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Sample records for murine epidermal maintenance

  1. CD133 Is a Marker For Long-Term Repopulating Murine Epidermal Stem Cells

    PubMed Central

    Charruyer, A; Strachan, LR; Yue, L; Toth, AS; Mancianti, ML; Ghadially, R

    2012-01-01

    Maintenance, repair and renewal of the epidermis are thought to depend on a pool of dedicated epidermal stem cells. Like for many somatic tissues, isolation of a nearly pure population of stem cells is a primary goal in cutaneous biology. We used a quantitative transplantation assay, using injection of keratinocytes into subcutis combined with limiting dilution analysis, to assess the long-term repopulating ability of putative murine epidermal stem populations. Putative epidermal stem cell populations were isolated by FACS sorting. The CD133+ population and the subpopulation of CD133+ cells that exhibits high mitochondrial membrane potential (DΨmhi), were enriched for long-term repopulating epidermal stem cells vs. unfractionated cells (3.9 and 5.2-fold, respectively). Evidence for self-renewal capacity was obtained by serial transplantation of long-term epidermal repopulating units derived from CD133+ and CD133+ΔΨmhi keratinocytes. CD133+ keratinocytes were multipotent and produced significantly more hair follicles than CD133− cells. CD133+ cells were a subset of the previously described integrin α6+CD34+ bulge cell population and 28.9±8.6% were label retaining cells. Thus, murine keratinocytes within the CD133+ and CD133+ΔΨmhi populations contain epidermal stem cells that regenerate epidermis for the long-term, are self-renewing, multipotent, and label-retaining cells. PMID:22763787

  2. Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis.

    PubMed

    Hatano, Yutaka; Man, Mao-Qiang; Uchida, Yoshikazu; Crumrine, Debra; Scharschmidt, Tiffany C; Kim, Esther G; Mauro, Theodora M; Feingold, Kenneth R; Elias, Peter M; Holleran, Walter M

    2009-07-01

    Neutralization of stratum corneum (SC) adversely impacts key epidermal functions, including permeability barrier homeostasis and SC integrity. Conversely, acidification of SC improves these functions in developmentally impaired (neonatal or aged) skin, and enhances function in normal skin. Hence, we hypothesized that acidification could alter the course of inflammatory dermatoses, which invariably exhibit an increased SC pH. Maintenance of a low pH by topical applications of the polyhydroxyl acid, lactobionic acid, during the repeated-challenge phase inhibited the development of oxazolone-induced atopic dermatitis (AD). Neither gross/histological dermatitis nor altered barrier function developed, and emergence of epidermal hyperplasia was prevented; however, cytokine generation decreased. Acidification also largely normalized the development of hapten-induced changes in eosinophil/mast cell densities, density of chemoattractant receptor-homologous molecule expressed on TH2-positive lymphocytes, and serum IgE levels. The pH-induced improvement in barrier function most likely accounts for the anti-inflammatory activity, which could be further attributed to normalization of both lamellar body secretion and lamellar bilayer formation. Acidification of SC alone substantially prevents development of barrier abnormalities and downstream immune abnormalities during the elicitation phase of murine AD. These results provide direct evidence for the "outside-inside" pathogenesis of AD and further suggest that maintenance of an acidic SC pH could prevent the emergence of AD in humans. PMID:19177139

  3. In vivo measurement of epidermal thickness changes associated with tumor promotion in murine models

    PubMed Central

    Phillips, Kevin G.; Samatham, Ravikant; Choudhury, Niloy; Gladish, James C.; Thuillier, Philippe; Jacques, Steven L.

    2010-01-01

    The characterization of tissue morphology in murine models of pathogenesis has traditionally been carried out by excision of affected tissues with subsequent immunohistological examination. Excision-based histology provides a limited two-dimensional presentation of tissue morphology at the cost of halting disease progression at a single time point and sacrifice of the animal. We investigate the use of noninvasive reflectance mode confocal scanning laser microscopy (rCSLM) as an alternative tool to biopsy in documenting epidermal hyperplasia in murine models exposed to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). An automated technique utilizing average axial rCSLM reflectance profiles is used to extract epidermal thickness values from rCSLM data cubes. In comparisons to epidermal thicknesses determined from hematoxylin and eosin (H&E) stained tissue sections, we find no significant correlation to rCSLM-derived thickness values. This results from method-specific artifacts: physical alterations of tissue during H&E preparation in standard histology and specimen-induced abberations in rCSLM imaging. Despite their disagreement, both histology and rCSLM methods reliably measure statistically significant thickness changes in response to TPA exposure. Our results demonstrate that in vivo rCSLM imaging provides epithelial biologists an accurate noninvasive means to monitor cutaneous pathogenesis. PMID:20799792

  4. Epidermal Differentiation in Barrier Maintenance and Wound Healing.

    PubMed

    Wikramanayake, Tongyu Cao; Stojadinovic, Olivera; Tomic-Canic, Marjana

    2014-03-01

    Significance: The epidermal barrier prevents water loss and serves as the body's first line of defense against toxins, chemicals, and infectious microbes. Disruption of the barrier, either through congenital disorders of barrier formation or through wounds, puts the individual at risk for dehydration, hypersensitivity, infection, and prolonged inflammation. Epidermal barrier disorders affect millions of patients in the United States, causing loss of productivity and diminished quality of life for patients and their families, and represent a burden to the health-care system and society. Recent Advances: The genetic basis of many congenital barrier disorders has been identified in recent years, and great advances have been made in the molecular mechanisms of the formation and homeostasis of epidermal barrier, as well as acute and chronic wound healing. Progress in stem cell (SC) biology, particularly in induced pluripotent stem cells (iPSCs) and allogeneic mesenchymal stem cells (MSCs), has opened new doors for cell-based therapy of chronic wounds. Critical Issues: Understanding of the molecular mechanisms of barrier homeostasis in health and disease, as well as contributions of iPSCs and allogeneic MSCs to wound healing, will lead to the identification of novel targets for developing therapeutics for congenital barrier and wound healing disorders. Future Directions: Future studies should focus on better understanding of molecular mechanisms leading to disrupted homeostasis of epidermal barrier to identify potential therapeutic targets to combat its associated diseases. PMID:24669361

  5. Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis.

    PubMed

    Clark, Jessica A; Gan, Heng; Samocha, Alexandr J; Fox, Amy C; Buchman, Timothy G; Coopersmith, Craig M

    2009-09-01

    Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes (IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion. PMID:19571236

  6. Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis

    PubMed Central

    Clark, Jessica A.; Gan, Heng; Samocha, Alexandr J.; Fox, Amy C.; Buchman, Timothy G.; Coopersmith, Craig M.

    2009-01-01

    Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes (IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion. PMID:19571236

  7. Epoc-1: a POU-domain gene expressed in murine epidermal basal cells and thymic stromal cells.

    PubMed

    Yukawa, K; Yasui, T; Yamamoto, A; Shiku, H; Kishimoto, T; Kikutani, H

    1993-11-15

    POU-domain transcription factors are known as developmental regulators which control organ development and cell phenotypes. In order to clarify the roles of POU-domain transcription factors in cell differentiation, we cloned a novel POU family gene, Epoc-1, from a murine thymus cDNA library. The amino acid (aa) sequence of the POU-specific domain of Epoc-1 is almost identical to those of Oct-1 and Oct-2. However, within the POU-homeodomain, 13 out of 60 aa differ between Epoc-1 and Oct-2. Recombinant Epoc-1 products were found to bind specifically to the octamer sequence. Epoc-1 was found to be expressed in skin, thymus, stomach and testis. In situ hybridization experiments and RNase protection assays indicated that Epoc-1 is expressed in the epidermal basal cells of the skin, which contain stem cells unipotent for keratinocyte differentiation and in thymic stromal elements. These results suggest that Epoc-1 might be one of the developmental regulators which controls epidermal development and thymic organogenesis. PMID:8224904

  8. Postnatal requirement of the epithelial sodium channel for maintenance of epidermal barrier function.

    PubMed

    Charles, Roch-Philippe; Guitard, Marjorie; Leyvraz, Céline; Breiden, Bernadette; Haftek, Marek; Haftek-Terreau, Zofia; Stehle, Jean-Christophe; Sandhoff, Konrad; Hummler, Edith

    2008-02-01

    In skin, the physiological consequence of an epithelial sodium channel (ENaC) deficiency is not obvious directly at birth. Nevertheless, within hours after birth, mice deficient for the alpha-subunit of the highly amiloride-sensitive epithelial sodium channel (alphaENaC/Scnn1a) suffer from a significant increased dehydration. This is characterized by a loss of body weight (by 6% in 6 h) and an increased transepidermal water loss, which is accompanied by a higher skin surface pH in 1-day-old pups. Although early and late differentiation markers, as well as tight junction protein distribution and function, seem unaffected, deficiency of alphaENaC severely disturbs the stratum corneum lipid composition with decreased ceramide and cholesterol levels, and increased pro-barrier lipids, whereas covalently bound lipids are drastically reduced. Ultrastructural analysis revealed morphological changes in the formation of intercellular lamellar lipids and the lamellar body secretion. Extracellular formation of the lamellar lipids proved to be abnormal in the knockouts. In conclusion, ENaC deficiency results in progressive dehydration and, consequently, weight loss due to severe impairment of lipid formation and secretion. Our data demonstrate that ENaC expression is required for the postnatal maintenance of the epidermal barrier function but not for its generation. PMID:18039670

  9. Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells.

    PubMed

    Zhang, Baojun; Wu, Jianxuan; Jiao, Yiqun; Bock, Cheryl; Dai, Meifang; Chen, Benny; Chao, Nelson; Zhang, Weiguo; Zhuang, Yuan

    2015-11-01

    Dendritic epidermal T cells (DETCs) are generated exclusively in the fetal thymus and maintained in the skin epithelium throughout postnatal life of the mouse. DETCs have restricted antigenic specificity as a result of their exclusive usage of a canonical TCR. Although the importance of the TCR in DETC development has been well established, the exact role of TCR signaling in DETC homeostasis and function remains incompletely defined. In this study, we investigated TCR signaling in fully matured DETCs by lineage-restricted deletion of the Lat gene, an essential signaling molecule downstream of the TCR. We found that Lat deletion impaired TCR-dependent cytokine gene activation and the ability of DETCs to undergo proliferative expansion. However, linker for activation of T cells-deficient DETCs were able to maintain long-term population homeostasis, although with a reduced proliferation rate. Mice with Lat deletion in DETCs exhibited delayed wound healing accompanied by impaired clonal expansion within the wound area. Our study revealed differential requirements for TCR signaling in homeostatic maintenance of DETCs and in their effector function during wound healing. PMID:26408667

  10. The aged epidermal permeability barrier. Structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model.

    PubMed Central

    Ghadially, R; Brown, B E; Sequeira-Martin, S M; Feingold, K R; Elias, P M

    1995-01-01

    Aged epidermis displays altered drug permeability, increased susceptibility to irritant contact dermatitis, and often severe xerosis, suggesting compromise of the aged epidermal barrier. To delineate the functional, structural, and lipid biochemical basis of epidermal aging, we compared barrier function in young (20-30 yr) vs aged (> 80 yr) human subjects, and in a murine model. Baseline transepidermal water loss in both aged humans and senescent mice was subnormal. However, the aged barrier was perturbed more readily with either acetone or tape stripping (18 +/- 2 strippings vs 31 +/- 5 strippings in aged vs young human subjects, respectively). Moreover, after either acetone treatment or tape stripping, the barrier recovered more slowly in aged than in young human subjects (50 and 80% recovery at 24 and 72 h, respectively, in young subjects vs 15% recovery at 24 h in aged subjects), followed by a further delay over the next 6 d. Similar differences in barrier recovery were seen in senescent vs young mice. Although the total lipid content was decreased in the stratum corneum of aged mice (approximately 30%), the distribution of ceramides (including ceramide 1), cholesterol, and free fatty acids was unchanged. Moreover, a normal complement of esterified, very long-chain fatty acids was present. Finally, stratum corneum lamellar bilayers displayed normal substructure and dimensions, but were focally decreased in number, with decreased secretion of lamellar body contents. Thus, assessment of barrier function in aged epidermis under basal conditions is misleading, since both barrier integrity and barrier repair are markedly abnormal. These functional changes can be attributed to a global deficiency in all key stratum corneum lipids, resulting in decreased lamellar bilayers in the stratum corneum interstices. This constellation of findings may explain the increased susceptibility of intrinsically aged skin to exogenous and environmental insults. Images PMID:7738193

  11. Emodin Suppresses Maintenance of Stemness by Augmenting Proteosomal Degradation of Epidermal Growth Factor Receptor/Epidermal Growth Factor Receptor Variant III in Glioma Stem Cells

    PubMed Central

    Kim, Jeongyub; Lee, Jong-Seon; Jung, Jieun; Lim, Inhye; Lee, Ji-Yun

    2015-01-01

    There is a growing body of evidence that small subpopulations of cells with stem cell-like characteristics within most solid tumors are responsible for the malignancy of aggressive cancer cells and that targeting these cells might be a good therapeutic strategy to reduce the risk of tumor relapse after therapy. Here, we examined the effects of emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component of the root and rhizome of Rheum palmatum that has several biological activities, including antitumor effects, on primary cultured glioma stem cells (GSCs). Emodin inhibited the self-renewal activity of GSCs in vitro as evidenced by neurosphere formation, limiting dilution, and soft agar clonogenic assays. Emodin inhibited the maintenance of stemness by suppressing the expression of Notch intracellular domain, nonphosphorylated β-catenin, and phosphorylated STAT3 proteins. In addition, treatment with emodin partially induced apoptosis, reduced cell invasiveness, and sensitized GSCs to ionizing radiation. Intriguingly, emodin induced proteosomal degradation of epidermal growth factor receptor (EGFR)/EGFR variant III (EGFRvIII) by interfering with the association of EGFR/EGFRvIII with heat shock protein 90, resulting in the suppression of stemness pathways. Based on these data, we propose that emodin could be considered as a potent therapeutic adjuvant that targets GSCs. PMID:25229646

  12. Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models

    PubMed Central

    Nguyen, Liem H.; Robinton, Daisy A.; Seligson, Marc; Wu, Linwei; Li, Lin; Rakheja, Dinesh; Comerford, Sarah; Ramezani, Saleh; Sun, Xiankai; Parikh, Monisha; Yang, Erin; Powers, John T.; Shinoda, Gen; Shah, Samar; Hammer, Robert; Daley, George Q.; Zhu, Hao

    2014-01-01

    SUMMARY Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Thus, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance. PMID:25117712

  13. Murine infection model for maintenance and amplification of Cryptosporidium parvum oocysts.

    PubMed Central

    Petry, F; Robinson, H A; McDonald, V

    1995-01-01

    Propagation of Cryptosporidium parvum is problematic because in vitro development of the parasite is poor and animals are only briefly susceptible as neonates. At present oocysts of the parasite are usually procured by passage in neonatal sheep or cattle. In the present study, large numbers of oocysts of C. parvum could be isolated following infection of dexamethasone-treated adult C57BL/6 mice. The amount of immunosuppressive drug and the regimen of administration were critical for successful maintenance of the parasite, however. Routinely, 10 mice (age, 8 to 12 weeks) were injected four times on alternate days with 1.0 mg of dexamethasone, and the last injection was given on the same day as oral inoculation with 10(6) oocysts. By using a simplified procedure for oocyst purification from mouse feces, approximately 10(9) oocysts were obtained. This model is inexpensive and comparatively safe to handle, and the numbers of animals inoculated can be varied to obtain the required number of oocysts. Thus, this murine infection model would be a suitable alternative to the use of neonatal calves or sheep for efficient oocyst propagation. PMID:7665672

  14. The Evolving Role of Maintenance Therapy Using Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) in the Management of Advanced Non-Small-Cell Lung Cancer

    PubMed Central

    Huang, Chao H.; Powers, Benjamin C.

    2012-01-01

    The epidermal growth factor receptor (EGFR) plays an important role in the development of many cancers, including non-small cell lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are a class of novel biologically-targeted agents widely used in the management of recurrent non-small cell lung cancer. Erlotinib, one of the EGFR TKIs, is currently FDA approved in second and third line therapy. However, recent studies showed that erlotinib is also effective as maintenance therapy after initial chemotherapy, improving disease free survival and possibly overall survival. Our current understanding of erlotinib’s mechanism of action, with the discovery that EGFR mutation confers higher response rate, has propelled this agent into the first line setting. Advances in molecular testing and clinical research of this agent and other agents in this class will eventually change the way we utilize EGFR TKIs in the near future. PMID:22550402

  15. Murine epidermal growth factor (EGF) fragment (33-42) inhibits both EGF- and laminin-dependent endothelial cell motility and angiogenesis.

    PubMed

    Nelson, J; Allen, W E; Scott, W N; Bailie, J R; Walker, B; McFerran, N V; Wilson, D J

    1995-09-01

    Laminin, murine epidermal growth factor (mEGF), and the synthetic laminin peptide Lam.B1(925-933) (a linear peptide from the B1 chain of murine laminin, CDPGY1GSR-amide) all stimulate endothelial cell motility above basal rates, whereas a synthetic mEGF fragment, mEGF33-42 (a linear peptide from the C-loop of mEGF, acetyl-C-[S-Acm]-VIGYSGDR-C-[S-Acm]-amide), inhibits motility. In both human SK HEP-1 and embryonic chick endothelial cells, mEGF33-42 blocks both EGF- and laminin-stimulated locomotion of endothelial cells. In vivo, mEGF33-42 also blocks both laminin- and mEGF-induced angiogenesis in the chick. In the human cell line. Lam.B1(925-933) has an additive effect in coincubation with either laminin or mEGF, but it blocks their effects in the chick cells. Lam.B1(925-933) alone stimulates angiogenesis in the chick but blocks laminin-induced angiogenesis. Thus, mEGF33-42 acts as a general laminin antagonist, whereas Lam.B1(925-933) acts as a laminin agonist in human cells, but in chick cells it acts as a partial antagonist. We propose that the presence of an anionic group at the eighth residue of mEGF33-42 may be the source of the antagonistic effects seen with this peptide as compared with the laminin fragment. These findings have important implications in the design of human antiangiogenic agents, and also in the use of chick models in the study of human disease. PMID:7543818

  16. Expression, purification, and characterization of recombinant human and murine milk fat globule-epidermal growth factor-factor 8.

    PubMed

    Castellanos, Erick R; Ciferri, Claudio; Phung, Wilson; Sandoval, Wendy; Matsumoto, Marissa L

    2016-08-01

    Milk fat globule-epidermal growth factor-factor 8 (MFG-E8), as its name suggests, is a major glycoprotein component of milk fat globules secreted by the mammary epithelium. Although its role in milk fat production is unclear, MFG-E8 has been shown to act as a bridge linking apoptotic cells to phagocytes for removal of these dying cells. MFG-E8 is capable of bridging these two very different cell types via interactions through both its epidermal growth factor (EGF)-like domain(s) and its lectin-type C domains. The EGF-like domain interacts with αVβ3 and αVβ5 integrins on the surface of phagocytes, whereas the C domains bind phosphatidylserine found on the surface of apoptotic cells. In an attempt to purify full-length, recombinant MFG-E8 expressed in either insect cells or CHO cells, we find that it is highly aggregated. Systematic truncation of the domain architecture of MFG-E8 indicates that the C domains are mainly responsible for the aggregation propensity. Addition of Triton X-100 to the conditioned cell culture media allowed partial recovery of non-aggregated, full-length MFG-E8. A more comprehensive detergent screen identified CHAPS as a stabilizer of MFG-E8 and allowed purification of a significant portion of non-aggregated, full-length protein. The CHAPS-stabilized recombinant MFG-E8 retained its natural ability to bind both αVβ3 and αVβ5 integrins and phosphatidylserine suggesting that it is properly folded and active. Herein we describe an efficient purification method for production of non-aggregated, full-length MFG-E8. PMID:27102803

  17. Development of pulmonary bronchiolo-alveolar adenocarcinomas in transgenic mice overexpressing murine c- myc and epidermal growth factor in alveolar type II pneumocytes

    PubMed Central

    Ehrhardt, A; Bartels, T; Geick, A; Klocke, R; Paul, D; Halter, R

    2001-01-01

    Transgenic mouse models were established to study tumorigenesis of bronchiolo-alveolar adenocarcinomas derived from alveolar type II pneumocytes (AT-II cells). Transgenic lines expressing the murine oncogene c- myc under the control of the lung-specific surfactant protein C promoter developed multifocal bronchiolo-alveolar hyperplasias, adenomas and carcinomas respectively, whereas transgenic lines expressing a secretable form of the epidermal growth factor (IgEGF), a structural and functional homologue of transforming growth factor α (TGFα), developed hyperplasias of the alveolar epithelium. Since the oncogenes c- myc and TGFα are frequently overexpressed in human lung bronchiolo-alveolar adenocarcinomas, these mouse lines are useful as models for human lung bronchiolo-alveolar adenocarcinomas. The average life expectancies of hemizygous and homozygous c- myc transgenics were 14.25 months and 9.2 months, respectively, suggesting that a dosage effect of c- myc caused an accelerated bronchiolo-alveolar adenocarcinoma formation. First analyses of double transgenics, hemizygous for both c- myc and IgEGF, show that these mice develop bronchiolo-alveolar adenocarcinomas at the average age of 9 months, indicating that these oncogenes cooperate during the lung cancer formation. Our results demonstrate that c- myc and EGF are directly involved and cooperate with one another during formation of bronchiolo-alveolar adenocarcinomas in the lung. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11259097

  18. Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity

    PubMed Central

    Grossman, Craig E.; Carter, Shirron L.; Czupryna, Julie; Wang, Le; Putt, Mary E.; Busch, Theresa M.

    2016-01-01

    Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor®)-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased EGFR activation in proliferative areas was detected only after treatment at the higher fluence rate of 150 mW/cm. These data suggest that fluence rate may affect the activation of survival factors, such as EGFR, and weaker activation at lower fluence rate could contribute to a smaller tumor burden after PDT at 75 mW/cm. PMID:26784170

  19. Effect of recombinant human epidermal growth factor against cutaneous scar formation in murine full-thickness wound healing.

    PubMed

    Kim, Young Seok; Lew, Dae Hyun; Tark, Kwan Chul; Rah, Dong Kyun; Hong, Joon Pio

    2010-04-01

    A visible cutaneous scar develops from the excess formation of immature collagen in response to an inflammatory reaction. This study examined the role of epidermal growth factor (EGF) in the formation of cutaneous scars. Twenty Crl:CD-1 (ICR) mice were used and 2 full-thickness skin wounds were made on the dorsum of each mouse. One of the wounds was treated with recombinant human EGF by local application and the other was treated with saline for control until complete healing was achieved. The EGF-treated group's wounds healed faster than the control group's. The width of the scar was smaller by 30% and the area was smaller by 26% in the EGF-treated group. Inflammatory cell numbers were significantly lower in the EGF-treated group. The expression of transforming growth factor (TGF)-beta(1) in the EGF-treated group was increased. It was observed that the amount of collagen in the EGF-treated group was larger than the control group. In the EGF-treated group, the visible external scars were less noticeable than that in the control group. These results suggest that EGF can reduce cutaneous scars by suppressing inflammatory reactions, decreasing expression of TGF-beta(1), and mediating the formation of collagen. PMID:20358003

  20. Epidermal growth factor improves survival and prevents intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia

    PubMed Central

    Dominguez, Jessica A.; Vithayathil, Paul J.; Khailova, Ludmila; Lawrance, Christopher P.; Samocha, Alexandr J.; Jung, Enjae; Leathersich, Ann M.; Dunne, W. Michael; Coopersmith, Craig M.

    2011-01-01

    Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either Pseudomonas aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 hours after the onset of pneumonia. Systemic EGF decreased seven-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 hours after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines, kidney and liver function were unaffected by EGF therapy although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments were done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF mice) which were compared to WT mice subjected to pneumonia. IFABP-EGF mice had improved survival compared to WT mice following pneumonia (50% vs. 28% respectively, p<0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine. PMID:21701422

  1. Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia.

    PubMed

    Dominguez, Jessica A; Vithayathil, Paul J; Khailova, Ludmila; Lawrance, Christopher P; Samocha, Alexandr J; Jung, Enjae; Leathersich, Ann M; Dunne, W Michael; Coopersmith, Craig M

    2011-10-01

    Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine. PMID:21701422

  2. The role of Hibiscus sabdariffa L. (Roselle) in maintenance of ex vivo murine bone marrow-derived hematopoietic stem cells.

    PubMed

    Abdul Hamid, Zariyantey; Lin Lin, Winnie Hii; Abdalla, Basma Jibril; Bee Yuen, Ong; Latif, Elda Surhaida; Mohamed, Jamaludin; Rajab, Nor Fadilah; Paik Wah, Chow; Wak Harto, Muhd Khairul Akmal; Budin, Siti Balkis

    2014-01-01

    Hematopoietic stem cells- (HSCs-) based therapy requires ex vivo expansion of HSCs prior to therapeutic use. However, ex vivo culture was reported to promote excessive production of reactive oxygen species (ROS), exposing HSCs to oxidative damage. Efforts to overcome this limitation include the use of antioxidants. In this study, the role of Hibiscus sabdariffa L. (Roselle) in maintenance of cultured murine bone marrow-derived HSCs was investigated. Aqueous extract of Roselle was added at varying concentrations (0-1000 ng/mL) for 24 hours to the freshly isolated murine bone marrow cells (BMCs) cultures. Effects of Roselle on cell viability, reactive oxygen species (ROS) production, glutathione (GSH) level, superoxide dismutase (SOD) activity, and DNA damage were investigated. Roselle enhanced the survival (P < 0.05) of BMCs at 500 and 1000 ng/mL, increased survival of Sca-1(+) cells (HSCs) at 500 ng/mL, and maintained HSCs phenotype as shown from nonremarkable changes of surface marker antigen (Sca-1) expression in all experimental groups. Roselle increased (P < 0.05) the GSH level and SOD activity but the level of reactive oxygen species (ROS) was unaffected. Moreover, Roselle showed significant cellular genoprotective potency against H2O2-induced DNA damage. Conclusively, Roselle shows novel property as potential supplement and genoprotectant against oxidative damage to cultured HSCs. PMID:25405216

  3. Murine complement receptor 1 is required for germinal center B cell maintenance but not initiation

    PubMed Central

    Donius, Luke R.; Weis, Janis J.; Weis, John H.

    2014-01-01

    Germinal centers are the anatomic sites for the generation of high affinity immunoglobulin expressing plasma cells and memory B cells. The germinal center B cells that are precursors of these cells circulate between the light zone B cell population that interact with antigen laden follicular dendritic cells (FDC) and the proliferative dark zone B cell population. Antigen retention by follicular dendritic cells is dependent on Fc receptors and complement receptors, and complement receptor 1 (Cr1) is the predominant complement receptor expressed by FDC. The newly created Cr1KO mouse was used to test the effect of Cr1-deficiency on the kinetics of the germinal center reaction and the generation of IgM and switched memory B cell formation. Immunization of Cr1KO mice with a T cell-dependent antigen resulted in the normal initial expansion of B cells with a germinal center phenotype however these cells were preferentially lost in the Cr1KO animal over time (days). Bone marrow chimera animals documented the surprising finding that the loss of germinal center B cell maintenance was linked to the expression of Cr1 on B cells, not the FDC. Cr1-deficiency further resulted in antigen-specific IgM titer and IgM memory B cell reductions, but not antigen-specific IgG after 35-37 days. Investigations of nitrophenyl (NP)-specific IgG demonstrated that Cr1 is not necessary for affinity maturation during the response to particulate antigen. These data, along with those generated in our initial description of the Cr1KO animal describe unique functions of Cr1 on the surface of both B cells and FDC. PMID:24636730

  4. T-cell-receptor dose and the time of treatment during murine retrovirus infection for maintenance of immune function.

    PubMed Central

    Liang, B; Ardestani, S; Marchalonis, J J; Watson, R R

    1996-01-01

    C57BL/6 mice were injected with different doses of human T-cell receptor (TCR) V beta 8.1 CDR1 peptide at different times after murine retrovirus (LP-BM5) infection. Injection with TCR V beta 8.1 CDR1 peptide largely prevented the retrovirus-induced reduction in B- and T-cell proliferation, and T-helper 1 (Th1) cytokines [interleukin-2 (IL-2) and interferon-gamma (IFN-gamma)] secretion. It also suppressed T-helper 2 (Th2) cytokines (IL-6 and IL-10) production, which was stimulated by retrovirus infection. These effects were accomplished using at least 100 micrograms of peptide per mouse and the most effective dose of peptide had to be given within 4 weeks after retrovirus infection. Immunization with doses above 100 micrograms/mouse as long as 4 weeks postinfection maintained natural killer (NK) cell activity during retrovirus infection. Reducing the dose of peptide or delaying it until the disease progressed towards early murine acquired immune deficiency syndrome (AIDS) allowed development of immune dysfunction. These studies provide data suggesting that immune dysfunction, induced by murine retrovirus infection, was largely prevented by TCR V beta CDR1 peptide injection. PMID:8698380

  5. Human mesenchymal and murine stromal cells support human lympho-myeloid progenitor expansion but not maintenance of multipotent haematopoietic stem and progenitor cells.

    PubMed

    Radtke, Stefan; Görgens, André; Liu, Bing; Horn, Peter A; Giebel, Bernd

    2016-02-16

    A major goal in haematopoietic stem cell (HSC) research is to define conditions for the expansion of HSCs or multipotent progenitor cells (MPPs). Since human HSCs/MPPs cannot be isolated, NOD/SCID repopulating cell (SRC) assays emerged as the standard for the quantification of very primitive haematopoietic cell. However, in addition to HSCs/MPPs, lympho-myeloid primed progenitors (LMPPs) were recently found to contain SRC activities, challenging this assay as clear HSC/MPP readout. Because our revised model of human haematopoiesis predicts that HSCs/MPPs can be identified as CD133(+)CD34(+) cells containing erythroid potentials, we investigated the potential of human mesenchymal and conventional murine stromal cells to support expansion of HSCs/MPPs. Even though all stromal cells supported expansion of CD133(+)CD34(+) progenitors with long-term myeloid and long-term lymphoid potentials, erythroid potentials were exclusively found within erythro-myeloid CD133(low)CD34(+) cell fractions. Thus, our data demonstrate that against the prevailing assumption co-cultures on human mesenchymal and murine stromal cells neither promote expansion nor maintenance of HSCs and MPPs. PMID:26818432

  6. Size-dependent effects of tungsten carbide-cobalt particles on oxygen radical production and activation of cell signaling pathways in murine epidermal cells

    SciTech Connect

    Ding, M.; Kisin, E.R.; Zhao, J.; Bowman, L.; Lu, Y.; Jiang, B.; Leonard, S.; Vallyathan, V.; Castranova, V.; Murray, A.R.; Fadeel, B.; Shvedova, A.A.

    2009-12-15

    Hard metal or cemented carbide consists of a mixture of tungsten carbide (WC) (85%) and metallic cobalt (Co) (5-15%). WC-Co is considered to be potentially carcinogenic to humans. However, no comparison of the adverse effects of nano-sized WC-Co particles is available to date. In the present study, we compared the ability of nano- and fine-sized WC-Co particles to form free radicals and propensity to activate the transcription factors, AP-1 and NF-kappaB, along with stimulation of mitogen-activated protein kinase (MAPK) signaling pathways in a mouse epidermal cell line (JB6 P{sup +}). Our results demonstrated that nano-WC-Co generated a higher level of hydroxyl radicals, induced greater oxidative stress, as evidenced by a decrease of GSH levels, and caused faster JB6 P{sup +} cell growth/proliferation than observed after exposure of cells to fine WC-Co. In addition, nano-WC-Co activated AP-1 and NF-kappaB more efficiently in JB6{sup +/+} cells as compared to fine WC-Co. Experiments using AP-1-luciferase reporter transgenic mice confirmed the activation of AP-1 by nano-WC-Co. Nano- and fine-sized WC-Co particles also stimulated MAPKs, including ERKs, p38, and JNKs with significantly higher potency of nano-WC-Co. Finally, co-incubation of the JB6{sup +/+} cells with N-acetyl-cysteine decreased AP-1 activation and phosphorylation of ERKs, p38 kinase, and JNKs, thus suggesting that oxidative stress is involved in WC-Co-induced toxicity and AP-1 activation.

  7. Maintenance and induction of murine embryonic stem cell differentiation using E-cadherin-Fc substrata without colony formation

    NASA Astrophysics Data System (ADS)

    Meng, Qing-Yuan; Akaike, Toshihiro

    2013-03-01

    Induced embryonic stem (ES) cells are expected to be promising cell resources for the observation of the cell behaviors in developmental biology as well as the implantation in cell treatments in human diseases. A recombinant E-cadherin substratum was developed as a cell recognizable substratum to maintain the ES cells' self-renewal and pluripotency at single cell level. Furthermore, the generation of various cell lineages in different germ layers, including hepatic or neural cells, was achieved on the chimeric protein layer precisely and effectively. The induction and isolation of specific cell population was carried out with the enhancing effect of other artificial extracellular matrices (ECMs) in enzyme-free process. The murine ES cell-derived cells showed highly morphological similarities and functional expressions to matured hepatocytes or neural progenitor cells.

  8. Critical role of microglial CD40 in the maintenance of mechanical hypersensitivity in a murine model of neuropathic pain.

    PubMed

    Cao, Ling; Palmer, Christopher D; Malon, Jennifer T; De Leo, Joyce A

    2009-12-01

    We recently demonstrated a contributing role of spinal cord infiltrating CD4+ T lymphocytes in the maintenance of mechanical hypersensitivity in a rodent model of neuropathic pain, spinal nerve L5 transection (L5Tx). It has been demonstrated that microglia play a role in the etiology of pain states. We hypothesized that infiltrating CD4+ T lymphocytes communicate with microglia via a CD40-CD154 interaction. Here, we investigated the role of CD40 in the development of mechanical hypersensitivity post-L5Tx. CD40 KO mice displayed significantly decreased mechanical sensitivity compared with WT mice starting from day 5 post-L5Tx. Using bone marrow chimeric mice, we further identified a pro-nociceptive role of CNS microglial CD40 rather than the peripheral leukocytic CD40. Flow cytometric analysis determined a significant increase of CD40+ microglia in the ipsilateral side of lumbar spinal cord post-L5Tx. Further, spinal cord proinflammatory cytokine (IL-1beta, IL-6, IL-12, and TNF-alpha) profiling demonstrated an induction of IL-6 in both WT and CD40 KO mice post-L5Tx prior to the increase of microglial CD40 expression, indicating a CD40-independent induction of IL-6 following L5Tx. These data establish a novel role of microglial CD40 in the maintenance of nerve injury-induced behavioral hypersensitivity, a behavioral sign of neuropathic pain. PMID:19750482

  9. Epidermal Fatty Acid Binding Protein (E-FABP) Is Not Required for the Generation or Maintenance of Effector and Memory T Cells following Infection with Listeria monocytogenes.

    PubMed

    Li, Bing; Schmidt, Nathan W

    2016-01-01

    Following activation of naïve T cells there are dynamic changes in the metabolic pathways used by T cells to support both the energetic needs of the cell and the macromolecules required for growth and proliferation. Among other changes, lipid metabolism undergoes dynamic transitions between fatty acid oxidation and fatty acid synthesis as cells progress from naïve to effector and effector to memory T cells. The hydrophobic nature of lipids requires that they be bound to protein chaperones within a cell. Fatty acid binding proteins (FABPs) represent a large class of lipid chaperones, with epidermal FABP (E-FABP) expressed in T cells. The objective of this study was to determine the contribution of E-FABP in antigen-specific T cell responses. Following infection with Listeria monocytogenes, we observed similar clonal expansion, contraction and formation of memory CD8 T cells in WT and E-FABP-/- mice, which also exhibited similar phenotypic and functional characteristics. Analysis of Listeria-specific CD4 T cells also revealed no defect in the expansion, contraction, and formation of memory CD4 T cells in E-FABP-/- mice. These data demonstrate that E-FABP is dispensable for antigen-specific T cell responses following a bacterial infection. PMID:27588422

  10. The DNA Replication Licensing Factor Miniature Chromosome Maintenance 7 Is Essential for RNA Splicing of Epidermal Growth Factor Receptor, c-Met, and Platelet-derived Growth Factor Receptor*

    PubMed Central

    Chen, Zhang-Hui; Yu, Yan P.; Michalopoulos, George; Nelson, Joel; Luo, Jian-Hua

    2015-01-01

    Miniature chromosome maintenance 7 (MCM7) is an essential component of DNA replication licensing complex. Recent studies indicate that MCM7 is amplified and overexpressed in a variety of human malignancies. In this report, we show that MCM7 binds SF3B3. The binding motif is located in the N terminus (amino acids 221–248) of MCM7. Knockdown of MCM7 or SF3B3 significantly increased unspliced RNA of epidermal growth factor receptor, platelet-derived growth factor receptor, and c-Met. A dramatic drop of reporter gene expression of the oxytocin exon 1-intron-exon 2-EGFP construct was also identified in SF3B3 and MCM7 knockdown PC3 and DU145 cells. The MCM7 or SF3B3 depleted cell extract failed to splice reporter RNA in in vitro RNA splicing analyses. Knockdown of SF3B3 and MCM7 leads to an increase of cell death of both PC3 and DU145 cells. Such cell death induction is partially rescued by expressing spliced c-Met. To our knowledge, this is the first report suggesting that MCM7 is a critical RNA splicing factor, thus giving significant new insight into the oncogenic activity of this protein. PMID:25425645

  11. Genetics Home Reference: epidermal nevus

    MedlinePlus

    ... primarily of a specific cell type called a keratinocyte. One group of epidermal nevi, called keratinocytic or nonorganoid epidermal nevi, includes nevi that involve only keratinocytes. Keratinocytic epidermal nevi are typically found on the ...

  12. [Biology of epidermal stem cells: impact on medicine].

    PubMed

    Pikuła, Michał; Trzonkowski, Piotr

    2009-01-01

    The epidermis is a self-renewing tissue which regenerates constantly. It consists mainly of keratinocytes of various degree of differentiation, from the proliferative basal layer to the terminally differentiated horny layer. Keratinocytes are specialized cells responsible for cohesion, barrier functions, and immunological reactions. The maintenance of homeostasis in the epidermis is possible via the self-renewing ability of the epidermal stem-cell population, which gives rise to differentiated keratinocytes. It is believed that epidermal stem cells play an important role in cellular regeneration, wound healing, and the pathogenesis of skin cancers. Epidermal stem cells reside in the basal layer of the epidermis, the bulge region of the hair follicle, and the germinal hair follicle matrix. Epidermal stem cells are relatively quiescent, slow-cycling cells defined by their great proliferative potential and unlimited capacity for self-renewal. Adult human epidermal stem cells can be activated and expanded in vitro under appropriate conditions. Cultured human keratinocytes and epidermal stem cells may be then transplanted as a biological dressing in burn injuries, chronic wounds, and various skin diseases. Additionally, epidermal stem cells have become a target for gene therapy and drug testing. In this review the fundamental characteristics of epidermal stem cells and the signaling pathways involved in the regulation of their proliferation and differentiation are discussed. The possibilities of using epidermal stem cells in medicine are also presented. PMID:19837987

  13. Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors.

    PubMed

    Ji, Hongbin; Zhao, Xiaojun; Yuza, Yuki; Shimamura, Takeshi; Li, Danan; Protopopov, Alexei; Jung, Boonim L; McNamara, Kate; Xia, Huili; Glatt, Karen A; Thomas, Roman K; Sasaki, Hidefumi; Horner, James W; Eck, Michael; Mitchell, Albert; Sun, Yangping; Al-Hashem, Ruqayyah; Bronson, Roderick T; Rabindran, Sridhar K; Discafani, Carolyn M; Maher, Elizabeth; Shapiro, Geoffrey I; Meyerson, Matthew; Wong, Kwok-Kin

    2006-05-16

    The tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) have shown anti-tumor activity in the treatment of non-small cell lung cancer (NSCLC). Dramatic and durable responses have occurred in NSCLC tumors with mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). In contrast, these inhibitors have shown limited efficacy in glioblastoma, where a distinct EGFR mutation, the variant III (vIII) in-frame deletion of exons 2-7, is commonly found. In this study, we determined that EGFRvIII mutation was present in 5% (3/56) of analyzed human lung squamous cell carcinoma (SCC) but was not present in human lung adenocarcinoma (0/123). We analyzed the role of the EGFRvIII mutation in lung tumorigenesis and its response to tyrosine kinase inhibition. Tissue-specific expression of EGFRvIII in the murine lung led to the development of NSCLC. Most importantly, these lung tumors depend on EGFRvIII expression for maintenance. Treatment with an irreversible EGFR inhibitor, HKI-272, dramatically reduced the size of these EGFRvIII-driven murine tumors in 1 week. Similarly, Ba/F3 cells transformed with the EGFRvIII mutant were relatively resistant to gefitinib and erlotinib in vitro but proved sensitive to HKI-272. These findings suggest a therapeutic strategy for cancers harboring the EGFRvIII mutation. PMID:16672372

  14. Penile epidermal inclusion cyst.

    PubMed

    Saini, Pradeep; Mansoor, M N; Jalali, Sanjay; Sharma, Abhishek

    2010-07-01

    We report a case of epidermal inclusion cyst of penis in a five-year-old boy, who had presented to the outpatient department of our hospital. Epidermal inclusion cysts are benign lesions that can develop in any part of the body. However, the finding of an epidermal inclusion cyst in the penis is rare. The child was operated and discharged uneventfully. The objective of reporting this case is to highlight the rare possibility of an inclusion cyst arising from penis as a late complication of circumcision. PMID:20589475

  15. Epidermal nevi with aberrant epidermal structure in keratinocytes and melanocytes.

    PubMed

    Oiso, Naoki; Sugawara, Koji; Yonamine, Ayano; Tsuruta, Daisuke; Kawada, Akira

    2015-04-01

    Epidermal nevi are congenital cutaneous hamartomas caused by embryonic somatic mutations. Ultrastructural features of adult epidermal nevi have rarely been investigated. Herein, we report a case involving a Japanese adult who had epidermal nevi with right congenital blindness and a right accessory nipple. The histopathologic and ultrastructural studies showed divergent abnormal epidermal structures in both melanocytes and keratinocytes. Our case indicates the need to further investigate histopathologic, ultrastructural, and genetic associations in adult epidermal nevi. PMID:25657059

  16. STAT3 Signaling in B Cells Is Critical for Germinal Center Maintenance and Contributes to the Pathogenesis of Murine Models of Lupus.

