and the analysis reveals important insights into the dynamics of an epithelium close to its steady state. When the proliferative cells occupy a thin region close to the basal membrane, the relaxation rate towards the steady state is enhanced by cell division and cell apoptosis. On the other hand, when the region where proliferative cells reside becomes sufficiently thick, a flow induced by cell apoptosis close to the apical surface enhances small perturbations. This destabilizing mechanism is general for continuous self-renewal multilayered tissues; it could be related to the origin of certain tissue morphology, tumor growth, and the development pattern.

  20. The dorsal lingual epithelium of Rhinoclemmys pulcherrima incisa (Chelonia, Cryptodira).

    PubMed

    Josef Beisser, Christian; Lemell, Patrick; Weisgram, Josef

    2004-03-01

    This study employed light microscopic (LM), scanning electron microscopic (SEM), and transmission electron microscopic (TEM) methods to provide detailed morphological information on the histological and ultrastructural features of the dorsal tongue epithelium of Rhinoclemmys pulcherrima incisa. SEM revealed columnar papillae laterally, as well as papillae, which tend to have a ridge-like appearance in the center of the tongue. LM and TEM showed three different zones of lingual epithelium: a stratified apical area with serous cells at the top of the papillae, a stratified lateral area with both serous and mucus cells, and an unstratified glandular area consisting of distinct glandular ducts with mucus cells. Comparison with morphological data from other turtles shows that the lingual epithelial structure in R. p. incisa is in accordance with that observed for other generalized omnivores which prefer a terrestrial lifestyle, thus matching the ecological information about this species.

  1. Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium.

    PubMed

    Ferrari, S; Kitson, C; Farley, R; Steel, R; Marriott, C; Parkins, D A; Scarpa, M; Wainwright, B; Evans, M J; Colledge, W H; Geddes, D M; Alton, E W

    2001-09-01

    Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier can, in part, be overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine using either a cationic lipid or a cationic polymer as the gene transfer agent. Further, in vivo application of either Nacystelyn or the anticholinergic glycopyrrolate, both clinically used agents, resulted in increased reporter gene expression in the mouse lung, but no significant correction of the bioelectric defect in CF null mice. These results, whilst unlikely to be sufficient in themselves to achieve clinically relevant gene therapy, may be a further useful step in the attainment of this goal.

  2. Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

    PubMed Central

    Magenheim, Judith; Klein, Allon M.; Stanger, Ben Z.; Ashery-Padan, Ruth; Sosa-Pineda, Beatriz; Gu, Guoqiang; Dor, Yuval

    2013-01-01

    Summary During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3−/− mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta-cells from stem cells. PMID:21888903

  3. Excess NF-κB induces ectopic odontogenesis in embryonic incisor epithelium.

    PubMed

    Blackburn, J; Kawasaki, K; Porntaveetus, T; Kawasaki, M; Otsuka-Tanaka, Y; Miake, Y; Ota, M S; Watanabe, M; Hishinuma, M; Nomoto, T; Oommen, S; Ghafoor, S; Harada, F; Nozawa-Inoue, K; Maeda, T; Peterková, R; Lesot, H; Inoue, J; Akiyama, T; Schmidt-Ullrich, R; Liu, B; Hu, Y; Page, A; Ramírez, Á; Sharpe, P T; Ohazama, A

    2015-01-01

    Nuclear factor kappa B (NF-κB) signaling plays critical roles in many physiological and pathological processes, including regulating organogenesis. Down-regulation of NF-κB signaling during development results in hypohidrotic ectodermal dysplasia. The roles of NF-κB signaling in tooth development, however, are not fully understood. We examined mice overexpressing IKKβ, an essential component of the NF-κB pathway, under keratin 5 promoter (K5-Ikkβ). K5-Ikkβ mice showed supernumerary incisors whose formation was accompanied by up-regulation of canonical Wnt signaling. Apoptosis that is normally observed in wild-type incisor epithelium was reduced in K5-Ikkβ mice. The supernumerary incisors in K5-Ikkβ mice were found to phenocopy extra incisors in mice with mutations of Wnt inhibitor, Wise. Excess NF-κB activity thus induces an ectopic odontogenesis program that is usually suppressed under physiological conditions.

  4. The localization of lectin binding sites on photoreceptor outer segments and pigment epithelium of dystrophic retinas.

    PubMed

    McLaughlin, B J; Wood, J G

    1980-07-01

    Carbohydrate-containing macromolecules on pigment epithelium (PE) and photoreceptor outer segment (OS) membranes of 14 to 16-day-old Royal College of Surgeons (RCS) rats and their genetic control (RCS-rdy+) have been localized with peroxidase-conjugated lectins from wheat germ agglutinin (WGA), Ricinus communis (RCA), Lens culinaris (LCA), and concanavalin A (Con A). All lectins stain the plasma membranes of photoreceptor inner segments and intact OSs of normal (RCS-rdy+) and dystrophic (RCS) retinas. In the normal retinas, all lectins stain also the plasma membranes of shed OSs, and WGA stains some intradisc membranes. In contrast, WGA, RCA, and Con A do not label the OS debris membranes in dystrophic retinas, but LCA labels some of them. In both normal and dystophic retinas, WGA uniformly labels both proximal and distal membrane surfaces of PE mcirovilli, whereas RCA labels primarily the distal regions. Con A labels both normal and dystrophic PE microvilli sparsely, and LCA stains the PE microvilli in RCS-rdy+ retinas more intensely than those in the RCS retinas. The major differences between the lectin labeling in normal and dystrophic retinas are the presence of LCA staining on OS debris and the absence of any other lectin staining on these membranes. Other differences are the sparse LCA staining on dystrophic PE microvillous membranes vs. the normal and the presence of WGA staining on OS intradisc membranes of normal retinas. These differences may reflect changes in the accessibility or composition of certain cell surface sugars on OS membranes and PE microvilli which may be related to the diminished rate of phagocytosis in RCS retinas. PMID:6156139

  5. Gallbladder epithelium as a niche for chronic Salmonella carriage.

    PubMed

    Gonzalez-Escobedo, Geoffrey; Gunn, John S

    2013-08-01

    Although typhoid fever has been intensively studied, chronic typhoid carriage still represents a problem for the transmission and persistence of the disease in areas of endemicity. This chronic state is highly associated with the presence of gallstones in the gallbladder of infected carriers upon which Salmonella can form robust biofilms. However, we hypothesize that in addition to gallstones, the gallbladder epithelium aids in the establishment/maintenance of chronic carriage. In this work, we present evidence of the role of the gallbladder epithelium in chronic carriage by a mechanism involving invasion, intracellular persistence, and biofilm formation. Salmonella was able to adhere to and invade polarized gallbladder epithelial cells apically in the absence and presence of bile in a Salmonella pathogenicity island 1 (SPI-1)-dependent manner. Intracellular replication of Salmonella was also evident at 12 and 24 h postinvasion. A flowthrough system revealed that Salmonella is able to adhere to and form extensive bacterial foci on gallbladder epithelial cells as early as 12 h postinoculation. In vivo experiments using a chronic mouse model of typhoid carriage showed invasion and damage of the gallbladder epithelium and lamina propria up to 2 months after Salmonella infection, with an abundant presence of macrophages, a relative absence of neutrophils, and extrusion of infected epithelial cells. Additionally, microcolonies of Salmonella cells were evident on the surface of the mouse gallbladder epithelia up to 21 days postinfection. These data reveal a second potential mechanism, intracellular persistence and/or bacterial aggregation in/on the gallbladder epithelium with luminal cell extrusion, for Salmonella maintenance in the gallbladder.

  6. Intraocular involvement with subretinal pigment epithelium infiltrates by mycosis fungoides.

    PubMed Central

    Erny, B. C.; Egbert, P. R.; Peat, I. M.; Shorrock, K.; Rosenthal, A. R.

    1991-01-01

    We report a case of intraocular mycosis fungoides in a 48-year-old man. The patient presented with decreased visual acuity, white subretinal lesions, and vitritis. Post-mortem histopathology revealed malignant T cell infiltrates consistent with mycosis fungoides in the retina, vitreous, and between the retinal pigment epithelium (RPE) and Bruch's membrane Focal atrophy of the RPE, along with the sub-RPE infiltrates, correlated with the clinically visible fundus lesions. Images PMID:1751471

  7. Dietary nitrogen reduction enhances urea transport across goat rumen epithelium.

    PubMed

    Muscher, A S; Schröder, B; Breves, G; Huber, K

    2010-10-01

    Ruminants are very capable of adapting their N homeostasis to a reduced dietary N intake. However, the limits of this physiological adaptation are still unknown. The aim of the present study was to determine the quantity of dietary N intake at which the needs of the animal are still satisfied. A study was performed in young White Saanen goats under conditions of dietary N reduction. Different semisynthetic diets with 19 to 7% CP were fed. Urea transport rates across the rumen epithelium from the blood into the ruminal fluid were quantified by Ussing chamber experiments. Reduced N intake increased urea transport rates across the mucosa, which could be inhibited by phloretin. The role of parietal urease in driving urea transfer across the epithelium was negligible because its activity was inhibited by antibiotics during in vitro incubations of the epithelium. Concentrations of ammonia in the ruminal fluid were decreased by reducing dietary N intake, accompanied by diminished urease activity at the smallest dietary N intake. Over the range of plasma urea concentrations observed in the different feeding groups, salivary urea concentrations were 73% of plasma urea concentrations. By plotting plasma urea concentrations against serosal to mucosal urea flux rates, a threshold at 1.75 mmol of urea/L of plasma could be assessed, below which urea flux was strongly increased. This indicates that rumen urea transfer could be stimulated by decreased plasma urea concentrations via unknown mechanisms. The physiological relevance of this adaptation of the rumen epithelium is that it is considered a central mechanism in the N homeostasis of growing goats under reduced N intake.

  8. ORAL LICHEN PLANUS AND ORAL LICHENOID REACTION--AN UPDATE.

    PubMed

    Rotim, Zeljko; Bolanca, Zeljana; Rogulj, Ana Andabak; Andabak, Matej; Boras, Vanja Vucićević; Vrdoljak, Danko Velimir

    2015-12-01

    Oral lichen planus (OLP) and oral lichenoid reaction (OLR) are clinically and histopathologically similar diseases. Whereas OLP is a consequence of T cell mediated autoinflammatory process to a still unknown antigen, OLR might be caused by drugs, dental restorative materials and dental plaque. Pubmed was searched and 24 publications published over the last three years regarding etiology, diagnosis and malignant alteration were included in this study. Patients with OLR who have amalgam fillings near lesions should have them replaced, i.e. when possible they should be referred to patch test, as well as when drug-induced OLR are suspected. OLR lesions induced by drugs should disappear when the offending drug has been discontinued. Histology finding in OLR consists of more eosinophils, plasma cells and granulocytes in comparison to OLP lesions. Furthermore, OLP lesions showed more p53, bcl-2 and COX-2 positivity when compared to OLR. OLP is characterized by infiltration, atrophic epithelium, rete pegs and Max Joseph spaces, while deep infiltration into connective tissue and hyperkeratosis were the criteria for making the diagnosis of OLR. The number of degranulated mastocytes in the reticular layer, as well as the number of capillaries was higher in OLR in comparison to OLP. It seems that OLR are more prone to malignant alteration in comparison to OLP. PMID:27017728

  9. The oxidant role of 4-hydroxynonenal in corneal epithelium.

    PubMed

    Chen, Longlong; Zong, Rongrong; Zhou, Jing; Ge, Lianping; Zhou, Tong; Ma, Jian-xing; Liu, Zuguo; Zhou, Yueping

    2015-01-01

    4-Hydroxynonenal (4-HNE or HNE) is a main endogenous product of cellular lipid peroxidation in tissues and is reported to play pathogenic roles in eye diseases. Here we investigated the association between 4-HNE and oxidative stress in the corneal epithelium. 4-HNE suppressed the cell viability of human corneal epithelial cells (HCE) in a concentration dependent manner. 4-HNE significantly increased the level of 3-Nitrotyrosine (3-NT), a marker of oxidative stress, in HCE cells and corneal epithelium of rats by immunofluorescent staining and Western blot analysis. To its underlying mechanistic on ROS system, 4-HNE elevated the ROS generation enzyme NADPH oxidase 4 (NOX4) and induced the activation of NF-E2-related factor-2 (NRF2) and its downstream effectors: NAD(P)H dehydrogenase (quinone 1) (NQO1) and glutathione S-transferase P (GSTP). Furthermore, N-acetylcysteine (NAC), an antioxidant and ROS scavenger, antagonized the inhibitory and oxidant effects of 4-HNE on the corneal epithelial cells. In conclusion, 4-HNE plays an oxidant role in the corneal epithelium and this work provides a new strategy for the pathogenesis and treatment of corneal diseases.

  10. Zinc uptake in vitro by human retinal pigment epithelium

    SciTech Connect

    Newsome, D.A.; Rothman, R.J.

    1987-11-01

    Zinc, an essential trace element, is present in unusually high concentrations in the chorioretinal complex relative to most other tissues. Because little has been known about the interactions between the retinal pigment epithelium and free or protein-associated zinc, we studied /sup 65/Zn uptake by human retinal pigment epithelium in vitro. When monolayers were exposed to differing concentrations from 0 to 30 microM /sup 65/Zn in Dulbecco's modified Eagle's medium with 5.4 gm/l glucose at 37 degrees C and 4 degrees C, we observed a temperature-dependent saturable accumulation of the radiolabel. With 15 microM /sup 65/Zn, we saw a biphasic pattern of uptake with a rapid first phase and a slower second phase over 120 min. Uptake of /sup 65/Zn was inhibited by iodacetate and cold, and reduced approximately 50% by the addition of 2% albumin to the labelling medium. Neither ouabain nor 2-deoxyglucose inhibited uptake. Cells previously exposed to /sup 65/Zn retained approximately 70% of accumulated /sup 65/Zn 60 min after being changed to radiolabel-free medium. Following removal of cells from the extracellular matrix adherent to the dish bottom, a variable amount of nonspecific binding of /sup 65/Zn to the residual matrix was demonstrated. These observations are consistent with a facilitated type of transport and demonstrate the ability of human retinal pigment epithelium in vitro to accumulate and retain zinc.

