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Sample records for providing general epithelial

  1. Stromal-epithelial crosstalk provides a suitable microenvironment for the progression of ovarian cancer cells in vitro.

    Science.gov (United States)

    Fu, Shilong; Dong, Lihua; Sun, Wei; Xu, Yi; Gao, Li; Miao, Yi

    2013-11-01

    The tumor microenvironment plays an important role in the progression of cancer. This study focused on carcinoma-associated fibroblasts (CAFs) and stromal-epithelial interaction between CAFs and epithelial ovarian carcinoma (EOC) cells. We isolated and established primary cultures of CAFs and co-cultured CAFs and EOC cells in vitro. The co-culture conditioned medium (CC-CM) was harvested and its influence on EOC cells was examined. Cytokine, chemokine, and growth factor levels were screened using a biotin label-based human antibody array system. We found that the stromal-epithelial crosstalk provided a suitable microenvironment for the progression of ovarian cancer cells in vitro.

  2. Epithelial transport in The Journal of General Physiology.

    Science.gov (United States)

    Palmer, Lawrence G

    2017-10-02

    Epithelia define the boundaries of the body and often transfer solutes and water from outside to inside (absorption) or from inside to outside (secretion). Those processes involve dual plasma membranes with different transport components that interact with each other. Understanding those functions has entailed breaking down the problem to analyze properties of individual membranes (apical vs. basolateral) and individual transport proteins. It also requires understanding of how those components interact and how they are regulated. This article outlines the modern history of this research as reflected by publications in The Journal of General Physiology. © 2017 Palmer.

  3. Preparedness of Lithuanian general practitioners to provide mental healthcare services

    DEFF Research Database (Denmark)

    Jaruseviciene, Lina; Sauliune, Skirmante; Jarusevicius, Gediminas

    2014-01-01

    BACKGROUND: A large unmet need for mental healthcare in Lithuania is partially attributable to a lack of primary care providers with skills in this area. The aim of this study was to assess general practitioners' (GPs) experience in mental healthcare and their perceptions about how to increase th...

  4. Social Comparison Seeking: Providing General Comparison Curtails Local Comparison

    Science.gov (United States)

    Buckingham, Justin T.; Zell, Ethan; Schurtz, David R.

    2012-01-01

    Past research shows that people use local social comparison information more than general social comparison information when both are given (Zell & Alicke, 2010). The present studies examined the extent to which people seek local comparisons when they have already received general comparison information. In Study 1, students received their…

  5. STORM: a general model to determine the number and adaptive changes of epithelial stem cells in teleost, murine and human intestinal tracts.

    Directory of Open Access Journals (Sweden)

    Zhengyuan Wang

    Full Text Available Intestinal stem cells play a pivotal role in the epithelial tissue renewal, homeostasis and cancer development. The lack of a general marker for intestinal stem cells across species has hampered analysis of stem cell number in different species and their adaptive changes upon intestinal lesions or during development of cancer. Here a two-dimensional model, named STORM, has been developed to address this issue. By optimizing epithelium renewal dynamics, the model examines the epithelial stem cell number by taking experimental input information regarding epithelium proliferation and differentiation. As the results suggest, there are 2.0-4.1 epithelial stem cells on each pocket section of zebrafish intestine, 2.0-4.1 stem cells on each crypt section of murine small intestine and 1.8-3.5 stem cells on each crypt section of human duodenum. The model is able to provide quick results for stem cell number and its adaptive changes, which is not easy to measure through experiments. Its general applicability to different species makes it a valuable tool for analysis of intestinal stem cells under various pathological conditions.

  6. A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy

    DEFF Research Database (Denmark)

    Sánchez-Martínez, Ruth; Cruz-Gil, Silvia; Gómez de Cedrón, Marta

    2015-01-01

    an epithelial-mesenchymal transition (EMT) program that promotes migration and invasion of colon cancer cells. The mesenchymal phenotype produced upon overexpression of these enzymes is reverted through reactivation of AMPK signaling. Furthermore, this network expression correlates with poorer clinical outcome...... of stage-II colon cancer patients. Finally, combined treatment with chemical inhibitors of ACSL/SCD selectively decreases cancer cell viability without reducing normal cells viability. Thus, ACSL/SCD network stimulates colon cancer progression through conferring increased energetic capacity and invasive...... and migratory properties to cancer cells, and might represent a new therapeutic opportunity for colon cancer treatment....

  7. Is general dentistry dead? How mid-level dental providers will affect the profession.

    Science.gov (United States)

    Curtis, Eric K

    2012-01-01

    The rhetoric concerning mid-level providers and their impact on general dental practice is building in intensity. This is a complex issue and there is no clear picture of either the benefits or dangers to the public of such a delivery model, whether such plans are economically sustainable, or the role of general dentists in the configuration of future practices. The opinions of a representative sample of thinkers from various perspectives are sampled.

  8. General practitioners' knowledge, attitudes and views of providing preconception care: a qualitative investigation

    OpenAIRE

    Ojukwu, O; Patel, D.; Stephenson, J; Howden, B; Shawe, J

    2016-01-01

    Background: Preconception health and care aims to reduce parental risk factors before pregnancy through health promotion and intervention. Little is known about the preconception interventions that general practitioners (GPs) provide. The aim of this study was to examine GPs’ knowledge, attitudes, and views towards preconception health and care in the general practice setting. Methods: As part of a large mixed-methods study to explore preconception care in England, we surveyed 1,173 women...

  9. Vertical integration of teaching in Australian general practice--a survey of regional training providers.

    Science.gov (United States)

    Stocks, Nigel P; Frank, Oliver; Linn, Andrew M; Anderson, Katrina; Meertens, Sarah

    2011-06-06

    To examine vertical integration of teaching and clinical training in general practice and describe practical examples being undertaken by Australian general practice regional training providers (RTPs). A qualitative study of all RTPs in Australia, mid 2010. All 17 RTPs in Australia responded. Eleven had developed some vertical integration initiatives. Several encouraged registrars to teach junior doctors and medical students, others encouraged general practitioner supervisors to run multilevel educational sessions, a few coordinated placements, linkages and support across their region. Three RTPs provided case studies of vertical integration. Many RTPs in Australia use vertical integration of teaching in their training programs. RTPs with close associations with universities and rural clinical schools seem to be leading these initiatives.

  10. Frequent attenders in general practice: problem solving treatment provided by nurses [ISRCTN51021015

    Directory of Open Access Journals (Sweden)

    van Oppen P

    2005-10-01

    Full Text Available Abstract Background There is a need for assistance from primary care mental health workers in general practice in the Netherlands. General practitioners (GPs experience an overload of frequent attenders suffering from psychological problems. Problem Solving Treatment (PST is a brief psychological treatment tailored for use in a primary care setting. PST is provided by nurses, and earlier research has shown that it is a treatment at least as effective as usual care. However, research outcomes are not totally satisfying. This protocol describes a randomized clinical trial on the effectiveness of PST provided by nurses for patients in general practice. The results of this study, which currently being carried out, will be presented as soon as they are available. Methods/design This study protocol describes the design of a randomized controlled trial to investigate the effectiveness and cost-effectiveness of PST and usual care compared to usual care only. Patients, 18 years and older, who present psychological problems and are frequent attenders in general practice are recruited by the research assistant. The participants receive questionnaires at baseline, after the intervention, and again after 3 months and 9 months. Primary outcome is the reduction of symptoms, and other outcomes measured are improvement in problem solving skills, psychological and physical well being, daily functioning, social support, coping styles, problem evaluation and health care utilization. Discussion Our results may either confirm that PST in primary care is an effective way of dealing with emotional disorders and a promising addition to the primary care in the UK and USA, or may question this assumption. This trial will allow an evaluation of the effects of PST in practical circumstances and in a rather heterogeneous group of primary care patients. This study delivers scientific support for this use and therefore indications for optimal treatment and referral.

  11. Informal Consultations Provided to General Internists by the Gastroenterology Department of an HMO

    Science.gov (United States)

    Pearson, Steven D; Moreno, Ricardo; Trnka, Yvona

    1998-01-01

    OBJECTIVE To study the process, outcomes, and time spent on informal consultations provided by gastroenterologists to the primary care general internists of an HMO. DESIGN Observational study. SETTING A large, urban staff-model HMO. PATIENTS/PARTICIPANTS Seven gastroenterologists constituting the total workforce of the gastroenterology department of the HMO. MEASUREMENTS AND MAIN RESULTS Data on 91 informal consultations were obtained, of which 55 (60%) involved the acute management of a patient with new symptoms or test results, and 36 (40%) were for questions related to nonacute diagnostic test selection or medical therapy. Questions regarding patients previously unknown to the gastroenterology department accounted for 74 (81%) of the consultations. Formal referral was recommended in only 16 (22%) of these cases. As judged by the time data gathered on the 91 consultations, the gastroenterologists spent approximately 7.2 hours per week to provide informal consultation for the entire HMO. CONCLUSIONS Gastroenterologists spend a significant amount of time providing informal consultation to their general internist colleagues in this HMO. The role informal consultation plays in the workload of physicians and in the clinical care of populations is an important question for health care system design, policy, and research. PMID:9686708

  12. Review of patient satisfaction with services provided by general practitioners in an antenatal shared care program.

    Science.gov (United States)

    Lucas, Catherine; Charlton, Karen; Brown, Lucy; Brock, Erin; Cummins, Leanne

    2015-05-01

    Antenatal shared care (ANSC) is a model of care in Australia whereby pregnant women are managed by their general practitioner (GP) and an obstetrician at a public antenatal clinic throughout the pregnancy. The aim of this study was to assess pregnant women's satisfaction with the ANSC program and the adequacy of advice provided to pregnant women. Women participating in ANSC in the Illawarra region of NSW were invited to complete a satisfaction survey, which included questions on relevant topics discussed with their GP. Most women reported being highly satisfied with the ANSC service. Over half of the women had not received any information about breastfeeding and nutritional supplementation of iodine.

  13. Preference of Chinese general public and healthcare providers for a good death.

    Science.gov (United States)

    Haishan, Huang; Hongjuan, Liu; Tieying, Zeng; Xuemei, Pu

    2015-03-01

    The aim of this study is to find and compare the current situation between common people and healthcare providers' preferences for a good death in the context of Chinese culture. A cross-sectional anonymous questionnaire survey covering 190 ordinary Chinese people and 323 healthcare providers was conducted. An inventory of the good death was translated and the subjects were surveyed about their attitude toward it. Permission to conduct the study was granted by department chiefs, nurse managers and the participants themselves. The participants were informed that they took part on a voluntary and anonymous basis, that they could withdraw at any time, that they had the right to ignore questions they did not wish to answer, and that whatever they chose to do would not jeopardize their employment conditions. The attributes that were perceived as important by major respondents for a good death were maintaining hope and pleasure, good relationship with medical staff, good relationship with family, independence, environment comfort, being respected as an individual, preparation for death, physical and psychological comfort, dying in a favorite place, and not being a burden to others. And some relatively less important characteristics were life completion, receiving enough treatment, natural death, controlling over the future, unawareness of death, pride and beauty, feeling that one's life is worth living, and religious and spiritual comfort. We also found that healthcare providers were more likely than general out-patients to perceive "physical and psychological comfort," "dying in a favorite place," "good relationship with medical staff," and "natural death" as important for a good death. This study offers healthcare providers in China a fundamental understanding of the normal expectations of the general public for a good death. It is believed that these findings in our study are valuable to improve palliative care in China. We compared the attitudes of Chinese and

  14. RESEARCH OF PROBLEMS OF DESIGN OF COMPLEX TECHNICAL PROVIDING AND THE GENERALIZED MODEL OF THEIR DECISION

    Directory of Open Access Journals (Sweden)

    A. V. Skrypnikov

    2015-01-01

    Full Text Available Summary. In this work the general ideas of a method of V. I. Skurikhin taking into account the specified features develop and questions of the analysis and synthesis of a complex of technical means, with finishing them to the level suitable for use in engineering practice of design of information management systems are in more detail considered. In work the general system approach to the solution of questions of a choice of technical means of the information management system is created, the general technique of the sys tem analysis and synthesis of a complex of the technical means and its subsystems providing achievement of extreme value of criterion of efficiency of functioning of a technical complex of the information management system is developed. The main attention is paid to the applied party of system researches of complex technical providing, in particular, to definition of criteria of quality of functioning of a technical complex, development of methods of the analysis of information base of the information management system and definition of requirements to technical means, and also methods of structural synthesis of the main subsystems of complex technical providing. Thus, the purpose is research on the basis of system approach of complex technical providing the information management system and development of a number of methods of the analysis and the synthesis of complex technical providing suitable for use in engineering practice of design of systems. The well-known paradox of development of management information consists of that parameters of the system, and consequently, and requirements to the complex hardware, can not be strictly reasonable to development of algorithms and programs, and vice versa. The possible method of overcoming of these difficulties is prognostication of structure and parameters of complex hardware for certain management informations on the early stages of development, with subsequent clarification and

  15. Providing dental care to pregnant patients: a survey of Oregon general dentists.

    Science.gov (United States)

    Huebner, Colleen E; Milgrom, Peter; Conrad, Douglas; Lee, Rosanna Shuk Yin

    2009-02-01

    A growing number of studies and reports indicate preventive, routine and emergency dental procedures can be provided safely to pregnant patients to alleviate dental problems and promote oral health of mothers and children. In 2006 and 2007, the authors conducted a survey of 1,604 general dentists in Oregon. The survey asked dentists about their attitudes, beliefs and practices regarding dental care for pregnant patients. The authors compared the responses with 2006 guidelines from a New York State Department of Health expert panel. The response rate was 55.2 percent. Most respondents (91.7 percent) agreed that dental treatment should be part of prenatal care. Two-thirds of respondents (67.7 percent) were interested in receiving continuing dental education (CDE) regarding the care of pregnant patients. Comparisons of self-reported knowledge and practice with the aforementioned guidelines revealed several points of difference; the greatest regarded obtaining full-mouth radiographs, providing nitrous oxide, administering long-acting anesthetic injections and use of over-the-counter pain medications. Dentists need pregnancy-specific education to provide up-to-date preventive and curative care to pregnant patients. The results of the study identified specific skills and misinformation that could be addressed through CDE. Comprehensive dental care provided during pregnancy is needed to ensure the oral health of all women at risk of experiencing pregnancy-specific problems, as well as the prevention of early childhood caries.

  16. Collaboration of general practitioners and exercise providers in promotion of physical activity a written survey among general practitioners.

    NARCIS (Netherlands)

    Leemrijse, C.J.; Bakker, D.H. de; Ooms, L.; Veenhof, C.

    2015-01-01

    Background: General practitioners have an ideal position to motivate inactive patients to increase their physical activity. Most patients are able to exercise in regular local facilities outside the health care setting. The purpose of this study was to get insight into general practitioners

  17. Collaboration of general practitioners and exercise providers in promotion of physical activity a written survey among general practitioners

    NARCIS (Netherlands)

    Leemrijse, C J; de Bakker, D H; Ooms, L; Veenhof, C

    2015-01-01

    BACKGROUND: General practitioners have an ideal position to motivate inactive patients to increase their physical activity. Most patients are able to exercise in regular local facilities outside the health care setting. The purpose of this study was to get insight into general practitioners

  18. Wound classification in pediatric general surgery: significant variation exists among providers.

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    Snyder, Rebecca A; Johnson, Lisa; Tice, Jamie; Wingo, Tammy; Williams, Dana; Wang, Li; Blakely, Martin L

    2013-11-01

    Risk-adjusted rates of surgical site infections (SSI) are used as a quality metric to facilitate improvement within a hospital system and allow comparison across institutions. The NSQIP-Pediatric, among others, uses surgical wound classification as a variable in models designed to predict risk-adjusted postoperative morbidity, including SSI rates. The purpose of this study was to measure the level of agreement in wound classification assignment among 3 providers: surgeons, operating room (OR) nurses, and NSQIP surgical clinical reviewers (SCR). An analysis was performed of pediatric general surgery operations from 2010 to 2011. Wound classification was assigned at the time of operation by the OR nurse and surgeon, and by the NSQIP SCR postoperatively, according to NSQIP methodology. Disagreement was defined as any discrepancy in classification among the 3 providers, and the level of agreement was determined using the kappa statistic. For the 374 procedures reviewed, there was an overall disagreement of 48% among all providers, kappa 0.48 (95% CI 0.43 to 0.53). When comparing wound classification by surgeon and NSQIP SCR, 23% of cases were in disagreement, kappa 0.74 (95% CI 0.68 to 0.78). Disagreement between OR nurse and either surgeon or NSQIP SCR was higher: 38%, kappa 0.45 (95% CI 0.38 to 0.53) and 40%, kappa 0.44 (95% CI 0.37 to 0.51). Fundoplication, appendectomy, and cholecystectomy demonstrated the highest overall disagreement (73%, 71%, and 60%, respectively). There is significant variation in assigning surgical wound classification among health care providers. For future SSI comparative analyses, it will be critical to improve uniformity and understanding of wound class assignment among providers and institutions. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Dental care and treatments provided under general anaesthesia in the Helsinki Public Dental Service

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    Savanheimo Nora

    2012-10-01

    Full Text Available Abstract Background Dental general anaesthesia (DGA is a very efficient treatment modality, but is considered only in the last resort because of the risks posed by general anaesthesia to patients’ overall health. Health services and their treatment policies regarding DGA vary from country to country. The aims of this work were to determine the reasons for DGA in the Helsinki Public Dental Service (PDS and to assess the role of patient characteristics in the variation in reasons and in the treatments given with special focus on preventive care. Methods The data covered all DGA patients treated in the PDS in Helsinki in 2010. The data were collected from patient documents and included personal background: age ( Results The DGA patients (n=349 were aged 2.3 to 67.2 years. Immigrants predominated in the youngest age group (p Conclusions Extreme non-cooperation, dental fear and an excessive need for treatment were the main reasons for the use of comprehensive, conservative DGA in the Helsinki PDS. The reasons for the use of DGA and the treatments provided varied according to personal and medical background, and immigration status with no gender-differences. Preventive measures formed only a minor part of the dental care given under DGA.

  20. Measuring factors that influence the utilisation of preventive care services provided by general practitioners in Australia

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    Oldenburg Brian

    2009-12-01

    Full Text Available Abstract Background Relatively little research attention has been given to the development of standardised and psychometrically sound scales for measuring influences relevant to the utilisation of health services. This study aims to describe the development, validation and internal reliability of some existing and new scales to measure factors that are likely to influence utilisation of preventive care services provided by general practitioners in Australia. Methods Relevant domains of influence were first identified from a literature review and formative research. Items were then generated by using and adapting previously developed scales and published findings from these. The new items and scales were pre-tested and qualitative feedback was obtained from a convenience sample of citizens from the community and a panel of experts. Principal Components Analyses (PCA and internal reliability testing (Cronbach's alpha were then conducted for all of the newly adapted or developed scales utilising data collected from a self-administered mailed survey sent to a randomly selected population-based sample of 381 individuals (response rate 65.6 per cent. Results The PCA identified five scales with acceptable levels of internal consistency were: (1 social support (ten items, alpha 0.86; (2 perceived interpersonal care (five items, alpha 0.87, (3 concerns about availability of health care and accessibility to health care (eight items, alpha 0.80, (4 value of good health (five items, alpha 0.79, and (5 attitudes towards health care (three items, alpha 0.75. Conclusion The five scales are suitable for further development and more widespread use in research aimed at understanding the determinants of preventive health services utilisation among adults in the general population.

  1. Frequent attenders in general practice: problem solving treatment (PST) provided by nurses

    NARCIS (Netherlands)

    Schreuder, B.; van Oppen, P.C.; van Marwijk, H.W.J.; Smit, J.H.; Stalman, W.A.B.

    2005-01-01

    Background: There is a need for assistance from primary care mental health workers in general practice in the Netherlands. General practitioners (GPs) experience an overload of frequent attenders suffering from psychological problems. Problem Solving Treatment (PST) is a brief psychological

  2. Frequent attenders in general practice: problem solving treatment provided by nurses [ISRCTN51021015

    NARCIS (Netherlands)

    Schreuders, B.; van Oppen, P.C.; van Marwijk, H.W.J.; Smit, J.H.; Stalman, W.A.B.

    2005-01-01

    Background: There is a need for assistance from primary care mental health workers in general practice in the Netherlands. General practitioners (GPs) experience an overload of frequent attenders suffering from psychological problems. Problem Solving Treatment (PST) is a brief psychological

  3. Frequent attenders in general practice: problem solving treatment provided by nurses [ISRCTN51021015

    NARCIS (Netherlands)

    Schreuders, B.; Oppen, van P.C.; Marwijk, van H.W.J.; Smit, J.H.; Stalman, W.A.B.

    2005-01-01

    BACKGROUND: There is a need for assistance from primary care mental health workers in general practice in the Netherlands. General practitioners (GPs) experience an overload of frequent attenders suffering from psychological problems. Problem Solving Treatment (PST) is a brief psychological

  4. Success Rate of Treatments Provided for Early Childhood Caries under General Anesthesia: A Retrospective Cohort Study.

    Science.gov (United States)

    Amin, Maryam; Nouri, M-Reza; Hulland, Sarah; ElSalhy, Mohamed; Azarpazhooh, Amir

    2016-01-01

    The purpose of this study was to assess the success rate of various treatments provided under general anesthesia for early childhood caries (ECC) over three-year follow-up period. ECC children no older than 72 months at the time of dental surgery, who had completed a three-year follow-up, were included. The success rate of every treatment was evaluated. The longevity of each treatment and significant factors associated with failures were assessed. A total of 818 children (55.8 percent were males with a mean age of 46.2±13.4 months old) were included. Of these, 32.9 percent had restored teeth that required further treatment during the three-year follow-up. Amalgam restorations and stainless steel crowns (SSCs) showed significantly longer survival than composite restorations in all types of restorations (Pindirect pulp capping and pulpotomies were the same (P=0.234), and they were significantly higher than that for pulpectomies (P=0.001, P=0.039, respectively). The lower lingual holding arch (LLHA) had a significantly lower survival rate than other space maintainers (Prestorations were clinically more successful and had better survival times than composite restorations. The survival rate for the LLHA was low compared to other space maintainers.

  5. Computational modeling of epithelial tissues.

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    Smallwood, Rod

    2009-01-01

    There is an extensive literature on the computational modeling of epithelial tissues at all levels from subcellular to whole tissue. This review concentrates on behavior at the individual cell to whole tissue level, and particularly on organizational aspects, and provides an indication of where information from other areas, such as the modeling of angiogenesis, is relevant. The skin, and the lining of all of the body cavities (lung, gut, cervix, bladder etc) are epithelial tissues, which in a topological sense are the boundary between inside and outside the body. They are thin sheets of cells (usually of the order of 0.5 mm thick) without extracellular matrix, have a relatively simple structure, and contain few types of cells. They have important barrier, secretory and transport functions, which are essential for the maintenance of life, so homeostasis and wound healing are important aspects of the behavior of epithelial tissues. Carcinomas originate in epithelial tissues.There are essentially two approaches to modeling tissues--to start at the level of the tissue (i.e., a length scale of the order of 1 mm) and develop generalized equations for behavior (a continuum approach); or to start at the level of the cell (i.e., a length scale of the order of 10 µm) and develop tissue behavior as an emergent property of cellular behavior (an individual-based approach). As will be seen, these are not mutually exclusive approaches, and they come in a variety of flavors.

  6. Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia – a novel mouse model providing insights into geleophysic dysplasia

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    Dirk Hubmacher

    2015-05-01

    Full Text Available Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic dysplasia (GD in humans and Musladin–Lueke syndrome (MLS in dogs. GD is a severe, often lethal, condition presenting with short stature, brachydactyly, stiff skin, joint contractures, tracheal-bronchial stenosis and cardiac valve anomalies, whereas MLS is non-lethal and characterized by short stature and severe skin fibrosis. Although most mutations in fibrillin-1 (FBN1 cause Marfan syndrome (MFS, a microfibril disorder leading to transforming growth factor-β (TGFβ dysregulation, domain-specific FBN1 mutations result in dominant GD. ADAMTSL2 has been previously shown to bind FBN1 and latent TGFβ-binding protein-1 (LTBP1. Here, we investigated mice with targeted Adamtsl2 inactivation as a new model for GD (Adamtsl2−/− mice. An intragenic lacZ reporter in these mice showed that ADAMTSL2 was produced exclusively by bronchial smooth muscle cells during embryonic lung development. Adamtsl2−/− mice, which died at birth, had severe bronchial epithelial dysplasia with abnormal glycogen-rich inclusions in bronchial epithelium resembling the cellular anomalies described previously in GD. An increase in microfibrils in the bronchial wall was associated with increased FBN2 and microfibril-associated glycoprotein-1 (MAGP1 staining, whereas LTBP1 staining was increased in bronchial epithelium. ADAMTSL2 was shown to bind directly to FBN2 with an affinity comparable to FBN1. The observed extracellular matrix (ECM alterations were associated with increased bronchial epithelial TGFβ signaling at 17.5 days of gestation; however, treatment with TGFβ-neutralizing antibody did not correct the epithelial dysplasia. These investigations reveal a new function of ADAMTSL2 in modulating microfibril formation, and a previously unsuspected association with FBN2. Our studies suggest that the bronchial epithelial dysplasia accompanying microfibril dysregulation in Adamtsl2−/− mice

  7. General Systems Theory Provides a Conceptual Scheme for the Classification of Variables in Future Research Designs.

    Science.gov (United States)

    Smith, Albert B.

    The growth of research in the community college field is reviewed. The need for a general systems approach to classifying and organizing research designs is stressed. A taxonomy is proposed with major categories of input, process, and outcome variables. A community college is considered ideal for "open systems." The practical value of this…

  8. Lay Beliefs about Autism Spectrum Disorder among the General Public and Childcare Providers

    Science.gov (United States)

    Mitchell, Gwen E.; Locke, Kenneth D.

    2015-01-01

    We conducted a survey of beliefs about autism among the general public in the United States and Canada (n = 823) and among individuals working in childcare facilities in the state of Idaho (n = 176). Results included the following. Almost all respondents correctly believed that autism's primary causes are genetic and neurological (not parenting,…

  9. Pharmacist services provided in general practice clinics: a systematic review and meta-analysis.

    Science.gov (United States)

    Tan, Edwin C K; Stewart, Kay; Elliott, Rohan A; George, Johnson

    2014-01-01

    Integration of pharmacists into primary care general practice clinics has the potential to improve interdisciplinary teamwork and patient care; however this practice is not widespread. The aim of this study was to review the effectiveness of clinical pharmacist services delivered in primary care general practice clinics. A systematic review of English language randomized controlled trials cited in the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and International Pharmaceutical Abstracts was conducted. Studies were included if pharmacists had a regular and ongoing relationship with the clinic; delivered an intervention aimed at optimizing prescribing for, and/or medication use by, clinic patients; and were physically present within the clinic for all or part of the intervention, or for communication with staff. The search generated 1484 articles. After removal of duplicates and screening of titles and abstracts against inclusion criteria, 131 articles remained. A total of 38 studies were included in the review and assessed for quality. Seventeen studies had common endpoints (blood pressure, glycosylated hemoglobin, cholesterol and/or Framingham risk score) and were included in meta-analyses. Twenty-nine of the 38 studies recruited patients with specific medical conditions, most commonly cardiovascular disease (15 studies) and/or diabetes (9 studies). The remaining 9 studies recruited patients at general risk of medication misadventure. Pharmacist interventions usually involved medication review (86.8%), with or without other activities delivered collaboratively with the general practitioner (family physician). Positive effects on primary outcomes related to medication use or clinical outcomes were reported in 19 studies, mixed effects in six studies, and no effect in 13 studies. The results of meta-analyses favored the pharmacist intervention, with significant improvements in blood pressure, glycosylated hemoglobin, cholesterol and Framingham

  10. Perspectives on Obesity and Its Treatment: Health Care Providers and the General Public in Rural West Virginia and Urban Baltimore

    Science.gov (United States)

    Menez, Steven; Cheskin, Lawrence; Geller, Gail

    2013-01-01

    Objective: To determine and compare the perspectives of the general public and health care providers (HCPs) on obesity and its treatment in rural West Virginia (WV) and Baltimore, MD. Method: Surveys were completed in both locations by the general public (WV: "n" = 200; Baltimore: "n" = 171) and HCPs (WV: "n" = 25;…

  11. Providing Dental Care to Pregnant Patients: A Survey of Oregon General Dentists

    National Research Council Canada - National Science Library

    Huebner, Colleen E; Milgrom, Peter; Conrad, Douglas; Lee, Rosanna Shuk Yin

    2009-01-01

    A growing number of studies and reports indicate preventive, routine and emergency dental procedures can be provided safely to pregnant patients to alleviate dental problems and promote oral health...

  12. Functionalization of reactive polymer multilayers with RGD and an anti-fouling motif: RGD density provides control over human corneal epithelial cell-substrate interactions

    Science.gov (United States)

    Tocce, Elizabeth J.; Broderick, Adam H.; Murphy, Kaitlin C.; Liliensiek, Sara J.; Murphy, Christopher J.; Lynn, David M.; Nealey, Paul F.

    2011-01-01

    Our study demonstrates that substrates fabricated using a ‘reactive’ layer-by-layer approach promote well-defined cell-substrate interactions of human corneal epithelial cells. Specifically, crosslinked and amine-reactive polymer multilayers were produced by alternating ‘reactive’ deposition of an azlactone-functionalized polymer [poly(2-vinyl-4,4-dimethylazlactone)] and a primary amine-containing polymer [branched poly(ethylene imine)]. Advantages of our system include a 5 to 30-fold decrease in deposition time compared to traditional polyelectrolyte films and direct modification of the films with peptides. Our films react with mixtures of an adhesion-promoting peptide containing Arg-Gly-Asp (RGD) and the small molecule d-glucamine, a chemical motif which is non-fouling. Resulting surfaces prevent protein adsorption and promote cell attachment through specific peptide interactions. The specificity of cell attachment via immobilized RGD sequences was verified using both a scrambled RDG peptide control as well as soluble-RGD competitive assays. Films were functionalized with monotonically increasing surface densities of RGD which resulted in both increased cell attachment and the promotion of a tri-phasic proliferative response of a human corneal epithelial cell line (hTCEpi). The ability to treat PEI/PVDMA films with peptides for controlled cell-substrate interactions enables the use of these films in a wide range of biological applications. PMID:21972074

  13. Postoperative complications of pediatric dental general anesthesia procedure provided in Jeddah hospitals, Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Almushayt Abdullah

    2009-02-01

    Full Text Available Abstract Background Review of post-operative morbidity reports for pediatric dental care under general anesthesia (GA show great variations. Until now, no morbidity data has been available to estimate the safety of pediatric patients under GA for dental rehabilitation in Saudi Arabia. The purposes of this study were to (1 investigate post-operative complications associated with dental care under GA and (2 correlate morbidity reports with patient's characteristics, dental procedures, and hospital protocol. Methods Study sample included 90 children attending GA for dental treatment at major governmental hospitals in Jeddah. Data were collected from every patient on three occasions, intra-operatively at the operating room, and post-operatively via phone calls in the first and third days after operation. Results Results showed that 99% of the children had one or more complaints in the first day in contrast to only 33% in the third day. Inability to eat (86%, sleepiness (71%, and pain (48% were the most common complaints in the first day, followed by bleeding (40%, drowsiness (39%, sore throat (34%, vomiting (26%, psychological changes (24%, fever (21%, cough (12%, and nausea (8%. A great significant complaints reduction was reported by the third post-operative day. Age, gender, admission type of the patients and GA duration were the factors that showed a significant relationship with post-operative complaints. Conclusion Post-operative morbidity was common, but mostly of mild severity and limited to the first day. Hospital staff efforts should be directed to control commonly reported postoperative complaints.

  14. How do general practitioners experience providing care to refugees with mental health problems? A qualitative study from Denmark.

    Science.gov (United States)

    Jensen, Natasja Koitzsch; Norredam, Marie; Priebe, Stefan; Krasnik, Allan

    2013-01-28

    Refugees are a particularly vulnerable group in relation to the development of mental illness and many may have been subjected to torture or other traumatic experiences. General practitioners are gatekeepers for access to several parts of the psychiatric system and knowledge of their patients' refugee background is crucial to secure adequate care. The aim of this study is to investigate how general practitioners experience providing care to refugees with mental health problems. The study was conducted as part of an EU project on European Best Practices in Access, Quality and Appropriateness of Health Services for Immigrants in Europe (EUGATE). Semi-structured interviews were carried out with nine general practitioners in the vicinity of Copenhagen purposively selected from areas with a high proportion of immigrants. The analysis of the interviews is inspired by qualitative content analysis. One of the main themes identified in the analysis is communication. This includes the use of professional interpreters and that communication entails more than sharing a common language. Quality of care is another theme that emerges and includes awareness of possible trauma history, limited possibilities for refugees to participate in certain treatments due to language barriers and feelings of hopelessness in the general practitioners. The general practitioners may also choose different referral pathways for refugees and they report that their patients lack understanding regarding the differences between psychological problems and physical symptoms. General practitioners experience that providing care to refugees differs from providing care for patients from the majority population. The different strategies employed by the general practitioners in the health care treatment of refugees may be the result of the great diversity in the organisation of general practice in Denmark and the lack of a national strategy in the health care management of refugees. The findings from this

  15. How do general practitioners experience providing care to refugees with mental health problems? A qualitative study from Denmark

    OpenAIRE

    Jensen Natasja Koitzsch; Norredam Marie; Priebe Stefan; Krasnik Allan

    2013-01-01

    Abstract Background Refugees are a particularly vulnerable group in relation to the development of mental illness and many may have been subjected to torture or other traumatic experiences. General practitioners are gatekeepers for access to several parts of the psychiatric system and knowledge of their patients’ refugee background is crucial to secure adequate care. The aim of this study is to investigate how general practitioners experience providing care to refugees with mental health prob...

  16. Providing health information to the general public: a survey of current practices in academic health sciences libraries*

    Science.gov (United States)

    Hollander, Sue M.

    2000-01-01

    A questionnaire was mailed to 148 publicly and privately supported academic health sciences libraries affiliated with Association of American Medical Colleges (AAMC)–accredited medical schools in the United States and Canada to determine level of access and services provided to the general public. For purposes of this study, “general public” was defined as nonaffiliated students or health care professionals, attorneys and other nonhealth-related professionals, patients from affiliated or other hospitals or clinics, and general consumers. One hundred five (71%) libraries responded. Results showed 98% of publicly supported libraries and 88% of privately supported libraries provided access to some or all of the general public. Publicly supported libraries saw greater numbers of public patrons, often provided more services, and were more likely to circulate materials from their collections than were privately supported libraries. A significant number of academic health sciences libraries housed a collection of consumer-oriented materials and many provided some level of document delivery service, usually for a fee. Most allowed the public to use some or all library computers. Results of this study indicated that academic health sciences libraries played a significant role in serving the information-seeking public and suggested a need to develop written policies or guidelines covering the services that will be provided to minimize the impact of this service on primary clientele. PMID:10658965

  17. Caenorhabditis elegans SNAP-29 is required for organellar integrity of the endomembrane system and general exocytosis in intestinal epithelial cells

    Science.gov (United States)

    Sato, Miyuki; Saegusa, Keiko; Sato, Katsuya; Hara, Taichi; Harada, Akihiro; Sato, Ken

    2011-01-01

    It is generally accepted that soluble N-ethylmaleimide–sensitive factor attachment protein receptors mediate the docking and fusion of transport intermediates with target membranes. Our research identifies Caenorhabditis elegans homologue of synaptosomal-associated protein 29 (SNAP-29) as an essential regulator of membrane trafficking in polarized intestinal cells of living animals. We show that a depletion of SNAP-29 blocks yolk secretion and targeting of apical and basolateral plasma membrane proteins in the intestinal cells and results in a strong accumulation of small cargo-containing vesicles. The loss of SNAP-29 also blocks the transport of yolk receptor RME-2 to the plasma membrane in nonpolarized oocytes, indicating that its function is required in various cell types. SNAP-29 is essential for embryogenesis, animal growth, and viability. Functional fluorescent protein–tagged SNAP-29 mainly localizes to the plasma membrane and the late Golgi, although it also partially colocalizes with endosomal proteins. The loss of SNAP-29 leads to the vesiculation/fragmentation of the Golgi and endosomes, suggesting that SNAP-29 is involved in multiple transport pathways between the exocytic and endocytic organelles. These observations also suggest that organelles comprising the endomembrane system are highly dynamic structures based on the balance between membrane budding and fusion and that SNAP-29–mediated fusion is required to maintain proper organellar morphology and functions. PMID:21613542

  18. How Providing Mentoring Relates to Career Success and Organizational Commitment: A Study in the General Managerial Population

    Science.gov (United States)

    Bozionelos, Nikos; Bozionelos, Giorgos; Kostopoulos, Konstantinos; Polychroniou, Panagiotis

    2011-01-01

    Purpose: This study aims to investigate the relationship of mentoring provided with career success and organizational commitment in the general managerial population. Design/methodology/approach: Participants were 194 native British who were employed in a variety of jobs, professions and industries in the United Kingdom. Findings: Mentoring…

  19. How do general practitioners experience providing care to refugees with mental health problems? A qualitative study from Denmark

    Directory of Open Access Journals (Sweden)

    Jensen Natasja Koitzsch

    2013-01-01

    Full Text Available Abstract Background Refugees are a particularly vulnerable group in relation to the development of mental illness and many may have been subjected to torture or other traumatic experiences. General practitioners are gatekeepers for access to several parts of the psychiatric system and knowledge of their patients’ refugee background is crucial to secure adequate care. The aim of this study is to investigate how general practitioners experience providing care to refugees with mental health problems. Methods The study was conducted as part of an EU project on European Best Practices in Access, Quality and Appropriateness of Health Services for Immigrants in Europe (EUGATE. Semi-structured interviews were carried out with nine general practitioners in the vicinity of Copenhagen purposively selected from areas with a high proportion of immigrants. The analysis of the interviews is inspired by qualitative content analysis. Results One of the main themes identified in the analysis is communication. This includes the use of professional interpreters and that communication entails more than sharing a common language. Quality of care is another theme that emerges and includes awareness of possible trauma history, limited possibilities for refugees to participate in certain treatments due to language barriers and feelings of hopelessness in the general practitioners. The general practitioners may also choose different referral pathways for refugees and they report that their patients lack understanding regarding the differences between psychological problems and physical symptoms. Conclusion General practitioners experience that providing care to refugees differs from providing care for patients from the majority population. The different strategies employed by the general practitioners in the health care treatment of refugees may be the result of the great diversity in the organisation of general practice in Denmark and the lack of a national strategy

  20. [EBM Service: evidence-based answers provided by general practitioners to questions asked by general practitioners--a project from South Tyrol/Italy].

    Science.gov (United States)

    Piccoliori, Giuliano; Kostner, Simon; Abholz, Heinz-Harald

    2010-01-01

    General practices also require more and more evidence-based decision-making. But knowledge is increasing rapidly and guidelines produced to help doctors to find answers to their problems seem to exclude a number of problems that are important in general practices. Here we report on the introduction and activities of an EbM Service provided by general practitioners to answer questions of their colleagues. The aim is to give EBM answers, but also, in doing so, to teach the application of EBM and--in the long run--to enable the users themselves to find EBM answers. The provision of EBM answers is fairly pragmatic: after using the service the inquiring physician should be better informed, i.e., have more evidence-based information, but sometimes this need not be the "ultimate truth" that experts might deliver. EBM answers are published both on the homepage of the College of General Practitioners and in their journal. It took quite a while to implement this service, and the number of those using it has increased slowly but constantly.

  1. Women's knowledge of taking oral contraceptive pills correctly and of emergency contraception: effect of providing information leaflets in general practice.

    OpenAIRE

    Smith, L F; Whitfield, M J

    1995-01-01

    BACKGROUND. About one third of all pregnancies are unplanned and 20% of all pregnancies end in abortion. More than 170,000 legal abortions are performed in the United Kingdom annually. Nearly all general practitioners provide contraceptive advice; the most commonly used form of reversible contraception is the oral contraceptive pill. AIM. The aim of this study was to determine factors associated with women's knowledge of taking the contraceptive pill correctly and of emergency contraception, ...

  2. Factors affecting the intention of providers to deliver more effective continuing medical education to general practitioners: a pilot study

    Directory of Open Access Journals (Sweden)

    Higginbotham Nick

    2003-12-01

    Full Text Available Abstract Background Despite the importance of continuing medical education (CME for GPs, there has been little research into how providers decide what types of CME to deliver to GPs. This study aimed to identify factors affecting the intention of providers to provide more effective types of CME; and to design a survey instrument which can be used to test the applicability of Triandis' model of social behaviour to the provision of CME to general practitioners. Methods This was a cross-sectional study on a convenience sample of 11 Australian providers of CME for interviews and a random sample of 25 providers for the pilot test. Open-ended interviews structured on Triandis' theory were performed with key informants who provide CME to GPs. These were used to develop a pilot survey instrument to measure the factors affecting intention, resulting in a revised instrument for use in further research. Results There was a broad range of factors affecting providers' intention to deliver more effective forms of CME identified, and these were classifiable in a manner which was consistent with Triandis' model. Key factors affecting providers' intention were the attitude toward CME within organisations and the time and extra work involved. Conclusions We identified a range of potential factors influencing the intention of providers to provide more effective forms of CME, in all categories of Triandis model. Those interested in increasing the choice of more effective CME activities available to GPs may need to broaden the methods used in working with providers to influence them to use more effective CME techniques. The interview material and questionnaire analysis of the pilot survey support the use of Triandis model. Further research is needed to validate Triandis'model for the intention to deliver more effective forms of CME. Such research will inform future strategies aimed at increasing the amount and choice of effective CME activities available for GPs.

  3. Women's knowledge of taking oral contraceptive pills correctly and of emergency contraception: effect of providing information leaflets in general practice.

    Science.gov (United States)

    Smith, L F; Whitfield, M J

    1995-01-01

    BACKGROUND. About one third of all pregnancies are unplanned and 20% of all pregnancies end in abortion. More than 170,000 legal abortions are performed in the United Kingdom annually. Nearly all general practitioners provide contraceptive advice; the most commonly used form of reversible contraception is the oral contraceptive pill. AIM. The aim of this study was to determine factors associated with women's knowledge of taking the contraceptive pill correctly and of emergency contraception, and to investigate if their knowledge could be improved in general practice by providing women with Family Planning Association information leaflets. METHOD. An uncontrolled intervention study was performed in one rural and one urban English general practice, using a self-completion questionnaire that was initially administered to women attending their general practitioner for oral contraception over six months from 1 October 1992. The questionnaire asked for: sociodemographic information; knowledge of how late women can be taking an oral contraceptive pill and still be protected against unplanned pregnancy; for how many days after being late with a pill they need to use other precautions; sources and methods of emergency contraception; and for how long the methods are effective after the primary contraceptive failure. After completing the questionnaire women were given two leaflets: one about how to take their prescribed contraceptive pill correctly and one about emergency contraception. Three to 12 months later the same questionnaire was administered in the same manner. RESULTS. Of 449 women completing the first questionnaire, 233 (52%) completed the second questionnaire. Initially 71% of 406 women taking an oestrogen/progestogen combined pill knew about the '12-hour rule' and 17% knew about the 'seven-day rule'; giving women information about the pill they were taking increased the extent of knowledge about these rules among 212 respondents to 82% (P emergency contraception

  4. Crystallographic studies with xenon and nitrous oxide provide evidence for protein-dependent processes in the mechanisms of general anesthesia.

    Science.gov (United States)

    Abraini, Jacques H; Marassio, Guillaume; David, Helene N; Vallone, Beatrice; Prangé, Thierry; Colloc'h, Nathalie

    2014-11-01

    The mechanisms by which general anesthetics, including xenon and nitrous oxide, act are only beginning to be discovered. However, structural approaches revealed weak but specific protein-gas interactions. To improve knowledge, we performed x-ray crystallography studies under xenon and nitrous oxide pressure in a series of 10 binding sites within four proteins. Whatever the pressure, we show (1) hydrophobicity of the gas binding sites has a screening effect on xenon and nitrous oxide binding, with a threshold value of 83% beyond which and below which xenon and nitrous oxide, respectively, binds to their sites preferentially compared to each other; (2) xenon and nitrous oxide occupancies are significantly correlated respectively to the product and the ratio of hydrophobicity by volume, indicating that hydrophobicity and volume are binding parameters that complement and oppose each other's effects; and (3) the ratio of occupancy of xenon to nitrous oxide is significantly correlated to hydrophobicity of their binding sites. These data demonstrate that xenon and nitrous oxide obey different binding mechanisms, a finding that argues against all unitary hypotheses of narcosis and anesthesia, and indicate that the Meyer-Overton rule of a high correlation between anesthetic potency and solubility in lipids of general anesthetics is often overinterpreted. This study provides evidence that the mechanisms of gas binding to proteins and therefore of general anesthesia should be considered as the result of a fully reversible interaction between a drug ligand and a receptor as this occurs in classical pharmacology.

  5. Epithelial ovarian cancer: focus on genetics and animal models.

    Science.gov (United States)

    Shan, Weiwei; Liu, Jinsong

    2009-03-01

    Despite rapid advances in understanding ovarian cancer etiology, epithelial ovarian cancer remains the most lethal form of gynecologic cancers in the United States. The four morphologically-defined epithelial ovarian cancer subtypes-serous, endometrioid, mucinous, and clear cell carcinomas--are generally believed to originate from ovarian epithelial cells. Although it remains unclear how this single cell layer gives rise to morphologically distinct cancers, it has been suggested that early genetic events may direct the differentiation of ovarian epithelial cells. A number of genetic alterations are frequently encountered during ovarian tumorigenesis, including oncogenic activities of KRAS, BRAF and AKT, and silencing mutations of TP53, RB and PTEN. However, knowledge about how these genetic elements are coordinated during ovarian cancer initiation and progression is very limited. The establishment of cell-culture systems and rodent-based models has made big strides towards a better understanding of the genetic bases of human epithelial ovarian tumorigenesis. More importantly, the rise of genetically-engineered rodent and human models, particularly in the past five years, has provided key insight in the role of specific genes during ovarian tumorigenesis. In this review, we offer a comprehensive coverage of currently-available in vitro and in vivo models of human epithelial ovarian cancer, focusing on latest updates of genetically-modified rodent and human models and the valuable information conveyed by them.

  6. Dexmedetomidine infusion during middle ear surgery under general anaesthesia to provide oligaemic surgical field: A prospective study

    Directory of Open Access Journals (Sweden)

    Kumkum Gupta

    2015-01-01

    Full Text Available Background and Aims: Middle ear surgery requires bloodless surgical field for better operating conditions, deep level of anaesthesia and rapid emergence. Recent studies suggest that α2 agonists could provide desired surgical field, sedation and analgesia. The present study was aimed to evaluate the clinical effects of dexmedetomidine infusion as anaesthetic adjuvant during middle ear surgery using operating microscope. Methods: Sixty four adult patients aged 18-58 years, American Society of Anaesthesiologists Grades I and II, of both gender were randomised into two comparable equal groups of 32 patients each for middle ear surgery under general anaesthesia with standard anaesthetic technique. After induction of general anaesthesia, patients of Group I were given dexmedetomidine infusion of 0.5 μg/kg/h and patients of Group II were given placebo infusion of normal saline. Isoflurane concentration was titrated to achieve a systolic blood pressure 30% below the baseline value. All patients were assessed intra-operatively for bleeding at surgical field, haemodynamic changes, awakening time and post-operative recovery. Results: Statistically significant reduction was observed in the required percentage of isoflurane (0.8 ± 0.6% to maintain the systolic blood pressure 30% below the baseline values in patients receiving dexmedetomidine infusion when compared to those receiving placebo infusion (1.6 ± 0.7%. Patients receiving dexmedetomidine infusion had statistically significant lesser bleeding at surgical field (P < 0.05. The mean awakening time and recovery from anaesthesia did not show any significant difference between the groups. Conclusion: Dexmedetomidine infusion can be safely used to provide oligaemic surgical field for better visualization using operating microscope for middle ear surgery.

  7. General practice out-of-hours service in Ireland provides a new source of syndromic surveillance data on influenza.

    LENUS (Irish Health Repository)

    Brabazon, E D

    2010-01-01

    The use of routinely available electronic sources of healthcare data on the spread of influenza has the potential to enhance current surveillance activities. This study aimed to develop a method for identifying influenza-related records from general practitioner(GP) out-of-hours (OOH) services in Ireland. Data from one such service were interrogated for keywords relating to influenza-like illness (ILI) and a proxy measure of influenza activity in the community setting was developed. Comparison of this syndromic surveillance measure with national data on ILI consultation rates demonstrated a statistically significant temporal correlation.In five out of six influenza seasons investigated,peaks in the GP OOH influenza-related calls appeared at least one week ahead of peaks in the national ILI consultation rates. The method described in this paper has been extended to nine OOH services in Ireland (covering 70% of the Irish population) to provide weekly figures on self-reported illness for influenza in the community and its data have been incorporated into the national weekly influenza reports produced by the Health Protection Surveillance Centre. These data should provide early warnings of both seasonal and pandemic influenza in Ireland.

  8. Combining QOF data with the care bundle approach may provide a more meaningful measure of quality in general practice

    Directory of Open Access Journals (Sweden)

    de Wet Carl

    2012-10-01

    Full Text Available Abstract Background A significant minority of patients do not receive all the evidence-based care recommended for their conditions. Health care quality may be improved by reducing this observed variation. Composite measures offer a different patient-centred perspective on quality and are utilized in acute hospitals via the ‘care bundle’ concept as indicators of the reliability of specific (evidence-based care delivery tasks and improved outcomes. A care bundle consists of a number of time-specific interventions that should be delivered to every patient every time. We aimed to apply the care bundle concept to selected QOF data to measure the quality of evidence-based care provision. Methods Care bundles and components were selected from QOF indicators according to defined criteria. Five clinical conditions were suitable for care bundles: Secondary Prevention of Coronary Heart Disease (CHD, Stroke & Transient Ischaemic Attack (TIA, Chronic Kidney Disease (CKD, Chronic Obstructive Pulmonary Disease (COPD and Diabetes Mellitus (DM. Each bundle has 3-8 components. A retrospective audit was undertaken in a convenience sample of nine general medical practices in the West of Scotland. Collected data included delivery (or not of individual bundle components to all patients included on specific disease registers. Practice level and overall compliance with bundles and components were calculated in SPSS and expressed as a percentage. Results Nine practices (64.3% with a combined patient population of 56,948 were able to provide data in the format requested. Overall compliance with developed QOF-based care bundles (composite measures was as follows: CHD 64.0%, range 35.0-71.9%; Stroke/TIA 74.1%, range 51.6-82.8%; CKD 69.0%, range 64.0-81.4%; and COPD 82.0%, range 47.9-95.8%; and DM 58.4%, range 50.3-65.2%. Conclusions In this small study compliance with individual QOF-based care bundle components was high, but overall (‘all or nothing’ compliance was

  9. Treatment of mental health problems in general practice: a survey of psychotropics prescribed and other treatments provided.

    NARCIS (Netherlands)

    Rijswijk, E. van; Borghuis, M.; Lisdonk, E.H. van de; Zitman, F.G.; Weel, C. van

    2007-01-01

    OBJECTIVE: Real-life data on the treatment of patients with mental health problems are important as a reference to evaluate care and benchmarking. This study describes the treatment of mental health problems in general practice as diagnosed by general practitioners (GP). MATERIAL AND METHODS: Data

  10. Transversus abdominis plane block in combination with general anesthesia provides better intraoperative hemodynamic control and quicker recovery than general anesthesia alone in high-risk abdominal surgery patients.

    Science.gov (United States)

    Tsuchiya, M; Takahashi, R; Furukawa, A; Suehiro, K; Mizutani, K; Nishikawa, K

    2012-11-01

    Patients with severe cardiovascular disease are frequently hemodynamically unstable during abdominal surgery. Improving the safety of such patients by stabilizing intraoperative hemodynamics remains a major concern for anesthesiologists. Transversus abdominis plane (TAP) block in combination with general anesthesia may facilitate optimum anesthetic management of these high-risk patients. Patients with cardiovascular disease classified as American Society of Anesthesiologists (ASA) physical status 3 were enrolled. The patients were undergoing elective abdominal surgery and were randomized to a group receiving general anesthesia and TAP block (Group T, N.=33) or a group receiving general anesthesia alone (Group G, N.=35). We compared the groups for intraoperative hemodynamic stability, anesthesia emergence time, amounts of anesthetics and opioids given, and frequency of emergency treatment with cardiovascular agents. A preliminary study demonstrated that systolic blood pressure and heart rate were maintained stable within 70-110% of their preanesthesia values throughout surgery in ASA 1 elderly patients without cardiovascular disease. Thus, the hemodynamically stable time was defined as the time when systolic blood pressure and heart rate were 70-110% of their preanesthesia values. The ratio of hemodynamically stable time to total operative time was used as an index of hemodynamic stability. The median (minimum-maximum) percentage of hemodynamically stable time was longer in Group T (91[50-100]%) than Group G (79[40-91]%, Pabdominal surgery in patients with severe cardiovascular disease, combining TAP block with general anesthesia promotes intraoperative hemodynamic stability and early emergence from anesthesia.

  11. General

    Indian Academy of Sciences (India)

    Page S20: NMR compound 4i. Page S22: NMR compound 4j. General: Chemicals were purchased from Fluka, Merck and Aldrich Chemical Companies. All the products were characterized by comparison of their IR, 1H NMR and 13C NMR spectroscopic data and their melting points with reported values. General procedure ...

  12. Trends and Correlates of Consenting to Provide Social Security Numbers: Longitudinal Findings from the General Social Survey (1993-2010)

    Science.gov (United States)

    Kim, Jibum; Shin, Hee-Choon; Rosen, Zohn; Kang, Jeong-han; Dykema, Jennifer; Muennig, Peter

    2015-01-01

    Privacy and confidentiality are often of great concern to respondents answering sensitive questions posed by interviewers. Using the 1993-2010 General Social Survey, we examined trends in the provision of social security numbers (SSNs) and correlates of those responses. Results indicate that the rate of SSN provision has declined over the past…

  13. General practitioner management of genetic aspects of a cardiac disease: a scenario-based study to anticipate providers' practices.

    NARCIS (Netherlands)

    Challen, K.; Harris, H.; Kristoffersson, U.; Nippert, I.; Schmidtke, J.; Kate, L.P. ten; Benjamin, C.; Anionwu, E.; Plass, A.M.; Julian-Reynier, C.; Harris, R.

    2010-01-01

    It is increasingly recognised that genetics will have to be integrated into all parts of primary health care. Previous research has demonstrated that involvement and confidence in genetics varies amongst primary care providers. We aimed to analyse perceptions of primary care providers regarding

  14. General practitioner management of genetic aspects of a cardiac disease: a scenario-based study to anticipate providers' practices

    NARCIS (Netherlands)

    Challen, K.; Harris, H.; Kristoffersson, U.; Nippert, I.; Schmidtke, J.; ten Kate, L.P.; Benjamin, C.; Anionwu, E.; Plass, A.M.C.; Julian-Reynier, C.; Harris, R

    2010-01-01

    It is increasingly recognised that genetics will have to be integrated into all parts of primary health care. Previous research has demonstrated that involvement and confidence in genetics varies amongst primary care providers. We aimed to analyse perceptions of primary care providers regarding

  15. An Analysis of Social Skills Instruction Provided in Teacher Education and In-Service Training Programs for General and Special Educators

    Science.gov (United States)

    Dobbins, Nicole; Higgins, Kyle; Pierce, Tom; Tandy, Richard D.; Tincani, Matt

    2010-01-01

    An adapted version of the "Teacher/Staff Skillstreaming Checklist" was used to determine the level, type, and area of social skills instruction provided to general and special education teachers. Nine universities participated in the study in which facilitators advertised the adapted questionnaire to licensed general and special education teachers…

  16. DoD Did Not Negotiate Rates With Overseas Health Care Providers and Generally Paid Claims as Billed

    Science.gov (United States)

    2014-04-01

    rate than necessary for health care provided in Guam in the following instances. • A provider billed $945 for a sleep study in March 2011—TMA paid...the amount in full. However, the highest Medicare allowable rate for a sleep study in Guam was $603, about 36 percent less than the full amount that... Malaysia 51,034 51,938 70,959 74,572 46.1 Appendixes 24 │ DODIG-2014-052 Location1 FY 2009 FY 2010 FY 2011 FY 2012 Percent Change (FY09-12)2 Bermuda

  17. Use of Flumazenil to Provide Adequate Recovery Time Post-Midazolom Infusion in a General Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    MOJTABA MOJTAHEDZADEH

    1999-08-01

    Full Text Available Sedation permits patients to tolerate the various treatment modalities to which they are subjected. However it may sometimes cause prolonged sedation in critically ill patients. Flumazenil, a benzo¬diazepine antagonist, reverses midazolam-induced sedation and amnesia. We prospectively designed a double-blind randomized study to evaluate the effects of flumazenil on thirty (30 Iranian General Intensive Care Unit (ICU patients. They were requiring mechanical ventilation for more than 12 hours and they were sedated by midazolam infusions. Sedation levels were measured hourly during the infusion, at the end of the infusion, and at 5, 15, 30, 60, and 120 min after cessation of the mida¬zolam infusion. Reversal of sedation was observed in all patients who received flumazenil, and re-sedation occurred in seven of these patients. Reversal was not seen in any of the patients who receiv-ed placebo.

  18. New graduates’ perceptions of preparedness to provide speech-language therapy services in general and dysphagia services in particular

    Directory of Open Access Journals (Sweden)

    Shajila Singh

    2015-02-01

    Full Text Available Background: Upon graduation, newly qualified speech-language therapists are expected to provide services independently. This study describes new graduates’ perceptions of their preparedness to provide services across the scope of the profession and explores associations between perceptions of dysphagia theory and clinical learning curricula with preparedness for adult and paediatric dysphagia service delivery.Methods: New graduates of six South African universities were recruited to participate in a survey by completing an electronic questionnaire exploring their perceptions of the dysphagia curricula and their preparedness to practise across the scope of the profession of speechlanguage therapy. Results: Eighty graduates participated in the study yielding a response rate of 63.49%. Participants perceived themselves to be well prepared in some areas (e.g. child language: 100%; articulation and phonology: 97.26%, but less prepared in other areas (e.g. adult dysphagia: 50.70%; paediatric dysarthria: 46.58%; paediatric dysphagia: 38.36% and most unprepared to provide services requiring sign language (23.61% and African languages (20.55%. There was a significant relationship between perceptions of adequate theory and clinical learning opportunities with assessment and management of dysphagia and perceptions of preparedness to provide dysphagia services. Conclusion: There is a need for review of existing curricula and consideration of developing a standard speech-language therapy curriculum across universities, particularly in service provision to a multilingual population, and in both the theory and clinical learning of the assessment and management of adult and paediatric dysphagia, to better equip graduates for practice.

  19. Resident duty hour modification affects perceptions in medical education, general wellness, and ability to provide patient care.

    Science.gov (United States)

    Moeller, Andrew; Webber, Jordan; Epstein, Ian

    2016-07-13

    Resident duty hours have recently been under criticism, with concerns for resident and patient well-being. Historically, call shifts have been long, and some residency training programs have now restricted shift lengths. Data and opinions about the effects of such restrictions are conflicting. The Internal Medicine Residency Program at Dalhousie University recently moved from a traditional call structure to a day float/night float system. This study evaluated how this change in duty hours affected resident perceptions in several key domains. Senior residents from an internal medicine training program in Canada responded to an anonymous online survey immediately before and 6 months after the implementation of duty hour reform. The survey contained questions relating to three major domains: resident wellness, ability to deliver quality health care, and medical education experience. Mean pre- and post-intervention scores were compared using the t-test for paired samples. Twenty-three of 27 (85 %) senior residents completed both pre- and post-reform surveys. Residents perceived significant changes in many domains with duty hour reform. These included improved general wellness, less exposure to personal harm, fewer feelings of isolation, less potential for error, improvement in clinical skills expertise, increased work efficiency, more successful teaching, increased proficiency in medical skills, more successful learning, and fewer rotation disruptions. Senior residents in a Canadian internal medicine training program perceived significant benefits in medical education experience, ability to deliver healthcare, and resident wellness after implementation of duty hour reform.

  20. New graduates’ perceptions of preparedness to provide speech-language therapy services in general and dysphagia services in particular

    Directory of Open Access Journals (Sweden)

    Shajila Singh

    2015-06-01

    Methods: New graduates of six South African universities were recruited to participate in a survey by completing an electronic questionnaire exploring their perceptions of the dysphagia curricula and their preparedness to practise across the scope of the profession of speechlanguage therapy. Results: Eighty graduates participated in the study yielding a response rate of 63.49%. Participants perceived themselves to be well prepared in some areas (e.g. child language: 100%; articulation and phonology: 97.26%, but less prepared in other areas (e.g. adult dysphagia: 50.70%; paediatric dysarthria: 46.58%; paediatric dysphagia: 38.36% and most unprepared to provide services requiring sign language (23.61% and African languages (20.55%. There was a significant relationship between perceptions of adequate theory and clinical learning opportunities with assessment and management of dysphagia and perceptions of preparedness to provide dysphagia services. Conclusion: There is a need for review of existing curricula and consideration of developing a standard speech-language therapy curriculum across universities, particularly in service provision to a multilingual population, and in both the theory and clinical learning of the assessment and management of adult and paediatric dysphagia, to better equip graduates for practice.

  1. Evaluation of efficacy of restorative dental treatment provided under general anesthesia at hospitalized pediatric dental patients of Isfahan

    Science.gov (United States)

    Eshghi, Alireza; Samani, Mahdi Jafarzadeh; Najafi, Naghme Feyzi; Hajiahmadi, Maryam

    2012-01-01

    Background: General anesthesia (GA) allows dental treatment to be rendered under optimal conditions, theoretically ensuring ideal outcomes. The aim of this study was to determine the efficacy of restorative dental procedures performed under GA. Materials and Methods: In this cross-sectional retrospective study, 305 pediatric patients who had been treated under GA 6 to 24 months before our survey at Isfahan's hospitalized dentistry center were examined. The examination was performed on dental chair with oral mirror and dental probe. The results were recorded in a special form for each patient for statistical analysis and evaluation of restorations to be successful or failed. Statistical analysis was performed by chi-square and fisher exact tests for comparison between success rates of restorations and Kendall's tau-b test for evaluating the effect of time on success rates of them (P crown restorations had significantly better results vs class I and class II amalgam and class I and class II tooth color restorations. All types of posterior tooth color restorations had statistically same results with amalgam restorations. Anterior composite resin build-up represented significantly low success rates. The failure rates of stainless steel crown and anterior composite resin build-up restorations did not correlate with the time of follow-up (P = 0.344 and P = 0.091, respectively). Conclusion: Stainless steel crown restorations had significantly better results vs other posterior restorations. The failure rates of stainless steel crown and anterior composite resin build-up restorations did not correlate with the time of follow-up in comparison of other restorations. PMID:23162592

  2. Intracellular Mycoplasma genitalium infection of human vaginal and cervical epithelial cells elicits distinct patterns of inflammatory cytokine secretion and provides a possible survival niche against macrophage-mediated killing

    Directory of Open Access Journals (Sweden)

    Pyles Richard B

    2009-07-01

    Full Text Available Abstract Background Mycoplasma genitalium is an emerging sexually transmitted pathogen that has been associated with significant reproductive tract inflammatory syndromes in women. In addition, the strong association between severity of M. genitalium infection and Human Immunodeficiency Virus type 1 (HIV-1 shedding from the cervix suggests that innate responses to M. genitalium may influence pathogenesis of other sexually transmitted infections. Epithelial cells (ECs of the reproductive mucosa are the first cells contacted by sexually transmitted pathogens. Therefore, we first characterized the dynamics of intracellular and extracellular localization and resultant innate immune responses from human vaginal, ecto- and endocervical ECs to M. genitalium type strain G37 and a low-pass contemporary isolate, M2300. Results Both M. genitalium strains rapidly attached to vaginal and cervical ECs by 2 h post-infection (PI. By 3 h PI, M. genitalium organisms also were found in intracellular membrane-bound vacuoles of which approximately 60% were adjacent to the nucleus. Egress of M. genitalium from infected ECs into the culture supernatant was observed but, after invasion, viable intracellular titers were significantly higher than extracellular titers at 24 and 48 h PI. All of the tested cell types responded by secreting significant levels of pro-inflammatory cytokines and chemokines in a pattern consistent with recruitment and stimulation of monocytes and macrophages. Based on the elaborated cytokines, we next investigated the cellular interaction of M. genitalium with human monocyte-derived macrophages and characterized the resultant cytokine responses. Macrophages rapidly phagocytosed M. genitalium resulting in a loss of bacterial viability and a potent pro-inflammatory response that included significant secretion of IL-6 and other cytokines associated with enhanced HIV-1 replication. The macrophage-stimulating capacity of M. genitalium was independent

  3. Flagellar activation of epithelial signaling.

    Science.gov (United States)

    Prince, Alice

    2006-05-01

    Mucosal epithelial cells are an important component of the innate immune system forming a physical and immunologic barrier to inhaled bacteria. As polarized cells with tight junctions, the immunologic signaling functions of airway epithelial cells differ from those of professional immune cells. While many bacterial gene products activate airway mucosal cells, flagella are especially immunostimulatory. The motility function provided by flagella is essential for the initial stages of respiratory infection associated with opportunists such as Pseudomonas aeruginosa. Apically presented toll-like receptor 5 responds specifically to bacterial flagellin transducing a number of epithelial proinflammatory signaling cascades, including the induction of Ca2+ fluxes; activation of NF-kappaB, IL-8, and matrilysin; and mucin expression. The complexities of flagella and flagellin structures, how these bacterial components initiate host signaling and their potential as a vaccine target are reviewed.