    PubMed

    Ding, Chuanlin; Chen, Xingguo; Dascani, Paul; Hu, Xiaoling; Bolli, Roberto; Zhang, Huang-Ge; Mcleish, Kenneth R; Yan, Jun

    2016-06-01

    Ab maturation as well as memory B and plasma cell differentiation occur primarily in the germinal centers (GCs). Systemic lupus erythematosus (SLE) may develop as a result of enhanced GC activity. Previous studies have shown that the dysregulated STAT3 pathway is linked to lupus pathogenesis. However, the exact role of STAT3 in regulating SLE disease progression has not been fully understood. In this study, we demonstrated that STAT3 signaling in B cells is essential for GC formation and maintenance as well as Ab response. Increased cell apoptosis and downregulated Bcl-xL and Mcl-1 antiapoptotic gene expression were found in STAT3-deficient GC B cells. The follicular helper T cell response positively correlated with GC B cells and was significantly decreased in immunized B cell STAT3-deficient mice. STAT3 deficiency also led to the defect of plasma cell differentiation. Furthermore, STAT3 deficiency in autoreactive B cells resulted in decreased autoantibody production. Results obtained from B cell STAT3-deficient B6.MRL/lpr mice suggest that STAT3 signaling significantly contributes to SLE pathogenesis by regulation of GC reactivity, autoantibody production, and kidney pathology. Our findings provide new insights into the role of STAT3 signaling in the maintenance of GC formation and GC B cell differentiation and identify STAT3 as a novel target for treatment of SLE. PMID:27183592

  17. Epidermal skin grafting.

    PubMed

    Herskovitz, Ingrid; Hughes, Olivia B; Macquhae, Flor; Rakosi, Adele; Kirsner, Robert

    2016-09-01

    Autologous skin grafts, such as full- and split-thickness, have long been part of the reconstructive ladder as an option to close skin defects. Although they are effective in providing coverage, they require the need for a trained surgeon, use of anaesthesia and operating room and creation of a wound at the donor site. These drawbacks can be overcome with the use of epidermal skin grafts (ESGs), which can be harvested without the use of anaesthesia in an office setting and with minimal to no scarring at the donor site. ESGs consist only of the epidermal layer and have emerged as an appealing alternative to other autologous grafts for the treatment of acute and chronic wounds. In this article, we provide an overview of epidermal grafting and its role in wound management. PMID:27547964

  18. A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia

    PubMed Central

    Gordon, William M.; Zeller, Michael D.; Klein, Rachel H.; Swindell, William R.; Ho, Hsiang; Espetia, Francisco; Gudjonsson, Johann E.; Baldi, Pierre F.; Andersen, Bogi

    2014-01-01

    Dermal infiltration of T cells is an important step in the onset and progression of immune-mediated skin diseases such as psoriasis; however, it is not known whether epidermal factors play a primary role in the development of these diseases. Here, we determined that the prodifferentiation transcription factor grainyhead-like 3 (GRHL3), which is essential during epidermal development, is dispensable for adult skin homeostasis, but required for barrier repair after adult epidermal injury. Consistent with activation of a GRHL3-regulated repair pathway in psoriasis, we found that GRHL3 is upregulated in lesional skin and binds known epidermal differentiation gene targets. Using an imiquimod-induced model of immune-mediated epidermal hyperplasia, we found that mice lacking GRHL3 have an exacerbated epidermal damage response, greater sensitivity to disease induction, delayed resolution of epidermal lesions, and resistance to anti–IL-22 therapy compared with WT animals. ChIP-Seq and gene expression profiling of murine skin revealed that while GRHL3 regulates differentiation pathways both during development and during repair from immune-mediated damage, it targets distinct sets of genes in the 2 processes. In particular, GRHL3 suppressed a number of alarmin and other proinflammatory genes after immune injury. This study identifies a GRHL3-regulated epidermal barrier repair pathway that suppresses disease initiation and helps resolve existing lesions in immune-mediated epidermal hyperplasia. PMID:25347468

  19. Murine Typhus

    PubMed Central

    Dzul-Rosado, Karla R; Zavala Velázquez, Jorge Ernesto; Zavala-Castro, Jorge

    2012-01-01

    Rickettsia typhi: is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against Rickettsia typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of R. typhi are rats (some species belonging the Rattus Genus) and fleas (Xenopsylla cheopis) are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi. PMID:24893060

  20. [Toxic epidermal necrolysis].

    PubMed

    Carrillo-Esper, Raúl; Elizondo-Argueta, Sandra; Sánchez-Zúñiga, Martín de Jesús; Visoso-Palacios, Porfirio; Cedillo-Torres, Héctor; Carrillo-Córdova, Jorge Raúl

    2006-01-01

    Toxic epidermal necrolysis is the prototype of a proapoptotic disease characterized by system CD95 dysrregulation. Drugs constitute the main antigenic triggers. Hystopatologically it is characterized by epidermis detachment and necrosis with apoptotic keratinocytes. Clinical presentation includes erithematous-ampullous lesions in the skin and mucous membranes. It is associated with serious complications such as severe sepsis and septic shock. The management in the intensive care unit includes support treatment and specific treatment with immunoglobulins that alter disease course. Recombinant activated Factor VII is effective to control the associated microvascular haemorraghe. PMID:17022310

  1. Ultraviolet B-induced alterations of the skin barrier and epidermal calcium gradient.

    PubMed

    Jiang, Shao Jun; Chu, Ai Wu; Lu, Zhen Feng; Pan, Min Hong; Che, Dun Fa; Zhou, Xiao Jun

    2007-12-01

    Ultraviolet irradiation induces a variety of cutaneous changes, including epidermal permeability barrier disruption. In the present study, we assessed the effects of ultraviolet B (UVB) irradiation in epidermal barrier function and calcium distribution in murine epidermis. Adult hairless mice were exposed to a single dose of UVB (0.15 J/cm(2)). Barrier function was evaluated by transepidermal water loss (TEWL), lanthanum perfusion. The morphological alterations were examined by histology, immunohistochemistry and electron microscopy using ruthenium tetroxide (RuO(4)) postfixation. For evaluation of the effect on epidermal calcium distribution, the ion-capture cytochemistry was employed. UVB irradiation caused a significant increase in TEWL, which peaked at day 4. In parallel, the increased number of sunburn cells and the changes in epidermal hyperplasia and proliferation were observed. Electron microscopic observation demonstrated that the water-soluble lanthanum tracer was present in the extracellular stratum corneum domains, and the increased intercellular permeability was correlated with defective organization of the extracellular lipid lamellar bilayers of the stratum corneum. Moreover, UVB irradiation also caused an appearance of calcium precipitates in the stratum corneum and transitional cell layers as well as the increased cytosolic calcium in the lower epidermis, reflecting the alterations of the epidermal calcium gradient. These results suggest that the changes of the epidermal calcium distribution pattern may correlate with the perturbation of the epidermal barrier induced by UVB irradiation. PMID:18031457

  2. Toxic epidermal necrolysis

    PubMed Central

    Hoetzenecker, Wolfram; Mehra, Tarun; Saulite, Ieva; Glatz, Martin; Schmid-Grendelmeier, Peter; Guenova, Emmanuella; Cozzio, Antonio; French, Lars E.

    2016-01-01

    Toxic epidermal necrolysis (TEN) is a rare, life-threatening drug-induced skin disease with a mortality rate of approximately 30%. The clinical hallmark of TEN is a marked skin detachment caused by extensive keratinocyte cell death associated with mucosal involvement. The exact pathogenic mechanism of TEN is still uncertain. Recent advances in this field have led to the identification of several factors that might contribute to the induction of excessive apoptosis of keratinocytes. In addition, specific human leukocyte antigen types seem to be associated with certain drugs and the development of TEN. As well-controlled studies are lacking, patients are treated with various immunomodulators (e.g. intravenous immunoglobulin) in addition to the best supportive care. PMID:27239294

  3. Calmodulin 4 is dispensable for epidermal barrier formation and wound healing in mice.

    PubMed

    Lessard, Juliane C; Kalinin, Alexandr; Bible, Paul W; Morasso, Maria I

    2015-01-01

    Calcium-mediated signals play important roles in epidermal barrier formation, skin homoeostasis and wound repair. Calmodulin 4 (Calm4) is a small, Ca2+ -binding protein with strong expression in suprabasal keratinocytes. In mice, Calm4 first appears in the skin at the time of barrier formation, and its expression increases in response to epidermal barrier challenges. In this study, we report the generation of Calm4 knockout mice and provide evidence that Calm4 is dispensable for epidermal barrier formation, maintenance and repair. PMID:25316000

  4. Toxic Epidermal Necrolysis.

    PubMed

    Castelain, Florence; Humbert, Phillip

    2013-02-01

    Toxic epidermal necrolysis (TEN) is a severe mucocutaneous drug-induced syndrome that causes massive keratinocyte apoptosis and therefore hydro-electrolytic disorders and systemic infection. TEN approximately affects one to two cases per million per year. Mortality rate may reach thirty percent of cases. Thus, TEN constitute a therapeutic emergency at diagnosis. Typically, clinical examination shows a mucocutaneous detachment involving more than thirty percent of body area. Definitive diagnosis is made on cutaneous biopsy with histological exam that shows the blister of necrotic keratinocytes. Main differential diagnosis are acute staphylococcus epidermis, acute generalized exanthematous pustulosis, linear IgA bullous dermatosis, paraneoplastic pemphigus, bullous fixed pigmented erythema, acute lupus erythematosus. In the early days, SCORTEN gives a good estimation and is now widely used as prognostic score. Drugs are generally considered as the main etiology of TEN but in some cases bacterial or viral infections could be involved. Physiopathology remains unclear even if recent advances have reported the possible implication of immune pathways based on activation of T and NK cells. Treatment of TEN requires to be instituted as soon as the diagnosis is made and the patient is preferentially referred to a specialized unit. Supportive care consist in covering areas of cutaneous detachment. No other therapy have demonstrated its efficiency, but high-dose intravenous immunoglobulin might improve the prognosis. PMID:23373551

  5. Toxic epidermal necrolysis.

    PubMed

    Castelain, Florence; Humbert, Philippe

    2012-11-01

    Toxic epidermal necrolysis (TEN) is a severe mucocutaneous drug-induced syndrome that causes massive keratinocyte apoptosis and therefore hydro-electrolytic disorders and systemic infection. TEN approximately affects one to two cases per million per year. Mortality rate may reach thirty percent of cases. Thus, TEN constitutes a therapeutic emergency at diagnosis. Typically, clinical examination shows a mucocutaneous detachment involving more than thirty percent of body area. Definitive diagnosis is made on cutaneous biopsy with histological exam that shows the blister of necrotic keratinocytes. Main differential diagnosis are acute staphylococcus epidermis, acute generalized exanthematous pustulosis, linear IgA bullous dermatosis, paraneoplastic pemphigus, bullous fixed pigmented erythema, acute lupus erythematosus. In the early days, SCORTEN gives a good estimation and is now widely used as prognostic score. Drugs are generally considered as the main etiology of TEN but in some cases bacterial or viral infections could be involved. Physiopathology remains unclear even if recent advances have reported the possible implication of immune pathways based on activation of T and NK cells. Treatment of TEN requires to be instituted as soon as the diagnosis is made and the patient is preferentially referred to a specialized unit. Supportive care consist of covering areas of cutaneous detachment. No other therapy has demonstrated its efficiency, but high-dose intravenous immunoglobulin might improve the prognosis. PMID:23441982

  6. Role of 3'-5'-cyclic adenosine monophosphate on the epidermal growth factor dependent survival in mammary epithelial cells.

    PubMed

    Grinman, Diego Y; Romorini, Leonardo; Presman, Diego M; Rocha-Viegas, Luciana; Coso, Omar A; Davio, Carlos; Pecci, Adali

    2016-01-01

    Epidermal growth factor (EGF) has been suggested to play a key role in the maintenance of epithelial cell survival during lactation. Previously, we demonstrated that EGF dependent activation of PI3K pathway prevents apoptosis in confluent murine HC11 cells cultured under low nutrient conditions. The EGF protective effect is associated with increased levels of the antiapoptotic protein Bcl-XL. Here, we identify the EGF-dependent mechanism involved in cell survival that converges in the regulation of bcl-X expression by activated CREB. EGF induces Bcl-XL expression through activation of a unique bcl-X promoter, the P1; being not only the PI3K/AKT signaling pathway but also the increase in cAMP levels and the concomitant PKA/CREB activation necessary for both bcl-XL upregulation and apoptosis avoidance. Results presented in this work suggest the existence of a novel connection between the EGF receptor and the adenylate cyclase that would have an impact in preventing apoptosis under low nutrient conditions. PMID:26522133

  7. Secreted Frizzled related protein-4 (sFRP4) promotes epidermal differentiation and apoptosis

    SciTech Connect

    Maganga, Richard; Giles, Natalie; Adcroft, Katharine; Unni, Ambili; Keeney, Diane; Wood, Fiona; Fear, Mark Dharmarajan, Arunasalam

    2008-12-12

    The skin provides vital protection from infection and dehydration. Maintenance of the skin is through a constant program of proliferation, differentiation and apoptosis of epidermal cells, whereby proliferating cells in the basal layer differentiating to form the keratinized, anucleated stratum corneum. The WNT signalling pathway is known to be important in the skin. WNT signalling has been shown to be important both in epidermal development and in the maintenance and cycling of hair follicles and epidermal stem cells. However, the precise role for this pathway in epidermal differentiation remains unknown. We investigated the role of the WNT signalling inhibitor sFRP4 in epidermal differentiation. sFRP4 is expressed in both normal skin and keratinocytes in culture. Expression of sFRP4 mRNA and protein increases with keratinocyte differentiation and apoptosis, whilst exposure of keratinocytes to exogenous sFRP4 promotes apoptosis and expression of the terminal differentiation marker Involucrin. These data suggest sFRP4 promotes epidermal differentiation.

  8. Genetic and pharmacological analysis identifies a physiological role for the AHR in epidermal differentiation

    PubMed Central

    van den Bogaard, Ellen; Podolsky, Michael; Smits, Jos; Cui, Xiao; John, Christian; Gowda, Krishne; Desai, Dhimant; Amin, Shantu; Schalkwijk, Joost; Perdew, Gary H.

    2015-01-01

    Stimulation of the aryl hydrocarbon receptor (AHR) by xenobiotics is known to affect epidermal differentiation and skin barrier formation. The physiological role of endogenous AHR signaling in keratinocyte differentiation is not known. We used murine and human skin models to address the hypothesis that AHR activation is required for normal keratinocyte differentiation. Using transcriptome analysis of Ahr-/- and Ahr+/+ murine keratinocytes, we found significant enrichment of differentially expressed genes linked to epidermal differentiation. Primary Ahr-/- keratinocytes showed a significant reduction in terminal differentiation gene and protein expression, similar to Ahr+/+ keratinocytes treated with AHR antagonists GNF351 and CH223191, or the selective AHR modulator (SAhRM), SGA360. In vitro keratinocyte differentiation led to increased AHR levels and subsequent nuclear translocation, followed by induced CYP1A1 gene expression. Monolayer cultured primary human keratinocytes treated with AHR antagonists also showed an impaired terminal differentiation program. Inactivation of AHR activity during human skin equivalent development severely impaired epidermal stratification, terminal differentiation protein expression and stratum corneum formation. As disturbed epidermal differentiation is a main feature of many skin diseases, pharmacological agents targeting AHR signaling or future identification of endogenous keratinocyte-derived AHR ligands should be considered as potential new drugs in dermatology. PMID:25602157

  9. Epigenetic Regulation of Epidermal Stem Cell Biomarkers and Their Role in Wound Healing

    PubMed Central

    Saldanha, Sabita N.; Royston, Kendra J.; Udayakumar, Neha; Tollefsbol, Trygve O.

    2015-01-01

    As an actively renewable tissue, changes in skin architecture are subjected to the regulation of stem cells that maintain the population of cells responsible for the formation of epidermal layers. Stems cells retain their self-renewal property and express biomarkers that are unique to this population. However, differential regulation of the biomarkers can initiate the pathway of terminal cell differentiation. Although, pockets of non-clarity in stem cell maintenance and differentiation in skin still exist, the influence of epigenetics in epidermal stem cell functions and differentiation in skin homeostasis and wound healing is clearly evident. The focus of this review is to discuss the epigenetic regulation of confirmed and probable epidermal stem cell biomarkers in epidermal stratification of normal skin and in diseased states. The role of epigenetics in wound healing, especially in diseased states of diabetes and cancer, will also be conveyed. PMID:26712738

  10. Egr-5 is a post-mitotic regulator of planarian epidermal differentiation.

    PubMed

    Tu, Kimberly C; Cheng, Li-Chun; T K Vu, Hanh; Lange, Jeffrey J; McKinney, Sean A; Seidel, Chris W; Sánchez Alvarado, Alejandro

    2015-01-01

    Neoblasts are an abundant, heterogeneous population of adult stem cells (ASCs) that facilitate the maintenance of planarian tissues and organs, providing a powerful system to study ASC self-renewal and differentiation dynamics. It is unknown how the collective output of neoblasts transit through differentiation pathways to produce specific cell types. The planarian epidermis is a simple tissue that undergoes rapid turnover. We found that as epidermal progeny differentiate, they progress through multiple spatiotemporal transition states with distinct gene expression profiles. We also identified a conserved early growth response family transcription factor, egr-5, that is essential for epidermal differentiation. Disruption of epidermal integrity by egr-5 RNAi triggers a global stress response that induces the proliferation of neoblasts and the concomitant expansion of not only epidermal, but also multiple progenitor cell populations. Our results further establish the planarian epidermis as a novel paradigm to uncover the molecular mechanisms regulating ASC specification in vivo. PMID:26457503

  11. Photoacoustic measurement of epidermal melanin

    NASA Astrophysics Data System (ADS)

    Viator, John A.; Svaasand, Lars O.; Aguilar, Guillermo; Choi, Bernard; Nelson, J. Stuart

    2003-06-01

    Most dermatologic laser procedures must consider epidermal melanin, as it is a broadband optical absorber which affects subsurface fluence, effectively limiting the amount of light reaching the dermis and targeted chromophores. An accurate method for quantifying epidermal melanin content would aid clinicians in determining proper light dosage for therapeutic laser procedures. While epidermal melanin content has been quantified non-invasively using optical methods, there is currently no way to determine the melanin distribution in the epidermis. We have developed a photoacoustic probe that uses a Q-switched, frequency doubled Nd:YAG laser operating at 532nm to generate acoustic pulses in skin in vivo. The probe contained a piezoelectric element that detected photoacoustic waves which were then analyzed for epidermal melanin content, using a photoacoustic melanin index (PAMI). We tested 15 human subjects with skin types I--VI using the photoacoustic probe. We also present photoacoustic data for a human subject with vitiligo. Photoacoustic measurement showed melanin in the vitiligo subject was almost completely absent.

  12. Epidermal and urethroid penile cyst.

    PubMed

    Claudy, A L; Dutoit, M; Boucheron, S

    1991-01-01

    The authors describe a 74-year-old man who presented with a 2-cm nodule on the ventral face of the penis, showing histologically a cyst lined by both epidermal and urethroid epithelium. The authors discuss the various histological forms of raphe median cysts of the penis. PMID:1676220

  13. Epidermal cyst of median raphe.

    PubMed

    LaNasa, J A

    1976-10-01

    Cysts of the penis are rare and references to them in standard textbooks are sketchy. A case report of a congenital epidermal cyst of the median raphe of the penis is presented; therapy involved excision of the mass. Review of the literature is given. PMID:973298

  14. Examination of endothelial cell-induced epidermal regeneration in a mice-based chimney wound model.

    PubMed

    Seo, Joseph; Park, Soon-Jung; Choi, Jong-Jin; Kang, Sun-Woong; Lim, Joa-Jin; Lee, Hye-Jin; Kim, Jong-Soo; Yang, Heung-Mo; Kim, Sung-Joo; Kim, Eun-Young; Park, Se-Pil; Moon, Sung-Hwan; Chung, Hyung-Min

    2016-07-01

    As wound contraction in the cutaneous layer occurs rapidly in mice, mechanical means are typically used to deliberately expose the wound to properly investigate healing by secondary intention. Previously, silicon rings and splinting models were attempted to analyze histological recovery but prevention of surrounding epidermal cell migration and subsequent closure was minimal. Here, we developed an ideal chimney wound model to evaluate epidermal regeneration in murine under hESC-EC transplantation through histological analysis encompassing the three phases of regeneration: migration, proliferation, and remodeling. Human embryonic stem cell derived endothelial cells (hESC-EC) were transplanted due to possessing a well-known therapeutic effect in angiogenesis which also enhances epidermal repair to depict the process of regeneration. Following a standard 1 mm biopsy punch, a chimney manufactured by modifying a 1.7 mL microtube was simply inserted into the excisional wound to complete the modeling process. Under this model, the excisional wound remained fully exposed for 14 days and even after 4 weeks, only a thin transparent layer of epidermal tissue covered the wound site. This approach is able to more accurately depict epidermal repair in relation to histology while also being a user-friendly and cost-effective way to mimic human recovery in rodents and evaluate epithelial repair induced by a form of therapy. PMID:27237949

  15. Towards a Quantitative Theory of Epidermal Calcium Profile Formation in Unwounded Skin

    PubMed Central

    Adams, Matthew P.; Mallet, Daniel G.; Pettet, Graeme J.

    2015-01-01

    We propose and mathematically examine a theory of calcium profile formation in unwounded mammalian epidermis based on: changes in keratinocyte proliferation, fluid and calcium exchange with the extracellular fluid during these cells’ passage through the epidermal sublayers, and the barrier functions of both the stratum corneum and tight junctions localised in the stratum granulosum. Using this theory, we develop a mathematical model that predicts epidermal sublayer transit times, partitioning of the epidermal calcium gradient between intracellular and extracellular domains, and the permeability of the tight junction barrier to calcium ions. Comparison of our model’s predictions of epidermal transit times with experimental data indicates that keratinocytes lose at least 87% of their volume during their disintegration to become corneocytes. Intracellular calcium is suggested as the main contributor to the epidermal calcium gradient, with its distribution actively regulated by a phenotypic switch in calcium exchange between keratinocytes and extracellular fluid present at the boundary between the stratum spinosum and the stratum granulosum. Formation of the extracellular calcium distribution, which rises in concentration through the stratum granulosum towards the skin surface, is attributed to a tight junction barrier in this sublayer possessing permeability to calcium ions that is less than 15 nm s−1 in human epidermis and less than 37 nm s−1 in murine epidermis. Future experimental work may refine the presented theory and reduce the mathematical uncertainty present in the model predictions. PMID:25625723

  16. Maintenance Budgeting.

    ERIC Educational Resources Information Center

    Smith, J. McCree

    Three methods for the preparation of maintenance budgets are discussed--(1) a traditional method, inconclusive and obsolete, based on gross square footage, (2) the formula approach method based on building classification (wood-frame, masonry-wood, masonry-concrete) with maintenance cost factors for each type plus custodial service rates by type of…

  17. Preventative Maintenance.

    ERIC Educational Resources Information Center

    Migliorino, James

    Boards of education must be convinced that spending money up front for preventive maintenance will, in the long run, save districts' tax dollars. A good program of preventive maintenance can minimize disruption of service; reduce repair costs, energy consumption, and overtime; improve labor productivity and system equipment reliability; handle…

  18. Software Maintenance.

    ERIC Educational Resources Information Center

    Cannon, Glenn; Jobe, Holly

    Proper cleaning and storage of audiovisual aids is outlined in this brief guide. Materials and equipment needed for first line maintenance are listed, as well as maintenance procedures for records, audio and video tape, film, filmstrips, slides, realia, models, prints, graphics, maps, and overhead transparencies. A 15-item quiz on software…

  19. Maintenance Downtime

    Atmospheric Science Data Center

    2013-07-10

    ... will be unavailable March 5, 2013 8:00 am to 5:00 pm due to database maintenance. Date(s):  Tuesday, March 5, 2013 ... will be unavailable March 5, 2013 8:00 am to 5:00 pm due to database maintenance. ...

  20. Evolution of dinosaur epidermal structures.

    PubMed

    Barrett, Paul M; Evans, David C; Campione, Nicolás E

    2015-06-01

    Spectacularly preserved non-avian dinosaurs with integumentary filaments/feathers have revolutionized dinosaur studies and fostered the suggestion that the dinosaur common ancestor possessed complex integumentary structures homologous to feathers. This hypothesis has major implications for interpreting dinosaur biology, but has not been tested rigorously. Using a comprehensive database of dinosaur skin traces, we apply maximum-likelihood methods to reconstruct the phylogenetic distribution of epidermal structures and interpret their evolutionary history. Most of these analyses find no compelling evidence for the appearance of protofeathers in the dinosaur common ancestor and scales are usually recovered as the plesiomorphic state, but results are sensitive to the outgroup condition in pterosaurs. Rare occurrences of ornithischian filamentous integument might represent independent acquisitions of novel epidermal structures that are not homologous with theropod feathers. PMID:26041865

  1. Evolution of dinosaur epidermal structures

    PubMed Central

    Barrett, Paul M.; Evans, David C.; Campione, Nicolás E.

    2015-01-01

    Spectacularly preserved non-avian dinosaurs with integumentary filaments/feathers have revolutionized dinosaur studies and fostered the suggestion that the dinosaur common ancestor possessed complex integumentary structures homologous to feathers. This hypothesis has major implications for interpreting dinosaur biology, but has not been tested rigorously. Using a comprehensive database of dinosaur skin traces, we apply maximum-likelihood methods to reconstruct the phylogenetic distribution of epidermal structures and interpret their evolutionary history. Most of these analyses find no compelling evidence for the appearance of protofeathers in the dinosaur common ancestor and scales are usually recovered as the plesiomorphic state, but results are sensitive to the outgroup condition in pterosaurs. Rare occurrences of ornithischian filamentous integument might represent independent acquisitions of novel epidermal structures that are not homologous with theropod feathers. PMID:26041865

  2. Characterization of microfluidic human epidermal keratinocyte culture

    PubMed Central

    O’Neill, Adrian T.; Monteiro-Riviere, Nancy A.

    2008-01-01

    Human epidermal keratinocytes (HEK) are skin cells of primary importance in maintaining the body’s defensive barrier and are used in vitro to assess the irritation potential and toxicity of chemical compounds. Microfluidic systems hold promise for high throughput irritant and toxicity assays, but HEK growth kinetics have yet to be characterized within microscale culture chambers. This research demonstrates HEK patterning on microscale patches of Type I collagen within microfluidic channels and maintenance of these cells under constant medium perfusion for 72 h. HEK were shown to maintain 93.0%–99.6% viability at 72 h under medium perfusion ranging from 0.025–0.4 μl min−1. HEK maintained this viability while ∼100% confluent—a level not possible in 96 well plates. Microscale HEK cultures offer the ability to precisely examine the morphology, behavior and viability of individual cells which may open the door to new discoveries in toxicological screening methods and wound healing techniques. PMID:19002858

  3. sPLA2 and the epidermal barrier

    PubMed Central

    Ilic, Dusko; Bollinger, James M.; Gelb, Michael; Mauro, Theodora M.

    2015-01-01

    The mammalian epidermis provides both an interface and a protective barrier between the organism and its environment. Lipid, processed into water-impermeable bilayers between the outermost layers of the epidermal cells, forms the major barrier that prevents water from exiting the organism, and also prevents toxins and infectious agents from entering. The secretory phospholipase 2 (sPLA2) enzymes control important processes in skin and other organs, including inflammation and differentiation. sPLA2 activity contributes to epidermal barrier formation and homeostasis by generating free fatty acids, which are required both for formation of lamellar membranes and also for acidification of the stratum corneum (SC). sPLA2 is especially important in controlling SC acidification and establishment of an optimum epidermal barrier during the first postnatal week. Several sPLA2 isoforms are present in the epidermis. We find that two of these isoforms, sPLA2 IIA and sPLA2 IIF, localize to the upper stratum granulosum and increase in response to experimental barrier perturbation. sPLA2F−/− mice also demonstrate a more neutral SC pH than do their normal littermates, and their initial recovery from barrier perturbation is delayed. These findings confirm that sPLA2 enzymes perform important roles in epidermal development, and suggest that the sPLA2IIF isoform may be central to SC acidification and barrier function. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. PMID:24269828

  4. 25 YEARS OF EPIDERMAL STEM CELLS

    PubMed Central

    Ghadially, Ruby

    2012-01-01

    This is a chronicle of concepts in the field of epidermal stem cell biology and a historic look at their development over time. The last 25 years have seen the evolution of epidermal stem cell science, from first fundamental studies to a sophisticated science. The study of epithelial stem cell biology was aided by the ability to visualize the distribution of stem cells and their progeny through lineage analysis studies. The excellent progress we have made in understanding epidermal stem cell biology is discussed in this article. The challenges we still face in understanding epidermal stem cell include defining molecular markers for stem and progenitor subpopulations, determining the locations and contributions of the different stem cell niches, and mapping regulatory pathways of epidermal stem cell proliferation and differentiation. However, our rapidly evolving understanding of epidermal stem cells has many potential uses that promise to translate into improved patient therapy. PMID:22205306

  5. Caspase deficiency alters the murine gut microbiome

    PubMed Central

    Brinkman, B M; Hildebrand, F; Kubica, M; Goosens, D; Del Favero, J; Declercq, W; Raes, J; Vandenabeele, P

    2011-01-01

    Caspases are aspartate-specific cysteine proteases that have an essential role in apoptosis and inflammation, and contribute to the maintenance of homeostasis in the intestine. These facts, together with the knowledge that caspases are implicated in host-microbe crosstalk, prompted us to investigate the effect of caspase (Casp)1, -3 and -7 deficiency on the composition of the murine gut microbiota. We observed significant changes in the abundance of the Firmicutes and Bacteroidetes phyla, in particular the Lachnospiraceae, Porphyromonodaceae and Prevotellacea families, when comparing Casp-1, -7 and -3 knockout mice with wild-type mice. Our data point toward an intricate relationship between these caspases and the composition of the murine gut microflora. PMID:22012254

  6. Cloning of murine ferrochelatase.

    PubMed Central

    Brenner, D A; Frasier, F

    1991-01-01

    Ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) catalyzes the last step in the heme biosynthetic pathway, the chelation of ferrous iron and protoporphyrin to form heme. The activity of ferrochelatase is deficient in the inherited disease protoporphyria. In this study, murine ferrochelatase cDNAs were obtained by screening cDNA libraries with an oligonucleotide probe. The derived amino acid sequence of murine ferrochelatase has 47% identity with the recently cloned Saccharomyces cerevisiae ferrochelatase, but it is not significantly similar to other published sequences. Results of Southern blotting are consistent with a single murine ferrochelatase gene, while Northern blotting demonstrates two ferrochelatase transcripts in all tissues examined. The ferrochelatase protein and mRNAs have different relative concentrations in different tissues. The cloning of murine ferrochelatase cDNAs provides the basis for future studies on ferrochelatase gene expression and on the identification of the molecular defect in protoporphyria. Images PMID:1704134

  7. Penile Epidermal Cyst: A Case Report.

    PubMed

    Kumaraguru, Veerapandian; Prabhu, Ravi; Kannan, Narayanasamy Subbaraju

    2016-05-01

    Epidermal cysts also known as epidermoid cysts, is one of the common benign tumours presenting anywhere in the body. However, epidermal cyst in the penis is very rare. This condition in children is usually congenital due to abnormal embryologic closure of the median raphe; hence, it is termed as median raphe cysts (MRCs). Penile epidermal cysts may occur in adults following trauma or surgery due to epidermal elements being trapped within closed space. During wound healing, trapped squamous epithelium, undergoing keratinisation leads to cyst formation. Here, we report a rare case of patient with a penile epidermoid cyst whose main complaints was discomfort during coitus. PMID:27437298

  8. Penile Epidermal Cyst: A Case Report

    PubMed Central

    Kumaraguru, Veerapandian; Prabhu, Ravi

    2016-01-01

    Epidermal cysts also known as epidermoid cysts, is one of the common benign tumours presenting anywhere in the body. However, epidermal cyst in the penis is very rare. This condition in children is usually congenital due to abnormal embryologic closure of the median raphe; hence, it is termed as median raphe cysts (MRCs). Penile epidermal cysts may occur in adults following trauma or surgery due to epidermal elements being trapped within closed space. During wound healing, trapped squamous epithelium, undergoing keratinisation leads to cyst formation. Here, we report a rare case of patient with a penile epidermoid cyst whose main complaints was discomfort during coitus. PMID:27437298

  9. Cross-reactivity of autoantibodies from patients with epidermolysis bullosa acquisita with murine collagen VII.

    PubMed

    Csorba, Kinga; Sesarman, Alina; Oswald, Eva; Feldrihan, Vasile; Fritsch, Anja; Hashimoto, Takashi; Sitaru, Cassian

    2010-04-01

    The pathomechanism of antibody-mediated tissue damage in autoimmune diseases can be best studied in experimental models by passively transferring specific autoantibodies into animals. The reproduction of the disease in animals depends on several factors, including the cross-reactivity of patient autoantibodies with the animal tissue. Here, we show that autoantibodies from patients with epidermolysis bullosa acquisita (EBA), a subepidermal autoimmune blistering disease, recognize multiple epitopes on murine collagen VII. Indirect immunofluorescence microscopy revealed that EBA patients' IgG cross-reacts with mouse skin. Overlapping, recombinant fragments of murine collagen VII were used to characterize the reactivity of EBA sera and to map the epitopes on the murine antigen by ELISA and immunoblotting. The patients' autoantibody binding to murine collagen VII triggered pathogenic events as demonstrated by a complement fixing and an ex vivo granulocyte-dependent dermal-epidermal separation assay. These findings should greatly facilitate the development of improved disease models and novel therapeutic strategies. PMID:20084423

  10. Proteins deposited in the dermis are rapidly captured and presented by epidermal Langerhans cells

    PubMed Central

    Flacher, Vincent; Tripp, Christoph H.; Stoitzner, Patrizia; Haid, Bernhard; Ebner, Susanne; Koch, Franz; Park, Chae Gyu; Steinman, Ralph M.; Idoyaga, Juliana; Romani, Nikolaus

    2010-01-01

    Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DC) such as epidermal Langerhans cells (LC), dermal DC and dermal langerin+ DC. To evaluate access of dermal antigens to skin DC, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAb were efficiently taken up by epidermal LC. Additionally, anti-DEC-205 targeted langerin+ CD103+ and langerin− CD103− mouse dermal DC. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labelling of LC in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LC targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells. Thus, epidermal LC play a major role in uptake of lectin-binding ligands under standard vaccination conditions. PMID:19890348

  11. [Staphylococcal epidermal exfoliation (Ritter's disease)].

    PubMed

    Ruiz Maldonado, R; Tamayo, L; Vazquez, V; Dominguez, J

    1976-01-01

    According to the authors the best designation of Ritter's disease would be "staphilococcic epidermal exfoliation" SEE. The physiopathological and agnoslogical basis for this denomination could be the following: 1st The "S. aureus" is the ehtiological agent of the SSE in man. The Koch postulates necessary to confirm this hypothesis have been accomplished. 2nd "Staphylococcus aureus" produces a thermostable toxin that is active indepently of the staphilococcus and gives rise to the separation of the cells of the stratum granulosus of the epidermis and eventually exfoliation in suckling babies and in the newborn mouse. 3rd The "Staphylococcus aureus" may be present on the skin or in other localisations such as the bowel or pharinx. 4th The viable "S. aureus" when administered subcutaneously to the adult mice gives rise to lesions clinically and histologically similar to the impetigo observed in children. 5th The "S. aureus" killed by means of autoclave (that is, the staphylococcic toxine by itself does not give rise to any lesion when administered to the healthy adult mouse). Neijther has the SEE been observed in healthy adult man. The authors reach the conclusion that the SSE and the toxic epidermal necrolysis are basically different according to the histopathology therapeutic response and prognosis and they must be considered as independant entities. PMID:138775

  12. Privatizing Maintenance.

    ERIC Educational Resources Information Center

    Hounsell, Dan

    1996-01-01

    Schools and other government facilities want to see whether privatization of maintenance can provide services as efficiently and at less cost than inhouse workers. Privatization proponents say that everyone will benefit the most if the bidding process involves competition. Offers examples from the Memphis City Schools and the Union Public Schools…

  13. Epidermal Stem Cells in Orthopaedic Regenerative Medicine

    PubMed Central

    Li, Jin; Zhen, Gehua; Tsai, Shin-Yi; Jia, Xiaofeng

    2013-01-01

    In the last decade, great advances have been made in epidermal stem cell studies at the cellular and molecular level. These studies reported various subpopulations and differentiations existing in the epidermal stem cell. Although controversies and unknown issues remain, epidermal stem cells possess an immune-privileged property in transplantation together with easy accessibility, which is favorable for future clinical application. In this review, we will summarize the biological characteristics of epidermal stem cells, and their potential in orthopedic regenerative medicine. Epidermal stem cells play a critical role via cell replacement, and demonstrate significant translational potential in the treatment of orthopedic injuries and diseases, including treatment for wound healing, peripheral nerve and spinal cord injury, and even muscle and bone remodeling. PMID:23727934

  14. Epidermal Viral Immunity Induced by CD8α+ Dendritic Cells But Not by Langerhans Cells

    NASA Astrophysics Data System (ADS)

    Allan, Rhys S.; Smith, Chris M.; Belz, Gabrielle T.; van Lint, Allison L.; Wakim, Linda M.; Heath, William R.; Carbone, Francis R.

    2003-09-01

    The classical paradigm for dendritic cell function derives from the study of Langerhans cells, which predominate within skin epidermis. After an encounter with foreign agents, Langerhans cells are thought to migrate to draining lymph nodes, where they initiate T cell priming. Contrary to this, we show here that infection of murine epidermis by herpes simplex virus did not result in the priming of virus-specific cytotoxic T lymphocytes by Langerhans cells. Rather, the priming response required a distinct CD8α+ dendritic cell subset. Thus, the traditional view of Langerhans cells in epidermal immunity needs to be revisited to accommodate a requirement for other dendritic cells in this response.

  15. Epidermal changes following application of 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate to human skin transplanted to nude mice studied with histological species markers

    SciTech Connect

    Graem, N.

    1986-01-01

    Effects of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) and of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on epidermis of human fetal and adult skin were studied in the nude mouse/human skin model. Human skin grafts on NC nude mice were exposed to two topical applications of 1 mg of DMBA in 50 microliter of acetone with an interval of 3 days and/or to applications of 10 micrograms of TPA in 50 microliter of acetone twice weekly. In some animals, it was attempted to augment the susceptibility of the grafts to the tumor-initiating effect of DMBA by pretreatment with TPA or ultraviolet light. The mice were sacrificed 8-32 wk after the initial treatment. Tumors did not appear in the central portions of any of the grafts, but epidermal tumors were seen at the graft border in 34.9% of the DMBA-treated animals. To identify human epidermis on the grafts and to determine the species origin of the induced tumors, two independently working histological marker methods were applied. (a) The first is detection of a human Blood Group B-like antigen present in mouse epidermis and in chemically induced murine epidermal tumors. This antigen cannot be demonstrated in human epidermis and in epidermal tumors of human patients. (b) The second is histological staining with the DNA-specific fluorochrome, bisbenzimide, displaying a characteristic pattern of 5-10 intranuclear fluorescent bodies in murine nonneoplastic epidermal cells and in murine epidermal tumor cells. Such a pattern is not seen in human epidermis and in epidermal tumors of human patients. The studies showed that TPA treatment resulted in epidermal hyperplasia in both the human epidermis and the adjacent mouse epidermis and that the induced tumors were derived from murine tissue.

  16. Periodontal maintenance.

    PubMed

    Tan, A E S

    2009-09-01

    The main goal of periodontal therapy is to establish an oral environment compatible with periodontal health by the physical disruption of the plaque biofilm and adjunctive chemical means if required. Implicit in this objective is the ongoing requirement of detection and interception of new and recurrent disease, which continues at selected intervals for the life of the dentition after the initial ("active") phase of periodontal treatment. This concept of ongoing periodontal maintenance therapy has been embraced as the mandatory requirement for favourable periodontal outcomes based on institutional clinical trials and in practice-based studies in various parts of the world. This review examines the ramifications of periodontal maintenance therapy based upon a multi-level assessment of logistic issues and risk factors at three levels: (1) The patient level - treatment time; patient attendance compliance; and homecare measures, antiseptics/antibiotics and smoking. (2) The level of the individual tooth - tooth loss; and evaluation of success versus survival. (3) The level of each tooth surface ("site") - probing depth, loss of attachment and bleeding on probing; and changes in clinical attachment levels. In spite of the diversity of studies conducted, there is agreement on the efficacy of periodontal maintenance therapy when compared with studies on untreated populations and in treated cases that were not maintained. PMID:19737263

  17. Human and murine erythropoiesis

    PubMed Central

    An, Xiuli; Schulz, Vincent P.; Mohandas, Narla; Gallagher, Patrick G.