  11. In vitro biology of corneal epithelium and endothelium.

    PubMed Central

    Yanoff, M

    1975-01-01

    Four main areas are explored: (1) the proper culture medium for corneal tissue; (2) the effect of serum on in vitro tissue growth; (3) the in vitro interrelationships between corneal epithelium and endothelium; and (4) the biology of cultures of whole corneas (organ cultures). Modified Eagle's minimal essential medium (MEM) proved to be an excellent culture fluid. Corneal tissue could be grown in MEM without serum or clot, thus providing a defined culture medium. The in vitro biology of outgrowths of multilayered corneal epithelium and monolayered corneal endothelium are discussed. Contact inhibition between epithelium and endothelium is demonstrated in whole corneal (organ) cultures. Images FIGURE 5 A FIGURE 5 B FIGURE 10 A FIGURE 10 B FIGURE 1 A FIGURE 1 B FIGURE 1 C FIGURE 2 A FIGURE 2 B FIGURE 3 A FIGURE 3 B FIGURE 4 A FIGURE 4 B FIGURE 6 A FIGURE 6 B FIGURE 7 A FIGURE 7 B FIGURE 8 A FIGURE 8 B FIGURE 9 A FIGURE 9 B FIGURE 11 A FIGURE 11 B FIGURE 12 A FIGURE 12 B FIGURE 12 C FIGURE 13 FIGURE 14 A FIGURE 14 B FIGURE 15 A FIGURE 15 B FIGURE 16 A FIGURE 16 B FIGURE 17 A FIGURE 17 B FIGURE 17 C FIGURE 18 A FIGURE 18 B PMID:1246815

  12. Mucosal adenosine stimulates chloride secretion in canine tracheal epithelium

    SciTech Connect

    Pratt, A.D.; Clancy, G.; Welsh, M.J.

    1986-08-01

    Adenosine is a local regulator of a variety of physiological functions in many tissues and has been observed to stimulate secretion in several Cl-secreting epithelia. In canine tracheal epithelium the authors found that adenosine stimulates Cl secretion from both the mucosal and submucosal surfaces. Addition of adenosine, or its analogue 2-chloroadenosine, to the mucosal surface potently stimulated Cl secretion with no effect on the rate of Na absorption. Stimulation resulted from an interaction of adenosine with adenosine receptors, because it was blocked by the adenosine receptor blocker, 8-phenyltheophylline. The adenosine receptor was a stimulatory receptor as judged by the rank-order potency of adenosine and its analogues and by the increase in cellular adenosine 3',5'-cyclic monophosphate levels produced by 2-chloroadenosine. Adenosine also stimulated Cl secretion when it was added to the submucosal surface, although the maximal increase in secretion was less and it was much less potent. The observation that mucosal 8-phenyletheophylline blocked the effect of submucosal 2-chloroadenosine, whereas submucosal 8-phenyltheophylline did not prevent a response to mucosal or submucosal 2-chloroadenosine, suggests that adenosine receptors are located on the mucosal surface. Thus submucosal adenosine may stimulate secretion by crossing the epithelium and interacting with receptors located on the mucosal surface. Because adenosine can be released from mast cells located in the airway lumen in response to inhaled material, and because adenosine stimulated secretion from the mucosal surface, it may be in a unique position to control the epithelium on a regional level.

  13. The pocket epithelium: a light- and electronmicroscopic study.

    PubMed

    Müller-Glauser, W; Schroeder, H E

    1982-03-01

    The POCKET epithelium is important for the pathogenesis of gingivitis and periodontitis. However, this epithelial variant has never been adequately described. The bioptic material with supraalveolar pockets originated from previous studies in which cotton floss ligatures were placed around the crowns of premolars in eight dogs. After periods of 4 to 21 days or up to 5 months, block biopsies comprising dental and gingival tissues were taken on the buccal side. The tissues were processed for light- and electron microscopic examination. The observations revealed that the pocket epithelium (1) does not attach to the tooth, (2) forms irregular ridges and, over connective tissue papillae, thin coverings which occasionally ulcerate, (3) consists of cells only some of which show a tendency to differentiate, (4) presents a basal lamina complex with discontinuities and multiplications, and (5) is infiltrated mainly by lymphocytes, T- and B-blasts and plasma cells, and is transmigrated by neutrophilic granulocytes. It is concluded that the mosaic-like structure of the pocket epithelium reflects the heterogeneity of the adjacent plaque, that this structure together with the absence of membrane coating granules is the basis for an extremely high permeability, and that epithelial ridges may conduct and collect foreign substances which thereby become more easily recognizable for leukocytes.

  14. Developmental Readiness of Normal Full Term Infants To Progress from Exclusive Breastfeeding to the Introduction of Complementary Foods: Reviews of the Relevant Literature Concerning Infant Immunologic, Gastrointestinal, Oral Motor and Maternal Reproductive and Lactational Development.

    ERIC Educational Resources Information Center

    Naylor, Audrey J., Ed.; Morrow, Ardythe L., Ed.

    This review of the developmental readiness of normal, full-term infants to progress from exclusive breastfeeding to the introduction of complementary foods is the result of the international debate regarding the best age to introduce complementary foods into the diet of the breastfed human infant. After a list of definitions, four papers focus on:…

  15. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium. PMID:26927796

  16. T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium

    PubMed Central

    Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

    2016-01-01

    An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an “inverse” configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this

  17. T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium.

    PubMed

    Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

    2016-01-01

    An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an "inverse" configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this

  18. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.

  19. Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium

    PubMed Central

    Gao, Xia; Vockley, Christopher M.; Pauli, Florencia; Newberry, Kimberly M.; Xue, Yan; Randell, Scott H.; Reddy, Timothy E.; Hogan, Brigid L. M.

    2013-01-01

    Most of the airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated basal progenitor cells. The integrity of this epithelium and its ability to act as a selective barrier are critical for normal lung function. In other epithelia, there is evidence that transcription factors of the evolutionarily conserved grainyheadlike (GRHL) family play key roles in coordinating multiple cellular processes required for epithelial morphogenesis, differentiation, remodeling, and repair. However, only a few target genes have been identified, and little is known about GRHL function in the adult lung. Here we focus on the role of GRHL2 in primary human bronchial epithelial cells, both as undifferentiated progenitors and as they differentiate in air–liquid interface culture into an organized mucociliary epithelium with transepithelial resistance. Using a dominant-negative protein or shRNA to inhibit GRHL2, we follow changes in epithelial phenotype and gene transcription using RNA sequencing or microarray analysis. We identify several hundreds of genes that are directly or indirectly regulated by GRHL2 in both undifferentiated cells and air–liquid interface cultures. Using ChIP sequencing to map sites of GRHL2 binding in the basal cells, we identify 7,687 potential primary targets and confirm that GRHL2 binding is strongly enriched near GRHL2-regulated genes. Taken together, the results support the hypothesis that GRHL2 plays a key role in regulating many physiological functions of human airway epithelium, including those involving cell morphogenesis, adhesion, and motility. PMID:23690579

  20. Anti-inflammatory and protective effects of 2-methacryloyloxyethyl phosphorylcholine polymer on oral epithelial cells.

    PubMed

    Yumoto, Hiromichi; Hirota, Katsuhiko; Hirao, Kouji; Miyazaki, Tsuyoshi; Yamamoto, Nobuyuki; Miyamoto, Koji; Murakami, Keiji; Fujiwara, Natsumi; Matsuo, Takashi; Miyake, Yoichiro

    2015-02-01

    Periodontitis is a chronic inflammatory disease initiated by a microbial biofilm formed in the periodontal pocket. Gingival epithelium plays important roles as the first physical barrier to bacterial invasion and in orchestrating the innate immune reaction via toll-like receptors (TLRs), which recognize various bacterial products, and maintaining its function. Newly developed oral care products to inhibit bacterial adherence, subsequent inflammatory reaction and protect the gingival epithelium are expected. We previously reported that 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer coating decreased bacterial adhesion to human oral keratinocytes, RT-7, and mouth-rinsing with MPC-polymer inhibited the increase of oral bacteria. In this study, regarding the possibility of MPC-polymer application for preventing the adherence of periodontal pathogen, subsequent inflammatory reaction and protection of gingival epithelium, we examined the effects of MPC-polymer on the adherence of Porphyromonas gingivalis, major periodontitis-related pathogen, and TLR2 ligand to RT-7 and subsequent interleukin (IL)-8 production. MPC-polymer treatment significantly reduced P. gingivalis adherence by 44% and TLR2-mediated IL-8 production by blocking the binding of its specific-ligand in a concentration-dependent manner. Furthermore, MPC-polymer pretreatment protected RT-7 from injury by chemical irritants, cetylpyridinium chloride. These findings suggest that MPC-polymer is potentially useful for oral care to prevent oral infection and to maintain oral epithelial function. PMID:24753309

  1. Quantitative Immunoexpression of EGFR in Oral Potentially Malignant Disorders: Oral Leukoplakia and Oral Submucous Fibrosis.

    PubMed

    Jyothi Meka, Naga; Ugrappa, Sridevi; Velpula, Nagalaxmi; Kumar, Sravan; Naik Maloth, Kotya; Kodangal, Srikanth; Ch, Lalitha; Goyal, Stuti

    2015-01-01

    Background and aims. Many oral squamous cell carcinomas develop from potentially malignant disorders (PMDs)which include a variety of lesions and conditions characterized by an increased risk for malignant transformation. Thisstudy evaluated the quantitative expression of EGFR in normal oral mucosa, oral leukoplakia and oral submucous fibrosis to predict the malignant risk in compliance with the intensity of staining with EGFR. Materials and methods. Thirty subjects were included in the study, consisting of 10 oral leukoplakia (OL), 10 oral submucous fibrosis (OSMF) and 10 normal oral mucosa (NOM) as the control group. Owing to the histopathological confirmation of precancerous state of tissue, 4-μm-thick sections of tissue were taken from paraffin-embedded wax blocks for immunohistochemical staining for EGFR. Results. All the control cases showed positive expression for EGFR, while 20% of oral leukoplakia and 40% of OSMF cases showed strong expression (3+), 40% of OL and 30% of OSMF cases showed weak expression (2+), and 40% of OLand 30% of OSMF cases showed poor expression (1+) compared to controls (P=0.012). Conclusion. EGFR expression levels in the premalignant lesion appear to be a sensitive factor in predicting the neoplastic potential. This suggests that EGFR may serve as a biological marker to identify high-risk subgroups and guide prophylactic therapy with chemopreventive drugs or surgical intervention to prevent progression to carcinoma. Hence, further investigations in the direction of chemopreventive trials with a larger sample size are suggested to determine its role in the head and neck tumorigenesis. PMID:26697149

  2. Stromal myofibroblasts in oral leukoplakia and oral squamous cell carcinoma

    PubMed Central

    de-Assis, Eliene M.; Pimenta, Luiz G.G.S.; Costa-e-Silva, Edson; Souza, Paulo E.A.

    2012-01-01

    Objectives: Oral leukoplakia (OL) is the main potentially malignant disorder and oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. This study aimed to evaluate the presence of stromal myofibroblasts in OL and OSCC. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between histologically high- and low-invasive OSCC were also assessed. Study Design: A total of 30 OL and 41 OSCC from archival formalin-fixed, paraffin-embedded specimens were evaluated. 10 samples of normal oral mucosa were used as a control. Myofibroblasts were identified by immunohistochemical detection of alpha smooth muscle actin and its presence was classified as negative, scanty or abundant. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between high- and low-invasive OSCC were analyzed using the Mann-Whitney test. Results: Myofibroblasts were not detected in normal oral mucosa and OL, whatever its histological grade. In OSCC, the presence of stromal myofibroblasts was classified as negative in 11 (26.8%), scanty in 15 (36.6%), and abundant in 15 samples (36.6%). The presence of stromal myofibroblasts was statistically higher in high-invasive OSCC than in low-invasive OSCC (p<0.05). Conclusions: Stromal myofibroblasts were not detected in OL, indicating that these cells are not important during oral carcinogenesis. Nevertheless, stromal myofibroblasts were heterogeneously detected in OSCC and its presence was higher in tumors with a more diffuse histological pattern of invasion. These findings suggest that myofibroblasts are associated with the creation of a permissive environment for tumor invasion in OSCC. Key words:Leukoplakia, oral squamous cell carcinoma, myofibroblast. PMID:22322518

  3. The sertolian epithelium in the testis of men affected by 'Sertoli-cell-only syndrome'.

    PubMed

    Tedde, G; Montella, A; Fiocca, D; Delrio, A N

    1993-01-01

    Because of the architectural complexity of the seminiferous epithelium, the Sertoli cell is extremely difficult to study. The individual cellular constituents of the tubular wall are intimately associated with one another; especially Sertoli cells and germinal cells are tightly connected. As implied by the name, Sertoli-cell-only syndrome (SCOS) is characterized by the presence of only Sertoli cells in the seminiferous tubule. The absence of germinal cells makes this condition ideal for the morphological study of Sertoli cell. Testicular biopsy specimens of subjects affected by SCOS were studied under light and electron microscopy. The Sertoli cells appeared to be morphologically normal, except for their shape, that appears to be columnar as result of the complete absence of the germinal cells. The cellular outlines were irregular, particularly at the base, but the cytoplasm contained normal organelles and inclusions. The presence of both pale and dark elements was evident. These differences in staining reflect the variability in concentration of glycogen particles and intermediate microfilaments in the cytoplasm. In spite of these differences between Sertoli cells in SCOS and those in normal subjects, SCOS represents a satisfactory model for the morphological and functional analysis of the Sertoli cells. PMID:7694556

  4. Concentration dependent effects of tobacco particulates from different types of cigarettes on expression of drug metabolizing proteins, and benzo(a)pyrene metabolism in primary normal human oral epithelial cells

    PubMed Central

    Sacks, Peter G.; Zhao, Zhong-Lin; Kosinska, Wieslawa; Fleisher, Kenneth E.; Gordon, Terry; Guttenplan, Joseph B.