  4. The management of cervical intra-epithelial neoplasia (CIN): Extensiveness and costs in The Netherlands

    NARCIS (Netherlands)

    M. van Ballegooijen (Marjolein); M.A. Koopmanschap (Marc); J.D.F. Habbema (Dik)

    1995-01-01

    textabstractIn order to provide greater insight into both the extensiveness and the medical costs of the diagnosis and treatment of screen-detected cervical intra-epithelial neoplasia (CIN) in general medical practice in The Netherlands, data from national registries and gynaecology departments were

  5. Providing psychiatric services in general medical settings in South Africa: Mental health-friendly services in mental health-friendly hoaspitals

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    Margaretha S van Heerden

    2008-03-01

    Full Text Available Neuropsychiatric disorders rank high on the list of the mostdisabling medical disorders in both the developed anddeveloping worlds.1Significant comorbidity also exists betweenneuropsychiatric disorders and general medical disorders;2this iskey in the South African context where HIV/AIDS and substanceuse disorders are highly prevalent.3,4It has therefore becomeessential to provide mental health services in a range of settings,including those that focus on the delivery of general medicalservices. Furthermore, the Mental Health Care Act 17 of 2002underlines the importance of providing integrated, accessiblemental health care in the local community.

  6. [Expectations and attitudes concerning geriatric counseling : Results of a survey among general practitioners and hospital-based providers in two German states].

    Science.gov (United States)

    Burkhardt, H; Trojan, C

    2017-01-31

    Expertise in geriatrics in the field of ambulatory and hospital-based treatment does not have access to comparable medical specialist structures, such as those in internal medicine and neurology; therefore, it is recommended that geriatric diagnostics by general practitioners can be supported by networking with hospital-based geriatric centers for geriatric counseling. The attitudes and experiences of both faculties in Germany are, however, not well known. Representative samples of general practitioners and hospital-based faculty departments for internal medicine in two regions of Germany (Baden-Württemberg and Hessen) were identified using a systematic selection method. All departments of geriatrics in these regions were also contacted. Participants were asked to give their attitudes and experiences regarding geriatric counseling using a questionnaire. Responses to the questionnaire were received from 48 general practices (14.9%), 42 internal medicine departments (38.5%) and 25 hospital-based geriatric centers (34.7%). Of the general practices 79.2% reported performing geriatric assessments but only 31.3% had access to geriatric counseling. Of the faculties of internal medicine 71.4% reported providing geriatric counseling of which 16.7% also provided counseling on an outpatient basis. With respect to the spectrum of actual reasons for geriatric counseling, initiation of rehabilitative measures was the main reason in both geriatric and internal medicine departments. There were differences in the estimation of suitable rating topics for geriatric counseling. Geriatric departments more frequently indicated preventive aspects compared to general internal medicine (80% vs 47.6%) and general practices (56.3%). With respect to the domain level, general practitioners rated these in the order of cognition (72.9%), social situation (70.8%), emotion (50%), locomotion (50%) and incontinence (27.1%). Noteworthy was that they also rated much lower compared to hospital

  7. Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Celeste M.; Khauv, Davitte; Bissell, Mina J.; Radisky, Derek C.

    2008-06-26

    Cell morphology dictates response to a wide variety of stimuli, controlling cell metabolism, differentiation, proliferation, and death. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire migratory characteristics, and in the process convert from a 'cuboidal' epithelial structure into an elongated mesenchymal shape. We had shown previously that matrix metalloproteinase-3 (MMP3) can stimulate EMT of cultured mouse mammary epithelial cells through a process that involves increased expression of Rac1b, a protein that stimulates alterations in cytoskeletal structure. We show here that cells treated with MMP-3 or induced to express Rac1b spread to cover a larger surface, and that this induction of cell spreading is a requirement of MMP-3/Rac1b-induced EMT. We find that limiting cell spreading, either by increasing cell density or by culturing cells on precisely defined micropatterned substrata, blocks expression of characteristic markers of EMT in cells treated with MMP-3. These effects are not caused by general disruptions in cell signaling pathways, as TGF-{beta}-induced EMT is not affected by similar limitations on cell spreading. Our data reveal a previously unanticipated cell shape-dependent mechanism that controls this key phenotypic alteration and provide insight into the distinct mechanisms activated by different EMT-inducing agents.

  8. A Batch Arrival Single Server Queue with Server Providing General Service in Two Fluctuating Modes and Reneging during Vacation and Breakdowns

    Directory of Open Access Journals (Sweden)

    Monita Baruah

    2014-01-01

    Full Text Available We study the behavior of a batch arrival queuing system equipped with a single server providing general arbitrary service to customers with different service rates in two fluctuating modes of service. In addition, the server is subject to random breakdown. As soon as the server faces breakdown, the customer whose service is interrupted comes back to the head of the queue. As soon as repair process of the server is complete, the server immediately starts providing service in mode 1. Also customers waiting for service may renege (leave the queue when there is breakdown or when server takes vacation. The system provides service with complete or reduced efficiency due to the fluctuating rates of service. We derive the steady state queue size distribution. Some special cases are discussed and numerical illustration is provided to see the effect and validity of the results.

  9. Declarativity and efficiency in providing services of general economic interest. Empirical study regarding the relation between heating costs and budget constraints

    Directory of Open Access Journals (Sweden)

    Dumitru Miron

    2013-06-01

    Full Text Available Defined by each country separately, according to real options, circumstances and traditions, the services of general economic interest have an objective purpose in ensuring protection and security for population. The services of general economic interest involve both public and economic services and show characteristics of both fields, reflecting the capabilities of communities to organize, regulate and provide them. Considering the accessibility to the essential service of general economic interest of providing household heating, as an undeniable condition of consumer protection, an analysis has been made in this field, with reference to the concrete manner of providing these services. The goal of this endeavor was to emphasize the actual conditionalities induced by the budget constraints of households while ensuring the universality of the access to the essential heating service. The empirical study is based on a survey of 55 households in sector 2 of Bucharest that have access to gas heating systems, while they have different revenues and equipments. The processing of the gathered data allowed the procurement of certain indicators that explain how household revenues determine the access to the heating services and how the deficiencies of the insurance system of these services deepen the social polarization and increase the weightings of those living at the limit of subsistence.

  10. General Information about Ovarian Epithelial Cancer

    Science.gov (United States)

    ... cancer. Some ovarian, fallopian tube, and primary peritoneal cancers are caused by inherited gene mutations (changes). The genes in cells carry the hereditary information that is received from a person’s parents. ...

  11. Mechanocellular models of epithelial morphogenesis.

    Science.gov (United States)

    Fletcher, Alexander G; Cooper, Fergus; Baker, Ruth E

    2017-05-19

    Embryonic epithelia achieve complex morphogenetic movements, including in-plane reshaping, bending and folding, through the coordinated action and rearrangement of individual cells. Technical advances in molecular and live-imaging studies of epithelial dynamics provide a very real opportunity to understand how cell-level processes facilitate these large-scale tissue rearrangements. However, the large datasets that we are now able to generate require careful interpretation. In combination with experimental approaches, computational modelling allows us to challenge and refine our current understanding of epithelial morphogenesis and to explore experimentally intractable questions. To this end, a variety of cell-based modelling approaches have been developed to describe cell-cell mechanical interactions, ranging from vertex and 'finite-element' models that approximate each cell geometrically by a polygon representing the cell's membrane, to immersed boundary and subcellular element models that allow for more arbitrary cell shapes. Here, we review how these models have been used to provide insights into epithelial morphogenesis and describe how such models could help future efforts to decipher the forces and mechanical and biochemical feedbacks that guide cell and tissue-level behaviour. In addition, we discuss current challenges associated with using computational models of morphogenetic processes in a quantitative and predictive way.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'. © 2017 The Author(s).

  12. Characteristics of service users and provider organisations associated with experience of out of hours general practitioner care in England: population based cross sectional postal questionnaire survey

    Science.gov (United States)

    Abel, Gary; Lyratzopoulos, Georgios; Elliott, Marc N; Richards, Suzanne; Barry, Heather E; Roland, Martin; Campbell, John L

    2015-01-01

    Objective To investigate the experience of users of out of hours general practitioner services in England, UK. Design Population based cross sectional postal questionnaire survey. Setting General Practice Patient Survey 2012-13. Main outcome measures Potential associations between sociodemographic factors (including ethnicity and ability to take time away from work during working hours to attend a healthcare consultation) and provider organisation type (not for profit, NHS, or commercial) and service users’ experience of out of hours care (timeliness, confidence and trust in the out of hours clinician, and overall experience of the service), rated on a scale of 0-100. Which sociodemographic/provider characteristics were associated with service users’ experience, the extent to which any observed differences could be because of clustering of service users of a particular sociodemographic group within poorer scoring providers, and the extent to which observed differences in experience varied across types of provider. Results The overall response rate was 35%; 971 232/2 750 000 patients returned surveys. Data from 902 170 individual service users were mapped through their registered practice to one of 86 providers of out of hours GP care with known organisation type. Commercial providers of out of hours GP care were associated with poorer reports of overall experience of care, with a mean difference of −3.13 (95% confidence interval −4.96 to −1.30) compared with not for profit providers. Asian service users reported lower scores for all three experience outcomes than white service users (mean difference for overall experience of care −3.62, −4.36 to −2.89), as did service users who were unable to take time away from work compared with service users who did not work (mean difference for overall experience of care −4.73, −5.29 to −4.17). Conclusions Commercial providers of out of hours GP care were associated with poorer experience of care

  13. High tolerance to simultaneous active-site mutations in TEM-1 beta-lactamase: Distinct mutational paths provide more generalized beta-lactam recognition.

    Science.gov (United States)

    De Wals, Pierre-Yves; Doucet, Nicolas; Pelletier, Joelle N

    2009-01-01

    The diversity in substrate recognition spectra exhibited by various beta-lactamases can result from one or a few mutations in the active-site area. Using Escherichia coli TEM-1 beta-lactamase as a template that efficiently hydrolyses penicillins, we performed site-saturation mutagenesis simultaneously on two opposite faces of the active-site cavity. Residues 104 and 105 as well as 238, 240, and 244 were targeted to verify their combinatorial effects on substrate specificity and enzyme activity and to probe for cooperativity between these residues. Selection for hydrolysis of an extended-spectrum cephalosporin, cefotaxime (CTX), led to the identification of a variety of novel mutational combinations. In vivo survival assays and in vitro characterization demonstrated a general tendency toward increased CTX and decreased penicillin resistance. Although selection was undertaken with CTX, productive binding (K(M)) was improved for all substrates tested, including benzylpenicillin for which catalytic turnover (k(cat)) was reduced. This indicates broadened substrate specificity, resulting in more generalized (or less specialized) variants. In most variants, the G238S mutation largely accounted for the observed properties, with additional mutations acting in an additive fashion to enhance these properties. However, the most efficient variant did not harbor the mutation G238S but combined two neighboring mutations that acted synergistically, also providing a catalytic generalization. Our exploration of concurrent mutations illustrates the high tolerance of the TEM-1 active site to multiple simultaneous mutations and reveals two distinct mutational paths to substrate spectrum diversification.

  14. Leukocyte-epithelial interactions.

    Science.gov (United States)

    Zen, Ke; Parkos, Charles A

    2003-10-01

    As a 'double-edged sword', neutrophil (polymorphonuclear leukocyte) migration across epithelial-lined organs is an important component of host defense, but it also results in epithelial pathophysiology and disease symptoms. There have been significant advances in better understanding the mechanisms of how leukocytes cross the vascular endothelium to exit the bloodstream; however, many of the mechanisms that govern polymorphonuclear leukocyte transepithelial migration are different and we are only just beginning to understand them. Recent findings include new junctional adhesion molecules and carbohydrate moieties as receptors for migrating neutrophils. In addition, new insights into leukocyte-epithelial signaling events have emerged that are beginning to shed light on the role of SIRP-CD47 interactions in regulating the rate of neutrophil transepithelial migration and how neutrophils modulate epithelial barrier function.

  15. Raising awareness of carrier testing for hereditary haemoglobinopathies in high-risk ethnic groups in the Netherlands: a pilot study among the general public and primary care providers

    Directory of Open Access Journals (Sweden)

    Cornel Martina C

    2009-09-01

    Full Text Available Abstract Background In the Netherlands no formal recommendations exist concerning preconceptional or antenatal testing for carriership of hereditary haemoglobinopathies. Those at highest risk may be unaware of the possibility of carrier screening. While universal newborn screening has recently been introduced, neither preconceptional nor antenatal carrier testing is routinely offered by health care services to the general public. A municipal health service and a foundation for public information on medical genetics undertook a pilot project with the aim of increasing knowledge and encouraging informed choice. Two groups were targeted: members of the public from ethnic groups at increased risk, and primary health care providers. This study examines the effectiveness of culturally specific 'infotainment' to inform high-risk ethnic groups about their increased risk for haemoglobinopathies. In addition, the study explores attitudes and intentions of primary care providers towards haemoglobinopathy carrier testing of their patients from high-risk ethnic groups. Methods Informational sessions tailored to the public or professionals were organised in Amsterdam, and evaluated for their effect. Psychological parameters were measured using structured questionnaires based on the Theory of Planned Behaviour. Results The pre-test/post-test questionnaire showed that members of the public gained understanding of inheritance and carriership of haemoglobinopathies from the "infotainment" session (p Conclusion The "infotainment" programme may have a positive effect on people from high-risk groups, but informed general practitioners and midwives were reluctant to facilitate their patients' getting tested. Additional initiatives are needed to motivate primary care providers to facilitate haemoglobinopathy carrier testing for their patients from high-risk backgrounds.

  16. Force transmission in epithelial tissues.

    Science.gov (United States)

    Vasquez, Claudia G; Martin, Adam C

    2016-03-01

    In epithelial tissues, cells constantly generate and transmit forces between each other. Forces generated by the actomyosin cytoskeleton regulate tissue shape and structure and also provide signals that influence cells' decisions to divide, die, or differentiate. Forces are transmitted across epithelia because cells are mechanically linked through junctional complexes, and forces can propagate through the cell cytoplasm. Here, we review some of the molecular mechanisms responsible for force generation, with a specific focus on the actomyosin cortex and adherens junctions. We then discuss evidence for how these mechanisms promote cell shape changes and force transmission in tissues. © 2016 Wiley Periodicals, Inc.

  17. Who has the worst attitudes toward sexual minorities? Comparison of transphobia and homophobia levels in gender dysphoric individuals, the general population and health care providers.

    Science.gov (United States)

    Fisher, A D; Castellini, G; Ristori, J; Casale, H; Giovanardi, G; Carone, N; Fanni, E; Mosconi, M; Ciocca, G; Jannini, E A; Ricca, V; Lingiardi, V; Maggi, M

    2017-03-01

    To date, few studies have addressed attitudes toward transgender individuals. In addition, little is known about health care providers' (HCP) attitudes toward sexual minorities. The aim of the present study is to compare attitudes toward homosexual and transgender individuals between gender dysphoric individuals (GDs), general population controls (C) and HCP. A total of 310 subjects were considered, including 122 GDs (63 transwomen and 59 transmen), 53 heterosexual HCP (26 males and 27 females) and 135 C. Participants completed the Modern Homophobia Scale (MHS) and the Attitudes Toward Transgendered Individuals Scale (ATTI) in order to assess attitudes toward gay men and lesbian women and toward transgender individuals, respectively. In addition, GDs completed the Gender Identity/Gender Dysphoria Questionnaire (GIDYQ-AA) and ATTI to measure, respectively, gender dysphoria levels and internalized transphobia. Religious attitudes were evaluated by means of the Religious Fundamentalism Scale (RFS), and Discrimination and Stigma Scale (DISC-12) was used to measure perceived discrimination. (1) Men showed significantly higher levels of homophobia and transphobia when compared to women (p homophobia and transphobia (both p < 0.001). Our results underline the need to promote awareness and acceptance of the sexual minorities, who are more at risk of discriminatory attitudes, which are strongly dependent on religious precepts and dogma.

  18. Cryptococcus–Epithelial Interactions

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    Leanne M. Taylor-Smith

    2017-10-01

    Full Text Available The fungal pathogen, Cryptococcus neoformans, causes devastating levels of morbidity and mortality. Infections with this fungus tend to be predominantly in immunocompromised individuals, such as those with HIV. Infections initiate with inhalation of cryptococcal cells and entry of the pathogen into the lungs. The bronchial epithelial cells of the upper airway and the alveolar epithelial cells of the lower airway are likely to be the first host cells that Cryptococcus engage with. Thus the interaction of cryptococci and the respiratory epithelia will be the focus of this review. C. neoformans has been shown to adhere to respiratory epithelial cells, although if the role of the capsule is in aiding or hindering this adhesion is debatable. The epithelia are also able to react to cryptococci with the release of cytokines and chemokines to start the immune response to this invading pathogen. The activity of surfactant components that line this mucosal barrier towards Cryptococcus and the metabolic and transcriptional reaction of cryptococci when encountering epithelial cells will also be discussed.

  19. Normal morphogenesis of epithelial tissues and progression of epithelial tumors

    Science.gov (United States)

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.

    2011-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857

  20. Skin temperature over the carotid artery provides an accurate noninvasive estimation of core temperature in infants and young children during general anesthesia.

    Science.gov (United States)

    Jay, Ollie; Molgat-Seon, Yannick; Chou, Shirley; Murto, Kimmo

    2013-12-01

    The accurate measurement of core temperature is an essential aspect of intraoperative management in children. Invasive measurement sites are accurate but carry some health risks and cannot be used in certain patients. An accurate form of noninvasive thermometry is therefore needed. Our aim was to develop, and subsequently validate, separate models for estimating core temperature using different skin temperatures with an individualized correction factor. Forty-eight pediatric patients (0-36 months) undergoing elective surgery were separated into a modeling group (MG, n = 28) and validation group (VG, n = 20). Skin temperature was measured over the carotid artery (Tsk_carotid ), upper abdomen (Tsk_abd ), and axilla (Tsk_axilla ), while nasopharyngeal temperature (Tnaso ) was measured as a reference. In the MG, derived models for estimating Tnaso were: Tsk_carotid  + 0.52; Tsk_abd  + (0.076[body mass] + 0.02); and Tsk_axilla  + (0.081[body mass]-0.66). After adjusting raw Tsk_carotid, Tsk_abd , and Tsk_axilla values in the independent VG using these models, the mean bias (Predicted Tnaso - Actual Tnaso [with 95% confidence intervals]) was +0.03[+0.53, -0.50]°C, -0.05[+1.02, -1.07]°C, and -0.06[+1.21, -1.28°C], respectively. The percentage of values within ±0.5°C of Tnaso was 93.2%, 75.4%, and 66.1% for Tsk_carotid, Tsk_abd , and Tsk_axilla , respectively. Sensitivity and specificity for detecting hypothermia (Tnaso  Skin temperature over the carotid artery, with a simple correction factor of +0.52°C, provides a viable noninvasive estimate of Tnaso in young children during elective surgery with a general anesthetic. © 2013 John Wiley & Sons Ltd.

  1. Patient-provider concordance in the perception of illness and disease: a cross-sectional study among multimorbid patients and their general practitioners in Switzerland

    Directory of Open Access Journals (Sweden)

    Neuner-Jehle S

    2017-08-01

    Full Text Available Stefan Neuner-Jehle, Stefan Zechmann, Daniela Grundmann Maissen, Thomas Rosemann, Oliver Senn Institute of Primary Care, University of Zurich, Zurich, Switzerland Background: Multiple chronic health conditions are leading to multiple treatment procedures and polypharmacy. Prioritizing treatment according to patients’ needs and preferences may be helpful for deprescribing. Thus, for improving health care, it is crucial for general practitioners (GPs to perceive the chief complaints (CCs of patients. The primary aim of this study was to investigate the patient–provider concordance of CCs and the secondary aim was to investigate the concordance between CCs and diagnosis, in a sample of Swiss multimorbid patients. Materials and methods: A cross-sectional analysis based on a cluster randomized controlled trial (RCT among 46 GPs, recruited between March 2015 to July 2016, and 334 multimorbid patients (≥60 years taking ≥5 drugs for at least 6 months in Northern Switzerland was performed. CCs listed by GPs and by patients (n=128 were classified according to the International Classification of Primary Care, version 2 (ICPC-2 coding system on chapter and component level and defined as concordant if ICPC-2 codes of patients and GPs were identical. Concordance was classified into full, moderate or low, depending on the ranking of patients’ CCs on GPs’ list. As secondary outcome, we compared patients’ CCs to GPs’ diagnosis. Statistics included descriptive measures and a multivariate regression analysis of factors that are modifying concordance. Results: The mean age of patients was 76.9 (SD 8.1 years, where 38% were male, taking 7.9 (SD 2.6 drugs on the long term. The most frequent complaint was pain. Concordance of the CC was given in 101/128 (78.9% on the ICPC-2 chapter level, whereby 86/128 (67.2% showed full, 8/128 (6.3% moderate and 7/128 (5.5% low concordance; 27/128 (21.1% were discordant. Concordance between CCs and diagnosis was 53

  2. Epithelial-Mesenchymal Transition and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yanyuan Wu

    2016-01-01

    Full Text Available Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges.

  3. Epithelial Intermediate Filaments: Guardians against Microbial Infection?

    Directory of Open Access Journals (Sweden)

    Florian Geisler

    2016-06-01

    Full Text Available Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection.

  4. Development of a validated clinical case definition of generalized tonic-clonic seizures for use by community-based health care providers.

    Science.gov (United States)

    Anand, Krishnan; Jain, Satish; Paul, Eldho; Srivastava, Achal; Sahariah, Sirazul A; Kapoor, Suresh K

    2005-05-01

    To develop and test a clinical case definition for identification of generalized tonic-clonic seizures (GTCSs) by community-based health care providers. To identify symptoms that can help identify GTCSs, patients with history of a jerky movements or rigidity in any part of the body ever in life were recruited from three sites: the community, secondary care hospital, and tertiary care hospital. These patients were administered a 14-item structured interview schedule focusing on the circumstances surrounding the seizure. Subsequently, a neurologist examined each patient and, based on available investigations, classified them as GTCS or non-GTCS cases. A logistic regression analysis was performed to select symptoms that were to be used for case definition of GTCSs. Validity parameters for the case definition at different cutoff points were calculated in another set of subjects. In total, 339 patients were enrolled in the first phase of the study. The tertiary care hospital contributed the maximal number of GTCS cases, whereas cases of non-GTCS were mainly from the community. At the end of phase I, the questionnaire was shortened from 14 to eight questions based on statistical association and clinical judgment. After phase II, which was conducted among 170 subjects, three variables were found to be significantly related to the presence of GTCSs by logistic regression: absence of stress (13.1; 4.1-41.3), presence of frothing (13.7; 4.0-47.3), and occurrence in sleep (8.3; 2.0-34.9). As a case definition using only three variables did not provide sufficient specificity, three more variables were added based on univariate analysis of the data (incontinence during the episode and unconsciousness) and review of literature (injury during episode). A case definition consisting of giving one point to an affirmative answer for each of the six questions was tested. At a cutoff point of four, sensitivity was 56.9 (47.4-66.0) and specificity, 96.3 (86.2-99.4). Among the 197 GTCS

  5. Polarity in Mammalian Epithelial Morphogenesis

    Science.gov (United States)

    Roignot, Julie; Peng, Xiao; Mostov, Keith

    2013-01-01

    Cell polarity is fundamental for the architecture and function of epithelial tissues. Epithelial polarization requires the intervention of several fundamental cell processes, whose integration in space and time is only starting to be elucidated. To understand what governs the building of epithelial tissues during development, it is essential to consider the polarization process in the context of the whole tissue. To this end, the development of three-dimensional organotypic cell culture models has brought new insights into the mechanisms underlying the establishment and maintenance of higher-order epithelial tissue architecture, and in the dynamic remodeling of cell polarity that often occurs during development of epithelial organs. Here we discuss some important aspects of mammalian epithelial morphogenesis, from the establishment of cell polarity to epithelial tissue generation. PMID:23378592

  6. Gastric Epithelial Stem Cells

    Science.gov (United States)

    MILLS, JASON C.; SHIVDASANI, RAMESH A.

    2013-01-01

    Advances in our understanding of stem cells in the gastrointestinal tract include the identification of molecular markers of stem and early progenitor cells in the small intestine. Although gastric epithelial stem cells have been localized, little is known about their molecular biology. Recent reports describe the use of inducible Cre recombinase activity to indelibly label candidate stem cells and their progeny in the distal stomach, (ie, the antrum and pylorus). No such lineage labeling of epithelial stem cells has been reported in the gastric body (corpus). Among stem cells in the alimentary canal, those of the adult corpus are unique in that they lie close to the lumen and increase proliferation following loss of a single mature progeny lineage, the acid-secreting parietal cell. They are also unique in that they neither depend on Wnt signaling nor express the surface marker Lgr5. Because pathogenesis of gastric adenocarcinoma has been associated with abnormal patterns of gastric differentiation and with chronic tissue injury, there has been much research on the response of stomach epithelial stem cells to inflammation. Chronic inflammation, as induced by infection with Helicobacter pylori, affects differentiation and promotes metaplasias. Several studies have identified cellular and molecular mechanisms in spasmolytic polypeptide–expressing (pseudopyloric) metaplasia. Researchers have also begun to identify signaling pathways and events that take place during embryonic development that eventually establish the adult stem cells to maintain the specific features and functions of the stomach mucosa. We review the cytologic, molecular, functional, and developmental properties of gastric epithelial stem cells. PMID:21144849

  7. Calcifying epithelial odontogenic tumor.

    Science.gov (United States)

    Pereira, Olavo Hoston Gonçalves; de Carvalho, Laura Priscila Barboza; Lacerda Brasileiro Junior, Vilson; de Figueiredo, Cláudia Roberta Leite Vieira

    2013-01-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare benign epithelial odontogenic neoplasm of slow growth that is locally aggressive and tends to invade bone and adjacent soft tissue. Here is reported the case of a 21-year-old female patient with a CEOT in the left mandibular posterior region. The computerized tomography in coronal plane revealed a hypodense lesion in the posterior region of the left mandibular body with hyperdense areas inside and was associated with element 37. An incisional biopsy of the lesion was performed and the histopathological analysis revealed the presence of layers of epithelial odontogenic cells that formed prominent intercellular bridges. A large quantity of extracellular, eosinophilic, and amyloid-like material and an occasional formation of concentric calcifications (Liesegang rings) were also found. The histopathological diagnosis was a Pindborg tumor. Resection of the tumor with a safety margin was performed and after 6 months of follow-up there has been no sign of recurrence of the lesion.

  8. Calcifying Epithelial Odontogenic Tumor

    Directory of Open Access Journals (Sweden)

    Olavo Hoston Gonçalves Pereira

    2013-01-01

    Full Text Available The calcifying epithelial odontogenic tumor (CEOT is a rare benign epithelial odontogenic neoplasm of slow growth that is locally aggressive and tends to invade bone and adjacent soft tissue. Here is reported the case of a 21-year-old female patient with a CEOT in the left mandibular posterior region. The computerized tomography in coronal plane revealed a hypodense lesion in the posterior region of the left mandibular body with hyperdense areas inside and was associated with element 37. An incisional biopsy of the lesion was performed and the histopathological analysis revealed the presence of layers of epithelial odontogenic cells that formed prominent intercellular bridges. A large quantity of extracellular, eosinophilic, and amyloid-like material and an occasional formation of concentric calcifications (Liesegang rings were also found. The histopathological diagnosis was a Pindborg tumor. Resection of the tumor with a safety margin was performed and after 6 months of follow-up there has been no sign of recurrence of the lesion.

  9. Role of the epithelial cell rests of Malassez in the development, maintenance and regeneration of periodontal ligament tissues.

    Science.gov (United States)

    Xiong, Jimin; Gronthos, Stan; Bartold, P Mark

    2013-10-01

    Periodontitis is a highly prevalent inflammatory disease that results in damage to the tooth-supporting tissues, potentially leading to tooth loss. Periodontal tissue regeneration is a complex process that involves the collaboration of two hard tissues (cementum and alveolar bone) and two soft tissues (gingiva and periodontal ligament). To date, no periodontal-regenerative procedures provide predictable clinical outcomes. To understand the rational basis of regenerative procedures, a better understanding of the events associated with the formation of periodontal components will help to establish reliable strategies for clinical practice. An important aspect of this is the role of the Hertwig's epithelial root sheath in periodontal development and that of its descendants, the epithelial cell rests of Malassez, in the maintenance of the periodontium. An important structure during tooth root development, the Hertwig's epithelial root sheath is not only a barrier between the dental follicle and dental papilla cells but is also involved in determining the shape, size and number of roots and in the development of dentin and cementum, and may act as a source of mesenchymal progenitor cells for cementoblasts. In adulthood, the epithelial cell rests of Malassez are the only odontogenic epithelial population in the periodontal ligament. Although there is no general agreement on the functions of the epithelial cell rests of Malassez, accumulating evidence suggests that the putative roles of the epithelial cell rests of Malassez in adult periodontal ligament include maintaining periodontal ligament homeostasis to prevent ankylosis and maintain periodontal ligament space, to prevent root resorption, to serve as a target during periodontal ligament innervation and to contribute to cementum repair. Recently, ovine epithelial cell rests of Malassez cells have been shown to harbor clonogenic epithelial stem-cell populations that demonstrate similar properties to mesenchymal stromal

  10. Multi-functionality and plasticity characterize epithelial cells in Hydra

    Science.gov (United States)

    Buzgariu, W; Al Haddad, S; Tomczyk, S; Wenger, Y; Galliot, B

    2015-01-01

    Epithelial sheets, a synapomorphy of all metazoans but porifers, are present as 2 layers in cnidarians, ectoderm and endoderm, joined at their basal side by an extra-cellular matrix named mesoglea. In the Hydra polyp, epithelial cells of the body column are unipotent stem cells that continuously self-renew and concomitantly express their epitheliomuscular features. These multifunctional contractile cells maintain homeostasis by providing a protective physical barrier, by digesting nutrients, by selecting a stable microbiota, and by rapidly closing wounds. In addition, epithelial cells are highly plastic, supporting the adaptation of Hydra to physiological and environmental changes, such as long starvation periods where survival relies on a highly dynamic autophagy flux. Epithelial cells also play key roles in developmental processes as evidenced by the organizer activity they develop to promote budding and regeneration. We propose here an integrative view of the homeostatic and developmental aspects of epithelial plasticity in Hydra. PMID:26716072

  11. Homeostatic Imbalance in Epithelial Ducts and Its Role in Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Katarzyna A. Rejniak

    2012-01-01

    Full Text Available An epithelial duct is a well-defined multicellular structure composed of tightly packed cells separating and protecting body compartments that are used for enzyme secretion and its transport across the internal. The structural and functional integrity (homeostasis of such ducts is vital in carrying many life functions (breathing, lactation, production of hormones. However, the processes involved in maintaining the homeostatic balance are not yet fully understood. On the other hand, the loss of epithelial tissue architecture, such as filled lumens or ductal disorganization, are among the first symptoms of the emerging epithelial tumors (carcinomas. Using the previously developed biomechanical model of epithelial ducts: IBCell, we investigated how different signals and mechanical stimuli imposed on individual epithelial cells can impact the homeostatic (imbalance and integrity of the whole epithelial tissue. We provide a link between erroneous responses of individual epithelial cells to specific signals and the emerging ductal morphologies characteristic for preinvasive cancers observed in pathology specimens, or characteristic for multicellular structures arising from mutated cells cultured in vitro. We summarize our finding in terms of altered properties of epithelial cell polarization, and discuss the relative importance of various polarization signals on the formation of tumor-like multicellular structures.

  12. Polarity in Mammalian Epithelial Morphogenesis

    OpenAIRE

    Roignot, Julie; Peng, Xiao; Mostov, Keith

    2013-01-01

    Cell polarity is fundamental for the architecture and function of epithelial tissues. Epithelial polarization requires the intervention of several fundamental cell processes, whose integration in space and time is only starting to be elucidated. To understand what governs the building of epithelial tissues during development, it is essential to consider the polarization process in the context of the whole tissue. To this end, the development of three-dimensional organotypic cell culture model...

  13. Ocular Surface Epithelialization Pattern After Simple Limbal Epithelial Transplantation: An In Vivo Observational Study.

    Science.gov (United States)

    Mittal, Vikas; Jain, Rajat; Mittal, Ruchi

    2015-10-01

    To study the in vivo pattern of ocular surface epithelialization after simple limbal epithelial transplantation (SLET). A retrospective interventional case series was performed at a cornea and anterior segment services of a referral tertiary care center between June 2012 and March 2015. Patients with unilateral limbal stem cell deficiency who underwent SLET and whose medical records had serial and detailed photographic documentation of ocular surface healing were reviewed. The outcome measures consisted of the pattern of ocular surface epithelialization, time taken for complete ocular surface epithelialization, and assessment of the possible variations in the explants' characteristics in vivo. Five patients fulfilled the inclusion criteria. Mean age was 30.8 years, the male:female ratio was 4:1. Mean follow-up after the SLET period was 10.8 months. A 2-line improvement in visual acuity was seen in 3 of 5 patients. The mean number of explants was 11.4 (range, 5-19). The first clinical evidence of proliferation of the corneal epithelium from the limbal explants was seen on the second day in all patients, and ocular surface epithelialization was complete in all cases within 14 days. The explants disappeared within 1 to 2 months in all but 1 case (24 weeks). Variations were seen in explant activity with the size and age of the explants. The in vivo pattern of ocular surface epithelialization after SLET appears to be similar to in vitro epithelialization observed after CLET. The observations in this study provide a lead for performing further laboratory and clinical research in SLET.

  14. Attitudes to long-term use of benzodiazepine hypnotics by older people in general practice: findings from interviews with service users and providers.

    Science.gov (United States)

    Iliffe, S; Curran, H V; Collins, R; Yuen Kee, S C; Fletcher, S; Woods, B

    2004-05-01

    The aim of this study was to explore beliefs and attitudes about continuing or stopping benzodiazepine hypnotics amongst older patients using such medicines, and amongst their general practitioners. One hundred and ninety two patients aged 65 and over who were long-term users of benzodiazepine hypnotics were recruited from 25 general practices in inner city and suburban London, as were 83 practice staff. The practices had been recruited into a randomised controlled trial of benzodiazepine withdrawal in long-term users. Semi-structured interviews were conducted with patients recruited to the trial, and non-standardized (conversational) interviews with practice staff. Sixty percent of long-term benzodiazepine users had taken their hypnotic for more than 10 years, and one-third for more than 20 years. Beliefs in the efficacy of hypnotics, and self-report of insomnia despite their use, varied according to the willingness to attempt withdrawal. The majority of patients reported no warnings from professionals about adverse effects of using benzodiazepine hypnotics. Half had tried to stop at some time but most attempts had been short-lived. Patients and doctors had distinctly different views of the advantages, disadvantages and risks of stopping benzodiazepine hypnotic use. Both increased patient awareness of the problems of long-term benzodiazepine use and an evidence-based approach to withdrawal efforts in primary care are necessary to reduce the consumption of medication that has little real benefit.

  15. Clinical care provided on post-graduate dental clinical training course at Tokyo Dental College Chiba Hospital, Department of General Dentistry.

    Science.gov (United States)

    Takahashi, Toshiyuki; Tsunoda, Masatake; Sugiyama, Toshiko; Yamakura, Daiki; Kondo, Yoshihiro; Noro, Akio

    2009-01-01

    Number of patients assigned to dental residents, course of treatment and number of various technical tasks performed as described in the Reports on Clinical Training of Dentists published by the Department of General Dentistry, Tokyo Dental College Chiba Hospital since its establishment in 2002 were compared between before (2003-2005) and after (2006-2007) clinical training was made mandatory, and the state of clinical residency evaluated. Number of patients assigned generally increased, and mean number of patients treated by each resident in 2007 (15.08) was approximately 2 times higher than that in 2003 (8.47). Total number of treatments was 1.38 times higher in 2007 than in 2003, and periodontal treatment accounted for approximately 40% of all treatment both before and after clinical training became mandatory. Number of technical tasks in 2004-2007 was less than half the peak in 2003. To further improve clinical training, evaluation and implementation of effective approaches is necessary to secure an adequate number of patients, widen the variety of cases and increase the number of technical tasks.

  16. Normal morphogenesis of epithelial tissues and progression of epithelial tumors.

    Science.gov (United States)

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A

    2012-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. Copyright © 2011 John Wiley & Sons, Inc.

  17. Guiding Principles for Implementing School-Based Management Programs: An Online Toolkit Providing General Principles That Can Be Applied to the Implementation of School-Based Management Reforms

    Science.gov (United States)

    Patrinos, Harry Anthony; Fasih, Tazeen; Barrera, Felipe; Garcia-Moreno, Vicente A.; Bentaouet-Kattan, Raja; Baksh, Shaista; Wickramasekera, Inosha

    2007-01-01

    School-based management (SBM) has become a very popular movement over the past decade. The World Bank Education Team's SBM work program emerged out of a need to define the concept more clearly, review the evidence, support impact assessments in various countries, and provide some initial feedback to teams preparing education projects. During the…

  18. Epithelial-stromal interaction 1 (EPSTI1) substitutes for peritumoral fibroblasts in the tumor microenvironment

    DEFF Research Database (Denmark)

    De Neergaard, Michala; Kim, Jiyoung; Villadsen, René

    2010-01-01

    Tumor cells can activate stroma, yet the implication of this activation in terms of reciprocal induction of gene expression in tumor cells is poorly understood. Epithelial Stromal Interaction 1 (EPSTI1) is an interferon response gene originally isolated from heterotypic recombinant cultures...... of human breast cancer cells and activated breast myofibroblasts. Here we describe the first immunolocalization of EPSTI1 in normal and cancerous breast tissue, and we provide evidence for a role of this molecule in the regulation of tumor cell properties and epithelial-mesenchymal transition. In general...... cell line and silenced endogenous EPSTI1 by RNA interference in another. Irrespective of the experimental approach, EPSTI1 expression led to an increase in tumorsphere formation-a property associated with breast stem/progenitor cells. Most remarkably, we show that EPSTI1, by conveying spread of tumor...

  19. Preventive Dental Service Utilization for Medicaid-Enrolled Children in New Hampshire: A Comparison of Care Provided by Pediatric Dentists and General Dentists

    Science.gov (United States)

    Chi, Donald; Milgrom, Peter

    2013-01-01

    In this study, we compared preventive dental utilization through visits to a pediatric dentist (PD) vs. visits to a general dentist (GD) among Medicaid-enrolled children in New Hampshire (n=12,964). Dental claims were analyzed using conditional logistic regression models. After adjusting for covariates, children seen by a PD were 51% more likely to have received fluoride treatment, 26% more likely to have had at least two dental examinations, and 19% more likely to have received a sealant than children seen by a GD. Overall, our results suggest that children seen by a PD were more likely to have received preventive services than those seen by a GD. Because Medicaid-enrolled children are at increased risk for poor oral health, policies should be enacted to ensure that high-risk children receive appropriate and regular prevention-oriented dental care. PMID:19395842

  20. Proteoglycan synthesis and Golgi organization in polarized epithelial cells.

    Science.gov (United States)

    Dick, Gunnar; Akslen-Hoel, Linn K; Grøndahl, Frøy; Kjos, Ingrid; Prydz, Kristian

    2012-12-01

    A large number of complex glycosylation mechanisms take place in the Golgi apparatus. In epithelial cells, glycosylated protein molecules are transported to both the apical and the basolateral surface domains. Although the prevailing view is that the Golgi apparatus provides the same lumenal environment for glycosylation of apical and basolateral cargo proteins, there are indications that proteoglycans destined for the two opposite epithelial surfaces are exposed to different conditions in transit through the Golgi apparatus. We will here review data relating proteoglycan and glycoprotein synthesis to characteristics of the apical and basolateral secretory pathways in epithelial cells.

  1. Epithelial adhesion molecules and the regulation of intestinal homeostasis during neutrophil transepithelial migration

    Science.gov (United States)

    Sumagin, Ronen; Parkos, Charles A

    2014-01-01

    Epithelial adhesion molecules play essential roles in regulating cellular function and maintaining mucosal tissue homeostasis. Some form epithelial junctional complexes to provide structural support for epithelial monolayers and act as a selectively permeable barrier separating luminal contents from the surrounding tissue. Others serve as docking structures for invading viruses and bacteria, while also regulating the immune response. They can either obstruct or serve as footholds for the immune cells recruited to mucosal surfaces. Currently, it is well appreciated that adhesion molecules collectively serve as environmental cue sensors and trigger signaling events to regulate epithelial function through their association with the cell cytoskeleton and various intracellular adapter proteins. Immune cells, particularly neutrophils (PMN) during transepithelial migration (TEM), can modulate adhesion molecule expression, conformation, and distribution, significantly impacting epithelial function and tissue homeostasis. This review discusses the roles of key intestinal epithelial adhesion molecules in regulating PMN trafficking and outlines the potential consequences on epithelial function. PMID:25838976

  2. Epithelial rotation is preceded by planar symmetry breaking of actomyosin and protects epithelial tissue from cell deformations.

    Directory of Open Access Journals (Sweden)

    Ivana Viktorinová

    2017-11-01

    Full Text Available Symmetry breaking is involved in many developmental processes that form bodies and organs. One of them is the epithelial rotation of developing tubular and acinar organs. However, how epithelial cells move, how they break symmetry to define their common direction, and what function rotational epithelial motions have remains elusive. Here, we identify a dynamic actomyosin network that breaks symmetry at the basal surface of the Drosophila follicle epithelium of acinar-like primitive organs, called egg chambers, and may represent a candidate force-generation mechanism that underlies the unidirectional motion of this epithelial tissue. We provide evidence that the atypical cadherin Fat2, a key planar cell polarity regulator in Drosophila oogenesis, directs and orchestrates transmission of the intracellular actomyosin asymmetry cue onto a tissue plane in order to break planar actomyosin symmetry, facilitate epithelial rotation in the opposite direction, and direct the elongation of follicle cells. In contrast, loss of this rotational motion results in anisotropic non-muscle Myosin II pulses that are disorganized in plane and causes cell deformations in the epithelial tissue of Drosophila eggs. Our work demonstrates that atypical cadherins play an important role in the control of symmetry breaking of cellular mechanics in order to facilitate tissue motion and model epithelial tissue. We propose that their functions may be evolutionarily conserved in tubular/acinar vertebrate organs.

  3. Epithelial rotation is preceded by planar symmetry breaking of actomyosin and protects epithelial tissue from cell deformations.

    Science.gov (United States)

    Viktorinová, Ivana; Henry, Ian; Tomancak, Pavel

    2017-11-01

    Symmetry breaking is involved in many developmental processes that form bodies and organs. One of them is the epithelial rotation of developing tubular and acinar organs. However, how epithelial cells move, how they break symmetry to define their common direction, and what function rotational epithelial motions have remains elusive. Here, we identify a dynamic actomyosin network that breaks symmetry at the basal surface of the Drosophila follicle epithelium of acinar-like primitive organs, called egg chambers, and may represent a candidate force-generation mechanism that underlies the unidirectional motion of this epithelial tissue. We provide evidence that the atypical cadherin Fat2, a key planar cell polarity regulator in Drosophila oogenesis, directs and orchestrates transmission of the intracellular actomyosin asymmetry cue onto a tissue plane in order to break planar actomyosin symmetry, facilitate epithelial rotation in the opposite direction, and direct the elongation of follicle cells. In contrast, loss of this rotational motion results in anisotropic non-muscle Myosin II pulses that are disorganized in plane and causes cell deformations in the epithelial tissue of Drosophila eggs. Our work demonstrates that atypical cadherins play an important role in the control of symmetry breaking of cellular mechanics in order to facilitate tissue motion and model epithelial tissue. We propose that their functions may be evolutionarily conserved in tubular/acinar vertebrate organs.

  4. Ultrastructural localization of Charcot-Leyden crystal protein (lysophospholipase) to intracytoplasmic crystals in tumor cells of primary solid and papillary epithelial neoplasm of the pancreas.

    Science.gov (United States)

    Dvorak, A M; Letourneau, L; Weller, P F; Ackerman, S J

    1990-05-01

    Charcot-Leyden crystals (CLC), composed of a single protein with lysophospholipase activity, have been traditionally associated with eosinophil-rich disorders. Atypically shaped and typical CLC were noted by electron microscopy in the surgical sample from a patient with solid and papillary epithelial neoplasm of the pancreas. This rare primary tumor of the pancreas with limited aggressive behavior also contained damaged and partially or completely degranulated eosinophils in the tumor stroma. We localized CLC protein by ultrastructural immunogold staining to the CLC within vacuolar structures and in vesicles of tumor cell cytoplasm as well as to the cytoplasm and nucleus of eosinophils in the tumor stroma. These findings provide evidence that epithelial tumor cells contain Charcot-Leyden crystal protein that most likely originates from tumor stroma eosinophils. Tumor stroma eosinophils have generally been associated with improved prognoses in a wide variety of epithelial neoplasms. The role of tumor CLC protein (lysophospholipase) in these settings deserves further investigation.

  5. Etiology and Pathogenesis of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Samuel C. Mok

    2007-01-01

    Full Text Available Ovarian cancer is complex disease composed of different histological grades and types. However, the underlying molecular mechanisms involved in the development of different phenotypes remain largely unknown. Epidemiological studies identified multiple exogenous and endogenous risk factors for ovarian cancer development. Among them, an inflammatory stromal microenvironment seems to play a critical role in the initiation of the disease. The interaction between such a microenvironment, genetic polymorphisms, and different epithelial components such as endosalpingiosis, endometriosis, and ovarian inclusion cyst in the ovarian cortex may induce different genetic changes identified in the epithelial component of different histological types of ovarian tumors. Genetic studies on different histological grades and types provide insight into the pathogenetic pathways for the development of different disease phenotypes. However, the link between all these genetic changes and the etiological factors remains to be established.

  6. Provider Info

    Data.gov (United States)

    U.S. Department of Health & Human Services — General information on currently active nursing homes, including number of certified beds, quality measure scores, staffing and other information used in the...

  7. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Atsushi Yasukawa

    Full Text Available Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT plays a critical role in airway remodelling. In this study, we hypothesized that infiltrating eosinophils promote airway remodelling in bronchial asthma. To demonstrate this hypothesis we evaluated the effect of eosinophils on EMT by in vitro and in vivo studies. EMT was assessed in mice that received intra-tracheal instillation of mouse bone marrow derived eosinophils and in human bronchial epithelial cells co-cultured with eosinophils freshly purified from healthy individuals or with eosinophilic leukemia cell lines. Intra-tracheal instillation of eosinophils was associated with enhanced bronchial inflammation and fibrosis and increased lung concentration of growth factors. Mice instilled with eosinophils pre-treated with transforming growth factor(TGF-β1 siRNA had decreased bronchial wall fibrosis compared to controls. EMT was induced in bronchial epithelial cells co-cultured with human eosinophils and it was associated with increased expression of TGF-β1 and Smad3 phosphorylation in the bronchial epithelial cells. Treatment with anti-TGF-β1 antibody blocked EMT in bronchial epithelial cells. Eosinophils induced EMT in bronchial epithelial cells, suggesting their contribution to the pathogenesis of airway remodelling.

  8. Apical constriction and epithelial invagination are regulated by BMP activity

    Directory of Open Access Journals (Sweden)

    Vijay K. Jidigam

    2015-12-01

    Full Text Available Epithelial invagination is a morphological process in which flat cell sheets transform into three-dimensional structures through bending of the tissue. It is accompanied by apical constriction, in which the apical cell surface is reduced in relation to the basal cell surface. Although much is known about the intra-cellular molecular machinery driving apical constriction and epithelial invagination, information of how extra-cellular signals affect these processes remains insufficient. In this study we have established several in vivo assays of placodal invagination to explore whether the external signal BMP regulates processes connected to epithelial invagination. By inhibiting BMP activity in prospective cranial placodes, we provide evidence that BMP signals are required for RhoA and F-actin rearrangements, apical constriction, cell elongation and epithelial invagination. The failure of placode invagination after BMP inhibition appears to be a direct consequence of disrupted apical accumulation of RhoA and F-actin, rather than changes in cell death or proliferation. In addition, our results show that epithelial invagination and acquisition of placode-specific identities are two distinct and separable developmental processes. In summary, our results provide evidence that BMP signals promote epithelial invagination by acting upstream of the intracellular molecular machinery that drives apical constriction and cell elongation.

  9. Apical constriction and epithelial invagination are regulated by BMP activity.

    Science.gov (United States)

    Jidigam, Vijay K; Srinivasan, Raghuraman C; Patthey, Cedric; Gunhaga, Lena

    2015-11-30

    Epithelial invagination is a morphological process in which flat cell sheets transform into three-dimensional structures through bending of the tissue. It is accompanied by apical constriction, in which the apical cell surface is reduced in relation to the basal cell surface. Although much is known about the intra-cellular molecular machinery driving apical constriction and epithelial invagination, information of how extra-cellular signals affect these processes remains insufficient. In this study we have established several in vivo assays of placodal invagination to explore whether the external signal BMP regulates processes connected to epithelial invagination. By inhibiting BMP activity in prospective cranial placodes, we provide evidence that BMP signals are required for RhoA and F-actin rearrangements, apical constriction, cell elongation and epithelial invagination. The failure of placode invagination after BMP inhibition appears to be a direct consequence of disrupted apical accumulation of RhoA and F-actin, rather than changes in cell death or proliferation. In addition, our results show that epithelial invagination and acquisition of placode-specific identities are two distinct and separable developmental processes. In summary, our results provide evidence that BMP signals promote epithelial invagination by acting upstream of the intracellular molecular machinery that drives apical constriction and cell elongation. © 2015. Published by The Company of Biologists Ltd.

  10. Medicare Provider Data - Hospice Providers

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Hospice Utilization and Payment Public Use File provides information on services provided to Medicare beneficiaries by hospice providers. The Hospice PUF...

  11. Oral epithelial dysplasia classification systems

    DEFF Research Database (Denmark)

    Warnakulasuriya, S; Reibel, J; Bouquot, J

    2008-01-01

    At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the United Kingdom issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers....... In this report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine...... use. Although most oral pathologists possibly recognize and accept the criteria for grading epithelial dysplasia, firstly based on architectural features and then of cytology, there is great variability in their interpretation of the presence, degree and significance of the individual criteria...

  12. Role of calcium signaling in epithelial bicarbonate secretion.

    Science.gov (United States)

    Jung, Jinsei; Lee, Min Goo

    2014-06-01

    Transepithelial bicarbonate secretion plays a key role in the maintenance of fluid and protein secretion from epithelial cells and the protection of the epithelial cell surface from various pathogens. Epithelial bicarbonate secretion is mainly under the control of cAMP and calcium signaling. While the physiological roles and molecular mechanisms of cAMP-induced bicarbonate secretion are relatively well defined, those induced by calcium signaling remain poorly understood in most epithelia. The present review summarizes the current status of knowledge on the role of calcium signaling in epithelial bicarbonate secretion. Specifically, this review introduces how cytosolic calcium signaling can increase bicarbonate secretion by regulating membrane transport proteins and how it synergizes with cAMP-induced mechanisms in epithelial cells. In addition, tissue-specific variations in the pancreas, salivary glands, intestines, bile ducts, and airways are discussed. We hope that the present report will stimulate further research into this important topic. These studies will provide the basis for future medicines for a wide spectrum of epithelial disorders including cystic fibrosis, Sjögren's syndrome, and chronic pancreatitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. RESEARCH Cervical intra-epithelial neoplasia in HIV-positive ...

    African Journals Online (AJOL)

    However, in patients treated for cervical intra-epithelial neoplasia (CIN), the risk of developing cancer is still 2.8 times greater than in the general population, and may be more in women with recurrent disease.5 Studies show that the recurrence of CIN after treatment was between 20% and 65% in HIV-infected women.6,7.

  14. Vitamin D induces interleukin-1β expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection.

    Directory of Open Access Journals (Sweden)

    Mark Verway

    Full Text Available Although vitamin D deficiency is a common feature among patients presenting with active tuberculosis, the full scope of vitamin D action during Mycobacterium tuberculosis (Mtb infection is poorly understood. As macrophages are the primary site of Mtb infection and are sites of vitamin D signaling, we have used these cells to understand the molecular mechanisms underlying modulation of the immune response by the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D. We found that the virulent Mtb strain H37Rv elicits a broad host transcriptional response. Transcriptome profiling also revealed that the profile of target genes regulated by 1,25D is substantially altered by infection, and that 1,25D generally boosts infection-stimulated cytokine/chemokine responses. We further focused on the role of 1,25D- and infection-induced interleukin 1β (IL-1β expression in response to infection. 1,25D enhanced IL-1β expression via a direct transcriptional mechanism. Secretion of IL-1β from infected cells required the NLRP3/caspase-1 inflammasome. The impact of IL-1β production was investigated in a novel model wherein infected macrophages were co-cultured with primary human small airway epithelial cells. Co-culture significantly prolonged survival of infected macrophages, and 1,25D/infection-induced IL-1β secretion from macrophages reduced mycobacterial burden by stimulating the anti-mycobacterial capacity of co-cultured lung epithelial cells. These effects were independent of 1,25D-stimulated autophagy in macrophages but dependent upon epithelial IL1R1 signaling and IL-1β-driven epithelial production of the antimicrobial peptide DEFB4/HBD2. These data provide evidence that the anti-microbial actions of vitamin D extend beyond the macrophage by modulating paracrine signaling, reinforcing its role in innate immune regulation in humans.

  15. Boston keratoprosthesis in epithelial downgrowth

    Science.gov (United States)

    Sa-ngiampornpanit, Tarinee; Thiagalingam, Sureka; Dohlman, Claes H.

    2009-01-01

    Introduction To report a case of histologically proven epithelial downgrowth after multiple failed penetrating keratoplasties and glaucoma filtering surgeries that was successfully treated with Boston keratoprosthesis implantation. Materials and Methods A 61-year-old monocular patient had severe congenital ocular syphilis with secondary glaucoma. He had undergone many intraocular surgeries with a history of epithelial downgrowth, and he presented with a failed graft after 7 penetrating keratoplasties. Implantation of a corneal graft with an aphakic type of Boston keratoprosthesis was performed, combined with anterior vitrectomy. The main outcome measures were visual acuity, ocular inflammation and media clarity. Results Media clarity was restored and revealed severe retinal scarring and a pale optic nerve. Best corrected visual acuity of 20/400 was maintained without any further surgical intervention during 6 years follow up. No retroprosthesis membrane or epithelial growth behind the keratoprosthesis was observed. Discussion This is, to our knowledge, the first case of long-term successful treatment of epithelial downgrowth with a Boston keratoprosthesis. This approach might be considered a suitable treatment of epithelial downgrowth. PMID:29276452

  16. Epithelial Mesenchymal Transition in Cancer Progression: Prev entive Phytochemicals.

    Science.gov (United States)

    Illam, Soorya P; Narayanankutty, Arunaksharan; Mathew, Shaji E; Valsalakumari, Remya; Jacob, Rosemol M; Raghavamenon, Achuthan C

    2017-01-01

    Epithelial-Mesenchymal Transition (EMT) is the conversion of epithelial cells into mesenchymal phenotype generally observed during embryogenesis and wound healing as well as in malignant transformation. Several signaling pathways and transcription factors associated with EMT have been explored. Dietary phytochemicals that are multi-targeted agents which interfere with these pathways, assume preventive potential against pathologic EMT. The present review aims to provide a detailed description of the nature and characteristics of EMT in physiological and pathophysiological conditions and the scope of phytochemicals in its prevention. Details regarding the initiation, progression as well as prevention of pathologic EMT and metastasis and recent patents on preventive phytochemicals were obtained from PubMed literatures and patent databases. The phenotypic changes during EMT are regulated by transcription factors like Snail, Slug, Twist and Zeb, which are activated through diverse signaling pathways of TGF-β, NF-kB, Wnt and Notch. s phytocompounds that are potent enough to interfere with these signaling pathways, which in turn prevent pathological implications of EMT. Present review also discusses 28 recent patents on those phytocompounds. EMT is a significant pharmacological target for developing preventive agents to combat pathological conditions like malignancy. Many of the phytochemicals cited in this review are being enrolled for different phases of clinical trials for their efficacy. In spite of the major limitations regarding bioavailability, sensitivity and tolerance of these compounds, their synthetic analogs, formulations and efficient drug delivery systems are also being attempted which will hopefully generate productive and promising results in near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways.

    Directory of Open Access Journals (Sweden)

    Roy Blum

    2010-09-01

    Full Text Available Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells. Here we investigate the distinctive molecular signals of these two stem cell compartments in a mammalian system.We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their differentially expressed genes. To distinguish transcripts that are shared by other developing epithelial/mesenchymal compartments from those that pertain to the prostate stem cell niche, we also determined the global gene expression of epidermis and dermis of the same embryos. Our analysis indicates that several of the key transcriptional components that are predicted to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2, lipid metabolism (e.g., Srebp1 and cell migration (e.g., Areb6 and Rreb1. Several of the enriched promoter binding motifs are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. Based on differential gene expression we also defined ligand-receptor interactions that may be part of the molecular interplay of the embryonic prostate stem cell niche.We provide a comprehensive description of the transcriptional program of the major regulators that are likely to control the cellular interactions in the embryonic prostatic stem cell niche, many of which may be common to mammalian niches in general. This study provides a

  18. Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways.

    Science.gov (United States)

    Blum, Roy; Gupta, Rashmi; Burger, Patricia E; Ontiveros, Christopher S; Salm, Sarah N; Xiong, Xiaozhong; Kamb, Alexander; Wesche, Holger; Marshall, Lisa; Cutler, Gene; Wang, Xiangyun; Zavadil, Jiri; Moscatelli, David; Wilson, E Lynette

    2010-09-30

    Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells. Here we investigate the distinctive molecular signals of these two stem cell compartments in a mammalian system. We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their differentially expressed genes. To distinguish transcripts that are shared by other developing epithelial/mesenchymal compartments from those that pertain to the prostate stem cell niche, we also determined the global gene expression of epidermis and dermis of the same embryos. Our analysis indicates that several of the key transcriptional components that are predicted to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2), lipid metabolism (e.g., Srebp1) and cell migration (e.g., Areb6 and Rreb1). Several of the enriched promoter binding motifs are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. Based on differential gene expression we also defined ligand-receptor interactions that may be part of the molecular interplay of the embryonic prostate stem cell niche. We provide a comprehensive description of the transcriptional program of the major regulators that are likely to control the cellular interactions in the embryonic prostatic stem cell niche, many of which may be common to mammalian niches in general. This study provides a comprehensive source

  19. Epithelial tumours of the lacrimal gland

    DEFF Research Database (Denmark)

    von Holstein, Sarah Linéa; Coupland, Sarah E; Briscoe, Daniel

    2013-01-01

    of the lacrimal gland, displacement of the eyeball, reduced eye motility and diplopia. Pain and symptoms of short duration before the first ophthalmic consultation are characteristic of malignant tumours. The histological diagnosis determines the subsequent treatment regimen and provides important clues regarding...... the prognosis. The purpose of this paper is to describe the various primary epithelial tumours of the lacrimal gland. In the first part of the review, the frequency, demographics, clinical presentation and diagnostic features are described. In the second part, primarily tumour-specific histological...

  20. Nanomaterial induction of oxidative stress in lung epithelial cells and macrophages

    Science.gov (United States)

    Wang, Lin; Pal, Anoop K.; Isaacs, Jacqueline A.; Bello, Dhimiter; Carrier, Rebecca L.

    2014-09-01

    Oxidative stress in the lung epithelial A549 cells and macrophages J774A.1 due to contact with commercially important nanomaterials [i.e., nano-silver (nAg), nano-alumina (nAl2O3), single-wall carbon nanotubes (CNT), and nano-titanium oxide anatase (nTiO2)] was evaluated. Nanomaterial-induced intracellular oxidative stress was analyzed by both H2DCFDA fluorescein probe and GSH depletion, extracellular oxidative stress was assessed by H2HFF fluorescein probes, and the secretion of chemokine IL-8 by A549 cells due to elevation of cellular oxidative stress was also monitored, in order to provide a comprehensive in vitro study on nanomaterial-induced oxidative stress in lung. In addition, results from this study were also compared with an acellular "ferric reducing ability of serum" (FRAS) assay and a prokaryotic cell-based assay in evaluating oxidative damage caused by the same set of nanomaterials, for comparison purposes. In general, it was found that nanomaterial-induced oxidative stress is highly cell-type dependent. In A549 lung epithelial cells, nAg appeared to induce highest level of oxidative stress and cell death followed by CNT, nTiO2, and nAl2O3. Different biological oxidative damage (BOD) assays' (i.e., H2DCFA, GSH, and IL-8 release) results generally agreed with each other, and the same trends of nanomaterial-induced BOD were also observed in acellular FRAS and prokaryotic E. coli K12-based assay. In macrophage J774A.1 cells, nAl2O3 and nTiO2 appeared to induce highest levels of oxidative stress. These results suggest that epithelial and macrophage cell models may provide complimentary information when conducting cell-based assays to evaluate nanomaterial-induced oxidative damage in lung.

  1. Modulation of epithelial sodium channel in human alveolar epithelial ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of lipoxin A4 (LXA4) on the expressions of protein and mRNA of alveolar epithelial sodium channel (ENaC) in normal and lipopolysaccharide (LPS)-stimulated A549 cells. Methods: A549 cell-lines were randomized into 11 groups (N = 8) and treated. EnaC level was evaluated by Western ...