    2015-01-01

    Purpose of review Research into the fundamental mechanisms of erythropoiesis has provided critical insights into inherited and acquired disorders of the erythrocyte. Studies of human erythropoiesis have primarily utilized in-vitro systems, whereas murine models have provided insights from in-vivo studies. This report reviews recent insights into human and murine erythropoiesis gained from transcriptome-based analyses. Recent findings The availability of high-throughput genomic methodologies has allowed attainment of detailed gene expression data from cells at varying developmental and differentiation stages of erythropoiesis. Transcriptome analyses of human and murine reveal both stage and species-specific similarities and differences across terminal erythroid differentiation. Erythroid-specific long noncoding RNAs exhibit poor sequence conservation between human and mouse. Genome-wide analyses of alternative splicing reveal that complex, dynamic, stage-specific programs of alternative splicing program are utilized during terminal erythroid differentiation. Transcriptome data provide a significant resource for understanding mechanisms of normal and perturbed erythropoiesis. Understanding these processes will provide innovative strategies to detect, diagnose, prevent, and treat hematologic disease. Summary Understanding the shared and different mechanisms controlling human and murine erythropoiesis will allow investigators to leverage the best model system to provide insights in normal and perturbed erythropoiesis. PMID:25719574

  18. Microtubules CLASP to Adherens Junctions in epidermal progenitor cells.

    PubMed

    Shahbazi, Marta N; Perez-Moreno, Mirna

    2014-01-01

    Cadherin-mediated cell adhesion at Adherens Junctions (AJs) and its dynamic connections with the microtubule (MT) cytoskeleton are important regulators of cellular architecture. However, the functional relevance of these interactions and the molecular players involved in different cellular contexts and cellular compartments are still not completely understood. Here, we comment on our recent findings showing that the MT plus-end binding protein CLASP2 interacts with the AJ component p120-catenin (p120) specifically in progenitor epidermal cells. Absence of either protein leads to alterations in MT dynamics and AJ functionality. These findings represent a novel mechanism of MT targeting to AJs that may be relevant for the maintenance of proper epidermal progenitor cell homeostasis. We also discuss the potential implication of other MT binding proteins previously associated to AJs in the wider context of epithelial tissues. We hypothesize the existence of adaptation mechanisms that regulate the formation and stability of AJs in different cellular contexts to allow the dynamic behavior of these complexes during tissue homeostasis and remodeling. PMID:24522006

  19. Microtubules CLASP to Adherens Junctions in epidermal progenitor cells

    PubMed Central

    Shahbazi, Marta N; Perez-Moreno, Mirna

    2014-01-01

    Cadherin-mediated cell adhesion at Adherens Junctions (AJs) and its dynamic connections with the microtubule (MT) cytoskeleton are important regulators of cellular architecture. However, the functional relevance of these interactions and the molecular players involved in different cellular contexts and cellular compartments are still not completely understood. Here, we comment on our recent findings showing that the MT plus-end binding protein CLASP2 interacts with the AJ component p120-catenin (p120) specifically in progenitor epidermal cells. Absence of either protein leads to alterations in MT dynamics and AJ functionality. These findings represent a novel mechanism of MT targeting to AJs that may be relevant for the maintenance of proper epidermal progenitor cell homeostasis. We also discuss the potential implication of other MT binding proteins previously associated to AJs in the wider context of epithelial tissues. We hypothesize the existence of adaptation mechanisms that regulate the formation and stability of AJs in different cellular contexts to allow the dynamic behavior of these complexes during tissue homeostasis and remodeling. PMID:24522006

  20. Galectin-7 in the Control of Epidermal Homeostasis after Injury

    PubMed Central

    Gendronneau, Gaëlle; Sidhu, Sukhvinder S.; Delacour, Delphine; Dang, Tien; Calonne, Chloé; Houzelstein, Denis; Magnaldo, Thierry

    2008-01-01

    Galectins, a family of β-galactoside binding lectins, have recently emerged as novel regulators of tissue homeostasis. Galectin-7 is predominantly expressed in stratified epithelia, especially in epidermis. We report here the generation of galectin-7–deficient mice that are viable and do not display phenotypical abnormalities in skin structure or expression of epidermal markers. However, these mice show unique defects in the maintenance of epidermal homeostasis in response to environmental challenges. First, after UVB irradiation in vivo, the apoptotic response is prematurely triggered and lasts longer in the mutant epidermis. This result contrasts with the proapoptotic role that had been proposed for galectin-7. Second, wound-healing experiments in vivo revealed that galectin-7–deficient mice displayed a reduced reepithelialization potential compared with wild-type littermates. This effect could be attributed to a defect in cell migration. Because galectin-7 is located in the podosomes of keratinocytes migrating out of skin explants in culture, we propose that this glycan-binding protein may directly influence cell/extracellular matrix interactions. Finally, we also detected an unexpected intense hyperproliferative reaction consecutive to both types of stress in galectin-7–deficient mice. Together, these studies provide the first genetic evidence showing that galectin-7 can modulate keratinocyte apoptosis, proliferation, and migration during skin repair. PMID:18829868

  1. Loss of desmocollin 3 in mice leads to epidermal blistering.

    PubMed

    Chen, Jiangli; Den, Zhining; Koch, Peter J

    2008-09-01

    Desmocollin 3 (DSC3) belongs to a subfamily of cadherins and is a major component of desmosomes in keratinocytes of stratified epithelia, such as the epidermis. Based on its amino acid sequence homology to classical cadherins, such as E-cadherin, it has been postulated that DSC3 functions as a cell-adhesion molecule. To test this hypothesis, we assessed the function of DSC3 in the development and maintenance of stratified epithelia, in particular the epidermis and hair follicles. Using a conditional null allele, we show that loss of Dsc3 function in the epidermis causes impaired cell-cell adhesion, leading to intra-epidermal blistering and telogen hair loss. Furthermore, the lesions in Dsc3-null skin resemble those observed in individuals with pemphigus vulgaris (PV), indicating that impaired Dsc3 function could be a potential cause of PV-like inherited or acquired skin blistering diseases. PMID:18682494

  2. Calcium, Orai1 and Epidermal Proliferation

    PubMed Central

    Bikle, DD; Mauro, T

    2014-01-01

    Ca2+ influx controls essential epidermal functions, including proliferation, differentiation, cell migration, itch, and barrier homeostasis. The Orai1 ion channel allows capacitive Ca2+ influx after Ca2+ release from the endoplasmic reticulum, and it has now been shown to modulate epidermal atrophy. These findings reveal new interactions among various Ca2+ signaling pathways and uncover novel functions for Ca2+ signaling via the Orai1 channel. PMID:24825060

  3. Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice.

    PubMed

    Aberg, Karin M; Radek, Katherine A; Choi, Eung-Ho; Kim, Dong-Kun; Demerjian, Marianne; Hupe, Melanie; Kerbleski, Joseph; Gallo, Richard L; Ganz, Tomas; Mauro, Theodora; Feingold, Kenneth R; Elias, Peter M

    2007-11-01

    The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased the severity of group A Streptococcus pyogenes (GAS) cutaneous skin infection in mice; this was accompanied by increased production of endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis and decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), and PS or systemic or topical GC administration downregulated epidermal expression of murine AMPs cathelin-related AMP and beta-defensin 3. Pharmacological blockade of the stress hormone corticotrophin-releasing factor or of peripheral GC action, as well as topical administration of physiologic lipids, normalized epidermal AMP levels and delivery to LBs and decreased the severity of GAS infection during PS. Our results show that PS decreases the levels of 2 key AMPs in the epidermis and their delivery into LBs and that this is attributable to increased endogenous GC production. These data suggest that GC blockade and/or topical lipid administration could normalize cutaneous antimicrobial defense during PS or GC increase. We believe this to be the first mechanistic link between PS and increased susceptibility to infection by microbial pathogens. PMID:17975669

  4. Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice

    PubMed Central

    Aberg, Karin M.; Radek, Katherine A.; Choi, Eung-Ho; Kim, Dong-Kun; Demerjian, Marianne; Hupe, Melanie; Kerbleski, Joseph; Gallo, Richard L.; Ganz, Tomas; Mauro, Theodora; Feingold, Kenneth R.; Elias, Peter M.

    2007-01-01

    The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased the severity of group A Streptococcus pyogenes (GAS) cutaneous skin infection in mice; this was accompanied by increased production of endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis and decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), and PS or systemic or topical GC administration downregulated epidermal expression of murine AMPs cathelin-related AMP and β-defensin 3. Pharmacological blockade of the stress hormone corticotrophin-releasing factor or of peripheral GC action, as well as topical administration of physiologic lipids, normalized epidermal AMP levels and delivery to LBs and decreased the severity of GAS infection during PS. Our results show that PS decreases the levels of 2 key AMPs in the epidermis and their delivery into LBs and that this is attributable to increased endogenous GC production. These data suggest that GC blockade and/or topical lipid administration could normalize cutaneous antimicrobial defense during PS or GC increase. We believe this to be the first mechanistic link between PS and increased susceptibility to infection by microbial pathogens. PMID:17975669

  5. Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

    PubMed Central

    Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean

    2012-01-01

    Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868

  6. The ontogeny of epidermal growth factor receptors during mouse development

    SciTech Connect

    Adamson, E.D.; Meek, J.

    1984-05-01

    In an attempt to understand the role(s) of epidermal growth factor (EGF) in vivo during murine development, we have examined the /sup 125/I-EGF binding characteristics of EGF-receptors in membrane preparations of tissues from the 12th day of gestation to parturition. Using autoradiography, the earliest time that we could detect EGF-receptors was on trophoblast cells cultured for 3 days as blastocyst outgrowths. Trophoblast eventually forms a large portion of the placenta, where EGF-receptors have long been recognized. We measured the number and affinity of EGF-receptors on tissues dissected from conceptuses from the 12th day of gestation in order to identify a stage when tissues may be most sensitive to EGF. Whereas the number of EGF receptors increases during gestation for all tissues examined, the affinity of the receptors declines for carcass and placenta and remains relatively unchanged for brain and liver. This suggests that EGF may function differently throughout development. Our hypothesis is that EGF (or its embryonic equivalent) initially stimulates proliferation in embryonic cells and then stimulates differentiation as the tissues mature. In the adult, its main role could be to stimulate tissue repair after damage.

  7. Mechanotransduction in epidermal Merkel cells

    PubMed Central

    Nakatani, Masashi; Maksimovic, Srdjan; Baba, Yoshichika; Lumpkin, Ellen A.

    2014-01-01

    The cellular and molecular basis of vertebrate touch reception remains least understood among the traditional five senses. Somatosensory afferents that innervate the skin encode distinct tactile qualities, such as flutter, slip and pressure. Gentle touch is thought to be transduced by somatosensory afferents whose tactile end organs selectively filter mechanical stimuli. These tactile end organs comprise afferent terminals in association with non-neuronal cell types such as Merkel cells, keratinocytes and Schwann cells. An open question is whether these non-neuronal cells serve primarily as passive mechanical filters or whether they actively participate in mechanosensory transduction. This question has been most extensively studied in Merkel cells, which are epidermal cells that complex with sensory afferents in regions of high tactile acuity such as fingertips, whisker follicles, and touch domes. Merkel cell-neurite complexes mediate slowly adapting type I (SAI) responses, which encode sustained pressure and represent object features with high fidelity. How Merkel cells contribute to unique SAI firing patterns has been debated for decades; however, three recent studies in rodent models provide some direct answers. First, whole-cell recordings demonstrate that Merkel cells are touch-sensitive cells with fast, mechanically activated currents that require Piezo2. Second, optogenetics and intact recordings show that Merkel cells mediate sustained SAI firing. Finally, loss-of-function studies in transgenic mouse models reveal that SAI afferents are also touch sensitive. Together, these studies identify molecular mechanisms of mechanotransduction in Merkel cells, reveal unexpected functions for these cells in touch and support a revised, two-receptor site model of mechanosensory transduction. PMID:25053537

  8. Egr-5 is a post-mitotic regulator of planarian epidermal differentiation

    PubMed Central

    Tu, Kimberly C; Cheng, Li-Chun; TK Vu, Hanh; Lange, Jeffrey J; McKinney, Sean A; Seidel, Chris W; Sánchez Alvarado, Alejandro

    2015-01-01

    Neoblasts are an abundant, heterogeneous population of adult stem cells (ASCs) that facilitate the maintenance of planarian tissues and organs, providing a powerful system to study ASC self-renewal and differentiation dynamics. It is unknown how the collective output of neoblasts transit through differentiation pathways to produce specific cell types. The planarian epidermis is a simple tissue that undergoes rapid turnover. We found that as epidermal progeny differentiate, they progress through multiple spatiotemporal transition states with distinct gene expression profiles. We also identified a conserved early growth response family transcription factor, egr-5, that is essential for epidermal differentiation. Disruption of epidermal integrity by egr-5 RNAi triggers a global stress response that induces the proliferation of neoblasts and the concomitant expansion of not only epidermal, but also multiple progenitor cell populations. Our results further establish the planarian epidermis as a novel paradigm to uncover the molecular mechanisms regulating ASC specification in vivo. DOI: http://dx.doi.org/10.7554/eLife.10501.001 PMID:26457503

  9. Persistence of skin-resident memory T cells within an epidermal niche.

    PubMed

    Zaid, Ali; Mackay, Laura K; Rahimpour, Azad; Braun, Asolina; Veldhoen, Marc; Carbone, Francis R; Manton, Jonathan H; Heath, William R; Mueller, Scott N

    2014-04-01

    Barrier tissues such as the skin contain various populations of immune cells that contribute to protection from infections. These include recently identified tissue-resident memory T cells (TRM). In the skin, these memory CD8(+) T cells reside in the epidermis after being recruited to this site by infection or inflammation. In this study, we demonstrate prolonged persistence of epidermal TRM preferentially at the site of prior infection despite sustained migration. Computational simulation of TRM migration within the skin over long periods revealed that the slow rate of random migration effectively constrains these memory cells within the region of skin in which they form. Notably, formation of TRM involved a concomitant local reduction in dendritic epidermal γδ T-cell numbers in the epidermis, indicating that these populations persist in mutual exclusion and may compete for local survival signals. Accordingly, we show that expression of the aryl hydrocarbon receptor, a transcription factor important for dendritic epidermal γδ T-cell maintenance in skin, also contributes to the persistence of skin TRM. Together, these data suggest that skin tissue-resident memory T cells persist within a tightly regulated epidermal T-cell niche. PMID:24706879

  10. Persistence of skin-resident memory T cells within an epidermal niche

    PubMed Central

    Zaid, Ali; Mackay, Laura K.; Rahimpour, Azad; Braun, Asolina; Veldhoen, Marc; Carbone, Francis R.; Manton, Jonathan H.; Heath, William R.; Mueller, Scott N.

    2014-01-01

    Barrier tissues such as the skin contain various populations of immune cells that contribute to protection from infections. These include recently identified tissue-resident memory T cells (TRM). In the skin, these memory CD8+ T cells reside in the epidermis after being recruited to this site by infection or inflammation. In this study, we demonstrate prolonged persistence of epidermal TRM preferentially at the site of prior infection despite sustained migration. Computational simulation of TRM migration within the skin over long periods revealed that the slow rate of random migration effectively constrains these memory cells within the region of skin in which they form. Notably, formation of TRM involved a concomitant local reduction in dendritic epidermal γδ T-cell numbers in the epidermis, indicating that these populations persist in mutual exclusion and may compete for local survival signals. Accordingly, we show that expression of the aryl hydrocarbon receptor, a transcription factor important for dendritic epidermal γδ T-cell maintenance in skin, also contributes to the persistence of skin TRM. Together, these data suggest that skin tissue-resident memory T cells persist within a tightly regulated epidermal T-cell niche. PMID:24706879

  11. Rab3Gap1 mediates exocytosis of Claudin-1 and tight junction formation during epidermal barrier acquisition

    PubMed Central

    Youssef, G.; Gerner, L.; Naeem, A.S.; Ralph, O.; Ono, M.; O’Neill, C.A.; O’Shaughnessy, R.F.L.

    2013-01-01

    Epidermal barrier acquisition during late murine gestation is accompanied by an increase in Akt kinase activity and cJun dephosphorlyation. The latter is directed by the Ppp2r2a regulatory subunit of the Pp2a phosphatase. This was accompanied by a change of Claudin-1 localisation to the cell surface and interaction between Occludin and Claudin-1 which are thought to be required for tight junction formation. The aim of this study was to determine the nature of the barrier defect caused by the loss of AKT/Ppp2r2a function. There was a paracellular barrier defect in rat epidermal keratinocytes expressing a Ppp2r2a siRNA. In Ppp2r2a knockdown cells, Claudin-1 was located to the cytoplasm and its expression was increased. Inhibiting cJun phosphorylation restored barrier function and plasma membrane localisation of Claudin-1. Expression of the Rab3 GTPase activating protein, Rab3Gap1, was restored in Ppp2r2a siRNA cells when cJun phosphorylation was inhibited. During normal mouse epidermal development, Claudin-1 plasma membrane localisation and Rab3Gap1 cell surface expression were co-incident with Akt activation in mouse epidermis, strongly suggesting a role of Rab3Gap1 in epidermal barrier acquisition. Supporting this hypothesis, siRNA knockdown of Rab3Gap1 prevented plasma membrane Claudin-1 expression and the formation of a barrier competent epithelium. Replacing Rab3Gap1 in Ppp2r2a knockdown cells was sufficient to rescue Claudin-1 transport to the cell surface. Therefore these data suggest Rab3Gap1 mediated exocytosis of Claudin-1 is an important component of epidermal barrier acquisition during epidermal development. PMID:23685254

  12. The cutaneous epidermal growth factor network: Can it be translated clinically to stimulate hair growth?

    PubMed

    Alexandrescu, Doru T; Kauffman, C Lisa; Dasanu, Constantin A

    2009-01-01

    The influences exerted by the epidermal growth factor receptor (EGFR) on the skin act at multiple levels, which involve compartments that normally express EGFR. These include the basal and suprabasal layers of the epidermis, sebaceous glands, and the outer root sheath of the hair follicles. The physiological roles of EGFR ensure epidermal renewal and integrity, along with a gatekeeping and function and hair growth stimulation functions. Important cellular functions that are altered during EGF receptor blocking therapy consist of epidermal differentiation, proliferation, apoptosis, and migration, with an overall dominating effect of inducing growth arrest and terminal differentiation of the keratinocytes in the basal layers. The effects of EGFR blockage on the hair cycle include terminal differentiation of the hair follicle, which in certain cases may be associated with trichomegaly. Trichomegaly of the eyelashes may occur as an isolated occurrence or, frequently, as part of a generalized phenomenon that may be associated with the use of the EGFR inhibitors. Molecular changes associated with EGFR blockage are discussed, relevant to their association with hair growth. Modulation of Akt, AP2alpha, CDK4, Notch-1, p27KIP1, and Hedgehog expression are involved in the initiation of the hair cycle and inducement of the anagen phase, followed by proliferation and differentiation of the hair follicles. Epidermal growth factor receptor inhibitors have been developed as therapeutic molecules directed against cancer; in these regimens the knowledge of EGF receptor signaling functions has been translated into significant clinical results. However, among their various collateral effects on the skin, hair growth is observed to occur in certain patients. A particular "wavy" hair phenotype is observed during the pharmacological EGFR receptor blockade, just as in murine transgenic models that carry loss of function of TGF-alpha or EGFR genes. A better characterization of the

  13. Epidermal melanin absorption in human skin

    NASA Astrophysics Data System (ADS)

    Norvang Nilsen, Lill T.; Fiskerstrand, Elisanne J.; Nelson, J. Stuart; Berns, Michael W.; Svaasand, Lars O.

    1996-01-01

    The principle of laser induced selective photothermolysis is to induced thermal damage to specific targets in such a manner that the temperature of the surrounding tissue is maintained below the threshold for thermal damage. The selectivity is obtained by selection of a proper wavelength and pulse duration. The technique is presently being used in the clinic for removal of port-wine stains. The presence of melanin in the epidermal layer can represent a limitation to the selectivity. Melanin absorption drops off significantly with increasing wavelength, but is significant in the entire wavelength region where the blood absorption is high. Treatment of port-wine stain in patients with high skin pigmentation may therefore give overheating of the epidermis, resulting in epidermal necrosis. Melanosomal heating is dependent on the energy and duration of the laser pulse. The heating mechanism for time scales less than typically 1 microsecond(s) corresponds to a transient local heating of the individual melanosomes. For larger time scales, heat diffusion out of the melanosomes become of increased importance, and the temperature distribution will reach a local steady state condition after typically 10 microsecond(s) . For even longer pulse duration, heat diffusing from neighboring melanosomes becomes important, and the temperature rise in a time scale from 100 - 500 microsecond(s) is dominated by this mechanism. The epidermal heating during the typical 450 microsecond(s) pulse used for therapy is thus dependent on the average epidermal melanin content rather than on the absorption coefficient of the individual melanosomes. This study will present in vivo measurements of the epidermal melanin absorption of human skin when exposed to short laser pulses (< 0.1 microsecond(s) ) from a Q-switched ruby laser and with long laser pulses (approximately 500 microsecond(s) ) from a free-running ruby laser or a long pulse length flashlamp pumped dye laser. The epidermal melanin

  14. Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates UV induced melanocyte homeostasis

    PubMed Central

    Hyter, Stephen; Coleman, Daniel J.; Ganguli-Indra, Gitali; Merrill, Gary F.; Ma, Steven; Yanagisawa, Masashi; Indra, Arup K.

    2013-01-01

    Summary Keratinocytes contribute to melanocyte activity by influencing their microenvironment, in part, through secretion of paracrine factors. Here we discovered that p53 directly regulates Edn1 expression in epidermal keratinocytes and controls UV-induced melanocyte homeostasis. Selective ablation of EDN1 in murine epidermis (EDN1ep−/−) does not alter melanocyte homeostasis in newborn skin but decreases dermal melanocytes in adult skin. Results showed that keratinocytic EDN1 in a non-cell autonomous manner controls melanocyte proliferation, migration, DNA damage and apoptosis after UVB irradiation. Expression of other keratinocyte derived paracrine factors did not compensate for the loss of EDN1. Topical treatment with EDN1 receptor (EDNRB) antagonist BQ788 abrogated UV induced melanocyte activation and recapitulated the phenotype seen in EDN1ep−/− mice. Altogether, present studies establish an essential role of EDN1 in epidermal keratinocytes to mediate UV induced melanocyte homeostasis in vivo. PMID:23279852

  15. Maintenance Business Plans.

    ERIC Educational Resources Information Center

    Adams, Matt

    2002-01-01

    Discusses maintenance business plans, statements which provide accountability for facilities maintenance organizations' considerable budgets. Discusses the plan's components: statement of plan objectives, macro and detailed description of the facility assets, maintenance function descriptions, description of key performance indicators, milestone…

  16. Penile Epidermal Cyst in a Patient With Augmentation Penoplasty

    PubMed Central

    Jung, Jae Hung; Eom, Minseob; Arkoncel, Francis Raymond P.; Sung, Yun Hsien; Kim, Won; Byun, Hyun Keun; Joo, Jung Min; Kim, Kwang Jin

    2013-01-01

    A 44-year-old male patient who had undergone augmentation penoplasty 20 years previously presented with a slowly growing penoscrotal mass. The penile mass was excised totally and the pathologic diagnosis was an epidermal cyst. Epidermal cysts are benign disorders that can occur in any part of the body. However, an epidermal cyst as a late complication of augmentation penoplasty is extremely rare. We report this case of a penile epidermal cyst that developed after augmentation penoplasty. PMID:23524950

  17. [Verrucous epidermal nevus of the face].

    PubMed

    Larroque, G; Cantaloube, D; Ndiaye, B; Jouen, F; Combemale, P

    1991-01-01

    The authors report a case of extensive verrucous epidermal naevus of the face in a 15 year old Senegalese boy. This is the second reported case in Western Africa following the case presented to the French Language African Medical Society in 1984 (B. Ndiaye). The skin lesion in the form of a naevus of variable dimensions is an essential manifestation of the epidermal naevus syndrome described by Solomon, Fretzin and Dewald in 1968. This syndrome consists of a variable but inconstant association of dysembryoplastic abnormalities affecting the central nervous system (epilepsy, mental retardation, hydrocephalus, localized central deficits), the eye (fibrous conjunctival tumours, corneal opacities, colobomas) and the bones (spine, clavicle, pelvis, limb bones). The bones may be affected by malformations or hypoplasia. The epidermal naevus generally has a linear verrucous appearance, but it is not exceptional to find Jadassohn's sebaceous naevus or even localized erythroderma ichthyosiformis. Mucosal lesions, especially oral, well described in 1960 by Brown and Gorlin, correspond to a particular localization of epidermal naevus and must be differentiated histologically from white sponge naevus, which has a fairly similar clinical appearance. This non-hereditary disease must be systematically investigated looking for visceral abnormalities which are very common. Lastly, in terms of therapy, surgery may be justified when the facial lesions are unsightly, extensive or disabling. Various techniques may be applied depending on the extent and the site of these naevi. PMID:1718208

  18. Constitutive Autophagy and Nucleophagy during Epidermal Differentiation.

    PubMed

    Akinduro, Olufolake; Sully, Katherine; Patel, Ankit; Robinson, Deborah J; Chikh, Anissa; McPhail, Graham; Braun, Kristin M; Philpott, Michael P; Harwood, Catherine A; Byrne, Carolyn; O'Shaughnessy, Ryan F L; Bergamaschi, Daniele

    2016-07-01

    Epidermal keratinocytes migrate through the epidermis up to the granular layer where, on terminal differentiation, they progressively lose organelles and convert into anucleate cells or corneocytes. Our report explores the role of autophagy in ensuring epidermal function providing the first comprehensive profile of autophagy marker expression in developing epidermis. We show that autophagy is constitutively active in the epidermal granular layer where by electron microscopy we identified double-membrane autophagosomes. We demonstrate that differentiating keratinocytes undergo a selective form of nucleophagy characterized by accumulation of microtubule-associated protein light chain 3/lysosomal-associated membrane protein 2/p62 positive autolysosomes. These perinuclear vesicles displayed positivity for histone interacting protein, heterochromatin protein 1α, and localize in proximity with Lamin A and B1 accumulation, whereas in newborn mice and adult human skin, we report LC3 puncta coincident with misshaped nuclei within the granular layer. This process relies on autophagy integrity as confirmed by lack of nucleophagy in differentiating keratinocytes depleted from WD repeat domain phosphoinositide interacting 1 or Unc-51 like autophagy activating kinase 1. Final validation into a skin disease model showed that impaired autophagy contributes to the pathogenesis of psoriasis. Lack of LC3 expression in psoriatic skin lesions correlates with parakeratosis and deregulated expression or location of most of the autophagic markers. Our findings may have implications and improve treatment options for patients with epidermal barrier defects. PMID:27021405

  19. Epidermal Basement Membrane in Health and Disease.

    PubMed

    Has, Cristina; Nyström, Alexander

    2015-01-01

    Skin, as the organ protecting the individual from environmental aggressions, constantly meets external insults and is dependent on mechanical toughness for its preserved function. Accordingly, the epidermal basement membrane (BM) zone has adapted to enforce tissue integrity. It harbors anchoring structures created through unique organization of common BM components and expression of proteins exclusive to the epidermal BM zone. Evidence for the importance of its correct assembly and the nonredundancy of its components for skin integrity is apparent from the multiple skin blistering disorders caused by mutations in genes coding for proteins associated with the epidermal BM and from autoimmune disorders in which autoantibodies target these molecules. However, it has become clear that these proteins not only provide mechanical support but are also critically involved in tissue homeostasis, repair, and regeneration. In this chapter, we provide an overview of the unique organization and components of the epidermal BM. A special focus will be given to its function during regeneration, and in inherited and acquired diseases. PMID:26610913

  20. Thy-1+ dendritic cells in murine epidermis are bone marrow-derived

    SciTech Connect

    Breathnach, S.M.; Katz, S.I.

    1984-07-01

    Thy-1+, Ly-5+ dendritic cells have recently been described as a resident cell population in murine epidermis, but their ontogeny and function are unknown. The origin and turnover of epidermal Thy-1+ cells utilizing chimeric mice were investigated. Lethally x-irradiated AKR/J (Thy-1.1+) and AKR/Cum (Thy-1.2+) mice were reconstituted with allogeneic bone marrow cells with or without thymocytes from congenic AKR/Cum or AKR/J mice, respectively. The density of residual indigenous Thy-1.1+ cells in AKR/J chimeras and Thy-1.2+ cells in AKR/Cum chimeras was substantially reduced following x-irradiation, as determined by immunofluorescence staining of epidermal sheets. Epidermal repopulation by allogeneic Thy-1+ dendritic epidermal cells was first observed at 5 weeks in AKR/J chimeras and at 7 weeks in AKR/Cum chimeras and progressed slowly. Repopulation was not enhanced by increasing the number of allogeneic bone marrow cells injected from 2 X 10(7) to 10(8) cells or by the addition of 8 X 10(7) allogeneic thymocytes to the donor inoculate. Epidermal repopulation by allogeneic Thy-1.2+ cells was not seen in AKR/J mice reconstituted with syngeneic bone marrow cells and allogeneic Thy-1.2+ AKR/Cum thymocytes. Taken together, these results indicate that Thy-1+ dendritic epidermal cells are derived from the bone marrow and suggest that they are not related to conventional peripheral T-lymphocytes.

  1. Micro-fractional epidermal powder delivery for improved skin vaccination

    PubMed Central

    Chen, Xinyuan; Kositratna, Garuna; Zhou, Chang; Manstein, Dieter; Wu, Mei X.

    2014-01-01

    Skin vaccination has gained increasing attention in the last two decades due to its improved potency compared to intramuscular vaccination. Yet, the technical difficulty and frequent local reactions hamper its broad application in the clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is developed to facilitate skin vaccination and minimize local adverse effects. EPD is based on ablative fractional laser or microneedle treatment of the skin to generate microchannel (MC) arrays in the epidermis followed by topical application of powder drug/vaccine-coated array patches to deliver drug/vaccine into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and model antigen ovalbumin (OVA) into murine, swine, and human skin within 1 hour. EPD of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID) injection and was much more efficient than tape stripping in both delivery efficiency and immune responses. Strikingly, the micro-fractional delivery significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine, leading to complete skin recovery. In contrast, ID injection induced severe local reactions that persisted for weeks. While reducing local reactogenicity, EPD of OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID injection. EPD of vaccinia virus encoding OVA induced significantly higher and long-lasting interferon γ-secreting CD8+ T cells than ID injection. In conclusion, EPD represents a promising technology for needle-free, painless skin vaccination with reduced local reactogenicity and improved immunogenicity. PMID:25135790

  2. Nuclear hormone receptor functions in keratinocyte and melanocyte homeostasis, epidermal carcinogenesis and melanomagenesis

    PubMed Central

    Hyter, Stephen; Indra, Arup K

    2013-01-01

    Skin homeostasis is maintained, in part, through regulation of gene expression orchestrated by type II nuclear hormone receptors in a cell and context specific manner. This group of transcriptional regulators is implicated in various cellular processes including epidermal proliferation, differentiation, permeability barrier formation, follicular cycling and inflammatory responses. Endogenous ligands for the receptors regulate actions during skin development and maintenance of tissue homeostasis. Type II nuclear receptor signaling is also important for cellular crosstalk between multiple cell types in the skin. Overall, these nuclear receptors are critical players in keratinocyte and melanocyte biology and present targets for cutaneous disease management. PMID:23395795

  3. Identification of a novel lymphoid population in the murine epidermis

    PubMed Central

    Almeida, Francisca F.; Tenno, Mari; Brzostek, Joanna; Li, Jackson LiangYao; Allies, Gabriele; Hoeffel, Guillaume; See, Peter; Ng, Lai Guan; Fehling, Hans Jörg; Gascoigne, Nicholas R. J.; Taniuchi, Ichiro; Ginhoux, Florent

    2015-01-01

    T cell progenitors are known to arise from the foetal liver in embryos and the bone marrow in adults; however different studies have shown that a pool of T cell progenitors may also exist in the periphery. Here, we identified a lymphoid population resembling peripheral T cell progenitors which transiently seed the epidermis during late embryogenesis in both wild-type and T cell-deficient mice. We named these cells ELCs (Epidermal Lymphoid Cells). ELCs expressed Thy1 and CD2, but lacked CD3 and TCRαβ/γδ at their surface, reminiscent of the phenotype of extra- or intra- thymic T cell progenitors. Similarly to Dendritic Epidermal T Cells (DETCs), ELCs were radioresistant and capable of self-renewal. However, despite their progenitor-like phenotype and expression of T cell lineage markers within the population, ELCs did not differentiate into conventional T cells or DETCs in in vitro, ex vivo or in vivo differentiation assays. Finally, we show that ELC expressed NK markers and secreted IFN-γ upon stimulation. Therefore we report the discovery of a unique population of lymphoid cells within the murine epidermis that appears related to NK cells with as-yet-unidentified functions. PMID:26223192

  4. Cryogenics maintenance strategy

    NASA Astrophysics Data System (ADS)

    Cruzat, Fabiola

    2012-09-01

    ALMA is an interferometer composed of 66 independent systems, with specific maintenance requirements for each subsystem. To optimize the observation time and reduce downtime maintenance, requirements are very demanding. One subsystem with high maintenance efforts is cryogenics and vacuum. To organize the maintenance, the Cryogenic and Vacuum department is using and implementing different tools. These are monitoring and problem reporting systems and CMMS. This leads to different maintenance approaches: Preventive Maintenance, Corrective Maintenance and Condition Based Maintenance. In order to coordinate activities with other departments the preventive maintenance schedule is kept as flexible as systems allow. To cope with unavoidable failures, the team has to be prepared to work under any condition with the spares on time. Computerized maintenance management system (CMMS) will help to manage inventory control for reliable spare part handling, the correct record of work orders and traceability of maintenance activities. For an optimized approach the department is currently evaluating where preventive or condition based maintenance applies to comply with the individual system demand. Considering the change from maintenance contracts to in-house maintenance will help to minimize costs and increase availability of parts. Due to increased number of system and tasks the cryo team needs to grow. Training of all staff members is mandatory, in depth knowledge must be built up by doing complex maintenance activities in the Cryo group, use of advanced computerized metrology systems.

  5. In vitro differentiation of murine embryonic stem cells into keratinocyte-like cells.

    PubMed

    Haase, Ingo; Knaup, Renate; Wartenberg, Maria; Sauer, Heinrich; Hescheler, Jürgen; Mahrle, Gustav

    2007-12-01

    Embryonic stem (ES) cells are omnipotent; they can differentiate into every cell type of the body. The development of culture conditions that allow their differentiation has made it conceivable to produce large numbers of cells with lineage-specific characteristics in vitro. Here, we describe a method by which murine ES cells can be differentiated into cells with characteristics of epidermal keratinocytes. Keratinocyte-like cells were isolated from embryoid bodies and grown in culture. Potential applications of this method are the in vitro differentiation of cells of interest from ES cells of mice with lethal phenotypes during embryonic development and the production of genetically modified epidermal keratinocytes that could be used as temporary wound dressing or as carriers of genes of interest in gene therapeutic treatments. PMID:17716780

  6. Epidermal Growth Factor and Intestinal Barrier Function.

    PubMed

    Tang, Xiaopeng; Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng; Fang, Rejun

    2016-01-01

    Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health. PMID:27524860

  7. Epidermal Growth Factor and Intestinal Barrier Function

    PubMed Central

    Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng

    2016-01-01

    Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health. PMID:27524860

  8. Neurological involvement in the epidermal naevus syndrome.

    PubMed Central

    McAuley, D L; Isenberg, D A; Gooddy, W

    1978-01-01

    The case of a left handed girl aged 18 years suffering from the "epidermal maevus syndrome" is described. She presented with dysphasia, transient left hemiparesis, and sensory symptoms due to an occlusion of the right internal carotid artery. Arterial occlusion, abnormal retinal vessels, and Raynaud's phenomenon have not been previously documented. The neurological complications of this syndrome are discussed. It is suggested that the arterial occlusion may have been caused by a dysplastic artery. Images PMID:660212

  9. Epidermal RAF prevents allergic skin disease

    PubMed Central

    Raguz, Josipa; Jeric, Ines; Niault, Theodora; Nowacka, Joanna Daniela; Kuzet, Sanya Eduarda; Rupp, Christian; Fischer, Irmgard; Biggi, Silvia; Borsello, Tiziana; Baccarini, Manuela

    2016-01-01

    The RAS pathway is central to epidermal homeostasis, and its activation in tumors or in Rasopathies correlates with hyperproliferation. Downstream of RAS, RAF kinases are actionable targets regulating keratinocyte turnover; however, chemical RAF inhibitors paradoxically activate the pathway, promoting epidermal proliferation. We generated mice with compound epidermis-restricted BRAF/RAF1 ablation. In these animals, transient barrier defects and production of chemokines and Th2-type cytokines by keratinocytes cause a disease akin to human atopic dermatitis, characterized by IgE responses and local and systemic inflammation. Mechanistically, BRAF and RAF1 operate independently to balance MAPK signaling: BRAF promotes ERK activation, while RAF1 dims stress kinase activation. In vivo, JNK inhibition prevents disease onset, while MEK/ERK inhibition in mice lacking epidermal RAF1 phenocopies it. These results support a primary role of keratinocytes in the pathogenesis of atopic dermatitis, and the animals lacking BRAF and RAF1 in the epidermis represent a useful model for this disease. DOI: http://dx.doi.org/10.7554/eLife.14012.001 PMID:27431613

  10. Vanadate induces apoptosis in epidermal JB6 P+ cells via hydrogen peroxide-mediated reactions.

    PubMed

    Ye, J; Ding, M; Leonard, S S; Robinson, V A; Millecchia, L; Zhang, X; Castranova, V; Vallyathan, V; Shi, X

    1999-12-01

    Apoptosis is a physiological mechanism for the control of DNA integrity in mammalian cells. Vanadium induces both DNA damage and apoptosis. It is suggested that vanadium-induced apoptosis serves to eliminate DNA-damaged cells. This study is designed to clarify a role of reactive oxygen species in the mechanism of apoptosis induced by vanadium. We established apoptosis model with murine epidermal JB6 P+ cells in the response to vanadium stimulation. Apoptosis was detected by a cell death ELISA assay and morphological analysis. The result shows that apoptosis induced by vanadate is dose-dependent, reaching its saturation level at a concentration of 100 microM vanadate. Vanadyl (IV) can also induce apoptosis albeit with lesser potency. A role of reactive oxygen species was analyzed by multiple reagents including specific scavengers of different reactive oxygen species. The result shows that vanadate-induced apoptosis is enhanced by NADPH, superoxide dismutase and sodium formate, but was inhibited by catalase and deferoxamine. Cells exposed to vanadium consume more molecular oxygen and at the same time, produce more H2O2 as measured by the change in fluorescence of scopoletin in the presence of horseradish peroxidase. This change in oxygen consumption and H2O2 production is enhanced by NADPH. Taken together, these results show that vanadate induces apoptosis in epidermal cells and H2O2 induced by vanadate plays a major role in this process. PMID:10705990

  11. Stem cell factor rescues dark epidermal pigmentation in discreet anatomic locations in albino and fair-skinned mice

    PubMed Central

    Vanover, Jillian C.; Spry, Malinda L.; Hamilton, Laura; Wakamatsu, Kazumasa; Ito, Shosuke; D’Orazio, John A.

    2016-01-01

    We previously reported a transgenic animal model of variant pigmentation based on epidermal expression of stem cell factor (SCF) and well-characterized coat color genes bred into the C57Bl/6 background. In this system, constitutive expression of SCF by epidermal keratinocytes results in the maintenance of epidermal melanocytes in the interfollicular basal epidermal layer and subsequent pigmentation of the epidermis itself. In this report, we describe extending this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci. We have observed SCF-dependent pigment deposition in specific anatomic regions regardless of tyrosinase (Tyr) or Mc1r genetic status. Thus, in the presence of K14-Scf, tyrosinase-null animals (previously thought incapable of synthesizing melanin) exhibited progressive robust epidermal pigmentation with age in the ears and tails. Furthermore, in the presence of the K14-Scf transgene, Tyr-defective animals demonstrated tyrosinase activity, suggesting that the c2j Tyr promoter defect is leaky and that Tyr expression can be rescued in part by SCF in the ears and tail. Lastly, we found that UV sensitivity of K14-Scf congenic animals differing only at the Mc1r or Tyr loci depended mainly on the amount of eumelanin present in the skin. These findings suggest that c-kit signaling can overcome the c2j Tyr promoter mutation in the ears and tails of aging animals but that UV resistance depends on accumulation of epidermal eumelanin. PMID:19682281

  12. Chinese herbal medicine (Tuhuai extract) exhibits topical anti-proliferative and anti-inflammatory activity in murine disease models.

    PubMed

    Man, Mao-Qiang; Shi, Yuejun; Man, Mona; Lee, Seung Hun; Demerjian, Marianne; Chang, Sandra; Feingold, Kenneth R; Elias, Peter M

    2008-08-01

    While psoriasis is one of the most common skin disorders in humans, effective, safe and inexpensive treatments are still largely unavailable. Chinese herbal medicine (CHM) has been used for centuries for treating psoriasis and several reports claim that systemic administration of one such CHM, Tuhuai, mainly composed of flos sophorae, smilax glabra roxb and licorice, is effective in psoriasis. However, the mechanisms by which this CHM improves psoriasis are not yet clear. Two universal features of psoriasis are epidermal hyperplasia and inflammation. Moreover, drugs that specifically inhibit epidermal hyperplasia and/or inflammation are widely used to treat psoriasis. Here, we investigated whether topical applications of Tuhuai extract exhibit anti-proliferative and anti-inflammatory activities in two murine models of inflammatory dermatoses. To assess Tuhuai's potential anti-proliferative effect, we disrupted epidermal barrier function twice-daily for 4 days in normal hairless mice followed by topical applications of either 1% Tuhuai extract or Vehicle to both flanks immediately after each barrier perturbation. Changes in epidermal proliferation and apoptosis were evaluated by immunohistochemistry and TUNEL staining. To assess the anti-inflammatory effects of Tuhuai, both irritant (phorbol ester) and acute allergic contact dermatitis (oxazolone) models were used. Whereas topical Tuhuai extract did not alter epidermal proliferation or induce irritation in normal skin, it both reduced epidermal hyperplasia in the epidermal hyperproliferative model, and reduced inflammation in both irritant and allergic contact dermatitis models. As topical Tuhuai extract exhibits anti-proliferative and anti-inflammatory properties in a variety of human models of inflammatory dermatoses, Tuhuai could provide an effective, relatively safe and inexpensive therapeutic alternative for the treatment of inflammatory dermatoses, including psoriasis. PMID:18341576

  13. Establishment of Two Mouse Models for CEDNIK Syndrome Reveals the Pivotal Role of SNAP29 in Epidermal Differentiation.