    2011-01-01

    The ability of tobacco smoke (TS) to modulate phase I and II enzymes and affect metabolism of tobacco carcinogens is likely an important factor in its carcinogenicity. For the first time several types of TS particulates (TSP) were compared in different primary cultured human oral epithelial cells (NOE) for their abilities to affect metabolism of the tobacco carcinogen, (BaP) to genotoxic products, and expression of drug metabolizing enzymes. TSP from, reference filtered (2RF4), mentholated (MS), reference unfiltered, (IR3), ultra low tar (UL), and cigarettes that primarily heat tobacco (ECL) were tested. Cells pretreated with TSP concentrations of 0.2 – 10 µg/ml generally showed increased rates of BaP metabolism; those treated with TSP concentrations above 10 µg/ml showed decreased rates. Effects of TSPs were similar when expressed on a weight basis. Weights of TSP/cigarette varied in the order: MS ≈ IR3 > 2RF4 > ECL > UL. All TSPs induced the phase I proteins, cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1), phase II proteins, NAD(P)H dehydrogenase quinone 1 (NQO1), and microsomal glutathione S-transferase 1 (MGST1), and additionally, hydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2), as assessed by qRT-PCR. The pattern of gene induction at probable physiological levels favored activation over detoxification. PMID:21722697

  5. Baicalein induces apoptosis and reduces inflammation in LPS-stimulated keratinocytes by blocking the activation of NF-κB: implications for alleviating oral lichen planus.

    PubMed

    Wang, J; Luo, H; Yang, L; Li, Y

    2016-01-01

    ic inflammatory diseases, including OLP, involves in the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Baicalein (BAI) is an alcohol soluble flavonoid known for its anti-inflammatory effect. However, its effectiveness on keratinocytes in OLP remains unclear. In the present study, we examined inflammation in oral mucosa tissue from OLP patients. Hematoxylin and eosin staining showed denser subepithelial lymphocytes infiltration compared to the normal oral mucosa epithelium. TNF-α and IL-6 were up-regulated in oral mucosa tissue of OLP patients. We next stimulated humans keratinocytes (HaCaT cells) with lipopolysaccharide (LPS) to create an inflammatory environment like that in the OLP tissue and assessed the effect of BAI on OLP and NF-κB signaling pathways. Our results showed that BAI treatment inhibited the level of TNF-α and IL-6 induced by LPS. However, the cells apoptosis was promoted after BAI treatment. Furthermore, BAI not only inhibited LPS-induced p38 MAPK and ERK1/2 phosphorylation, but also NF-κB activation by reducing IκBα phosphorylation and the nuclear translocation of NFκB-p65 and NFκB-p50 from cytoplasm to nucleus in keratinocytes. Our findings suggest that BAI inhibits the production of inflammatory cytokines by negatively regulating the NF-κB signaling pathway under LPS simulation in HaCaT cells. PMID:27453273

  6. Nateglinide Oral

    MedlinePlus

    ... normally and therefore cannot control the amount of sugar in the blood) in people whose diabetes cannot ... helps your body regulate the amount of glucose (sugar) in your blood. It decreases the amount of ...

  7. Feasibility of a porcine oral mucosa equivalent: a preclinical study.

    PubMed

    Kinikoglu, Beste; Hemar, Julie; Hasirci, Vasif; Breton, Pierre; Damour, Odile

    2012-08-01

    Oral tissue engineering aims to treat and fill tissue deficits caused by congenital defects, facial trauma, or malignant lesion surgery, as well as to study the biology of oral mucosa. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require a large animal model to evaluate cell-based devices, including tissue-engineered oral mucosa, prior to initiating human clinical studies. Porcine oral mucosa is non-keratinized and resembles that of humans more closely than any other animal in terms of structure and composition; however, there have not been any reports on the reconstruction of a porcine oral mucosa equivalent, probably due to the difficulty to culture porcine fibroblasts. In this study, we demonstrate the feasibility of a 3D porcine oral mucosa equivalent based on a collagen-GAG-chitosan scaffold, as well as reconstructed porcine epithelium by using an amniotic membrane as support, or without any support in form of epithelial cell sheets by using thermoresponsive culture plates. Explants technique was used for the isolation of the porcine fibroblasts and a modified fibroblast medium containing 20% fetal calf serum was used for their culture. The histological and transmission electron microscopic analyses of the resulting porcine oral mucosa models showed the presence of non-keratinized epithelia expressing keratin 13, the major differentiation marker of non-keratinized oral mucosa, in all models, and the presence of newly synthesized collagen fibers in the lamina propria equivalent of the full-thickness model, indicating the functionality of porcine fibroblasts. PMID:22309108

  8. Goblet cell targeting nanoparticle containing drug-loaded micelle cores for oral delivery of insulin.

    PubMed

    Zhang, Peiwen; Xu, Yining; Zhu, Xi; Huang, Yuan

    2015-12-30

    Oral administration of insulin remains a challenge due to its poor enzymatic stability and inefficient permeation across epithelium. We herein developed a novel self-assembled polyelectrolyte complex nanoparticles by coating insulin-loaded dodecylamine-graft-γ-polyglutamic acid micelles with trimethyl chitosan (TMC). The TMC material was also conjugated with a goblet cell-targeting peptide to enhance the affinity of nanoparticles with epithelium. The developed nanoparticle possessed significantly enhanced colloid stability, drug protection ability and ameliorated drug release profile compared with graft copolymer micelles or ionic crosslinked TMC nanoparticles. For in vitro evaluation, Caco-2/HT29-MTX-E12 cell co-cultures, which composed of not only enterocyte-like cells but also mucus-secreting cells and secreted mucus layer, were applied to mimic the epithelium. Intracellular uptake and transcellular permeation of encapsulated drug were greatly enhanced for NPs as compared with free insulin or micelles. Goblet cell-targeting modification further increased the affinity of NPs with epithelium with changed cellular internalization mechanism. The influence of mucus on the cell uptake was also investigated. Ex vivo performed with rat mucosal tissue demonstrated that the nanoparticle could facilitate the permeation of encapsulated insulin across the intestinal epithelium. In vivo study preformed on diabetic rats showed that the orally administered nanoparticles elicited a prolonged hypoglycemic response with relative bioavailability of 7.05%.

  9. Ultrastructural effects of the nonsteroidal contraceptive centchroman on rat uterine luminal epithelium in early pregnancy.

    PubMed

    Mehrotra, P K; Nilsson, B O

    1984-01-01

    Centchroman (3,4-trans-2,2-dimethyl-3-phenyl-4-p-(beta-pyrrolidinoethoxy) -phenyl-7-methoxychroman), a nonsteroidal contraceptive developed by the Central Drug Research Institute, Lucknow, India, was administered orally (1.25 mg/kg) to rats in a state of experimentally delayed implantation both during the progesterone treatment (preattachment stage) and in conjunction with the addition of estradiol (attachment stage). When given during preattachment, centchroman did not change the characteristic ultrastructure of the uterine epithelium significantly, except that there was an increase in the size and number of secondary lysosomes. Thus, no definite estrogenic or antiprogestational potency of centchroman was observed in this test system. However, when administered simultaneously with, before, or after estrogen during attachment, centchroman both abolished the estradiol-induced attachment reaction and produced or potentiated some changes of an estrogen type. Thus, no typical antiestrogen action but the sign of an estrogen action was observed in this test system. Further, the drug also produced certain specific changes in the lysosomal system of the epithelial cells during attachment. It is suggested that, in addition to some estrogenic effects, centchroman also possesses specific cellular effects, probably of a nonhormonal nature.

  10. Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer.

    PubMed

    Ness, R B; Grisso, J A; Cottreau, C; Klapper, J; Vergona, R; Wheeler, J E; Morgan, M; Schlesselman, J J

    2000-03-01

    Previous epidemiologic observations consistently suggest that suppression of ovulation, tubal ligation, and hysterectomy reduce the risk of ovarian cancer and that perineal talc use increases the risk. We examined these and other risk factors in the context of a new hypothesis: that inflammation may play a role in ovarian cancer risk. Ovulation entails ovarian epithelial inflammation; talc, endometriosis, cysts, and hyperthyroidism may be associated with inflammatory responses of the ovarian epithelium; gynecologic surgery may preclude irritants from reaching the ovaries via ascension from the lower genital tract. We evaluated these risk factors in a population-based case-control study. Cases 20-69 years of age with a recent diagnosis of epithelial ovarian cancer (767) were compared with community controls (1,367). We found that a number of reproductive and contraceptive factors that suppress ovulation, including gravidity, breast feeding, and oral contraception, reduced the risk of ovarian cancer. Environmental factors and medical conditions that increased risk included talc use, endometriosis, ovarian cysts, and hyperthyroidism. Gynecologic surgery including hysterectomy and tubal ligation were protective. Tubal ligation afforded a risk reduction even 20 or more years after the surgery. The spectrum of associations provides support for the hypothesis that inflammation may mediate ovarian cancer risk.

  11. Ion transport across an isolated preparation of sheep rumen epithelium.

    PubMed

    Ferreira, H G; Harrison, F A; Keynes, R D; Zurich, L

    1972-04-01

    1. The fluxes of isotopically labelled sodium, potassium and chloride passing in each direction across isolated sheets of rumen epithelium from the sheep have been measured under short-circuit conditions.2. With both sides of the epithelium bathed in chloride Ringer the mean sodium fluxes were 2.85 mumole/cm(2).hr from rumen to blood and 1.28 mumole/cm(2).hr in the reverse direction. In sulphate Ringer the sodium fluxes were 1.64 mumole/cm(2).hr from rumen to blood and 0.54 mumole/cm(2).hr from blood to rumen.3. In chloride Ringer the mean potassium fluxes were 0.18 mumole/cm(2).hr from rumen to blood and 0.54 mumole/cm(2).hr from blood to rumen. In sulphate Ringer the potassium fluxes were 0.07 mumole/cm(2).hr from rumen to blood and 0.35 mumole/cm(2).hr from blood to rumen.4. In chloride Ringer the mean chloride fluxes were 4.89 mumole/cm(2).hr from rumen to blood and 3.78 mumole/cm(2).hr from blood to rumen.5. In chloride Ringer the mean value of the short-circuit current was 13 muA/cm(2), corresponding to a flux of 0.49 muequiv/cm(2).hr. When sulphate was substituted for chloride, the short-circuit current was increased by about 40%, and the net flux of sodium from rumen to blood fell by 30%.6. Neither the sodium nor the chloride fluxes changed significantly when the epithelium was temporarily open-circuited.

  12. Lack of Dystrophin Affects Bronchial Epithelium in mdx Mice.

    PubMed

    Morici, Giuseppe; Rappa, Francesca; Cappello, Francesco; Pace, Elisabetta; Pace, Andrea; Mudò, Giuseppa; Crescimanno, Grazia; Belluardo, Natale; Bonsignore, Maria R

    2016-10-01

    Mild exercise training may positively affect the course of Duchenne Muscular Dystrophy (DMD). Training causes mild bronchial epithelial injury in both humans and mice, but no study assessed the effects of exercise in mdx mice, a well known model of DMD. The airway epithelium was examined in mdx (C57BL/10ScSn-Dmdmdx) mice, and in wild type (WT, C57BL/10ScSc) mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days of training (5 d/wk for 6 weeks), epithelial morphology and markers of regeneration, apoptosis, and cellular stress were assessed. The number of goblet cells in bronchial epithelium was much lower in mdx than in WT mice under all conditions. At 30 days, epithelial regeneration (PCNA positive cells) was higher in EX than SD animals in both groups; however, at 45 days, epithelial regeneration decreased in mdx mice irrespective of training, and the percentage of apoptotic (TUNEL positive) cells was higher in mdx-EX than in WT-EX mice. Epithelial expression of HSP60 (marker of stress) progressively decreased, and inversely correlated with epithelial apoptosis (r = -0.66, P = 0.01) only in mdx mice. Lack of dystrophin in mdx mice appears associated with defective epithelial differentiation, and transient epithelial regeneration during mild exercise training. Hence, lack of dystrophin might impair repair in bronchial epithelium, with potential clinical consequences in DMD patients. J. Cell. Physiol. 231: 2218-2223, 2016. © 2016 Wiley Periodicals, Inc.

  13. Response of macaque bronchiolar epithelium to ambient concentrations of ozone

    SciTech Connect

    Harkema, J.R.; Plopper, C.G.; Hyde, D.M.; St. George, J.A.; Wilson, D.W.; Dungworth, D.L. )

    1993-09-01

    Recently, we reported that exposure to ambient concentrations of ozone, near the U.S. National Ambient Air Quality Standard (0.12 ppm), induced significant nasal epithelial lesions in a non-human primate, the bonnet monkey. The present study defines the effects of ambient concentrations of ozone on the surface epithelium lining respiratory bronchioles and on the underlying bronchiolar interstitium in these same monkeys. Bonnet monkeys were exposed to filtered air or to 0.15 or 0.30 ppm ozone 8 hours/day for 6 or 90 days. At the end of exposures, monkeys were anesthetized and killed by exsanguination. Microdissected bronchiolar airways of infusion-fixed lungs were evaluated morphometrically by light microscopy and quantitatively by scanning and transmission electron microscopy for ozone-induced epithelial changes. Hyperplasia of nonciliated, cuboidal epithelial cells and intraluminal accumulation of macrophages characterized ozone-induced lesions in respiratory bronchioles. There were no significant differences in epithelial thickness or cell numbers among ozone-exposed groups. Ozone-exposed epithelium was composed of 80% cuboidal and 20% squamous cells compared with 40% cuboidal and 60% squamous cells in filtered air controls. In addition, the arithmetic mean thickness of the surface epithelium, a measure of tissue mass per unit area of basal lamina, was significantly increased in all of the ozone-exposed groups. The number of cuboidal epithelial cells per surface area of basal lamina was increased above control values by 780% after 6 days exposure to 0.15 ppm, 777% after 90 days to 0.15 ppm, and 996% after 90 days exposure to 0.30 ppm. There was also a significant ozone-induced increase in the thickness of the bronchiolar interstitium that was due to an increase in both cellular and acellular components.