  2. Surgery for advanced epithelial ovarian cancer.

    Science.gov (United States)

    Hacker, Neville F; Rao, Archana

    2017-05-01

    Cytoreductive surgery for patients with advanced epithelial ovarian cancer has been practised since the pioneering work of Tom Griffiths in 1975. Further research has demonstrated the prognostic significance of the extent of metastatic disease pre-operatively, and of complete cytoreduction post-operatively. Patients with advanced epithelial ovarian cancer should be referred to high volume cancer units, and managed by multidisciplinary teams. The role of thoracoscopy and resection of intrathoracic disease is presently investigational. In recent years, there has been increasing use of neoadjuvant chemotherapy and interval cytoreductive surgery in patients with poor performance status, which is usually due to large volume ascites and/or large pleural effusions. Neoadjuvant chemotherapy reduces the post-operative morbidity, but if the tumour responds well to the chemotherapy, the inflammatory response makes the surgery more difficult. Post-operative morbidity is generally tolerable, but increases in older patients, and in those having multiple, aggressive surgical procedures, such as bowel resection or diaphragmatic stripping. Primary cytoreductive surgery should be regarded as the gold standard for most patients until a test is developed which would allow the prediction of platinum resistance pre-operatively. Copyright © 2016. Published by Elsevier Ltd.

  3. Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Joseph U Igietseme

    Full Text Available Chlamydia trachomatis genital infection in women causes serious adverse reproductive complications, and is a strong co-factor for human papilloma virus (HPV-associated cervical epithelial carcinoma. We tested the hypothesis that Chlamydia induces epithelial-mesenchyme transition (EMT involving T cell-derived TNF-alpha signaling, caspase activation, cleavage inactivation of dicer and dysregulation of micro-RNA (miRNA in the reproductive epithelium; the pathologic process of EMT causes fibrosis and fertility-related epithelial dysfunction, and also provides the co-factor function for HPV-related cervical epithelial carcinoma. Using a combination of microarrays, immunohistochemistry and proteomics, we showed that chlamydia altered the expression of crucial miRNAs that control EMT, fibrosis and tumorigenesis; specifically, miR-15a, miR-29b, miR-382 and MiR-429 that maintain epithelial integrity were down-regulated, while miR-9, mi-R-19a, miR-22 and miR-205 that promote EMT, fibrosis and tumorigenesis were up-regulated. Chlamydia induced EMT in vitro and in vivo, marked by the suppression of normal epithelial cell markers especially E-cadherin but up-regulation of mesenchymal markers of pathological EMT, including T-cadherin, MMP9, and fibronectin. Also, Chlamydia upregulated pro-EMT regulators, including the zinc finger E-box binding homeobox protein, ZEB1, Snail1/2, and thrombospondin1 (Thbs1, but down-regulated anti-EMT and fertility promoting proteins (i.e., the major gap junction protein connexin 43 (Cx43, Mets1, Add1Scarb1 and MARCKSL1. T cell-derived TNF-alpha signaling was required for chlamydial-induced infertility and caspase inhibitors prevented both infertility and EMT. Thus, chlamydial-induced T cell-derived TNF-alpha activated caspases that inactivated dicer, causing alteration in the expression of reproductive epithelial miRNAs and induction of EMT. EMT causes epithelial malfunction, fibrosis, infertility, and the enhancement of

  4. From cells to tissue: A continuum model of epithelial mechanics

    Science.gov (United States)

    Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

    2017-08-01

    A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

  5. Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice

    NARCIS (Netherlands)

    Reikvam, D.H.; Derrien, M.M.N.; Islam, R.; Erofeev, A.; Grcic, V.; Sandvik, A.; Gaustad, P.; Meza-Zepeda, L.A.; Jahnsen, F.L.; Smidt, H.; Johansen, F.E.

    2012-01-01

    Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with the large and complex mutualistic gut microbiota. Dimeric IgA and pentameric IgM are transported across the intestinal epithelium via the epithelial polymeric Ig receptor (pIgR) and provide a significant portion of

  6. Simulated Reflux Decreases Vocal Fold Epithelial Barrier Resistance

    Science.gov (United States)

    Erickson, Elizabeth; Sivasankar, Mahalakshmi

    2010-01-01

    Objectives/Hypothesis The vocal fold epithelium provides a barrier to the entry of inhaled and systemic challenges. However, the location of the epithelium makes it vulnerable to damage. Past research suggests, but does not directly demonstrate, that exposure to gastric reflux adversely affects the function of the epithelial barrier. Understanding the nature of reflux-induced epithelial barrier dysfunction is necessary to better recognize the mechanisms for vocal fold susceptibility to this disease. Therefore, we examined the effects of physiologically relevant reflux challenges on vocal fold transepithelial resistance and gross epithelial and subepithelial appearance. Study Design Ex vivo, mixed design with between-group and repeated-measures analyses. Methods Healthy, native porcine vocal folds (N = 52) were exposed to physiologically relevant acidic pepsin, acid-only, or pepsin-only challenges and examined with electrophysiology and light microscopy. For all challenges, vocal folds exposed to a neutral pH served as control. Results Acidic pepsin and acid-only challenges, but not pepsin-only or control challenges significantly reduced transepithelial resistance within 30 minutes. Reductions in transepithelial resistance were irreversible. Challenge exposure produced minimal gross changes in vocal fold epithelial or subepithelial appearance as evidenced by light microscopy. Conclusions These findings demonstrate that acidic environments characteristic of gastric reflux compromise epithelial barrier function without gross structural changes. In healthy, native vocal folds, reductions in transepithelial resistance could reflect reflux-related epithelial disruption. These results might guide the development of pharmacologic and therapeutic recommendations for patients with reflux, such as continued acid-suppression therapy and patient antireflux behavioral education. PMID:20564752

  7. Activated alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor.

    Science.gov (United States)

    Yang, Jibing; Velikoff, Miranda; Canalis, Ernesto; Horowitz, Jeffrey C; Kim, Kevin K

    2014-04-15

    Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis remains poorly defined. Profibrotic cytokines may activate epithelial cells with protein expression and functions that overlap with the functions of active fibroblasts. We found that alveolar epithelial cells undergoing TGF-β-mediated mesenchymal transition in vitro were also capable of activating lung fibroblasts through production of CTGF. Alveolar epithelial cell expression of CTGF was dramatically reduced by inhibition of Rho signaling. CTGF reporter mice demonstrated increased CTGF promoter activity by lung epithelial cells acutely after bleomycin in vivo. Furthermore, mice with lung epithelial cell-specific deletion of CTGF had an attenuated fibrotic response to bleomycin. These studies provide direct evidence that epithelial cell activation initiates a cycle of fibrogenic effector cell activation during progressive fibrosis. Therapy targeted at epithelial cell production of CTGF offers a novel pathway for abrogating this progressive cycle and limiting tissue fibrosis.

  8. Intestinal transport: studies with isolated epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kimmich, G.A.

    1979-12-01

    Isolated intestinal epithelial cells have been extremely useful for characterizing the nature of intestinal absorption processes and for providing insight into the energetics of Na/sup +/-dependent transport systems. This report describes a number of experimental approaches which have been used for investigating the specific epithelial transport systems involved in sugar absorption, but provides information which ultimately should prove useful for characterizing a number of different intestinal transport events. Similar experiments should also prove useful for exploring the effect of environmental agents on the function of intestinal tissue. In the case of sugars, net absorption is accomplished via a mucosal, Na/sup +/-dependent concentrative transport system acting in sequence with a passive serosal system which does not require Na/sup +/. The serosal system limits the full gradient-forming capability of the muscosal system. Agents such as phloretin or cytochalasin B which inhibit serosal transport allow the cells to establish sugar gradients as high as 70 fold in contrast to 10 to 15 fold gradients observed for control cells. Sevety-fold sugar gradients cannot be explained in terms of the energy available in the electrochemical potential for Na/sup +/ if the Na/sub 2/: sugar coupling stoichiometry is 1:1 as commonly assumed. New information indicates that the true Na/sup +/:sugar stoichiometry is in fact 2:1. Flow of two Na/sup +/ ions per sugar molecule down the transmembrane electrochemical potential for Na/sup +/ provides more than sufficient energy to account for observed 70 fold sugar gradients. If flow of sugar by other routes could be completely inhibited, theoretical sugar gradients as high as 400 could be achieved assuming that the cells maintain a membrane potential of -36 mV as measured for intact tissue.

  9. Hyperinsulinemia-induced PAX6 expression promotes endometrial epithelial cell proliferation via negatively modulating p27 signaling.

    Science.gov (United States)

    Zheng, Xue-Rong; Pan, Xia; Zhang, Jin; Cao, Xin

    2018-01-01

    Polycystic ovarian syndrome (PCOS) is thought to involve hyperinsulinism (insulin resistance, IR) and high prevalence of endometrial epithelial hyperplasia, but how these two pathologies are synergistically regulated in endometrial epithelial cells remains largely unknown. Here, we report a key role for the transcription factor PAX6 in the modulation of PCOS-induced endometrial epithelial proliferation. PAX6 was significantly induced in the endometrial tissues from PCOS patients, and this induction, regulated upstream by high levels of insulin, was closely correlated to the pathogenesis of IR in endometrial epithelial cells. Overexpression of the exogenous PAX6 potentiated the insulin-elicited accumulation of S phase in endometrial epithelial cells and thereby promoted endometrial epithelial proliferation. In parallel, by using luciferase reporter and ChIP assay, we found that PAX6 directly bound to the promoter of CDKN1B gene (the gene encoding p27 protein, a negative regulator of cell cycle) and inhibited CDKN1B transcription in the insulin-stimulated endometrial epithelial cells. We conclude that excessive PAX6 expression in insulin-challenged endometrial epithelial cells may contribute to the uncontrollable endometrial epithelial proliferation. Our results also provide a mechanistic explanation for the functional link between hyperinsulinemia and p27 loss in the pathogenesis of endometrial epithelial hyperplasia in PCOS patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Acinetobacter baumannii invades epithelial cells and outer membrane protein A mediates interactions with epithelial cells

    National Research Council Canada - National Science Library

    Choi, Chul Hee; Lee, Jun Sik; Lee, Yoo Chul; Park, Tae In; Lee, Je Chul

    2008-01-01

    ... of A. baumannii outer membrane protein A (AbOmpA) in interactions with epithelial cells. A. baumannii invaded epithelial cells by a zipper-like mechanism, which is associated with microfilament- and microtubule-dependent uptake mechanisms...

  11. Isolation and culture of biliary epithelial cells.

    OpenAIRE

    Joplin, R

    1994-01-01

    At one time it was thought that biliary epithelial cells simply formed the lining to the tubular conduits which constitute the biliary tract. Development of in vitro systems for culturing biliary epithelial cells has enabled functional studies which increasingly show that this is far from true, and that biliary epithelial cells do have important functional roles. Disruption of these functions may be involved in the generation of pathology. Most functional studies to date have utilised cells i...

  12. Gene expression correlations in human cancer cell lines define molecular interaction networks for epithelial phenotype.

    Science.gov (United States)

    Kohn, Kurt W; Zeeberg, Barry M; Reinhold, William C; Pommier, Yves

    2014-01-01

    Using gene expression data to enhance our knowledge of control networks relevant to cancer biology and therapy is a challenging but urgent task. Based on the premise that genes that are expressed together in a variety of cell types are likely to functions together, we derived mutually correlated genes that function together in various processes in epithelial-like tumor cells. Expression-correlated genes were derived from data for the NCI-60 human tumor cell lines, as well as data from the Broad Institute's CCLE cell lines. NCI-60 cell lines that selectively expressed a mutually correlated subset of tight junction genes served as a signature for epithelial-like cancer cells. Those signature cell lines served as a seed to derive other correlated genes, many of which had various other epithelial-related functions. Literature survey yielded molecular interaction and function information about those genes, from which molecular interaction maps were assembled. Many of the genes had epithelial functions unrelated to tight junctions, demonstrating that new function categories were elicited. The most highly correlated genes were implicated in the following epithelial functions: interactions at tight junctions (CLDN7, CLDN4, CLDN3, MARVELD3, MARVELD2, TJP3, CGN, CRB3, LLGL2, EPCAM, LNX1); interactions at adherens junctions (CDH1, ADAP1, CAMSAP3); interactions at desmosomes (PPL, PKP3, JUP); transcription regulation of cell-cell junction complexes (GRHL1 and 2); epithelial RNA splicing regulators (ESRP1 and 2); epithelial vesicle traffic (RAB25, EPN3, GRHL2, EHF, ADAP1, MYO5B); epithelial Ca(+2) signaling (ATP2C2, S100A14, BSPRY); terminal differentiation of epithelial cells (OVOL1 and 2, ST14, PRSS8, SPINT1 and 2); maintenance of apico-basal polarity (RAB25, LLGL2, EPN3). The findings provide a foundation for future studies to elucidate the functions of regulatory networks specific to epithelial-like cancer cells and to probe for anti-cancer drug targets.

  13. Activation of epithelial STAT3 regulates intestinal homeostasis.

    Science.gov (United States)

    Neufert, Clemens; Pickert, Geethanjali; Zheng, Yan; Wittkopf, Nadine; Warntjen, Moritz; Nikolaev, Alexei; Ouyang, Wenjun; Neurath, Markus F; Becker, Christoph

    2010-02-15

    The intestinal epithelium that lines the mucosal surface along the GI-tract is a key player for the intestinal homeostasis of the healthy individual. In case of a mucosal damage or a barrier defect as seen in patients with inflammatory bowel disease, the balance is disturbed, and translocation of intestinal microbes to the submucosa is facilitated. We recently demonstrated a pivotal role of STAT3 activation in intestinal epithelial cells (IEC) for the restoration of the balance at the mucosal surface of the gut in an experimental colitis model. STAT3 was rapidly induced in intestinal epithelial cells upon challenge of mice in both experimental colitis and intestinal wound healing models. STAT3 activation was found to be dispensable in the steady-state conditions but was important for efficient regeneration of the epithelium in response to injury. Here, we extend our previous findings by showing epithelial STAT3 activation in human patients suffering from IBD and provide additional insights how the activation of epithelial STAT3 by IL-22 regulates intestinal homeostasis and mucosal wound healing. We also demonstrate that antibody-mediated neutralization of IL-22 has little impact on the development of experimental colitis in mice, but significantly delays recovery from colitis. Thus, our data suggest that targeting the STAT3 signaling pathway in IEC is a promising therapeutic approach in situations when the intestinal homeostasis is disturbed, e.g., as seen in Crohn's disease or Ulcerative colitis.

  14. Crosstalk between epithelial and mesenchymal tissues in tumorigenesis and imaginal disc development.

    Science.gov (United States)

    Herranz, Héctor; Weng, Ruifen; Cohen, Stephen M

    2014-07-07

    Cancers develop in a complex mutational landscape. Interaction of genetically abnormal cancer cells with normal stromal cells can modify the local microenvironment to promote disease progression for some tumor types. Genetic models of tumorigenesis provide the opportunity to explore how combinations of cancer driver mutations confer distinct properties on tumors. Previous Drosophila models of EGFR-driven cancer have focused on epithelial neoplasia. Here, we report a Drosophila genetic model of EGFR-driven tumorigenesis in which the neoplastic transformation depends on interaction between epithelial and mesenchymal cells. We provide evidence that the secreted proteoglycan Perlecan can act as a context-dependent oncogene cooperating with EGFR to promote tumorigenesis. Coexpression of Perlecan in the EGFR-expressing epithelial cells potentiates endogenous Wg/Wnt and Dpp/BMP signals from the epithelial cells to support expansion of a mesenchymal compartment. Wg activity is required in the epithelial compartment, whereas Dpp activity is required in the mesenchymal compartment. This genetically normal mesenchymal compartment is required to support growth and neoplastic transformation of the genetically modified epithelial population. We report a genetic model of tumor formation that depends on crosstalk between a genetically modified epithelial cell population and normal host mesenchymal cells. Tumorigenesis in this model co-opts a regulatory mechanism that is normally involved in controlling growth of the imaginal disc during development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Inhibition of activated Ras suppresses multiple oncogenic Hub genes in human epithelial tumors.

    Science.gov (United States)

    Cao, Lei; Wang, Ping; Luo, Hui; Wang, Xi-Rui; Wang, Xie-Feng; Zhang, Jun-Xia; Wang, Ying-Yi; Yao, Lei; Liu, Ning; You, Yong-Ping

    2014-10-01

    Cancer cells may involve diverse mutations, but they often rely on continued expression of a single oncoprotein for survival, as a response to targeting this protein. Generally, Ras is overexpressed in human epithelial tumors and cancellation of activated Ras inhibits carcinoma cell proliferation and differentiation ability, and induces apoptotosis of tumor cells. However, the mechanisms of inhibition of activated Ras that suppress the malignancy activity of human epithelial tumors remain to be illuminated. We utilized text-mining of MEDLINE abstracts with natural language processing to establish the Ras biologic association network, and identified several interactions of this network with the Ras pathway. Our investigation not only examined the expression of Ras and Hub genes (PIK3CA, MDM2, CCND1, EGFR, JUN, MYC, VEGFA, ERK1 and ERK2) but also confirmed inhibition of activated Ras reduced expression of multiple oncogene in vitro studies. Our studies provide strong support for the conclusion that cancellation of activated Ras specifically regulates defective Ras pathways in human tumor cells.

  16. Dual-mode endomicroscopy for detection of epithelial dysplasia in the mouth: a descriptive pilot study

    Science.gov (United States)

    Bodenschatz, Nico; Poh, Catherine F.; Lam, Sylvia; Lane, Pierre; Guillaud, Martial; MacAulay, Calum E.

    2017-08-01

    Dual-mode endomicroscopy is a diagnostic tool for early cancer detection. It combines the high-resolution nuclear tissue contrast of fluorescence endomicroscopy with quantified depth-dependent epithelial backscattering as obtained by diffuse optical microscopy. In an in vivo pilot imaging study of 27 oral lesions from 21 patients, we demonstrate the complementary diagnostic value of both modalities and show correlations between grade of epithelial dysplasia and relative depth-dependent shifts in light backscattering. When combined, the two modalities provide diagnostic sensitivity to both moderate and severe epithelial dysplasia in vivo.

  17. Gastrin and gastric epithelial physiology

    Science.gov (United States)

    Dockray, G J

    1999-01-01

    Transepithelial transducing cells, particularly the gastrin (G) cell, co-ordinate gastric acid secretion with the arrival of food in the stomach. Recent work suggests that multiple active products are generated from the gastrin precursor, and that there are multiple control points in gastrin biosynthesis. Biosynthetic precursors and intermediates (progastrin and Gly-gastrins) are putative growth factors; their products, the amidated gastrins, regulate epithelial cell proliferation, the differentiation of acid-producing parietal cells and histamine-secreting enterochromaffin-like (ECL) cells, and the expression of genes associated with histamine synthesis and storage in ECL cells, as well as acutely stimulating acid secretion. Gastrin also stimulates the production of members of the epidermal growth factor (EGF) family, which in turn inhibit parietal cell function but stimulate the growth of surface epithelial cells. Plasma gastrin concentrations are elevated in subjects with Helicobacter pylori, who are known to have increased risk of duodenal ulcer disease and gastric cancer. Studies of the physiology of gastrin may therefore contribute to an understanding of the mechanisms relevant to major upper gastrointestinal tract disease. PMID:10381581

  18. Epithelial Cells in Urine: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... page: https://medlineplus.gov/labtests/epithelialcellsinurine.html Epithelial Cells in Urine To use the sharing features on ... page, please enable JavaScript. What is an Epithelial Cells in Urine Test? Epithelial cells are a type ...

  19. Engineering stromal-epithelial interactions in vitro for toxicology assessment

    Science.gov (United States)

    Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo t...

  20. Andrographolide suppresses epithelial mesenchymal transition by ...

    Indian Academy of Sciences (India)

    Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown.

  1. Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression.

    Science.gov (United States)

    Chen, Huanhuan; Deng, Zaian; Huang, Chuncui; Wu, Hongmei; Zhao, Xia; Li, Yan

    2017-07-01

    Aberrant changes of N-glycan modifications on proteins have been linked to various diseases including different cancers, suggesting possible avenue for exploring their etiologies based on N-glycomic analysis. Changes in N-glycan patterns during epithelial ovarian cancer development have so far been investigated mainly using serum, plasma, ascites, and cell lines. However, changes in patterns of N-glycans in tumor tissues during epithelial ovarian cancer progression have remained largely undefined. To investigate whether changes in N-glycan patterns correlate with oncogenesis and progression of epithelial ovarian cancer, we profiled N-glycans from formalin-fixed paraffin-embedded tissue slides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitatively compared among different pathological grades of epithelial ovarian cancer and healthy controls. Our results show that among the 80 compositions of N-glycan detected, expression levels of high-mannose type were higher in epithelial ovarian cancer samples than that observed in healthy controls, accompanied by reduced levels of hybrid-type glycans. By applying receiver operating characteristic analysis, we show that a combined panel composed of four high-mannose and three fucosylated neutral complex N-glycans allows for good discrimination of epithelial ovarian cancer from healthy controls. Furthermore, using a statistical analysis of variance assay, we found that different N-glycan patterns, including 2 high-mannose-type, 2 fucosylated and sialylated complex structures, and 10 fucosylated neutral complex N-glycans, exhibited specific changes in N-glycan abundance across epithelial ovarian cancer grades. Together, our results provide strong evidence that N-glycomic changes are a strong indicator for epithelial ovarian cancer pathological grades and should provide avenues to identify novel biomarkers for epithelial ovarian cancer diagnosis and monitoring.

  2. Epithelial cell adhesion and gastrointestinal colonization of Lactobacillus in poultry.

    Science.gov (United States)

    Spivey, Megan A; Dunn-Horrocks, Sadie L; Duong, Tri

    2014-11-01

    Administration of probiotic Lactobacillus cultures is an important alternative to the use of antibiotic growth promoters and has been demonstrated to improve animal health, growth performance, and preharvest food safety in poultry production. Whereas gastrointestinal colonization is thought to be critical to their probiotic functionality, factors important to Lactobacillus colonization in chickens are not well understood. In this study we investigate epithelial cell adhesion in vitro and colonization of Lactobacillusin vivo in broiler chickens. Adhesion of Lactobacillus cultures to epithelial cells was evaluated using the chicken LMH cell line. Lactobacillus cultures were able adhere effectively to LMH cells relative to Bacillus subtilis and Salmonella Typhimurium. Epithelial cell adhesion was similar for Lactobacillus crispatus TDCC 75, L. cristpatus TDCC 76, and Lactobacillus gallinarum TDCC 77, and all 3 were more adherent than L. gallinarum TDCC 78. However, when colonization was evaluated in the ileum and cecum of broiler chicks, L. crispatus TDCC 75 and L. gallinarum TDCC 77 were more persistent than L. crispatus TDCC 76 and L. gallinarum TDCC 78. The reduction of growth in medium supplemented with oxgal was greater for L. gallinarum TDCC 78 than L. gallinarum TDCC 77, suggesting that whereas adhesion was similar for the 2 strains, the difference in colonization between L. gallinarum strains may be due in part to their bile sensitivity. This study demonstrates that whereas adhesion to epithelial cells may be important in predicting gastrointestinal colonization, other factors including bile tolerance may also contribute to the colonization of Lactobacillus in poultry. Additionally, the chicken LMH cell line is expected to provide a platform for investigating mechanisms of Lactobacillus adhesion to epithelial tissue and evaluating the probiotic potential Lactobacillus in poultry. ©2014 Poultry Science Association Inc.

  3. Biomaterial surface proteomic signature determines interaction with epithelial cells.

    Science.gov (United States)

    Abdallah, Mohamed-Nur; Tran, Simon D; Abughanam, Ghada; Laurenti, Marco; Zuanazzi, David; Mezour, Mohamed A; Xiao, Yizhi; Cerruti, Marta; Siqueira, Walter L; Tamimi, Faleh

    2017-05-01

    Cells interact with biomaterials indirectly through extracellular matrix (ECM) proteins adsorbed onto their surface. Accordingly, it could be hypothesized that the surface proteomic signature of a biomaterial might determine its interaction with cells. Here, we present a surface proteomic approach to test this hypothesis in the specific case of biomaterial-epithelial cell interactions. In particular, we determined the surface proteomic signature of different biomaterials exposed to the ECM of epithelial cells (basal lamina). We revealed that the biomaterial surface chemistry determines the surface proteomic profile, and subsequently the interaction with epithelial cells. In addition, we found that biomaterials with surface chemistries closer to that of percutaneous tissues, such as aminated PMMA and aminated PDLLA, promoted higher selective adsorption of key basal lamina proteins (laminins, nidogen-1) and subsequently improved their interactions with epithelial cells. These findings suggest that mimicking the surface chemistry of natural percutaneous tissues can improve biomaterial-epithelial integration, and thus provide a rationale for the design of improved biomaterial surfaces for skin regeneration and percutaneous medical devices. Failure of most biomaterials originates from the inability to predict and control the influence of their surface properties on biological phenomena, particularly protein adsorption, and cellular behaviour, which subsequently results in unfavourable host response. Here, we introduce a surface-proteomic screening approach using a label-free mass spectrometry technique to decipher the adsorption profile of extracellular matrix (ECM) proteins on different biomaterials, and correlate it with cellular behaviour. We demonstrated that the way a biomaterial selectively interacts with specific ECM proteins of a given tissue seems to determine the interactions between the cells of that tissue and biomaterials. Accordingly, this approach can

  4. Computational investigation of epithelial cell dynamic phenotype in vitro

    Directory of Open Access Journals (Sweden)

    Debnath Jayanta

    2009-05-01

    Full Text Available Abstract Background When grown in three-dimensional (3D cultures, epithelial cells typically form cystic organoids that recapitulate cardinal features of in vivo epithelial structures. Characterizing essential cell actions and their roles, which constitute the system's dynamic phenotype, is critical to gaining deeper insight into the cystogenesis phenomena. Methods Starting with an earlier in silico epithelial analogue (ISEA1 that validated for several Madin-Darby canine kidney (MDCK epithelial cell culture attributes, we built a revised analogue (ISEA2 to increase overlap between analogue and cell culture traits. Both analogues used agent-based, discrete event methods. A set of axioms determined ISEA behaviors; together, they specified the analogue's operating principles. A new experimentation framework enabled tracking relative axiom use and roles during simulated cystogenesis along with establishment of the consequences of their disruption. Results ISEA2 consistently produced convex cystic structures in a simulated embedded culture. Axiom use measures provided detailed descriptions of the analogue's dynamic phenotype. Dysregulating key cell death and division axioms led to disorganized structures. Adhering to either axiom less than 80% of the time caused ISEA1 to form easily identified morphological changes. ISEA2 was more robust to identical dysregulation. Both dysregulated analogues exhibited characteristics that resembled those associated with an in vitro model of early glandular epithelial cancer. Conclusion We documented the causal chains of events, and their relative roles, responsible for simulated cystogenesis. The results stand as an early hypothesis–a theory–of how individual MDCK cell actions give rise to consistently roundish, cystic organoids.

  5. Epithelial antibiotic induced in states of disease

    Science.gov (United States)

    Stolzenberg, Ethan D.; Anderson, G. Mark; Ackermann, Mark R.; Whitlock, Robert H.; Zasloff, Michael

    1997-01-01

    Epithelial defensins provide an active defense against the external microbial environment. We investigated the distribution and expression of this class of antimicrobial peptides in normal cattle and in animals in varying states of disease. β-defensin mRNA was found to be widely expressed in numerous exposed epithelia but was found at higher levels in tissues that are constantly exposed to and colonized by microorganisms. We observed induction in ileal mucosa during chronic infection with Mycobacterium paratuberculosis and in bronchial epithelium after acute infection with Pasteurella haemolytica. It has been proposed that expression of antimicrobial peptides is an integral component of the inflammatory response. The results reported here support this hypothesis and suggest that epithelial defensins provide a rapidly mobilized local defense against infectious organisms. PMID:9238038

  6. A multicellular view of cytokinesis in epithelial tissue.

    Science.gov (United States)

    Herszterg, Sophie; Pinheiro, Diana; Bellaïche, Yohanns

    2014-05-01

    The study of cytokinesis in single-cell systems provided a wealth of knowledge on the molecular and biophysical mechanisms controlling daughter cell separation. In this review, we outline recent advances in the understanding of cytokinesis in epithelial tissues. These findings provide evidence for how the cytokinetic machinery adapts to a multicellular context and how the cytokinetic machinery is itself exploited by the tissue for the preservation of tissue function and architecture during proliferation. We propose that cytokinesis in epithelia should be viewed as a multicellular process, whereby the biochemical and mechanical interactions between the dividing cell and its neighbors are essential for successful daughter cell separation while defining epithelial tissue organization and preserving tissue integrity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. γδ T cells in homeostasis and host defence of epithelial barrier tissues.

    Science.gov (United States)

    Nielsen, Morten M; Witherden, Deborah A; Havran, Wendy L

    2017-12-01

    Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body - namely, the epidermis and the intestine - and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity and repair, host homeostasis and protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance. Finally, we describe epithelium-specific butyrophilin-like molecules and briefly review their emerging role in selectively shaping and regulating epidermal and intestinal γδ T cell repertoires.

  8. Ovarian Epithelial-Stromal Interactions: Role of Interleukins 1 and 6

    Directory of Open Access Journals (Sweden)

    Kamisha T. Woolery

    2011-01-01

    Full Text Available Ovarian epithelial cancer is the most lethal gynecologic malignancy. The high mortality is attributed to the fact that most cases typically present in late stage when ovarian cancer (OC has already spread beyond the ovary. Ovarian epithelial cancer cells are shed into intraperitoneal ascites and easily disseminate throughout the peritoneal cavity with preferential metastasis to the omentum, peritoneum, and local organs. Understanding how ovarian epithelial cells interact with and modulate their microenvironment can provide insight into the molecular mechanism(s involved with malignant transformation and progression which may eventually identify novel diagnostic, prognostic, and therapeutic targets. The objective of this paper is to provide a brief consideration of ovarian surface epithelial-stromal interactions in regard to normal physiological function and tumor progression as influenced by two potentially key interleukins, interleukins-1 (IL-1 and -6 (IL-6, present in the microenvironment. Lastly, we will consider the clinical implications of IL-1 and IL-6 for OC patients.

  9. [Epithelial dysfunction associated with pyo-inflammatory diseases of the ENT organs].

    Science.gov (United States)

    Petukhova, N A

    2017-01-01

    The modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome associated with pyo-inflammatory ENT diseases is presented. It has provided a basis for the analysis of the initial stages of etiopathogenesis of acute and chronic inflammation in the ENT system including the mucous and associated lymphoid tissues as well as the Pirogov-Waldeyer limphopharyngeal ring making up the first protective barrier. The leading role of dysbiosis of synanthropic microflora and endotoxins of the Gram-negative bacteria in the mechanisms of regional responsiveness of the organism to the infection and chronic endotoxic aggression is demonstrated. The regional and synthetic mechanisms underlying the interaction between the external and internal media of the organism are subjected to the analysis with special reference to those operating in epithelium. The possible variants of the outcome of these processes are considered including both the recovery and the development of chronic inflammation. It has been proved that the exhaustion of the internal reserves for the stabilization of the epithelium-associated lymphoid tissue system including the Pirogov-Waldeyer limphopharyngeal ring leads to the formation of epithelial dysfunction as the initial stage of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome. It is concluded that the modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome is a fundamental interdisciplinary phenomenon.

  10. Effects of Weaning on Intestinal Upper Villus Epithelial Cells of Piglets

    Science.gov (United States)

    Wang, Xiaocheng; Tan, Bie; Li, Tiejun; Yin, Yulong

    2016-01-01

    The intestinal upper villus epithelial cells represent the differentiated epithelial cells and play key role in digesting and absorbing lumenal nutrients. Weaning stress commonly results in a decrease in villus height and intestinal dysfunction in piglets. However, no study have been conducted to test the effects of weaning on the physiology and functions of upper villus epithelial cells. A total of 40 piglets from 8 litters were weaned at 14 days of age and one piglet from each litter was killed at 0 d (w0d), 1 d (w1d), 3 d (w3d), 5 d (w5d), and 7 d (w7d) after weaning, respectively. The upper villus epithelial cells in mid-jejunum were isolated using the distended intestinal sac method. The expression of proteins in upper villus epithelial cells was analyzed using the isobaric tags for relative and absolute quantification or Western blotting. The expression of proteins involved in energy metabolism, Golgi vesicle transport, protein amino acid glycosylation, secretion by cell, transmembrane transport, ion transport, nucleotide catabolic process, translational initiation, and epithelial cell differentiation and apoptosis, was mainly reduced during the post-weaning period, and these processes may be regulated by mTOR signaling pathway. These results indicated that weaning inhibited various cellular processes in jejunal upper villus epithelial cells, and provided potential new directions for exploring the effects of weaning on the functions of intestine and improving intestinal functions in weaning piglets. PMID:27022727

  11. Peritoneal inflammation – A microenvironment for Epithelial Ovarian Cancer (EOC)

    OpenAIRE

    Liu Jinsong; Deavers Michael; Freedman Ralph S; Wang Ena

    2004-01-01

    Abstract Epithelial ovarian cancer (EOC) is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relati...

  12. Developing an ancient epithelial appendage: FGF signalling regulates early tail denticle formation in sharks

    OpenAIRE

    Rory L. Cooper; Kyle J. Martin; Liam J. Rasch; Gareth J. Fraser

    2017-01-01

    Background Vertebrate epithelial appendages constitute a diverse group of organs that includes integumentary structures such as reptilian scales, avian feathers and mammalian hair. Recent studies have provided new evidence for the homology of integumentary organ development throughout amniotes, despite their disparate final morphologies. These structures develop from conserved molecular signalling centres, known as epithelial placodes. It is not yet certain whether this homology extends beyon...

  13. Alternaria induces STAT-6 dependent acute airway eosinophila and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness

    Science.gov (United States)

    Doherty, Taylor A.; Khorram, Naseem; Sugimoto, Kotaro; Sheppard, Dean; Rosenthal, Peter; Youn Cho, Jae; Pham, Alexa; Miller, Marina; Croft, Michael; Broide, David H.

    2012-01-01

    The fungal allergen, Alternaria, is specifically associated with severe asthma, including life-threatening exacerbations. To better understand the acute innate airway response to Alternaria, naïve WT mice were challenged once intranasally with Alternaria. Naïve WT mice developed significant BAL eosinophila following Alternaria challenge when analyzed 24 hours later. In contrast to Alternaria, neither Aspergillus nor Candida induced BAL eosinophilia. Gene microarray analysis of airway epithelial cell brushings demonstrated that Alternaria-challenged naïve WT mice had an over 20 fold increase level of expression of “Found in Inflammatory Zone 1” (FIZZ1/Retnla), a resistin-like molecule. Lung immunostaining confirmed strong airway epithelial FIZZ1 expression present as early as 3 hours after a single Alternaria challenge that persisted for at least 5 days and was significantly reduced in STAT6-deficient, but not PAR-2-deficient mice. Bone marrow chimera studies revealed that STAT6 expressed in lung cells was required for epithelial FIZZ1 expression, while in contrast, STAT6 present in bone marrow derived cells contributed to airway eosinophilia. Studies investigating which cells in the non-challenged lung bind FIZZ1 demonstrated that CD45+CD11c+ (macrophages and dendritic cells) as well as collagen-1 producing CD45 negative cells (fibroblasts) can bind to FIZZ1. Importantly, direct administration of recombinant FIZZ1 to naïve WT mice led to airway eosinophilia, peribronchial fibrosis, and increased thickness of the airway epithelium. Thus, Alternaria induces STAT-6 dependent acute airway eosinophila and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness. This may provide some insight into the uniquely pathogenic aspects of Alternaria-associated asthma. PMID:22327070

  14. Epithelial Antimicrobial Peptides: Guardian of the Oral Cavity

    Directory of Open Access Journals (Sweden)

    Mayank Hans

    2014-01-01

    Full Text Available Gingival epithelium provides first line of defence from the microorganisms present in dental plaque. It not only provides a mechanical barrier but also has an active immune function too. Gingival epithelial cells participate in innate immunity by producing a range of antimicrobial peptides to protect the host against oral pathogens. These epithelial antimicrobial peptides (EAPs include the β-defensin family, cathelicidin (LL-37, calprotectin, and adrenomedullin. While some are constitutively expressed in gingival epithelial cells, others are induced upon exposure to microbial insults. It is likely that these EAPs have a role in determining the initiation and progression of oral diseases. EAPs are broad spectrum antimicrobials with a different but overlapping range of activity. Apart from antimicrobial activity, they participate in several other crucial roles in host tissues. Some of these, for instance, β-defensins, are chemotactic to immune cells. Others, such as calprotectin are important for wound healing and cell proliferation. Adrenomedullin, a multifunctional peptide, has its biological action in a wide range of tissues. Not only is it a potent vasodilator but also it has several endocrine effects. Knowing in detail the various bioactions of these EAPs may provide us with useful information regarding their utility as therapeutic agents.

  15. Epithelial myoepithelial carcinoma of the parotid gland

    Directory of Open Access Journals (Sweden)

    Sachin A Badge

    2015-01-01

    Full Text Available Epithelial-myoepithelial carcinoma (EMC is a low-grade malignant tumor of the salivary glands. It is extremely rare neoplasm accounting for <1% of all salivary gland neoplasms. It is most commonly seen in parotid gland, but has also been described in the submandibular gland, minor salivary glands and extra oral sites. It is most commonly seen in females; with a peak occurrence in the seventh decade. We present a case of EMC of parotid gland in a 55-year-old male patient presented with painless swelling of 8 cm × 8 cm in preauricular region since 1-year. There was no history of fever and no palpable cervical lymphadenopathy. Facial nerve function was intact. All other findings in general examination were within normal limit. As EMC is a very rare tumor having high rate of recurrence we must aware of this entity while giving diagnosis on histopathological examination. Surgeons and oncologist must focus on the best treatment approach to prevent the recurrence of this tumor. Wide local excision, followed by radiotherapy remains the treatment of choice.

  16. Patterning bacterial communities on epithelial cells.

    Directory of Open Access Journals (Sweden)

    Mohammed Dwidar

    Full Text Available Micropatterning of bacteria using aqueous two phase system (ATPS enables the localized culture and formation of physically separated bacterial communities on human epithelial cell sheets. This method was used to compare the effects of Escherichia coli strain MG1655 and an isogenic invasive counterpart that expresses the invasin (inv gene from Yersinia pseudotuberculosis on the underlying epithelial cell layer. Large portions of the cell layer beneath the invasive strain were killed or detached while the non-invasive E. coli had no apparent effect on the epithelial cell layer over a 24 h observation period. In addition, simultaneous testing of the localized effects of three different bacterial species; E. coli MG1655, Shigella boydii KACC 10792 and Pseudomonas sp DSM 50906 on an epithelial cell layer is also demonstrated. The paper further shows the ability to use a bacterial predator, Bdellovibriobacteriovorus HD 100, to selectively remove the E. coli, S. boydii and P. sp communities from this bacteria-patterned epithelial cell layer. Importantly, predation and removal of the P. Sp was critical for maintaining viability of the underlying epithelial cells. Although this paper focuses on a few specific cell types, the technique should be broadly applicable to understand a variety of bacteria-epithelial cell interactions.

  17. Role of CFTR in epithelial physiology.

    Science.gov (United States)

    Saint-Criq, Vinciane; Gray, Michael A

    2017-01-01

    Salt and fluid absorption and secretion are two processes that are fundamental to epithelial function and whole body fluid homeostasis, and as such are tightly regulated in epithelial tissues. The CFTR anion channel plays a major role in regulating both secretion and absorption in a diverse range of epithelial tissues, including the airways, the GI and reproductive tracts, sweat and salivary glands. It is not surprising then that defects in CFTR function are linked to disease, including life-threatening secretory diarrhoeas, such as cholera, as well as the inherited disease, cystic fibrosis (CF), one of the most common life-limiting genetic diseases in Caucasian populations. More recently, CFTR dysfunction has also been implicated in the pathogenesis of acute pancreatitis, chronic obstructive pulmonary disease (COPD), and the hyper-responsiveness in asthma, underscoring its fundamental role in whole body health and disease. CFTR regulates many mechanisms in epithelial physiology, such as maintaining epithelial surface hydration and regulating luminal pH. Indeed, recent studies have identified luminal pH as an important arbiter of epithelial barrier function and innate defence, particularly in the airways and GI tract. In this chapter, we will illustrate the different operational roles of CFTR in epithelial function by describing its characteristics in three different tissues: the airways, the pancreas, and the sweat gland.

  18. Identification of epithelial cells in bronchoalveolar lavage.

    Science.gov (United States)

    Finotto, S; Rado, V; Dal Vecchio, A; Milani, G; Fabbri, L M; Maestrelli, P

    1993-01-01

    1. Damage to the bronchial epithelium occurs after the inhalation of toxic substances and allergens, and through virus infections and it may lead to increased desquamation of epithelial cells in bronchoalveolar lavage (BAL). 2. In this study we compared two methods of staining the epithelial cells of BAL, the conventional cytochemical May Grunwald-Giemsa stain (MGG) and an immunocytochemical technique using a monoclonal antibody anti-human cytokeratin (CK) detected with APAAP immuno-alkaline phosphatase. BAL was obtained from 13 subjects and the epithelial cells were cytocentrifuged either immediately after collection (fraction A) or after washing (fraction B). 3. Higher percentages of epithelial cells were identified in fraction A with CK (20.0 +/- 5.1%) than in fraction A with MGG (11.2 +/- 2.3%), which recognized only ciliated epithelial cells. In fact a proportion of CK-positive cells (34%) in fraction A were not ciliated. Underestimation of epithelial cells by MGG compared to CK was more pronounced in fraction B (8.0 +/- 2.9% and 22.9 +/- 3.0%, respectively) as there was a relative loss of ciliated CK+ cells after washings. 4. These results suggest that immunocytochemical staining with an anti-cytokeratin monoclonal antibody is more sensitive than using the MGG stain in detecting epithelial cells in BAL.

  19. Sodium selectivity of semicircular canal duct epithelial cells

    Directory of Open Access Journals (Sweden)

    Harbidge Donald G

    2011-09-01

    Full Text Available Abstract Background Sodium absorption by semicircular canal duct (SCCD epithelial cells is thought to contribute to the homeostasis of the volume of vestibular endolymph. It was previously shown that the epithelial cells could absorb Na+ under control of a glucocorticoid hormone (dexamethasone and the absorptive transepithelial current was blocked by amiloride. The most commonly-observed target of amiloride is the epithelial sodium channel (ENaC, comprised of the three subunits α-, β- and γ-ENaC. However, other cation channels have also been observed to be sensitive in a similar concentration range. The aim of this study was to determine whether SCCD epithelial cells absorb only Na+ or also K+ through an amiloride-sensitive pathway. Parasensory K+ absorption could contribute to regulation of the transduction current through hair cells, as found to occur via vestibular transitional cells [S. H. Kim and D. C. Marcus. Regulation of sodium transport in the inner ear. Hear.Res. doi:10.1016/j.heares.2011.05.003, 2011]. Results We determined the molecular and functional expression of candidate cation channels with gene array (GEO GSE6197, whole-cell patch clamp and transepithelial recordings in primary cultures of rat SCCD. α-, β- and γ-ENaC were all previously reported as present. The selectivity of the amiloride-sensitive transepithelial and cell membrane currents was observed in Ussing chamber and whole-cell patch clamp recordings. The cell membrane currents were carried by Na+ but not K+, but the Na+ selectivity disappeared when the cells were cultured on impermeable supports. Transepithelial currents across SCCD were also carried exclusively by Na+. Conclusions These results are consistent with the amiloride-sensitive absorptive flux of SCCD mediated by a highly Na+-selective channel, likely αβγ-ENaC. These epithelial cells therefore absorb only Na+ via the amiloride-sensitive pathway and do not provide a parasensory K+ efflux from the

  20. “Prescribing sunshine”: a national, cross-sectional survey of 1,089 New Zealand general practitioners regarding their sun exposure and vitamin D perceptions, and advice provided to patients

    Directory of Open Access Journals (Sweden)

    Reeder Anthony

    2012-08-01

    Full Text Available Abstract Background The health effects of ultraviolet radiation vary according to wavelength, timing and pattern of exposure, personal characteristics and practices. Negative effects include skin cancers, eye diseases and immune suppression; positive effects primarily relate to endogenous vitamin D production which protects against bone disease. Drafting comprehensive guidelines regarding appropriate sun protective behaviours and vitamin D sufficiency is challenging. Advice given by general practitioners is potentially influential because they are widely respected. Methods A survey instrument was developed, pre-tested and provided to practising GP’s, either by on-line link or mailed, reply paid hard-copy. Odds ratios, differences in means, or ratios of geometric means from regression models are reported for potential predictor variables with 95% confidence intervals. Results Data (demographic, training, practicing, information accessing, confidence in vitamin D knowledge suitable for analysis were obtained from 1,089 GPs (32% participation. Many (43% were ‘not at all confident’ about their vitamin D knowledge. Recent information led 29% to recommend less sun protection during winter months and 10% less all year. Confidence was positively associated with non-‘Western’ medical training, information sources read and practising in a metropolitan centre with a medical school. Reading the Melanoma Clinical Practice Guidelines was associated with lower estimates of the amount of summer sun exposure required to obtain adequate vitamin D. Increasing years in practice was negatively associated with provision of recommended advice about summer and winter sun protection. Greater concern about vitamin D than skin cancer was expressed by females and those in practice longer. Conclusions Concern about the potentially negative impact of skin cancer prevention on vitamin D status may undermine appropriate sun protective recommendations. Reading some

  1. Epithelial cell polarity, stem cells and cancer

    DEFF Research Database (Denmark)

    Martin-Belmonte, Fernando; Perez-Moreno, Mirna

    2011-01-01

    , deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

  2. Epithelial Inclusion Cyst in Conjunctival Melanoma.

    Science.gov (United States)

    Esposito, Evangelina; Zoroquiain, Pablo; Mastromonaco, Christina; Morales, Melina C; Belfort Neto, Rubens; Burnier, Miguel

    2016-09-01

    Conjunctival melanoma is the second most common conjunctival malignancy. Its differential diagnosis with other conjunctival melanocytic neoplasms is inherently difficult. The presence of epithelial cysts is a useful feature in conjunctival tumors and favors a benign lesion. Herein 2 cases of conjunctival melanoma with cysts are presented. To the best of our knowledge, this is the first series of conjunctival melanoma with epithelial inclusion cysts. This series emphasizes the importance of considering several malignant features when reviewing conjunctival melanocytic lesions, as malignancy can exist even in the presence of epithelial inclusion cysts. © The Author(s) 2016.

  3. Permissiveness of bovine epithelial cells from lung, intestine, placenta and udder for infection with Coxiella burnetii.

    Science.gov (United States)

    Sobotta, Katharina; Bonkowski, Katharina; Liebler-Tenorio, Elisabeth; Germon, Pierre; Rainard, Pascal; Hambruch, Nina; Pfarrer, Christiane; Jacobsen, Ilse D; Menge, Christian

    2017-04-12

    Ruminants are the main source of human infections with the obligate intracellular bacterium Coxiella (C.) burnetii. Infected animals shed high numbers of C. burnetii by milk, feces, and birth products. In goats, shedding by the latter route coincides with C. burnetii replication in epithelial (trophoblast) cells of the placenta, which led us to hypothesize that epithelial cells are generally implicated in replication and shedding of C. burnetii. We therefore aimed at analyzing the interactions of C. burnetii with epithelial cells of the bovine host (1) at the entry site (lung epithelium) which govern host immune responses and (2) in epithelial cells of gut, udder and placenta decisive for the quantity of pathogen excretion. Epithelial cell lines [PS (udder), FKD-R 971 (small intestine), BCEC (maternal placenta), F3 (fetal placenta), BEL-26 (lung)] were inoculated with C. burnetii strains Nine Mile I (NMI) and NMII at different cultivation conditions. The cell lines exhibited different permissiveness for C. burnetii. While maintaining cell viability, udder cells allowed the highest replication rates with formation of large cell-filling Coxiella containing vacuoles. Intestinal cells showed an enhanced susceptibility to invasion but supported C. burnetii replication only at intermediate levels. Lung and placental cells also internalized the bacteria but in strikingly smaller numbers. In any of the epithelial cells, both Coxiella strains failed to trigger a substantial IL-1β, IL-6 and TNF-α response. Epithelial cells, with mammary epithelial cells in particular, may therefore serve as a niche for C. burnetii replication in vivo without alerting the host's immune response.

  4. Risk Factors for Invasive Epithelial Ovarian Cancer by Histologic Subtype

    Directory of Open Access Journals (Sweden)

    Quirk JT

    2004-10-01

    Full Text Available It is unclear whether the different histologic subtypes of epithelial ovarian carcinoma have different risk factors. We investigated the relationships between selected epidemiologic variables (i.e., parity, family history of ovarian cancer, oral contraceptive use, a history of tubal ligation and noncontraceptive estrogen use and the major histologic subtypes of epithelial ovarian cancer in a hospital-based case-control study of adult women at Roswell Park Cancer Institute in Buffalo, NY, USA. Multivariate unconditional logistic regression models were used for statistical analysis. We observed a pattern of increased risk associated with family history and a pattern of risk reduction associated with parity, noncontraceptive estrogen use and tubal ligation across all histologic subtype groups. However, we did not observe a consistent pattern of risk associated with oral contraceptive use. These results provide some additional support for the hypothesis that the effects of various ovarian cancer risk factors may differ according to the histologic subtype.

  5. Contraction and elongation: Mechanics underlying cell boundary deformations in epithelial tissue.

    Science.gov (United States)

    Hara, Yusuke

    2017-06-01

    The cell-cell boundaries of epithelial cells form cellular frameworks at the apical side of tissues. Deformations in these boundaries, for example, boundary contraction and elongation, and the associated forces form the mechanical basis of epithelial tissue morphogenesis. In this review, using data from recent Drosophila studies on cell boundary contraction and elongation, I provide an overview of the mechanism underlying the bi-directional deformations in the epithelial cell boundary, that are sustained by biased accumulations of junctional and apico-medial non-muscle myosin II. Moreover, how the junctional tensions exist on cell boundaries in different boundary dynamics and morphologies are discussed. Finally, some future perspectives on how recent knowledge about single cell boundary-level mechanics will contribute to our understanding of epithelial tissue morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

  6. Gut microbiota, epithelial function and derangements in obesity.

    Science.gov (United States)

    Raybould, Helen E

    2012-02-01

    The gut epithelium is a barrier between the 'outside' and 'inside' world. The major function of the epithelium is to absorb nutrients, ions and water, yet it must balance these functions with that of protecting the 'inside' world from potentially harmful toxins, irritants, bacteria and other pathogens that also exist in the gut lumen. The health of an individual depends upon the efficient digestion and absorption of all required nutrients from the diet. This requires sensing of meal components by gut enteroendocrine cells, activation of neural and humoral pathways to regulate gastrointestinal motor, secretory and absorptive functions, and also to regulate food intake and plasma levels of glucose. In this way, there is a balance between the delivery of food and the digestive and absorptive capacity of the intestine. Maintenance of the mucosal barrier likewise requires sensory detection of pathogens, toxins and irritants; breakdown of the epithelial barrier is associated with gut inflammation and may ultimately lead to inflammatory bowel disease. However, disruption of the barrier alone is not sufficient to cause frank inflammatory bowel disease. Several recent studies have provided compelling new evidence to suggest that changes in epithelial barrier function and inflammation are associated with and may even lead to altered regulation of body weight and glucose homeostasis. This article provides a brief review of some recent evidence to support the hypothesis that changes in the gut microbiota and alteration of gut epithelial function will perturb the homeostatic humoral and neural pathways controlling food intake and body weight.

  7. Epithelial microvilli establish an electrostatic barrier to microbial adhesion.

    Science.gov (United States)

    Bennett, Kaila M; Walker, Sharon L; Lo, David D

    2014-07-01

    Microvilli are membrane extensions on the apical surface of polarized epithelia, such as intestinal enterocytes and tubule and duct epithelia. One notable exception in mucosal epithelia is M cells, which are specialized for capturing luminal microbial particles; M cells display a unique apical membrane lacking microvilli. Based on studies of M cell uptake under different ionic conditions, we hypothesized that microvilli may augment the mucosal barrier by providing an increased surface charge density from the increased membrane surface and associated glycoproteins. Thus, electrostatic charges may repel microbes from epithelial cells bearing microvilli, while M cells are more susceptible to microbial adhesion. To test the role of microvilli in bacterial adhesion and uptake, we developed polarized intestinal epithelial cells with reduced microvilli ("microvillus-minus," or MVM) but retaining normal tight junctions. When tested for interactions with microbial particles in suspension, MVM cells showed greatly enhanced adhesion and uptake of particles compared to microvillus-positive cells. This preference showed a linear relationship to bacterial surface charge, suggesting that microvilli resist binding of microbes by using electrostatic repulsion. Moreover, this predicts that pathogen modification of electrostatic forces may contribute directly to virulence. Accordingly, the effacement effector protein Tir from enterohemorrhagic Escherichia coli O157:H7 expressed in epithelial cells induced a loss of microvilli with consequent enhanced microbial binding. These results provide a new context for microvillus function in the host-pathogen relationship, based on electrostatic interactions. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  8. Corneal ulcers: For the general practitioner

    African Journals Online (AJOL)

    153 CME April 2013 Vol. 31 No. 4. Corneal ulcers: For the general practitioner. A corneal ulcer is a defect in the epithelial layer of the cornea. e general practitioner may play an important role in early management and appropriate referral. Incidence varies and depends on aetiology. S Ballim, MB ChB, Dip Ophth (SA), FC ...

  9. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

    OpenAIRE

    Amankwah, Ernest K.; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line

    2015-01-01

    Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphi...

  10. Thrombomodulin promotes corneal epithelial wound healing

    National Research Council Canada - National Science Library

    Huang, Yi-Hsun; I, Ching-Chang; Kuo, Cheng-Hsiang; Hsu, Yun-Yan; Lee, Fang-Tzu; Shi, Guey-Yueh; Tseng, Sung-Huei; Wu, Hua-Lin

    2015-01-01

    To determine the role of thrombomodulin (TM) in corneal epithelial wound healing, and to investigate whether recombinant TM epidermal growth factor-like domain plus serine/threonine-rich domain (rTMD23...

  11. Multifocal calcifying epithelial odontogenic tumor.

    Science.gov (United States)

    Sedghizadeh, Parish P; Wong, Derek; Shuler, Charles F; Linz, Vincent; Kalmar, John R; Allen, Carl M

    2007-08-01

    The calcifying epithelial odontogenic tumor (CEOT), or Pindborg tumor, is a rare and benign odontogenic neoplasm that affects the jaw. The most common manifestation of CEOT is a unifocal or localized lesion of the involved jaw, which may appear clinically as a hard tissue swelling and radiographically as a mixed radiolucent-radiopaque mass. In this article, we present a unique case of CEOT affecting multiple sites in the maxilla and mandible of a 51-year-old white man. Though biopsy samples from all involved sites revealed similar histopathologic features consistent with CEOT, the fact that there was a multifocal presentation is an unusual phenomenon for CEOT and has never been reported. Multifocal odontogenic lesions are not typical but have been observed in conditions associated with known genetic mutations. For example, multiple odontogenic keratocysts are the most common feature of the inherited condition known as nevoid basal cell carcinoma syndrome. This case, however, is the first one to demonstrate that there may be a multifocal variant of CEOT that has not been previously recognized.

  12. Experimental study of plasmid TGF-beta 1 DNA gene transfer with lipofectamine into rabbit corneal epithelial cells in vitro.

    Science.gov (United States)

    Huang, Qiong; Hu, Yanhua; Jiang, Fagang; Chen, Hong

    2002-01-01

    To investigate whether the TGF-beta 1 plasmid DNA carried by lipofectamine could be introduced into cultured rabbit corneal epithelial cells, specific expression of the plasmid pMAM TGF-beta 1 in the cultured corneal epithelial cells was studied. Two days after 12 h of transfection of pMAMT-GF-beta 1 mediated by lipofectamine into the cultured corneal epithelial cells, the TGF-beta 1 protein expression specific for pMAMTGF-beta 1 in the cells was detected by means of immunohistochemical staining and the positive rate was 23.37%. The results suggested that foreign plasmid DNA could be effectively delivered into cultured rabbit corneal epithelial cells by means of lipofectamine, and this will provide a promising method of studying TGF-beta 1 on the mechanism of physiology and pathology concerned with corneal epithelial cells.

  13. Nuclear expression of Snail1 in borderline and malignant epithelial ovarian tumours is associated with tumour progression

    Directory of Open Access Journals (Sweden)

    Tuhkanen Hanna

    2009-08-01

    Full Text Available Abstract Background Transcription factor Snail1 has a central role in induction of epithelial-mesenchymal transition (EMT. The aim of the present study was to elucidate the expression of Snail1 protein during epithelial ovarian tumourigenesis and to study the association of Snail1 expression with clinicopathological factors and prognosis. Methods Epithelial and stromal fibroblast-like fusiform cells of 14 normal ovarian samples, 21 benign, 24 borderline and 74 malignant epithelial ovarian tumours were studied for Snail1 protein using immunohistochemistry. Results Nuclei of surface peritoneal cells of normal ovaries (n = 14 were regarded as negative for Snail1. Nuclear expression of Snail1 protein in epithelial ovarian tumours was increased during tumour progression from precursor lesions into carcinomas both in epithelial (p = 0.006 and stromal cells (p = 0.007. Nuclei of benign tumours (n = 21 were negative for Snail1. In borderline tumours (n = 24 occasional positive epithelial cells were found in 2 (8% samples and in 3 (13% samples stromal cells were focally positive for Snail1. In carcinomas (n = 74 focal Snail1 staining in epithelial cells was present in 17 (23% tumours, and in stromal cells in 18 (24% tumours. Nuclear expression of Snail1 in epithelial or stromal cells was not associated with clinicopathological factors or prognosis. Conclusion Nuclear Snail1 expression seems to be related to tumour progression, and expression in borderline tumours indicates a role for Snail1 in early epithelial ovarian tumour development. Snail1 also appears to function more generally in tissue remodelling as positive staining was demonstrated in stromal cells.

  14. Corneal ulcers: For the general practitioner | Ballim | Continuing ...

    African Journals Online (AJOL)

    Abstract. A corneal ulcer is a defect in the epithelial layer of the cornea. e general practitioner may play an important role in early management and appropriate referral. Incidence varies and depends on aetiology.

  15. Sodium selectivity of Reissner's membrane epithelial cells

    Directory of Open Access Journals (Sweden)

    Kim Kyunghee X

    2011-02-01

    Full Text Available Abstract Background Sodium absorption by Reissner's membrane is thought to contribute to the homeostasis of the volume of cochlear endolymph. It was previously shown that the absorptive transepithelial current was blocked by amiloride and benzamil. The most commonly-observed target of these drugs is the epithelial sodium channel (ENaC, which is composed of the three subunits α-,β- and γ-ENaC. However, other less-selective cation channels have also been observed to be sensitive to benzamil and amiloride. The aim of this study was to determine whether Reissner's membrane epithelial cells could support parasensory K+ absorption via amiloride- and benzamil-sensitive electrogenic pathways. Results We determined the molecular and functional expression of candidate cation channels with gene array (GEO GSE6196, RT-PCR, and whole-cell patch clamp. Transcript expression analysis of Reissner's membrane detected no amiloride-sensitive acid-sensing ion channels (ASIC1a, ASIC2a, ASIC2b nor amiloride-sensitive cyclic-nucleotide gated channels (CNGA1, CNGA2, CNGA4, CNGB3. By contrast, α-,β- and γ-ENaC were all previously reported as present in Reissner's membrane. The selectivity of the benzamil-sensitive cation currents was observed in whole-cell patch clamp recordings under Cl--free conditions where cations were the only permeant species. The currents were carried by Na+ but not K+, and the permeability of Li+ was greater than that of Na+ in Reissner's membrane. Complete replacement of bath Na+ with the inpermeable cation NMDG+ led to the same inward current as with benzamil in a Na+ bath. Conclusions These results are consistent with the amiloride/benzamil-sensitive absorptive flux of Reissner's membrane mediated by a highly Na+-selective channel that has several key characteristics in common with αβγ-ENaC. The amiloride-sensitive pathway therefore absorbs only Na+ in this epithelium and does not provide a parasensory K+ efflux route from scala

  16. General Relativity

    CERN Document Server

    Canuto, V

    2015-01-01

    This is an English translation of the Italian version of an encyclopedia chapter that appeared in the Italian Encyclopedia of the Physical Sciences, edited by Bruno Bertotti (1994). Following requests from colleagues we have decided to make it available to a more general readership. We present the motivation for constructing General Relativity, provide a short discussion of tensor algebra, and follow the set up of Einstein equations. We discuss briefly the initial value problem, the linear approximation and how should non gravitational physics be described in curved spacetime.

  17. Haemophilia, AIDS and lung epithelial permeability

    Energy Technology Data Exchange (ETDEWEB)

    O' Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G. (Haemophilia Centre and Coagulation Research Unit, Department of Nuclear Medicine, Rayne Institute, St. Thomas' Hospital, London (United Kingdom))

    1990-01-01

    Lung {sup 99m}Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung {sup 99m}Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of {sup 99m}Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au).

  18. Cancer Stem Cells and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Sheetal Dyall

    2010-01-01

    Full Text Available The cancer stem cell hypothesis is becoming more widely accepted as a model for carcinogenesis. Tumours are heterogeneous both at the molecular and cellular level, containing a small population of cells that possess highly tumourigenic “stem-cell” properties. Cancer stem cells (CSCs, or tumour-initiating cells, have the ability to self-renew, generate xenografts reminiscent of the primary tumour that they were derived from, and are chemoresistant. The characterisation of the CSC population within a tumour that drives its growth could provide novel target therapeutics against these cells specifically, eradicating the cancer completely. There have been several reports describing the isolation of putative cancer stem cell populations in several cancers; however, no defined set of markers has been identified that conclusively characterises “stem-like” cancer cells. This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer.

  19. Interactions of Candida albicans with host epithelial surfaces

    Directory of Open Access Journals (Sweden)

    David W. Williams

    2013-10-01

    Full Text Available Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. The organism is however, commonly encountered as a commensal in healthy individuals where it is a component of the normal microflora. The key determinant in the type of relationship that Candida has with its host is how it interacts with the epithelial surface it colonises. A delicate balance clearly exists between the potentially damaging effects of Candida virulence factors and the nature of the immune response elicited by the host. Frequently, it is changes in host factors that lead to Candida seemingly changing from a commensal to pathogenic existence. However, given the often reported heterogeneity in morphological and biochemical factors that exist between Candida species and indeed strains of C. albicans, it may also be the fact that colonising strains differ in the way they exploit resources to allow persistence at mucosal surfaces and as a consequence this too may affect the way Candida interacts with epithelial cells. The aim of this review is to provide an overview of some of the possible interactions that may occur between C. albicans and host epithelial surfaces that may in turn dictate whether Candida removal, its commensal persistence or infection follows.

  20. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang, E-mail: wenfang64@hotmail.com; Zhang, Yi, E-mail: syzi960@yahoo.com

    2013-11-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  1. Three-dimensional Mammary Epithelial Cell Morphogenesis Model for Analysis of TGFß Signaling.

