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Sample records for mouse oral epithelium

  1. Cytokeratin expression in mouse lacrimal gland germ epithelium.

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    Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo

    2016-05-01

    The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

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    Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

    2016-01-01

    Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells.

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

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    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. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Epithelium

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    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Kierszenbaum AL, Tres LL. Epithelium. In: Kierszenbaum AL, Tres LL, ... to Pathology . 4th ed. Philadelphia, PA: Elsevier Saunders; ...

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

    OpenAIRE

    Yilmaz, Özlem

    2008-01-01

    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 oute...

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

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

    2017-06-08

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

  7. Tissue fixation and autoradiographic negative chemography in rat oral epithelium

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    Prime, S.S.; MacDonald, D.G. (Glasgow Dental Hospital (UK))

    1983-01-01

    The effect of routine methods of tissue fixation on autoradiographic negative chemography was investigated in adult rat palatal and tongue epithelia following the incorporation of /sup 3/H thymidine in vivo. Tissues fixed in formalin or Bouin's without acetic acid demonstrated more negative chemography than those fixed in Bouin's fluid, formol-acetic-methanol or Carnoy's solutions. These findings were associated with the lowest silver grain counts per nucleus in the formalin fixed tissues, low grain counts in tissues fixed in Bouin's without acetic acid, but the addition of acetic acid to make complete Bouin's fluid gave results similar to those following fixation with Carnoy's solution. The highest silver grain counts were obtained with tissues fixed in formol-acetic-methanol. The relationship between negative chemography and the labelling indices of tissues was unclear except where the negative chemographic effects were severe. Formalin fixed tissues showed the maximum negative chemographic effects and the lowest labelling indices. Carnoy's solution appeared to be the fixative of choice for cell kinetic studies of oral epithelium.

  8. Tissue fixation and autoradiographic negative chemography in rat oral epithelium

    International Nuclear Information System (INIS)

    Prime, S.S.; MacDonald, D.G.

    1983-01-01

    The effect of routine methods of tissue fixation on autoradiographic negative chemography was investigated in adult rat palatal and tongue epithelia following the incorporation of 3 H thymidine in vivo. Tissues fixed in formalin or Bouin's without acetic acid demonstrated more negative chemography than those fixed in Bouin's fluid, formol-acetic-methanol or Carnoy's solutions. These findings were associated with the lowest silver grain counts per nucleus in the formalin fixed tissues, low grain counts in tissues fixed in Bouin's without acetic acid, but the addition of acetic acid to make complete Bouin's fluid gave results similar to those following fixation with Carnoy's solution. The highest silver grain counts were obtained with tissues fixed in formol-acetic-methanol. The relationship between negative chemography and the labelling indices of tissues was unclear except where the negative chemographic effects were severe. Formalin fixed tissues showed the maximum negative chemographic effects and the lowest labelling indices. Carnoy's solution appeared to be the fixative of choice for cell kinetic studies of oral epithelium. (author)

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

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    Dariusz Dobrowolski

    2015-01-01

    Full Text Available 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.

  10. Cytological changes in oral epithelium due to Sudanese homemade alcoholic beverages

    OpenAIRE

    Awdah M. Al-hazimi; Shima Bushra Bakhet; Hussain Gadelkarim Ahmed

    2013-01-01

    Introduction and Objective: The aim of this study was to assess the cytological changes in oral epithelium that might be induced by Sudanese homemade alcoholic beverages. Material and methods: Oral Exfoliative Cytology (OEFC) was applied to a case control study to assess the presence and severity of oral epithelial atypia (ET) in 300 subjects (150 alcohol abuse individuals (cases); 150 non-alcohol abuse individuals (controls)). All cases were using homemade alcoholic drinks, locally known as,...

  11. Cell flux through S phase in the mouse duodenal epithelium determined by cell sorting and radioautography

    International Nuclear Information System (INIS)

    Bjerknes, M.; Cheng, H.

    1982-01-01

    An accumulation of cells in early S phase was observed in normal mouse duodenal epithelium studied with flow cytometry. To determine if this accumulation of cells was the result of a lower rate of DNA synthesis, animals were given a single injection of 3 H-thymidine and the epithelium collected one hour later. The epithelium was processed for flow cytometry. Seven sort windows were established in different portions of the DNA histogram. Cells from each window were sorted onto glass slides that were then processed for radioautography. The number of silver grains over the nuclei of each sorted population was counted. It was found that cells in early S phase had significantly fewer grains over their nuclei than did mid- or late-S phase cells. We conclude that the accumulation of cells in early S phase is due, at least in part, to a lower rate of DNA synthesis in early than in mid or late S phase

  12. Regional variations of cell surface carbohydrates in human oral stratified epithelium

    DEFF Research Database (Denmark)

    Vedtofte, P; Dabelsteen, Erik; Hakomori, S

    1984-01-01

    The distribution of blood group carbohydrate chains with antigen A, B, H type 2 chain (A and B precursor), and N-acetyllactosamine (H type 2 precursor) specificity was studied in human oral epithelium from different anatomical regions. These represented various epithelial differentiation patterns...... epithelium from nine blood group A, two blood group B, and nine blood group O individuals. The blood group carbohydrate chains were examined in tissue sections by immunofluorescence microscopy. The A and B blood group antigens were detected by human blood group sera, and antigen H type 2 chains and N...... antigen H type 2 chains in metaplastically keratinized buccal epithelium was found to differ significantly from that seen in normal non-keratinized buccal epithelium. The regional variations demonstrated in cell surface carbohydrates are suggested to reflect differences in tissue differentiation....

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

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

    2014-01-01

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

  14. Gene expression and functional annotation of the human and mouse choroid plexus epithelium.

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    Sarah F Janssen

    Full Text Available BACKGROUND: The choroid plexus epithelium (CPE is a lobed neuro-epithelial structure that forms the outer blood-brain barrier. The CPE protrudes into the brain ventricles and produces the cerebrospinal fluid (CSF, which is crucial for brain homeostasis. Malfunction of the CPE is possibly implicated in disorders like Alzheimer disease, hydrocephalus or glaucoma. To study human genetic diseases and potential new therapies, mouse models are widely used. This requires a detailed knowledge of similarities and differences in gene expression and functional annotation between the species. The aim of this study is to analyze and compare gene expression and functional annotation of healthy human and mouse CPE. METHODS: We performed 44k Agilent microarray hybridizations with RNA derived from laser dissected healthy human and mouse CPE cells. We functionally annotated and compared the gene expression data of human and mouse CPE using the knowledge database Ingenuity. We searched for common and species specific gene expression patterns and function between human and mouse CPE. We also made a comparison with previously published CPE human and mouse gene expression data. RESULTS: Overall, the human and mouse CPE transcriptomes are very similar. Their major functionalities included epithelial junctions, transport, energy production, neuro-endocrine signaling, as well as immunological, neurological and hematological functions and disorders. The mouse CPE presented two additional functions not found in the human CPE: carbohydrate metabolism and a more extensive list of (neural developmental functions. We found three genes specifically expressed in the mouse CPE compared to human CPE, being ACE, PON1 and TRIM3 and no human specifically expressed CPE genes compared to mouse CPE. CONCLUSION: Human and mouse CPE transcriptomes are very similar, and display many common functionalities. Nonetheless, we also identified a few genes and pathways which suggest that the CPE

  15. Comparative quantitative studies on the radiosensitivity of the oral cavity epithelium

    International Nuclear Information System (INIS)

    Lyubenov, T.

    1986-01-01

    A series of 146 patients with miscellaneous localizations of malignant tumors in the head and neck area, in whom different portions of the oral cavity epithelium came within the field subject to irradiation were included in the study. Using the Kirk's formula for cumulative radiation effect, quantitative relationships in the manifestation of radioepithelitis were searched for. With increasing the intervals of the cumulative radiation effect, the number of patients and the number of interruptions in treatment with different localizations of the tumor depended on epithelium radiosensitivity

  16. Conditional inactivation of p53 in mouse ovarian surface epithelium does not alter MIS driven Smad2-dominant negative epithelium-lined inclusion cysts or teratomas.

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    Suzanne M Quartuccio

    Full Text Available 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

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

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

    2015-11-01

    Specific biomarkers are urgently needed for the detection and progression of oral cancer. The objective of this study was to discover cancer biomarkers from oral epithelium through utilizing high throughput quantitative proteomics approaches. Morphologically malignant, epithelial dysplasia, and adjacent normal epithelial tissues were laser capture microdissected (LCM) from 19 patients and used for proteomics analysis. Total proteins from each group were extracted, digested and then labelled with corresponding isobaric tags for relative and absolute quantitation (iTRAQ). Labelled peptides from each sample were combined and analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) for protein identification and quantification. In total, 500 proteins were identified and 425 of them were quantified. When compared with adjacent normal oral epithelium, 17 and 15 proteins were consistently up-regulated or down-regulated in malignant and epithelial dysplasia, respectively. Half of these candidate biomarkers were discovered for oral cancer for the first time. Cornulin was initially confirmed in tissue protein extracts and was further validated in tissue microarray. Its presence in the saliva of oral cancer patients was also explored. Myoglobin and S100A8 were pre-validated by tissue microarray. These data demonstrated that the proteomic biomarkers discovered through this strategy are potential targets for oral cancer detection and salivary diagnostics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Identification of Lgr5-Independent Spheroid-Generating Progenitors of the Mouse Fetal Intestinal Epithelium

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    Roxana C. Mustata

    2013-10-01

    Full Text Available Immortal spheroids were generated from fetal mouse intestine using the culture system initially developed to culture organoids from adult intestinal epithelium. Spheroid proportion progressively decreases from fetal to postnatal period, with a corresponding increase in production of organoids. Like organoids, spheroids show Wnt-dependent indefinite self-renewing properties but display a poorly differentiated phenotype reminiscent of incompletely caudalized progenitors. The spheroid transcriptome is strikingly different from that of adult intestinal stem cells, with minimal overlap of Wnt target gene expression. The receptor LGR4, but not LGR5, is essential for their growth. Trop2/Tacstd2 and Cnx43/Gja1, two markers highly enriched in spheroids, are expressed throughout the embryonic-day-14 intestinal epithelium. Comparison of in utero and neonatal lineage tracing using Cnx43-CreER and Lgr5-CreERT2 mice identified spheroid-generating cells as developmental progenitors involved in generation of the prenatal intestinal epithelium. Ex vivo, spheroid cells have the potential to differentiate into organoids, qualifying as a fetal type of intestinal stem cell.

  19. Glycoproteins of mouse vaginal epithelium: differential expression related to estrous cyclicity

    DEFF Research Database (Denmark)

    Horvat, B; Multhaupt, H A; Damjanov, I

    1993-01-01

    We used lectin overlay blotting and SDS-PAGE to analyze the estrous cycle-specific expression of mouse vaginal epithelial glycoproteins. Seven lectins chosen for their differential carbohydrate-binding specificity revealed 15 glycoproteins that showed cycle-related expression. Each lectin had...... in proestrus, coincident with the transformation of two superficial layers of vaginal squamous epithelium into mucinous cuboidal cells. Electron microscopic lectin histochemistry revealed the glycoproteins in the mucinous granules of surface cuboidal cells and in the lumen of the vagina. Our results illustrate...... the complexity of glycoconjugate synthesis in mouse vagina and reveal the distinct cycle-specific patterns of individual glycoprotein expression. These cyclic glycoproteins could serve as vaginal biochemical markers for the specific phases of the estrous cycle....

  20. Recovery of the spermatogenetic epithelium in the mouse after irradiation with 1-MeV fission neutrons

    International Nuclear Information System (INIS)

    Aardweg, G.J.M.J. van den.

    1983-01-01

    In this thesis the recovery of the spermatogenetic epithelium in the mouse is studied after damage with 1-MeV fission neutrons. A severe depletion of A-spermatogonia and radiosensitive stem cells occurs after neutron irradiation. Recovery of the epithelium is initiated by surviving radioresistant stem cells giving rise to colonies, which grow into the empty seminiferous tubules. After discussing properties of normal and irradiated spermatogenetic epithelium, the growth and the differentiation of spermatogenetic colonies in the mouse testis after irradiation, as well as response and kinetics of colony-forming spermatogonial stem cells in CBA mice up to 30 weeks after a first neutron dose and recovery of the epithelium after a second irradiation are investigated. These four subjects are dealt with in separate papers. Finally, a discussion and a summary of these studies is presented. (Auth.)

  1. Immunolocalization of osteopontin in dysplasias and squamous cell carcinomas arising from oral epithelium.

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    Aravind, Thara; Janardhanan, Mahija; Rakesh, S; Savithri, Vindhya; Unnikrishnan, U G

    2017-01-01

    Early detection of oral squamous cell carcinoma (OSCC) remains one of the most efficient ways to ensure patient survival and improved quality of life. Although specific biomarkers related to OSCC have been investigated, a useful biomarker that assesses the transition potential of potentially malignant lesion to OSCC remains to be found. Osteopontin (OPN) has been recognized as an important factor in tumorigenesis and their expression in OSCC have been investigated earlier. In the present study, evaluation of OPN expression in premalignant and malignant lesions has been carried out to assess their possible role as a biomarker in the early diagnosis and prognosis of OSCC. The objective of this study is to evaluate the role of OPN as a biomarker in the diagnosis and prognosis of OSCC. The study group consisted of archival paraffin-embedded blocks of ten cases each of varying grades of OSCC, oral epithelial dysplasias and epithelial hyperplasias. Sections were subjected to immunohistochemical staining for the biomarker OPN. A positive OPN expression was noticed in epithelial dysplasias and SCC arising from the oral epithelium. A progressive increase in the intensity of staining was seen with increasing grades of dysplasias and a decrease in OPN expression with an increase in grades was observed in OSCC. The expression of OPN in full thickness of epithelium in severe dysplasias, carcinoma in situ, and in the superficial epithelium of OSCC suggest the possibility of considering OPN expression in full epithelial thickness in dysplasias as an indicator for malignant transformation.

  2. Effects of x-irradiation on cell kinetics of oral epithelium in mice

    International Nuclear Information System (INIS)

    Jinnouchi, Kenichi

    1982-01-01

    The acute radiation effects on the tongue and lip mucosa epithelium were cytokinetically investigated after the local irradiation at the head part of C 3 Hf/He mice with single dose of 516 mC/kg(2000R) of X rays. The microautoradiographic study was performed for these two kinds of oral epithelium at various times after the pulse-labeling with 3 H-thymidine, which followed immediately after the irradiation. The cell kinetics of irradiated as well as unirradiated basal cells were investigated by observing the changes in frequencies of the labeled cells and the labeled mitoses in the epithelium along the time course after irradiation. The results of the analysis of the percent frequencies of mitotic cells as a function of time after the labeling and the irradiation showed that the movement of the labeled cells were blocked at G 2 phase for about 6 hr and that the cell cycle time after the 1st post irradiation mitoses became shorter than that of the unirradiated cells. However, no change was found in the migration rate of the tongue epithelium, i.e., the time required for labeled cells to migrate from basal cell layer to prickle-granular cell layer. On the other hand, only 25% of labeled cells in the lip mucosa epithelium migrated into prickle-granular cell layer until 40 hr after irradiation, and it was hardly observed that the labeled cells moved into mitotic phase. These results suggest that basal cell of the lip mucosa is more radiosensitive than that of the tongue epithelium. (author)

  3. Ontogeny and innervation of taste buds in mouse palatal gustatory epithelium.

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    Rashwan, Ahmed; Konishi, Hiroyuki; El-Sharaby, Ashraf; Kiyama, Hiroshi

    2016-01-01

    We investigated the relationship between mouse taste bud development and innervation of the soft palate. We employed scanning electron microscopy and immunohistochemistry using antibodies against protein gene product 9.5 and peripherin to detect sensory nerves, and cytokeratin 8 and α-gustducin to stain palatal taste buds. At E14, nerve fibers were observed along the medial border of the palatal shelves that tracked toward the epithelium. At E15.5, primordial stages of taste buds in the basal lamina of the soft palate first appeared. At E16, the taste buds became large spherical masses of columnar cells scattered in the soft palate basal lamina. At E17, the morphology and also the location of taste buds changed. At E18-19, some taste buds acquired a more elongated shape with a short neck, extending a variable distance from the soft palate basal lamina toward the surface epithelium. At E18, mature taste buds with taste pores and perigemmal nerve fibers were observed on the surface epithelium of the soft palate. The expression of α-gustducin was demonstrated at postnatal day 1 and the number of pored taste buds increased with age and they became pear-shaped at 8 weeks. The percent of pored fungiform-like papillae at birth was 58.3% of the whole palate; this increased to 83.8% at postnatal day 8 and reached a maximum of 95.7% at 12 weeks. The innervation of the soft palate was classified into three types of plexuses in relation to taste buds: basal nerve plexus, intragemmal and perigemmal nerve fibers. This study reveals that the nerve fibers preceded the development of taste buds in the palate of mice, and therefore the nerve fibers have roles in the initial induction of taste buds in the soft palate. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Yilmaz, Ozlem

    2008-10-01

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

  5. Analysis of micronuclei of the oral epithelium in workers of a banana zone exposed to pesticides

    International Nuclear Information System (INIS)

    Castro Achi, R.

    1999-01-01

    The following study was realized with workers of the zone of Guapiles (Limon, Costa Rica), to determine the possible damage to the genetic material occasioned by labour exhibition to pesticides. The presence of micronuclei in cells of the oral epithelium was used as a biomarcador of effect . Besides, an analysis of frequency of other abnormalities was made in the nucleus of the epithelial cells, which can be an indication of genotoxicity or cytotoxicity. The group of women exposed to pesticides (cases) was formed by workers of packing plants of different independent banana states. The group of women who constituted the group of control were persons that neither them nor their spouses or companions had never worked at agricultural labours and that had not lived inside a banana estate. The samples of the controls were gathered not only from women who are employed at the Hospital of Guapiles, but also from patients who were expecting to be attended in the external consultation of the same hospital, or, in the Healthy Child consultation in the health center of the same city. It is the first time that a study of control-case is done in the country to detect genotoxicidad, using micronuclei of the oral epithelium (MNOE) as a biomarcador. The participants were interviewed to obtain information about his or her customs and family history that could be relevant for the study. The preparation and the analysis of the cells of the oral epithelium of every individual was done in the laboratories of the Instituto de Investigaciones en Salud (INISA), of the Universidad de Costa Rica. Although there are indications of cytotoxic and genotoxicity in the controls showed by an increase of the frequencies of other nuclear abnormalities, the results demonstrated that there is not a significant increase in MNOE's frequency between the group of cases and of controls. (Author) [es

  6. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, A.; Gorgels, T.G.M.F.; ten Brink, J.B.; van der Spek, P.J.; Bossers, K.; Heine, V.M.; Bergen, A.A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  7. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles : Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G M F; Ten Brink, Jacoline B; van der Spek, Peter J; Bossers, Koen; Heine, Vivi M; Bergen, Arthur A

    2015-01-01

    BACKGROUND: The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  8. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new

  9. A Mouse Model of Hyperproliferative Human Epithelium Validated by Keratin Profiling Shows an Aberrant Cytoskeletal Response to Injury

    Directory of Open Access Journals (Sweden)

    Samal Zhussupbekova

    2016-07-01

    Full Text Available A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7 demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.

  10. Induction of Functional 3D Ciliary Epithelium-Like Structure From Mouse Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Kinoshita, Hirofumi; Suzuma, Kiyoshi; Kaneko, Jun; Mandai, Michiko; Kitaoka, Takashi; Takahashi, Masayo

    2016-01-01

    To generate ciliary epithelium (CE) from mouse induced pluripotent stem (iPS) cells. Recently, a protocol for self-organizing optic cup morphogenesis in three-dimensional culture was reported, and it was suggested that ocular tissue derived from neural ectoderm could be differentiated. We demonstrated that a CE-like double-layered structure could be induced in simple culture by using a modified Eiraku differentiation protocol. Differentiation of a CE-like double-layered structure could be promoted by glycogen synthase kinase 3β (GSK-3β) inhibitor. Connexin43 and aquaporin1 were expressed in both thin layers, and induced CE-like cells expressed ciliary marker genes, such as cyclinD2, zic1, tgfb2, aldh1a3, wfdc1, otx1, BMP4, and BMP7. Increases in cytoplasmic and nuclear β-catenin in aggregates of the CE-like double-layered structure were confirmed by Western blot analysis. In addition, tankyrase inhibitor prevented the induction of the CE-like double-layered structure by GSK-3β inhibitor. Dye movement from pigmented cells to nonpigmented cells in the mouse iPS cell-derived CE-like structure was observed in a fluid movement experiment, consistent with the physiological function of CE in vivo. We could differentiate CE from mouse iPS cells in the present study. In the future, we hope that this CE-like complex will become useful as a graft for transplantation therapy in pathologic ocular hypotension due to CE dysfunction, and as a screening tool for the development of drugs for diseases associated with CE function.

  11. Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory epithelium

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    Hayoz Sébastien

    2012-05-01

    Full Text Available Abstract Background ATP is an extracellular signaling molecule with many ascribed functions in sensory systems, including the olfactory epithelium. The mechanism(s by which ATP is released in the olfactory epithelium has not been investigated. Quantitative luciferin-luciferase assays were used to monitor ATP release, and confocal imaging of the fluorescent ATP marker quinacrine was used to monitor ATP release via exocytosis in Swiss Webster mouse neonatal olfactory epithelial slices. Results Under control conditions, constitutive release of ATP occurs via exocytosis, hemichannels and ABC transporters and is inhibited by vesicular fusion inhibitor Clostridium difficile toxin A and hemichannel and ABC transporter inhibitor probenecid. Constitutive ATP release is negatively regulated by the ATP breakdown product ADP through activation of P2Y receptors, likely via the cAMP/PKA pathway. In vivo studies indicate that constitutive ATP may play a role in neuronal homeostasis as inhibition of exocytosis inhibited normal proliferation in the OE. ATP-evoked ATP release is also present in mouse neonatal OE, triggered by several ionotropic P2X purinergic receptor agonists (ATP, αβMeATP and Bz-ATP and a G protein-coupled P2Y receptor agonist (UTP. Calcium imaging of P2X2-transfected HEK293 “biosensor” cells confirmed the presence of evoked ATP release. Following purinergic receptor stimulation, ATP is released via calcium-dependent exocytosis, activated P2X1,7 receptors, activated P2X7 receptors that form a complex with pannexin channels, or ABC transporters. The ATP-evoked ATP release is inhibited by the purinergic receptor inhibitor PPADS, Clostridium difficile toxin A and two inhibitors of pannexin channels: probenecid and carbenoxolone. Conclusions The constitutive release of ATP might be involved in normal cell turn-over or modulation of odorant sensitivity in physiological conditions. Given the growth-promoting effects of ATP, ATP-evoked ATP

  12. Endorsing cellular competitiveness in aberrant epithelium of oral submucous fibrosis progression: neighbourhood analysis of immunohistochemical attributes.

    Science.gov (United States)

    Anura, Anji; Kazi, Anees; Pal, Mousumi; Paul, Ranjan Rashmi; Sengupta, Sanghamitra; Chatterjee, Jyotirmoy

    2018-04-23

    Epithelial abnormality during the transformation of oral submucous fibrosis (OSF) into oral squamous cell carcinoma has been well studied and documented. However, the differential contribution of atrophy and hyperplasia for malignant potentiality of OSF is yet to be resolved. Existing diagnostic conjectures lack precise diagnostic attributes which may be effectively resolved by substantiation of specific molecular pathology signatures. Present study elucidates existence of cellular competitiveness in OSF conditions using computer-assisted neighbourhood analysis in quantitative immunohistochemistry (IHC) framework. The concept of field cancerization was contributory in finding correspondence among neighbouring cells of epithelial layers with reference to differential expression of cardinal cancer-related genes [c-Myc (oncogene), p53 (tumour suppressor), and HIF-1α (hypoxia regulator)] which are known to be important sensors in recognizing cellular competitive interface. Our analyses indicate that different states of OSF condition may be associated with different forms of competitiveness within epithelial neighbouring cells which might be responsible to shape the present and future of the pre-malignant condition. Analytical findings indicated association of atrophic epithelium with stress-driven competitive environment having low c-Myc, high-p53, and stable HIF-1α (the looser cells) which undergo apoptosis. Whereas, the cells with high c-Myc + (winner cells) give rise to hyperplastic epithelium via possible mutation in p53. The epithelial dysplasia plausibly occurs due to clonal expansion of c-Myc and p53 positive supercompetitor cells. Present study proposes quantitative IHC along with neighbourhood analysis which might help us to dig deeper on to the interaction among epithelial cell population to provide a better understanding of field cancerization and malignant transformation of pre-malignancy.

  13. The layered-resolved microstructure and spectroscopy of mouse oral mucosa using multiphoton microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Zhuo Shuangmu [Key Laboratory of Optoelectronic Science and Technology for Medicine, Fujian Normal University, Ministry of Education, Fuzhou 350007 (China); Chen Jianxin [Key Laboratory of Optoelectronic Science and Technology for Medicine, Fujian Normal University, Ministry of Education, Fuzhou 350007 (China); Jiang Xingshan [Key Laboratory of Optoelectronic Science and Technology for Medicine, Fujian Normal University, Ministry of Education, Fuzhou 350007 (China); Xie Shusen [Key Laboratory of Optoelectronic Science and Technology for Medicine, Fujian Normal University, Ministry of Education, Fuzhou 350007 (China); Chen Rong [Key Laboratory of Optoelectronic Science and Technology for Medicine, Fujian Normal University, Ministry of Education, Fuzhou 350007 (China); Cao Ning [Fujian Medical University, Fuzhou 350004 (China); Zou Qilian [Fujian Medical University, Fuzhou 350004 (China); Xiong Shuyuan [Fujian Medical University, Fuzhou 350004 (China)

    2007-08-21

    The layered-resolved microstructure and spectroscopy of mouse oral mucosa are obtained using a combination of multiphoton imaging and spectral analysis with different excitation wavelengths. In the keratinizing layer, the keratinocytes microstructure can be characterized and the keratinizing thickness can be measured. The keratin fluorescence signal can be further characterized by emission maxima at 510 nm. In the epithelium, the cellular microstructure can be quantitatively visualized with depth and the epithelium thickness can be determined by multiphoton imaging excited at 730 nm. The study also shows that the epithelial spectra excited at 810 nm, showing a combination of NADH and FAD fluorescence, can be used for the estimation of the metabolic state in epithelium. Interestingly, a second-harmonic generation (SHG) signal from DNA was observed for the first time within the epithelial layer in backscattering geometry and provides the possibility of analyzing the chromatin structure. In the stroma, the combination of multiphoton imaging and spectral analysis excited at 850 nm in tandem can obtain quantitative information regarding the biomorphology and biochemistry of stroma. Specifically, the microstructure of collagen, minor salivary glands and elastic fibers, and the optical property of the stroma can be quantitatively displayed. Overall, these results suggest that the combination of multiphoton imaging and spectral analysis with different excitation wavelengths has the potential to provide important and comprehensive information for early diagnosis of oral cancer.

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

    Science.gov (United States)

    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).

  15. Conditional ablation of the choroideremia gene causes age-related changes in mouse retinal pigment epithelium.

    Science.gov (United States)

    Wavre-Shapton, Silène T; Tolmachova, Tanya; Lopes da Silva, Mafalda; da Silva, Mafalda Lopes; Futter, Clare E; Seabra, Miguel C

    2013-01-01

    The retinal pigment epithelium (RPE) is a pigmented monolayer of cells lying between the photoreceptors and a layer of fenestrated capillaries, the choriocapillaris. Choroideremia (CHM) is an X-linked progressive degeneration of these three layers caused by the loss of function of Rab Escort protein-1 (REP1). REP1 is involved in the prenylation of Rab proteins, key regulators of membrane trafficking. To study the pathological consequences of chronic disruption of membrane traffic in the RPE we used a cell type-specific knock-out mouse model of the disease, where the Chm/Rep1 gene is deleted only in pigmented cells (Chm(Flox), Tyr-Cre+). Transmission electron microscopy (TEM) was used to quantitate the melanosome distribution in the RPE and immunofluorescent staining of rhodopsin was used to quantitate phagocytosed rod outer segments in retinal sections. The ultrastructure of the RPE and Bruch's membrane at different ages was characterised by TEM to analyse age-related changes occurring as a result of defects in membrane traffic pathways. Chm/Rep1 gene knockout in RPE cells resulted in reduced numbers of melanosomes in the apical processes and delayed phagosome degradation. In addition, the RPE accumulated pathological changes at 5-6 months of age similar to those observed in 2-year old controls. These included the intracellular accumulation of lipofuscin-containing deposits, disorganised basal infoldings and the extracellular accumulation of basal laminar and basal linear deposits. The phenotype of the Chm(Flox), Tyr-Cre+ mice suggests that loss of the Chm/Rep1 gene causes premature accumulation of features of aging in the RPE. Furthermore, the striking similarities between the present observations and some of the phenotypes reported in age-related macular degeneration (AMD) suggest that membrane traffic defects may contribute to the pathogenesis of AMD.

  16. Conditional ablation of the choroideremia gene causes age-related changes in mouse retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Silène T Wavre-Shapton

    Full Text Available The retinal pigment epithelium (RPE is a pigmented monolayer of cells lying between the photoreceptors and a layer of fenestrated capillaries, the choriocapillaris. Choroideremia (CHM is an X-linked progressive degeneration of these three layers caused by the loss of function of Rab Escort protein-1 (REP1. REP1 is involved in the prenylation of Rab proteins, key regulators of membrane trafficking. To study the pathological consequences of chronic disruption of membrane traffic in the RPE we used a cell type-specific knock-out mouse model of the disease, where the Chm/Rep1 gene is deleted only in pigmented cells (Chm(Flox, Tyr-Cre+. Transmission electron microscopy (TEM was used to quantitate the melanosome distribution in the RPE and immunofluorescent staining of rhodopsin was used to quantitate phagocytosed rod outer segments in retinal sections. The ultrastructure of the RPE and Bruch's membrane at different ages was characterised by TEM to analyse age-related changes occurring as a result of defects in membrane traffic pathways. Chm/Rep1 gene knockout in RPE cells resulted in reduced numbers of melanosomes in the apical processes and delayed phagosome degradation. In addition, the RPE accumulated pathological changes at 5-6 months of age similar to those observed in 2-year old controls. These included the intracellular accumulation of lipofuscin-containing deposits, disorganised basal infoldings and the extracellular accumulation of basal laminar and basal linear deposits. The phenotype of the Chm(Flox, Tyr-Cre+ mice suggests that loss of the Chm/Rep1 gene causes premature accumulation of features of aging in the RPE. Furthermore, the striking similarities between the present observations and some of the phenotypes reported in age-related macular degeneration (AMD suggest that membrane traffic defects may contribute to the pathogenesis of AMD.

  17. Response of mouse tongue epithelium to single doses of bleomycin and radiation

    International Nuclear Information System (INIS)

    Dorr, W.; Hirler, E.; Honig, M.

    1993-01-01

    Both bleomycin (BLM) and local X-irradiation (25 kV) induce denudation in the tongue epithelium of the C3H-Neuherberg mouse in a dose-dependent manner. In the present study the effect of BLM alone and of combined single doses of drug and radiation were studied using the incidence of epithelial denudation as the end-point. In 'time-line' experiments, 8 mg/kg BLM were given before or after graded doses of X-rays. BLM treatment required a reduction of the radiation dose (ED 50 ) from 15 Gy to 5-7 Gy, independent of sequence or time interval. In contrast, the time course of the response was clearly dependent on the treatment interval. Latency decreased when the drug was injected less than 2 h before irradiation with minimum latency observed at 30 min. Isobologram analysis of experiments with varying combinations of X-rays and BLM demonstrated that small drug doses were relatively more effective than larger doses, suggesting an upward concavity of the BLM dose-effective curve in vivo, i.e. a 'negative shoulder' of the curve in the low dose region. In contrast to the response to X-rays alone, which has a constant latent time to ulcer of 10 days, the latency in combined treatment was clearly shortened with increasing drug dose and at high doses eventually approximated the epithelial turnover time of 5 days. The data suggest that BLM both as a single agent and in combination with X-rays reduced the probability of abortive divisions and through this effect shortened the latent time to epithelial denudation. (author)

  18. Analysis of in situ proliferative activity in oral gingival epithelium in patients with xerostomia.

    Science.gov (United States)

    Celenligil-Nazliel, Haviye; Palali, Ali; Ayhan, Ayşe; Ruacan, Sevket

    2003-02-01

    Sjögren's syndrome is an autoimmune disease characterized by xerostomia and keratoconjunctivitis sicca. The relationship between xero-stomia and proliferative activity in human gingival epithelium is not known. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. The aims of this study were to evaluate PCNA expression in oral gingival epithelium of healthy and inflamed gingiva obtained from patients with Sjögren's syndrome, and to compare the results to age- and gender-matched subjects with normal salivary function. Eighteen Sjögren's syndrome patients and 28 controls (14 with chronic periodontitis and 14 with no clinical evidence of periodontal disease) were included in the study. Biopsies were obtained from both inflamed and healthy gingiva. The expression of PCNA was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and PC10 monoclonal antibody to PCNA. PCNA expression was observed both in the basal and suprabasal layers, and was found to be more prominent in the suprabasal layers. Proliferative index (PI) in inflamed gingiva was significantly lower in the Sjögren's syndrome group. However, no significant difference was observed between the study and control groups with respect to PI in healthy gingiva. In both groups, PI was found to be increased due to inflammation. Our data indicate that proliferative activity is observed in the suprabasal layers and, less frequently, in the basal layer. Inflammation caused increased proliferative activity. However, this positive effect of inflammation on epithelial cell proliferation decreased significantly with a lack of saliva. Therefore, it appears that saliva-derived biological mediators may also contribute to increased proliferative activity observed during inflammation.

  19. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability.

    Science.gov (United States)

    Boretto, Matteo; Cox, Benoit; Noben, Manuel; Hendriks, Nikolai; Fassbender, Amelie; Roose, Heleen; Amant, Frédéric; Timmerman, Dirk; Tomassetti, Carla; Vanhie, Arne; Meuleman, Christel; Ferrante, Marc; Vankelecom, Hugo

    2017-05-15

    The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and human endometrium. Dissociated endometrial tissue, embedded in Matrigel under WNT-activating conditions, swiftly formed organoid structures that showed long-term expansion capacity, and reproduced the molecular and histological phenotype of the tissue's epithelium. The supplemented WNT level determined the type of mouse endometrial organoids obtained: high WNT yielded cystic organoids displaying a more differentiated phenotype than the dense organoids obtained in low WNT. The organoids phenocopied physiological responses of endometrial epithelium to hormones, including increased cell proliferation under estrogen and maturation upon progesterone. Moreover, the human endometrial organoids replicated the menstrual cycle under hormonal treatment at both the morpho-histological and molecular levels. Together, we established an organoid culture system for endometrium, reproducing tissue epithelium physiology and allowing long-term expansion. This novel model provides a powerful tool for studying mechanisms underlying the biology as well as the pathology of this key reproductive organ. © 2017. Published by The Company of Biologists Ltd.

  20. Expression of the type VI intermediate filament proteins CP49 and filensin in the mouse lens epithelium.

    Science.gov (United States)

    FitzGerald, Paul; Sun, Ning; Shibata, Brad; Hess, John F

    2016-01-01

    The differentiated lens fiber cell assembles a filamentous cytoskeletal structure referred to as the beaded filament (BF). The BF requires CP49 (bfsp2) and filensin (bfsp1) for assembly, both of which are highly divergent members of the large intermediate filament (IF) family of proteins. Thus far, these two proteins have been reported only in the differentiated lens fiber cell. For this reason, both proteins have been considered robust markers of fiber cell differentiation. We report here that both proteins are also expressed in the mouse lens epithelium, but only after 5 weeks of age. Localization of CP49 was achieved with immunocytochemical probing of wild-type, CP49 knockout, filensin knockout, and vimentin knockout mice, in sections and in the explanted lens epithelium, at the light microscope and electron microscope levels. The relationship between CP49 and other cytoskeletal elements was probed using fluorescent phalloidin, as well as with antibodies to vimentin, GFAP, and α-tubulin. The relationship between CP49 and the aggresome was probed with antibodies to γ-tubulin, ubiquitin, and HDAC6. CP49 and filensin were expressed in the mouse lens epithelium, but only after 5 weeks of age. At the light microscope level, these two proteins colocalize to a large tubular structure, approximately 7 × 1 μm, which was typically present at one to two copies per cell. This structure is found in the anterior and anterolateral lens epithelium, including the zone where mitosis occurs. The structure becomes smaller and largely undetectable closer to the equator where the cell exits the cell cycle and commits to fiber cell differentiation. This structure bears some resemblance to the aggresome and is reactive with antibodies to HDAC6, a marker for the aggresome. However, the structure does not colocalize with antibodies to γ-tubulin or ubiquitin, also markers for the aggresome. The structure also colocalizes with actin but appears to largely exclude vimentin and

  1. Differentiation/Purification Protocol for Retinal Pigment Epithelium from Mouse Induced Pluripotent Stem Cells as a Research Tool.

    Directory of Open Access Journals (Sweden)

    Yuko Iwasaki

    Full Text Available To establish a novel protocol for differentiation of retinal pigment epithelium (RPE with high purity from mouse induced pluripotent stem cells (iPSC.Retinal progenitor cells were differentiated from mouse iPSC, and RPE differentiation was then enhanced by activation of the Wnt signaling pathway, inhibition of the fibroblast growth factor signaling pathway, and inhibition of the Rho-associated, coiled-coil containing protein kinase signaling pathway. Expanded pigmented cells were purified by plate adhesion after Accutase® treatment. Enriched cells were cultured until they developed a cobblestone appearance with cuboidal shape. The characteristics of iPS-RPE were confirmed by gene expression, immunocytochemistry, and electron microscopy. Functions and immunologic features of the iPS-RPE were also evaluated.We obtained iPS-RPE at high purity (approximately 98%. The iPS-RPE showed apical-basal polarity and cellular structure characteristic of RPE. Expression levels of several RPE markers were lower than those of freshly isolated mouse RPE but comparable to those of primary cultured RPE. The iPS-RPE could form tight junctions, phagocytose photoreceptor outer segments, express immune antigens, and suppress lymphocyte proliferation.We successfully developed a differentiation/purification protocol to obtain mouse iPS-RPE. The mouse iPS-RPE can serve as an attractive tool for functional and morphological studies of RPE.

  2. Differential proteiomic analysis of mouse intestinal epithelium irradiated by γ-ray

    International Nuclear Information System (INIS)

    Zhang Bo; Su Yongping; Liu Xiaohong; Ai Guoping; Ran Xinze; Wei Yongjiang; Wang Junping; Cheng Tianmin

    2003-01-01

    Objective: For elucidating the molecular mechanism of reconstruction of intestinal epithelium damaged by ionizing radiation, the proteomes of murine intestinal epithelium from normal and irradiated mice were compared by 2-D electrophoresis. Methods: Histopathologic sections of whole small intestine made from BALB/c mice 3 h and 72 h after total-body irradiation were stained with hematoxylin-eosin. Intestinal epithelial cells were isolated from normal and irradiated mice. The total protein samples prepared by one-step method were used in 2-D electrophoresis, the protein maps were compared and the differential spots were detected with PDQuest analysis software. Twenty-eight different spots were cut off from the gels, digested in gel with trypsin, measured with MALDI-TOF-MS and searched in database. Results: Small intestinal epithelium was damaged as early as 3 h after irradiation, and reconstructed 72 h later. After Coomassie-staining, the 2-DE image analysis by PDQuest software detected 638 ± 39 protein spots in normal mice group, 566 ± 32 spots in 3 hours post irradiation group, and 591 ± 29 spots in 3 days post irradiation group. The 2-DE images showed that proteomes of intestinal epithelium were altered with γ-irradiation. The proteins identified by peptide mass fingerprinting involved in cellular events, including signal transduction, metabolism and oxidative stress responses. Conclusions: Gamma-irradiation can induce the protein expression of intestinal epithelium. The technique of 2-D electrophoresis is a useful tool in the study of molecular mechanism of radiation damage

  3. The oral mucosa of the MRL/I mouse: a synoptic picture of systemic autoimmune disorders.

    Science.gov (United States)

    Barbeau, J; Deslauriers, N

    1991-07-01

    The oral manifestations of systemic autoimmunity were investigated in a kinetic study of the MRL/1 mouse. Lesions in the epithelium, connective tissue and minor salivary glands were characterized in serial sections of the soft palate and the cheeks with respect to 1) the type of inflammatory cells present, 2) the presence and type of vasculitis, 3) the presence of necrosis, 4) the occurrence of deposits. By the age of 16 wk, 100% of our animals had developed mild to severe lesions in at least one compartment of the mucosa. Between 16 and 32 wk of age, pathologic manifestations affected the epithelial and subepithelial tissues, the striated muscle tissue, the vascular system and, much less frequently, the minor salivary gland network.

  4. Interkinetic nuclear migration in the mouse embryonic ureteric epithelium: Possible implication for congenital anomalies of the kidney and urinary tract.

    Science.gov (United States)

    Motoya, Tomoyuki; Ogawa, Noriko; Nitta, Tetsuya; Rafiq, Ashiq Mahmood; Jahan, Esrat; Furuya, Motohide; Matsumoto, Akihiro; Udagawa, Jun; Otani, Hiroki

    2016-05-01

    Interkinetic nuclear migration (INM) is a phenomenon in which progenitor cell nuclei migrate along the apico-basal axis of the pseudostratified epithelium, which is characterized by the presence of apical primary cilia, in synchrony with the cell cycle in a manner of apical mitosis. INM is suggested to regulate not only stem/progenitor cell proliferation/differentiation but also organ size and shape. INM has been reported in epithelia of both ectoderm and endoderm origin. We examined whether INM exists in the mesoderm-derived ureteric epithelium. At embryonic day (E) 11.5, E12.5 and E13.5, C57BL/6J mouse dams were injected with 5-bromo-2'-deoxyuridine (BrdU) and embryos were killed 1, 2, 4, 6, 8, 10 and 12 h later. We immunostained transverse sections of the ureter for BrdU, and measured the position of BrdU (+) nuclei in the ureteric epithelia along the apico-basal axis at each time point. We analyzed the distribution patterns of BrdU (+) nuclei in histograms using the multidimensional scaling. Changes in the nucleus distribution patterns suggested nucleus movement characteristic of INM in the ureteric epithelia, and the mode of INM varied throughout the ureter development. While apical primary cilia are related with INM by providing a centrosome for the apical mitosis, congenital anomalies of the kidney and urinary tract (CAKUT) include syndromes linked to primary ciliary dysfunction affecting epithelial tubular organs such as kidney, ureter, and brain. The present study showed that INM exists in the ureteric epithelium and suggests that INM may be related with the CAKUT etiology via primary ciliary protein function. © 2015 Japanese Teratology Society.

  5. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis.

    Science.gov (United States)

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-03-30

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

  6. Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2012-02-01

    BACKGROUND: Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. RESULTS: Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. CONCLUSION: Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

  7. Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2011-08-22

    Abstract Background Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. Results Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. Conclusion Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

  8. Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium

    Directory of Open Access Journals (Sweden)

    Hatt Hanns

    2011-08-01

    Full Text Available Abstract Background Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. Results Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. Conclusion Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

  9. Repopulation response of mouse oral mucosa during unconventional radiotherapy protocols

    International Nuclear Information System (INIS)

    Doerr, Wolfgang; Weber-Frisch, Marion

    1995-01-01

    Repopulation in mouse tongue epithelium was determined during unconventional fractionation schedules, i.e., hyperfractionation (2 x 1.5 and 2 x 1.75 Gy/day) and accelerated treatment (2 x 3 Gy/day). The residual tolerance of the epithelium at defined days of the fractionated treatment was tested by graded single test doses (top-up design). The dose required to induce complete epithelial denudation in 50% of the animals (ED50) was used to calculate the number of fractions repopulated during the preceding treatment. After the first week of hyperfractionation, tolerance was reduced compared to untreated epithelium. However, subsequently no further change was observed, indicating complete compensation of the weekly dose with all doses per fraction used. Epithelial cell density, defined by histological examination in additional experiments, in all fractionation arms decreased similarly by ∼40% during the first week and remained constant at 60-80% in the subsequent 2 weeks. During accelerated fractionation, the residual mucosal tolerance decreased continuously with treatment time and resulted in epithelial denudation after 12 fractions. However, a substantial repopulation effect was observed, compensating 1.5 fractions by day 2, and 5 fractions by day 5, respectively. After cessation of the therapy the repopulation rate clearly decelerated to compensate a dose equivalent to about 0.5 fractions per day. Cell density decreased linearly during the treatment with 5, 10 or 12 fractions at a rate close to normal cell loss. Marked cell production, dependent on the total fractionated dose, was seen from one day after the last fraction in each experimental arm. These results indicate that maximum stem cell repopulation occurs predominantly during treatment, while major production of differentiating cells takes place in treatment splits

  10. Alterations in Factors Involved in Differentiation and Barrier Function in the Epithelium in Oral and Genital Lichen Planus.

    Science.gov (United States)

    Danielsson, Karin; Ebrahimi, Majid; Nylander, Elisabet; Wahlin, Ylva Britt; Nylander, Karin

    2017-02-08

    Lichen planus is a chronic recurrent inflammatory disease affecting both skin and mucosa, mainly in oral and/or genital regions. Keratinocytes go through a well-regulated process of proliferation and differentiation, alterations in which may result in defects in the protective epithelial barrier. Long-term barrier impairment might lead to chronic inflammation. In order to broaden our understanding of the differentiation process in mucosal lichen planus, we mapped the expression of 4 factors known to be involved in differentiation. Biopsies were collected from oral and genital lichen planus lesions and normal controls. Altered expression of all 4 factors in epithelium from lichen planus lesions was found, clearly indicating disturbed epithelial differentiation in lichen planus lesions.

  11. Langerhans cells from human oral epithelium are more effective at stimulating allogeneic T cells in vitro than Langerhans cells from skin.

    Science.gov (United States)

    Hasséus, B; Jontell, M; Bergenholtz, G; Dahlgren, U I

    2004-06-01

    This report is focused on the functional capacity of Langerhans cells (LC) in the epithelium of skin and oral mucosa, which both meet different antigenic challenges. The capacity of LC from human oral and skin epithelium to provide co-stimulatory signals to T cells in vitro was compared. LC in a crude suspension of oral epithelial cells had a significantly enhanced T cell co-stimulatory capacity compared to skin epithelial cells. This applied both to cultures with concanavalin A (con-A)-stimulated syngeneic T cells and to a mixed epithelial cell lymphocyte reaction involving allogeneic T cells. The co-stimulatory capacity of oral and skin epithelial cells was reduced by >70% if monoclonal antibodies against HLA-DR, -DP and -DQ were added to the cultures with allogeneic T cells, indicating the involvement of HLA class II expressing LC. Immunohistochemistry revealed that 6% of the epithelial cells were CD1a + LC in sections from both oral and skin epithelium. Interleukin (IL)-8 production was higher in cultures of oral epithelial cells and con-A stimulated T cells than in corresponding cultures with skin epithelial cells as accessory cells. The results suggest that LC in human oral epithelium are more efficient at stimulating T cells than those of skin.

  12. Determination of ABO blood grouping from human oral squamous epithelium by the highly sensitive immunohistochemical staining method EnVision+.

    Science.gov (United States)

    Noda, Hiroshi; Yokota, Makoto; Tatsumi, Shinji; Sugiyama, Shizuyuki

    2002-03-01

    Using the highly sensitive immunohistochemical staining method EnVision+, which employs a dextran polymer reagent for the secondary antibody, the detection of the ABH antigens was attempted in the oral squamous epithelium. This new technique uses monoclonal antibody as a primary antibody and it takes about three hours for staining. The time is much shorter than conventional absorption-elution testing or absorption-inhibition testing for the determination of ABO blood grouping. Secretor saliva samples were stained at strong intensity by the antibody, which corresponded to its blood group and anti-H. On the one hand, nonsecretor saliva samples were stained at strong intensity only by the antibody that corresponded to its blood group, and at weak intensity only by anti-H. Since human oral squamous epithelium antigens were stained specifically by this method, we can examine the ABO blood group of saliva samples and perform cytodiagnosis at the same time. Our research suggested that the EnVision+ Method is a useful technique for ABO blood grouping of saliva in forensic cases.

  13. Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs

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    Philipp eHohenbrink

    2014-09-01

    Full Text Available The vomeronasal organ (VNO is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR genes comprise two families of chemosensory genes (V1R and V2R that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the grey mouse lemur (Microcebus murinus, the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83% – 97% of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29% to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information.

  14. Cytotoxicity of nano-hydroxyapatite on human-derived oral epithelium cell line: an in vitro study

    Directory of Open Access Journals (Sweden)

    Farid Abassi

    2016-08-01

    Full Text Available Background: Hydroxyapatite nanoparticles have a more surface contact and solubility than conventional hydroxyapatite. Hydroxynanoparticles enhances the biological and mechanical properties of new regenerated tissues. The hydroxyapatite nanoparticles have received attention as a new and effective osseous graft for using as scaffolds in bone regeneration. The reports on hydroxyapatite nanoparticles biocompatibility are controversial. It has been shown that hydroxyapatite nanoparticles induces inflammatory reaction and apoptosis. The aim of the present study was to evaluate the cytotoxicity of nano-hydroxyapatite on the human epithelial cells. Methods: The study was experimental and completed in vitro. The study was carried out in department of Immonulogy, Faculty of Medicine, Shahid Beheshti University of Medical Sciences in November 2014. The human-derived oral epithelium cell line (KB obtained from Pasteur Institute, Tehran, Iran were exposed to hydroxyapatite nanoparticles at 0.01, 0.05, 0.1, 0.5, 0.75, 1, 2.5 and 5 mg/ml concentrations in 24, 48 and 72 hours. Rod-shaped hydroxyapatite nanoparticles with 99% purity and maximum 100 nm sized particles were used. Methylthiazol tetrazolium bromide (MTT method was employed for cell vitality evaluation. Enzyme-linked immunosorbent assay (ELISA was used for assessing the viability of cells. Distilled water and fetal bovine serum (FBS were positive and negative controls. ANOVA and Duncan tests were used for statistical analysis. Results: The cytotoxicity of different concentrations of hydroxyapatite nanoparticles on human-derived oral epithelium cell line in 24 (P< 0.001, 48 (P< 0.001 and 72 hours (P< 0.001 was significantly different. The nano-hydroxyapatite particles at 0.5 to 1 mg/ml had the highest cytotoxicity effect on human-derived oral epithelium cells in 24, 48 and 72 hours. Lower concentrations than 0.05 mg/ml had the best biocompatibility properties in 24, 48 and 72 hours. Conclusion

  15. Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery

    DEFF Research Database (Denmark)

    Fan, Weiwei; Xia, Dengning; Zhu, Quanlei

    2018-01-01

    , especially to avoid lysosomal degradation, and basolateral release. Here, the functional material, deoxycholic acid-conjugated chitosan, is synthesized and loaded with the model protein drug insulin into deoxycholic acid-modified nanoparticles (DNPs). The DNPs designed in this study are demonstrated......Oral absorption of protein/peptide-loaded nanoparticles is often limited by multiple barriers of the intestinal epithelium. In addition to mucus translocation and apical endocytosis, highly efficient transepithelial absorption of nanoparticles requires successful intracellular trafficking...... to endolysosomal escape of DNPs. Additionally, DNPs can interact with a cytosolic ileal bile acid-binding protein that facilitates the intracellular trafficking and basolateral release of insulin. In rats, intravital two-photon microscopy also reveals that the transport of DNPs into the intestinal villi...

  16. Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo.

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    You Me Sung

    2009-10-01

    Full Text Available The normal function of Syk in epithelium of the developing or adult breast is not known, however, Syk suppresses tumor growth, invasion, and metastasis in breast cancer cells. Here, we demonstrate that in the mouse mammary gland, loss of one Syk allele profoundly increases proliferation and ductal branching and invasion of epithelial cells through the mammary fat pad during puberty. Mammary carcinomas develop by one year. Syk also suppresses proliferation and invasion in vitro. siRNA or shRNA knockdown of Syk in MCF10A breast epithelial cells dramatically increased proliferation, anchorage independent growth, cellular motility, and invasion, with formation of functional, extracellular matrix-degrading invadopodia. Morphological and gene microarray analysis following Syk knockdown revealed a loss of luminal and differentiated epithelial features with epithelial to mesenchymal transition and a gain in invadopodial cell surface markers CD44, CD49F, and MMP14. These results support the role of Syk in limiting proliferation and invasion of epithelial cells during normal morphogenesis, and emphasize the critical role of Syk as a tumor suppressor for breast cancer. The question of breast cancer risk following systemic anti-Syk therapy is raised since only partial loss of Syk was sufficient to induce mammary carcinomas.

  17. Cloning of radiation-induced new gene RS1 expressed in mouse intestinal epithelium by enhanced RACE

    International Nuclear Information System (INIS)

    Wang Fengchao; Wang Junping; Su Yongping; Gao Jinsheng; Lou Shufen; Liu Xiaohong; Ren Jiong; Zhang Bo

    2003-01-01

    Objective: To obtain full-length cDNA of radiation-induced new gene RS1 expressed in mouse intestinal epithelium. Methods: The tissue expression profile of RS1 was analyzed by semi-quantitative RT-PCR to find the target tissue which highly expresses RS1. The total RNA extracted from the corresponding tissue was taken as the template for reverse-transcription. Enhanced RACE PCR was used to clone the full-length cDNA of RS1, including enrichment of the target gene through biotin-labeled probe for magnetic bead purification and nested PCR. Results: About a 2 kb long 3' end was successfully cloned and cloning of the 5' end proceeded well. Conclusion: The result is consistent with our experiment design. The set of combined techniques has been identified with the cloning of full-length cDNA from EST sequence especially when the optimal gene-specific primers are not available or the expression level of target gene is low

  18. Accelerated repopulation of mouse tongue epithelium during fractionated irradiations or following single doses

    International Nuclear Information System (INIS)

    Doerr, W.; Kummermehr, J.

    1990-01-01

    Mouse tongue mucosa was established as an animal model to study repopulation after large single doses or during continuous irradiation. A top-up irradiation technique was used employing priming doses or fractionated treatment to the whole snout (300 kV X-rays) followed by local test doses (25 kV X-rays) to elicit denudation in a confined field of the inferior tongue surface. Clearcut quantal dose-response curves of ulcer incidence were obtained to all protocols; animal morbidity, i.e. body weight loss was minimal. Repopulation following priming doses of 10 and 13 Gy started with a delay of at least 3 days and then progressed rapidly to nearly restore original tissue tolerance by day 11. During continuous fractionation over 1 to 3 weeks with 5 fractions/week and doses per fraction of 2.5, 3 and 3.5 Gy, repopulation was small in week one but subsequently increased to fully compensate the weekly dose at all dose levels. Additional measurements of cell density during a 4 weeks course of 5 x 3 Gy or 5 x 4 Gy per week showed only moderate depletion to 67% of the control figures. The fact that rapid repopulation is achieved at relatively moderate damage levels should be taken into account when the timing of a treatment split is considered. (author). 18 refs.; 7 figs.; 1 tab

  19. A dielectrophoretic method of discrimination between normal oral epithelium, and oral and oropharyngeal cancer in a clinical setting.

    Science.gov (United States)

    Graham, K A; Mulhall, H J; Labeed, F H; Lewis, M P; Hoettges, K F; Kalavrezos, N; McCaul, J; Liew, C; Porter, S; Fedele, S; Hughes, M P

    2015-08-07

    Despite the accessibility of the oral cavity to clinical examination, delays in diagnosis of oral and oropharyngeal carcinoma (OOPC) are observed in a large majority of patients, with negative impact on prognosis. Diagnostic aids might help detection and improve early diagnosis, but there remains little robust evidence supporting the use of any particular diagnostic technology at the moment. The aim of the present feasibility first-in-human study was to evaluate the preliminary diagnostic validity of a novel technology platform based on dielectrophoresis (DEP). DEP does not require labeling with antibodies or stains and it is an ideal tool for rapid analysis of cell properties. Cells from OOPC/dysplasia tissue and healthy oral mucosa were collected from 57 study participants via minimally-invasive brush biopsies and tested with a prototype DEP platform using median membrane midpoint frequency as main analysis parameter. Results indicate that the current DEP platform can discriminate between brush biopsy samples from cancerous and healthy oral tissue with a diagnostic sensitivity of 81.6% and a specificity of 81.0%. The present ex vivo results support the potential application of DEP testing for identification of OOPC. This result indicates that DEP has the potential to be developed into a low-cost, rapid platform as an assistive tool for the early identification of oral cancer in primary care; given the rapid, minimally-invasive and non-expensive nature of the test, dielectric characterization represents a promising platform for cost-effective early cancer detection.