  14. Expression of signaling components in embryonic eyelid epithelium.

    PubMed

    Meng, Qinghang; Jin, Chang; Chen, Yinglei; Chen, Jing; Medvedovic, Mario; Xia, Ying

    2014-01-01

    Closure of an epithelium opening is a critical morphogenetic event for development. An excellent example for this process is the transient closure of embryonic eyelid. Eyelid closure requires shape change and migration of epithelial cells at the tip of the developing eyelids, and is dictated by numerous signaling pathways. Here we evaluated gene expression in epithelial cells isolated from the tip (leading edge, LE) and inner surface epithelium (IE) of the eyelid from E15.5 mouse fetuses by laser capture microdissection (LCM). We showed that the LE and IE cells are different at E15.5, such that IE had higher expression of muscle specific genes, while LE acquired epithelium identities. Despite their distinct destinies, these cells were overall similar in expression of signaling components for the "eyelid closure pathways". However, while the LE cells had more abundant expression of Fgfr2, Erbb2, Shh, Ptch1 and 2, Smo and Gli2, and Jag1 and Notch1, the IE cells had more abundant expression of Bmp5 and Bmpr1a. In addition, the LE cells had more abundant expression of adenomatosis polyposis coli down-regulated 1 (Apcdd1), but the IE cells had high expression of Dkk2. Our results suggest that the functionally distinct LE and IE cells have also differential expression of signaling molecules that may contribute to the cell-specific responses to morphogenetic signals. The expression pattern suggests that the EGF, Shh and NOTCH pathways are preferentially active in LE cells, the BMP pathways are effective in IE cells, and the Wnt pathway may be repressed in LE and IE cells via different mechanisms.

  15. Nonequilibrium thermodynamic model of the rat proximal tubule epithelium.

    PubMed

    Weinstein, A M

    1983-11-01

    The rat proximal tubule epithelium is represented as well-stirred, compliant cellular and paracellular compartments bounded by mucosal and serosal bathing solutions. With a uniform pCO2 throughout the epithelium, the model variables include the concentrations of Na, K, Cl, HCO3, H2PO4, HPO4, and H, as well as hydrostatic pressure and electrical potential. Except for a metabolically driven Na-K exchanger at the basolateral cell membrane, all membrane transport within the epithelium is passive and is represented by the linear equations of nonequilibrium thermodynamics. In particular, this includes the cotransport of Na-Cl and Na-H2PO4 and countertransport of Na-H at the apical cell membrane. Experimental constraints on the choice of ionic conductivities are satisfied by allowing K-Cl cotransport at the basolateral membrane. The model equations include those for mass balance of the nonreacting species, as well as chemical equilibrium for the acidification reactions. Time-dependent terms are retained to permit the study of transient phenomena. In the steady state the energy dissipation is computed and verified equal to the sum of input from the Na-K exchanger plus the Gibbs free energy of mass addition to the system. The parameter dependence of coupled water transport is studied and shown to be consistent with the predictions of previous analytical models of the lateral intercellular space. Water transport in the presence of an end-proximal (HCO3-depleted) luminal solution is investigated. Here the lower permeability and higher reflection coefficient of HCO3 enhance net sodium and water transport. Due to enhanced flux across the tight junction, this process may permit proximal tubule Na transport to proceed with diminished energy dissipation.

  16. Expression of Signaling Components in Embryonic Eyelid Epithelium

    PubMed Central

    Meng, Qinghang; Jin, Chang; Chen, Yinglei; Chen, Jing; Medvedovic, Mario; Xia, Ying

    2014-01-01

    Closure of an epithelium opening is a critical morphogenetic event for development. An excellent example for this process is the transient closure of embryonic eyelid. Eyelid closure requires shape change and migration of epithelial cells at the tip of the developing eyelids, and is dictated by numerous signaling pathways. Here we evaluated gene expression in epithelial cells isolated from the tip (leading edge, LE) and inner surface epithelium (IE) of the eyelid from E15.5 mouse fetuses by laser capture microdissection (LCM). We showed that the LE and IE cells are different at E15.5, such that IE had higher expression of muscle specific genes, while LE acquired epithelium identities. Despite their distinct destinies, these cells were overall similar in expression of signaling components for the “eyelid closure pathways”. However, while the LE cells had more abundant expression of Fgfr2, Erbb2, Shh, Ptch1 and 2, Smo and Gli2, and Jag1 and Notch1, the IE cells had more abundant expression of Bmp5 and Bmpr1a. In addition, the LE cells had more abundant expression of adenomatosis polyposis coli down-regulated 1 (Apcdd1), but the IE cells had high expression of Dkk2. Our results suggest that the functionally distinct LE and IE cells have also differential expression of signaling molecules that may contribute to the cell-specific responses to morphogenetic signals. The expression pattern suggests that the EGF, Shh and NOTCH pathways are preferentially active in LE cells, the BMP pathways are effective in IE cells, and the Wnt pathway may be repressed in LE and IE cells via different mechanisms. PMID:24498290

  17. Stomatin immunoreactivity in ciliated cells of the human airway epithelium.

    PubMed

    Fricke, Britta; Stewart, Gordon W; Treharne, Kathryn J; Mehta, Anil; Knöpfle, Gisela; Friedrichs, Nicolaus; Müller, Klaus-Michael; von Düring, Monika

    2003-07-01

    Stomatin is a widely distributed 32kD membrane protein of unknown function. In biochemical studies it is associated with cholesterol+sphingomyelin-rich 'rafts' in the cytomembrane. Genetic studies in C. elegans, supported by microscopic studies in mammalian tissue and co-expression studies in oocytes, suggest a functional link with the DEG/ENaC (degenerin/epithelial Na+ channel) superfamily of monovalent ion channels. Since ENaC channels play a prominent role in the physiology of the respiratory epithelium, we have studied the immunolocalization of stomatin in mature and developing human airway epithelium by means of Western blot analysis, immunocytochemistry, and immunoelectron microscopy. Stomatin immunoreactivity (stomatin-IR) was found in the ciliated cells of the conductive airway epithelium in a distinct distribution pattern with the strongest signal along the cilia. Immunogold labelling revealed immunogold particles at the basal bodies, along the cilia, and at the membrane of the microvilli. The presence of stomatin-IR paralleled the stages of ciliogenesis in airway development, and its appearance preceded the elongation of the axoneme and the cilial outgrowth. Due to its presence in the different cellular locations in the ciliated cell, we suggest that stomatin is involved in various cellular functions. From its ultrastructural position, stomatin could be a candidate for a membrane-associated mechanotransducer with a role in the control of ciliary motility. Stomatin as a raft protein might be a microtubule associated protein moving along the outer surface of the microtubules to its terminal site of action in the cilia. Stomatin-IR in microvilli supports the hypothesis of a co-localization with beta- and gamma- ENaC and, in conclusion, their potential functional interaction to control the composition of periciliary mucus electrolytes. PMID:12759749

  18. Diet, Microbiome, and the Intestinal Epithelium: An Essential Triumvirate?

    PubMed Central

    Guzman, Javier Rivera; Conlin, Victoria Susan; Jobin, Christian

    2013-01-01

    The intestinal epithelium represents a critical barrier protecting the host against diverse luminal noxious agents, as well as preventing the uncontrolled uptake of bacteria that could activate an immune response in a susceptible host. The epithelial monolayer that constitutes this barrier is regulated by a meshwork of proteins that orchestrate complex biological function such as permeability, transepithelial electrical resistance, and movement of various macromolecules. Because of its key role in maintaining host homeostasis, factors regulating barrier function have attracted sustained attention from the research community. This paper will address the role of bacteria, bacterial-derived metabolism, and the interplay of dietary factors in controlling intestinal barrier function. PMID:23586037

  19. Expression of stanniocalcin in the epithelium of human choroid plexus.

    PubMed

    Franzén, A M; Zhang, K Z; Westberg, J A; Zhang, W M; Arola, J; Olsen, H S; Andersson, L C

    2000-12-29

    Stanniocalcin (STC) is a 28 kD glycoprotein hormone originally found in bony fish in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized mammalian STC shows about 70% homology with fish STC. The epithelial cells of proximal tubuli in human and rat kidney and brain neurons have been found to express STC. Here we show that the epithelium of the choroid plexus, already at 16 weeks of fetal age, and of plexus papillomas, synthesize and express STC. Our findings suggest that STC may be of importance for the distribution of calcium and phosphate between the cerebrospinal fluid and blood. PMID:11134638

  20. Combined hamartoma of the retina and retinal pigment epithelium

    PubMed Central

    Xue, Kanmin; Mellington, Faye; Gout, Irina; Rokerya, Sofia; Olurin, Oyinkan Ibironke; El-Amir, Ahmed

    2012-01-01

    We report two cases of combined hamatoma of the retina and retinal pigment epithelium (CHR-RPE), illustrated with ultrasonography, optical coherence tomography, fundus fluorescein angiography and indocyanine green angiography images. CHR-RPE could clinically mimic several other retinal conditions. Failure to distinguish it from serious malignancies such as choroidal melanoma or retinoblastoma has led to unnecessary enucleation in the past. Through these case reports and a review of literature, we show the diagnostic features of CHR-RPE, its key differential diagnoses and the management options. PMID:23162024

  1. Epithelial barrier and oral bacterial infection.

    PubMed

    Groeger, Sabine E; Meyle, Joerg

    2015-10-01

    The oral epithelial barrier separates the host from the environment and provides the first line of defense against pathogens, exogenous substances and mechanical stress. It consists of underlying connective tissue and a stratified keratinized epithelium with a basement membrane, whose cells undergo terminal differentiation resulting in the formation of a mechanically resistant surface. Gingival keratinocytes are connected by various transmembrane proteins, such as tight junctions, adherens junctions and gap junctions, each of which has a specialized structure and specific functions. Periodontal pathogens are able to induce inflammatory responses that lead to attachment loss and periodontal destruction. A number of studies have demonstrated that the characteristics of pathogenic oral bacteria influence the expression and structural integrity of different cell-cell junctions. Tissue destruction can be mediated by host cells following stimulation with cytokines and bacterial products. Keratinocytes, the main cell type in gingival epithelial tissues, express a variety of proinflammatory cytokines and chemokines, including interleukin-1alpha, interleukin-1beta, interleukin-6, interleukin-8 and tumor necrosis factor-alpha. Furthermore, the inflammatory mediators that may be secreted by oral keratinocytes are vascular endothelial growth factor, prostaglandin E2 , interleukin-1 receptor antagonist and chemokine (C-C motif) ligand 2. The protein family of matrix metalloproteinases is able to degrade all types of extracellular matrix protein, and can process a number of bioactive molecules. Matrix metalloproteinase activities under inflammatory conditions are mostly deregulated and often increased, and those mainly relevant in periodontal disease are matrix metalloproteinases 1, 2, 3, 8, 9, 13 and 24. Viral infection may also influence the epithelial barrier. Studies show that the expression of HIV proteins in the mucosal epithelium is correlated with the disruption of

  2. CFTR gene transfer to lung epithelium--on the trail of a target cell.

    PubMed

    O'Dea, S; Harrison, D J

    2002-05-01

    Cystic fibrosis (CF) is a lethal inherited disease that afflicts up to 1 in 2,500 people in the western world. Since 1989, when mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene were identified as responsible for the disease, intense effort has been applied to the development of replacement gene therapy strategies to cure CF. Problems with basic gene delivery techniques along with limited knowledge of the pathogenesis of CF have hindered progress so far. However, recent insights into the expression patterns and functions of CFTR in developing and adult lungs are now advancing our understanding of this disease. It is becoming apparent that progress in gene delivery to cure CF may be best served by identification of a target cell(s) around which gene transfer strategies can be specifically tailored to most closely reproduce the effects of normal CFTR expression. In fact, accurate restoration of endogenous expression patterns may be crucial, not only for disease reversal, but also to avoid potentially deleterious effects of inappropriate expression. This approach is in turn confounded however, by ill-defined stem and progenitor cell pathways within the lung epithelium. Nonetheless, studies to date suggest that these pathways are relatively plastic and may respond differently during homeostasis compared with repair following injury. It may therefore be feasible to target the lung epithelium in a non-cell specific manner and allow endogenous differentiation pathways to subsequently establish correct CFTR distribution patterns. In this review, emerging information on CFTR expression and function in developing and adult lungs is discussed in the context of putative stem cell populations and their potential for current gene delivery approaches. PMID:12109214

  3. Normal flora: living vehicles for non-invasive protein drug delivery.

    PubMed

    Shao, Jun; Kaushal, Gagan

    2004-11-22

    Feasibility to use probiotic bacteria as a living protein delivery system through oral route was assessed in vitro. Lactococcus lactis transformed with a plasmid to express and secret beta-lactamase was used to deliver beta-lactamase through Caco-2 monolayer, an intestine epithelium. Transport of beta-lactamase through Caco-2 monolayer was carried out in the transwells. The viability and integrity of the cell monolayers co-cultured with L. lactis was examined by trypan blue exclusion method and by measuring the transport of mannitol and propranolol as well as the transepithelial electrical resistance (TEER). Results show that it is feasible to use cell culture technique to evaluate the drug delivery by normal flora. The transport rate of beta-lactamase when delivered by L. lactis was 2.0 +/- 0.1 x 10(-2)h(-1) (n = 9) and through free solution form was 1.0 +/- 0.1 x 10(-2)h-1. When co-cultured with L. lactis, Caco-2 cell viability decreased to 98, 96, and 94% at 6, 8, and 10h, respectively. Transport of mannitol through Caco-2 cell monolayer was significantly increased and the transport of propranolol through Caco-2 cell monolayer was significantly decreased in the presence of L. lactis. Increase in the amount of protein delivered is probably due to the concentrate of the protein by L. lactis on the monolayer (absorption surface) and the opening of the tight junction of Caco-2 monolayer by L. lactis.