    Science.gov (United States)

    Rashidian, Juliet; Luo, Kunxin

    2016-01-01

    Culturing mammary epithelial cells in laminin-rich extracellular matrices (three dimensional or 3D culture) offers significant advantages over that in the conventional two-dimensional (2D) tissue culture system in that it takes into considetation the impact of extracellular matrix (ECM) microenvironment on the proliferation, survival, and differentiation of mammary epithelial cells. When grown in the 3D culture, untransformed mammary epithelial cells undergo morphogenesis to form a multicellular and polarized acini-like structure that functionally mimics the differentiated alveoli in the pregnancy mammary gland. This process is subjected to regulation by many growth factors and cytokines. The transforming growth factor-ß (TGFß) is a multipotent cytokine that regulates multiple aspects of development and tumorigenesis. In addition to its effects on epithelial cell proliferation, survival, and differentiation, it is also a potent regulator of the cell-matrix interaction. Thus, the 3D culture model may recapitulate the complex in vivo epithelial cell microenvironment and allow us to fully evaluate the role of TGFß signaling in multiple aspects of normal and cancerous cell behavior. In this chapter we provide detailed protocols for growing mammary epithelial cells in the 3D Matrigel for analysis of signaling pathways.

  2. Human amniotic epithelial cells combined with silk fibroin scaffold in the repair of spinal cord injury

    Directory of Open Access Journals (Sweden)

    Ting-gang Wang

    2016-01-01

    Full Text Available Treatment and functional reconstruction after central nervous system injury is a major medical and social challenge. An increasing number of researchers are attempting to use neural stem cells combined with artificial scaffold materials, such as fibroin, for nerve repair. However, such approaches are challenged by ethical and practical issues. Amniotic tissue, a clinical waste product, is abundant, and amniotic epithelial cells are pluripotent, have low immunogenicity, and are not the subject of ethical debate. We hypothesized that amniotic epithelial cells combined with silk fibroin scaffolds would be conducive to the repair of spinal cord injury. To test this, we isolated and cultured amniotic epithelial cells, and constructed complexes of these cells and silk fibroin scaffolds. Implantation of the cell-scaffold complex into a rat model of spinal cord injury resulted in a smaller glial scar in the damaged cord tissue than in model rats that received a blank scaffold, or amniotic epithelial cells alone. In addition to a milder local immunological reaction, the rats showed less inflammatory cell infiltration at the transplant site, milder host-versus-graft reaction, and a marked improvement in motor function. These findings confirm that the transplantation of amniotic epithelial cells combined with silk fibroin scaffold can promote the repair of spinal cord injury. Silk fibroin scaffold can provide a good nerve regeneration microenvironment for amniotic epithelial cells.

  3. [Construction of human mucosa oral epithelial cell lines overexpressing telomerase reverse transcriptase gene mediated by lentivirus].

    Science.gov (United States)

    Sa, Zeng; Xiaodong, Qin; Xiangyi, He; Chunxiao, Che; Xiao, Zhang; Siyu, Xie; Guijun, Sun; Lihe, Wang

    2016-10-01

    To construct a cell line of oral mucosa epithelial cells that stably express human telomerase reverse transcriptase (hTERT) by lentiviral vectors, approaches for the establishment of stable and efficient immortalized oral mucosa epithelial cell lines were explored. Whole RNA was extracted from 293T cells. The hTERT gene was amplified by polymerase chain reaction (PCR) and cloned into the lentiviral vector as pLVX-puro-hTERT. The lentivirus particles were successfully packaged and used to infect primary oral epithelial cells. The positive cell clones were selected by puromycin. Finally, the expression of hTERT was examined by real-time fluorescent quantitative PCR (qRT-PCR) and Western blot analysis. The sequencing results confirmed the construction of the recombinant lentivirus pLVX-puro-hTERT. The morphology of infected cells was similar to that of normal oral mucosal epithelial cells, with a cobble stone-like appearance. The qRT-PCR and Western blot results showed that hTERT was overexpressed in infected cells compared with the normal group (Poral epithelial cell line with stable expression of hTERT was successfully established by the lentivirus, which provides an experimental basis for the establishment of a highly efficient and stable oral epithelial immortalized cell line.

  4. MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition.

    Science.gov (United States)

    Luo, Huacheng; Shenoy, Anitha K; Li, Xuehui; Jin, Yue; Jin, Lihua; Cai, Qingsong; Tang, Ming; Liu, Yang; Chen, Hao; Reisman, David; Wu, Lizi; Seto, Edward; Qiu, Yi; Dou, Yali; Casero, Robert A; Lu, Jianrong

    2016-06-21

    The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT) and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that LSD1 is acetylated in epithelial but not mesenchymal cells. Acetylation of LSD1 reduces its association with nucleosomes, thus increasing histone H3K4 methylation at its target genes and activating transcription. The MOF acetyltransferase interacts with LSD1 and is responsible for its acetylation. MOF is preferentially expressed in epithelial cells and is downregulated by EMT-inducing signals. Expression of exogenous MOF impedes LSD1 binding to epithelial gene promoters and histone demethylation, thereby suppressing EMT and tumor invasion. Conversely, MOF depletion enhances EMT and tumor metastasis. In human cancer, high MOF expression correlates with epithelial markers and a favorable prognosis. These findings provide insight into the regulation of LSD1 and EMT and identify MOF as a critical suppressor of EMT and tumor progression. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Transdifferentiation of Peripheral Blood Mononuclear Cells into Epithelial-Like Cells

    Science.gov (United States)

    Medina, Abelardo; Kilani, Ruhangiz T.; Carr, Nicholas; Brown, Erin; Ghahary, Aziz

    2007-01-01

    Bone marrow-derived stem cells have the potential to transdifferentiate into unexpected peripheral cells. We hypothesize that circulating bone marrow-derived stem cells might have the capacity to transdifferentiate into epithelial-like cells and release matrix metalloproteinase-1-modulating factors such as 14-3-3ς for dermal fibroblasts. We have characterized a subset of peripheral blood mononuclear cells (PBMCs) that develops an epithelial-like profile. Our findings show that these cells develop epithelial-like morphology and express 14-3-3ς and keratin-5, -8 as early as day 7 and day 21, respectively. When compared with control, conditioned media collected from PBMCs in advanced epithelial-like differentiation (cultures on days 28, 35, and 42) increased the matrix metalloproteinase-1 expression in dermal fibroblasts (P ≤ 0.01). The depletion of 14-3-3ς from these conditioned media by immunoprecipitation reduced the effect by 39.5% (P value, 0.05). Therefore, the releasable 14-3-3ς from PBMC-derived epithelial-like cells is involved in this process. Our findings provide new insights into the PBMC transdifferentiation to generate epithelial-like cells and subsequently release of 14-3-3ς that will disclose new therapeutic alternatives for different dermal clinical settings. PMID:17717137

  6. Hydrogen peroxide contributes to the epithelial cell death induced by the oral mitis group of streptococci.

    Directory of Open Access Journals (Sweden)

    Nobuo Okahashi

    Full Text Available Members of the mitis group of streptococci are normal inhabitants of the commensal flora of the oral cavity and upper respiratory tract of humans. Some mitis group species, such as Streptococcus oralis and Streptococcus sanguinis, are primary colonizers of the human oral cavity. Recently, we found that hydrogen peroxide (H2O2 produced by S. oralis is cytotoxic to human macrophages, suggesting that streptococcus-derived H2O2 may act as a cytotoxin. Since epithelial cells provide a physical barrier against pathogenic microbes, we investigated their susceptibility to infection by H2O2-producing streptococci in this study. Infection by S. oralis and S. sanguinis was found to stimulate cell death of Detroit 562, Calu-3 and HeLa epithelial cell lines at a multiplicity of infection greater than 100. Catalase, an enzyme that catalyzes the decomposition of H2O2, inhibited S. oralis cytotoxicity, and H2O2 alone was capable of eliciting epithelial cell death. Moreover, S. oralis mutants lacking the spxB gene encoding pyruvate oxidase, which are deficient in H2O2 production, exhibited reduced cytotoxicity toward Detroit 562 epithelial cells. In addition, enzyme-linked immunosorbent assays revealed that both S. oralis and H2O2 induced interleukin-6 production in Detroit 562 epithelial cells. These results suggest that streptococcal H2O2 is cytotoxic to epithelial cells, and promotes bacterial evasion of the host defense systems in the oral cavity and upper respiratory tracts.

  7. Epithelial cell adhesion molecule - More than a carcinoma marker and adhesion molecule

    NARCIS (Netherlands)

    Trzpis, Monika; McLaughlin, Pamela M. J.; de Leij, Lou M. F. H.; Harmsen, Martin C.

    The epithetial cell adhesion molecule (EpCAM, CD326) is a glycoprotein of similar to 40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally

  8. Lack of FasL expression in cultured human retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Kaestel, C G; Madsen, H O; Prause, J U

    2001-01-01

    Retinal pigment epithelial (RPE) cells have been proposed to play a part in maintaining the eye as an immune privileged organ. However, our knowledge of the implicated mechanism is still sparse. Fas ligand (FasL) expression of RPE cells is generally recognized to be essential for the immune...

  9. Lens epithelial cell layer formation related to hydrogel foldable intraocular lenses

    NARCIS (Netherlands)

    Koch, M.W.; Kalicharan, D; van der Want, JJL

    1999-01-01

    Purpose: To determine the incidence of postoperative lens epithelial cel (LEC) layer formation anterior to the Hydroview hydrogel foldable intraocular lens (IOL), the effect on vision, and the appearance under scanning electron microscopy (SEM). Setting: Eye Unit of district general hospital,

  10. Querying Data Providing Web Services

    OpenAIRE

    Sabesan, Manivasakan

    2010-01-01

    Web services are often used for search computing where data is retrieved from servers providing information of different kinds. Such data providing web services return a set of objects for a given set of parameters without any side effects. There is need to enable general and scalable search capabilities of data from data providing web services, which is the topic of this Thesis. The Web Service MEDiator (WSMED) system automatically provides relational views of any data providing web service ...

  11. Epithelial Ovarian Cancer Experimental Models

    Science.gov (United States)

    Lengyel, E; Burdette, JE; Kenny, HA; Matei, D; Pilrose, J; Haluska, P.; Nephew, KP; Hales, DB; Stack, MS

    2014-01-01

    Epithelial ovarian cancer (OvCa) is associated with high mortality and, as the majority (>75%) of women with OvCa have metastatic disease at the time of diagnosis, rates of survival have not changed appreciably over 30 years. A mechanistic understanding of OvCa initiation and progression is hindered by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell(s) or tissue(s) of origin. Metastasis of OvCa involves direct extension or exfoliation of cells and cellular aggregates into the peritoneal cavity, survival of matrix-detached cells in a complex ascites fluid phase, and subsequent adhesion to the mesothelium lining covering abdominal organs to establish secondary lesions containing host stromal and inflammatory components. Development of experimental models to recapitulate this unique mechanism of metastasis presents a remarkable scientific challenge and many approaches used to study other solid tumors (lung, colon, and breast, for example) are not transferable to OvCa research given the distinct metastasis pattern and unique tumor microenvironment. This review will discuss recent progress in the development and refinement of experimental models to study OvCa. Novel cellular, three-dimensional organotypic, and ex vivo models are considered and the current in vivo models summarized. The review critically evaluates currently available genetic mouse models of OvCa, the emergence of xenopatients, and the utility of the hen model to study OvCa prevention, tumorigenesis, metastasis, and chemoresistance. As these new approaches more accurately recapitulate the complex tumor microenvironment, it is predicted that new opportunities for enhanced understanding of disease progression, metastasis and therapeutic response will emerge. PMID:23934194

  12. Intestinal epithelial dysplasia (tufting enteropathy

    Directory of Open Access Journals (Sweden)

    de Serres Natacha

    2007-04-01

    Full Text Available Abstract Intestinal epithelial dysplasia (IED, also known as tufting enteropathy, is a congenital enteropathy presenting with early-onset severe intractable diarrhea causing sometimes irreversible intestinal failure. To date, no epidemiological data are available, however, the prevalence can be estimated at around 1/50,000–100,000 live births in Western Europe. The prevalence seems higher in areas with high degree of consanguinity and in patients of Arabic origin. Infants develop within the first days after birth a watery diarrhea persistent in spite of bowel rest and parenteral nutrition. Some infants are reported to have associated choanal rectal or esophageal atresia. IED is thought to be related to abnormal enterocytes development and/or differentiation. Nonspecific punctuated keratitis was reported in more than 60% of patients. Histology shows various degree of villous atrophy, with low or without mononuclear cell infiltration of the lamina propria but specific histological abnormalities involving the epithelium with disorganization of surface enterocytes with focal crowding, resembling tufts. Several associated specific features were reported, including abnormal deposition of laminin and heparan sulfate proteoglycan (HSPG in the basement membrane, increased expression of desmoglein and ultrastructural changes in the desmosomes, and abnormal distribution of α2β1 integrin adhesion molecules. One model of transgenic mice in which the gene encoding the transcription factor Elf3 is disrupted have morphologic features resembling IED. Parental consanguinity and/or affected siblings suggest an autosomal recessive transmission but the causative gene(s have not been yet identified making prenatal diagnosis unavailable. Some infants have a milder phenotype than others but in most patients, the severity of the intestinal malabsorption even with enteral feeding make them totally dependent on daily long-term parenteral nutrition with a subsequent

  13. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

    DEFF Research Database (Denmark)

    Amankwah, Ernest K.; Lin, Hui-Yi; Tyrer, Jonathan P.

    2015-01-01

    Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants co...

  14. Epithelial-mesenchymal transition and its role in the pathogenesis of colorectal cancer.

    Science.gov (United States)

    Zhu, Qing-Chao; Gao, Ren-Yuan; Wu, Wen; Qin, Huan-Long

    2013-01-01

    Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogen- activated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-to- mesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

  15. Pancreatic mesenchyme regulates epithelial organogenesis throughout development.

    Directory of Open Access Journals (Sweden)

    Limor Landsman

    2011-09-01

    Full Text Available The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for the mesenchyme in regulating the expansion of progenitor cells in the early pancreas epithelium. However, due to the lack of genetic tools directing expression specifically to the mesenchyme, the potential roles of this supporting tissue in vivo, especially in guiding later stages of pancreas organogenesis, have not been elucidated. We employed transgenic tools and fetal surgical techniques to ablate mesenchyme via Cre-mediated mesenchymal expression of Diphtheria Toxin (DT at the onset of pancreas formation, and at later developmental stages via in utero injection of DT into transgenic mice expressing the Diphtheria Toxin receptor (DTR in this tissue. Our results demonstrate that mesenchymal cells regulate pancreatic growth and branching at both early and late developmental stages by supporting proliferation of precursors and differentiated cells, respectively. Interestingly, while cell differentiation was not affected, the expansion of both the endocrine and exocrine compartments was equally impaired. To further elucidate signals required for mesenchymal cell function, we eliminated β-catenin signaling and determined that it is a critical pathway in regulating mesenchyme survival and growth. Our study presents the first in vivo evidence that the embryonic mesenchyme provides critical signals to the epithelium throughout pancreas organogenesis. The findings are novel and relevant as they indicate a critical role for the mesenchyme during late expansion of endocrine and exocrine compartments. In addition, our results provide a molecular mechanism for mesenchymal expansion and survival by identifying β-catenin signaling as an

  16. Effects of a hindered amine light stabilizer and a UV light absorber used in maxillofacial elastomers on human gingival epithelial cells and fibroblasts.

    Science.gov (United States)

    Tipton, David A; Lewis, J West

    2008-09-01

    Ultraviolet light absorber (UVA) and hindered amine light stabilizer (HALS) retard sun-induced pigment degradation in silicone elastomeric maxillofacial prostheses. HALS inhibits polymer degradation and UVA dissipates UV radiation. Their effects on oral cells are unknown. The purpose of this study was to evaluate the effects of UVA and HALS on membrane integrity, viability, and proliferation of human gingival fibroblasts and epithelial cells. Tinuvin 123 (HALS) and Tinuvin 213 (UVA) were assessed for cytotoxicity, individually and in a 1:1 ratio (used in elastomers; HALS/UVA). The cells were exposed to HALS, UVA, or HALS/UVA (or control media containing only the diluent), and colorimetric assays measured membrane damage, viability, and proliferation. The data (% cytotoxicity or % control) were analyzed using 3-way cross-classified fixed effects ANOVA (alpha=.05). HALS did not negatively affect either cell type. UVA or HALS/UVA (>or= approximately 0.004%) decreased viability by >or=90% in both cell lines; lower concentrations decreased activity in epithelial cells while increasing it in fibroblasts. UVA or HALS/UVA damaged membranes of both cell lines, but epithelial cells were more resistant. UVA or HALS/UVA inhibited proliferation of both cell types similarly. There was a slight synergistic effect of HALS and UVA on membrane damage in both cell lines, but generally not on other parameters. Although it is unknown if HALS or UVA leaches from silicone elastomers in vivo, these data suggest that relative resistance of epithelial cells to UVA-induced membrane damage, and UVA's stimulation of fibroblast viability at some concentrations, might provide some protective effect.

  17. Celiac Disease: Role of the Epithelial Barrier.

    Science.gov (United States)

    Schumann, Michael; Siegmund, Britta; Schulzke, Jörg D; Fromm, Michael

    2017-03-01

    In celiac disease (CD) a T-cell-mediated response to gluten is mounted in genetically predisposed individuals, resulting in a malabsorptive enteropathy histologically highlighted by villous atrophy and crypt hyperplasia. Recent data point to the epithelial layer as an under-rated hot spot in celiac pathophysiology to date. This overview summarizes current functional and genetic evidence on the role of the epithelial barrier in CD, consisting of the cell membranes and the apical junctional complex comprising sealing as well as ion and water channel-forming tight junction proteins and the adherens junction. Moreover, the underlying mechanisms are discussed, including apoptosis of intestinal epithelial cells, biology of intestinal stem cells, alterations in the apical junctional complex, transcytotic uptake of gluten peptides, and possible implications of a defective epithelial polarity. Current research is directed toward new treatment options for CD that are alternatives or complementary therapeutics to a gluten-free diet. Thus, strategies to target an altered epithelial barrier therapeutically also are discussed.

  18. Culture and Characterization of Oral Mucosal Epithelial Cells on a Fibrin Gel for Ocular Surface Reconstruction.

    Science.gov (United States)

    Sheth, Radhika; Neale, Michael H; Shortt, Alex J; Massie, Isobel; Vernon, Amanda J; Daniels, Julie T

    2015-01-01

    To develop a clinical grade fibrin gel for the culture of oral mucosal epithelial cells (OMEC) intended for ocular surface reconstruction in the treatment of limbal stem cell deficiency (LSCD). Transparent fibrin gels composed of fibrinogen and thrombin were developed for the culture of epithelial cells. Oral mucosa was harvested from the buccal region of healthy volunteers and cultured as explants on fibrin gels. Tranexamic acid (TA), a clinically approved anti-fibrinolytic agent was added to prevent the fibrin gel from digesting due to cellular activity. The gels were stained for p63α (as a marker of poorly differentiated epithelial cells), CK19, CK13 and CK3 (expressed by OMEC). Epithelial cell stratification was observed using hematoxylin-eosin staining. Addition of TA prevented gels from dissolving during the culture period. OMEC proliferated on the fibrin gel and attained confluence over a 2-week period (±2 d) and exhibited a typical epithelial, cobblestone morphology. Basal OMEC exhibited positive staining for p63α while the superficial cells exhibited positive staining for CK3. The cells expressed a strong immunoreactivity for CK19 and CK13 suggesting that they retained a normal oral epithelial phenotype. Fibrin gels, maintained in the presence of TA, to control the rate of substrate degradation, provide a more robust yet transparent substrate for the culture and transplantation of cultured OMEC. The fibrin gels are easily standardized, the components commercially available, and produced from clinically approved materials. The resulting stratified OMEC-derived epithelium displays characteristics similar to that of a human cornea, e.g. CK3 expression. The conventional dependence on a murine feeder layer for support of epithelial cells is unnecessary with this technique and hence, provides for an attractive alternative for treatment of LSCD.

  19. Inhibition of IFN-γ-dependent antiviral airway epithelial defense by cigarette smoke

    Directory of Open Access Journals (Sweden)

    El-Mahdy Sherif

    2010-05-01

    Full Text Available Abstract Background Although individuals exposed to cigarette smoke are more susceptible to respiratory infection, the effects of cigarette smoke on lung defense are incompletely understood. Because airway epithelial cell responses to type II interferon (IFN are critical in regulation of defense against many respiratory viral infections, we hypothesized that cigarette smoke has inhibitory effects on IFN-γ-dependent antiviral mechanisms in epithelial cells in the airway. Methods Primary human tracheobronchial epithelial cells were first treated with cigarette smoke extract (CSE followed by exposure to both CSE and IFN-γ. Epithelial cell cytotoxicity and IFN-γ-induced signaling, gene expression, and antiviral effects against respiratory syncytial virus (RSV were tested without and with CSE exposure. Results CSE inhibited IFN-γ-dependent gene expression in airway epithelial cells, and these effects were not due to cell loss or cytotoxicity. CSE markedly inhibited IFN-γ-induced Stat1 phosphorylation, indicating that CSE altered type II interferon signal transduction and providing a mechanism for CSE effects. A period of CSE exposure combined with an interval of epithelial cell exposure to both CSE and IFN-γ was required to inhibit IFN-γ-induced cell signaling. CSE also decreased the inhibitory effect of IFN-γ on RSV mRNA and protein expression, confirming effects on viral infection. CSE effects on IFN-γ-induced Stat1 activation, antiviral protein expression, and inhibition of RSV infection were decreased by glutathione augmentation of epithelial cells using N-acetylcysteine or glutathione monoethyl ester, providing one strategy to alter cigarette smoke effects. Conclusions The results indicate that CSE inhibits the antiviral effects of IFN-γ, thereby presenting one explanation for increased susceptibility to respiratory viral infection in individuals exposed to cigarette smoke.

  20. The Ets Transcription Factor EHF as a Regulator of Cornea Epithelial Cell Identity*

    Science.gov (United States)

    Stephens, Denise N.; Klein, Rachel Herndon; Salmans, Michael L.; Gordon, William; Ho, Hsiang; Andersen, Bogi

    2013-01-01

    The cornea is the clear, outermost portion of the eye composed of three layers: an epithelium that provides a protective barrier while allowing transmission of light into the eye, a collagen-rich stroma, and an endothelium monolayer. How cornea development and aging is controlled is poorly understood. Here we characterize the mouse cornea transcriptome from early embryogenesis through aging and compare it with transcriptomes of other epithelial tissues, identifying cornea-enriched genes, pathways, and transcriptional regulators. Additionally, we profiled cornea epithelium and stroma, defining genes enriched in these layers. Over 10,000 genes are differentially regulated in the mouse cornea across the time course, showing dynamic expression during development and modest expression changes in fewer genes during aging. A striking transition time point for gene expression between postnatal days 14 and 28 corresponds with completion of cornea development at the transcriptional level. Clustering classifies co-expressed, and potentially co-regulated, genes into biologically informative categories, including groups that exhibit epithelial or stromal enriched expression. Based on these findings, and through loss of function studies and ChIP-seq, we show that the Ets transcription factor EHF promotes cornea epithelial fate through complementary gene activating and repressing activities. Furthermore, we identify potential interactions between EHF, KLF4, and KLF5 in promoting cornea epithelial differentiation. These data provide insights into the mechanisms underlying epithelial development and aging, identifying EHF as a regulator of cornea epithelial identity and pointing to interactions between Ets and KLF factors in promoting epithelial fate. Furthermore, this comprehensive gene expression data set for the cornea is a powerful tool for discovery of novel cornea regulators and pathways. PMID:24142692

  1. Quiescent epithelial cell rests of Malassez can differentiate into ameloblast-like cells.

    Science.gov (United States)

    Shinmura, Yuka; Tsuchiya, Shuhei; Hata, Ken-Ichiro; Honda, Masaki J

    2008-12-01

    Epithelial cell rests of Malassez (ERM) are quiescent epithelial remnants of Hertwig's epithelial root sheath (HERS) that are involved in the formation of tooth roots. After completion of crown formation, HERS are converted from cervical loop cells, which have the potential to generate enamel for tooth crown formation. Cervical loop cells have the potential to differentiate into ameloblasts. Generally, no new ameloblasts can be generated from HERS, however this study demonstrated that subcultured ERM can differentiate into ameloblast-like cells and generate enamel-like tissues in combination with dental pulp cells at the crown formation stage. Porcine ERM were obtained from periodontal ligament tissue by explant culture and were subcultured with non-serum medium. Thereafter, subcultured ERM were expanded on 3T3-J2 feeder cell layers until the tenth passage. The in vitro mRNA expression pattern of the subcultured ERM after four passages was found to be different from that of enamel organ epithelial cells and oral gingival epithelial cells after the fourth passage using the same expansion technique. When subcultured ERM were combined with subcultured dental pulp cells, ERM expressed cytokeratin14 and amelogenin proteins in vitro. In addition, subcultured ERM combined with primary dental pulp cells seeded onto scaffolds showed enamel-like tissues at 8 weeks post-transplantation. Moreover, positive staining for amelogenin was observed in the enamel-like tissues, indicating the presence of well-developed ameloblasts in the implants. These results suggest that ERM can differentiate into ameloblast-like cells.

  2. Cigarette smoke inhibits airway epithelial cell innate immune responses to bacteria.

    Science.gov (United States)

    Kulkarni, Ritwij; Rampersaud, Ryan; Aguilar, Jorge L; Randis, Tara M; Kreindler, James L; Ratner, Adam J

    2010-05-01

    The human upper respiratory tract, including the nasopharynx, is colonized by a diverse array of microorganisms. While the host generally exists in harmony with the commensal microflora, under certain conditions, these organisms may cause local or systemic disease. Respiratory epithelial cells act as local sentinels of the innate immune system, responding to conserved microbial patterns through activation of signal transduction pathways and cytokine production. In addition to colonizing microbes, these cells may also be influenced by environmental agents, including cigarette smoke (CS). Because of the strong relationship among secondhand smoke exposure, bacterial infection, and sinusitis, we hypothesized that components in CS might alter epithelial cell innate immune responses to pathogenic bacteria. We examined the effect of CS condensate (CSC) or extract (CSE) on signal transduction and cytokine production in primary and immortalized epithelial cells of human or murine origin in response to nontypeable Haemophilus influenzae and Staphylococcus aureus. We observed that epithelial production of interleukin-8 (IL-8) and IL-6 in response to bacterial stimulation was significantly inhibited in the presence of CS (P 0.05 compared to cells without CSC treatment). These results identify a novel oxidant-mediated immunosuppressive role for CS in epithelial cells.

  3. Mouse hair cycle expression dynamics modeled as coupled mesenchymal and epithelial oscillators.

    Directory of Open Access Journals (Sweden)

    Ryan Tasseff

    2014-11-01

    Full Text Available The hair cycle is a dynamic process where follicles repeatedly move through phases of growth, retraction, and relative quiescence. This process is an example of temporal and spatial biological complexity. Understanding of the hair cycle and its regulation would shed light on many other complex systems relevant to biological and medical research. Currently, a systematic characterization of gene expression and summarization within the context of a mathematical model is not yet available. Given the cyclic nature of the hair cycle, we felt it was important to consider a subset of genes with periodic expression. To this end, we combined several mathematical approaches with high-throughput, whole mouse skin, mRNA expression data to characterize aspects of the dynamics and the possible cell populations corresponding to potentially periodic patterns. In particular two gene clusters, demonstrating properties of out-of-phase synchronized expression, were identified. A mean field, phase coupled oscillator model was shown to quantitatively recapitulate the synchronization observed in the data. Furthermore, we found only one configuration of positive-negative coupling to be dynamically stable, which provided insight on general features of the regulation. Subsequent bifurcation analysis was able to identify and describe alternate states based on perturbation of system parameters. A 2-population mixture model and cell type enrichment was used to associate the two gene clusters to features of background mesenchymal populations and rapidly expanding follicular epithelial cells. Distinct timing and localization of expression was also shown by RNA and protein imaging for representative genes. Taken together, the evidence suggests that synchronization between expanding epithelial and background mesenchymal cells may be maintained, in part, by inhibitory regulation, and potential mediators of this regulation were identified. Furthermore, the model suggests that

  4. Membrane lipidome of an epithelial cell line

    DEFF Research Database (Denmark)

    Sampaio, Julio L; Gerl, Mathias J; Klose, Christian

    2011-01-01

    Tissue differentiation is an important process that involves major cellular membrane remodeling. We used Madin-Darby canine kidney cells as a model for epithelium formation and investigated the remodeling of the total cell membrane lipidome during the transition from a nonpolarized morphology...... to an epithelial morphology and vice versa. To achieve this, we developed a shotgun-based lipidomics workflow that enabled the absolute quantification of mammalian membrane lipidomes with minimal sample processing from low sample amounts. Epithelial morphogenesis was accompanied by a major shift from sphingomyelin...... to glycosphingolipid, together with an increase in plasmalogen, phosphatidylethanolamine, and cholesterol content, whereas the opposite changes took place during an epithelial-to-mesenchymal transition. Moreover, during polarization, the sphingolipids became longer, more saturated, and more hydroxylated as required...

  5. Studying cytokinesis in Drosophila epithelial tissues.

    Science.gov (United States)

    Pinheiro, D; Bellaïche, Y

    2017-01-01

    Epithelial tissue cohesiveness is ensured through cell-cell junctions that maintain both adhesion and mechanical coupling between neighboring cells. During development, epithelial tissues undergo intensive cell proliferation. Cell division, and particularly cytokinesis, is coupled to the formation of new adhesive contacts, thereby preserving tissue integrity and propagating cell polarity. Remarkably, the geometry of the new interfaces is determined by the combined action of the dividing cell and its neighbors. To further understand the interplay between the dividing cell and its neighbors, as well as the role of cell division for tissue morphogenesis, it is important to analyze cytokinesis in vivo. Here we present methods to perform live imaging of cell division in Drosophila epithelial tissues and discuss some aspects of image processing and analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Novel application of artificial dermis plus autologous vital epithelial cells: improved wound epithelialization.

    Science.gov (United States)

    Lee, Li-Tzu; Kwan, Po-Cheung; Wong, Yong-Kie

    2010-02-01

    The purpose of this study was to evaluate artificial dermis with the simultaneous addition of autologous epithelial cells for oral lesion defect reconstruction. Surgical wounds reconstructed with artificial dermis plus scraped epithelial cells were evaluated in 5 patients with oral benign lesions or squamous cell carcinoma. Clinical follow-up indices included scar formation and tissue surface texture observation. The neomucosal layers were analyzed histologically to establish the degree of epithelialization. Clinical observation showed that the oral mucosal texture was smoother in artificial dermis with added epithelial cells at 4 weeks postoperation compared with artificial dermis alone. The wound contraction and scar formation processes were slow. Viable epithelial cells with flat rete ridges remained in the artificial dermis, and a neoepithelial layer was present in the histological findings. We showed that healthy granulation tissue and neoepithelial formation in artificial dermis with epithelial cells was beneficial for the repair of oral defects. Scraping oral epithelial cells and applying them to artificial dermis assisted in the early preparation of composite grafts and minimized requirement for donor sites. This technique may improve the treatment of patients with oral benign tumors and early-stage squamous cell carcinoma. Copyright 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

  7. General Relativity

    CERN Document Server

    Straumann, Norbert

    2013-01-01

    This book provides a completely revised and expanded version of the previous classic edition ‘General Relativity and Relativistic Astrophysics’. In Part I the foundations of general relativity are thoroughly developed, while Part II is devoted to tests of general relativity and many of its applications. Binary pulsars – our best laboratories for general relativity – are studied in considerable detail. An introduction to gravitational lensing theory is included as well, so as to make the current literature on the subject accessible to readers. Considerable attention is devoted to the study of compact objects, especially to black holes. This includes a detailed derivation of the Kerr solution, Israel’s proof of his uniqueness theorem, and a derivation of the basic laws of black hole physics. Part II ends with Witten’s proof of the positive energy theorem, which is presented in detail, together with the required tools on spin structures and spinor analysis. In Part III, all of the differential geomet...

  8. Calcifying epithelial odontogenic tumor (Pindborg tumor).

    Science.gov (United States)

    Singh, Neeraj; Sahai, Sharad; Singh, Sourav; Singh, Smita

    2011-07-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare entity and represents less than 1% of all odontogenic tumors. Dr. J J Pindborg (1958) first described four cases of this unusual lesion; subsequently Shafer et al coined the term Pindborg tumor. This lesion is a locally aggressive benign odontogenic neoplasm arising from epithelial tissue. It occurs most commonly in 4(th)-5(th)-6(th) decade of life and bears no gender predilection. A case of CEOT in a 50-year-old male arising in the left body region is described.

  9. Targeted Therapies in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Nicanor I. Barrena Medel

    2010-01-01

    Full Text Available Epithelial ovarian cancer remains a major women's health problem due to its high lethality. Despite great efforts to develop effective prevention and early detection strategies, most patients are still diagnosed at advanced stages of disease. This pattern of late presentation has resulted in significant challenges in terms of designing effective therapies to achieve long-term cure. One potential promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. This review examines three of the most provocative targeted therapies with current or future applicability in epithelial ovarian cancer.

  10. Segmentation and Quantitative Analysis of Epithelial Tissues.

    Science.gov (United States)

    Aigouy, Benoit; Umetsu, Daiki; Eaton, Suzanne

    2016-01-01

    Epithelia are tissues that regulate exchanges with the environment. They are very dynamic and can acquire virtually any shape; at the cellular level, they are composed of cells tightly connected by junctions. Most often epithelia are amenable to live imaging; however, the large number of cells composing an epithelium and the absence of informatics tools dedicated to epithelial analysis largely prevented tissue scale studies. Here we present Tissue Analyzer, a free tool that can be used to segment and analyze epithelial cells and monitor tissue dynamics.

  11. Epithelial-Mesenchymal Transition in Pancreatic Carcinoma

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    Thomas Wirth

    2010-12-01

    Full Text Available Pancreatic carcinoma is the fourth-leading cause of cancer death and is characterized by early invasion and metastasis. The developmental program of epithelial-mesenchymal transition (EMT is of potential importance for this rapid tumor progression. During EMT, tumor cells lose their epithelial characteristics and gain properties of mesenchymal cells, such as enhanced motility and invasive features. This review will discuss recent findings pertinent to EMT in pancreatic carcinoma. Evidence for and molecular characteristics of EMT in pancreatic carcinoma will be outlined, as well as the connection of EMT to related topics, e.g., cancer stem cells and drug resistance.

  12. Regulated Mucin Secretion from Airway Epithelial Cells

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    Kenneth Bruce Adler

    2013-09-01

    Full Text Available Secretory epithelial cells of the proximal airways synthesize and secrete gel-forming polymeric mucins. The secreted mucins adsorb water to form mucus that is propelled by neighboring ciliated cells, providing a mobile barrier which removes inhaled particles and pathogens from the lungs. Several features of the intracellular trafficking of mucins make the airway secretory cell an interesting comparator for the cell biology of regulated exocytosis. Polymeric mucins are exceedingly large molecules (up to 3x10^6 D per monomer whose folding and initial polymerization in the ER requires the protein disulfide isomerase Agr2. In the Golgi, mucins further polymerize to form chains and possibly branched networks comprising more than 20 monomers. The large size of mucin polymers imposes constraints on their packaging into transport vesicles along the secretory pathway. Sugar side chains account for >70% of the mass of mucins, and their attachment to the protein core by O-glycosylation occurs in the Golgi. Mature polymeric mucins are stored in large secretory granules ~1 um in diameter. These are translocated to the apical membrane to be positioned for exocytosis by cooperative interactions among MARCKS, cysteine string protein (CSP, HSP70 and the cytoskeleton. Mucin granules undergo exocytic fusion with the plasma membrane at a low basal rate and a high stimulated rate. Both rates are mediated by a regulated exocytic mechanism as indicated by phenotypes in both basal and stimulated secretion in mice lacking Munc13-2, a sensor of the second messengers calcium and diacylglycerol (DAG. Basal secretion is induced by low levels of activation of P2Y2 purinergic and A3 adenosine receptors by extracellular ATP released in paracrine fashion and its metabolite adenosine. Stimulated secretion is induced by high levels of the same ligands, and possibly by inflammatory mediators as well. Activated receptors are coupled to phospholipase C by Gq, resulting in the

  13. Thymic epithelial cells. I. Expression of strong suppressive (veto) activity in mouse thymic epithelial cell cultures

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg; Ropke, C

    1990-01-01

    We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level. It is conclu....... It is concluded that the epithelial stromal cells of the thymus, by acting as veto cells, may be responsible for the negative intrathymic selection of self-reactive thymocytes leading to elimination of the vast majority of immature thymic lymphocytes....

  14. Oxidant-induced corticosteroid unresponsiveness in human bronchial epithelial cells

    NARCIS (Netherlands)

    Heijink, Irene; van Oosterhout, Antoon; Kliphuis, Nathalie; Jonker, Marnix; Hoffmann, Roland; Telenga, Eef; Klooster, Karin; Slebos, Dirk-Jan; ten Hacken, Nick; Postma, Dirkje; van den Berge, Maarten

    Background We hypothesised that increased oxidative stress, as present in the airways of asthma and chronic obstructive pulmonary disease (COPD) patients, induces epithelial damage and reduces epithelial responsiveness to suppressive effects of corticosteroids on proinflammatory cytokine production

  15. Evidence from a mouse model that epithelial cell migration and mesenchymal-epithelial transition contribute to rapid restoration of uterine tissue integrity during menstruation.

    Science.gov (United States)

    Cousins, Fiona L; Murray, Alison; Esnal, Arantza; Gibson, Douglas A; Critchley, Hilary O D; Saunders, Philippa T K

    2014-01-01

    In women dynamic changes in uterine tissue architecture occur during each menstrual cycle. Menses, characterised by the shedding of the upper functional layer of the endometrium, is the culmination of a cascade of irreversible changes in tissue function including stromal decidualisation, inflammation and production of degradative enzymes. The molecular mechanisms that contribute to the rapid restoration of tissue homeostasis at time of menses are poorly understood. A modified mouse model of menses was developed to focus on the events occurring within the uterine lining during endometrial shedding/repair. Decidualisation, vaginal bleeding, tissue architecture and cell proliferation were evaluated at 4, 8, 12, and 24 hours after progesterone (P4) withdrawal; mice received a single injection of bromodeoxyuridine (BrdU) 90 mins before culling. Expression of genes implicated in the regulation of mesenchymal to epithelial transition (MET) was determined using a RT2 PCR profiler array, qRTPCR and bioinformatic analysis. Mice exhibited vaginal bleeding between 4 and 12 hours after P4 withdrawal, concomitant with detachment of the decidualised cell mass from the basal portion of the endometrial lining. Immunostaining for BrdU and pan cytokeratin revealed evidence of epithelial cell proliferation and migration. Cells that appeared to be in transition from a mesenchymal to an epithelial cell identity were identified within the stromal compartment. Analysis of mRNAs encoding genes expressed exclusively in the epithelial or stromal compartments, or implicated in MET, revealed dynamic changes in expression, consistent with a role for reprogramming of mesenchymal cells so that they could contribute to re-epithelialisation. These studies have provided novel insights into the cellular processes that contribute to re-epithelialisation post-menses implicating both epithelial cell migration and mesenchymal cell differentiation in restoration of an intact epithelial cell layer. These

  16. The interplay between Entamoeba and enteropathogenic bacteria modulates epithelial cell damage.

    Science.gov (United States)

    Galván-Moroyoqui, José Manuel; Del Carmen Domínguez-Robles, M; Franco, Elizabeth; Meza, Isaura

    2008-07-23

    Mixed intestinal infections with Entamoeba histolytica, Entamoeba dispar and bacteria with exacerbated manifestations of disease are common in regions where amoebiasis is endemic. However, amoeba-bacteria interactions remain largely unexamined. Trophozoites of E. histolytica and E. dispar were co-cultured with enteropathogenic bacteria strains Escherichia coli (EPEC), Shigella dysenteriae and a commensal Escherichia coli. Amoebae that phagocytosed bacteria were tested for a cytopathic effect on epithelial cell monolayers. Cysteine proteinase activity, adhesion and cell surface concentration of Gal/GalNAc lectin were analyzed in amoebae showing increased virulence. Structural and functional changes and induction of IL-8 expression were determined in epithelial cells before and after exposure to bacteria. Chemotaxis of amoebae and neutrophils to human IL-8 and conditioned culture media from epithelial cells exposed to bacteria was quantified. E. histolytica digested phagocytosed bacteria, although S. dysenteriae retained 70% viability after ingestion. Phagocytosis of pathogenic bacteria augmented the cytopathic effect of E. histolytica and increased expression of Gal/GalNAc lectin on the amoebic surface and increased cysteine proteinase activity. E. dispar remained avirulent. Adhesion of amoebae and damage to cells exposed to bacteria were increased. Additional increases were observed if amoebae had phagocytosed bacteria. Co-culture of epithelial cells with enteropathogenic bacteria disrupted monolayer permeability and induced expression of IL-8. Media from these co-cultures and human recombinant IL-8 were similarly chemotactic for neutrophils and E. histolytica. Epithelial monolayers exposed to enteropathogenic bacteria become more susceptible to E. histolytica damage. At the same time, phagocytosis of pathogenic bacteria by amoebae further increased epithelial cell damage. The in vitro system presented here provides evidence that the Entamoeba

  17. Increased mammogram-induced DNA damage in mammary epithelial cells aged in vitro.

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    Laia Hernández

    Full Text Available Concerned about the risks of mammography screening in the adult population, we analyzed the ability of human mammary epithelial cells to cope with mammogram-induced DNA damage. Our study shows that an X-ray dose of 20 mGy, which is the standard dose received by the breast surface per two-view mammogram X-ray exploration, induces increased frequencies of DNA double-strand breaks to in vitro aged-but not to young-human mammary epithelial cells. We provide evidence that aged epithelial breast cells are more radiosensitive than younger ones. Our studies point to an inefficient damage response of aged cells to low-dose radiation, this being due to both delayed and incomplete mobilization of repair proteins to DNA strand breaks. This inefficient damage response is translated into an important delay in double-strand break disappearance and consequent accumulation of unrepaired DNA breaks. The result of this is a significant increase in micronuclei frequency in the in vitro aged mammary epithelial cells exposed to doses equivalent to a single mammogram X-ray exploration. Since our experiments were carried out in primary epithelial cell cultures in which cells age at the same time as they undergo replication-dependent telomere shortening, we needed to determine the contribution of these two factors to their phenotype. In this paper, we report that the exogenous expression of human telomerase retrotranscriptase in late population doubling epithelial cells does not rescue its delayed repair phenotype. Therefore, retarded DNA break repair is a direct consequence of cellular aging itself, rather than a consequence of the presence of dysfunctional telomeres. Our findings of long-lasting double strand breaks and incomplete DNA break repair in the in vitro aged epithelial cells are in line with the increased carcinogenic risks of radiation exposures at older ages revealed by epidemiologic studies.

  18. The interplay between Entamoeba and enteropathogenic bacteria modulates epithelial cell damage.

    Directory of Open Access Journals (Sweden)

    José Manuel Galván-Moroyoqui

    : The in vitro system presented here provides evidence that the Entamoeba/enteropathogenic bacteria interplay modulates epithelial cell responses to the pathogens. In mixed intestinal infections, where such interactions are possible, they could influence the outcome of disease. The results offer insights to continue research on this phenomenon.

  19. Increased Mammogram-Induced DNA Damage in Mammary Epithelial Cells Aged In Vitro

    Science.gov (United States)

    Hernández, Laia; Terradas, Mariona; Martín, Marta; Feijoo, Purificación; Soler, David; Tusell, Laura; Genescà, Anna

    2013-01-01

    Concerned about the risks of mammography screening in the adult population, we analyzed the ability of human mammary epithelial cells to cope with mammogram-induced DNA damage. Our study shows that an X-ray dose of 20 mGy, which is the standard dose received by the breast surface per two-view mammogram X-ray exploration, induces increased frequencies of DNA double-strand breaks to in vitro aged–but not to young–human mammary epithelial cells. We provide evidence that aged epithelial breast cells are more radiosensitive than younger ones. Our studies point to an inefficient damage response of aged cells to low-dose radiation, this being due to both delayed and incomplete mobilization of repair proteins to DNA strand breaks. This inefficient damage response is translated into an important delay in double-strand break disappearance and consequent accumulation of unrepaired DNA breaks. The result of this is a significant increase in micronuclei frequency in the in vitro aged mammary epithelial cells exposed to doses equivalent to a single mammogram X-ray exploration. Since our experiments were carried out in primary epithelial cell cultures in which cells age at the same time as they undergo replication-dependent telomere shortening, we needed to determine the contribution of these two factors to their phenotype. In this paper, we report that the exogenous expression of human telomerase retrotranscriptase in late population doubling epithelial cells does not rescue its delayed repair phenotype. Therefore, retarded DNA break repair is a direct consequence of cellular aging itself, rather than a consequence of the presence of dysfunctional telomeres. Our findings of long-lasting double strand breaks and incomplete DNA break repair in the in vitro aged epithelial cells are in line with the increased carcinogenic risks of radiation exposures at older ages revealed by epidemiologic studies. PMID:23667571

  20. Isolation and characterization of stromal progenitor cells from ascites of patients with epithelial ovarian adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ho Chih-Ming

    2012-02-01

    Full Text Available Abstract Background At least one-third of epithelial ovarian cancers are associated with the development of ascites containing heterogeneous cell populations, including tumor cells, inflammatory cells, and stromal elements. The components of ascites and their effects on the tumor cell microenvironment remain poorly understood. This study aimed to isolate and characterize stromal progenitor cells from the ascites of patients with epithelial ovarian adenocarcinoma (EOA. Methods Seventeen ascitic fluid samples and 7 fresh tissue samples were collected from 16 patients with EOA. The ascites samples were then cultured in vitro in varying conditions. Flow cytometry and immunocytochemistry were used to isolate and characterize 2 cell populations with different morphologies (epithelial type and mesenchymal type deriving from the ascites samples. The in vitro cell culture model was established using conditional culture medium. Results The doubling times of the epithelial type and mesenchymal type cells were 36 h and 48 h, respectively, indicating faster growth of the epithelial type cells compared to the mesenchymal type cells. Cultured in vitro, these ascitic cells displayed the potential for self-renewal and long-term proliferation, and expressed the typical cancer stem/progenitor cell markers CD44high, CD24low, and AC133+. These cells also demonstrated high BMP-2, BMP4, TGF-β, Rex-1, and AC133 early gene expression, and expressed EGFR, integrin α2β1, CD146, and Flt-4, which are highly associated with tumorigenesis and metastasis. The epithelial type cells demonstrated higher cytokeratin 18 and E-cadherin expression than the mesenchymal type cells. The mesenchymal type cells, in contrast, demonstrated higher AC133, CD73, CD105, CD117, EGFR, integrin α2β1, and CD146 surface marker expression than the epithelial type cells. Conclusion The established culture system provides an in vitro model for the selection of drugs that target cancer

  1. Isolation and characterization of stromal progenitor cells from ascites of patients with epithelial ovarian adenocarcinoma.

    Science.gov (United States)

    Ho, Chih-Ming; Chang, Shwu-Fen; Hsiao, Chih-Chiang; Chien, Tsai-Yen; Shih, Daniel Tzu-Bi

    2012-02-14

    At least one-third of epithelial ovarian cancers are associated with the development of ascites containing heterogeneous cell populations, including tumor cells, inflammatory cells, and stromal elements. The components of ascites and their effects on the tumor cell microenvironment remain poorly understood. This study aimed to isolate and characterize stromal progenitor cells from the ascites of patients with epithelial ovarian adenocarcinoma (EOA). Seventeen ascitic fluid samples and 7 fresh tissue samples were collected from 16 patients with EOA. The ascites samples were then cultured in vitro in varying conditions. Flow cytometry and immunocytochemistry were used to isolate and characterize 2 cell populations with different morphologies (epithelial type and mesenchymal type) deriving from the ascites samples. The in vitro cell culture model was established using conditional culture medium. The doubling times of the epithelial type and mesenchymal type cells were 36 h and 48 h, respectively, indicating faster growth of the epithelial type cells compared to the mesenchymal type cells. Cultured in vitro, these ascitic cells displayed the potential for self-renewal and long-term proliferation, and expressed the typical cancer stem/progenitor cell markers CD44(high), CD24(low), and AC133(+). These cells also demonstrated high BMP-2, BMP4, TGF-β, Rex-1, and AC133 early gene expression, and expressed EGFR, integrin α2β1, CD146, and Flt-4, which are highly associated with tumorigenesis and metastasis. The epithelial type cells demonstrated higher cytokeratin 18 and E-cadherin expression than the mesenchymal type cells. The mesenchymal type cells, in contrast, demonstrated higher AC133, CD73, CD105, CD117, EGFR, integrin α2β1, and CD146 surface marker expression than the epithelial type cells. The established culture system provides an in vitro model for the selection of drugs that target cancer-associated stromal progenitor cells, and for the development of ovarian

  2. 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.

  3. Cadherin-6B stimulates an epithelial mesenchymal transition and the delamination of cells from the neural ectoderm via LIMK/cofilin mediated non-canonical BMP receptor signaling

    Science.gov (United States)

    Park, Ki-Sook; Gumbiner, Barry M.

    2012-01-01

    We previously provided evidence that cadherin-6B induces de-epithelialization of the neural crest prior to delamination and is required for the overall epithelial mesenchymal transition (EMT). Furthermore, de-epithelialization induced by cadherin-6B was found to be mediated by BMP receptor signaling independent of BMP. We now find that de-epithelialization is mediated by non-canonical BMP signaling through the BMP type II receptor (BMPRII) and not by canonical Smad dependent signaling through BMP Type I receptor. The LIM kinase/cofilin pathway mediates non-canonical BMPRII induced de-epithelialization, in response to either cadherin-6B or BMP. LIMK1 induces de-epithelialization in the neural tube and dominant negative LIMK1 decreases de-epithelialization induced by either cadherin-6B or BMP. Cofilin is the major known LIMK1 target and a S3A phosphorylation deficient mutated cofilin inhibits de-epithelialization induced by cadherin-6B as well as LIMK1. Importantly, LIMK1 as well as cadherin-6B can trigger ectopic delamination when co-expressed with the competence factor SOX9, showing that this cadherin-6B stimulated signaling pathway can mediate the full EMT in the appropriate context. These findings suggest that the de-epithelialization step of the neural crest EMT by cadherin-6B/BMPRII involves regulation of actin dynamics via LIMK/cofilin. PMID:22537493

  4. Epithelial to Mesenchymal Transition in a Clinical Perspective

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    Jennifer Pasquier

    2015-01-01

    Full Text Available Tumor growth and metastatic dissemination rely on cellular plasticity. Among the different phenotypes acquired by cancer cells, epithelial to mesenchymal transition (EMT has been extensively illustrated. Indeed, this transition allows an epithelial polarized cell to acquire a more mesenchymal phenotype with increased mobility and invasiveness. The role of EMT is quite clear during developmental stage. In the neoplastic context in many tumors EMT has been associated with a more aggressive tumor phenotype including local invasion and distant metastasis. EMT allows the cell to invade surrounding tissues and survive in the general circulation and through a stem cell phenotype grown in the host organ. The molecular pathways underlying EMT have also been clearly defined and their description is beyond the scope of this review. Here we will summarize and analyze the attempts made to block EMT in the therapeutic context. Indeed, till today, most of the studies are made in animal models. Few clinical trials are ongoing with no obvious benefits of EMT inhibitors yet. We point out the limitations of EMT targeting such tumor heterogeneity or the dynamics of EMT during disease progression.

  5. Protective Effects of Trehalose on the Corneal Epithelial Cells

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    Pasquale Aragona

    2014-01-01

    Full Text Available Purpose. Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Methods. Twelve patients undergoing laser subepithelial keratomileusis (LASEK were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. Results. In both trehalose-untreated eyes (TUE and trehalose-treated eyes (TTE, the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Conclusions. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.

  6. The origin of stroma surrounding epithelial ovarian cancer cells.

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    Akahane, Tomoko; Hirasawa, Akira; Tsuda, Hiroshi; Kataoka, Fumio; Nishimura, Sadako; Tanaka, Hideo; Tominaga, Eiichiro; Nomura, Hiroyuki; Chiyoda, Tatsuyuki; Iguchi, Yoko; Yamagami, Wataru; Susumu, Nobuyuki; Aoki, Daisuke

    2013-01-01

    Cancer stroma is thought to play an important role in tumor behavior, including invasion or metastasis and response to therapy. Cancer stroma is generally thought either to be non-neoplastic cells, including tissue-marrow or bone-marrow-derived fibroblasts, or to originate in epithelial mesenchymal transition of cancer cells. In this study, we evaluated the status of the p53 gene in both the cancer cells and the cancer stroma in epithelial ovarian cancer (EOC) to elucidate the origin of the stroma. Samples from 16 EOC patients were included in this study. Tumor cells and adjacent nontumor stromal cells were microdissected and DNA was extracted separately. We analyzed p53 sequences (exons 5-8) of both cancer and stromal tissues in all cases. Furthermore, we examined p53 protein expression in all cases. Mutations in p53 were detected in 9 of the 16 EOCs: in 8 of these cases, the mutations were detected only in cancer cells. In 1 case, the same mutation (R248Q) was detected in both cancer and stromal tissues, and p53 protein expression was detected in both the cancer cells and the cancer stroma. Most cancer stroma in EOC is thought to originate from non-neoplastic cells, but some parts of the cancer stroma might originate from cancer cells.

  7. Neoplastic transformation of human thyroid epithelial cells by ionizing radiation

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    Herceg, Zdenko

    Neoplastic transformation of human thyroid epithelial cells has been investigated following exposure to ionizing radiation in vitro. The effects of radiation type, irradiation regime, and postirradiation passaging were examined using a human thyroid epithelial cell line, designated HToriS, which was previously immortalized with SV40 genome. Exponentially growing HToriS cells were irradiated with graded doses of 137 Cs gamma- and 238pu alpha-irradiation. Cells were irradiated with either a single or multiple doses of 0.5, 1, 2, 3, or 4 Gy gamma-radiation, or single doses of 0.125, 0.25, 0.5, 1, or 1.5 Gy gamma-radiation. Following passaging, the cells were transplanted into the athymic nude mice, and the animals were screened for tumour formation. Statistically significant increases in tumour incidence were obtained with both gamma- and alpha-irradiation and with both single and multiple irradiation regimes as compared with the un-irradiated group. Regardless of radiation type and or radiation regime there appears to be a trend, with increasing doses of radiation, in which tumour incidence increases and reaches a maximum, after which the tumour incidence decreases. Tumours were characterized by histopathological examination as undifferentiated carcinomas. Investigation of expression time following irradiation demonstrated that post-irradiation passaging, generally regarded as a critical step for expression of radiation-induced DNA damage, was not a prerequisite for the neoplastic conversion of irradiated cells with this system. Cell lines were established from the tumours and their identification and characterization carried out. All cell lines established were determined to be derived from the parent HTori3 cells by DNA fingerprinting, karyotype analysis, cytokeratin staining, and SV40 large T-antigen staining. Tumorigenicity of the cell lines was confirmed by retransplantation. Comparison of the morphology in vitro showed that the tumour cell lines retained the

  8. Extraosseous calcifying epithelial odontogenic tumor (Pindborg tumor).

    Science.gov (United States)

    Wertheimer, F W; Zielinski, R J; Wesley, R K

    1977-10-01

    A 20-year-old man presented with a painless enlargement of the maxillary gingiva with no bone involvement. Microscopic examination with special stains confirmed the diagnosis of a clear cell variant of a calcifying epithelial odontogenic tumor (Pindborg tumor). This is the second reported case of such a variant in an extraosseous location.

  9. THE BUFFER CAPACITY OF AIRWAY EPITHELIAL SECRETIONS

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    Dusik eKim

    2014-06-01

    Full Text Available The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF. The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 µl volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO3- is the major buffer. Peak buffer capacity (β increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO3- secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO3- secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

  10. The buffer capacity of airway epithelial secretions.

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    Kim, Dusik; Liao, Jie; Hanrahan, John W

    2014-01-01

    The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF). The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 μl) volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO(-) 3 is the major buffer. Peak buffer capacity (β) increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR)-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO(-) 3 secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO(-) 3 secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

  11. Prevalence of cysts in epithelial ovarian cancer.

    NARCIS (Netherlands)

    Kolwijck, E.; Lybol, C.; Bulten, J.; Vollebergh, J.H.A.; Wevers, R.A.; Massuger, L.F.A.G.

    2010-01-01

    OBJECTIVE: Ovarian carcinomas mostly appear as large cystic masses. However, the exact prevalence of cysts in epithelial ovarian cancer (EOC) has never been documented as well as the tumor factors that are related to the presence of cysts. Demonstrating the prevalence of cysts in EOC is essential

  12. Coronavirus infection of polarized epithelial cells

    NARCIS (Netherlands)

    Rossen, J W; Horzinek, M C; Rottier, P J

    1995-01-01

    Epithelial cells are the first host cells to be infected by incoming c oronaviruses. Recent observations in vitro show that coronaviruses are released from a specific side of these polarized cells, and this polarized release might be important for the spread of the infection in vivo. Mechanisms for

  13. The Epithelial Gatekeeper Against Food Allergy

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    Linda Chia-Hui Yu

    2009-12-01

    Full Text Available The rapid rise of allergic disorders in developed countries has been attributed to the hygiene hypothesis, implicating that increased environmental sanitation in early childhood may be associated with higher incidence of hypersensitivity. Intestinal epithelial barriers play a crucial role in the maintenance of gut homeostasis by limiting penetration of luminal bacteria and dietary allergens, yet allowing antigen sampling via the follicle-associated epithelium for generation of tolerance. However, this intricate balance is upset in allergic intestines, whereby luminal proteins with antigenic properties gain access to the subepithelial compartment and stimulate mast cell degranulation. Recent studies demonstrated that food allergens were protected from lysosomal degradation, and were transported in large quantities across the epithelium by binding to cell surface IgE/CD23 (FceRII that prevented the antigenic protein from lysosomal degradation in enterocytes. IL-4 (a Th2-type cytokine not only increased production of IgE from B cells, but also upregulated the expression of CD23 on intestinal epithelial cells. Further studies indicated that CD23 was responsible for the bidirectional transport of IgE across epithelium. The presence of IgE/CD23 opens a gate for intact dietary allergens to transcytose across the epithelial cells, and thus foments the mast cell-dependent anaphylactic responses. The understanding of the molecular mechanism responsible for epithelial barrier defects may be helpful in designing novel therapies to treat food allergy and other allergic diseases.

  14. Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

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    The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

  15. Molecular mechanisms of epithelial host defense in the airways

    NARCIS (Netherlands)

    Vos, Joost Bastiaan

    2007-01-01

    Airway epithelial cells are indispensable for the host defense system in the lungs. Various strategies by which epithelial cells protect the lungs against inhaled pathogens have been described. In spite of that, the molecular mechanisms by which epithelial cells initiate and control the host defense

  16. Snail involves in the transforming growth factor β1-mediated epithelial-mesenchymal transition of retinal pigment epithelial cells.

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    Hui Li

    Full Text Available BACKGROUND: The proliferation of retinal pigment epithelium (RPE cells resulting from an epithelial-mesenchymal transition (EMT plays a key role in proliferative vitreoretinopathy (PVR, which leads to complex retinal detachment and the loss of vision. Genes of Snail family encode the zinc finger transcription factors that have been reported to be essential in EMT during embryonic development and cancer metastasis. However, the function of Snail in RPE cells undergoing EMT is largely unknown. PRINCIPAL FINDINGS: Transforming growth factor beta(TGF-β-1 resulted in EMT in human RPE cells (ARPE-19, which was characterized by the expected decrease in E-cadherin and Zona occludin-1(ZO-1 expression, and the increase in fibronectin and α-smooth muscle actin (α-SMA expression, as well as the associated increase of Snail expression at both mRNA and protein levels. Furthermore, TGF-β1 treatment caused a significant change in ARPE-19 cells morphology, with transition from a typical epithelial morphology to mesenchymal spindle-shaped. More interestingly, Snail silencing significantly attenuated TGF-β1-induced EMT in ARPE-19 cells by decreasing the mesenchymal markers fibronectin and a-SMA and increasing the epithelial marker E-cadherin and ZO-1. Snail knockdown could effectively suppress ARPE-19 cell migration. Finally, Snail was activated in epiretinal membranes from PVR patients. Taken together, Snail plays very important roles in TGF-β-1-induced EMT in human RPE cells and may contribute to the development of PVR. SIGNIFICANCE: Snail transcription factor plays a critical role in TGF-β1-induced EMT in human RPE cells, which provides deep insight into the pathogenesis of human PVR disease. The specific inhibition of Snail may provide a new approach to treat and prevent PVR.

  17. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

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    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  18. Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling.

    Science.gov (United States)

    Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru

    2016-07-19

    Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity.

  19. Protons sensitize epithelial cells to mesenchymal transition.

    Science.gov (United States)

    Wang, Minli; Hada, Megumi; Saha, Janapriya; Sridharan, Deepa M; Pluth, Janice M; Cucinotta, Francis A

    2012-01-01

    Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1.

  20. Airway epithelial cell tolerance to Pseudomonas aeruginosa

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    Verghese Margrith W

    2005-04-01

    Full Text Available Abstract Background The respiratory tract epithelium is a critical environmental interface that regulates inflammation. In chronic infectious airway diseases, pathogens may permanently colonize normally sterile luminal environments. Host-pathogen interactions determine the intensity of inflammation and thus, rates of tissue injury. Although many cells become refractory to stimulation by pathogen products, it is unknown whether the airway epithelium becomes either tolerant or hypersensitive in the setting of chronic infection. Our goals were to characterize the response of well-differentiated primary human tracheobronchial epithelial cells to Pseudomonas aeruginosa, to understand whether repeated exposure induced tolerance and, if so, to explore the mechanism(s. Methods The apical surface of well-differentiated primary human tracheobronchial epithelial cell cultures was repetitively challenged with Pseudomonas aeruginosa culture filtrates or the bacterial media control. Toxicity, cytokine production, signal transduction events and specific effects of dominant negative forms of signaling molecules were examined. Additional experiments included using IL-1β and TNFα as challenge agents, and performing comparative studies with a novel airway epithelial cell line. Results An initial challenge of the apical surface of polarized human airway epithelial cells with Pseudomonas aeruginosa culture filtrates induced phosphorylation of IRAK1, JNK, p38, and ERK, caused degradation of IκBα, generation of NF-κB and AP-1 transcription factor activity, and resulted in IL-8 secretion, consistent with activation of the Toll-like receptor signal transduction pathway. These responses were strongly attenuated following a second Pseudomonas aeruginosa, or IL-1β, but not TNFα, challenge. Tolerance was associated with decreased IRAK1 protein content and kinase activity and dominant negative IRAK1 inhibited Pseudomonas aeruginosa -stimulated NF-κB transcriptional

  1. Establishment of an In Vitro Intestinal Epithelial Cell Culture Model of Avian Origin.

    Science.gov (United States)

    Kaiser, Annette; Willer, Thomas; Steinberg, Pablo; Rautenschlein, Silke

    2017-06-01

    The role of intestinal epithelial cells (IECs) in the physiology of the gastrointestinal tract (GIT) of chickens and pathogenesis of various diseases in chickens is still poorly understood. IECs line the GIT and represent the border between the unsterile environment and the sterile internal tissues. Bacterial, viral, fungal, or parasitic pathogens are able to invade or pass IECs under certain circumstances and cause various diseases. Pathogen-host interactions in the chicken gut are poorly understood because of the lack of suitable in vitro and ex vivo models. In this context, there is a need to optimize the cell isolation and culture conditions to be able to provide reproducible IEC cultures with defined epithelial characteristics. We compared different mechanical IEC isolation protocols and cell culture media and established a reproducible primary intestinal epithelial cell culture model from specific-pathogen-free layer-type chickens. By using isolated crypts from the duodenum of 5- to 12-wk-old birds to create the starting material, we were able to culture replicating cells between 7 and 10 days. Cells built an almost closed monolayer and showed epithelial-like characteristics, such as the expression of cytokeratin and epithelial cadherin. The primary IEC cultures described in this study represent a suitable model with which to investigate in vitro pathogen-host interactions relevant to the chicken gut.