  20. Proliferation equivalent of 'accelerated repopulation' in mouse oral mucosa

    International Nuclear Information System (INIS)

    Doerr, W.; Emmendoerfer, H.; Haide, E.; Kummermehr, J.

    1994-01-01

    The proliferation response and changes in cellularity of mouse tongue epithelium were studied after single doses of X-rays and during 3 weeks of daily irradiation. A single dose of 13 Gy resulted in minimum cellularity (70% of control values) on days 3-5 and complete restoration on day 7. Mitotic activity ceased for 1 day followed by normal-to-supranormal values until day 15. A wave of abnormal mitoses was observed with a peak at days 4-7. Daily irradiation with 3 or 4 Gy induced neither major structural nor visible cellular damage. Cellularity decreased to ∼ 60% during week 1 and subsequently remained at 60-70%. The proliferation activity was reduced to ∼ 8% by day 2. Mitotic activity during weeks 2 and 3 was subnormal-to-normal, with dose-dependent increase to normal counts during the first weekend and a distinct overshoot over the second weekend respectively. A proliferation model is presented to explain the present findings and previous functional measurements of changes in tissue tolerance. Its major features are accelerated symmetrical stem cell divisions and abortive divisions of sterilized cells. (author)

  1. Differential expression of the P2X7 receptor in ovarian surface epithelium during the oestrous cycle in the mouse.

    Science.gov (United States)

    Vázquez-Cuevas, F G; Cruz-Rico, A; Garay, E; García-Carrancá, A; Pérez-Montiel, D; Juárez, B; Arellano, R O

    2013-01-01

    Purinergic signalling has been proposed as an intraovarian regulatory mechanism. Of the receptors responsible for purinergic transmission, the P2X7 receptor is an ATP-gated cationic channel that displays a broad spectrum of cellular functions ranging from apoptosis to cell proliferation and tumourigenesis. In the present study, we investigated the functional expression of P2X7 receptors in ovarian surface epithelium (OSE). P2X7 protein was detected in the OSE layer of the mouse, both in situ and in primary cultures. In cultures, 2'(3')-O-(4-Benzoylbenzoyl)adenosine-5'-triphosphate (BzATP) activation of P2X7 receptors increased [Ca(2+)]i and induced apoptosis. The functionality of the P2X7 receptor was investigated in situ by intrabursal injection of BzATP on each day of the oestrous cycle and evaluation of apoptosis 24h using the terminal deoxyribonucleotidyl transferase-mediated dUTP-fluorescein nick end-labelling (TUNEL) assay. Maximum effects of BzATP were observed during pro-oestrus, with the effects being blocked by A438079, a specific P2X7 receptor antagonist. Immunofluorescence staining for P2X7 protein revealed more robust expression during pro-oestrus and in OSE regions behind the antral follicles, strongly supporting the notion that the differences in apoptosis can be explained by increased receptor expression, which is regulated during the oestrous cycle. Finally, P2X7 receptor expression was detected in the OSE layer of human ovaries, with receptor expression maintained in human ovaries diagnosed with cancer, as well as in the human ovarian carcinoma SKOV3 cell line.

  2. Increased Micronuclei Frequency in Oral and Lingual Epithelium of Treated Diabetes Mellitus Patients

    Directory of Open Access Journals (Sweden)

    Jesús Emilo Quintero Ojeda

    2018-01-01

    Full Text Available Diabetes mellitus (DM is a metabolic disease characterized by persistent high levels of glucose in plasma. Chronic hyperglycemia is thought to increase oxidative stress and the formation of free radicals that in turn damage cells. Thus, we decided to determine the frequency of nuclear abnormalities in epithelial cells from cheek and tongue mucosa of DM patients with type 1 (DM1, treated only with insulin and type 2 (DM2, treated with metformin using the buccal micronucleus cytome (BMCyt assay. Micronuclei frequency in cheek epithelial cells was higher in both DM1 (0.75 ± 0.31, P<0.001 and DM2 (0.52 ± 0.27, P<0.001 patients, as compared to healthy controls (0.07  ±  0.06. Similarly, micronuclei frequency in tongue epithelium was increased in DM1 (0.81  ±  0.22, P<0.001 and DM2 (0.41  ±  0.21, P<0.001 groups, in comparison to controls (0.06  ±  0.05. Besides, we found a positive correlation between micronuclei frequency and the onset time of DM2 in both cheek (ρ = 0.69, P<0.001 and tongue epithelial cells (ρ = 0.71, P<0.001, but not with onset time of DM1 or age of the patients. Considering all this, we pose that BMCyt could serve as a fast and easily accessible test to assess genotoxic damage during dental visits of DM patients, helping to monitor their disease.

  3. Oral Lesions Induced by Chronic Khat Use Consist Essentially of Thickened Hyperkeratinized Epithelium

    Directory of Open Access Journals (Sweden)

    Ochiba Mohammed Lukandu

    2015-01-01

    Full Text Available Objectives. The habit of khat chewing is prevalent in many Middle Eastern and African cultures and has been associated with various adverse conditions in humans. This study aimed to describe histological changes induced by chronic khat chewing on the buccal mucosa. Methods. Biopsies of the buccal mucosa from 14 chronic khat chewers, 20 chronic khat chewers who also smoked tobacco, and 8 nonchewers were compared for epithelial thickness, degree and type of keratinization, and connective tissue changes. Results. Tissues from khat chewers depicted abnormal keratinization of the superficial cell layer and showed increased epithelial thickness affecting all layers. Epithelial thickness in control samples was 205 ± 26 μm whereas thickness in khat chewers and khat chewers who smoked tobacco was significantly higher measuring 330 ± 35 μm and 335 ± 19 μm, respectively. Tissues from khat chewers also showed increased intracellular edema, increased melanin pigment deposits, and increased number of rete pegs most of which were thin and deep. Conclusions. These results show that oral lesions induced by chronic chewing of khat in the buccal mucosa present with white and brown discoloration due to increased epithelial thickness, increased keratinization, and melanin deposition.

  4. Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo

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    Dustin J. Flanagan

    2017-08-01

    Full Text Available The gastric epithelium consists of tubular glandular units, each containing several differentiated cell types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. Very little is known about which cell signalling pathways are required for homeostasis of the gastric epithelium. Many diseases, such as cancer, arise as a result of deregulation of signalling pathways that regulate homeostasis of the diseased organ. Therefore, it is important to understand the biology of how normal conditions are maintained in a tissue to help inform the mechanisms driving disease in that same tissue, and to identify potential points of therapeutic intervention. Wnt signalling regulates several cell functions, including proliferation, differentiation and migration, and plays a crucial role during homeostasis of several tissues, including the intestinal epithelium. Wnt3a is required in the culture medium of gastric organoids, suggesting it is also important for the homeostasis of the gastric epithelium, but this has not been investigated in vivo. Here, we show that the Wnt receptor frizzled 7 (Fzd7, which is required for the homeostasis of the intestine, is expressed in the gastric epithelium and is required for gastric organoid growth. Gastric-specific loss of Fzd7 in the adult gastric epithelium of mice is deleterious and triggers rapid epithelial repopulation, which we believe is the first observation of this novel function for this tissue. Taken together, these data provide functional evidence of a crucial role for Wnt signalling, via the Fzd7 receptor, during homeostasis of the gastric epithelium.

  5. Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo.

    Science.gov (United States)

    Flanagan, Dustin J; Barker, Nick; Nowell, Cameron; Clevers, Hans; Ernst, Matthias; Phesse, Toby J; Vincan, Elizabeth

    2017-08-01

    The gastric epithelium consists of tubular glandular units, each containing several differentiated cell types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. Very little is known about which cell signalling pathways are required for homeostasis of the gastric epithelium. Many diseases, such as cancer, arise as a result of deregulation of signalling pathways that regulate homeostasis of the diseased organ. Therefore, it is important to understand the biology of how normal conditions are maintained in a tissue to help inform the mechanisms driving disease in that same tissue, and to identify potential points of therapeutic intervention. Wnt signalling regulates several cell functions, including proliferation, differentiation and migration, and plays a crucial role during homeostasis of several tissues, including the intestinal epithelium. Wnt3a is required in the culture medium of gastric organoids, suggesting it is also important for the homeostasis of the gastric epithelium, but this has not been investigated in vivo Here, we show that the Wnt receptor frizzled 7 (Fzd7), which is required for the homeostasis of the intestine, is expressed in the gastric epithelium and is required for gastric organoid growth. Gastric-specific loss of Fzd7 in the adult gastric epithelium of mice is deleterious and triggers rapid epithelial repopulation, which we believe is the first observation of this novel function for this tissue. Taken together, these data provide functional evidence of a crucial role for Wnt signalling, via the Fzd7 receptor, during homeostasis of the gastric epithelium. © 2017. Published by The Company of Biologists Ltd.

  6. Downregulation of keratin 76 expression during oral carcinogenesis of human, hamster and mouse.

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    Srikant Ambatipudi

    Full Text Available 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.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.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.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.

  7. Mouse Models for Studying Oral Cancer: Impact in the Era of Cancer Immunotherapy.

    Science.gov (United States)

    Luo, J J; Young, C D; Zhou, H M; Wang, X J

    2018-04-01

    Model systems for oral cancer research have progressed from tumor epithelial cell cultures to in vivo systems that mimic oral cancer genetics, pathological characteristics, and tumor-stroma interactions of oral cancer patients. In the era of cancer immunotherapy, it is imperative to use model systems to test oral cancer prevention and therapeutic interventions in the presence of an immune system and to discover mechanisms of stromal contributions to oral cancer carcinogenesis. Here, we review in vivo mouse model systems commonly used for studying oral cancer and discuss the impact these models are having in advancing basic mechanisms, chemoprevention, and therapeutic intervention of oral cancer while highlighting recent discoveries concerning the role of immune cells in oral cancer. Improvements to in vivo model systems that highly recapitulate human oral cancer hold the key to identifying features of oral cancer initiation, progression, and invasion as well as molecular and cellular targets for prevention, therapeutic response, and immunotherapy development.

  8. YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues.

    Science.gov (United States)

    Liu, Ming; Zhao, Shuangyun; Lin, Qingjie; Wang, Xiu-Ping

    2015-04-01

    Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. The membrane-associated MUC1 improves adhesion of salivary MUC5B on buccal cells. Application to development of an in vitro cellular model of oral epithelium.

    Science.gov (United States)

    Ployon, Sarah; Belloir, Christine; Bonnotte, Aline; Lherminier, Jeannine; Canon, Francis; Morzel, Martine

    2016-01-01

    The mucosal pellicle is a thin layer of salivary proteins, mostly MUC5B mucins, anchored to epithelial oral cells. This pellicle is involved in protection of oral mucosae against abrasion, pathogenic microorganisms or chemical xenobiotics. The present study aimed at studying the involvement of MUC1 in mucosal pellicle formation and more specifically in salivary MUC5B binding using a cell-based model of oral epithelium. MUC1 mRNAs were not detected in TR146 cells, and therefore a stable cell line named TR146/MUC1 expressing this protein was developed by transfection. TR146 and TR146/MUC1 were incubated with human saliva in order to evaluate retention of MUC5B by epithelial cells. The cell surface of both TR146 and TR146/MUC1 was typical of a squamous non-keratinized epithelium, with the presence of numerous microplicae. After incubation for 2h with saliva diluted in culture medium (1:1) and two washes with PBS, saliva deposits on cells appeared as a loose filamentous thin network. MUC5B fluorescent immunostaining evidenced a heterogeneous lining of confluent cell cultures by this salivary mucin but with higher fluorescence on TR146/MUC1 cells. Semi-quantification of MUC5B bound to cells confirmed a better retention by TR146/MUC1, evaluated by Dot Blot (+34.1%, p<0.05) or by immunocytochemistry (+44%, p<0.001). The membrane-bound mucin MUC1 is a factor enhancing the formation of the mucosal pellicle by increasing the binding of salivary MUC5B to oral epithelial cells. An in vitro model suitable to study specifically the function and properties of the mucosal pellicle is proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability

    NARCIS (Netherlands)

    Boretto, Matteo; Cox, Benoit; Noben, Manuel; Hendriks, Nikolai; Fassbender, Amelie; Roose, Heleen; Amant, Frédéric; Timmerman, Dirk; Tomassetti, Carla; Vanhie, Arne; Meuleman, Christel; Ferrante, Marc; Vankelecom, Hugo

    2017-01-01

    The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and

  11. EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON FETAL MOUSE URINARY TRACT EPITHELIUM IN VITRO

    Science.gov (United States)

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), produces hydronephrosis by altering the differentiation and proliferation of ureteric epithelial cells in the embryonic C57BL/6N mouse urinary tract. This study examines the effects of TCDD on late gestation fetal urinary tract cells u...

  12. Cadherins in the retinal pigment epithelium (RPE revisited: P-cadherin is the highly dominant cadherin expressed in human and mouse RPE in vivo.

    Directory of Open Access Journals (Sweden)

    Xue Yang

    Full Text Available The retinal pigment epithelium (RPE supports the health and function of retinal photoreceptors and is essential for normal vision. RPE cells are post-mitotic, terminally differentiated, and polarized epithelial cells. In pathological conditions, however, they lose their epithelial integrity, become dysfunctional, even dedifferentiate, and ultimately die. The integrity of epithelial cells is maintained, in part, by adherens junctions, which are composed of cadherin homodimers and p120-, β-, and α-catenins linking to actin filaments. While E-cadherin is the major cadherin for forming the epithelial phenotype in most epithelial cell types, it has been reported that cadherin expression in RPE cells is different from other epithelial cells based on results with cultured RPE cells. In this study, we revisited the expression of cadherins in the RPE to clarify their relative contribution by measuring the absolute quantity of cDNAs produced from mRNAs of three classical cadherins (E-, N-, and P-cadherins in the RPE in vivo. We found that P-cadherin (CDH3 is highly dominant in both mouse and human RPE in situ. The degree of dominance of P-cadherin is surprisingly large, with mouse Cdh3 and human CDH3 accounting for 82-85% and 92-93% of the total of the three cadherin mRNAs, respectively. We confirmed the expression of P-cadherin protein at the cell-cell border of mouse RPE in situ by immunofluorescence. Furthermore, we found that oxidative stress induces dissociation of P-cadherin and β-catenin from the cell membrane and subsequent translocation of β-catenin into the nucleus, resulting in activation of the canonical Wnt/β-catenin pathway. This is the first report of absolute comparison of the expression of three cadherins in the RPE, and the results suggest that the physiological role of P-cadherin in the RPE needs to be reevaluated.

  13. Conditional inactivation of Brca1 in the mouse ovarian surface epithelium results in an increase in preneoplastic changes

    International Nuclear Information System (INIS)

    Clark-Knowles, Katherine V.; Garson, Kenneth; Jonkers, Jos; Vanderhyden, Barbara C.

    2007-01-01

    Epithelial ovarian cancer (EOC) is thought to arise from the ovarian surface epithelium (OSE); however, the molecular events underlying this transformation are poorly understood. Germline mutations in the BRCA1 tumor suppressor gene result in a significantly increased risk of developing EOC and a large proportion of sporadic EOCs display some sort of BRCA1 dysfunction. Using mice with conditional expression of Brca1, we inactivated Brca1 in the murine OSE and demonstrate that this inactivation results in the development of preneoplastic changes, such as hyperplasia, epithelial invaginations, and inclusion cysts, which arise earlier and are more numerous than in control ovaries. These changes resemble the premalignant lesions that have been reported in human prophylactic oophorectomy specimens from women with BRCA1 germline mutation. We also report that inactivation of Brca1 in primary cultures of murine OSE cells leads to a suppression of proliferation due to increased apoptosis that can be rescued by concomitant inactivation of p53. These observations, along with our finding that these cells display an increased sensitivity to the DNA-damaging agent cisplatin, indicate that loss of function of Brca1 in OSE cells impacts both cellular growth control and DNA-damage repair which results in altered cell behavior manifested as morphological changes in vivo that arise earlier and are more numerous than what can be attributed to ageing

  14. Circulating Reactive Oxidant Causes Apoptosis of Retinal Pigment Epithelium and Cone Photoreceptors in the Mouse Central Retina

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2011-01-01

    Full Text Available Reactive oxidants damage the retinal pigment epithelium (RPE, which is required for viability of overlying photoreceptors. Smoking which leads to chronic accumulation of reactive oxidants in the circulation is linked to age-related macular degeneration (AMD where RPE death is seen along with photoreceptor loss in the central macular region of the retina. It is unclear why this damage is concentrated in the central retina. We asked whether circulating oxidant might specifically target the central retina. Mice were administered the classic reactive oxidant iodate through tail vein injection, and visual acuity was followed by optokinetic response. Histology and apoptosis was examined by H&E and immunostaining. Iodate indeed selectively damaged the central retina, and this damage was highlighted by early apoptosis of RPE in the central retina followed by apoptosis of photoreceptors adjacent to the region of RPE loss–-cones were lost preferentially. The pattern and extent of this damage was independent of exposure to light. We then conclude that circulating oxidant is sufficient to selectively damage the central retina highlighted by sequential apoptosis of RPE and photoreceptors, with cones being the most sensitivity to this RPE loss.

  15. A mouse model of mammary hyperplasia induced by oral hormone ...

    African Journals Online (AJOL)

    Methods and Materials: To address the mechanism, we developed a mouse model of mammary hyperplasia. We gave mice estradiol valerate tablets and progesterone capsules sequentially for one month by intragastric administration. Results: Mice treated by this method had a series of pathological changes which are ...

  16. TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION

    Science.gov (United States)

    TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATIONMichael F. Hughes, Ph.D., Brenda C. Edwards, Carol T. Mitchell and Elaina M. Kenyon, Ph.D. United States Environmental Protection Agency, Office of Research and Development, Nation...

  17. Development of teeth in chick embryos after mouse neural crest transplantations.

    Science.gov (United States)

    Mitsiadis, Thimios A; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

    2003-05-27

    Teeth were lost in birds 70-80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick chimeras obtained show evidence of tooth formation showing that avian oral epithelium is able to induce a nonavian developmental program in mouse neural crest-derived mesenchymal cells.

  18. Recent mouse and rat methods for the study of experimental oral candidiasis.

    Science.gov (United States)

    Costa, Anna C B P; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio O C

    2013-07-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis.

  19. Recent mouse and rat methods for the study of experimental oral candidiasis

    Science.gov (United States)

    Costa, Anna CBP; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio OC

    2013-01-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis. PMID:23715031

  20. Progenitor Epithelium

    Science.gov (United States)

    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

  1. Oral administration of yessotoxin stabilizes E-cadherin in mouse colon

    International Nuclear Information System (INIS)

    Callegari, Federica; Sosa, Silvio; Ferrari, Sara; Soranzo, Maria Rosa; Pierotti, Silvia; Yasumoto, Takeshi; Tubaro, Aurelia; Rossini, Gian Paolo

    2006-01-01

    YTX has been shown to disrupt the E-cadherin-catenin system in cultured epithelial cells, raising some concern that ingestion of seafood contaminated by YTX might favour tumour spreading and metastasis formation in vivo. In order to probe whether YTX might affect cadherin systems in vivo, we have set up a study involving repeated oral dosing of the toxin in mice (1 mg/kg/day, for 7 days) and analysis of E-cadherin and N-cadherin in tissue extracts obtained at the end of the dosing scheme, as well as 1 and 3 months after YTX administration. We found that the E-cadherin pools obtained from lung and kidney were not altered by YTX in any of our experimental conditions. Extracts from mouse colon contained intact E-cadherin and an E-cadherin fragment of about 90 kDa (ECRA 9 ), displaying a molecular alteration resembling that caused by YTX in cultured cells. We found that the relative proportion of ECRA 9 , as compared to intact E-cadherin, was higher in colon extracts from control mice than from YTX-treated animals, indicating that oral administration of YTX to mice stabilizes E-cadherin of mouse colon. No significant difference could be detected in samples prepared from colons obtained 30 or 90 days after termination of YTX treatment. Oral administration of YTX to mice did not lead to a significant increase in the fragments of E-cadherin detectable in serum, neither it altered the N-cadherin pool of mouse heart. Electron microscopy analysis showed no substantial ultrastructural differences between controls and YTX-treated mice. Our findings show that ingestion of food contaminated by YTX poses a low risk of disruption of the E-cadherin system in vivo

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

    Science.gov (United States)

    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.

  3. Expression pattern of adhesion molecules in junctional epithelium differs from that in other gingival epithelia.

    Science.gov (United States)

    Hatakeyama, S; Yaegashi, T; Oikawa, Y; Fujiwara, H; Mikami, T; Takeda, Y; Satoh, M

    2006-08-01

    The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues, requiring protection from exposure to bacteria and their products. However, of the three epithelia comprising the gingival epithelium, the junctional epithelium has much wider intercellular spaces than the sulcular epithelium and oral gingival epithelium. Hence, the aim of the present study was to characterize the cell adhesion structure in the junctional epithelium compared with the other two epithelia. Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were examined for expression of adhesion molecules by immunofluorescence. In the oral gingival epithelium and sulcular epithelium, but not in the junctional epithelium, desmoglein 1 and 2 in cell-cell contact sites were more abundant in the upper than the suprabasal layers. E-cadherin, the main transmembranous molecule of adherens junctions, was present in spinous layers of the oral gingival epithelium and sulcular epithelium, but was scarce in the junctional epithelium. In contrast, desmoglein 3 and P-cadherin were present in all layers of the junctional epithelium as well as the oral gingival epithelium and sulcular epithelium. Connexin 43 was clearly localized to spinous layers of the oral gingival epithelium, sulcular epithelium and parts of the junctional epithelium. Claudin-1 and occludin were expressed in the cell membranes of a few superficial layers of the oral gingival epithelium. These findings indicated that the junctional epithelium contains only a few desmosomes, composed of only desmoglein 3; adherens junctions are probably absent because of defective E-cadherin. Thus, the anchoring junctions connecting junctional epithelium cells are lax, causing widened intercellular spaces. In contrast, the oral gingival epithelium, which has a few tight junctions, functions as a barrier.

  4. Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis

    Science.gov (United States)

    Ryan, Lisa K.; Freeman, Katie B.; Masso-Silva, Jorge A.; Falkovsky, Klaudia; Aloyouny, Ashwag; Markowitz, Kenneth; Hise, Amy G.; Fatahzadeh, Mahnaz; Scott, Richard W.

    2014-01-01

    There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis. PMID:24752272

  5. Tracking vaginal, anal and oral infection in a mouse papillomavirus infection model.

    Science.gov (United States)

    Hu, Jiafen; Budgeon, Lynn R; Cladel, Nancy M; Balogh, Karla; Myers, Roland; Cooper, Timothy K; Christensen, Neil D

    2015-12-01

    Noninvasive and practical techniques to longitudinally track viral infection are sought after in clinical practice. We report a proof-of-principle study to monitor the viral DNA copy number using a newly established mouse papillomavirus (MmuPV1) mucosal infection model. We hypothesized that viral presence could be identified and quantified by collecting lavage samples from cervicovaginal, anal and oral sites. Nude mice infected at these sites with infectious MmuPV1 were tracked for up to 23 weeks starting at 6 weeks post-infection. Viral DNA copy number was determined by SYBR Green Q-PCR analysis. In addition, we tracked viral DNA load through three complete oestrous cycles to pinpoint whether there was a correlation between the DNA load and the four stages of the oestrous cycle. Our results showed that high viral DNA copy number was reproducibly detected from both anal and cervicovaginal lavage samples. The infection and disease progression were further confirmed by histology, cytology, in situ hybridization, immunohistochemistry and transmission electron microscopy. Interestingly, the viral copy number fluctuated over the oestrous cycle, with the highest level at the oestrus stage, implying that multiple sampling might be necessary to provide a reliable diagnosis. Virus DNA was detected in oral lavage samples at a later time after infection. Lower viral DNA load was found in oral samples when compared with those in anal and vaginal tracts. To our knowledge, our study is the first in vivo study to sequentially monitor papillomavirus infection from mucosal anal, oral and vaginal tracts in a preclinical model.

  6. Lineage tracing in the adult mouse corneal epithelium supports the limbal epithelial stem cell hypothesis with intermittent periods of stem cell quiescence

    Directory of Open Access Journals (Sweden)

    Natalie J. Dorà

    2015-11-01

    Full Text Available 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.

  7. Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway.

    Science.gov (United States)

    Pelegrino, F S A; Pflugfelder, S C; De Paiva, C S

    2012-01-01

    Patients with tear dysfunction often experience increased irritation symptoms when subjected to drafty and/or low humidity environmental conditions. The purpose of this study was to investigate the effects of low humidity stress (LHS) on corneal barrier function and expression of cornified envelope (CE) precursor proteins in the epithelium of C57BL/6 and c-jun N-terminal kinase 2 (JNK2) knockout (KO) mice. LHS was induced in both strains by exposure to an air draft for 15 (LHS15D) or 30 days (LHS30D) at a relative humidity LHS15D showed corneal barrier dysfunction, decreased apical corneal epithelial cell area, higher MMP-9 expression and gelatinase activity and increased involucrin and SPRR-2 immunoreactivity in the corneal epithelium compared to NS mice. JNK2KO mice were resistant to LHS-induced corneal barrier disruption. MMP-3,-9,-13, IL-1α, IL-1β, involucrin and SPRR-2a RNA transcripts were significantly increased in C57BL/6 mice at LHS15D, while no change was noted in JNK2KO mice. LHS is capable of altering corneal barrier function, promoting pathologic alteration of the TJ complex and stimulating production of CE proteins by the corneal epithelium. Activation of the JNK2 signaling pathway contributes to corneal epithelial barrier disruption in LHS. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. The dynamics of gene expression changes in a mouse model of oral tumorigenesis may help refine prevention and treatment strategies in patients with oral cancer.

    Science.gov (United States)

    Foy, Jean-Philippe; Tortereau, Antonin; Caulin, Carlos; Le Texier, Vincent; Lavergne, Emilie; Thomas, Emilie; Chabaud, Sylvie; Perol, David; Lachuer, Joël; Lang, Wenhua; Hong, Waun Ki; Goudot, Patrick; Lippman, Scott M; Bertolus, Chloé; Saintigny, Pierre

    2016-06-14

    A better understanding of the dynamics of molecular changes occurring during the early stages of oral tumorigenesis may help refine prevention and treatment strategies. We generated genome-wide expression profiles of microdissected normal mucosa, hyperplasia, dysplasia and tumors derived from the 4-NQO mouse model of oral tumorigenesis. Genes differentially expressed between tumor and normal mucosa defined the "tumor gene set" (TGS), including 4 non-overlapping gene subsets that characterize the dynamics of gene expression changes through different stages of disease progression. The majority of gene expression changes occurred early or progressively. The relevance of these mouse gene sets to human disease was tested in multiple datasets including the TCGA and the Genomics of Drug Sensitivity in Cancer project. The TGS was able to discriminate oral squamous cell carcinoma (OSCC) from normal oral mucosa in 3 independent datasets. The OSCC samples enriched in the mouse TGS displayed high frequency of CASP8 mutations, 11q13.3 amplifications and low frequency of PIK3CA mutations. Early changes observed in the 4-NQO model were associated with a trend toward a shorter oral cancer-free survival in patients with oral preneoplasia that was not seen in multivariate analysis. Progressive changes observed in the 4-NQO model were associated with an increased sensitivity to 4 different MEK inhibitors in a panel of 51 squamous cell carcinoma cell lines of the areodigestive tract. In conclusion, the dynamics of molecular changes in the 4-NQO model reveal that MEK inhibition may be relevant to prevention and treatment of a specific molecularly-defined subgroup of OSCC.

  9. Effect of oral calcium and calcium + fluoride treatments on mouse bone properties during suspension

    Science.gov (United States)

    Simske, S. J.; Luttges, M. W.; Allen, K. A.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    The bone effects of oral dosages of calcium chloride with or without supplementary sodium fluoride were assessed in antiorthostatically suspended mice. Two calcium dosages were used to replace half (3.1 mM) or all(6.3 mM) of the dietary calcium lost due to reduced food intake by the suspended mice. Two groups of 6.3 mM CaCl2-treated mice were additionally treated with 0.25 or 2.5 mM NaF. The results indicate that supplementation of the mouse drinking water with calcium salts prevents bone changes induced by short-term suspension, while calcium salts in combination with fluoride are less effective as fluoride dosage increases. However, the calcium supplements change the relationship between the femur mechanical properties and the mineral composition of the bone. Because of this, it appears that oral calcium supplements are effective through a mechanism other than simple dietary supplementation and may indicate a dependence of bone consistency on systemic and local fluid conditions.

  10. Early inflammatory changes in radiation-induced oral mucositis. Effect of pentoxifylline in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, Sylvia; Bozsaky, Eva; Roitinger, Eva; Schwarz, Karoline [Medical University/AKH Vienna, Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Vienna (Austria); Schmidt, Margret [Technische Universitaet Dresden, Dept. Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany); Technische Universitaet Dresden, Helmholtz-Zentrum Dresden - Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany); Doerr, Wolfgang [Medical University/AKH Vienna, Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Vienna (Austria); Technische Universitaet Dresden, Dept. Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany); Technische Universitaet Dresden, Helmholtz-Zentrum Dresden - Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany)

    2017-06-15

    Early inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug. The present study hence focuses on the manifestation of early inflammatory changes in mouse tongue during daily fractionated irradiation and their potential modulation by pentoxifylline. Daily fractionated irradiation with 5 fractions of 3 Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 3 animals per day were euthanized every second day between day 0 and 14. Pentoxifylline (15 mg/kg, s. c.) was administered daily from day 5 to the day before sacrifice. The expression of the inflammatory proteins TNFα, NF-κB, and IL-1β were analysed. Fractionated irradiation increased the expression of all inflammatory markers. Pentoxifylline significantly reduced the expression of TNFα and IL-1β, but not NF-κB. Early inflammation, as indicated by the expression of the inflammatory markers TNFα, NF-κB, and IL-1β, is an essential component of early radiogenic oral mucositis. Pentoxifylline differentially modulated the expression of different inflammatory markers. The mucoprotective effect of pentoxifylline does not appear to be based on modulation of NF-κB-associated inflammation. (orig.) [German] Fruehe entzuendliche Veraenderungen sind ein bedeutender Faktor waehrend der Strahlenreaktion der Schleimhaut. Die Behandlung mit Pentoxifyllin erzielte eine signifikante Minderung strahleninduzierter oraler Mukositis im Mauszungenmodel. Die zugrundeliegenden Mechanismen sind potenziell auf die immunomodulatorischen Eigenschaften des Wirkstoffs zurueckzufuehren. Die vorliegenden Untersuchungen fokussieren daher auf die Manifestation frueher entzuendlicher Veraenderungen in der Mauszunge waehrend taeglich fraktionierter Bestrahlung und deren potenzieller Modifikation

  11. Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

    Science.gov (United States)

    Wang, Le; Wang, Chong; Mei, Huan; Shen, Yongnian; Lv, Guixia; Zeng, Rong; Zhan, Ping; Li, Dongmei; Liu, Weida

    2016-02-01

    Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

  12. ATP-ase positive cells in human oral mucosa transplanted to nude mice

    DEFF Research Database (Denmark)

    Dabelsteen, E; Kirkeby, S

    1981-01-01

    A model to study the differentiation of human oral epithelium in vivo utilizing transplantation of human tissue to nude mice has been described. Previous studies have described the epithelial cells in this model. In this study we demonstrate that 8 d after transplantation, Langerhans cells, ident......, identified as ATP-ase positive dendritic cells, have almost disappeared from the transplanted epithelium whereas at day 21 after transplantation such cells were abundant. It is suggested that the ATP-ase positive cells which reappear in the transplanted epithelium are of mouse origin....

  13. Development of teeth in chick embryos after mouse neural crest transplantations

    OpenAIRE

    Mitsiadis, Thimios A.; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

    2003-01-01

    Teeth were lost in birds 70–80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick ...

  14. The therapeutic effect of PLAG against oral mucositis in hamster and mouse model

    Directory of Open Access Journals (Sweden)

    Ha-Reum Lee

    2016-10-01

    Full Text Available Chemotherapy-induced mucositis can limit the effectiveness of cancer therapy and increase the risk of infections. However, no specific therapy for protection against mucositis is currently available. In this study, we investigated the therapeutic effect of PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride in 5-fluorouracil (5-FU-induced oral mucositis animal models. Hamsters were administered 5-FU (80 mg/kg intraperitoneally on days 0, 6, and 9. The animals’ cheek pouches were then scratched equally with the tip of an 18-gauge needle on days 1, 2, and 7. PLAG was administered daily at 250 mg/kg/day. PLAG administration significantly reduced 5-FU/scratching–induced mucositis. Dramatic reversal of weight loss in PLAG-treated hamsters with mucositis was observed. Histochemical staining data also revealed newly differentiated epidermis and blood vessels in the cheek pouches of PLAG-treated hamsters, indicative of recovery. Whole blood analyses indicated that PLAG prevents 5-FU–induced excessive neutrophil transmigration to the infection site and eventually stabilizes the number of circulating neutrophils. In a mouse mucositis model, mice with 5-FU–induced disease treated with PLAG exhibited resistance to body-weight loss compared with mice that received 5-FU or 5-FU/scratching alone. PLAG also dramatically reversed mucositis-associated weight loss and inhibited mucositis-induced inflammatory responses in the tongue and serum. These data suggest that PLAG enhances recovery from 5-FU–induced oral mucositis and may therefore be a useful therapeutic agent for treating side effects of chemotherapy, such as mucositis and cachexia.

  15. Oral fungal immunomodulatory protein-Flammulina velutipes has influence on pulmonary inflammatory process and potential treatment for allergic airway disease: A mouse model

    Directory of Open Access Journals (Sweden)

    Po-Yu Chu

    2017-06-01

    Conclusion: Oral FIP-fve had an anti-inflammatory effect on the acute phase of the airway inflammatory process induced by HDM in the mouse model and might have a potentially therapeutic role for allergic airway diseases.

  16. Early life exposure to bisphenol A investigated in mouse models of airway allergy, food allergy and oral tolerance.

    Science.gov (United States)

    Nygaard, Unni Cecilie; Vinje, Nina Eriksen; Samuelsen, Mari; Andreassen, Monica; Groeng, Else-Carin; Bølling, Anette Kocbach; Becher, Rune; Lovik, Martinus; Bodin, Johanna

    2015-09-01

    The impact of early life exposure to bisphenol A (BPA) through drinking water was investigated in mouse models of respiratory allergy, food allergy and oral tolerance. Balb/c mice were exposed to BPA (0, 10 or 100 μg/ml), and the offspring were intranasally exposed to the allergen ovalbumin (OVA). C3H/HeJ offspring were sensitized with the food allergen lupin by intragastric gavage, after exposure to BPA (0, 1, 10 or 100 μg/ml). In separate offspring, oral tolerance was induced by gavage of 5 mg lupin one week before entering the protocol for the food allergy induction. In the airway allergy model, BPA (100 μg/ml) caused increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and a trend of increased OVA-specific IgE levels. In the food allergy and tolerance models, BPA did not alter the clinical anaphylaxis or antibody responses, but induced alterations in splenocyte cytokines and decreased mouse mast cell protease (MMCP)-1 serum levels. In conclusion, early life exposure to BPA through drinking water modestly augmented allergic responses in a mouse model of airway allergy only at high doses, and not in mouse models for food allergy and tolerance. Thus, our data do not support that BPA promotes allergy development at exposure levels relevant for humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Systemic and oral immunogenicity of hemagglutinin protein of rinderpest virus expressed by transgenic peanut plants in a mouse model

    International Nuclear Information System (INIS)

    Khandelwal, Abha; Renukaradhya, G.J.; Rajasekhar, M.; Sita, G. Lakshmi; Shaila, M.S.

    2004-01-01

    Rinderpest causes a devastating disease, often fatal, in wild and domestic ruminants. It has been eradicated successfully using a live, attenuated vaccine from most part of the world leaving a few foci of disease in parts of Africa, the Middle East, and South Asia. We have developed transgenic peanut (Arachis hypogaea L.) plants expressing hemagglutinin (H) protein of rinderpest virus (RPV), which is antigenically authentic. In this work, we have evaluated the immunogenicity of peanut-expressed H protein using mouse model, administered parenterally as well as orally. Intraperitoneal immunization of mice with the transgenic peanut extract elicited antibody response specific to H. These antibodies neutralized virus infectivity in vitro. Oral immunization of mice with transgenic peanut induced H-specific serum IgG and IgA antibodies. The systemic and oral immunogenicity of plant-derived H in absence of any adjuvant indicates the potential of edible vaccine for rinderpest

  18. Oral administration of methysticin improves cognitive deficits in a mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Athanassios Fragoulis

    2017-08-01

    Full Text Available Introduction: There is increasing evidence for the involvement of chronic inflammation and oxidative stress in the pathogenesis of Alzheimer's disease (AD. Nuclear factor erythroid 2-related factor 2 (Nrf2 is an anti-inflammatory transcription factor that regulates the oxidative stress defense. Our previous experiments demonstrated that kavalactones protect neuronal cells against Amyloid β (Aβ-induced oxidative stress in vitro by Nrf2 pathway activation. Here, we tested an in vivo kavalactone treatment in a mouse model of AD. Methods: The kavalactone methysticin was administered once a week for a period of 6 months to 6 month old transgenic APP/Psen1 mice by oral gavage. Nrf2 pathway activation was measured by methysticin treatment of ARE-luciferase mice, by qPCR of Nrf2-target genes and immunohistochemical detection of Nrf2. Aβ burden was analyzed by CongoRed staining, immunofluorescent detection and ELISA. Neuroinflammation was assessed by immunohistochemical stainings for microglia and astrocytes. Pro-inflammatory cytokines in the hippocampus was determined by Luminex multi-plex assays. The hippocampal oxidative damage was detected by oxyblot technique and immunohistochemical staining against DT3 and 4-HNE. The cognitive ability of mice was evaluated using Morris water maze. Results: Methysticin treatment activated the Nrf2 pathway in the hippocampus and cortex of mice. The Aβ deposition in brains of methysticin-treated APP/Psen1 mice was not altered compared to untreated mice. However, methysticin treatment significantly reduced microgliosis, astrogliosis and secretion of the pro-inflammatory cytokines TNF-α and IL-17A. In addition, the oxidative damage of hippocampi from APP/Psen1 mice was reduced by methysticin treatment. Most importantly, methysticin treatment significantly attenuated the long-term memory decline of APP/Psen1 mice. Conclusion: In summary, these findings show that methysticin administration activates the Nrf2 pathway

  19. Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

    Science.gov (United States)

    Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

    2015-02-01

    Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

  20. Oral-Only Linezolid-Rifampin Is Highly Effective Compared with Other Antibiotics for Periprosthetic Joint Infection: Study of a Mouse Model.

    Science.gov (United States)

    Thompson, John M; Saini, Vikram; Ashbaugh, Alyssa G; Miller, Robert J; Ordonez, Alvaro A; Ortines, Roger V; Wang, Yu; Sterling, Robert S; Jain, Sanjay K; Miller, Lloyd S

    2017-04-19

    The medical treatment of periprosthetic joint infection (PJI) involves prolonged systemic antibiotic courses, often with suboptimal clinical outcomes including increased morbidity and health-care costs. Oral and intravenous monotherapies and combination antibiotic regimens were evaluated in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) PJI. Oral linezolid with or without oral rifampin, intravenous vancomycin with oral rifampin, intravenous daptomycin or ceftaroline with or without oral rifampin, oral doxycycline, or sham treatment were administered at human-exposure doses for 6 weeks in a mouse model of PJI. Bacterial burden was assessed by in vivo bioluminescent imaging and ex vivo counting of colony-forming units (CFUs), and reactive bone changes were evaluated with radiographs and micro-computed tomography (μCT) imaging. Oral-only linezolid-rifampin and all intravenous antibiotic-rifampin combinations resulted in no recoverable bacteria and minimized reactive bone changes. Although oral linezolid was the most effective monotherapy, all oral and intravenous antibiotic monotherapies failed to clear infection or prevent reactive bone changes. Combination antibiotic-rifampin regimens, including oral-only linezolid-rifampin and the newer ceftaroline-rifampin combinations, were highly effective and more efficacious than monotherapies when used against a preclinical MRSA PJI. This study provides important preclinical evidence to better optimize future antibiotic therapy against PJIs. In particular, the oral-only linezolid-rifampin option might reduce venous access complications and health-care costs.

  1. RT-PCR detection of Candida albicans ALS gene expression in the reconstituted human epithelium (RHE) model of oral candidiasis and in model biofilms.

    Science.gov (United States)

    Green, Clayton B; Cheng, Georgina; Chandra, Jyotsna; Mukherjee, Pranab; Ghannoum, Mahmoud A; Hoyer, Lois L

    2004-02-01

    An RT-PCR assay was developed to analyse expression patterns of genes in the Candida albicans ALS (agglutinin-like sequence) family. Inoculation of a reconstituted human buccal epithelium (RHE) model of mucocutaneous candidiasis with strain SC5314 showed destruction of the epithelial layer by C. albicans and also formation of an upper fungal layer that had characteristics similar to a biofilm. RT-PCR analysis of total RNA samples extracted from C. albicans-inoculated buccal RHE showed that ALS1, ALS2, ALS3, ALS4, ALS5 and ALS9 were consistently detected over time as destruction of the RHE progressed. Detection of transcripts from ALS7, and particularly from ALS6, was more sporadic, but not associated with a strictly temporal pattern. The expression pattern of ALS genes in C. albicans cultures used to inoculate the RHE was similar to that observed in the RHE model, suggesting that contact of C. albicans with buccal RHE does little to alter ALS gene expression. RT-PCR analysis of RNA samples extracted from model denture and catheter biofilms showed similar gene expression patterns to the buccal RHE specimens. Results from the RT-PCR analysis of biofilm RNA specimens were consistent between various C. albicans strains during biofilm development and were comparable to gene expression patterns in planktonic cells. The RT-PCR assay described here will be useful for analysis of human clinical specimens and samples from other disease models. The method will provide further insight into the role of ALS genes and their encoded proteins in the diverse interactions between C. albicans and its host.

  2. RELATIVE POTENCY OF ORAL ANTIGENS IN PROVOKING FOOD ALLERGY IN THE MOUS

    Science.gov (United States)

    Rationale: An animal model for food allergy is needed to test novel proteins produced through biotechnology for potential allergenicity. While the oral route is the most relevant method of exposure, oral tolerance is an impediment. We demonstrate that mice can distinguish...

  3. DIGESTIBILITY AND ORAL TOLERANCE IN A MOUSE MODEL FOR FOOD ALLERGY

    Science.gov (United States)

    An animal model for food allergy is needed to test novel proteins produced through biotechnology for potential allergenicity. We demonstrate that mice can distinguish allergens from non-allergens when exposed to foods orally, both in terms of oral tolerance and allergic antibody ...

  4. Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation

    International Nuclear Information System (INIS)

    Schmidt, M.; Haagen, J.; Noack, R.; Siegemund, A.; Gabriel, P.; Doerr, W.

    2014-01-01

    Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation. Daily fractionated irradiation (5 x 3 Gy/week) was given over 1 (days 0-4) or 3 weeks (days 0-4, 7-11, 14-18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose-effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols. Transplantation of 6 x 10 6 , but not of 3 x 10 6 bone marrow stem cells on day -1, +4, +8, +11 or +15 significantly increased the ED 50 values (dose, at which an ulcer is expected in 50% of the mice); transplantation on day +2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day -1, 2 or +8 significantly, and on day +4 marginally increased the ED 50 values. Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation. (orig.)

  5. Oral carcinogenesis is not achieved in different carcinogen-treated PAI-1 transgenic and wild-type mouse models.

    Science.gov (United States)

    Avgoustidis, Dimitris; Nisyrios, Themistoklis; Nkenke, Emeka; Lijnen, Roger; Ragos, Vassilis; Perrea, Despina; Donta, Ismini; Vaena, Apostolia; Yapijakis, Christos; Vairaktaris, Eleftherios

    2012-01-01

    In an effort to assess the role of plasminogen activator inhibitor-1 (PAI-1) in oral squamous cancer development and progression, two different carcinogen treatment protocols were conducted. Protocol I included mice from a PAI-1 transgenic (Tg) breed (n=56) and their wild-type (WT) counterparts (n=56), divided into one control group and two main experimental groups, treated with 7,12-dimethylbenz[a]anthracene (DMBA) for 8 and 16 weeks, respectively. Protocol II included the same number and types of animals and groups, which were similarly treated with 4-Nitroquinoline 1-oxide (4-NQO) in drinking water. Two drugs that affect plasma PAI-1 levels, enalapril and pravastatin, were administered to certain subgroups of animals in both protocols. None of the animals developed macroscopically-visible oral cancer lesions. Eleven animals under Protocol I and 52 animals under Protocol II died. Skin lesions were noted only in DMBA-treated animals (n=9). Almost all animals administered with 4-NQO developed alopecia and lost weight, while two of them developed stomach tumours, and one female mouse developed a large ovarian cyst. Transgenic mice may respond differently when used in well-established carcinogen models and oral carcinogenesis is hard to achieve in these rodents.

  6. Expression of p75NGFR, a Proliferative and Basal Cell Marker, in the Buccal Mucosa Epithelium during Re-epithelialization

    International Nuclear Information System (INIS)

    Ishii, Akihiro; Muramatsu, Takashi; Lee, Jong-Min; Higa, Kazunari; Shinozaki, Naoshi; Jung, Han-Sung; Shibahara, Takahiko

    2014-01-01

    We investigated the expression of p75 NGFR , a proliferative and basal cell marker, in the mouse buccal mucosa epithelium during wound healing in order to elucidate the role of epithelial stem cells. Epithelial defects were generated in the epithelium of the buccal mucosa of 6-week-old mice using CO 2 laser irradiation. BrdU was immediately administered to mice following laser irradiation. They were then sacrificed after 1, 3, 7, and 14 days. Paraffin sections were prepared and the irradiated areas were analyzed using immunohistochemistry with anti-p75 NGFR , BrdU, PCNA, and CK14 antibodies. During re-epithelialization, PCNA (–)/p75 NGFR (+) cells extended to the wound, which then closed, whereas PCNA (+)/p75 NGFR (+) cells were not observed at the edge of the wound. In addition, p75 NGFR (–)/CK14 (+), which reflected the presence of post-mitotic differentiating cells, was observed in the supra-basal layers of the extended epithelium. BrdU (+)/p75 NGFR (+), which reflected the presence of epithelial stem cells, was detected sparsely in buccal basal epithelial cells after healing, and disappeared after 7 days. These results suggest that p75 NGFR (+) keratinocytes are localized in the basal layer, which contains oral epithelial stem cells, and retain the ability to proliferate in order to regenerate the buccal mucosal epithelium

  7. An orally active Cannabis extract with high content in cannabidiol attenuates chemical induced intestinal inflammation and hypermotility in the mouse

    Directory of Open Access Journals (Sweden)

    Ester Pagano

    2016-10-01

    Full Text Available Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD, here named CBD BDS for CBD botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS. Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol. The amounts of CBD in the colon, brain and liver after the oral treatments were measured by HPLC coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion or orally (only at one dose. In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  8. Estudo de p27, p21, p16 em epitélio escamoso normal, papiloma escamoso e carcinoma de células escamosas da cavidade oral Comparative analysis of the immunohistochemistry expression of p27, p21WAF/Cip1, and p16INK4a in oral normal epithelium, squamous papilloma and squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ana Beatriz Piazza Queiroz

    2009-12-01

    infections caused by the human papilloma virus(21. The analysis of medical literature shows changes in cell cycle regulatory genes (p27, p21WAF/Cip1 and p16INK4a, but does not define their roles in oral carcinogenesis. Objective: Characterize the immuno-histochemical expression of p27, p21WAF/Cip1 and p16INK4a in oral normal squamous epithelium, oral squamous papilloma and oral squamous cell carcinoma. METHODS: Immuno-histochemical evaluation of p27, p21WAF/Cip1 and p16INK4a in 32 samples of oral normal squamous epithelium, 30 of oral squamous papilloma and 34 of oral squamous cell carcinoma. RESULTS: 97.06% of the oral squamous cell carcinoma group, 33.33% of the squamous papilloma group and 18.75% of the control group showed focal immunopositivity for p27. 100% of both control and oral squamous cell carcinoma groups and 90% of the oral squamous papilloma group showed focal immunopositivity for p21WAF/Cip1. 100% of both control and oral squamous papilloma groups and 94% of the oral squamous cell carcinoma group showed focal immunopositivity for p16INK4a. CONCLUSIONS: The study revealed a statistically significant difference for p27 expression when comparing the control and oral squamous papilloma groups with the oral squamous cell carcinoma group. p21WAF/Cip1 did not prove to be useful to differentiate the groups. p16INK4a showed diffuse immunopositivity in a minority of the oral squamous cell carcinoma cases. The oral squamous papilloma group behaved similarly to the control group as to the three markers.

  9. 4-N-pyridin-2-yl-benzamide nanotubes compatible with mouse stem cell and oral delivery in Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Yadav, Jhillu S; Das, Pragna P; Bag, Indira; Krishnan, Anita; Jagannadh, Bulusu; Mohapatra, Debendra K; Bhadra, Manika Pal [Division of Organic Chemistry-I, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007 (India); Lavanya, Madugula P; Bhadra, Utpal [Functional Genomics and Gene Silencing Group, Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007 (India)

    2010-04-16

    p-aminobenzoic acid (PABA), a structural moiety of many commercial drugs, is self-assembled with linker alkyl side chains to form tubular nanostructures. The tubes exhibited fluorescence either intrinsic or from fluorescent molecules embedded in the wall during self-assembly. Uptake and inter-cellular delivery of the conjugated nanotubes in human cancer cells and in mouse embryonic stem cells were demonstrated by fluorescence imaging and flow cytometry. Biocompatibility, cytotoxicity and clearance were monitored both ex vivo in mouse multipotent embryonic stem cells and in vivo in adult Drosophila. Accumulation of nanotubes had no adverse effects and abnormalities on stem cell morphology and proliferation rate. A distinct distribution of two separate nanotubes in various internal organs of Drosophila interprets that accumulation of nanomaterials might be interdependent on the side chain modifications and physiological settings of cell or tissue types. Unlike carbon nanomaterials, exposure of PABA nanotubes does not produce any hazards including locomotion defects and mortality of adult flies. Despite differential uptake and clearance from multiple live tissues, the use of self-assembled nanotubes can add new dimensions and scope to the development of dual-purpose oral carriers for the fulfilment of many biological promises.

  10. 4-N-pyridin-2-yl-benzamide nanotubes compatible with mouse stem cell and oral delivery in Drosophila

    International Nuclear Information System (INIS)

    Yadav, Jhillu S; Das, Pragna P; Bag, Indira; Krishnan, Anita; Jagannadh, Bulusu; Mohapatra, Debendra K; Bhadra, Manika Pal; Lavanya, Madugula P; Bhadra, Utpal

    2010-01-01

    p-aminobenzoic acid (PABA), a structural moiety of many commercial drugs, is self-assembled with linker alkyl side chains to form tubular nanostructures. The tubes exhibited fluorescence either intrinsic or from fluorescent molecules embedded in the wall during self-assembly. Uptake and inter-cellular delivery of the conjugated nanotubes in human cancer cells and in mouse embryonic stem cells were demonstrated by fluorescence imaging and flow cytometry. Biocompatibility, cytotoxicity and clearance were monitored both ex vivo in mouse multipotent embryonic stem cells and in vivo in adult Drosophila. Accumulation of nanotubes had no adverse effects and abnormalities on stem cell morphology and proliferation rate. A distinct distribution of two separate nanotubes in various internal organs of Drosophila interprets that accumulation of nanomaterials might be interdependent on the side chain modifications and physiological settings of cell or tissue types. Unlike carbon nanomaterials, exposure of PABA nanotubes does not produce any hazards including locomotion defects and mortality of adult flies. Despite differential uptake and clearance from multiple live tissues, the use of self-assembled nanotubes can add new dimensions and scope to the development of dual-purpose oral carriers for the fulfilment of many biological promises.

  11. Mouse single oral dose toxicity test of bupleuri radix aqueous extracts.

    Science.gov (United States)

    Kim, Kyung-Hu; Gam, Cheol-Ou; Choi, Seong-Hun; Ku, Sae-Kwang

    2012-03-01

    The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

  12. Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model.

    Science.gov (United States)

    Perelló, Maria; González-Foruria, Iñaki; Castillo, Paola; Martínez-Florensa, Mario; Lozano, Francisco; Balasch, Juan; Carmona, Francisco

    2017-06-01

    Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm 3 vs 276.75 ± 94.30 mm 3 and 145.33 ± 38.20 mm 3 , respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm 2 ) versus group 2 (1.35 ± 0.43 mm 2 ) and control (2.84 ± 0.60 mm 2 ; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

  13. Bilateral lesions of suprachiasmatic nuclei affect circadian rhythms in [3H]-thymidine incorporation into deoxyribonucleic acid in mouse intestinal tract, mitotic index of corneal epithelium, and serum corticosterone

    International Nuclear Information System (INIS)

    Scheving, L.E.; Tsai, T.H.; Powell, E.W.; Pasley, J.N.; Halberg, F.; Dunn, J.

    1983-01-01

    Investigations into the role of the suprachiasmatic nuclei (SCN) in the coordination of circadian rhythms have presented differing results. Several reports have shown that ablation of the suprachiasmatic nuclei (SCNA) alters the phase and amplitude of rhythms but does not abolish them. The present study investigates the effect of SCNA on the rhythms in cell proliferation in various regions of the intestinal tract as measured by the incorporation of [ 3 H]-thymidine into deoxyribonucleic acid, in the mitotic activity of the corneal epithelium, and in serum corticosterone levels. The study involved mice with verified lesions of the SCN (six to 13 mice per time point) and control groups of both sham-operated and unoperated mice (seven of each per time point). The mice were killed in groups that represented seven time points over a single 24 hr span (3 hr intervals with the 0800 hr sampled both at start and end of the series). The tissues examined were the tongue, esophagus, gastric stomach, and colon for DNA synthesis, the corneal epithelium for mitotic index, and blood serum for corticosterone level. The most consistent result of SCNA was a phase advance in the rhythms in cell proliferation in the tongue, esophagus, gastric stomach, colon, and corneal epithelium. A reduction in rhythm amplitude occurred in the tongue, esophagus, and corneal epithelium; however, there was an amplitude increase for the stomach, colon, and serum corticosterone. The mesor (rhythm-adjusted mean) was increased by SCNA in all tissues except the corneal epithelium. These findings further support the role of the suprachiasmatic nuclear area in the control of rhythms in cell proliferation and corticosterone production, by acting as a ''phase-resetter'' and as a modulator of rhythm amplitude

  14. Antimalarial Pyrido[1,2-a]benzimidazoles: Lead Optimization, Parasite Life Cycle Stage Profile, Mechanistic Evaluation, Killing Kinetics, and in Vivo Oral Efficacy in a Mouse Model.

    Science.gov (United States)

    Singh, Kawaljit; Okombo, John; Brunschwig, Christel; Ndubi, Ferdinand; Barnard, Linley; Wilkinson, Chad; Njogu, Peter M; Njoroge, Mathew; Laing, Lizahn; Machado, Marta; Prudêncio, Miguel; Reader, Janette; Botha, Mariette; Nondaba, Sindisiwe; Birkholtz, Lyn-Marie; Lauterbach, Sonja; Churchyard, Alisje; Coetzer, Theresa L; Burrows, Jeremy N; Yeates, Clive; Denti, Paolo; Wiesner, Lubbe; Egan, Timothy J; Wittlin, Sergio; Chibale, Kelly

    2017-02-23

    Further structure-activity relationship (SAR) studies on the recently identified pyrido[1,2-a]benzimidazole (PBI) antimalarials have led to the identification of potent, metabolically stable compounds with improved in vivo oral efficacy in the P. berghei mouse model and additional activity against parasite liver and gametocyte stages, making them potential candidates for preclinical development. Inhibition of hemozoin formation possibly contributes to the mechanism of action.