  4. Histological changes in radial forearm skin flaps in the oral cavity.

    PubMed

    Sinclair, A; Johnston, E; Badran, D H; Neilson, M; Soutar, D S; Robertson, A G; McDonald, S W

    2004-04-01

    We reported previously that skin flaps transplanted to the oral cavity in reconstructive surgery for oral cancer frequently acquired the gross appearance of buccal mucosa. The changes were shown to be reactive in nature. The "changed" flaps generally had a heavier infiltration of leukocytes in the dermis and appeared to have thicker epithelium. The present study quantifies these parameters, as well as the numbers of intraepithelial leukocytes. The flaps that had acquired the gross appearance of oral mucosa had significantly thicker epithelium, larger numbers of dermal leukocytes, and more intraepidermal inflammatory cells per unit length than flaps that retained the gross appearance of thin skin. No correlation was found between these changes and radiotherapy. PMID:15042571

  5. Role of topical drugs in treatment of oral mucosal diseases. A literature review.

    PubMed

    Sheikh, Soheyl; Gupta, Deepak; Pallagatti, Shambulingappa; Singla, Isha; Gupta, Rajesh; Goel, Varun

    2013-11-01

    Few topical formulations have been designed specifically to treat oral mucosal diseases. Local drug delivery may provide a more targeted and efficient option than systemic delivery for diseases of the oral mucosa. The permeability to the topical drugs differs according to the thickness of the epithelium and the extent of keratinization. The loss of the permeability barrier in the oral mucosa, due to ulceration or erosion, leads to rapid diffusion of the drug into tissues as compared to the intact areas of the mucosa. Oral mucosal delivery has the potential to treat many different conditions and diseases, such as oral cancer, mucositis, lichen planus, herpes simplex, candidiasis, recurrent aphthous stomatitis, vesiculo-bullous diseases, neuropathic pain and salivary dysfunction. Each therapy requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. In this paper, topical medications are discussed, as these are advantageous for the treatment of oral mucosal lesions with fewer side effects.

  6. Expression of Human β-Defensins in Conjunctival Epithelium: Relevance to Dry Eye Disease

    PubMed Central

    Narayanan, Srihari; Miller, William L.; McDermott, Alison M.

    2006-01-01

    Purpose. The goals of this study were to investigate whether β-defensins are differentially expressed in the conjunctival epithelium of patients with moderate dry eye when compared with normal subjects and whether proinflammatory cytokines or bacteria can modulate the expression of human β-defensins (hBDs)-1, -2, and -3 by conjunctival epithelial cells. Methods. RNA extracted from conjunctival impression cytology specimens of eight normal subjects and nine patients with moderate dry eye was used in RT-PCR to detect mRNA for hBDs-1, -2, and -3. Two conjunctival epithelial cell lines and primary cultured conjunctival epithelial cells were treated with proinflammatory cytokines or heat-killed Pseudomonas aeruginosa. RT-PCR and immunoblot analysis were used to detect mRNA for hBD-1, -2, and -3 and protein secretion of hBD-2, respectively. Results. hBD-2 message was detected in RNA samples of eight of nine patients with dry eye, but not in any of the normal subjects’ samples, whereas hBD-1 and -3 were detected in all subjects tested. RT-PCR revealed an upregulation of hBD-2 but no difference in expression of hBD-1 and -3 in cultured conjunctival cells after a 24-hour treatment with 10 ng/mL interleukin (IL)-1β, IL-1β and tumor necrosis factor-α (10 ng/mL) or heat-killed Pseudomonas aeruginosa (1 million colony-forming units; n = 3). hBD-2 expression was upregulated from 4 hours of treatment with IL-1β (at 10 ng/mL; (n = 2–3) and at a concentration of 0.1 ng/mL IL-1β (24-hour treatment; n = 2–3). Immunoblots demonstrated protein secretion results corresponding to the RT-PCR data. Conclusions. hBD-2 was expressed only in the conjunctival epithelium of patients with moderate dry eye. Because cytokines such as IL-1β and TNF-α induced the expression of hBD-2 by conjunctival epithelial cells and because increased proinflammatory cytokine activity is a feature of dry eye disease, it can be speculated that the hBD-2 upregulation observed in subjects with moderate

  7. The effects of lithogenic bile on gallbladder epithelium.

    PubMed Central

    Moody, F G; Haley-Russell, D; Li, Y F; Husband, K J; Weisbrodt, N W; Dewey, R B

    1989-01-01

    Prairie dogs were fed a 1.2% cholesterol diet for up to 24 weeks to evaluate the effects of lithogenic bile on the mucosa of the gallbladder. There was a progressive increase in the lithogenic index of the gallbladder bile (1.44 +/- 0.15 at 4 weeks, p less than 0.05). Fifty-five of 70 animals developed gallstones between the second and fourth week. Increasing stone burden was associated with a 27% (p less than 0.05) decrease in the electrical resistance of the epithelium and a 60% (p less than 0.05) decrease in net sodium transport when measured isotopically in an Ussing chamber (3 weeks). After 4 months, seven of ten animals developed inflammatory mucosal polyps characterized by a heavy infiltration of plasma cells into an expanded matrix. Cellular infiltration began as early as 2 weeks. These changes occurred without alterations in the ultrastructural appearance of the epithelium. Images Figs. 3A and B. Figs. 4A and B. Figs. 4A and B. Figs. 5A and B. PMID:2774711

  8. The growth and differentiation of transitional epithelium in vitro

    PubMed Central

    1979-01-01

    The development of rat transitional epithelial cells grown on conventional non-permeable surfaces was compared with development on permeable collagen supports. On glass or plastic surfaces, cells grew as expanding nomolayer sheets. Once confluent, growth continued with a bilayer being formed in most areas and apical cells being continuously sloughed off. Although most cells were interconnected by desmosomes, and junctional complexes were formed, no other indications of differentiation were observed. After 2-3 wk of growth, division stopped and cel death ensued. In contrast, single-cell suspensions plated on collagen-coated nylon disks reassociated into multicellular islands and commenced growth. Mitoses were confined to the basal cells in contact with the permeable substrate. The islands developed into epithelial trilayers, tapering to monolayers along spreading edges. Once the islands were confluent, stratification was completed and appeared similar to that observed in vivo. Germinal cells formed a basal lamina, and the upper layer was composed of large, flattened cells with an unusually thick asymmetrical plasma membrane on the apical surface. Electron microscopic and radioactive tracers demonstrated "leaky" zonulae occludentes with a restricted permeability to small molecules. The movement of urea was retarded in comparison to water. Unlike the slow turnover of adult epithelium in vivo, maturation and sloughing of apical cells were measurable. Transfer of cells could be effected and growth maintained for up to 4 mo. These results may indicate the necessity of a nutrient-permeable growth surface for the polarized differentiation of adult transitional epithelium. PMID:574872

  9. 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

  10. Electrodeposition of pronectin for titanium to augment gingival epithelium adhesion.

    PubMed

    Kawabata, Shingo; Asano, Kazunari; Miyazawa, Atsuko; Satoh, Tazuko; Tabata, Yasuhiko

    2013-05-01

    This paper is one trial of surface modification of titanium with pronectin F+ (PN) of an artificial protein to enhance gingival adhesion. Titanium plates were electrodeposited in the PN solution to prepare PN-electrodeposited titanium plates. When PN detachment from the PN-electrodeposited titanium plates was investigated, no detachment was observed, in contrast to the case of titanium plates simply coated with PN. A cell culture experiment demonstrated that electrodeposited PN had an inherent ability to enhance the initial attachment of gingival epithelial cells. The PN-electrodeposited titanium plates were implanted between the gingival epithelium and the underlying bone tissue of rabbits to evaluate epithelial growth on the plates and their gingival adhesion. Non-treated and PN-coated titanium plates were used as controls. PN electrodeposition enhanced epithelial growth and adhesion of titanium plates to a significantly great extent compared with PN-coated plates. These findings demonstrate that PN electrodeposition is a promising method to enhance epithelium adhesion onto a titanium surface.

  11. Regulation of gene expression in the intestinal epithelium.

    PubMed

    Richmond, Camilla A; Breault, David T

    2010-01-01

    Regulation of gene expression within the intestinal epithelium is complex and controlled by various signaling pathways that regulate the balance between proliferation and differentiation. Proliferation is required both to grow and to replace cells lost through apoptosis and attrition, yet in all but a few cells, differentiation must take place to prevent uncontrolled growth (cancer) and to provide essential functions. In this chapter, we review the major signaling pathways underlying regulation of gene expression within the intestinal epithelium, based primarily on data from mouse models, as well as specific morphogens and transcription factor families that have a major role in regulating intestinal gene expression, including the Hedgehog family, Forkhead Box (FOX) factors, Homeobox (HOX) genes, ParaHox genes, GATA transcription factors, canonical Wnt/β-catenin signaling, EPH/Ephrins, Sox9, BMP signaling, PTEN/PI3K, LKB1, K-RAS, Notch pathway, HNF, and MATH1. We also briefly highlight important emerging areas of gene regulation, including microRNA (miRNA) and epigenetic regulation. PMID:21075346

  12. Aldehyde dehydrogenase induction in arsenic-exposed rat bladder epithelium.

    PubMed

    Huang, Ya-Chun; Yu, Hsin-Su; Chai, Chee-Yin

    2016-01-01

    Arsenic is widely distributed in the environment. Many human cancers, including urothelial carcinoma (UC), show a dose-dependent relationship with arsenic exposure in the south-west coast of Taiwan (also known as the blackfoot disease (BFD) areas). However, the molecular mechanisms of arsenic-mediated UC carcinogenesis has not yet been defined. In vivo study, the rat bladder epithelium were exposed with arsenic for 48 h. The proteins were extracted from untreated and arsenic-treated rat bladder cells and utilized two-dimensional gel electrophoresis and mass spectrometry. Selected peptides were extracted from the gel and identified by quadrupole-time of flight (Q-TOF) Ultima-Micromass spectra. The significantly difference expression of proteins in arsenic-treated groups as compared with untreated groups was confirmed by immunohistochemistry (IHC) and western blotting. We found that thirteen proteins were down-regulated and nine proteins were up-regulated in arsenic-treated rat bladder cells when compared with untreated groups. The IHC and western blotting results confirmed that aldehyde dehydrogenase (ALDH) protein was up-regulated in arsenic-treated rat bladder epithelium. Expression of ALDH protein was significantly higher in UC patients from BFD areas than those from non-BFD areas using IHC (p=0.018). In conclusion, the ALDH protein expression could be used as molecular markers for arsenic-induced transformation.

  13. REGULATION OF GENE EXPRESSION IN THE INTESTINAL EPITHELIUM

    PubMed Central

    Richmond, Camilla A.; Breault, David T.

    2013-01-01

    Regulation of gene expression within the intestinal epithelium is complex and controlled by various signaling pathways that regulate the balance between proliferation and differentiation. Proliferation is required both to grow and to replace cells lost through apoptosis and attrition, yet in all but a few cells, differentiation must take place to prevent uncontrolled growth (cancer) and to provide essential functions. In this chapter, we will review the major signaling pathways underlying regulation of gene expression within the intestinal epithelium, based primarily on data from mouse models, as well as specific morphogens and transcription factor families that have a major role in regulating intestinal gene expression, including: the Hedgehog family, Forkhead Box (FOX) factors, Homeobox (HOX) genes, ParaHox genes, GATA transcription factors, canonical Wnt/β-catenin signaling, EPH/Ephrins, Sox9, BMP signaling, PTEN/PI3K, LKB1, K-RAS, Notch pathway, HNF and MATH1. We will also briefly highlight important emerging areas of gene regulation including microRNA and epigenetic regulation. PMID:21075346

  14. Expression of acid phosphatase in the seminiferous epithelium of vertebrates.

    PubMed

    Peruquetti, R L; Taboga, S R; Azeredo-Oliveira, M T V

    2010-01-01

    Acid phosphatases (AcPs) are known to provide phosphate to tissues that have high energy requirements, especially during development, growth and maturation. During spermatogenesis AcP activity is manifested in heterophagous lysosomes of Sertoli cells. This phagocytic function appears to be hormone-independent. We examined the expression pattern of AcP during the reproductive period of four species belonging to different vertebrate groups: Tilapia rendalli (Teleostei, Cichlidae), Dendropsophus minutus (Amphibia, Anura), Meriones unguiculatus (Mammalia, Rodentia), and Oryctolagus cuniculus (Mammalia, Lagomorpha). To demonstrate AcP activity, cryosections were processed for enzyme histochemistry by a modification of the method of Gömöri. AcP activity was similar in the testes of these four species. Testes of T. rendalli, D. minutus and M. unguiculatus showed an intense reaction in the Sertoli cell region. AcP activity was detected in the testes of D. minutus and O. cuniculus in seminiferous epithelium regions, where cells are found in more advanced stages of development. The seminiferous epithelium of all four species exhibited AcP activity, mainly in the cytoplasm of either Sertoli cells or germ cells. These findings reinforce the importance of AcP activity during the spermatogenesis process in vertebrates. PMID:20391346

  15. Selective gene expression by rat gastric corpus epithelium

    PubMed Central

    Goebel, M.; Stengel, A.; Sachs, G.

    2011-01-01

    The gastrointestinal (GI) tract is divided into several segments that have distinct functional properties, largely absorptive. The gastric corpus is the only segment thought of as largely secretory. Microarray hybridization of the gastric corpus mucosal epithelial cells was used to compare gene expression with other segments of the columnar GI tract followed by statistical data subtraction to identify genes selectively expressed by the rat gastric corpus mucosa. This provides a means of identifying less obvious specific functions of the corpus in addition to its secretion-related genes. For example, important properties found by this GI tract comparative transcriptome reflect the energy demand of acid secretion, a role in lipid metabolism, the large variety of resident neuroendocrine cells, responses to damaging agents and transcription factors defining differentiation of its epithelium. In terms of overlap of gastric corpus genes with the rest of the GI tract, the distal small bowel appears to express many of the gastric corpus genes in contrast to proximal small and large bowel. This differential map of gene expression by the gastric corpus epithelium will allow a more detailed description of major properties of the gastric corpus and may lead to the discovery of gastric corpus cell differentiation genes and those mis-regulated in gastric carcinomas. PMID:21177383

  16. Nanotopography follows force in TGF-β1 stimulated epithelium

    NASA Astrophysics Data System (ADS)

    Thoelking, Gerold; Reiss, Bjoern; Wegener, Joachim; Oberleithner, Hans; Pavenstaedt, Hermann; Riethmuller, Christoph

    2010-07-01

    Inflammation and cellular fibrosis often imply an involvement of the cytokine TGF-β1. TGF-β1 induces epithelial-to-mesenchymal transdifferentiation (EMT), a term describing the loss of epithelium-specific function. Indicative for this process are an elongated cell shape parallel to stress fibre formation. Many signalling pathways of TGF-β1 have been discovered, but mechanical aspects have not yet been investigated. In this study, atomic force microscopy (AFM) was used to analyse surface topography and mechanical properties of EMT in proximal kidney tubule epithelium (NRK52E). Elongated cells, an increase of stress fibre formation and a loss of microvillus compatible structures were observed as characteristic signs of EMT. Furthermore, AFM could identify an increase in stiffness by 71% after six days of stimulation with TGF-β1. As a novel topographical phenomenon, nodular protrusions emerged at the cell-cell junctions. They occurred preferentially at sites where stress fibres cross the border. Since these nodular protrusions were sensitive to inhibitors of force generation, they can indicate intracellular tension. The results demonstrate a manifest impact of elevated tension on the cellular topography.