  2. Dual effect of neutrophils on secretory component production by human bronchial epithelial cells

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    C. Pilette

    2006-12-01

    Full Text Available A decreased bronchial expression of secretory component (SC was demonstrated in severe COPD, and correlated with neutrophils. Mechanisms of epithelial cell/neutrophils interactions remain however poorly understood. Calu-3 (human bronchial epithelial cells were incubated after confluence (in triplicate conditions with various ratios of activated neutrophils (0.5:1 to 15:1, neutrophils: Calu-3 cells. After 48hrs of co-culture supernatants were assayed for SC by ELISA. SC production by Calu-3 cells increased at intermediate neutrophil numbers (316±32 versus 193±19ng·ml–1, ratio of 5:1 versus control, mean±SEM of 3 experiments, p = 0.05. In contrast, a trend for decrease in SC was observed with high neutrophil numbers (111±19 versus 193±19ng·ml–1, ratio of 15:1 versus control, p = 0.06. The addition of secretory leukocyte protease inhibitor further increased SC upregulation at intermediate ratios, and inhibited the SC decrease at high neutrophil numbers. The mechanism of SC up-regulation by neutrophils did not implicate TNF-alpha or IL-1beta. This study provides direct evidence of a dual effect of neutrophils on epithelial SC. Our data suggest that neutrophils could differently affect epithelial immune secretory function according to the extent of neutrophil influx and/or to the reactivity of airway epithelial cells.

  3. Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases.

    Science.gov (United States)

    Schleimer, Robert P; Berdnikovs, Sergejs

    2017-06-01

    Epithelial barriers of the skin, gastrointestinal tract, and airway serve common critical functions, such as maintaining a physical barrier against environmental insults and allergens and providing a tissue interface balancing the communication between the internal and external environments. We now understand that in patients with allergic disease, regardless of tissue location, the homeostatic balance of the epithelial barrier is skewed toward loss of differentiation, reduced junctional integrity, and impaired innate defense. Importantly, epithelial dysfunction characterized by these traits appears to pre-date atopy and development of allergic disease. Despite our growing appreciation of the centrality of barrier dysfunction in initiation of allergic disease, many important questions remain to be answered regarding mechanisms disrupting normal barrier function. Although our external environment (proteases, allergens, and injury) is classically thought of as a principal contributor to barrier disruption associated with allergic sensitization, there is a need to better understand contributions of the internal environment (hormones, diet, and circadian clock). Systemic drivers of disease, such as alterations of the endocrine system, metabolism, and aberrant control of developmental signaling, are emerging as new players in driving epithelial dysfunction and allergic predisposition at various barrier sites. Identifying such central mediators of epithelial dysfunction using both systems biology tools and causality-driven laboratory experimentation will be essential in building new strategic interventions to prevent or reverse the process of barrier loss in allergic patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Evolutionary conserved role of c-Jun-N-terminal kinase in CO2-induced epithelial dysfunction.

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    István Vadász

    Full Text Available Elevated CO(2 levels (hypercapnia occur in patients with respiratory diseases and impair alveolar epithelial integrity, in part, by inhibiting Na,K-ATPase function. Here, we examined the role of c-Jun N-terminal kinase (JNK in CO(2 signaling in mammalian alveolar epithelial cells as well as in diptera, nematodes and rodent lungs. In alveolar epithelial cells, elevated CO(2 levels rapidly induced activation of JNK leading to downregulation of Na,K-ATPase and alveolar epithelial dysfunction. Hypercapnia-induced activation of JNK required AMP-activated protein kinase (AMPK and protein kinase C-ζ leading to subsequent phosphorylation of JNK at Ser-129. Importantly, elevated CO(2 levels also caused a rapid and prominent activation of JNK in Drosophila S2 cells and in C. elegans. Paralleling the results with mammalian epithelial cells, RNAi against Drosophila JNK fully prevented CO(2-induced downregulation of Na,K-ATPase in Drosophila S2 cells. The importance and specificity of JNK CO(2 signaling was additionally demonstrated by the ability of mutations in the C. elegans JNK homologs, jnk-1 and kgb-2 to partially rescue the hypercapnia-induced fertility defects but not the pharyngeal pumping defects. Together, these data provide evidence that deleterious effects of hypercapnia are mediated by JNK which plays an evolutionary conserved, specific role in CO(2 signaling in mammals, diptera and nematodes.

  5. Identifying the cellular mechanisms of symbiont-induced epithelial morphogenesis in the squid-Vibrio association.

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    Koropatnick, Tanya; Goodson, Michael S; Heath-Heckman, Elizabeth A C; McFall-Ngai, Margaret

    2014-02-01

    The symbiotic association between the Hawaiian bobtail squid Euprymna scolopes and the luminous marine bacterium Vibrio fischeri provides a unique opportunity to study epithelial morphogenesis. Shortly after hatching, the squid host harvests bacteria from the seawater using currents created by two elaborate fields of ciliated epithelia on the surface of the juvenile light organ. After light organ colonization, the symbiont population signals the gradual loss of the ciliated epithelia through apoptosis of the cells, which culminates in the complete regression of these tissues. Whereas aspects of this process have been studied at the morphological, biochemical, and molecular levels, no in-depth analysis of the cellular events has been reported. Here we describe the cellular structure of the epithelial field and present evidence that the symbiosis-induced regression occurs in two steps. Using confocal microscopic analyses, we observed an initial epithelial remodeling, which serves to disable the function of the harvesting apparatus, followed by a protracted regression involving actin rearrangements and epithelial cell extrusion. We identified a metal-dependent gelatinolytic activity in the symbiont-induced morphogenic epithelial fields, suggesting the involvement of Zn-dependent matrix metalloproteinase(s) (MMP) in light organ morphogenesis. These data show that the bacterial symbionts not only induce apoptosis of the field, but also change the form, function, and biochemistry of the cells as part of the morphogenic program.

  6. Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas.

    Science.gov (United States)

    Krivova, Yuliya; Proshchina, Alexandra; Barabanov, Valeriy; Leonova, Olga; Saveliev, Sergey

    2016-12-01

    In the pancreas of many mammals including humans, endocrine islet cells can be integrated with the nervous system components into neuro-insular complexes. The mechanism of the formation of such complexes is not clearly understood. The present study evaluated the interactions between the nervous system components, epithelial cells and endocrine cells in the human pancreas. Foetal pancreas, gestational age 19-23 weeks (13 cases) and 30-34 weeks (7 cases), were studied using double immunohistochemical labeling with neural markers (S100 protein and beta III tubulin), epithelial marker (cytokeratin 19 (CK19)) and antibodies to insulin and glucagon. We first analyse the structure of neuro-insular complexes using confocal microscopy and provide immunohistochemical evidences of the presence of endocrine cells within the ganglia or inside the nerve bundles. We showed that the nervous system components contact with the epithelial cells located in ducts or in clusters outside the ductal epithelium and form complexes with separate epithelial cells. We observed CK19-positive cells inside the ganglia and nerve bundles which were located separately or were integrated with the islets. Therefore, we conclude that neuro-insular complexes may forms as a result of integration between epithelial cells and nervous system components at the initial stages of islets formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Identification of novel genetic regulations associated with airway epithelial homeostasis using next-generation sequencing data and bioinformatics approaches.

    Science.gov (United States)

    Sheu, Chau-Chyun; Tsai, Ming-Ju; Chen, Feng-Wei; Chang, Kuo-Feng; Chang, Wei-An; Chong, Inn-Wen; Kuo, Po-Lin; Hsu, Ya-Ling

    2017-10-10

    Airway epithelial cells play important roles in airway remodeling. Understanding gene regulations in airway epithelial homeostasis may provide new insights into pathogenesis and treatment of asthma. This study aimed to combine gene expression (GE) microarray, next generation sequencing (NGS), and bioinformatics to explore genetic regulations associated with airway epithelial homeostasis. We analyzed expression profiles of mRNAs (GE microarray) and microRNAs (NGS) in normal and asthmatic bronchial epithelial cells, and identified 9 genes with potential microRNA-mRNA interactions. Of these 9 dysregulated genes, downregulation of MEF2C and MDGA1 were validated in a representative microarray (GSE43696) from the gene expression omnibus (GEO) database. Our findings suggested that upregulated mir-203a may repress MEF2C, a transcription factor, leading to decreased cellular proliferation. In addition, upregulated mir-3065-3p may repress MDGA1, a cell membrane anchor protein, resulting in suppression of cell-cell adhesion. We also found that KCNJ2, a potassium channel, was downregulated in severe asthma and may promote epithelial cell apoptosis. We proposed that aberrant regulations of mir-203a-MEF2C and mir-3065-3p-MDGA1, as well as downregulation of KCNJ2, play important roles in airway epithelial homeostasis in asthma. These findings provide new perspectives on diagnostic or therapeutic strategies targeting bronchial epithelium for asthma. The approach in this study also provides a new aspect of studying asthma.

  8. Differential expression of living mammary epithelial cell subpopulations in milk during lactation in dairy cows.

    Science.gov (United States)

    Baratta, M; Volpe, M G; Nucera, D; Gabai, G; Guzzo, N; Fustini, M; Faustini, M; Martignani, E

    2015-10-01

    Epithelial cells are shed into milk during lactation, and although they generally reflect the cellular characteristics of terminally differentiated luminal cells, previously the detection of more primitive cells was described in human milk where a cell population of epithelial lineage was detected expressing markers typical of progenitor cells. In this investigation, we report the development of flow cytometry analysis to allow multiparametric assessment of mammary epithelial cells observed in milk. Cells collected from milk samples of 10 healthy dairy cows were directly analyzed for 6 different markers: CD45, CD49f, cytokeratin 14, cytokeratin 18, presence of nucleus, and cell viability. Milk samples were collected in 3 different periods of lactation: early lactation (EL=d 0-30), mid-lactation (ML=d 90-120), and late lactation (LL=210-250). Here we identify the differential expression of precursor or differentiated cell markers (or both) in mammary epithelial cells present in bovine milk. Myoepithelial cells, as indicated by cells staining positively for cytokeratin 14(+)/cytokeratin 18(-), were observed to increase from EL to LL with a high correlation with nuclear staining inferring potential proliferative activity. Furthermore, a significant increase in CD49f(+) and cytokeratin 14(+)/cytokeratin 18(+) positive cells was observed in LL. This assay is a sensitive approach for evaluating the variations in the frequency and features of living epithelial cells, whose reciprocal balance may be significant in understanding mammary gland cellular function throughout lactation. These observations suggest that mammary epithelial cell immunophenotypes could be investigated as biomarkers for mammary gland function in dairy cows. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. Active Vertex Model for cell-resolution description of epithelial tissue mechanics.

    Science.gov (United States)

    Barton, Daniel L; Henkes, Silke; Weijer, Cornelis J; Sknepnek, Rastko

    2017-06-01

    We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.

  10. An epithelial tissue in Dictyostelium challenges the traditional origin of metazoan multicellularity.

    Science.gov (United States)

    Dickinson, Daniel J; Nelson, W James; Weis, William I

    2012-10-01

    We hypothesize that aspects of animal multicellularity originated before the divergence of metazoans from fungi and social amoebae. Polarized epithelial tissues are a defining feature of metazoans and contribute to the diversity of animal body plans. The recent finding of a polarized epithelium in the non-metazoan social amoeba Dictyostelium discoideum demonstrates that epithelial tissue is not a unique feature of metazoans, and challenges the traditional paradigm that multicellularity evolved independently in social amoebae and metazoans. An alternative view, presented here, is that the common ancestor of social amoebae, fungi, and animals spent a portion of its life cycle in a multicellular state and possessed molecular machinery necessary for forming an epithelial tissue. Some descendants of this ancestor retained multicellularity, while others reverted to unicellularity. This hypothesis makes testable predictions regarding tissue organization in close relatives of metazoans and provides a novel conceptual framework for studies of early animal evolution. Copyright © 2012 WILEY Periodicals, Inc.

  11. Use of scanning electron microscopy to monitor nanofibre/cell interaction in digestive epithelial cells.

    Science.gov (United States)

    Millaku, Agron; Drobne, Damjana; Torkar, Matjaz; Novak, Sara; Remškar, Maja; Pipan-Tkalec, Živa

    2013-09-15

    We provide data obtained by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) on the interaction of ingested tungsten nanofibers with epithelial cells of the digestive tubes of a test organism Porcellio scaber. Conventional toxicity endpoints including feeding behaviour, weight loss and mortality were also measured in each investigated animal. No toxicity was detected in any of exposed animals after 14 days of feeding on tungsten nanofiber dosed food, but when nanofibers enter the digestive system they can react with epithelial cells of the digestive tubes, becoming physically inserted into the cells. In this way, nanofibers can injure the epithelial cells of digestive gland tubes when they are ingested with food. Our SEM data suggest that peristaltic forces may have an important role, not predicted by in vitro experiments, in the interactions of nanomaterials with digestive intestinal cells. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate

    Science.gov (United States)

    Laresgoiti, Usua; Rao, Chandrika; Brady, Jane L.; Richardson, Rachel V.; Batchen, Emma J.; Chapman, Karen E.

    2016-01-01

    Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar-to-alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. We show that both glucocorticoid and STAT3 signalling can control the timing of alveolar initiation, but that neither pathway is absolutely required for alveolar fate specification; rather, glucocorticoid receptor and STAT3 work in parallel to promote alveolar differentiation. Thus, developmental acquisition of lung alveolar fate is a robust process controlled by at least two independent extrinsic signalling inputs. Further elucidation of these pathways might provide therapeutic opportunities for restoring alveolar capacity. PMID:27578791

  13. The use of contact lenses in the treatment of persistent epithelial defects.

    Science.gov (United States)

    Blackmore, Sally Jayne

    2010-10-01

    The types and applications of bandage contact lenses are varied and diverse. This article provides a summary of the corneal pathologies that will predispose patients to persistent epithelial defects (PEDs) along with an overview of the types of contact lenses that can be utilised to treat these conditions. Copyright (c) 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  14. Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial Cell Death

    Science.gov (United States)

    Novaleski, Carolyn K.; Carter, Bruce D.; Sivasankar, M. Preeti; Ridner, Sheila H.; Dietrich, Mary S.; Rousseau, Bernard

    2017-01-01

    Purpose: Vocal fold diseases affecting the epithelium have a detrimental impact on vocal function. This review article provides an overview of apoptosis, the most commonly studied type of programmed cell death. Because apoptosis can damage epithelial cells, this article examines the implications of apoptosis on diseases affecting the vocal fold…

  15. Quantitative Changes In Human Epithelial Cancers And Osteogenesis Imperfecta Disease Detected Using Nonlinear Multicontrast Microscopy.

    OpenAIRE

    Adur, Javier; Vitor B Pelegati; de Thomaz, Andre A.; D'Souza-Li, Lilia; Assunção, Maria do Carmo; Bottcher-Luiz, Fátima; Andrade, Liliana A L A; CESAR, CARLOS L.

    2015-01-01

    We show that combined multimodal nonlinear optical (NLO) microscopies, including two-photon excitation fluorescence, second-harmonic generation (SHG), third harmonic generation, and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation during the progression of cancer and osteogenesis imperfecta (OI) disease. NLO microscopes provide complementary information about tissue microstructure, sh...

  16. Epithelial dysplasia in Caroli's disease.

    OpenAIRE

    Fozard, J. B.; Wyatt, J I; Hall, R.I.

    1989-01-01

    We report a young patient with a solitary intrahepatic cyst without demonstrable connection with the biliary tree. The operative appearances suggested hydatid disease but histological examination of the resected cyst showed that it was the result of Caroli's disease already complicated by severe dysplasia. This case provides further evidence for the premalignant nature of Caroli's disease.

  17. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang

    2010-03-01

    Full Text Available Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo.To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo.Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  18. Multiple cellular responses to serotonin contribute to epithelial homeostasis.

    Directory of Open Access Journals (Sweden)

    Vaibhav P Pai

    Full Text Available Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A, we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers.

  19. Ascorbic Acid Promotes the Stemness of Corneal Epithelial Stem/Progenitor Cells and Accelerates Epithelial Wound Healing in the Cornea.

    Science.gov (United States)

    Chen, Jialin; Lan, Jie; Liu, Dongle; Backman, Ludvig J; Zhang, Wei; Zhou, Qingjun; Danielson, Patrik

    2017-05-01

    High concentration of ascorbic acid (vitamin C) has been found in corneal epithelium of various species. However, the specific functions and mechanisms of ascorbic acid in the repair of corneal epithelium are not clear. In this study, it was found that ascorbic acid accelerates corneal epithelial wound healing in vivo in mouse. In addition, ascorbic acid enhanced the stemness of cultured mouse corneal epithelial stem/progenitor cells (TKE2) in vitro, as shown by elevated clone formation ability and increased expression of stemness markers (especially p63 and SOX2). The contribution of ascorbic acid on the stemness enhancement was not dependent on the promotion of Akt phosphorylation, as concluded by using Akt inhibitor, nor was the stemness found to be dependent on the regulation of oxidative stress, as seen by the use of two other antioxidants (GMEE and NAC). However, ascorbic acid was found to promote extracellular matrix (ECM) production, and by using two collagen synthesis inhibitors (AzC and CIS), the increased expression of p63 and SOX2 by ascorbic acid was decreased by around 50%, showing that the increased stemness by ascorbic acid can be attributed to its regulation of ECM components. Moreover, the expression of p63 and SOX2 was elevated when TKE2 cells were cultured on collagen I coated plates, a situation that mimics the in vivo situation as collagen I is the main component in the corneal stroma. This study shows direct therapeutic benefits of ascorbic acid on corneal epithelial wound healing and provides new insights into the mechanisms involved. Stem Cells Translational Medicine 2017;6:1356-1365. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  20. Molecular cloning, sequence analysis, and function of the intestinal epithelial stem cell marker Bmi1 in pig intestinal epithelial cells.

    Science.gov (United States)

    Li, C-M; Yan, H-C; Fu, H-L; Xu, G-F; Wang, X-Q

    2014-01-01

    In the present work, we cloned the full-length cDNA of the pig Bmi1 gene (BMI1 polycomb ring finger oncogene), which has been indicated as an intestinal epithelial stem cell (IESC) marker in other mammals. This paper provides the first report of the function of Bmi1 in pig intestinal epithelial cells and a brief description of its underlying mechanism. Rapid amplification of cDNA ends technology was used to clone the complete pig Bmi1 sequence, and a Bmi1-pcDNA3.1 vector was constructed for transfection into an intestinal porcine epithelial cell line (IPEC-1). The proliferation ability of the cells was estimated using the MTT assay and the EdU incorporation method at different time points after seeding. Cell cycle information was detected by flow cytometry. The mRNA abundances of cell cycle-related genes were also measured. The results indicated that the pig Bmi1 cDNA is 3,193 bp in length and consists of a 981 bp open reading frame, a 256 bp 5´ untranslated region (UTR), and a 1,956 bp 3' UTR. The transcript contains no signal peptides, and there are no transmembrane regions in the pig Bmi1 coded protein, which has a total of 326 AA. The overexpression of the pig Bmi1 in the IPEC-1 cells led to increased cell proliferation and a lower percentage of cells in the G1 and S phases (P cells in the G2 phase (P 0.05). Our data suggested that pig Bmi1 can increase the proliferation of IPEC-1 cells by promoting the G1/S transition and the overall cell cycle process.

  1. RNA Interference-based Investigation of the Function of Heat Shock Protein 27 during Corneal Epithelial Wound Healing.

    Science.gov (United States)

    Yoo, Aeri; Park, Hyun-Min; Kang, Soon-Suk; Kim, Eun-Soon; Tchah, Hungwon; Kim, Jae Yong

    2016-09-27

    Small interfering RNA (siRNA) is among the most widely used RNA interference methods for the short-term silencing of protein-coding genes. siRNA is a synthetic RNA duplex created to specifically target a mRNA transcript to induce its degradation and it has been used to identify novel pathways in various cellular processes. Few reports exist regarding the role of phosphorylated heat shock protein 27 (HSP27) in corneal epithelial wound healing. Herein, cultured human corneal epithelial cells were divided into a scrambled control-siRNA transfected group and a HSP27-specific siRNA-transfected group. Scratch-induced directional wounding assays, and western blotting, and flow cytometry were then performed. We conclude that HSP27 has roles in corneal epithelial wound healing that may involve epithelial cell apoptosis and migration. Here, step-by-step descriptions of sample preparation and the study protocol are provided.

  2. 42 CFR 442.12 - Provider agreement: General requirements.

    Science.gov (United States)

    2010-10-01

    ... to meet the civil rights requirements set forth in 45 CFR parts 80, 84, and 90. ... Section 442.12 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS STANDARDS FOR PAYMENT TO NURSING FACILITIES AND...

  3. Abstract This paper provides an introduction to the general mask ...

    African Journals Online (AJOL)

    Tracie1

    The rhetoric of Igbo language has such agents of imagery as proverbs, idioms and riddles .Thus almost invariably, those poems which contain enough of appropriate and integrated proverbs are likely to be aesthetically satisfying than ones lacking in them. (9 ). The proverbs, idioms, and other figures of speech which are.

  4. Low p16INK4a Expression in Early Passage Human Prostate Basal Epithelial Cells Enables Immortalization by Telomerase Expression Alone.

    Science.gov (United States)

    Graham, Mindy Kim; Principessa, Lorenzo; Antony, Lizamma; Meeker, Alan K; Isaacs, John T

    2017-03-01

    There are two principal senescence barriers that must be overcome to successfully immortalize primary human epithelial cells in culture, stress-induced senescence, and replicative senescence. The p16INK4a /retinoblastoma protein (p16/Rb) pathway mediates stress-induced senescence, and is generally upregulated by primary epithelial cells in response to the artificial conditions from tissue culture. Replicative senescence is associated with telomere loss. Following each round of cell division, telomeres progressively shorten. Once telomeres shorten to a critical length, the DNA damage response pathway is activated, and the tumor suppressor p53 pathway triggers replicative senescence. Exogenous expression of telomerase in normal human epithelial cells extends the replicative capacity of cells, and in some cases, immortalizes cells. However reliable immortalization of epithelial cells usually requires telomerase activity coupled with inactivation of the p16/Rb pathway. A lentiviral vector, pLOX-TERT-iresTK (Addgene #12245), containing a CMV promoter upstream of a bicistronic coding cassette that includes loxP sites flanking the catalytic subunit of human telomerase gene (TERT) and herpes simplex virus type-1 thymidine kinase gene (HSV1-tk) was used to transduce normal prostate basal epithelial cells (PrECs) initiated in cell culture from prostate cancer patients undergoing radical prostatectomies. Transduction of early (i.e., 7) passage PrECs were unsuccessful. Late passage PrECs, which acquired elevated p16, were unable to overcome the senescence barrier. Immortalized PrECs (TERT-PrECs) retained a normal male karyotype and low p16 expression. Additionally, TERT-PrECs were non-tumorigenic when inoculated into intact male immunodeficient NSG mice. The present studies document that early passage human PrECs have sufficiently low p16 to permit immortalization by TERT expression alone. TERT-PrECs developed using this transduction approach provides an appropriate and

  5. Epithelial dysplasia in Caroli's disease.

    Science.gov (United States)

    Fozard, J B; Wyatt, J I; Hall, R I

    1989-01-01

    We report a young patient with a solitary intrahepatic cyst without demonstrable connection with the biliary tree. The operative appearances suggested hydatid disease but histological examination of the resected cyst showed that it was the result of Caroli's disease already complicated by severe dysplasia. This case provides further evidence for the premalignant nature of Caroli's disease. Images Fig. 1 Fig. 2 Fig. 3 PMID:2767513

  6. Hypoxic conditions induce a cancer-like phenotype in human breast epithelial cells.

    Directory of Open Access Journals (Sweden)

    Marica Vaapil

    morphogenesis was associated with global histone deacetylation whereas the hypoxic breast epithelial cells showed sustained global histone acetylation, which is generally associated with active transcription and an undifferentiated proliferative state.

  7. Pellino-1 Selectively Regulates Epithelial Cell Responses to Rhinovirus

    Science.gov (United States)

    Bennett, Julie A.; Prince, Lynne R.; Parker, Lisa C.; Stokes, Clare A.; de Bruin, Harold G.; van den Berge, Maarten; Heijink, Irene H.; Whyte, Moira K.

    2012-01-01

    Pellino-1 has recently been identified as a regulator of interleukin-1 (IL-1) signaling, but its roles in regulation of responses of human cells to human pathogens are unknown. We investigated the potential roles of Pellino-1 in the airways. We show for the first time that Pellino-1 regulates responses to a human pathogen, rhinovirus minor group serotype 1B (RV-1B). Knockdown of Pellino-1 by small interfering RNA (siRNA) was associated with impaired production of innate immune cytokines such as CXCL8 from human primary bronchial epithelial cells in response to RV-1B, without impairment in production of antiviral interferons (IFN), and without loss of control of viral replication. Pellino-1 actions were likely to be independent of interleukin-1 receptor-associated kinase-1 (IRAK-1) regulation, since Pellino-1 knockdown in primary epithelial cells did not alter responses to IL-1 but did inhibit responses to poly(I·C), a Toll-like receptor 3 (TLR3) activator that does not signal via IRAK-1 to engender a response. These data indicate that Pellino-1 represents a novel target that regulates responses of human airways to human viral pathogens, independently of IRAK signaling. Neutralization of Pellino-1 may therefore provide opportunities to inhibit potentially harmful neutrophilic inflammation of the airways induced by respiratory viruses, without loss of control of the underlying viral infection. PMID:22514342

  8. Peritoneal inflammation – A microenvironment for Epithelial Ovarian Cancer (EOC

    Directory of Open Access Journals (Sweden)

    Liu Jinsong

    2004-06-01

    Full Text Available Abstract Epithelial ovarian cancer (EOC is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relationship between the tumor itself and its surrounding microenvironment. This review focuses on the anatomy, physiology, and current immunobiologic research of peritoneal structures, and addresses certain potentially useful animal models. Changes in both the inflammatory and non-inflammatory cell compartments, as well as alterations to the extracellular matrix, appear to be signal events that contribute to the remodeling effects of the peritoneal stroma and surface epithelial cells on tumor growth and spread. These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins. Interactions between these molecules and molecular structures within the extracellular matrix, such as collagens and the proteoglycans, may contribute to a peritoneal mesothelial surface and stromal environment that is conducive to tumor cell proliferation and invasion. These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

  9. [Calcifying epithelial odontogenic tumor (Pindborg tumor)].

    Science.gov (United States)

    Szporek, Bozena J; Cieślik, Tadeusz; Jedrzejewski, Piotr W; Lipiarz, Ludwik Z

    2005-01-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic neoplasm which was first described by Pindborg in 1955 representing only 1% of all odontogenic tumors. The tumor has an ectodermal odontogenic origin. This tumor are considered benign but can be locally aggressive in nature with recurrence rates of 10-15% reported. Surgical treatment varies from simply enucleation to partial resection of the affected bone. Since 1973 three cases only of the Pinborg tumor have been presented in the Polish literature. We described the case of a 44-year-old man with Pindborg tumor in the right maxilla. Standard x-ray examinations and CT scan were performed in order to obtain information about tumor's localization. Autors discuss the radiologic features of calcifying epithelial odontogenic tumor and treatment method and the relevant literature.

  10. Gastrointestinal Epithelial Organoid Cultures from Postsurgical Tissues.

    Science.gov (United States)

    Hahn, Soojung; Yoo, Jongman

    2017-08-17

    An organoid is a cellular structure three-dimensionally (3D) cultured from self-organizing stem cells in vitro, which has a cell population, architectures, and organ specific functions like the originating organs. Recent advances in the 3D culture of isolated intestinal crypts or gastric glands have enabled the generation of human gastrointestinal epithelial organoids. Gastrointestinal organoids recapitulate the human in vivo physiology because of all the intestinal epithelial cell types that differentiated and proliferated from tissue resident stem cells. Thus far, gastrointestinal organoids have been extensively used for generating gastrointestinal disease models. This protocol describes the method of isolating a gland or crypt using stomach or colon tissue after surgery and establishing them into gastroids or colonoids.

  11. Claudins in morphogenesis: Forming an epithelial tube.

    Science.gov (United States)

    Baumholtz, Amanda I; Gupta, Indra R; Ryan, Aimee K

    2017-10-02

    The claudin family of tetraspan transmembrane proteins is essential for tight junction formation and regulation of paracellular transport between epithelial cells. Claudins also play a role in apical-basal cell polarity, cell adhesion and link the tight junction to the actin cytoskeleton to exert effects on cell shape. The function of claudins in paracellular transport has been extensively studied through loss-of-function and gain-of-function studies in cell lines and in animal models, however, their role in morphogenesis has been less appreciated. In this review, we will highlight the importance of claudins during morphogenesis by specifically focusing on their critical functions in generating epithelial tubes, lumens, and tubular networks during organ formation.

  12. Streptococcus pyogenes translocates across an epithelial barrier.

    Science.gov (United States)

    Sumitomo, Tomoko

    2017-01-01

    Streptococcus pyogenes is a β-hemolytic organism responsible for a wide variety of human diseases that commonly occur as self-limiting purulent diseases of the pharynx and skin. Although the occurrence of invasive infections by S. pyogenes is rare, mortality rates remain high even with progressive medical therapy. As a prerequisite for causing the severe invasive disease, S. pyogenes must invade underlying sterile tissues by translocating across the epithelial barrier. In this study, streptolysin S and SpeB were identified as the novel factors that facilitate bacterial translocation via degradation of intercellular junctions. Furthermore, we found that S. pyogenes exploits host plasminogen for acceleration of bacterial invasion into deeper tissues via tricellular tight junctions. Here, I would like to show our study on bacterial translocation across the epithelial barrier through paracellular route.

  13. Invasion of epithelial cells by Trichinella spiralis: in vitro observations

    Directory of Open Access Journals (Sweden)

    Romarís F.

    2001-06-01

    Full Text Available It has been known for many years that Trichinella spiralis initiates infection by penetrating the columnar epithelium of the small intestine, however, the mechanisms used by the parasite in the establishment of its intramulticellular niche in the intestine are unknown. The recent demonstration that invasion also occurs in vitro when infective larvae of T. spiralis are inoculated onto cultures of epithelial cells provides a model that allows the direct observation of the process by which the parasite recognizes, invades and migrates within the epithelium. The finding that penetration of the cell membrane or Induction of plasma membrane wounds by larvae do not always result in invasion argue in favor of some kind of host-parasite communication in successful invasion. In this sense, the in vitro model of invasion provides a readily manipulated and controlled system to investigate both parasite, and host cell requirements for invasion.

  14. Cells of Origin of Epithelial Ovarian Cancers

    Science.gov (United States)

    2015-09-01

    lethal malignancy of the female reproductive system, largely due to the fact that most EOCs are diagnosed only after the cancer has metastasized into the...Epithelial ovarian cancer (EOC) is the most lethal malignancy of the female reproductive system, largely due to the fact that most EOCs are diagnosed only...experience in ovary research (ovarian physiology , oogonial stem cells) to work on this project. We also ! 5! obtained approval of our animal

  15. Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Araki Hiromasa

    2007-04-01

    Full Text Available Abstract Background Proteinase-activated receptors (PARs; PAR1–4 that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells. Results Stimulation of PAR with thrombin (1 U/ml or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β. Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial

  16. General Relativity

    CERN Document Server

    Khriplovich, I. B

    2005-01-01

    This book offers an alternative to other textbooks on the subject, providing a more specific discussion of numerous general relativistic effects for readers who have knowledge of classical mechanics and electrodynamics, including special relativity. Coverage includes gravitational lensing, signal retardation in the gravitational field of the Sun, the Reissner-Nordström solution, selected spin effects, the resonance transformation of an electromagnetic wave into a gravitational one, and the entropy and temperature of black holes. The book includes numerous problems at various levels of difficulty, making it ideal also for independent study by a broad readership of advanced students and researchers. I.B. Khriplovich is Chief Researcher, Budker Institute of Nuclear Physics, Novosibirsk, and Chair of Theoretical Physics at Novosibirsk University. Dr. Khriplovich is a Corresponding Member of the Russian Academy of Sciences. He has been awarded the Dirac Medal ``For the advancement of theoretical physics'' by Univ...

  17. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Malizia, Andrea P.; Lacey, Noreen [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland); Walls, Dermot [School of Biotechnology, Dublin City University. Dublin, 9. Ireland (Ireland); Egan, Jim J. [Advanced Lung Disease and Lung Transplant Program, Mater Misericordiae University Hospital. 44, Eccles Street. Dublin, 7. Ireland (Ireland); Doran, Peter P., E-mail: peter.doran@ucd.ie [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland)

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  18. Transcriptional networks in epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Christo Venkov

    Full Text Available Epithelial-mesenchymal transition (EMT changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis.Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts. DNA microarray in cultured epithelia undergoing EMT, validated in vivo, were used to detect various patterns of gene expression. In particular, the promoter sequences of differentially expressed genes and their transcription factors were analyzed to identify potential binding sites and partners. The four most frequent cis-regulatory elements (CREs in up-regulated genes were SRY, FTS-1, Evi-1, and GC-Box, and RNA inhibition of the four transcription factors, Atf2, Klf10, Sox11, and SP1, most frequently binding these CREs, establish their importance in the initiation and propagation of EMT. Oligonucleotides that block the most frequent CREs restrain EMT at early and intermediate stages through apoptosis of the cells.Our results identify new transcriptional interactions with high frequency CREs that modulate the stability of cellular plasticity, and may serve as targets for modulating these transitional states in fibroblasts.

  19. Robust cell tracking in epithelial tissues through identification of maximum common subgraphs.

    Science.gov (United States)

    Kursawe, Jochen; Bardenet, Rémi; Zartman, Jeremiah J; Baker, Ruth E; Fletcher, Alexander G

    2016-11-01

    Tracking of cells in live-imaging microscopy videos of epithelial sheets is a powerful tool for investigating fundamental processes in embryonic development. Characterizing cell growth, proliferation, intercalation and apoptosis in epithelia helps us to understand how morphogenetic processes such as tissue invagination and extension are locally regulated and controlled. Accurate cell tracking requires correctly resolving cells entering or leaving the field of view between frames, cell neighbour exchanges, cell removals and cell divisions. However, current tracking methods for epithelial sheets are not robust to large morphogenetic deformations and require significant manual interventions. Here, we present a novel algorithm for epithelial cell tracking, exploiting the graph-theoretic concept of a 'maximum common subgraph' to track cells between frames of a video. Our algorithm does not require the adjustment of tissue-specific parameters, and scales in sub-quadratic time with tissue size. It does not rely on precise positional information, permitting large cell movements between frames and enabling tracking in datasets acquired at low temporal resolution due to experimental constraints such as phototoxicity. To demonstrate the method, we perform tracking on the Drosophila embryonic epidermis and compare cell-cell rearrangements to previous studies in other tissues. Our implementation is open source and generally applicable to epithelial tissues. © 2016 The Authors.

  20. Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis.

    Science.gov (United States)

    Zhang, Qi; Dong, Peixin; Liu, Xishi; Sakuragi, Noriaki; Guo, Sun-Wei

    2017-07-28

    EZH2, a subunit of the polycomb repressive complex 2 (PRC2) catalyzing trimethylation of histone H3 lysine 27 (H3K27), induces epithelial-mesenchymal transition (EMT) in cancers. However, whether EZH2 regulates EMT in endometriosis is unclear. Here, we show that EZH2 expression, along with its associated PRC2 proteins, is significantly elevated in ectopic and eutopic endometrium from women with endometriosis as compared with control endometrium. EZH2 knockdown or inhibition restored the epithelial phenotypes of endometriotic epithelial cells, concomitant with the upregulation of E-cadherin and downregulation of vimentin and transcription factors (Snail and Slug) as well as reduced cellular migratory and invasive propensity. Conversely, overexpression of EZH2 induced the expression of Snail, Slug and vimentin and suppresses E-cadherin expression. In vivo administration of 3-Deazaneplanocin A (DZNep), an EZH2 inhibitor, significantly inhibited the growth of endometriotic lesions and improved generalized hyperalgesia, along with attenuated EMT and reduced fibrosis in endometriosis. Notably, platelets induced EZH2 upregulation and increased H3K27 and H3K9 trimethylation levels in endometriotic epithelial cells. These data identify EZH2 as a novel driver of EMT in endometriosis, implicates the link between wound healing and epigenetic changes in the context of endometriosis, and underscore the role of platelets in the development of endometriosis.

  1. Intracellular Position of Centrioles and the Direction of Homeostatic Epithelial Cell Movements in the Mouse Cornea.

    Science.gov (United States)

    Silverman, Erika; Zhao, Jin; Merriam, John C; Nagasaki, Takayuki

    2017-02-01

    Corneal epithelial cells exhibit continuous centripetal movements at a rate of about 30 µm per day, but neither the driving force nor the mechanism that determines the direction of movements is known. To facilitate the investigation of homeostatic cell movement, we examined if the intracellular position of a centriole can be used as a directional marker of epithelial cell movements in the mouse cornea. A direction of cell movements was estimated in fixed specimens from a pattern of underlying subepithelial nerve fibers. Intracellular position of centrioles was determined by gamma-tubulin immunohistology and plotted in a narrow strip along the entire diameter of a cornea from limbus to limbus. When we determined the position of centrioles in the peripheral cornea where cell movements proceed generally along a radial path, about 55% of basal epithelial cells contained a centriole in the front half of a cell. However, in the central cornea where cells exhibit a spiral pattern of movements, centrioles were distributed randomly. These results suggest that centrioles tend to be positioned toward the direction of movement in corneal basal epithelial cells when they are moving centripetally at a steady rate.

  2. Cultured alveolar epithelial cells from septic rats mimic in vivo septic lung.

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    Taylor S Cohen

    2010-06-01

    Full Text Available Sepsis results in the formation of pulmonary edema by increasing in epithelial permeability. Therefore we hypothesized that alveolar epithelial cells isolated from septic animals develop tight junctions with different protein composition and reduced barrier function relative to alveolar epithelial cells from healthy animals. Male rats (200-300 g were sacrificed 24 hours after cecal ligation and double puncture (2CLP or sham surgery. Alveolar epithelial cells were isolated and plated on fibronectin-coated flexible membranes or permeable, non-flexible transwell substrates. After a 5 day culture period, cells were either lysed for western analysis of tight junction protein expressin (claudin 3, 4, 5, 7, 8, and 18, occludin, ZO-1, and JAM-A and MAPk (JNK, ERK, an p38 signaling activation, or barrier function was examined by measuring transepithelial resistance (TER or the flux of two molecular tracers (5 and 20 A. Inhibitors of JNK (SP600125, 20 microM and ERK (U0126, 10 microM were used to determine the role of these pathways in sepsis induced epithelial barrier dysfunction. Expression of claudin 4, claudin 18, and occludin was significantly lower, and activation of JNK and ERK signaling pathways was significantly increased in 2CLP monolayers, relative to sham monolayers. Transepithelial resistance of the 2CLP monolayers was reduced significantly compared to sham (769 and 1234 ohm-cm(2, respectively, however no significant difference in the flux of either tracer was observed. Inhibition of ERK, not JNK, significantly increased TER and expression of claudin 4 in 2CLP monolayers, and prevented significant differences in claudin 18 expression between 2CLP and sham monolayers. We conclude that alveolar epithelial cells isolated from septic animals form confluent monolayers with impaired barrier function compared to healthy monolayers, and inhibition of ERK signaling partially reverses differences between these monolayers. This model provides a unique

  3. Strategies to enhance epithelial-mesenchymal interactions for human hair follicle bioengineering.

    Science.gov (United States)

    Ohyama, Manabu; Veraitch, Ophelia

    2013-05-01

    Hair follicle morphogenesis and regeneration depend on intensive but well-orchestrated interactions between epithelial and mesenchymal components. Accordingly, the enhancement of this crosstalk represents a promising approach to achieve successful bioengineering of human hair follicles. The present article summarizes the techniques, both currently available and potentially feasible, to promote epithelial-mesenchymal interactions (EMIs) necessary for human hair follicle regeneration. The strategies include the preparation of epithelial components with high receptivity to trichogenic dermal signals and/or mesenchymal cell populations with potent hair inductive capacity. In this regard, bulge epithelial stem cells, keratinocytes predisposed to hair follicle fate or keratinocyte precursor cells with plasticity may provide favorable epithelial cell populations. Dermal papilla cells sustaining intrinsic hair inductive capacity, putative dermal papilla precursor cells in the dermal sheath/neonatal dermis or trichogenic dermal cells derived from undifferentiated stem/progenitor cells are promising candidates as hair inductive dermal cells. The most established protocol for in vivo hair follicle reconstitution is co-grafting of epithelial and mesenchymal components into immunodeficient mice. In theory, combination of individually optimized cellular components of respective lineages should elicit most intensive EMIs to form hair follicles. Still, EMIs can be further ameliorated by the modulation of non-cell autonomous conditions, including cell compartmentalization to replicate the positional relationship in vivo and humanization of host environment by preparing human stromal bed. These approaches may not always synergistically intensify EMIs, however, step-by-step investigation probing optimal combinations should maximally enhance EMIs to achieve successful human hair follicle bioengineering. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by

  4. Transcriptome analysis of epithelial and stromal contributions to mammogenesis in three week prepartum cows.

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    Theresa Casey

    Full Text Available Transcriptome analysis of bovine mammary development has provided insight into regulation of mammogenesis. However, previous studies primarily examined expression of epithelial and stromal tissues combined, and consequently did not account for tissue specific contribution to mammary development. Our objective was to identify differences in gene expression in epithelial and intralobular stromal compartments. Tissue was biopsied from non-lactating dairy cows 3 weeks prepartum, cut into explants and incubated for 2 hr with insulin and hydrocortisone. Epithelial and intralobular stromal tissues were isolated with laser capture microdissection. Global gene expression was measured with Bovine Affymetrix GeneChips, and data were preprocessed using RMA method. Moderated t-tests from gene-specific linear model analysis with cell type as a fixed effect showed more than 3,000 genes were differentially expressed between tissues (P<0.05; FDR<0.17. Analysis of epithelial and stromal transcriptomes using Database for Annotation, Visualization and Integrated Discovery (DAVID and Ingenuity Pathways Analysis (IPA showed that epithelial and stromal cells contributed distinct molecular signatures. Epithelial signatures were enriched with gene sets for protein synthesis, metabolism and secretion. Stromal signatures were enriched with genes that encoded molecules important to signaling, extracellular matrix composition and remodeling. Transcriptome differences also showed evidence for paracrine interactions between tissues in stimulation of IGF1 signaling pathway, stromal reaction, angiogenesis, neurogenesis, and immune response. Molecular signatures point to the dynamic role the stroma plays in prepartum mammogenesis and highlight the importance of examining the roles of cell types within the mammary gland when targeting therapies and studying mechanisms that affect milk production.

  5. Comparison of calcium supplementation or low-fat dairy foods on epithelial cell proliferation and differentiation.

    Science.gov (United States)

    Holt, P R; Wolper, C; Moss, S F; Yang, K; Lipkin, M

    2001-01-01

    Epidemiological evidence suggests that dietary calcium and vitamin D intake are inversely related to incidence of colon cancer. Previous studies have demonstrated that supplementation of the diet with calcium in the form of calcium tablets or low-fat dairy foods alters colonic epithelial cell proliferation from a higher- to a lower-risk pattern. The present study compared relative effects of administration of calcium carbonate at approximately 900 mg/day (calcium) with those of a low-fat dairy food diet providing about the same amount of calcium (dairy) in a cross-over "head-to-head" study of 40 subjects at risk for colonic neoplasia. Dietary intake of macronutrients was similar in the two study periods, except for a slight increase in protein intake during dairy calcium supplementation. Rectal epithelial cell proliferation was studied in flat endoscopically normal-appearing mucosa at baseline and at the end of each of the two study periods and showed a significant reduction in epithelial crypt cell labeling index from 12.5% to 9.1% (calcium) or 9.3% (dairy) as well as in proliferating cells in the upper 40% of the crypt from 0.09 to 0.03 in the calcium- and low-fat dairy-supplemented intervention groups. No significant changes in two epithelial cell differentiation markers, cytokeratin AE1 and acidic mucins, were found. Furthermore, there were no differences in epithelial cell apoptosis or expression of the proapoptotic gene product BAK. These data indicate that increased dietary calcium given as supplements or in the diet in low-fat dairy foods lowers epithelial cell proliferation indexes from a higher- to a lower-risk pattern. Because supplemental calcium has been shown to reduce the recurrence of colonic adenomatous polyps in patients at increased risk for colonic neoplasia, our data suggest that supplemental low-fat dairy foods may also be effective.

  6. In vivo assessment of wound re-epithelialization by UV fluorescence excitation imaging

    Science.gov (United States)

    Wang, Ying; Ortega-Martinez, Antonio; Padilla-Martinez, Juan Pablo; Williams, Maura; Farinelli, William; Anderson, R. R.; Franco, Walfre

    2017-02-01

    Background and Objectives: We have previously demonstrated the efficacy of a non-invasive, non-contact, fast and simple but robust fluorescence imaging (u-FEI) method to monitor the healing of skin wounds in vitro. This system can image highly-proliferating cellular processes (295/340 nm excitation/emission wavelengths) to study epithelialization in a cultured wound model. The objective of the current work is to evaluate the suitability of u-FEI for monitoring wound re-epithelialization in vivo. Study Design: Full-thickness wounds were created in the tail of rats and imaged weekly using u-FEI at 295/340nm excitation/emission wavelengths. Histology was used to investigate the correlation between the spatial distribution and intensity of fluorescence and the extent of wound epithelialization. In addition, the expression of the nuclear protein Ki67 was used to confirm the association between the proliferation of keratinocyte cells and the intensity of fluorescence. Results: Keratinocytes forming neo-epidermis exhibited higher fluorescence intensity than the keratinocytes not involved in re-epithelialization. In full-thickness wounds the fluorescence first appeared at the wound edge where keratinocytes initiated the epithelialization process. Fluorescence intensity increased towards the center as the keratinocytes partially covered the wound. As the wound healed, fluorescence decreased at the edges and was present only at the center as the keratinocytes completely covered the wound at day 21. Histology demonstrated that changes in fluorescence intensity from the 295/340nm band corresponded to newly formed epidermis. Conclusions: u-FEI at 295/340nm allows visualization of proliferating keratinocyte cells during re-epithelialization of wounds in vivo, potentially providing a quantitative, objective and simple method for evaluating wound closure in the clinic.

  7. Therapy Provider Phase Information

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Therapy Provider Phase Information dataset is a tool for providers to search by their National Provider Identifier (NPI) number to determine their phase for...

  8. Combining large area fluorescence with multiphoton microscopy for improved detection of oral epithelial neoplasia (Conference Presentation)

    Science.gov (United States)

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

    2016-03-01

    Volumetric Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia representing the complex microstructural organization of mucosa, potentially providing high specificity for detection of neoplasia, but is limited by small imaging area. Large area fluorescence methods on the other hand show high sensitivity appropriate for screening but are hampered by low specificity. In this study, we apply MPAM-SHGM following guidance from large area fluorescence, by either autofluorescence or a targeted metabolic fluorophore, as a potentially clinically viable approach for detection of oral neoplasia. Sites of high neoplastic potentially were identified by large area red/green autofluorescence or by a fluorescently labelled deoxy-glucose analog, 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) to highlight areas of high glucose uptake across the buccal pouch of a hamster model for OSCC. Follow-up MPAM-SHGM was conducted on regions of interests (ROIs) to assess whether microscopy would reveal microscopic features associated with neoplasia to confirm or exclude large area fluorescence findings. Parameters for analysis included cytologic metrics, 3D epithelial connective tissue interface metrics (MPAM-SHGM) and intensity of fluorescence (widefield). Imaged sites were biopsied and processed for histology and graded by a pathologist. A small sample of human ex vivo tissues were also imaged. A generalized linear model combining image metrics from large area fluorescence and volumetric MPAM-SHGM indicated the ability to delineate normal and inflammation from neoplasia.

  9. Epithelial estrogen receptor 1 intrinsically mediates squamous differentiation in the mouse vagina.

    Science.gov (United States)

    Miyagawa, Shinichi; Iguchi, Taisen

    2015-10-20

    Estrogen-mediated actions in female reproductive organs are tightly regulated, mainly through estrogen receptor 1 (ESR1). The mouse vaginal epithelium cyclically exhibits cell proliferation and differentiation in response to estrogen and provides a unique model for analyzing the homeostasis of stratified squamous epithelia. To address the role of ESR1-mediated tissue events during homeostasis, we analyzed mice with a vaginal epithelium-specific knockout of Esr1 driven by keratin 5-Cre (K5-Esr1KO). We show here that loss of epithelial ESR1 in the vagina resulted in aberrant epithelial cell proliferation in the suprabasal cell layers and led to failure of keratinized differentiation. Gene expression analysis showed that several known estrogen target genes, including erbB growth factor ligands, were not induced by estrogen in the K5-Esr1KO mouse vagina. Organ culture experiments revealed that the addition of erbB growth factor ligands, such as amphiregulin, could activate keratinized differentiation in the absence of epithelial ESR1. Thus, epithelial ESR1 integrates estrogen and growth factor signaling to mediate regulation of cell proliferation in squamous differentiation, and our results provide new insights into estrogen-mediated homeostasis in female reproductive organs.

  10. Hypoxia Inducible Factor (HIF Hydroxylases as Regulators of Intestinal Epithelial Barrier FunctionSummary

    Directory of Open Access Journals (Sweden)

    Mario C. Manresa

    2017-05-01

    Full Text Available Human health is dependent on the ability of the body to extract nutrients, fluids, and oxygen from the external environment while at the same time maintaining a state of internal sterility. Therefore, the cell layers that cover the surface areas of the body such as the lung, skin, and gastrointestinal mucosa provide vital semipermeable barriers that allow the transport of essential nutrients, fluid, and waste products, while at the same time keeping the internal compartments free of microbial organisms. These epithelial surfaces are highly specialized and differ in their anatomic structure depending on their location to provide appropriate and effective site-specific barrier function. Given this important role, it is not surprising that significant disease often is associated with alterations in epithelial barrier function. Examples of such diseases include inflammatory bowel disease, chronic obstructive pulmonary disease, and atopic dermatitis. These chronic inflammatory disorders often are characterized by diminished tissue oxygen levels (hypoxia. Hypoxia triggers an adaptive transcriptional response governed by hypoxia-inducible factors (HIFs, which are repressed by a family of oxygen-sensing HIF hydroxylases. Here, we review recent evidence suggesting that pharmacologic hydroxylase inhibition may be of therapeutic benefit in inflammatory bowel disease through the promotion of intestinal epithelial barrier function through both HIF-dependent and HIF-independent mechanisms. Keywords: Epithelial Barrier, Inflammatory Bowel Disease, Hypoxia, Hypoxia-Inducible Factor (HIF Hydroxylases

  11. Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

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    Joseph Kwong

    2009-06-01

    Full Text Available In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.

  12. Methods to Study Epithelial Transport Protein Function and Expression in Native Intestine and Caco-2 Cells Grown in 3D.

    Science.gov (United States)

    Anabazhagan, Arivarasu N; Chatterjee, Ishita; Priyamvada, Shubha; Kumar, Anoop; Tyagi, Sangeeta; Saksena, Seema; Alrefai, Waddah A; Dudeja, Pradeep K; Gill, Ravinder K

    2017-03-16

    The intestinal epithelium has important transport and barrier functions that play key roles in normal physiological functions of the body while providing a barrier to foreign particles. Impaired epithelial transport (ion, nutrient, or drugs) has been associated with many diseases and can have consequences that extend beyond the normal physiological functions of the transporters, such as by influencing epithelial integrity and the gut microbiome. Understanding the function and regulation of transport proteins is critical for the development of improved therapeutic interventions. The biggest challenge in the study of epithelial transport is developing a suitable model system that recapitulates important features of the native intestinal epithelial cells. Several in vitro cell culture models, such as Caco-2, T-84, and HT-29-Cl.19A cells are typically used in epithelial transport research. These cell lines represent a reductionist approach to modeling the epithelium and have been used in many mechanistic studies, including their examination of epithelial-microbial interactions. However, cell monolayers do not accurately reflect cell-cell interactions and the in vivo microenvironment. Cells grown in 3D have shown to be promising models for drug permeability studies. We show that Caco-2 cells in 3D can be used to study epithelial transporters. It is also important that studies in Caco-2 cells are complemented with other models to rule out cell specific effects and to take into account the complexity of the native intestine. Several methods have been previously used to assess the functionality of transporters, such as everted sac and uptake in isolated epithelial cells or in isolated plasma membrane vesicles. Taking into consideration the challenges in the field with respect to models and the measurement of transport function, we demonstrate here a protocol to grow Caco-2 cells in 3D and describe the use of an Ussing chamber as an effective approach to measure serotonin

  13. Effects of cigarette smoke condensate on proliferation and wound closure of bronchial epithelial cells in vitro: role of glutathione

    Directory of Open Access Journals (Sweden)

    Rabe Klaus F

    2005-11-01

    and the anti-oxidant status. These findings are consistent with increased epithelial proliferation in smokers, and may provide further insight in the development of lung cancer.

  14. Providing Personalised Nutrition

    NARCIS (Netherlands)

    Poínhos, Rui; Oliveira, Bruno M.P.M.; Lans, Van Der Ivo A.; Fischer, Arnout R.H.; Berezowska, Aleksandra; Rankin, Audrey; Kuznesof, Sharron; Stewart-Knox, Barbara; Frewer, Lynn J.; Almeida, De Maria D.V.

    2017-01-01

    Background/Aims: Personalised nutrition has potential to revolutionise dietary health promotion if accepted by the general public. We studied trust and preferences regarding personalised nutrition services, how they influence intention to adopt these services, and cultural and social differences

  15. Glutathione Transferase as a Potential Marker for Gut Epithelial Injury versus the Protective Role of Breast Milk sIgA in Infants with Rota Virus Gastroenteritis

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    Lobna S. Sherif

    2015-11-01

    CONCLUSION: Breast feeding should be encouraged and highly recommended in the first two years of life as it provides Secretory IgA to breast fed infants who in turn protect them against epithelial damage caused by Rota viral gastroenteritis.

  16. Using Drugs to Probe the Variability of Trans-Epithelial Airway Resistance.

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    Kendra Tosoni

    Full Text Available Precision medicine aims to combat the variability of the therapeutic response to a given medicine by delivering the right medicine to the right patient. However, the application of precision medicine is predicated on a prior quantitation of the variance of the reference range of normality. Airway pathophysiology provides a good example due to a very variable first line of defence against airborne assault. Humans differ in their susceptibility to inhaled pollutants and pathogens in part due to the magnitude of trans-epithelial resistance that determines the degree of epithelial penetration to the submucosal space. This initial 'set-point' may drive a sentinel event in airway disease pathogenesis. Epithelia differentiated in vitro from airway biopsies are commonly used to model trans-epithelial resistance but the 'reference range of normality' remains problematic. We investigated the range of electrophysiological characteristics of human airway epithelia grown at air-liquid interface in vitro from healthy volunteers focusing on the inter- and intra-subject variability both at baseline and after sequential exposure to drugs modulating ion transport.Brushed nasal airway epithelial cells were differentiated at air-liquid interface generating 137 pseudostratified ciliated epithelia from 18 donors. A positively-skewed baseline range exists for trans-epithelial resistance (Min/Max: 309/2963 Ω·cm2, trans-epithelial voltage (-62.3/-1.8 mV and calculated equivalent current (-125.0/-3.2 μA/cm2; all non-normal, P<0.001. A minority of healthy humans manifest a dramatic amiloride sensitivity to voltage and trans-epithelial resistance that is further discriminated by prior modulation of cAMP-stimulated chloride transport.Healthy epithelia show log-order differences in their ion transport characteristics, likely reflective of their initial set-points of basal trans-epithelial resistance and sodium transport. Our data may guide the choice of the background set

  17. Polarized protein transport and lumen formation during epithelial tissue morphogenesis.

    Science.gov (United States)

    Blasky, Alex J; Mangan, Anthony; Prekeris, Rytis

    2015-01-01

    One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo.

  18. Autophagy protects gastric mucosal epithelial cells from ethanol-induced oxidative damage via mTOR signaling pathway.

    Science.gov (United States)

    Chang, Weilong; Bai, Jie; Tian, Shaobo; Ma, Muyuan; Li, Wei; Yin, Yuping; Deng, Rui; Cui, Jinyuan; Li, Jinjin; Wang, Guobin; Zhang, Peng; Tao, Kaixiong

    2017-05-01

    Alcohol abuse is an important cause of gastric mucosal epithelial cell injury and gastric ulcers. A number of studies have demonstrated that autophagy, an evolutionarily conserved cellular mechanism, has a protective effect on cell survival. However, it is not known whether autophagy can protect gastric mucosal epithelial cells against the toxic effects of ethanol. In the present study, gastric mucosal epithelial cells (GES-1 cells) and Wistar rats were treated with ethanol to detect the adaptive response of autophagy. Our results demonstrated that ethanol exposure induced gastric mucosal epithelial cell damage, which was accompanied by the downregulation of mTOR signaling pathway and activation of autophagy. Suppression of autophagy with pharmacological agents resulted in a significant increase of GES-1 cell apoptosis and gastric mucosa injury, suggesting that autophagy could protect cells from ethanol toxicity. Furthermore, we evaluated the cellular oxidative stress response following ethanol treatment and found that autophagy induced by ethanol inhibited generation of reactive oxygen species and degradation of antioxidant and lipid peroxidation. In conclusion, these findings provide evidence that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate oxidative damage induced by ethanol in gastric mucosal epithelial cells. Therefore, modifying autophagy may provide a therapeutic strategy against alcoholic gastric mucosa injury. Impact statement The effect and mechanism of autophagy on ethanol-induced cell damage remain controversial. In this manuscript, we report the results of our study demonstrating that autophagy can protect gastric mucosal epithelial cells against ethanol toxicity in vitro and in vivo. We have shown that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate ethanol-induced oxidative damage in

  19. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

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    Nagayasu Egawa

    2015-07-01

    Full Text Available Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.

  20. Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias

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    Kajiki Akira

    2011-03-01

    Full Text Available Abstract Background It is difficult to predict survival in patients with idiopathic pulmonary fibrosis. Recently, several proteins, such as surfactant protein (SP and KL-6, have been reported to be useful biologic markers for prediction of prognosis for interstitial pneumonias. It is not clear whether there is any relationship between expression of these proteins in regenerative/hyperplastic alveolar epithelial cells and prognosis of idiopathic interstitial pneumonias (IIPs. Objectives This study aimed to elucidate the clinical significance of the expression of such lung secretory proteins as SP-A and KL-6 in lung tissues of patients with IIPs. Methods We retrospectively investigated the immunohistochemical expression of SP-A, KL-6, cytokeratin (CK, and epithelial membrane antigen (EMA in alveolar epithelial cells in lung tissues obtained from surgical lung biopsy in 43 patients with IIPs, and analyzed the correlation between expression of these markers and the prognosis of each IIP patient. CK and EMA were used as general markers for epithelial cells. Results In patients with usual interstitial pneumonia (UIP, the ratio of SP-A positive epithelial cells to all alveolar epithelial cells (SP-A positive ratio in the collapsed and mural fibrosis areas varied, ranging from cases where almost all alveolar epithelial cells expressed SP-A to cases where only a few did. On the other hand, in many patients with nonspecific interstitial pneumonia (NSIP, many of the alveolar epithelial cells in the diseased areas expressed SP-A. The SP-A positive ratio was significantly lower in patients who died from progression of UIP than in patients with UIP who remained stable or deteriorated but did not die. In NSIP patients, a similar tendency was noted between the SP-A positive ratio and prognosis. Conclusions The results suggest that the paucity of immunohistochemical SP-A expression in alveolar epithelial cells in diseased areas (i.e. regenerative

  1. Graft epithelial defects after deep anterior lamellar keratoplasty.

    Science.gov (United States)

    Feizi, Sepehr; Javadi, Fatemeh; Javadi, Mohammad Ali

    2014-11-01

    The aim of this study was to report the incidence of epithelial defects and identify donor factors that might correlate with the presence of epithelial defects and graft reepithelialization time after a deep anterior lamellar keratoplasty (DALK). In this retrospective study, 283 consecutive keratoconic eyes underwent DALK using donor corneas of different qualities, ranging from fair to excellent. The donor data included age and sex, cause of death, death-to-preservation time, preservation-to-surgery time, epithelial and stromal status, endothelial cell density and morphology, and graft rating. On the first postoperative day, the corneal surface was carefully examined before and after the application of fluorescein stain, and the patients were followed up daily until complete reepithelialization occurred. A multivariate regression analysis was used to assess the correlation between donor characteristics and graft epithelial defects on postoperative day 1. The mean donor and recipient ages were 33.5 ± 13.2 and 27.6 ± 7.9 years, respectively. Two hundred sixty-four (93.3%) grafts had epithelial defects on day 1. The epithelial defects completely healed after 3.5 ± 2.7 (range, 1-37) days. In the univariate analysis, the presence of epithelial defects on postoperative day 1 had a significant correlation with donor preservation-to-surgery time (P = 0.01), epithelial sloughing (P < 0.001), and graft rating (P = 0.004). In the multivariate analysis, only donor epithelial sloughing significantly influenced the presence of epithelial defects on postoperative day 1 (odds ratio = 9.26, P < 0.001). Graft epithelial defects were very common after DALK. The epithelial status of donors was the only independent factor predictive of the surface integrity on the first postoperative day.

  2. MUCOUS CELLS IN THE EPITHELIAL LINING OF DENTIGEROUS CYST

    OpenAIRE

    Pratiksha; Sangeeta; Sumanta; Prashanti; Sathyajitraje; Rajkumar

    2014-01-01

    The epithelial lining of both the developmental and inflammatory cysts of odontogenic origin are primarily composed of squamous epithelium. Various forms of metaplasia and degenerations are observed in these epithelial linings e.g. mucous cells, ciliated cells, para and/or orthokeratinization and formation of hyaline bodies. The present study was designed to investigate the incidences of mucous cells in the epithelial lining of dentigerous cyst. Mucous cells were observed ...

  3. The Contribution of the Airway Epithelial Cell to Host Defense

    OpenAIRE

    Frauke Stanke

    2015-01-01

    In the context of cystic fibrosis, the epithelial cell has been characterized in terms of its ion transport capabilities. The ability of an epithelial cell to initiate CFTR-mediated chloride and bicarbonate transport has been recognized early as a means to regulate the thickness of the epithelial lining fluid and recently as a means to regulate the pH, thereby determining critically whether or not host defense proteins such as mucins are able to fold appropriately. This review describes how t...

  4. Effects of epiplakin-knockdown in cultured corneal epithelial cells

    OpenAIRE

    Kokado, Masahide; Okada, Yuka; Miyamoto, Takeshi; Yamanaka, Osamu; Saika, Shizuya

    2016-01-01

    Background To investigate effects of knockdown of epiplakin gene expression on the homeostasis of cultured corneal epithelial cell line. We previously reported acceleration of corneal epithelial wound healing in an epiplakin-null mouse. Methods Gene expression of epiplakin was knockdowned by employing siRNA transfection in SV40-immortalized human corneal epithelial cell line. Protein expression of E-cadherin, keratin 6 and vimentin was examined by western blotting. Cell migration and prolifer...