    PubMed

    Schiller, Stina A; Seebode, Christina; Wieser, Georg L; Goebbels, Sandra; Möbius, Wiebke; Horowitz, Mia; Sarig, Ofer; Sprecher, Eli; Emmert, Steffen

    2016-03-01

    Loss-of-function mutations in the synaptosomal-associated protein 29 (SNAP29) gene cause the cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome. In this study, we created total (Snap29(-/-)) as well as keratinocyte-specific (Snap29(fl/fl)/K14-Cre) Snap29 knockout mice. Both mutant mice exhibited a congenital distinct ichthyotic phenotype resulting in neonatal lethality. Mutant mice revealed acanthosis and hyperkeratosis as well as abnormal keratinocyte differentiation and increased proliferation. In addition, the epidermal barrier was severely impaired. These results indicate an essential role of SNAP29 in epidermal differentiation and barrier formation. Markedly decreased deposition of lamellar body contents in mutant mice epidermis and the observation of malformed lamellar bodies indicate severe impairments in lamellar body function due to the Snap29 knockout. We also found increased microtubule associated protein-1 light chain 3, isoform B-II levels, unchanged p62/SQSTM1 protein amounts, and strong induction of the endoplasmic reticulum stress marker C/EBP homologous protein in mutant mice. This emphasizes a role of SNAP29 in autophagy and endoplasmic reticulum stress. Our murine models serve as powerful tools for investigating keratinocyte differentiation processes and provide insights into the essential contribution of SNAP29 to epidermal differentiation. PMID:26747696

  14. Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair.

    PubMed

    Kuo, I-Hsin; Carpenter-Mendini, Amanda; Yoshida, Takeshi; McGirt, Laura Y; Ivanov, Andrei I; Barnes, Kathleen C; Gallo, Richard L; Borkowski, Andrew W; Yamasaki, Kenshi; Leung, Donald Y; Georas, Steve N; De Benedetto, Anna; Beck, Lisa A

    2013-04-01

    Atopic dermatitis (AD) is characterized by epidermal tight junction (TJ) defects and a propensity for Staphylococcus aureus skin infections. S. aureus is sensed by many pattern recognition receptors, including Toll-like receptor 2 (TLR2). We hypothesized that an effective innate immune response will include skin barrier repair, and that this response is impaired in AD subjects. S. aureus-derived peptidoglycan (PGN) and synthetic TLR2 agonists enhanced TJ barrier and increased expression of TJ proteins, claudin-1 (CLDN1), claudin-23 (CLDN23), occludin, and Zonulae occludens 1 (ZO-1) in primary human keratinocytes. A TLR2 agonist enhanced skin barrier recovery in human epidermis wounded by tape stripping. Tlr2(-/-) mice had a delayed and incomplete barrier recovery following tape stripping. AD subjects had reduced epidermal TLR2 expression as compared with nonatopic subjects, which inversely correlated (r=-0.654, P=0.0004) with transepidermal water loss (TEWL). These observations indicate that TLR2 activation enhances skin barrier in murine and human skin and is an important part of a wound repair response. Reduced epidermal TLR2 expression observed in AD patients may have a role in their incompetent skin barrier. PMID:23223142

  15. Facilities maintenance handbook

    NASA Technical Reports Server (NTRS)

    1991-01-01

    This handbook is a guide for facilities maintenance managers. Its objective is to set minimum facilities maintenance standards. It also provides recommendations on how to meet the standards to ensure that NASA maintains its facilities in a manner that protects and preserves its investment in the facilities in a cost-effective manner while safely and efficiently performing its mission. This handbook implements NMI 8831.1, which states NASA facilities maintenance policy and assigns organizational responsibilities for the management of facilities maintenance activities on all properties under NASA jurisdiction. It is a reference for facilities maintenance managers, not a step-by-step procedural manual. Because of the differences in NASA Field Installation organizations, this handbook does not assume or recommend a typical facilities maintenance organization. Instead, it uses a systems approach to describe the functions that should be included in any facilities maintenance management system, regardless of its organizational structure. For documents referenced in the handbook, the most recent version of the documents is applicable. This handbook is divided into three parts: Part 1 specifies common definitions and facilities maintenance requirements and amplifies the policy requirements contained in NMI 8831. 1; Part 2 provides guidance on how to meet the requirements of Part 1, containing recommendations only; Part 3 contains general facilities maintenance information. One objective of this handbook is to fix commonality of facilities maintenance definitions among the Centers. This will permit the application of uniform measures of facilities conditions, of the relationship between current replacement value and maintenance resources required, and of the backlog of deferred facilities maintenance. The utilization of facilities maintenance system functions will allow the Centers to quantitatively define maintenance objectives in common terms, prepare work plans, and

  16. Light Vehicle Preventive Maintenance.

    ERIC Educational Resources Information Center

    Marine Corps Inst., Washington, DC.

    This correspondence course, originally developed for the Marine Corps, is designed to instruct students in the performance of preventive maintenance on motor vehicles. Instructional materials are presented in three chapters as follows: (1) Major Maintenance Areas (maintenance system, tires, batteries, cooling systems, and vehicle lubrication; (2)…

  17. Asphalt in Pavement Maintenance.

    ERIC Educational Resources Information Center

    Asphalt Inst., College Park, MD.

    Maintenance methods that can be used equally well in all regions of the country have been developed for the use of asphalt in pavement maintenance. Specific information covering methods, equipment and terminology that applies to the use of asphalt in the maintenance of all types of pavement structures, including shoulders, is provided. In many…

  18. Defer Maintenance, Invite Disaster

    ERIC Educational Resources Information Center

    Bowman, William W.

    1977-01-01

    An AGB- and NACUBO-sponsored survey showed that "wish lists" are accumulating overdue major maintenance projects because energy costs are consuming physical plant budgets. Problem areas are discussed: budget "guesstimation," preventive maintenance, deferred maintenance inventory, the APPA accounting format, resource allocation, and inflation.…

  19. Late Onset Epidermal Nevus with Hypertrichosis and Facial Hemihypertrophy

    PubMed Central

    Saritha, M; Chandrashekar, Laxmisha; Thappa, Devinder Mohan; Ramesh, A; Basu, Debdatta

    2014-01-01

    Epidermal nevus syndromes are rare conditions, characterized by different types of keratinocytic or organoid epidermal nevi in association with ocular, neurological, and skeletal manifestations. We present a case of late onset epidermal nevus with hypertrichosis and hemihypertrophy of face. Genetic analysis did not reveal presence of FGFR3 or PIK3CA mutations. The patient has features that cannot be categorized into the present well-known syndromes. PMID:24700959

  20. Murine typhus in travelers returning from Indonesia.

    PubMed Central

    Parola, P.; Vogelaers, D.; Roure, C.; Janbon, F.; Raoult, D.

    1998-01-01

    We report the first three documented cases of murine typhus imported into Europe from Indonesia, discuss clues for the diagnosis of the disease, and urge that murine fever be considered in the diagnosis of febrile disease in travelers. PMID:9866749

  1. Antibacterial activity of recombinant murine beta interferon.

    PubMed Central

    Fujiki, T; Tanaka, A

    1988-01-01

    Recombinant murine beta interferon was protective and therapeutic for mice against Listeria monocytogenes infection in vivo. The recombinant murine beta interferon caused enhanced H2O2 release by macrophages in vivo, but not in vitro. PMID:3343048

  2. Immunosuppressive effect of murine cytomegalovirus.

    PubMed Central

    Loh, L; Hudson, J B

    1980-01-01

    Murine cytomegalovirus suppressed the ability of spleen cells to respond to mitogens in vitro. The degree of suppression was proportional to the multiplicity of infection. This effect could not be explained by cytolysis of lymphocytes, an alteration in the kinetics of the response to mitogen, or a direct competition between virions and mitogen molecules for cell-surface receptors. Nor was it due to simple contact between cell and virus, since ultraviolet-inactivated murine cytomegalovirus failed to suppress the response to mitogens. Reconstitution experiments were performed which involved mixing various combinations of infected and uninfected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages had an impaired capacity to mediate the response ot T lymphocytes to concanavalin A. This suggests that murine cytomegalovirus may cause immunosuppression indirectly by interfering with macrophage function. PMID:6244228

  3. [Bilateral segmental neurofibromatosis simulating epidermal nevus].

    PubMed

    Gambichler, T; Küster, W; Wolter, M; Rapp, S; Altmeyer, P; Hoffmann, K

    2000-11-01

    Neurofibromatosis is a neuroectodermal systemic disease. A rare variant of this condition is bilateral segmental neurofibromatosis. A 29-year-old man presented with bilateral papillomatous plaques in the lumbar dermatomes. Clinically, the lesions were very similar to an epidermal nevus but histologic examination revealed superficial neurofibromas. Family history, ophthalmologic and neurologic investigations were unremarkable. The unusual morphologic presentation of bilateral segmental neurofibromas in this case points to the wide clinical spectrum of the disease and the significance of histologic examination in systematic nevoid lesions. PMID:11116852

  4. Systemic treatment: maintenance compared with holiday.

    PubMed

    Punt, Cornelis J A; Simkens, Lieke H J; Koopman, Miriam

    2015-01-01

    With the currently available cytotoxic and targeted drugs, metastatic colorectal cancer (mCRC) may be controlled by systemic treatment for a substantial period of time. However, many questions remain about the optimal use of drugs and duration of treatment. The feasibility of chemotherapy-free intervals has been studied in patients with mCRC treated with chemotherapy alone, but the results are conflicting. Current data show that oxaliplatin may be safely interrupted, but they do not allow a firm conclusion on the safety of a full treatment break of chemotherapy. For targeted therapy, continuous inhibition of intracellular signaling by prolonged administration would theoretically be beneficial for efficacy of treatment. Recent data support the use of maintenance treatment with chemotherapy and bevacizumab. No data on the optimal duration of treatment with anti-epidermal growth factor receptor (EGFR) agents are currently available. PMID:25993146

  5. Adverse Reaction to Cetuximab, an Epidermal Growth Factor Receptor Inhibitor.

    PubMed

    Štulhofer Buzina, Daška; Martinac, Ivana; Ledić Drvar, Daniela; Čeović, Romana; Bilić, Ivan; Marinović, Branka

    2016-04-01

    Dear Editor, Inhibition of the epidermal growth factor receptor (EGFR) is a new strategy in treatment of a variety of solid tumors, such as colorectal carcinoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and pancreatic cancer (1). Cetuximab is a chimeric human-murine monoclonal antibody against EGFR. Cutaneous side effects are the most common adverse reactions occurring during epidermal growth factor receptor inhibitors (EGFRI) therapy. Papulopustular rash (acne like rash) develop with 80-86% patients receiving cetuximab, while xerosis, eczema, fissures, teleangiectasiae, hyperpigmentations, and nail and hair changes occur less frequently (2). The mechanism underlying these skin changes has not been established and understood. It seems EGFRI alter cell growth and differentiation, leading to impaired stratum corneum and cell apoptosis (3-5). An abdominoperineal resection of the rectal adenocarcinoma (Dukes C) was performed on a 43-year-old female patient. Following surgery, adjuvant chemo-radiotherapy was applied. After two years, the patient suffered a metastatic relapse. Abdominal lymphadenopathy was detected on multi-slice computer tomography (MSCT) images, with an increased value of the carcinoembryonic antigen (CEA) tumor marker (maximal value 57 ng/mL). Hematological and biochemical tests were within normal limits, so first-line chemotherapy with oxaliplatin and a 5-fluorouracil (FOLFOX4) protocol was introduced. A wild type of the KRAS gene was confirmed in tumor tissue (diagnostic prerequisite for the introduction of EGFRI) and cetuximab (250 mg per m2 of body surface) was added to the treatment protocol. The patient responded well to the treatment with confirmed partial regression of the tumor formations. Three months after the patient started using cetuximab, an anti-EGFR monoclonal antibody, the patient presented with a papulopustular eruption in the seborrhoeic areas (Figure 1) and eczematoid reactions on the extremities

  6. Photocrosslinkable Gelatin Hydrogel for Epidermal Tissue Engineering.

    PubMed

    Zhao, Xin; Lang, Qi; Yildirimer, Lara; Lin, Zhi Yuan; Cui, Wenguo; Annabi, Nasim; Ng, Kee Woei; Dokmeci, Mehmet R; Ghaemmaghami, Amir M; Khademhosseini, Ali

    2016-01-01

    Natural hydrogels are promising scaffolds to engineer epidermis. Currently, natural hydrogels used to support epidermal regeneration are mainly collagen- or gelatin-based, which mimic the natural dermal extracellular matrix but often suffer from insufficient and uncontrollable mechanical and degradation properties. In this study, a photocrosslinkable gelatin (i.e., gelatin methacrylamide (GelMA)) with tunable mechanical, degradation, and biological properties is used to engineer the epidermis for skin tissue engineering applications. The results reveal that the mechanical and degradation properties of the developed hydrogels can be readily modified by varying the hydrogel concentration, with elastic and compressive moduli tuned from a few kPa to a few hundred kPa, and the degradation times varied from a few days to several months. Additionally, hydrogels of all concentrations displayed excellent cell viability (>90%) with increasing cell adhesion and proliferation corresponding to increases in hydrogel concentrations. Furthermore, the hydrogels are found to support keratinocyte growth, differentiation, and stratification into a reconstructed multilayered epidermis with adequate barrier functions. The robust and tunable properties of GelMA hydrogels suggest that the keratinocyte laden hydrogels can be used as epidermal substitutes, wound dressings, or substrates to construct various in vitro skin models. PMID:25880725

  7. Sulfation of estradiol in human epidermal keratinocyte.

    PubMed

    Kushida, Akira; Hattori, Kenji; Yamaguchi, Nozomi; Kobayashi, Tetsuyuki; Date, Akira; Tamura, Hiroomi

    2011-01-01

    Epidermis is one of the well-known estrogen target tissues. Information regarding estrogen metabolism in epidermis is still very limited compared to that of estrogen action. In the breast cancer tissue, 17β-estradiol (E(2)) is inactivated by sulfation and the expression level of estrogen sulfotransferase (SULT1E1) is inversely correlated with its malignancy. However, there is little datum about inactivation of estradiol in skin. In order to detect and measure E(2) and its metabolites simultaneously, we established an assay method with radio HPLC. A majority of [(3)H] labeled E(2) was converted to E(2) sulfate in normal human epidermal keratinocyte (NHEK) cells. The estimated activity of sulfotransferase toward E(2) at 20 nM was 0.11±0.01 (pmol/min/mg protein). Significant induction of estrogen sulfotransferase activity was observed in calcium-differentiated NHEK cells (0.58±0.07 (pmol/min/mg protein)). The gene expression of SULT1E1 was fifteen-fold higher in differentiated keratinocyte than in proliferating keratinocyte, whereas that of steroid sulfatase was reduced. These results suggest that E(2) inactivation is primarily mediated by SULT1E1 in keratinocyte and E(2) action is likely suppressed in epidermal differentiation. PMID:21720030

  8. Innovation for maintenance technology improvements

    NASA Technical Reports Server (NTRS)

    Shives, T. R. (Editor); Willard, W. A. (Editor)

    1982-01-01

    A group of 34 submitted entries (32 papers and 2 abstracts) from the 33rd meeting of the Mechanical Failures Prevention Group whose subject was maintenance technology improvement through innovation. Areas of special emphasis included maintenance concepts, maintenance analysis systems, improved maintenance processes, innovative maintenance diagnostics and maintenance indicators, and technology improvements for power plant applications.

  9. Assessment of cryotherapy for the treatment of verrucous epidermal naevi.

    PubMed

    Panagiotopoulos, Antonios; Chasapi, Vasiliki; Nikolaou, Vasiliki; Stavropoulos, Panagiotis G; Kafouros, Kyriockos; Petridis, Athanasios; Katsambas, Andreas

    2009-01-01

    Epidermal naevi are hamartomas that are characterized by hyperplasia of the epidermis and adnexal structures and may be associated with serious disfiguration. Management of epidermal naevi is challenging. We present here our experience with cryosurgery in the treatment of verrucous epidermal naevi. The aim of this study was to determine the efficacy and safety of cryosurgery for the treatment of epidermal naevi. Nine patients with verrucous epidermal naevi and two with extensive unilateral epidermal naevus were treated with cryosurgery. Two cycles of open spray technique were used, 10-15 sec each, depending on the size and extent of the naevus. Ten patients had their naevi treated successfully in 2-5 sessions with two cycles of therapy, and the cosmetic result was excellent with no scarring. One patient showed a relapse within 8 months after the treatment. One patient with phototype IV developed hypochromic scarring, but repigmentation occurred after 6 months. Postoperative healing time was 10-20 days. Cryosurgery is an extremely effective therapeutic modality for the treatment of epidermal naevi. The low cost, the simplicity of the technique and the good cosmetic result makes cryosurgery an excellent therapeutic modality for the treatment of epidermal naevus. PMID:19479129

  10. Carbon Dioxide Metabolism in Leaf Epidermal Tissue 1

    PubMed Central

    Willmer, C. M.; Pallas, J. E.; Black, C. C.

    1973-01-01

    A number of plant species were surveyed to obtain pure leaf epidermal tissue in quantity. Commelina communis L. and Tulipa gesnariana L. (tulip) were chosen for further work. Chlorophyll a/b ratios of epidermal tissues were 2.41 and 2.45 for C. communis and tulip, respectively. Phosphoenolpyruvate carboxylase, ribulose-1,5-diphosphate carboxylase, malic enzyme, and NAD+ and NADP+ malate dehydrogenases were assayed with epidermal tissue and leaf tissue minus epidermal tissue. In both species, there was less ribulose 1,5-diphosphate than phosphoenolpyruvate carboxylase activity in epidermal tissue whether expressed on a protein or chlorophyll basis whereas the reverse was true for leaf tissue minus epidermal tissue. In both species, malic enzyme activities were higher in epidermal tissue than in the remaining leaf tissue when expressed on a protein or chlorophyll basis. In both species, NAD+ and NADP+ malate dehydrogenase activities were higher in the epidermal tissue when expressed on a chlorophyll basis; however, on a protein basis, the converse was true. Microautoradiography of C. communis epidermis and histochemical tests for keto acids suggested that CO2 fixation occurred predominantly in the guard cells. The significance and possible location of the enzymes are discussed in relation to guard cell metabolism. Images PMID:16658581

  11. [Verrucose epidermal nevus with belated grow and pregnancy. Case report].

    PubMed

    Aguilera Martínez, Verónica; Cervantes Villarreal, Gustavo Enrique; Ramos Garibay, Alberto; Ruiz Mondragón, María Eugenia

    2007-10-01

    Verrucose epidermal nevus is a benign and congenital hyperplasia of the superficial epidermis and annexes. It expresses itself during the firs year of life, grows during childhood and in adolescence reaches its largest size. It can appear everywhere in skin surface. We present a case of late verrucose epidermal nevus with genital onset. Differential diagnosis was done with acuminated condylomas. PMID:18800583

  12. Antimicrobial proteins of murine macrophages.

    PubMed Central

    Hiemstra, P S; Eisenhauer, P B; Harwig, S S; van den Barselaar, M T; van Furth, R; Lehrer, R I

    1993-01-01

    Three murine microbicidal proteins (MUMPs) were purified from cells of the murine macrophage cell line RAW264.7 that had been activated by gamma interferon. Similar proteins were also present in nonactivated RAW264.7 cells, in cells of the murine macrophage cell line J774A.1, and in resident and activated murine peritoneal macrophages. MUMP-1, MUMP-2, and MUMP-3 killed Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Mycobacterium fortuitum, and Cryptococcus neoformans in vitro. MUMP-1 resembled an H1 histone but was unusual because its N-terminal residue (serine) was not N acetylated. Although MUMP-2 was N terminally blocked, its high lysine/arginine ratio and its reactivity with an antibody to H1 histones suggested that it also belonged to the H1 histone family. MUMP-3 was identical to histone H2B in 30 of 30 amino-terminal residues. Although the antimicrobial properties of histones have been recognized for decades, this is the first evidence that such proteins may endow the lysosomal apparatus of macrophages with nonoxidative antimicrobial potential. Other MUMPs, including some with a more restricted antimicrobial spectrum and one that appeared to be induced in RAW264.7 cells after gamma interferon stimulation, were noted but remain to be characterized. Images PMID:8514411

  13. Murine model of otitis media with effusion: immunohistochemical demonstration of IL-1 alpha antigen expression.

    PubMed

    Johnson, M D; Contrino, A; Contrino, J; Maxwell, K; Leonard, G; Kreutzer, D

    1994-09-01

    Recent studies have suggested that cytokines likely play a central role in the formation and maintenance of otitis media with effusion (OME). Currently, there is no immunologically defined animal model for the study of cytokines as they contribute to the formation of OME. In the present study, a murine model of OME, using eustachian tube blockage via an external surgical approach, was developed. The murine model temporal bone histology appears to mimic the histology found in chronic otitis media with effusion in humans. Additionally, using this murine model, interleukin-1 alpha (IL-1 alpha) expression was detected in the middle ear using standard immunohistochemical techniques. IL-1 alpha seemed localized to the epithelial lining of the middle ear as well as 5% to 10% of inflammatory cells. This model should provide the necessary tool to further study the immunologic aspects of OME. PMID:8072363

  14. Industrial Maintenance Strategies

    SciTech Connect

    Sajjad Akbar

    2006-07-01

    Industrial plants have become more complex due to technological advancement. This has made the task of maintenance more difficult. The maintenance costs in terms of resources and downtime loss are so high that maintenance function has become a critical factor in a plant's profitability. Industry should devote as much forethought to the management of maintenance function as to production. Maintenance has grown from an art to a precise, technical engineering science. Planning, organizing scheduling and control of maintenance using modern techniques pays dividends in the form of reduced costs and increased reliability. The magnitude and the dimension of maintenance have multiplied due to development in the engineering technologies. Production cost and capacities are directly affected by the breakdown time. Total operating cost including the maintenance cost plays an important role in replacement dimension. The integrated system approach would bring forth the desired results of high maintenance standards. The standards once achieved and sustained, would add to the reliability of the plan and relieve heavy stresses and strains on the engineering logistic support. (author)

  15. Assay of lapatinib in murine models of cigarette smoke carcinogenesis

    PubMed Central

    Balansky, Roumen; Izzotti, Alberto; D’Agostini, Francesco; Longobardi, Mariagrazia; Micale, Rosanna T.; La Maestra, Sebastiano; Camoirano, Anna; Ganchev, Gancho; Iltcheva, Marietta; Steele, Vernon E.; De Flora, Silvio

    2014-01-01

    Lapatinib, a dual tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), is prescribed for the treatment of patients with metastatic breast cancer overexpressing HER-2. Involvement of this drug in pulmonary carcinogenesis has been poorly investigated. We used murine models suitable to evaluate cigarette smoke-related molecular and histopathological alterations. A total of 481 Swiss H mice were used. The mice were exposed to mainstream cigarette smoke (MCS) during the first four months of life. After 10 weeks, MCS caused an elevation of bulky DNA adducts, oxidative DNA damage and an extensive downregulation of microRNAs in lung. After four months, an increase in micronucleus frequency was observed in peripheral blood erythrocytes. After 7.5 months, histopathological alterations were detected in the lung, also including benign tumors and malignant tumors, and in the urinary tract. A subchronic toxicity study assessed the non-toxic doses of lapatinib, administered daily with the diet after weaning. After 10 weeks, lapatinib significantly attenuated the MCS-related nucleotide changes and upregulated several low-intensity microRNAs in lung. The drug poorly affected the MCS systemic genotoxicity and had modest protective effects on MCS-induced preneoplastic lesions in lung and kidney, when administered under conditions that temporarily mimicked interventions either in current smokers or ex-smokers. On the other hand, it caused some toxicity to the liver. Thus, on the whole, lapatinib appears to have a low impact in the smoke-related lung carcinogenesis models used, especially in terms of tumorigenic response. PMID:25053627

  16. Acantholytic dyskeratosis occurring within an epidermal nevus.

    PubMed

    Khetarpal, Shilpi; Tarbox, Michelle; Tuthill, Ralph J; Vidimos, Allison

    2013-08-01

    A 25-year-old woman presented with a large area of flesh-colored verrucous plaques following the lines of Blaschko on the left side of the body that had been present since 6 months of age. The plaques had been stable and grew proportionately with the patient's body until she reached 20 years of age when they began to thicken and enlarge. Her medical and family history was unremarkable. A shave biopsy revealed a papillomatous epidermis with 3 discrete foci of acantholytic dyskeratosis, with corps ronds and grains that were similar to the histologic findings of Darier disease (DD). Epidermolytic hyperkeratosis was not identified. Our patient's lack of a family history of DD, early-onset disease, and linear presentation along the lines of Blaschko all favored a diagnosis of acantholytic dyskeratotic epidermal nevi (ADEN) versus localized DD. PMID:24087780

  17. Update on the epidermal differentiation complex.

    PubMed

    Henry, Julie; Toulza, Eve; Hsu, Chiung-Yueh; Pellerin, Laurence; Balica, Stefana; Mazereeuw-Hautier, Juliette; Paul, Carle; Serre, Guy; Jonca, Nathalie; Simon, Michel

    2012-01-01

    On human chromosome 1q21, a 2-Mb region called the epidermal differentiation complex comprises many genes encoding structural and regulatory proteins that are of crucial importance for keratinocyte differentiation and stratum corneum properties. Apart from those for involucrin and loricrin, most of the genes are organized in four families: the genes encoding EF-hand calcium-binding proteins of the S100A family, the genes encoding the small proline rich proteins (SPRRs) and the late cornified envelope (LCE) proteins, two families of cornified cell envelope components, and the genes encoding the S100-fused type proteins (SFTPs). This review focuses on the SPRRs, LCE proteins and SFTPs. It describes their structures, their specific functions and, when known, the mechanisms involved in the regulation of their expression. It also highlights their possible involvement in skin diseases. PMID:22201818

  18. Psychological stress and epidermal barrier function.

    PubMed

    Orion, Edith; Wolf, Ronni

    2012-01-01

    The skin is the organ that acts as a barrier between the outer and inner environments of the body. It is thus exposed not only to a wide variety of physical, chemical, and thermal insults from the outside world but also to inner endogenous stimuli. Stress, once an abstract psychologic phenomenon, has taken research's center stage in recent years. The "mind-body connection" is now less of an obscure New Age term and more of an elaborate physiologic pathway by which bilateral communication occurs between body and brain. Dermatologists and dermatologic patients have long acknowledged the effect of stress on the skin and its capability to initiate, maintain, or exacerbate several skin diseases. Because disruption of epidermal barrier integrity may be important in the development of some common skin diseases, it is crucial to understand its vulnerability to psychologic stress. PMID:22507042

  19. Cell motion predicts human epidermal stemness

    PubMed Central

    Toki, Fujio; Tate, Sota; Imai, Matome; Matsushita, Natsuki; Shiraishi, Ken; Sayama, Koji; Toki, Hiroshi; Higashiyama, Shigeki

    2015-01-01

    Image-based identification of cultured stem cells and noninvasive evaluation of their proliferative capacity advance cell therapy and stem cell research. Here we demonstrate that human keratinocyte stem cells can be identified in situ by analyzing cell motion during their cultivation. Modeling experiments suggested that the clonal type of cultured human clonogenic keratinocytes can be efficiently determined by analysis of early cell movement. Image analysis experiments demonstrated that keratinocyte stem cells indeed display a unique rotational movement that can be identified as early as the two-cell stage colony. We also demonstrate that α6 integrin is required for both rotational and collective cell motion. Our experiments provide, for the first time, strong evidence that cell motion and epidermal stemness are linked. We conclude that early identification of human keratinocyte stem cells by image analysis of cell movement is a valid parameter for quality control of cultured keratinocytes for transplantation. PMID:25897083

  20. Epidermal growth factor-nonresponsive 3T3 variants do not contain epidermal growth factor receptor-related antigens or mRNA

    SciTech Connect

    Schneider, C.A.; Lim, R.W.; Terwilliger, E.; Herschman, H.R.

    1986-01-01

    The authors have previously isolated three independent variants of Swiss 3T3 cells that are unable to generate a mitogenic response to epidermal growth factor (EGF). Each of the variants is unable to bind /sup 125/I-labeled EGF; each lacks a functional EGF receptor. They used an antiserum to murine EGF receptor to look for an EGF-receptor gene product in wild-type 3T3 cells and in the three EGF-nonresponsive variants. No cross-reactive material could be detected in any of the three variants, either in /sup 125/I-labeled cell extracts or in (/sup 35/S)methionine metabolically labeled cells. 3T3 cells contained mRNA molecules homologous to a cDNA probe for the human EGF-receptor coding region. In contrast, no homologous RNA could be detected in any of the three variants. Analysis of genomic Southern blots of the DNA from 3T3 cells and the three EGF-nonresponsive variants indicated sequences from the EGF-receptor gene are present in the DNA of all four cell lines. These EGF-nonresponsive lines, which demonstrate proliferative responses to a variety of mitogens, will be ideal recipients for structure-function studies of the EGF receptor by transfection of the cloned gene.

  1. Halt Runaway Maintenance Costs.

    ERIC Educational Resources Information Center

    Trotter, Andrew

    1988-01-01

    To keep expensive computer software and hardware functioning requires good housekeeping, some protective equipment, ground rules, and supervision. Schools can arrange microcomputer maintenance through service agreements with computer manufacturers, pay-as-you-go service from local computer stores, or setting up their own maintenance and repair…

  2. Fixing Maintenance Productivity.

    ERIC Educational Resources Information Center

    Fickes, Michael

    2003-01-01

    Describes how one university's facility managers use Nextel communications technology in conjunction with a Famis Software maintenance management system to improve the productivity of its maintenance technicians. The system uses a wireless Internet connection to automate the flow of work order information to and from technicians. The key to these…

  3. Maintenance of School Gymnasiums.

    ERIC Educational Resources Information Center

    Finchum, R. N.

    1965-01-01

    Procedures are suggested that may be helpful to those responsible for the operation and maintenance of school buildings and gymnasiums. Most schools with gymnasiums utilize them for both instructional and sports purposes. Maintenance of the multipurpose gym are discussed under four subject areas--(1) floors, (2) lighting, (3) sanitation, and (4)…

  4. Maintenance Trades Guidelines

    ERIC Educational Resources Information Center

    Weidner, Theodore J.

    2008-01-01

    In 2002, APPA published "Maintenance Staffing Guidelines for Educational Facilities," the first building maintenance trades staffing guideline designed to assist educational facilities professionals with their staffing needs. addresses how facilities professionals can determine the appropriate size and mix of their organization. Contents include…

  5. Maximizing Hard Floor Maintenance.

    ERIC Educational Resources Information Center

    Steger, Michael

    2000-01-01

    Explains the maintenance options available for hardwood flooring that can help ensure long life cycles and provide inviting spaces. Developing a maintenance system, knowing the type of traffic that the floor must endure, using entrance matting, and adhering to manufacturers guidelines are discussed. Daily, monthly or quarterly, and long-term…

  6. Polymeric membranes modulate human keratinocyte differentiation in specific epidermal layers.

    PubMed

    Salerno, Simona; Morelli, Sabrina; Giordano, Francesca; Gordano, Amalia; Bartolo, Loredana De

    2016-10-01

    In vitro models of human bioengineered skin substitutes are an alternative to animal experimentation for testing the effects and toxicity of drugs, cosmetics and pollutants. For the first time specific and distinct human epidermal strata were engineered by using membranes and keratinocytes. To this purpose, biodegradable membranes of chitosan (CHT), polycaprolactone (PCL) and a polymeric blend of CHT-PCL were prepared by phase-inversion technique and characterized in order to evaluate their morphological, physico-chemical and mechanical properties. The capability of membranes to modulate keratinocyte differentiation inducing specific interactions in epidermal membrane systems was investigated. The overall results demonstrated that the membrane properties strongly influence the cell morpho-functional behaviour of human keratinocytes, modulating their terminal differentiation, with the creation of specific epidermal strata or a fully proliferative epidermal multilayer system. In particular, human keratinocytes adhered on CHT and CHT-PCL membranes, forming the structure of the epidermal top layers, such as the corneum and granulosum strata, characterized by withdrawal or reduction from the cell cycle and cell proliferation. On the PCL membrane, keratinocytes developed an epidermal basal lamina, with high proliferating cells that stratified and migrated over time to form a complete differentiating epidermal multilayer system. PMID:27371895

  7. Spatiotemporal Expression of p63 in Mouse Epidermal Commitment

    PubMed Central

    Zhao, Qian; Liu, Shuang; Zhang, Huishan; Li, Na; Wang, Xinyue; Cao, Yujing; Ning, Lina; Duan, Enkui; Xia, Guoliang

    2015-01-01

    The embryonic surface ectoderm is a simple flat epithelium consisting of cells that express the cytokeratins K8/K18. Before stratification, K5/K14 expression substitutes K8/K18 expression, marking the event called epidermal commitment. Previous studies show that the transcription factor p63 plays an essential role in epidermal commitment. However, detailed expression information of p63 during early epidermal development in mice is still unclear. We systematically studied the expression pattern of p63 in mouse epidermal commitment, together with K8 and K5. We show that p63 expression could be detected as early as E8.5 in mouse embryos preceding epidermal commitment. p63 expression first appears near the newly formed somites and the posterior part of the embryo, further expanding to the whole embryonic surface with particular enrichment in the first branchial arches and the limb buds. ΔNp63 is the major class of isoforms expressed in this period. Relative expression intensity of p63 depends on the embryonic position. In summary, there is a sequential and regular expression pattern of K8, p63 and K5 in mouse epidermal commitment. Our study not only contributes to understanding the early events during epidermal development but also provides a basal tool to study the function of p63 in mammals. PMID:26690418

  8. Linear Epidermal Nevus of the Oral Cavity: A Rare Diagnosis

    PubMed Central

    Santos, Mariana Dutra de Cássia Ferreira; Duarte, Alexandre Scalli Mathias; Carvalho, Guilherme Machado; Guimarães, Alexandre Caixeta; Zappelini, Carlos Eduardo Monteiro; Coelho Dal Rio, Ana Cristina; Corrêa, Maria Elvira Pizzigatti; Milani Altemani, Albina Messias de Almeida; Danielli Nicola, Ester Maria

    2012-01-01

    Linear epidermal nevus is an uncommon diagnosis of benign lesions of the oral cavity. It is characterized by a congenital malformation arising from the ectoderm cells, which are arranged according to a typical linear configuration known as Blaschko's lines. We report a case of linear epidermal nevus of oral cavity in a 51-year-old lady or woman. The linear epidermal nevus of the oral cavity, although rare, can be considered a differential diagnosis of oral papillomatosis (OP). The histopathological studies and detailed description are the center of the diagnostic and clinical evolution. PMID:22811716

  9. UVB-induced epidermal hyperproliferation is modified by a single, topical treatment with a mitosis inhibitory epidermal pentapeptide

    SciTech Connect

    Olsen, W.M.; Elgjo, K. )

    1990-01-01

    A single application of a water-miscible cream base containing the recently identified mitosis inhibitory epidermal pentapeptide pyroGlu-Glu-Asp-Ser-GlyOH (EPP) to hairless mouse skin is followed by a long-lasting period of reduced epidermal cell proliferation. To examine if a similar growth inhibition could be achieved in stimulated and rapidly proliferating epidermis, EPP was applied at two different concentrations, 0.005 or 0.02%, to hairless mouse skin immediately after exposure of the left flank to an erythemic dose of ultraviolet B light (UVB). This dose of UVB alone induces a sustained period of rapid epidermal cell proliferation, starting at about 18 h after the irradiation. Epidermal cell proliferation was followed from 18 to 54 h (0.005% cream) or from 18 to 30 h (0.02% cream) after the treatment by estimating the rate of G2-M cell flux (the mitotic rate) by means of Colcemid, and epidermal DNA synthesis by counting labeled cells after pulse-labeling with 3H-thymidine. The unirradiated side of the mice was used as reference. The results showed that topical treatment with a 0.02% EPP cream partially inhibited UVB-induced epidermal hyperproliferation, while the 0.005% EPP cream inhibited as well as stimulated the UVB-induced hyperproliferation. Thus, EPP is effective even in rapidly proliferating epidermal cell populations, but the outcome is obviously dose-dependent in this test system.

  10. Effect of epidermal growth factor/urogastrone on glycosaminoglycan synthesis and accumulation in vitro in the developing mouse palate.

    PubMed

    Turley, E A; Hollenberg, M D; Pratt, R M

    1985-01-01

    Epidermal growth factor/urogastrone (EGF-URO) has previously been implicated in murine secondary-palate formation. We report here that, in correlation with its effects on palate fusion, EGF-URO in physiological amounts (1.7 nmol/l) markedly affects glycosaminoglycan (GAG) production in organ cultures of mouse palate tissue; the effects of EGF-URO are dependent on the developmental stage of the palate. GAG production, particularly that of hyaluronic acid (HA), is stimulated two- to eight-fold by EGF-URO in cultures of palate tissue obtained between days 11-12 and 13-15 of development; by the time of birth, EGF-URO no longer stimulates GAG production in such cultures. EGF-URO increases the amount and alters the distribution of HA within the palate. The results suggest a role for EGF-URO and for HA in the process of normal palatal development. PMID:3888761

  11. Receptor-purified, Bolton-Hunter radioiodinated, recombinant, human epidermal growth factor: An improved radioligand for receptor studies

    SciTech Connect

    Kermode, J.C.; Tritton, T.R. )

    1990-01-01

    We report an assessment of the applicability of the Bolton-Hunter method to the radioiodination of epidermal growth factor (EGF). Recombinant human EGF (hEGF) could be radioiodinated successfully by this method, whereas murine EGF could not. Bolton-Hunter {sup 125}I-labeled hEGF was compared with commercial 125I-labeled hEGF prepared by the chloramine-T radioiodination method. Neither radioligand was sufficiently pure for a detailed characterization of the purportedly heterogeneous pattern of binding of EGF to its receptors. A procedure based on receptor adsorption was thus developed for repurification of the Bolton-Hunter 125I-labeled hEGF. This provided a much purer radioligand suitable for detailed studies of receptor-binding heterogeneity.

  12. The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling

    PubMed Central

    Weber, Silvio; Niessen, Michaela T.; Prox, Johannes; Lüllmann-Rauch, Renate; Schmitz, Annika; Schwanbeck, Ralf; Blobel, Carl P.; Jorissen, Ellen; de Strooper, Bart; Niessen, Carien M.; Saftig, Paul

    2011-01-01

    The disintegrin and metalloproteinase Adam10 has been implicated in the regulation of key signaling pathways that determine skin morphogenesis and homeostasis. To address the in vivo relevance of Adam10 in the epidermis, we have selectively disrupted Adam10 during skin morphogenesis and in adult skin. K14-Cre driven epidermal Adam10 deletion leads to perinatal lethality, barrier impairment and absence of sebaceous glands. A reduction of spinous layers, not associated with differences in either proliferation or apoptosis, indicates that loss of Adam10 triggers a premature differentiation of spinous keratinocytes. The few surviving K14-Adam10-deleted mice and mice in which Adam10 was deleted postnatally showed loss of hair, malformed vibrissae, epidermal hyperproliferation, cyst formation, thymic atrophy and upregulation of the cytokine thymic stromal lymphopoetin (TSLP), thus indicating non cell-autonomous multi-organ disease resulting from a compromised barrier. Together, these phenotypes closely resemble skin specific Notch pathway loss-of-function phenotypes. Notch processing is indeed strongly reduced resulting in decreased levels of Notch intracellular domain fragment and functional Notch signaling. The data identify Adam10 as the major Site-2 processing enzyme for Notch in the epidermis in vivo, and thus as a central regulator of skin development and maintenance. PMID:21205794

  13. Powerful drivers for maintenance.

    PubMed

    Mason, Steve

    2013-10-01

    A UPS system is the central building block of a Power Continuity Plan in medical facilities, but such equipment requires careful maintenance to continue fulfilling its vital role in delivering power resilience, and avoid catastrophic downtime, and potentially tens of thousands of pounds in costs to rectify the issues caused by poor maintenance. In our latest technical guidance article, Steve Mason, MD at Bender UK, one of the leading providers of isolated power supplies, theatre control panels, UPS systems, and Steris surgical products, and a turnkey provider of solutions for safe handling of electrical power and advanced provision of critical care products, examines some of the issue surrounding UPS maintenance. PMID:24341105

  14. Maintenance of Automated Library Systems.

    ERIC Educational Resources Information Center

    Epstein, Susan Baerg

    1983-01-01

    Discussion of the maintenance of both the software and hardware in an automated library system highlights maintenance by the vendor, contracts and costs, the maintenance log, downtime, and planning for trouble. (EJS)

  15. Epidermal and dermal integumentary structures of ankylosaurian dinosaurs.

    PubMed

    Arbour, Victoria M; Burns, Michael E; Bell, Phil R; Currie, Philip J

    2014-01-01

    Ankylosaurian dinosaurs are most notable for their abundant and morphologically diverse osteoderms, which would have given them a spiky appearance in life. Isolated osteoderms are relatively common and provide important information about the structure of the ankylosaur dermis, but fossilized impressions of the soft-tissue epidermis of ankylosaurs are rare. Nevertheless, well-preserved integument exists on several ankylosaur fossils that shows osteoderms were covered by a single epidermal scale, but one or many millimeter-sized ossicles may be present under polygonal, basement epidermal scales. Evidence for the taxonomic utility of ankylosaurid epidermal scale architecture is presented for the first time. This study builds on previous osteological work that argues for a greater diversity of ankylosaurids in the Dinosaur Park Formation of Alberta than has been traditionally recognized and adds to the hypothesis that epidermal skin impressions are taxonomically relevant across diverse dinosaur clades. PMID:24105904

  16. Lowered Humidity Produces Human Epidermal Equivalents with Enhanced Barrier Properties

    PubMed Central

    Sun, Richard; Celli, Anna; Crumrine, Debra; Hupe, Melanie; Adame, Lillian C.; Pennypacker, Sally D.; Park, Kyungho; Uchida, Yoshikazu; Feingold, Kenneth R.; Elias, Peter M.; Ilic, Dusko

    2015-01-01

    Multilayered human keratinocyte cultures increasingly are used to model human epidermis. Until now, studies utilizing human epidermal equivalents (HEEs) have been limited because previous preparations do not establish a normal epidermal permeability barrier. In this report, we show that reducing environmental humidity to 50% relative humidity yields HEEs that closely match human postnatal epidermis and have enhanced repair of the permeability barrier. These cultures display low transepidermal water loss and possess a calcium and pH gradient that resembles those seen in human epidermis. These cultures upregulate glucosylceramide synthase and make normal-appearing lipid lamellar bilayers. The epidermal permeability barrier of these cultures can be perturbed, using the identical tools previously described for human skin, and recover in the same time course seen during in vivo barrier recovery. These cultures will be useful for basic and applied studies on epidermal barrier function. PMID:24803151

  17. Fluconazole induced toxic epidermal necrolysis: a case report

    PubMed Central

    2009-01-01

    Drug induced toxic epidermal necrolysis and Stevens Johnson syndrome are more commonly associated with medications such as sulfonamides, penicillin, anticonvulsants, oxicam non-steroidal anti-inflammatory drugs, allopurinol and corticosteroids. Isolated instances secondary to drugs outside of the aforementioned classes have also been reported. We report a case of probable toxic epidermal necrolysis induced by fluconazole in a 52 year old woman. PMID:20062708

  18. [Medical Equipment Maintenance Methods].