  15. DIFFERENTIAL HISTOMORPHOMETRIC CHANGES IN NORMAL AND INFLAMED GINGIVAL EPITHELIUM

    Directory of Open Access Journals (Sweden)

    Tanaskovic Stankovic Sanja

    2016-12-01

    Full Text Available Introduction and aim: In recent decades, many factors such as smoking, unhealthy diet as well as high alcohol intake were marked as risk factors that can lead to increased incidence of malignant alterations, gingivitis, periodontal disease and other oral epithelium pathological changes. Having in mind that in the group of non-malignant and non-dental oral pathology gingivitis and periodontal disease are the most common oral mucosa alterations aim of our research was to investigate histomorphometric characteristics of healthy and altered oral and gingival epithelium. Material and methods: Tissue samples of 24 oral and gingival mucosa specimens were collected. Samples were fixed in 10% buffered paraformaldehyde, routinely processed and embedded in paraffin blocks. From each block sections 5 micrometer thin were made and standard H/E staining as well as immunocytochemical detection of Ki-67 proliferation marker and CD79a lymphocyte marker were performed. Measurements and image analysis was performed with Image Pro Plus software (Media Cybernetics, USA and Axiovision (Ziess, USA. Results: We showed that inflamed gingival epithelium is increasing its thickness in proportion to the severity of adjacent inflammation. Furthermore, mitotic index is rising (up to 132% in the same manner as well as basal lamina length (up to 70% when normal and inflamed gingiva is compared. Architecture of epithelial ridges is changed from straightforward to mesh-like. Conclusion: Assessment of the free gingival epithelium thickness is directly related to the severity of the inflammation process i

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

    Science.gov (United States)

    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...

  17. Novel orally available salvinorin A analog PR-38 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndrome.

    Science.gov (United States)

    Sałaga, M; Polepally, P R; Sobczak, M; Grzywacz, D; Kamysz, W; Sibaev, A; Storr, M; Do Rego, J C; Zjawiony, J K; Fichna, J

    2014-07-01

    The opioid and cannabinoid systems play a crucial role in multiple physiological processes in the central nervous system and in the periphery. Selective opioid as well as cannabinoid (CB) receptor agonists exert a potent inhibitory action on gastrointestinal (GI) motility and pain. In this study, we examined (in vitro and in vivo) whether PR-38 (2-O-cinnamoylsalvinorin B), a novel analog of salvinorin A, can interact with both systems and demonstrate therapeutic effects. We used mouse models of hypermotility, diarrhea, and abdominal pain. We also assessed the influence of PR-38 on the central nervous system by measurement of motoric parameters and exploratory behaviors in mice. Subsequently, we investigated the pharmacokinetics of PR-38 in mouse blood samples after intraperitoneal and oral administration. PR-38 significantly inhibited mouse colonic motility in vitro and in vivo. Administration of PR-38 significantly prolonged the whole GI transit time, and this effect was mediated by µ- and κ-opioid receptors and the CB1 receptor. PR-38 reversed hypermotility and reduced pain in mouse models mimicking functional GI disorders. These data expand our understanding of the interactions between opioid and cannabinoid systems and their functions in the GI tract. We also provide a novel framework for the development of future potential treatments of functional GI disorders. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Fate of the Molar Dental Lamina in the Monophyodont Mouse

    Science.gov (United States)

    Dosedělová, Hana; Dumková, Jana; Lesot, Hervé; Glocová, Kristýna; Kunová, Michaela; Tucker, Abigail S.; Veselá, Iva; Krejčí, Pavel; Tichý, František; Hampl, Aleš; Buchtová, Marcela

    2015-01-01

    The successional dental lamina (SDL) plays an essential role in the development of replacement teeth in diphyodont and polyphyodont animals. A morphologically similar structure, the rudimental successional dental lamina (RSDL), has been described in monophyodont (only one tooth generation) lizards on the lingual side of the developing functional tooth. This rudimentary lamina regresses, which has been proposed to play a role in preventing the formation of future generations of teeth. A similar rudimentary lingual structure has been reported associated with the first molar in the monophyodont mouse, and we show that this structure is common to all murine molars. Intriguingly, a lingual lamina is also observed on the non-replacing molars of other diphyodont mammals (pig and hedgehog), initially appearing very similar to the successional dental lamina on the replacing teeth. We have analyzed the morphological as well as ultrastructural changes that occur during the development and loss of this molar lamina in the mouse, from its initiation at late embryonic stages to its disappearance at postnatal stages. We show that loss appears to be driven by a reduction in cell proliferation, down-regulation of the progenitor marker Sox2, with only a small number of cells undergoing programmed cell death. The lingual lamina was associated with the dental stalk, a short epithelial connection between the tooth germ and the oral epithelium. The dental stalk remained in contact with the oral epithelium throughout tooth development up to eruption when connective tissue and numerous capillaries progressively invaded the dental stalk. The buccal side of the dental stalk underwent keratinisation and became part of the gingival epithelium, while most of the lingual cells underwent programmed cell death and the tissue directly above the erupting tooth was shed into the oral cavity. PMID:26010446

  19. Oral pre-exposure prophylaxis by anti-retrovirals raltegravir and maraviroc protects against HIV-1 vaginal transmission in a humanized mouse model.

    Directory of Open Access Journals (Sweden)

    C Preston Neff

    Full Text Available Sexual HIV-1 transmission by vaginal route is the most predominant mode of viral transmission, resulting in millions of new infections every year. In the absence of an effective vaccine, there is an urgent need to develop other alternative methods of pre-exposure prophylaxis (PrEP. Many novel drugs that are currently approved for clinical use also show great potential to prevent viral sexual transmission when administered systemically. A small animal model that permits rapid preclinical evaluation of potential candidates for their systemic PrEP efficacy will greatly enhance progress in this area of investigation. We have previously shown that RAG-hu humanized mouse model permits HIV-1 mucosal transmission via both vaginal and rectal routes and displays CD4 T cell loss typical to that seen in the human. Thus far systemic PrEP studies have been primarily limited to RT inhibitors exemplified by tenofovir and emtricitabine. In these proof-of-concept studies we evaluated two new classes of clinically approved drugs with different modes of action namely, an integrase inhibitor raltegravir and a CCR5 inhibitor maraviroc as potential systemically administered chemo-prophylactics. Our results showed that oral administration of either of these drugs fully protects against vaginal HIV-1 challenge in the RAG-hu mouse model. Based on these results both these drugs show great promise for further development as orally administered PrEPs.

  20. Effect of syngeneic thymocytes on proliferation of the small intestinal epithelium in mice

    International Nuclear Information System (INIS)

    Shmakov, A.N.; Aparovich, G.G.; Trufakin, V.A.

    1986-01-01

    This paper describes the study of the action of syngeneic thymocytes on proliferation of the epithelium of the mouse small intestine. The mice were injected with 3 H-thymidine in the experiments. Under the experimental conditions presented here, syngeneic thymocytes can reduce the number of DNA-synthesizing cells in the intestinal epithelium, causing narrowing of the zone of proliferation and enlargement of the zone of differentiation of the enterocytes

  1. The drug efficacy and adverse reactions in a mouse model of oral squamous cell carcinoma treated with oxaliplatin at different time points during a day

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    Yang K

    2013-06-01

    Full Text Available Kai Yang,1,2 Ningbo Zhao,1 Dan Zhao,1,2 Dan Chen,1 Yadong Li1 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 2Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, People’s Republic of China Background: Recent studies have shown that the growth and proliferation of cancer cells in vivo exhibit circadian rhythm, and the efficacy and adverse reactions of platinum-based anticancer drugs administered at different times of the day vary significantly on colon cancer. However, since the circadian rhythms of growth and proliferation of various cancer cells often differ, the question of whether the administration of platinum anticancer drugs at different times of the day exerts significantly different efficacy and adverse effects on oral cancers remains to be elucidated. This study has compared the efficacy and adverse effects of oxaliplatin (L-OHP administration at different times during a day on oral squamous cell carcinoma in mice and has analyzed cellular circadian rhythms. Methods: The mouse model for oral squamous cell carcinoma was established in 75 nude mice, housed in a 12 hour light/12 hour dark cycle environment. The mice were randomly divided into five groups; four experimental groups were intravenously injected with L-OHP at four time points within a 24-hour period (4, 10, 16, and 22 hours after lights on [HALO]. The control group was intravenously injected with the same volume of saline. Treatment efficacy and adverse reactions were compared on the seventh day after the injection, at 22 HALO. The existence of circadian rhythms was determined by cosine analysis. Results: Only injections of L-OHP at 16 and 22 HALO significantly prolonged animal survival time. The adverse reactions in mice injected with L-OHP at 16 and 22 HALO were significantly less than those observed in mice administered L-OHP at 4 and 10 HALO

  2. Cranberry extract inhibits in vitro adhesion of F4 and F18+Escherichia coli to pig intestinal epithelium and reduces in vivo excretion of pigs orally challenged with F18+ verotoxigenic E. coli.

    Science.gov (United States)

    Coddens, Annelies; Loos, Michaela; Vanrompay, Daisy; Remon, Jean Paul; Cox, Eric

    2017-04-01

    F4 + E. coli and F18 + E. coli infections are an important threat for pig industry worldwide. Antibiotics are commonly used to treat infected piglets, but the emerging development of resistance against antibiotics raises major concerns. Hence, alternative therapies to prevent pigs from F4 + E. coli and F18 + E. coli infections need to be developed. Since cranberry previously showed anti-adhesive activity against uropathogenic E. coli, we aimed to investigate whether cranberry extract could also inhibit binding of F4 + E. coli and F18 + E. coli to pig intestinal epithelium. Using the in vitro villus adhesion assay, we found that low concentrations of cranberry extract (20μg or 100μg/ml) have strong inhibitory activity on F4 + E. coli (75.3%, S.D.=9.31 or 95.8%, S.D.=2.56, respectively) and F18 + E. coli adherence (100% inhibition). This effect was not due to antimicrobial activity. Moreover, cranberry extract (10mg or 100mg) could also abolish in vivo binding of F4 and F18 fimbriae to the pig intestinal epithelium in ligated loop experiments. Finally, two challenge experiments with F18 + E. coli were performed to address the efficacy of in-feed or water supplemented cranberry extract. No effect could be observed in piglets that received cranberry extract only in feed (1g/kg or 10g/kg). However, supplementation of feed (10g/kg) and drinking water (1g/L) significantly decreased excretion and diarrhea. The decreased infection resulted in a decreased serum antibody response indicating reduced exposure to F18 + E. coli. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Anti-podocalyxin antibody exerts antitumor effects via antibody-dependent cellular cytotoxicity in mouse xenograft models of oral squamous cell carcinoma.

    Science.gov (United States)

    Itai, Shunsuke; Ohishi, Tomokazu; Kaneko, Mika K; Yamada, Shinji; Abe, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Ohba, Shun-Ichi; Nishioka, Yasuhiko; Kawada, Manabu; Harada, Hiroyuki; Kato, Yukinari

    2018-04-27

    Podocalyxin (PODXL) overexpression is associated with progression, metastasis, and poor outcomes in cancers. We recently produced the novel anti-PODXL monoclonal antibody (mAb) PcMab-47 (IgG 1 , kappa). Herein, we engineered PcMab-47 into 47-mG 2a , a mouse IgG 2a -type mAb, to add antibody-dependent cellular cytotoxicity (ADCC). We further developed 47-mG 2a -f, a core fucose-deficient type of 47-mG 2a to augment its ADCC. Immunohistochemical analysis of oral cancer tissues using PcMab-47 and 47-mG 2a revealed that the latter stained oral squamous cell carcinoma (OSCC) cells in a cytoplasmic pattern at a much lower concentration. PcMab-47 and 47-mG 2a detected PODXL in 163/201 (81.1%) and in 197/201 (98.0%) OSCC samples, respectively. 47-mG 2a -f also detected PODXL in OSCCs at a similar frequency as 47-mG 2a . In vitro analysis revealed that both 47-mG 2a and 47-mG 2a -f exhibited strong complement-dependent cytotoxicity (CDC) against CHO/hPODXL cells. In contrast, 47-mG 2a -f exhibited much stronger ADCC than 47-mG 2a against OSCC cells, indicating that ADCC and CDC of those anti-PODXL mAbs depend on target cells. In vivo analysis revealed that both 47-mG 2a and 47-mG 2a -f exerted antitumor activity in CHO/hPODXL xenograft models at a dose of 100 μg or 500 μg/mouse/week administered twice. 47-mG 2a -f, but not 47-mG 2a , exerted antitumor activity in SAS and HSC-2 xenograft models at a dose of 100 μg/mouse/week administered three times. Although both 47-mG 2a and 47-mG 2a -f exerted antitumor activity in HSC-2 xenograft models at a dose of 500 μg/mouse/week administered twice, 47-mG 2a -f also showed higher antitumor activity than 47-mG 2a . These results suggested that a core fucose-deficient anti-PODXL mAb could be useful for antibody-based therapy against PODXL-expressing OSCCs.

  4. Efficacy of an oral and tropically stable lipid-based formulation of Amphotericin B (iCo-010) in an experimental mouse model of systemic candidiasis.

    Science.gov (United States)

    Ibrahim, Fady; Sivak, Olena; Wasan, Ellen K; Bartlett, Karen; Wasan, Kishor M

    2013-10-29

    An oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of systemic candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of systemic candidiasis in mice. Mice were infected with 0.6 to 1×108 CFUs of Candida albicans ATCC 18804 strain by tail vein injection and were left for three days to develop the infection after which time treatment was initiated. The infected animals were assigned to the following treatment groups: no treatment (control) or iCo-010 at 5, 10 and 20 mg/kg administered by oral gavage once daily (QD) for 5 consecutive days. The animals were sacrificed 7 days after the last dose and the concentration of AmB and the fungal burden were assessed within the liver, kidneys, heart, lungs, spleen and brain. Although the infection was relatively low (~ 60-100 CFUs/ 1 ml tissue homogenate) in the liver, lungs and heart, the infection level was very high (70 000 CFUs / 1 ml tissue homogenate) in the kidney tissues for the control group. The highest concentrations of AmB were recovered in the kidneys and the spleen. The fungal burden in the tissues was lowered by 69-96% in the treatment groups when compared to the control group. Oral iCo-010 is an effective treatment of systemic candidiasis in the mouse model.

  5. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

    Science.gov (United States)

    Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A; Borrelli, Francesca

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for "CBD botanical drug substance," on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  6. Use of dexpanthenol and aloe vera to influence the irradiation response of the oral mucous membrane (mouse)

    International Nuclear Information System (INIS)

    Schlichting, S.; Spekl, K.; Doerr, W.

    2004-01-01

    In summarising the outcome of the present study it can be said spraying the agent on the oral mucous membrane once a day had an effect on the incidence of mucous membrane ulceration in the case of both placebo and dexpanthenol treatment. However, there was no significant difference between placebo and dexpanthenol treatment, the only finding being a slight prolongation of latency time through aloe vera. These experimental findings give good reason to critically reconsider the clinical use of dexpanthenol as a supportive treatment for the prevention of radiogenic mucositis enoralis following irradiation of tumours in the head and neck region. However thorough oral lavage is an effective means of moderating the irradiation response of the oral mucous membrane [de

  7. Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds.

    Science.gov (United States)

    Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M

    2012-08-15

    The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from "local epithelium", in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Improvement of Antioxidant Defences and Mood Status by Oral GABA Tea Administration in a Mouse Model of Post-Stroke Depression

    Directory of Open Access Journals (Sweden)

    Maria Daglia

    2017-04-01

    Full Text Available Green GABA (GGABA and Oolong GABA (OGABA teas are relatively new varieties of tea, whose chemical composition and functional properties are largely under-studied, despite their promising health capacities. Post stroke depression (PSD is a complication of stroke with high clinical relevance, yielding increasing mortality and morbidity rates, and a lower response to common therapies and rehabilitation. Methods: Two chemically characterized commercial samples of GGABA and OGABA were investigated for effects on mood following oral administration using a mouse model of PSD, through common validated tests including the Despair Swimming Test and Tail Suspension Test. Moreover, the antioxidant activity of GGABA and OGABA was evaluated by determining the levels of lipid peroxidation products and the activity of antioxidant enzymes in the mouse brain in vivo. Results: GGABA and OGABA attenuated depressed mood by influencing behavioral parameters linked to depression. GGABA was more active than OGABA in this study, and this effect may be likely due to a higher content of polyphenolic substances and amino acids in GGABA compared to OGABA. GGABA also exerted a greater antioxidant activity. Conclusions: Our data suggests that GABA tea is a promising candidate that can be used as an adjuvant in the management of PSD.

  9. An orally active Cannabis extract with high content in cannabidiol attenuates chemical induced intestinal inflammation and hypermotility in the mouse

    OpenAIRE

    Ester Pagano; Raffaele Capasso; Fabiana Piscitelli; Barbara Romano; Olga Alessandra Parisi; Stefania Finizio; Anna Lauritano; Vincenzo Di Marzo; Angelo A Izzo; Francesca Borrelli

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for CBD botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was ev...

  10. Receptor-mediated oral delivery of a bioencapsulated green fluorescent protein expressed in transgenic chloroplasts into the mouse circulatory system.

    Science.gov (United States)

    Limaye, Arati; Koya, Vijay; Samsam, Mohtashem; Daniell, Henry

    2006-05-01

    Oral delivery of biopharmaceutical proteins expressed in plant cells should reduce their cost of production, purification, processing, cold storage, transportation, and delivery. However, poor intestinal absorption of intact proteins is a major challenge. To overcome this limitation, we investigate here the concept of receptor-mediated oral delivery of chloroplast-expressed foreign proteins. Therefore, the transmucosal carrier cholera toxin B-subunit and green fluorescent protein (CTB-GFP), separated by a furin cleavage site, was expressed via the tobacco chloroplast genome. Polymerase chain reaction (PCR) and Southern blot analyses confirmed site-specific transgene integration and homoplasmy. Immunoblot analysis and ELISA confirmed expression of monomeric and pentameric forms of CTB-GFP, up to 21.3% of total soluble proteins. An in vitro furin cleavage assay confirmed integrity of the engineered furin cleavage site, and a GM1 binding assay confirmed the functionality of CTB-GFP pentamers. Following oral administration of CTB-GFP expressing leaf material to mice, GFP was observed in the mice intestinal mucosa, liver, and spleen in fluorescence and immunohistochemical studies, while CTB remained in the intestinal cell. This report of receptor-mediated oral delivery of a foreign protein into the circulatory system opens the door for low-cost production and delivery of human therapeutic proteins.

  11. Role of tumor necrosis factor-α and interleukin-1β in anorexia induction following oral exposure to the trichothecene deoxynivalenol (vomitoxin) in the mouse.

    Science.gov (United States)

    Wu, Wenda; Zhang, Haibin

    2014-01-01

    The trichothecene deoxynivalenol (DON), a foodborne mycotoxin found in grain-based foods, has been associated with human and animal food poisoning. Although induction of anorexia has been described as a hallmark of DON-induced toxicity in many animal species, the mechanistic basis for this adverse effect is not fully understood. The purpose of this research was to determine the role of two proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in DON-induced anorexia. In a nocturnal mouse food consumption model, DON-induced anorectic response occurred at 1 hr and lasted up to 6 hr. Similar anorectic effects were observed following acute administration of exogenous TNF-α and IL-1β. Oral exposure to DON at 5 mg/kg bw stimulated splenic and hepatic mRNA and plasma protein elevations of TNF-α and IL-1β that corresponded to anorexia induction. Pretreatment with the TNF-α receptor (TNFR) antagonist R-7050 dose-dependently attenuated both TNF-α- and DON-induced anorexia. While, the type 1 IL-1 receptor (IL-1R1) antagonist IL-1RA dose-dependently attenuated both IL-1β- and DON-induced anorexia. Taken together, the results suggest that both TNF-α and IL-1β play contributory role in anorexia induction following oral exposure to DON.

  12. Zein-Based Nanoparticles Improve the Oral Bioavailability of Resveratrol and Its Anti-inflammatory Effects in a Mouse Model of Endotoxic Shock.

    Science.gov (United States)

    Penalva, Rebeca; Esparza, Irene; Larraneta, Eneko; González-Navarro, Carlos J; Gamazo, Carlos; Irache, Juan M

    2015-06-17

    Resveratrol offers pleiotropic health benefits including a reported ability to inhibit lipopolysaccharide (LPS)-induced cytokine production. The aim of this work was to prepare, characterize, and evaluate a resveratrol nanoparticulate formulation based on zein. For this purpose, the oral bioavailability of the encapsulated polyphenol as well as its anti-inflammatory effects in a mouse model of endotoxic shock was studied. The resveratrol-loaded nanoparticles displayed a mean size of 307 ± 3 nm, with a negative zeta potential (-51.1 ± 1.55 mV), and a polyphenol loading of 80.2 ± 3.26 μg/mg. In vitro, the release of resveratrol from the nanoparticles was found to be pH independent and adjusted well to the Peppas-Sahlin kinetic model, suggesting a mechanism based on the combination of diffusion and erosion of the nanoparticle matrix. Pharmacokinetic studies demonstrated that zein-based nanoparticles provided high and prolonged plasma levels of the polyphenol for at least 48 h. The oral bioavailability of resveratrol when administered in these nanoparticles increased up to 50% (19.2-fold higher than for the control solution of the polyphenol). Furthermore, nanoparticles administered daily for 7 days at 15 mg/kg were able to diminish the endotoxic symptoms induced in mice by the intraperitoneal administration of LPS (i.e., hypothermia, piloerection, and stillness). In addition, serum tumor necrosis factor-alpha (TNF-α) levels were slightly lower (approximately 15%) than those observed in the control.

  13. Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model

    Directory of Open Access Journals (Sweden)

    Yoshiharu Okamoto

    2012-10-01

    Full Text Available We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5–40 kDa, intermediate-molecular-weight fucoidan (IMWF: 110–138 kDa and high-molecular-weight fucoidan (HMWF: 300–330 kDa. The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet. The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food.

  14. Direct comparison of the efficacy and safety of oral treatments with oleylphosphocholine (OlPC and miltefosine in a mouse model of L. major cutaneous leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Anny Fortin

    2014-09-01

    Full Text Available Cutaneous leishmaniasis (CL represents a range of skin diseases caused by infection with Leishmania parasites and associated with tissue inflammation and skin ulceration. CL is clinically widespread in both the Old and New World but lacks treatments that are well tolerated, effective and inexpensive. Oleylphosphocholine (OlPC is a new orally bioavailable drug of the alkylphosphocholine family with potent antileishmanial activity against a broad range of Leishmania species/strains.The potential of OlPC against Old World CL was evaluated in a mouse model of Leishmania (L. major infection in BALB/c mice. Initial dose-response experiments showed that an oral daily dose of 40 mg/kg of OlPC was needed to impact time to cure and lesion sizes. This dose was then used to directly compare the efficacy of OlPC to the efficacy of the antileishmanial drugs miltefosine (40 mg/kg/day, fluconazole (160 mg/kg/day and amphotericin B (25 mg/kg/day. OlPC, miltefosine and fluconazole were given orally for 21 days while amphotericin B was administered intraperitoneally for 10 days. Ulcer sizes and animal weights were followed up on a weekly basis and parasitemia was determined by means of a real-time in vivo imaging system which detects luminescence emitted from luciferase-expressing infecting L. major parasites. Amphotericin B and OlPC showed excellent efficacy against L. major lesions in terms of reduction of parasitic loads and by inducing complete healing of established lesions. In contrast, treatment with miltefosine did not significantly affect parasitemia and lesion sizes, while fluconazole was completely ineffective at the dose regimen tested.Given the data showing the outstanding efficacy and tolerability of OlPC, our results suggest that OlPC is a promising new drug candidate to improve and simplify current clinical management of L. major CL.

  15. Expression of verocytotoxic Escherichia coli antigens in tobacco seeds and evaluation of gut immunity after oral administration in mouse model

    OpenAIRE

    Rossi, Luciana; Di Giancamillo, Alessia; Reggi, Serena; Domeneghini, Cinzia; Baldi, Antonella; Sala, Vittorio; Dell'Orto, Vittorio; Coddens, Annelies; Cox, Eric; Fogher, Corrado

    2013-01-01

    Verocytotoxic Escherichia (E.) coli strains are responsible for swine oedema disease, which is an enterotoxaemia that causes economic losses in the pig industry. The production of a vaccine for oral administration in transgenic seeds could be an efficient system to stimulate local immunity. This study was conducted to transform tobacco plants for the seed-specific expression of antigenic proteins from a porcine verocytotoxic E. coli strain. Parameters related to an immunological response and ...

  16. Distinct transmissibility features of TSE sources derived from ruminant prion diseases by the oral route in a transgenic mouse model (TgOvPrP4 overexpressing the ovine prion protein.

    Directory of Open Access Journals (Sweden)

    Jean-Noël Arsac

    Full Text Available Transmissible spongiform encephalopathies (TSEs are a group of fatal neurodegenerative diseases associated with a misfolded form of host-encoded prion protein (PrP. Some of them, such as classical bovine spongiform encephalopathy in cattle (BSE, transmissible mink encephalopathy (TME, kuru and variant Creutzfeldt-Jakob disease in humans, are acquired by the oral route exposure to infected tissues. We investigated the possible transmission by the oral route of a panel of strains derived from ruminant prion diseases in a transgenic mouse model (TgOvPrP4 overexpressing the ovine prion protein (A136R154Q171 under the control of the neuron-specific enolase promoter. Sources derived from Nor98, CH1641 or 87V scrapie sources, as well as sources derived from L-type BSE or cattle-passaged TME, failed to transmit by the oral route, whereas those derived from classical BSE and classical scrapie were successfully transmitted. Apart from a possible effect of passage history of the TSE agent in the inocula, this implied the occurrence of subtle molecular changes in the protease-resistant prion protein (PrPres following oral transmission that can raises concerns about our ability to correctly identify sheep that might be orally infected by the BSE agent in the field. Our results provide proof of principle that transgenic mouse models can be used to examine the transmissibility of TSE agents by the oral route, providing novel insights regarding the pathogenesis of prion diseases.

  17. Presence of orally administered rice bran oil γ-oryzanol in its intact form in mouse plasma.

    Science.gov (United States)

    Kobayashi, Eri; Ito, Junya; Kato, Shunji; Sawada, Kazue; Matsuki, Midori; Hashimoto, Hiroyuki; Miyazawa, Teruo; Nakagawa, Kiyotaka

    2016-12-07

    Although the beneficial effects (e.g., lipid-lowering activity) of γ-oryzanol (OZ), a mixture of ferulic acid esters of plant sterols and triterpene alcohols, have been extensively investigated, few studies have evaluated the absorption and metabolism of OZ. Moreover, it is unclear whether OZ, once ingested, is directly absorbed by the intestine into the bloodstream at a sufficient level to exhibit activity. Here, we prepared OZ concentrate from purified rice bran oil (Rice Oil OZ), determined the concentration of OZ in the preparation (cycloartenyl ferulate equivalent concentration; 52.2%), and then carried out chromatography-mass spectrometry analysis of plasma samples from mice after oral administration of Rice Oil OZ. The OZ concentrations of plasma from the control (vehicle-treated) mice were low (trace levels); however, at 5 h after a single oral administration of the Rice Oil OZ (600 mg per kg body weight), the levels significantly increased, reaching 17.6 ng mL -1 for cycloartenyl ferulate, 28.2 ng mL -1 for 24-methylenecycloartanyl ferulate isomers, 15.6 ng mL -1 for campesteryl ferulate, and 5.1 ng mL -1 for β-sitosteryl ferulate, respectively, expressed in equivalence of cycloartenyl ferulate in plasma. These results provided the first mass spectrometric evidence suggesting that a portion of orally administered OZ is directly absorbed by the intestine and is present in the intact form in plasma. The presence of a significant amount of OZ in its intact form in plasma may explain the beneficial effects of OZ in vivo.

  18. Histomorphology of the corneal epithelium of anastrozole treated rabbits

    International Nuclear Information System (INIS)

    Khalil, A.; Qamar, K.; Butt, S.A.

    2013-01-01

    Objective: To evaluate the effects of prolonged use of anastrozole as an endocrine treatment of breast cancer on the corneal epithelium in an animal model. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Anatomy, Army Medical College, Rawalpindi in collaboration with National Institute of Health, Islamabad, six months from Jun 2012 to Nov 2012. Material and Methods: Twenty adult female NewZealand white rabbits were taken. Ten rabbits were placed in control group taking normal diet and 10 were given anastrozole orally in the normal dose of 1 mg/day (0.02 mg/kg/day). After the completion of the study, corneas were removed and grossly examined. The specimen were fixed and slides prepared for histomorphological examination. The epithelium in each slide was examined for any deposits, edema or increase in stratification and the height of the epithelium was measured for each eye. The results were compared between the groups for statistical significance. Results: The epithelium had normal shape with no areas of any deposits, edema or ulceration. The mean epithelial height in the control group was 21.25 +- 4.29 mu m and 21.00 +- 4.28 mu m in the right corneas and left corneas, respectively. The mean epithelial height taken from the experimental group was 20.50 +- 4.97 mu m and 21.00 +- 4.28 mu m in right sided and left sided corneas, respectively. The p value was calculated to be 0.722 and 1.00 for the right and left corneas, respectively and no statistical significance was found in between the two groups. Conclusion: Long term administration of anastrozole has no effect on the histological morphology of the corneal epithelium. (author)

  19. Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

    Science.gov (United States)

    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

  20. Preventive effect of oral administration of 6-(methylsulfinyl)hexyl isothiocyanate derived from wasabi (Wasabia japonica Matsum) against pulmonary metastasis of B16-BL6 mouse melanoma cells.

    Science.gov (United States)

    Fuke, Yoko; Shinoda, Shoko; Nagata, Ikuko; Sawaki, Saeko; Murata, Mituyoshi; Ryoyama, Kazuo; Koizumi, Keiichi; Saiki, Ikuo; Nomura, Takahiro

    2006-01-01

    Effect of oral administration of 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) or a 6-MITC-containing T-wasabi fraction from wasabi root (Wasabia japonica Matsum) to inhibit the macroscopic pulmonary metastasis was studied with a murine B16-BL6 melanoma model. Two administration routes, subcutaneous or intravenous, and two administration times, prior to or concomitant with tumor inoculation, of 6-MITC or T-wasabi against the metastatic foci formation in C57BL/6J mouse lungs were compared. The number of metastasized foci per lung in either subcutaneous or intravenous injection was significantly reduced by intake of 6-MITC or a T-wasabi fraction. The maximum reduction by a T-wasabi fraction reached to 82%. Fifty-six percent of foci formation was inhibited by a 2 week-prior administration of 6-MITC (200 microM), whereas only 27% inhibition was obtained by a concomitant administration with tumor inoculation. Neither 6-MITC nor T-wasabi at tested concentrations showed any toxic effects. Together with our previous results, a component of the Japanese pungent spice, wasabi appears to inhibit not only tumor cell growth but also tumor metastasis. Therefore, 6-MITC from wasabi is apparently a useful dietary candidate for controlling tumor progression.

  1. Buccal Epithelium in treating Ocular Surface Disorders

    Directory of Open Access Journals (Sweden)

    Srinivas KR

    2008-11-01

    Full Text Available Background - Ocular surface disorders due to limbal stem cell deficiency are an important cause of ocular morbidity and visual loss. Although autologous limbal stem cell transplants have helped in the management of unilateral disease, allografts in those with bilateral disease often fail due to immunological reasons. The use of autologous buccal epithelium cultivated on amniotic membrane has been described as a useful approach in the management of this condition. It is the purpose of this study to explore the feasibility of using a novel thermo-gelatin polymer (TGP as a substrate to culture these cells, and to characterize them using RNA extraction and RT-PCR. Methods - Oral cheek mucosal biopsies were obtained from 5 adult patients undergoing Modified Osteo-Odonto Keratoprosthesis surgery. The specimens were transported to the laboratory in transport medium. The cells were released using enzymatic digestion and seeded in both convention culture medium and TGP. The resulting cellular growth was characterized using RNA extraction and RT-PCR. Results - Cells could be cultured from 4 of the 5 specimens. In one specimen, contamination occurred and this was discarded. In the other specimens, the cheek epithelial cells could be cultured in both the conventional culture medium and TGP, with equal ease. RT-PCR revealed the presence of K3, a marker for epithelial cells, and GAPDH indicating the presence of some adipose tissue as well. Conclusions - It is possible to culture autologous cheek mucosal epithelial cells using TGP, a synthetic scaffold, without the need for other biological substrates. Since the specimens are obtained from the oral cavity, stringent asepsis is required. Further studies are required for histopathological characterization of the cultured cells and to create a model for delivery onto the ocular surface of eyes with bilateral surface disease due to limbal stem cell deficiency.

  2. Integration of Oncogenes via Sleeping Beauty as a Mouse Model of HPV16+ Oral Tumors and Immunologic Control.

    Science.gov (United States)

    Lin, Yi-Hsin; Yang, Ming-Chieh; Tseng, Ssu-Hsueh; Jiang, Rosie; Yang, Andrew; Farmer, Emily; Peng, Shiwen; Henkle, Talia; Chang, Yung-Nien; Hung, Chien-Fu; Wu, T-C

    2018-01-23

    Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-associated buccal tumors. However, they fail to address precancerous phases of disease progression and display tumor microenvironments distinct from those observed in patients. Previously, K14-E6/E7 transgenic mouse models have been used to generate spontaneous tumors. However, the rate of tumor formation is inconsistent, and the host often develops immune tolerance to the viral oncoproteins. We developed a preclinical, spontaneous, HPV16 + buccal tumor model using submucosal injection of oncogenic plasmids expressing HPV16-E6/E7, NRas G12V , luciferase, and sleeping beauty (SB) transposase, followed by electroporation in the buccal mucosa. We evaluated responses to immunization with a pNGVL4a-CRT/E7(detox) therapeutic HPV DNA vaccine and tumor cell migration to distant locations. Mice transfected with plasmids encoding HPV16-E6/E7, NRas G12V , luciferase, and SB transposase developed tumors within 3 weeks. We also found transient anti-CD3 administration is required to generate tumors in immunocompetent mice. Bioluminescence signals from luciferase correlated strongly with tumor growth, and tumors expressed HPV16-associated markers. We showed that pNGVL4a-CRT/E7(detox) administration resulted in antitumor immunity in tumor-bearing mice. Lastly, we demonstrated that the generated tumor could migrate to tumor-draining lymph nodes. Our model provides an efficient method to induce spontaneous HPV + tumor formation, which can be used to identify effective therapeutic interventions, analyze tumor migration, and conduct tumor biology research. Cancer Immunol Res; 6(3); 1-15. ©2018 AACR. ©2018 American Association for Cancer Research.

  3. The defence architecture of the superficial cells of the oral mucosa

    NARCIS (Netherlands)

    Asikainen, P.; Ruotsalainen, T.J.; Mikkonen, J.J.W.; Koistinen, A.; ten Bruggenkate, C.M.; Kullaa, A.M.

    2012-01-01

    The oral epithelium together with the saliva and its components forms a complex structure which is the first line of defence in the oral cavity. The surface of superficial cells of the oral epithelium contains ridge-like folds, microplicae (MPL), which are typical of the surfaces of areas covered

  4. Red wine and green tea reduce H pylori- or VacA-induced gastritis in a mouse model

    Science.gov (United States)

    Ruggiero, Paolo; Rossi, Giacomo; Tombola, Francesco; Pancotto, Laura; Lauretti, Laura; Del Giudice, Giuseppe; Zoratti, Mario

    2007-01-01

    AIM: To investigate whether red wine and green tea could exert anti-H pylori or anti-VacA activity in vivo in a mouse model of experimental infection. METHODS: Ethanol-free red wine and green tea concentrates were administered orally as a mixture of the two beverages to H pylori infected mice, or separately to VacA-treated mice. Gastric colonization and gastric inflammation were quantified by microbiological, histopathological, and immunohistochemical analyses. RESULTS: In H pylori-infected mice, the red wine and green tea mixture significantly prevented gastritis and limited the localization of bacteria and VacA to the surface of the gastric epithelium. Similarly, both beverages significantly prevented gastric epithelium damage in VacA-treated mice; green tea, but not red wine, also altered the VacA localization in the gastric epithelium. CONCLUSION: Red wine and green tea are able to prevent H pylori-induced gastric epithelium damage, possibly involving VacA inhibition. This observation supports the possible relevance of diet on the pathological outcome of H pylori infection. PMID:17230601

  5. [Characterization of stem cells derived from the neonatal auditory sensory epithelium].

    Science.gov (United States)

    Diensthuber, M; Heller, S

    2010-11-01

    In contrast to regenerating hair cell-bearing organs of nonmammalian vertebrates the adult mammalian organ of Corti appears to have lost its ability to maintain stem cells. The result is a lack of regenerative ability and irreversible hearing loss following auditory hair cell death. Unexpectedly, the neonatal auditory sensory epithelium has recently been shown to harbor cells with stem cell features. The origin of these cells within the cochlea's sensory epithelium is unknown. We applied a modified neurosphere assay to identify stem cells within distinct subregions of the neonatal mouse auditory sensory epithelium. Sphere cells were characterized by multiple markers and morphologic techniques. Our data reveal that both the greater and the lesser epithelial ridge contribute to the sphere-forming stem cell population derived from the auditory sensory epithelium. These self-renewing sphere cells express a variety of markers for neural and otic progenitor cells and mature inner ear cell types. Stem cells can be isolated from specific regions of the auditory sensory epithelium. The distinct features of these cells imply a potential application in the development of a cell replacement therapy to regenerate the damaged sensory epithelium.

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

    Science.gov (United States)

    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...

  7. Expression of C4.4A, a structural uPAR homolog, reflects squamous epithelial differentiation in the adult mouse and during embryogenesis

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Jacobsen, Benedikte; Hald, Andreas

    2011-01-01

    by a comprehensive immunohistochemical mapping. This task was accomplished by staining paraffin-embedded tissues with a specific rabbit polyclonal anti-C4.4A antibody. In the adult mouse, C4.4A was predominantly expressed in the suprabasal layers of the squamous epithelia of the oral cavity, esophagus, non...... expression first appears in the developing squamous epithelium at embryonic day 13.5. This anatomical location of C4.4A is thus concordant with a possible functional role in early differentiation of stratified squamous epithelia....

  8. Topographical organization of TRPV1-immunoreactive epithelium and CGRP-immunoreactive nerve terminals in rodent tongue

    Directory of Open Access Journals (Sweden)

    M. Kawashima

    2012-05-01

    Full Text Available Transient receptor potential vanilloid subfamily member 1 (TRPV1 is activated by capsaicin, acid, and heat and mediates pain through peripheral nerves. In the tongue, TRPV1 expression has been reported also in the epithelium. This indicates a possibility that sensation is first received by the epithelium. However, how nerves receive sensations from the epithelium remains unclear. To clarify the anatomical basis of this interaction, we performed immunohistochemical studies in the rodent tongue to detect TRPV1 and calcitonin gene-related peptide (CGRP, a neural marker. Strong expression of TRPV1 in the epithelium was observed and was restricted to the apex of the tongue. Double immunohistochemical staining revealed that CGRP-expressing nerve terminals were in close apposition to the strongly TRPV1-expressing epithelium of fungiform papilla in the apex of rodent tongues. These results suggest that the TRPV1-expressing epithelium monitors the oral environment and acquired information may then be conducted to the adjacent CGRPexpressing terminals.

  9. Reinstatement of "germinal epithelium" of the ovary

    Directory of Open Access Journals (Sweden)

    Nishida Naoyo

    2006-08-01

    Full Text Available Abstract Background The existing dogma that the former term ovarian "germinal epithelium" resulted from a mistaken belief that it could give rise to new germ cells is now strongly challenged. Discussion Two years ago, a research group of the University of Tennessee led by Antonin Bukovsky successfully demonstrated the oogenic process from the human ovarian covering epithelium now commonly called the ovarian surface epithelium. They showed the new oocyte with zona pellucida and granulosa cells, both originated from the surface epithelium arising from mesenchymal cells in the tunica albuginea, and stressed that the human ovary could form primary follicles throughout the reproductive period. This gives a big impact not only to the field of reproductive medicine, but also to the oncologic area. The surface epithelium is regarded as the major source of ovarian cancers, and most of the neoplasms exhibit the histology resembling müllerian epithelia. Since the differentiating capability of the surface epithelium has now expanded, the histologic range of the neoplasms in this category may extend to include both germ cell tumors and sex cord-stromal cell tumors. Summary Since the oogenic capability of ovarian surface cells has been proven, it is now believed that the oocytes can originate from them. The term "germinal epithelium", hence, might reasonably be reinstated.

  10. Metabolic activation of carbon tetrachloride by the cervico-vaginal epithelium in rodents

    International Nuclear Information System (INIS)

    Brittebo, E.B.; Brandt, I.

    1989-01-01

    The metabolism and binding of 14 C-labelled carbon tetrachloride (CCl 4 ) in the genital tract of female adult or juvenile NMRI-mice and Sprague-Dawly rats (mainly in the pro-oestrous/oestrous stage) and an adult New Zealand rabbit were studied. A marked irreversible binding of radioactivity in the squamous cervico-vaginal epithelium of mice given intravenous injections of 14 C-CCl 4 was revealed by autoradiography of solvent-extracted tissue. The localization of binding in the mouse genital tract incubated with 14 C-CCl 4 under air was similar to that observed in vivo. Bound radioactivity was also present in the cylindrical epithelium of the rabbit vagina incubated with 14 C-CCl 4 in vitro. For a comparison, no preferential binding of radiolabelled diethylstilbestrol or ethinylestradiol was observed in the mouse cervico-vaginal epithelium. The level of irreversible binding to PMSG-primed (pregnant mare's serum gonadotrophin) vaginal epithelial 100 x g supernatants of mice and rats incubated with 14 C-CCl 4 under air was low. Addition of the reducing agent dithionite to the incubations increased the binding in the vaginal epithelium 20-fold. In juvenile mice and rats injected with 14 C-CCl 4 , the levels of metabolites in the epithelium were low, whereas PMSG-primed juvenile rats contained a higher level of metabolites. The results show that the cervico-vaginal epithelium can metabolically activate CCl 4 to reactive metabolites and suggest that the metabolism is under endocrine control. (author)

  11. Oral candidosis in relation to oral immunity.

    Science.gov (United States)

    Feller, L; Khammissa, R A G; Chandran, R; Altini, M; Lemmer, J

    2014-09-01

    Symptomatic oral infection with Candida albicans is characterized by invasion of the oral epithelium by virulent hyphae that cause tissue damage releasing the inflammatory mediators that initiate and sustain local inflammation. Candida albicans triggers pattern-recognition receptors of keratinocytes, macrophages, monocytes and dendritic cells, stimulating the production of IL-1β, IL-6 and IL-23. These cytokines induce the differentiation of Th17 cells and the generation of IL-17- and/or IL-22-mediated antifungal protective immuno-inflammatory responses in infected mucosa. Some immune cells including NKT cells, γδ T cells and lymphoid cells that are innate to the oral mucosa have the capacity to produce large quantities of IL-17 in response to C. albicans, sufficient to mediate effective protective immunity against C. albicans. On the other hand, molecular structures of commensal C. albicans blastoconidia, although detected by pattern-recognition receptors, are avirulent, do not invade the oral epithelium, do not elicit inflammatory responses in a healthy host, but induce regulatory immune responses that maintain tissue tolerance to the commensal fungi. The type, specificity and sensitivity of the protective immune response towards C. albicans is determined by the outcome of the integrated interactions between the intracellular signalling pathways of specific combinations of activated pattern-recognition receptors (TLR2, TLR4, Dectin-1 and Dectin-2). IL-17-mediated protective immune response is essential for oral mucosal immunity to C. albicans infection. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium.

    Directory of Open Access Journals (Sweden)

    Nicholas Lahar

    Full Text Available The intestinal crypt-niche interaction is thought to be essential to the function, maintenance, and proliferation of progenitor stem cells found at the bases of intestinal crypts. These stem cells are constantly renewing the intestinal epithelium by sending differentiated cells from the base of the crypts of Lieberkühn to the villus tips where they slough off into the intestinal lumen. The intestinal niche consists of various cell types, extracellular matrix, and growth factors and surrounds the intestinal progenitor cells. There have recently been advances in the understanding of the interactions that regulate the behavior of the intestinal epithelium and there is great interest in methods for isolating and expanding viable intestinal epithelium. However, there is no method to maintain primary human small intestinal epithelium in culture over a prolonged period of time. Similarly no method has been published that describes isolation and support of human intestinal epithelium in an in vivo model. We describe a technique to isolate and maintain human small intestinal epithelium in vitro from surgical specimens. We also describe a novel method to maintain human intestinal epithelium subcutaneously in a mouse model for a prolonged period of time. Our methods require various growth factors and the intimate interaction between intestinal sub-epithelial myofibroblasts (ISEMFs and the intestinal epithelial cells to support the epithelial in vitro and in vivo growth. Absence of these myofibroblasts precluded successful maintenance of epithelial cell formation and proliferation beyond just a few days, even in the presence of supportive growth factors. We believe that the methods described here can be used to explore the molecular basis of human intestinal stem cell support, maintenance, and growth.

  13. Binding of the aliphatic halides 1,2-dibromoethane and chloroform in the rodent vaginal epithelium

    International Nuclear Information System (INIS)

    Brittebo, E.B.; Brandt, I.; Kowalski, B.

    1987-01-01

    Whole-body and light microscopic autoradiography were used to study the binding of 1,2-dibromo( 14 C)ethane ( 14 C-DBE) and 14 C-chloroform ( 14 C-CF) in the mouse and rat vaginal epithelium in vitro and in vivo. In pregnant mice, mice pretreated with pregnant mare's serum gonadotropin (PMSG) or ovariectomized mice primed with medroxyprogesterone, a high level of bound 14 C-DBE metabolites were present in the epithelium, while in ovariectomized oestradiol-primed mice or intact oestradiol-primed mice, the binding was low. Similar results were obtained with 14 C-CF, although the level of binding generally was lower than that observed after 14 C-DBE-exposure. No binding of 14 C-DBE-metabolites was observed in the juvenile rat vaginal epithelium, whereas a high binding was present in the PMSG-primed adult rat vaginal epithelium. Collectively, these data show that 14 C-DBE and 14 C-CF are transformed in situ to metabolites that are irreversibly bound to the vaginal epithelium. The results also suggest that the activating enzyme is under endocrine control and has a low activity in the juvenile and oestradiol-primed adult animal. (author)

  14. Permeability and ultrastructure of human bladder epithelium

    DEFF Research Database (Denmark)

    Eldrup, J; Thorup, Jørgen Mogens; Nielsen, S L

    1983-01-01

    Leakage of tight junctions as observed with electron microscopy and demonstration of solute transport across bladder epithelium was investigated in 13 patients with different bladder diseases: urinary retention and infection, bladder tumours and interstitial cystitis. The latter group showed...

  15. Transport across the choroid plexus epithelium

    DEFF Research Database (Denmark)

    Praetorius, Jeppe; Damkier, Helle Hasager

    2017-01-01

    The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus...... is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature......, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1) the choroid plexus epithelium as the source of mediators necessary for central nervous system...

  16. Modulation of radiation-induced oral mucositis by pentoxifylline: Preclinical studies

    International Nuclear Information System (INIS)

    Gruber, Sylvia; Bozsaky, Eva; Schmidt, Margret; Doerr, Wolfgang

    2015-01-01

    Oral mucositis is a frequent early side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is accompanied by inflammatory reactions; their interaction with epithelial processes remains unclear. The aim of the present study was to investigate the effect of pentoxifylline (PTX) on the oral mucosal radiation response in the mouse tongue model. Irradiation comprised fractionation (5 fractions of 3 Gy/week) over 1 (days 0-4) or 2 weeks (days 0-4, 7-11), followed by graded local top-up doses (day 7/14), in order to generate complete dose-effect curves. PTX (15 mg/kg subcutaneously) was applied once daily over varying time intervals. Ulceration of mouse tongue epithelium, corresponding to confluent mucositis, was analyzed as the clinically relevant endpoint. With fractionated irradiation over 1 week, PTX administration significantly reduced the incidence of mucosal reactions when initiated before (day - 5) the onset of fractionation; a trend was observed for start of PTX treatment on day 0. Similarly, PTX treatment combined with 2 weeks of fractionation had a significant effect on ulcer incidence in all but one experiment. This clearly illustrates the potential of PTX to ameliorate oral mucositis during daily fractionated irradiation. PTX resulted in a significant reduction of oral mucositis during fractionated irradiation, which may be attributed to stimulation of mucosal repopulation processes. The biological basis of this effect, however, needs to be clarified in further, detailed mechanistic studies. (orig.) [de

  17. Intestinal epithelium in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet

    2014-01-01

    The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...... of inflammatory bowel disease (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets....

  18. Early Detection of Ovarian Cancer by Tumor Epithelium-Targeted Molecular Ultrasound

    Science.gov (United States)

    2014-10-01

    successful pregnancy outcome. *PIF Proprietary G-12 IL-33-responsive group 2 innate lymphoid cells are present in mouse uterine tissue and may play roles in... innate lymphoid cells (ILC2s) that are responsive to IL-33 drive helminth immunity, type 2 immune responses, and tissue pathology and homeostasis in...16 (IL-16) secreted by immune cells . Inflammation of the ovary and tubal epithelium due to frequent ovulation leads to the development of oxidative

  19. An in vitro model of murine middle ear epithelium.

    Science.gov (United States)

    Mulay, Apoorva; Akram, Khondoker M; Williams, Debbie; Armes, Hannah; Russell, Catherine; Hood, Derek; Armstrong, Stuart; Stewart, James P; Brown, Steve D M; Bingle, Lynne; Bingle, Colin D

    2016-11-01

    Otitis media (OM), or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well-characterised in vitro model of the middle ear (ME) epithelium that replicates the complex cellular composition of the middle ear. Here, we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs) at an air-liquid interface (ALI) that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We showed that the mMECs supported the growth of the otopathogen, nontypeable Haemophilus influenzae (NTHi), suggesting that the model can be successfully utilised to study host-pathogen interactions in the middle ear. Overall, our mMEC culture system can help to better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling that underpin OM development. © 2016. Published by The Company of Biologists Ltd.

  20. Ethanol impedes embryo transport and impairs oviduct epithelium

    International Nuclear Information System (INIS)

    Xu, Tonghui; Yang, Qiuhong; Liu, Ruoxi; Wang, Wenfu; Wang, Shuanglian; Liu, Chuanyong; Li, Jingxin

    2016-01-01

    Most studies have demonstrated that alcohol consumption is associated with decreased fertility. The aim of this study was to investigate the effects of alcohol on pre-implantation embryo transport and/or early embryo development in the oviduct. We reported here that ethanol concentration-dependently suppressed the spontaneous motility of isolated human oviduct strips (EC50 50 ± 6 mM), which was largely attenuated in the present of L-NAME, a classical nitric oxide synthase(NOS) competitive inhibitor. Notably, either acute or chronic alcohol intake delayed egg transport and retarded early development of the embryo in the mouse oviduct, which was largely rescued by co-administration of L-NAME in a acute alcohol intake group but not in chronic alcohol intake group. It is worth mentioning that the oviductal epithelium destruction was verified by scanning electron microscope (SEM) observations in chronic alcohol intake group. In conclusion, alcohol intake delayed egg transport and retarded early development of the embryo in the oviduct by suppressing the spontaneous motility of oviduct and/or impairing oviductal epithelium. These findings suggested that alcohol abuse increases the incident of ectopic pregnancy.

  1. An in vitro model of murine middle ear epithelium

    Directory of Open Access Journals (Sweden)

    Apoorva Mulay

    2016-11-01

    Full Text Available Otitis media (OM, or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well-characterised in vitro model of the middle ear (ME epithelium that replicates the complex cellular composition of the middle ear. Here, we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs at an air–liquid interface (ALI that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We showed that the mMECs supported the growth of the otopathogen, nontypeable Haemophilus influenzae (NTHi, suggesting that the model can be successfully utilised to study host–pathogen interactions in the middle ear. Overall, our mMEC culture system can help to better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling that underpin OM development.

  2. Ethanol impedes embryo transport and impairs oviduct epithelium.

    Science.gov (United States)

    Xu, Tonghui; Yang, Qiuhong; Liu, Ruoxi; Wang, Wenfu; Wang, Shuanglian; Liu, Chuanyong; Li, Jingxin

    2016-05-16

    Most studies have demonstrated that alcohol consumption is associated with decreased fertility. The aim of this study was to investigate the effects of alcohol on pre-implantation embryo transport and/or early embryo development in the oviduct. We reported here that ethanol concentration-dependently suppressed the spontaneous motility of isolated human oviduct strips (EC50 50±6mM), which was largely attenuated in the present of L-NAME, a classical nitric oxide synthase(NOS) competitive inhibitor. Notably, either acute or chronic alcohol intake delayed egg transport and retarded early development of the embryo in the mouse oviduct, which was largely rescued by co-administration of L-NAME in a acute alcohol intake group but not in chronic alcohol intake group. It is worth mentioning that the oviductal epithelium destruction was verified by scanning electron microscope (SEM) observations in chronic alcohol intake group. In conclusion, alcohol intake delayed egg transport and retarded early development of the embryo in the oviduct by suppressing the spontaneous motility of oviduct and/or impairing oviductal epithelium. These findings suggested that alcohol abuse increases the incident of ectopic pregnancy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Tissue-specific metabolic activation and mutagenicity of 3-nitrobenzanthrone in MutaMouse.

    Science.gov (United States)

    Chen, Guosheng; Gingerich, John; Soper, Lynda; Douglas, George R; White, Paul A

    2008-10-01

    3-Nitrobenzanthrone (3-NBA) is a mutagen and suspected human carcinogen detected in diesel exhaust, airborne particulate matter, and urban soil. We investigated the tissue specific mutagenicity of 3-NBA at the lacZ locus of transgenic MutaMouse following acute single dose or 28-day repeated-dose oral administration. In the acute high dose (50 mg/kg) exposure, increased lacZ mutant frequency was observed in bone marrow and colonic epithelium, but not in liver and bladder. In the repeated-dose study, a dose-dependent increase in lacZ mutant frequency was observed in bone marrow and liver (2- and 4-fold increase above control), but not in lung or intestinal epithelium. In addition, a concentration-dependent increase in mutant frequency (8.5-fold above control) was observed for MutaMouse FE1 lung epithelial cells exposed in vitro. 1-Nitropyrene reductase, 3-NBA reductase, and acetyltransferase activities were measured in a variety of MutaMouse specimens in an effort to link metabolic activation and mutagenicity. High 3-NBA nitroreductase activities were observed in lung, liver, colon and bladder, and detectable N-acetyltransferase activities were found in all tissues except bone marrow. The relatively high 3-NBA nitroreductase activity in MutaMouse tissues, as compared with those in Salmonella TA98 and TA100, suggests that 3-NBA is readily reduced and activated in vivo. High 3-NBA nitroreductase levels in liver and colon are consistent with the elevated lacZ mutant frequency values, and previously noted inductions of hepatic DNA adducts. Despite an absence of induced lacZ mutations, the highest 3-NBA reductase activity was detected in lung. Further studies are warranted, especially following inhalation or intratracheal exposures. Published 2008 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2015-09-01

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

  5. Oral tolerance is determined at the level of draining lymph nodes

    NARCIS (Netherlands)

    Wilsem, van E.G.; BrevÃ, J.; Savelkoul, H.; Claessen, A.; Scheper, R.J.; Kraal, G.

    1995-01-01

    In the skin and in the epithelium of the oral mucosa a comparable network of Langerhans cells can be found. Antigen application on either epithelium leads to rapid emigration of Langerhans cells to the draining lymph nodes. Application on the oral mucosa leads to tolerance induction while

  6. V-set and Ig domain-containing 4 (VSIG4)-expressing hepatic F4/80+ cells regulate oral antigen-specific responses in mouse.