  5. Primary Biliary Cirrhosis Is a Generalized Autoimmune Epithelitis

    Directory of Open Access Journals (Sweden)

    Jun Gao

    2015-03-01

    Full Text Available Primary biliary cirrhosis (PBC is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs may contribute to apotope presentation to the immune system, causing unique tissue damage in PBC. Perpetuation of inflammation may result in senescence of BECs, contributing to irreversible loss of bile duct. In addition to the classic liver manifestations, focal inflammation and tissue damage are also seen in salivary glands and urinary tract in a significant proportion of PBC patients. These findings provide potent support to the idea that molecular mimicry may be involved in the breakdown of autoimmune tolerance and mucosal immunity may lead to a systematic epithelitis in PBC patients. Thus, PBC is considered a generalized epithelitis in clinical practice.

  6. Culture of Oral Mucosal Epithelial Cells for the Purpose of Treating Limbal Stem Cell Deficiency.

    Science.gov (United States)

    Utheim, Tor Paaske; Utheim, Øygunn Aass; Khan, Qalb-E-Saleem; Sehic, Amer

    2016-03-01

    The cornea is critical for normal vision as it allows allowing light transmission to the retina. The corneal epithelium is renewed by limbal epithelial cells (LEC), which are located in the periphery of the cornea, the limbus. Damage or disease involving LEC may lead to various clinical presentations of limbal stem cell deficiency (LSCD). Both severe pain and blindness may result. Transplantation of cultured autologous oral mucosal epithelial cell sheet (CAOMECS) represents the first use of a cultured non-limbal autologous cell type to treat this disease. Among non-limbal cell types, CAOMECS and conjunctival epithelial cells are the only laboratory cultured cell sources that have been explored in humans. Thus far, the expression of p63 is the only predictor of clinical outcome following transplantation to correct LSCD. The optimal culture method and substrate for CAOMECS is not established. The present review focuses on cell culture methods, with particular emphasis on substrates. Most culture protocols for CAOMECS used amniotic membrane as a substrate and included the xenogeneic components fetal bovine serum and murine 3T3 fibroblasts. However, it has been demonstrated that tissue-engineered epithelial cell sheet grafts can be successfully fabricated using temperature-responsive culture surfaces and autologous serum. In the studies using different substrates for culture of CAOMECS, the quantitative expression of p63 was generally poorly reported; thus, more research is warranted with quantification of phenotypic data. Further research is required to develop a culture system for CAOMECS that mimics the natural environment of oral/limbal/corneal epithelial cells without the need for undefined foreign materials such as serum and feeder cells.

  7. Molecular dissection of mesenchymal-epithelial interactions in the hair follicle.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available De novo hair follicle formation in embryonic skin and new hair growth in adult skin are initiated when specialized mesenchymal dermal papilla (DP cells send cues to multipotent epithelial stem cells. Subsequently, DP cells are enveloped by epithelial stem cell progeny and other cell types to form a niche orchestrating hair growth. Understanding the general biological principles that govern the mesenchymal-epithelial interactions within the DP niche, however, has been hampered so far by the lack of systematic approaches to dissect the complete molecular make-up of this complex tissue. Here, we take a novel multicolor labeling approach, using cell type-specific transgenic expression of red and green fluorescent proteins in combination with immunolabeling of specific antigens, to isolate pure populations of DP and four of its surrounding cell types: dermal fibroblasts, melanocytes, and two different populations of epithelial progenitors (matrix and outer root sheath cells. By defining their transcriptional profiles, we develop molecular signatures characteristic for the DP and its niche. Validating the functional importance of these signatures is a group of genes linked to hair disorders that have been largely unexplored. Additionally, the DP signature reveals novel signaling and transcription regulators that distinguish them from other cell types. The mesenchymal-epithelial signatures include key factors previously implicated in ectodermal-neural fate determination, as well as a myriad of regulators of bone morphogenetic protein signaling. These findings establish a foundation for future functional analyses of the roles of these genes in hair development. Overall, our strategy illustrates how knowledge of the genes uniquely expressed by each cell type residing in a complex niche can reveal important new insights into the biology of the tissue and its associated disease states.

  8. Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis.

    LENUS (Irish Health Repository)

    O'Connell, J

    2012-02-03

    Homeostasis in the colonic epithelium is achieved by a continuous cycle of proliferation and apoptosis, in which imbalances are associated with disease. Inflammatory bowel disease (IBD) and colon cancer are associated with either excessive or insufficient apoptosis of colonic epithelial cells, respectively. By using two colonic epithelial cell lines, HT29 and SW620, we investigated how the epithelial cell\\'s sensitivity to apoptosis was regulated by the proinflammatory cytokine interferon-gamma (IFN-gamma). We found that IFN-gamma sensitized HT29 cells, and to a lesser extent SW620, to diverse inducers of apoptosis of physiologic or therapeutic relevance to the colon. These apoptosis inducers included Fas (CD95\\/APO-1) ligand (FasL), short-chain fatty acids, and chemotherapeutic drugs. The extent of IFN-gamma-mediated apoptosis sensitization in these two cell lines correlated well with the degree of IFN-gamma-mediated upregulation of the proapoptotic protease caspase-1. Although IFN-gamma alone effectively sensitized HT29 cells to apoptosis, inclusion of the protein synthesis inhibitor cyclohexamide (CHX) during apoptotic challenge was necessary for maximal sensitization of SW620. The requirement of CHX to sensitize SW620 cells to apoptosis implies a need to inhibit translation of antiapoptotic proteins absent from HT29. In particular, the antiapoptotic protein Bcl-2 was strongly expressed in SW620 cells but absent from HT29. Our results indicate that IFN-gamma increases the sensitivity of colonic epithelial cells to diverse apoptotic stimuli in concert, via upregulation of caspase-1. Our findings implicate caspase-1 and Bcl-2 as important central points of control determining the general sensitivity of colonic epithelial cells to apoptosis.

  9. Calcifying epithelial odontogenic tumor: A clinico-radio-pathological dilemma

    Directory of Open Access Journals (Sweden)

    M S Hada

    2014-01-01

    Full Text Available The calcifying epithelial odontogenic tumor (CEOT is a rare benign neoplasm of mandible in adults. The presentation of this entity is varied and often confused with a variety of mucosal and jaw lesions and clinical, radiological, and pathological feature of CEOT often-mimic malignancy. The objective of this report is to highlight the clinical features and radiological findings which should arouse suspicion of a benign lesion and importance of providing adequate clinical information to the pathologist to attain accurate diagnosis.We discussed two cases with tumors located in the maxilla. Both presented as expansile lesions with one biopsy proven squamous cell carcinoma. Both were pursued with clinico-radiological suspicion of benign lesions and confirmed with pathological correlation of histology and immunohistochemistry as CEOT. Therefore a High index of suspicion and clinico-radiological information are the key feature for diagnosis of this rare tumor.

  10. Small molecule mediated proliferation of primary retinal pigment epithelial cells.

    Science.gov (United States)

    Swoboda, Jonathan G; Elliott, Jimmy; Deshmukh, Vishal; de Lichtervelde, Lorenzo; Shen, Weijun; Tremblay, Matthew S; Peters, Eric C; Cho, Charles Y; Lu, Bin; Girman, Sergej; Wang, Shaomei; Schultz, Peter G

    2013-07-19

    Retinal pigment epithelial (RPE) cells form a monolayer adjacent to the retina and play a critical role in the visual light cycle. Degeneration of RPE cells results in retinal disorders such as age-related macular degeneration. Cell transplant strategies have potential therapeutic value for such disorders; however, risks associated with an inadequate supply of donor cells limit their therapeutic success. The identification of factors that proliferate RPE cells ex vivo could provide a renewable source of cells for transplantation. Here, we report that a small molecule (WS3) can reversibly proliferate primary RPE cells isolated from fetal and adult human donors. Following withdrawal of WS3, RPE cells differentiate into a functional monolayer, as exhibited by their expression of mature RPE genes and phagocytosis of photoreceptor outer segments. Furthermore, chemically expanded RPE cells preserve vision when transplanted into dystrophic Royal College of Surgeons (RCS) rats, a well-established model of retinal degeneration.

  11. Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer

    Science.gov (United States)

    2014-05-06

    Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

  12. Intra-Subtype Variation in Enteroadhesion Accounts for Differences in Epithelial Barrier Disruption and Is Associated with Metronidazole Resistance in Blastocystis Subtype-7

    Science.gov (United States)

    Tan, Kevin Shyong Wei

    2014-01-01

    Blastocystis is an extracellular, enteric pathogen that induces intestinal disorders in a range of hosts including humans. Recent studies have identified potential parasite virulence factors in and host responses to this parasite; however, little is known about Blastocystis-host attachment, which is crucial for colonization and virulence of luminal stages. By utilizing 7 different strains of the parasite belonging to two clinically relevant subtypes ST-4 and ST-7, we investigated Blastocystis-enterocyte adhesion and its association with parasite-induced epithelial barrier disruption. We also suggest that drug resistance in ST-7 strains might result in fitness cost that manifested as impairment of parasite adhesion and, consequently, virulence. ST-7 parasites were generally highly adhesive to Caco-2 cells and preferred binding to intercellular junctions. These strains also induced disruption of ZO-1 and occludin tight junction proteins as well as increased dextran-FITC flux across epithelial monolayers. Interestingly, their adhesion was correlated with metronidazole (Mz) susceptibility. Mz resistant (Mzr) strains were found to be less pathogenic, owing to compromised adhesion. Moreover, tolerance of nitrosative stress was also reduced in the Mzr strains. In conclusion, the findings indicate that Blastocystis attaches to intestinal epithelium and leads to epithelial barrier dysfunction and that drug resistance might entail a fitness cost in parasite virulence by limiting entero-adhesiveness. This is the first study of the cellular basis for strain-to-strain variation in parasite pathogenicity. Intra- and inter-subtype variability in cytopathogenicity provides a possible explanation for the diverse clinical outcomes of Blastocystis infections. PMID:24851944

  13. Modulation of epithelial cell polarity by bacterial pathogens.

    Science.gov (United States)

    Tapia, Rocio; Kralicek, Sarah E; Hecht, Gail A

    2017-10-01

    Epithelial cells constitute a physical barrier that aids in protecting the host from microbial pathogens. Polarized epithelial cells contain distinct apical and basolateral membrane domains separated by intercellular junctions, including tight junctions (TJs), which contribute to the maintenance of apical-basal polarity. Polarity complexes also contribute to the establishment of TJ formation. Several pathogens perturb epithelial TJ barrier function and structure in addition to causing a loss of apical-basal polarity. Here, we review the impact of pathogenic bacteria on the disruption of cell-cell junctions and epithelial polarity. © 2017 New York Academy of Sciences.

  14. Engineering epithelial-stromal interactions in vitro for toxicology assessment.

    Science.gov (United States)

    Belair, David G; Abbott, Barbara D

    2017-05-01

    Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues. Published by Elsevier B.V.

  15. Development and Novel Uses of Antibodies in Epithelial Ovarian Cancer

    National Research Council Canada - National Science Library

    Curtin, John P

    2003-01-01

    .... Further understanding of the host response to epithelial cancers and the potential capability of innovative immunologic technologies to ovarian cancer may play a key role in therapeutic advances...

  16. Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro.

    Directory of Open Access Journals (Sweden)

    Ussama M Abdel-Motal

    Full Text Available Although cervico-vaginal epithelial cells of the female lower genital tract provide the initial defense system against HIV-1 infection, the protection is sometimes incomplete. Thus, enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of anti-HIV-1 broadly neutralizing antibodies (BnAb that block HIV-1 entry would provide an important new intervention that could slow the spread of HIV/AIDS.This study tested the hypothesis that adeno-associated virus (AAV-BnAb gene transfer to cervico-vaginal epithelial cells will lead to protection against HIV-1. Accordingly, a recombinant AAV vector that encodes human b12 anti-HIV gp120 BnAb as a single-chain variable fragment Fc fusion (scFvFc, or "minibody" was constructed. The secreted b12 minibody was shown to be biologically functional in binding to virus envelope protein, neutralizing HIV-1 and importantly, blocking transfer and infectivity of HIV-1(bal in an organotypic human vaginal epithelial cell (VEC model. Furthermore, cervico-vaginal epithelial stem cells were found to be efficiently transduced by the optimal AAV serotype mediated expression of GFP.This study provides the foundation for a novel microbicide strategy to protect against sexual transmission of HIV-1 by AAV transfer of broadly neutralizing antibody genes to cervico-vaginal epithelial stem cells that could replenish b12 BnAb secreting cells through multiple menstrual cycles.

  17. The autologus graft of epithelial tissue culture

    Directory of Open Access Journals (Sweden)

    Minaee B

    1999-08-01

    Full Text Available With the intention of research about culture and autologus graft of epithelial tissue we used 4 french Albino Rabbits with an average age of 2 months. After reproduction on the support in EMEM (Eagle's Minimum Essential Medium we used this for graft after 4 weeks. This region which grafted total replaced. After fixation of this sample and passing them through various process, histological sections were prepared. These sections were stained with H & E and masson's trichrome and studied by light microscope. We succeeded in graft. We hope in the near future by using the method of epithelium tissue culture improving to treat burned patients.

  18. Corneal epithelial inclusion cyst in a dog

    Directory of Open Access Journals (Sweden)

    Campos Carla de Freitas

    2002-01-01

    Full Text Available An unilateral corneal epithelial inclusion cyst in a 7-year-old male Boxer dog is reported. The cyst had been observed for thirty days, was unique, not congenital and only one eye was involved. Seven months prior to the referral the dog had manifested indolent corneal ulcer treated with grade keratotomy and third eyelid flap. The cyst was removed by superficial keratectomy followed by a conjunctival pedicle graft. Recovery was uncomplicated and there wasn?t recurrence seven months after the surgery.

  19. FOCAL EPITHELIAL HYPERPLASIA: HECK’S DISEASE

    Directory of Open Access Journals (Sweden)

    Brzeziński Piotr

    2010-10-01

    Full Text Available Heck's disease (focal epithelial hyperplasia (FEH is clinically characterized by multiple circumscribed, soft elevated nodules of the oral mucosa. Papules and plaques are usually the color of normal mucosa, but may be pale or, rarely, white. Disease may persist for years, producing a significant reduction in quality of life. Lessions may be located in the area of mucous membranes of the lips, cheeks and tongue. It is believed that the two virus types are responsible for the FEH, are: HPV 13 and HPV 32. Different therapeutic procedures have been reported: surgical excision, laser ablation, cryotherapy, electrocauterization, interferon, retinoic acid, 5% immiquimod.

  20. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

    Directory of Open Access Journals (Sweden)

    Magnusson Magnus K

    2010-07-01

    Full Text Available Abstract Background Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D co-culture assay. Methods Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.

  1. Surface differentiation antigens of human mammary epithelial cells carried on the human milk fat globule.

    Science.gov (United States)

    Ceriani, R L; Thompson, K; Peterson, J A; Abraham, S

    1977-02-01

    Rabbit antibodies against components of the human milk fat globule bind specifically to normal human breast epithelial cells and cell lines derived from breast carcinomas, as well as to the outer surface of the human milk fat globule. Variation in indirect immunofluorescence staining in both intensity per cell and percentage of cells stained is observed for the different brest cell lines. Cells derived from other epithelial and other ectodermal tissues, fetal fibroblasts, cells of the blood buffy coat, and even fibroblasts of the breast itself do not bind the antibodies. This suggests that these antibodies are detecting cell-type-specific antigens. These normal breast epithelial cell antigens are on the cell surface and their expression is stable in long-term cultured cell lines, even after much chromosomal variation in a given line. By affinity chromatography, three distinct antigenic components can be isolated from the milk fat globule, one of which contains carbohydrate. These differentiation antigens of the human breast epithelial cell are not only useful as specific cell-type markers, but also can provide a tool to study the role of the cell surface in normal and neoplastic mammary development.

  2. Transmigration route of Campylobacter jejuni across polarized intestinal epithelial cells: paracellular, transcellular or both?

    Science.gov (United States)

    2013-01-01

    Intact intercellular junctions and cellular matrix contacts are crucial structural components for the formation and maintenance of epithelial barrier functions in humans to control the commensal flora and protect against intruding microbes. Campylobacter jejuni is one of the most important zoonotic pathogens causing food-borne gastroenteritis and potentially more severe diseases such as reactive arthritis or Guillain–Barré syndrome. Crossing the intestinal epithelial barrier and host cell invasion by C. jejuni are considered to represent the primary reasons of gut tissue damage in humans and various animal model systems including monkeys, piglets, rabbits, hamsters and ferrets. C. jejuni is also able to invade underlying tissues such as the lamina propria, can enter the bloodstream, and possibly reach distinct organs such as spleen, liver or mesenteric lymph nodes. However, the molecular mechanisms as well as major bacterial and host cell factors involved in these activities are poorly understood. Various models exist by which the pathogen can trigger its own transmigration across polarized intestinal epithelial cells in vitro, the paracellular and/or transcellular mechanism. Recent studies suggest that bacterial factors such as flagellum, serine protease HtrA and lipooligosaccharide LOS may play an active role in bacterial transmigration. Here we review our knowledge on transmigration of C. jejuni as well as some other Campylobacter species, and discuss the pros and cons for the route(s) taken to travel across polarized epithelial cell monolayers. These studies provide fresh insights into the infection strategies employed by this important pathogen. PMID:24079544

  3. The protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Xue - Fang Chen

    2013-06-01

    Full Text Available AIM: To investigate the protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis. METHODS:Subcultured human lens epithelial cell line, ultraviolet induced cell apoptosis, 20μmol/L resveratrol pretreated cell, the indicators change was observed: rate of apoptosis was detected by flow cytometry and apoptosis-related factors of caspses-3 and caspase-9 were detected by colorimetric detection, ultrastructure changes were observed under transmission electron microscope. RESULTS: Flow cytometry instrument testing found that resveratrol can suppress the apoptosis induced by ultraviolet irradiation, caspses-3 and caspase-9 content in positive control group were significantly higher than that of the negative control group at the same time period, the difference was statistically significant(P<0.05; caspses-3 and caspase-9 content in experimental group were lower than that in the positive control group at the same time, the difference was statistically significant(P<0.05. In addition, the damage of human lens epithelial cells was alleviated with the incubation time of resveratrol elongated. CONCLUSION:Resveratrol may inhibit ultraviolet-induced apoptosis of human lens epithelial cells, it has preventive function against radioactive cataract, and it can provide reliable evidence for pursuing effective medicine to prevent and treat cataract.

  4. Selective functionalization of nanofiber scaffolds to regulate salivary gland epithelial cell proliferation and polarity

    Science.gov (United States)

    Cantara, Shraddha I.; Soscia, David A.; Sequeira, Sharon; Jean-Gilles, Riffard; Castracane, James; Larsen, Melinda

    2012-01-01

    Epithelial cell types typically lose apicobasal polarity when cultured on 2D substrates, but apicobasal polarity is required for directional secretion by secretory cells, such as salivary gland acinar cells. We cultured salivary gland epithelial cells on poly(lactic-co-glycolic acid) (PLGA) nanofiber scaffolds that mimic the basement membrane, a specialized extracellular matrix, and examined cell proliferation and apicobasal polarization. Although cells proliferated on nanofibers, chitosan-coated nanofiber scaffolds stimulated proliferation of salivary gland epithelial cells. Although apicobasal cell polarity was promoted by the nanofiber scaffolds relative to flat surfaces, as determined by the apical localization of ZO-1, it was antagonized by the presence of chitosan. Neither salivary gland acinar nor ductal cells fully polarized on the nanofiber scaffolds, as determined by the homogenous membrane distribution of the mature tight junction marker, occludin. However, nanofiber scaffolds chemically functionalized with the basement membrane protein, laminin-111, promoted more mature tight junctions, as determined by apical localization of occludin but did not affect cell proliferation. To emulate the multifunctional capabilities of the basement membrane, bifunctional PLGA nanofibers were generated. Both acinar and ductal cell lines responded to signals provided by bifunctional scaffolds coupled to chitosan and laminin-111, demonstrating the applicability of such scaffolds for epithelial cell types. PMID:22938763

  5. Porphyromonas gingivalis Initiates a Mesenchymal-like Transition through ZEB1 in Gingival Epithelial Cells

    Science.gov (United States)

    Sztukowska, Maryta N.; Ojo, Akintunde; Ahmed, Saira; Carenbauer, Anne L.; Wang, Qian; Shumway, Brain; Jenkinson, Howard F.; Wang, Huizhi; Darling, Douglas S.; Lamont, Richard J.

    2016-01-01

    Summary The oral anaerobe Porphyromonas gingivalis is associated with the development of cancers including oral squamous cell carcinoma (OSCC). Here we show that infection of gingival epithelial cells with P. gingivalis induces expression and nuclear localization of the ZEB1 transcription factor which controls epithelial-mesenchymal transition (EMT). P. gingivalis also caused an increase in ZEB1 expression as a dual species community with Fusobacterium nucleatum or Streptococcus gordonii. Increased ZEB1 expression was associated with elevated ZEB1 promoter activity and did not require suppression of the miR-200 family of micro RNAs. P. gingivalis strains lacking the FimA fimbrial protein were attenuated in their ability to induce ZEB1 expression. ZEB1 levels correlated with an increase in expression of mesenchymal markers, including vimentin and MMP-9, and with enhanced migration of epithelial cells into matrigel. Knockdown of ZEB1 with siRNA prevented the P. gingivalis-induced increase in mesenchymal markers and epithelial cell migration. Oral infection of mice by P. gingivalis increased ZEB1 levels in gingival tissues, and intracellular P. gingivalis were detected by antibody staining in biopsy samples from OSCC. These findings indicate that FimA-driven ZEB1 expression could provide a mechanistic basis for a P. gingivalis contribution to OSCC. PMID:26639759

  6. Neural differentiation of choroid plexus epithelial cells: role of human traumatic cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Elham Hashemi

    2017-01-01

    Full Text Available As the key producer of cerebrospinal fluid (CSF, the choroid plexus (CP provides a unique protective system in the central nervous system. CSF components are not invariable and they can change based on the pathological conditions of the central nervous system. The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells. CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF. Alterations in mRNA expression of Nestin and microtubule-associated protein (MAP2, as the specific markers of neurogenesis, and astrocyte marker glial fibrillary acidic protein (GFAP in cultured CP epithelial cells were evaluated using quantitative real-time PCR. The data revealed that treatment with CSF (non-traumatic and traumatic led to increase in mRNA expression levels of MAP2 and GFAP. Moreover, the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF, while treatment with traumatic CSF significantly increased its mRNA level compared to the cells cultured only in DMEM/F12 as control. It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.

  7. Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography

    Science.gov (United States)

    Chu, Kengyeh K.; Kusek, Mark E.; Liu, Linbo; Som, Avira; Yonker, Lael M.; Leung, Huimin; Cui, Dongyao; Ryu, Jinhyeob; Eaton, Alexander D.; Tearney, Guillermo J.; Hurley, Bryan P.

    2017-04-01

    A model of neutrophil migration across epithelia is desirable to interrogate the underlying mechanisms of neutrophilic breach of mucosal barriers. A co-culture system consisting of a polarized mucosal epithelium and human neutrophils can provide a versatile model of trans-epithelial migration in vitro, but observations are typically limited to quantification of migrated neutrophils by myeloperoxidase correlation, a destructive assay that precludes direct longitudinal study. Our laboratory has recently developed a new isotropic 1-μm resolution optical imaging technique termed micro-optical coherence tomography (μOCT) that enables 4D (x,y,z,t) visualization of neutrophils in the co-culture environment. By applying μOCT to the trans-epithelial migration model, we can robustly monitor the spatial distribution as well as the quantity of neutrophils chemotactically crossing the epithelial boundary over time. Here, we demonstrate the imaging and quantitative migration results of our system as applied to neutrophils migrating across intestinal epithelia in response to a chemoattractant. We also demonstrate that perturbation of a key molecular event known to be critical for effective neutrophil trans-epithelial migration (CD18 engagement) substantially impacts this process both qualitatively and quantitatively.

  8. Transcytosis of HIV-1 through vaginal epithelial cells is dependent on trafficking to the endocytic recycling pathway.

    Directory of Open Access Journals (Sweden)

    Ballington L Kinlock

    Full Text Available While it is accepted that viruses can enter epithelial cells by endocytosis, the lack of an established biological mechanism for the trafficking of infectious virions through vaginal epithelial cells and their release from the plasma membrane has contributed to ongoing controversy about whether endocytosis is a mere artifact of some cell culture systems and whether squamous vaginal epithelial cells are even relevant as it pertains to HIV-1 transmission.In this study, we investigated the intracellular trafficking pathway that HIV-1 exploits to transcytose vaginal epithelial cells. The reduction of endosome tubulation by recycling endosome inhibitors blocked transcytosis of HIV-1 in a cell culture and transwell system. In addition, we demonstrate that although heat-inactivated virus was endocytosed as efficiently as native virus, heat-inactivated virus was trafficked exclusively to the lysosomal pathway for degradation following endocytosis. Lysosomal protease-specific inhibitors blocked the degradation of inactivated virions. Immunofluorescence analysis not only demonstrated that HIV-1 was inside the cells but the different colocalization pattern of native vs. heat inactivated virus with transferrin provided conclusive evidence that HIV-1 uses the recycling pathway to get across vaginal epithelial cells.Altogether, our findings demonstrate the precise intracellular trafficking pathway utilized by HIV-1 in epithelial cells, confirms that HIV-1 transcytosis through vaginal epithelial cells is a biological phenomenon and brings to light the differential intracellular trafficking of native vs heat-inactivated HIV-1 which with further exploration could prove to provide valuable insights that could be used in the prevention of transcytosis/transmission of HIV-1 across the mucosal epithelia.

  9. Developing an ancient epithelial appendage: FGF signalling regulates early tail denticle formation in sharks

    Directory of Open Access Journals (Sweden)

    Rory L. Cooper

    2017-05-01

    Full Text Available Abstract Background Vertebrate epithelial appendages constitute a diverse group of organs that includes integumentary structures such as reptilian scales, avian feathers and mammalian hair. Recent studies have provided new evidence for the homology of integumentary organ development throughout amniotes, despite their disparate final morphologies. These structures develop from conserved molecular signalling centres, known as epithelial placodes. It is not yet certain whether this homology extends beyond the integumentary organs of amniotes, as there is a lack of knowledge regarding their development in basal vertebrates. As the ancient sister lineage of bony vertebrates, extant chondrichthyans are well suited to testing the phylogenetic depth of this homology. Elasmobranchs (sharks, skates and rays possess hard, mineralised epithelial appendages called odontodes, which include teeth and dermal denticles (placoid scales. Odontodes constitute some of the oldest known vertebrate integumentary appendages, predating the origin of gnathostomes. Here, we used an emerging model shark (Scyliorhinus canicula to test the hypothesis that denticles are homologous to other placode-derived amniote integumentary organs. To examine the conservation of putative gene regulatory network (GRN member function, we undertook small molecule inhibition of fibroblast growth factor (FGF signalling during caudal denticle formation. Results We show that during early caudal denticle morphogenesis, the shark expresses homologues of conserved developmental gene families, known to comprise a core GRN for early placode morphogenesis in amniotes. This includes conserved expression of FGFs, sonic hedgehog (shh and bone morphogenetic protein 4 (bmp4. Additionally, we reveal that denticle placodes possess columnar epithelial cells with a reduced rate of proliferation, a conserved characteristic of amniote skin appendage development. Small molecule inhibition of FGF signalling revealed

  10. Increased epithelial-free areas in thymuses with altered EphB-mediated thymocyte-thymic epithelial cell interactions.

    Science.gov (United States)

    García-Ceca, Javier; Montero-Herradón, Sara; Alfaro, David; Zapata, Agustín G

    2017-10-01

    Epithelial-free areas, present in both thymic cortex and medulla, have been studied in WT and EphB-deficient mice that have important alterations in the development of thymic epithelium due to the lack of proper thymocyte-thymic epithelial cell interactions. In both WT and mutant thymuses, the number and size of epithelial-free areas are significantly larger in the medulla than in the cortex. The two parameters show a reverse correlation: low numbers of these areas course with large epithelial-free areas and vice versa. However, their structure and cell content are similar in mutant and WT thymuses. Cortical epithelial-free areas just contain DP thymocytes, while the medullary ones consist of SP cells, blood vessels, mesenchyme-derived ER-TR7+ cells and components of the extracellular matrix (i.e., collagen IV, fibronectin, laminin). Other components, such as desmin, αSMA, PDGFRβ and Ng2, frequently associated with blood vessel walls, also appear. Vimentin, although present in medullary epithelial-free areas, does not co-express with epithelial cells. Other markers related to epithelial-mesenchymal transitions, such as Snail, Slug or FSP1, are not expressed. These results suggest that alterations in the cell interactions between distinct thymic cell components that induce both increased proportions of apoptotic thymic epithelial cells and altered behavior of the mesenchyme associated with the medullary vasculature could explain the appearance of these areas and their differences in the cortex and medulla.

  11. Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)

    Science.gov (United States)

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

    2016-03-01

    The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .

  12. High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells.

    Science.gov (United States)

    Chen, Yu-Ching; Statt, Sarah; Wu, Reen; Chang, Hao-Teng; Liao, Jiunn-Wang; Wang, Chien-Neng; Shyu, Woei-Cherng; Lee, Chen-Chen

    2016-01-07

    Epithelial-mesenchymal transition (EMT) is implicated in bronchial remodeling and loss of lung function in chronic inflammatory airway diseases. Previous studies showed the involvement of the high mobility group box 1 (HMGB1) protein in the pathology of chronic pulmonary inflammatory diseases. However, the role of HMGB1 in EMT of human airway epithelial cells is still unclear. In this study, we used RNA sequencing to show that HMGB1 treatment regulated EMT-related gene expression in human primary-airway epithelial cells. The top five upregulated genes were SNAI2, FGFBP1, VIM, SPARC (osteonectin), and SERPINE1, while the downregulated genes included OCLN, TJP1 (ZO-1), FZD7, CDH1 (E-cadherin), and LAMA5. We found that HMGB1 induced downregulation of E-cadherin and ZO-1, and upregulation of vimentin mRNA transcription and protein translation in a dose-dependent manner. Additionally, we observed that HMGB1 induced AKT phosphorylation, resulting in GSK3β inactivation, cytoplasmic accumulation, and nuclear translocation of β-catenin to induce EMT in human airway epithelial cells. Treatment with PI3K inhibitor (LY294006) and β-catenin shRNA reversed HMGB1-induced EMT. Moreover, HMGB1 induced expression of receptor for advanced glycation products (RAGE), but not that of Toll-like receptor (TLR) 2 or TLR4, and RAGE shRNA inhibited HMGB1-induced EMT in human airway epithelial cells. In conclusion, we found that HMGB1 induced EMT through RAGE and the PI3K/AKT/GSK3β/β-catenin signaling pathway.

  13. Preferred provider organizations.

    Science.gov (United States)

    Davy, J D

    1984-05-01

    The 1980s has marked the beginning of a new alternative health care delivery system: the preferred provider organization ( PPO ). This system has developed from the health maintenance organization model and is predominant in California and Colorado. A PPO is a group of providers, usually hospitals and doctors, who agree to provide health care to subscribers for a negotiated fee that is usually discounted. Preferred provider organizations are subject to peer review and strict use controls in exchange for a consistent volume of patients and speedy turnaround on claims payments. This article describes the factors leading to the development of PPOs and the implications for occupational therapy.

  14. Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells

    Directory of Open Access Journals (Sweden)

    Li Qianqian

    2010-10-01

    Full Text Available Abstract Background Spontaneous immortalisation of cultured mammary epithelial cells (MECs is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs and the changes in gene expression associated with BME65Cs cells. Results BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line. In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16INK4a in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16INK4a. Conclusions Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and

  15. Corneal Epithelial Thickness Measured by Manual Electronic Caliper Spectral Domain Optical Coherence Tomography: Distributions and Demographic Correlations in Preoperative Refractive Surgery Patients.

    Science.gov (United States)

    Rush, Sloan W; Matulich, Jennifer; Biskup, Joel; Cofoid, Philip; Rush, Ryan B

    2016-01-01

    The aim of this study was to report the distributions and demographic correlations of corneal epithelial thickness measured by manual electronic caliper spectral domain optical coherence tomography in preoperative refractive surgery patients. This was a retrospective review. The charts of 218 consecutive patients (413 eyes) who presented for refractive surgery evaluation from April 2013 through September 2013 were retrospectively reviewed. The mean corneal epithelial thickness was 51.0 μm with a range of 43 to 61 μm. Corneal epithelial thickness was significantly correlated with sex (P refractive status of the eye (P = 0.5135). Corneal epithelial thickness measured by manual electronic caliper optical coherence tomography in preoperative refractive surgery patients is comparable with the findings for the general population using other measurement techniques, the awareness of which may be useful in the preoperative assessment of these patients.

  16. Nuclear microscopy of rat colon epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Ren, M., E-mail: phyrenmq@nus.edu.sg [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Rajendran, Reshmi [Lab of Molecular Imaging, Singapore Bioimaging Consotium, 11 Biopolis Way, 02-02 Helios, Singapore 138667 (Singapore); Ng, Mary [Department of Pharmacology, National University of Singapore (Singapore); Udalagama, Chammika; Rodrigues, Anna E.; Watt, Frank [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Jenner, Andrew Michael [Illawara Health and Medical Research Institute (IHMRI), University of Wollongong, NSW 2522 (Australia)

    2011-10-15

    Using Nuclear microscopy, we have investigated iron distributions in the colons of Sprague Dawley rats, in order to elucidate heme uptake. Four groups of five Sprague Dawley rats (mean weight 180 g) were fed different purified diets containing either heme diet (2.5% w/w hemoglobin), high fat diet (HFD) (18% w/w fat, 1% w/w cholesterol), 'western' diet (combination of hemoglobin 2.5% and 18% fat, 1% cholesterol) or control diet (7% w/w fat). After 4 weeks, animals were sacrificed by exsanguination after anaesthesia. Thin sections of frozen colon tissue were taken, freeze dried and scanned using nuclear microscopy utilising the techniques PIXE, RBS and STIM. The new data acquisition system (IonDaq) developed in CIBA was used to obtain high resolution images and line scans were used to map the iron distributions across the colon boundaries. The nuclear microscope results indicate that when HFD is given in addition to heme, the iron content of the epithelial cells that line the colon decreases, and the zinc in the smooth muscle wall increases. This implies that the level of heme and fat in diet has an important role in colon health, possibly by influencing epithelial cells directly or changing luminal composition such as bacterial flora or levels of metabolites and cytotoxins.

  17. Generalized product

    OpenAIRE

    Greco,Salvatore; Mesiar, Radko; Rindone, Fabio

    2014-01-01

    Aggregation functions on [0,1] with annihilator 0 can be seen as a generalized product on [0,1]. We study the generalized product on the bipolar scale [–1,1], stressing the axiomatic point of view. Based on newly introduced bipolar properties, such as the bipolar increasingness, bipolar unit element, bipolar idempotent element, several kinds of generalized bipolar product are introduced and studied. A special stress is put on bipolar semicopulas, bipolar quasi-copulas and bipolar copulas.

  18. Building Service Provider Capabilities

    DEFF Research Database (Denmark)

    Brandl, Kristin; Jaura, Manya; Ørberg Jensen, Peter D.

    In this paper we study whether and how the interaction between clients and the service providers contributes to the development of capabilities in service provider firms. In situations where such a contribution occurs, we analyze how different types of activities in the production process...

  19. Providing free autopoweroff plugs

    DEFF Research Database (Denmark)

    Jensen, Carsten Lynge; Hansen, Lars Gårn; Fjordbak, Troels

    2012-01-01

    Experimental evidence of the effect of providing households with cheap energy saving technology is sparse. We present results from a field experiment in which autopoweroff plugs were provided free of charge to randomly selected households. We use propensity score matching to find treatment effects...

  20. Digital image analysis versus clinical assessment of wound epithelialization: A validation study

    NARCIS (Netherlands)

    Bloemen, M.C.T.; Boekema, B.K.H.L.; Vlig, M.; van Zuijlen, P.P.M.; Middelkoop, E.

    2012-01-01

    To evaluate the progress in wound healing, wound assessment is mandatory. Epithelialization is traditionally assessed subjectively by the clinician. In a previous study, subjective assessment of epithelialization was shown to be reliable. In this study, reliability of epithelialization measured by

  1. The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras.

    Science.gov (United States)

    Fu, Qiang; Deng, Chen-Liang; Zhao, Ren-Yan; Wang, Ying; Cao, Yilin

    2014-01-01

    Urethral defects are common and frequent disorders and are difficult to treat. Simple natural or synthetic materials do not provide a satisfactory curative solution for long urethral defects, and urethroplasty with large areas of autologous tissues is limited and might interfere with wound healing. In this study, adipose-derived stem cells were used. These cells can be derived from a wide range of sources, have extensive expansion capability, and were combined with oral mucosal epithelial cells to solve the problem of finding seeding cell sources for producing the tissue-engineered urethras. We also used the synthetic biodegradable polymer poly-glycolic acid (PGA) as a scaffold material to overcome issues such as potential pathogen infections derived from natural materials (such as de-vascular stents or animal-derived collagen) and differing diameters. Furthermore, we used a bioreactor to construct a tissue-engineered epithelial-muscular lumen with a double-layer structure (the epithelial lining and the muscle layer). Through these steps, we used an epithelial-muscular lumen built in vitro to repair defects in a canine urethral defect model (1 cm). Canine urethral reconstruction was successfully achieved based on image analysis and histological techniques at different time points. This study provides a basis for the clinical application of tissue engineering of an epithelial-muscular lumen. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Native and synthetic scaffolds for limbal epithelial stem cell transplantation.

    Science.gov (United States)

    Nguyen, Kim N; Bobba, Samantha; Richardson, Alexander; Park, Mijeong; Watson, Stephanie L; Wakefield, Denis; Di Girolamo, Nick

    2018-01-01

    Limbal stem cell deficiency (LSCD) is a complex blinding disease of the cornea, which cannot be treated with conventional corneal transplants. Instead, a stem cell (SC) graft is required to replenish the limbal epithelial stem cell (LESC) reservoir, which is ultimately responsible for regenerating the corneal epithelium. Current therapies utilize limbal tissue biopsies that harbor LESCs as well as tissue culture expanded cells. Typically, this tissue is placed on a scaffold that supports the formation of corneal epithelial cell sheets, which are then transferred to diseased eyes. A wide range of biological and synthetic materials have been identified as carrier substrates for LESC, some of which have been used in the clinic, including amniotic membrane, fibrin, and silicon hydrogel contact lenses, each with their own advantages and limitations. This review will provide a brief background of LSCD, focusing on bio-scaffolds that have been utilized in limbal stem cell transplantation (LSCT) and materials that are being developed as potentially novel therapeutics for patients with this disease. The outcome of patients with corneal blindness that receive stem cell grafts to restore eye health and correct vision varies considerably and may be due to the different biological and synthetic scaffolds used to deliver these cells to the ocular surface. This review will highlight the positive attributes and limitations of the myriad of carriers developed for clinical use as well as those that are being trialled in pre-clinical models. The overall focus is on developing a standardized therapy for patients, however due to the multiple causes of corneal blindness, a personal regenerative medicine approach may be the best option. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Foxc2 influences alveolar epithelial cell differentiation during lung development.

    Science.gov (United States)

    Tsuji, Mayoko; Morishima, Masae; Shimizu, Kazuhiko; Morikawa, Shunichi; Heglind, Mikael; Enerbäck, Sven; Ezaki, Taichi; Tamaoki, Jun

    2017-08-01

    FOXC2, a forkhead transcriptional factor, is a candidate gene for congenital heart diseases and lymphedema-distichiasis syndrome and yellow nail syndrome; however, there are no reports on Foxc2 and the development of the lung. We have identified lung abnormalities in Foxc2-knockout embryos during investigation of cardiac development. The aim of this study was to clarify the morphological characteristics during lung development using ICR-Foxc2 knockout lungs. Mutant fetuses at embryonic days 10.5-18.5 were obtained from mating of Foxc2+/- mice and then analyzed. Notably, Foxc2-knockout lungs appeared parenchymatous and much smaller than those of the wild-type littermates. In the Foxc2 knockout lungs, the capillary beds remained distant from the alveolar epithelium until the late stages, the number of type2 alveolar cells per alveolar progenitor cell was lower and the type1 alveolar cells were thicker in Foxc2 knockout mice. In contrast, Foxc2 expression was only detected in the mesenchyme of the lung buds at E10.5, and it disappeared at E11.5 in Foxc2-LacZ knockin mice. Furthermore, the expression of Lef1 was significantly inhibited in E11.5 lungs. All of these results suggest that the abnormalities in Foxc2 knockout mice may involve maldifferentiation of alveolar epithelial cells and capillary vessel endothelial-alveolar epithelial approach as well as lymph vessel malformation. This is the first report about relationship between Foxc2 and lung development. This animal model might provide an important clue for elucidating the mechanism of lung development and the cause of respiratory diseases. © 2017 Japanese Society of Developmental Biologists.

  4. Calcifying epithelial odontogenic tumour-case series from five ...

    African Journals Online (AJOL)

    Background: Calcifying epithelial odontogenic tumour (CEOT) also known as Pindborg's tumour is a relatively rare odontogenic neoplasm of epithelial derivation that constitutes about 0.4-3% of all intraosseous odontogenic tumours. Objectives: To document all cases of CEOT encountered in five tertiary centres in Nigeria ...

  5. Growth of cultured porcine retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Wiencke, A.K.; Kiilgaard, Jens Folke; Nicolini, Jair

    2003-01-01

    To establish and characterize cultures of porcine retinal pigment epithelial (pRPE) cells in order to produce confluent monolayers of cells for transplantation.......To establish and characterize cultures of porcine retinal pigment epithelial (pRPE) cells in order to produce confluent monolayers of cells for transplantation....

  6. Epithelial cell-cell junctions and plasma membrane domains

    NARCIS (Netherlands)

    Giepmans, Ben N. G.; van Ijzendoorn, Sven C. D.

    Epithelial cells form a barrier against the environment, but are also required for the regulated exchange of molecules between an organism and its surroundings. Epithelial cells are characterised by a remarkable polarization of their plasma membrane, evidenced by the appearance of structurally,

  7. Engineering stromal-epithelial interactions in vitro for ...

    Science.gov (United States)

    Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo tissue recombination, and in vitro co-cultures. Although these approaches have elucidated signaling mechanisms underlying morphogenetic processes and adult mammalian epithelial tissue function, they are limited by the availability of human tissue, low throughput, and human developmental or physiological relevance. Objectives: Bioengineering strategies to promote EMIs using human epithelial and mesenchymal cells have enabled the development of human in vitro models of adult epidermal and glandular tissues. In this review, we describe recent bioengineered models of human epithelial tissue and organs that can instruct the design of organotypic models of human developmental processes.Methods: We reviewed current bioengineering literature and here describe how bioengineered EMIs have enabled the development of human in vitro epithelial tissue models.Discussion: Engineered models to promote EMIs have recapitulated the architecture, phenotype, and function of adult human epithelial tissue, and similar engineering principles could be used to develop models of developmental morphogenesis. We describe how bioengineering strategies including bioprinting and spheroid culture could be implemented to

  8. Fruits and vegetables and the risk of epithelial cancer

    NARCIS (Netherlands)

    Jansen, M.C.J.F.

    2001-01-01

    In this thesis, prospective studies on fruit and vegetable consumption in relation to epithelial cancer risk were described. The main research question was whether higher intakes were related to lower risks of epithelial cancers, mainly of lung cancer.

    In the Seven

  9. Nutrients released by gastric epithelial cells enhance Helicobacter pylori growth

    NARCIS (Netherlands)

    van Amsterdam, Karin; van der Ende, Arie

    2004-01-01

    Background. Helicobacter pylori survives and proliferates in the human gastric mucosa. In this niche, H. pylori adheres to the gastric epithelial cells near the tight junctions. In vitro, H. pylori proliferated well in tissue-culture medium near gastric epithelial cells. However, in the absence of

  10. ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity.

    Science.gov (United States)

    Daley, William P; Gervais, Elise M; Centanni, Samuel W; Gulfo, Kathryn M; Nelson, Deirdre A; Larsen, Melinda

    2012-01-01

    The basement membrane is crucial for epithelial tissue organization and function. However, the mechanisms by which basement membrane is restricted to the basal periphery of epithelial tissues and the basement membrane-mediated signals that regulate coordinated tissue organization are not well defined. Here, we report that Rho kinase (ROCK) controls coordinated tissue organization by restricting basement membrane to the epithelial basal periphery in developing mouse submandibular salivary glands, and that ROCK inhibition results in accumulation of ectopic basement membrane throughout the epithelial compartment. ROCK-regulated restriction of PAR-1b (MARK2) localization in the outer basal epithelial cell layer is required for basement membrane positioning at the tissue periphery. PAR-1b is specifically required for basement membrane deposition, as inhibition of PAR-1b kinase activity prevents basement membrane deposition and disrupts overall tissue organization, and suppression of PAR-1b together with ROCK inhibition prevents interior accumulations of basement membrane. Conversely, ectopic overexpression of wild-type PAR-1b results in ectopic interior basement membrane deposition. Significantly, culture of salivary epithelial cells on exogenous basement membrane rescues epithelial organization in the presence of ROCK1 or PAR-1b inhibition, and this basement membrane-mediated rescue requires functional integrin β1 to maintain epithelial cell-cell adhesions. Taken together, these studies indicate that ROCK1/PAR-1b-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland.

  11. Straylight measurements before and after removal of epithelial ingrowth

    NARCIS (Netherlands)

    Lapid-Gortzak, Ruth; van der Meulen, Ivanka; van der Linden, Jan Willem; Nieuwendaal, Carla; Mourits, Maarten; van den Berg, Tom

    2009-01-01

    In 3 eyes with epithelial ingrowth after laser in situ keratomileusis, straylight was measured before and after the ingrowth was removed. In 2 eyes of 1 patient, epithelial ingrowth reached the pupillary axis. Straylight decreased (improved) significantly after ingrowth removal: a 3.6-fold decrease

  12. In vitro effect of smokeless tobacco on gingival epithelial cells

    Directory of Open Access Journals (Sweden)

    Arzu Beklen

    2017-05-01

    Epithelial cells are the first line of defense against pathogens in the oral cavity. The results suggest that smokeless tobacco not only inhibits the growth of epithelial cells but also induce the generation of inflammatory cytokines which leads to smokeless tobacco-exacerbated disease.

  13. Abdominal wall reconstruction using De-epithelialized dermal flap: A ...

    African Journals Online (AJOL)

    The aim of this study is to determine the place of de-epithelialized dermal flap in the reconstruction of abdominal wall hernias. Materials and Methods: A five-year prospective, descriptive analysis of eligible patients with difficult abdominal wall hernias closed with de-epithelialized dermal flap in a Nigerian Tertiary Health ...

  14. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

    Science.gov (United States)

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-03-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (Pepithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

  15. Severe airway epithelial injury, aberrant repair and bronchiolitis obliterans develops after diacetyl instillation in rats.

    Directory of Open Access Journals (Sweden)

    Scott M Palmer

    2011-03-01

    Full Text Available Bronchiolitis obliterans (BO is a fibrotic lung disease that occurs in a variety of clinical settings, including toxin exposures, autoimmunity and lung or bone marrow transplant. Despite its increasing clinical importance, little is known regarding the underlying disease mechanisms due to a lack of adequate small animal BO models. Recent epidemiological studies have implicated exposure to diacetyl (DA, a volatile component of artificial butter flavoring, as a cause of BO in otherwise healthy factory workers. Our overall hypothesis is that DA induces severe epithelial injury and aberrant repair that leads to the development of BO. Therefore, the objectives of this study were 1 to determine if DA, delivered by intratracheal instillation (ITI, would lead to the development of BO in rats and 2 to characterize epithelial regeneration and matrix repair after ITI of DA.Male Sprague-Dawley rats were treated with a single dose of DA (125 mg/kg or sterile water (vehicle control by ITI. Instilled DA resulted in airway specific injury, followed by rapid epithelial regeneration, and extensive intraluminal airway fibrosis characteristic of BO. Increased airway resistance and lung fluid neutrophilia occurred with the development of BO, similar to human disease. Despite rapid epithelial regeneration after DA treatment, expression of the normal phenotypic markers, Clara cell secretory protein and acetylated tubulin, were diminished. In contrast, expression of the matrix component Tenascin C was significantly increased, particularly evident within the BO lesions.We have established that ITI of DA results in BO, creating a novel chemical-induced animal model that replicates histological, biological and physiological features of the human disease. Furthermore, we demonstrate that dysregulated epithelial repair and excessive matrix Tenacin C deposition occur in BO, providing new insights into potential disease mechanisms and therapeutic targets.

  16. Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures.

    Directory of Open Access Journals (Sweden)

    Cara L Sherwood

    Full Text Available Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE cell model we found that both micromolar (3.9 μM and submicromolar (0.8 μM arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-. We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway.

  17. p120 Catenin is required for normal tubulogenesis but not epithelial integrity in developing mouse pancreas.

    Science.gov (United States)

    Hendley, Audrey M; Provost, Elayne; Bailey, Jennifer M; Wang, Yue J; Cleveland, Megan H; Blake, Danielle; Bittman, Ross W; Roeser, Jeffrey C; Maitra, Anirban; Reynolds, Albert B; Leach, Steven D

    2015-03-01

    The intracellular protein p120 catenin aids in maintenance of cell-cell adhesion by regulating E-cadherin stability in epithelial cells. In an effort to understand the biology of p120 catenin in pancreas development, we ablated p120 catenin in mouse pancreatic progenitor cells, which resulted in deletion of p120 catenin in all epithelial lineages of the developing mouse pancreas: islet, acinar, centroacinar, and ductal. Loss of p120 catenin resulted in formation of dilated epithelial tubules, expansion of ductal epithelia, loss of acinar cells, and the induction of pancreatic inflammation. Aberrant branching morphogenesis and tubulogenesis were also observed. Throughout development, the phenotype became more severe, ultimately resulting in an abnormal pancreas comprised primarily of duct-like epithelium expressing early progenitor markers. In pancreatic tissue lacking p120 catenin, overall epithelial architecture remained intact; however, actin cytoskeleton organization was disrupted, an observation associated with increased cytoplasmic PKCζ. Although we observed reduced expression of adherens junction proteins E-cadherin, β-catenin, and α-catenin, p120 catenin family members p0071, ARVCF, and δ-catenin remained present at cell membranes in homozygous p120(f/f) pancreases, potentially providing stability for maintenance of epithelial integrity during development. Adult mice homozygous for deletion of p120 catenin displayed dilated main pancreatic ducts, chronic pancreatitis, acinar to ductal metaplasia (ADM), and mucinous metaplasia that resembles PanIN1a. Taken together, our data demonstrate an essential role for p120 catenin in pancreas development. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

    Energy Technology Data Exchange (ETDEWEB)

    Lasalvia, Maria [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Castellani, Stefano [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); D’Antonio, Palma [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Perna, Giuseppe [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Carbone, Annalucia [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); Colia, Anna Laura; Maffione, Angela Bruna [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Capozzi, Vito [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Conese, Massimo, E-mail: massimo.conese@unifg.it [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy)

    2016-10-15

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in

  19. Crossroads of Wnt and Hippo in epithelial tissues.

    Science.gov (United States)

    Bernascone, Ilenia; Martin-Belmonte, Fernando

    2013-08-01

    Epithelial tissues undergo constant growth and differentiation during embryonic development and to replace damaged tissue in adult organs. These processes are governed by different signaling pathways that ultimately control the expression of genes associated with cell proliferation, patterning, and death. One essential pathway is Wnt, which controls tubulogenesis in several epithelial organs. Recently, Wnt has been closely linked to other signaling pathways, such as Hippo, that orchestrate proliferation and apoptosis to control organ size. There is evidence that epithelial cell junctions may sequester the transcription factors that act downstream of these signaling pathways, which would represent an important aspect of their functional regulation and their influence on cell behavior. Here, we review the transcriptional control exerted by the Wnt and Hippo signaling pathways during epithelial growth, patterning, and differentiation and recent advances in understanding of the regulation and crosstalk of these pathways in epithelial tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Regulation of epithelial immunity by IL-17 family cytokines.

    Science.gov (United States)

    Pappu, Rajita; Rutz, Sascha; Ouyang, Wenjun

    2012-07-01

    Cutaneous and mucosal epithelial cells function as both a physical barrier and as immune sentinels against environmental challenges, such as microbial pathogens, allergens and stress. The crosstalk between epithelial cells and leukocytes is essential for orchestrating proper immune responses during host defense. Interleukin (IL)-17 family cytokines are important players in regulating innate epithelial immune responses. Although IL-17A and IL-17F promote antibacterial and antifungal responses, IL-17E is essential for defense against parasitic infections. Emerging data indicate that another member of this family, IL-17C, specifically regulates epithelial immunity. IL-17C production serves as an immediate defense mechanism by epithelial cells, utilizing an autocrine mechanism to promote antibacterial responses at barrier surfaces. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations

    Directory of Open Access Journals (Sweden)

    Aaron H Fronk

    2016-07-01

    Full Text Available The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included.

  2. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment......ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment...

  3. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment......ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment...

  4. Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis

    Directory of Open Access Journals (Sweden)

    Shigehisa Yanagi

    2015-01-01

    Full Text Available Individual alveolar epithelial cells (AECs collaboratively form a tight barrier between atmosphere and fluid-filled tissue to enable normal gas exchange. The tight junctions of AECs provide intercellular sealing and are integral to the maintenance of the AEC barrier integrity. Disruption and failure of reconstitution of AEC barrier result in catastrophic consequences, leading to alveolar flooding and subsequent devastating fibrotic scarring. Recent evidences reveal that many of the fibrotic lung diseases involve AECs both as a frequent target of injury and as a driver of ongoing pathological processes. Aberrantly activated AECs express most of the growth factors and chemokines responsible for the proliferation, migration, and activation of fibroblasts. Current evidences suggest that AECs may acquire overdrive activation in the initial step of fibrosis by several mechanisms, including abnormal recapitulation of the developmental pathway, defects of the molecules essential for epithelial integrity, and acceleration of aging-related properties. Among these initial triggering events, epithelial Pten, a multiple phosphatase that negatively regulates the PI3K/Akt pathway and is crucial for lung development, is essential for the prevention of alveolar flooding and lung fibrosis through the regulation of AEC barrier integrity after injury. Reestablishment of AEC barrier integrity also involves the deployment of specialized stem/progenitor cells.

  5. PGRN promotes migration and invasion of epithelial ovarian cancer cells through an epithelial mesenchymal transition program and the activation of cancer associated fibroblasts.

    Science.gov (United States)

    Dong, Taotao; Yang, Dong; Li, Rui; Zhang, Lu; Zhao, Hongchao; Shen, Yihang; Zhang, Xiaoli; Kong, Beihua; Wang, Linlin

    2016-02-01

    In this paper, we aimed to explore whether progranulin (PGRN) could induce epithelial ovarian cancer cells to undergo an epithelial mesenchymal transition (EMT) program directly and through its activation of cancer associated fibroblasts (CAFs) indirectly. Immunohistochemistry(IHC) staining of tissue samples of 78 cases of epithelial ovarian cancer (EOC) patients found that PGRN expression levels were negatively correlated with E-cadherin levels (r=-0.289, P=0.013) and positively correlated with Slug levels (r=0.332, P=0.003); Cell experiments showed that PGRN overexpression could increase the migratory and invasive abilities of A2780 cells significantly. Moreover, high doses (62ng/ml) of recombinant PGRN could induce 14.7 fold high expression of smooth muscle actin α (α-SMA) in human normal fibroblasts. In addition, patients with both high levels of PGRN and α-SMA in their tissue samples had the worst disease free survival (DFS) and overall survival (OS) than those with low levels of PGRN or α-SMA. All the results suggest that PGRN could promote invasiveness of EOC cells through an EMT program directly and through activation of CAFs indirectly. This may provide a new effective therapy target for EOC. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells.

    Science.gov (United States)

    Martinez-Outschoorn, Ubaldo E; Goldberg, Allison; Lin, Zhao; Ko, Ying-Hui; Flomenberg, Neal; Wang, Chenguang; Pavlides, Stephanos; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2011-11-15

    Here, we show that tamoxifen resistance is induced by cancer-associated fibroblasts (CAFs). Coculture of estrogen receptor positive (ER+) MCF7 cells with fibroblasts induces tamoxifen and fulvestrant resistance with 4.4 and 2.5-fold reductions, respectively, in apoptosis compared with homotypic MCF7 cell cultures. Treatment of MCF7 cells cultured alone with high-energy mitochondrial "fuels" (L-lactate or ketone bodies) is sufficient to confer tamoxifen resistance, mimicking the effects of coculture with fibroblasts. To further demonstrate that epithelial cancer cell mitochondrial activity is the origin of tamoxifen resistance, we employed complementary pharmacological and genetic approaches. First, we studied the effects of two mitochondrial "poisons," namely metformin and arsenic trioxide (ATO), on fibroblast-induced tamoxifen resistance. We show here that treatment with metformin or ATO overcomes fibroblast-induced tamoxifen resistance in MCF7 cells. Treatment with the combination of tamoxifen plus metformin or ATO leads to increases in glucose uptake in MCF7 cells, reflecting metabolic uncoupling between epithelial cancer cells and fibroblasts. In coculture, tamoxifen induces the upregulation of TIGAR (TP53-induced glycolysis and apoptosis regulator), a p53 regulated gene that simultaneously inhibits glycolysis, autophagy and apoptosis and reduces ROS generation, thereby promoting oxidative mitochondrial metabolism. To genetically mimic the effects of coculture, we next recombinantly overexpressed TIGAR in MCF7 cells. Remarkably, TIGAR overexpression protects epithelial cancer cells from tamoxifen-induced apoptosis, providing genetic evidence that increased mitochondrial function confers tamoxifen resistance. Finally, CAFs also protect MCF7 cells against apoptosis induced by other anticancer agents, such as the topoisomerase inhibitor doxorubicin (adriamycin) and the PARP-1 inhibitor ABT-888. These results suggest that the tumor microenvironment may be a general

  7. Novel flow cytometry approach to identify bronchial epithelial cells from healthy human airways

    OpenAIRE

    Danay Maestre-Batlle; Pena, Olga M.; Hirota, Jeremy A.; Evelyn Gunawan; Rider, Christopher F.; Darren Sutherland; Alexis, Neil E.; Chris Carlsten

    2017-01-01

    Sampling various compartments within the lower airways to examine human bronchial epithelial cells (HBEC) is essential for understanding numerous lung diseases. Conventional methods to identify HBEC in bronchoalveolar lavage (BAL) and wash (BW) have throughput limitations in terms of efficiency and ensuring adequate cell numbers for quantification. Flow cytometry can provide high-throughput quantification of cell number and function in BAL and BW samples, while requiring low cell numbers. To ...

  8. 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.

  9. Pten Regulates Epithelial Cytodifferentiation during Prostate Development

    DEFF Research Database (Denmark)

    Lokody, Isabel B; Francis, Jeffrey C; Gardiner, Jennifer R

    2015-01-01

    Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic...... deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses...... that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study...

  10. Oral epithelial hyperplasia in diabetes mellitus.

    Science.gov (United States)

    Girtan, Mihaela; Zurac, Sabina; Stăniceanu, Florica; Bastian, Alexandra; Popp, Cristiana; Nichita, Luciana; Laba, Elisabeta; Forna, Norina

    2009-01-01

    Diabetes mellitus is one of the chronic systemic disorders with major influences of the oral cavity microenvironment. Oral manifestations of diabetes are diverse; they are represented by candidose, lichen plan, recurrent aphthous stomatitis, gingivitis, salivary disorders, oral mucosa atrophy and rarely hypertrophy; a possible link between oral cancer and diabetes is suspected, both in animal models and humans. We report a case of a young woman with type 1 diabetes with class I Kennedy edentation with mobile denture prosthesis; latter in the clinical follow-up, a hyperplasic lesion of the oral mucosa with p53 expression within the epithelial nuclei was identified, p53 being the more likely pathogenic pathway involved in diabetes-related oral cancer. The approach of this patient required multidisciplinary investigations and careful follow-up.

  11. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology.

    Science.gov (United States)

    Lasalvia, Maria; Castellani, Stefano; D'Antonio, Palma; Perna, Giuseppe; Carbone, Annalucia; Colia, Anna Laura; Maffione, Angela Bruna; Capozzi, Vito; Conese, Massimo

    2016-10-15

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Tomoyo Yoshinaga

    Full Text Available Epithelial-mesenchymal transition (EMT of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1 and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1 and an agonist for the G protein-coupled receptor 55 (GRP55, the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-β signaling pathway. Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis.

  13. Epithelial Barrier Regulation by Hypoxia-Inducible Factor.

    Science.gov (United States)

    Glover, Louise E; Colgan, Sean P

    2017-09-01

    Mucosal tissues represent surfaces that are exposed to the outside world and provide a conduit for internal and external communication. Tissues such as the intestine and the lung are lined by layer(s) of epithelial cells that, when organized in three dimensions, provide a critical barrier to the flux of luminal contents. This selective barrier is provided through the regulated expression of junctional proteins and mucins. Tissue oxygen metabolism is central to the maintenance of homeostasis in the mucosa. In some organs (e.g., the colon), low baseline Po2 determines tissue metabolism and results in basal expression of the transcription factor, hypoxia-inducible factor (HIF), which is enhanced after ischemia/inflammation. Recent studies have indicated that HIF contributes fundamentally to the expression of barrier-related genes and in the regulation of barrier-adaptive responses within the mucosa. Here, we briefly review recent literature on the topic of hypoxia and HIF regulation of barrier in mucosal health and during disease.

  14. Epithelial topography for repetitive tooth formation

    Directory of Open Access Journals (Sweden)

    Marcia Gaete

    2015-12-01

    Full Text Available During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2+ cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2+/Sox9+ cells.

  15. Generalized Riemann derivative

    Directory of Open Access Journals (Sweden)

    Sorin Radulescu

    2013-03-01

    Full Text Available Initiated by Marshall Ash in 1966, the study of generalized Riemann derivative draw significant attention of the mathematical community and numerous studies where carried out since then. One of the major areas that benefits from these developments is the numerical analysis, as the use of generalized Riemann derivatives leads to solving a wider class of problems that are not solvable with the classical tools. This article studies the generalized Riemann derivative and its properties and establishes relationships between Riemann generalized derivative and the classical one. The existence of classical derivative implies the existence of the Riemann generalized derivative, and we study conditions necessary for the generalized Riemann derivative to imply the existence of the classical derivative. Furthermore, we provide conditions on the generalized Riemann derivative that are sufficient for the existence of the classical derivative.

  16. General Conformity

    Science.gov (United States)

    The General Conformity requirements ensure that the actions taken by federal agencies in nonattainment and maintenance areas do not interfere with a state’s plans to meet national standards for air quality.

  17. Provider of Services File

    Data.gov (United States)

    U.S. Department of Health & Human Services — The POS file consists of two data files, one for CLIA labs and one for 18 other provider types. The file names are CLIA and OTHER. If downloading the file, note it...

  18. The Provident Principal.

    Science.gov (United States)

    McCall, John R.

    This monograph offers leadership approaches for school principals. Discussion applies the business leadership theory of Warren Bennis and Burt Nanus to the role of the principal. Each of the booklet's three parts concludes with discussion questions. Part 1, "Visions and Values for the Provident Principal," demonstrates the importance of…

  19. What HERA may provide?

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hannes [DESY, Hamburg (Germany); De Roeck, Albert [CERN, Genf (Switzerland); Bartles, Jochen [Univ. Hamburg (DE). Institut fuer Theoretische Physik II] (and others)

    2008-09-15

    More than 100 people participated in a discussion session at the DIS08 workshop on the topic What HERA may provide. A summary of the discussion with a structured outlook and list of desirable measurements and theory calculations is given. (orig.)