    PubMed

    Liu, Hongbin

    2015-09-01

    Due to the high technology and the complexity of medical equipment, as well as to the safety and effectiveness, it determines the high requirements of the medical equipment maintenance work. This paper introduces some basic methods of medical instrument maintenance, including fault tree analysis, node method and exclusive method which are the three important methods in the medical equipment maintenance, through using these three methods for the instruments that have circuit drawings, hardware breakdown maintenance can be done easily. And this paper introduces the processing methods of some special fault conditions, in order to reduce little detours in meeting the same problems. Learning is very important for stuff just engaged in this area. PMID:26904890

  19. Getting into Motorcycle Maintenance

    ERIC Educational Resources Information Center

    Mosher, Lynn

    1978-01-01

    This article tells how to start a high school course in motorcycle maintenance and includes names and addresses of some motorcycle manufacturers and a list of needed tools, equipment, and materials. (MF)

  20. Computerized Fleet Maintenance.

    ERIC Educational Resources Information Center

    Cataldo, John J.

    1985-01-01

    The Computerized Fleet Maintenance (CFM) program of a New York school district has major component areas of garage operation, vehicle replacement, and fuel consumption. CFM detects high expenditures and provides the rationale for bus replacement. (MLF)

  1. Carpet Maintenance Guide.

    ERIC Educational Resources Information Center

    Griffin, William R.

    1999-01-01

    Discusses ways to make carpet maintenance in schools easier and effective for keeping carpeted areas in schools attractive and long lasting. Covers cleaning tips for basic spills, ideas for staying on top of stains, and suggestions for eliminating odors. (GR)

  2. Automating Preventive Maintenance.

    ERIC Educational Resources Information Center

    Oshier, Michael J.

    1984-01-01

    Describes the following aspects of the State University of New York-Brockport's preventive maintenance computerization project: (1) software selection, (2) project implementation; and (3) problems and benefits of the system. (MCG)

  3. Care and Maintenance.

    ERIC Educational Resources Information Center

    Hampton, Carolyn H.; Hampton, Carol D.

    1979-01-01

    The classroom care and maintenance of terrestrial isopods is described. Includes illustrations of isopod external anatomy, a potato trap for collecting isopods, and a constructed habitat for raising isopods. (MA)

  4. Lunar robotic maintenance module

    NASA Technical Reports Server (NTRS)

    Ayres, Michael L.

    1988-01-01

    A design for a robotic maintenance module that will assist a mobile 100-meter lunar drill is introduced. The design considers the following areas of interest: the atmospheric conditions, actuator systems, power supply, material selection, weight, cooling system and operation.

  5. Woodwind Instrument Maintenance.

    ERIC Educational Resources Information Center

    Sperl, Gary

    1980-01-01

    The author presents a simple maintenance program for woodwind instruments which includes the care of tendon corks, the need for oiling keys, and methods of preventing cracks in woodwind instruments. (KC)

  6. Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration.

    PubMed

    Simkin, Jennifer; Sammarco, Mimi C; Dawson, Lindsay A; Tucker, Catherine; Taylor, Louis J; Van Meter, Keith; Muneoka, Ken

    2015-06-01

    Mammalian digit regeneration progresses through consistent stages: histolysis, inflammation, epidermal closure, blastema formation, and finally redifferentiation. What we do not yet know is how each stage can affect others. Questions of stage timing, tissue interactions, and microenvironmental states are becoming increasingly important as we look toward solutions for whole limb regeneration. This study focuses on the timing of epidermal closure which, in mammals, is delayed compared to more regenerative animals like the axolotl. We use a standard wound closure device, Dermabond (2-octyl cyanoacrylate), to induce earlier epidermal closure, and we evaluate the effect of fast epidermal closure on histolysis, blastema formation, and redifferentiation. We find that fast epidermal closure is reliant upon a hypoxic microenvironment. Additionally, early epidermal closure eliminates the histolysis stage and results in a regenerate that more closely replicates the amputated structure. We show that tools like Dermabond and oxygen are able to independently influence the various stages of regeneration enabling us to uncouple histolysis, wound closure, and other regenerative events. With this study, we start to understand how each stage of mammalian digit regeneration is controlled. PMID:27499872

  7. Epidermal differentiation gene regulatory networks controlled by MAF and MAFB.

    PubMed

    Labott, Andrew T; Lopez-Pajares, Vanessa

    2016-06-01

    Numerous regulatory factors in epidermal differentiation and their role in regulating different cell states have been identified in recent years. However, the genetic interactions between these regulators over the dynamic course of differentiation have not been studied. In this Extra-View article, we review recent work by Lopez-Pajares et al. that explores a new regulatory network in epidermal differentiation. They analyze the changing transcriptome throughout epidermal regeneration to identify 3 separate gene sets enriched in the progenitor, early and late differentiation states. Using expression module mapping, MAF along with MAFB, are identified as transcription factors essential for epidermal differentiation. Through double knock-down of MAF:MAFB using siRNA and CRISPR/Cas9-mediated knockout, epidermal differentiation was shown to be impaired both in-vitro and in-vivo, confirming MAF:MAFB's role to activate genes that drive differentiation. Lopez-Pajares and collaborators integrated 42 published regulator gene sets and the MAF:MAFB gene set into the dynamic differentiation gene expression landscape and found that lncRNAs TINCR and ANCR act as upstream regulators of MAF:MAFB. Furthermore, ChIP-seq analysis of MAF:MAFB identified key transcription factor genes linked to epidermal differentiation as downstream effectors. Combined, these findings illustrate a dynamically regulated network with MAF:MAFB as a crucial link for progenitor gene repression and differentiation gene activation. PMID:27097296

  8. Tight junction regulates epidermal calcium ion gradient and differentiation

    SciTech Connect

    Kurasawa, Masumi; Maeda, Tetsuo; Oba, Ai; Yamamoto, Takuya; Sasaki, Hiroyuki

    2011-03-25

    Research highlights: {yields} We disrupted epidermal tight junction barrier in reconstructed epidermis. {yields} It altered Ca{sup 2+} distribution and consequentially differentiation state as well. {yields} Tight junction should affect epidermal homeostasis by maintaining Ca{sup 2+} gradient. -- Abstract: It is well known that calcium ions (Ca{sup 2+}) induce keratinocyte differentiation. Ca{sup 2+} distributes to form a vertical gradient that peaks at the stratum granulosum. It is thought that the stratum corneum (SC) forms the Ca{sup 2+} gradient since it is considered the only permeability barrier in the skin. However, the epidermal tight junction (TJ) in the granulosum has recently been suggested to restrict molecular movement to assist the SC as a secondary barrier. The objective of this study was to clarify the contribution of the TJ to Ca{sup 2+} gradient and epidermal differentiation in reconstructed human epidermis. When the epidermal TJ barrier was disrupted by sodium caprate treatment, Ca{sup 2+} flux increased and the gradient changed in ion-capture cytochemistry images. Alterations of ultrastructures and proliferation/differentiation markers revealed that both hyperproliferation and precocious differentiation occurred regionally in the epidermis. These results suggest that the TJ plays a crucial role in maintaining epidermal homeostasis by controlling the Ca{sup 2+} gradient.

  9. Specification of epidermal cell fate in plant shoots.

    PubMed

    Takada, Shinobu; Iida, Hiroyuki

    2014-01-01

    Land plants have evolved a single layer of epidermal cells, which are characterized by mostly anticlinal cell division patterns, formation of a waterproof coat called cuticle, and unique cell types such as stomatal guard cells and trichomes. The shoot epidermis plays important roles not only to protect plants from dehydration and pathogens but also to ensure their proper organogenesis and growth control. Extensive molecular genetic studies in Arabidopsis and maize have identified a number of genes that are required for epidermal cell differentiation. However, the mechanism that specifies shoot epidermal cell fate during plant organogenesis remains largely unknown. Particularly, little is known regarding positional information that should restrict epidermal cell fate to the outermost cell layer of the developing organs. Recent studies suggested that certain members of the HD-ZIP class IV homeobox genes are possible master regulators of shoot epidermal cell fate. Here, we summarize the roles of the regulatory genes that are involved in epidermal cell fate specification and discuss the possible mechanisms that limit the expression and/or activity of the master transcriptional regulators to the outermost cell layer in plant shoots. PMID:24616724

  10. Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration

    PubMed Central

    Simkin, Jennifer; Sammarco, Mimi C.; Dawson, Lindsay A.; Tucker, Catherine; Taylor, Louis J.; Van Meter, Keith

    2015-01-01

    Abstract Mammalian digit regeneration progresses through consistent stages: histolysis, inflammation, epidermal closure, blastema formation, and finally redifferentiation. What we do not yet know is how each stage can affect others. Questions of stage timing, tissue interactions, and microenvironmental states are becoming increasingly important as we look toward solutions for whole limb regeneration. This study focuses on the timing of epidermal closure which, in mammals, is delayed compared to more regenerative animals like the axolotl. We use a standard wound closure device, Dermabond (2‐octyl cyanoacrylate), to induce earlier epidermal closure, and we evaluate the effect of fast epidermal closure on histolysis, blastema formation, and redifferentiation. We find that fast epidermal closure is reliant upon a hypoxic microenvironment. Additionally, early epidermal closure eliminates the histolysis stage and results in a regenerate that more closely replicates the amputated structure. We show that tools like Dermabond and oxygen are able to independently influence the various stages of regeneration enabling us to uncouple histolysis, wound closure, and other regenerative events. With this study, we start to understand how each stage of mammalian digit regeneration is controlled. PMID:27499872

  11. [Epidermal growth factor, innovation and safety].

    PubMed

    Esquirol Caussa, Jordi; Herrero Vila, Elisabeth

    2015-10-01

    Bioidentical recombinant human epidermal growth factor (rhEGF) is available in concentrations and purity suitable for therapeutic use in long time stable formulations. Beneficial effects in several skin pathologies and lesions have been reported (traumatic and surgical wound healing, laser induced wounds, abnormal scars, keloids, radiation or chemotherapy induced dermatitis, post inflammatory hyperpigmentation or for skin aging damage repairing) and also may be considered for the treatment of several oropharingeal and high gastroesophageal tract mucosa diseases (mouth sores, pharyngeal fistulas, ulcers), and several corneal or conjunctive mucosa lesions. rhEGF has not shown any important side or collateral effects in humans or in laboratory experimentation animals, showing optimal tolerability and safety with continuous use for months. Compounding gives advantages of versatility, individualization, personalization, molecular stability, safety and effectiveness in ideal conditions, showing good tissue penetration, both on intact skin and skin lesions that expose the lower planes to the surface. rhEGF compounds can be considered for prevention or as a treatment of diverse skin and mucosa diseases and conditions through compounding preparations. PMID:25433777

  12. Linking Mechanics and Statistics in Epidermal Tissues

    NASA Astrophysics Data System (ADS)

    Kim, Sangwoo; Hilgenfeldt, Sascha

    2015-03-01

    Disordered cellular structures, such as foams, polycrystals, or living tissues, can be characterized by quantitative measurements of domain size and topology. In recent work, we showed that correlations between size and topology in 2D systems are sensitive to the shape (eccentricity) of the individual domains: From a local model of neighbor relations, we derived an analytical justification for the famous empirical Lewis law, confirming the theory with experimental data from cucumber epidermal tissue. Here, we go beyond this purely geometrical model and identify mechanical properties of the tissue as the root cause for the domain eccentricity and thus the statistics of tissue structure. The simple model approach is based on the minimization of an interfacial energy functional. Simulations with Surface Evolver show that the domain statistics depend on a single mechanical parameter, while parameter fluctuations from cell to cell play an important role in simultaneously explaining the shape distribution of cells. The simulations are in excellent agreement with experiments and analytical theory, and establish a general link between the mechanical properties of a tissue and its structure. The model is relevant to diagnostic applications in a variety of animal and plant tissues.

  13. Metabolic profiling of Arabidopsis thaliana epidermal cells

    PubMed Central

    Ebert, Berit; Zöller, Daniela; Erban, Alexander; Fehrle, Ines; Hartmann, Jürgen; Niehl, Annette; Kopka, Joachim; Fisahn, Joachim

    2010-01-01

    Metabolic phenotyping at cellular resolution may be considered one of the challenges in current plant physiology. A method is described which enables the cell type-specific metabolic analysis of epidermal cell types in Arabidopsis thaliana pavement, basal, and trichome cells. To achieve the required high spatial resolution, single cell sampling using microcapillaries was combined with routine gas chromatography-time of flight-mass spectrometry (GC-TOF-MS) based metabolite profiling. The identification and relative quantification of 117 mostly primary metabolites has been demonstrated. The majority, namely 90 compounds, were accessible without analytical background correction. Analyses were performed using cell type-specific pools of 200 microsampled individual cells. Moreover, among these identified metabolites, 38 exhibited differential pool sizes in trichomes, basal or pavement cells. The application of an independent component analysis confirmed the cell type-specific metabolic phenotypes. Significant pool size changes between individual cells were detectable within several classes of metabolites, namely amino acids, fatty acids and alcohols, alkanes, lipids, N-compounds, organic acids and polyhydroxy acids, polyols, sugars, sugar conjugates and phenylpropanoids. It is demonstrated here that the combination of microsampling and GC-MS based metabolite profiling provides a method to investigate the cellular metabolism of fully differentiated plant cell types in vivo. PMID:20150518

  14. Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation

    PubMed Central

    Nakamura, Takashi; Yoshitomi, Yasuo; Sakai, Kiyoshi; Patel, Vyomesh; Fukumoto, Satoshi; Yamada, Yoshihiko

    2014-01-01

    ABSTRACT The basal layer of the epidermis contains stem cells and transit amplifying cells that rapidly proliferate and differentiate further into the upper layers of the epidermis. A number of molecules have been identified as regulators of this process, including p63 (also known as tumor protein 63) and Notch1. However, little is known about the mechanisms that regulate the transitions from stem cell to proliferating or differentiating transit amplifying cell. Here, we demonstrate that epiprofin (Epfn, also known as Sp6) plays crucial distinct roles in these transition stages as a cell cycle regulator and a transcription factor. Epfn knockout mice have a thickened epidermis, in which p63-expressing basal cells form multiple layers owing to the accumulation of premature transit amplifying cells with reduced proliferation and a reduction in the number of differentiating keratinocytes expressing Notch1. We found that low levels of Epfn expression increased the proliferation of human immortalized keratinocyte (HaCaT) cells by increasing EGF responsiveness and superphosphorylation of Rb. By contrast, high levels of Epfn expression promoted cell cycle exit and differentiation, by reducing E2F transactivation and inducing Notch1 expression. Our findings identify multiple novel functions of Epfn in epidermal development. PMID:25344255

  15. Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation.

    PubMed

    Nakamura, Takashi; Yoshitomi, Yasuo; Sakai, Kiyoshi; Patel, Vyomesh; Fukumoto, Satoshi; Yamada, Yoshihiko

    2014-12-15

    The basal layer of the epidermis contains stem cells and transit amplifying cells that rapidly proliferate and differentiate further into the upper layers of the epidermis. A number of molecules have been identified as regulators of this process, including p63 (also known as tumor protein 63) and Notch1. However, little is known about the mechanisms that regulate the transitions from stem cell to proliferating or differentiating transit amplifying cell. Here, we demonstrate that epiprofin (Epfn, also known as Sp6) plays crucial distinct roles in these transition stages as a cell cycle regulator and a transcription factor. Epfn knockout mice have a thickened epidermis, in which p63-expressing basal cells form multiple layers owing to the accumulation of premature transit amplifying cells with reduced proliferation and a reduction in the number of differentiating keratinocytes expressing Notch1. We found that low levels of Epfn expression increased the proliferation of human immortalized keratinocyte (HaCaT) cells by increasing EGF responsiveness and superphosphorylation of Rb. By contrast, high levels of Epfn expression promoted cell cycle exit and differentiation, by reducing E2F transactivation and inducing Notch1 expression. Our findings identify multiple novel functions of Epfn in epidermal development. PMID:25344255

  16. A modelling approach towards epidermal homoeostasis control.

    PubMed

    Schaller, Gernot; Meyer-Hermann, Michael

    2007-08-01

    In order to grasp the features arising from cellular discreteness and individuality, in large parts of cell tissue modelling agent-based models are favoured. The subclass of off-lattice models allows for a physical motivation of the intercellular interaction rules. We apply an improved version of a previously introduced off-lattice agent-based model to the steady-state flow equilibrium of skin. The dynamics of cells is determined by conservative and drag forces, supplemented with delta-correlated random forces. Cellular adjacency is detected by a weighted Delaunay triangulation. The cell cycle time of keratinocytes is controlled by a diffusible substance provided by the dermis. Its concentration is calculated from a diffusion equation with time-dependent boundary conditions and varying diffusion coefficients. The dynamics of a nutrient is also taken into account by a reaction-diffusion equation. It turns out that the analysed control mechanism suffices to explain several characteristics of epidermal homoeostasis formation. In addition, we examine the question of how in silico melanoma with decreased basal adhesion manage to persist within the steady-state flow equilibrium of the skin. Interestingly, even for melanocyte cell cycle times being substantially shorter than for keratinocytes, tiny stochastic effects can lead to completely different outcomes. The results demonstrate that the understanding of initial states of tumour growth can profit significantly from the application of off-lattice agent-based models in computer simulations. PMID:17466340

  17. Epidermal growth factor signaling in transformed cells

    PubMed Central

    Lindsey, Stephan; Langhans, Sigrid A.

    2016-01-01

    Members of the epidermal growth factor receptor (EGFR/ErbB) family play a critical role in normal cell growth and development. However, many ErbB family members, especially EGFR, are aberrantly expressed or deregulated in tumors and are thought to play crucial roles in cancer development and metastatic progression. In this chapter, we provide an overview of key mechanisms contributing to aberrant EGFR/ErbB signaling in transformed cells which results in many phenotypic changes associated with the earliest stages of tumor formation, including several hallmarks of epithelial-to-mesenchymal transition (EMT). These changes often occur through interaction with other major signaling pathways important to tumor progression resulting in a multitude of transcriptional changes that ultimately impact cell morphology, proliferation and adhesion, all of which are crucial for tumor progression. The resulting mesh of signaling networks will need to be taken into account as new regimens are designed for targeting EGFR for therapeutic intervention. As new insights into the molecular mechanisms of the cross-talk of EGFR signaling with other signaling pathways and their role in therapeutic resistance to anti-EGFR therapies are gained a continual reassessment of clinical therapeutic regimes and strategies will be required. Understanding the consequences and complexity of EGF signaling and how it relates to tumor progression is critical for the development of clinical compounds and establishing clinical protocols for the treatment of cancer. PMID:25619714

  18. Althaea rosea Cavanil and Plantago major L. suppress neoplastic cell transformation through the inhibition of epidermal growth factor receptor kinase.

    PubMed

    Choi, Eun-Sun; Cho, Sung-Dae; Shin, Ji-Ae; Kwon, Ki Han; Cho, Nam-Pyo; Shim, Jung-Hyun

    2012-10-01

    For thousands of years in Asia, Althaea rosea Cavanil (ARC) and Plantago major L. (PML) have been used as powerful non-toxic therapeutic agents that inhibit inflammation. However, the anticancer mechanisms and molecular targets of ARC and PML are poorly understood, particularly in epidermal growth factor (EGF)-induced neoplastic cell transformation. The aim of this study was to evaluate the chemopreventive effects and mechanisms of the methanol extracts from ARC (MARC) and PML (MPML) in EGF-induced neoplastic cell transformation of JB6 P+ mouse epidermal cells using an MTS assay, anchorage-independent cell transformation assay and western blotting. Our results showed that MARC and MPML significantly suppressed neoplastic cell transformation by inhibiting the kinase activity of the EGF receptor (EGFR). The activation of EGFR by EGF was suppressed by MARC and MPML treatment in EGFR(+/+) cells, but not in EGFR(-/-) cells. In addition, MARC and MPML inhibited EGF-induced cell proliferation in EGFR-expressing murine embryonic fibroblasts (EGFR(+/+)). These results strongly indicate that EGFR targeting by MARC and MPML may be a good strategy for chemopreventive or chemotherapeutic applications. PMID:22767187

  19. Murine Typhus, Reunion, France, 2011–2013

    PubMed Central

    Camuset, Guillaume; Socolovschi, Cristina; Moiton, Marie-Pierre; Kuli, Barbara; Foucher, Aurélie; Poubeau, Patrice; Borgherini, Gianandrea; Wartel, Guillaume; Audin, Héla; Raoult, Didier; Filleul, Laurent; Parola, Philippe; Pagès, Fréderic

    2015-01-01

    Murine typhus case was initially identified in Reunion, France, in 2012 in a tourist. Our investigation confirmed 8 autochthonous cases that occurred during January 2011–January 2013 in Reunion. Murine typhus should be considered in local patients and in travelers returning from Reunion who have fevers of unknown origin. PMID:25625653

  20. Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen

    PubMed Central

    Sitaru, Cassian; Mihai, Sidonia; Otto, Christoph; Chiriac, Mircea T.; Hausser, Ingrid; Dotterweich, Barbara; Saito, Hitoshi; Rose, Christian; Ishiko, Akira; Zillikens, Detlef

    2005-01-01

    Epidermolysis bullosa acquisita (EBA) is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies specific to type VII collagen, a major constituent of the dermal-epidermal junction. Previous attempts to transfer the disease by injection of patient autoantibodies into mice have been unsuccessful. To study the pathogenic relevance of antibodies specific to type VII collagen in vivo, we generated and characterized rabbit antibodies specific to a murine form of this antigen and passively transferred them into adult nude, BALB/c, and C57BL/6 mice. Immune rabbit IgG bound to the lamina densa of murine skin and immunoblotted type VII collagen. Mice injected with purified IgG specific to type VII collagen, in contrast to control mice, developed subepidermal skin blisters, reproducing the human disease at the clinical, histological, electron microscopical, and immunopathological levels. Titers of rabbit IgG in the serum of mice correlated with the extent of the disease. F(ab′)2 fragments of rabbit IgG specific to type VII collagen were not pathogenic. When injected into C5-deficient mice, antibodies specific to type VII collagen failed to induce the disease, whereas C5-sufficient mice were susceptible to blister induction. This animal model for EBA should facilitate further dissection of the pathogenesis of this disease and development of new therapeutic strategies. PMID:15841176

  1. Recombinant modular transporters on the basis of epidermal growth factor for targeted intracellular delivery of photosensitizers

    NASA Astrophysics Data System (ADS)

    Gilyazova, Dinara G.; Rosenkranz, Andrey A.; Gulak, Pavel V.; Lunin, Vladimir G.; Sergienko, Olga V.; Grin, Mikhail A.; Mironov, Andrey F.; Rubin, Andrey B.; Sobolev, Alexander S.

    2005-08-01

    The search for new pharmaceuticals has raised interest in locally-acting drugs which act over short distances within the cell, and for which different cell compartments have different sensitivities. Thus, photosensitizers used in anti-cancer therapy should be transported to the most sensitive subcellular compartments where their action is most pronounced. Earlier, we described the effects of bacterially expressed modular recombinant transporters for photosensitizers comprising a-melanocyte-stimulating hormone as an internalizable, cell-specific ligand, an optimized nuclear localization sequence, an Escherichia coli hemoglobin-like protein as a carrier, and an endosomolytic amphipathic polypeptide. These transporters delivered photosensitizers into the murine melanoma cells nuclei to result in cytotoxic effects 2 orders of magnitude greater than those of nonmodified photosensitizers. Here we describe new transporters possessing the same modules except for a ligand that is replaced with epidermal growth factor specific for other cancer cell types. The new transporter modules retained their functional activities within the chimera, this transporter delivered photosensitizers into the human carcinoma cells nuclei to result in photocytotoxic effects almost 3 orders of magnitude greater than those of nonmodified photosensitizers. The obtained results show that ligand modules of such transporters are interchangeable, meaning that they can be tailored for particular applications.

  2. The Epidermal Growth Factor Receptor Increases Cytokine Production and Cutaneous Inflammation in Response to Ultraviolet Irradiation

    PubMed Central

    El-Abaseri, Taghrid Bahig; Repertinger, Susan K.; Hansen, Laura A.

    2013-01-01

    The epidermal growth factor receptor (EGFR) is activated in cutaneous keratinocytes upon ultraviolet (UV) exposure and has been implicated in ultraviolet-(UV-)induced inflammation and skin tumorigenesis. Egfr mutant mice and EGFR inhibitors were used to investigate the hypothesis that EGFR activation augments inflammation following UV irradiation. Topical treatment of mouse skin with the EGFR inhibitor AG1478 before UV exposure suppressed UV-induced erythema, edema, mast cell infiltration, and neutrophil infiltration. Genetic ablation of Egfr and EGFR inhibition by AG1478 also suppressed the increase in the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin-1α, KC (murine IL-8), and cyclooxygenase-2 (COX-2) after UV exposure of cultured keratinocytes. Finally, genetic ablation of inhibition of EGFR in cultured keratinocytes decreased p38 activation after UV, while inhibition of p38 kinase reduced COX-2 expression after UV. These data demonstrate that EGFR regulates multiple aspects of UV-induced inflammation and suggest activation of p38 kinase leading to increased COX-2 and cytokine expression as one mechanism through which it acts. PMID:23878744

  3. Co-Regulation and Interdependence of the Mammalian Epidermal Permeability and Antimicrobial Barriers

    PubMed Central

    Aberg, Karin M.; Man, Mao-Qiang; Gallo, Richard L.; Ganz, Tomas; Crumrine, Debra; Brown, Barbara E.; Choi, Eung-Ho; Kim, Dong-Kun; Schröder, Jens M.; Feingold, Kenneth R.; Elias, Peter M.

    2009-01-01

    Human epidermis elaborates two small cationic, highly hydrophobic antimicrobial peptides (AMP), β-defensin 2 (hBD2), and the carboxypeptide cleavage product of human cathelicidin (hCAP18), LL-37, which are co-packaged along with lipids within epidermal lamellar bodies (LBs) before their secretion. Because of their colocalization, we hypothesized that AMP and barrier lipid production could be coregulated by altered permeability barrier requirements. mRNA and immunostainable protein levels for mBD3 and cathelin-related antimicrobial peptide (CRAMP) (murine homologues of hBD2 and LL-37, respectively) increase 1–8 hours after acute permeability barrier disruption and normalize by 24 hours, kinetics that mirror the lipid metabolic response to permeability barrier disruption. Artificial permeability barrier restoration, which inhibits the lipid-synthetic response leading to barrier recovery, blocks the increase in AMP mRNA/protein expression, further evidence that AMP expression is linked to permeability barrier function. Conversely, LB-derived AMPs are also important for permeability barrier homeostasis. Despite an apparent increase in mBD3 protein, CRAMP−/− mice delayed permeability barrier recovery, attributable to defective LB contents and abnormalities in the structure of the lamellar membranes that regulate permeability barrier function. These studies demonstrate that (1) the permeability and antimicrobial barriers are coordinately regulated by permeability barrier requirements and (2) CRAMP is required for permeability barrier homeostasis. PMID:17943185

  4. Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney.

    PubMed

    Sheng, Lili; Yang, Min; Ding, Wei; Zhang, Minmin; Niu, Jianying; Qiao, Zhongdong; Gu, Yong

    2016-08-01

    Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangial cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. PMID:27317889

  5. Modulation of influenza vaccine immune responses using an epidermal growth factor receptor kinase inhibitor

    PubMed Central

    Pulit-Penaloza, Joanna A.; Sapkota, Bishu; Stein Esser, E.; Compans, Richard W.; Pollack, Brian P.; Skountzou, Ioanna

    2015-01-01

    Systemic use of epidermal growth factor receptor inhibitors (EGFRIs) has been shown to alter MHC expression and that of several chemokines, and to enhance immune cell recruitment into human skin. We hypothesized that EGFRIs may have value as cutaneous immune response modifiers, and determined the effects of topical application of an irreversible EGFRI on a well-established murine model of influenza vaccination. We found that a single topical application of an EGFRI led to increased levels of antibodies that inhibit influenza mediated hemagglutination and viral cytopathic effects. The topically applied EGFRI significantly enhanced the generation of vaccine-specific IL-4 and IFN-γ producing cells within skin-draining lymph nodes as early as one week following vaccination. The EGFRI/vaccine group showed a twelve-fold reduction in detectable pulmonary viral load four days after infection as compared to the vaccine alone control group. The reduction in the lung viral titers correlated with the survival rate, which demonstrated 100% protection in the EGFRI/vaccine immunized group but only 65% protection in the mice immunized with vaccine alone. These findings are significant because they demonstrate that inhibition of defined signaling pathways within the skin using small molecule kinase inhibitors provides a novel approach to enhance immune responses to vaccines. PMID:26227481

  6. Epidermal growth factor and growth in vivo

    SciTech Connect

    Rhodes, J.A.

    1986-01-01

    Epidermal growth factor (EGF) causes a dose-dependent thickening of the epidermis in suckling mice. The cellular mechanisms underlying this thickening were analyzed by measuring the effect of EGF on the cell-cycle. Neonatal mice were given daily injections of either 2ug EGF/g body weight/day or an equivalent volume of saline, and on the seventh day received a single injection of /sup 3/H-thymidine. At various times the mice were perfused with fixative; 1um sections of skin were stained with a modification of Harris' hematoxylin and were autoradiographed. The sections were analyzed using three methods based on the dependence on time after injection of /sup 3/H-thymidine of: frequency of labelled mitoses, labelling index, and reciprocal grains/nucleus. It was found that EGF caused a two-fold increase in the cell production rate. The effect of exogenous EGF on the morphology of gastric mucosa and incisors of suckling mice was also studied. The gastric mucosa appeared thicker in EGF-treated animals, but the effect was not statistically significant. In contrast to its effect on epidermis and gastric mucosa, EGF caused a significant, dose-dependent decrease in the size of the incisors. Because the mouse submandibular salivary gland is the major source of EGF the effect of sialoadenectomy on female reproductive functions was examined. Ablation of the submandibular gland had no effect on: length of estrus cycle, ability of the female to produce litters, length of the gestation period, litter size, and weight of the litter at birth. There was also no effect on survival of the offspring or on age at which the eyelids separated.

  7. Fluorescence lifetime to image epidermal ionic concentrations

    NASA Astrophysics Data System (ADS)

    Behne, Martin J.; Barry, Nicholas P.; Moll, Ingrid; Gratton, Enrico; Mauro, Theodora M.

    2004-09-01

    Measurements of ionic concentrations in skin have traditionally been performed with an array of methods which either did not reveal detailed localization information, or only provided qualitative, not quantitative information. FLIM combines a number of advantages into a method ideally suited to visualize concentrations of ions such as H+ in intact, unperturbed epidermis and stratum corneum (SC). Fluorescence lifetime is dye concentration-independent, the method requires only low light intensities and is therefore not prone to photobleaching or phototoxic artifacts, and because multiphoton lasers of IR wavelength are used, light penetrates deep into intact tissue. The standard method to measure SC pH is the flat pH electrode, which provides reliable information only about surface pH changes, without further vertical or subcellular spatial resolution; i.e., specific microdomains such as the corneocyte interstices are not resolved, and the deeper SC is inaccessible without resorting to inherently disruptive stripping methods. Furthermore, the concept of a gradient of pH through the SC stems from such stripping experiments, but other confirmation for this concept is lacking. Our investigations into the SC pH distribution so far have revealed the crucial role of the Sodium/Hydrogen Antiporter NHE1 in generation of SC acidity, the colocalization of enzymatic lipid processing activity in the SC with acidic domains of the SC, and the timing and localization of emerging acidity in the SC of newborns. Together, these results have led to an improved understanding of the SC pH, its distribution, origin, and regulation. Future uses for this method include measurements of other ions important for epidermal processes, such as Ca2+, and a quantitative approach to topical drug penetration.

  8. Maintenance strategies for greater availability

    SciTech Connect

    Pradhan, S. )

    1994-01-01

    Benchmark studies have confirmed there is a very wide gap in perceived world-class versus actual maintenance performance. To bridge this gap, companies will have to quickly adopt appropriate preventive and predictive maintenance practices and implement total productive maintenance (TPM) and reliability centered maintenance (RCM) practices. In process plants the whole approach to maintenance is slipshod, with a jumble of acronyms like PM/RM/CPM/flexing/multi-skilling, etc., giving a false sense of progress. North American maintenance benchmarks and British maintenance best practice give a very clear picture of current maintenance practices. Both of these studies indicate that breakdown maintenance is the dominant mode of maintenance in the progress industries. There are several key steps to be followed in establishing a strategy for maintenance improvements: (1) Recognize maintenance as an executive function; (2) Establish a solid maintenance performance database; (3) Review the existing plant maintenance practices; (4) Review and understand world-class maintenance practices; and (5) Design a master plan for a world-class system: Define the plant and maintenance resources; Define multi-skilling strategy; Define training and education levels for each job grouping; and Apply, and don't just talk about TPM and RCM.

  9. Reliability Centered Maintenance - Methodologies

    NASA Technical Reports Server (NTRS)

    Kammerer, Catherine C.

    2009-01-01

    Journal article about Reliability Centered Maintenance (RCM) methodologies used by United Space Alliance, LLC (USA) in support of the Space Shuttle Program at Kennedy Space Center. The USA Reliability Centered Maintenance program differs from traditional RCM programs because various methodologies are utilized to take advantage of their respective strengths for each application. Based on operational experience, USA has customized the traditional RCM methodology into a streamlined lean logic path and has implemented the use of statistical tools to drive the process. USA RCM has integrated many of the L6S tools into both RCM methodologies. The tools utilized in the Measure, Analyze, and Improve phases of a Lean Six Sigma project lend themselves to application in the RCM process. All USA RCM methodologies meet the requirements defined in SAE JA 1011, Evaluation Criteria for Reliability-Centered Maintenance (RCM) Processes. The proposed article explores these methodologies.

  10. Antimicrobials in periodontal maintenance.

    PubMed

    Jorgensen, M G; Slots, J

    2001-01-01

    Mechanical and chemical antimicrobial intervention is the mainstay of preventive periodontal therapy. Successful periodontal maintenance care depends upon the ability of oral health care professionals to combat periodontal infections, and patient compliance with prescribed follow-up care. Since tooth brushing, flossing, and oral rinsing do not reach pathogens present in furcations and at the depths of deep periodontal pockets, adequate oral hygiene should include subgingival treatment with home irrigators or other appropriate self-care remedies in patients with these conditions. Povidone-iodine for professional use and diluted bleach for self-care are inexpensive and valuable antimicrobial agents in periodontal maintenance. The present article outlines the prudent use of antimicrobial therapy in periodontal maintenance. PMID:11603305

  11. Maintenance simulation: Software issues

    SciTech Connect

    Luk, C.H.; Jette, M.A.

    1995-07-01

    The maintenance of a distributed software system in a production environment involves: (1) maintaining software integrity, (2) maintaining and database integrity, (3) adding new features, and (4) adding new systems. These issues will be discussed in general: what they are and how they are handled. This paper will present our experience with a distributed resource management system that accounts for resources consumed, in real-time, on a network of heterogenous computers. The simulated environments to maintain this system will be presented relate to the four maintenance areas.

  12. Do epidermal lens cells facilitate the absorptance of diffuse light?

    PubMed

    Brodersen, Craig R; Vogelmann, Thomas C

    2007-07-01

    Many understory plants rely on diffuse light for photosynthesis because direct light is usually scattered by upper canopy layers before it strikes the forest floor. There is a considerable gap in the literature concerning the interaction of direct and diffuse light with leaves. Some understory plants have well-developed lens-shaped epidermal cells, which have long been thought to increase the absorption of diffuse light. To assess the role of epidermal cell shape in capturing direct vs. diffuse light, we measured leaf reflectance and transmittance with an integrating sphere system using leaves with flat (Begonia erythrophylla, Citrus reticulata, and Ficus benjamina) and lens-shaped epidermal cells (B. bowerae, Colocasia esculenta, and Impatiens velvetea). In all species examined, more light was absorbed when leaves were irradiated with direct as opposed to diffuse light. When leaves were irradiated with diffuse light, more light was transmitted and more was reflected in both leaf types, resulting in absorptance values 2-3% lower than in leaves irradiated with direct light. These data suggest that lens-shaped epidermal cells do not aid the capture of diffuse light. Palisade and mesophyll cell anatomy and leaf thickness appear to have more influence in the capture and absorption of light than does epidermal cell shape. PMID:21636475

  13. Epidermal skin grafting in vitiligo: a pilot study.

    PubMed

    Janowska, Agata; Dini, Valentina; Panduri, Salvatore; Macchia, Michela; Oranges, Teresa; Romanelli, Marco

    2016-09-01

    Vitiligo is a multifactorial acquired dermatosis characterised by achromic or hypochromic macules and by the absence of functioning melanocytes. Treatment depends on the extent of the affected areas and on disease activity. Surgical techniques have proven to be effective in stable cases but can be time-consuming and, in some cases, aesthetically unsatisfying or painful for the patients. The aim of the study was to assess the clinical safety and effectiveness of a new automatic epidermal skin harvesting device in patients with stable localised vitiligo over a minimum 12-month period. This new system (CELLUTOME™ Epidermal Harvesting System, KCI, an ACELITY Company, San Antonio, TX) is a commercially available epidermal skin harvesting system that can be used without local anaesthesia or other pre-treatments and has been shown to have low rates of donor site morbidity. Epidermal skin grafts can used in patients with acute and hard to heal chronic wounds, burns and stable vitiligo. The use of advanced therapies may improve the quality of life, have cost benefits and accelerate re-pigmentation of patients with vitiligo. In our preliminary study, this system was seen to be a safe and efficacious means of harvesting epidermal micrografts containing melanocytes for use in patients with stable vitiligo unresponsive to standard therapies. PMID:27547963

  14. IκBNS regulates murine Th17 differentiation during gut inflammation and infection.

    PubMed

    Annemann, Michaela; Wang, Zuobai; Plaza-Sirvent, Carlos; Glauben, Rainer; Schuster, Marc; Ewald Sander, Frida; Mamareli, Panagiota; Kühl, Anja A; Siegmund, Britta; Lochner, Matthias; Schmitz, Ingo

    2015-03-15

    IL-17-producing Th17 cells mediate immune responses against a variety of fungal and bacterial infections. Signaling via NF-κB has been linked to the development and maintenance of Th17 cells. We analyzed the role of the unusual inhibitor of NF-κB, IκBNS, in the proliferation and effector cytokine production of murine Th17 cells. Our study demonstrates that nuclear IκBNS is crucial for murine Th17 cell generation. IκBNS is highly expressed in Th17 cells; in the absence of IκBNS, the frequencies of IL-17A-producing cells are drastically reduced. This was measured in vitro under Th17-polarizing conditions and confirmed in two colitis models. Mechanistically, murine IκBNS (-/-) Th17 cells were less proliferative and expressed markedly reduced levels of IL-2, IL-10, MIP-1α, and GM-CSF. Citrobacter rodentium was used as a Th17-inducing infection model, in which IκBNS (-/-) mice displayed an increased bacterial burden and diminished tissue damage. These results demonstrate the important function of Th17 cells in pathogen clearance, as well as in inflammation-associated pathology. We identified IκBNS to be crucial for the generation and function of murine Th17 cells upon inflammation and infection. Our findings may have implications for the therapy of autoimmune conditions, such as inflammatory bowel disease, and for the treatment of gut-tropic infections. PMID:25694610

  15. Home Maintenance Manual.

    ERIC Educational Resources Information Center

    Richmond, Jim; And Others

    This manual, written especially for the Navajo and Hopi Indian Relocation Commission, is a simply worded, step-by-step guide to home maintenance for new homeowners. It can be used for self-study or it can serve as instructional material for a training class on home ownership. The manual is organized in nine sections that cover the following…

  16. CH Packaging Maintenance Manual

    SciTech Connect

    Washington TRU Solutions

    2002-01-02

    This procedure provides instructions for performing inner containment vessel (ICV) and outer containment vessel (OCV) maintenance and periodic leakage rate testing on the following packaging seals and corresponding seal surfaces using a nondestructive helium (He) leak test. In addition, this procedure provides instructions for performing ICV and OCV structural pressure tests.

  17. Floors: Care and Maintenance.

    ERIC Educational Resources Information Center

    Post Office Dept., Washington, DC.

    Guidelines, methods and policies regarding the care and maintenance of post office building floors are overviewed in this handbook. Procedures outlined are concerned with maintaining a required level of appearance without wasting manpower. Flooring types and characteristics and the particular cleaning requirements of each type are given along with…

  18. Diesel Vehicle Maintenance Competencies.

    ERIC Educational Resources Information Center

    Braswell, Robert; And Others

    Designed to provide a model set of competencies, this manual presents tasks which were identified by employers, employees, and teachers as important in a postsecondary diesel vehicle maintenance curriculum. The tasks are divided into seven major component areas of instruction: chassis and suspension, diesel engines, diesel fuel, electrical,…

  19. Operations and maintenance philosophy

    SciTech Connect

    DUNCAN, G.P.

    1999-10-28

    This Operations and Maintenance (O&M) Philosophy document is intended to establish a future O&M vision, with an increased focus on minimizing worker exposure, ensuring uninterrupted retrieval operations, and minimizing operation life-cycle cost. It is intended that this document would incorporate O&M lessons learned into on-going and future project upgrades.