    Science.gov (United States)

    Shin, Wonhwa; Jeon, Youkyoung; Choi, Inhak; Kim, Yeon-Jeong

    2018-04-01

    Oral tolerance can prevent unnecessary immune responses against dietary antigens. Members of the B7 protein family play critical roles in the positive and/or negative regulation of T cell responses to interactions between APCs and T cells. V-set and Ig domain-containing 4 (VSIG4), a B7-related co-signaling molecule, has been known to act as a co-inhibitory ligand and may be critical in establishing immune tolerance. Therefore, we investigated the regulation of VSIG4 signaling in a food allergy and experimental oral tolerance murine models. We analyzed the contributions of the two main sites involved in oral tolerance, the mesenteric lymph node (MLN) and the liver, in VSIG4-mediated oral tolerance induction. Through the comparative analysis of major APCs, dendritic cells (DCs) and macrophages, we found that Kupffer cells play a critical role in inducing regulatory T cells (Tregs) and establishing immune tolerance against oral antigens via VSIG4 signaling. Taken together, these results suggest the possibility of VSIG4 signaling-based regulation of orally administered antigens. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1

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    Anja Meyer

    2017-04-01

    Full Text Available Niemann–Pick disease type C1 (NPC1 is a fatal neurovisceral lysosomal lipid storage disorder. The mutation of the NPC1 protein affects the homeostasis and transport of cholesterol and glycosphingolipids from late endosomes/lysosomes to the endoplasmic reticulum resulting in progressive neurodegeneration. Since olfactory impairment is one of the earliest symptoms in many neurodegenerative disorders, we focused on alterations of the olfactory epithelium in an NPC1 mouse model. Previous findings revealed severe morphological and immunohistochemical alterations in the olfactory system of NPC1−/− mutant mice compared with healthy controls (NPC1+/+. Based on immunohistochemical evaluation of the olfactory epithelium, we analyzed the impact of neurodegeneration in the olfactory epithelium of NPC1−/− mice and observed considerable loss of mature olfactory receptor neurons as well as an increased number of proliferating and apoptotic cells. Additionally, after administration of two different therapy approaches using either a combination of miglustat, 2-hydroxypropyl-β-cyclodextrin (HPβCD and allopregnanolone or a monotherapy with HPβCD, we recorded a remarkable reduction of morphological damages in NPC1−/− mice and an up to four-fold increase of proliferating cells within the olfactory epithelium. Numbers of mature olfactory receptor neurons doubled after both therapy approaches. Interestingly, we also observed therapy-induced alterations in treated NPC1+/+ controls. Thus, olfactory testing may provide useful information to monitor pharmacologic treatment approaches in human NPC1.

  8. Expression of Ricinus communis receptors on epithelial cells in oral carcinomas and oral wounds.

    Science.gov (United States)

    Dabelsteen, E; Mackenzie, I C

    1978-12-01

    The histological distribution of receptors for Ricinus communis Fraction 1 (RCA1) in oral carcinomas and in oral epithelial cells during wound healing has been studied by use of fluorescein-tagged RCA1. Biopsies from 15 human oral carcinomas and adjacent normal mucosa showed RCA1 receptors at the cell membranes in the basal and spinous layer of the normal epithelium, whereas receptors could not be demonstrated in invading islands of the tumors. In healing oral wounds from eight humans and three monkeys, RCA1 receptors were demonstrated both in normal epithelium adjacent to the wounds and in the epithelial outgrowth from the wound margin. Titrations, however, showed that the epithelial outgrowth reacted more weakly than did the normal adjacent epithelium. These results support previous in vitro studies showing changes in carbohydrate composition of moving normal cells and of malignant cells, a finding that may be of interest in relation to formation of metastases.

  9. Expressions of TRPVs in the cholesteatoma epithelium.

    Science.gov (United States)

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

    2017-10-01

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

  10. Transport across the choroid plexus epithelium.

    Science.gov (United States)

    Praetorius, Jeppe; Damkier, Helle Hasager

    2017-06-01

    The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

  11. Neoplasia versus hyperplasia of the retinal pigment epithelium

    DEFF Research Database (Denmark)

    Heegaard, Steffen; Larsen, J.N.B.; Fledelius, Hans C.

    2001-01-01

    ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography......ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography...

  12. The Structure of Urethral Epithelium in Merinos Lambs

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    Vasile RUS

    2018-05-01

    Full Text Available The aim of this study was to investigate by histological techniques the structure of urethral epithelium in lambs. In this study, we harvested several fragments (prostatic, membranous and cavernous from urethra from 5 merino’s lambs of 3 months old. The first anatomical segment, the prostatic urethra, is lined by a urinary epithelium. The intermediary layer of this epithelium is formed of 5-6 rows of oval cells. The second segment of urethra has the same type of epithelium but the intermediary layer is formed of 6-7 rows of oval cells. In the last anatomical segment, the penile urethra, the epithelium is the same, but the intermediary layer has 3-4 rows of oval cells. In lambs, the urethra is lined by urinary epithelium. The urethral epithelium does not have the same thickness in all segments. The thinner epithelium it is in the cavernous urethra, the ticker is the membranous urethra.

  13. Poly(amido amine) dendrimers in oral delivery.

    Science.gov (United States)

    Yellepeddi, Venkata K; Ghandehari, Hamidreza

    2016-01-01

    Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed.

  14. Chronic oral nicotine increases brain [3H]epibatidine binding and responsiveness to antidepressant drugs, but not nicotine, in the mouse forced swim test

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Nielsen, Elsebet O; Redrobe, John P

    2009-01-01

    Smoking rates among depressed individuals is higher than among healthy subjects, and nicotine alleviates depressive symptoms. Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. In mice, acute nicotine administration enhances...... the activity of antidepressants in the mouse forced swim (mFST) and tail suspension tests. Here, we investigated if this action of nicotine is also reflected in a chronic treatment regimen....

  15. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse

    OpenAIRE

    Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A.; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A.; Borrelli, Francesca

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was ...

  16. Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Brodin, Birger; Nielsen, Robert

    1995-01-01

    Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium.......Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium....

  17. Intestinal epithelium in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mehmet eCoskun

    2014-08-01

    Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

  18. Radiobiology of intestinal epithelium stem cells

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.

    1988-01-01

    After a single or three-fold whole body irradiation of mice with a dose of 4 Gy and the time interval for the proliferation to be restored (5 days or 3 weeks) the survival curve for stem cells of small intestine epithelium with regard to radiation dose was the same as that for non-preirradiated mice. This indicated that the proliferative potential of stem cells in these experimental conditions was not reduced

  19. Barrier properties of cultured retinal pigment epithelium.

    Science.gov (United States)

    Rizzolo, Lawrence J

    2014-09-01

    The principal function of an epithelium is to form a dynamic barrier that regulates movement between body compartments. Each epithelium is specialized with barrier functions that are specific for the tissues it serves. The apical surface commonly faces a lumen, but the retinal pigment epithelium (RPE) appears to be unique by a facing solid tissue, the sensory retina. Nonetheless, there exists a thin (subretinal) space that can become fluid filled during pathology. RPE separates the subretinal space from the blood supply of the outer retina, thereby forming the outer blood-retinal barrier. The intricate interaction between the RPE and sensory retina presents challenges for learning how accurately culture models reflect native behavior. The challenge is heightened by findings that detail the variation of RPE barrier proteins both among species and at different stages of the life cycle. Among the striking differences is the expression of claudin family members. Claudins are the tight junction proteins that regulate ion diffusion across the spaces that lie between the cells of a monolayer. Claudin expression by RPE varies with species and life-stage, which implies functional differences among commonly used animal models. Investigators have turned to transcriptomics to supplement functional studies when comparing native and cultured tissue. The most detailed studies of the outer blood-retinal barrier have focused on human RPE with transcriptome and functional studies reported for human fetal, adult, and stem-cell derived RPE. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Development of the ovarian follicular epithelium.

    Science.gov (United States)

    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.

  1. Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

    Science.gov (United States)

    Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

    2017-07-01

    Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

  2. In vivo models of human airway epithelium repair and regeneration

    Directory of Open Access Journals (Sweden)

    C. Coraux

    2005-12-01

    Full Text Available Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks. Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium. A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.

  3. Use of dexpanthenol and aloe vera to influence the irradiation response of the oral mucous membrane (mouse); Beeinflussung der Strahlenreaktion der Mundschleimhaut (Maus) durch Dexpanthenol {+-} Aloe vera

    Energy Technology Data Exchange (ETDEWEB)

    Schlichting, S. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Dresden Univ. (Germany); Spekl, K.; Doerr, W. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Dresden Univ. (Germany)]|[Experimentelles Zentrum, Medizinische Fakultaet Carl Gustav Carus, Dresden Univ. (Germany)

    2004-07-01

    In summarising the outcome of the present study it can be said spraying the agent on the oral mucous membrane once a day had an effect on the incidence of mucous membrane ulceration in the case of both placebo and dexpanthenol treatment. However, there was no significant difference between placebo and dexpanthenol treatment, the only finding being a slight prolongation of latency time through aloe vera. These experimental findings give good reason to critically reconsider the clinical use of dexpanthenol as a supportive treatment for the prevention of radiogenic mucositis enoralis following irradiation of tumours in the head and neck region. However thorough oral lavage is an effective means of moderating the irradiation response of the oral mucous membrane. [German] Zusammenfassend ist festzustellen, dass in den vorliegenden Versuchen mit einmal taeglichem Aufspruehen des Praeparates auf die Mundschleimhaut sowohl die Placebo - wie auch die Dexpanthenol-Behandlung die Inzidenz von Schleimhautulzerationen modifiziert hat; zwischen Placebo- und Dexpanthenol-Behandlung ergab sich jedoch kein signifikanter Unterschied. Lediglich eine geringe Verlaengerung der Latenzzeit durch Aloe vera war zu beobachten. Auf der Basis dieser experimentellen Ergebnisse muss der klinische Einsatz von Dexpanthenol im Rahmen der Supportivtherapie zur Prophylaxe der radiogenen Mucositis enoralis bei der Bestrahlung von Kopf-Hals-Tumoren kritisch ueberdacht werden. Regelmaessige, intensive Mundspuelungen sind jedoch ein probates Mittel zur Verminderung der Strahlenreaktion der Mundschleimhaut. (orig.)

  4. Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

    Science.gov (United States)

    Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T

    2015-12-01

    Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma. © 2013 John Wiley & Sons Ltd.

  5. SPDEF regulates goblet cell hyperplasia in the airway epithelium

    Science.gov (United States)

    Park, Kwon-Sik; Korfhagen, Thomas R.; Bruno, Michael D.; Kitzmiller, Joseph A.; Wan, Huajing; Wert, Susan E.; Khurana Hershey, Gurjit K.; Chen, Gang; Whitsett, Jeffrey A.

    2007-01-01

    Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo. PMID:17347682

  6. Garlic ameliorates histological changes in the uterine epithelium of lead induced mice

    International Nuclear Information System (INIS)

    Waseem, N.; Butt, S.A.; Hamid, S.

    2015-01-01

    To evaluate the protective role of garlic extract on the histology of the uterine epithelium exposed to lead acetate in an animal model. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Anatomy, Army Medical College in collaboration with National Institute of health from April to June 2013. Material and Methods: Thirty female BALBc mice were selected. Ten animals were placed in each group. Group A being the control was given normal diet. Group B was given lead acetate at a dose of 30 mg/kg/day. Group C was given lead acetate 30 mg/kg/day and garlic extract 500 mg/kg/day through oral gavage tube for 60 days. Animals were sacrificed and dissected at the end of 60 days. Right uterine horn was processed, embedded and stained for histological study. Height of epithelium was measured. It was taken from apical to basal end of the cells. Results: There was increase in height of the lining epithelium of uterus in group B, mean value 19.70 ± 4.81 meu m when compared to Group A, with mean value 13.25 ± 2.37 meu m. The height of the epithelium was relatively reduced in group C, with mean value 14.50 ± 2.30 meu m when compared with group B. In group C results were same as Group A. The p values were 0.001 when group A was compared to group B, 0.688 when group A was compared to group C and 0.005 when group B was compared to group C. Conclusion: The height of epithelium was markedly increased in lead acetate treated group which returned to normal when co treated with garlic extract. Hence garlic ameliorated the changes induced by lead. (author)

  7. Oral complications of cancer therapies. Mucosal alterations

    International Nuclear Information System (INIS)

    Squier, C.A.

    1990-01-01

    The initial effect of anticancer therapy, such as radiation and chemotherapy, is on the rapidly proliferating cells of the oral epithelium. As a consequence, the epithelium may show atrophy and ulceration. The sites of these alterations are related to the rate of epithelial proliferation. Regions of rapid proliferation, such as the oral lining mucosa, show a greater frequency of ulceration than masticatory mucosa or skin. Subsequent changes in the mucosa reflect damage to connective tissue, including fibroblasts and blood vessels. This results in hyalinization of collagen, hypovascularity, and ischemia. Indirect effects of anticancer therapy may include granulocytopenia and reduced salivary secretion, so that the protective mucin coating of the epithelium is compromised. These changes result in tissue with reduced barrier function and impaired ability to heal and to resist entry of pathogens, thus increasing the risk of systemic infections

  8. Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening.

    Science.gov (United States)

    Bhatnagar, Sumit; Verma, Kirti Dhingra; Hu, Yongjun; Khera, Eshita; Priluck, Aaron; Smith, David E; Thurber, Greg M

    2018-05-07

    Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a "disease screening pill" capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents.

  9. Effect of orally-administered Lactobacillus plantarum LPLM-O1 strain in an immunosuppressed mouse model of urinary tract infection.

    Science.gov (United States)

    de Arellano, A Ramírez; Sánchez, M; Vera, R; Jara, S; González, M; Castro, E

    2012-03-01

    Urinary tract infections (UTIs) affect both healthy and immunocompromised people, and they are treated with antibiotics. However, the high recurrence of UTIs obliges the use of natural mechanisms to regulate the normal microbiota through the use of e.g. lactic acid bacteria. In order to induce a UTI, 20 µl of the Escherichia coli (Ec-01) strain, in doses of 2.7×10(7) cfu/ml, was inoculated by way of the urethra in female Balb/c mice, all of them immunosuppressed with dexamethasone (10 mg/kg). Lactobacillus plantarum LPLM-O1 was used as a treatment, in daily doses of 1×10(7) cfu/ml, which were orally administered for seven days before the infection (preventive) or alongside the infection for seven days (curative). The oral administration of LPLM-O1 did not cause any adverse effects when used in an immunosuppressed animal model. It was observed that, when used as a preventive measure, LPLM-O1 induces a decrease in the infection, in the concentration of urinary leukocytes, and in the bacterial load. This study proposes the use of this lactic bacterium as a probiotic.

  10. Oral foregut cyst in a neonate.

    Science.gov (United States)

    Rosa, Ana Cláudia Garcia; Hiramatsu, Daniel Martins; de Moraes, Fábio Roberto Ruiz; Passador-Santos, Fabrício; de Araújo, Vera Cavalcanti; Soares, Andresa Borges

    2013-11-01

    Oral foregut cysts are congenital choristomas that arise in the oral cavity during embryonic development from remnants of foregut-derived epithelium. This is an unusual report of a neonate with a large congenital sublingual cystic lesion, extending superficially from the left ventral tongue to the anterior floor of the mouth, impeding breast-feeding. The differential diagnosis included dermoid cyst, epidermoid cyst, mucous retention cyst, and oral lymphangioma. The treatment of choice was enucleation under general anesthesia. Histology showed a cystic lesion with a ciliated pseudostratified columnar epithelium with numerous goblet cells. Immunohistochemistry was positive for cytokeratin 7 and thyroid transcription factor 1 and negative for cytokeratin 20, resulting in a final diagnosis of an oral foregut cyst. Three weeks after surgery, the tongue had healed with good mobility, and breast-feeding could be established. No recurrence was present at 6 months of follow-up.

  11. Smoking influences on the thickness of marginal gingival epithelium

    Directory of Open Access Journals (Sweden)

    Villar Cristina Cunha

    2003-01-01

    Full Text Available Smoking patients show reduction of inflammatory clinical signs that might be associated with local vasoconstriction and an increased gingival epithelial thickness. The purpose of this work was to evaluate the thickness of the marginal gingival oral epithelium in smokers and non-smokers, with clinically healthy gingivae or with gingivitis. Twenty biopsies were obtained from four different groups. Group I: non-smokers with clinically healthy gingivae (n = 5. Group II: non-smokers with gingivitis (n = 5. Group III: smokers with clinically healthy gingivae (n = 5. Group IV: smokers with gingivitis (n = 5. These biopsies were histologically processed, serially sectioned at 5 mm, stained with H. E., and examined by image analysis software (KS400, which was used to perform the morphometric evaluation and the quantification of the major epithelial thickness, the epithelial base thickness and the external and internal epithelial perimeters. Differences between the four groups were analyzed using ANOVA test and Tukey's test. The criteria for statistical significance were accepted at the probability level p < 0.05. A greater epithelial thickness was observed in smokers independent of the gingival health situation.

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

    Directory of Open Access Journals (Sweden)

    Vasavada Abhay

    1993-01-01

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

  13. Oxidative Stress as a Mechanism Involved in Kidney Damage After Subchronic Exposure to Vanadium Inhalation and Oral Sweetened Beverages in a Mouse Model.

    Science.gov (United States)

    Espinosa-Zurutuza, Maribel; González-Villalva, Adriana; Albarrán-Alonso, Juan Carlos; Colín-Barenque, Laura; Bizarro-Nevares, Patricia; Rojas-Lemus, Marcela; López-Valdéz, Nelly; Fortoul, Teresa I

    Kidney diseases have notably increased in the last few years. This is partially explained by the increase in metabolic syndrome, diabetes, and systemic blood hypertension. However, there is a segment of the population that has neither of the previous risk factors, yet suffers kidney damage. Exposure to atmospheric pollutants has been suggested as a possible risk factor. Air-suspended particles carry on their surface a variety of fuel combustion-related residues such as metals, and vanadium is one of these. Vanadium might produce oxidative stress resulting in the damage of some organs such as the kidney. Additionally, in countries like Mexico, the ingestion of sweetened beverages is a major issue; whether these beverages alone are responsible for direct kidney damage or whether their ingestion promotes the progression of an existing renal damage generates controversy. In this study, we report the combined effect of vanadium inhalation and sweetened beverages ingestion in a mouse model. Forty CD-1 male mice were distributed in 4 groups: control, vanadium inhalation, 30% sucrose in drinking water, and vanadium inhalation plus sucrose 30% in drinking water. Our results support that vanadium inhalation and the ingestion of 30% sucrose induce functional and histological kidney damage and an increase in oxidative stress biomarkers, which were higher in the combined effect of vanadium plus 30% sucrose. The results also support that the ingestion of 30% sucrose alone without hyperglycemia also produces kidney damage.

  14. Comparison of the Intraperitoneal, Retroorbital and per Oral Routes for F 18 FDG Administration as Effective Alternatives to Intravenous Administration in Mouse Tumor Models Using Small Animal PET/CT Studies

    International Nuclear Information System (INIS)

    Kim, Chulhan; Kim, In Hye; Kim, Seo il; Kim, Young Sang; Kang, Se Hun; Moon, Seung Hwan; Kim, Tae Sung; Kim, Seok ki

    2011-01-01

    We compared alternative routes for 18F fluorodeoxyglucose (FDG) administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral (PO) routes, with the intravenous (IV) route in normal tissues and tumors of mice. CRL 1642 (ATCC, Lewis lung carcinoma) cells were inoculated in female BALB/c nu/nu mice 6 to 10 weeks old. When the tumor grew to about 9mm in diameter, positron emission tomography (PET) scans were performed after FDG administration via the RO, IP, PO or IV route. Additional serial PET scans were performed using the RO, IV or IP route alternatively from 5 to 29 days after the tumor cell injection. There was no significant difference in the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP and IV routes. PO administration, however, showed delayed distribution and unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar temporal pattern and increased until 60 min after FDG administration in the RO, IP and IV injection groups. In the PO administration group, tumoral uptake was delayed and reduced. There was no statistical difference among the RO, IP and IV administration groups for additional serial PET scans. RO administration is an effective alternative route to IV administration for mouse FDG PET scans using normal mice and tumor models. In addition, IP administration can be a practical alternative in the late phase, although the initial uptake is lower than those in the IV and RO groups.

  15. Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Wenda [College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095 (China); Dept. of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); He, Kaiyu [Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Dept. of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States); Zhou, Hui-Ren [Dept. of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Berthiller, Franz [Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, University of Natural Resources and Life Sciences, Tulln (Austria); Adam, Gerhard [Dept. of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna (Austria); Sugita-Konishi, Yoshiko [Food and Life Sciences, Azabu University, 1-17-71 Fuchinobe Chuo-ku, Sagamihara, Kanagawa Pref., 252-5201 (Japan); Watanabe, Maiko [Division of Microbiology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501 (Japan); Krantis, Anthony [Dept. of Cellular and Molecular Medicine, University of Ottawa (Canada); Durst, Tony [Dept. of Chemistry, University of Ottawa (Canada); Zhang, Haibin [College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095 (China); Pestka, James J., E-mail: pestka@msu.edu [Dept. of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Dept. of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States)

    2014-07-15

    The foodborne mycotoxin deoxynivalenol (DON) induces a ribotoxic stress response in mononuclear phagocytes that mediate aberrant multi-organ upregulation of TNF-α, interleukins and chemokines in experimental animals. While other DON congeners also exist as food contaminants or pharmacologically-active derivatives, it is not known how these compounds affect expression of these cytokine genes in vivo. To address this gap, we compared in mice the acute effects of oral DON exposure to that of seven relevant congeners on splenic expression of representative cytokine mRNAs after 2 and 6 h. Congeners included the 8-ketotrichothecenes 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), nivalenol (NIV), the plant metabolite DON-3-glucoside (D3G) and two synthetic DON derivatives with novel satiety-inducing properties (EN139528 and EN139544). DON markedly induced transient upregulation of TNF-α IL-1β, IL-6, CXCL-2, CCL-2 and CCL-7 mRNA expressions. The two ADONs also evoked mRNA expression of these genes but to a relatively lesser extent. FX induced more persistent responses than the other DON congeners and, compared to DON, was: 1) more potent in inducing IL-1β mRNA, 2) approximately equipotent in the induction of TNF-α and CCL-2 mRNAs, and 3) less potent at upregulating IL-6, CXCL-2, and CCL-2 mRNAs. EN139528's effects were similar to NIV, the least potent 8-ketotrichothecene, while D3G and EN139544 were largely incapable of eliciting cytokine or chemokine mRNA responses. Taken together, the results presented herein provide important new insights into the potential of naturally-occurring and synthetic DON congeners to elicit aberrant mRNA upregulation of cytokines associated with acute and chronic trichothecene toxicity. - Highlights: • We compared effects of DON congeners on biomarker proinflammatory genes in mice. • Oral DON induced splenic IL-1β, IL-6, TNF-α,CXCL-2, CCL-2 and CCL-7 mRNAs. • 8-Ketotrichothecene ranking

  16. Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse

    International Nuclear Information System (INIS)

    Wu, Wenda; He, Kaiyu; Zhou, Hui-Ren; Berthiller, Franz; Adam, Gerhard; Sugita-Konishi, Yoshiko; Watanabe, Maiko; Krantis, Anthony; Durst, Tony; Zhang, Haibin; Pestka, James J.

    2014-01-01

    The foodborne mycotoxin deoxynivalenol (DON) induces a ribotoxic stress response in mononuclear phagocytes that mediate aberrant multi-organ upregulation of TNF-α, interleukins and chemokines in experimental animals. While other DON congeners also exist as food contaminants or pharmacologically-active derivatives, it is not known how these compounds affect expression of these cytokine genes in vivo. To address this gap, we compared in mice the acute effects of oral DON exposure to that of seven relevant congeners on splenic expression of representative cytokine mRNAs after 2 and 6 h. Congeners included the 8-ketotrichothecenes 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), nivalenol (NIV), the plant metabolite DON-3-glucoside (D3G) and two synthetic DON derivatives with novel satiety-inducing properties (EN139528 and EN139544). DON markedly induced transient upregulation of TNF-α IL-1β, IL-6, CXCL-2, CCL-2 and CCL-7 mRNA expressions. The two ADONs also evoked mRNA expression of these genes but to a relatively lesser extent. FX induced more persistent responses than the other DON congeners and, compared to DON, was: 1) more potent in inducing IL-1β mRNA, 2) approximately equipotent in the induction of TNF-α and CCL-2 mRNAs, and 3) less potent at upregulating IL-6, CXCL-2, and CCL-2 mRNAs. EN139528's effects were similar to NIV, the least potent 8-ketotrichothecene, while D3G and EN139544 were largely incapable of eliciting cytokine or chemokine mRNA responses. Taken together, the results presented herein provide important new insights into the potential of naturally-occurring and synthetic DON congeners to elicit aberrant mRNA upregulation of cytokines associated with acute and chronic trichothecene toxicity. - Highlights: • We compared effects of DON congeners on biomarker proinflammatory genes in mice. • Oral DON induced splenic IL-1β, IL-6, TNF-α,CXCL-2, CCL-2 and CCL-7 mRNAs. • 8-Ketotrichothecene ranking

  17. Scanning electron microscopical study of the lingual epithelium of green iguana (Iguana iguana).

    Science.gov (United States)

    Abbate, F; Latella, G; Montalbano, G; Guerrera, M C; Levanti, M B; Ciriaco, E

    2008-08-01

    During the last few years, green iguanas (Iguana iguana) have turned out to be one of the most popular pets. They are omnivorous. In their way of feeding, this crucial function is performed by capturing of the preys and mostly, this is carried out by the tongue. The role of the tongue is also fundamental during the intra-oral transport and during the swallowing of food. This has been reported in several studies about chameleons, agamids and iguanids, nevertheless published data about the mechanisms of capturing and swallowing the prey, and the morphological descriptions about the tongue epithelium, are scarce. Therefore, the aim of this present study was to analyse the morphology of the lingual epithelium in green iguanas by scanning electron microscopy. Three different areas were demonstrated on the tongue surface: the tongue tip, characterized by a smooth epithelium without papillae, a foretongue, completely covered by numerous closely packed cylindriform papillae, and a hindtongue with conical-like papillae. Some taste buds were recognized on the middle and the posterior parts of the tongue. Different functional roles could be hypothesized for the three tongue areas: the tongue tip could have a role related to the movements of the prey immediately after the capturing, while the middle papillae and the hindtongue could have an important role concerning the swallowing phase.

  18. Oncofetal fibronectins in oral carcinomas

    DEFF Research Database (Denmark)

    Mandel, U; Gaggero, B; Reibel, J

    1994-01-01

    -B-containing isoform and the oncofetal FN isoform derived by O-glycosylation, in oral squamous cell carcinomas, premalignant lesions, and normal oral mucosa. A selective expression of the ED-B-containing isoform was demonstrated in close relation to the invading carcinoma (38/38), whereas there was virtually...... no staining in submucosa underlying premalignant lesions (1/11) and normal epithelium (0/5). The ED-B-containing FN showed close co-distribution and staining pattern with the oncofetal isoform derived by O-glycosylation. These results demonstrate that accumulation of FN adjacent to oral carcinomas includes...... in breast and oral tumors. Another oncofetal FN isoform containing the ED-B sequence is derived by alternative splicing, and FN containing ED-B has been found to be a stromal marker of malignancies in various tissues. Here we report a comparative study by immunohistology of the distribution of the ED...

  19. Determination of lymph flow in murine oral mucosa using depot clearance of near-infrared-labeled albumin.

    Science.gov (United States)

    Papadakou, Panagiota; Karlsen, Tine Veronica; Wiig, Helge; Berggreen, Ellen

    2015-10-01

    The lymphatic vessels are playing an important role in inflammation since they return extravasated fluid, proteins, and cells back into the circulation and regulate immune cell trafficking. The oral mucosa, including gingiva, is well supplied with lymphatic vessels and is frequently challenged with inflammatory insults. Lymphatic vessels in gingiva protect against periodontal disease development, but quantification of lymph flow in this area has so far never been performed, due to lack of reliable methods. Mice of FVB strain (n=17) were anesthetized with isoflurane and placed on a jaw retraction board allowing the mouth to be kept open and stable. Albumin conjugated with Alexa680-fluorochrome (with or without LPS from Porphyromonas gingivalis) was injected superficially in oral mucosa mesio-buccal to the left first molar in each mouse. 60 min post-injection the mouse was transferred to an OptixMX3 optical imager where the total fluorescence was measured in the posterior facial area. The measurements continued further every 60 min for 7h for each mouse. The mice were awake and active between measurements. The in vivo washout of Alexa680-albumin was calculated using the natural logarithm of the relative values creating a negative slope for each mouse. Statistical analysis of variance was performed. The injection and distribution site for tracer was verified with India ink and shown to be in the interstitium below the oral mucosal epithelium, in an area well supplied with initial lymphatic vessels. Washout of the tracer Alexa680-albumin was log-linear, and the basal lymph flow calculated from depot clearance averaged -0.28 ± 0.08%/min (n=8). The clearance was significantly faster (-0.30 ± 0.08%/min, n=9) in acutely inflamed oral mucosa (p=0.0326). We developed a method that can successfully quantify the lymph flow in oral mucosa in steady state conditions and under acute perturbation. By use of this method, new information about the lymphatic function in oral mucosa

  20. Oral epithelial stem cells – implications in normal development and cancer metastasis

    Science.gov (United States)

    Papagerakis, Silvana; Pannone, Giuseppe; Zheng, Li; About, Imad; Taqi, Nawar; Nguyen, Nghia P.T.; Matossian, Margarite; McAlpin, Blake; Santoro, Angela; McHugh, Jonathan; Prince, Mark E.; Papagerakis, Petros

    2014-01-01

    Oral mucosa is continuously exposed to environmental forces and has to be constantly renewed. Accordingly, the oral mucosa epithelium contains a large reservoir of epithelial stem cells necessary for tissue homeostasis. Despite considerable scientific advances in stem cell behavior in a number of tissues, fewer studies have been devoted to the stem cells in the oral epithelium. Most of oral mucosa stem cells studies are focused on identifying cancer stem cells (CSC) in oral squamous cell carcinomas (OSCCs) among other head and neck cancers. OSCCs are the most prevalent epithelial tumors of the head and neck region, marked by their aggressiveness and invasiveness. Due to their highly tumorigenic properties, it has been suggested that CSC may be the critical population of cancer cells in the development of OSCC metastasis. This review presents a brief overview of epithelium stem cells with implications in oral health, and the clinical implications of the CSC concept in OSCC metastatic dissemination. PMID:24803391

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

    Science.gov (United States)

    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.

  2. Oral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency.

    Science.gov (United States)

    Saheki, Takeyori; Inoue, Kanako; Ono, Hiromi; Fujimoto, Yuki; Furuie, Sumie; Yamamura, Ken-Ichi; Kuroda, Eishi; Ushikai, Miharu; Asakawa, Akihiro; Inui, Akio; Eto, Kazuhiro; Kadowaki, Takashi; Moriyama, Mitsuaki; Sinasac, David S; Yamamoto, Takashi; Furukawa, Tatsuhiko; Kobayashi, Keiko

    2017-04-01

    Mice carrying simultaneous homozygous mutations in the genes encoding citrin, the mitochondrial aspartate-glutamate carrier 2 (AGC2) protein, and mitochondrial glycerol-3-phosphate dehydrogenase (mGPD), are a phenotypically representative model of human citrin (a.k.a., AGC2) deficiency. In this study, we investigated the voluntary oral intake and preference for sucrose, glycerol or ethanol solutions by wild-type, citrin (Ctrn)-knockout (KO), mGPD-KO, and Ctrn/mGPD double-KO mice; all substances that are known or suspected precipitating factors in the pathogenesis of human citrin deficiency. The double-KO mice showed clear suppressed intake of sucrose, consuming less with progressively higher concentrations compared to the other mice. Similar observations were made when glycerol or ethanol were given. The preference of Ctrn-KO and mGPD-KO mice varied with the different treatments; essentially no differences were observed for sucrose, while an intermediate intake or similar to that of the double-KO mice was observed for glycerol and ethanol. We next examined the hepatic glycerol 3-phosphate, citrate, citrulline, lysine, glutamate and adenine nucleotide levels following forced enteral administration of these solutions. A strong correlation between the simultaneous increased hepatic glycerol 3-phosphate and decreased ATP or total adenine nucleotide content and observed aversion of the mice during evaluation of their voluntary preferences was found. Overall, our results suggest that the aversion observed in the double-KO mice to these solutions is initiated and/or mediated by hepatic metabolic perturbations, resulting in a behavioral response to increased hepatic cytosolic NADH and a decreased cellular adenine nucleotide pool. These findings may underlie the dietary predilections observed in human citrin deficient patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Increased susceptibility to otitis media in a Splunc1-deficient mouse model

    Science.gov (United States)

    Bartlett, Jennifer A.; Meyerholz, David K.; Wohlford-Lenane, Christine L.; Naumann, Paul W.; Salzman, Nita H.; McCray, Paul B.

    2015-01-01

    ABSTRACT Otitis media (inflammation of the middle ear) is one of the most common diseases of early childhood. Susceptibility to otitis is influenced by a number of factors, including the actions of innate immune molecules secreted by the epithelia lining the nasopharynx, middle ear and Eustachian tube. The SPLUNC1 (short palate, lung, nasal epithelial clone 1) protein is a highly abundant secretory product of the mammalian nasal, oral and respiratory mucosa that is thought to play a multifunctional role in host defense. In this study we investigated Splunc1 expression in the ear of the mouse, and examined whether this protein contributes to overall host defense in the middle ear and/or Eustachian tube. We found that Splunc1 is highly expressed in both the surface epithelium and in submucosal glands in these regions in wild-type mice. In mice lacking Splunc1, we noted histologically an increased frequency of otitis media, characterized by the accumulation of leukocytes (neutrophils with scattered macrophages), proteinaceous fluid and mucus in the middle ear lumens. Furthermore, many of these mice had extensive remodeling of the middle ear wall, suggesting a chronic course of disease. From these observations, we conclude that loss of Splunc1 predisposes mice to the development of otitis media. The Splunc1−/− mouse model should help investigators to better understand both the biological role of Splunc1 as well as host defense mechanisms in the middle ear. PMID:25765466

  4. Oral delivery of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics: Immunofluorescent localization in the mouse hypothalamus.

    Science.gov (United States)

    Anderson, Brian M; Jacobson, Lauren; Novakovic, Zachary M; Grasso, Patricia

    2017-06-01

    This study describes the localization of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics, in the hypothalamus of Swiss Webster and C57BL/6J wild-type mice, leptin-deficient ob/ob mice, and leptin-resistant diet-induced obese (DIO) mice. The mice were given [D-Leu-4]-OB3 or MA-[D-Leu-4]-OB3 in 0.3% dodecyl maltoside by oral gavage. Once peak serum concentrations were reached, the mice received a lethal dose of pentobarbital and were subjected to intracardiac perfusion fixation. The brains were excised, post-fixed in paraformaldehyde, and cryo-protected in sucrose. Free-floating frozen coronal sections were cut at 25-µm and processed for imaging by immunofluorescence microscopy. In all four strains of mice, dense staining was concentrated in the area of the median eminence, at the base and/or along the inner wall of the third ventricle, and in the brain parenchyma at the level of the arcuate nucleus. These results indicate that [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 cross the blood-brain barrier and concentrate in an area of the hypothalamus known to regulate energy balance and glucose homeostasis. Most noteworthy is the localization of [D-Leu-4]-OB3 immunoreactivity within the hypothalamus of DIO mice via a conduit that is closed to leptin in this rodent model, and in most cases of human obesity. Together with our previous studies describing the effects of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on energy balance, glucose regulation, and signal transduction pathway activation, these findings are consistent with a central mechanism of action for these synthetic peptide leptin mimetics, and suggest their potential usefulness in the management of leptin-resistant obesity and type 2 diabetes in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. File list: Unc.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.10.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.10.AllAg.Olfactory_epithelium.bed ...

  6. File list: Unc.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.20.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.20.AllAg.Olfactory_epithelium.bed ...

  7. File list: Unc.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.05.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.05.AllAg.Olfactory_epithelium.bed ...

  8. An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium.

    Science.gov (United States)

    Droguett, Karla; Rios, Mariana; Carreño, Daniela V; Navarrete, Camilo; Fuentes, Christian; Villalón, Manuel; Barrera, Nelson P

    2017-07-15

    Extracellular ATP, in association with [Ca 2+ ] i regulation, is required to maintain basal ciliary beat frequency. Increasing extracellular ATP levels increases ciliary beating in airway epithelial cells, maintaining a sustained response by inducing the release of additional ATP. Extracellular ATP levels in the millimolar range, previously associated with pathophysiological conditions of the airway epithelium, produce a transient arrest of ciliary activity. The regulation of ciliary beat frequency is dependent on ATP release by hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of which may even stop ciliary movement. The force exerted by cilia, measured by atomic force microscopy, is reduced following extracellular ATP hydrolysis. This result complements the current understanding of the ciliary beating regulatory mechanism, with special relevance to inflammatory diseases of the airway epithelium that affect mucociliary clearance. Extracellular nucleotides, including ATP, are locally released by the airway epithelium and stimulate ciliary activity in a [Ca 2+ ] i -dependent manner after mechanical stimulation of ciliated cells. However, it is unclear whether the ATP released is involved in regulating basal ciliary activity and mediating changes in ciliary activity in response to chemical stimulation. In the present study, we evaluated ciliary beat frequency (CBF) and ciliary beating forces in primary cultures from mouse tracheal epithelium, using videomicroscopy and atomic force microscopy (AFM), respectively. Extracellular ATP levels and [Ca 2+ ] i were measured by luminometric and fluorimetric assays, respectively. Uptake of ethidium bromide was measured to evaluate hemichannel functionality. We show that hydrolysis of constitutive extracellular ATP levels with apyrase (50 U ml -1 ) reduced basal CBF by 45% and ciliary force by 67%. The apyrase effect on CBF was potentiated by carbenoxolone, a hemichannel inhibitor, and oxidized ATP, an

  9. Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*

    Science.gov (United States)

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

    2013-01-01

    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. PMID:23950179

  10. Mouse adhalin

    DEFF Research Database (Denmark)

    Liu, L; Vachon, P H; Kuang, W

    1997-01-01

    . To analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin...... was specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation...

  11. EP3 receptors inhibit antidiuretic-hormone-dependent sodium transport across frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Nielsen, Robert

    1999-01-01

    Antidiuretic hormone; tight epithelium; prostaglandin receptors; sulprostone; misoprostol; cAMP; cellular Ca2+......Antidiuretic hormone; tight epithelium; prostaglandin receptors; sulprostone; misoprostol; cAMP; cellular Ca2+...

  12. Ultraviolet induced lysosome activity in corneal epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, A.P.

    1980-01-01

    A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm/sup -2/ to 10.000 Jm/sup -2/ and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm/sup -2/ and lens threshold (Hsub(L)) was 7.500 Jm/sup -2/. The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared.

  13. Ultraviolet induced lysosome activity in corneal epithelium

    International Nuclear Information System (INIS)

    Cullen, A.P.

    1980-01-01

    A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm -2 to 10.000 Jm -2 and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm -2 and lens threshold (Hsub(L)) was 7.500 Jm -2 . The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared. (orig.) [de

  14. Changes in the Adult Vertebrate Auditory Sensory Epithelium After Trauma

    Science.gov (United States)

    Oesterle, Elizabeth C.

    2012-01-01

    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. PMID:23178236

  15. Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.

    Directory of Open Access Journals (Sweden)

    Masami Watabe-Rudolph

    Full Text Available Atrophy of the olfactory epithelium (OE associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc(-/- with short telomeres compared to wild type mice (mTerc(+/+ with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc(-/- mice compared to mTerc(+/+ mice. Seven days after chemical induced damage, G3 mTerc(-/- mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc(+/+ mice (p = 0.031. Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21 rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people.

  16. A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

    Science.gov (United States)

    Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

    2017-10-01

    Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Valérie Fontaine

    Full Text Available The accumulation of N-retinylidene-N-retinylethanolamine (A2E, a toxic by-product of the visual pigment cycle in the retinal pigment epithelium (RPE is a major cause of visual impairment in the elderly. Photooxidation of A2E results in retinal pigment epithelium degeneration followed by that of associated photoreceptors. Present treatments rely on nutrient supplementation with antioxidants. 9'-cis-Norbixin (a natural diapocarotenoid, 97% purity was prepared from Bixa orellana seeds. It was first evaluated in primary cultures of porcine retinal pigment epithelium cells challenged with A2E and illuminated with blue light, and it provided an improved photo-protection as compared with lutein or zeaxanthin. In Abca4-/- Rdh8-/- mice (a model of dry AMD, intravitreally-injected norbixin maintained the electroretinogram and protected photoreceptors against light damage. In a standard rat blue-light model of photodamage, norbixin was at least equally as active as phenyl-N-tert-butylnitrone, a free radical spin-trap. Chronic experiments performed with Abca4-/- Rdh8-/- mice treated orally for 3 months with norbixin showed a reduced A2E accumulation in the retina. Norbixin appears promising for developing an oral treatment of macular degeneration. A drug candidate (BIO201 with 9'-cis-norbixin as the active principle ingredient is under development, and its potential will be assessed in a forthcoming clinical trial.

  18. Oral Cancer

    Science.gov (United States)

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  19. Cyclosporine a inhibits apoptosis of rat gingival epithelium.

    Science.gov (United States)

    Ma, Su; Liu, Peihong; Li, Yanwu; Hou, Lin; Chen, Li; Qin, Chunlin

    2014-08-01

    The use of cyclosporine A (CsA) induces hyperplasia of the gingival epithelium in a site-specific response manner, but the molecular mechanism via which the lesion occurs is unclear. The present research aims to investigate the site-specific effect of CsA on the apoptosis of gingival epithelium associated with gingival hyperplasia. Forty Wistar rats were divided into CsA-treated and non-treated groups. Paraffin-embedded sections of mandibular first molars were selected for hematoxylin and eosin staining, immunohistochemistry analyses of bcl-2 and caspase-3, and the staining of terminal deoxynucleotidyl transfer-mediated dUTP nick-end labeling (TUNEL). The area of the whole gingival epithelium and the length of rete pegs were measured, and the number of bcl-2- and caspase-3-positive cells in the longest rete peg were counted. The analysis of variance for factorial designs and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. In CsA-treated rats, bcl-2 expression was significantly upregulated, whereas caspase-3 expression was downregulated, along with a reduced number of TUNEL-positive cells. The site-specific distribution of bcl-2 was consistent with the site-specific hyperplasia of the gingival epithelium in CsA-treated rats. CsA inhibited gingival epithelial apoptosis via the mitochondrial pathway and common pathway. The antiapoptotic protein bcl-2 might play a critical role in the pathogenesis of the site-specific hyperplasia of gingival epithelium induced by CsA. There were mechanistic differences in the regulation of apoptosis for cells in the attached gingival epithelium, free gingival epithelium, and junctional epithelium.

  20. Biological and genetic properties of the p53 null preneoplastic mammary epithelium

    Science.gov (United States)

    Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

    2002-01-01

    The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

  1. Growth of intestinal epithelium in organ culture is dependent on EGF signalling

    International Nuclear Information System (INIS)

    Abud, Helen E.; Watson, Nadine; Heath, Joan K.

    2005-01-01

    Differentiation of endoderm into intestinal epithelium is initiated at E13.5 of mouse development when there are significant changes in morphology resulting in the conversion of undifferentiated stratified epithelium into a mature epithelial monolayer. Here we demonstrate that monolayer formation is associated with the selective apoptosis of superficial cells lining the lumen while cell proliferation is progressively restricted to cells adjacent to the basement membrane. We describe an innovative embryonic gut culture system that maintains the three-dimensional architecture of gut and in which these processes are recapitulated in vitro. Explants taken from specific regions of the gut and placed into organ culture develop and express molecular markers (Cdx1, Cdx2 and A33 antigen) in the same spatial and temporal pattern observed in vivo indicating that regional specification is maintained. Inhibition of the epidermal growth factor receptor (EGFR) tyrosine kinase using the specific inhibitor AG1478 significantly reduced the proliferation and survival of cells within the epithelial cell layer of cultured gut explants. This demonstrates an essential role for the EGF signalling pathway during the early stages of intestinal development

  2. Age- and Gene-Dosage–Dependent Cre-Induced Abnormalities in the Retinal Pigment Epithelium

    Science.gov (United States)

    He, Lizhi; Marioutina, Mariya; Dunaief, Joshua L.; Marneros, Alexander G.

    2015-01-01

    To conditionally inactivate genes in the retinal pigment epithelium (RPE) transgenic mouse strains have been developed, in which Cre recombinase (Cre) expression is driven by an RPE-specific gene promoter. The RPE is a quiescent epithelium, and continuous expression of Cre could affect its function. Here, we tested the hypothesis that continuous postnatal Cre expression in the RPE may lead to cellular abnormalities, which may depend on both age and Cre gene dosage. We therefore examined the eyes of homozygous and heterozygous VMD2-Cre mice at various ages. In VMD2-Cre heterozygous mice variable progressive age-dependent RPE abnormalities were noticed, including attenuation of phalloidin and cytoplasmic active β-catenin staining, reduced cell size, and loss of the typical honeycomb pattern of RPE morphology in those RPE cells that stained for Cre. These morphological RPE abnormalities were not noticed in Cre-negative RPE cells in VMD2-Cre or age-matched control mice. In addition, an abnormal number and morphology of cell nuclei were noticed in a subset of Cre-expressing RPE cells in aged heterozygous VMD2-Cre mice, whereas more severe nuclear abnormalities were observed already in young homozygous VMD2-Cre mice. Thus, continuous postnatal expression of Cre causes abnormalities in the RPE in an age- and Cre gene dosage-dependent manner, which needs to be considered in the interpretation of gene targeting studies in the RPE. PMID:24854863

  3. Integrins beta 5, beta 3 and alpha v are apically distributed in endometrial epithelium.

    Science.gov (United States)

    Aplin, J D; Spanswick, C; Behzad, F; Kimber, S J; Vićovac, L

    1996-07-01

    Several adhesion molecules have been shown to occur at the surface of endometrial cells. One of these is the integrin alpha v subunit which associates with various beta chains including beta 5. We demonstrate the presence of integrin beta 5 polypeptide in human endometrial epithelial cells throughout the menstrual cycle using immunocytochemistry with monospecific antibodies, and at the mRNA level by thermal amplification from endometrial cDNA. Integrin beta 5 is also found in a population of bone marrow-derived cells. A notable feature of the distribution of the beta 5 subunit in the glandular and luminal epithelium is its apical localization, which may suggest an involvement in implantation. However, no evidence was found for regulated expression of epithelial beta 5. In mouse, the beta 5 subunit is found at both the apical and basal surface of epithelial cells and expression is essentially oestrous cycle-independent. Comparisons are made in both species with the distribution of the alpha v and beta 3 subunits which also localize to the apical epithelium.

  4. Quantification of oral palatine Langerhans cells in HIV/AIDS associated oral Kaposi sarcoma with and without oral candidiasis.

    Science.gov (United States)

    Jivan, Vibha; Meer, Shabnum

    2016-01-01

    Langerhans cells (LCs) are effective antigen-presenting cells that function as "custodians" of mucosa, modifying the immune system to pathogen entry, and tolerance to self-antigen and commensal microbes. A reduction in number of LCs in human immunodeficiency virus (HIV)-positive individuals may predispose to local mucosal infections. To quantitatively determine the number of oral mucosal LCs in HIV/acquired immunodeficiency syndrome HIV/acquired immunodeficiency syndrome (AIDS) associated oral Kaposi sarcoma (KS) with/without oral candidiasis (OC) and to define in situ interrelationships between the cells, OC, and HIV infection. Thirty-two periodic acid-Schiff. (PAS) stained histologic sections of palatal HIV/AIDS associated KS with intact oral epithelium were examined for Candida and divided into two groups: . (1) KS coinfected with Candida and. (2) KS noninfected with Candida. Sections were immunohistochemically stained with CD1a. The standard length of surface epithelium was measured and number of positively stained LCs counted per unit length. Control cases included non-Candida infected palatal mucosa overlying pleomorphic adenoma. (PA) and oral mucosa infected with Candida in otherwise healthy individuals. LC number per unit length of surface epithelium was statistically significantly greatest in uninfected PA mucosa and lowest in KS coinfected with Candida (P = 0.0001). A statistically significant difference was also noted between uninfected PA mucosa and non-Candida infected KS (P = 0.0014), in KS coinfected with Candida and non-infected KS (P = 0.0035), between OC and PA (P = 0.0001), and OC and KS coinfected with Candida (P = 0.0247). LC numbers are significantly reduced in oral tissues of HIV/AIDS infected patients by Candida infection when compared to oral tissues without.

  5. Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death

    Directory of Open Access Journals (Sweden)

    Rodrigo Meléndez García

    2016-05-01

    Full Text Available The identification of pathways necessary for retinal pigment epithelium (RPE function is fundamental to uncover therapies for blindness. Prolactin (PRL receptors are expressed in the retina, but nothing is known about the role of PRL in RPE. Using the adult RPE 19 (ARPE-19 human cell line and mouse RPE, we identified the presence of PRL receptors and demonstrated that PRL is necessary for RPE cell survival via anti-apoptotic and antioxidant actions. PRL promotes the antioxidant capacity of ARPE-19 cells by reducing glutathione. It also blocks the hydrogen peroxide-induced increase in deacetylase sirtuin 2 (SIRT2 expression, which inhibits the TRPM2-mediated intracellular Ca2+ rise associated with reduced survival under oxidant conditions. RPE from PRL receptor-null (prlr−/− mice showed increased levels of oxidative stress, Sirt2 expression and apoptosis, effects that were exacerbated in animals with advancing age. These observations identify PRL as a regulator of RPE homeostasis.

  6. [Effect of topical application of a recombinant adenovirus carrying promyelocytic leukemia gene in a psoriasis-like mouse model].

    Science.gov (United States)

    Wang, Qiongyu; Zhang, Aijun; Ma, Huiqun; Wang, Shijie; Ma, Yunyun; Zou, Xingwei; Li, Ruilian

    2013-03-01

    To investigate the effects of topical treatment with adenovirus-mediated promyelocytic leukemia gene (PML) gene in a psoriasis-like mouse model. The effect of adenovirus-mediated PML gene on the granular layer of mouse tail scale epidermis and epithelial mitosis were observed on longitudinal histological sections prepared from the tail skin and vaginal epithelium of the mice. Adenovirus-mediated PML gene significantly inhibited mitosis of mouse vaginal epithelial cells and promoted the formation of granular layer in mouse tail scale epidermis. The therapeutic effect of PML gene in the psoriasis-like mouse model may be associated with increased granular cells and suppressed epidemic cell proliferation.

  7. Ultrastructural study on the embryonic development of the orthokeratinized epithelium and its cornified layer (lingual nail) on the ventral surface of the lingual apex in the domestic duck (Anas platyrhynchos f. domestica).

    Science.gov (United States)

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

    2018-02-01

    The lingual nail as the cornified layer of the orthokeratinized epithelium in birds is responsible for the collection of solid food by pecking. The aim of the present study is to determine the manner of orthokeratinized epithelium development and assess the degree of readiness of the epithelium to fulfill its mechanical function at hatching. Three developmental phases are distinguished, i.e. embryonic, transformation and pre-hatching stage. In the embryonic stage lasting until day 13 of incubation the epithelium is composed of several layers of undifferentiated cells. During the transformation stage, from day 14 to 20 of incubation, the epithelium becomes differentiated to form three layers. A characteristic feature is the formation of osmophilic granules in the superficial layer, referred to as periderm granules. Until the pre-hatching stage the fibrous cytoskeleton of epithelial cells and an impermeable epithelial barrier are gradually developed. In the pre-hatching stage, a cornified lingual nail is formed, while the periderm is exfoliated. At hatching the orthokeratinized epithelium and lingual nail are fully developed and ready to perform feeding activities. The presence of periderm, similarly as in the epidermis, indicates the ectodermal derivation of the oral cavity epithelium. Moreover, occurrence of osmophilic granules may be considered as evidence for the phylogenetic affinity of birds and reptiles. Copyright © 2018 Elsevier GmbH. All rights reserved.

  8. Prevalence of ciliated epithelium in apical periodontitis lesions.

    Science.gov (United States)

    Ricucci, Domenico; Loghin, Simona; Siqueira, José F; Abdelsayed, Rafik A

    2014-04-01

    This article reports on the morphologic features and the frequency of ciliated epithelium in apical cysts and discusses its origin. The study material consisted of 167 human apical periodontitis lesions obtained consecutively from patients presenting for treatment during a period of 12 years in a dental practice operated by one of the authors. All of the lesions were obtained still attached to the root apices of teeth with untreated (93 lesions) or treated canals (74 lesions). The former were obtained by extraction and the latter by extraction or apical surgery. Specimens were processed for histopathologic and histobacteriologic analyses. Lesions were classified, and the type of epithelium, if present, was recorded. Of the lesions analyzed, 49 (29%) were diagnosed as cysts. Of these, 26 (53%) were found in untreated teeth, and 23 (47%) related to root canal-treated teeth. Ciliated columnar epithelium was observed partially or completely lining the cyst wall in 4 cysts, and all of them occurred in untreated maxillary molars. Three of these lesions were categorized as pocket cysts, and the other was a true cyst. Ciliated columnar epithelium-lined cysts corresponded to approximately 2% of the apical periodontitis lesions and 8% of the cysts of endodontic origin in the population studied. This epithelium is highly likely to have a sinus origin in the majority of cases. However, the possibility of prosoplasia or upgraded differentiation into ciliated epithelium from the typical cystic lining squamous epithelium may also be considered. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  9. Hair cell regeneration in the avian auditory epithelium.

    Science.gov (United States)

    Stone, Jennifer S; Cotanche, Douglas A

    2007-01-01

    Regeneration of sensory hair cells in the mature avian inner ear was first described just over 20 years ago. Since then, it has been shown that many other non-mammalian species either continually produce new hair cells or regenerate them in response to trauma. However, mammals exhibit limited hair cell regeneration, particularly in the auditory epithelium. In birds and other non-mammals, regenerated hair cells arise from adjacent non-sensory (supporting) cells. Hair cell regeneration was initially described as a proliferative response whereby supporting cells re-enter the mitotic cycle, forming daughter cells that differentiate into either hair cells or supporting cells and thereby restore cytoarchitecture and function in the sensory epithelium. However, further analyses of the avian auditory epithelium (and amphibian vestibular epithelium) revealed a second regenerative mechanism, direct transdifferentiation, during which supporting cells change their gene expression and convert into hair cells without dividing. In the chicken auditory epithelium, these two distinct mechanisms show unique spatial and temporal patterns, suggesting they are differentially regulated. Current efforts are aimed at identifying signals that maintain supporting cells in a quiescent state or direct them to undergo direct transdifferentiation or cell division. Here, we review current knowledge about supporting cell properties and discuss candidate signaling molecules for regulating supporting cell behavior, in quiescence and after damage. While significant advances have been made in understanding regeneration in non-mammals over the last 20 years, we have yet to determine why the mammalian auditory epithelium lacks the ability to regenerate hair cells spontaneously and whether it is even capable of significant regeneration under additional circumstances. The continued study of mechanisms controlling regeneration in the avian auditory epithelium may lead to strategies for inducing

  10. Comparison of transepithelial corneal crosslinking with epithelium-off crosslinking (epithelium-off CXL in adult Pakistani population with progressive keratoconus

    Directory of Open Access Journals (Sweden)

    Bushra Akbar

    2017-01-01

    CONCLUSION: Transepithelial CXL is not recommended to be replaced completely by standard epithelium-off CXL due to continued ectatic progression in 25% of cases. However, thin corneas, unfit for standard epithelium-off CXL, can benefit from transepithelial CXL.

  11. Increase of corneal epithelium cell radioresistance during regeneration

    International Nuclear Information System (INIS)

    Popova, M.F.; Bulyakova, N.V.; Azarova, V.S.