  20. care Providers in Ibadan

    African Journals Online (AJOL)

    Three hundred and eighty six respondents (77.7%) were aware of intermittent preventive treatment (IPT). Awareness ... Key Words: malaria in pregnancy, intermittent preventive treatment, malaria control, health care providers. Department of Obstetrics .... Auxiliary nurses do not have formal training prior to employment.

  1. Montelukast suppresses epithelial to mesenchymal transition of bronchial epithelial cells induced by eosinophils.

    Science.gov (United States)

    Hosoki, Koa; Kainuma, Keigo; Toda, Masaaki; Harada, Etsuko; Chelakkot-Govindalayathila, Ayshwarya-Lakshmi; Roeen, Ziaurahman; Nagao, Mizuho; D'Alessandro-Gabazza, Corina N; Fujisawa, Takao; Gabazza, Esteban C

    2014-07-04

    Epithelial to mesenchymal transition (EMT) is a mechanism by which eosinophils can induce airway remodeling. Montelukast, an antagonist of the cysteinyl leukotriene receptor, can suppress airway remodeling in asthma. The purpose of this study was to evaluate whether montelukast can ameliorate airway remodeling by blocking EMT induced by eosinophils. EMT induced was assessed using a co-culture system of human bronchial epithelial cells and human eosinophils or the eosinophilic leukemia cell lines, Eol-1. Montelukast inhibited co-culture associated morphological changes of BEAS-2b cells, decreased the expression of vimentin and collagen I, and increased the expression of E-cadherin. Montelukast mitigated the rise of TGF-β1 production and Smad3 phosphorylation. Co-culture of human eosinophils with BEAS-2B cells significantly enhanced the production of CysLTs compared with BEAS-2B cells or eosinophils alone. The increase of CysLTs was abolished by montelukast pre-treatment. Montelukast had similar effects when co-culture system of Eol-1 and BEAS-2B was used. This study showed that montelukast suppresses eosinophils-induced EMT of airway epithelial cells. This finding may explain the mechanism of montelukast-mediated amelioration of airway remodeling in bronchial asthma. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Aneuploidy, oncogene amplification and epithelial to mesenchymal transition define spontaneous transformation of murine epithelial cells.

    Science.gov (United States)

    Padilla-Nash, Hesed M; McNeil, Nicole E; Yi, Ming; Nguyen, Quang-Tri; Hu, Yue; Wangsa, Danny; Mack, David L; Hummon, Amanda B; Case, Chanelle; Cardin, Eric; Stephens, Robert; Difilippantonio, Michael J; Ried, Thomas

    2013-08-01

    Human epithelial cancers are defined by a recurrent distribution of specific chromosomal aneuploidies, a trait less typical for murine cancer models induced by an oncogenic stimulus. After prolonged culture, mouse epithelial cells spontaneously immortalize, transform and become tumorigenic. We assessed genome and transcriptome alterations in cultures derived from bladder and kidney utilizing spectral karyotyping, array CGH, FISH and gene expression profiling. The results show widespread aneuploidy, yet a recurrent and tissue-specific distribution of genomic imbalances, just as in human cancers. Losses of chromosome 4 and gains of chromosome 15 are common and occur early during the transformation process. Global gene expression profiling revealed early and significant transcriptional deregulation. Chromosomal aneuploidy resulted in expression changes of resident genes and consequently in a massive deregulation of the cellular transcriptome. Pathway interrogation of expression changes during the sequential steps of transformation revealed enrichment of genes associated with DNA repair, centrosome regulation, stem cell characteristics and aneuploidy. Genes that modulate the epithelial to mesenchymal transition and genes that define the chromosomal instability phenotype played a dominant role and were changed in a directionality consistent with loss of cell adhesion, invasiveness and proliferation. Comparison with gene expression changes during human bladder and kidney tumorigenesis revealed remarkable overlap with changes observed in the spontaneously transformed murine cultures. Therefore, our novel mouse models faithfully recapitulate the sequence of genomic and transcriptomic events that define human tumorigenesis, hence validating them for both basic and preclinical research.

  3. Laminin-511 and -521-based matrices for efficient ex vivo-expansion of human limbal epithelial progenitor cells.

    Science.gov (United States)

    Polisetti, Naresh; Sorokin, Lydia; Okumura, Naoki; Koizumi, Noriko; Kinoshita, Shigeru; Kruse, Friedrich E; Schlötzer-Schrehardt, Ursula

    2017-07-11

    Optimization of culture conditions for human limbal epithelial stem/progenitor cells (LEPC) that incorporate the in vivo cell-matrix interactions are essential to enhance LEPC ex vivo-expansion and transplantation efficiency. Here, we investigate the efficacy of laminin (LN) isoforms preferentially expressed in the limbal niche as culture matrices for epithelial tissue engineering. Analyses of expression patterns of LN chains in the human limbal niche provided evidence for enrichment of LN-α2, -α3, -α5, -β1, -β2, -β3, -γ1, -γ2 and -γ3 chains in the limbal basement membrane, with LN-α5 representing a signature component specifically produced by epithelial progenitor cells. Recombinant human LN-521 and LN-511 significantly enhanced in vitro LEPC adhesion, migration and proliferation compared to other isoforms, and maintained phenotype stability. The bioactive LN-511-E8 fragment carrying only C-terminal domains showed similar efficacy as full-length LN-511. Functional blocking of α3β1 and α6β1 integrins suppressed adhesion of LEPC to LN-511/521-coated surfaces. Cultivation of LEPC on fibrin-based hydrogels incorporating LN-511-E8 resulted in firm integrin-mediated adhesion to the scaffold and well-stratified epithelial constructs, with maintenance of a progenitor cell phenotype in their (supra)basal layers. Thus, the incorporation of chemically defined LN-511-E8 into biosynthetic scaffolds represents a promising approach for xeno-free corneal epithelial tissue engineering for ocular surface reconstruction.

  4. Internet Medline providers.

    Science.gov (United States)

    Vine, D L; Coady, T R

    1998-01-01

    Each database in this review has features that will appeal to some users. Each provides a credible interface to information available within the Medline database. The major differences are pricing and interface design. In this context, features that cost more and might seem trivial to the occasional searcher may actually save time and money when used by the professional. Internet Grateful Med is free, but Ms. Coady and I agree the availability of only three ANDable search fields is a major functional limitation. PubMed is also free but much more powerful. The command line interface that permits very sophisticated searches requires a commitment that casual users will find intimidating. Ms. Coady did not believe the feedback currently provided during a search was sufficient for sustained professional use. Paper Chase and Knowledge Finder are mature, modestly priced Medline search services. Paper Chase provides a menu-driven interface that is very easy to use, yet permits the user to search virtually all of Medline's data fields. Knowledge Finder emphasizes the use of natural language queries but fully supports more traditional search strategies. The impact of the tradeoff between fuzzy and Boolean strategies offered by Knowledge Finder is unclear and beyond the scope of this review. Additional software must be downloaded to use all of Knowledge Finders' features. Other providers required no software beyond the basic Internet browser, and this requirement prevented Ms. Coady from evaluating Knowledge Finder. Ovid and Silver Platter offer well-designed interfaces that simplify the construction of complex queries. These are clearly services designed for professional users. While pricing eliminates these for casual use, it should be emphasized that Medline citation access is only a portion of the service provided by these high-end vendors. Finally, we should comment that each of the vendors and government-sponsored services provided prompt and useful feedback to e

  5. Defibrillators in general practice.

    OpenAIRE

    Clyde, C; Kerr, A; Varghese, A; Wilson, C

    1984-01-01

    After a successful pilot scheme introduced in 1975, when six portable defibrillators were provided for health centres, an additional 50 defibrillators were provided in February 1982 for general practitioners to use. Between December 1975 and February 1984 defibrillation was attempted in 54 patients who collapsed with clinical cardiac arrest in the presence of general practitioners or less than five minutes before their arrival. A cardiac output was achieved in 32 patients, 28 survived to reac...

  6. Effect of age on pulmonary epithelial permeability in unanesthetized lambs

    Energy Technology Data Exchange (ETDEWEB)

    Hutchison, A.A.; McNicol, K.J.; Loughlin, G.M.

    1985-01-01

    Pulmonary epithelial permeability was measured 1) in unanesthetized sheep, and 2) longitudinally in growing lambs. Awake sheep were intubated and a solution of /sup 51/Cr-ethylenediaminetetraacetic acid and /sup 125/I-antipyrine was instilled in the intrathoracic trachea via the nasotracheal tube. Arterial blood was drawn 1-25 minutes after the instillation. The ratios of the counts of /sup 51/Cr to /sup 125/I at 7, 10, and 13 min were calculated and averaged for each animal. Data from six adult sheep showed that the mean +/- SE of the permeability ratio was 0.012 +/- 0.003 and was reproducible over three months. When measured twice within two hours, the second ratio was significantly higher than the first. One hour of general anesthesia with methoxyflurane did not alter the permeability ratio significantly. Ten lambs were studied longitudinally 10 hours and 5, 10, 20, and 30 days after delivery. Within the first 24 hours of life the permeability ratio was, significantly greater than the adult value. At five days there was no significant difference between lambs and adult sheep. Throughout the first month of life, the permeability ratio in lambs remained at at the adult level.

  7. Epithelial borderline ovarian tumor: Diagnosis and treatment strategy.

    Science.gov (United States)

    Ushijima, Kimio; Kawano, Kouichiro; Tsuda, Naotake; Nishio, Shin; Terada, Atsumu; Kato, Hiroyuki; Tasaki, Kazuto; Matsukuma, Ken

    2015-05-01

    Epithelial borderline ovarian tumors (BOT) are distinctive from benign tumors and carcinoma. They occur in younger women more often than carcinoma, and there is some difficulty making correct diagnosis of BOT. Two subtypes of BOT, serous and mucinous borderline tumor have different characteristics and very different clinical behavior. Serous borderline tumor (SBT) with micropapillary pattern shows more incidence of extra ovarian disease and often coexists with invasive implant. SBT with micropapillary pattern in advanced stage has showed a worse prognosis than typical SBT. Huge mucinous borderline tumors have histologic heterogeneity, and the accuracy of frozen section diagnosis is relatively low. Extensive sampling is required to reach a correct pathological diagnosis. Mucinous adenoma (intestinal type) also runs the risk of recurrence after cystectomy, or intraoperative rupture of cyst. Laparoscopic procedure for BOT has not increased the risk of recurrence. Fertility preserving procedures are generally accepted, except in advanced stage SBT with invasive implants. Only cystectomy shows a significant risk of recurrence. Re-staging surgery and full staging surgery is not necessary for all BOT. We should not attempt to treat them uniformly, by the single diagnosis of "borderline tumor". It depends on histologic type. Close communication with the pathologist is necessary to gain more detail and ask more pathological samples in order to make the optimal treatment strategy for each individual patients.

  8. Providing plastic zone extrusion

    Science.gov (United States)

    Manchiraju, Venkata Kiran; Feng, Zhili; David, Stan A.; Yu, Zhenzhen

    2017-04-11

    Plastic zone extrusion may be provided. First, a compressor may generate frictional heat in stock to place the stock in a plastic zone of the stock. Then, a conveyer may receive the stock in its plastic zone from the compressor and transport the stock in its plastic zone from the compressor. Next, a die may receive the stock in its plastic zone from the conveyer and extrude the stock to form a wire.

  9. Genetic analysis of the early natural history of epithelial ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Bhavana Pothuri

    Full Text Available BACKGROUND: The high mortality rate associated with epithelial ovarian carcinoma (EOC reflects diagnosis commonly at an advanced stage, but improved early detection is hindered by uncertainty as to the histologic origin and early natural history of this malignancy. METHODOLOGY/PRINCIPAL FINDINGS: Here we report combined molecular genetic and morphologic analyses of normal human ovarian tissues and early stage cancers, from both BRCA mutation carriers and the general population, indicating that EOCs frequently arise from dysplastic precursor lesions within epithelial inclusion cysts. In pathologically normal ovaries, molecular evidence of oncogenic stress was observed specifically within epithelial inclusion cysts. To further explore potential very early events in ovarian tumorigenesis, ovarian tissues from women not known to be at high risk for ovarian cancer were subjected to laser catapult microdissection and gene expression profiling. These studies revealed a quasi-neoplastic expression signature in benign ovarian cystic inclusion epithelium compared to surface epithelium, specifically with respect to genes affecting signal transduction, cell cycle control, and mitotic spindle formation. Consistent with this gene expression profile, a significantly higher cell proliferation index (increased cell proliferation and decreased apoptosis was observed in histopathologically normal ovarian cystic compared to surface epithelium. Furthermore, aneuploidy was frequently identified in normal ovarian cystic epithelium but not in surface epithelium. CONCLUSIONS/SIGNIFICANCE: Together, these data indicate that EOC frequently arises in ovarian cystic inclusions, is preceded by an identifiable dysplastic precursor lesion, and that increased cell proliferation, decreased apoptosis, and aneuploidy are likely to represent very early aberrations in ovarian tumorigenesis.

  10. Commensal-derived OMVs elicit a mild proinflammatory response in intestinal epithelial cells.

    Science.gov (United States)

    Patten, Daniel A; Hussein, Enas; Davies, Scott P; Humphreys, Paul N; Collett, Andrew

    2017-05-01

    Under normal physiological conditions, the intestinal immunity remains largely hyporesponsive to the commensal microbiota, yet also retains the inherent ability to rapidly respond to pathogenic antigens. However, immunomodulatory activities of extracellular products from commensal bacteria have been little studied, with previous investigations generally utilizing the live bacterium to study microbiota-epithelial interactions. In this study, we demonstrate that extracellular products of a commensal bacterium, Escherichia coli C25, elicit a moderate release of proinflammatory IL-8 and stimulate transcriptional up-regulation of Toll-like receptors (TLRs) in intestinal epithelial cell lines HT29-19A and Caco-2. Additionally, we show that removal of outer membrane vesicles (OMVs) reduces the proinflammatory effect of secreted products from E. coli C25. Furthermore, we show that isolated OMVs have a dose-dependent proinflammatory effect on intestinal epithelial cells (IECs). Interestingly, a relatively high concentration (40 µg ml-1 protein) of OMVs had no significant regulatory effects on TLR mRNA expression in both cell lines. Finally, we also demonstrate that pre-incubation with E. coli C25-derived OMVs subsequently inhibited the internalization of the bacterium itself in both cell lines. Taken together, our results suggest that commensal-derived extracellular products, in particular OMVs, could significantly contribute to intestinal homeostasis. We also demonstrate a unique interaction between commensal-derived OMVs and host cells.

  11. Autophagy controls an intrinsic host defense to bacteria by promoting epithelial cell survival: a murine model.

    Directory of Open Access Journals (Sweden)

    Sun-Young Chang

    Full Text Available Cell death is a critical host response to regulate the fate of bacterial infections, innate immune responses, and ultimately, disease outcome. Shigella spp. invade and colonize gut epithelium in human and nonhuman primates but adult mice are naturally resistant to intra-gastric Shigella infection. In this study, however, we found Shigella could invade the terminal ileum of the mouse small intestine by 1 hour after infection and be rapidly cleared within 24 h. These early phase events occurred shortly after oral infection resulting in epithelial shedding, degranulation of Paneth cells, and cell death in the intestine. During this process, autophagy proceeded without any signs of inflammation. In contrast, blocking autophagy in epithelial cells enhanced host cell death, leading to tissue destruction and to inflammation, suggesting that autophagic flow relieves cellular stress associated with host cell death and inflammation. Herein we propose a new concept of "epithelial barrier turnover" as a general intrinsic host defense mechanism that increases survival of host cells and inhibits inflammation against enteric bacterial infections, which is regulated by autophagy.

  12. Predictors of re-epithelialization in pediatric burn.

    Science.gov (United States)

    Brown, Nadia J; Kimble, Roy M; Gramotnev, Galina; Rodger, Sylvia; Cuttle, Leila

    2014-06-01

    An important treatment goal for burn wounds is to promote early wound closure. This study identifies factors associated with delayed re-epithelialization following pediatric burn. Data were collected from August 2011 to August 2012, at a pediatric tertiary burn center. A total of 106 burn wounds were analyzed from 77 participants aged 4-12 years. Percentage of wound re-epithelialization at each dressing change was calculated using Visitrak™. Mixed effect regression analysis was performed to identify the demographic factors, wound and clinical characteristics associated with delayed re-epithelialization. Burn depth determined by laser Doppler imaging, ethnicity, pain scores, total body surface area (TBSA), mechanism of injury and days taken to present to the burn center were significant predictors of delayed re-epithelialization, accounting for 69% of variance. Flame burns delayed re-epithelialization by 39% compared to all other mechanisms (p = 0.003). When initial presentation to the burn center was on day 5, burns took an average of 42% longer to re-epithelialize, compared to those who presented on day 2 post burn (p Burn depth, mechanism of injury and TBSA are always considered when developing the treatment and surgical management plan for patients with burns. This study identifies other factors influencing re-epithelialization, which can be controlled by the treating team, such as effective pain management and rapid referral to a specialized burn center, to achieve optimal outcomes. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  13. Quantitative assessment of cytosolic Salmonella in epithelial cells.

    Directory of Open Access Journals (Sweden)

    Leigh A Knodler

    Full Text Available Within mammalian cells, Salmonella enterica serovar Typhimurium (S. Typhimurium inhabits a membrane-bound vacuole known as the Salmonella-containing vacuole (SCV. We have recently shown that wild type S. Typhimurium also colonizes the cytosol of epithelial cells. Here we sought to quantify the contribution of cytosolic Salmonella to the total population over a time course of infection in different epithelial cell lines and under conditions of altered vacuolar escape. We found that the lysosomotropic agent, chloroquine, acts on vacuolar, but not cytosolic, Salmonella. After chloroquine treatment, vacuolar bacteria are not transcriptionally active or replicative and appear degraded. Using a chloroquine resistance assay, in addition to digitonin permeabilization, we found that S. Typhimurium lyses its nascent vacuole in numerous epithelial cell lines, albeit with different frequencies, and hyper-replication in the cytosol is also widespread. At later times post-infection, cytosolic bacteria account for half of the total population in some epithelial cell lines, namely HeLa and Caco-2 C2Bbe1. Both techniques accurately measured increased vacuole lysis in epithelial cells upon treatment with wortmannin. By chloroquine resistance assay, we also determined that Salmonella pathogenicity island-1 (SPI-1, but not SPI-2, the virulence plasmid nor the flagellar apparatus, was required for vacuolar escape and cytosolic replication in epithelial cells. Together, digitonin permeabilization and the chloroquine resistance assay will be useful, complementary tools for deciphering the mechanisms of SCV lysis and Salmonella replication in the epithelial cell cytosol.

  14. Redefining epithelial characterization in oral submucous fibrosis using morphometric analysis.

    Science.gov (United States)

    Rathore, Ajit Singh; Gupta, Amit; Shetty, Devi Charan; Kumar, Kiran; Dhanapal, Raghu

    2017-01-01

    Oral submucous fibrosis (OSMF) is a chronic oral mucosal disease characterized by progressive deposition of collagen in subepithelial connective tissue and epithelial atrophy. The present study was conducted to evaluate the changes in epithelial thickness and cellular and nuclear morphometric characteristics of parabasal and spinous compartments of the epithelium in various stages of OSMF in comparison to normal epithelium. Sample included 30 cases of OSMF of various stages and five cases of normal buccal mucosa. Measurements for epithelial thickness and cellular morphology using morphometric analysis were performed on captured digital images using image analysis software. The ANOVA analysis of epithelial thickness and correlation of epithelial thickness with cell contour and cell roundness was done using Karl Pearson's coefficient of correlation. There was a statistically significant decrease in epithelial thickness with increase in severity/stage of OSMF. It was also observed that there is a highly statistically significant correlation (P = 0.000) between the thickness of epithelium and cell morphology in varying stages of OSMF. The morphometric parameters and the use of quantitative histological methods in determining the squamous epithelial structures thus made it possible to evaluate that there is reduction in thickness of epithelium or "atrophy" with increasing stages of OSMF which may be due to actual change in cell morphology of the individual cells of specific compartment or all compartments in the epithelium.

  15. The Contribution of the Airway Epithelial Cell to Host Defense.

    Science.gov (United States)

    Stanke, Frauke

    2015-01-01

    In the context of cystic fibrosis, the epithelial cell has been characterized in terms of its ion transport capabilities. The ability of an epithelial cell to initiate CFTR-mediated chloride and bicarbonate transport has been recognized early as a means to regulate the thickness of the epithelial lining fluid and recently as a means to regulate the pH, thereby determining critically whether or not host defense proteins such as mucins are able to fold appropriately. This review describes how the epithelial cell senses the presence of pathogens and inflammatory conditions, which, in turn, facilitates the activation of CFTR and thus directly promotes pathogens clearance and innate immune defense on the surface of the epithelial cell. This paper summarizes functional data that describes the effect of cytokines, chemokines, infectious agents, and inflammatory conditions on the ion transport properties of the epithelial cell and relates these key properties to the molecular pathology of cystic fibrosis. Recent findings on the role of cystic fibrosis modifier genes that underscore the role of the epithelial ion transport in host defense and inflammation are discussed.

  16. The Contribution of the Airway Epithelial Cell to Host Defense

    Directory of Open Access Journals (Sweden)

    Frauke Stanke

    2015-01-01

    Full Text Available In the context of cystic fibrosis, the epithelial cell has been characterized in terms of its ion transport capabilities. The ability of an epithelial cell to initiate CFTR-mediated chloride and bicarbonate transport has been recognized early as a means to regulate the thickness of the epithelial lining fluid and recently as a means to regulate the pH, thereby determining critically whether or not host defense proteins such as mucins are able to fold appropriately. This review describes how the epithelial cell senses the presence of pathogens and inflammatory conditions, which, in turn, facilitates the activation of CFTR and thus directly promotes pathogens clearance and innate immune defense on the surface of the epithelial cell. This paper summarizes functional data that describes the effect of cytokines, chemokines, infectious agents, and inflammatory conditions on the ion transport properties of the epithelial cell and relates these key properties to the molecular pathology of cystic fibrosis. Recent findings on the role of cystic fibrosis modifier genes that underscore the role of the epithelial ion transport in host defense and inflammation are discussed.

  17. Epithelial Dysplasia in Ameloblastic Fibrosarcoma Arising from Recurrent Ameloblastic Fibroma in a 26-Year-Old Iranian Man

    Science.gov (United States)

    Mohsenifar, Zhaleh; Behrad, Samira; Abbas, Fatemeh Mashhadi

    2015-01-01

    Patient: Male, 26 Final Diagnosis: Ameloblastic fibrosarcoma Symptoms: Swelling Medication: — Clinical Procedure: Hemimandibulectomy Specialty: Dentistry Objective: Rare disease Background: Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumor with a mesenchymal component, showing sarcomatous features and epithelial nests resembling ameloblastic fibroma (AF). Case Report: We report a case of AFS showing epithelial dysplasia arising in a recurrent AF in the left mandible after 3 years in a 26-year-old man, which is regarded as an uncommon histopathologic finding in AFS. We also emphasize the comprehensive clinical, radiographic, and histopathologic evaluation, and immunohistochemical staining of this patient. Conclusions: We conclude that it is important to consider malignancy alternations in the epithelial component of AFS, along with that of the mesenchymal component, to provide a proper diagnosis and treatment of recurrent AF. PMID:26289384

  18. Epithelial phenotype and the RPE: is the answer blowing in the Wnt?

    Science.gov (United States)

    Burke, Janice M

    2008-11-01

    Cells of the human retinal pigment epithelium (RPE) have a regular epithelial cell shape within the tissue in situ, but for reasons that remain elusive the RPE shows an incomplete and variable ability to re-develop an epithelial phenotype after propagation in vitro. In other epithelial cell cultures, formation of an adherens junction (AJ) composed of E-cadherin plays an important early inductive role in epithelial morphogenesis, but E-cadherin is largely absent from the RPE. In this review, the contribution of cadherins, both minor (E-cadherin) and major (N-cadherin), to RPE phenotype development is discussed. Emphasis is placed on the importance for future studies of actin cytoskeletal remodeling during assembly of the AJ, which in epithelial cells results in an actin organization that is characteristically zonular. Other markers of RPE phenotype that are used to gauge the maturation state of RPE cultures including tissue-specific protein expression, protein polarity, and pigmentation are described. An argument is made that RPE epithelial phenotype, cadherin-based cell-cell adhesion and melanization are linked by a common signaling pathway: the Wnt/beta-catenin pathway. Analyzing this pathway and its intersecting signaling networks is suggested as a useful framework for dissecting the steps in RPE morphogenesis. Also discussed is the effect of aging on RPE phenotype. Preliminary evidence is provided to suggest that light-induced sub-lethal oxidative stress to cultured ARPE-19 cells impairs organelle motility. Organelle translocation, which is mediated by stress-susceptible cytoskeletal scaffolds, is an essential process in cell phenotype development and retention. The observation of impaired organelle motility therefore raises the possibility that low levels of stress, which are believed to accompany RPE aging, may produce subtle disruptions of cell phenotype. Over time these would be expected to diminish the support functions performed by the RPE on behalf of

  19. Epithelial cells as alternative human biomatrices for comet assay

    Directory of Open Access Journals (Sweden)

    Emilio eRojas

    2014-11-01

    Full Text Available The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many organs, have the potential to serve as biomatrices that can be used to evaluate genotoxicity and may also serve as early effect biomarkers. Furthermore, 80% of solid cancers are of epithelial origin, which points to the importance of studying DNA damage in these tissues. Indeed, studies including comet assay in epithelial cells have either clear clinical applications (lens and corneal epithelial cells or examine genotoxicity within human biomonitoring and in vitro studies. We here review improvements in determining DNA damage using the comet assay by employing lens, corneal, tear duct, buccal, and nasal epithelial cells. For some of these tissues invasive sampling procedures are needed. Desquamated epithelial cells must be obtained and dissociated prior to examination using the comet assay, and such procedures may induce varying amounts of DNA damage. Buccal epithelial cells require lysis enriched with proteinase K to obtain free nucleosomes.Over a thirty year period, the comet assay in epithelial cells has been litlle employed, however its use indicates that it could be an extraordinary tool not only for risk assessment, but also for diagnosis, prognosis of treatments and diseases.

  20. Epithelial cells as alternative human biomatrices for comet assay.

    Science.gov (United States)

    Rojas, Emilio; Lorenzo, Yolanda; Haug, Kristiane; Nicolaissen, Bjørn; Valverde, Mahara

    2014-01-01

    The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many organs, have the potential to serve as biomatrices that can be used to evaluate genotoxicity and may also serve as early effect biomarkers. Furthermore, 80% of solid cancers are of epithelial origin, which points to the importance of studying DNA damage in these tissues. Indeed, studies including comet assay in epithelial cells have either clear clinical applications (lens and corneal epithelial cells) or examine genotoxicity within human biomonitoring and in vitro studies. We here review improvements in determining DNA damage using the comet assay by employing lens, corneal, tear duct, buccal, and nasal epithelial cells. For some of these tissues invasive sampling procedures are needed. Desquamated epithelial cells must be obtained and dissociated prior to examination using the comet assay, and such procedures may induce varying amounts of DNA damage. Buccal epithelial cells require lysis enriched with proteinase K to obtain free nucleosomes. Over a 30 year period, the comet assay in epithelial cells has been little employed, however its use indicates that it could be an extraordinary tool not only for risk assessment, but also for diagnosis, prognosis of treatments and diseases.

  1. Isolation of fibroblasts and epithelial cells in bronchoalveolar lavage (BAL).

    Science.gov (United States)

    Pollock, Kathryn; Albares, Luke; Wendt, Chris; Hubel, Allison

    2013-04-01

    The long-term outcome of lung transplants is poor with 60%-70% of patients developing chronic rejection. Chronic rejection is manifested histologically by obliterative bronchiolitis with bronchiolitis obliterans syndrome (BOS), the clinical surrogate. Recent studies suggest that fibroblasts and epithelial cells present in bronchoalveolar lavage (BAL) may be a clinically relevant biomarker for BOS. The goal of this investigation was to develop a fast, repeatable method to individually isolate these low-frequency cell types. Fibroblasts and epithelial cells were isolated from BAL using attachment methods and the phenotype of the cells confirmed using immunostaining for vimentin (fibroblasts) and epithelial cell adhesion molecule (EpCAM, epithelial cells). Both fibroblasts and epithelial cells were isolated in every sample of BAL processed with the frequency of fibroblasts ranging from 0.03% to 0.48% and epithelial cells ranging from 0.05% to 1.5% of the total sample. Additional studies were performed using cytospins of cells after macrophages were depleted; cells exhibiting characteristics of both fibroblasts and epithelial cells were observed. The frequency of the cells of interest suggests that conventional methods of immunomagnetic isolation will not be effective in isolating these subpopulations. Finally, some of the low-frequency cells isolated via cytospin exhibit characteristics of epithelial to mesenchymal transition (which was not observed in plating incubations), indicating that the epithelial to mesenchymal cell transition fibroblasts may be nonadherent. In future studies, this technique and dataset may be of use to statistically correlate low-frequency cell type abundance to the onset and development of BOS.

  2. Enhanced efficiency of lactosylated poly-L-lysine-mediated gene transfer into cystic fibrosis airway epithelial cells

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Knollen, W.J.W.; Schembri, F.M.; Gerwig, G.J.; Glick, M.C.; Scanlin, T.F.

    1999-01-01

    Lactosylated poly-L-lysine is a nonviral vector that transfers genes into airway epithelial cells, including those from individuals with cystic fibrosis (CF). Substitution of 40% of the -amino groups of poly-L-lysine with lactosyl residues not only provided a ligand for receptor-mediated

  3. Strain-Dependent Induction of Human Enterocyte Apoptosis by Blastocystis Disrupts Epithelial Barrier and ZO-1 Organization in a Caspase 3- and 9-Dependent Manner

    Science.gov (United States)

    Teo, Joshua D. W.; Tan, Kevin S. W.

    2014-01-01

    Blastocystis is an emerging protistan parasite colonizing the human intestine. It is frequently reported to cause general intestinal symptoms of vomiting, diarrhea, and abdominal pain. We recently demonstrated that Blastocystis rearranged cytoskeletal proteins and induced intestinal epithelial barrier compromise. The effect of Blastocystis on enterocyte apoptosis is unknown, and a possible link between microbially induced enterocyte apoptosis and increased epithelial permeability has yet to be determined. The aim of this study is to assess if Blastocystis induces human enterocyte apoptosis and whether this effect influences human intestinal epithelial barrier function. Monolayers of polarized human colonic epithelial cell-line Caco-2 were incubated with Blastocystis subtype 7 and subtype 4. Assays for both early and late markers of apoptosis, phosphatidylserine externalization, and nuclear fragmentation, respectively, showed that Blastocystis ST-7, but not ST-4, significantly increased apoptosis in enterocytes, suggesting that Blastocystis exhibits host specificity and strain-to-strain variation in pathogenicity. ST-7 also activated Caco-2 caspases 3 and 9 but not 8. ST-7 induced changes in epithelial resistance, permeability, and tight junction (ZO-1) localization. Pretreatment of Caco-2 monolayers with a pan-caspase inhibitor z-VAD-fmk significantly inhibited these changes. This suggests a role for enterocyte apoptosis in Blastocystis-mediated epithelial barrier compromise in the human intestine. PMID:24822183

  4. Strain-Dependent Induction of Human Enterocyte Apoptosis by Blastocystis Disrupts Epithelial Barrier and ZO-1 Organization in a Caspase 3- and 9-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Zhaona Wu

    2014-01-01

    Full Text Available Blastocystis is an emerging protistan parasite colonizing the human intestine. It is frequently reported to cause general intestinal symptoms of vomiting, diarrhea, and abdominal pain. We recently demonstrated that Blastocystis rearranged cytoskeletal proteins and induced intestinal epithelial barrier compromise. The effect of Blastocystis on enterocyte apoptosis is unknown, and a possible link between microbially induced enterocyte apoptosis and increased epithelial permeability has yet to be determined. The aim of this study is to assess if Blastocystis induces human enterocyte apoptosis and whether this effect influences human intestinal epithelial barrier function. Monolayers of polarized human colonic epithelial cell-line Caco-2 were incubated with Blastocystis subtype 7 and subtype 4. Assays for both early and late markers of apoptosis, phosphatidylserine externalization, and nuclear fragmentation, respectively, showed that Blastocystis ST-7, but not ST-4, significantly increased apoptosis in enterocytes, suggesting that Blastocystis exhibits host specificity and strain-to-strain variation in pathogenicity. ST-7 also activated Caco-2 caspases 3 and 9 but not 8. ST-7 induced changes in epithelial resistance, permeability, and tight junction (ZO-1 localization. Pretreatment of Caco-2 monolayers with a pan-caspase inhibitor z-VAD-fmk significantly inhibited these changes. This suggests a role for enterocyte apoptosis in Blastocystis-mediated epithelial barrier compromise in the human intestine.

  5. Generalized polygons

    CERN Document Server

    Van Maldeghem, Hendrik

    1998-01-01

    Generalized Polygons is the first book to cover, in a coherent manner, the theory of polygons from scratch. In particular, it fills elementary gaps in the literature and gives an up-to-date account of current research in this area, including most proofs, which are often unified and streamlined in comparison to the versions generally known. Generalized Polygons will be welcomed both by the student seeking an introduction to the subject as well as the researcher who will value the work as a reference. In particular, it will be of great value for specialists working in the field of generalized polygons (which are, incidentally, the rank 2 Tits-buildings) or in fields directly related to Tits-buildings, incidence geometry and finite geometry. The approach taken in the book is of geometric nature, but algebraic results are included and proven (in a geometric way!). A noteworthy feature is that the book unifies and generalizes notions, definitions and results that exist for quadrangles, hexagons, octagons - in the ...

  6. Using organotypic (raft) epithelial tissue cultures for the biosynthesis and isolation of infectious human papillomaviruses.

    Science.gov (United States)

    Ozbun, Michelle A; Patterson, Nicole A

    2014-08-01

    Papillomaviruses have a strict tropism for epithelial cells, and they are fully reliant on cellular differentiation for completion of their life cycles, resulting in the production of progeny virions. Thus, a permissive environment for full viral replication in vitro-wherein virion morphogenesis occurs under cooperative viral and cellular cues-requires the cultivation of epithelium. Presented in the first section of this unit is a protocol to grow differentiating epithelial tissues that mimic many important morphological and biochemical aspects of normal skin. The technique involves growing epidermal cells atop a dermal equivalent consisting of live fibroblasts and a collagen lattice. Epithelial stratification and differentiation ensues when the keratinocyte-dermal equivalent is placed at the air-liquid interface. The apparent floating nature of the cell-matrix in this method led to the nickname "raft" cultures. The general technique can be applied to normal low passage keratinocytes, to cells stably transfected with papillomavirus genes or genomes, or keratinocytes established from neoplastic lesions. However, infectious papillomavirus particles have only been isolated from organotypic epithelial cultures initiated with cells that maintain oncogenic human papillomavirus genomes in an extrachomosomal replicative form. The second section of this unit is dedicated to a virion isolation method that minimizes aerosol and skin exposure to these human carcinogens. Although the focus of the protocols is on the growth of tissues that yields infectious papillomavirus progeny, this culture system facilitates the investigation of these fastidious viruses during their complex replicative cycles, and raft tissues can be manipulated and harvested at any point during the process. Importantly, a single-step virus growth cycle is achieved in this process, as it is unlikely that progeny virions are released to initiate subsequent rounds of infection. Copyright © 2014 John Wiley

  7. Depth sensitive oblique polarized reflectance spectroscopy of oral epithelial tissue

    Science.gov (United States)

    Jimenez, Maria K.; Lam, Sylvia; Poh, Catherine; Sokolov, Konstantin

    2014-05-01

    Identifying depth-dependent alterations associated with epithelial cancerous lesions can be challenging in the oral cavity where variable epithelial thicknesses and troublesome keratin growths are prominent. Spectroscopic methods with enhanced depth resolution would immensely aid in isolating optical properties associated with malignant transformation. Combining multiple beveled fibers, oblique collection geometry, and polarization gating, oblique polarized reflectance spectroscopy (OPRS) achieves depth sensitive detection. We report promising results from a clinical trial of patients with oral lesions suspected of dysplasia or carcinoma demonstrating the potential of OPRS for the analysis of morphological and architectural changes in the context of multilayer, epithelial oral tissue.

  8. Providing Compassion through Flow

    Directory of Open Access Journals (Sweden)

    Lydia Royeen

    2015-07-01

    Full Text Available Meg Kral, MS, OTR/L, CLT, is the cover artist for the Summer 2015 issue of The Open Journal of Occupational Therapy. Her untitled piece of art is an oil painting and is a re-creation of a photograph taken while on vacation. Meg is currently supervisor of outpatient services at Rush University Medical Center. She is lymphedema certified and has a specific interest in breast cancer lymphedema. Art and occupational therapy serve similar purposes for Meg: both provide a sense of flow. She values the outcomes, whether it is a piece of art or improved functional status

  9. Providing Contraception to Adolescents.

    Science.gov (United States)

    Raidoo, Shandhini; Kaneshiro, Bliss

    2015-12-01

    Adolescents have high rates of unintended pregnancy and face unique reproductive health challenges. Providing confidential contraceptive services to adolescents is important in reducing the rate of unintended pregnancy. Long-acting contraception such as the intrauterine device and contraceptive implant are recommended as first-line contraceptives for adolescents because they are highly effective with few side effects. The use of barrier methods to prevent sexually transmitted infections should be encouraged. Adolescents have limited knowledge of reproductive health and contraceptive options, and their sources of information are often unreliable. Access to contraception is available through a variety of resources that continue to expand. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Ysla S. Catalina & Providence

    OpenAIRE

    Diazgranados, Carlos Nicolás; Torres Carreño, Guillermo Andrés; Castell, Edmon; Moreno, Santiago; Ramirez, Natalia

    2010-01-01

    Esta Hoja de Mano pertenece a la exposición temporal "Ysla S. Catalina & Providence". Contiene un resumen histórico de las Islas de Santa Catalina y Providencia en los idiomas inglés y español y un mapa del siglo VI que lo hace más didáctico apoyado por figuras recortables. Esta muestra hace parte del proyecto IDA y VUELTA del Sistema de Patrimonio Cultural y Museos SPM que gestiona la descentralización del patrimonio cultural de la Universidad Nacional de Colombia a otras ciudades del pa...

  11. Notch-dependent epithelial fold determines boundary formation between developmental fields in the Drosophila antenna.

    Science.gov (United States)

    Ku, Hui-Yu; Sun, Y Henry

    2017-07-01

    Compartment boundary formation plays an important role in development by separating adjacent developmental fields. Drosophila imaginal discs have proven valuable for studying the mechanisms of boundary formation. We studied the boundary separating the proximal A1 segment and the distal segments, defined respectively by Lim1 and Dll expression in the eye-antenna disc. Sharp segregation of the Lim1 and Dll expression domains precedes activation of Notch at the Dll/Lim1 interface. By repressing bantam miRNA and elevating the actin regulator Enable, Notch signaling then induces actomyosin-dependent apical constriction and epithelial fold. Disruption of Notch signaling or the actomyosin network reduces apical constriction and epithelial fold, so that Dll and Lim1 cells become intermingled. Our results demonstrate a new mechanism of boundary formation by actomyosin-dependent tissue folding, which provides a physical barrier to prevent mixing of cells from adjacent developmental fields.

  12. Self-assembled monolayer facilitates epithelial-mesenchymal interactions mimicking odontogenesis.

    Science.gov (United States)

    Muni, Tanvi; Mrksich, Milan; George, Anne

    2014-01-01

    Cell-cell interactions are vital for embryonic organ development and normal function of differentiated cells and tissues. In this study we have developed a self-assembled monolayer-based co-culture system to study tooth morphogenesis. Specifically, we designed a 2-D microenvironment present in the dental tissue by creating a well-structured, laterally organized epithelial and mesenchymal cell co-culture system by patterning the cell-attachment substrate. Chemical modifications were used to develop tunable surface patterns to facilitate epithelial-mesenchymal interactions mimicking the developing tooth. Such a design promoted interactions between monolayer's of the 2 cell types and provided signaling cues that resulted in cellular differentiation and mineralized matrix formation. Gene expression analysis showed that these co-cultures mimicked in-vivo conditions than monolayer cultures of a single cell type.

  13. Notch-dependent epithelial fold determines boundary formation between developmental fields in the Drosophila antenna.

    Directory of Open Access Journals (Sweden)

    Hui-Yu Ku

    2017-07-01

    Full Text Available Compartment boundary formation plays an important role in development by separating adjacent developmental fields. Drosophila imaginal discs have proven valuable for studying the mechanisms of boundary formation. We studied the boundary separating the proximal A1 segment and the distal segments, defined respectively by Lim1 and Dll expression in the eye-antenna disc. Sharp segregation of the Lim1 and Dll expression domains precedes activation of Notch at the Dll/Lim1 interface. By repressing bantam miRNA and elevating the actin regulator Enable, Notch signaling then induces actomyosin-dependent apical constriction and epithelial fold. Disruption of Notch signaling or the actomyosin network reduces apical constriction and epithelial fold, so that Dll and Lim1 cells become intermingled. Our results demonstrate a new mechanism of boundary formation by actomyosin-dependent tissue folding, which provides a physical barrier to prevent mixing of cells from adjacent developmental fields.

  14. Notch-dependent epithelial fold determines boundary formation between developmental fields in the Drosophila antenna

    Science.gov (United States)

    2017-01-01

    Compartment boundary formation plays an important role in development by separating adjacent developmental fields. Drosophila imaginal discs have proven valuable for studying the mechanisms of boundary formation. We studied the boundary separating the proximal A1 segment and the distal segments, defined respectively by Lim1 and Dll expression in the eye-antenna disc. Sharp segregation of the Lim1 and Dll expression domains precedes activation of Notch at the Dll/Lim1 interface. By repressing bantam miRNA and elevating the actin regulator Enable, Notch signaling then induces actomyosin-dependent apical constriction and epithelial fold. Disruption of Notch signaling or the actomyosin network reduces apical constriction and epithelial fold, so that Dll and Lim1 cells become intermingled. Our results demonstrate a new mechanism of boundary formation by actomyosin-dependent tissue folding, which provides a physical barrier to prevent mixing of cells from adjacent developmental fields. PMID:28708823

  15. Hypoxia, Epithelial-Mesenchymal Transition, and TET-Mediated Epigenetic Changes

    Directory of Open Access Journals (Sweden)

    Shih-Han Kao

    2016-02-01

    Full Text Available Tumor hypoxia is a pathophysiologic outcome of disrupted microcirculation with inadequate supply of oxygen, leading to enhanced proliferation, epithelial-mesenchymal transition (EMT, metastasis, and chemo-resistance. Epigenetic changes induced by hypoxia are well documented, and they lead to tumor progression. Recent advances show that DNA demethylation mediated by the Ten-eleven translocation (TET proteins induces major epigenetic changes and controls key steps of cancer development. TET enzymes serve as 5mC (5-methylcytosine-specific dioxygenases and cause DNA demethylation. Hypoxia activates the expression of TET1, which also serves as a co-activator of HIF-1α transcriptional regulation to modulate HIF-1α downstream target genes and promote epithelial-mesenchymal transition. As HIF is a negative prognostic factor for tumor progression, hypoxia-activated prodrugs (HAPs may provide a favorable therapeutic approach to lessen hypoxia-induced malignancy.

  16. Enterohemorrhagic Escherichia coli infection stimulates Shiga toxin 1 macropinocytosis and transcytosis across intestinal epithelial cells.

    Science.gov (United States)

    Lukyanenko, Valeriy; Malyukova, Irina; Hubbard, Ann; Delannoy, Michael; Boedeker, Edgar; Zhu, Chengru; Cebotaru, Liudmila; Kovbasnjuk, Olga

    2011-11-01

    Gastrointestinal infection with Shiga toxins producing enterohemorrhagic Escherichia coli causes the spectrum of gastrointestinal and systemic complications, including hemorrhagic colitis and hemolytic uremic syndrome, which is fatal in ∼10% of patients. However, the molecular mechanisms of Stx endocytosis by enterocytes and the toxins cross the intestinal epithelium are largely uncharacterized. We have studied Shiga toxin 1 entry into enterohemorrhagic E. coli-infected intestinal epithelial cells and found that bacteria stimulate Shiga toxin 1 macropinocytosis through actin remodeling. This enterohemorrhagic E. coli-caused macropinocytosis occurs through a nonmuscle myosin II and cell division control 42 (Cdc42)-dependent mechanism. Macropinocytosis of Shiga toxin 1 is followed by its transcytosis to the basolateral environment, a step that is necessary for its systemic spread. Inhibition of Shiga toxin 1 macropinocytosis significantly decreases toxin uptake by intestinal epithelial cells and in this way provides an attractive, antibiotic-independent strategy for prevention of the harmful consequences of enterohemorrhagic E. coli infection.

  17. IASLC/ITMIG Staging System and Lymph Node Map for Thymic Epithelial Neoplasms.

    Science.gov (United States)

    Carter, Brett W; Benveniste, Marcelo F; Madan, Rachna; Godoy, Myrna C; Groot, Patricia M de; Truong, Mylene T; Rosado-de-Christenson, Melissa L; Marom, Edith M

    2017-01-01

    Thymic epithelial neoplasms are rare malignancies that arise from the thymus and include thymoma, thymic carcinoma, and thymic neuroendocrine tumors. At least 15 different stage classifications have been proposed for thymic epithelial neoplasms and used to varying degrees in clinical practice, many of which have been constructed from small groups of patients. Traditionally, the Masaoka and Masaoka-Koga staging systems have been the schemes most commonly employed, and the latter has been recommended for use by the International Thymic Malignancy Interest Group (ITMIG). An official, consistent stage classification system has recently been recognized by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC), which are responsible for defining stage classifications for neoplasms. To establish this stage classification system, the International Association for the Study of Lung Cancer (IASLC) and ITMIG amassed a large retrospective database and evaluated this group of cases to develop proposals for the eighth edition of the stage classification manuals. For this endeavor, IASLC provided funding and statistical analysis and ITMIG provided the involvement of the clinicians and researchers actively participating in the study of thymic epithelial neoplasms. To accomplish this, a Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC) was established to formulate the rationale, methodology, and definitions of this tumor-node-metastasis (TNM) staging system, which is presented in this article. © RSNA, 2017.

  18. Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment.

    Science.gov (United States)

    Rojas, Veronica; Hirshfield, Kim M; Ganesan, Shridar; Rodriguez-Rodriguez, Lorna

    2016-12-15

    Epithelial ovarian cancer is a highly heterogeneous disease characterized by multiple histological subtypes. Molecular diversity has been shown to occur within specific histological subtypes of epithelial ovarian cancer, between different tumors of an individual patient, as well as within individual tumors. Recent advances in the molecular characterization of epithelial ovarian cancer tumors have provided the basis for a simplified classification scheme in which these cancers are classified as either type I or type II tumors, and these two categories have implications regarding disease pathogenesis and prognosis. Molecular analyses, primarily based on next-generation sequencing, otherwise known as high-throughput sequencing, are allowing for further refinement of ovarian cancer classification, facilitating the elucidation of the site(s) of precursor lesions of high-grade serous ovarian cancer, and providing insight into the processes of clonal selection and evolution that may be associated with development of chemoresistance. Potential therapeutic targets have been identified from recent molecular profiling studies of these tumors, and the effectiveness and safety of a number of specific targeted therapies have been evaluated or are currently being studied for the treatment of women with this disease.

  19. Quantitative analysis of the epithelial lining architecture in radicular cysts and odontogenic keratocysts

    Directory of Open Access Journals (Sweden)

    Landini Gabriel

    2006-02-01

    Full Text Available Abstract Background This paper describes a quantitative analysis of the cyst lining architecture in radicular cysts (of inflammatory aetiology and odontogenic keratocysts (thought to be developmental or neoplastic including its 2 counterparts: solitary and associated with the Basal Cell Naevus Syndrome (BCNS. Methods Epithelial linings from 150 images (from 9 radicular cysts, 13 solitary keratocysts and 8 BCNS keratocysts were segmented into theoretical cells using a semi-automated partition based on the intensity of the haematoxylin stain which defined exclusive areas relative to each detected nucleus. Various morphometrical parameters were extracted from these "cells" and epithelial layer membership was computed using a systematic clustering routine. Results Statistically significant differences were observed across the 3 cyst types both at the morphological and architectural levels of the lining. Case-wise discrimination between radicular cysts and keratocyst was highly accurate (with an error of just 3.3%. However, the odontogenic keratocyst subtypes could not be reliably separated into the original classes, achieving discrimination rates slightly above random allocations (60%. Conclusion The methodology presented is able to provide new measures of epithelial architecture and may help to characterise and compare tissue spatial organisation as well as provide useful procedures for automating certain aspects of histopathological diagnosis.

  20. Acidosis increases the susceptibility of respiratory epithelial cells to Pseudomonas aeruginosa-induced cytotoxicity.

    Science.gov (United States)

    Torres, Iviana M; Demirdjian, Sally; Vargas, Jennifer; Goodale, Britton C; Berwin, Brent

    2017-07-01

    Bacterial infection can lead to acidosis of the local microenvironment, which is believed to exacerbate disease pathogenesis; however, the mechanisms by which changes in pH alter disease progression are poorly understood. We test the hypothesis that acidosis enhances respiratory epithelial cell death in response to infection with Pseudomonas aeruginosa Our findings support the idea that acidosis in the context of P. aeruginosa infection results in increased epithelial cell cytotoxicity due to ExoU intoxication. Importantly, enforced maintenance of neutral pH during P. aeruginosa infection demonstrates that cytotoxicity is dependent on the acidosis. Investigation of the underlying mechanisms revealed that host cell cytotoxicity correlated with increased bacterial survival during an acidic infection that was due to reduced bactericidal activity of host-derived antimicrobial peptides. These findings extend previous reports that the activities of antimicrobial peptides are pH-dependent and provide novel insights into the consequences of acidosis on infection-derived pathology. Therefore, this report provides the first evidence that physiological levels of acidosis increase the susceptibility of epithelial cells to acute Pseudomonas infection and demonstrates the benefit of maintaining pH homeostasis during a bacterial infection. Copyright © 2017 the American Physiological Society.

  1. Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment

    Science.gov (United States)

    Rojas, Veronica; Hirshfield, Kim M.; Ganesan, Shridar; Rodriguez-Rodriguez, Lorna

    2016-01-01

    Epithelial ovarian cancer is a highly heterogeneous disease characterized by multiple histological subtypes. Molecular diversity has been shown to occur within specific histological subtypes of epithelial ovarian cancer, between different tumors of an individual patient, as well as within individual tumors. Recent advances in the molecular characterization of epithelial ovarian cancer tumors have provided the basis for a simplified classification scheme in which these cancers are classified as either type I or type II tumors, and these two categories have implications regarding disease pathogenesis and prognosis. Molecular analyses, primarily based on next-generation sequencing, otherwise known as high-throughput sequencing, are allowing for further refinement of ovarian cancer classification, facilitating the elucidation of the site(s) of precursor lesions of high-grade serous ovarian cancer, and providing insight into the processes of clonal selection and evolution that may be associated with development of chemoresistance. Potential therapeutic targets have been identified from recent molecular profiling studies of these tumors, and the effectiveness and safety of a number of specific targeted therapies have been evaluated or are currently being studied for the treatment of women with this disease. PMID:27983698

  2. In vivo administration of dental epithelial stem cells at the apical end of the mouse incisor

    Directory of Open Access Journals (Sweden)

    Giovanna eOrsini

    2015-04-01

    Full Text Available Cell-based tissue regeneration is an attractive approach that complements traditional surgical techniques for replacement of injured and lost tissues. The continuously growing rodent incisor provides an excellent model system for investigating cellular and molecular mechanisms that underlie tooth renewal and regeneration. An active population of dental epithelial progenitor/stem cells located at the posterior part of the incisor, commonly called cervical loop area, ensures the continuous supply of cells that are responsible for the secretion of enamel matrix. To explore the potential of these epithelial cells in therapeutic approaches dealing with enamel defects, we have developed a new method for their in vivo administration in the posterior part of the incisor. Here we provide the step-by-step protocol for the isolation of dental epithelial stem cells and their delivery at targeted areas of the jaw. This simple and yet powerful protocol, consisting in drilling a hole in the mandibular bone, in close proximity to the cervical loop area of the incisor, followed up by injection of stem cells, is feasible, reliable, and effective. This in vivo approach opens new horizons and possibilities for cellular therapies involving pathological and injured dental tissues.

  3. Malignant transformation of human benign prostate epithelial cells by high linear energy transfer alpha-particles.

    Science.gov (United States)

    Li, Hongzhen; Gu, Yongpeng; Miki, Jun; Hukku, Bharati; McLeod, David G; Hei, Tom K; Rhim, Johng S

    2007-09-01

    Although epidemiological studies have suggested a positive correlation between environmental radon exposure and prostate cancer, the mechanism involved is not clear. In the present study, we examined the oncogenic transforming potency of alpha-particles using non-tumorigenic, telomerase-immortalized human benign prostate epithelial cells. We report the malignant transformation of human benign prostate epithelial cells after a single exposure to 0.6 Gy dose of alpha-particles. Transformed cells showed anchorage-independent growth in soft agar and induced progressively growing tumors when transplanted into SCID mice. The tumors were characterized histologically as poorly differentiated adenocarcinomas. The cell line derived from tumor (SCID 5015), like the unirradiated cells, expressed cytokeratin 5, 8 and 18, NKX3.1 and AMACR. The malignant cells showed increased secretion of MMP2. Stepwise chromosomal changes in the progression to tumorigenicity were observed. Chromosome abnormalities were identified in both irradiated and tumorigenic cells relative to the non-irradiated control cells. Prominent changes in chromosomes 6, 11 and 16, as well as mutations and deletions of the p53 gene were observed in the tumor outgrowth and tumor cells. These findings provide the first evidence of malignant transformation of human benign prostate epithelial cells exposed to a single dose of alpha-particles. This model provides an opportunity to study the cellular and molecular alterations that occur in radiation carcinogenesis in human prostate cells.

  4. Persistent Transmissible Gastroenteritis Virus Infection Enhances Enterotoxigenic Escherichia coli K88 Adhesion by Promoting Epithelial-Mesenchymal Transition in Intestinal Epithelial Cells.

    Science.gov (United States)

    Xia, Lu; Dai, Lei; Yu, Qinghua; Yang, Qian

    2017-11-01

    that persistent TGEV infection induces an EMT in porcine intestinal columnar epithelial cells (IPEC-J2) and enhances the adhesion of the secondary pathogen ETEC K88. Additional experiments suggest that integrin α5 and fibronectin play an important role in TGEV-enhanced ETEC K88 adhesion. Reversal of EMT reduces the expression of integrin α5 and fibronectin and also reduces ETEC K88 adhesion. We conclude that TGEV infection triggers EMT and facilitates dual infection. Our results provide new insights into secondary infection and suggest that targeted anti-EMT therapy may have implications for the prevention and treatment of secondary infection. Copyright © 2017 American Society for Microbiology.

  5. Direct repression of MYB by ZEB1 suppresses proliferation and epithelial gene expression during epithelial-to-mesenchymal transition of breast cancer cells

    Science.gov (United States)

    2013-01-01

    epithelial colony morphology in two dimensional monolayer cultures. Finally, we detected binding of ZEB1 to MYB promoter in PMC42-ET cells, and ZEB1 overexpression repressed MYB promoter activity. Conclusions This work identifies ZEB1 as a transcriptional repressor of MYB and suggests a reciprocal MYB-ZEB1 repressive relation, providing a mechanism through which proliferation and the epithelial phenotype may be coordinately modulated in breast cancer cells. PMID:24283570

  6. Ciliary neurotrophic factor promotes the activation of corneal epithelial stem/progenitor cells and accelerates corneal epithelial wound healing.

    Science.gov (United States)

    Zhou, Qingjun; Chen, Peng; Di, Guohu; Zhang, Yangyang; Wang, Yao; Qi, Xia; Duan, Haoyun; Xie, Lixin

    2015-05-01

    Ciliary neurotrophic factor (CNTF), a well-known neuroprotective cytokine, has been found to play an important role in neurogenesis and functional regulations of neural stem cells. As one of the most innervated tissue, however, the role of CNTF in cornea epithelium remains unclear. This study was to explore the roles and mechanisms of CNTF in the activation of corneal epithelial stem/progenitor cells and wound healing of both normal and diabetic mouse corneal epithelium. In mice subjecting to mechanical removal of corneal epithelium, the corneal epithelial stem/progenitor cell activation and wound healing were promoted by exogenous CNTF application, while delayed by CNTF neutralizing antibody. In cultured corneal epithelial stem/progenitor cells, CNTF enhanced the colony-forming efficiency, stimulated the mitogenic proliferation, and upregulated the expression levels of corneal epithelial stem/progenitor cell-associated transcription factors. Furthermore, the promotion of CNTF on the corneal epithelial stem/progenitor cell activation and wound healing was mediated by the activation of STAT3. Moreover, in diabetic mice, the content of CNTF in corneal epithelium decreased significantly when compared with that of normal mice, and the supplement of CNTF promoted the diabetic corneal epithelial wound healing, accompanied with the advanced activation of corneal epithelial stem/progenitor cells and the regeneration of corneal nerve fibers. Thus, the capability of expanding corneal epithelial stem/progenitor cells and promoting corneal epithelial wound healing and nerve regeneration indicates the potential application of CNTF in ameliorating limbal stem cell deficiency and treating diabetic keratopathy. © 2014 AlphaMed Press.

  7. A positive role of cadherin in Wnt/β-catenin signalling during epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Sara Howard

    Full Text Available The Wnt/β-catenin signalling pathway shares a key component, β-catenin, with the cadherin-based adhesion system. The signalling function of β-catenin is conferred by a soluble cytoplasmic pool that is unstable in the absence of a Wnt signal, whilst the adhesion function is based on a cadherin-bound, stable pool at the membrane. The cadherin complex is dynamic, allowing for cell-cell rearrangements such as epithelial-mesenchymal transition (EMT, where the complex turns over through internalisation. Potential interplay between the two pools remains poorly understood, but cadherins are generally considered negative regulators of Wnt signalling because they sequester cytoplasmic β-catenin. Here we explore how cellular changes at EMT affect the signalling capacity of β-catenin using two models of EMT: hepatocyte growth factor (HGF treatment of MDCK cells, and gastrulation in embryonic development. We show that EMT not only provides a pool of signalling-competent β-catenin following internalisation of cadherin, but also significantly facilitates activation of the Wnt pathway in response to both Wnt signals and exogenous β-catenin. We further demonstrate that availability of β-catenin in the cytoplasm does not necessarily correlate with Wnt/β-catenin pathway activity, since blocking endocytosis or depleting endogenous cadherin abolishes pathway activation despite the presence of β-catenin in the cytoplasm. Lastly we present data suggesting that cadherins are required for augmented activation of the Wnt/β-catenin pathway in vivo. This suggests that cadherins play a crucial role in β-catenin-dependent transcription.

  8. Proliferation of epithelial rests of Malassez following auto-transplantation of third molars: a case report

    Directory of Open Access Journals (Sweden)

    Schepers Serge

    2010-10-01

    Full Text Available Abstract Introduction Auto-transplantation of third molars is frequently undertaken in order to restore a perfect occlusion and to improve mastication following a substantial loss of molars. However, little is known about the precise role of the periodontal membrane during this procedure. Therefore, we investigated if the epithelial rests of Malassez persist in the periodontal ligament of auto-transplanted teeth and, if so, whether these may show signs of a neuro-epithelial relationship. Case presentation We report a case of a 21-year-old Caucasian woman who underwent an auto-transplantation of two third molars. After two years, renewed progressive caries of the auto-transplanted teeth led to the removal of the auto-transplanted elements. The periodontal ligament was removed and studied with a light and transmission electron microscope. Conclusion In this report we examined the ultrastructure of the periodontal ligament after auto-transplantation in order to see if the periodontal ligament recovers completely from this intervention. We observed fully developed blood vessels and a re-innervation of the epithelial rests of Malassez which were proliferating following auto-transplantation. This proliferation might be critical in the remodelling of the alveolar socket in order to provide a perfect fit for the transplanted tooth. In order to minimalise the damage to the epithelial rests of Malassez, the extraction of the tooth should be as atraumatic as possible in order to provide an optimal conservation of the periodontal ligament which will be beneficial to the healing-process.

  9. General Perspective

    African Journals Online (AJOL)

    2013-09-25

    Sep 25, 2013 ... general pedagogical knowledge (e.g. classroom control, using group work), pedagogical content knowledge, curriculum knowledge, knowledge of learners and their characteristics, knowledge of educational contexts (e.g. schools and the wider community), and knowledge of educational ends purposes ...

  10. General anesthesia

    Science.gov (United States)

    ... Affect your ability to breathe Make you uncomfortable Cause too much anxiety You may also be able to have conscious sedation for your procedure. Sometimes, though, it is not enough to make you comfortable. Children may need general anesthesia for a medical or ...

  11. GENERAL Iarticle

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 3. Twin Primes and the Pentium Chip. C S Yogananda. General Article Volume 8 Issue 3 March 2003 pp 32-32. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/008/03/0032-0032. Author Affiliations.

  12. Generalized Recovery

    DEFF Research Database (Denmark)

    Jensen, Christian Skov; Lando, David; Pedersen, Lasse Heje

    We characterize when physical probabilities, marginal utilities, and the discount rate can be recovered from observed state prices for several future time periods. We make no assumptions of the probability distribution, thus generalizing the time-homogeneous stationary model of Ross (2015). Recov...... our model empirically, testing the predictive power of the recovered expected return and other recovered statistics....

  13. GENERAL SURGERY

    African Journals Online (AJOL)

    services at public hospitals across the country are currently delivered by IMGs.6 Although some IMGs wish to stay on in the hope of entering ... accredited by the Health Professions Council of South Africa. (HPCSA), the national regulatory authority for medical licensing. The general surgery registrar programme lasts for a.

  14. General Assembly

    CERN Multimedia

    Staff Association

    2016-01-01

    5th April, 2016 – Ordinary General Assembly of the Staff Association! In the first semester of each year, the Staff Association (SA) invites its members to attend and participate in the Ordinary General Assembly (OGA). This year the OGA will be held on Tuesday, April 5th 2016 from 11:00 to 12:00 in BE Auditorium, Meyrin (6-2-024). During the Ordinary General Assembly, the activity and financial reports of the SA are presented and submitted for approval to the members. This is the occasion to get a global view on the activities of the SA, its financial management, and an opportunity to express one’s opinion, including taking part in the votes. Other points are listed on the agenda, as proposed by the Staff Council. Who can vote? Only “ordinary” members (MPE) of the SA can vote. Associated members (MPA) of the SA and/or affiliated pensioners have a right to vote on those topics that are of direct interest to them. Who can give his/her opinion? The Ordinary General Asse...

  15. Generale preventie

    NARCIS (Netherlands)

    1949-01-01

    In part I of this study a survey has veen given of what Dutch authors have written since 1870, when capital punishment was abolished, on subjects concerning the general preventive effect of punishment. This historical survey ends where, during the years 1940-1945, under the stress of the occupation

  16. GENERAL SURGERY

    African Journals Online (AJOL)

    Of these, patients with external abdominal hernias constituted nine hundred and eighteen. (918). Operation for hernias constituted about 12.5% of the operative workload of the general surgeons in this hospital. The descending order of occurrence of external abdominal hernias was inguinal, femoral and incisional.

  17. COMPARISON OF EPITHELIAL DYSPLASIA - THE 4NQO RAT PALATE MODEL AND HUMAN ORAL-MUCOSA

    NARCIS (Netherlands)

    NAUTA, M; ROODENBURG, JLN; NIKKELS, PGJ; WITJES, MJH; VERMEY, A

    Epithelial dysplasia in the rat palatal mucosa was induced by application three times a week of the carcinogen 4-nitroquinoline 1-oxide (4NQO). With the Epithelial Atypia Index (EAI), the successive stages;of 4NQO-induced epithelial dysplasia were compared with specimens of human oral epithelial

  18. Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients.