  20. Maintenance Crisis vs Solutions.

    ERIC Educational Resources Information Center

    Haggard, Susie

    Industrial maintenance in Northeast Georgia is facing an acute crisis. Contributing factors are economic development that is depleting the work force, aging of the population, downsizing of the military, and lack of technical school graduates. Solutions to the crisis fall into three categories: short-term, mid-term, and long-term. For short-term…

  1. Floors: Selection and Maintenance.

    ERIC Educational Resources Information Center

    Berkeley, Bernard

    Flooring for institutional, commercial, and industrial use is described with regard to its selection, care, and maintenance. The following flooring and subflooring material categories are discussed--(1) resilient floor coverings, (2) carpeting, (3) masonry floors, (4) wood floors, and (5) "formed-in-place floors". The properties, problems,…

  2. Industrial Mechanical Maintenance.

    ERIC Educational Resources Information Center

    Hendrix, Laborn J.

    This manual was developed to assist teachers in Oklahoma in preparing students for industrial mechanical maintenance. The materials in this teacher's guide are organized in 14 units of instruction covering the following four areas: receiving and setting equipment; equipment hookup and operation; equipment layout, anchoring, and setup; and…

  3. Electrical Maintenance Technician.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This document contains 30 units to consider for use in a tech prep competency profile for the occupation of electrical maintenance technician. All the units listed will not necessarily apply to every situation or tech prep consortium, nor will all the competencies within each unit be appropriate. Several units appear within each specific…

  4. Care and Maintenance.

    ERIC Educational Resources Information Center

    Hampton, Carol D.; Hampton, Carolyn H.

    1980-01-01

    Described is a method for bringing the sea into the classroom by setting up a saltwater aquarium. Included is selection of an aquarium, filtering systems, water (whether natural salt or synthetic sea salts), bottom materials, setting up an aquarium, system stabilization, stocking an aquarium, and maintenance of the aquarium. (DS)

  5. Computerized Fleet Maintenance.

    ERIC Educational Resources Information Center

    Cataldo, John J.

    The computerization of school bus maintenance records by the Niskayuna (New York) Central School District enabled the district's transportation department to engage in management practices resulting in significant savings. The district obtains computer analyses of the work performed on all vehicles, including time spent, parts, labor, costs,…

  6. Summer Roof Maintenance.

    ERIC Educational Resources Information Center

    Liscum, Curtis L.

    1999-01-01

    Presents the items to review in roofing maintenance to prepare for the impact of summer, including checking drainage, roof-field surface and membrane, flashings, sheet metal, and rooftop equipment, such as skylights and penthouses. A list of roofing facts facility managers should know are highlighted. (GR)

  7. School Maintenance Needs

    ERIC Educational Resources Information Center

    Erickson, Paul W.

    2011-01-01

    The United States is full of schools built in the 1950s and 60s that supported the boomer school-age enrollment increase. These schools, once beacons of the neighborhood, are 50 to 60 years old and susceptible to becoming the community "eyesore." Budgeting for maintenance was fairly systematic for school districts for the first 10 to 20 years…

  8. Epidermal Choristoma of the Tongue Mimicking a Congenital Melanotic Macule.

    PubMed

    Curto-Barredo, Laia; Vicente, Asunción; Rovira, Carlota; García-Diez, Eloy; Pujol, Ramón M; González-Enseñat, Maria Antonia

    2015-01-01

    We report the fifth case of epidermal choristoma of the oral cavity in a Caucasian newborn with a congenital melanotic macule on the dorsum of the tongue. Epidermal choristoma is an exceedingly rare and benign condition probably caused by a developmental abnormality. It is identified according to the presence of normal skin in an abnormal location. Histologically it is identified according to areas of stratified epithelium and hyperpigmentation of the basal layer along with cutaneous adnexal structures (hair follicles, sebaceous or sweat glands). The clinical presentation is variable, but most of the cases described presented with a congenital lingual pigmented macule. These lesions should be included within the differential diagnosis of congenital lingual macules and distinguished from other entities such as congenital lingual melanotic macules and melanocytic lesions. Surgical excision is the treatment of choice. Epidermal choristoma is a benign condition that probably is underdiagnosed because it is a new and rare entity, and dermatologists should be aware of it. PMID:25529319

  9. A Ruptured Digital Epidermal Inclusion Cyst: A Sinister Presentation

    PubMed Central

    Fletcher, Phillip; Ragg, Amanda; Vane, Andrew

    2016-01-01

    Epidermal inclusion cysts are benign cutaneous lesions caused by dermal or subdermal implantation and proliferation of epidermal squamous epithelium as a result of trauma or surgery. They are typically located on the scalp, face, trunk, neck, or back; however they can be found anywhere on the body. Lesions are asymptomatic unless complicated by rupture, malignant transformation to squamous cell carcinoma, or infection at which point they can clinically appear as more sinister pathologies. We present the case of a 45-year-old laborer with a ruptured epidermal inclusion cyst, manifesting clinically and radiographically as a malignancy. Following MRI, definitive surgical management may appear to be a logical progression in management of the patient. This case however is a good example of why meticulously following surgical protocol when evaluating an unknown soft tissue mass is imperative. By following protocol, an alternate diagnosis was made and the patient has since gone on to a make a full recovery without life transforming surgery. PMID:27418992

  10. A Ruptured Digital Epidermal Inclusion Cyst: A Sinister Presentation.

    PubMed

    Bohler, Iain; Fletcher, Phillip; Ragg, Amanda; Vane, Andrew

    2016-01-01

    Epidermal inclusion cysts are benign cutaneous lesions caused by dermal or subdermal implantation and proliferation of epidermal squamous epithelium as a result of trauma or surgery. They are typically located on the scalp, face, trunk, neck, or back; however they can be found anywhere on the body. Lesions are asymptomatic unless complicated by rupture, malignant transformation to squamous cell carcinoma, or infection at which point they can clinically appear as more sinister pathologies. We present the case of a 45-year-old laborer with a ruptured epidermal inclusion cyst, manifesting clinically and radiographically as a malignancy. Following MRI, definitive surgical management may appear to be a logical progression in management of the patient. This case however is a good example of why meticulously following surgical protocol when evaluating an unknown soft tissue mass is imperative. By following protocol, an alternate diagnosis was made and the patient has since gone on to a make a full recovery without life transforming surgery. PMID:27418992

  11. Cutaneous adverse reactions specific to epidermal growth factor receptor inhibitors

    PubMed Central

    Lupu, I; Voiculescu, VM; Bacalbasa, N; Prie, BE; Cojocaru, I; Giurcaneanu, C

    2015-01-01

    Classical antineoplastic therapy is encumbered by extensively studied adverse reactions, most often of systemic nature. The emergence of new generations of anticancer treatments, including epidermal growth factor receptor inhibitors, besides improving the response to treatment and the survival rate, is accompanied by the occurrence of new specific side effects, incompletely studied. These side effects are most often cutaneous (hand foot syndrome, acneiform reactions), and in some cases are extremely severe, requiring dose reduction or drug discontinuation. The prevention of the cutaneous adverse effects and their treatment require a close collaboration between the oncologist and the dermatologist. The occurrence of some of these skin adverse effects may be a favorable prognostic factor for the response to the cancer treatment and the overall survival. Abbreviations: EGFR = epidermal growth factor receptors; EGFRI = epidermal growth factor receptors inhibitors PMID:26361513

  12. Dermal and epidermal chromatophores of the Antarctic teleost Trematomus bernacchii.

    PubMed

    Obika, M; Meyer-Rochow, V B

    1990-01-01

    The physiological response and ultrastructure of the pigment cells of Trematomus bernacchii, an Antarctic teleost that lives under the sea ice north of the Ross Ice Shelf, were studied. In the integument, two types of epidermal chromatophores, melanophores and xanthophores, were found; in the dermis, typically three types of chromatophores--melanophores, xanthophores, and iridophores--were observed. The occurrence of epidermal xanthophore is reported for the first time in fish. Dermal melanophores and xanthophores have well-developed arrays of cytoplasmic microtubules. They responded rapidly to epinephrine and teleost melanin-concentrating hormone (MCH) with pigment aggregation and to theophylline with pigment dispersion. Total darkness elicited pigment aggregation in the majority of dermal xanthophores of isolated scales, whereas melanophores remained dispersed under both light and dark conditions. Pigment organelles of epidermal and dermal xanthophores that translocate during the pigmentary responses are carotenoid droplets of relatively large size. Dermal iridophores containing large reflecting platelets appeared to be immobile. PMID:2377579

  13. IL-10 regulates murine lupus.

    PubMed

    Yin, Zhinan; Bahtiyar, Gul; Zhang, Na; Liu, Lanzhen; Zhu, Ping; Robert, Marie E; McNiff, Jennifer; Madaio, Michael P; Craft, Joe

    2002-08-15

    MRL/MpJ-Tnfrsf6(lpr) (MRL/MpJ-Fas(lpr); MRL-Fas(lpr)) mice develop a spontaneous lupus syndrome closely resembling human systemic lupus erythematosus. To define the role of IL-10 in the regulation of murine lupus, IL-10 gene-deficient (IL-10(-/-)) MRL-Fas(lpr) (MRL-Fas(lpr) IL-10(-/-)) mice were generated and their disease phenotype was compared with littermates with one or two copies of an intact IL-10 locus (MRL-Fas(lpr) IL-10(+/-) and MRL-Fas(lpr) IL-10(+/+) mice, respectively). MRL-Fas(lpr) IL-10(-/-) mice developed severe lupus, with earlier appearance of skin lesions, increased lymphadenopathy, more severe glomerulonephritis, and higher mortality than their IL-10-intact littermate controls. The increased severity of lupus in MRL-Fas(lpr) IL-10(-/-) mice was closely associated with enhanced IFN-gamma production by both CD4(+) and CD8(+) cells and increased serum concentration of IgG2a anti-dsDNA autoantibodies. The protective effect of IL-10 in this lupus model was further supported by the observation that administration of rIL-10 reduced IgG2a anti-dsDNA autoantibody production in wild-type MRL-Fas(lpr) animals. In summary, our results provide evidence that IL-10 can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses. Modulation of the level of IL-10 may be of potential therapeutic benefit for human lupus. PMID:12165544

  14. K6PC-5, a novel sphingosine kinase activator, improves long-term ultraviolet light-exposed aged murine skin.

    PubMed

    Park, Hwa-young; Youm, Jong-Kyung; Kwon, Mi Jung; Park, Byeong Deog; Lee, Seung Hun; Choi, Eung Ho

    2008-10-01

    Sphingosine-1-phosphate (S1P), which is formed by phosphorylation of sphingosine through a process catalysed by sphingosine kinase (SK), is a multifunctional mediator of a variety of cellular responses including proliferation, differentiation, motility, and survival. K6PC-5, which was recently synthesized as a novel SK activator, is expected to increase S1P levels. Indeed studies have already demonstrated that K6PC-5 exhibits anti-aging effects on intrinsic aged murine skin by increasing fibroblasts, collagen synthesis, dermal thickness, and epidermal differentiation. However, photoaging and intrinsic aging have highly different clinical and histopathological properties. In this study, we developed a photoaged murine model by exposing mice that were 56 weeks old to ultraviolet (UV)B and UVA radiation for 8 weeks. We then investigated whether K6PC-5, as an SK activator, had anti-aging effects on photoaged murine skin in addition to its effects on intrinsic aged murine skin and determined the mechanism. K6PC-5 increased dermal collagen density in photoaged skin through increases in fibroblasts and collagen production. Photoaged murine skin treated with K6PC-5 showed an increase in stratum corneum (SC) integrity with increased corneodesmosome density and an improvement in barrier recovery rate. Matrix metalloproteinase 13 remained unchanged. These results indicate that topical application of K6PC-5 improves photoaged skin by improving skin barrier and increasing fibroblast count and function. In conclusion, K6PC-5, as an S1P activator, improves long-term UV-exposed aged skin as well as intrinsic aged skin. PMID:18341573

  15. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis

    PubMed Central

    Simpson, Cory L.; Patel, Dipal M.; Green, Kathleen J.

    2012-01-01

    To provide a stable environmental barrier, the epidermis requires an integrated network of cytoskeletal elements and cellular junctions. Nevertheless, the epidermis ranks among the body’s most dynamic tissues, continually regenerating itself and responding to cutaneous insults. As keratinocytes journey from the basal compartment towards the cornified layers, they completely reorganize their adhesive junctions and cytoskeleton. These architectural components are more than just rivets and scaffolds — they are active participants in epidermal morphogenesis that regulate epidermal polarization, signalling and barrier formation. PMID:21860392

  16. Epidermal Inclusion Cyst Presenting as a Palpable Scrotal Mass

    PubMed Central

    Correa, Andres F.; Gayed, Bishoy A.; Tublin, Mitchell E.; Parwani, Anil V.; Gingrich, Jeffrey R.

    2012-01-01

    We report a scrotal epidermal inclusion cyst located outside the median raphe which a rare entity in the absence of trauma and few cases have been reported. 47 year old male presents with a complaint of right sided testicular swelling and discomfort. On examination a 3 cm mass was palpated between the scrotum and the medial thigh on the subcutaneous tissue with a positive slip sign. Complete surgical excision of the cyst was performed. Histopathology confirmed epidermal inclusion cyst with no evidence of malignancy. PMID:23094187

  17. Bilateral Systematized Epidermolytic Verrucous Epidermal Nevus: A Rare Entity

    PubMed Central

    Mishra, Vivek; Saha, Abanti; Bandyopadhyay, Debabrata; Das, Anirban

    2015-01-01

    Verrucous epidermal nevi are congenital, noninflammatory cutaneous hamartomas composed of keratinocytes. They follow the lines of Blaschko and show hyperkeratosis without cellular atypia. The routine histology shows variable amount of hyperkeratosis, acanthosis and papillomatosis and rarely epidermolytic hyperkeratosis. We saw a 3-year-old boy with bilaterally symmetrical, systematized verrucous plaques along the lines of Blaschko extensively involving the trunk and extremities but sparing the face and palmoplantar skin. Histopathology showed features of epidermal nevi with prominent epidermolytic hyperkeratosis. We report here the case for the rarity of this entity. PMID:26288413

  18. Epidermal nevus syndrome associated with polyostotic fibrous dysplasia, CNS lipoma, and aplasia cutis.

    PubMed

    Cabanillas, Miguel; Aneiros, Angel; Monteagudo, Benigno; Santos-García, Diego; Suárez-Amor, Oscar; Ramírez-Santos, Aquilina

    2009-01-01

    Epidermal nevus syndrome is a rare congenital sporadic neurocutaneous disorder characterized by an epidermal nevus and various developmental abnormalities of the skin, eyes, nervous, cardiovascular and urogenital systems. We describe a patient with an extensive epidermal nevus associated with various organ abnormalities, particularly polyostotic fibrous dysplasia, central nervous system lipoma, and aplasia cutis. Our patient demonstrates the polymorphic spectrum of involvement in epidermal nevus syndrome. PMID:19951625

  19. Immunobiology of primary murine melanomas.

    PubMed

    Donawho, C; Evans, R; Kripke, M L

    1992-10-01

    Primary cutaneous melanomas can be induced in inbred mice by applying a dose of dimethylbenz[a]anthracene to the skin of 4-day-old mice, and then applying repeated doses of a tumor promoter to the same site over a long period of time. Preliminary experiments suggest that the final incidence of melanomas is strongly influenced by the age at which the initiating dose of carcinogen is applied. Melanomas induced by this method in C3H mice are immunogenic and exhibit a high degree of cross-reactivity when tested by immunization and challenge in vivo. Exposing the mice to ultraviolet (UV) radiation during carcinogenesis dramatically accelerates the appearance of melanoma. We are attempting to determine how UV radiation potentiates melanoma induction by studying the growth of melanoma cells transplanted into UV-irradiated skin. Our studies suggest that UV irradiation accelerates the outgrowth of melanoma cells by means of a local, immunosuppressive effect on the skin. However, this effect is distinct from the ability of UV irradiation to alter epidermal Langerhans cells and interfere with the induction of contact hypersensitivity responses. We postulate that UV irradiation augments melanoma development by interfering with the efferent arm of the immune response in the UV-irradiated site. PMID:1445809

  20. Anti-epidermal-cell-surface pemphigus antibody detaches viable epidermal cells from culture plates by activation of proteinase.

    PubMed Central

    Farb, R M; Dykes, R; Lazarus, G S

    1978-01-01

    Immunoglobulin from pemphigus patients binds to the surface of mouse epidermal cells in culture. Cells incubated with the pemphigus antibody are easily detached from culture plates whereas cells incubated with serum from normal patients remain on the plate. Pemphigus antibody-mediated cell detachment is blocked by the addition of the proteinase inhibitors soybean trypsin inhibitor and alpha2-macroglobulin to the culture media. Detachable cells are viable, and activation of the complement cascade is not necessary for cell detachment. The anti-cell-surface antibody of pemphigus appears to disrupt adhesion between viable epidermal cells by activation of proteinase. Images PMID:272663

  1. Terminal automation system maintenance

    SciTech Connect

    Coffelt, D.; Hewitt, J.

    1997-01-01

    Nothing has improved petroleum product loading in recent years more than terminal automation systems. The presence of terminal automation systems (TAS) at loading racks has increased operational efficiency and safety and enhanced their accounting and management capabilities. However, like all finite systems, they occasionally malfunction or fail. Proper servicing and maintenance can minimize this. And in the unlikely event a TAS breakdown does occur, prompt and effective troubleshooting can reduce its impact on terminal productivity. To accommodate around-the-clock loading at racks, increasingly unattended by terminal personnel, TAS maintenance, servicing and troubleshooting has become increasingly demanding. It has also become increasingly important. After 15 years of trial and error at petroleum and petrochemical storage and transfer terminals, a number of successful troubleshooting programs have been developed. These include 24-hour {open_quotes}help hotlines,{close_quotes} internal (terminal company) and external (supplier) support staff, and {open_quotes}layered{close_quotes} support. These programs are described.

  2. Cigarette Smoke Induces Human Epidermal Receptor 2-Dependent Changes in Epithelial Permeability.

    PubMed

    Mishra, Rangnath; Foster, Daniel; Vasu, Vihas T; Thaikoottathil, Jyoti V; Kosmider, Beata; Chu, Hong Wei; Bowler, Russell P; Finigan, James H

    2016-06-01

    The airway epithelium constitutes a protective barrier against inhaled insults, such as viruses, bacteria, and toxic fumes, including cigarette smoke (CS). Maintenance of bronchial epithelial integrity is central for airway health, and defective epithelial barrier function contributes to the pathogenesis of CS-mediated diseases, such as chronic obstructive pulmonary disease. Although CS has been shown to increase epithelial permeability, current understanding of the mechanisms involved in CS-induced epithelial barrier disruption remains incomplete. We have previously identified that the receptor tyrosine kinase human epidermal receptor (HER) 2 growth factor is activated by the ligand neuregulin-1 and increases epithelial permeability in models of inflammatory acute lung injury. We hypothesized that CS activates HER2 and that CS-mediated changes in barrier function would be HER2 dependent in airway epithelial cells. We determined that HER2 was activated in whole lung, as well as isolated epithelial cells, from smokers, and that acute CS exposure resulted in HER2 activation in cultured bronchial epithelial cells. Mechanistic studies determined that CS-mediated HER2 activation is independent of neuregulin-1 but required upstream activation of the epidermal growth factor receptor. HER2 was required for CS-induced epithelial permeability as knockdown of HER2 blocked increases in permeability after CS. CS caused an increase in IL-6 production by epithelial cells that was dependent on HER2-mediated extracellular signal-regulated kinases (Erk) activation. Finally, blockade of IL-6 attenuated CS-induced epithelial permeability. Our data indicate that CS activates pulmonary epithelial HER2 and that HER2 is a central mediator of CS-induced epithelial barrier dysfunction. PMID:26600084

  3. Effect of Storage Temperature on Cultured Epidermal Cell Sheets Stored in Xenobiotic-Free Medium

    PubMed Central

    Jackson, Catherine; Aabel, Peder; Eidet, Jon R.; Messelt, Edward B.; Lyberg, Torstein; von Unge, Magnus; Utheim, Tor P.

    2014-01-01

    Cultured epidermal cell sheets (CECS) are used in regenerative medicine in patients with burns, and have potential to treat limbal stem cell deficiency (LSCD), as demonstrated in animal models. Despite widespread use, short-term storage options for CECS are limited. Advantages of storage include: flexibility in scheduling surgery, reserve sheets for repeat operations, more opportunity for quality control, and improved transportation to allow wider distribution. Studies on storage of CECS have thus far focused on cryopreservation, whereas refrigeration is a convenient method commonly used for whole skin graft storage in burns clinics. It has been shown that preservation of viable cells using these methods is variable. This study evaluated the effect of different temperatures spanning 4°C to 37°C, on the cell viability, morphology, proliferation and metabolic status of CECS stored over a two week period in a xenobiotic–free system. Compared to non-stored control, best cell viability was obtained at 24°C (95.2±9.9%); reduced cell viability, at approximately 60%, was demonstrated at several of the temperatures (12°C, 28°C, 32°C and 37°C). Metabolic activity was significantly higher between 24°C and 37°C, where glucose, lactate, lactate/glucose ratios, and oxygen tension indicated increased activation of the glycolytic pathway under aerobic conditions. Preservation of morphology as shown by phase contrast and scanning electron micrographs was best at 12°C and 16°C. PCNA immunocytochemistry indicated that only 12°C and 20°C allowed maintenance of proliferative function at a similar level to non-stored control. In conclusion, results indicate that 12°C and 24°C merit further investigation as the prospective optimum temperature for short-term storage of cultured epidermal cell sheets. PMID:25170754

  4. Maintenance of hydrostatic transmissions

    NASA Astrophysics Data System (ADS)

    Esposito, A.

    1981-10-01

    Problems in hydrostatic transmission maintenance are identified and ways of overcoming them are suggested. It is found that problems arise from lack of lubrication, impurities in the oil, and cavitation at the pump and at the motor. It is under suggested that under nonsevere operating conditions, oil and filter should be changed every year, or every 1500 to 2000 hr running time. Under severe operating conditions or in dusty environments, the interval should be every 6 months or 1000 hr.

  5. Flight Crew Health Maintenance

    NASA Technical Reports Server (NTRS)

    Gullett, C. C.

    1970-01-01

    The health maintenance program for commercial flight crew personnel includes diet, weight control, and exercise to prevent heart disease development and disability grounding. The very high correlation between hypertension and overweight in cardiovascular diseases significantly influences the prognosis for a coronary prone individual and results in a high rejection rate of active military pilots applying for civilian jobs. In addition to physical fitness the major items stressed in pilot selection are: emotional maturity, glucose tolerance, and family health history.

  6. Proposed SOLCOST maintenance activities

    SciTech Connect

    1980-01-01

    This document provides a short description of work that has been accomplished to date and work in progress. A discussion of the program status as it is currently configured follows and finally proposed work by Solar Environmental Engineering Company (SEEC) in its most recently signed contract with the Department of Energy (DOE) is given. Early statements are designed to give the reader a good background so that the suggested SOLCOST maintenance activities will be more easily understood.

  7. Evaluation of Epidermal Conductance as a Potential Drought Tolerant Trait of Peanut

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidermal conductance (ge) is the loss of water vapor from leaves when stomata are closed. An experiment was conducted to compare epidermal conductance values of peanut genotypes with varied levels of field resistance to drought to assess ge as a potential drought response trait in peanut. Epidermal...

  8. Fate by Chance, not by Choice: Epidermal Stem Cells Go Live.

    PubMed

    Gonzalez-Celeiro, Meryem; Zhang, Bing; Hsu, Ya-Chieh

    2016-07-01

    The skin epidermis is constantly renewed by epidermal stem cells. In a recent Science paper, Rompolas et al. utilize live imaging to track epidermal stem cells over their lifetimes. Their findings provide new insights into epidermal stem cell behaviors and unravel how newly generated cells are integrated into pre-existing tissues. PMID:27392221

  9. Genetics Home Reference: Stevens-Johnson syndrome/toxic epidermal necrolysis

    MedlinePlus

    ... Conditions Stevens-Johnson syndrome/toxic epidermal necrolysis Stevens-Johnson syndrome/toxic epidermal necrolysis Enable Javascript to view ... Download PDF Open All Close All Description Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a ...

  10. AUTOMOTIVE DIESEL MAINTENANCE. PROGRAM OUTLINE.

    ERIC Educational Resources Information Center

    Human Engineering Inst., Cleveland, OH.

    INFORMATIONAL TOPICS COVERED IN THE TEXT MATERIALS AND SELF-INSTRUCTIONAL BRANCH PROGRAMED TRAINING FILMS FOR A 2-YEAR, 55 MODULE PROGRAM IN AUTOMOTIVE DIESEL MAINTENANCE ARE GIVEN. THE 30 MODULES FOR "AUTOMOTIVE DIESEL MAINTENANCE 1" ARE AVAILABLE AS VT 005 655 - VT 005 684, AND THE 25 MODULES FOR "AUTOMOTIVE DIESEL MAINTENANCE 2" ARE AVAILABLE…

  11. PREVENTIVE MAINTENANCE. HONEYWELL PLANNING GUIDE.

    ERIC Educational Resources Information Center

    Honeywell, Inc., Minneapolis, Minn.

    THIS HONEYWELL PAMPHLET DISCUSSES SOME ASPECTS OF PREVENTIVE MAINTENANCE OF AUTOMATIC CONTROLS, HEATING, VENTILATING, AND AIR CONDITIONING, AND COMPARES IN-PLANT WITH CONTRACT SERVICE, CONCLUDING THAT CONTRACT SERVICE IS PREFERABLE AND DESCRIBING A NUMBER OF MAINTENANCE PLANS WHICH THEY FURNISH. PREVENTIVE MAINTENANCE PROVIDES--(1) MORE EFFICIENT…

  12. Designing with Maintenance in Mind.

    ERIC Educational Resources Information Center

    Hoffman, Kisty

    2002-01-01

    When planning for a new facility, consideration of maintenance needs is crucial to successful design. Designing for maintenance needs involves considering such factors as the durability of materials used, the cost and lifecycle of the materials, and the flexibility of the maintenance staff. Stresses the importance of including key members of the…

  13. TAp63 prevents premature aging by promoting adult stem cell maintenance

    PubMed Central

    Su, Xiaohua; Paris, Maryline; Gi, Young Jin; Tsai, Kenneth Y.; Cho, Min Soon; Lin, Yu-Li; Biernaskie, Jeffrey A.; Sinha, Satrajit; Prives, Carol; Pevny, Larysa H.; Miller, Freda D.; Flores, Elsa R.

    2012-01-01

    SUMMARY The cellular mechanisms that regulate the maintenance of adult tissue stem cells are still largely unknown. We show here that the p53 family member, TAp63, is essential for maintenance of epidermal and dermal precursors and that, in its absence, these precursors senesce and skin ages prematurely. Specifically, we have developed a TAp63 conditional knockout mouse and used it to ablate TAp63 in the germline (TAp63−/−) or in K14-expressing cells in the basal layer of the epidermis (TAp63fl/fl;K14cre+). TAp63−/− mice age prematurely and develop blisters, skin ulcerations, senescence of hair follicle-associated dermal and epidermal cells, and decreased hair morphogenesis. These phenotypes are likely due to loss of TAp63 in dermal and epidermal precursors since both cell types show defective proliferation, early senescence, and genomic instability. These data indicate that TAp63 serves to maintain adult skin stem cells by regulating cellular senescence and genomic stability, thereby preventing premature tissue aging. PMID:19570515

  14. Fatal case of cephalexin-induced toxic epidermal necrolysis

    PubMed Central

    Barber, Gerard R; Dreskin, Stephen C; Lindberg, Gordon K

    2014-01-01

    Purpose: To describe a case of toxic epidermal necrolysis likely caused by cephalexin with a review of the literature. Case: An 80-year-old male with a known allergy to cephalosporins, residing at a long-term acute care hospital, received cephalexin for a urinary tract infection. And 1 day after starting therapy, the patient developed an extensive erythematous rash accompanied by skin sloughing; 4 days after receiving cephalexin, the patient was directly admitted to the burn intensive care unit and was diagnosed with toxic epidermal necrolysis involving 56% of the total body surface area. Progressive deterioration to multisystem organ failure ensued, and the patient died 5 days following his admission to the burn intensive care unit. At the time of death, ulcerations were noted over approximately 80% of his body. Summary: The temporal association of the patient’s ingestion of cephalexin for a urinary tract infection to his onset of toxic epidermal necrolysis suggests that this 80-year-old man developed toxic epidermal necrolysis following the administration of cephalexin for a urinary tract infection. PMID:27489646

  15. The "caveolae brake hypothesis" and the epidermal barrier.

    PubMed

    Roelandt, Truus; Giddelo, Christina; Heughebaert, Carol; Denecker, Geertrui; Hupe, Melanie; Crumrine, Debra; Kusuma, Andy; Haftek, Marek; Roseeuw, Diane; Declercq, Wim; Feingold, Kenneth R; Elias, Peter M; Hachem, Jean-Pierre

    2009-04-01

    Epidermal permeability barrier formation depends upon lamellar body (LB) secretion/fusion with the apical plasma membrane (APM) of outermost stratum granulosum (SG) cell, creating cholesterol/glycosphingolipid-enriched lipid rafts-like domains. We found that the dimensions of these domains are comparable to lipid raft in other cell types; and that acute barrier disruption regulates their size and dynamics. To assess the function of these LB-derived raft-like domains, we assessed APM dynamics and barrier recovery in methyl-beta-cyclodextrin (MbetaCD)-treated hairless mice and caveolin-1 knockouts (cav-1(-/-)). MbetaCD treatment impaired APM raft-like domain formation and barrier recovery. Accelerated barrier recovery is observed in cav-1(-/-) in parallel with expansion of raft-like domains. Barrier abrogation of normal epidermis resulted in translocation of cav-1 from the cytoplasm to raft-like membrane domains, restricting further raft-like domain formation and initiating terminal differentiation. Inhibition of LB secretion by monensin and absence of cav-1 delayed terminal differentiation. Furthermore, cav-1(-/-) mice exhibited an increased propensity to develop experimentally induced epidermal hyperplasia correlating with lipid raft persistence. Finally, the epidermal hyperplasia in psoriasis and Netherton syndrome is paralleled by increased lipid raft formation. These studies demonstrate that cav-1 delivery to the APM by LB trafficking to APM "brakes" further LB secretion, signals terminal differentiation, and regulates epidermal hyperproliferation. PMID:19005485

  16. Epidermal electronics for electromyography: An application to swallowing therapy.

    PubMed

    Constantinescu, Gabriela; Jeong, Jae-Woong; Li, Xinda; Scott, Dylan K; Jang, Kyung-In; Chung, Hyun-Joong; Rogers, John A; Rieger, Jana

    2016-08-01

    Head and neck cancer treatment alters the anatomy and physiology of patients. Resulting swallowing difficulties can lead to serious health concerns. Surface electromyography (sEMG) is used as an adjuvant to swallowing therapy exercises. sEMG signal collected from the area under the chin provides visual biofeedback from muscle contractions and is used to help patients perform exercises correctly. However, conventional sEMG adhesive pads are relatively thick and difficult to effectively adhere to a patient's altered chin anatomy, potentially leading to poor signal acquisition in this population. Here, the emerging technology of epidermal electronics is introduced, where ultra-thin geometry allows for close contouring of the chin. The two objectives of this study were to (1) assess the potential of epidermal electronics technology for use with swallowing therapy and (2) assess the significance of the reference electrode placement. This study showed comparative signals between the new epidermal sEMG patch and the conventional adhesive patches used by clinicians. Furthermore, an integrated reference yielded optimal signal for clinical use; this configuration was more robust to head movements than when an external reference was used. Improvements for future iterations of epidermal sEMG patches specific to day-to-day clinical use are suggested. PMID:27255865

  17. Quantitative proteogenomic profiling of epidermal barrier formation in vitro

    PubMed Central

    Winget, Jason M.; Watts, Julian D.; Hoopmann, Michael R.; DiColandrea, Teresa; Robinson, Michael K.; Huggins, Tom; Bascom, Charles C.; Isfort, Robert J.; Moritz, Robert L.

    2015-01-01

    Background The barrier function of the epidermis is integral to personal well-being, and defects in the skin barrier are associated with several widespread diseases. Currently there is a limited understanding of system-level proteomic changes during epidermal stratification and barrier establishment. Objective Here we report the quantitative proteogenomic profile of an in vitro reconstituted epidermis at three time points of development in order to characterize protein changes during stratification. Methods The proteome was measured using data-dependent “shotgun” mass spectrometry and quantified with statistically validated label-free proteomic methods for 20 replicates at each of three time points during the course of epidermal development. Results Over 3600 proteins were identified in the reconstituted epidermis, with more than 1200 of these changing in abundance over the time course. We also collected and discuss matched transcriptomic data for the three time points, allowing alignment of this new dataset with previously published characterization of the reconstituted epidermis system. Conclusion These results represent the most comprehensive epidermal-specific proteome to date, and therefore reveal several aspects of barrier formation and skin composition. The limited correlation between transcript and protein abundance underscores the importance of proteomic analysis in developing a full understanding of epidermal maturation. PMID:25862149

  18. Apoptosis in irradiated murine tumors.

    PubMed

    Stephens, L C; Ang, K K; Schultheiss, T E; Milas, L; Meyn, R E

    1991-09-01

    Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors. PMID:1886987

  19. Chemoimmunotherapy of murine bladder cancer.

    PubMed

    Stogdill, B J; Lamm, D L; Livingston, R B

    1981-11-01

    The lethality of invasive transitional cell carcinoma (TCC) has prompted a search for effective, minimally toxic, adjuvant therapy. Such agents were evaluated in a murine bladder cancer (MBT2) model which parallels the clinical disease. One hundred C3H/He mice were inoculated i.d. with 2.5 x 10(4) viable MBT2 tumor cells and randomized to receive either normal saline (control), cis-Platinum (CPT), cyclophosphamide (CY), methotrexate (MTX), BCG, (CY + MTX), or (CY + MTX + BCG). Chemotherapy was given intraperitoneally weekly starting on day 7 after inoculation. Immunotherapy was given intralesionally on days 1 and 10 only. All mice were treated for 5 weeks followed by 5 weeks of observation. At 5 weeks, tumors of mice receiving cyclophosphamide alone or either of the combinations of therapy were smaller (P less than 0.01) than tumors of controls or other single agents alone. Each regimen increased survival, but only the combination regimen increase survival significantly (P less than 0.01). In the doses and schedule used in this model. Combination chemotherapy and chemoimmunotherapy significantly delay tumor growth and increase duration of survival (P less than 0.01) when compared with controls or single agent groups. PMID:7298287

  20. General aviation avionics equipment maintenance

    NASA Technical Reports Server (NTRS)

    Parker, C. D.; Tommerdahl, J. B.

    1978-01-01

    Maintenance of general aviation avionics equipment was investigated with emphasis on single engine and light twin engine general aviation aircraft. Factors considered include the regulatory agencies, avionics manufacturers, avionics repair stations, the statistical character of the general aviation community, and owners and operators. The maintenance, environment, and performance, repair costs, and reliability of avionics were defined. It is concluded that a significant economic stratification is reflected in the maintenance problems encountered, that careful attention to installations and use practices can have a very positive impact on maintenance problems, and that new technologies and a general growth in general aviation will impact maintenance.

  1. Paranal maintenance and CMMS experience

    NASA Astrophysics Data System (ADS)

    Montano, Nelson

    2004-10-01

    During the last four years of operations, low technical downtime has been one of the relevant records of the Paranal Observatory. From the beginning of the Very Large Telescope (VLT) project, European Southern Observatory (ESO) has considered the implementation of a proper maintenance strategy a fundamental point in order to ensure low technical down time and preserve the Observatory's assets. The implementation of the maintenance strategy was based on the following aspects: - Strong maintenance sense during the design stage. Line Replacement Unit (LRU) concept, standardization and modularity of the Observatory equipment - Creation of a dedicated team for Maintenance - The implementation of a Computerized Maintenance Management System After four operational years, the result of these aspects has exceeded the expectations; the Observatory has been operating with high availability under a sustainable strategy. The strengths of the maintenance strategy have been based on modern maintenance concepts applied by regular production companies, where any minute of down time involves high cost. The operation of the actual Paranal Maintenance System is based mainly on proactive activities, such as regular inspections, preventive maintenance (PM) and predictive maintenance (PdM) plans. Nevertheless, it has been necessary to implement a strong plan for corrective maintenance (CM). The Spare Parts Strategy has also been an important point linked to the Maintenance Strategy and CMMS implementation. At present, almost 4,000 items related to the Observatory spare parts are loaded into the CMMS database. Currently, we are studying the implementation of a Reliability Centered Maintenance (RCM) project in one of our critical systems The following document presents the actual status of the Paranal Maintenance Strategy and which have been the motivations to implement the established strategy.

  2. Towards automated traceability maintenance.

    PubMed

    Mäder, Patrick; Gotel, Orlena

    2012-10-01

    Traceability relations support stakeholders in understanding the dependencies between artifacts created during the development of a software system and thus enable many development-related tasks. To ensure that the anticipated benefits of these tasks can be realized, it is necessary to have an up-to-date set of traceability relations between the established artifacts. This goal requires the creation of traceability relations during the initial development process. Furthermore, the goal also requires the maintenance of traceability relations over time as the software system evolves in order to prevent their decay. In this paper, an approach is discussed that supports the (semi-) automated update of traceability relations between requirements, analysis and design models of software systems expressed in the UML. This is made possible by analyzing change events that have been captured while working within a third-party UML modeling tool. Within the captured flow of events, development activities comprised of several events are recognized. These are matched with predefined rules that direct the update of impacted traceability relations. The overall approach is supported by a prototype tool and empirical results on the effectiveness of tool-supported traceability maintenance are provided. PMID:23471308

  3. Towards automated traceability maintenance

    PubMed Central

    Mäder, Patrick; Gotel, Orlena

    2012-01-01

    Traceability relations support stakeholders in understanding the dependencies between artifacts created during the development of a software system and thus enable many development-related tasks. To ensure that the anticipated benefits of these tasks can be realized, it is necessary to have an up-to-date set of traceability relations between the established artifacts. This goal requires the creation of traceability relations during the initial development process. Furthermore, the goal also requires the maintenance of traceability relations over time as the software system evolves in order to prevent their decay. In this paper, an approach is discussed that supports the (semi-) automated update of traceability relations between requirements, analysis and design models of software systems expressed in the UML. This is made possible by analyzing change events that have been captured while working within a third-party UML modeling tool. Within the captured flow of events, development activities comprised of several events are recognized. These are matched with predefined rules that direct the update of impacted traceability relations. The overall approach is supported by a prototype tool and empirical results on the effectiveness of tool-supported traceability maintenance are provided. PMID:23471308

  4. Maintenance and supply options

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The object of the Maintenance and Supply Option was to develop a high level operational philosophy related to maintenance and supply operations and incorporate these concepts into the Lunar Base Study. Specific products to be generated during this task were three trade studies and a conceptual design of the Logistic Supply Module. The crew size study was performed to evaluate crew sizes from the baseline size of four to a crew size of eight and determine the preferred crew size. The second trade study was to determine the impact of extending surface stay times and recommend a preferred duration of stay time as a function of crew, consumables, and equipment support capabilities. The third trade study was an evaluation of packaging and storage methods to determine the preferred logistics approach to support the lunar base. A modified scenario was developed and served as the basis of the individual trade studies. Assumptions and guidelines were also developed from experience with Apollo programs, Space Shuttle operations, and Space Station studies. With this information, the trade studies were performed and a conceptual design for the Logistic Supply Module was developed.

  5. Remote maintenance monitoring system

    NASA Technical Reports Server (NTRS)

    Simpkins, Lorenz G. (Inventor); Owens, Richard C. (Inventor); Rochette, Donn A. (Inventor)

    1992-01-01

    A remote maintenance monitoring system retrofits to a given hardware device with a sensor implant which gathers and captures failure data from the hardware device, without interfering with its operation. Failure data is continuously obtained from predetermined critical points within the hardware device, and is analyzed with a diagnostic expert system, which isolates failure origin to a particular component within the hardware device. For example, monitoring of a computer-based device may include monitoring of parity error data therefrom, as well as monitoring power supply fluctuations therein, so that parity error and power supply anomaly data may be used to trace the failure origin to a particular plane or power supply within the computer-based device. A plurality of sensor implants may be rerofit to corresponding plural devices comprising a distributed large-scale system. Transparent interface of the sensors to the devices precludes operative interference with the distributed network. Retrofit capability of the sensors permits monitoring of even older devices having no built-in testing technology. Continuous real time monitoring of a distributed network of such devices, coupled with diagnostic expert system analysis thereof, permits capture and analysis of even intermittent failures, thereby facilitating maintenance of the monitored large-scale system.

  6. INCREASED SUSCEPTIBILITY TO PARATHION POISONING FOLLOWING MURINE CYTOMEGALOVIRUS INFECTION

    EPA Science Inventory

    Increased Susceptibility to Parathion Poisoning Following Murine Cytomegalovirus Infection. Fifty to 100 percent mortality occurred in mice treated with ordinarily sublethal doses of parathion 2 to 5 days post infection with murine cytomegalovirus (MCMV). These mortalities appear...

  7. Proteomic assessment of sulfur mustard-induced protein adducts and other protein modifications in human epidermal keratinocytes

    SciTech Connect

    Mol, Marijke A.E. Berg, Roland M. van den; Benschop, Henk P.

    2008-07-01

    Although some toxicological mechanisms of sulfur mustard (HD) have been uncovered, new knowledge will allow for advanced insight in the pathways that lead towards epidermal-dermal separation in skin. In the present investigation, we aimed to survey events that occur at the protein level in human epidermal keratinocytes (HEK) during 24 h after exposure to HD. By using radiolabeled {sup 14}C-HD, it was found that proteins in cultured HEK are significant targets for alkylation by HD. HD-adducted proteins were visualized by two-dimensional gel electrophoresis and analyzed by mass spectrometry. Several type I and II cytokeratins, actin, stratifin (14-3-3{sigma}) and galectin-7 were identified. These proteins are involved in the maintenance of the cellular cytoskeleton. Their alkylation may cause changes in the cellular architecture and, in direct line with that, be determinative for the onset of vesication. Furthermore, differential proteomic analysis was applied to search for novel features of the cellular response to HD. Partial breakdown of type I cytokeratins K14, K16 and K17 as well as the emergence of new charge variants of the proteins heat shock protein 27 and ribosomal protein P0 were observed. Studies with caspase inhibitors showed that caspase-6 is probably responsible for the breakdown of type I cytokeratins in HEK. The significance of the results is discussed in terms of toxicological relevance and possible clues for therapeutic intervention.