    1985-01-01

    A comparative study of the radiosensitivity of the normal and regenerating cornea epithelium of C 57 Bl mice was performed on the cellular level, the duration of the cell cycle being taken into account. Criteria of radiation injuries were the number of chromosome aberrations, mitotic index and duration of mitotic block. The anterior part of the head was irradiated singly with 1.75, 3.5 or 7.0 Gy and also repeatedly 3.5 + 3.5 at a 24-hours interval. The corneas were fixed 2, 4, 6, 12, 24, 48, 72 and 96 hours after irradiation. In all cases of irradiated mice the regenerating epithelium showed a shorter mitotic block and significantly lower cytogenetic injury as compared with the controls. Effects of fractionated irradiation were only shown in the regenerating epithelium. The results obtained indicate that regenerating epithelium cells of the cornea are significantly more radioresistant than normal epithelium due to activation of post-radiation recovery, and also, possibly, due to an increase in the content of endogenous radioprotectors. (author)

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

    Science.gov (United States)

    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.

  13. Respiratory Epithelium Lined Cyst of the Maxilla: Differential Diagnosis

    Directory of Open Access Journals (Sweden)

    C. P. Martinelli-Kläy

    2017-01-01

    Full Text Available Maxillary cysts, including the cysts lined by respiratory epithelium, can present a diagnostic challenge. We report an unusual case of a maxillary cyst on an endodontically treated tooth #16, in which the cavity was totally lined by a respiratory epithelium. The patient, a 35-year-old male, presented with a generalized chronic periodontitis and complained of a pain in the tooth #16 region. A periodontal pocket extending to the root apices with pus coming out from the gingival was found. A combined endodontic periodontal was observed on a panoramic radiography. CBCT-scan revealed a well-circumscribed radiolucent lesion at the apices of the distobuccal root of the 16. A communication with the right maxillary sinus cavity and a maxillary and ethmoidal sinusitis were also observed. The lesion was removed and histological examination revealed a cyst lined exclusively by respiratory epithelium. Ciliated and rare mucous cells were also observed. The diagnosis could evoke a surgical ciliated cyst mimicking the radicular cyst but the patient has no previous history of trauma or surgery in the maxillofacial region. It could also be an unusual radicular cyst in which the stratified squamous epithelium was destroyed by inflammation and replaced by a respiratory epithelium of the maxillary sinus.

  14. Gene expression underlying enhanced, steroid-dependent auditory sensitivity of hair cell epithelium in a vocal fish.

    Science.gov (United States)

    Fergus, Daniel J; Feng, Ni Y; Bass, Andrew H

    2015-10-14

    Successful animal communication depends on a receiver's ability to detect a sender's signal. Exemplars of adaptive sender-receiver coupling include acoustic communication, often important in the context of seasonal reproduction. During the reproductive summer season, both male and female midshipman fish (Porichthys notatus) exhibit similar increases in the steroid-dependent frequency sensitivity of the saccule, the main auditory division of the inner ear. This form of auditory plasticity enhances detection of the higher frequency components of the multi-harmonic, long-duration advertisement calls produced repetitively by males during summer nights of peak vocal and spawning activity. The molecular basis of this seasonal auditory plasticity has not been fully resolved. Here, we utilize an unbiased transcriptomic RNA sequencing approach to identify differentially expressed transcripts within the saccule's hair cell epithelium of reproductive summer and non-reproductive winter fish. We assembled 74,027 unique transcripts from our saccular epithelial sequence reads. Of these, 6.4 % and 3.0 % were upregulated in the reproductive and non-reproductive saccular epithelium, respectively. Gene ontology (GO) term enrichment analyses of the differentially expressed transcripts showed that the reproductive saccular epithelium was transcriptionally, translationally, and metabolically more active than the non-reproductive epithelium. Furthermore, the expression of a specific suite of candidate genes, including ion channels and components of steroid-signaling pathways, was upregulated in the reproductive compared to the non-reproductive saccular epithelium. We found reported auditory functions for 14 candidate genes upregulated in the reproductive midshipman saccular epithelium, 8 of which are enriched in mouse hair cells, validating their hair cell-specific functions across vertebrates. We identified a suite of differentially expressed genes belonging to neurotransmission and

  15. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Thalaimalai Saravanan

    2015-01-01

    Full Text Available Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  16. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

  17. The Retinal Pigment Epithelium: a Convenient Source of New Photoreceptor cells?

    Directory of Open Access Journals (Sweden)

    Shu-Zhen Wang

    2014-01-01

    Full Text Available Recent success in restoring visual function through photoreceptor replacement in mouse models of photoreceptor degeneration intensifies the need to generate or regenerate photoreceptor cells for the ultimate goal of using cell replacement therapy for blindness caused by photoreceptor degeneration. Current research on deriving new photoreceptors for replacement, as regenerative medicine in general, focuses on the use of embryonic stem cells and induced pluripotent stem (iPS cells to generate transplantable cells. Nonetheless, naturally occurring regeneration, such as wound healing, involves awakening cells at or near a wound site to produce new cells needed to heal the wound. Here we discuss the possibility of tweaking an ocular tissue, the retinal pigment epithelium (RPE, to produce photoreceptor cells in situ in the eye. Unlike the neural retina, the RPE in adult mammals maintains cell proliferation capability. Furthermore, progeny cells from RPE proliferation may differentiate into cells other than RPE. The combination of proliferation and plasticity opens a question of whether they could be channeled by a regulatory gene with pro-photoreceptor activity towards photoreceptor production. Studies using embryonic chick and transgenic mouse showed that indeed photoreceptor-like cells were produced in culture and in vivo in the eye using genedirected reprogramming of RPE cells, supporting the feasibility of using the RPE as a convenient source of new photoreceptor cells for in situ retinal repair without involving cell transplantation.

  18. The distribution of free calcium ions in the cholesteatoma epithelium

    DEFF Research Database (Denmark)

    Svane-Knudsen, Viggo; Rasmussen, Gurli; Ottosen, Peter D

    2005-01-01

    The distribution of free calcium ions in normal skin and cholesteatoma epithelium was investigated using the oxalate precipitation method. In agreement with previous observations, we could demonstrate a calcium ion gradient in normal epidermis where the cells in stratum basale and spinosum reside...... appeared where oblong accumulations of free calcium ions were found basally in the stratum. These findings provide evidence that fluctuations in epidermal calcium in cholesteatoma epithelium may underlie the abnormal desquamation, may contribute to the formation of an abnormal permeability barrier and may...

  19. Oral cancer

    Science.gov (United States)

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... National Cancer Institute. PDQ lip and oral cavity cancer ... September 25, 2015. www.cancer.gov/types/head-and-neck/hp/lip- ...

  20. Oral Ketamine

    African Journals Online (AJOL)

    Oral Ketamine: A Four-years Experience in ... Key words: Oral Ketamine, Premedication and Oncology. .... form of a letter published in 19835. .... Acta. Anaesthesiol Scandinavica, 1998; 42: 750-758. 4. Murray P. Substitution of another opioid ...

  1. Olfaction in three genetic and two MPTP-induced Parkinson's disease mouse models.

    Directory of Open Access Journals (Sweden)

    Stefan Kurtenbach

    Full Text Available Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson's disease (PD mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs and an olfactory behavior test (cookie-finding test. We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.

  2. The toxicity of silver and silica nanoparticles in comparable human and mouse cell lines

    DEFF Research Database (Denmark)

    Foldbjerg, Rasmus; Beer, Christiane; Sutherland, Duncan S

    The toxicity of silica (SiO2) and PVP-coated silver (Ag) nanoparticles (NPs) was investigated in two pairs of human or mouse cell lines originating from lung epithelium (A549 and ASB-XIV) and macrophages (THP-1 and J744A.1). Both NPs were characterized in H2O and cell media and demonstrated to be...

  3. Scrapie infectivity is quickly cleared in tissues of orally-infected farmed fish

    Directory of Open Access Journals (Sweden)

    Faoro Franco

    2006-06-01

    Full Text Available Abstract Background Scrapie and bovine spongiform encephalopathy (BSE belongs to the group of animal transmissible spongiform encephalopathy (TSE. BSE epidemic in the UK and elsewhere in Europe has been linked to the use of bovine meat and bone meals (MBM in the feeding of cattle. There is concern that pigs, poultry and fish bred for human consumption and fed with infected MBM would eventually develop BSE or carry residual infectivity without disease. Although there has been no evidence of infection in these species, experimental data on the susceptibility to the BSE agent of farm animals other than sheep and cow are limited only to pigs and domestic chicken. In the framework of a EU-granted project we have challenged two species of fish largely used in human food consumption, rainbow trout (Oncorhynchus mykiss and turbot (Scophthalmus maximus, with a mouse-adapted TSE strain (scrapie 139A, to assess the risk related to oral consumption of TSE contaminated food. In trout, we also checked the "in vitro" ability of the pathological isoform of the mouse prion protein (PrPSc to cross the intestinal epithelium when added to the mucosal side of everted intestine. Results Fish challenged with a large amount of scrapie mouse brain homogenate by either oral or parenteral routes, showed the ability to clear the majority of infectivity load. None of the fish tissues taken at different time points after oral or parenteral inoculation was able to provoke scrapie disease after intracerebral inoculation in recipient mice. However, a few recipient mice were positive for PrPSc and spongiform lesions in the brain. We also showed a specific binding of PrPSc to the mucosal side of fish intestine in the absence of an active uptake of the prion protein through the intestinal wall. Conclusion These results indicate that scrapie 139A, and possibly BSE, is quickly removed from fish tissues despite evidence of a prion like protein in fish and of a specific binding of Pr

  4. Effects of fission neutrons and X-rays on the epithelium of the mouse stomach

    International Nuclear Information System (INIS)

    Kingma-ter Haar, J.M.

    1982-07-01

    A quantitative study is presented of the effects of whole-body irradiation on the stomach of mice. Two types of ionizing radiation were compared - fast fission neutrons of 1.0 MeV mean energy and 300 kVp X-rays. The effects on the functional cell populations, on gastric secretion and on gastric stem cell populations were studied. These effects have been investigated a) for a neutron dose in the lethal dose-range of 4.0 Gy as a function of time and b) at a post-irradiation interval of 3 weeks as a function of neutron and X-ray dose. (Auth.)

  5. Role of the Stem Cell Niche in Hormone-induced Tumorigenesis in Fetal Mouse Mammary Epithelium

    National Research Council Canada - National Science Library

    Chepko, Gloria; Hilakivi-Clarke, Leena

    2006-01-01

    Develop an immunohistochemical method for identifying stem cells and stem cell niches, and to use this to determine if in utero estrogenic overstimulation causes changes in the number of stem cells or their niches...

  6. TRPV3, a thermosensitive channel is expressed in mouse distal colon epithelium

    International Nuclear Information System (INIS)

    Ueda, Takashi; Yamada, Takahiro; Ugawa, Shinya; Ishida, Yusuke; Shimada, Shoichi

    2009-01-01

    The thermo-transient receptor potential (thermoTRP) subfamily is composed of channels that are important in nociception and thermo-sensing. Here, we show a selective expression of TRPV3 channel in the distal colon throughout the gastrointestinal tract. Expression analyses clearly revealed that TRPV3 mRNA and proteins were expressed in the superficial epithelial cells of the distal colon, but not in those of the stomach, duodenum or proximal colon. In a subset of primary epithelial cells cultured from the distal colon, carvacrol, an agonist for TRPV3, elevated cytosolic Ca 2+ concentration in a concentration-dependent manner. This response was inhibited by ruthenium red, a TRPV channel antagonist. Organotypic culture supported that the carvacrol-responsive cells were present in superficial epithelial cells. Moreover, application of carvacrol evoked ATP release in primary colonic epithelial cells. We conclude that TRPV3 is present in absorptive cells in the distal colon and may be involved in a variety of cellular functions.

  7. Hedgehog Signaling and Maintenance of Homeostasis in the Intestinal Epithelium

    NARCIS (Netherlands)

    Büller, Nikè V. J. A.; Rosekrans, Sanne L.; Westerlund, Jessica; van den Brink, Gijs R.

    2012-01-01

    Homeostasis of the rapidly renewing intestinal epithelium depends on a balance between cell proliferation and loss. Indian hedgehog (Ihh) acts as a negative feedback signal in this dynamic equilibrium. We discuss recent evidence that Ihh may be one of the key epithelial signals that indicates

  8. Coelomic epithelium-derived cells in visceral morphogenesis.

    Science.gov (United States)

    Ariza, Laura; Carmona, Rita; Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón

    2016-03-01

    Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. © 2015 Wiley Periodicals, Inc.

  9. Relative permeability of the endothelium and epithelium of rabbit lungs

    International Nuclear Information System (INIS)

    Effros, R.M.; Mason, G.R.; Silverman, P.; Hukkanen, J.

    1986-01-01

    Electron micrographic studies of lungs suggest that the epithelial cells are more tightly joined than the underlying endothelium, and macromolecules penetrate the endothelium more readily than the epithelium. Comparisons of epithelial and endothelial permeability to small molecules have been based upon the relative rates at which solutes traverse the alveolar-capillary barrier in fluid filled lungs and those at which they equilibrate across the capillaries in air-filled lungs. Because the former process is much slower than the latter, it has been concluded that the epithelium is less permeable to small solutes than the endothelium. However this difference may be related to inadequate access of solutes to airway surfaces. In this study, solute losses from the vascular space were compared to those from the airspace in perfused, fluid-filled rabbit lungs. 36 Cl - and 125 I - were lost from air-spaces almost twice as rapidly as 22 Na + . In contrast, the endothelium is equally permeable to 22 Na + and these anions. Loss of 3 H-mannitol from the perfusate resembled that of 22 Na + for about 30 minutes, after which diffusion of 3 H-mannitol into the tissue nearly ceased. These observations suggest that the epithelium is more permselective than the endothelium. By resisting solute and water transport, the epithelium tends to prevent alveolar flooding and confines edema to the interstitium, where it is less likely to interfere with gas exchange

  10. Wnt signaling in the intestinal epithelium: from endoderm to cancer.

    NARCIS (Netherlands)

    Gregorieff, A.; Clevers, J.C.

    2005-01-01

    The Wnt pathway controls cell fate during embryonic development. It also persists as a key regulator of homeostasis in adult self-renewing tissues. In these tissues, mutational deregulation of the Wnt cascade is closely associated with malignant transformation. The intestinal epithelium represents

  11. Structure and development of the saccular sensory epithelium in ...

    African Journals Online (AJOL)

    Structure and development of the saccular sensory epithelium in relation to otolith growth in the perch Perca fluviatilis (Telostei) ... Electron microscopy indicated: 1) The apical surface of each hair cell is covered with a ciliary bundle which varies in length in different epithelial regions. Each bundle is formed from a long ...

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

    Science.gov (United States)

    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.

  13. Adhesion of Porphyromonas gingivalis serotypes to pocket epithelium

    NARCIS (Netherlands)

    Dierickx, K; Pauwels, M; Laine, ML; Van Eldere, J; Cassiman, JJ; van Winkelhoff, AJ; van Steenberghe, D; Quirynen, M

    Background: Porphyromonas gingivalis, a key pathogen in periodontitis, is able to adhere to and invade the pocket epithelium. Different capsular antigens of P gingivalis have been identified (K-serotyping). These P gingivalis capsular types show differences in adhesion capacity to human cell lines

  14. Radioautographic DNA synthesis study on mice Mus musculus gingival epithelium

    International Nuclear Information System (INIS)

    Silveira Tarelho, Z.V. da; Hetem, S.

    1984-01-01

    The DNA-synthetizing cells frequency in the gingival epithelium basal layer of the first lower molar region in young and adult mice were studied. The 3H-thymidine and radioautography were used. The labeled cells frequency was determined by calculating their proportions. The data were statiscally analysed. (M.A.C.) [pt

  15. The ultrastructure of the midgut epithelium in millipedes (Myriapoda, Diplopoda)

    Czech Academy of Sciences Publication Activity Database

    Sosinka, A.; Rost-Roszkowska, M.M.; Vilímová, J.; Tajovský, Karel; Kszuk-Jendrysik, M.; Chajec, Ł.; Sonakowska, L.; Kamińska, K.; Hyra, M.; Poprawa, I.

    2014-01-01

    Roč. 43, č. 5 (2014), s. 477-492 ISSN 1467-8039 Institutional support: RVO:60077344 Keywords : digestive cells * midgut epithelium * millipedes * regenerative cells * secretory cells * ultrastructure Subject RIV: EG - Zoology Impact factor: 1.650, year: 2014

  16. Kinetics of corneal epithelium turnover in vivo. Studies of lovastatin

    International Nuclear Information System (INIS)

    Cenedella, R.J.; Fleschner, C.R.

    1990-01-01

    The authors developed a direct chemical approach for estimating the rate of turnover of the corneal epithelium in vivo. The method was used to examine the effects of lovastatin, a potent inhibitor of cholesterol biosynthesis, on proliferation and turnover of the epithelium. Corneal DNA was labeled by pulse injection (IP) of the rat with 3H-thymidine, and 3H-labeled DNA was recovered from peripheral and central corneas over the next 15 days. Only the epithelium became labeled, and the loss of label by cell desquamation began 3 days after injection. The loss of 3H-DNA from the cornea (peripheral plus central region) followed first-order kinetics. The half-life of the disappearance was about 3 days. The peripheral cornea became more highly labeled than the central cornea and began to lose 3H-DNA before the central cornea. These observations support the possibility of a higher mitotic rate in the peripheral region and the centripetal movement of a population of peripheral epithelial cells in the normal cornea. The half-lives of the disappearance of 3H-DNA from peripheral and central corneas measured between days 5 and 15 postinjection were identical, both at 3 days. Complete turnover of the corneal epithelium would, therefore, require about 2 weeks (4-5 half-lives). Treatment of the rat with lovastatin had no obvious effects upon the proliferation or turnover of the corneal epithelium. Although lovastatin inhibited corneal 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme of cholesterol synthesis, the cornea compensated by induction of this enzyme so that there was no net inhibition of cholesterol synthesis in the cornea

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

    Science.gov (United States)

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

  18. Aberrant activation of NF-κB signaling in mammary epithelium leads to abnormal growth and ductal carcinoma in situ

    International Nuclear Information System (INIS)

    Barham, Whitney; Chen, Lianyi; Tikhomirov, Oleg; Onishko, Halina; Gleaves, Linda; Stricker, Thomas P.; Blackwell, Timothy S.; Yull, Fiona E.

    2015-01-01

    Approximately 1 in 5 women diagnosed with breast cancer are considered to have in situ disease, most often termed ductal carcinoma in situ (DCIS). Though recognized as a risk factor for the development of more invasive cancer, it remains unclear what factors contribute to DCIS development. It has been shown that inflammation contributes to the progression of a variety of tumor types, and nuclear factor kappa B (NF-κB) is recognized as a master-regulator of inflammatory signaling. However, the contributions of NF-κB signaling to tumor initiation are less well understood. Aberrant up-regulation of NF-κB activity, either systemically or locally within the breast, could occur due to a variety of commonly experienced stimuli such as acute infection, obesity, or psychological stress. In this study, we seek to determine if activation of NF-κB in mammary epithelium could play a role in the formation of hyperplastic ductal lesions. Our studies utilize a doxycycline-inducible transgenic mouse model in which constitutively active IKKβ is expressed specifically in mammary epithelium. All previously published models of NF-κB modulation in the virgin mammary gland have been constitutive models, with transgene or knock-out present throughout the life and development of the animal. For the first time, we will induce activation at later time points after normal ducts have formed, thus being able to determine if NF-κB activation can promote pre-malignant changes in previously normal mammary epithelium. We found that even a short pulse of NF-κB activation could induce profound remodeling of mammary ductal structures. Short-term activation created hyperproliferative, enlarged ducts with filled lumens. Increased expression of inflammatory markers was concurrent with the down-regulation of hormone receptors and markers of epithelial differentiation. Furthermore, the oncoprotein mucin 1, known to be up-regulated in human and mouse DCIS, was over-expressed and mislocalized in the

  19. Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa

    DEFF Research Database (Denmark)

    Gao, Shan; Nielsen, Boye Schnack; Krogdahl, Annelise

    2010-01-01

    cells in oral carcinomas by immunohistochemistry, we found that PAI-1 was expressed in 18 of the 20 patients, mainly by cancer cells. Two showed PAI-1 positive stromal cells surrounding the tumor areas and five showed PAI-1 positive cells in tumor-adjacent normal epithelium. By real-time RT-PCR analysis......A high level of plasminogen activator inhibitor-1 (PAI-1 or SERPINE1) in tumor extracts is a marker of a poor prognosis in human cancers, including oral carcinomas. However, the mechanisms responsible for the upregulation of PAI-1 in cancers remain unclear. Investigating specific PAI-1 expressing...

  20. IMMUNOHISTOCHEMICAL ANALYSIS OF ORAL MUCOSA LEUKOPLAKIA

    Directory of Open Access Journals (Sweden)

    Yu. G. KOLENKO

    2016-06-01

    Full Text Available In recent years, substantial changes have occurred in the structure of oral mucosa diseases, in particular an increased ratio of precancerous diseases, so that an effective non-invasive detection of any sign of malignancy appears as an urgent and most actual task of dentistry. Aim: To study the proliferative activity of epithelial cells in Ki-67 antigenin patients with leukoplakia of the oral mucosa. Materials and method: A complex clinical and laboratory examination was performed on 155 patients with oral leukoplakia, who addressed the Operative Dentistry Department of the “A.A.Bogomolets” National Medical University of Kiev between 2010 and 2014. All patients have been subjected to a careful clinical examination, which included: dental anamnesis, visual inspection, oral examination and digital palpation of oral mucosa and tongue mucosa, biopsy of leukoplakia lesions for cytological and histological examination. Results: Histological evaluation of the material has been performed according to the WHO (2005 classification of leukoplakia. 10 (14% sites of unaltered mucosa, 10 (14% samples of hyperkeratosis without atypia, 14 (19% biopsy specimens of hyperkeratosis SIN1, 15 (21% – hyperkeratosis SIN2, 10 (14% - SIN3 and 13 (18% cases of squamous cell carcinoma were evidenced. Immunohistochemical investigation evidenced the presence of protein Ki-67 in the nuclei of epithelial cells. In the unmodified epithelium of the oral mucosa, all epithelial cells with stained nuclei are virtually located in the basal layer. Conclusion: Against the general increase of the proliferative activity of epithelial cells with increasing SIN, a characteristic distribution of proliferating cells in the thickness of the epithelium was revealed for each studied group, as follows: in the control group and in leukoplakia without atypia, immunopositive cells are located in the basal layer, in leukoplakia (SIN1, SIN2 and SIN3 – in parabasal position while, in squamous

  1. File list: InP.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: InP.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Oth.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  4. File list: Pol.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: InP.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: InP.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: NoD.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: ALL.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: DNS.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. Dynamics of Bovine Sperm Interaction with Epithelium Differ Between Oviductal Isthmus and Ampulla1

    Science.gov (United States)

    Ardon, Florencia; Markello, Ross D.; Hu, Lian; Deutsch, Zarah I.; Tung, Chih-Kuan; Wu, Mingming; Suarez, Susan S.

    2016-01-01

    In mammals, many sperm that reach the oviduct are held in a reservoir by binding to epithelium. To leave the reservoir, sperm detach from the epithelium; however, they may bind and detach again as they ascend into the ampulla toward oocytes. In order to elucidate the nature of binding interactions along the oviduct, we compared the effects of bursts of strong fluid flow (as would be caused by oviductal contractions), heparin, and hyperactivation on detachment of bovine sperm bound in vitro to epithelium on intact folds of isthmic and ampullar mucosa. Intact folds of oviductal mucosa were used to represent the strong attachments of epithelial cells to each other and to underlying connective tissue that exist in vivo. Effects of heparin on binding were tested because heparin binds to the Binder of SPerm (BSP) proteins that attach sperm to oviductal epithelium. Sperm bound by their heads to beating cilia on both isthmic and ampullar epithelia and could not be detached by strong bursts of fluid flow. Addition of heparin immediately detached sperm from isthmic epithelium but not ampullar epithelium. Addition of 4-aminopyridine immediately stimulated hyperactivation of sperm but did not detach them from isthmic or ampullar epithelium unless added with heparin. These observations indicate that the nature of binding of sperm to ampullar epithelium differs from that of binding to isthmic epithelium; specifically, sperm bound to isthmic epithelium can be detached by heparin alone, while sperm bound to ampullar epithelium requires both heparin and hyperactivation to detach from the epithelium. PMID:27605344

  12. File list: NoD.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  13. File list: ALL.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  14. File list: Pol.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  15. File list: His.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  16. File list: NoD.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  17. File list: ALL.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  18. File list: His.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  19. File list: His.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  20. File list: Oth.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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  1. File list: Oth.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: DNS.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Oth.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: NoD.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: His.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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    Full Text Available His.Oth.20.AllAg.Olfactory_epithelium mm9 Histone Others Olfactory epithelium SRX18...378533,SRX378536,SRX378534,SRX472910 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.20.AllAg.Olfactory_epithelium.bed ...

  6. File list: DNS.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.20.AllAg.Olfactory_epithelium mm9 DNase-seq Others Olfactory epithelium SRX...378537 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Oth.20.AllAg.Olfactory_epithelium.bed ...

  7. File list: Pol.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.05.AllAg.Olfactory_epithelium mm9 RNA polymerase Others Olfactory epithelium... SRX143827,SRX112963 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.05.AllAg.Olfactory_epithelium.bed ...

  8. Oral lichen planus: An update on pathogenesis and treatment

    Science.gov (United States)

    Lavanya, N; Jayanthi, P; Rao, Umadevi K; Ranganathan, K

    2011-01-01

    Oral lichen planus (OLP) is a chronic inflammatory disease that affects the mucus membrane of the oral cavity. It is a T-cell mediated autoimmune disease in which the cytotoxic CD8+ T cells trigger apoptosis of the basal cells of the oral epithelium. Several antigen-specific and nonspecific inflammatory mechanisms have been put forward to explain the accumulation and homing of CD8+ T cells subepithelially and the subsequent keratinocyte apoptosis. A wide spectrum of treatment modalities is available, from topical corticosteroids to laser ablation of the lesion. In this review, we discuss the various concepts in the pathogenesis and current treatment modalities of OLP. PMID:22529568

  9. Distinct functions and regulation of epithelial progesterone receptor in the mouse cervix, vagina, and uterus.

    Science.gov (United States)

    Mehta, Fabiola F; Son, Jieun; Hewitt, Sylvia C; Jang, Eunjung; Lydon, John P; Korach, Kenneth S; Chung, Sang-Hyuk

    2016-04-05

    While the function of progesterone receptor (PR) has been studied in the mouse vagina and uterus, its regulation and function in the cervix has not been described. We selectively deleted epithelial PR in the female reproductive tracts using the Cre/LoxP recombination system. We found that epithelial PR was required for induction of apoptosis and suppression of cell proliferation by progesterone (P4) in the cervical and vaginal epithelium. We also found that epithelial PR was dispensable for P4 to suppress apoptosis and proliferation in the uterine epithelium. PR is encoded by the Pgr gene, which is regulated by estrogen receptor α (ERα) in the female reproductive tracts. Using knock-in mouse models expressing ERα mutants, we determined that the DNA-binding domain (DBD) and AF2 domain of ERα were required for upregulation of Pgr in the cervix and vagina as well as the uterine stroma. The ERα AF1 domain was required for upregulation of Pgr in the vaginal stroma and epithelium and cervical epithelium, but not in the uterine and cervical stroma. ERα DBD, AF1, and AF2 were required for suppression of Pgr in the uterine epithelium, which was mediated by stromal ERα. Epithelial ERα was responsible for upregulation of epithelial Pgr in the cervix and vagina. Our results indicate that regulation and functions of epithelial PR are different in the cervix, vagina, and uterus.

  10. Polymeric nanocarriers for transport modulation across the pulmonary epithelium: dendrimers, polymeric nanoparticles, and their nanoblends.

    Science.gov (United States)

    Bharatwaj, Balaji; Dimovski, Radovan; Conti, Denise S; da Rocha, Sandro R P

    2014-05-01

    The purpose of this study was to (a) Determine the cellular transport and uptake of amine-terminated generation 3 (G3) poly(amido amine) (PAMAM) dendrimers across an in vitro model of the pulmonary epithelium, and the ability to modulate their transport by forming nanoblends of the dendrimers with biodegradable solid polymeric nanoparticles (NPs) and (b) to formulate dendrimer nanocarriers in portable oral inhalation devices and evaluate their aerosol characteristics. To that end, fluorescein isothiocyanate (FITC)-labeled G3 PAMAM dendrimer nanocarriers (DNCs) were synthesized, and also encapsulated within poly lactide-co-glycolide nanoparticles (NPs). Transport and uptake of both DNCs encapsulated within NPs (nanoblends) and unencapsulated DNCs were tracked across polarized monolayers of airway epithelial cells, Calu-3. DNCs were also formulated as core-shell microparticles in pressurized metered-dose inhalers (pMDIs) and their aerodynamic properties evaluated by Andersen cascade impaction. The apparent permeability of DNCs across the airway epithelial model was similar to that of a paracellular marker of comparable molar mass--order of 10(-7) cm s(-1). The transport and cellular internalization of the DNCs can be modulated by formulating them as nanoblends. The transport of the DNCs across the lung epithelium was completely suppressed within the time of the experiment (5 h) when formulated as blends. The encapsulation also prevents saturation of the cellular internalization profile. Nanoblending may be a potential strategy to modulate the rate of transport and cellular uptake of DNCs, and thus be used as a design strategy to achieve enhanced local or systemic drug delivery.

  11. Immunohistochemical expression of Notch signaling in the lining epithelium of periapical cysts.

    Science.gov (United States)

    Meliou, Eleni; Kerezoudis, Nikolaos; Tosios, Konstantinos; Lafkas, Daniel; Kiaris, Hippokratis

    2011-02-01

    In this study we evaluated the immunohistochemical expression of the receptors Notch 1 and Notch 2, the ligand Delta 1, and the transcription factors HES 1 and HES 5 in the epithelium of well-defined periapical cysts. Immunohistochemistry was carried out on 55 formalin-fixed and paraffin-embedded, well-defined periapical cysts with minimum inflammation, obtained from the archival tissue database of the Department of Oral Pathology and Surgery. Western blotting was performed to evaluate the specificity of the anti-Notch antibody and the expression of Notch signaling in 5 fresh-frozen periapical cysts. The levels of staining intensity were estimated by the performance of a semiautomated image analysis system. Descriptive statistic of mean values obtained by computerized image analysis method was performed. Immunostaining reaction of all Notch signaling components was observed in the cytoplasm and/or the cytoplasmic membrane in the majority of epithelial cells of periapical cysts. Nuclear staining was observed occasionally in all cases. Notch 2 showed strong staining in 52.83% of the cases, followed by Notch 1 (35.85%), HES 1 and HES 5 moderate staining in 72.73% and 57.69% of the cases, respectively, and Delta 1 weak staining in 58.33% of the cases. No statistical correlation was found between the antibodies and the sex or the age of the study group. Notch is an evolutionarily conserved signaling mechanism that regulates cell fate decisions during development and postnatal life in organisms as diverse as worms, flies, and humans. The present observations indicate that Notch pathway is active downstream in the lining epithelium of periapical cysts, suggesting an involvement of this pathway in periapical cyst growth and expansion. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  12. Hydrodynamics of stratified epithelium: Steady state and linearized dynamics

    Science.gov (United States)

    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.

  13. Nested Expression Domains for Odorant Receptors in Zebrafish Olfactory Epithelium

    Science.gov (United States)

    Weth, Franco; Nadler, Walter; Korsching, Sigrun

    1996-11-01

    The mapping of high-dimensional olfactory stimuli onto the two-dimensional surface of the nasal sensory epithelium constitutes the first step in the neuronal encoding of olfactory input. We have used zebrafish as a model system to analyze the spatial distribution of odorant receptor molecules in the olfactory epithelium by quantitative in situ hybridization. To this end, we have cloned 10 very divergent zebrafish odorant receptor molecules by PCR. Individual genes are expressed in sparse olfactory receptor neurons. Analysis of the position of labeled cells in a simplified coordinate system revealed three concentric, albeit overlapping, expression domains for the four odorant receptors analyzed in detail. Such regionalized expression should result in a corresponding segregation of functional response properties. This might represent the first step of spatial encoding of olfactory input or be essential for the development of the olfactory system.

  14. Measurement of the thickness of the bronchial epithelium

    International Nuclear Information System (INIS)

    Bowden, D.H.; Baldwin, F.

    1989-02-01

    Cancer of the lung in uranium miners is thought to be related to the inhalation of gaseous radon daughters which become attached to molecules of water vapour or to dust particles. Since, the depth of tissue penetration by alpha particles is short, the thickness of the epithelium that lines the bronchial tree may be a critical factor in the development of cancers at specific sites in the lung. The objectives of the present study were: 1) to measure the thickness of human bronchial epithelium; 2) to determine the distribution and depth of the nuclei of basal cells in the bronchial epithelium; and 3) to compare these parameters in groups of smokers and non-smokers. Twenty-nine surgically removed specimens of the lung were examined (26 smokers, 3 non-smokers). The specimens were fixed and prepared for examination by light and electron microscopy. Blocks of tissue were oriented so that the maximum number of bronchi were cut in cross-section; measurements included bronchi of all sizes from bronchial generations (1≥ 9.01 mm) diameter to the smallest bronchioles, generations 7 - 16 (0.26 - 2.0 mm). Comparison of measurements in smokers and non-smokers show no significant differences, so that the 29 cases are considered to represent a homogeneous group. With progressive divisions of the bronchi, the epithelium decreases in thickness. Of more importance are the figures relating to the distance from the cell surface to the underlying nucleus. Here too, with the exception of goblet cells, the measurements are significantly smaller in generations 7 - 16 than in generation 1

  15. Oral Hygiene

    DEFF Research Database (Denmark)

    Sørensen, Marie Toftdahl; Villadsen, Dorte Buxbom

    The aim of the study was to explore how adults with schizo- phrenia describe their lived experiences with oral hygiene. 23 adults with schizophrenia were interviewed within a period of four months in late 2015. Transcriptions of the interviews were analysed using the Reflective Lifeworld Research...... health care professionals and adults with schizophrenia in order to improve oral health, well-being and recovery....

  16. Oral Hygiene

    DEFF Research Database (Denmark)

    Villadsen, Dorte Buxbom; Sørensen, Marie Toftdahl

    2017-01-01

    The aim of the study is to explore how adults with schizophrenia describe their lived experiences with oral hygiene. 23 adults with schizophrenia were interviewed within a period of four months in late 2015. Transcriptions of the interviews were analysed using the Reflective Lifeworld Research ph...... health care professionals and adults with schizophrenia in order to improve oral health, well-being and recovery....

  17. Cytogenetic damage and postradiation restoration of eye cornea epithelium of Rodentia characterizing by different radiosensitivity

    International Nuclear Information System (INIS)

    Popova, M.F.; Bulyakova, N.V.

    1983-01-01

    Intensity of beam damage and reparation of eye cornea epithelium of animals inhabiting under different conditions and differing by radiosensitivity has been studied. Mice differing by high radiosensitivity have the hardest cytogenetic damage. Cornea epithelium of bank voles is more radiostable than that of mice. The most negligible damages of cornea epithelium is observed in Mongolian sandwort despite the fact that their total radiation stability is lower than that of bank voles. High protective-restoring properties of eye cornea epithelium of Mongolian sandwort are explained by the structure of epithelium cells diffe-- ring by a large number of cytoplasm

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

    LENUS (Irish Health Repository)

    MacCarthy, Denise

    2011-08-01

    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.

  19. Zinc uptake in vitro by human retinal pigment epithelium

    International Nuclear Information System (INIS)

    Newsome, D.A.; Rothman, R.J.

    1987-01-01

    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 65 Zn uptake by human retinal pigment epithelium in vitro. When monolayers were exposed to differing concentrations from 0 to 30 microM 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 65 Zn, we saw a biphasic pattern of uptake with a rapid first phase and a slower second phase over 120 min. Uptake of 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 65 Zn retained approximately 70% of accumulated 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 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

  20. Recovery of Vocal Fold Epithelium after Acute Phonotrauma.

    Science.gov (United States)

    Rousseau, Bernard; Kojima, Tsuyoshi; Novaleski, Carolyn K; Kimball, Emily E; Valenzuela, Carla V; Mizuta, Masanobu; Daniero, James J; Garrett, C Gaelyn; Sivasankar, M Preeti

    2017-01-01

    We investigated the timeline of tissue repair of vocal fold epithelium after acute vibration exposure using an in vivo rabbit model. Sixty-five New Zealand white breeder rabbits were randomized to 120 min of modal- or raised-intensity phonation. After the larynges were harvested at 0, 4, 8, and 24 h, and at 3 and 7 days, the vocal fold tissue was evaluated using electron microscopy and quantitative real-time polymerase chain reaction. There was an immediate decrease in the microprojection depth and height following raised-intensity phonation, paired with upregulation of cyclooxygenase-2. This initial 24-h period was also characterized by the significant downregulation of junction proteins. Interleukin 1β and transforming growth factor β1 were upregulated for 3 and 7 days, respectively, followed by an increase in epithelial cell surface depth at 3 and 7 days. These data appear to demonstrate a shift from inflammatory response to the initiation of a restorative process in the vocal fold epithelium between 24 h and 3 days. Despite the initial damage from raised-intensity phonation, the vocal fold epithelium demonstrates a remarkable capacity for the expeditious recovery of structural changes from transient episodes of acute phonotrauma. While structurally intact, the return of functional barrier integrity may be delayed by repeated episodes of phonotrauma and may also play an important role in the pathophysiology of vocal fold lesions. © 2017 S. Karger AG, Basel.

  1. Solitary chemoreceptor cell proliferation in adult nasal epithelium.

    Science.gov (United States)

    Gulbransen, Brian D; Finger, Thomas E

    2005-03-01

    Nasal trigeminal chemosensitivity in mice and rats is mediated in part by solitary chemoreceptor cells (SCCs) in the nasal epithelium (Finger et al., 2003). Many nasal SCCs express the G-protein alpha-gustducin as well as other elements of the bitter-taste signaling cascade including phospholipase Cbeta2, TRPM5 and T2R bitter-taste receptors. While some populations of sensory cells are replaced throughout life (taste and olfaction), others are not (hair cells and carotid body chemoreceptors). These experiments were designed to test whether new SCCs are generated within the epithelium of adult mice. Wild type C57/B6 mice were injected with the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to label dividing cells. At various times after injection (1-40 days), the mice were perfused with 4% paraformaldehyde and prepared for dual-label immunocytochemistry. Double labeled cells were detected as early as 3 days post BrdU injection and remained for as long as 12 days post-injection suggesting that SCCs do undergo turnover like the surrounding nasal epithelium. No BrdU labeled cells were detected after 24 days suggesting relatively rapid replacement of the SCCs.

  2. Tissue kinetics in mouse tongue mucosa during daily fractionated radiotherapy

    International Nuclear Information System (INIS)

    Doerr, W.; Emmendoerfer, H.; Weber-Frisch, M.

    1996-01-01

    The purpose of the present investigation was to quantify cell flux between the distinct layers of the epithelial lining of the ventral surface of mouse tongue during daily fractionated radiotherapy. In tongue epithelium of untreated mice, the minimum residence time of cells in the germinal layer is 2-3 days. Migration through the functional layers requires an additional 2-3 days before labelled cells are observed in the most superficial layer of nucleated cells. A plateau in LI is observed for several days post-labelling in control epithelium, indicating an equilibrium between loss and proliferation of labelled cells. During fractionated radiotherapy, the minimum time from division to occurrence of labelled cells in the stratum lucidum is less than 2 days, and hence significantly shorter than in control epithelium. In contrast to untreated epithelium, no plateau in the germinal layer LI is seen, indicating that frequently both labelled daughters from dividing labelled cells are being lost from this compartment. In conclusion, the present data support a recently described model of radiation-induced accelerated repopulation in squamous epithelia, which postulates that the majority of damaged cells undergoes abortive divisions resulting in two differentiating daughters. (Author)

  3. Peripheral Exophytic Oral Lesions: A Clinical Decision Tree

    Directory of Open Access Journals (Sweden)

    Hamed Mortazavi

    2017-01-01

    Full Text Available Diagnosis of peripheral oral exophytic lesions might be quite challenging. This review article aimed to introduce a decision tree for oral exophytic lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and “oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals were appraised. Upon compilation of data, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated and rough (squamous epithelium-originated. Lesions with smooth surface were also categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and neoplastic, and mesenchymal lesions (benign and malignant neoplasms. In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method.

  4. Stem/progenitor cells derived from the cochlear sensory epithelium give rise to spheres with distinct morphologies and features.

    Science.gov (United States)

    Diensthuber, Marc; Oshima, Kazuo; Heller, Stefan

    2009-06-01

    Nonmammalian vertebrates regenerate lost sensory hair cells by means of asymmetric division of supporting cells. Inner ear or lateral line supporting cells in birds, amphibians, and fish consequently serve as bona fide stem cells resulting in high regenerative capacity of hair cell-bearing organs. Hair cell regeneration does not happen in the mammalian cochlea, but cells with proliferative capacity can be isolated from the neonatal cochlea. These cells have the ability to form clonal floating colonies, so-called spheres, when cultured in nonadherent conditions. We noticed that the sphere population derived from mouse cochlear sensory epithelium cells was heterogeneous, consisting of morphologically distinct sphere types, hereby classified as solid, transitional, and hollow. Cochlear sensory epithelium-derived stem/progenitor cells initially give rise to small solid spheres, which subsequently transition into hollow spheres, a change that is accompanied by epithelial differentiation of the majority of sphere cells. Only solid spheres, and to a lesser extent, transitional spheres, appeared to harbor self-renewing stem cells, whereas hollow spheres could not be consistently propagated. Solid spheres contained significantly more rapidly cycling Pax-2-expressing presumptive otic progenitor cells than hollow spheres. Islet-1, which becomes upregulated in nascent sensory patches, was also more abundant in solid than in hollow spheres. Likewise, hair cell-like cells, characterized by the expression of multiple hair cell markers, differentiated in significantly higher numbers in cell populations derived from solid spheres. We conclude that cochlear sensory epithelium cell populations initially give rise to small solid spheres that have self-renewing capacity before they subsequently convert into hollow spheres, a process that is accompanied by loss of stemness and reduced ability to spontaneously give rise to hair cell-like cells. Solid spheres might, therefore, represent

  5. Functional evidence of multidrug resistance transporters (MDR in rodent olfactory epithelium.

    Directory of Open Access Journals (Sweden)

    Adrien Molinas

    Full Text Available P-glycoprotein (Pgp and multidrug resistance-associated protein (MRP1 are membrane transporter proteins which function as efflux pumps at cell membranes and are considered to exert a protective function against the entry of xenobiotics. While evidence for Pgp and MRP transporter activity is reported for olfactory tissue, their possible interaction and participation in the olfactory response has not been investigated.Functional activity of putative MDR transporters was assessed by means of the fluorometric calcein acetoxymethyl ester (calcein-AM accumulation assay on acute rat and mouse olfactory tissue slices. Calcein-AM uptake was measured as fluorescence intensity changes in the presence of Pgp or MRP specific inhibitors. Epifluorescence microscopy measured time course analysis in the olfactory epithelium revealed significant inhibitor-dependent calcein uptake in the presence of each of the selected inhibitors. Furthermore, intracellular calcein accumulation in olfactory receptor neurons was also significantly increased in the presence of either one of the Pgp or MRP inhibitors. The presence of Pgp or MRP1 encoding genes in the olfactory mucosa of rat and mouse was confirmed by RT-PCR with appropriate pairs of species-specific primers. Both transporters were expressed in both newborn and adult olfactory mucosa of both species. To assess a possible involvement of MDR transporters in the olfactory response, we examined the electrophysiological response to odorants in the presence of the selected MDR inhibitors by recording electroolfactograms (EOG. In both animal species, MRPs inhibitors induced a marked reduction of the EOG magnitude, while Pgp inhibitors had only a minor or no measurable effect.The findings suggest that both Pgp and MRP transporters are functional in the olfactory mucosa and in olfactory receptor neurons. Pgp and MRPs may be cellular constituents of olfactory receptor neurons and represent potential mechanisms for modulation

  6. Exophytic oral verrucous hyperplasia: a new entity.

    Science.gov (United States)

    Patil, Shankargouda; Warnakulasuriya, Saman; Raj, Thirumal; Sanketh, D S; Rao, Roopa S

    2016-11-01

    Exophytic oral verrucous hyperplasia (OVH) is a new entity described by an expert working group from South Asia. First reported in Taiwan, there are no reports so far from an Indian population. The aim was to use the microscopic features described by the expert group to differentiate OVH from other oral verruco-papillary lesions in an Indian archive. In a retrospective multicentre study, using pathology archives, 188 verruco-papillary lesions were retrieved from pathology archives. A proforma listing histopathological criteria for OVH based on published guidelines (Annals of Dentistry, University of Malaya, 2013) was used. Patients' demographic and clinical data were transcribed from patient charts. The Pearson chi-square test was used to determine associations between clinical and histopathological features. Of 188 oral verruco-papillary lesions that were evaluated, based on microscopic features the cases were reclassified as OVH (57), verrucous carcinoma (VC) (84), oral squamous cell carcinoma (16), and other verruco-papillary lesions (31). Both OVH (70%) and VC (60%) showed male predominance and commonly affected buccal mucosa (OVH 74% and VC 57%). Absence of downward growth of the hyperplastic epithelium into lamina propria when compared with the level of the basement membrane of the adjacent normal epithelium was a distinct feature in OVH. Keratin plugging, epithelial dysplasia and subepithelial lymphocytic infiltration were found to be significantly different (P < 0.05) in OVH versus VC. The sample size of other verruco-papillary lesions was insufficient for statistical comparison. Apart from the absence of an endophytic growth pattern in OVH, we noted the presence of dysplasia in OVH. This significant observation does institute a debate as to whether this enigmatic lesion could possibly be a precedent of oral squamous or verrucous carcinoma. We propose OVH is a distinct entity in our Indian population and should be considered in the classification of oral

  7. Comparison of the effects of an ornithine decarboxylase inhibitor on the intestinal epithelium and on intestinal tumors.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1986-12-01

    Ornithine decarboxylase (ODC) catalyzes the rate-limiting step in the synthesis of polyamines, it has a short half-life, and its synthesis is under hormonal control. Recently, insight into the role of ODC and thus into the physiology of polyamines has been gained by the use of an inhibitor of ODC, difluoromethylornithine (DFMO). In the present report cell proliferation was measured by a stathmokinetic method in the crypt epithelium of the jejunum and colon of normal rats and in dimethylhydrazine-induced colonic tumors. Growth of human colon tumor xenografts in immunosuppressed mice and mouse colon tumor isografts was also assessed. Cell proliferation in primary colonic tumors was substantially suppressed by a single dose of DFMO at 100 mg/kg whereas the normal crypt epithelium of the small and large intestine required two doses at 400 mg/kg to produce a similar magnitude of inhibition of cell proliferation. DFMO was also found to suppress cell proliferation in, and the growth of, the transplantable colon cancers. Because of the apparent selectivity of the antimitotic activity of DFMO towards tumors, ODC inhibitors may prove to be useful anticancer drugs.

  8. Expression of a single, viral oncoprotein in skin epithelium is sufficient to recruit lymphocytes.

    Directory of Open Access Journals (Sweden)

    Allison Choyce

    Full Text Available Established cancers are frequently associated with a lymphocytic infiltrate that fails to clear the tumour mass. In contrast, the importance of recruited lymphocytes during premalignancy is less well understood. In a mouse model of premalignant skin epithelium, transgenic mice that express the human papillomavirus type 16 (HPV16 E7 oncoprotein under a keratin 14 promoter (K14E7 mice display epidermal hyperplasia and have a predominant infiltrate of lymphocytes consisting of both CD4 and CD8 T cells. Activated, but not naïve T cells, were shown to preferentially traffic to hyperplastic skin with an increased frequency of proliferative CD8+ T cells and CD4+ T cells expressing CCR6 within the tissue. Disruption of the interaction between E7 protein and retinoblastoma tumour suppressor protein (pRb led to reduced epithelial hyperplasia and T cell infiltrate. Finally, while K14E7 donor skin grafts are readily accepted onto syngeneic, non-transgenic recipients, these same skin grafts lacking skin-resident lymphocytes were rejected. Our data suggests that expression of a single oncoprotein in the epidermis is sufficient for lymphocyte trafficking (including immunosuppressive lymphocytes to premalignant skin.

  9. Differential modulation by Akkermansia muciniphila and faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids

    NARCIS (Netherlands)

    Lukovac, S.; Belzer, C.; Pellis, L.; Keijser, B.J.; Vos, W.M. de; Montijn, R.C.; Roeselers, G.

    2014-01-01

    The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ileal

  10. Oral leukoplakia

    DEFF Research Database (Denmark)

    Holmstrup, Palle; Dabelsteen, Erik

    2016-01-01

    The idea of identifying oral lesions with a precancerous nature, i.e. in the sense of pertaining to a pathologic process with an increased risk for future malignant development, of course is to prevent frank malignancy to occur in the affected area. The most common oral lesion with a precancerous...... nature is oral leukoplakia, and for decades it has been discussed how to treat these lesions. Various treatment modalities, such as systemic therapies and surgical removal, have been suggested. The systemic therapies tested so far include retinoids, extracts of green tea, inhibitors of cyclooxygenase-2...

  11. Increased Expression of FoxM1 Transcription Factor in Respiratory Epithelium Inhibits Lung Sacculation and Causes Clara Cell Hyperplasia

    Science.gov (United States)

    Wang, I-Ching; Zhang, Yufang; Snyder, Jonathan; Sutherland, Mardi J.; Burhans, Michael S.; Shannon, John M.; Park, Hyun Jung; Whitsett, Jeffrey A.; Kalinichenko, Vladimir V.

    2010-01-01

    Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors. Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in multiple cell types and plays important roles in cellular proliferation, differentiation and tumorigenesis. Genetic deletion of Foxm1 from mouse respiratory epithelium during initial stages of lung development inhibits lung maturation and causes respiratory failure after birth. However, the role of Foxm1 during postnatal lung morphogenesis remains unknown. In the present study, Foxm1 expression was detected in epithelial cells of conducting and peripheral airways and changing dynamically with lung maturation. To discern the biological role of Foxm1 in the prenatal and postnatal lung, a novel transgenic mouse line that expresses a constitutively active form of FoxM1 (FoxM1 N-terminal deletion mutant or FoxM1-ΔN) under the control of lung epithelial-specific SPC promoter was produced. Expression of the FoxM1-ΔN transgene during embryogenesis caused epithelial hyperplasia, inhibited lung sacculation and expression of the type II epithelial marker, pro-SPC. Expression of FoxM1-ΔN mutant during the postnatal period did not influence alveologenesis but caused focal airway hyperplasia and increased proliferation of Clara cells. Likewise, expression of FoxM1-ΔN mutant in conducting airways with Scgb1a1 promoter was sufficient to induce Clara cell hyperplasia. Furthermore, FoxM1-ΔN cooperated with activated K-Ras to induce lung tumor growth in vivo. Increased activity of Foxm1 altered lung sacculation, induced proliferation in the respiratory epithelium and accelerated lung tumor growth, indicating that precise regulation of Foxm1 is critical for normal lung morphogenesis and development of lung cancer. PMID:20816795

  12. Characterization of a spontaneously generated murine retinal pigmented epithelium cell line; a model for in vitro experiments

    International Nuclear Information System (INIS)

    Ranaei Pirmardan, Ehsan; Soheili, Zahra-Soheila; Samiei, Shahram; Ahmadieh, Hamid; Mowla, Seyed Javad; Ezzati, Razie; Naseri, Marzieh

    2016-01-01

    Retinal pigmented epithelium (RPE), the outermost layer of the retina, has a key role in maintaining retinal cells’ functions. Severity of the culture of RPE cells has exerted many limitations to both in vitro and in vivo studies and its therapeutic applications. Therefore, establishment of RPE cell lines with high proliferative potential can considerably improve study of RPE cell biology. Here we report generation of a spontaneously immortalized murine RPE cell line in primary mouse RPE cell culture. Founded colonized cells were picked up and expression of RPE and retinal progenitor cells’ (RPC) markers were studied using immunocytochemistry (ICC). Emerged cells cultured over 35 passages and population doubling times in different serum concentrations were calculated. We also investigated the ability of cells for becoming transfected by calcium-phosphate method and for becoming infected by adeno-associated virus serotype 2 (AAV2) using flow cytometry. Data showed that the cobblestone constituent cells expressed RPE65, cytokeratin and ZO1 and moreover several progenitor markers such as Pax6, Sox2, Nestin and Chx10. It revealed that, despite primary RPE cells, the newly emerged cells were easily transfectable and were highly infectable when compared with HEK293T cells. Our data indicated that the emerged mouse RPE cell line pretended RPC-like phenotype and also simultaneously expressed RPE markers. It would be a promising model for leading studies on RPE and RPC cells and substantially confirmed the great RPE plasticity and its invaluable potential in research studies. - Highlights: • Isolation of a spontaneously generated retinal pigmented epithelium cell line is reported. • The cells express some of the retinal progenitor cell markers in addition to the RPE markers. • The aforesaid cell line is highly transfecable and considerably infectable by AAV2. • These results confirm the great RPE plasticity and its invaluable potential in research studies.

  13. Characterization of a spontaneously generated murine retinal pigmented epithelium cell line; a model for in vitro experiments

    Energy Technology Data Exchange (ETDEWEB)

    Ranaei Pirmardan, Ehsan [Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Soheili, Zahra-Soheila [Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran (Iran, Islamic Republic of); Samiei, Shahram [Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran (Iran, Islamic Republic of); Ahmadieh, Hamid [Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Mowla, Seyed Javad [Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ezzati, Razie [Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran (Iran, Islamic Republic of); Naseri, Marzieh [Department of Molecular Medicine, Faculty of Advanced Technology, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2016-10-01

    Retinal pigmented epithelium (RPE), the outermost layer of the retina, has a key role in maintaining retinal cells’ functions. Severity of the culture of RPE cells has exerted many limitations to both in vitro and in vivo studies and its therapeutic applications. Therefore, establishment of RPE cell lines with high proliferative potential can considerably improve study of RPE cell biology. Here we report generation of a spontaneously immortalized murine RPE cell line in primary mouse RPE cell culture. Founded colonized cells were picked up and expression of RPE and retinal progenitor cells’ (RPC) markers were studied using immunocytochemistry (ICC). Emerged cells cultured over 35 passages and population doubling times in different serum concentrations were calculated. We also investigated the ability of cells for becoming transfected by calcium-phosphate method and for becoming infected by adeno-associated virus serotype 2 (AAV2) using flow cytometry. Data showed that the cobblestone constituent cells expressed RPE65, cytokeratin and ZO1 and moreover several progenitor markers such as Pax6, Sox2, Nestin and Chx10. It revealed that, despite primary RPE cells, the newly emerged cells were easily transfectable and were highly infectable when compared with HEK293T cells. Our data indicated that the emerged mouse RPE cell line pretended RPC-like phenotype and also simultaneously expressed RPE markers. It would be a promising model for leading studies on RPE and RPC cells and substantially confirmed the great RPE plasticity and its invaluable potential in research studies. - Highlights: • Isolation of a spontaneously generated retinal pigmented epithelium cell line is reported. • The cells express some of the retinal progenitor cell markers in addition to the RPE markers. • The aforesaid cell line is highly transfecable and considerably infectable by AAV2. • These results confirm the great RPE plasticity and its invaluable potential in research studies.

  14. A dimensionless ordered pull-through model of the mammalian lens epithelium evidences scaling across species and explains the age-dependent changes in cell density in the human lens

    Science.gov (United States)

    Wu, Jun Jie; Wu, Weiju; Tholozan, Frederique M.; Saunter, Christopher D.; Girkin, John M.; Quinlan, Roy A.