  17. New insights in wound response and repair of epithelium.

    PubMed

    Chi, Cheryl; Trinkaus-Randall, Vickery

    2013-05-01

    Epithelial wounds usually heal relatively quickly, but repair may be impaired by environmental stressors, such as hypoxic or diabetic states, rendering patients vulnerable to a number of corneal pathologies. Though this response appears simple, at first, years of research have uncovered the complicated biochemical pathways coordinating the wound healing response. Here, we investigate signaling cascades and individual proteins involved in the corneal epithelium's self-repair. We will explore how an epithelial cell migrates across the wound bed and attaches itself to its new post-injury surroundings, including its neighboring cells and the basement membrane, through focal adhesions and hemidesmosomes. We will also discuss how the cell coordinates this motion physiologically, through calcium signaling and protein phosphorylation, focusing on the communication through purinergic, glutamatergic, and growth factor receptors. Many of these aspects reflect and can be extended to similar epithelial surfaces, and can be used to facilitate wound healing in patients with various underlying pathologies. The collective library of laboratory and clinical research done around the world has demonstrated how important precise regulation of these processes is in order for the injured corneal epithelium to properly heal.

  18. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    NASA Astrophysics Data System (ADS)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  19. Esophageal epithelium of women with AIDS: thickness and local immunity.

    PubMed

    Rocha, Laura; Silva, Renata; Olegário, Janaínna; Corrêa, Rosana; Teixeira, Vicente; Cavellani, Camila

    2010-04-15

    The aim of this study was to evaluate the morphological characteristics of the esophageal epithelium (EE) and its local immunity. Esophageal fragments of autopsied women were collected from 1980 to 2008, and two groups were analyzed: with AIDS (n=17) and without AIDS (n=12). The measurement of the esophageal epithelium was carried out through the image analysis software ImageJ, and the immunostaining of Langerhans cells (LCs) was carried out using anti-S100 antibody. Women with AIDS, when compared with women without AIDS, had significantly thinner EE (220.6 versus 243.5 microm), a less number of LCs (6.2 versus 18.8 LCs/mm(2)), and a higher percentage of immature or morphologically altered LCs (66.6 versus 40.0%). The malnourished women, when compared with normonourished women, regardless of AIDS, had significantly thinner EE (227.1 versus 238.0 microm) and a less number of LCs (6.2 versus 12.5 LCs/mm(2)). The percentage of immature or morphologically altered LCs was the same in both groups. Additionally, the women with AIDS (7.0 versus 2.8%) and the malnourished women (5.8 versus 3.1%) presented a significantly higher percentage of fibrosis. We concluded that AIDS and malnutrition contribute to the decrease in esophagus local immunity and, therefore, to a possible increase in local opportunistic infections.

  20. Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations.

    PubMed

    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. Aldehyde dehydrogenase induction in arsenic-exposed rat bladder epithelium.

    PubMed

    Huang, Ya-Chun; Yu, Hsin-Su; Chai, Chee-Yin

    2016-01-01

    Arsenic is widely distributed in the environment. Many human cancers, including urothelial carcinoma (UC), show a dose-dependent relationship with arsenic exposure in the south-west coast of Taiwan (also known as the blackfoot disease (BFD) areas). However, the molecular mechanisms of arsenic-mediated UC carcinogenesis has not yet been defined. In vivo study, the rat bladder epithelium were exposed with arsenic for 48 h. The proteins were extracted from untreated and arsenic-treated rat bladder cells and utilized two-dimensional gel electrophoresis and mass spectrometry. Selected peptides were extracted from the gel and identified by quadrupole-time of flight (Q-TOF) Ultima-Micromass spectra. The significantly difference expression of proteins in arsenic-treated groups as compared with untreated groups was confirmed by immunohistochemistry (IHC) and western blotting. We found that thirteen proteins were down-regulated and nine proteins were up-regulated in arsenic-treated rat bladder cells when compared with untreated groups. The IHC and western blotting results confirmed that aldehyde dehydrogenase (ALDH) protein was up-regulated in arsenic-treated rat bladder epithelium. Expression of ALDH protein was significantly higher in UC patients from BFD areas than those from non-BFD areas using IHC (p=0.018). In conclusion, the ALDH protein expression could be used as molecular markers for arsenic-induced transformation. PMID:26482281

  2. [Oral pain].

    PubMed

    Benslama, Lotfi

    2002-02-15

    Pain, a major symptom of stomatological disease, usually leads to a specialist consultation. Most commonly it is caused by dental caries and differs in nature and in intensity according to the stage of disease: dentinitis, pulpitis, desmodontitis and dental abscess. Added to this is peridental pain and the pre- and post-operative pains related to these diseases. Almost all oral-maxillary pathology is painful, be it boney such as in osteomyelitis and fractures, mucosal in gingivo-stomatitis and aphthous ulcers, or tumourous. However, besides the "multidisciplinary" facial pains such as facial neuralgia and vascular pain, two pain syndromes are specific to stomatology: pain of the tempero-mandibular joint associated with problems of the bite and glossodynia, a very common somatic expression of psychological problems.

  3. [Oral contraception].

    PubMed

    Guillat, J C

    1980-04-20

    OC (oral contraception) includes the combined and sequential methods, postcoital and progestin only contraception, mini pills, and macro pills. The mechanism of action of OC modifies the hypothalamo-hypophysary secretion, the uterine mucosa, and the cervical mucus. Effectiveness of OC is nearly 100%; prescription of OC requires a complete clinical and biological evaluation of the patient. Contraindications to OC are any form of cancer, hypertension, vascular or thrombotic antecedents, obesity, tabagism, diabetes. OC users must be checked at least every 6 months, and treatment can last, if there are no evident signs of side effects, until about age 40. The most commonly known side effects of OC are menstruation disorders, cardio- and cerebrovascular effects, hepatic and metabolic effects; there is no evidence that OC can cause carcinogenic effects, but it can increase teratogenic risk. The association of OC with such drugs as Rifampicine, anticonvulsants and/or tranquillizers, can nullify contraceptive effectiveness. PMID:6900393

  4. Oral geotrichosis: report of 12 cases.

    PubMed

    Bonifaz, Alexandro; Vázquez-González, Denisse; Macías, Berenice; Paredes-Farrera, Fernando; Hernández, Marco A; Araiza, Javier; Ponce, Rosa M

    2010-09-01

    Oral geotrichosis is an uncommon opportunistic infection caused by Geotrichum candidum, a habitual contaminant and component of the flora of various parts of the body. This communication reports both a 20-year retrospective study of clinically and mycologically proven cases of oral geotrichosis, and a prospective study of fungal oral flora in 200 individuals divided into two groups: normal individuals and individuals with associated conditions. Twelve patients with proven oral geotrichosis were included: 9 females and 3 males, with a mean age of 48.5 years; the associated conditions were diabetes mellitus (66.6%), leukemia, Hodgkin's lymphoma and HIV/AIDS infection. The oral geotrichoses showed three clinical varieties: pseudomembranous (75%), hyperplastic, and palatine ulcer. G. candidum was isolated in 11 cases and G. capitatum in one. Positive fungal cultures were obtained from the two groups, and 48% and 78% of cultures were positive, respectively, for Candida spp. In 2.8% and 6.33% of the cases, G. candidum was isolated, respectively, together with one strain of G. capitatum. Oral geotrichosis is an exceptional infection that clinically presents, and is treated, as oral candidiasis. G. candidum may be isolated from the oral flora of a small proportion of patients, either normal individuals or those with associated conditions.

  5. microRNA-dependent Temporal Gene Expression in the Ureteric Bud Epithelium during Mammalian Kidney Development

    PubMed Central

    Nagalakshmi, Vidya K.; Lindner, Volkhard; Wessels, Andy; Yu, Jing

    2014-01-01

    Background Our previous study on mouse mutants with the ureteric bud (UB) epithelium-specific Dicer deletion (Dicer UB mutants) demonstrated the significance of UB epithelium-derived miRNAs in UB development. Results Our whole-genome transcriptional profiling showed that the Dicer mutant UB epithelium abnormally retained transcriptional features of the early UB epithelium and failed to express many genes associated with collecting duct differentiation. Further, we identified a temporal expression pattern of early UB genes during UB epithelium development in which gene expression was detected at early developmental stages and became undetectable by E14.5. In contrast, expression of early UB genes persisted at later stages in the Dicer mutant UB epithelium and increased at early stages. Our bioinformatics analysis of the abnormally persistently expressed early genes in the Dicer mutant UB epithelium showed significant enrichment of the let-7 family miRNA targets. We further identified a temporal expression pattern of let-7 miRNAs in the UB epithelium that is anti-parallel to that of some early UB genes during kidney development. Conclusions We propose a model in which the let-7 family miRNAs silence the expression of a subset of early genes in the UB epithelium at later developmental stages in order to promote collecting duct differentiation. PMID:25369991

  6. Diacylglycerol O-Acyltransferase Type-1 Synthesizes Retinyl Esters in the Retina and Retinal Pigment Epithelium

    PubMed Central

    Kaylor, Joanna J.; Radu, Roxana A.; Bischoff, Nicholas; Makshanoff, Jacob; Hu, Jane; Lloyd, Marcia; Eddington, Shannan; Bianconi, Tran; Bok, Dean; Travis, Gabriel H.

    2015-01-01

    Retinyl esters represent an insoluble storage form of vitamin A and are substrates for the retinoid isomerase (Rpe65) in cells of the retinal pigment epithelium (RPE). The major retinyl-ester synthase in RPE cells is lecithin:retinol acyl-transferase (LRAT). A second palmitoyl coenzyme A-dependent retinyl-ester synthase activity has been observed in RPE homogenates but the protein responsible has not been identified. Here we show that diacylglycerol O-acyltransferase-1 (DGAT1) is expressed in multiple cells of the retina including RPE and Müller glial cells. DGAT1 catalyzes the synthesis of retinyl esters from multiple retinol isomers with similar catalytic efficiencies. Loss of DGAT1 in dgat1 -/- mice has no effect on retinal anatomy or the ultrastructure of photoreceptor outer-segments (OS) and RPE cells. Levels of visual chromophore in dgat1 -/- mice were also normal. However, the normal build-up of all-trans-retinyl esters (all-trans-RE’s) in the RPE during the first hour after a deep photobleach of visual pigments in the retina was not seen in dgat1 -/- mice. Further, total retinyl-ester synthase activity was reduced in both dgat1 -/- retina and RPE. PMID:25974161

  7. Diacylglycerol O-acyltransferase type-1 synthesizes retinyl esters in the retina and retinal pigment epithelium.

    PubMed

    Kaylor, Joanna J; Radu, Roxana A; Bischoff, Nicholas; Makshanoff, Jacob; Hu, Jane; Lloyd, Marcia; Eddington, Shannan; Bianconi, Tran; Bok, Dean; Travis, Gabriel H

    2015-01-01

    Retinyl esters represent an insoluble storage form of vitamin A and are substrates for the retinoid isomerase (Rpe65) in cells of the retinal pigment epithelium (RPE). The major retinyl-ester synthase in RPE cells is lecithin:retinol acyl-transferase (LRAT). A second palmitoyl coenzyme A-dependent retinyl-ester synthase activity has been observed in RPE homogenates but the protein responsible has not been identified. Here we show that diacylglycerol O-acyltransferase-1 (DGAT1) is expressed in multiple cells of the retina including RPE and Müller glial cells. DGAT1 catalyzes the synthesis of retinyl esters from multiple retinol isomers with similar catalytic efficiencies. Loss of DGAT1 in dgat1(-/-) mice has no effect on retinal anatomy or the ultrastructure of photoreceptor outer-segments (OS) and RPE cells. Levels of visual chromophore in dgat1(-/-) mice were also normal. However, the normal build-up of all-trans-retinyl esters (all-trans-RE's) in the RPE during the first hour after a deep photobleach of visual pigments in the retina was not seen in dgat1(-/-) mice. Further, total retinyl-ester synthase activity was reduced in both dgat1(-/-) retina and RPE.

  8. Bifidobacterium bifidum reduces apoptosis in the intestinal epithelium in necrotizing enterocolitis

    PubMed Central

    Khailova, Ludmila; Mount Patrick, Sarah K.; Arganbright, Kelly M.; Halpern, Melissa D.; Kinouchi, Toshi

    2010-01-01

    Necrotizing enterocolitis (NEC) is a devastating intestinal disease of neonates, and clinical studies suggest the beneficial effect of probiotics in NEC prevention. Recently, we have shown that administration of Bifidobacterium bifidum protects against NEC in a rat model. Intestinal apoptosis can be suppressed by activation of cyclooxygenase-2 (COX-2) and increased production of prostaglandin E2 (PGE2). The present study investigates the effect of B. bifidum on intestinal apoptosis in the rat NEC model and in an intestinal epithelial cell line (IEC-6), as a mechanism of protection against mucosal injury. Premature rats were divided into the following three groups: dam fed, hand fed with formula (NEC), or hand fed with formula supplemented with B. bifidum (NEC + B. bifidum). Intestinal Toll-like receptor-2 (TLR-2), COX-2, PGE2, and apoptotic regulators were measured. The effect of B. bifidum was verified in IEC-6 cells using a model of cytokine-induced apoptosis. Administration of B. bifidum increased expression of TLR-2, COX-2, and PGE2 and significantly reduced apoptosis in the intestinal epithelium of both in vivo and in vitro models. The Bax-to-Bcl-w ratio was shifted toward cell survival, and the number of cleaved caspase-3 positive cells was markedly decreased in B. bifidum-treated rats. Experiments in IEC-6 cells showed anti-apoptotic effect of B. bifidum. Inhibition of COX-2 signaling blocked the protective effect of B. bifidum treatment in both in vivo and in vitro models. In conclusion, oral administration of B. bifidum activates TLR-2 in the intestinal epithelium. B. bifidum increases expression of COX-2, which leads to higher production of PGE2 in the ileum and protects against intestinal apoptosis associated with NEC. This study indicates the ability of B. bifidum to downregulate apoptosis in the rat NEC model and in IEC-6 cells by a COX-2-dependent matter and suggests a molecular mechanism by which this probiotic reduces mucosal injury and preserves

  9. Ultrastructural studies of the transitional zone in the nasopharyngeal epithelium, with special reference to the keratinizing process in the mouse.