  8. Epidermal Micrografts Produced via an Automated and Minimally Invasive Tool Form at the Dermal/Epidermal Junction and Contain Proliferative Cells That Secrete Wound Healing Growth Factors

    PubMed Central

    Osborne, Sandra N.; Schmidt, Marisa A.; Derrick, Kathleen; Harper, John R.

    2015-01-01

    ABSTRACT OBJECTIVE: The aim of this scientific study was to assess epidermal micrografts for formation at the dermal-epidermal (DE) junction, cellular outgrowth, and growth factor secretion. Epidermal harvesting is an autologous option that removes only the superficial epidermal layer of the skin, considerably limiting donor site damage and scarring. Use of epidermal grafting in wound healing has been limited because of tedious, time-consuming, and inconsistent methodologies. Recently, a simplified, automated epidermal harvesting tool (CelluTome Epidermal Harvesting System; Kinetic Concepts Inc, San Antonio, Texas) that applies heat and suction concurrently to produce epidermal micrografts has become commercially available. The new technique of epidermal harvesting was shown to create viable micrografts with minimal patient discomfort and no donor-site scarring. DESIGN: This study was a prospective institutional review board–approved healthy human study. SETTING: This study was conducted at the multispecialty research facility, Clinical Trials of Texas, Inc, in San Antonio, Texas. PATIENTS: The participants were 15 healthy human volunteers. RESULTS: Epidermal micrografts formed at the DE junction, and migratory basal layer keratinocytes and melanocytes were proliferative in culture. Basement membrane–specific collagen type IV was also found to be present in the grafts, suggesting that the combination of heat and vacuum might cause partial delamination of the basement membrane. Viable basal cells actively secreted key growth factors important for modulating wound healing responses, including vascular endothelial growth factor, hepatocyte growth factor, granulocyte colony-stimulating factor, platelet-derived growth factor, and transforming growth factor α. CONCLUSIONS: Harvested epidermal micrografts retained their original keratinocyte structure, which is critical for potential re-epithelialization and repigmentation of a wound environment. PMID:26258460

  9. 22 CFR 120.38 - Maintenance levels.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... § 120.38 Maintenance levels. (a) Organizational-level maintenance (or basic-level maintenance) is the first level of maintenance that can be performed “on-equipment” (directly on the defense article or... defense article. (b) Intermediate-level maintenance is second-level maintenance performed...

  10. Murine Norovirus: Propagation, Quantification and Genetic Manipulation

    PubMed Central

    Hwang, Seungmin; Alhatlani, Bader; Arias, Armando; Caddy, Sarah L; Christodoulou, Constantina; Cunha, Juliana; Emmott, Ed; Gonzalez-Hernandez, Marta; Kolawole, Abimbola; Lu, Jia; Rippinger, Christine; Sorgeloos, Frédéric; Thorne, Lucy; Vashist, Surender; Goodfellow, Ian

    2014-01-01

    Murine norovirus (MNV) is a positive-sense, plus-stranded RNA virus in the Caliciviridae family. It is the most common pathogen in biomedical research colonies. MNV is also related to the human noroviruses, which cause the majority of non-bacterial gastroenteritis worldwide. Like the human noroviruses, MNV is an enteric virus that replicates in the intestine and is transmitted by the fecal-oral route. MNV replicates in murine macrophages and dendritic cells in cells in culture and in the murine host. This virus is often used to study mechanisms in norovirus biology, because the human noroviruses are refractory to growth in cell culture. MNV combines the availability of a cell culture and reverse genetics system with the ability to study infection in the native host. Herein, we describe a panel of techniques that are commonly used to study MNV biology. PMID:24789596

  11. Murine typhus in Kuwait in 1978

    PubMed Central

    Al-Awadi, Abdul Rahman; Al-Kazemi, Nouri; Ezzat, Gaafar; Saah, Alfred J.; Shepard, Charles; Zaghloul, Talaat; Gherdian, Beatriz

    1982-01-01

    Murine typhus occurred in 254 individuals in Kuwait between April and August 1978; 81% of patients were aged between 15 and 44 years, and 63% were male. The highest attack rate occurred among people in the lowest socioeconomic class. The outbreak coincided with a period of high rat and flea density. A study of the first 104 cases suggested that infection was acquired in the home, but a case — control study revealed no significant differences between patients and control subjects in terms of exposure to rats or domestic animals, and other factors. This suggests that murine typhus is hyperendemic rather than epidemic in Kuwait. The disease is being controlled through reduction of both flea and rat populations. Murine typhus may be much more common in many areas than is generally realized, and its status should be re-evaluated regularly in all known and potential foci. PMID:6980739

  12. Communication is key: Reducing DEK1 activity reveals a link between cell-cell contacts and epidermal cell differentiation status.

    PubMed

    Galletti, Roberta; Ingram, Gwyneth C

    2015-01-01

    Plant epidermis development requires not only the initial acquisition of tissue identity, but also the ability to differentiate specific cell types over time and to maintain these differentiated states throughout the plant life. To set-up and maintain differentiation, plants activate specific transcriptional programs. Interfering with these programs can prevent differentiation and/or force differentiated cells to lose their identity and re-enter a proliferative state. We have recently shown that the Arabidopsis Defective Kernel 1 (DEK1) protein is required both for the differentiation of epidermal cells and for the maintenance of their fully differentiated state. Defects in DEK1 activity lead to a deregulation of the expression of epidermis-specific differentiation-promoting HD-ZIP IV transcription factors. Here we propose a working model in which DEK1, by maintaining cell-cell contacts, and thus communication between neighboring cells, influences HD-ZIP IV gene expression and epidermis differentiation. PMID:27064205

  13. Design, expression and evaluation of a novel humanized single chain antibody against epidermal growth factor receptor (EGFR).

    PubMed

    Akbari, Bahman; Farajnia, Safar; Zarghami, Nosratollah; Mahdieh, Nejat; Rahmati, Mohammad; Khosroshahi, Shiva Ahdi; Rahbarnia, Leila

    2016-11-01

    Various strategies have been attempted for targeting of epidermal growth factor receptor (EGFR), as an essential biomarker in a variety of cancers. Several anti-EGFR antibodies including cetuximab are used in clinics for treatment of EGFR-overexpressing colorectal and head and neck cancers but the efficiency of these antibodies is threatened by their large size and chimeric nature. Humanized single chains antibodies (huscFv) are smaller generation of antibodies with lower immunogenicity may overcome these limitations. This article reports production and evaluation of a novel humanized anti-EGFR scFv. The CDRs of cetuximab heavy and light chains were grafted onto human antibody frameworks as framework donors. To maintain the antigen binding affinity of murine antibody, the murine vernier zone residues were retained in framework regions of huscFv. Additionally, two point mutations in CDR-L1 and CDR-L3 and three point mutations in CDR-H2 and CDR-H3 loops of the humanized scFv (huscFv) were introduced to increase affinity of the huscFv to EGFR. Analysis of results demonstrated that the humanness degree of resultant huscFv was increased as 19%. HuscFv was expressed in BL21 (DE3) and affinity purified via Ni-NTA column. The reactivity of huscFv with EGFR was evaluated by ELISA and dot blot techniques. Analysis by ELISA and dot blot showed that the huscFv was able to recognize and react with EGFR. Toxicity analysis by MTT assay indicated an inhibitory effect on growth of EGFR-overexpressing A431 cells. In conclusion, the huscFv produced in this study revealed decreased immunogenicity while retained growth inhibitory effect on EGFR-overexpressing tumor cells. PMID:27298212

  14. Neoplastic transformation of immortalized human epidermal keratinocytes by ionizing radiation

    SciTech Connect

    Thraves, P.; Salehi, Z.; Dritschilo, A.; Rhim, J.S. )

    1990-02-01

    Efforts to investigate the progression of events that cause human cells to become neoplastic in response to ionizing radiation have been aided by the development of tissue culture systems of epithelial cells. In the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus type 12 and simian virus 40 have been transformed by exposure to x-ray irradiation. Such transformants showed morphological alterations, formed colonies in soft agar, and induced carcinomas when transplanted into nude mice, whereas primary human epidermal keratinocytes exposed to radiation in this manner failed to show any evidence of transformation. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of a DNA tumor virus and radiation, indicating a multistep process for radiation-induced neoplastic conversion. This in vitro system may be useful as a tool for dissecting the process of radiation-induced neoplastic transformation of human epithelial cells and for detecting previously unreported human oncogenes.

  15. The biology of human epidermal growth factor receptor 2.

    PubMed

    Sundaresan, S; Penuel, E; Sliwkowski, M X

    1999-09-01

    Our understanding of the normal signaling mechanisms and functions of human epidermal growth factor receptor 2 (HER2) and other members of the HER family, namely epidermal growth factor receptor, HER3, and HER4, is growing rapidly. Activation of these receptors results in a diverse array of signals through the formation of homodimeric and heterodimeric receptor complexes; HER2 is the preferred dimerization partner for the other HERs. These oligomeric receptor complexes activate distinct signaling pathways, such as the Ras-MAPK and PI3-kinase pathways. These, in turn, affect various cellular processes. Recent gene deletion experiments in mice point to an important role for HER2 in cardiac and neural development, and evidence from other studies indicates that HER2 is involved in normal breast growth and development. Thus, HER2 is a key component of a complex signaling network that plays a critical role in the regulation of tissue development, growth, and differentiation. PMID:11122793

  16. Estimating the Size of Onion Epidermal Cells from Diffraction Patterns

    NASA Astrophysics Data System (ADS)

    Groff, Jeffrey R.

    2012-10-01

    Bioscience and premedical profession students are a major demographic served by introductory physics courses at many colleges and universities. Exposing these students to biological applications of physical principles will help them to appreciate physics as a useful tool for their future professions. Here I describe an experiment suitable for introductory physics where principles of wave optics are applied to probe the size of onion epidermal cells. The epidermis tissue is composed of cells of relatively uniform size and shape (Fig. 1) so the tissue acts like a one-dimensional transmission diffraction grating. The diffraction patterns generated when a laser beam passes through the tissue (Fig. 2) are analyzed and an estimate of the average width of individual onion epidermal cells is calculated. The results are compared to direct measurements taken using a light microscope. The use of microscopes and plant-cell tissue slides creates opportunities for cross-discipline collaboration between physics and biology instructors.

  17. Ecthyma gangrenosum in a patient with toxic epidermal necrolysis.

    PubMed

    Downey, Douglas M; O'Bryan, Meghan C; Burdette, Steve D; Michael, Johnson R; Saxe, Jonathan M

    2007-01-01

    Toxic epidermal necrolysis and Stevens-Johnson syndrome are a spectrum of disease characterized by a delayed hypersensitivity reaction that involves the skin and mucous membranes and typically is associated with either recent upper respiratory infection or with certain medications. Ecthyma gangrenosum is a rare necrotizing vasculitis that most commonly affects immunocompromised and burn patients and is often a sequela of Pseudomonas aeruginosa bacteremia. The cutaneous lesions of ecthyma gangrenosum are characterized by an erythematous halo surrounding a dark gray or black nodule. P. aeruginosa preferentially invades the venules, resulting in secondary thrombosis of the arterioles, tissue edema, and separation of the epidermis. Management of ecthyma gangrenosum includes systemic treatment with antipseudomonal antibiotics and débridment of the lesions, as well as improving the patient's immune status if possible. We present a case of a patient admitted to the burn unit for toxic epidermal necrolysis who developed pseudomonal bacteremia with ecthyma gangrenosum. PMID:17211226

  18. Risk-based maintenance modeling. Prioritization of maintenance importances and quantification of maintenance effectiveness

    SciTech Connect

    Vesely, W.E.; Rezos, J.T.

    1995-09-01

    This report describes methods for prioritizing the risk importances of maintenances using a Probabilistic Risk Assessment (PRA). Approaches then are described for quantifying their reliability and risk effects. Two different PRA importance measures, minimal cutset importances and risk reduction importances, were used to prioritize maintenances; the findings show that both give similar results if appropriate criteria are used. The justifications for the particular importance measures also are developed. The methods developed to quantify the reliability and risk effects of maintenance actions are extensions of the usual reliability models now used in PRAs. These extended models consider degraded states of the component, and quantify the benefits of maintenance in correcting degradations and preventing failures. The negative effects of maintenance, including downtimes, also are included. These models are specific types of Markov models. The data for these models can be obtained from plant maintenance logs and from the Nuclear Plant Reliability Data System (NPRDS). To explore the potential usefulness of these models, the authors analyzed a range of postulated values of input data. These models were used to examine maintenance effects on a components reliability and performance for various maintenance programs and component data. Maintenance schedules were analyzed to optimize the component`s availability. In specific cases, the effects of maintenance were found to be large.

  19. Epidermal differentiation: the role of proteases and their inhibitors.

    PubMed

    Zeeuwen, Patrick L J M

    2004-12-01

    Dermatological diseases range from minor cosmetic problems to life-threatening conditions, as seen in some severe disorders of keratinization and cornification. These disorders are commonly due to abnormal epidermal differentiation processes, which result in disturbed barrier function of human skin. Elucidation of the cellular differentiation programs that regulate the formation and homeostasis of the epidermis is therefore of great importance for the understanding and therapy of these disorders. Much of the barrier function of human epidermis against the environment is provided by the cornified cell envelope (CE), which is assembled by transglutaminase (TGase)-mediated cross-linking of several structural proteins and lipids during the terminal stages of normal keratinocyte differentiation. The major constituents of the stratum corneum and the current knowledge on the formation of the stratum corneum will be briefly reviewed here. The discovery of mutations that underlie several human diseases caused by genetic defects in the protein or lipid components of the CE, and recent analyses of mouse mutants with defects in the structural components of the CE, catalyzing enzymes, and lipid processing, have highlighted their essential function in establishing the epidermal barrier. In addition, recent findings have provided evidence that a disturbed protease-antiprotease balance could cause faulty differentiation processes in the epidermis and hair follicle. The importance of regulated proteolysis in epithelia is well demonstrated by the recent identification of the SPINK5 serine proteinase inhibitor as the defective gene in Netherton syndrome, cathepsin C mutations in Papillon-Lefevre syndrome, cathepsin L deficiency infurless mice, targeted ablation of the serine protease Matriptase/MTSP1, targeted ablation of the aspartate protease cathepsin D, and the phenotype of targeted epidermal overexpression of stratum corneum chymotryptic enzyme in mice. Notably, our recent

  20. Epidermal EGFR controls cutaneous host defense and prevents inflammation.

    PubMed

    Lichtenberger, Beate M; Gerber, Peter A; Holcmann, Martin; Buhren, Bettina A; Amberg, Nicole; Smolle, Viktoria; Schrumpf, Holger; Boelke, Edwin; Ansari, Parinaz; Mackenzie, Colin; Wollenberg, Andreas; Kislat, Andreas; Fischer, Jens W; Röck, Katharina; Harder, Jürgen; Schröder, Jens M; Homey, Bernhard; Sibilia, Maria

    2013-08-21

    The epidermal growth factor receptor (EGFR) plays an important role in tissue homeostasis and tumor progression. However, cancer patients treated with EGFR inhibitors (EGFRIs) frequently develop acneiform skin toxicities, which are a strong predictor of a patient's treatment response. We show that the early inflammatory infiltrate of the skin rash induced by EGFRI is dominated by dendritic cells, macrophages, granulocytes, mast cells, and T cells. EGFRIs induce the expression of chemokines (CCL2, CCL5, CCL27, and CXCL14) in epidermal keratinocytes and impair the production of antimicrobial peptides and skin barrier proteins. Correspondingly, EGFRI-treated keratinocytes facilitate lymphocyte recruitment but show a considerably reduced cytotoxic activity against Staphylococcus aureus. Mice lacking epidermal EGFR (EGFR(Δep)) show a similar phenotype, which is accompanied by chemokine-driven skin inflammation, hair follicle degeneration, decreased host defense, and deficient skin barrier function, as well as early lethality. Skin toxicities were not ameliorated in a Rag2-, MyD88-, and CCL2-deficient background or in mice lacking epidermal Langerhans cells. The skin phenotype was also not rescued in a hairless (hr/hr) background, demonstrating that skin inflammation is not induced by hair follicle degeneration. Treatment with mast cell inhibitors reduced the immigration of T cells, suggesting that mast cells play a role in the EGFRI-mediated skin pathology. Our findings demonstrate that EGFR signaling in keratinocytes regulates key factors involved in skin inflammation, barrier function, and innate host defense, providing insights into the mechanisms underlying EGFRI-induced skin pathologies. PMID:23966300

  1. Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits.

    PubMed

    Narurkar, Vic A; Fabi, Sabrina G; Bucay, Vivian W; Tedaldi, Ruth; Downie, Jeanine B; Zeichner, Joshua A; Butterwick, Kimberly; Taub, Amy; Kadoya, Kuniko; Makino, Elizabeth T; Mehta, Rahul C; Vega, Virginia L

    2016-01-01

    Skin aging is a combination of multifactorial mechanisms that are not fully understood. Intrinsic and extrinsic factors modulate skin aging, activating distinctive processes that share similar molecular pathways. One of the main characteristics of youthful skin is its large capacity to retain water, and this decreases significantly as we age. A key molecule involved in maintaining skin hydration is hyaluronic acid (HA). Concentration of HA in the skin is determined by the complex balance between its synthesis, deposition, association with cellular structures, and degradation. HA bio-equivalency and bio-compatibility have been fundamental in keeping this macromolecule as the favorite of the skincare industry for decades. Scientific evidence now shows that topically applied HA is unable to penetrate the skin and is rapidly degraded on the skin surface. SkinMedica's HA5 Rejuvenating Hydrator (SkinMedica Inc., an Allergan company, Irvine, CA) promotes restoration of endogenous epidermal HA homeostasis and provides instant smoothing and hydration of the skin. These dual benefits are accomplished through the combination of 2 breakthrough technologies: 1) a unique blend of actives powered by SkinMedica proprietary flower-derived stem cell extract that restores the endogenous production of HA; and 2) a proprietary mix of 5 HA forms that plump the skin, decreasing the appearance of fine lines/wrinkles. Pre-clinical studies demonstrated that HA5 induces expression of key epidermal differentiation and barrier markers as well as epidermal HA synthases. A decrease expression of hyaluronidases was also observed upon HA5 application. Initial clinical studies showed that within 15 minutes of application, HA5 instantly improves the appearance of fine lines/wrinkles and skin hydration. Subjects that continue using HA5 (for 8 weeks) demonstrated significant improvements in fine lines/wrinkles, tactile roughness, and skin hydration. In summary, the blend of these 2 key technologies

  2. Insect maintenance and transmission.

    PubMed

    Kingdom, Heather

    2013-01-01

    Phytoplasmas are plant pathogens of huge economic importance due to responsibility for crop yield losses worldwide. Institutions around the world are trying to understand and control this yield loss at a time when food security is high on government agendas. In order to fully understand the mechanisms of phytoplasma infection and spread, more insect vector and phytoplasma colonies will need to be established for research worldwide. Rearing and study of these colonies is essential in the research and development of phytoplasma control measures. This chapter highlights general materials and methods for raising insect vector colonies and maintenance of phytoplasmas. Specific methods of rearing the maize leafhopper and maize bushy stunt phytoplasma and the aster leafhopper and aster yellows phytoplasma strain witches' broom are also included. PMID:22987405

  3. DCSP hardware maintenance system

    SciTech Connect

    Pazmino, M.

    1995-11-01

    This paper discusses the necessary changes to be implemented on the hardware side of the DCSP database. DCSP is currently tracking hardware maintenance costs in six separate databases. The goal is to develop a system that combines all data and works off a single database. Some of the tasks that will be discussed in this paper include adding the capability for report generation, creating a help package and preparing a users guide, testing the executable file, and populating the new database with data taken from the old database. A brief description of the basic process used in developing the system will also be discussed. Conclusions about the future of the database and the delivery of the final product are then addressed, based on research and the desired use of the system.

  4. Maintenance of certification.

    PubMed

    Rhodes, Robert S

    2007-02-01

    Maintenance of Certification (MOC) is the most recent stage in the evolution of specialty board certification. Driven by increasing concerns over the quality and safety of medical care, MOC represents a change in the frequency and the nature of the requirements of existing recertification. Under MOC, the every 10-year snapshot of professionalism, participation in continuing medical education, and medical expertise that are part of current recertification will become a more continuous process. MOC adds the assessment of practice performance to these measures and represents a philosophical change as well as a requirement change. The focus of these assessments is for improvement rather than judgment. The extent to which MOC succeeds will reflect surgeons' ability to improve the quality of care through voluntary efforts. PMID:17305290

  5. Antioxidative effects in vivo and colonization of Lactobacillus plantarum MA2 in the murine intestinal tract.

    PubMed

    Tang, Wei; Xing, Zhuqing; Hu, Wei; Li, Chao; Wang, Jinju; Wang, Yanping

    2016-08-01

    Lactobacillus plantarum MA2 was isolated from traditional Chinese Tibet kefir grains, which possess several excellent properties and functions. We previously demonstrated the antioxidant activities of this bacterium in vitro. However, the maintenance and survival of L. plantarum MA2 inside the murine intestinal tract, where it exerts its probiotic properties, and whether its effects are elicited directly on the host remain unknown. Therefore, this study investigated the mechanisms of L. plantarum MA2 in aging mice following D-galactose administration. The levels of malondialdehyde decreased significantly in the L. plantarum MA2 groups after oral ingestion compared to the D-galactose model group, and total antioxidant capacity and glutathione peroxidase and superoxide dismutase activities increased significantly in the serum and liver. We combined fluorescein isothiocyanate labeling and green fluorescent protein expression to dynamically monitor the colonization and distribution of L. plantarum MA2 in the murine intestinal tract. The results indicated that L. plantarum MA2 was detected in the ileum, colon, and feces after single and continuous oral administration at day 21 and was maintained at 10(4)-10(5) CFU/g. These results suggest that L. plantarum MA2 colonizes and survives in the murine intestinal tract to exert its antioxidative effects. PMID:27178180

  6. Interplay of Murine Gammaherpesvirus 68 with NF-kappaB Signaling of the Host

    PubMed Central

    Cieniewicz, Brandon; Santana, Alexis L.; Minkah, Nana; Krug, Laurie T.

    2016-01-01

    Herpesviruses establish a chronic infection in the host characterized by intervals of lytic replication, quiescent latency, and reactivation from latency. Murine gammaherpesvirus 68 (MHV68) naturally infects small rodents and has genetic and biologic parallels with the human gammaherpesviruses (gHVs), Kaposi’s sarcoma-associated herpesvirus and Epstein–Barr virus. The murine gammaherpesvirus model pathogen system provides a platform to apply cutting-edge approaches to dissect the interplay of gammaherpesvirus and host determinants that enable colonization of the host, and that shape the latent or lytic fate of an infected cell. This knowledge is critical for the development of novel therapeutic interventions against the oncogenic gHVs. The nuclear factor kappa B (NF-κB) signaling pathway is well-known for its role in the promotion of inflammation and many aspects of B cell biology. Here, we review key aspects of the virus lifecycle in the host, with an emphasis on the route that the virus takes to gain access to the B cell latency reservoir. We highlight how the murine gammaherpesvirus requires components of the NF-κB signaling pathway to promote replication, latency establishment, and maintenance of latency. These studies emphasize the complexity of gammaherpesvirus interactions with NF-κB signaling components that direct innate and adaptive immune responses of the host. Importantly, multiple facets of NF-κB signaling have been identified that might be targeted to reduce the burden of gammaherpesvirus-associated diseases. PMID:27582728

  7. Interplay of Murine Gammaherpesvirus 68 with NF-kappaB Signaling of the Host.

    PubMed

    Cieniewicz, Brandon; Santana, Alexis L; Minkah, Nana; Krug, Laurie T

    2016-01-01

    Herpesviruses establish a chronic infection in the host characterized by intervals of lytic replication, quiescent latency, and reactivation from latency. Murine gammaherpesvirus 68 (MHV68) naturally infects small rodents and has genetic and biologic parallels with the human gammaherpesviruses (gHVs), Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus. The murine gammaherpesvirus model pathogen system provides a platform to apply cutting-edge approaches to dissect the interplay of gammaherpesvirus and host determinants that enable colonization of the host, and that shape the latent or lytic fate of an infected cell. This knowledge is critical for the development of novel therapeutic interventions against the oncogenic gHVs. The nuclear factor kappa B (NF-κB) signaling pathway is well-known for its role in the promotion of inflammation and many aspects of B cell biology. Here, we review key aspects of the virus lifecycle in the host, with an emphasis on the route that the virus takes to gain access to the B cell latency reservoir. We highlight how the murine gammaherpesvirus requires components of the NF-κB signaling pathway to promote replication, latency establishment, and maintenance of latency. These studies emphasize the complexity of gammaherpesvirus interactions with NF-κB signaling components that direct innate and adaptive immune responses of the host. Importantly, multiple facets of NF-κB signaling have been identified that might be targeted to reduce the burden of gammaherpesvirus-associated diseases. PMID:27582728

  8. Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract

    PubMed Central

    Becknell, Brian; Eichler, Tad; Beceiro, Susana; Li, Birong; Easterling, Robert; Carpenter, Ashley R.; James, Cindy; McHugh, Kirk M.; Hains, David S.; Partida-Sanchez, Santiago; Spencer, John David

    2014-01-01

    Recent evidence suggests antimicrobial peptides protect the urinary tract from infection. Ribonuclease 7 (RNase 7), a member of the RNase A superfamily, is a potent epithelial-derived protein that maintains human urinary tract sterility. RNase 7 expression is restricted to primates, limiting evaluation of its antimicrobial activity in vivo. Here we identified Ribonuclease 6 (RNase 6) as the RNase A Superfamily member present in humans and mice that is most conserved at the amino acid level relative to RNase 7. Like RNase 7, recombinant human and murine RNase 6 has potent antimicrobial activity against uropathogens. Quantitative real-time PCR and immunoblot analysis indicate that RNase 6 mRNA and protein are up-regulated in the human and murine urinary tract during infection. Immunostaining located RNase 6 to resident and infiltrating monocytes, macrophages, and neutrophils. Uropathogenic E. coli induces RNase 6 peptide expression in human CD14+ monocytes and murine bone marrow derived macrophages. Thus, RNase 6 is an inducible, myeloid-derived protein with markedly different expression from the epithelial-derived RNase 7 but with equally potent antimicrobial activity. Our studies suggest RNase 6 serves as an evolutionarily conserved antimicrobial peptide that participates in the maintenance of urinary tract sterility. PMID:25075772

  9. Coregulation of Epidermal Growth Factor Receptor/Human Epidermal Growth Factor Receptor 2 (HER2) Levels and Locations: Quantitative Analysis of HER2 Overexpression Effects

    SciTech Connect

    Hendriks, Bart S.; Opresko, Lee; Wiley, H. S.; Lauffenburger, Douglas A.

    2003-03-01

    Elevated expression of human epidermal growth factor receptor 2 (HER2) is know to alter cell signalilng and behavioral responses implicated in tumor progression. However, multiple diverse mechanisms may be involved in these overall effects, including signaling by HER2 itself, modulation of signalilng by epidermal growth factor receptor (EGFR) and modification of trafficking dynamics for both EGFR and HER2. Continued....

  10. Immunolocalization of FGF8/10 in the Apical Epidermal Peg and Blastema of the regenerating tail in lizard marks this apical growing area.

    PubMed

    Alibardi, Lorenzo

    2016-07-01

    Previous studies have shown that Fibroblast Growth Factors are present in the regenerating tail tissues of lizards where they may stimulate the process of regeneration. The present study is focused on the immunolocalization of FGF8 and FGF10 in the regenerating lizard tail, two signaling proteins of the apical epidermal cup/ridge and mesenchymal blastema sustaining tail and limb regeneration in amphibians and the development of the tail and limbs in vertebrate embryos. Main immunoreactive protein bands at 15-18kDa for FGF8/10 are detected in the regenerating epidermis and only a band at 30 or 35kDa in the underlying connective tissues. FGF8 appears particularly localized in cells and nuclei of the apical epidermal peg and of the ependymal ampulla present at the tip of the regenerating tail. FGF10 is also immuno-localized in the apical epidermis but is particularly intensely localized in the mesenchyme of the apical blastema. In accordance with previous studies, the present observations supports the hypothesis that the apical epidermal peg and the ependymal tube with the few regenerated neurons present within it, release FGF8/10 that may contribute to maintenance of cell proliferation in the apical front of the mesenchyme for the growth of the regenerating tail. PMID:27113329

  11. Epidermal growth in the bottlenose dolphin, Tursiops truncatus

    SciTech Connect

    Hicks, B.D.; St. Aubin, D.J.; Geraci, J.R.; Brown, W.R.

    1985-07-01

    Epidermal growth in two mature female bottlenose dolphins, Tursiops truncatus, was investigated by following the movement of a cohort of tritiated thymidine-labeled epidermal cells for 59 days. The majority of the cells migrated in a cluster which was estimated to reach the skin surface in 73 days. The authors calculate that the outermost cell layer is sloughed 12 times per day. Turnover time and sloughing rate are estimated to be 1.7 times longer and 8.5 times faster than the respective values for epidermal cell kinetics in humans. This apparent inconsistency of slow transit time and rapid sloughing rate is reconciled by the convoluted structure of the stratum germinativum in the dolphin which results in a ratio of germinatival to superficial cells of 876:1. The stratum germinativum of dolphin epidermis appears to lack morphologically distinct, spatially segregated subpopulations of anchoring and stem cells. Dolphin epidermis has a large capacity for cell population, relatively long turnover time, and rapid sloughing rate. The adaptive advantages of these characteristics are discussed.

  12. Does therapeutic intervention in atopic dermatitis normalize epidermal Notch deficiency?

    PubMed

    Melnik, Bodo C

    2014-10-01

    This viewpoint presents a unifying concept for the treatment of atopic dermatitis (AD) that is based on the improvement of deficient Notch signalling, which appears to represent the fundamental epithelial defect of AD resulting in epidermal and immunological barrier dysfunction. One study of AD patients demonstrated a marked epidermal deficiency of Notch receptors and several mouse models with genetically suppressed Notch signalling exhibit dry skin, signs of scratching, skin barrier abnormalities, increased transepidermal water loss and Th2 cell-mediated immunological changes closely resembling human AD. Notch signalling is critically involved in the differentiation of regulatory T cells, in the feedback inhibition of activated innate immunity, in the repression of activating protein-1 (AP-1), the regulation of late epidermal differentiation associated with filaggrin- and stratum corneum barrier lipid processing, in aquaporin 3- and claudin-1 expression and in keratinocyte-mediated release of thymic stromal lymphopoietin (TSLP), which promotes Th2-driven immune responses with TSLP- and IL-31-mediated stimulation of cutaneous sensory neurons involved in the induction of itch. Translational evidence will be provided that all major therapeutic regimens employed for the treatment of AD such as glucocorticoids, calcineurin inhibitors and UV radiation may converge in the upregulation of impaired Notch signalling, the proposed pathogenic defect of AD. PMID:24889007

  13. Epidermal cyst in an unusual site: A case report

    PubMed Central

    Pehlivan, Mustafa; Özbay, Pelin Özün; Temur, Muzaffer; Yılmaz, Özgür; Gümüş, Zekeriya; Güzel, Ahmet

    2015-01-01

    Introduction Epidermoid cysts can occur in a variety of locations including face, trunk, neck, extremities and scalp. Up to now, those vulvar epidermal cysts reported in the literature were localized on the labia majora and the clitoris. This is the first case of epidermal cyst reported on the labia minora. Presentation of case A 47-year-old, multiparous woman presented with a history of a palpable vulvar mass, without pain but causing difficulty in walking. The large mass was 6 cm in diameter and located in the left labium minus. The labial mass was surgically removed. The final pathologic diagnosis was a vulvar epidermoid cyst. The patient was discharged from hospital without any complications. Discussion Total surgical excision of the mass is more appropriate for definitive histopathological diagnosis and for the prevention of future development of complications. MRI is very important in the localization of the mass and relationship with other tissues regarding treatment planning of larger vulvar masses. Conclusion Epidermal cysts should be considered in the differential diagnosis of a vulvar mass. PMID:25658206

  14. Nrf2 links epidermal barrier function with antioxidant defense.

    PubMed

    Schäfer, Matthias; Farwanah, Hany; Willrodt, Ann-Helen; Huebner, Aaron J; Sandhoff, Konrad; Roop, Dennis; Hohl, Daniel; Bloch, Wilhelm; Werner, Sabine

    2012-05-01

    The skin provides an efficient permeability barrier and protects from microbial invasion and oxidative stress. Here, we show that these essential functions are linked through the Nrf2 transcription factor. To test the hypothesis that activation of Nrf2 provides skin protection under stress conditions, we determined the consequences of pharmacological or genetic activation of Nrf2 in keratinocytes. Surprisingly, mice with enhanced Nrf2 activity in keratinocytes developed epidermal thickening, hyperkeratosis and inflammation resembling lamellar ichthyosis. This resulted from upregulation of the cornified envelope proteins small proline-rich proteins (Sprr) 2d and 2h and of secretory leukocyte peptidase inhibitor (Slpi), which we identified as novel Nrf2 targets in keratinocytes. Since Sprrs are potent scavengers of reactive oxygen species and since Slpi has antimicrobial activities, their upregulation contributes to Nrf2's protective function. However, it also caused corneocyte fragility and impaired desquamation, followed by alterations in the epidermal lipid barrier, inflammation and overexpression of mitogens that induced keratinocyte hyperproliferation. These results identify an unexpected role of Nrf2 in epidermal barrier function, which needs to be considered for pharmacological use of Nrf2 activators. PMID:22383093

  15. The Role of Impaired Epidermal Barrier Function in Atopic Dermatitis.

    PubMed

    Jurakić Tončić, Ružica; Marinović, Branka

    2016-06-01

    Atopic dermatitis (AD) is a chronic, inflammatory, pruritic skin disease with increasing prevalence. The etiopathogenesis of atopic dermatitis is multifactorial and involves a complex interplay of environmental and genetic factors that induce derangements in the structure and function of the epidermal barrier and immune system. Due to great heterogeneity of etiopathogenesis, there is also great variability of clinical presentation, and diagnosis can sometimes be challenging and difficult. Diagnosis mostly relies on clinical features and laboratory tests, but morphology alone cannot reliably establish the diagnosis, so the spectrum of features associated with AD must be considered. Traditionally, patients with AD have been separated into two different subgroups, i.e. intrinsic and extrinsic. Today, most of authors prefer the outside to inside and back to outside hypothesis, suggesting that the primary disorder lies in epidermal structure and function, resulting in inflammation and immunological downstream activation which further provokes secondary barrier abnormalities. In this review, we discuss the structure and function of the epidermal barrier and the role of impaired barrier function in etiopathogenesis of atopic dermatitis. PMID:27477169

  16. Eph/ephrin signaling in epidermal differentiation and disease

    PubMed Central

    Lin, Samantha; Wang, Bingcheng; Getsios, Spiro

    2012-01-01

    Eph receptor tyrosine kinases mediate cell–cell communication by interacting with ephrin ligands residing on adjacent cell surfaces. In doing so, these juxtamembrane signaling complexes provide important contextual information about the cellular microenvironment that helps orchestrate tissue morphogenesis and maintain homeostasis. Eph/ephrin signaling has been implicated in various aspects of mammalian skin physiology, with several members of this large family of receptor tyrosine kinases and their ligands present in the epidermis, hair follicles, sebaceous glands, and underlying dermis. This review focuses on the emerging role of Eph receptors and ephrins in epidermal keratinocytes where they can modulate proliferation, migration, differentiation, and death. The activation of Eph receptors by ephrins at sites of cell–cell contact also appears to play a key role in the maturation of intercellular junctional complexes as keratinocytes move out of the basal layer and differentiate in the suprabasal layers of this stratified, squamous epithelium. Furthermore, alterations in the epidermal Eph/ephrin axis have been associated with cutaneous malignancy, wound healing defects and inflammatory skin conditions. These collective observations suggest that the Eph/ephrin cell–cell communication pathway may be amenable to therapeutic intervention for the purpose of restoring epidermal tissue homeostasis and integrity in dermatological disorders. PMID:22040910

  17. Optimal allocation of leaf epidermal area for gas exchange.

    PubMed

    de Boer, Hugo J; Price, Charles A; Wagner-Cremer, Friederike; Dekker, Stefan C; Franks, Peter J; Veneklaas, Erik J

    2016-06-01

    A long-standing research focus in phytology has been to understand how plants allocate leaf epidermal space to stomata in order to achieve an economic balance between the plant's carbon needs and water use. Here, we present a quantitative theoretical framework to predict allometric relationships between morphological stomatal traits in relation to leaf gas exchange and the required allocation of epidermal area to stomata. Our theoretical framework was derived from first principles of diffusion and geometry based on the hypothesis that selection for higher anatomical maximum stomatal conductance (gsmax ) involves a trade-off to minimize the fraction of the epidermis that is allocated to stomata. Predicted allometric relationships between stomatal traits were tested with a comprehensive compilation of published and unpublished data on 1057 species from all major clades. In support of our theoretical framework, stomatal traits of this phylogenetically diverse sample reflect spatially optimal allometry that minimizes investment in the allocation of epidermal area when plants evolve towards higher gsmax . Our results specifically highlight that the stomatal morphology of angiosperms evolved along spatially optimal allometric relationships. We propose that the resulting wide range of viable stomatal trait combinations equips angiosperms with developmental and evolutionary flexibility in leaf gas exchange unrivalled by gymnosperms and pteridophytes. PMID:26991124

  18. Epidermal Wound Healing in the Nematode Caenorhabditis elegans

    PubMed Central

    Chisholm, Andrew D.

    2015-01-01

    Significance: Healing of epidermal wounds is a fundamentally conserved process found in essentially all multicellular organisms. Studies of anatomically simple and genetically tractable model invertebrates can illuminate the roles of key genes and mechanisms in wound healing. Recent Advances: The nematode skin is composed of a simple epithelium, the epidermis (also known as hypodermis), and an associated extracellular cuticle. Nematodes likely have a robust capacity for epidermal repair; yet until recently, relatively few studies have directly analyzed wound healing. Here we review epidermal wound responses and repair in the model nematode Caenorhabditis elegans. Critical Issues: Wounding the epidermis triggers a cutaneous innate immune response and wound closure. The innate immune response involves upregulation of a suite of antimicrobial peptides. Wound closure involves a Ca2+-triggered rearrangement of the actin cytoskeleton. These processes appear to be initiated independently, yet, their coordinated activity allows the animal to survive otherwise fatal skin wounds. Future Directions: Unanswered questions include the nature of the damage-associated molecular patterns sensed by the epidermis, the signaling pathways relaying Ca2+ to the cytoskeleton, and the mechanisms of permeability barrier repair. PMID:25945288

  19. TEMPRANILLO Reveals the Mesophyll as Crucial for Epidermal Trichome Formation.

    PubMed

    Matías-Hernández, Luis; Aguilar-Jaramillo, Andrea E; Osnato, Michela; Weinstain, Roy; Shani, Eilon; Suárez-López, Paula; Pelaz, Soraya

    2016-03-01

    Plant trichomes are defensive specialized epidermal cells. In all accepted models, the epidermis is the layer involved in trichome formation, a process controlled by gibberellins (GAs) in Arabidopsis rosette leaves. Indeed, GA activates a genetic cascade in the epidermis for trichome initiation. Here we report that TEMPRANILLO (TEM) genes negatively control trichome initiation not only from the epidermis but also from the leaf layer underneath the epidermis, the mesophyll. Plants over-expressing or reducing TEM specifically in the mesophyll, display lower or higher trichome numbers, respectively. We surprisingly found that fluorescently labeled GA3 accumulates exclusively in the mesophyll of leaves, but not in the epidermis, and that TEM reduces its accumulation and the expression of several newly identified GA transporters. This strongly suggests that TEM plays an essential role, not only in GA biosynthesis, but also in regulating GA distribution in the mesophyll, which in turn directs epidermal trichome formation. Moreover, we show that TEM also acts as a link between GA and cytokinin signaling in the epidermis by negatively regulating downstream genes of both trichome formation pathways. Overall, these results call for a re-evaluation of the present theories of trichome formation as they reveal mesophyll essential during epidermal trichome initiation. PMID:26802039

  20. Why do so many petals have conical epidermal cells?

    PubMed Central

    Whitney, Heather M.; Bennett, K. M. Veronica; Dorling, Matthew; Sandbach, Lucy; Prince, David; Chittka, Lars; Glover, Beverley J.

    2011-01-01

    Background The conical epidermal cells found on the petals of most Angiosperm species are so widespread that they have been used as markers of petal identity, but their function has only been analysed in recent years. This review brings together diverse data on the role of these cells in pollination biology. Scope The published effects of conical cells on petal colour, petal reflexing, scent production, petal wettability and pollinator grip on the flower surface are considered. Of these factors, pollinator grip has been shown to be of most significance in the well-studied Antirrhinum majus/bumble-bee system. Published data on the relationship between epidermal cell morphology and floral temperature were limited, so an analysis of the effects of cell shape on floral temperature in Antirrhinum is presented here. Statistically significant warming by conical cells was not detected, although insignificant trends towards faster warming at dawn were found, and it was also found that flat-celled flowers could be warmer on warm days. The warming observed is less significant than that achieved by varying pigment content. However, the possibility that the effect of conical cells on temperature might be biologically significant in certain specific instances such as marginal habitats or weather conditions cannot be ruled out. Conclusions Conical epidermal cells can influence a diverse set of petal properties. The fitness benefits they provide to plants are likely to vary with pollinator and habitat, and models are now required to understand how these different factors interact. PMID:21470973

  1. TCMS operations and maintenance philosophy

    NASA Technical Reports Server (NTRS)

    Buehler, David P.; Griffin, Rock E.