    2015-01-01

    We present a mathematical (ordered pull-through; OPT) model of the cell-density profile for the mammalian lens epithelium together with new experimental data. The model is based upon dimensionless parameters, an important criterion for inter-species comparisons where lens sizes can vary greatly (e.g. bovine (approx. 18 mm); mouse (approx. 2 mm)) and confirms that mammalian lenses scale with size. The validated model includes two parameters: β/α, which is the ratio of the proliferation rate in the peripheral and in the central region of the lens; and γGZ, a dimensionless pull-through parameter that accounts for the cell transition and exit from the epithelium into the lens body. Best-fit values were determined for mouse, rat, rabbit, bovine and human lens epithelia. The OPT model accounts for the peak in cell density at the periphery of the lens epithelium, a region where cell proliferation is concentrated and reaches a maximum coincident with the germinative zone. The β/α ratio correlates with the measured FGF-2 gradient, a morphogen critical to lens cell survival, proliferation and differentiation. As proliferation declines with age, the OPT model predicted age-dependent changes in cell-density profiles, which we observed in mouse and human lenses. PMID:26236824

  15. Noninvasive molecular screening for oral precancer in Fanconi anemia patients.

    Science.gov (United States)

    Smetsers, Stephanie E; Velleuer, Eunike; Dietrich, Ralf; Wu, Thijs; Brink, Arjen; Buijze, Marijke; Deeg, Dorly J H; Soulier, Jean; Leemans, C René; Braakhuis, Boudewijn J M; Brakenhoff, Ruud H

    2015-11-01

    LOH at chromosome arms 3p, 9p, 11q, and 17p are well-established oncogenetic aberrations in oral precancerous lesions and promising biomarkers to monitor the development of oral cancer. Noninvasive LOH screening of brushed oral cells is a preferable method for precancer detection in patients at increased risk for head and neck squamous cell carcinoma (HNSCC), such as patients with Fanconi anemia. We determined the prevalence of LOH in brushed samples of the oral epithelium of 141 patients with Fanconi anemia and 144 aged subjects, and studied the association between LOH and HNSCC. LOH was present in 14 (9.9%) nontransplanted patients with Fanconi anemia, whereas LOH was not detected in a low-risk group (n = 50, >58 years, nonsmoking/nonalcohol history) and a group with somewhat increased HNSCC risk (n = 94, >58 years, heavy smoking/excessive alcohol use); Fisher exact test, P = 0.023 and P = 0.001, respectively. Most frequent genetic alteration was LOH at 9p. Age was a significant predictor of LOH (OR, 1.13, P = 0.001). Five patients with Fanconi anemia developed HNSCC during the study at a median age of 39.6 years (range, 24.8-53.7). LOH was significantly associated with HNSCC (Fisher exact test, P = 0.000). Unexpectedly, the LOH assay could not be used for transplanted patients with Fanconi anemia because donor DNA in brushed oral epithelium, most likely from donor leukocytes present in the oral cavity, disturbed the analysis. Noninvasive screening using a LOH assay on brushed samples of the oral epithelium has a promising outlook in patients with Fanconi anemia. However, assays need to be adapted in case of stem cell transplantation, because of contaminating donor DNA. ©2015 American Association for Cancer Research.

  16. Oral cancer.

    Science.gov (United States)

    Gerson, S J

    1990-01-01

    In the U.S. oral cancer accounts for 2.1% of all cancers and 1% of cancer deaths. Two to three times as many males as females are affected. Blacks have more intra-oral cancer than whites, and their incidence and mortality rates have increased in recent years. The etiologic process very likely involves several factors. The major etiologic agents are tobacco (all types) and alcoholic beverages. Herpes simplex virus, human papilloma virus, and Candida have been implicated. Host factors include poor state of dentition, nutritional aberrations, cirrhosis of liver, lichen planus, and immunologic impairmant. Cellular changes include amplification of some oncogenes, alterations in antigen expression, production of gamma-glutamyl transpeptidase, and disturbance of keratin and involucrin production. Experimentally, cancer is readily produced on the hamster cheek pouch and rat oral mucosa. Unlike oral cancer in humans, most experimental lesions are exophytic, and they rarely metastasize.

  17. Oral sex.

    Science.gov (United States)

    1996-04-05

    The Gay and Lesbian Medical Association urges HIV prevention specialists to regard male-to-male oral-genital sex as a low-risk activity and concentrate instead on the danger of unprotected anal intercourse. According to the association, the confusion and mixed messages surrounding oral sex are harming efforts to encourage gay men to make rational choices about truly risky behavior. The recommendations appear in the association's position paper issued March 19, 1996.

  18. Oral Cancer Screening

    Science.gov (United States)

    ... decrease the risk of oral cavity and oropharyngeal cancer. Oral cavity, pharyngeal, and laryngeal cancer are diseases in ... and treatment of oral cavity, pharyngeal, and laryngeal cancer: Oral Cavity and Oropharyngeal Cancer Prevention Lip and Oral ...

  19. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant.

    Science.gov (United States)

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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 ∼ 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.

  1. STUDIES ON HUMAN FALLOPIAN TUBAL EPITHELIUM IN DIFFERENT AGE GROUPS

    Directory of Open Access Journals (Sweden)

    Jayasri

    2016-02-01

    Full Text Available BACKGROUND AND AIMS The “fallopian tubes” (oviducts or uterine tubes are long paired flexuous reproductive organ which transports ova, spermatozoa, zygotes, the pre-implantation morulae and blastocyst. It has major role during reproductive period, but it remains as if vestigial organ before puberty and after menopause. Due to increasing rate of tubal block and infertility, oviducts and their structures gaining importance and have become a subject of research in present days particularly epithelium. The aim of the study is to ascertain any histological difference of tubal epithelium in different age groups and the research work could be utilized for investigation and management of infertility. MATERIALS AND METHODS Seven samples of each group i.e., prereproductive, reproductive & postmenopausal were collected from fresh unembalmed human cadavers received in the department of Anatomy, FAA Medical College, Barpeta, Assam. The slides were prepared using the standard laboratory procedure. Under low and high power objectives the type of cells were observed and epithelial height was measured in the different segments. Stress was given for any significant difference of epithelial height between the different age groups. RESULTS Study revealed that among the groups within the same segment, epithelial height was recorded highest (33.57µm in reproductive group as against the lowest (22.91µm in post-menopausal group. Epithelial structures of the prereproductive and reproductive groups were significantly differed (p<0.01 from the postmenopausal group. CONCLUSIONS From the findings of the present study it can be concluded that: 1. In all the groups fallopian tubal epithelium is of simple columnar type and contains three types of cells. Cells are ciliated, secretory & peg (intercalary cells. 2. In all the groups same type of increasing trend of epithelial height from intramural segment to ampullary segment was recorded. 3. In intergroup comparison of

  2. Centralized mouse repositories.

    Science.gov (United States)

    Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

    2012-10-01

    Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

  3. Solitary Chemoreceptor Cell Proliferation in Adult Nasal Epithelium

    OpenAIRE

    Gulbransen, Brian D.; Finger, Thomas E.

    2005-01-01

    Nasal trigeminal chemosensitivity in mice and rats is mediated in part by solitary chemoreceptor cells (SCCs) in the nasal epithelium (Finger et al., 2003). Many nasal SCCs express the G-protein α-gustducin as well as other elements of the bitter-taste signaling cascade including phospholipase Cβ2, TRPM5 and T2R bitter-taste receptors. While some populations of sensory cells are replaced throughout life (taste and olfaction), others are not (hair cells and carotid body chemoreceptors). These ...

  4. Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium.

    Science.gov (United States)

    Pukkila-Worley, Read; Ausubel, Frederick M

    2012-02-01

    Intestinal epithelial cells provide an essential line of defense for Caernohabditis elegans against ingested pathogens. Because nematodes consume microorganisms as their food source, there has presumably been selection pressure to evolve and maintain immune defense mechanisms within the intestinal epithelium. Here we review recent advances that further define the immune signaling network within these cells and suggest mechanisms used by the nematode to monitor for infection. In reviewing studies of pathogenesis that use this simple model system, we hope to illustrate some of the basic principles of epithelial immunity that may also be of relevance in higher order hosts. Copyright © 2012. Published by Elsevier Ltd.

  5. Radiosensitivity of mice of different lines and age as determinated with reference to ''intestinal'' death and DNA repair in intestinal epithelium cells

    Energy Technology Data Exchange (ETDEWEB)

    Konoplyannikova, O.A.; Sklobovskaya, M.V.; Konoplyannikov, A.G.; Saenko, A.S. (Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii)

    A study was made of the influence of strain- and age-related differences on mouse mortality after irradiation with doses lying within the ''intestinal'' dose range, and also damages to stem cells of intestinal epithelium and induction and repair of single-strand DNA breaks in intestinal epitherium cells. Mice of different lines and age vary in LDsub(50/4) and stem cell radiosensitivity. There are no differences in the sedimentation constants of DNA fragments in alkaline lysates of intestinal crypts of intact mice of different age. Radiosensitivity determined with reference to single-strand breaks induction in DNA is similar with different mouse groups. Repair of single-strand DNA breaks of elderly mice is slower than that of young animals.

  6. Respiratory distress associated with heterotopic gastrointestinal cysts of the oral cavity: A case report

    Directory of Open Access Journals (Sweden)

    Marco Antonio Méndez Sáenz

    2016-12-01

    Full Text Available Heterotopic gastrointestinal cysts of the oral cavity are benign lesions usually discovered during infancy. Their pathogenesis is not very clear. They are rare congenital anomalies that result from remnants of foregut-derived epithelium in the head, neck, thorax or abdomen during embryonic development. The majority of these lesions occur in the anterior ventral surface of the tongue and extend to the floor of the mouth. They are confused clinically by surgeons in cases of head and neck masses in children as ranulas, dermoid and thyroglossal cysts, and lymphangioma. We report the case of a 28-day newborn with a 3.6 cm oval mass on the floor of the mouth causing difficulty eating and cyanosis during crying. Complete surgical excision was performed by an oral approach under general anesthesia. Microscopic examination revealed gastric epithelium with tall columnar mucous cells on the surface and numerous short closed crypts, resembling fundal glands and mature gastric epithelium.

  7. Ultrastructure of respiratory tract epithelium following irradiation or application of cytostatics

    International Nuclear Information System (INIS)

    Konradova, V.; Smelhaus, V.; Kanta, J.

    1988-01-01

    The ultrastructure was studied of the large bronchi epithelium in 3 patients with malignant tumors where signs of pulmonary fibrosis were found following irradiation and combined therapy. In 2 patients, pseudostratified cylindrical epithelium was observed with signs of pathological alteration, in the third patient an altered pseudostratified cylindrical epithelium with ultrastructural signs of commencing reconstructure into stratified squamous epithelium. The findings in the respiratory track epithelium of the patients were similar to those observed in a group of children with chronic or relapsing bronchitis and bronchopneumonia. The findings show marked disturbance of the ciliary border caused by reduction in the number of kinocilia which is associated with an impairment of the self-cleaning capacity of epithelium. (author). 1 tab., 10 refs

  8. Regional differences in DNA replication in nasal epithelium following acute ozone or cigarette smoke exposure

    International Nuclear Information System (INIS)

    Johnson, N.F.; Hotchkiss, J.A.; Harkema, J.R.; Henderson, R.F.; Mauderly, J.L.; Cuddihy, R.G.

    1988-01-01

    The epithelium of the anterior nasal cavity is composed of four cell types, squamous, respiratory, cuboidal, and olfactory cells. We monitored proliferation In these tissues by bromodeoxy-uridine (BrdUrd) incorporation; the labeled cells were identified by using a monoclonal antibody that recognizes BrdUrd. The respiratory, cuboidal and olfactory epithelia had low cell turnover (1-labeled ceIl/mm basal lamina). Squamous epithelium contained 40-labeled cells per mm basal lamina. Following exposure to diluted mainstream cigarette smoke, a transient, but marked increase in DNA replication was seen in the cuboidal epithelium. In contrast, ozone exposure was associated with DNA replication in the olfactory and respiratory epithelium, as well as in the cuboidal epithelium. These studies show that the sensitivity of nasal epithelium to irritants can be assayed by measuring DNA replication. (author)

  9. Regional differences in DNA replication in nasal epithelium following acute ozone or cigarette smoke exposure

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, N F; Hotchkiss, J A; Harkema, J R; Henderson, R F; Mauderly, J L; Cuddihy, R G

    1988-12-01

    The epithelium of the anterior nasal cavity is composed of four cell types, squamous, respiratory, cuboidal, and olfactory cells. We monitored proliferation In these tissues by bromodeoxy-uridine (BrdUrd) incorporation; the labeled cells were identified by using a monoclonal antibody that recognizes BrdUrd. The respiratory, cuboidal and olfactory epithelia had low cell turnover (1-labeled ceIl/mm basal lamina). Squamous epithelium contained 40-labeled cells per mm basal lamina. Following exposure to diluted mainstream cigarette smoke, a transient, but marked increase in DNA replication was seen in the cuboidal epithelium. In contrast, ozone exposure was associated with DNA replication in the olfactory and respiratory epithelium, as well as in the cuboidal epithelium. These studies show that the sensitivity of nasal epithelium to irritants can be assayed by measuring DNA replication. (author)

  10. A novel lens epithelium gene, LEP503, is highly conserved in different vertebrate species and is developmentally regulated in postnatal rat lens.

    Science.gov (United States)

    Wen, Y; Sachs, G; Athmann, C

    2000-02-01

    The development of the lens is dependent on the proliferation of lens epithelial cells and their differentiation into fiber cells near the lens bow/equator. Identification of genes specifically expressed in the lens epithelial cells and their functions may provide insight into molecular events that regulate the processes of lens epithelial cell differentiation. In this study, a novel lens epithelium gene product, LEP503, identified from rat by a subtractive cDNA cloning strategy was investigated in the genome organization, mRNA expression and protein localization. The genomic sequences for LEP503 isolated from rat, mouse and human span 1754 bp, 1694 bp and 1895 bp regions encompassing the 5'-flanking region, two exons, one intron and 3'-flanking region. All exon-intron junction sequences conform to the GT/AG rule. Both mouse and human LEP503 genes show very high identity (93% for mouse and 79% for human) to rat LEP503 gene in the exon 1 that contains an open reading frame coding for a protein of 61 amino acid residues with a leucine-rich domain. The deduced protein sequences also show high identity (91% between mouse and rat and 77% between human and rat). Western blot shows that LEP503 is present as a specific approximately 6.9 kDa band in the water-insoluble-urea-soluble fraction of lens cortex where lens epithelium is included. Immuno-staining shows that LEP503 is localized in the epithelial cells along the entire anterior surface of rat lens. Developmentally, LEP503 is expressed at a low level at newborn, and then the expression level increases by about ten-fold around postnatal day 14 and remains at this high level for about 25 days before it drops back to the low level by postnatal day 84. These data suggest that the LEP503 may be an important lens epithelial cell gene involving the processes of epithelial cell differentiation. Copyright 2000 Academic Press.

  11. Embryo-epithelium interactions during implantation at a glance.

    Science.gov (United States)

    Aplin, John D; Ruane, Peter T

    2017-01-01

    At implantation, with the acquisition of a receptive phenotype in the uterine epithelium, an initial tenuous attachment of embryonic trophectoderm initiates reorganisation of epithelial polarity to enable stable embryo attachment and the differentiation of invasive trophoblasts. In this Cell Science at a Glance article, we describe cellular and molecular events during the epithelial phase of implantation in rodent, drawing on morphological studies both in vivo and in vitro, and genetic models. Evidence is emerging for a repertoire of transcription factors downstream of the master steroidal regulators estrogen and progesterone that coordinate alterations in epithelial polarity, delivery of signals to the stroma and epithelial cell death or displacement. We discuss what is known of the cell interactions that occur during implantation, before considering specific adhesion molecules. We compare the rodent data with our much more limited knowledge of the human system, where direct mechanistic evidence is hard to obtain. In the accompanying poster, we represent the embryo-epithelium interactions in humans and laboratory rodents, highlighting similarities and differences, as well as depict some of the key cell biological events that enable interstitial implantation to occur. © 2017. Published by The Company of Biologists Ltd.

  12. Nanotopography follows force in TGF-β1 stimulated epithelium

    International Nuclear Information System (INIS)

    Thoelking, Gerold; Oberleithner, Hans; Riethmuller, Christoph; Reiss, Bjoern; Wegener, Joachim; Pavenstaedt, Hermann

    2010-01-01

    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.

  13. Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations

    Science.gov (United States)

    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

  14. The epithelium in idiopathic pulmonary fibrosis: breaking the barrier

    Directory of Open Access Journals (Sweden)

    Ana eCamelo

    2014-01-01

    Full Text Available Idiopathic pulmonary fibrosis is a progressive disease of unknown etiology characterised by a dysregulated wound healing response that leads to fatal accumulation of fibroblasts and extracellular matrix in the lung, which compromises tissue architecture and lung function capacity. Injury to type II alveolar epithelial cells is thought to be the key event for the initiation of the disease, and so far both genetic factors, such as mutations in telomerase and MUC5b genes as well as environmental components, like cigarette smoking, exposure to asbestos and viral infections have been implicated as potential initiating triggers. The injured epithelium then enters a state of senescence-associated secretory phenotype whereby it produces both pro-inflammatory and pro-fibrotic factors that contribute to the wound healing process in the lung. Immune cells, like macrophages and neutrophils as well as activated myofibroblasts then perpetuate this cascade of epithelial cell apoptosis and proliferation by release of pro-fibrotic TGF-β and continuous deposition of extracellular matrix stiffens the basement membrane, altogether having a deleterious impact on epithelial cell function. In this review we describe the role of the epithelium as both a physical and immunological barrier between environment and self in the homeostatic versus diseased lung and explore the potential mechanisms of epithelial cell injury and the impact of loss of epithelial cell permeability and function on cytokine production, inflammation and myofibroblast activation in the fibrotic lung.

  15. Radio-iodination of plasma membranes of toad bladder epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, H J; Edelman, I S [California Univ., San Francisco (USA). Cardiovascular Research Inst.; California Univ., San Francisco (USA). Dept. of Medicine; California Univ., San Francisco (USA). Dept. of Biochemistry and Biophysics)

    1979-01-01

    The present report describes high yield enzymatic radio-iodination of the apical and basal-lateral plasma membranes of toad bladder epithelium with /sup 125/I-Na, by a procedure that does not breach the functional integrity of the epithelium, as assessed by the basal and vasopressin-sensitive short-circuit current (SCC). Iodination of basal-lateral plasma membranes, at a yield comparable to that obtained with apical labelling, was attained after about 30 min of exposure of the intact bladder to the labelling solutions. Approximately 25% of the basal-lateral labeling was lost when the epithelial cells were harvested after collagenase treatment, implying that some iodination of the basement membrane had taken place. Less than 10% of iodination of the apical or basal-lateral surfaces was accounted for by lipid-labeling. Analysis of the labeled apical and basal-lateral species by enzymatic digestion and thin layer chromatography disclosed that virtually all the radioactivity was present as mono-iodotyrosine (MIT). (orig./AJ).

  16. Choline transport in the isolated rabbit corneal epithelium

    International Nuclear Information System (INIS)

    Faust, R.L.

    1988-01-01

    In the present study, isolated epithelial sheets were obtained by performing two sequential anterior keratectomies, three weeks apart, on rabbit corneas. Light microscopy of the isolated sheets revealed a multilayered epithelium with an intact basal cell layer without contamination from other cell types. The accumulation of [ 3 H]choline into the epithelial sheets was studied at substrate concentrations varying from 1 to 100 μMoles with and without the addition of specific metabolic and stereochemical inhibitors. Accumulation of [ 3 H]choline into these sheets was saturable. Kinetic analysis, performed by estimation from double-reciprocal plots, revealed a single component system with a K m of 24.9 μM. The metabolic inhibitors potassium cyanide and ouabain showed no effect on the uptake of [ 3 H]choline; however, the stereochemical inhibitor hemicholinium-3 significantly reduced the accumulation of radiolabel at both high and low substrate concentrations. The results suggest a non-energy dependent yet a highly specific transport system for the accumulation of choline into the rabbit epithelium

  17. Oral candidiasis.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Treville Pereira

    2010-01-01

    Full Text Available Myiasis is a relatively rare condition arising from the invasion of body tissues or cavities of living animals or humans by maggots or larvae of certain species of flies. It is an uncommon clinical condition, being more frequent in underdeveloped countries and hot climate regions, and is associated with poor hygiene, suppurative oral lesions; alcoholism and senility. Its diagnosis is made basically by the presence of larvae. The present article reports a case of oral myiasis involving 20 larvae in a patient with neurological deficiency.

  19. The Role of Na:K:2Cl Cotransporter 1 (NKCC1/SLC12A2) in Dental Epithelium during Enamel Formation in Mice

    Science.gov (United States)

    Jalali, Rozita; Lodder, Johannes C.; Zandieh-Doulabi, Behrouz; Micha, Dimitra; Melvin, James E.; Catalan, Marcelo A.; Mansvelder, Huibert D.; DenBesten, Pamela; Bronckers, Antonius

    2017-01-01

    Na+:K+:2Cl− cotransporters (NKCCs) belong to the SLC12A family of cation-coupled Cl− transporters. We investigated whether enamel-producing mouse ameloblasts express NKCCs. Transcripts for Nkcc1 were identified in the mouse dental epithelium by RT-qPCR and NKCC1 protein was immunolocalized in outer enamel epithelium and in the papillary layer but not the ameloblast layer. In incisors of Nkcc1-null mice late maturation ameloblasts were disorganized, shorter and the mineral density of the enamel was reduced by 10% compared to wild-type controls. Protein levels of gap junction protein connexin 43, Na+-dependent bicarbonate cotransporter e1 (NBCe1), and the Cl−-dependent bicarbonate exchangers SLC26A3 and SLC26A6 were upregulated in Nkcc1-null enamel organs while the level of NCKX4/SLC24A4, the major K+, Na+ dependent Ca2+ transporter in maturation ameloblasts, was slightly downregulated. Whole-cell voltage clamp studies on rat ameloblast-like HAT-7 cells indicated that bumetanide increased ion-channel activity conducting outward currents. Bumetanide also reduced cell volume of HAT-7 cells. We concluded that non-ameloblast dental epithelium expresses NKCC1 to regulate cell volume in enamel organ and provide ameloblasts with Na+, K+ and Cl− ions required for the transport of mineral- and bicarbonate-ions into enamel. Absence of functional Nkcc1 likely is compensated by other types of ion channels and ion transporters. The increased amount of Cx43 in enamel organ cells in Nkcc1-null mice suggests that these cells display a higher number of gap junctions to increase intercellular communication. PMID:29209227

  20. Ultrastructure of the cortical epithelium of the rat thymus after in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    Energy Technology Data Exchange (ETDEWEB)

    Waal, E.J. de (National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)); Rademakers, L.H.P.M. (Dept. of Pathology, University Hospital, Utrecht (Netherlands)); Schuurman, H.J. (National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands) Dept. of Pathology, University Hospital, Utrecht (Netherlands) Dept. of Internal Medicine, University Hospital, Utrecht (Netherlands)); Loveren, H. van (National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)); Vos, J.G. (National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands))

    1993-09-01

    The present study was conducted to provide ultrastructural evidence for the cortical epithelium to be a target for TCDD in vivo. Juvenile male Wistar rats were orally intubated once with either 50 or 150 [mu]g/kg TCDD and killed 4 or 10 days thereafter. Major changes were found in the cortical thymic epithelium. First, a relative shift occurred from 'pale' to darker cortical epithelial cell types, as judged by their nuclear and cytoplasmic electron density. This effect was most prominent at 10 days after exposure to 150 [mu]g/kg TCDD. The increased electron density of the cortical epithelium indicates an altered state of cellular differentiation. Secondly, at the 150 [mu]g/kg dose level focal epithelial cell aggregated were seen both at day 4 and day 10 after administration. This aggregation may either be compound induced or represent a secondary event to the collapse of the thymic stroma. Thirdly, increased vacuolation of cortical epithelial cells was apparent. This effect is interpreted as a consequence rather than a cause of thymocyte depletion from the cortex. (orig./MG)

  1. Bacillus licheniformis in geogenic dust induces inflammation in respiratory epithelium.

    Science.gov (United States)

    Pickering, Janessa; Teo, Teck Hui; Thornton, Ruth B; Kirkham, Lea-Ann; Zosky, Graeme R; Clifford, Holly D

    2018-07-01

    Exposure to environmental geogenic (or earth-derived) dust can lead to more frequent and severe infections in the human airway. Particulate matter respiratory diseases. We have previously demonstrated that mice exposed to geogenic dust PM 10 experienced an exacerbation of inflammatory responses to influenza A virus. Whether geogenic dust PM 10 also exacerbates respiratory bacterial infection is not yet known, nor are the components of the dust that drive these responses. We treated airway bronchial epithelial cells (NuLi-1) with UV-irradiated geogenic dust PM 10 from six remote Western Australian towns. High levels of IL-6 and IL-8 production were observed, as well as persistent microbial growth. 16 S rRNA sequencing of the growth identified the microbe as Bacillus licheniformis, a spore-forming, environmentally abundant bacterium. We next investigated the interaction of B. licheniformis with respiratory epithelium in vitro to determine whether this exacerbated infection with a bacterial respiratory pathogen (non-typeable Haemophilus influenzae, NTHi). Heat treatment (100 °C) of all PM 10 samples eliminated B. licheniformis contamination and reduced epithelial inflammatory responses, suggesting that heat-labile and/or microbial factors were involved in the host response to geogenic dust PM 10 . We then exposed NuLi-1 epithelium to increasing doses of the isolated Bacillus licheniformis (multiplicity of infection of 10:1, 1:1 or 0.1:1 bacteria: cells) for 1, 3, and 24 h. B. licheniformis and NTHi infection (association and invasion) was assessed using a standard gentamicin survival assay, and epithelial release of IL-6 and IL-8 was measured using a bead based immunoassay. B. licheniformis was cytotoxic to NuLi-1 cells at 24 h. At 3 h post-challenge, B. licheniformis elicited high IL-6 and IL-8 inflammatory responses from NuLi-1 cells compared with cells treated with heat-treated geogenic dust PM 10 (p respiratory epithelium. The impact on respiratory

  2. Oral calcitonin

    Directory of Open Access Journals (Sweden)

    Hamdy RC

    2012-09-01

    Full Text Available Ronald C Hamdy,1,2 Dane N Daley11Osteoporosis Center, College of Medicine, East Tennessee State University, 2Veterans Affairs Medical Center, Johnson City, TN, USAAbstract: Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget's disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through β-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen® 8-(N-2hydroxy-5-chloro-benzoyl-amino-caprylic acid (5-CNAC (Emisphere Technologies, Cedar Knolls, NJ. Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis failed to

  3. Oral care.

    Science.gov (United States)

    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. Copyright © 2011 S. Karger AG, Basel.

  4. Probiotic Lactobacillus rhamnosus GG prevents alveolar bone loss in a mouse model of experimental periodontitis.

    Science.gov (United States)

    Gatej, Simona M; Marino, Victor; Bright, Richard; Fitzsimmons, Tracy R; Gully, Neville; Zilm, Peter; Gibson, Rachel J; Edwards, Suzanne; Bartold, Peter M

    2018-02-01

    This study investigated the role of Lactobacillus rhamnosus GG (LGG) on bone loss and local and systemic inflammation in an in vivo mouse model of experimental periodontitis (PD). Experimental PD was induced in mice by oral inoculation with Porphyromonas gingivalis and Fusobacterium nucleatum over a period of 44 days. The probiotic LGG was administered via oral inoculation or oral gavage prior to, and during disease induction. The antimicrobial activity of LGG on the inoculum was also tested. Alveolar bone levels and gingival tissue changes were assessed using in vivo microcomputed tomography and histological analysis. Serum levels of mouse homologues for IL-8 were measured using multiplex assays. Pre-treatment with probiotics either via oral gavage or via oral inoculation significantly reduced bone loss (p loss in a mouse model of induced PD irrespective of the mode of administration. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Piezoelectric materials mimic the function of the cochlear sensory epithelium.

    Science.gov (United States)

    Inaoka, Takatoshi; Shintaku, Hirofumi; Nakagawa, Takayuki; Kawano, Satoyuki; Ogita, Hideaki; Sakamoto, Tatsunori; Hamanishi, Shinji; Wada, Hiroshi; Ito, Juichi

    2011-11-08

    Cochlear hair cells convert sound vibration into electrical potential, and loss of these cells diminishes auditory function. In response to mechanical stimuli, piezoelectric materials generate electricity, suggesting that they could be used in place of hair cells to create an artificial cochlear epithelium. Here, we report that a piezoelectric membrane generated electrical potentials in response to sound stimuli that were able to induce auditory brainstem responses in deafened guinea pigs, indicating its capacity to mimic basilar membrane function. In addition, sound stimuli were transmitted through the external auditory canal to a piezoelectric membrane implanted in the cochlea, inducing it to vibrate. The application of sound to the middle ear ossicle induced voltage output from the implanted piezoelectric membrane. These findings establish the fundamental principles for the development of hearing devices using piezoelectric materials, although there are many problems to be overcome before practical application.

  6. Asymmetric [14C]albumin transport across bullfrog alveolar epithelium

    International Nuclear Information System (INIS)

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

    1985-01-01

    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, 14 C-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, [ 14 C]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

  7. Alcohol-assisted versus Mechanical Epithelium Removal in Photorefractive Keratectomy

    Directory of Open Access Journals (Sweden)

    Mohammad Ghoreishi,

    2010-01-01

    Full Text Available Purpose: To compare the outcomes and complications of alcohol-assisted versus mechanical corneal epithelial debridement for photorefractive keratectomy (PRK. Methods: This randomized controlled trial included 1,250 eyes of 625 patients undergoing PRK for correction of myopia and myopic astigmatism. Each patient was randomly assigned to alcohol-assisted or mechanical epithelial removal. Results: A total of 658 eyes underwent alcohol-assisted epithelial removal while the epithelium was removed mechanically in 592 eyes. Mean spherical equivalent was ‑4.37}2.3 D in the alcohol group and ‑3.8}1.3 D in the mechanical group (P = 0.78. There was no significant difference in postoperative pain between the study groups (P = 0.22. Uncorrected visual acuity ≥ 20/20 and ≥ 20/40 was achieved in 90.9% versus 93.4% (P = 0.08, and 98.9% versus 99.5% (P = 0.36 of eyes in the alcohol and mechanical groups, respectively. Final refractive error within 1D of emmetropia was achieved in 90% versus 92.2% of eyes in the alcohol and mechanical groups, respectively (P = 0.23. Alcohol-assisted debridement required less time than mechanical debridement (96±18 vs. 118±26 seconds, P=0.035. There was no significant difference between the two groups in terms of early and late postoperative complications. Conclusion: Alcohol-assisted and mechanical epithelium removal are comparable in terms of efficacy and side effects. The method of epithelial debridement in PRK may be left to the surgeon′s choice.

  8. Waterpipe smoking induces epigenetic changes in the small airway epithelium.

    Directory of Open Access Journals (Sweden)

    Matthew S Walters

    Full Text Available Waterpipe (also called hookah, shisha, or narghile smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use waterpipe smoking on DNA methylation of the small airway epithelium (SAE and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05 representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05 change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling. Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking.

  9. Passive ionic properties of frog retinal pigment epithelium.

    Science.gov (United States)

    Miller, S S; Steinberg, R H

    1977-09-15

    The isolated pigment epithelium and choroid of frog was mounted in a chamber so that the apical surfaces of the epithelial cells and the choroid were exposed to separate solutions. The apical membrane of these cells was penetrated with microelectrodes and the mean apical membrane potential was --88 mV. The basal membrane potential was depolarized by the amount of the transepithelial potential (8--20 mV). Changes in apical and basal cell membrane voltage were produced by changing ion concentrations on one or both sides of the tissue. Although these voltage changes were altered by shunting and changes in membrane resistance, it was possible to estimate apical and basal cell membrane and shunt resistance, and the relative ionic conductance Ti of each membrane. For the apical membrane: TK approximately equal to 0.52, THCO3 approximately equal to 0.39 and TNa approximately equal to 0.05, and its specific resistance was estimated to be 6000--7000 omega cm2. For the basal membrane: TK approximately equal to 0.90 and its specific resistance was estimated to be 400--1200 omega cm2. From the basal potassium voltage responses the intracellular potassium concentration was estimated at 110 mM. The shunt resistance consisted of two pathways: a paracellular one, due to the junctional complexes and another, around the edge of the tissue, due to the imperfect nature of the mechanical seal. In well-sealed tissues, the specific resistance of the shunt was about ten times the apical plus basal membrane specific resistances. This epithelium, therefore, should be considered "tight". The shunt pathway did not distinguish between anions (HCO--3, Cl--, methylsulfate, isethionate) but did distinguish between Na+ and K+.

  10. Time- and temperature-dependent autolysis of urinary bladder epithelium during ex vivo preservation.

    Science.gov (United States)

    Erman, Andreja; Veranič, Peter

    2011-07-01

    Morphological and functional preservation of urinary bladder epithelium-urothelium after extirpation from an organism enables physiological studies of that tissue and provides the basis for successful organ transplantations. The aim of this study was to determine the optimal temperature for maintaining urothelium in ex vivo conditions. Mouse urinary bladders were kept at the three temperatures usually used for maintaining tissue during transportation: at the temperature of melting ice (1°C), at room temperature (22-24°C), and at the body temperature of most mammals (37°C). Autolytic structural changes were followed with electron microscopy, while destruction of cytoskeleton and intercellular junctions was observed by immunolabeling. The first ultrastructural changes, swelling of mitochondria and necrosis of individual cells, became evident 30 min after extirpation if the tissue was kept at 1°C. After 60 and 120 min in ex vivo conditions, the most severe changes with increasing plasma membrane ruptures were detected at 1°C, while at room temperature only mild changes were detected. At 37°C, the extent of ultrastructural changes was between those of the other two experimental temperatures. Autolytic destruction of cytoskeleton and intercellular junctions was not observed before 2 h after extirpation. After 4 h, severe degradation of cytokeratin 20 and microtubules were found at 1°C and 37°C, while being almost undisturbed at room temperature. On the other hand, the reduction of desmoplakin and ZO-1 labeling was more evident at 37°C than at 1°C and room temperature. These findings provide evidence that room temperature is most appropriate for short ex vivo preservation of urothelial tissue.

  11. Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium.

    Science.gov (United States)

    Yu, Weiqun; Hill, Warren G; Apodaca, Gerard; Zeidel, Mark L

    2011-01-01

    The urothelium is proposed to be a sensory tissue that responds to mechanical stress by undergoing dynamic membrane trafficking and neurotransmitter release; however, the molecular basis of this function is poorly understood. Transient receptor potential (TRP) channels are ideal candidates to fulfill such a role as they can sense changes in temperature, osmolarity, and mechanical stimuli, and several are reported to be expressed in the bladder epithelium. However, their complete expression profile is unknown and their cellular localization is largely undefined. We analyzed expression of all 33 TRP family members in mouse bladder and urothelium by RT-PCR and found 22 specifically expressed in the urothelium. Of the latter, 10 were chosen for closer investigation based on their known mechanosensory or membrane trafficking functions in other cell types. Western blots confirmed urothelial expression of TRPC1, TRPC4, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, TRPML1, and polycystins 1 and 2 (PKD1 and PKD2) proteins. We further defined the cellular and subcellular localization of all 10 TRP channels. TRPV2 and TRPM4 were prominently localized to the umbrella cell apical membrane, while TRPC4 and TRPV4 were identified on their abluminal surfaces. TRPC1, TRPM7, and TRPML1 were localized to the cytoplasm, while PKD1 and PKD2 were expressed on the apical and basolateral membranes of umbrella cells as well as in the cytoplasm. The cellular location of TRPV1 in the bladder has been debated, but colocalization with neuronal marker calcitonin gene-related peptide indicated clearly that it is present on afferent neurons that extend into the urothelium, but may not be expressed by the urothelium itself. These findings are consistent with the hypothesis that the urothelium acts as a sentinel and by expressing multiple TRP channels it is likely it can detect and presumably respond to a diversity of external stimuli and suggest that it plays an important role in urothelial signal

  12. Gene Expression Profiles of Main Olfactory Epithelium in Adenylyl Cyclase 3 Knockout Mice

    Directory of Open Access Journals (Sweden)

    Zhenshan Wang

    2015-11-01

    Full Text Available Adenylyl Cyclase 3 (AC3 plays an important role in the olfactory sensation-signaling pathway in mice. AC3 deficiency leads to defects in olfaction. However, it is still unknown whether AC3 deficiency affects gene expression or olfactory signal transduction pathways within the main olfactory epithelium (MOE. In this study, gene microarrays were used to screen differentially expressed genes in MOE from AC3 knockout (AC3−/− and wild-type (AC3+/+ mice. The differentially expressed genes identified were subjected to bioinformatic analysis and verified by qRT-PCR. Gene expression in the MOE from AC3−/− mice was significantly altered, compared to AC3+/+ mice. Of the 41266 gene probes, 3379 had greater than 2-fold fold change in expression levels between AC3−/− and AC3+/+ mice, accounting for 8% of the total gene probes. Of these genes, 1391 were up regulated, and 1988 were down regulated, including 425 olfactory receptor genes, 99 genes that are specifically expressed in the immature olfactory neurons, 305 genes that are specifically expressed in the mature olfactory neurons, and 155 genes that are involved in epigenetic regulation. Quantitative RT-PCR verification of the differentially expressed epigenetic regulation related genes, olfactory receptors, ion transporter related genes, neuron development and differentiation related genes, lipid metabolism and membrane protein transport etc. related genes showed that P75NTR, Hinfp, Gadd45b, and Tet3 were significantly up-regulated, while Olfr370, Olfr1414, Olfr1208, Golf, Faim2, Tsg101, Mapk10, Actl6b, H2BE, ATF5, Kirrrel2, OMP, Drd2 etc. were significantly down-regulated. In summary, AC3 may play a role in proximal olfactory signaling and play a role in the regulation of differentially expressed genes in mouse MOE.

  13. MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.

    Science.gov (United States)

    Shelby, Shameka J; Colwill, Karen; Dhe-Paganon, Sirano; Pawson, Tony; Thompson, Debra A

    2013-01-01

    The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE). A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2)-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999)), purified and phosphorylated. Ni(2+)-NTA pull downs were performed using 6xHis-rMERTK(571-999) in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999) and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α), VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS), siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.

  14. MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Shameka J Shelby

    Full Text Available The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE. A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999, purified and phosphorylated. Ni(2+-NTA pull downs were performed using 6xHis-rMERTK(571-999 in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999 and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α, VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS, siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.

  15. Oral Health and Aging

    Science.gov (United States)

    ... please turn JavaScript on. Feature: Oral Health and Aging Oral Health and Aging Past Issues / Summer 2016 Table of Contents Jerrold ... they may need. Read More "Oral Health and Aging" Articles Oral Health and Aging / 4 Myths About ...

  16. Airway responses towards allergens - from the airway epithelium to T cells

    DEFF Research Database (Denmark)

    Papazian, Dick; Hansen, Søren; Würtzen, Peter A

    2015-01-01

    -damaged, healthy epithelium lowers the DCs ability to induce inflammatory T cell responses towards allergens. The purpose of this review is to summarize the current knowledge on which signals from the airway epithelium, from first contact with inhaled allergens all the way to the ensuing Th2 cell responses...

  17. Congenital choristomas of the oral cavity in children.

    Science.gov (United States)

    Chai, Raymond L; Ozolek, John A; Branstetter, Barton F; Mehta, Deepak K; Simons, Jeffrey P

    2011-10-01

    To review our institutional experience with oral cavity choristomas in children. Retrospective case series and medical record review. Medical records including clinic notes, operative reports, radiologic studies, and pathology specimens were reviewed. All imaging studies and pathology material were reviewed by a head and neck radiologist and pediatric pathologist, respectively. Sixteen patients (10 males and 6 females) with congenital oral cavity choristomas were identified. Mean age at diagnosis was 1.8 months. Location of the lesions included tongue (n = 9) and floor of mouth (n = 7). Preoperative imaging included magnetic resonance imaging (n = 6), computed tomography (n = 5), plain radiography (n = 1), and no imaging (n = 4). Radiographically, the lesions were consistently lobular with well-defined margins, but other imaging features often mimicked other masses that can arise in the tongue and floor of mouth. Symptoms were present in five of 16 patients and included difficulty feeding, swelling with upper respiratory infection, and partial airway obstruction. Complete surgical excision was performed in 15 of 16 patients; mean age at the time of surgery was 12.7 months. One patient underwent marsupialization. No complications were noted perioperatively. No recurrences of choristoma were seen. On histologic examination, the predominant component was cystic with cyst linings of respiratory epithelium (n = 5), gastric (foveolar) epithelium (n = 1), or both (n = 10). This study supports surgical excision as an effective intervention for children with oral cavity choristomas. Because the etiology of these cysts is unknown and diagnostic terminology is widely variable, we propose a more descriptive diagnosis based on the histology (i.e., lingual choristoma [or lingual developmental cyst] with respiratory epithelium or lingual choristoma [or lingual developmental cyst] with gastric epithelium). Copyright © 2011 The American Laryngological, Rhinological, and Otological

  18. Proliferation of cultured mouse choroid plexus epithelial cells.

    Directory of Open Access Journals (Sweden)

    Basam Z Barkho

    Full Text Available The choroid plexus (ChP epithelium is a multifunctional tissue found in the ventricles of the brain. The major function of the ChP epithelium is to produce cerebrospinal fluid (CSF that bathes and nourishes the central nervous system (CNS. In addition to the CSF, ChP epithelial cells (CPECs produce and secrete numerous neurotrophic factors that support brain homeostasis, such as adult hippocampal neurogenesis. Accordingly, damage and dysfunction to CPECs are thought to accelerate and intensify multiple disease phenotypes, and CPEC regeneration would represent a potential therapeutic approach for these diseases. However, previous reports suggest that CPECs rarely divide, although this has not been extensively studied in response to extrinsic factors. Utilizing a cell-cycle reporter mouse line and live cell imaging, we identified scratch injury and the growth factors insulin-like growth factor 1 (IGF-1 and epidermal growth factor (EGF as extrinsic cues that promote increased CPEC expansion in vitro. Furthermore, we found that IGF-1 and EGF treatment enhances scratch injury-induced proliferation. Finally, we established whole tissue explant cultures and observed that IGF-1 and EGF promote CPEC division within the intact ChP epithelium. We conclude that although CPECs normally have a slow turnover rate, they expand in response to external stimuli such as injury and/or growth factors, which provides a potential avenue for enhancing ChP function after brain injury or neurodegeneration.

  19. A dose-surviving fraction curve for mouse colonic mucosa

    International Nuclear Information System (INIS)

    Tucker, S.L.; Thames, H.D. Jr.; Withers, H.R.; Mason, K.A.

    1983-01-01

    A dose-surviving fraction curve representing the response of the mouse colonic mucosa to single doses of 137 Cs gamma radiation was obtained from the results of a multifraction in vivo colony assay. Construction of the curve required an estimated of the average number of clonogens initially present per colonic crypt. The estimated clonogen count (88) was determined by a statistical method based on the use of doses per fraction common to different fractionation protocols. Parameters for the LQ and TC models of cell survival were obtained by weighted least-squares fits to the data. A comparison of the survival characteristics of cells from the mouse colonic and jejunal crypts suggested that the epithelium of the colon is less radiosensitive than that of the jejunum. (author)

  20. Hypotonicity induced K+ and anion conductive pathways activation in eel intestinal epithelium

    DEFF Research Database (Denmark)

    Lionetto, M G; Giordano, M E; De Nuccio, F

    2005-01-01

    , the activation of 'emergency' systems of rapid cell volume regulation is fundamental in their physiology. The aim of the present work was to study the physiological response to hypotonic stress in a salt-transporting epithelium, the intestine of the euryhaline teleost Anguilla anguilla. Eel intestinal epithelium......, when symmetrically bathed with Ringer solution, develops a net Cl- current giving rise to a negative transepithelial potential at the basolateral side of the epithelium. The eel intestinal epithelium responded to a hypotonic challenge with a biphasic decrease in the transepithelial voltage (V......(te)) and the short circuit current (I(sc)). This electrophysiological response correlated with a regulatory volume decrease (RVD) response, recorded by morphometrical measurement of the epithelium height. Changes in the transepithelial resistance were also observed following the hypotonicity exposure...

  1. The ureteric bud epithelium: morphogenesis and roles in metanephric kidney patterning.

    Science.gov (United States)

    Nagalakshmi, Vidya K; Yu, Jing

    2015-03-01

    The mammalian metanephric kidney is composed of two epithelial components, the collecting duct system and the nephron epithelium, that differentiate from two different tissues -the ureteric bud epithelium and the nephron progenitors, respectively-of intermediate mesoderm origin. The collecting duct system is generated through reiterative ureteric bud branching morphogenesis, whereas the nephron epithelium is formed in a process termed nephrogenesis, which is initiated with the mesenchymal-epithelial transition of the nephron progenitors. Ureteric bud branching morphogenesis is regulated by nephron progenitors, and in return, the ureteric bud epithelium regulates nephrogenesis. The metanephric kidney is physiologically divided along the corticomedullary axis into subcompartments that are enriched with specific segments of these two epithelial structures. Here, we provide an overview of the major molecular and cellular processes underlying the morphogenesis and patterning of the ureteric bud epithelium and its roles in the cortico-medullary patterning of the metanephric kidney. © 2015 Wiley Periodicals, Inc.

  2. Oral supplementations with L-glutamine or L-alanyl-L-glutamine do not change metabolic alterations induced by long-term high-fat diet in the B6.129F2/J mouse model of insulin resistance.

    Science.gov (United States)

    Bock, Patricia Martins; Krause, Mauricio; Schroeder, Helena Trevisan; Hahn, Gabriela Fernandes; Takahashi, Hilton Kenji; Schöler, Cinthia Maria; Nicoletti, Graziella; Neto, Luiz Domingos Zavarize; Rodrigues, Maria Inês Lavina; Bruxel, Maciel Alencar; Homem de Bittencourt, Paulo Ivo

    2016-01-01

    In this work, we aimed to investigate the effects of long-term supplementations with L-glutamine or L-alanyl-L-glutamine in the high-fat diet (HFD)-fed B6.129SF2/J mouse model over insulin sensitivity response and signaling, oxidative stress markers, metabolism and HSP70 expression. Mice were fed in a standard low-fat diet (STA) or a HFD for 20 weeks. In the 21th week, mice from the HFD group were allocated in five groups and supplemented for additional 8 weeks with different amino acids: HFD control group (HFD-Con), HFD + dipeptide L-alanyl-L-glutamine group (HFD-Dip), HFD + L-alanine group (HFD-Ala), HFD + L-glutamine group (HFD-Gln), or the HFD + L-alanine + L-glutamine (in their free forms) group (HFD-Ala + Gln). HFD induced higher body weight, fat pad, fasted glucose, and total cholesterol in comparison with STA group. Amino acid supplementations did not induce any modifications in these parameters. Although insulin tolerance tests indicated insulin resistance in all HFD groups, amino acid supplementations did not improve insulin sensitivity in the present model. There were also no significant differences in the immunocontents of insulin receptor, Akt, and Toll-like receptor-4. Notably, total 70 kDa heat shock protein (HSP72 + HSP73) contents in the liver was markedly increased in HFD-Con group as compared to STA group, which might suggest that insulin resistance is only in the beginning. Apparently, B6.129SF2/J mice are more resistant to the harmful effects of HFD through a mechanism that may include gut adaptation, reducing the absorption of nutrients, including amino acids, which may explain the lack of improvements in our intervention.

  3. Leveraging model-based study designs and serial micro-sampling techniques to understand the oral pharmacokinetics of the potent LTB4 inhibitor, CP-105696, for mouse pharmacology studies.

    Science.gov (United States)

    Spilker, Mary E; Chung, Heekyung; Visswanathan, Ravi; Bagrodia, Shubha; Gernhardt, Steven; Fantin, Valeria R; Ellies, Lesley G

    2017-07-01

    1. Leukotriene B4 (LTB4) is a proinflammatory mediator important in the progression of a number of inflammatory diseases. Preclinical models can explore the role of LTB4 in pathophysiology using tool compounds, such as CP-105696, that modulate its activity. To support preclinical pharmacology studies, micro-sampling techniques and mathematical modeling were used to determine the pharmacokinetics of CP-105696 in mice within the context of systemic inflammation induced by a high-fat diet (HFD). 2. Following oral administration of doses > 35 mg/kg, CP-105696 kinetics can be described by a one-compartment model with first order absorption. The compound's half-life is 44-62 h with an apparent volume of distribution of 0.51-0.72 L/kg. Exposures in animals fed an HFD are within 2-fold of those fed a normal chow diet. Daily dosing at 100 mg/kg was not tolerated and resulted in a >20% weight loss in the mice. 3. CP-105696's long half-life has the potential to support a twice weekly dosing schedule. Given that most chronic inflammatory diseases will require long-term therapies, these results are useful in determining the optimal dosing schedules for preclinical studies using CP-105696.

  4. Oral delivery of bioencapsulated exendin-4 expressed in chloroplasts lowers blood glucose level in mice and stimulates insulin secretion in beta-TC6 cells.

    Science.gov (United States)

    Kwon, Kwang-Chul; Nityanandam, Ramya; New, James S; Daniell, Henry

    2013-01-01

    Glucagon-like peptide (GLP-1) increases insulin secretion but is rapidly degraded (half-life: 2 min in circulation). GLP-1 analogue, exenatide (Byetta) has a longer half-life (3.3-4 h) with potent insulinotropic effects but requires cold storage, daily abdominal injections with short shelf life. Because patients with diabetes take >60 000 injections in their life time, alternative delivery methods are highly desired. Exenatide is ideal for oral delivery because insulinotropism is glucose dependent, with reduced risk of hypoglycaemia even at higher doses. Therefore, exendin-4 (EX4) was expressed as a cholera toxin B subunit (CTB)-fusion protein in tobacco chloroplasts to facilitate bioencapsulation within plant cells and transmucosal delivery in the gut via GM1 receptors present in the intestinal epithelium. The transgene integration was confirmed by PCR and Southern blot analysis. Expression level of CTB-EX4 reached up to 14.3% of total leaf protein (TLP). Lyophilization of leaf material increased therapeutic protein concentration by 12- to 24-fold, extended their shelf life up to 15 months when stored at room temperature and eliminated microbes present in fresh leaves. The pentameric structure, disulphide bonds and functionality of CTB-EX4 were well preserved in lyophilized materials. Chloroplast-derived CTB-EX4 showed increased insulin secretion similar to the commercial EX4 in beta-TC6, a mouse pancreatic cell line. Even when 5000-fold excess dose of CTB-EX4 was orally delivered, it stimulated insulin secretion similar to the intraperitoneal injection of commercial EX4 but did not cause hypoglycaemia in mice. Oral delivery of the bioencapsulated EX4 should eliminate injections, increase patient compliance/convenience and significantly lower their cost. © 2012 The Authors Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  5. Oral Field Cancerization: A Review

    Directory of Open Access Journals (Sweden)

    Raviraj Jayam

    2010-01-01

    Full Text Available The concept of oral field cancerization (OFC has been ever changing since its first description by Slaughter et al in 1953. The concept of OFC explains the mechanisms by which second primary tumors (OPTs develop- OPTs are the tumor-, which develop in the oral cavity in succession to the primary malignant tumors, which might vary in duration ranging from few months to years. The "classical" mechanism, which was originally observed by Slaughter describes that in the individuals with adverse habits, large areas of the aerodigestive tissue are affected by long-term exposure to carcinogens. In this preconditioned epithelium, multifocal carcinomas can develop as a result of independent mutations, and thus would not be genetically related. Although this mechanism was accepted for a quite a long time, the controversies began with the advent of new mechanism called the "clonal theory-, which explains that a single cell, on exposure to carcinogens, is transformed and give- rise to one large extended premalignant field by clonal expansion and gradual replacement of normal mucosa. In this field of various subclones, two separate tumors can develop after accumulation of additional genetic alteration-. Both tumors have the same clonal origin, and would thus share at least one early genetic event, which occurred before the initial clonal expansion. Also, the molecular studies regarding OFC have been expanding exponentially since a few years. The need for chemoprevention and the management of OFC with its resultant effect of development of second primary tumors has been challenging till today. Hence, the article tries to explain the conflicting aspects of various mechanisms by which SPTs develop, the molecular techniques, chemoprevention and therapeutic implications for oral field cancerization.

  6. Epithelium percentage estimation facilitates epithelial quantitative protein measurement in tissue specimens.

    Science.gov (United States)

    Chen, Jing; Toghi Eshghi, Shadi; Bova, George Steven; Li, Qing Kay; Li, Xingde; Zhang, Hui

    2013-12-01

    The rapid advancement of high-throughput tools for quantitative measurement of proteins has demonstrated the potential for the identification of proteins associated with cancer. However, the quantitative results on cancer tissue specimens are usually confounded by tissue heterogeneity, e.g. regions with cancer usually have significantly higher epithelium content yet lower stromal content. It is therefore necessary to develop a tool to facilitate the interpretation of the results of protein measurements in tissue specimens. Epithelial cell adhesion molecule (EpCAM) and cathepsin L (CTSL) are two epithelial proteins whose expressions in normal and tumorous prostate tissues were confirmed by measuring staining intensity with immunohistochemical staining (IHC). The expressions of these proteins were measured by ELISA in protein extracts from OCT embedded frozen prostate tissues. To eliminate the influence of tissue heterogeneity on epithelial protein quantification measured by ELISA, a color-based segmentation method was developed in-house for estimation of epithelium content using H&E histology slides from the same prostate tissues and the estimated epithelium percentage was used to normalize the ELISA results. The epithelium contents of the same slides were also estimated by a pathologist and used to normalize the ELISA results. The computer based results were compared with the pathologist's reading. We found that both EpCAM and CTSL levels, measured by ELISA assays itself, were greatly affected by epithelium content in the tissue specimens. Without adjusting for epithelium percentage, both EpCAM and CTSL levels appeared significantly higher in tumor tissues than normal tissues with a p value less than 0.001. However, after normalization by the epithelium percentage, ELISA measurements of both EpCAM and CTSL were in agreement with IHC staining results, showing a significant increase only in EpCAM with no difference in CTSL expression in cancer tissues. These results

  7. Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Roberts, Blaine R; Lim, Nastasia K H; McAllum, Erin J; Donnelly, Paul S; Hare, Dominic J; Doble, Philip A; Turner, Bradley J; Price, Katherine A; Lim, Sin Chun; Paterson, Brett M; Hickey, James L; Rhoads, Timothy W; Williams, Jared R; Kanninen, Katja M; Hung, Lin W; Liddell, Jeffrey R; Grubman, Alexandra; Monty, Jean-Francois; Llanos, Roxana M; Kramer, David R; Mercer, Julian F B; Bush, Ashley I; Masters, Colin L; Duce, James A; Li, Qiao-Xin; Beckman, Joseph S; Barnham, Kevin J; White, Anthony R; Crouch, Peter J

    2014-06-04

    Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper(II) [Cu(II)(atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with Cu(II)(atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of fully metallated (holo) SOD1. Tracking isotopically enriched (65)Cu(II)(atsm) confirmed the increase in holo-SOD1 involved transfer of Cu from Cu(II)(atsm) to SOD1, suggesting the improved locomotor function and survival of the Cu(II)(atsm)-treated SOD1G37R mice involved, at least in part, the ability of the compound to improve the Cu content of the mutant SOD1. This was supported by improved survival of SOD1G37R mice that expressed the human gene for the Cu uptake protein CTR1. Improving the metal content of mutant SOD1 in vivo with Cu(II)(atsm) did not decrease levels of misfolded SOD1. These outcomes indicate the metal content of SOD1 may be a greater determinant of the toxicity of the protein in mutant SOD1-associated forms of ALS than the mutations themselves. Improving the metal content of SOD1 therefore represents a valid therapeutic strategy for treating ALS caused by SOD1. Copyright © 2014 the authors 0270-6474/14/348021-11$15.00/0.

  8. Evaluation of different toxicity assays applied to proliferating cells and to stratified epithelium in relation to permeability enhancement with glycocholate

    DEFF Research Database (Denmark)

    Eirheim, Heidi Ugelstad; Bundgaard, Christoffer; Nielsen, Hanne Mørck

    2004-01-01

    The purpose of the present study was to evaluate different toxicity assays for use on proliferating buccal TR146 cells and on stratified TR146 epithelium and to compare these results to the permeability enhancing effect of glycocholate (GC). Both the proliferating cells and the epithelium were...... across the epithelium concurrent with a decrease in the transepithelial electrical resistance (TEER) was also determined. The robustness of the epithelium was significantly higher than that of the proliferating cells (P...