    PubMed

    Nakano, T

    1986-01-01

    In the nasopharynx of the SMA mouse, the 'intermediate epithelium' occupies the transitional zone between the ciliated columnar and the stratified squamous epithelia. The intermediate epithelium showed gradations ranging from ciliated stratified low-columnar through stratified cuboidal to stratified squamous type. It is suggested that the intermediate epithelium shows the various stages of the epithelium transforming from the ciliated columnar to the stratified squamous epithelium, and that the basal cells of the ciliated columnar epithelium serve as the germinal layer for the transformation. The intermediate epithelium containing a few keratohyalin granules and many membrane-coating granules represented earlier stages of keratinization. The width of the microprojections in the stratified squamous epithelium was about doubled compared to that in the intermediate epithelium. It is suggested that the difference in width is caused by cell membrane distortion associated with keratinization and is regarded as an important marker of the start of keratinization.

  10. Approaches for Enhancing Oral Bioavailability of Peptides and Proteins

    PubMed Central

    Renukuntla, Jwala; Vadlapudi, Aswani Dutt; Patel, Ashaben; Boddu, Sai HS.; Mitra, Ashim K

    2013-01-01

    Oral delivery of peptide and protein drugs faces immense challenge partially due to the gastrointestinal (GI) environment. In spite of considerable efforts by industrial and academic laboratories, no major breakthrough in the effective oral delivery of polypeptides and proteins has been accomplished. Upon oral administration, gastrointestinal epithelium acts as a physical and biochemical barrier for absorption of proteins resulting in low bioavailability (typically less than 1–2%). An ideal oral drug delivery system should be capable of a) maintaining the integrity of protein molecules until it reaches the site of absorption, b) releasing the drug at the target absorption site, where the delivery system appends to that site by virtue of specific interaction, and c) retaining inside the gastrointestinal tract irrespective of its transitory constraints. Various technologies have been explored to overcome the problems associated with the oral delivery of macromolecules such as insulin, gonadotropin-releasing hormones, calcitonin, human growth factor, vaccines, enkephalins, and interferons, all of which met with limited success. This review article intends to summarize the physiological barriers to oral delivery of peptides and proteins and novel pharmaceutical approaches to circumvent these barriers and enhance oral bioavailability of these macromolecules. PMID:23428883

  11. Response of macaque bronchiolar epithelium to ambient concentrations of ozone.

    PubMed Central

    Harkema, J. R.; Plopper, C. G.; Hyde, D. M.; St George, J. A.; Wilson, D. W.; Dungworth, D. L.

    1993-01-01

    Recently, we reported that exposure to ambient concentrations of ozone, near the U.S. National Ambient Air Quality Standard (0.12 ppm), induced significant nasal epithelial lesions in a non-human primate, the bonnet monkey. The present study defines the effects of ambient concentrations of ozone on the surface epithelium lining respiratory bronchioles and on the underlying bronchiolar interstitium in these same monkeys. Bonnet monkeys were exposed to filtered air or to 0.15 or 0.30 ppm ozone 8 hours/day for 6 or 90 days. At the end of exposures, monkeys were anesthetized and killed by exsanguination. Microdissected bronchiolar airways of infusion-fixed lungs were evaluated morphometrically by light microscopy and quantitatively by scanning and transmission electron microscopy for ozone-induced epithelial changes. Hyperplasia of nonciliated, cuboidal epithelial cells and intraluminal accumulation of macrophages characterized ozone-induced lesions in respiratory bronchioles. There were no significant differences in epithelial thickness or cell numbers among ozone-exposed groups. Ozone-exposed epithelium was composed of 80% cuboidal and 20% squamous cells compared with 40% cuboidal and 60% squamous cells in filtered air controls. In addition, the arithmetic mean thickness of the surface epithelium, a measure of tissue mass per unit area of basal lamina, was significantly increased in all of the ozone-exposed groups. The number of cuboidal epithelial cells per surface area of basal lamina was increased above control values by 780% after 6 days exposure to 0.15 ppm, 777% after 90 days to 0.15 ppm, and 996% after 90 days exposure to 0.30 ppm. There was also a significant ozone-induced increase in the thickness of the bronchiolar interstitium that was due to an increase in both cellular and acellular components. These results demonstrate that exposure to low ambient concentrations of ozone, near the current. National Ambient Air Quality Standard, induces pulmonary lesions

  12. Non-thermal electromagnetic radiation damage to lens epithelium.

    PubMed

    Bormusov, Elvira; P Andley, Usha; Sharon, Naomi; Schächter, Levi; Lahav, Assaf; Dovrat, Ahuva

    2008-05-21

    High frequency microwave electromagnetic radiation from mobile phones and other modern devices has the potential to damage eye tissues, but its effect on the lens epithelium is unknown at present. The objective of this study was to investigate the non-thermal effects of high frequency microwave electromagnetic radiation (1.1GHz, 2.22 mW) on the eye lens epithelium in situ. Bovine lenses were incubated in organ culture at 35°C for 10-15 days. A novel computer-controlled microwave source was used to investigate the effects of microwave radiation on the lenses. 58 lenses were used in this study. The lenses were divided into four groups: (1) Control lenses incubated in organ culture for 10 to15 days. (2) Electromagnetic radiation exposure group treated with 1.1 GHz, 2.22 mW microwave radiation for 90 cycles of 50 minutes irradiation followed by 10 minutes pause and cultured up to 10 days. (3) Electromagnetic radiation exposure group treated as group 2 with 192 cycles of radiation and cultured for 15 days. (4) Lenses exposed to 39.5°C for 2 hours 3 times with 24 hours interval after each treatment beginning on the second day of the culture and cultured for 11 days. During the culture period, lens optical quality was followed daily by a computer-operated scanning laser beam. At the end of the culture period, control and treated lenses were analyzed morphologically and by assessment of the lens epithelial ATPase activity. Exposure to 1.1 GHz, 2.22 mW microwaves caused a reversible decrease in lens optical quality accompanied by irreversible morphological and biochemical damage to the lens epithelial cell layer. The effect of the electromagnetic radiation on the lens epithelium was remarkably different from those of conductive heat. The results of this investigation showed that electromagnetic fields from microwave radiation have a negative impact on the eye lens. The lens damage by electromagnetic fields was distinctly different from that caused by conductive heat.

  13. Structural alteration of tight and adherens junctions in villous and crypt epithelium of the small and large intestine of conventional nursing piglets infected with porcine epidemic diarrhea virus.

    PubMed

    Jung, Kwonil; Eyerly, Bryan; Annamalai, Thavamathi; Lu, Zhongyan; Saif, Linda J

    2015-06-12

    Integrity of the intestinal epithelium is critical for proper functioning of the barrier that regulates absorption of water and restricts uptake of luminal bacteria. It is maintained mainly by tight junctions (TJs) and adherens junctions (AJs). We conducted immunofluorescence (IF) staining for in situ identification of zonula occludin (ZO)-1 proteins for TJ and E-Cadherin proteins for AJ in the small and large intestinal villous and crypt epithelium of nursing pigs infected with porcine epidemic diarrhea virus (PEDV). Twenty 9-day-old piglets [PEDV-infected (n=9) and Mock (n=11)] from PEDV seronegative sows, were orally inoculated [8.9 log₁₀ genomic equivalents/pig] with PEDV PC21A strain or mock. At post-inoculation days (PIDs) 1-5, infected pigs showed severe watery diarrhea and/or vomiting and severe atrophic enteritis. By immunohistochemistry, PEDV antigens were evident in enterocytes lining the villous epithelium. At PIDs 1-5, PEDV-infected pigs exhibited mildly to extensively disorganized, irregular distribution and reduced expression of ZO-1 or E-Cadherin in villous, but not crypt epithelial cells of the jejunum and ileum, but not in the large intestine, when compared to the negative controls. The structural destruction and disorganization of TJ and AJ were extensive in PEDV-infected pigs at PIDs 1-3, but then appeared to reversibly recover at PID 5, as evident by increased numbers of ZO-1-positive epithelial cells and markedly improved appearance of E-Cadherin-positive villous epithelium. Our results suggest a possible involvement of structurally impaired TJ and AJ in the pathogenesis of PEDV, potentially leading to secondary bacterial infections.

  14. Conditional inactivation of p53 in mouse ovarian surface epithelium does not alter MIS driven Smad2-dominant negative epithelium-lined inclusion cysts or teratomas.

    PubMed

    Quartuccio, Suzanne M; Lantvit, Daniel D; Bosland, Maarten C; Burdette, Joanna E

    2013-01-01

    Epithelial ovarian cancer is the most lethal gynecological malignancy among US women. The etiology of this disease, although poorly understood, may involve the ovarian surface epithelium or the epithelium of the fallopian tube fimbriae as the progenitor cell. Disruptions in the transforming growth factor beta (TGFβ) pathway and p53 are frequently found in chemotherapy-resistant serous ovarian tumors. Transgenic mice expressing a dominant negative form of Smad2 (Smad2DN), a downstream transcription factor of the TGFβ signaling pathway, targeted to tissues of the reproductive tract were created on a FVB background. These mice developed epithelium-lined inclusion cysts, a potential precursor lesion to ovarian cancer, which morphologically resembled oviductal epithelium but exhibited protein expression more closely resembling the ovarian surface epithelium. An additional genetic "hit" of p53 deletion was predicted to result in ovarian tumors. Tissue specific deletion of p53 in the ovaries and oviducts alone was attempted through intrabursal or intraoviductal injection of Cre-recombinase expressing adenovirus (AdCreGFP) into p53 (flox/flox) mice. Ovarian bursal cysts were detected in some mice 6 months after intrabursal injection. No pathological abnormalities were detected in mice with intraoviductal injections, which may be related to decreased infectivity of the oviductal epithelium with adenovirus as compared to the ovarian surface epithelium. Bitransgenic mice, expressing both the Smad2DN transgene and p53 (flox/flox), were then exposed to AdCreGFP in the bursa and oviductal lumen. These mice did not develop any additional phenotypes. Exposure to AdCreGFP is not an effective methodology for conditional deletion of floxed genes in oviductal epithelium and tissue specific promoters should be employed in future mouse models of the disease. In addition, a novel phenotype was observed in mice with high expression of the Smad2DN transgene as validated through q

  15. Intermediate Filaments and Polarization in the Intestinal Epithelium

    PubMed Central

    Coch, Richard A.; Leube, Rudolf E.

    2016-01-01

    The cytoplasmic intermediate filament cytoskeleton provides a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. This is particularly apparent in the intestinal epithelium, in which the intermediate filament network is localized below the apical terminal web region and is anchored to the apical junction complex. This arrangement is conserved from the nematode Caenorhabditis elegans to humans. The review summarizes compositional, morphological and functional features of the polarized intermediate filament cytoskeleton in intestinal cells of nematodes and mammals. We emphasize the cross talk of intermediate filaments with the actin- and tubulin-based cytoskeleton. Possible links of the intermediate filament system to the distribution of apical membrane proteins and the cell polarity complex are highlighted. Finally, we discuss how these properties relate to the establishment and maintenance of polarity in the intestine. PMID:27429003

  16. Sugar expressions on the vaginal epithelium in pregnant mice.

    PubMed

    Yasunaga, Youhei; Takeuchi, Takashi; Shimokawa, Tetsuya; Nabeta, Motowo; Matsuu, Aya; Asano, Atsushi; Ohta, Yasuhiko

    2012-06-01

    Sugar expressions were examined on the epithelium of both the middle portion of the vagina and the vaginal portion of the cervical canal (CC) in pregnant mice to understand the pathogenesis of bacterial infection in the female reproductive organ by using a panel of lectins. As a result, N-acetylglucosamine was positive before pregnant day (P) 7 but negative after P10 and at diestrus on both the vagina and the CC. In addition, some differences in sugar expressions were seen between them. These results suggest that sugar expressions on the mucosal surface would change not only site-specifically but also time-dependently, and these sugar differences indicate the possibility of the alteration of the settled bacterial species on the vaginal mucosa in pregnancy.

  17. Abl suppresses cell extrusion and intercalation during epithelium folding.

    PubMed

    Jodoin, Jeanne N; Martin, Adam C

    2016-09-15

    Tissue morphogenesis requires control over cell shape changes and rearrangements. In the Drosophila mesoderm, linked epithelial cells apically constrict, without cell extrusion or intercalation, to fold the epithelium into a tube that will then undergo epithelial-to-mesenchymal transition (EMT). Apical constriction drives tissue folding or cell extrusion in different contexts, but the mechanisms that dictate the specific outcomes are poorly understood. Using live imaging, we found that Abelson (Abl) tyrosine kinase depletion causes apically constricting cells to undergo aberrant basal cell extrusion and cell intercalation. abl depletion disrupted apical-basal polarity and adherens junction organization in mesoderm cells, suggesting that extruding cells undergo premature EMT. The polarity loss was associated with abnormal basolateral contractile actomyosin and Enabled (Ena) accumulation. Depletion of the Abl effector Enabled (Ena) in abl-depleted embryos suppressed the abl phenotype, consistent with cell extrusion resulting from misregulated ena Our work provides new insight into how Abl loss and Ena misregulation promote cell extrusion and EMT.

  18. Cytoarchitectural changes in lens epithelium of galactose-fed rats.

    PubMed

    Gona, O

    1984-06-01

    Whole mounts of lens epithelia from rats fed on a galactose-rich diet for one, two, three or seven days were examined for morphological alterations. The meridional rows of epithelia from lenses of animals fed on galactose for seven days were found to be grossly disorganized or abnormally elongated. There was some indication that the cells were edematous and that the epithelium had become multilayered. These abnormalities apparently extended into the transitional zone. Evidence of the cytoarchitectural changes was present as early as one day after institution of the 30% galactose diet and progressed steadily over the period of observation. The findings provide support for the hypothesis that loss of meridional row integrity is a phenomenon common to development of most types of cortical cataracts.