    Science.gov (United States)

    Sugita, Kazunari; Steer, Catherine A; Martinez-Gonzalez, Itziar; Altunbulakli, Can; Morita, Hideaki; Castro-Giner, Francesc; Kubo, Terufumi; Wawrzyniak, Paulina; Rückert, Beate; Sudo, Katsuko; Nakae, Susumu; Matsumoto, Kenji; O'Mahony, Liam; Akdis, Mübeccel; Takei, Fumio; Akdis, Cezmi A

    2018-01-01

    Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis; however, the influence of ILC2s on the bronchial epithelial barrier has not been investigated previously. We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic patients and healthy subjects and general innate lymphoid cell- and ILC2-deficient mice. Cocultures of human ILC2s and bronchial epithelial cells were used to determine transepithelial electrical resistance, paracellular flux, and TJ mRNA and protein expressions. The effect of ILC2s on TJs was examined by using a murine model of IL-33-induced airway inflammation in wild-type, recombination-activating gene 2 (Rag2) -/- , Rag2 -/- Il2rg -/- , and Rora sg/sg mice undergoing bone marrow transplantation to analyze the in vivo relevance of barrier disruption by ILC2s. ILC2s significantly impaired the epithelial barrier, as demonstrated by reduced transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran permeability in air-liquid interface cultures of human bronchial epithelial cells. This was in parallel to decreased mRNAs and disrupted protein expression of TJ proteins and was restored by neutralization of IL-13. Intranasal administration of recombinant IL-33 to wild-type and Rag2 -/- mice lacking T and B cells triggered TJ disruption, whereas Rag2 -/- Il2rg -/- and Rora sg/sg mice undergoing bone marrow transplantation that lack ILC2s did not show any barrier leakiness. Direct nasal administration of IL-13 was sufficient to induce deficiency in the TJ barrier in the bronchial epithelium of mice in vivo. These data highlight an essential mechanism in asthma pathogenesis by demonstrating that ILC2s are responsible for bronchial epithelial TJ barrier leakiness through IL-13. Copyright © 2017 American Academy of Allergy, Asthma & Immunology

  19. Overexpression of Telomerase Protects Human and Murine Lung Epithelial Cells from Fas- and Bleomycin-Induced Apoptosis via FLIP Upregulation.

    Directory of Open Access Journals (Sweden)

    Nissim Arish

    Full Text Available High doses of bleomycin administered to patients with lymphomas and other tumors lead to significant lung toxicity in general, and to apoptosis of epithelial cells, in particular. Apoptosis of alveolar epithelium is an important step in the pathogenesis of bleomycin-induced pulmonary fibrosis. The Fas-FasL pathway is one of the main apoptotic pathways involved. Telomerase is a ribonucleoprotein RNA-dependent DNA polymerase complex consisting of an RNA template and a catalytic protein, telomerase reverse transcriptase (TERT. Telomerase also possess extra-telomeric roles, including modulation of transcription of anti-apoptotic genes, differentiation signals, and more. We hypothesized that telomerase overexpression affects Fas-induced epithelial cell apoptosis by an extra-telomeric role such as regulation of anti-apoptotic genes, specifically FLICE-like inhibitory protein (FLIP. Telomerase in mouse (MLE and human (A549 lung epithelial cell lines was upregulated by transient transfection using cDNA hTERT expression vector. Telomerase activity was detected using a real-time PCR-based system. Bleomycin, and bleomycin-induced Fas-mediated apoptosis following treatment with anti-Fas activating mAb or control IgG, were assessed by Annexin V staining, FACS analysis, and confocal microscopy; caspase cleavage by Western blot; FLIP or Fas molecule detection by Western blot and flow cytometry. hTERT transfection of lung epithelial cells resulted in a 100% increase in their telomerase activity. Fas-induced lung epithelial cell apoptosis was significantly reduced in hTERT-transfected cells compared to controls in all experiments. Lung epithelial cells with increased telomerase activity had higher levels of FLIP expression but membrane Fas expression was unchanged. Upregulation of hTERT+ in human lung epithelial cells and subsequent downregulation of FLIP by shFLIP-RNA annulled hTERT-mediated resistance to apoptosis. Telomerase-mediated FLIP overexpression may

  20. Emergent material properties of developing epithelial tissues.

    Science.gov (United States)

    Machado, Pedro F; Duque, Julia; Étienne, Jocelyn; Martinez-Arias, Alfonso; Blanchard, Guy B; Gorfinkiel, Nicole

    2015-11-23

    Force generation and the material properties of cells and tissues are central to morphogenesis but remain difficult to measure in vivo. Insight is often limited to the ratios of mechanical properties obtained through disruptive manipulation, and the appropriate models relating stress and strain are unknown. The Drosophila amnioserosa epithelium progressively contracts over 3 hours of dorsal closure, during which cell apices exhibit area fluctuations driven by medial myosin pulses with periods of 1.5-6 min. Linking these two timescales and understanding how pulsatile contractions drive morphogenetic movements is an urgent challenge. We present a novel framework to measure in a continuous manner the mechanical properties of epithelial cells in the natural context of a tissue undergoing morphogenesis. We show that the relationship between apicomedial myosin fluorescence intensity and strain during fluctuations is consistent with a linear behaviour, although with a lag. We thus used myosin fluorescence intensity as a proxy for active force generation and treated cells as natural experiments of mechanical response under cyclic loading, revealing unambiguous mechanical properties from the hysteresis loop relating stress to strain. Amnioserosa cells can be described as a contractile viscoelastic fluid. We show that their emergent mechanical behaviour can be described by a linear viscoelastic rheology at timescales relevant for tissue morphogenesis. For the first time, we establish relative changes in separate effective mechanical properties in vivo. Over the course of dorsal closure, the tissue solidifies and effective stiffness doubles as net contraction of the tissue commences. Combining our findings with those from previous laser ablation experiments, we show that both apicomedial and junctional stress also increase over time, with the relative increase in apicomedial stress approximately twice that of other obtained measures. Our results show that in an epithelial

  1. Complex interactions between GSK3 and aPKC in Drosophila embryonic epithelial morphogenesis.

    Directory of Open Access Journals (Sweden)

    Nicole A Kaplan

    Full Text Available Generally, epithelial cells must organize in three dimensions to form functional tissue sheets. Here we investigate one such sheet, the Drosophila embryonic epidermis, and the morphogenetic processes organizing cells within it. We report that epidermal morphogenesis requires the proper distribution of the apical polarity determinant aPKC. Specifically, we find roles for the kinases GSK3 and aPKC in cellular alignment, asymmetric protein distribution, and adhesion during the development of this polarized tissue. Finally, we propose a model explaining how regulation of aPKC protein levels can reorganize both adhesion and the cytoskeleton.

  2. Cytologic findings in calcifying epithelial odontogenic tumor: a case report.

    Science.gov (United States)

    Shekarkhar, Mohammad Javad; Tabei, Seyed Z; Kumar, Perikala V; Hashemi, Seyed Baseer

    2005-01-01

    Calcifying epithelial odontogenic tumor (CEOT), or Pindborg's tumor, is a rare, benign, odontogenic neoplasm first described by Pindborg in 1955. It is most commonly seen in the fourth and fifth decades of life, usually arises in the mandibular premolar-molar areas and accounts for approximately 1% of all intraosseous odontogenic tumors. This report describes the cytologic findings in a case of CEOT. A 62-year-old woman was referred to the ear, nose and throat clinic with a right maxillary mass. The fine needle aspiration (FNA) smears showed numerous calcifications; amorphous, eosinophilic material; and clusters of round epithelial cells embedded in a bloody background. The smears were diagnosed as suspicious for malignancy. Maxillectomy was done. The histologic sections were diagnosed as CEOT. FNA findings of calcifying epithelial odontogenic tumor have been described rarely. The clusters of epithelial cells with prominent nucleoli are mistaken for features of a malignant tumor.

  3. A Pediatric Patient With an Orbital Respiratory Epithelial Cyst.

    Science.gov (United States)

    Cohn, Jason E; Bahrami, Arash; Monteleone, Christina; Pascasio, Judy Mae; Davis, Wellington J

    2017-11-01

    Respiratory epithelial cysts are rare orbital cysts that can arise secondary to choristomatous rests of respiratory epithelium. Approximately 15 congenital cases have been described in the literature, making it a rare disease entity. We present a case of a 14-month-old Middle Eastern male with a right infraorbital respiratory epithelial cyst. Magnetic resonance imaging of the brain and orbits revealed a right infraorbital cyst hyperintense on T1-weighted images and followed fluid density on T2-weighted images. This cyst was noted to displace the globe superiorly and inferior rectus muscle laterally. This cyst was excised using a transconjunctival approach. Histologically, the cyst wall was lined by ciliated columnar cells with interspersed mucus-containing cells and ciliated transitional epithelium was present, establishing the diagnosis of respiratory epithelial cyst. To our knowledge, this is the youngest patient with a respiratory epithelial cyst of the orbit reported in the literature.

  4. Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer

    Science.gov (United States)

    Klymenko, Yuliya; Kim, Oleg; Stack, M. Sharon

    2017-01-01

    Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular aggregates (MCAs), adhesion to and disruption of the mesothelial lining of the peritoneum, and submesothelial matrix anchoring and proliferation to generate widely disseminated metastases. This exceptional microenvironment is highly permissive for phenotypic plasticity, enabling mesenchymal-to-epithelial (MET) and epithelial-to-mesenchymal (EMT) transitions. In this review, we summarize current knowledge on EOC heterogeneity in an EMT context, outline major regulators of EMT in ovarian cancer, address controversies in EMT and EOC chemoresistance, and highlight computational modeling approaches toward understanding EMT/MET in EOC. PMID:28792442

  5. Modulation of airway epithelial antiviral immunity by fungal exposure

    National Research Council Canada - National Science Library

    Zhu, Lingxiang; Lee, Boram; Zhao, Fangkun; Zhou, Xu; Chin, Vanessa; Ling, Serena C; Chen, Yin

    2014-01-01

    .... However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthetic viral mimicker, double-stranded RNA (dsRNA...

  6. Human papillomavirus: cause of epithelial lacrimal sac neoplasia?

    DEFF Research Database (Denmark)

    Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia

    2007-01-01

    PURPOSE: Epithelial tumours of the lacrimal sac are rare but important entities that may carry grave prognoses. In this study the prevalence and possible role of human papillomavirus (HPV) infection in epithelial tumours of the lacrimal sac were evaluated. METHODS: Five papillomas and six...... 11 RNA was demonstrated in two papillomas. CONCLUSIONS: By analysing 11 epithelial lacrimal sac papillomas and carcinomas using PCR, DNA ISH and RNA ISH, we found HPV DNA in all investigated transitional epithelium tumours of the lacrimal sac. HPV RNA was present in two of eight epithelial lacrimal...... sac tumours positive for HPV DNA. As RNA degrades fast in paraffin-embedded tissue, only a small fraction of DNA-positive tumours can be expected to be RNA-positive. We therefore suggest that HPV infection is associated with the development of lacrimal sac papillomas and carcinomas....

  7. Epithelial apoptosis: cause or consequence of ulcerative colitis?

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Nielsen, Ole Haagen

    2009-01-01

    OBJECTIVE: Epithelial apoptosis rates are increased in ulcerative colitis (UC). The increased apoptosis rate could expose mucosal cells to luminal pathogens and thereby be regarded as a primary pathogenic factor in UC. On the other hand, the local inflammatory reaction could cause epithelial...... apoptosis secondary to the release of cytotoxic mediators. If apoptosis is a primary defect, apoptosis rates could influence the degree of spreading of inflammation and the clinical course of UC. If apoptosis is a side effect of local inflammation, apoptosis rates would be expected only to correlate...... with the degree of local inflammation. The aim of the study was to investigate the relationship between epithelial apoptosis and clinical characteristics of UC. MATERIAL AND METHODS: Twenty patients with UC (12 with active disease) and 20 control subjects were included. Freshly isolated colonic epithelial cells...

  8. Matriptase zymogen supports epithelial development, homeostasis and regeneration

    DEFF Research Database (Denmark)

    Friis, Stine; Tadeo, Daniel; Le-Gall, Sylvain M.

    2017-01-01

    Background Matriptase is a membrane serine protease essential for epithelial development, homeostasis, and regeneration, as well as a central orchestrator of pathogenic pericellular signaling in the context of inflammatory and proliferative diseases. Matriptase is an unusual protease in that its...

  9. IL-20 promotes epithelial healing of the injured mouse cornea

    Science.gov (United States)

    After corneal epithelial injury, the ensuing inflammatory response is necessary for efficient wound healing. While beneficial healing effects are attributed to recruited neutrophils and platelets, dysregulated inflammation (too little or too much) is associated with impaired wound healing. The purpo...

  10. Autoantibodies to Tumor-Associated Antigens in Epithelial Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Benjamin Piura

    2009-01-01

    Full Text Available This review will focus on recent knowledge related to circulating autoantibodies (AAbs to tumor-associated antigens (TAAs in epithelial ovarian carcinoma. So far, the following TAAs have been identified to elicit circulating AAbs in epithelial ovarian carcinoma: p53, homeobox proteins (HOXA7, HOXB7, heat shock proteins (HSP-27, HSP-90, cathepsin D, cancer-testis antigens (NY-ESO-1/LAGE-1, MUC1, GIPC-1, IL-8, Ep-CAM, and S100A7. Since AAbs to TAAs have been identified in the circulation of patients with early-stage cancer, it has been speculated that the assessment of a panel of AAbs specific for epithelial ovarian carcinoma TAAs might hold great potential as a novel tool for early diagnosis of epithelial ovarian carcinoma.

  11. Abdominal wall reconstruction using De-epithelialized dermal flap: A ...

    African Journals Online (AJOL)

    Abdominal wall reconstruction using De-epithelialized dermal flap: A new technique. ... hernias, nine healed exomphalos major and two giant umbilical hernias. ... Morbidity was minimal and included skin dimpling in 11 patients, seroma in ...

  12. Chronic recreational physical inactivity and epithelial ovarian cancer risk

    DEFF Research Database (Denmark)

    Cannioto, Rikki; LaMonte, Michael J.; Risch, Harvey A

    2016-01-01

    Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC ri...

  13. What HERA May Provide?

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hannes; /DESY; De Roeck, Albert; /CERN; Bartels, Jochen; /Hamburg U., Inst. Theor. Phys. II; Behnke, Olaf; Blumlein, Johannes; /DESY; Brodsky, Stanley; /SLAC /Durham U., IPPP; Cooper-Sarkar, Amanda; /Oxford U.; Deak, Michal; /DESY; Devenish, Robin; /Oxford U.; Diehl, Markus; /DESY; Gehrmann, Thomas; /Zurich U.; Grindhammer, Guenter; /Munich, Max Planck Inst.; Gustafson, Gosta; /CERN /Lund U., Dept. Theor. Phys.; Khoze, Valery; /Durham U., IPPP; Knutsson, Albert; /DESY; Klein, Max; /Liverpool U.; Krauss, Frank; /Durham U., IPPP; Kutak, Krzysztof; /DESY; Laenen, Eric; /NIKHEF, Amsterdam; Lonnblad, Leif; /Lund U., Dept. Theor. Phys.; Motyka, Leszek; /Hamburg U., Inst. Theor. Phys. II /Birmingham U. /Southern Methodist U. /DESY /Piemonte Orientale U., Novara /CERN /Paris, LPTHE /Hamburg U. /Penn State U.

    2011-11-10

    More than 100 people participated in a discussion session at the DIS08 workshop on the topic What HERA may provide. A summary of the discussion with a structured outlook and list of desirable measurements and theory calculations is given. The HERA accelerator and the HERA experiments H1, HERMES and ZEUS stopped running in the end of June 2007. This was after 15 years of very successful operation since the first collisions in 1992. A total luminosity of {approx} 500 pb{sup -1} has been accumulated by each of the collider experiments H1 and ZEUS. During the years the increasingly better understood and upgraded detectors and HERA accelerator have contributed significantly to this success. The physics program remains in full swing and plenty of new results were presented at DIS08 which are approaching the anticipated final precision, fulfilling and exceeding the physics plans and the previsions of the upgrade program. Most of the analyses presented at DIS08 were still based on the so called HERA I data sample, i.e. data taken until 2000, before the shutdown for the luminosity upgrade. This sample has an integrated luminosity of {approx} 100 pb{sup -1}, and the four times larger statistics sample from HERA II is still in the process of being analyzed.

  14. Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features.

    Science.gov (United States)

    Gelfand, Robert; Vernet, Dolores; Bruhn, Kevin; Vadgama, Jaydutt; Gonzalez-Cadavid, Nestor F

    2016-06-01

    Alcoholism is associated with breast cancer incidence and progression, and moderate chronic consumption of ethanol is a risk factor. The mechanisms involved in alcohol's oncogenic effects are unknown, but it has been speculated that they may be mediated by acetaldehyde. We used the immortalized normal human epithelial breast cell line MCF-12A to determine whether short- or long-term exposure to ethanol or to acetaldehyde, using in vivo compatible ethanol concentrations, induces their oncogenic transformation and/or the acquisition of epithelial mesenchymal transition (EMT). Cultures of MCF-12A cells were incubated with 25 mM ethanol or 2.5 mM acetaldehyde for 1 week, or with lower concentrations (1.0-2.5 mM for ethanol, 1.0 mM for acetaldehyde) for 4 weeks. In the 4-week incubation, cells were also tested for anchorage-independence, including isolation of soft agar selected cells (SASC) from the 2.5 mM ethanol incubations. Cells were analyzed by immunocytofluorescence, flow cytometry, western blotting, DNA microarrays, RT/PCR, and assays for miRs. We found that short-term exposure to ethanol, but not, in general, to acetaldehyde, was associated with transcriptional upregulation of the metallothionein family genes, alcohol metabolism genes, and genes suggesting the initiation of EMT, but without related phenotypic changes. Long-term exposure to the lower concentrations of ethanol or acetaldehyde induced frank EMT changes in the monolayer cultures and in SASC as demonstrated by changes in cellular phenotype, mRNA expression, and microRNA expression. This suggests that low concentrations of ethanol, with little or no mediation by acetaldehyde, induce EMT and some traits of oncogenic transformation such as anchorage-independence in normal breast epithelial cells.

  15. Resveratrol inhibits transforming growth factor-β2-induced epithelial-to-mesenchymal transition in human retinal pigment epithelial cells by suppressing the Smad pathway

    Directory of Open Access Journals (Sweden)

    Chen CL

    2017-01-01

    Full Text Available Ching-Long Chen,1,2 Yi-Hao Chen,1,2 Ming-Cheng Tai,2 Chang-Min Liang,2 Da-Wen Lu,1,2 Jiann-Torng Chen1,2 1Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; 2Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Abstract: Proliferative vitreoretinopathy (PVR is the main cause of failure following retinal detachment surgery. Transforming growth factor (TGF-β2-induced epithelial-to-mesenchymal transition (EMT plays an important role in the development of PVR, and EMT inhibition decreases collagen gel contraction and fibrotic membrane formation, resulting in prevention of PVR. Resveratrol is naturally found in red wine and has inhibitory effects on EMT. Resveratrol is widely used in cardioprotection, neuroprotection, chemotherapy, and antiaging therapy. The purpose of this study was to investigate the effects of resveratrol on TGF-β2-induced EMT in ARPE-19 cells in vitro. We found that resveratrol suppressed the decrease of zona occludens-1 (ZO-1 and caused an increase of alpha-smooth muscle actin expression in TGF-β2-treated ARPE-19 cells, assessed using Western blots; moreover, it also suppressed the decrease in ZO-1 and the increase of vimentin expression, observed using immunocytochemistry. Resveratrol attenuated TGF-β2-induced wound closure and cell migration in ARPE-19 cells in a scratch wound test and modified Boyden chamber assay, respectively. We also found that resveratrol reduced collagen gel contraction – assessed by collagen matrix contraction assay – and suppressed the phosphorylation of Smad2 and Smad3 in TGF-β2-treated ARPE-19 cells. These results suggest that resveratrol mediates anti-EMT effects, which could be used in the prevention of PVR. Keywords: resveratrol, epithelial-to-mesenchymal transition, proliferative vitreoretinopathy, transforming growth factor-β2, retinal pigment epithelial cells

  16. Irsogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.

    Science.gov (United States)

    Miyata, Ryo; Nomura, Kazuaki; Kakuki, Takuya; Takano, Ken-Ichi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi

    2015-04-01

    The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.

  17. Antioxidant Prophylaxis in the Prevention of Prostatic Epithelial Neoplasia

    Science.gov (United States)

    2005-02-01

    AD Award Number: W81XWH-04-1-0275 TITLE: Antioxidant Prophylaxis in the Prevention of Prostatic Epithelial Neoplasia PRINCIPAL INVESTIGATOR: A...5. FUNDING NUMBERS Antioxidant Prophylaxis in the Prevention of Prostatic W81XWH-04-1-0275 Epithelial Neoplasia 6. AUTHOR(S) A. Pratap Kumar, Ph.D...histological changes. 14. SUBJECT TERMS 15. NUMBER OF PAGES Oxidative Stress; Prostatic Intraepithelial Neoplasia (PIN); 5 Antioxidants and Prevention

  18. Mixed odontogenic tumor: ameloblastoma and calcifying epithelial odontogenic tumor.

    Science.gov (United States)

    Etit, Demet; Uyaroglu, Mehmet Ali; Erdogan, Nezahat

    2010-01-01

    Odontogenic tumors constitute a group of heterogeneous disease derived from epithelial, mesenchymal and/or ectomesenchymal elements. Ameloblastoma is the best known and the most frequent form of odontogenic tumors. Calcifying epithelial odontogenic tumor (CEOT), known as Pindborg tumor, is locally invasive lesion which has a characteristic amiloid deposition. Here a case of a peripheral ameloblastoma associated with CEOT is presented with clinical and morphological features.

  19. Epithelial cells as alternative human biomatrices for comet assay

    OpenAIRE

    Emilio eRojas; Yolanda eLorenzo; Kristiane eHuag-Berg; Bjørn eNicolaissen; Mahara eValverde

    2014-01-01

    The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many org...

  20. Apical constriction and epithelial invagination are regulated by BMP activity

    OpenAIRE

    Jidigam, Vijay K.; Raghuraman C. Srinivasan; Cedric Patthey; Lena Gunhaga

    2015-01-01

    ABSTRACT Epithelial invagination is a morphological process in which flat cell sheets transform into three-dimensional structures through bending of the tissue. It is accompanied by apical constriction, in which the apical cell surface is reduced in relation to the basal cell surface. Although much is known about the intra-cellular molecular machinery driving apical constriction and epithelial invagination, information of how extra-cellular signals affect these processes remains insufficient....

  1. Risk Factors for Invasive Epithelial Ovarian Cancer by Histologic Subtype

    OpenAIRE

    Quirk JT; Natarajan N; Mettlin CJ; Moysich KB; Swede H

    2004-01-01

    It is unclear whether the different histologic subtypes of epithelial ovarian carcinoma have different risk factors. We investigated the relationships between selected epidemiologic variables (i.e., parity, family history of ovarian cancer, oral contraceptive use, a history of tubal ligation and noncontraceptive estrogen use) and the major histologic subtypes of epithelial ovarian cancer in a hospital-based case-control study of adult women at Roswell Park Cancer Institute in Buffalo, NY, USA...

  2. Cell volume regulation in epithelial physiology and cancer

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Hoffmann, Else Kay; Novak, Ivana

    2013-01-01

    regulation both rely on the spatially and temporally coordinated function of ion channels and transporters. In healthy epithelia, specific ion channels/transporters localize to the luminal and basolateral membranes, contributing to functional epithelial polarity. In pathophysiological processes...... such as cancer, transepithelial and cell volume regulatory ion transport are dys-regulated. Furthermore, epithelial architecture and coordinated ion transport function are lost, cell survival/death balance is altered, and new interactions with the stroma arise, all contributing to drug resistance. Since altered...

  3. Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers

    OpenAIRE

    Bergstralh, Dan T.; Lovegrove, Holly?E.; St Johnston, Daniel

    2015-01-01

    This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncb3248 Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium. Here we test this assumption in three types of Drosophila epi...

  4. Human papilloma virus--its association with epithelial proliferative lesions.

    Science.gov (United States)

    Costa, L J; Silveira, F R; Batista, J M; Birman, E G

    1994-01-01

    The Papillomaviruses are DNA viruses which belong to the Papova family, having a great affinity for epithelial tissue. They can produce proliferative lesions either in the skin or mucosa, in man and other animals. Various kinds of lesions, mainly benign, are caused by numerous types of HPV involving the well-known verruca vulgaris, oral papilloma, condiloma acuminatum and the focal epithelial hyperplasia, as well as a possible association with other alterations and lesions.

  5. Proximal location of mouse prostate epithelial stem cells

    OpenAIRE

    Tsujimura, Akira; Koikawa, Yasuhiro; Salm, Sarah; Takao, Tetsuya; Coetzee, Sandra; Moscatelli, David; Shapiro, Ellen; Lepor, Herbert; Sun, Tung-Tien; Wilson, E. Lynette

    2002-01-01

    Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propos...

  6. Lactobacillus decelerates cervical epithelial cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Katarina Vielfort

    Full Text Available We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells.

  7. Uranium induces apoptosis in lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Periyakaruppan, Adaikkappan; Sarkar, Shubhashish; Sadanandan, Bindu; Thomas, Renard; Wilson, Bobby L. [Texas Southern University, Environmental Toxicology Program, Department of Chemistry, Houston, TX (United States); Ravichandran, Prabakaran; Sharma, Chidananda S.; Ramesh, Vani; Hall, Joseph C.; Ramesh, Govindarajan T. [Norfolk State University, Molecular Toxicology Laboratory, Department of Biology, Center for Biotechnology and Biomedical Sciences, Norfolk, VA (United States)

    2009-06-15

    Uranium is a naturally occurring radioactive material present everywhere in the environment. It is toxic because of its chemical or radioactive properties. Uranium enters environment mainly from mines and industry and cause threat to human health by accumulating in lungs as a result of inhalation. In our previous study, we have shown the effectiveness of antioxidant system response to the oxidative stress induced by uranyl acetate (UA) in rat lung epithelial (LE) cells. As part of our continuing studies; here, we investigated the mechanism underlying when LE cells are exposed to different concentration of UA. Oxidative stress may lead to apoptotic signaling pathways. LE cells treated with 0.25, 0.5 and 1 mM of UA results in dose and time-dependent increase in activity of both caspases-3 and -8. Increase in the concentration of cytochrome-c oxidase in cytosol was seen in LE cells treated with 1 mM UA as a result of mitochondria membrane permeability. The cytochrome-c leakage may trigger the apoptotic pathway. TUNEL assay performed in LE cells treated with 1 mM of UA showed significant incorporation of dNTPs in the nucleus after 24 h. In the presence of the caspase inhibitors, we observed the significant decrease in the activity of caspases-8 and -3 in 0.5 and 1 mM UA-treated LE cells. (orig.)

  8. General topology

    CERN Document Server

    Willard, Stephen

    2004-01-01

    Among the best available reference introductions to general topology, this volume is appropriate for advanced undergraduate and beginning graduate students. Its treatment encompasses two broad areas of topology: ""continuous topology,"" represented by sections on convergence, compactness, metrization and complete metric spaces, uniform spaces, and function spaces; and ""geometric topology,"" covered by nine sections on connectivity properties, topological characterization theorems, and homotopy theory. Many standard spaces are introduced in the related problems that accompany each section (340

  9. Generalized polygons

    CERN Document Server

    Maldeghem, Hendrik

    1998-01-01

    This book is intended to be an introduction to the fascinating theory ofgeneralized polygons for both the graduate student and the specialized researcher in the field. It gathers together a lot of basic properties (some of which are usually referred to in research papers as belonging to folklore) and very recent and sometimes deep results. I have chosen a fairly strict geometrical approach, which requires some knowledge of basic projective geometry. Yet, it enables one to prove some typically group-theoretical results such as the determination of the automorphism groups of certain Moufang polygons. As such, some basic group-theoretical knowledge is required of the reader. The notion of a generalized polygon is a relatively recent one. But it is one of the most important concepts in incidence geometry. Generalized polygons are the building bricks of Tits buildings. They are the prototypes and precursors of more general geometries such as partial geometries, partial quadrangles, semi-partial ge­ ometries, near...

  10. The role of Epstein–Barr virus in epithelial malignancies

    Science.gov (United States)

    Tsao, Sai-Wah; Tsang, Chi Man; To, Ka-Fai; Lo, Kwok-Wai

    2015-01-01

    The close association of Epstein–Barr virus (EBV) infection with non-keratinizing nasopharyngeal carcinomas and a subset of gastric carcinomas suggests that EBV infection is a crucial event in these cancers. The difficulties encountered in infecting and transforming primary epithelial cells in experimental systems suggest that the role of EBV in epithelial malignancies is complex and multifactorial in nature. Genetic alterations in the premalignant epithelium may support the establishment of latent EBV infection, which is believed to be an initiation event. Oncogenic properties have been reported in multiple EBV latent genes. The BamH1 A rightwards transcripts (BARTs) and the BART-encoded microRNAs (miR-BARTs) are highly expressed in EBV-associated epithelial malignancies and may induce malignant transformation. However, enhanced proliferation may not be the crucial function of EBV infection in epithelial malignancies, at least in the early stages of cancer development. EBV-encoded gene products may confer anti-apoptotic properties and promote the survival of infected premalignant epithelial cells harbouring genetic alterations. Multiple EBV-encoded microRNAs have been reported to have immune evasion functions. Genetic alterations in host cells, as well as inflammatory stroma, could modulate the expression of EBV genes and alter the growth properties of infected premalignant epithelial cells, encouraging their selection during carcinogenesis. PMID:25251730

  11. Celiac Disease: Role of the Epithelial BarrierSummary

    Directory of Open Access Journals (Sweden)

    Michael Schumann

    2017-03-01

    Full Text Available In celiac disease (CD a T-cell–mediated response to gluten is mounted in genetically predisposed individuals, resulting in a malabsorptive enteropathy histologically highlighted by villous atrophy and crypt hyperplasia. Recent data point to the epithelial layer as an under-rated hot spot in celiac pathophysiology to date. This overview summarizes current functional and genetic evidence on the role of the epithelial barrier in CD, consisting of the cell membranes and the apical junctional complex comprising sealing as well as ion and water channel-forming tight junction proteins and the adherens junction. Moreover, the underlying mechanisms are discussed, including apoptosis of intestinal epithelial cells, biology of intestinal stem cells, alterations in the apical junctional complex, transcytotic uptake of gluten peptides, and possible implications of a defective epithelial polarity. Current research is directed toward new treatment options for CD that are alternatives or complementary therapeutics to a gluten-free diet. Thus, strategies to target an altered epithelial barrier therapeutically also are discussed. Keywords: Celiac Sprue, Gluten-Sensitive Enteropathy, Tight Junction, Epithelial Polarity, Partitioning-Defective Proteins, α-Gliadin 33mer

  12. Media from macrophages co-incubated with Enterococcus faecalis induces epithelial cell monolayer reassembly and altered cell morphology.

    Science.gov (United States)

    Belogortseva, Natalia; Krezalek, Monika; Guyton, Kristina; Labno, Christine; Poroyko, Valeriy; Zaborina, Olga; Alverdy, John C

    2017-01-01

    Signal exchange between intestinal epithelial cells, microbes and local immune cells is an important mechanism of intestinal homeostasis. Given that intestinal macrophages are in close proximity to both the intestinal epithelium and the microbiota, their pathologic interactions may result in epithelial damage. The present study demonstrates that co-incubation of murine macrophages with E. faecalis strains producing gelatinase (GelE) and serine protease (SprE) leads to resultant condition media (CM) capable of inducing reassembly of primary colonic epithelial cell monolayers. Following the conditioned media (CM) exposure, some epithelial cells are shed whereas adherent cells are observed to undergo dissolution of cell-cell junctions and morphologic transformation with actin cytoskeleton reorganization resulting in flattened and elongated shapes. These cells exhibit marked filamentous filopodia and lamellipodia formation. Cellular reorganization is not observed when epithelial monolayers are exposed to: CM from macrophages co-incubated with E. faecalis GelE/SprE-deficient mutants, CM from macrophages alone, or E. faecalis (GelE/SprE) alone. Flow cytometry analysis reveals increased expression of CD24 and CD44 in cells treated with macrophage/E. faecalis CM. This finding in combination with the appearance colony formation in matrigel demonstrate that the cells treated with macrophage/E. faecalis CM contain a higher proportion progenitor cells compared to untreated control. Taken together, these findings provide evidence for a triangulated molecular dialogue between E. faecalis, macrophages and colonic epithelial cells, which may have important implications for conditions in the gut that involve inflammation, injury or tumorigenesis.

  13. Media from macrophages co-incubated with Enterococcus faecalis induces epithelial cell monolayer reassembly and altered cell morphology

    Science.gov (United States)

    Belogortseva, Natalia; Krezalek, Monika; Guyton, Kristina; Labno, Christine; Poroyko, Valeriy; Zaborina, Olga

    2017-01-01

    Signal exchange between intestinal epithelial cells, microbes and local immune cells is an important mechanism of intestinal homeostasis. Given that intestinal macrophages are in close proximity to both the intestinal epithelium and the microbiota, their pathologic interactions may result in epithelial damage. The present study demonstrates that co-incubation of murine macrophages with E. faecalis strains producing gelatinase (GelE) and serine protease (SprE) leads to resultant condition media (CM) capable of inducing reassembly of primary colonic epithelial cell monolayers. Following the conditioned media (CM) exposure, some epithelial cells are shed whereas adherent cells are observed to undergo dissolution of cell-cell junctions and morphologic transformation with actin cytoskeleton reorganization resulting in flattened and elongated shapes. These cells exhibit marked filamentous filopodia and lamellipodia formation. Cellular reorganization is not observed when epithelial monolayers are exposed to: CM from macrophages co-incubated with E. faecalis GelE/SprE-deficient mutants, CM from macrophages alone, or E. faecalis (GelE/SprE) alone. Flow cytometry analysis reveals increased expression of CD24 and CD44 in cells treated with macrophage/E. faecalis CM. This finding in combination with the appearance colony formation in matrigel demonstrate that the cells treated with macrophage/E. faecalis CM contain a higher proportion progenitor cells compared to untreated control. Taken together, these findings provide evidence for a triangulated molecular dialogue between E. faecalis, macrophages and colonic epithelial cells, which may have important implications for conditions in the gut that involve inflammation, injury or tumorigenesis. PMID:28793333

  14. General Healthcare Maintenance of IBD

    Science.gov (United States)

    ... Share It is important to continue general health maintenance. While working with your gastroenterologist, also remember to speak with your primary care health care provider about other important issues including: Vaccinations: Adults with IBD should generally follow ...

  15. YY1 modulates taxane response in epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Noriomi; Huang, Zhiqing; Baba, Tsukasa; Lee, Paula S.; Barnett, Jason C.; Mori, Seiichi; Chang, Jeffrey T.; Kuo, Wen-Lin; Gusberg, Alison H.; Whitaker, Regina S.; Gray, JoeW.; Fujii, Shingo; Berchuck, Andrew; Murphy, Susan K.

    2008-10-10

    The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed decisions regarding chemotherapeutic choice. Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer (SEOC) were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary SEOC and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using siRNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in SEOC and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA crosslinking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1

  16. Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions

    National Research Council Canada - National Science Library

    Peinado, Hector; Quintanilla, Miguel; Cano, Amparo

    2003-01-01

    .... We show here that transforming growth factor beta-1 (TGFbeta1) induces Snail expression in Madin-Darby canine kidney cells and triggers epithelial-mesenchymal transitions by a mechanism dependent on the MAPK signaling pathway...

  17. 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.

  18. Osteopontin—A Master Regulator of Epithelial-Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Anai N. Kothari

    2016-03-01

    Full Text Available Osteopontin (OPN plays an important functional role in both physiologic and pathologic states. OPN is implicated in the progression of fibrosis, cancer, and metastatic disease in several organ systems. The epithelial-mesenchymal transition (EMT, first described in embryology, is increasingly being recognized as a significant contributor to fibrotic phenotypes and tumor progression. Several well-established transcription factors regulate EMT and are conserved across tissue types and organ systems, including TWIST, zinc finger E-box-binding homeobox (ZEB, and SNAIL-family members. Recent literature points to an important relationship between OPN and EMT, implicating OPN as a key regulatory component of EMT programs. In this review, OPN’s interplay with traditional EMT activators, both directly and indirectly, will be discussed. Also, OPN’s ability to restructure the tissue and tumor microenvironment to indirectly modify EMT will be reviewed. Together, these diverse pathways demonstrate that OPN is able to modulate EMT and provide new targets for directing therapeutics.

  19. Quantitative methods to study epithelial morphogenesis and polarity.

    Science.gov (United States)

    Aigouy, B; Collinet, C; Merkel, M; Sagner, A

    2017-01-01

    Morphogenesis of an epithelial tissue emerges from the behavior of its constituent cells, including changes in shape, rearrangements, and divisions. In many instances the directionality of these cellular events is controlled by the polarized distribution of specific molecular components. In recent years, our understanding of morphogenesis and polarity highly benefited from advances in genetics, microscopy, and image analysis. They now make it possible to measure cellular dynamics and polarity with unprecedented precision for entire tissues throughout their development. Here we review recent approaches to visualize and measure cell polarity and tissue morphogenesis. The chapter is organized like an experiment. We first discuss the choice of cell and polarity reporters and describe the use of mosaics to reveal hidden cell polarities or local morphogenetic events. Then, we outline application-specific advantages and disadvantages of different microscopy techniques and image projection algorithms. Next, we present methods to extract cell outlines to measure cell polarity and detect cellular events underlying morphogenesis. Finally, we bridge scales by presenting approaches to quantify the specific contribution of each cellular event to global tissue deformation. Taken together, we provide an in-depth description of available tools and theoretical concepts to quantitatively study cell polarity and tissue morphogenesis over multiple scales. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Ferritinophagy drives uropathogenic Escherichia coli persistence in bladder epithelial cells.

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    Bauckman, Kyle A; Mysorekar, Indira U

    2016-05-03

    Autophagy is a cellular recycling pathway, which in many cases, protects host cells from infections by degrading pathogens. However, uropathogenic Escherichia coli (UPEC), the predominant cause of urinary tract infections (UTIs), persist within the urinary tract epithelium (urothelium) by forming reservoirs within autophagosomes. Iron is a critical nutrient for both host and pathogen, and regulation of iron availability is a key host defense against pathogens. Iron homeostasis depends on the shuttling of iron-bound ferritin to the lysosome for recycling, a process termed ferritinophagy (a form of selective autophagy). Here, we demonstrate for the first time that UPEC shuttles with ferritin-bound iron into the autophagosomal and lysosomal compartments within the urothelium. Iron overload in urothelial cells induces ferritinophagy in an NCOA4-dependent manner causing increased iron availability for UPEC, triggering bacterial overproliferation and host cell death. Addition of even moderate levels of iron is sufficient to increase and prolong bacterial burden. Furthermore, we show that lysosomal damage due to iron overload is the specific mechanism causing host cell death. Significantly, we demonstrate that host cell death and bacterial burden can be reversed by inhibition of autophagy or inhibition of iron-regulatory proteins, or chelation of iron. Together, our findings suggest that UPEC persist in host cells by taking advantage of ferritinophagy. Thus, modulation of iron levels in the bladder may provide a therapeutic avenue to controlling UPEC persistence, epithelial cell death, and recurrent UTIs.

  1. Limbal stem cells: Central concepts of corneal epithelial homeostasis.

    Science.gov (United States)

    Yoon, Jinny J; Ismail, Salim; Sherwin, Trevor

    2014-09-26

    A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferative potential when required, clonogenicity, absence of differentiation marker expression coupled with positive expression of progenitor markers, multipotency, centripetal migration, requirement for a distinct niche environment and the ability of transplanted limbal cells to regenerate the entire corneal epithelium. The existence of limbal stem cells supports the prevailing theory of corneal homeostasis, known as the XYZ hypothesis where X represents proliferation and stratification of limbal basal cells, Y centripetal migration of basal cells and Z desquamation of superficial cells. To maintain the mass of cornea, the sum of X and Y must equal Z and very elegant cell tracking experiments provide strong evidence in support of this theory. However, several recent studies have suggested the existence of oligopotent stem cells capable of corneal maintenance outside of the limbus. This review presents a summary of data which led to the current concepts of corneal epithelial homeostasis and discusses areas of controversy surrounding the existence of a secondary stem cell reservoir on the corneal surface.

  2. Cytoskeletal keratin glycosylation protects epithelial tissue from injury.

    Science.gov (United States)

    Ku, Nam-On; Toivola, Diana M; Strnad, Pavel; Omary, M Bishr

    2010-09-01

    Keratins 8 and 18 (K8 and K18) are heteropolymeric intermediate filament phosphoglycoproteins of simple-type epithelia. Mutations in K8 and K18 predispose the affected individual to liver disease as they protect hepatocytes from apoptosis. K18 undergoes dynamic O-linked N-acetylglucosamine glycosylation at Ser 30, 31 and 49. We investigated the function of K18 glycosylation by generating mice that overexpress human K18 S30/31/49A substitution mutants that cannot be glycosylated (K18-Gly(-)), and compared the susceptibility of these mice to injury with wild-type and other keratin-mutant mice. K18-Gly(-) mice are more susceptible to liver and pancreatic injury and apoptosis induced by streptozotocin or to liver injury by combined N-acetyl-D-glucosaminidase inhibition and Fas administration. The enhanced apoptosis in the livers of mice that express K18-Gly(-) involves the inactivation of Akt1 and protein kinase Ctheta as a result of their site-specific hypophosphorylation. Akt1 binds to K8, which probably contributes to the reciprocal hyperglycosylation and hypophosphorylation of Akt1 that occurs on K18 hypoglycosylation, and leads to decreased Akt1 kinase activity. Therefore, K18 glycosylation provides a unique protective role in epithelial injury by promoting the phosphorylation and activation of cell-survival kinases.

  3. Cytoskeletal keratin glycosylation protects from epithelial tissue injury

    Science.gov (United States)

    Ku, Nam-On; Toivola, Diana M.; Strnad, Pavel; Omary, M. Bishr

    2013-01-01

    Keratins 8 and 18 (K8/K18) are heteropolymeric intermediate filament phospho-glycoproteins of simple-type epithelia. K8/K18 protect hepatocytes from apoptosis and their mutations predispose to liver disease. K18 undergoes dynamic O-linked N-acetylglucosamine glycosylation at Ser30/31/49, the function of which is unknown. We addressed the function of K18 glycosylation by generating mice that overexpress human K18 S30/31/49A (Gly−), and compared their susceptibility to injury with wild-type and other keratin-mutant mice. Gly− mice are selectively more susceptible to liver and pancreas injury and apoptosis induced by streptozotocin or combined N-acetyl-D-glucosaminidase inhibition and Fas administration. The enhanced apoptosis in Gly− livers involves Akt1 and protein kinase Cθ inactivation due to their site-specific hypophosphorylation. Akt1 binds to K8 and this binding likely contributes to reciprocal Akt1 hyperglycosylation and hypophosphorylation upon K18 hypoglycosylation, with consequent decreased Akt1 kinase activity. Therefore, K18 glycosylation provides a unique protective role in epithelial injury by promoting the phosphorylation and activation of cell survival kinases. PMID:20729838

  4. Engineering human renal epithelial cells for transplantation in regenerative medicine.

    Science.gov (United States)

    Manzoli, Vita; Colter, David C; Dhanaraj, Sridevi; Fornoni, Alessia; Ricordi, Camillo; Pileggi, Antonello; Tomei, Alice A

    2017-10-01

    Cellular transplantation may treat several human diseases by replacing damaged cells and/or providing a local source of trophic factors promoting regeneration. We utilized human renal epithelial cells (hRECs) isolated from cadaveric donors as a cell model. For efficacious implementation of hRECs for treatment of kidney diseases, we evaluated a novel encapsulation strategy for immunoisolation of hRECs and lentiviral transduction of the Green Fluorescent Protein (GFP) as model gene for genetic engineering of hRECs to secrete desired trophic factors. In specific, we determined whether encapsulation through conformal coating and/or GFP transduction of hRECs allowed preservation of cell viability and of their trophic factor secretion. To that end, we optimized cultures of hRECs and showed that aggregation in three-dimensional spheroids significantly preserved cell viability, proliferation, and trophic factor secretion. We also showed that both wild type and GFP-engineered hRECs could be efficiently encapsulated within conformal hydrogel coatings through our fluid dynamic platform and that this resulted in further improvement of cell viability and trophic factors secretion. Our findings may lay the groundwork for future therapeutics based on transplantation of genetically engineered human primary cells for treatment of diseases affecting kidneys and potentially other tissues. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. Individual and Complementary Effects of Human Papillomavirus Oncogenes on Epithelial Cell Proliferation and Differentiation.

    Science.gov (United States)

    Bergner, Sven; Halec, Gordana; Schmitt, Markus; Aubin, François; Alonso, Angel; Auvinen, Eeva

    2016-01-01

    Previous studies on human papillomavirus (HPV) type 16 protein functions have established the oncogenic nature of three viral proteins: E5, E6 and E7. Here we have studied the functions of these proteins by functional deletion of the individual E5, E6 or E7, or both E6 and E7 oncogenes in the context of the whole viral genome. These mutants, or the intact wild-type genome, were expressed from the natural viral promoters along with differentiation of epithelial HaCaT cells in three-dimensional collagen raft cultures. High episomal viral copy numbers were obtained using a transfection-based loxp-HPV16-eGFP-N1 vector system. All epithelial equivalents carrying the different HPV type 16 genomes showed pronounced hyperplastic and dysplastic morphology. Particularly the E7 oncogene, with contribution of E6, was shown to enhance cell proliferation. Specifically, the crucial role of E7 in HPV-associated hyperproliferation was clearly manifested. Based on morphological characteristics, immunohistochemical staining for differentiation and proliferation markers, and low expression of E1^E4, we propose that our raft culture models produce cervical intraepithelial neoplasia (CIN)1 and CIN2-like tissue. Our experimental setting provides an alternative tool to study concerted functions of HPV proteins in the development of epithelial dysplasia. © 2015 S. Karger AG, Basel.

  6. Allergen recognition by innate immune cells: critical role of dendritic and epithelial cells

    Directory of Open Access Journals (Sweden)

    Fabian eSalazar

    2013-11-01

    Full Text Available Allergy is an exacerbated response of the immune system against non-self-proteins called allergens and is typically characterized by biased type-2 T helper cell and deleterious IgE mediated immune responses. The allergic cascade starts with the recognition of allergens by antigen presenting cells, mainly dendritic cells, culminating in mast cell sensitization and triggering. Dendritic cells have been demonstrated to play a crucial role in orchestrating allergic diseases. Using different C-type lectin receptors dendritic cells are able to recognize and internalize a number of allergens from diverse sources leading to sensitization. Furthermore, there is increasing evidence highlighting the role of epithelial cells in triggering and modulating immune responses to allergens. As well as providing a physical barrier, epithelial cells can interact with allergens and influence dendritic cells behaviour through the release of a number of Th2 promoting cytokines. In this review we will summarise current understanding of how allergens are recognised by dendritic cells and epithelial cells and what are the consequences of such interaction in the context of allergic sensitisation and downstream events leading to allergic inflammation. Better understanding of the molecular mechanisms of allergen recognition and associated signalling pathways could enable developing more effective therapeutic strategies that target the initial steps of allergic sensitisation hence hindering development or progression of allergic diseases.

  7. ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells.

    Science.gov (United States)

    Lima, Wânia R; Parreira, Kleber S; Devuyst, Olivier; Caplanusi, Adrian; N'kuli, Francisca; Marien, Benoit; Van Der Smissen, Patrick; Alves, Pedro M S; Verroust, Pierre; Christensen, Erik I; Terzi, Fabiola; Matter, Karl; Balda, Maria S; Pierreux, Christophe E; Courtoy, Pierre J

    2010-03-01

    Epithelial polarization modulates gene expression. The transcription factor zonula occludens 1 (ZO-1)-associated nucleic acid binding protein (ZONAB) can shuttle between tight junctions and nuclei, promoting cell proliferation and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA), but whether it also represses epithelial differentiation is unknown. Here, during mouse kidney ontogeny and polarization of proximal tubular cells (OK cells), ZONAB and PCNA levels decreased in parallel and inversely correlated with increasing apical differentiation, reflected by expression of megalin/cubilin, maturation of the brush border, and extension of the primary cilium. Conversely, ZONAB reexpression and loss of apical differentiation markers provided a signature for renal clear cell carcinoma. In confluent OK cells, ZONAB overexpression increased proliferation and PCNA while repressing megalin/cubilin expression and impairing differentiation of the brush border and primary cilium. Reporter and chromatin immunoprecipitation assays demonstrated that megalin and cubilin are ZONAB target genes. Sparsely plated OK cells formed small islands composed of distinct populations: Cells on the periphery, which lacked external tight junctions, strongly expressed nuclear ZONAB, proliferated, and failed to differentiate; central cells, surrounded by continuous junctions, lost nuclear ZONAB, stopped proliferating, and engaged in apical differentiation. Taken together, these data suggest that ZONAB is an important component of the mechanisms that sense epithelial density and participates in the complex transcriptional networks that regulate the switch between proliferation and differentiation.

  8. Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis

    Science.gov (United States)

    Humphreys, Benjamin D.; Xu, Fengfeng; Sabbisetti, Venkata; Grgic, Ivica; Naini, Said Movahedi; Wang, Ningning; Chen, Guochun; Xiao, Sheng; Patel, Dhruti; Henderson, Joel M.; Ichimura, Takaharu; Mou, Shan; Soeung, Savuth; McMahon, Andrew P.; Kuchroo, Vijay K.; Bonventre, Joseph V.

    2013-01-01

    Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1RECtg) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1RECtg mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1RECtg kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1–dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease. PMID:23979159

  9. Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis

    Science.gov (United States)

    Enemchukwu, Nduka O.; Cruz-Acuña, Ricardo; Bongiorno, Tom; Johnson, Christopher T.; García, José R.; Sulchek, Todd

    2016-01-01

    Epithelial cells cultured within collagen and laminin gels proliferate to form hollow and polarized spherical structures, recapitulating the formation of a rudimentary epithelial organ. However, the contributions of extracellular matrix (ECM) biochemical and biophysical properties to morphogenesis are poorly understood because of uncontrolled presentation of multiple adhesive ligands, limited control over mechanical properties, and lot-to-lot compositional variability in these natural ECMs. We engineered synthetic ECM-mimetic hydrogels with independent control over adhesive ligand density, mechanical properties, and proteolytic degradation to study the impact of ECM properties on epithelial morphogenesis. Normal cyst growth, polarization, and lumen formation were restricted to a narrow range of ECM elasticity, whereas abnormal morphogenesis was observed at lower and higher elastic moduli. Adhesive ligand density dramatically regulated apicobasal polarity and lumenogenesis independently of cell proliferation. Finally, a threshold level of ECM protease degradability was required for apicobasal polarity and lumen formation. This synthetic ECM technology provides new insights into how cells transduce ECM properties into complex morphogenetic behaviors. PMID:26711502

  10. Modular GAG-matrices to promote mammary epithelial morphogenesis in vitro.

    Science.gov (United States)

    Nowak, Mirko; Freudenberg, Uwe; Tsurkan, Mikhail V; Werner, Carsten; Levental, Kandice R

    2017-01-01

    Matrix systems used to study complex three-dimensional (3D) cellular processes like mammary epithelial tissue morphogenesis and tumorigenesis ex vivo often require ill-defined biological components, which lead to poor reproducibility and a lack of control over physical parameters. In this study, a well-defined, tunable synthetic biohybrid hydrogel composed of the glycosaminoglycan heparin, star-shaped poly(ethylene glycol) (starPEG), and matrix metalloproteinase- (MMP-) cleavable crosslinkers was applied to dissect the biophysical and biochemical signals promoting human mammary epithelial cell (MEC) morphogenesis. We show that compliant starPEG-heparin matrices promote the development of polarized MEC acini. Both the presence of heparin and MMP-cleavable crosslinks are essential in facilitating MEC morphogenesis without supplementation of exogenous adhesion ligands. In this system, MECs secrete and organize laminin in basement membrane-like assemblies to promote integrin signaling and drive acinar development. Therefore, starPEG-heparin hydrogels provide a versatile platform to study mammary epithelial tissue morphogenesis in a chemically defined and precisely tunable 3D in vitro microenvironment. The system allows investigation of biophysical and biochemical aspects of mammary gland biology and potentially a variety of other organoid culture studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Establishment and characterization of a differentiated epithelial cell culture model derived from the porcine cervix uteri

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    Miessen Katrin

    2012-03-01

    Full Text Available Abstract Background Cervical uterine epithelial cells maintain a physiological and pathogen-free milieu in the female mammalian reproductive tract and are involved in sperm-epithelium interaction. Easily accessible, differentiated model systems of the cervical epithelium are not yet available to elucidate the underlying molecular mechanisms within these highly specialized cells. Therefore, the aim of the study was to establish a cell culture of the porcine cervical epithelium representing in vivo-like properties of the tissue. Results We tested different isolation methods and culture conditions and validated purity of the cultured cells by immunohistochemistry against keratins. We could reproducibly culture pure epithelial cells from cervical tissue explants. Based on a morphology score and the WST-1 Proliferation Assay, we optimized the growth medium composition. Primary porcine cervical cells performed best in conditioned Ham's F-12, containing 10% FCS, EGF and insulin. After cultivation in an air-liquid interface for three weeks, the cells showed a discontinuously multilayered phenotype. Finally, differentiation was validated via immunohistochemistry against beta catenin. Mucopolysaccharide production could be shown via alcian blue staining. Conclusions We provide the first suitable protocol to establish a differentiated porcine epithelial model of the cervix uteri, based on easily accessible cells using slaughterhouse material.

  12. Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    D. Ben Sellem

    2011-01-01

    Full Text Available Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii generate statistical models capable of classifying borderline tumors and (iii establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using 1H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate and mucinous (N-acetyl-lysine carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients.

  13. Autocrine CSF-1R activation promotes Src-dependent disruption of mammary epithelial architecture.

    Science.gov (United States)

    Wrobel, Carolyn N; Debnath, Jayanta; Lin, Eva; Beausoleil, Sean; Roussel, Martine F; Brugge, Joan S

    2004-04-26

    Elevated coexpression of colony-stimulating factor receptor (CSF-1R) and its ligand, CSF-1, correlates with invasiveness and poor prognosis of a variety of epithelial tumors (Kacinski, B.M. 1995. Ann. Med. 27:79-85). Apart from recruitment of macrophages to the tumor site, the mechanisms by which CSF-1 may potentiate invasion are poorly understood. We show that autocrine CSF-1R activation induces hyperproliferation and a profound, progressive disruption of junctional integrity in acinar structures formed by human mammary epithelial cells in three-dimensional culture. Acini coexpressing receptor and ligand exhibit a dramatic relocalization of E-cadherin from the plasma membrane to punctate intracellular vesicles, accompanied by its loss from the Triton-insoluble fraction. Interfering with Src kinase activity, either by pharmacological inhibition or mutation of the Y561 docking site on CSF-1R, prevents E-cadherin translocation, suggesting that CSF-1R disrupts cell adhesion by uncoupling adherens junction complexes from the cytoskeleton and promoting cadherin internalization through a Src-dependent mechanism. These findings provide a mechanistic basis whereby CSF-1R could contribute to invasive progression in epithelial cancers.

  14. Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus

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    Svetlana Ulyanchenko

    2016-03-01

    Full Text Available Thymic epithelial cells (TECs are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam+UEA1−Ly-51+PLET1+MHC class IIhi, which comprises <0.5% of adult TECs, contains bipotent TEC progenitors that can efficiently generate both cortical (c TECs and medullary (m TECs. No other adult TEC population tested in this study contains this activity. We demonstrate persistence of PLET1+Ly-51+ TEC-derived cells for 9 months in vivo, suggesting the presence of thymic epithelial stem cells. Additionally, we identify cTEC-restricted short-term progenitor activity but fail to detect high efficiency mTEC-restricted progenitors in the adult thymus. Our data provide a phenotypically defined adult thymic epithelial progenitor/stem cell that is able to generate both cTECs and mTECs, opening avenues for improving thymus function in patients.

  15. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

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    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  16. Trichostatin A inhibits beta-casein expression in mammary epithelial cells

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    Pujuguet, Philippe; Radisky, Derek; Levy, Dinah; Lacza, Charlemagne; Bissell, Mina J.

    2002-02-22

    Many aspects of cellular behavior are affected by information derived from association of the extracellular matrix (ECM) and with cell membrane receptors. When cultured in the presence of laminin-containing ECM and prolactin (Prl), normal mammary epithelial cells express the milk protein beta-casein. Previously, we defined the minimal ECM- and Prl-responsive enhancer element BCE-1 from the upstream region of the beta-casein gene. We also found that BCE-1 was only active when stably integrated into chromatin, and that trichostatin A (TSA), a reagent that leads to alterations in chromatin structure, was able to activate the integrated enhancer element. We now show that endogenous b-casein gene, which is controlled by a genetic assembly that is highly similar to that of BCE-1 and which is also activated by incubation in ECM and Prl, is instead inhibited by TSA. We provide evidence that the differing response of b-casein and BCE-1 to TSA is neither due to an unusual effect of TSA on mammary epithelial cells, nor to secondary consequences from the expression of a separate gene, nor to a particular property of the BCE-1 construct. As a component of this investigation, we also showed that ECM could mediate rapid histone deacetylation in mammary epithelial cells. These results are discussed in combination with previous work showing that TSA mediates the differentiation of many types of cancer cells but inhibits differentiation of some nonmalignant cell types.

  17. Epithelial Remodeling as Basis for Machine-Based Identification of Keratoconus

    Science.gov (United States)

    Silverman, Ronald H.; Urs, Raksha; RoyChoudhury, Arindam; Archer, Timothy J.; Gobbe, Marine; Reinstein, Dan Z.

    2014-01-01

    Purpose. To develop and evaluate automated computerized algorithms for differentiation of normal and keratoconus corneas based solely on epithelial and stromal thickness data. Methods. Maps of the corneal epithelial and stromal thickness were generated from Artemis-1 very high-frequency ultrasound arc-scans of 130 normal and 74 keratoconic subjects diagnosed by combined topography and tomography examination. Keratoconus severity was graded based on anterior curvature, minimum corneal thickness, and refractive error. Computer analysis of maps produced 161 features for one randomly selected eye per subject. Stepwise linear discriminant analysis (LDA) and neural network (NN) analysis were then performed to develop multivariate models based on combinations of selected features to correctly classify cases. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined for each classifier. Results. Stepwise LDA resulted in a six-variable model that provided an AUC of 100%, indicative of complete separation of keratoconic from normal corneas. Leave-one-out analysis resulted in 99.2% specificity and 94.6% sensitivity. Neural network analysis using the same six variables resulted in an AUC of 100% for the training set. Test set performance averaged over 10 trials gave a specificity of 99.5 ± 1.5% and sensitivity of 98.9 ± 1.9%. The LDA function values correlated with keratoconus severity grade. Conclusions. The results demonstrate that epithelial remodeling in keratoconus represents an independent means for differentiation of normal from advanced keratoconus corneas. PMID:24557351

  18. RHBDL2 Is a Critical Membrane Protease for Anoikis Resistance in Human Malignant Epithelial Cells

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    Tsung-Lin Cheng

    2014-01-01

    Full Text Available Anoikis resistance allows metastatic tumor cells to survive in a homeless environment. Activation of epithelial growth factor receptor (EGFR signaling is one of the key mechanisms for metastatic tumor cells to resist anoikis, yet the regulation mechanisms of homeless-triggered EGFR activation in metastatic tumor cells remain unclear. Rhomboid-like-2 (RHBDL2, an evolutionally conserved intramembrane serine protease, can cleave the EGF ligand and thus trigger EGFR activation. Herein, we demonstrated that RHBDL2 overexpression in human epithelial cells resulted in promotion of cell proliferation, reduction of cell adhesion, and suppression of anoikis. During long-term suspension cultures, increased RHBDL2 was only detected in aggressive tumor cell lines. Treatment with the rhomboid protease inhibitor or RHBDL2 shRNA increased cleaved caspase 3, a marker of apoptosis. Finally, inhibition of EGFR activation increased the cleaved caspase 3 and attenuated the detachment-induced focal adhesion kinase phosphorylation. Taken together, these findings provide evidence for the first time that RHBDL2 is a critical molecule in anoikis resistance of malignant epithelial cells, possibly through the EGFR-mediated signaling. Our study demonstrates RHBDL2 as a new therapeutic target for cancer metastasis.

  19. Human normal bronchial epithelial cells: a novel in vitro cell model for toxicity evaluation.

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    Wenqiang Feng

    Full Text Available Human normal cell-based systems are needed for drug discovery and toxicity evaluation. hTERT or viral genes transduced human cells are currently widely used for these studies, while these cells exhibited abnormal differentiation potential or response to biological and chemical signals. In this study, we established human normal bronchial epithelial cells (HNBEC using a defined primary epithelial cell culture medium without transduction of exogenous genes. This system may involve decreased IL-1 signaling and enhanced Wnt signaling in cells. Our data demonstrated that HNBEC exhibited a normal diploid karyotype. They formed well-defined spheres in matrigel 3D culture while cancer cells (HeLa formed disorganized aggregates. HNBEC cells possessed a normal cellular response to DNA damage and did not induce tumor formation in vivo by xenograft assays. Importantly, we assessed the potential of these cells in toxicity evaluation of the common occupational toxicants that may affect human respiratory system. Our results demonstrated that HNBEC cells are more sensitive to exposure of 10~20 nm-sized SiO2, Cr(VI and B(aP compared to 16HBE cells (a SV40-immortalized human bronchial epithelial cells. This study provides a novel in vitro human cells-based model for toxicity evaluation, may also be facilitating studies in basic cell biology, cancer biology and drug discovery.

  20. Human normal bronchial epithelial cells: a novel in vitro cell model for toxicity evaluation.

    Science.gov (United States)

    Feng, Wenqiang; Guo, Juanjuan; Huang, Haiyan; Xia, Bo; Liu, Hongya; Li, Jie; Lin, Shaolin; Li, Tiyuan; Liu, Jianjun; Li, Hui

    2015-01-01

    Human normal cell-based systems are needed for drug discovery and toxicity evaluation. hTERT or viral genes transduced human cells are currently widely used for these studies, while these cells exhibited abnormal differentiation potential or response to biological and chemical signals. In this study, we established human normal bronchial epithelial cells (HNBEC) using a defined primary epithelial cell culture medium without transduction of exogenous genes. This system may involve decreased IL-1 signaling and enhanced Wnt signaling in cells. Our data demonstrated that HNBEC exhibited a normal diploid karyotype. They formed well-defined spheres in matrigel 3D culture while cancer cells (HeLa) formed disorganized aggregates. HNBEC cells possessed a normal cellular response to DNA damage and did not induce tumor formation in vivo by xenograft assays. Importantly, we assessed the potential of these cells in toxicity evaluation of the common occupational toxicants that may affect human respiratory system. Our results demonstrated that HNBEC cells are more sensitive to exposure of 10~20 nm-sized SiO2, Cr(VI) and B(a)P compared to 16HBE cells (a SV40-immortalized human bronchial epithelial cells). This study provides a novel in vitro human cells-based model for toxicity evaluation, may also be facilitating studies in basic cell biology, cancer biology and drug discovery.