  9. Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

    Science.gov (United States)

    Suzuki, Ryo; Katsuno, Tatsuya; Kishimoto, Yo; Nakamura, Ryosuke; Mizuta, Masanobu; Suehiro, Atsushi; Yamashita, Masaru; Nakamura, Tatsuo; Tateya, Ichiro; Omori, Koichi

    2018-04-01

    The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury. Animal experiments with controls. Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin. TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury. It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer. NA. Laryngoscope, 128:E150-E156, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Laser treatment of an oral squamous papilloma in a pediatric patient: A case report

    Directory of Open Access Journals (Sweden)

    Ahmet Ferhat Misir

    2013-01-01

    Full Text Available Oral squamous papilloma is a benign proliferation of the stratified squamous epithelium, which results in a papillary or verrucous exophytic mass induced by human papilloma virus (HPV. These oral mucosa lesions are most often asymptomatic and have small progression. Laser assisted surgery is common nowadays with several advantages including successful hemostasis, devoid of sutures, wound sterilization and minimal post-operative pain and edema. The aim of this report is to present the oral squamous papilloma in a pediatric patient and its treatment with soft tissue laser. The lesion was excised with diode laser and the healing was uneventful in follow-up visit after one year. Oral squamous papillomas can be found in child′s oral cavity and laser dentistry can be used by dental clinicians to treat these kinds of oral lesions and should be considered as an alternative to conventional surgery.

  11. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Extractions and Other Oral Surgeries Extractions and Other Oral Surgeries Oral and maxillofacial surgeons surgically treat the soft ... Extractions and Other Oral Surgeries Extractions and Other Oral Surgeries Oral and maxillofacial surgeons surgically treat the soft ...

  12. Paraoxonase Enzyme Protects Retinal Pigment Epithelium from Chlorpyrifos Insult

    Science.gov (United States)

    Jasna, Jagan Mohan; Anandbabu, Kannadasan; Bharathi, Subramaniam Rajesh; Angayarkanni, Narayanasamy

    2014-01-01

    Retinal pigment epithelium (RPE) provides nourishment and protection to the eye. RPE dysfunction due to oxidative stress and inflammation is one of the major reason for many of the retinal disorders. Organophosphorus pesticides are widely used in the agricultural, industrial and household activities in India. However, their effects on the eye in the context of RPE has not been studied. In this study the defense of the ARPE19 cells exposed to Chlorpyrifos (1 nM to 100 µM) in terms of the enzyme paraoxonase (PON) was studied at 24 hr and 9 days of treatment. Chlorpyrifos was found to induce oxidative stress in the ARPE19 cells as seen by significant increase in ROS and decrease in glutathione (GSH) levels without causing cell death. Tissue resident Paraoxonase 2 (PON2) mRNA expression was elevated with chlorpyrifos exposure. The three enzymatic activities of PON namely, paraoxonase (PONase), arylesterase (PON AREase) and thiolactonase (PON HCTLase) were also found to be significantly altered to detoxify and as an antioxidant defense. Among the transcription factors regulating PON2 expression, SP1 was significantly increased with chlorpyrifos exposure. PON2 expression was found to be crucial as ARPE19 cells showed a significant loss in their ability to withstand oxidative stress when the cells were subjected to chlorpyrifos after silencing PON2 expression. Treatment with N-acetyl cysteine positively regulated the PON 2 expression, thus promoting the antioxidant defense put up by the cells in response to chlorpyrifos. PMID:24979751

  13. Chronic Alcohol Ingestion Changes the Landscape of the Alveolar Epithelium

    Directory of Open Access Journals (Sweden)

    Charles A. Downs

    2013-01-01

    Full Text Available Similar to effects of alcohol on the heart, liver, and brain, the effects of ethanol (EtOH on lung injury are preventable. Unlike other vital organ systems, however, the lethal effects of alcohol on the lung are underappreciated, perhaps because there are no signs of overt pulmonary disorder until a secondary insult, such as a bacterial infection or injury, occurs in the lung. This paper provides overview of the complex changes in the alveolar environment known to occur following both chronic and acute alcohol exposures. Contemporary animal and cell culture models for alcohol-induced lung dysfunction are discussed, with emphasis on the effect of alcohol on transepithelial transport processes, namely, epithelial sodium channel activity (ENaC. The cascading effect of tissue and phagocytic Nadph oxidase (Nox may be triggered by ethanol exposure, and as such, alcohol ingestion and exposure lead to a prooxidative environment; thus impacting alveolar macrophage (AM function and oxidative stress. A better understanding of how alcohol changes the landscape of the alveolar epithelium can lead to improvements in treating acute respiratory distress syndrome (ARDS for which hospitalized alcoholics are at an increased risk.

  14. Regulation of Tight Junctions in Upper Airway Epithelium

    Directory of Open Access Journals (Sweden)

    Takashi Kojima

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Danielle Desjardins

    Full Text Available 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.

  16. Glucose, epithelium, and enteric nervous system: dialogue in the dark.

    Science.gov (United States)

    Pfannkuche, H; Gäbel, G

    2009-06-01

    The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.

  17. LOCALIZATION OF PERMEABILITY BARRIERS IN THE FROG SKIN EPITHELIUM

    Science.gov (United States)

    Martinez-Palomo, A.; Erlij, D.; Bracho, H.

    1971-01-01

    Ruthenium red and colloidal lanthanum were used to determine the site of the structural barriers to diffusion within the intercellular spaces of frog skin epithelium. Electron micrographs show that occluding zonules located at the outer border of the stratum corneum and at the outer layer of the stratum granulosum are true tight junctions since they are impermeable to these tracers. Measurement of 140La uptake by the living skin shows that lanthanum moves across the external surface of the skin readily, into and out of a compartment that has a limited capacity and is bounded on its internal side by a barrier impermeable to lanthanum. Examination of these skins with the electron microscope suggests that the compartment is localized between the external membrane of the cells at the outer layer of the s. granulosum and at the outermost surface of the skin. These observations and other findings described in the literature indicate that the site of the external high resistance barrier of the frog skin is localized at the outer border of the s. granulosum. PMID:4329611

  18. Regeneration of stem-cells in intestinal epithelium after irradiation

    International Nuclear Information System (INIS)

    Hendry, J.H.

    1979-01-01

    Stem-cells can be defined as pluripotent progenitor cells, capable of both self-renewal and differentitation into all the functional end-cells typical of that cell family. Intestinal crypts contain population of cells which is capable of a) self-renewal following the severe depletion after radiation injury, b) replacing all other cypt cell types, and c) regeneration following repeated depletion (in colon). These are the properties of stem cells. Most measurements of the rate of regeneration of these cells following the severe depletion by radiation have been made by employing large test dose at increasing times. Such measurements have produced widely differing rates of increase in the survival under the test dose, from 4 hours (macrocolonies in jejunum) to 43 hours (microcolonies in stomach). In other tissues, large single test doses have been used to derive the time of doubling survival ratio e.g. for epidermal clones. Although cryptogenic cell number per crypt can be virtually restored by day 4 after a single dose and probably after many such doses, the status quo cannot be reached until the number of crypts is restored to normal. Stem cell numbers form a necessary part of the integrity of epitheliums. The quality of the stem cell function of survivors as expressed in the differentiated progeny, and the maintenance of function of the supportive environment are equally important for late radiation damage. (Yamashita, S.)

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

    Science.gov (United States)

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

    2010-05-01

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

  20. Patient-specific three-dimensional explant spheroids derived from human nasal airway epithelium

    DEFF Research Database (Denmark)

    Marthin, June Kehlet; Stevens, Elizabeth Munkebjerg; Larsen, Lars Allan

    2017-01-01

    BACKGROUND: Three-dimensional explant spheroid formation is an ex vivo technique previously used in studies of airway epithelial ion and water transport. Explanted cells and sheets of nasal epithelium form fully differentiated spheroids enclosing a partly fluid-filled lumen with the ciliated apical...... surface facing the outside and accessible for analysis of ciliary function. METHODS: We performed a two-group comparison study of ciliary beat pattern and ciliary beat frequency in spheroids derived from nasal airway epithelium in patients with primary ciliary dyskinesia (PCD) and in healthy controls...... in the investigation of pathophysiological aspects and drug effects in human nasal airway epithelium....

  1. Palatal shelf epithelium: a morphologic and histochemical study in X-irradiated and normal mice

    International Nuclear Information System (INIS)

    Gartner, L.P.; Hiatt, J.L.; Provenza, D.V.

    1978-01-01

    The palatal shelf epithelium of normal and irradiated mice was examined morphologically and histochemically, utilizing the periodic acid-Schiff (PAS) technique for the demonstration of the basement membrane and the Nitro BT method for succinate dehydrogenase activity in order to demonstrate the metabolic competence of its cells. The 'programmed cell death theory' was not supported by the present investigation, since the cells of the medial ridge epithelium retained their structural and metabolic integrity even subsequent to the formation of cell nests. Additionally, the medial ridge epithelium of mice with radiation-induced cleft palates demonstrated normal structural and metabolic integrity long past the prospective time of fusion. (author)

  2. New Insights on the Morphology of Adult Mouse Penis1

    Science.gov (United States)

    Rodriguez, Esequiel; Weiss, Dana A.; Yang, Jennifer H.; Menshenina, Julia; Ferretti, Max; Cunha, Tristan J.; Barcellos, Dale; Chan, Lok Yun; Risbridger, Gail; Cunha, Gerald R.; Baskin, Laurence S.

    2011-01-01

    ABSTRACT The adult mouse penis represents the end point of masculine sex differentiation of the embryonic genital tubercle and contains bone, cartilage, the urethra, erectile bodies, several types of epithelium, and many individual cell types arrayed into specific anatomical structures. Using contemporary high-resolution imaging techniques, we sought to provide new insights to the current description of adult mouse penile morphology to enable understanding of penile abnormalities, including hypospadias. Examination of serial transverse and longitudinal sections, scanning electron microscopy, and three-dimensional (3D) reconstruction provided a new appreciation of the individual structures in the adult mouse penis and their 3D interrelationships. In so doing, we discovered novel paired erectile bodies, the male urogenital mating protuberance (MUMP), and more accurately described the urethral meatus. These morphological observations were quantified by morphometric analysis and now provide accurate morphological end points of sex differentiation of mouse penis that will be the foundation of future studies to identify normal and abnormal penile development. PMID:21918128

  3. Gaze beats mouse

    DEFF Research Database (Denmark)

    Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin

    2008-01-01

    Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze...

  4. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Ana M. C. Faria

    2006-01-01

    Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

  5. Towards understanding oral health

    NARCIS (Netherlands)

    Zaura, E.; ten Cate, J.M.

    2015-01-01

    During the last century, dental research has focused on unraveling the mechanisms behind various oral pathologies, while oral health was typically described as the mere absence of oral diseases. The term ‘oral microbial homeostasis' is used to describe the capacity of the oral ecosystem to maintain

  6. Cellular internalization and transport of biodegradable polyester dendrimers on a model of the pulmonary epithelium and their formulation in pressurized metered-dose inhalers.

    Science.gov (United States)

    Heyder, Rodrigo S; Zhong, Qian; Bazito, Reinaldo C; da Rocha, Sandro R P

    2017-03-30

    The purpose of this study was to evaluate the effect of generation and surface PEGylation of degradable polyester-based dendrimers nanocarriers on their interactions with an in vitro model of the pulmonary epithelium as well as to assess the ability to formulate such carriers in propellant-based, portable oral-inhalation devices to determine their potential for local and systemic delivery of drugs to and through the lungs. Hydroxyl (-OH) terminated polyester dendrimers of generation 3 and 4 (G3, and G4) were synthesized using a divergent approach. G4 was surface-modified with PEG (1,000Da). All dendrimers and their building blocks were determined to be highly compatible with the model pulmonary epithelium, with toxicity profiles much more favorable than non-degradable polyamidoamine dendrimers (PAMAM). The transport of the species from the apical to basolateral side across polarized Calu-3 monolayers showed to be generation and surface-chemistry (PEGylation) dependent. The extent of the transport is modulated by their interaction with the polarized epithelium and their transient opening of the tight junctions. G3 was the one most efficiently internalized by the epithelium, and had a small impact on the integrity of the monolayer. On the other hand, the PEGylated G4 was the one least internalized by the polarized epithelium, and at the same time had a more pronounced transient impact on the cellular junctions, resulting in more efficient transport across the cell monolayer. PEGylation of the dendrimer surface played other roles as well. PEGylation modulated the degradation profile of the dendrimer, slowing the process in a step-wise fashion - first the PEG layer is shed and then the dendrimer starts degrading. PEGylation also helped increase the solvation of the nanocarriers by the hydrofluoroalkane propellant used in pressurized metered-dose inhalers, resulting in formulations with excellent dispersibility and aerosol quality (deep lung deposition of 88

  7. Transcytosis of F4 fimbriae by villous and dome epithelia in F4-receptor positive pigs supports importance of receptor-dependent endocytosis in oral immunization strategies.

    Science.gov (United States)

    Snoeck, Veerle; Van den Broeck, Wim; De Colvenaer, Veerle; Verdonck, Frank; Goddeeris, Bruno; Cox, Eric

    2008-07-15

    Very few antigens have been described that induce an intestinal immunity when given orally. Our laboratory demonstrated that oral administration of isolated F4 (K88) fimbriae of Escherichia coli to F4-receptor positive (F4R(+)) pigs induces protective mucosal immunity against challenge infection. However, presence of F4-receptors (F4R) on villous enterocytes is a prerequisite for inducing the immune response, as no F4-specific antibody-secreting cells (ASC) can be induced in F4R(-) pigs. In this study, the in vivo binding of isolated F4 fimbriae (F4) to the gut epithelium was examined in F4R(+) and F4R(-) pigs. It was further investigated whether binding of F4 to the F4R results in endocytosis in and translocation across the gut epithelium using microscopy. F4 did not adhere to the intestinal epithelium of F4R(-) pigs, whereas it strongly adhered to the villous epithelium and the follicle-associated epithelium (FAE) of the jejunum and ileum of F4R(+) pigs. Following binding to F4R, F4 was endocytosed by villous enterocytes, follicle-associated enterocytes and M cells. Transcytosis of F4 across the epithelium resulted in the appearance of F4 in the lamina propria and dome region of the jejunal and ileal PP. This is the first study showing transcytosis of fimbriae across the gut epithelium. This receptor-dependent transcytosis can explain the success of F4 fimbriae as oral immunogen for inducing protective immunity in F4R(+) pigs strengthening the importance of receptor-dependent endocytosis and translocation in oral vaccine strategies. Further identification of the receptor responsible for this transport is in progress.

  8. Oral dirofilariasis

    Directory of Open Access Journals (Sweden)

    Mahija Janardhanan

    2014-01-01

    Full Text Available Filariasis affecting animals can rarely cause infections in human beings through the accidental bite of potential vectors. The resulting infection in man, known as zoonotic filariasis occur worldwide. Human dirofilariasis, the most common zoonotic filariasis, is caused by the filarial worm belonging to the genus Dirofilaria. Dirofilarial worms, which are recognized as pathogenic in man can cause nodular lesions in the lung, subcutaneous tissue, peritoneal cavity or eyes. Oral dirofilariasis is extremely rare and only a few cases have been documented. We report an interesting case of dirofilariasis due to Dirofilaria repens involving buccal mucosa in a patient who presented with a facial swelling. The clinical features, diagnostic issues and treatment aspects are discussed. This paper stresses the importance of considering dirofilariasis as differential diagnosis for subcutaneous swelling of the face, especially in areas where it is endemic.

  9. Oral dirofilariasis.

    Science.gov (United States)

    Janardhanan, Mahija; Rakesh, S; Savithri, Vindhya

    2014-01-01

    Filariasis affecting animals can rarely cause infections in human beings through the accidental bite of potential vectors. The resulting infection in man, known as zoonotic filariasis occur worldwide. Human dirofilariasis, the most common zoonotic filariasis, is caused by the filarial worm belonging to the genus Dirofilaria. Dirofilarial worms, which are recognized as pathogenic in man can cause nodular lesions in the lung, subcutaneous tissue, peritoneal cavity or eyes. Oral dirofilariasis is extremely rare and only a few cases have been documented. We report an interesting case of dirofilariasis due to Dirofilaria repens involving buccal mucosa in a patient who presented with a facial swelling. The clinical features, diagnostic issues and treatment aspects are discussed. This paper stresses the importance of considering dirofilariasis as differential diagnosis for subcutaneous swelling of the face, especially in areas where it is endemic.

  10. Oral sex, oral health and orogenital infections

    Directory of Open Access Journals (Sweden)

    Rajiv Saini

    2010-01-01

    Full Text Available Oral sex is commonly practiced by sexually active male-female and same-gender couples of various ages, including adolescents. The various type of oral sex practices are fellatio, cunnilingus and analingus. Oral sex is infrequently examined in research on adolescents; oral sex can transmit oral, respiratory, and genital pathogens. Oral health has a direct impact on the transmission of infection; a cut in your mouth, bleeding gums, lip sores or broken skin increases chances of infection. Although oral sex is considered a low risk activity, it is important to use protection and safer sex precautions. There are various methods of preventing infection during oral sex such as physical barriers, health and medical issues, ethical issues and oral hygiene and dental issues. The lesions or unhealthy periodontal status of oral cavity accelerates the phenomenon of transmission of infections into the circulation. Thus consequences of unhealthy or painful oral cavity are significant and oral health should be given paramount importance for the practice of oral sex.

  11. Prognostic potential of n-cadherin in oral squamous cell carcinoma via immunohistochemical methods

    International Nuclear Information System (INIS)

    Chandolia, B.; Arora, M.; Rajliwal, P.

    2017-01-01

    To assess the prognostic potential for N-cadherin in oral squamous cell carcinoma and oral epithelial dysplasia. Study Design: A cross-sectional study, analytical study. Place and Duration of Study: Maharishi Markandeshwar College of Dental Science Research (MMCDSR), Ambala, India, from 2011 to 2014. Methodology: Immunohistochemistry was used to observe the N-cadherin expression in 100 cases having epithelium with normal oral mucosa, oral epithelial dysplastic lesions and oral squamous cell carcinoma (OSCC). For statistical significance, SPSS 13.0 was used to calculate the data by Mann-Whitney and Kruskal-Wallis tests. Results: In OSCC, N-cadherin expression was more evident than in oral epithelial dysplasia followed by the normal oral epithelium that did not show any dysplastic changes (p=0.001). Conversely, N-cadherin expression was not significant among the histological grade of OSCC. Conclusion: N-cadherin can be used as a potential biomarker for early diagnosis of OSCC. However, the N-cadherin expression did not show any correlation with the histological grade of OSCC. (author)

  12. Prognostic Potential of N-Cadherin in Oral Squamous Cell Carcinoma via Immunohistochemical Methods.

    Science.gov (United States)

    Chandolia, Betina; Rajliwal, Jai Parkash; Bajpai, Manas; Arora, Manika

    2017-08-01

    To assess the prognostic potential for N-cadherin in oral squamous cell carcinoma and oral epithelial dysplasia. Across-sectional study, analytical study. Maharishi Markandeshwar College of Dental Science Research (MMCDSR), Ambala, India, from 2011 to 2014. Immunohistochemistry was used to observe the N-cadherin expression in 100 cases having epithelium with normal oral mucosa, oral epithelial dysplastic lesions and oral squamous cell carcinoma (OSCC). For statistical significance, SPSS 13.0 was used to calculate the data by Mann-Whitney and Kruskal-Wallis tests. In OSCC, N-cadherin expression was more evident than in oral epithelial dysplasia followed by the normal oral epithelium that did not show any dysplastic changes (p=0.001). Conversely, N-cadherin expression was not significant among the histological grade of OSCC. N-cadherin can be used as a potential biomarker for early diagnosis of OSCC. However, the N-cadherin expression did not show any correlation with the histological grade of OSCC.

  13. Intra-oral Sebaceous Gland Tumours in Two Dogs.

    Science.gov (United States)

    Go, D-M; Lee, S-H; Woo, S-H; Kim, D-Y

    2017-11-01

    A 12-year-old female miniature schnauzer and a 12-year-old neutered female cocker spaniel each had a grey-yellow nodular lesion arising from the gingiva. Microscopical examination showed that both nodules were composed of varied proportions of sebocytes and basal-type reserve cells with few ducts lined by stratified squamous epithelium. Based on the histopathological findings, the cases were diagnosed as sebaceous adenoma and sebaceous epithelioma, respectively. In man, the occurrence of sebaceous neoplasms in the oral cavity has been reported to some extent, but these lesions are very rare in animals. To the best of our knowledge, this is the first report of intra-oral sebaceous neoplasms in dogs. Intra-oral sebaceous epithelioma has never been reported in animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. FORMALDEHYDE-INDUCED GENE EXPRESSION IN F344 RAT NASAL RESPIRATORY EPITHELIUM.

    Science.gov (United States)

    Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium ABSTRACTFormaldehyde, an occupational and environmental toxicant used extensively in the manufacturing of many household and personal use products, is known to induce squamous cell carci...

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

    Science.gov (United States)

    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 epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Shigella infection of intestinal epithelium and circumvention of the host innate defense system.

    Science.gov (United States)

    Ashida, Hiroshi; Ogawa, Michinaga; Mimuro, Hitomi; Sasakawa, Chihiro

    2009-01-01

    Shigella, Gram-negative bacteria closely related to Escherichia coli, are highly adapted human pathogens that cause bacillary dysentery. Although Shigella have neither adherence factors nor flagella required for attaching or accessing the intestinal epithelium, Shigella are capable of colonizing the intestinal epithelium by exploiting epithelial-cell functions and circumventing the host innate immune response. During Shigella infection, they deliver many numbers of effectors through the type III secretion system into the surrounding space and directly into the host-cell cytoplasm. The effectors play pivotal roles from the onset of bacterial infection through to the establishment of the colonization of the intestinal epithelium, such as bacterial invasion, intracellular survival, subversion of the host immune defense response, and maintenance of the infectious foothold. These examples suggest that Shigella have evolved highly sophisticated infectious and intracellular strategies to establish replicative niches in the intestinal epithelium.

  17. The cytological status of the nasal mucosa and the buccal epithelium in coal miners

    Energy Technology Data Exchange (ETDEWEB)

    L.T. Bazeliuk; B.M. Salimbaeva

    2006-11-15

    Sixty-four persons were examined. The examination was undertaken to study the cytomophological parameters of the cells of the nasal mucosa and the buccal epithelium in coal miners. Group 1 consisted of 18 donors without contact with industrial dust; Group 2 comprised 24 apparently healthy miners; Group 3 included 22 workers (drift miners) with Stage 1 anthracosilicosis, grade 1 respiratory failure. The patients with Stage 1 anthracosilicosis had noticeably worse morphofunctional characteristics of the epithelium that displayed extensive fields with pronounced structural changes, such as destruction and desquamation of the integumentary epithelium of the nasal mucosa. Nasal mucosal atrophic changes were observed in 50% of the examined miners. Examination of the buccal epithelium in apparently healthy miners (code 0) and in workers with Stage I anthracosilicosis revealed the increased proportion of microfloral (Streptococcus) contamination by 79% and 3.7 times, respectively.

  18. Does autophagy in the midgut epithelium of centipedes depend on the day/night cycle?

    Czech Academy of Sciences Publication Activity Database

    Rost-Roszkowska, M.M.; Chajec, Ł.; Vilímová, J.; Tajovský, Karel; Kszuk-Jendrysik, M.

    2015-01-01

    Roč. 68, January (2015), s. 130-139 ISSN 0968-4328 Institutional support: RVO:60077344 Keywords : centipede * midgut epithelium * digestive cells * ultrastructure * autophagy Subject RIV: EG - Zoology Impact factor: 1.838, year: 2015

  19. Characterization of a spontaneously generated murine retinal pigmented epithelium cell line; a model for in vitro experiments.

    Science.gov (United States)

    Ranaei Pirmardan, Ehsan; Soheili, Zahra-Soheila; Samiei, Shahram; Ahmadieh, Hamid; Mowla, Seyed Javad; Ezzati, Razie; Naseri, Marzieh

    2016-10-01

    Retinal pigmented epithelium (RPE), the outermost layer of the retina, has a key role in maintaining retinal cells' functions. Severity of the culture of RPE cells has exerted many limitations to both in vitro and in vivo studies and its therapeutic applications. Therefore, establishment of RPE cell lines with high proliferative potential can considerably improve study of RPE cell biology. Here we report generation of a spontaneously immortalized murine RPE cell line in primary mouse RPE cell culture. Founded colonized cells were picked up and expression of RPE and retinal progenitor cells' (RPC) markers were studied using immunocytochemistry (ICC). Emerged cells cultured over 35 passages and population doubling times in different serum concentrations were calculated. We also investigated the ability of cells for becoming transfected by calcium-phosphate method and for becoming infected by adeno-associated virus serotype 2 (AAV2) using flow cytometry. Data showed that the cobblestone constituent cells expressed RPE65, cytokeratin and ZO1 and moreover several progenitor markers such as Pax6, Sox2, Nestin and Chx10. It revealed that, despite primary RPE cells, the newly emerged cells were easily transfectable and were highly infectable when compared with HEK293T cells. Our data indicated that the emerged mouse RPE cell line pretended RPC-like phenotype and also simultaneously expressed RPE markers. It would be a promising model for leading studies on RPE and RPC cells and substantially confirmed the great RPE plasticity and its invaluable potential in research studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Functional annotation of the human retinal pigment epithelium transcriptome

    Directory of Open Access Journals (Sweden)

    Gorgels Theo GMF

    2009-04-01

    Full Text Available Abstract Background To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE, the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years were laser dissected and used for 22k microarray studies (Agilent technologies. Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software. Results In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194 expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776 genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194 of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover. Conclusion Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the

  1. Age-related changes in the retinal pigment epithelium (RPE.

    Directory of Open Access Journals (Sweden)

    Xiaorong Gu

    Full Text Available Age-related changes in the retina are often accompanied by visual impairment but their mechanistic details remain poorly understood.Proteomic studies were pursued toward a better molecular understanding of retinal pigment epithelium (RPE aging mechanisms. RPE cells were isolated from young adults (3-4 month-old and old (24-25 month-old F344BN rats, and separated into subcellular fractions containing apical microvilli (MV and RPE cell bodies (CB lacking their apical microvilli. Proteins were extracted in detergent, separated by SDS-PAGE, digested in situ with trypsin and analyzed by LC MS/MS. Select proteins detected in young and old rat RPE were further studied using immunofluorescence and Western blot analysis.A total of 356 proteins were identified in RPE MV from young and 378 in RPE MV from old rats, 48% of which were common to each age group. A total of 897 proteins were identified in RPE CB from young rats and 675 in old CB, 56% of which were common to each age group. Several of the identified proteins, including proteins involved in response to oxidative stress, displayed both quantitative and qualitative changes in overall abundance during RPE aging. Numerous proteins were identified for the first time in the RPE. One such protein, collectrin, was localized to the apical membrane of apical brush border of proximal tubules where it likely regulates several amino acid transporters. Elsewhere, collectrin is involved in pancreatic β cell proliferation and insulin secretion. In the RPE, collectrin expression was significantly modulated during RPE aging. Another age-regulated, newly described protein was DJ-1, a protein extensively studied in brain where oxidative stress-related functions have been described.The data presented here reveals specific changes in the RPE during aging, providing the first protein database of RPE aging, which will facilitate future studies of age-related retinal diseases.

  2. Optical modulation of transgene expression in retinal pigment epithelium

    Science.gov (United States)

    Palanker, D.; Lavinsky, D.; Chalberg, T.; Mandel, Y.; Huie, P.; Dalal, R.; Marmor, M.

    2013-03-01

    Over a million people in US alone are visually impaired due to the neovascular form of age-related macular degeneration (AMD). The current treatment is monthly intravitreal injections of a protein which inhibits Vascular Endothelial Growth Factor, thereby slowing progression of the disease. The immense financial and logistical burden of millions of intravitreal injections signifies an urgent need to develop more long-lasting and cost-effective treatments for this and other retinal diseases. Viral transfection of ocular cells allows creation of a "biofactory" that secretes therapeutic proteins. This technique has been proven successful in non-human primates, and is now being evaluated in clinical trials for wet AMD. However, there is a critical need to down-regulate gene expression in the case of total resolution of retinal condition, or if patient has adverse reaction to the trans-gene products. The site for genetic therapy of AMD and many other retinal diseases is the retinal pigment epithelium (RPE). We developed and tested in pigmented rabbits, an optical method to down-regulate transgene expression in RPE following vector delivery, without retinal damage. Microsecond exposures produced by a rapidly scanning laser vaporize melanosomes and destroy a predetermined fraction of the RPE cells selectively. RPE continuity is restored within days by migration and proliferation of adjacent RPE, but since the transgene is not integrated into the nucleus it is not replicated. Thus, the decrease in transgene expression can be precisely determined by the laser pattern density and further reduced by repeated treatment without affecting retinal structure and function.

  3. Claudin-8d is a cortisol-responsive barrier protein in the gill epithelium of trout.

    Science.gov (United States)

    Kolosov, Dennis; Kelly, Scott P

    2017-10-01

    The influence of claudin (Cldn) 8 tight junction (TJ) proteins on cortisol-mediated alterations in gill epithelium permeability was examined using a primary cultured trout gill epithelium model. Genes encoding three Cldn-8 proteins ( cldn-8b, -8c and -8d ) have been identified in trout and all are expressed in the model gill epithelium. Cortisol treatment 'tightened' the gill epithelium, as indicated by increased transepithelial resistance (TER) and reduced paracellular [ 3 H]polyethylene glycol (MW 400 Da; PEG-400) flux. This occurred in association with elevated cldn-8d mRNA abundance, but no alterations in cldn-8b and -8c mRNA abundance were observed. Transcriptional knockdown (KD) of cldn-8d inhibited a cortisol-induced increase in Cldn-8d abundance and reduced the 'epithelium tightening' effect of cortisol in association with increased paracellular PEG-400 flux. Under simulated in vivo conditions (i.e. apical freshwater), cldn-8d KD hindered a cortisol-mediated reduction in basolateral to apical Na + and Cl - flux (i.e. reduced the ability of cortisol to mitigate ion loss). However, cldn-8d KD did not abolish the tightening effect of cortisol on the gill epithelium. This is likely due, in part, to the effect of cortisol on genes encoding other TJ proteins, which in some cases appeared to exhibit a compensatory response. Data support the idea that Cldn-8d is a barrier protein of the gill epithelium TJ that contributes significantly to corticosteroid-mediated alterations in gill epithelium permeability. © 2017 Society for Endocrinology.

  4. Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

    Science.gov (United States)

    Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

    2014-01-01

    We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

  5. Radiosensitivity of spermatogenous epithelium stem cells of mice of different strains and age

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.; Konoplyannikov, A.G.

    1988-01-01

    In experiments on CBA and BALB/c male mices (3 months of age) and F 1 (CBAxC57BL/6) hybrides (at the age of 3, 12, and 24 months) a difference was noted in the radiosensitivity of spermatogenous epithelium stem cells displayed by the changes in their colony-forming ability to testicular tubules 42 days following local 60 Co-γ-irradiation. The older the hybrid mice the smaller was the number of spermatogenous epithelium stem cells

  6. [Alterations in the metabolism of cornmeal epithelium during medium-term storage (author's transl)].

    Science.gov (United States)

    Schmidt-Martens, F W; Hennighausen, U; Wirz, K; Teping, C

    1977-08-08

    Freshly prepared bovine corneas were stored in medium TC 199 with penicillin and fetal calf serum at +4 degrees C over a storage period of 168h. Every 24h, the levels of glucose, lactate, and pyruvate in the corneal epithelium were estimated. Also the glucose levels in the corneal epithelium and stroma were compared at the same time intervals. Furthermore, alterations in the enzyme pattern of the epithelial cells during storage were observed.

  7. Phagocytosis of Giardia muris by macrophages in Peyer's patch epithelium in mice.

    OpenAIRE

    Owen, R L; Allen, C L; Stevens, D P

    1981-01-01

    No mechanism for the initiation of immunological clearance of Giardia from the mammalian intestinal tract has been identified. In normal and nude mice experimentally infected with G. muris, we examined antigen-sampling epithelium over Peyer's patch follicles by electron microscopy for evidence of interaction between G. muris and lymphoid cells. Invading G. muris were found in the epithelium near dying or desquamating columnar cells. Macrophages beneath the basal lamina extended pseudopods int...

  8. Plant lectins as carriers for oral drugs: Is wheat germ agglutinin a suitable candidate?

    International Nuclear Information System (INIS)

    Dalla Pellegrina, Chiara; Rizzi, Corrado; Mosconi, Silvia; Zoccatelli, Gianni; Peruffo, Angelo; Chignola, Roberto

    2005-01-01

    Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed also by gastrointestinal epithelial cells. WGA is currently investigated as an anti-tumor drug and as a carrier for oral drugs. Information on whether it can cross the gastrointestinal epithelium and on its possible effects on the integrity of the epithelial layer is however scanty or lacking, and herein we address these issues. Differentiated Caco2 cells have been used as a model of polarized intestinal epithelium. WGA concentration at both the apical and the basolateral side of the epithelium has been quantified using a sensitive ELISA assay (sensitivity threshold 0.84 nM). Trans epithelial electrical resistance (TEER) has been measured to evaluate the integrity of the epithelium upon treatments with WGA. 3 H-Mannitol (182.2 Da) and FITC-dextran (3000 Da) have been used to measure the permeability of the epithelium. Cell viability has been measured by the MTT, by 7-AAD uptake, and Annexin-V binding assays. Up to a concentration of 5.6 μM, ∼0.1% of intact WGA molecules only could cross the epithelial layer. WGA perturbed the integrity of the epithelium and increased the permeability of the tissue in a dose- and time-dependent manner. WGA did not induce cell death but increased the permeability of individual cells to 7-AAD which is normally not uptaken by viable cells. These data allowed us to define a toxicity threshold for WGA on epithelial cells. WGA suitability as a carrier for oral drugs can therefore be evaluated on a rational basis

  9. Gene expression changes in the colon epithelium are similar to those of intact colon during late inflammation in interleukin-10 gene deficient mice.

    Directory of Open Access Journals (Sweden)

    Anna E Russ

    Full Text Available In addition to their role in absorption and secretion, epithelial cells play an important role in the protection of the colon mucosa from the resident microbiota and are important for the maintenance of homeostasis. Microarray analysis of intact colon samples is widely used to gain an overview of the cellular pathways and processes that are active in the colon during inflammation. Laser microdissection of colon epithelial cells allows a more targeted analysis of molecular pathways in the mucosa, preceding and during inflammation, with potentially increased sensitivity to changes in specific cell populations. The aim of this study was to investigate the molecular changes that occur in early and late inflammation stages in colon epithelium of a mouse model of inflammatory bowel diseases. Microarray analysis of intact colon samples and microdissected colon epithelial cell samples from interleukin-10 gene deficient and control mice at 6 and 12 weeks of age was undertaken. Results of gene set enrichment analysis showed that more immune-related pathways were identified between interleukin-10 gene deficient and control mice at 6 weeks of age in epithelial cells than intact colon. This suggests that targeting epithelial cells could increase sensitivity for detecting immune changes that occur early in the inflammatory process. However, in the later stages of inflammation, microarray analyses of intact colon and epithelium both provide a similar overview of gene expression changes in the colon mucosa at the pathway level.

  10. A loss of profilin-1 in late-stage oral squamous cell carcinoma.

    Science.gov (United States)

    Adami, Guy R; O'Callaghan, Thomas N; Kolokythas, Antonia; Cabay, Robert J; Zhou, Yalu; Schwartz, Joel L

    2017-08-01

    The genes for PFN1 and TMSB4 are both highly expressed in oral tissue and both encode actin monomer binding proteins thought to play a role in cell motility and possibly other crucial parts of tumor progression. Oral brush cytology of epithelium from oral squamous cell carcinoma (OSCC) was used to measure PFN1 and TMSB4 mRNA in OSCC, while immunohistochemical analysis of tissue was used to check protein levels. High but variable expression of mRNAs encoding these two proteins was observed suggesting they may contribute to tumor characteristics in a subset of OSCCs. Both proteins were highly expressed in normal appearing basal epithelium, in the cytoplasm, and perinuclear area, while expression was minimal in upper epithelial layers. In OSCCs, expression of these proteins varied. In tumors classified as later stage, based on size and/or lymph node involvement, PFN1 levels were lower in tumor epithelium. A control gene, KRT13, showed expression in normal differentiated basal and suprabasal oral mucosa epithelial cells and as reported was lost in OSCC cells. Loss of PFN1 in tumor cells has been associated with lymph node invasion and metastasis in other tumor types, strengthening the argument that the protein has the potential to be a tumor suppressor in late-stage OSCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Radiosensitivity of mice of different lines and age as determinated with reference to ''intestinal'' death and DNA repair in intestinal epithelium cells

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.; Sklobovskaya, M.V.; Konoplyannikov, A.G.; Saenko, A.S.

    1982-01-01

    A study was made of the influence of strain- and age-related differences on mouse mortality after irradiation with doses lying within the ''intest+nal'' dose range, and also damages to stem cells of intestinal epithelium and induction and repair of single-strand DNA breaks in intestinal epitherium cells. Mice of different lines and age vary in LDsub(50/4) and stem cell radiosensitivity. There are no differences in the sedimentation constants of DNA fragments in alkaline lysates of intestinal crypts of intact mice of different age. Radiosensitivity determined with reference to single-strand breaks induction in DNA is similar with different mo use groups. Repair of single-strand DNA breaks of eldery mice is slower than that of young animals

  12. 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.

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    Win Kyaw Phyu

    Full Text Available 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.

  13. Spatial pattern of cell geometry and cell-division orientation in zebrafish lens epithelium

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    Toshiaki Mochizuki

    2014-09-01

    Full Text Available Cell proliferation is a key regulator of tissue morphogenesis. We examined cell proliferation and cell division in zebrafish lens epithelium by visualizing cell-cycle phases and nuclear positions, using fluorescent-labeled geminin and histone proteins. Proliferation was low in the anterior region of lens epithelium and higher in the marginal zone anterior to the equator, suggesting that the proliferation zone, called the germinative zone, is formed in zebrafish lens. Interestingly, cell-division orientation was biased longitudinally in the anterior region, shifted from longitudinal to circumferential along the anterior–posterior axis of lens sphere, and was biased circumferentially in the peripheral region. These data suggest that cell-division orientation is spatially regulated in zebrafish lens epithelium. The Hertwig rule indicates that cells tend to divide along their long axes. Orientation of long axes and cell division were biased similarly in zebrafish lens epithelium, suggesting that cell geometry correlates with cell-division orientation. A cell adhesion molecule, E-cadherin, is expressed in lens epithelium. In a zebrafish e-cadherin mutant, the long axes and cell-division orientation were shifted more longitudinally. These data suggest that E-cadherin is required for the spatial pattern of cell geometry and cell-division orientation in zebrafish lens epithelium.

  14. Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

    Science.gov (United States)

    Kennedy, M F; Tutton, P J; Barkla, D H

    1985-09-01

    Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour.

  15. Establishment of primary cultures for mouse ameloblasts as a model of their lifetime

    International Nuclear Information System (INIS)

    Suzawa, Tetsuo; Itoh, Nao; Takahashi, Naoyuki; Katagiri, Takenobu; Morimura, Naoko; Kobayashi, Yasuna; Yamamoto, Toshinori; Kamijo, Ryutaro

    2006-01-01

    To understand how the properties of ameloblasts are spatiotemporally regulated during amelogenesis, two primary cultures of ameloblasts in different stages of differentiation were established from mouse enamel epithelium. Mouse primary ameloblasts (MPAs) prepared from immature enamel epithelium (MPA-I) could proliferate, whereas those from mature enamel epithelium (MPA-M) could not. MPA-M but not MPA-I caused apoptosis during culture. The mRNA expression of amelogenin, a marker of immature ameloblasts, was down-regulated, and that of enamel matrix serine proteiase-1, a marker of mature ameloblasts, was induced in MPA-I during culture. Using green fluorescence protein as a reporter, a visualized reporter system was established to analyze the promoter activity of the amelogenin gene. The region between -1102 bp and -261 bp was required for the reporter expression in MPA-I. These results suggest that MPAs are valuable in vitro models for investigation of ameloblast biology, and that the visualized system is useful for promoter analysis in MPAs

  16. Inhibition of Inflammation-Associated Olfactory Loss by Etanercept in an Inducible Olfactory Inflammation Mouse Model.

    Science.gov (United States)

    Jung, Yong Gi; Lane, Andrew P

    2016-06-01

    To determine the effect of a soluble human tumor necrosis factor alpha (TNF-α) receptor blocker (etanercept) on an inducible olfactory inflammation (IOI) mouse model. An in vivo study using a transgenic mouse model. Research laboratory. To study the impact of chronic inflammation on the olfactory system, a transgenic mouse model of chronic rhinosinusitis-associated olfactory loss was utilized (IOI mouse), expressing TNF-α in a temporally controlled fashion within the olfactory epithelium. In one group of mice (n = 4), etanercept was injected intraperitoneally (100 μg/dose, 3 times/week) concurrent with a 2-week period of TNF-α expression. A second group of mice (n = 2) underwent induction of TNF-α expression for 8 weeks, with etanercept treatment administered during the final 2 weeks of inflammation. Olfactory function was assayed by elecro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Each group was compared with an equal-number control group. Compared with nontreated IOI mice, etanercept-treated IOI mice showed significantly improved EOG responses after 2 weeks (P loss of olfactory epithelium and no EOG response in nontreated IOI mice. However, in etanercept-treated mice, regeneration of olfactory epithelium was observed. Concomitant administration of etanercept in IOI mice results in interruption of TNF-α-induced olfactory loss and induction of neuroepithelial regeneration. This demonstrates that etanercept has potential utility as a tool for elucidating the role of TNF-α in other olfactory inflammation models. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  17. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  18. Mouse Phenome Database (MPD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mouse Phenome Database (MPD) has characterizations of hundreds of strains of laboratory mice to facilitate translational discoveries and to assist in selection...

  19. Indian hedgehog signaling from endothelial cells is required for sclera and retinal pigment epithelium development in the mouse eye.

    Science.gov (United States)

    Dakubo, Gabriel D; Mazerolle, Chantal; Furimsky, Marosh; Yu, Chuan; St-Jacques, Benoit; McMahon, Andrew P; Wallace, Valerie A

    2008-08-01

    The development of extraocular orbital structures, in particular the choroid and sclera, is regulated by a complex series of interactions between neuroectoderm, neural crest and mesoderm derivatives, although in many instances the signals that mediate these interactions are not known. In this study we have investigated the function of Indian hedgehog (Ihh) in the developing mammalian eye. We show that Ihh is expressed in a population of non-pigmented cells located in the developing choroid adjacent to the RPE. The analysis of Hh mutant mice demonstrates that the RPE and developing scleral mesenchyme are direct targets of Ihh signaling and that Ihh is required for the normal pigmentation pattern of the RPE and the condensation of mesenchymal cells to form the sclera. Our findings also indicate that Ihh signals indirectly to promote proliferation and photoreceptor specification in the neural retina. This study identifies Ihh as a novel choroid-derived signal that regulates RPE, sclera and neural retina development.

  20. Mechanism of induction of nuclear anomalies by gamma-radiation in the colonic epithelium of the mouse

    International Nuclear Information System (INIS)

    Duncan, A.M.; Heddle, J.A.; Blakey, D.H.

    1985-01-01

    The induction of karyorrhexis and nuclear anomalies in colonic crypt cells has been correlated positively with the induction of colonic tumors by chemical treatment. These nuclear anomalies occur in the proliferative region of the crypt and exhibit a variety of morphological characteristics. Some nuclear anomalies resemble the micronuclei that arise from chromosomal fragments after mitosis. Here, we report that the nuclear anomalies observed within the first few hr of insult with gamma-radiation are independent of mitosis for their expression, as evidenced by failure of colchicine to inhibit their induction, and do not arise from chromosomal material lost during mitosis

  1. LGR4 and LGR5 regulate hair cell differentiation in the sensory epithelium of the developing mouse cochlea

    NARCIS (Netherlands)

    Zak, Magdalena; Van Oort, Thijs; Hendriksen, Ferry G.; Garcia, Marie Isabelle; Vassart, Gilbert; Grolman, Wilko

    2016-01-01

    In the developing cochlea, Wnt/β-catenin signaling positively regulates the proliferation of precursors and promotes the formation of hair cells by up-regulating Atoh1 expression. Not much, however, is known about the regulation of Wnt/β-catenin activity in the cochlea. In multiple tissues, the

  2. Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

    Directory of Open Access Journals (Sweden)

    Rosemary C Challis

    Full Text Available We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII, a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found, similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

  3. Detection of Helicobacter pylori in Oral Lesions

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    Soussan Irani

    2013-12-01

    Full Text Available Background and aims. Helicobacter pylori is a microaerophilic gram-negative spiral organism. It is recognized as the etiologic factor for peptic ulcers, gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from dental plaque and the dorsum of the tongue. This study was designed to assess the association between H. pylori and oral lesions such as ulcerative/inflammatory lesions, squamous cell carcinoma (SCC and primary lymphoma. Materials and methods. A total of 228 biopsies diagnosed as oral ulcerative/inflammatory lesions, oral squamous cell carcinoma (OSCC and oral primary lymphoma were selected from the archives of the Pathology Department. Thirty-two samples that were diagnosed as being without any pathological changes were selected as the control group. All the paraffin blocks were cut for hematoxylin and eosin staining to confirm the diagnoses and then the samples were prepared for immunohistochemistry staining. Data were collected and analyzed. Results. Chi-squared test showed significant differences between the frequency of H. pylori positivity in normal tissue and the lesions were examined (P=0.000. In addition, there was a statistically significant difference between the lesions examined (P=0.042. Chi-squared test showed significant differences between H. pylori positivity and different tissue types except inside the muscle layer as follows: in epithelium and in lamina propria (P=0.000, inside the blood vessels (P=0.003, inside the salivary gland duct (P=0.036, and muscle layer (P=0.122. Conclusion. There might be a relation between the presence of H. pylori and oral lesions. Therefore, early detection and eradication of H. pylori in high-risk patients are suggested.

  4. Tracheal epithelium cell volume responses to hyperosmolar, isosmolar and hypoosmolar solutions: relation to epithelium-derived relaxing factor (EpDRF effects

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    Jeffrey S. Fedan

    2013-10-01

    Full Text Available In asthmatic patients, inhalation of hyperosmolar saline or D-mannitol (D-M elicits bronchoconstriction, but in healthy subjects exercise causes bronchodilation. Hyperventilation causes drying of airway surface liquid (ASL and increases its osmolarity. Hyperosmolar challenge of airway epithelium releases epithelium-derived relaxing factor (EpDRF, which relaxes the airway smooth muscle. This pathway could be involved in exercise-induced bronchodilation. Little is known of ASL hyperosmolarity effects on epithelial function. We investigated the effects of osmolar challenge maneuvers on dispersed and adherent guinea-pig tracheal epithelial cells to examine the hypothesis that EpDRF-mediated relaxation is associated with epithelial cell shrinkage. Enzymatically-dispersed cells shrank when challenged with ≥10 mOsM added D M, urea or NaCl with a concentration-dependence that mimics relaxation of the of isolated, perfused tracheas (IPT. Cells shrank when incubated in isosmolar N-methyl-D-glucamine (NMDG chloride, Na gluconate (Glu, NMDG-Glu, K-Glu and K2SO4, and swelled in isosmolar KBr and KCl. However, isosmolar challenge is not a strong stimulus of relaxation in IPTs. In previous studies amiloride and 4,4' diisothiocyano 2,2' stilbenedisulfonic acid (DIDS inhibited relaxation of IPT to hyperosmolar challenge, but had little effect on shrinkage of dispersed cells. Confocal microscopy in tracheal segments showed that adherent epithelium is refractory to low hyperosmolar concentrations that induce dispersed cell shrinkage and relaxation of IPT. Except for gadolinium and erythro 9 (2 hydroxy 3 nonyladenine (EHNA, actin and microtubule inhibitors and membrane permeabilizing agents did not affect on ion transport by adherent epithelium or shrinkage responses of dispersed cells. Our studies dissociate relaxation of IPT from cell shrinkage after hyperosmolar challenge of airway epithelium .

  5. Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

    Directory of Open Access Journals (Sweden)

    Laura A. Runck

    2014-04-01

    Full Text Available Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations

  6. Muscarinic cholinergic and alpha 2-adrenergic receptors in the epithelium and muscularis of the human ileum

    International Nuclear Information System (INIS)

    Lepor, H.; Rigaud, G.; Shapiro, E.; Baumann, M.; Kodner, I.J.; Fleshman, J.W.

    1990-01-01

    The aim of this study was to characterize the binding and functional properties of muscarinic cholinergic (MCh) and alpha 2-adrenergic receptors in the human ileum to provide insight into pharmacologic strategies for managing urinary and fecal incontinence after bladder and rectal replacement with intestinal segments. MCh and alpha 2-adrenergic binding sites were characterized in the epithelium and muscularis of eight human ileal segments with 3H-N-methylscopolamine and 3H-rauwolscine, respectively. The dissociation constant for 3H-N-methylscopolamine in the epithelium and muscularis was 0.32 +/- 0.07 nmol/L and 0.45 +/- 0.10 nmol/L, respectively (p = 0.32). The MCh receptor content was approximately eightfold greater in the muscularis compared with the epithelium (p = 0.008). The dissociation constant for 3H-rauwolscine in the muscularis and epithelium was 2.55 +/- 0.42 nmol/L and 2.03 +/- 0.19 nmol/L, respectively (p = 0.29). The alpha 2-adrenoceptor density was twofold greater in the epithelium compared with the muscularis (p = 0.05). Noncumulative concentration-response experiments were performed with carbachol, an MCh agonist, and UK-14304, a selective alpha 2-adrenergic agonist. The epithelium did not contract in the presence of high concentrations of carbachol and UK-14304. The muscularis preparations were responsive only to carbachol. The muscularis contains primarily MCh receptors mediating smooth muscle contraction. The alpha 2-adrenoceptors are localized primarily to the epithelium and may regulate water secretion in the intestine. The distribution and functional properties of ileal MCh and alpha 2-adrenergic receptors provide a theoretic basis for the treatment of incontinence after bladder and rectal replacement with intestinal segments

  7. deltaNp63 has a role in maintaining epithelial integrity in airway epithelium.

    Science.gov (United States)

    Arason, Ari Jon; Jonsdottir, Hulda R; Halldorsson, Skarphedinn; Benediktsdottir, Berglind Eva; Bergthorsson, Jon Thor; Ingthorsson, Saevar; Baldursson, Olafur; Sinha, Satrajit; Gudjonsson, Thorarinn; Magnusson, Magnus K

    2014-01-01

    The upper airways are lined with a pseudostratified bronchial epithelium that forms a barrier against unwanted substances in breathing air. The transcription factor p63, which is important for stratification of skin epithelium, has been shown to be expressed in basal cells of the lungs and its ΔN isoform is recognized as a key player in squamous cell lung cancer. However, the role of p63 in formation and maintenance of bronchial epithelia is largely unknown. The objective of the current study was to determine the expression pattern of the ΔN and TA isoforms of p63 and the role of p63 in the development and maintenance of pseudostratified lung epithelium in situ and in culture. We used a human bronchial epithelial cell line with basal cell characteristics (VA10) to model bronchial epithelium in an air-liquid interface culture (ALI) and performed a lentiviral-based silencing of p63 to characterize the functional and phenotypic consequences of p63 loss. We demonstrate that ΔNp63 is the major isoform in the human lung and its expression was exclusively found in the basal cells lining the basement membrane of the bronchial epithelium. Knockdown of p63 affected proliferation and migration of VA10 cells and facilitated cellular senescence. Expression of p63 is critical for epithelial repair as demonstrated by wound healing assays. Importantly, generation of pseudostratified VA10 epithelium in the ALI setup depended on p63 expression and goblet cell differentiation, which can be induced by IL-13 stimulation, was abolished by the p63 knockdown. After knockdown of p63 in primary bronchial epithelial cells they did not proliferate and showed marked senescence. We conclude that these results strongly implicate p63 in the formation and maintenance of differentiated pseudostratified bronchial epithelium.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-15

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. Copyright © 2016 the American Physiological Society.

  10. Immunocompromised and immunocompetent mouse models for head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lei ZG

    2016-01-01

    Full Text Available Zhen-ge Lei,1,* Xiao-hua Ren,2,* Sha-sha Wang,3 Xin-hua Liang,3,4 Ya-ling Tang3,5 1Department of Oral and Maxillofacial Surgery, Stomatological Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, 2Department of Stomatology, Sichuan Medical Science Academy and Sichuan Provincial People’s Hospital, 3State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 4Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, 5Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Abstract: Mouse models can closely mimic human oral squamous epithelial carcinogenesis, greatly expand the in vivo research possibilities, and play a critical role in the development of diagnosis, monitoring, and treatment of head and neck squamous cell carcinoma. With the development of the recent research on the contribution of immunity/inflammation to cancer initiation and progression, mouse models have been divided into two categories, namely, immunocompromised and immunocompetent mouse models. And thus, this paper will review these two kinds of models applied in head and neck squamous cell carcinoma to provide a platform to understand the complicated histological, molecular, and genetic changes of oral squamous epithelial tumorigenesis. Keywords: head and neck squamous cell carcinoma, HNSCC, mouse models, immunocompromised models, immunocompetent models, transgenic models

  11. Overexpression of mouse TTF-2 gene causes cleft palate

    Science.gov (United States)

    Meng, Tian; Shi, Jia-Yu; Wu, Min; Wang, Yan; Li, Ling; Liu, Yan; Zheng, Qian; Huang, Lei; Shi, Bing

    2012-01-01

    In humans, mutations of the gene encoding for thyroid transcription factor-2 (TTF-2 or FOXE1) result in Bamforth syndrome. Bamforth syndrome is characterized by agenesis, cleft palate, spiky hair and choanal atresia. TTF-2 null mice (TTF-2−/−) also exhibit cleft palate, suggesting its involvement in the palatogenesis. However, the molecular pathology and genetic regulation by TTF2 remain largely unknown. In the present study, the recombinant expression vector pBROAD3-TTF-2 containing the promoter of the mouse ROSA26 gene was created to form the structural gene of mouse TTF-2 and was microinjected into the male pronuclei of fertilized ova. Sequence analysis confirmed that the TTF-2 transgenic mouse model was established successfully. The transgenic mice displayed a phenotype of cleft palate. In addition, we found that TTF-2 was highly expressed in the medial edge epithelium (MEE) from the embryonic day 12.5 (E12.5) to E14.5 in TTF-2 transgenic mice. These observations suggest that overexpression of TTF-2 during palatogenesis may contribute to formation of cleft palate. PMID:22304410

  12. Spatiotemporal Expression of p63 in Mouse Epidermal Commitment

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    Qian Zhao

    2015-12-01

    Full Text Available The embryonic surface ectoderm is a simple flat epithelium consisting of cells that express the cytokeratins K8/K18. Before stratification, K5/K14 expression substitutes K8/K18 expression, marking the event called epidermal commitment. Previous studies show that the transcription factor p63 plays an essential role in epidermal commitment. However, detailed expression information of p63 during early epidermal development in mice is still unclear. We systematically studied the expression pattern of p63 in mouse epidermal commitment, together with K8 and K5. We show that p63 expression could be detected as early as E8.5 in mouse embryos preceding epidermal commitment. p63 expression first appears near the newly formed somites and the posterior part of the embryo, further expanding to the whole embryonic surface with particular enrichment in the first branchial arches and the limb buds. ΔNp63 is the major class of isoforms expressed in this period. Relative expression intensity of p63 depends on the embryonic position. In summary, there is a sequential and regular expression pattern of K8, p63 and K5 in mouse epidermal commitment. Our study not only contributes to understanding the early events during epidermal development but also provides a basal tool to study the function of p63 in mammals.