  19. An Investigation of Syntactic Abilities in Normal and Dyslexic Children.

    ERIC Educational Resources Information Center

    Vogel, Susan Ann

    Syntactic abilities in oral language of twenty normal and twenty dyslexic second grade boys were investigated. The major hypothesis was that dyslexic children with reading comprehension difficulties are deficient in oral syntax. The concept of syntax was subdivided into five categories: (1) recognition of melody pattern, (2) recognition of…

  20. Tongue Measures in Individuals with Normal and Impaired Swallowing

    ERIC Educational Resources Information Center

    Stierwalt, Julie A. G.; Youmans, Scott R.

    2007-01-01

    Purpose: This investigation sought to add to the extant literature on measures of normal tongue function, to provide information on measures of tongue function in a group of individuals with oral phase dysphagia, and to provide a comparison of these 2 groups matched for age and gender. Method: The Iowa Oral Performance Instrument was utilized to…

  1. Morphological and glycan features of the camel oviduct epithelium.

    PubMed

    Accogli, Gianluca; Monaco, Davide; El Bahrawy, Khalid Ahmed; El-Sayed, Ashraf Abd El-Halim; Ciannarella, Francesca; Beneult, Benedicte; Lacalandra, Giovanni Michele; Desantis, Salvatore

    2014-07-01

    This study describes regional differences in the oviduct of the one-humped camel (Camelus dromedarius) during the growth phase (GP) and the mature phase (MP) of the follicular wave by means of morphometry, scanning electron microscopy (SEM) and glycohistochemistry investigations. Epithelium height significantly increased in the ampulla and decreased in the isthmus passing from the GP to the MP. Under SEM, non-ciliated cells displayed apical blebs (secretory) or short microvilli. Cilia glycocalyx expressed glycans terminating with sialic acid linked α2,6 to Gal/GalNAc (SNA affinity) throughout the oviducts of GP and MP and sialic acid linked α2,3 to Galβ1,3GalNAc (MAL II and KOH-sialidase (K-s)-PNA staining) throughout the MP oviducts. Non-ciliated cells displayed lectin-binding sites from the supra-nuclear cytoplasm to the luminal surface. Ampulla non-ciliated cells showed O-linked (mucin-type) sialoglycans (MAL II and K-s-PNA) during GP and MP and N-linked sialoglycans (SNA) during the MP. Isthmus non-ciliated cells expressed SNA reactivity in GP and MP, also K-s-PNA binders in MP, and MAL II and PNA affinity (Galβ1,3GalNAc) during GP. Galβ1,3GalNAc was sialilated in the non-ciliated cells of GP UTJ. Luminal surface lacked of Galβ1,3GalNAc in GP and MP, whereas it expressed α2,6- and α2,3-linked sialic acids. In GP intraluminal substance reacted with SNA, MAL II, K-s-PNA in ampulla and only with MAL II in the isthmus and UTJ. These results demonstrate that the morphology and the glycan pattern of the camel oviductal epithelium vary during the follicular wave and that could relate to the region-specific functions.

  2. Lineage tracing in the adult mouse corneal epithelium supports the limbal epithelial stem cell hypothesis with intermittent periods of stem cell quiescence☆

    PubMed Central

    Dorà, Natalie J.; Hill, Robert E.; Collinson, J. Martin; West, John D.

    2015-01-01

    The limbal epithelial stem cell (LESC) hypothesis proposes that LESCs in the corneal limbus maintain the corneal epithelium both during normal homeostasis and wound repair. The alternative corneal epithelial stem cell (CESC) hypothesis proposes that LESCs are only involved in wound repair and CESCs in the corneal epithelium itself maintain the corneal epithelium during normal homeostasis. We used tamoxifen-inducible, CreER-loxP lineage tracing to distinguish between these hypotheses. Clones of labelled cells were induced in adult CAGG-CreER;R26R-LacZ reporter mice and their distributions analysed after different chase periods. Short-lived clones, derived from labelled transient amplifying cells, were shed during the chase period and long-lived clones, derived from stem cells, expanded. At 6 weeks, labelled clones appeared at the periphery, extended centripetally as radial stripes and a few reached the centre by 14 weeks. Stripe numbers depended on the age of tamoxifen treatment. Stripes varied in length, some were discontinuous, few reached the centre and almost half had one end at the limbus. Similar stripes extended across the cornea in CAGG-CreER;R26R-mT/mG reporter mice. The distributions of labelled clones are inconsistent with the CESC hypothesis and support the LESC hypothesis if LESCs cycle between phases of activity and quiescence, each lasting several weeks. PMID:26554513

  3. Kruppel-like factor 5 Controls Villus Formation and Initiation of Cytodifferentiation in the Embryonic Intestinal Epithelium

    PubMed Central

    Bell, Sheila. M.; Zhang, Liqian; Xu, Yan; Besnard, Valerie; Wert, Susan E.; Shroyer, Noah; Whitsett, Jeffrey A.

    2013-01-01

    Kruppel-like factor 5 (Klf5) is a transcription factor expressed by embryonic endodermal progenitors that form the lining of the gastrointestinal tract. A Klf5 floxed allele was efficiently deleted from the intestinal epithelium by a Cre transgene under control of the Shh promoter resulting in the inhibition of villus morphogenesis and epithelial differentiation. Although proliferation of the intestinal epithelium was maintained, the expression of Elf3, Pparγ, Atoh1, Ascl2, Neurog3, Hnf4α, Cdx1, and other genes associated with epithelial cell differentiation was inhibited in the Klf5-deficient intestines. At E18.5, Klf5Δ/Δ fetuses lacked the apical brush border characteristic of enterocytes, and a loss of goblet and enteroendocrine cells was observed. The failure to form villi was not attributable to the absence of HH or PDGF signaling, known mediators of this developmental process. Klf5-deletion blocked the decrease in FoxA1 and Sox9 expression that accompanies normal villus morphogenesis. KLF5 directly inhibited activity of the FoxA1 promoter, and in turn FOXA1 inhibited Elf3 gene expression in vitro, linking the observed loss of Elf3 with the persistent expression of FoxA1 observed in Klf5-deficient mice. Genetic network analysis identified KLF5 as a key transcription factor regulating intestinal cell differentiation and cell adhesion. These studies indicate a novel requirement for KLF5 to initiate morphogenesis of the early endoderm into a compartmentalized intestinal epithelium comprised of villi and terminally differentiated cells. PMID:23266329

  4. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

  5. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

  6. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

    PubMed Central

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4–8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer’s patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

  7. Electron microscopy of the seminiferous epithelium in the triploid (ZZZ and ZZW) fowl, Gallus domesticus.

    PubMed

    Lin, M; Thorne, M H; Martin, I C; Sheldon, B L; Jones, R C

    1995-06-01

    The ultrastructure of cells of the seminiferous epithelium is described in both triploid ZZZ and ZZW fowls, especially cytological aberrations influencing the development of morphologically abnormal spermatids and spermatozoa. Mitotic divisions in triploid fowls are similar to those in diploid fowls, but meiosis in both the ZZZ and ZZW triploid fowl is abnormal and many defective gametes are produced. The majority of spermatids have structural abnormalities and this is attributed to the aneuploidy expected from meiotic chromosome pairing in a triploid. Some spermatids were observed to possess an irregularly shaped head, 2 centriolar complexes, 2 acrosomes and 2 tails and this type differentiated into large-headed spermatoza. Such spermatids and spermatozoa are suggested to be near diploid due to their large nuclear size and 2 sets of organelles. Other spermatids, observed with only 1 centriolar complex, 1 acrosome and 1 tail, are suggested to be near haploid. Differentiation of these spermatids is similar to the process observed in diploid fowls except that there is a high percentage of abnormally shaped heads. The fact that morphologically normal spermatozoa were rare is consistent with the expectation that very few spermatozoa would be exactly haploid. In both ZZZ and ZZW triploid fowls, triple pairing of chromosomes is observed in synaptonemal complexes (SC) during meiosis and recombination nodules are distributed at random in the central regions of the triple pairing SC. In ZZW triploid fowls gamete formation is more severely affected than in ZZZ triploid fowls and it is suggested that many of the degenerative changes occurring in ZZW fowls could be attributed to those spermatids that possess a W sex chromosome, since normal male fowls are the homogametic sex (ZZ) and normal spermatids and spermatozoa contain only a Z sex chromosome. PMID:7559129

  8. Dissortativity and duplications in oral cancer

    NASA Astrophysics Data System (ADS)

    Shinde, Pramod; Yadav, Alok; Rai, Aparna; Jalan, Sarika

    2015-08-01

    More than 300 000 new cases worldwide are being diagnosed with oral cancer annually. Complexity of oral cancer renders designing drug targets very difficult. We analyse protein-protein interaction network for the normal and oral cancer tissue and detect crucial changes in the structural properties of the networks in terms of the interactions of the hub proteins and the degree-degree correlations. Further analysis of the spectra of both the networks, while exhibiting universal statistical behaviour, manifest distinction in terms of the zero degeneracy, providing insight to the complexity of the underlying system.

  9. Myofibroblasts in oral lesions: A review

    PubMed Central

    Pinisetti, Soujanya; Manyam, Ravikanth; Suresh, Babburi; Aparna, V

    2014-01-01

    Myofibroblasts (MFs) are modified fibroblasts that express features of smooth muscle differentiation and were first observed in granulation tissue during wound healing. These cells play a key role in physiologic and pathologic processes like wound healing and tumorigenesis. The presence of MFs has been reported in normal oral tissues and pathologic conditions like reactive lesions, benign tumors, locally aggressive tumors and malignancies affecting the oral cavity. This article briefly reviews the important hallmarks related to the discovery, characterization and tissue distribution of MFs in oral health and disease. PMID:24959038

  10. Denervation resulting in dento-alveolar ankylosis associated with decreased Malassez epithelium.

    PubMed

    Fujiyama, K; Yamashiro, T; Fukunaga, T; Balam, T A; Zheng, L; Takano-Yamamoto, T

    2004-08-01

    Inferior alveolar nerve denervation causes appreciable decreases in the distribution of epithelial rests of Malassez. To explore roles of the Malassez epithelium, we attempted to evaluate possible changes in dento-alveolar tissues surrounding this epithelium by experimental denervation. We found that denervation led to dento-alveolar ankylosis with a decrease in the width of the periodontal spaces. Interestingly, with regeneration of the Malassez epithelium 10 weeks after the denervation, the periodontal space width showed a correspondingly significant increase. These findings suggest that the Malassez epithelium may be involved in the maintenance of periodontal space and that sensory innervation might be indirectly associated with it. In addition, it is of interest that denervation activated root resorption of the coronal root surface and that the consequently resorbed lacunae were repaired by cellular cementum. It is suggested that Malassez epithelium may negatively regulate root resorption and induce acellular cementum formation. PMID:15271971

  11. Transepithelial Transport of Fc -Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery

    PubMed Central

    Pridgen, Eric M.; Alexis, Frank; Kuo, Timothy T.; Levy-Nissenbaum, Etgar; Karnik, Rohit; Blumberg, Richard S.; Langer, Robert; Farokhzad, Omid C.

    2014-01-01

    Nanoparticles are poised to have a tremendous impact on the treatment of many diseases, but their broad application is limited because currently they can only be administered by parenteral methods. Oral administration of nanoparticles is preferred but remains a challenge because transport across the intestinal epithelium is limited. Here, we show that nanoparticles targeted to the neonatal Fc receptor (FcRn), which is known to mediate the transport of IgG antibodies across epithelial barriers, are efficiently transported across the intestinal epithelium using both in vitro and in vivo models. In mice, orally administered FcRn-targeted nanoparticles crossed the intestinal epithelium and reached systemic circulation with a mean absorption efficiency of 13.7%*h compared with only 1.2%*h for non-targeted nanoparticles. In addition, targeted nanoparticles containing insulin as a model nanoparticle-based therapy for diabetes were orally administered at a clinically relevant insulin dose of 1.1 U/kg and elicited a prolonged hypoglycemic response in wild-type mice. This effect was abolished in FcRn knockout mice, indicating the enhanced nanoparticle transport was due specifically to FcRn. FcRn-targeted nanoparticles may have a major impact on the treatment of many diseases by enabling drugs currently limited by low bioavailability to be efficiently delivered though oral administration. PMID:24285486

  12. Scattering attenuation microscopy of oral epithelial dysplasia

    NASA Astrophysics Data System (ADS)

    Tomlins, Pete H.; Adegun, Oluyori; Hagi-Pavli, Eleni; Piper, Kim; Bader, Dan; Fortune, Farida

    2010-11-01

    We present a new method for quantitative visualization of premalignant oral epithelium called scattering attenuation microscopy (SAM). Using low-coherence interferometry, SAM projects measurements of epithelial optical attenuation onto an image of the tissue surface as a color map. The measured attenuation is dominated by optical scattering that provides a metric of the severity of oral epithelial dysplasia (OED). Scattering is sensitive to the changes in size and distribution of nuclear material that are characteristic of OED, a condition recognized by the occurrence of basal-cell-like features throughout the epithelial depth. SAM measures the axial intensity change of light backscattered from epithelial tissue. Scattering measurements are obtained from sequential axial scans of a 3-D tissue volume and displayed as a 2-D SAM image. A novel segmentation method is used to confine scattering measurement to epithelial tissue. This is applied to oral biopsy samples obtained from 19 patients. Our results show that imaging of tissue scattering can be used to discriminate between different dysplastic severities and furthermore presents a powerful tool for identifying the most representative tissue site for biopsy.

  13. Focal epithelial hyperplasia of the oral mucosa.

    PubMed

    Morency, R; Laliberte, H; Delamarre, R

    1982-02-01

    Focal epithelial hyperplasia (FEH) of the oral mucosa has been reported mainly among American Indians, Eskimos, and south Africans. Our investigation is the first among Canadian Indians and combines an epidemiological study of FEH in a Cree Indian population living in Fort Georges. P.Q., and a description of its histologic and ultrastructural features. The sample consists of 150 individuals divided into six age groups. The prevalence rate for all groups is 18.6%. Clinically the lesions are nodular, sessile, and tend to merge with the adjoining mucosa upon stretching. Histologically the hyperplasia is limited to the epithelium. E.M. shows papova-virus-like particles. Otolaryngologists' awareness of this lesion could possibly lead to its recognition on a larger scale.