  13. Members of Bitter Taste Receptor Cluster Tas2r143/Tas2r135/Tas2r126 Are Expressed in the Epithelium of Murine Airways and Other Non-gustatory Tissues

    Directory of Open Access Journals (Sweden)

    Shuya Liu

    2017-10-01

    Full Text Available The mouse bitter taste receptors Tas2r143, Tas2r135, and Tas2r126 are encoded by genes that cluster on chromosome 6 and have been suggested to be expressed under common regulatory elements. Previous studies indicated that the Tas2r143/Tas2r135/Tas2r126 cluster is expressed in the heart, but other organs had not been systematically analyzed. In order to investigate the expression of this bitter taste receptor gene cluster in non-gustatory tissues, we generated a BAC (bacterial artificial chromosome based transgenic mouse line, expressing CreERT2 under the control of the Tas2r143 promoter. After crossing this line with a mouse line expressing EGFP after Cre-mediated recombination, we were able to validate the Tas2r143-CreERT2 transgenic mouse line and monitor the expression of Tas2r143. EGFP-positive cells, indicating expression of members of the cluster, were found in about 47% of taste buds, and could also be found in several other organs. A population of EGFP-positive cells was identified in thymic epithelial cells, in the lamina propria of the intestine and in vascular smooth muscle cells of cardiac blood vessels. EGFP-positive cells were also identified in the epithelium of organs readily exposed to pathogens including lower airways, the gastrointestinal tract, urethra, vagina, and cervix. With respect to the function of cells expressing this bitter taste receptor cluster, RNA-seq analysis in EGFP-positive cells isolated from the epithelium of trachea and stomach showed expression of genes related to innate immunity. These data further support the concept that bitter taste receptors serve functions outside the gustatory system.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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

  15. Enhancing oral vaccine potency by targeting intestinal M cells.

    Directory of Open Access Journals (Sweden)

    Ali Azizi

    2010-11-01

    Full Text Available The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells.

  16. Ancestral amphibian v2rs are expressed in the main olfactory epithelium

    Science.gov (United States)

    Syed, Adnan S.; Sansone, Alfredo; Nadler, Walter; Manzini, Ivan; Korsching, Sigrun I.

    2013-01-01

    Mammalian olfactory receptor families are segregated into different olfactory organs, with type 2 vomeronasal receptor (v2r) genes expressed in a basal layer of the vomeronasal epithelium. In contrast, teleost fish v2r genes are intermingled with all other olfactory receptor genes in a single sensory surface. We report here that, strikingly different from both lineages, the v2r gene family of the amphibian Xenopus laevis is expressed in the main olfactory as well as the vomeronasal epithelium. Interestingly, late diverging v2r genes are expressed exclusively in the vomeronasal epithelium, whereas “ancestral” v2r genes, including the single member of v2r family C, are restricted to the main olfactory epithelium. Moreover, within the main olfactory epithelium, v2r genes are expressed in a basal zone, partially overlapping, but clearly distinct from an apical zone of olfactory marker protein and odorant receptor-expressing cells. These zones are also apparent in the spatial distribution of odor responses, enabling a tentative assignment of odor responses to olfactory receptor gene families. Responses to alcohols, aldehydes, and ketones show an apical localization, consistent with being mediated by odorant receptors, whereas amino acid responses overlap extensively with the basal v2r-expressing zone. The unique bimodal v2r expression pattern in main and accessory olfactory system of amphibians presents an excellent opportunity to study the transition of v2r gene expression during evolution of higher vertebrates. PMID:23613591

  17. Dynamic relationship of the epithelium and mesenchyme during salivary gland initiation: the role of Fgf10

    Science.gov (United States)

    Wells, Kirsty L.; Gaete, Marcia; Matalova, Eva; Deutsch, Danny; Rice, David; Tucker, Abigail S.

    2013-01-01

    Summary Salivary glands provide an excellent model for the study of epithelial–mesenchymal interactions. We have looked at the interactions involved in the early initiation and development of murine salivary glands using classic recombination experiments and knockout mice. We show that salivary gland epithelium, at thickening and initial bud stages, is able to direct salivary gland development in non-gland pharyngeal arch mesenchyme at early stages. The early salivary gland epithelium is therefore able to induce gland development in non-gland tissue. This ability later shifts to the mesenchyme, with non-gland epithelium, such as from the limb bud, able to form a branching gland when combined with pseudoglandular stage gland mesenchyme. This shift appears to involve Fgf signalling, with signals from the epithelium inducing Fgf10 in the mesenchyme. Fgf10 then signals back to the epithelium to direct gland down-growth and bud development. These experiments highlight the importance of epithelial–mesenchymal signalling in gland initiation, controlling where, when and how many salivary glands form. PMID:24167707

  18. Phagocytosis of Giardia muris by macrophages in Peyer's patch epithelium in mice.

    Science.gov (United States)

    Owen, R L; Allen, C L; Stevens, D P

    1981-08-01

    No mechanism for the initiation of immunological clearance of Giardia from the mammalian intestinal tract has been identified. In normal and nude mice experimentally infected with G. muris, we examined antigen-sampling epithelium over Peyer's patch follicles by electron microscopy for evidence of interaction between G. muris and lymphoid cells. Invading G. muris were found in the epithelium near dying or desquamating columnar cells. Macrophages beneath the basal lamina extended pseudopods into the epithelium, trapping invading G. muris and enclosing them in phagolysosomes. In normal mice, which clear G. muris in 4 to 6 weeks, macrophages containing digested G. muris were surrounded by rosettes of lymphoblasts in the epithelium. In nude mice deficient in lymphocytes, there was apparent hyperplasia of macrophages, which filled the follicle domes, resulting in more frequent entrapment of G. muris but no contact between macrophages and lymphoblasts in the epithelium. In nude mice, which require 6 months to control G. muris infection, lymphoblast contact with macrophages containing distinctive microtubular remnants of G. muris was only identified in the follicle dome. This close physical association of lymphoblasts and macrophages containing G. muris remnants suggests that this macrophage activity represents intraepithelial antigen processing as well as a defense against the effects of the uncontrolled entrance of microorganisms and other antigenic particles into Peyer's patch lymphoid follicles.

  19. Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.

    Science.gov (United States)

    Jiang, Nan; Zhou, Jian; Chen, Mo; Schiff, Michael D; Lee, Chang H; Kong, Kimi; Embree, Mildred C; Zhou, Yanheng; Mao, Jeremy J

    2014-02-01

    Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4-5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed towards bioengineered tooth regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Epstein–Barr virus (EBV-associated epithelial and non-epithelial lesions of the oral cavity

    Directory of Open Access Journals (Sweden)

    Kentaro Kikuchi

    2017-08-01

    Full Text Available Epstein–Barr virus (EBV is known to be associated with the development of malignant lymphoma and lymphoproliferative disorders (LPDs in immunocompromised patients. EBV, a B-lymphotropic gamma-herpesvirus, causes infectious mononucleosis and oral hairy leukoplakia, as well as various pathological types of lymphoid malignancy. Furthermore, EBV is associated with epithelial malignancies such as nasopharyngeal carcinoma (NPC, salivary gland tumor, gastric carcinoma and breast carcinoma. In terms of oral disease, there have been several reports of EBV-related oral squamous cell carcinoma (OSCC worldwide. However, the role of EBV in tumorigenesis of human oral epithelial or lymphoid tissue is unclear. This review summarizes EBV-related epithelial and non-epithelial tumors or tumor-like lesions of the oral cavity. In addition, we describe EBV latent genes and their expression in normal epithelium, inflamed gingiva, epithelial dysplasia and SCC, as well as considering LPDs (MTX- and age-related and DLBCLs of the oral cavity.

  1. Radiation effects of electromagnetic pulses on mouse blood-testis barrier

    International Nuclear Information System (INIS)

    Hou Wugang; Zhao Jie; Zhang Yuanqiang

    2005-01-01

    Radiation effects caused by 100 kV/m and 400 kV/m electromagnetic pulse (EMP) irradiations on mouse blood-testis barrier were studied by means of routine HE staining, Lanthanum traced electron microscope and injection of caudal vein with Evans Blue. The EMP irradiation of different dose rates damaged Sertoli's cell and blood-testis barrier of mouse testis in different levels. Severe injuries were observed with the 400 kV/m irradiation group, with apoptosis and necrosis in a large quantity of the spermatogenic cells, shape and structural changes of the Sertoli's cells, and serious injuries to the blood-testis barrier, one day after the irradiation. The basal compartment separated from the adluminal compartment in most of the VIII stage seminiferous epithelium, and a great number of apoptosis and necrosis spermatogenic cells were released into the cavities. Injuries of blood-testis barrier could be observed 21 days after the 400 kV/m irradiation. The injuries of 100 kV/m irradiation groups were less severe than the 400 kV/m groups, in which the damages to the Sertoli's cells, the seminiferous epithelium and blood-testis barrier recovered to some extent 14 days after the irradiation. The authors conclude that EMP irradiation can damage mouse blood-tests barrier. The injuries, and the time for recovery, are related to EMP power intensity. (authors)

  2. Immunostimulatory mouse granuloma protein.

    Science.gov (United States)

    Fontan, E; Fauve, R M; Hevin, B; Jusforgues, H

    1983-10-01

    Earlier studies have shown that from subcutaneous talc-induced granuloma in mice, a fraction could be extracted that fully protected mice against Listeria monocytogenes. Using standard biochemical procedures--i.e., ammonium sulfate fractionation, preparative electrophoresis, gel filtration chromatography, isoelectric focusing, and preparative polyacrylamide gel electrophoresis--we have now purified an active factor to homogeneity. A single band was obtained in NaDodSO4/polyacrylamide gel with an apparent Mr of 55,000. It migrated with alpha 1-globulins and the isoelectric point was 5 +/- 0.1. The biological activity was destroyed with Pronase but not with trypsin and a monospecific polyclonal rabbit antiserum was obtained. The intravenous injection of 5 micrograms of this "mouse granuloma protein" fully protects mice against a lethal inoculum of L. monocytogenes. Moreover, after their incubation with 10 nM mouse granuloma protein, mouse peritoneal cells became cytostatic against Lewis carcinoma cells.

  3. Burn mouse models

    DEFF Research Database (Denmark)

    Calum, Henrik; Høiby, Niels; Moser, Claus

    2014-01-01

    Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third...... with infected burn wound compared with the burn wound only group. The burn mouse model resembles the clinical situation and provides an opportunity to examine or develop new strategies like new antibiotics and immune therapy, in handling burn wound victims much....

  4. DHT deficiency perturbs the integrity of the rat seminiferous epithelium by disrupting tight and adherens junctions.

    Science.gov (United States)

    Kolasa, Agnieszka; Marchlewicz, Mariola; Wenda-Różewicka, Lidia; Wiszniewska, Barbara

    2011-01-01

    In rats with a DHT deficiency induced by finasteride, morphological changes in the seminiferous epithelium were observed. The structural alterations were manifested by the premature germ cells sloughing into the lumen of seminiferous tubules. The etiology of this disorder could be connected with intercellular junctions disintegration. We showed in the immunohistochemical study the changes in expression of some proteins building tight and adherens junctions. The depression of N-cadherin, β-catenin and occludin immunoexpressions could be the reason for the release of immature germ cells from the seminiferous epithelium. However, the observed increase of the immunohistochemical reaction intensity of vinculin, one of the cadherin/catenin complex regulators, could be insufficient to maintain the proper function of adherens junctions. The hormonal imbalance appears to influence the pattern of expression of junctional proteins in the seminiferous epithelium. It could lead to untimely germ cells sloughing, and ultimately could impair fertility.

  5. Cytofluorophotometrical study of the DNA content of the uterine cervical carcinoma and the vaginal epithelium

    International Nuclear Information System (INIS)

    Tokumoto, Yoshiaki

    1987-01-01

    The Feulgen DNA content in cells of uterine cervical carcinoma and that of its adjacent vaginal epithelium were measured by microfluorophotometry. The Feulgen DNA content in cells of uterine cervical carcinoma was increased and showed a greater variation of its DNA values compared with diploid cells. The Feulgen DNA content in cells of normal vaginal epithelium adjacent to cervical carcinoma was also increased compared with diploid cells in 6 out of 8 cases. The relativity between the cellular DNA content of cervical carcinoma and that of its adjacent normal vaginal epithelium was found. In 10 out of 14 cases of uterine cervical carcinoma, the mean value of cellular DNA content was increased after by therapuetic irradiation with 10 Gy. Radiation effects on the DNA content of vaginal epithelial cells were similar to those on the DNA content of carcinoma cells. (author)

  6. Effect of coffee drinking on cell proliferation in rat urinary bladder epithelium.

    Science.gov (United States)

    Lina, B A; Rutten, A A; Woutersen, R A

    1993-12-01

    A possible effect of freshly brewed drip coffee on urinary bladder carcinogenesis was investigated in male Wistar rats using cell proliferation in urinary bladder epithelium as the indicator of tumour promotion. Male rats were given either undiluted coffee brew (100% coffee), coffee diluted 10 times (10% coffee) or tap water (controls), as their only source of drinking fluid for 2 or 6 wk. Uracil, known to induce cell proliferation in urinary bladder epithelium, was included in the study as a positive control. In rats receiving 100% coffee, body weights, liquid intake and urinary volume were decreased. Neither histopathological examination of urinary bladder tissue nor the bromodeoxyuridine labelling index revealed biologically significant differences between rats receiving coffee and the tap water controls. Uracil increased the labelling index and induced hyperplasia of the urinary bladder epithelium, as expected. It was concluded that these results produced no evidence that drinking coffee predisposes to tumour development in the urinary bladder.

  7. Diverse regulation of retinal pigment epithelium phagocytosis of photoreceptor outer segments by calcium-independent phospholipase A₂, group VIA and secretory phospholipase A₂, group IB

    DEFF Research Database (Denmark)

    Zhan, Chen; Wang, Jinmei; Kolko, Miriam

    2012-01-01

    PURPOSE: To investigate the roles of the phospholipases A(2) (PLA(2)) subtypes, iPLA(2)-VIA and sPLA(2)-IB in retinal pigment epithelium (RPE) phagocytosis of photoreceptor outer segments (POS) and to explore a possible interaction between sPLA(2)-IB and iPLA(2)-VIA in the RPE. METHODS: To explore...... the role of iPLA(2)-VIA in RPE phagocytosis of POS, experiments with iPLA(2)-VIA vector transfection, iPLA(2)-VIA(-/-) knockout (KO) mice, and iPLA(2)-VIA inhibition by bromoenol lactone (BEL) were done. Exogenous addition of sPLA(2)-IB was used to investigate the role of sPLA(2)-IB in RPE phagocytosis....... A Luciferase Reporter Vector containing the iPLA(2)-VIA promoter was used to study the effects of sPLA(2)-IB on the iPLA(2)-VIA promoter. RESULTS: ARPE-19 and primary mouse RPE cells transfected with iPLA(2)-VIA showed increased phagocytosis. Phagocytosis was reduced in primary mouse RPE inhibited with BEL...

  8. Case Study: Polycystic Livers in a Transgenic Mouse Line

    Energy Technology Data Exchange (ETDEWEB)

    Lovaglio, Jamie A.; Artwohl, James E.; Ward, Christopher J.; Diekwisch, Thomas G. H.; Ito, Yoshihiro; Fortman, Jeffrey D.

    2014-04-01

    Three mice (2 male, 1 female; age, 5 to 16 mo) from a mouse line transgenic for keratin 14 (K14)-driven LacZ expression and on an outbred Crl:CD1(ICR) background, were identified as having distended abdomens and livers that were diffusely enlarged by numerous cysts (diameter, 0.1 to 2.0 cm). Histopathology revealed hepatic cysts lined by biliary type epithelium and mild chronic inflammation, and confirmed the absence of parasites. Among 21 related mice, 5 additional affected mice were identified via laparotomy. Breeding of these 5 mice (after 5 mo of age) did not result in any offspring; the K14 mice with olycystic livers failed to reproduce. Affected male mice had degenerative testicular lesions, and their sperm was immotile. Nonpolycystic K14 control male mice bred well, had no testicular lesions, and had appropriate sperm motility. Genetic analysis did not identify an association of this phenotype with the transgene or insertion site.

  9. Effects of the Loss of Conjunctival Muc16 on Corneal Epithelium and Stroma in Mice

    Science.gov (United States)

    Shirai, Kumi; Okada, Yuka; Cheon, Dong-Joo; Miyajima, Masayasu; Behringer, Richard R.; Yamanaka, Osamu; Saika, Shizuya

    2014-01-01

    Purpose. To examine the role of conjunctival Muc16 in the homeostasis of the ocular surface epithelium and stroma using Muc16-null knockout (KO) mice. Methods. We used KO mice (n = 58) and C57/BL6 (WT) mice (n = 58). Histology and immunohistochemistry were employed to analyze the phenotypes in the ocular surface epithelium. The expression of phospho-Stat3, AP-1 components, interleukin 6 (IL-6), and tumor necrosis factor-α (TNFα) in the cornea and conjunctiva was examined. The shape of the nuclei of corneal epithelial cells was examined to evaluate intraepithelial cell differentiation. Epithelial cell proliferation was studied using bromo-deoxyuridine labeling. Finally, the wound healing of a round defect (2-mm diameter) in the corneal epithelium was measured. The keratocyte phenotype and macrophage invasion in the stroma were evaluated after epithelial repair. Results. The loss of Muc16 activated Stat3 signal, affected JunB signal, and upregulated the expression of IL-6 in the conjunctiva. Basal-like cells were observed in the suprabasal layer of the corneal epithelium with an increase in proliferation. The loss of Muc16 accelerated the wound healing of the corneal epithelium. The incidence of myofibroblast appearance and macrophage invasion were more marked in KO stroma than in WT stroma after epithelial repair. Conclusions. The loss of Muc16 in the conjunctiva affected the homeostasis of the corneal epithelium and stroma. The mechanism might include the upregulation of the inflammatory signaling cascade (i.e., Stat3 signal, and IL-6 expression in the KO conjunctiva). Current data provides insight into the research of the pathophysiology of dry eye syndrome. PMID:24812549

  10. Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

    Enblad, Malin; Birgisson, Helgi; Wanders, Alkwin; Sköldberg, Filip; Ghanipour, Lana; Graf, Wilhelm

    2016-04-01

    The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

  11. Engineering Functional Epithelium for Regenerative Medicine and In Vitro Organ Models: A Review

    Science.gov (United States)

    Vrana, Nihal E.; Lavalle, Philippe; Dokmeci, Mehmet R.; Dehghani, Fariba; Ghaemmaghami, Amir M.

    2013-01-01

    Recent advances in the fields of microfabrication, biomaterials, and tissue engineering have provided new opportunities for developing biomimetic and functional tissues with potential applications in disease modeling, drug discovery, and replacing damaged tissues. An intact epithelium plays an indispensable role in the functionality of several organs such as the trachea, esophagus, and cornea. Furthermore, the integrity of the epithelial barrier and its degree of differentiation would define the level of success in tissue engineering of other organs such as the bladder and the skin. In this review, we focus on the challenges and requirements associated with engineering of epithelial layers in different tissues. Functional epithelial layers can be achieved by methods such as cell sheets, cell homing, and in situ epithelialization. However, for organs composed of several tissues, other important factors such as (1) in vivo epithelial cell migration, (2) multicell-type differentiation within the epithelium, and (3) epithelial cell interactions with the underlying mesenchymal cells should also be considered. Recent successful clinical trials in tissue engineering of the trachea have highlighted the importance of a functional epithelium for long-term success and survival of tissue replacements. Hence, using the trachea as a model tissue in clinical use, we describe the optimal structure of an artificial epithelium as well as challenges of obtaining a fully functional epithelium in macroscale. One of the possible remedies to address such challenges is the use of bottom-up fabrication methods to obtain a functional epithelium. Modular approaches for the generation of functional epithelial layers are reviewed and other emerging applications of microscale epithelial tissue models for studying epithelial/mesenchymal interactions in healthy and diseased (e.g., cancer) tissues are described. These models can elucidate the epithelial/mesenchymal tissue interactions at the

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

    Science.gov (United States)

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

    2016-01-01

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

  13. cAMP Stimulates Transepithelial Short-Circuit Current and Fluid Transport Across Porcine Ciliary Epithelium.

    Science.gov (United States)

    Cheng, Angela King-Wah; Civan, Mortimer M; To, Chi-Ho; Do, Chi-Wai

    2016-12-01

    To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc). Addition of niflumic acid (NFA) to the aqueous surface effectively blocked the cAMP-induced Isc stimulation. The administration of cAMP to the stromal side (pigmented ciliary epithelium, PE) triggered a significant stimulation of Isc only at 100 μM. No additive effect was observed with bilateral application of cAMP. Likewise, forskolin caused a significant stimulation of Isc when applied to the aqueous side. Concomitantly, cAMP and forskolin increased fluid transport across porcine ciliary epithelium, and this stimulation was effectively inhibited by aqueous NFA. Depleting Cl- in the bathing solution abolished the baseline Isc and inhibited the subsequent stimulation by cAMP. Pretreatment with protein kinase A (PKA) blockers (H89/KT5720) significantly inhibited the cAMP- and forskolin-induced Isc responses. Our results suggest that cAMP triggers a sustained stimulation of Cl- and fluid transport across porcine ciliary epithelium; Cl- channels in the NPE cells are potentially a cellular site for this PKA-sensitive cAMP-mediated response.

  14. Prolonged phonation impairs the integrity and barrier function of porcine vocal fold epithelium: a preliminary study.

    Science.gov (United States)

    Zhang, Chi; Paddock, Kieran; Chou, Adriana; Scholp, Austin; Gong, Ting; Jiang, Jack J

    2018-04-18

    Voice abuse is known to be a common risk factor of voice disorders and prolonged; high-intensity phonation has been shown to damage the vocal fold epithelium. We aim to evaluate the effects of phonation on the integrity and barrier function of vocal fold epithelium using a porcine laryngeal model. Ex vivo porcine larynges were phonated at low intensity or high intensity for 15, 30, or 60 min within 4 h after harvest. Vocal fold epithelium was visualized using transmission electron microscopy (TEM). The barrier function of vocal fold epithelium was evaluated by measuring the permeability to model molecules, fluorescein (376 Da), and fluorescein isothiocyanate (FITC)-dextrans of 4000 and 10,000 Da (FD4, FD10), in a Franz diffusing cell. Cell death and dilated intercellular space after phonation were observed using TEM. Thickness of vocal fold epithelium was significantly reduced after low-intensity phonation for 30 and 60 min and high-intensity phonation for 15, 30, and 60 min. Epithelial permeability to fluorescein was significantly increased after low-intensity phonation for 30 and 60 min, and high-intensity phonation. Permeability to FD4 was significantly increased after high-intensity phonation for 30 and 60 min. Phonation did not alter the permeability to FD10 significantly. Long-duration phonation destroys the integrity and barrier function of vocal fold epithelium. These effects likely make vocal folds more vulnerable to other environmental irritants, such as tobacco smoke, reflux components, allergens, and inhaled pollutants. Destroyed barrier function may be an important factor in the pathogenesis of voice lesions related to voice abuse.

  15. Growth of normal or irradiated vaginal epithelium in in vivo cultures

    International Nuclear Information System (INIS)

    Tileva, M.

    1975-01-01

    Growth of normal or irradiated vaginal epithelium was studied by the method of F.M.Lazarenko (1959). Pieces of vaginal mucosa from immature albino rats, normal or exposed to 1000 or 2000 R, were embedded in celloidin and implanted into the abdominal wall of female immature rats. Implants were recovered for histological examinations from day 1 to day 10 after surgery. At day 1 post implantation, vaginal epithelium was found to have dedifferentiated. Cells showed a high mitotic index (MI = 16.2%). Cell proliferation progressed further to attain a peak rate at 3 days (MI = 32.7%). At 5 days, newly formed structures began to differentiate, and concurrently manifested a gradual decrease in cell proliferative activity (at 10 days, MI = 15.6%). Following exposure to 1000 R, vaginal epithelium displayed a similar pattern of growth and differentiation, the only difference from non-irradiated epithelium being that there was a transient mitotic delay over the first 3 days; mitotic rates reached a peak at 5 days (MI = 47.0%), were still high at 7 days (MI = 31.3%), and fell to 19% at 10 days. With this longer proliferation period, newly formed structures appeared ''luxuriant''. After a dose of 2000 R, vaginal epithelium failed to show any signs of growth at all investigated time intervals. These data are in agreement with evidence obtained by K.M.Svetikova (1961) and L.I.Chekulaeva (1969, 1974) for a good restitutional ability of epithelia of epidermal origin following exposure to 1200 R X-rays. By Warren' rule (1944), i.e., that cells should be considered radiosensitive if severely damaged by less than 2500 R, vaginal epithelium cells may be designated as relatively susceptible to radiation. (author)

  16. [Structure of the epithelium of the parasitic turbellaria Notenera ivanovi (Turbellaria: Fecampiida)].

    Science.gov (United States)

    Kornakova, E E; Marchenkov, A V

    2000-01-01

    The ultrastructure of the epithelium in Notentera ivanovi (Turbellaria, Fecampiida) has been studied. Notentera ivanovi lacks the digestive system but has a pad of the epidermal cells on the dorsal side of the body, which seems to be similar to the digestive epidermis on LM. Both the ventral and dorsal epithelium are cellular, ciliated and not insunk (fig. 1, a). The ultrastructure of the ventral and dorsal epithelium is similar in essential features. The cells bear abundant microvilli, cilia and are very rich in mitochondria, but the cytoplasm does not contain lysosomes and shows no other indications of phago- or pinocytosis. The basal membrane of epithelial cells forms deep invaginations (fig. 1, [symbol: see text]), partly with dilations (fig. 1, a; 2, a) containing the lamellated material (3, [symbol: see text]). In the basal part of the cells the numerous Golgi apparatus and rare cysternae of the smooth endoplasmic reticulum were observed (fig. 2, a, [symbol: see text]). The epithelium consists of several types of cells, which differ in the structure of secretory granules. The most abundant type of cells contains the granules with the rough-fibrillated content (fig. 1, a; 2, [symbol: see text]; 3, a). The cells of this type cover most part of the body. In some cells the content of such granules becomes condensed and electron-dense granules appear (fig. 3, a, [symbol: see text]). Another type of cells contains the giant granules with the rough-fibrillated content (fig. 3, [symbol: see text]). Third type of the secret is the granules with the finely fibrillated content which is ejected by exocytosis. The cells of the second and third types form a separate areas of the epithelium of the dorsal side of the body but occasionally were observed in the ventral epithelium too. The epithelium of N. ivanovi differs from that in Kronborgia by the abundance and diversity of secretory contents. The role of the epithelium in the digestion remains conjectural. It seems to be

  17. Effect of irradiation on unscheduled DNA synthesis induced by 4-nitroquinoline in tracheal epithelium of rats

    International Nuclear Information System (INIS)

    Hahn, F.F.; Kennedy, R.; Brooks, A.L.

    1986-01-01

    Unscheduled DNA synthesis (UDS) was determined in rat epithelium by autoradiographic techniques to determine the influence of prior irradiation on the ability of the cells to repair mutagenic damage induced by 4-nitroquionoline (4NQO). UDS was stimulated by in vitro exposure to 4NPO. However, prior whole-body irradiation of rats with either 50 or 300 rad did not alter the UDS induced by 4NQO. The results of this study do not support the hypothesis that irradiation can induce DNA repair enzymes in respiratory tract epithelium. 5 references, 3 figures

  18. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Mørck Nielsen, H; Rømer Rassing, M; Nielsen, Hanne Mørck

    2000-01-01

    cell culture model, and human and porcine buccal epithelium were compared. The esterase activity in the intact cell culture model and in the porcine buccal mucosa was compared. Further, the TR146 cell culture model was used to study the permeability rate and metabolism of leu-enkephalin. The activity...... of the three enzymes in the TR146 homogenate supernatants was in the same range as the activity in homogenate supernatants of human buccal epithelium. In the TR146 cell culture model, the activity of aminopeptidase (13.70+/-2.10 nmol/min per mg protein) was approx. four times the activity of carboxypeptidase...

  19. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Nielsen, Hanne Mørck; Verhoef, J C; Ponec, M

    1999-01-01

    The aim of the present study was to characterize the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability of test substances with different molecular weights (M(w)). For this purpose, the apparent permeability (P(app)) values for mannitol...... and for fluorescein isothiocyanate (FITC)-labelled dextrans (FD) with various M(w) (4000-40000) were compared to the P(app) values obtained using porcine buccal mucosa as an in vitro model of the human buccal epithelium. The effect of 10 mM sodium glycocholate (GC) on the P(app) values was examined. To identify...

  20. Preparation and properties of monoclonal antibodies to individual prekeratins of simple rat epithelium

    International Nuclear Information System (INIS)

    Troyanovskii, S.M.; Krutovskikh, V.A.; Bannikov, G.A.

    1986-01-01

    The authors study the properties of a series of hybridoma clones producing antibodies to individual prekeratins (PK) from simple types of epithelium. BALB/c mice were immunized with a preparation of intermediate filaments isolated from the mucosa of the rat large intestine. The specificity of the five clones studied was studied by monoautoradiography. For a more detailed study of the specificity of the experimentally obtained antibodies, the authors used the same immunoautoradiographic method to study their reaction with proteins of cells of other types. The authors have obtained monoclonal antibodies to three individual PK of simple types of rat epithelium: PK40, PK49, and PK55

  1. Organ Culture as a Model System for Studies on Enterotoxin Interactions with the Intestinal Epithelium

    DEFF Research Database (Denmark)

    Lorenzen, Ulver Spangsberg; Hansen, Gert H; Danielsen, E Michael

    2015-01-01

    Studies on bacterial enterotoxin-epithelium interactions require model systems capable of mimicking the events occurring at the molecular and cellular levels during intoxication. In this chapter, we describe organ culture as an often neglected alternative to whole-animal experiments or enterocyte......-like cell lines. Like cell culture, organ culture is versatile and suitable for studying rapidly occurring events, such as enterotoxin binding and uptake. In addition, it is advantageous in offering an epithelium with more authentic permeability/barrier properties than any cell line, as well...

  2. Fine structure and function of the alimentary epithelium in Artemia salina nauplii

    Energy Technology Data Exchange (ETDEWEB)

    Hootman, S R; Conte, F P

    1974-01-01

    The fine structure of the alimentary tract in the second instar nauplius of the brine shrimp, Artemia salina, has been described. The foregut and hindgut of the larva are composed of cuboidal epithelium which is cuticularized. The epithelium of the midgut and gastric caeca is columnar and is characterized by apical microvilli, basal membrane infolds, and abundant mitochondria. The structural characteristics of the midgut cells correlate with previous physiological and biochemical evidence on both adult and larval brine shrimp which indicates that the midgut plays an important role in absorption and osmoregulation in these animals.

  3. Gut microbiota and probiotics in modulation of epithelium and gut-associated lymphoid tissue function.

    Science.gov (United States)

    Sanz, Yolanda; De Palma, Giada

    2009-01-01

    The intestinal tract mucosa is exposed to a vast number of environmental antigens and a large community of commensal bacteria. The mucosal immune system has to provide both protection against pathogens and tolerance to harmless bacteria. Immune homeostasis depends on the interaction of indigenous commensal and transient bacteria (probiotics) with various components of the epithelium and the gut-associated lymphoid tissue. Herein, an update is given of the mechanisms by which the gut microbiota and probiotics are translocated through the epithelium, sensed via pattern-recognition receptors, and activate innate and adaptive immune responses.

  4. Cytotoxicity of nano-hydroxyapatite on human-derived oral epithelium cell line: an in vitro study

    OpenAIRE

    Farid Abassi; Mandana Sattari; Noushin Jalayer Naderi; Marzie Sorooshzadeh

    2016-01-01

    Background: Hydroxyapatite nanoparticles have a more surface contact and solubility than conventional hydroxyapatite. Hydroxynanoparticles enhances the biological and mechanical properties of new regenerated tissues. The hydroxyapatite nanoparticles have received attention as a new and effective osseous graft for using as scaffolds in bone regeneration. The reports on hydroxyapatite nanoparticles biocompatibility are controversial. It has been shown that hydroxyapatite nanoparticles induces i...

  5. Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa

    DEFF Research Database (Denmark)

    Gao, Shan; Nielsen, Boye Schnack; Krogdahl, Annelise

    2010-01-01

    , 17 of 20 patients with oral carcinoma were found to have between 2.5- and 50-fold increased tumor PAI-1 mRNA level, as compared with the matched tumor-adjacent normal tissues. The PAI-1 mRNA level in connective tissues from 15 healthy volunteers was similar to the level in tumor-adjacent normal...... tissues, but the level in epithelium was 5- to 10-fold lower. Analyzing DNA methylation of 25 CpG sites within 960 bp around the transcription initiation site of the SERPINE1 gene by bisulfite sequencing, we did the surprising observation that both tumors and tumor-adjacent normal tissue had a significant...... level of methylation, whereas there was very little methylation in tissue from healthy volunteers, suggesting that tumor-adjacent normal tissue already contains transformation-associated epigenetic changes. However, there was no general inverse correlation between PAI-1 mRNA levels and SERPINE1 gene...

  6. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  7. Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids

    DEFF Research Database (Denmark)

    Sampaziotis, Fotios; Justin, Alexander W; Tysoe, Olivia C

    2017-01-01

    The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from....... The resulting bioengineered tissue can reconstruct the gallbladder wall and repair the biliary epithelium following transplantation into a mouse model of injury. Furthermore, bioengineered artificial ducts can replace the native CBD, with no evidence of cholestasis or occlusion of the lumen. In conclusion, ECOs...

  8. [Suppression of VEGF protein expression by arctigenin in oral squamous cell carcinoma].

    Science.gov (United States)

    Pu, Guang-rui; Liu, Fa-yu; Wang, Bo

    2015-08-01

    To observe arctigenin's inhibitory effect on oral squamous cell carcinoma, and explore the possible mechanism. The expression of VEGF in 32 cases of oral squamous cell cancer and 20 adjacent tissue specimen were detected with immunohistochemistry. Human nude mouse transplantation tumor model of oral squamous cell cancer was prepared with HSC-3 cells line. Transplanted tumor growth and VEGF expression in transplanted tumor tissues were assayed after treatment with arctigenin. One-way ANOVA was used for comparison between groups with SPSS 16.0 software package. Compared with the adjacent tissue, immunohistochemical staining score of VEGF was significantly higher (Parctigenin, the growth of oral squamous cell transplanted tumors in nude mouse was inhibited (Parctigenin group (PArctigenin can dose-dependently inhibit the growth of oral squamous cell carcinomas, and this effect may be related to down regulation of VEGF expression.

  9. Oral contraceptives induced hepatotoxicity

    OpenAIRE

    B. Akshaya Srikanth; V. Manisree

    2013-01-01

    Oral Contraceptives are the pharmacological agents used to prevent pregnancy. These are divided as the combined and progestogen methods and are administered orally, transdermally, systemically and via vaginal route. All these methods contain both oestrogen and progestogen. Vigorous usage of oral contraceptives and anabolic steroids as associated with cholestasis, vascular lesions and hepatic neoplasm. Benign hepatic neoplasms are clearly associated with oral contraceptives. In this article we...

  10. Oral vaccination of fish

    OpenAIRE

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...

  11. Serous goblet cells: the protein secreting cells in the oral cavity of a catfish, Rita rita (Hamilton, 1822) (Bagridae, Siluriformes).

    Science.gov (United States)

    Yashpal, Madhu; Mittal, Ajay Kumar

    2014-02-01

    Serous goblet cells in the oral epithelium of Rita rita are characterized by the presence of distinct eosinophilic granules occupying large parts of the cytoplasm. In R. rita, a range of histochemical results reveal that these cells are involved in proteinaceous secretions, and thus likely contribute to various functions analogous to those of mammalian saliva. The secretions of these cells have also been associated with specific functions and are discussed in relation to their physiological importance with special reference to their roles in lubrication, alteration in viscosity, various functions of mucus such as handling, maneuvering and driving of food items toward the esophagus, maintaining taste sensitivity and protection of the oral epithelium. In addition, the serous goblet cells may also be considered as the primary defensive cell of the oral epithelium of R. rita. The results significantly add to very limited set of literature on the serous goblet cells and provide noteworthy information on the mucous secretions in the oral cavity of fish. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    International Nuclear Information System (INIS)

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua; Guo, Renfeng; Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun; Zhu, Maoxiang

    2015-01-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4 + CD25 + FoxP3 + regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis

  13. Pax6 downregulation mediates abnormal lineage commitment of the ocular surface epithelium in aqueous-deficient dry eye disease.

    Directory of Open Access Journals (Sweden)

    Ying Ting Chen

    Full Text Available Keratinizing squamous metaplasia (SQM of the ocular surface is a blinding consequence of systemic autoimmune disease and there is no cure. Ocular SQM is traditionally viewed as an adaptive tissue response during chronic keratoconjunctivitis sicca (KCS that provokes pathological keratinization of the corneal epithelium and fibrosis of the corneal stroma. Recently, we established the autoimmune regulator-knockout (Aire KO mouse as a model of autoimmune KCS and identified an essential role for autoreactive CD4+ T cells in SQM pathogenesis. In subsequent studies, we noted the down-regulation of paired box gene 6 (Pax6 in both human patients with chronic KCS associated with Sjögren's syndrome and Aire KO mice. Pax6 encodes a pleiotropic transcription factor guiding eye morphogenesis during development. While the postnatal function of Pax6 is largely unknown, we hypothesized that its role in maintaining ocular surface homeostasis was disrupted in the inflamed eye and that loss of Pax6 played a functional role in the initiation and progression of SQM. Adoptive transfer of autoreactive T cells from Aire KO mice to immunodeficient recipients confirmed CD4+ T cells as the principal downstream effectors promoting Pax6 downregulation in Aire KO mice. CD4+ T cells required local signaling via Interleukin-1 receptor (IL-1R1 to provoke Pax6 loss, which prompted a switch from corneal-specific cytokeratin, CK12, to epidermal-specific CK10. The functional role of Pax6 loss in SQM pathogenesis was indicated by the reversal of SQM and restoration of ocular surface homeostasis following forced expression of Pax6 in corneal epithelial cells using adenovirus. Thus, tissue-restricted restoration of Pax6 prevented aberrant epidermal-lineage commitment suggesting adjuvant Pax6 gene therapy may represent a novel therapeutic approach to prevent SQM in patients with chronic inflammatory diseases of the ocular surface.

  14. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua [Beijing Institute of Radiation Medicine, Beijing (China); Guo, Renfeng [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun [Beijing Institute of Radiation Medicine, Beijing (China); Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn [Beijing Institute of Radiation Medicine, Beijing (China)

    2015-10-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.

  15. Delayed Treatment with a Small Pigment Epithelium Derived Factor (PEDF Peptide Prevents the Progression of Diabetic Renal Injury.

    Directory of Open Access Journals (Sweden)

    Alaa S Awad

    Full Text Available Our recent publication showed that a small bioactive pigment epithelium derived factor (PEDF peptide (P78-PEDF prevents the development of diabetic nephropathy (DN. However, its effects on the progression of established DN were not clear. Therefore, the purpose of this study was to determine the effect of P78-PEDF in the progression of DN and to compare the effects of P78-PEDF and an ACE inhibitor (ACEi, a standard of care in DN. Experiments were conducted in Ins2(Akita mice treated with P78-PEDF or captopril starting at 6 wks of age for 12 wks (early treatment or starting at 12 wks of age for 6 wks (late treatment. We first established the optimal dose of the P78-PEDF peptide to ameliorate DN in Ins2(Akita mouse for a 6 wk study period and found that the peptide was effective at 0.1- 0.5 µg/g/day. We next showed that early or late treatment with P78-PEDF resulted in protection from DN as indicated by reduced albuminuria, kidney macrophage recruitment, histological changes, inflammatory cytokines and fibrotic markers (kidney TNF-α, fibronectin, VEGFA and EGFR, and restored nephrin expression compared with vehicle-treated Ins2(Akita mice. Interestingly, only early but not late treatment with captopril was as effective as P78-PEDF in reducing most DN complications, despite its lack of effect on nephrin, VEGFA and EGFR expression. These findings highlight the importance of P78-PEDF peptide as a potential therapeutic modality in both the development and progression of diabetic renal injury.

  16. Suprabasal expression of Ki-67 as a marker for the severity of oral epithelial dysplasia and oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Nidhi Dwivedi

    2013-01-01

    Full Text Available Background: Transition of the normal oral epithelium to dysplasia and to malignancy is featured by increased cell proliferation. To evaluate the hypothesis of distributional disturbances in proliferating and stem cells in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC. Aim: To evaluate layer wise expression of Ki-67 in oral epithelial dysplasia and in OSCC. Materials and Methods: Thirty histologically confirmed cases of oral epithelial dysplasia, fifteen cases of OSCC and five cases of normal buccal mucosa were immunohistochemically examined and nuclear expression of Ki-67 was counted according to basal, parabasal, and suprabasal layers in epithelial dysplasia and number of positive cells per 100 cells in OSCC as labeling index (LI. Results: Suprabasal expression of Ki-67 increased according to the severity of epithelial dysplasia and the difference was statistically significant ( P < 0.001. The mean Ki-67LI was 12.78 for low risk lesions, 28.68 for high risk lesions, 39.45 for OSCC and 13.6 for normal buccal mucosa. Conclusion: The results of the present study demonstrate the use of proliferative marker Ki-67 in assessing the severity of epithelial dysplasia. Suprabasal expression of Ki-67 provides an objective criteria for determining the severity of epithelial dysplasia and histological grading of OSCC.

  17. Oral Delivery of Protein Drugs Bioencapsulated in Plant Cells.

    Science.gov (United States)

    Kwon, Kwang-Chul; Daniell, Henry

    2016-08-01

    Plants cells are now approved by the FDA for cost-effective production of protein drugs (PDs) in large-scale current Good Manufacturing Practice (cGMP) hydroponic growth facilities. In lyophilized plant cells, PDs are stable at ambient temperature for several years, maintaining their folding and efficacy. Upon oral delivery, PDs bioencapsulated in plant cells are protected in the stomach from acids and enzymes but are subsequently released into the gut lumen by microbes that digest the plant cell wall. The large mucosal area of the human intestine offers an ideal system for oral drug delivery. When tags (receptor-binding proteins or cell-penetrating peptides) are fused to PDs, they efficiently cross the intestinal epithelium and are delivered to the circulatory or immune system. Unique tags to deliver PDs to human immune or nonimmune cells have been developed recently. After crossing the epithelium, ubiquitous proteases cleave off tags at engineered sites. PDs are also delivered to the brain or retina by crossing the blood-brain or retinal barriers. This review highlights recent advances in PD delivery to treat Alzheimer's disease, diabetes, hypertension, Gaucher's or ocular diseases, as well as the development of affordable drugs by eliminating prohibitively expensive purification, cold chain and sterile delivery.

  18. Oral vaccination of fish

    NARCIS (Netherlands)

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen

  19. A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development.

    Science.gov (United States)

    Sherman-Baust, Cheryl A; Kuhn, Elisabetta; Valle, Blanca L; Shih, Ie-Ming; Kurman, Robert J; Wang, Tian-Li; Amano, Tomokazu; Ko, Minoru S H; Miyoshi, Ichiro; Araki, Yoshihiko; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G; Morin, Patrice J

    2014-07-01

    Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histological analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal-appearing p53-positive epithelium that are similar to 'p53 signatures' in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these non-invasive precursor lesions, we also identified invasive adenocarcinoma in the ovaries of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and wild-type (WT) C57BL/6. One of these genes, Top2a, which encodes topoisomerase IIα, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and was specifically elevated in mouse STICs but not in the surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumourigenesis, as well as

  20. Immunohistochemical characterization and evaluation of prognostic factors in canine oral melanomas with osteocartilaginous differentiation.

    Science.gov (United States)

    Sánchez, J; Ramirez, G A; Buendia, A J; Vilafranca, M; Martinez, C M; Altimira, J; Navarro, J A

    2007-09-01

    Melanomas are the most common malignant oral neoplasm in dogs. Osteocartilaginous differentiation in oral melanomas is a rare feature described both in veterinary and human medicine. Here, 10 cases of this type of neoplasm were used to study their immunohistochemical, biological, and clinical characteristics. Reactivity for S100 and melan A antigen was evaluated, and 4 prognosis factors (mitotic index, invasiveness of epithelium, nuclear atypia, and proliferation index) were analyzed and correlated with the clinical course of the neoplasms after diagnosis. Immunohistochemical analysis of the studied neoplasms, including the osteocartilaginous areas, showed positive immunoreaction for S100 and melan A, except in one dog, which was negative for melan A. Analysis of the results showed that oral melamonas with osteocartilaginous differentiation have a clinical course similar to that of other melanomas in the oral cavity. Analysis of the mitotic index and the expression of proliferation marker Ki-67 could be useful tools for predicting the biological behavior of these neoplasms.

  1. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... to detect oral cancer during your routine dental examinations. Don't risk it. Perform an oral cancer ... oral cancer self-exam each month. An oral examination is performed using a bright light and a ...

  2. Clearance of lead-212 ions from rabbit bronchial epithelium to blood

    International Nuclear Information System (INIS)

    James, A.C.; Greenhalgh, J.R.; Smith, H.

    1977-01-01

    The absorption of 212 Pb ions from bronchial epithelium to blood has been investigated in anaesthetized rabbits. The 212 Pb ions were introduced by intubation either into the trachea or into smaller, more distal bronchi. Removal from lung was followed by external γ-counting. Mucociliary clearance to the GI tract was blocked by tracheostomy. Two distinct phases of clearance from bronchial epithelium to blood were observed. Approximately 20% of deposited 212 Pb was rapidly absorbed with a half-time of about 4 min, the remainder with a biological half-time of about 9 h, irrespective of the site of instillation in the bronchial tree. Two hours after deposition, the 212 Pb remaining in lung was found to be partitioned between mucus and the bronchial epithelium, with a substantial but minor fraction in the epithelium. Uptake of 212 Pb in the skeleton was estimated to be about 20% of the 212 Pb entering the blood circulation. Removal by the kidneys, at 25%, was comparable with skeletal uptake. These results are compared with previously published work using rodents, dogs and man which demonstrated either rapid or slow absorption but not both phases occurring together. (author)

  3. Morphological featuresof metaplasia and dysplasia of epithelium in Barret’s esophagus

    OpenAIRE

    Vitkovska S.V.

    2012-01-01

    The article presents the morphological features of metaplasia and dysplasia of epithelium in Barret’s esophagus. The role of biopsy in the diagnostic of Barret’s esophagus and results of morphological research in the choice of follow-up and treatment of patients is shown.

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

    Science.gov (United States)

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

    1979-01-01

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

  5. Comparison of Effect of Hypoxia on Epithelium of Trachea and Terminal Bronchioles

    Czech Academy of Sciences Publication Activity Database

    Uhlík, J.; Konrádová, V.; Vajner, L.; Adášková, Jana; Herget, J.

    2003-01-01

    Roč. 9, Suppl. 3 (2003), s. 478-479 ISSN 1431-9276. [Microscopy Conference /31./. Dresden, 07.09.2003-12.09.2003] Source of funding: V - iné verejné zdroje Keywords : airway epithelium * Clara cells * ciliated cells * hypoxia * electron microscopy Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.648, year: 2003

  6. Epithelial Cell Damage Activates Bactericidal/Permeability Increasing-Protein (BPI Expression in Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Arjun Balakrishnan

    2017-08-01

    Full Text Available As the first line of defense against invading pathogen, intestinal epithelium produces various antimicrobial proteins (AMP that help in clearance of pathogen. Bactericidal/permeability-increasing protein (BPI is a 55 kDa AMP that is expressed in intestinal epithelium. Dysregulation of BPI in intestinal epithelium is associated with various inflammatory diseases like Crohn’s Disease, Ulcerative colitis, and Infectious enteritis’s. In this paper, we report a direct correlation between intestinal damage and BPI expression. In Caco-2 cells, we see a significant increase in BPI levels upon membrane damage mediated by S. aureus infection and pore-forming toxins (Streptolysin and Listeriolysin. Cells detect changes in potassium level as a Danger-associated molecular pattern associated with cell damage and induce BPI expression in a p38 dependent manner. These results are further supported by in vivo findings that the BPI expression in murine intestinal epithelium is induced upon infection with bacteria which cause intestinal damage (Salmonella Typhimurium and Shigella flexneri whereas mutants that do not cause intestinal damage (STM ΔfliC and STM ΔinvC did not induce BPI expression. Our results suggest that epithelial damage associated with infection act as a signal to induce BPI expression.

  7. Epithelium-innate immune cell axis in mucosal responses to SIV.

    Science.gov (United States)

    Shang, L; Duan, L; Perkey, K E; Wietgrefe, S; Zupancic, M; Smith, A J; Southern, P J; Johnson, R P; Haase, A T

    2017-03-01

    In the SIV (simian immunodeficiency virus)-rhesus macaque model of HIV-1 (human immunodeficiency virus type I) transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T-cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T-cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T-cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment, and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses.

  8. Expression of insulin signalling components in the sensory epithelium of the human saccule

    DEFF Research Database (Denmark)

    Degerman, Eva; Rauch, Uwe; Lindberg, Sven

    2013-01-01

    signalling components in the inner ear is sparce. Our immunohistochemistry approach has shown that the insulin receptor, insulin receptor substrate 1 (IRS1), protein kinase B (PKB) and insulin-sensitive glucose transporter (GLUT4) are expressed in the sensory epithelium of the human saccule, which also...

  9. Posttranslational regulation of glucose-6-phosphate dehydrogenase activity in tongue epithelium

    NARCIS (Netherlands)

    Biagiotti, E.; Bosch, K. S.; Ninfali, P.; Frederiks, W. M.; van Noorden, C. J.

    2000-01-01

    Expression of glucose-6-phosphate dehydrogenase (G6PD) activity is high in tongue epithelium, but its exact function is still unknown, it may be related;either to the high proliferation rate of this tissue or to protection against oxidative stress. To elucidate its exact role, we localized

  10. DNA damage in lens epithelium of cataract patients in vivo and ex vivo.

    Science.gov (United States)

    Øsnes-Ringen, Oyvind; Azqueta, Amaia O; Moe, Morten C; Zetterström, Charlotta; Røger, Magnus; Nicolaissen, Bjørn; Collins, Andrew R

    2013-11-01

    DNA damage has been described in the human cataractous lens epithelium, and oxidative stress generated by UV radiation and endogenous metabolic processes has been suggested to play a significant role in the pathogenesis of cataract. In this study, the aim was to explore the quality and relative quantity of DNA damage in lens epithelium of cataract patients in vivo and after incubation in a cell culture system. Capsulotomy specimens were analysed, before and after 1 week of ex vivo cultivation, using the comet assay to measure DNA strand breaks, oxidized purine and pyrimidine bases and UV-induced cyclobutane pyrimidine dimers. DNA strand breaks were barely detectable, oxidized pyrimidines and pyrimidine dimers were present at low levels, whereas there was a relatively high level of oxidized purines, which further increased after cultivation. The observed levels of oxidized purines in cataractous lens epithelium may support a theory consistent with light damage and oxidative stress as mediators of molecular damage to the human lens epithelium. Damage commonly associated with UV-B irradiation was relatively low. The levels of oxidized purines increased further in a commonly used culture system. This is of interest considering the importance and versatility of ex vivo systems in studies exploring the pathogenesis of cataract. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

  11. Proton nuclear magnetic resonance study on the barrier function of pig corneal epithelium and endothelium

    International Nuclear Information System (INIS)

    Yokoi, Norihiko; Kinoshita, Shigeru; Morimoto, Taketoshi; Yoshizaki, Kazuo.

    1995-01-01

    Using gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) as a tracer, the barrier function of the corneal epithelium and endothelium was evaluated by proton nuclear magnetic resonance. Whole pig eyes and cornea excised with scleral rim, which had been incubated in dextran-added Gd-DTPA solution, were subjected to T 1 relaxation measurement and magnetic resonance imaging (MRI). After incubation, the T 1 relaxation rate (1/T 1 ) of the excised cornea increased to a steady value, whereas that of the cornea from the whole eye increased only slightly. These results indicated that the increase in the T 1 relaxation rate of the excised cornea was attributable to Gd-DTPA penetration from the corneal endothelium and that the corneal epithelium exhibited a strong barrier function against Gd-DTPA entry. The MRI study also confirmed the strong barrier, enhanced signals being detected within the aqueous fluid in the T 1 -weighted image only when the corneal epithelium was abraded. Since Gd-DTPA scarcely penetrates the intact corneal epithelium, Gd-DTPA-enhanced MRI shows potential as a quantitative tracer in evaluating epithelial barrier disruption. (author)

  12. Sodium transport and intracellular sodium activity in cultured human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

     human nasal epithelium (HNE). Under control conditions, intracellular Na+ activity (acNa) was 23 +/- 1 mM (n = 44 preparations, 393 impalements).Amiloride (10(-4) M) hyperpolarized the apical membrane and increased the fractional apical membrane resistance but did not affect acNa. Exposure to...

  13. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Nielsen, Hanne Mørck; Rassing, M R

    1999-01-01

    The aim of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability enhancement by different pH values, different osmolality values or bile salts. For this purpose, the increase in the apparent permeability (P...

  14. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Nielsen, H M; Rassing, M R; Nielsen, Hanne Mørck

    2000-01-01

    The objective of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium. For this purpose, the permeability of water, mannitol and testosterone across the TR146 cell culture model was compared to the permeability across human, monkey...

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

    International Nuclear Information System (INIS)

    Bondeson, L.

    1987-01-01

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

  16. Impact of thymectomy and antilymphocytic serum on stem cells of the intestinal epithelium

    International Nuclear Information System (INIS)

    Aparovich, G.G.; Trufakin, V.A.

    1982-01-01

    The population of stem cells of the intestinal epithelium was studied under conditions of the disturbed balance in the immune system on F 1 (CBAxC57B1) mice. It has been shown that thymectomy in adult mice does not influence the stem region of the intestinal epithelium at early time of observation but causes a tendency to the changed number of epithelial stem cells in 4-6 months. Administration of specific sera against T-, B- and mixed lymphoid populations on the 1st day of observation produces an ambi us effect on the stem region and results in an increase of the number of epithelial stem cells on the 5th day. After administration of the antilymphocytic serum there have been determined morphological changes in the population of mature erythrocytes and undulatory fluctuations in the number of mitotic cells of the intestinal epithelium. These data suggest functional correlation of the intestinal epithelium and the state of the immunocompetent tissue [ru

  17. Quantification of transcriptome responses of the rumen epithelium to butyrate infusion

    Science.gov (United States)

    Short-chain fatty acids (SCFAs), such as butyrate, produced by gut microorganisms play an important role in energy metabolism and physiology in ruminants as well as in human health. Butyrate is a preferred substrate in the rumen epithelium where approximately 90% of butyrate is metabolized. Additi...

  18. Immunohistochemical expression of matrix metalloproteinases in the rabbit corneal epithelium upon UVA and UVB irradiation

    Czech Academy of Sciences Publication Activity Database

    Ardan, Taras; Čejková, Jitka

    2012-01-01

    Roč. 114, č. 6 (2012), s. 540-546 ISSN 0065-1281 R&D Projects: GA ČR GPP302/10/P155 Institutional research plan: CEZ:AV0Z50390512 Keywords : cornea * corneal epithelium * eye Subject RIV: FF - HEENT, Dentistry Impact factor: 1.608, year: 2012

  19. Loss of Retinal Function and Pigment Epithelium Changes in a Patient with Common Variable Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Jakob Halborg

    2012-01-01

    Full Text Available Common variable immunodeficiency (CVID has only scarcely been associated with ocular symptoms and rarely with retinal disease. In this case we describe a patient with distinct morphological and functional alterations in the retina. The patient presents with characteristic changes in retinal pigment epithelium, autofluorescence, and electrophysiology.

  20. Mannose-specific interaction of Lactobacillus plantarum with porcine jejunal epithelium

    NARCIS (Netherlands)

    Pretzer, G.; Meulen, van der J.; Snel, J.; Meer, van der R.; Kleerebezem, M.; Niewold, Th.; Hulst, M.M.; Smits, M.A.

    2008-01-01

    Host-microorganism interactions in the intestinal tract are complex, and little is known about specific nonpathogenic microbial factors triggering host responses in the gut. In this study, mannose-specific interactions of Lactobacillus plantarum 299v with jejunal epithelium were investigated using