    1992-01-01

    The purpose is to describe the basic philosophies of operating and maintaining the Test, Control, and Monitor System (TCMS) equipment. TCMS is a complex and sophisticated checkout system. Operations and maintenance processes developed to support it will be based upon current experience, but will be focused on the specific needs of TCMS in support of Space Station Freedom Program (SSFP) and related activities. An overview of the operations and maintenance goals and philosophies are presented. The assumptions, roles and responsibilities, concepts and interfaces for operation, on-line maintenance, off-line support, and Operations and Maintenance (O&M) personnel training on all TCMS equipment located at KSC are described.

  2. Epidermal control of floral organ identity by class B homeotic genes in Antirrhinum and Arabidopsis.

    PubMed

    Efremova, N; Perbal, M C; Yephremov, A; Hofmann, W A; Saedler, H; Schwarz-Sommer, Z

    2001-07-01

    To assess the contribution of the epidermis to the control of petal and stamen organ identity, we have used transgenic Antirrhinum and Arabidopsis plants that expressed the Antirrhinum class B homeotic transcription factors DEFICIENS (DEF) and GLOBOSA (GLO) in the epidermis. Transgene expression was controlled by the ANTIRRHINUM FIDDLEHEAD (AFI) promoter, which directs gene expression to the L1 meristematic layer and, later, to the epidermis of differentiating organs. Transgenic epidermal DEF and GLO chimeras display similar phenotypes, suggesting similar epidermal contributions by the two class B genes in ANTIRRHINUM: Epidermal B function autonomously controls the differentiation of Antirrhinum petal epidermal cell types, but cannot fully control the pattern of cell divisions and the specification of sub-epidermal petal cell-identity by epidermal signalling. This non-autonomous control is enhanced if the endogenous class B genes can be activated from the epidermis. The developmental influence of epidermal B function in Antirrhinum stamen development is very limited. In contrast, epidermal B function in Arabidopsis can control most if not all epidermal and sub-epidermal differentiation events in petals and stamens, without any contribution from the endogenous class B genes. Possible reasons for differences in the efficacy of B-function-mediated cell communication between the two species are discussed. Interestingly, our experiments uncovered partial incompatibility between class B functional homologues. Although the DEFICIENS/PISTILLATA heterodimer is functional in transgenic Arabidopsis plants, the APETALA3/GLOBOSA heterodimer is not. PMID:11526073

  3. Hyaluronan Participates in the Epidermal Response to Disruption of the Permeability Barrier in Vivo

    PubMed Central

    Maytin, Edward V.; Chung, Helen H.; Seetharaman, V. Mani

    2004-01-01

    Hyaluronan (hyaluronic acid, HA) is a glycosaminoglycan in the extracellular matrix of tissues that plays a role in cellular migration, proliferation and differentiation. Injury to the stratum corneum elicits an epidermal hyperproliferative response, a pathogenic feature in many cutaneous diseases including eczema and psoriasis. Because HA is abundant in the matrix between keratinocytes, we asked whether the presence of HA is required for epidermal hyperplasia to occur in response to barrier injury. Disruption of the stratum corneum, by acetone application on the skin of hairless mice, led to a marked accumulation of HA in the matrix between epidermal basal and spinous keratinocytes, and also within keratinocytes of the upper epidermis. To test whether HA may have a functional role in epidermal hyperplasia, we used Streptomyces hyaluronidase (StrepH), delivered topically, to degrade epidermal HA and blunt the accumulation of epidermal HA after acetone. StrepH signficantly reduced epidermal HA levels, and also significantly inhibited the development of epidermal hyperplasia. This reduction in epidermal thickness was not attributable to any decrease in keratinocyte proliferation, but rather to an apparent acceleration in terminal differentiation (ie, increased keratin 10 and filaggrin expression). Overall, the data show that HA is a significant participant in the epidermal response to barrier injury. PMID:15466397

  4. Keratin 16 regulates innate immunity in response to epidermal barrier breach

    PubMed Central

    Lessard, Juliane C.; Piña-Paz, Sylvia; Rotty, Jeremy D.; Hickerson, Robyn P.; Kaspar, Roger L.; Balmain, Allan; Coulombe, Pierre A.

    2013-01-01

    Mutations in the type I keratin 16 (Krt16) and its partner type II keratin 6 (Krt6a, Krt6b) cause pachyonychia congenita (PC), a disorder typified by dystrophic nails, painful hyperkeratotic calluses in glabrous skin, and lesions involving other epithelial appendages. The pathophysiology of these symptoms and its relationship to settings in which Krt16 and Krt6 are induced in response to epidermal barrier stress are poorly understood. We report that hyperkeratotic calluses arising in the glabrous skin of individuals with PC and Krt16 null mice share a gene expression signature enriched in genes involved in inflammation and innate immunity, in particular damage-associated molecular patterns. Transcriptional hyper-activation of damage-associated molecular pattern genes occurs following de novo chemical or mechanical irritation to ear skin and in spontaneously arising skin lesions in Krt16 null mice. Genome-wide expression analysis of normal mouse tail skin and benign proliferative lesions reveals a tight, context-dependent coregulation of Krt16 and Krt6 with genes involved in skin barrier maintenance and innate immunity. Our results uncover a role for Krt16 in regulating epithelial inflammation that is relevant to genodermatoses, psoriasis, and cancer and suggest a avenue for the therapeutic management of PC and related disorders. PMID:24218583

  5. Genetically Induced Cell Death in Bulge Stem Cells Reveals Their Redundancy for Hair and Epidermal Regeneration

    PubMed Central

    Driskell, Iwona; Oeztuerk-Winder, Feride; Humphreys, Peter; Frye, Michaela

    2015-01-01

    Adult mammalian epidermis contains multiple stem cell populations in which quiescent and more proliferative stem and progenitor populations coexist. However, the precise interrelation of these populations in homeostasis remains unclear. Here, we blocked the contribution of quiescent keratin 19 (K19)-expressing bulge stem cells to hair follicle formation through genetic ablation of the essential histone methyltransferase Setd8 that is required for the maintenance of adult skin. Deletion of Setd8 eliminated the contribution of bulge cells to hair follicle regeneration through inhibition of cell division and induction of cell death, but the growth and morphology of hair follicles were unaffected. Furthermore, ablation of Setd8 in the hair follicle bulge blocked the contribution of K19-postive stem cells to wounded epidermis, but the wound healing process was unaltered. Our data indicate that quiescent bulge stem cells are dispensable for hair follicle regeneration and epidermal injury in the short term and support the hypothesis that quiescent and cycling stem cell populations are equipotent. Stem Cells 2015;33:988–998 PMID:25447755

  6. aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation

    PubMed Central

    Niessen, Michaela T.; Scott, Jeanie; Zielinski, Julia G.; Vorhagen, Susanne; Sotiropoulou, Panagiota A.; Blanpain, Cédric

    2013-01-01

    The atypical protein kinase C (aPKC) is a key regulator of polarity and cell fate in lower organisms. However, whether mammalian aPKCs control stem cells and fate in vivo is not known. Here we show that loss of aPKCλ in a self-renewing epithelium, the epidermis, disturbed tissue homeostasis, differentiation, and stem cell dynamics, causing progressive changes in this tissue. This was accompanied by a gradual loss of quiescent hair follicle bulge stem cells and a temporary increase in proliferating progenitors. Lineage tracing analysis showed that loss of aPKCλ altered the fate of lower bulge/hair germ stem cells. This ultimately led to loss of proliferative potential, stem cell exhaustion, alopecia, and premature aging. Inactivation of aPKCλ produced more asymmetric divisions in different compartments, including the bulge. Thus, aPKCλ is crucial for homeostasis of self-renewing stratifying epithelia, and for the regulation of cell fate, differentiation, and maintenance of epidermal bulge stem cells likely through its role in balancing symmetric and asymmetric division. PMID:24019538

  7. aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation.

    PubMed

    Niessen, Michaela T; Scott, Jeanie; Zielinski, Julia G; Vorhagen, Susanne; Sotiropoulou, Panagiota A; Blanpain, Cédric; Leitges, Michael; Niessen, Carien M

    2013-09-16

    The atypical protein kinase C (aPKC) is a key regulator of polarity and cell fate in lower organisms. However, whether mammalian aPKCs control stem cells and fate in vivo is not known. Here we show that loss of aPKCλ in a self-renewing epithelium, the epidermis, disturbed tissue homeostasis, differentiation, and stem cell dynamics, causing progressive changes in this tissue. This was accompanied by a gradual loss of quiescent hair follicle bulge stem cells and a temporary increase in proliferating progenitors. Lineage tracing analysis showed that loss of aPKCλ altered the fate of lower bulge/hair germ stem cells. This ultimately led to loss of proliferative potential, stem cell exhaustion, alopecia, and premature aging. Inactivation of aPKCλ produced more asymmetric divisions in different compartments, including the bulge. Thus, aPKCλ is crucial for homeostasis of self-renewing stratifying epithelia, and for the regulation of cell fate, differentiation, and maintenance of epidermal bulge stem cells likely through its role in balancing symmetric and asymmetric division. PMID:24019538

  8. Space shuttle maintenance program planning document

    NASA Technical Reports Server (NTRS)

    Brown, D. V.

    1972-01-01

    A means for developing a space shuttle maintenance program which will be acceptable to the development centers, the operators (KSC and AF), and the manufacturer is presented. The general organization and decision processes for determining the essential scheduled maintenance requirements for the space shuttle orbiter are outlined. The development of initial scheduled maintenance programs is discussed. The remaining maintenance, that is non-scheduled or non-routine maintenance, is directed by the findings of the scheduled maintenance program and the normal operation of the shuttle. The remaining maintenance consists of maintenance actions to correct discrepancies noted during scheduled maintenance tasks, nonscheduled maintenance, normal operation, or condition monitoring.

  9. The Tryptophan-Derived Endogenous Aryl Hydrocarbon Receptor Ligand 6-Formylindolo[3,2-b]Carbazole Is a Nanomolar UVA Photosensitizer in Epidermal Keratinocytes.

    PubMed

    Park, Sophia L; Justiniano, Rebecca; Williams, Joshua D; Cabello, Christopher M; Qiao, Shuxi; Wondrak, Georg T

    2015-06-01

    Endogenous UVA chromophores may act as sensitizers of oxidative stress underlying cutaneous photoaging and photocarcinogenesis, but the molecular identity of non-DNA key chromophores displaying UVA-driven photodyamic activity in human skin remains largely undefined. Here we report that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct and endogenous high-affinity aryl hydrocarbon receptor (AhR) agonist, acts as a nanomolar photosensitizer potentiating UVA-induced oxidative stress irrespective of AhR ligand activity. In human HaCaT and primary epidermal keratinocytes, photodynamic induction of apoptosis was elicited by the combined action of solar-simulated UVA and FICZ, whereas exposure to the isolated action of UVA or FICZ did not impair viability. In a human epidermal tissue reconstruct, FICZ/UVA cotreatment caused pronounced phototoxicity inducing keratinocyte cell death, and FICZ photodynamic activity was also substantiated in a murine skin exposure model. Array analysis revealed pronounced potentiation of cellular heat shock, endoplasmic reticulum stress, and oxidative stress response gene expression observed only upon FICZ/UVA cotreatment. FICZ photosensitization caused intracellular oxidative stress, and comet analysis revealed introduction of formamidopyrimidine-DNA glycosylase (Fpg)-sensitive oxidative DNA lesions suppressible by antioxidant cotreatment. Taken together, our data demonstrate that the endogenous AhR ligand FICZ displays nanomolar photodynamic activity representing a molecular mechanism of UVA-induced photooxidative stress potentially operative in human skin. PMID:25431849

  10. The tryptophan-derived endogenous arylhydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole (FICZ) is a nanomolar UVA-photosensitizer in epidermal keratinocytes

    PubMed Central

    Williams, Joshua D.; Cabello, Christopher M.; Qiao, Shuxi; Wondrak, Georg T.

    2014-01-01

    Endogenous UVA-chromophores may act as sensitizers of oxidative stress underlying cutaneous photoaging and photocarcinogenesis, but the molecular identity of non-DNA key chromophores displaying UVA-driven photodyamic activity in human skin remains largely undefined. Here we report that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct and endogenous high affinity aryl hydrocarbon receptor (AhR) agonist, acts as a nanomolar photosensitizer potentiating UVA-induced oxidative stress irrespective of AhR ligand activity. In human HaCaT and primary epidermal keratinocytes, photodynamic induction of apoptosis was elicited by the combined action of solar simulated UVA and FICZ, whereas exposure to the isolated action of UVA or FICZ did not impair viability. In a human epidermal tissue reconstruct, FICZ/UVA-cotreatment caused pronounced phototoxicity inducing keratinocyte cell death, and FICZ photodynamic activity was also substantiated in a murine skin exposure model. Array analysis revealed pronounced potentiation of cellular heat shock, ER stress, and oxidative stress response gene expression observed only upon FICZ/UVA-cotreatment. FICZ photosensitization caused intracellular oxidative stress, and comet analysis revealed introduction of formamidopyrimidine-DNA glycosylase (FPG)-sensitive oxidative DNA lesions suppressible by antioxidant cotreatment. Taken together, our data demonstrate that the endogenous AhR ligand FICZ displays nanomolar photodynamic activity representing a molecular mechanism of UVA-induced photooxidative stress potentially operative in human skin. PMID:25431849

  11. Illinois Occupational Skill Standards: Industrial Maintenance General Maintenance Cluster.

    ERIC Educational Resources Information Center

    Illinois Occupational Skill Standards and Credentialing Council, Carbondale.

    These skill standards for the industrial maintenance general maintenance cluster are intended to be a guide to workforce preparation program providers in defining content for their programs and to employers to establish the skills and standards necessary for job acquisition. An introduction provides the Illinois perspective; Illinois Occupational…

  12. IMIS: Integrated Maintenance Information System. A maintenance information delivery concept

    NASA Technical Reports Server (NTRS)

    Vonholle, Joseph C.

    1987-01-01

    The Integrated Maintenance Information System (IMIS) will optimize the use of available manpower, enhance technical performance, improve training, and reduce the support equipment and documentation needed for deployment. It will serve as the technician's single, integrated source of all the technical information required to perform modern aircraft maintenance.

  13. Leaf epidermal appendages of desert plant: an ecological perspective

    NASA Astrophysics Data System (ADS)

    Liu, Yubing; Li, Xinrong; Li, Mengmeng

    2014-05-01

    Desert plant often have few, tiny or no leaves, which reduces transpiration. The epidermis of their leaves is often ornamented outgrowths called trichomes or hairs and a thick waxy cuticle. Hairs on the leaf surface trap humidity in dry climates and waxy leaf surfaces reduce water loss. Our present study is to investigate the characteristics of trichomes and waxy cuticle in leaf surface of desert plant, which in the long term acclimation in semi-humid, semi-arid and arid ecosystems of Northern China, from east (Zhangwu county, Liaoning province) to west (Korla city, Xinjiang Uygur Autonomous Region), passing through several provinces including the Inner Mongolia Autonomous Region, Shanxi province, the Ningxia Hui Autonomous Region and Gansu province. 68 shrubs and 7 trees were selected in the natural habitats which were artificial sand fixing vegetation and the adjacent natural vegetation in sandy areas. The leaf epidermis was observed by scanning electron microscopy (SEM) and the cuticle thickness was calculated in the leaf cross-section by transmission electron microscopy (TEM). The results indicated that the epidermis of selected materials was divided into five categories: (1) Trichomes with different forms covered completely on the adaxial and abaxial surfaces of leaf, and any other epidermal appendages could not been observed. (2) Epicuticular wax crystals with different forms almost completely covered in the epistomatal chambers as well as on the surrounding epidermis, and there were no other appendages on the leaf surface. (3) A lot of warty hairs arranged neatly on the surface and the stomatal index was too low. (4) Several or even dozens of papillary epidermal cells covered with waxy crystals enclosed a sunken stomata chamber, therefore the stomatal density is very low. (5) Like ordinary terrestrial plants, epidermal cells and cell outline are clear, with epidermal hairs or not, and the stomata and waxy crystals are visible. TEM showed that desert plants

  14. Murine neonatal intravascular injections: Modeling newborn disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability to perform murine neonatal intravascular injections likely will prove useful in studying many newborn-specific disease states that are modeled in mice. Unfortunately, effective intravascular injection in the neonatal mouse has been limited by developmental immaturity and small size. To e...

  15. Cognitive Load and Maintenance Rehearsal.

    ERIC Educational Resources Information Center

    Naveh-Benjamin, Moshe; and Jonides, John

    1984-01-01

    Studies the much-debated issue of the role of rote, repetitive rehearsal (maintenance rehearsal) on the establishment of memory traces that outlast the rehearsal process itself. Results show that there is an effect of maintenance rehearsal on long-term recognition performance and that this effect depends on the mental resources devoted to the…

  16. Landscaping With Maintenance in Mind.

    ERIC Educational Resources Information Center

    Sorensen, Randy

    2000-01-01

    Examines school ground landscape design that enhances attractive of the school and provides for easier maintenance. Landscape design issues discussed include choice of grass, trees, and shrubs; irrigation; and safety and access. Other considerations for lessening maintenance problems for facility managers are also highlighted. (GR)

  17. Automotive Engine Maintenance and Repair.

    ERIC Educational Resources Information Center

    Marine Corps Inst., Washington, DC.

    This correspondence course, originally developed for the Marine Corps, is designed to provide students with an understanding of automotive engine maintenance and repair. The course contains six study units covering automotive engine maintenance and repair; design classification; engine malfunction, diagnosis, and repair; engine disassembly; engine…

  18. Osmotic characteristics and fertility of murine spermatozoa collected in different solutions.

    PubMed

    Si, Wei; Men, Hongsheng; Benson, James D; Critser, John K

    2009-02-01

    Osmotic stress is an important factor that can result in cell damage during cryopreservation. Before ejaculation or collection for cryopreservation, murine spermatozoa are stored in epididymal fluid, a physiologically hyperosmotic environment (approximately 415 mmol/kg). The objectives of this study were to determine the osmotic tolerance limits of sperm motion parameters of ICR and C57BL/6 mouse spermatozoa collected in isosmotic (290 mmol/kg) and hyperosmotic (415 mmol/kg) media, and the effect of the osmolality of sperm collection media on sperm fertility after cryopreservation. Our results indicate that murine spermatozoa collected in media with different osmolalities (290 and 415 mmol/kg Dulbecco's phosphate buffered saline (DPBS)) appeared to have different osmotic tolerances for the maintenance of sperm motility and other motion parameters in both mouse strains. The hypo- and hyperosmotic treatments decreased motility and affected other motion parameters of spermatozoa collected in 290 mmol/kg DPBS. The extent of the change of motion parameters after treatments corresponded with the levels of osmotic stress. However, for spermatozoa collected in 415 mmol/kg DPBS, exposure to 290 mmol/kg DPBS tended to increase sperm motility and the quality of their motion parameters. The osmolality of sperm collection medium can affect murine sperm fertility. Spermatozoa collected in 415 mmol/kg medium showed higher fertility compared with spermatozoa collected in 290 mmol/kg as assessed by IVF. Results characterizing murine sperm osmotic tolerance collected in media with different osmolalities from different strains and the effect of collection media osmolality on sperm fertility after cryopreservation will be useful in designing cryopreservation protocols. PMID:19028924

  19. Retino-hypothalamic regulation of light-induced murine sleep

    PubMed Central

    Muindi, Fanuel; Zeitzer, Jamie M.; Heller, Horace Craig

    2014-01-01

    The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin-based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area (VLPO) and the suprachiasmatic nucleus (SCN). We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages. PMID:25140132

  20. The dynamics of murine mammary stem/progenitor cells

    PubMed Central

    DONG, Qiaoxiang; SUN, Lu-Zhe

    2014-01-01

    The stem/progenitor cells in the murine mammary gland are a highly dynamic population of cells that are responsible for ductal elongation in puberty, homeostasis maintenance in adult, and lobulo-alveolar genesis during pregnancy. In recent years understanding the epithelial cell hierarchy within the mammary gland is becoming particularly important as these different stem/progenitor cells were perceived to be the cells of origin for various subtypes of breast cancer. Although significant advances have been made in enrichment and isolation of stem/progenitor cells by combinations of antibodies against cell surface proteins together with flow cytometry, and in identification of stem/progenitor cells with multi-lineage differentiation and self-renewal using mammary fat pad reconstitution assay and in vivo genetic labeling technique, a clear understanding of how these different stem/progenitors are orchestrated in the mammary gland is still lacking. Here we discuss the different in vivo and in vitro methods currently available for stem/progenitor identification, their associated caveats, and a possible new hierarchy model to reconcile various putative stem/progenitor cell populations identified by different research groups. PMID:25580105

  1. Inflammatory linear verrucous epidermal nevus syndrome with its polymorphic presentation - A rare case report

    PubMed Central

    Kumar, C. Anand; Yeluri, Garima; Raghav, Namita

    2012-01-01

    Epidermal nevi are hamartomatous lesions that are typically present at birth, but can occur anytime during childhood and may rarely appear in adulthood. An estimated one-third of individuals with epidermal nevi have involvement of other organ systems; hence, this condition is considered to be an epidermal nevus syndrome. There are four distinct epidermal nevus syndromes recognizable by the different types of associated epithelial nevi: linear sebaceous nevi, linear nevus comedonicus, linear epidermal nevus, and inflammatory linear verrucous epidermal nevus (ILVEN). Each type may be regarded as a part of a syndrome with other systemic manifestations. We report a rare case of ILVEN syndrome in a 23-year-old female patient with a wide spectrum of mucosal, cutaneous, and skeletal abnormalities, demonstrating the polymorphic presentation of this condition. PMID:22557913

  2. Esterase Activity and Intracellular Localization in Reconstructed Human Epidermal Cultured Skin Models

    PubMed Central

    Katayanagi, Mishina; Hashimoto, Fumie

    2015-01-01

    Background Reconstructed human epidermal culture skin models have been developed for cosmetic and pharmaceutical research. Objective This study evaluated the total and carboxyl esterase activities (i.e., Km and Vmax, respectively) and localization in two reconstructed human epidermal culture skin models (LabCyte EPI-MODEL [Japan Tissue Engineering] and EpiDerm [MatTek/Kurabo]). The usefulness of the reconstruction cultured epidermis was also verified by comparison with human and rat epidermis. Methods Homogenized epidermal samples were fractioned by centrifugation. p-nitrophenyl acetate and 4-methylumbelliferyl acetate were used as substrates of total esterase and carboxyl esterase, respectively. Results Total and carboxyl esterase activities were present in the reconstructed human epidermal culture skin models and were localized in the cytosol. Moreover, the activities and localization were the same as those in human and rat epidermis. Conclusion LabCyte EPI-MODEL and EpiDerm are potentially useful for esterase activity prediction in human epidermis. PMID:26082583

  3. Space Telescope maintenance and refurbishment

    NASA Technical Reports Server (NTRS)

    Trucks, H. F.

    1983-01-01

    The Space Telescope (ST) represents a new concept regarding spaceborne astronomical observatories. Maintenance crews will be brought to the orbital worksite to make repairs and replace scientific instruments. For major overhauls the telescope can be temporarily returned to earth with the aid of the Shuttle. It will, thus, be possible to conduct astronomical studies with the ST for two decades or more. The five first-generation scientific instruments used with the ST include a wide field/planetary camera, a faint object camera, a faint object spectrograph, a high resolution spectrograph, and a high speed photometer. Attention is given to the optical telescope assembly, the support systems module, aspects of mission and science operations, unscheduled maintenance, contingency orbital maintenance, planned on-orbit maintenance, ground maintenance, ground refurbishment, and ground logistics.

  4. An in vitro skin irritation test (SIT) using the EpiDerm reconstructed human epidermal (RHE) model.

    PubMed

    Kandárová, Helena; Hayden, Patrick; Klausner, Mitchell; Kubilus, Joseph; Sheasgreen, John

    2009-01-01

    The EpiDerm Skin Irritation test (EpiDerm SIT) was developed and validated for in vitro skin irritation testing of chemicals, including cosmetic and pharmaceutical ingredients. The EpiDerm SIT utilizes the 3D in vitro reconstructed human epidermal (RHE) model EpiDerm. The procedure described in this protocol allows for discrimination between irritants of GHS category 2 and non-irritants. The test is performed over the course of a 4 day time period, consisting of pre-incubation, 60 minute exposure, 42 hour post-incubation and MTT viability assay. After tissue receipt and overnight pre-incubation (Day 0), tissues are topically exposed to the test chemicals (Day 1), which can be liquid, semisolid, solid or waxy. Three tissues are used for each test chemical, as well as for the positive control (5% aq. SDS solution), and a negative control (DPBS). Chemical exposure lasts for 60 minutes, 35 min of which the tissues are kept in an incubator at 37 degrees C. The test substances are then removed from the tissue surface by an extensive washing procedure. The tissue inserts are blotted and transferred to fresh medium. After a 24 hr incubation period (Day 2), the medium is exchanged. The medium can be saved for further analysis of cytokines or other endpoints of interest. After the medium exchange, tissues are incubated for an additional 18 hours. At the end of the entire 42 h post-incubation (day 3), the tissues are transferred into yellow MTT solution and incubated for 3 hours. The resultant purple-blue formazan salt, formed mainly by mitochondrial metabolism, is extracted for 2 hours using isopropanol. The optical density of the extracted formazan is determined using a spectrophotometer. A chemical is classified as an irritant if the tissue viability relative to the negative control treated tissues is reduced below 50%. This procedure can be used as full replacement of the in vivo rabbit skin irritation test for hazard identification and labeling of chemicals in line with

  5. Robots for Aircraft Maintenance

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Marshall Space Flight Center charged USBI (now Pratt & Whitney) with the task of developing an advanced stripping system based on hydroblasting to strip paint and thermal protection material from Space Shuttle solid rocket boosters. A robot, mounted on a transportable platform, controls the waterjet angle, water pressure and flow rate. This technology, now known as ARMS, has found commercial applications in the removal of coatings from jet engine components. The system is significantly faster than manual procedures and uses only minimal labor. Because the amount of "substrate" lost is minimal, the life of the component is extended. The need for toxic chemicals is reduced, as is waste disposal and human protection equipment. Users of the ARMS work cell include Delta Air Lines and the Air Force, which later contracted with USBI for development of a Large Aircraft Paint Stripping system (LARPS). LARPS' advantages are similar to ARMS, and it has enormous potential in military and civil aircraft maintenance. The technology may also be adapted to aircraft painting, aircraft inspection techniques and paint stripping of large objects like ships and railcars.

  6. Symbolic Constraint Maintenance Grid

    NASA Technical Reports Server (NTRS)

    James, Mark

    2006-01-01

    Version 3.1 of Symbolic Constraint Maintenance Grid (SCMG) is a software system that provides a general conceptual framework for utilizing pre-existing programming techniques to perform symbolic transformations of data. SCMG also provides a language (and an associated communication method and protocol) for representing constraints on the original non-symbolic data. SCMG provides a facility for exchanging information between numeric and symbolic components without knowing the details of the components themselves. In essence, it integrates symbolic software tools (for diagnosis, prognosis, and planning) with non-artificial-intelligence software. SCMG executes a process of symbolic summarization and monitoring of continuous time series data that are being abstractly represented as symbolic templates of information exchange. This summarization process enables such symbolic- reasoning computing systems as artificial- intelligence planning systems to evaluate the significance and effects of channels of data more efficiently than would otherwise be possible. As a result of the increased efficiency in representation, reasoning software can monitor more channels and is thus able to perform monitoring and control functions more effectively.

  7. Cell Maintenance Systems

    NASA Technical Reports Server (NTRS)

    Morrison, D. R.

    1985-01-01

    Living human cells require attachment to a suitable surface and special culture conditions in order to grow. These requirements are modified and amplified when cells are taken into a weightless environment. Special handling and maintenance systems are required for routine laboratory procedures conducted in the Orbiter and in the Spacelab. Methods were developed to maintain cells in special incubators designed for the Orbiter middeck, however, electrophoresis and other experiments require cells to be harvested off of the culture substrate before they can be processed or used. The cell transport assembly (CTA) was flown on STS-8, and results show that improvements are required to maintain adequate numbers of cells in this device longer than 48 hours. The life sciences middeck centrifuge probably can be used, but modifications will be required to transfer cells from the CTA and keep the cells sterile. Automated systems such as the Skylab SO-15 flight hardware and crew operated systems are being evaluated for use on the Space Shuttle, Spacelab, and Space Station research modules.

  8. Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

    SciTech Connect

    Ayyagari, R.R.; Khan-Dawood, F.S.

    1987-04-01

    Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2 hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol /sup 125/I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function.

  9. Nasal administration of interleukin-33 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma surrogate.

    PubMed

    Shan, Shan; Li, Yan; Wang, Jingjing; Lv, Zhe; Yi, Dawei; Huang, Qiong; Corrigan, Chris J; Wang, Wei; Quangeng, Zhang; Ying, Sun

    2016-05-01

    The T-helper cell type 2-promoting cytokine interleukin-33 (IL-33) has been implicated in asthma pathogenesis. Angiogenesis is a feature of airways remodelling in asthma. We hypothesized that IL-33 induces airways angiogenesis and expression of angiogenic factors in an established murine surrogate of asthma. In the present study, BALB/c mice were subjected to serial intranasal challenge with IL-33 alone for up to 70 days. In parallel, ovalbumin (OVA) -sensitized mice were subjected to serial intranasal challenge with OVA or normal saline to serve as positive and negative controls, respectively. Immunohistochemical analysis of expression of von Willebrand factor and erythroblast transformation-specific-related gene, both blood vessel markers, and angiogenic factors angiogenin, insulin-like growth factor-1, endothelin-1, epidermal growth factor and amphiregulin was performed in lung sections ex vivo. An established in-house assay was used to test whether IL-33 was able to induce microvessel formation by human vascular endothelial cells. Results showed that serial intranasal challenge of mice with IL-33 or OVA resulted in proliferation of peribronchial von Willebrand factor-positive blood vessels to a degree closely related to the total expression of the angiogenic factors amphiregulin, angiogenin, endothelin-1, epidermal growth factor and insulin-like growth factor-1. IL-33 also induced microvessel formation by human endothelial cells in a concentration-dependent fashion in vitro. Our data are consistent with the hypothesis that IL-33 has the capacity to induce angiogenesis at least partly by increasing local expression of multiple angiogenic factors in an allergen-independent murine asthma surrogate, and consequently that IL-33 or its receptor is a potential novel molecular target for asthma therapy. PMID:27035894

  10. The effect of Psoroptes ovis infestation on ovine epidermal barrier function

    PubMed Central

    2013-01-01

    Sheep scab is an intensively pruritic, exudative and allergic dermatitis of sheep caused by the ectoparasitic mite Psoroptes ovis. The purpose of the present study was to investigate the effect of P. ovis infestation on different components of the ovine epidermal barrier within the first 24 hours post-infestation (hpi). To achieve this, the expression of epidermal differentiation complex (EDC) genes and epidermal barrier proteins, the nature and severity of epidermal pathology and transepidermal water loss (TEWL) were evaluated. By 1 hpi a significant dermal polymorphonuclear infiltrate and a significant increase in TEWL with maximal mean TEWL (598.67 g/m2h) were observed. Epidermal pathology involving intra-epidermal pustulation, loss of epidermal architecture and damage to the basement membrane was seen by 3 hpi. Filaggrin and loricrin protein levels in the stratum corneum declined significantly in the first 24 hpi and qPCR validation confirmed the decrease in expression of the key EDC genes involucrin, filaggrin and loricrin observed by microarray analysis, with 5.8-fold, 4.5-fold and 80-fold decreases, respectively by 24 hpi. The present study has demonstrated that early P. ovis infestation disrupts the ovine epidermal barrier causing significant alterations in the expression of critical barrier components, epidermal pathology, and TEWL. Many of these features have also been documented in human and canine atopic dermatitis suggesting that sheep scab may provide a model for the elucidation of events occurring in the early phases of atopic sensitisation. PMID:23398847

  11. Health maintenance in women.

    PubMed

    Riley, Margaret; Dobson, Margaret; Jones, Elizabeth; Kirst, Nell

    2013-01-01

    The health maintenance examination is an opportunity to focus on disease prevention and health promotion. The patient history should include screening for tobacco use, alcohol misuse, intimate partner violence, and depression. Premenopausal women should receive preconception counseling and contraception as needed, and all women planning or capable of pregnancy should take 400 to 800 mcg of folic acid per day. High-risk sexually active women should be counseled on reducing the risk of sexually transmitted infections, and screened for chlamydia, gonorrhea, and syphilis. All women should be screened for human immunodeficiency virus. Adults should be screened for obesity and elevated blood pressure. Women 20 years and older should be screened for dyslipidemia if they are at increased risk of coronary heart disease. Those with sustained blood pressure greater than 135/80 mm Hg should be screened for type 2 diabetes mellitus. Women 55 to 79 years of age should take 75 mg of aspirin per day when the benefits of stroke reduction outweigh the increased risk of gastrointestinal hemorrhage. Women should begin cervical cancer screening by Papanicolaou test at 21 years of age, and if results have been normal, screening may be discontinued at 65 years of age or after total hysterectomy. Breast cancer screening with mammography may be considered in women 40 to 49 years of age based on patients' values, and potential benefits and harms. Mammography is recommended biennially in women 50 to 74 years of age. Women should be screened for colorectal cancer from 50 to 75 years of age. Osteoporosis screening is recommended in women 65 years and older, and in younger women with a similar risk of fracture. Adults should be immunized at recommended intervals according to guidelines from the Centers for Disease Control and Prevention. PMID:23317023

  12. [Maintenance therapy for colorectal cancer].

    PubMed

    Yamaguchi, Shigeo; Kato, Shunsuke

    2014-08-01

    Some trials have demonstrated the benefits of maintenance chemotherapy for advanced colorectal cancer. In chemotherapeutic strategies for advanced colorectal cancer, chemotherapy-related toxicity prevention and quality of life(QOL)maintenance are more important than the introduction of a strong regimen, especially when additional surgery is not possible. In Japan, the combination of a folinic acid/5-fluorouracil/oxaliplatin(FOLFOX)regimen and bevacizumab is a popular first-line chemotherapy regimen. However, despite its effectiveness, neuropathy or hand-foot syndrome after 5 or 6 cycles tends to lead to chemotherapy withdrawal. CAIRO3 trial reported the effectiveness of capecitabine and bevacizumab as a maintenance chemotherapy regimen. Additionally, the ML18147 trial demonstrated that bevacizumab beyond progression(BBP)prolonged overall survival(OS)and progression free survival(PFS)in patients with advanced colorectal cancer. Although those trials demonstrated the effectiveness of continuous or maintenance bevacizumab administration, no trials have compared the effectiveness of cytotoxic drugs with bevacizumab as maintenance therapies. Moreover, controversy exists regarding the selection of drugs as a maintenance therapy and the identification of patients who would benefit from maintenance therapy. PMID:25132024

  13. Operational Interventions to Maintenance Error

    NASA Technical Reports Server (NTRS)

    Kanki, Barbara G.; Walter, Diane; Dulchinos, VIcki

    1997-01-01

    A significant proportion of aviation accidents and incidents are known to be tied to human error. However, research of flight operational errors has shown that so-called pilot error often involves a variety of human factors issues and not a simple lack of individual technical skills. In aircraft maintenance operations, there is similar concern that maintenance errors which may lead to incidents and accidents are related to a large variety of human factors issues. Although maintenance error data and research are limited, industry initiatives involving human factors training in maintenance have become increasingly accepted as one type of maintenance error intervention. Conscientious efforts have been made in re-inventing the team7 concept for maintenance operations and in tailoring programs to fit the needs of technical opeRAtions. Nevertheless, there remains a dual challenge: 1) to develop human factors interventions which are directly supported by reliable human error data, and 2) to integrate human factors concepts into the procedures and practices of everyday technical tasks. In this paper, we describe several varieties of human factors interventions and focus on two specific alternatives which target problems related to procedures and practices; namely, 1) structured on-the-job training and 2) procedure re-design. We hope to demonstrate that the key to leveraging the impact of these solutions comes from focused interventions; that is, interventions which are derived from a clear understanding of specific maintenance errors, their operational context and human factors components.

  14. In vitro human epidermal penetration of 1-bromopropane.

    PubMed

    Frasch, H Frederick; Dotson, G Scott; Barbero, Ana M

    2011-01-01

    1-Bromopropane (1-BP; CAS number 106-94-5), also known as n-propyl bromide, is a halogenated short-chain alkane used as an organic solvent with numerous commercial and industrial applications, including garment dry cleaning and vapor degreasing of metals. The purpose of this study was to determine the dermal absorption characteristics and corrosivity of 1-BP. Heat-separated human epidermal membranes were mounted on static diffusion cells. Different exposure scenarios were studied (infinite dose, finite dose, and transient exposure) using neat 1-BP and saturated aqueous solution as donor. Steady-state fluxes for infinite-dose neat 1-BP exposure averaged 625 to 960 μg cm(-2) h(-1). The finite-dose (10 μl/cm(2) = 13.5 mg/cm(2)) unoccluded donor resulted in penetration of <0.2% of the applied dose (22 μg/cm(2)). A 10-min transient exposure to infinite dose resulted in total penetration of 179 μg/cm(2). Steady-state 1-BP fluxes from neat application of a commercial dry cleaning solvent were similar (441 to 722 μg cm(-2) h(-1)). The permeability coefficient of 1-BP in water vehicle was 0.257 ± 0.141 cm/h. The absorption potential of 1-BP following dermal exposure is dependent upon the type and duration of exposure. Donor losses due to evaporation were approximately 500-fold greater than dermal absorption flux; evaporation flux was 420 mg cm(-2) h(-1). 1-BP is cytotoxic but not corrosive, based on results from a cultured reconstructed human epidermal model (EpiDerm Skin Corrosivity Test). PMID:21830855

  15. A murine model of epicutaneous protein sensitization is useful to study efficacies of topical drugs in atopic dermatitis.

    PubMed

    Lehto, Maili; Savinko, Terhi; Wolff, Henrik; Kvist, Peter H; Kemp, Kaare; Lauerma, Antti; Alenius, Harri

    2010-04-01

    We studied the suitability of our murine model for the treatment trials of atopic dermatitis (AD). In this model topical application of ovalbumin (OVA) together with bacterial superantigen, staphylococcal enterotoxin B (SEB) induces a cutaneous disease resembling AD. Injured mouse skin was treated with three different drugs: a class III corticosteroid, a calcineurin inhibitor and a type 4 phosphodiesterase inhibitor. One-week treatment with corticosteroid and phosphodiesterase inhibitor remarkably decreased both epidermal and dermal thickness, whereas the calcineurin inhibitor affected only the epidermal thickness. All investigated drugs reduced the infiltration of eosinophils and mast cells onto OVA/SEB sensitized skin areas, whereas CD4+ and CD8+ T cells as well as CD11c+ dendritic cells variously diminished after corticosteroid and calcineurin inhibitor treatments. Cutaneous expression of interleukin -4, -13, -10 and interferon-gamma also decreased differently depending on drug type. Interestingly, the calcineurin inhibitor and phosphodiesterase inhibitor increased total IgE antibodies and decreased SEB-specific IgG2a antibodies in OVA/SEB sensitized mice. All these drugs can ameliorate cutaneous inflammation, although the degree of recovery depends on the type of the drug. In summary, our results show that this mouse model can be used to test new topical treatments for AD. PMID:20074670

  16. Comparison of the effects of vitamin D products in a psoriasis plaque test and a murine psoriasis xenograft model.

    PubMed

    Kvist, Peter H; Svensson, Lars; Hagberg, Oskar; Hoffmann, Vibeke; Kemp, Kaare; Røpke, Mads A

    2009-01-01

    The aim of the present study was to compare the effects of Daivobet and calcipotriol on clinical score and biomarker responses in a modified version of the Scholtz-Dumas psoriasis plaque assay. Furthermore, it was the aim to compare the effects of calcipotriol and betamethasone in the murine psoriasis xenograft model. Twenty four patients with psoriasis were treated topically once daily for three weeks, whereas the grafted mice were treated for four weeks. Clinical responses were scored twice weekly and biopsies were taken at the end of each study to analyse for skin biomarkers by histology and immunohistochemistry. The results clearly demonstrate effects on both clinical signs and biomarkers. In the patient study the total clinical score was reduced significantly with both Daivobet and calcipotriol. Both treatments reduced epidermal thickness, Ki-67 and cytokeratin 16 expression. T cell infiltration was significantly reduced by Daivobet but only marginally by calcipotriol. Both treatments showed strong effects on the epidermal psoriatic phenotype.Results from the xenograft model essentially showed the same results. However differences were observed when investigating subtypes of T cells.The study demonstrates the feasibility of obtaining robust biomarker data in the psoriasis plaque test that correlate well with those obtained in other clinical studies. Furthermore, the biomarker data from the plaque test correlate with biopsy data from the grafted mice. PMID:20017943

  17. A murine monoclonal antibody (VM-1) against human basal cells inhibits the growth of human keratinocytes in culture.

    PubMed

    Oseroff, A R; Pfendt, E A; DiCicco, L; Morhenn, V B

    1985-04-01

    Using epidermal cells from psoriatic plaques as the immunogen, an IgG1 murine monoclonal antibody, VM-1, has been produced which stains basal keratinocytes on frozen sections of skin obtained from normal individuals and from psoriatic plaques. In some areas of both normal and psoriatic epidermis, the cell layer immediately above the basal cells is also stained. Cells in the external root sheath of the hair follicles also bind VM-1. The antibody binding site is trypsin-resistant, and is not blocked by bullous pemphigoid serum. If dispersed epidermal cells are preincubated with VM-1 for 1 h or more before plating, the majority of the cells do not attach and spread out on a collagen-coated Petri dish surface or on a fibroblast feeder layer. When added to attached, preconfluent cultures of keratinocytes, VM-1 inhibits growth and alters cell morphology. The growth inhibition is specific for keratinocytes, and viability studies show that it is not due to an immediate toxic effect of the antibody. The VM-1-induced inhibition of keratinocyte growth is not reversed by soy bean or lima bean trypsin inhibitors added at the time of cell plating or at the time of addition of antibody. PMID:3981036

  18. Comparison of the effects of vitamin D products in a psoriasis plaque test and a murine psoriasis xenograft model

    PubMed Central

    2009-01-01

    The aim of the present study was to compare the effects of Daivobet® and calcipotriol on clinical score and biomarker responses in a modified version of the Scholtz-Dumas psoriasis plaque assay. Furthermore, it was the aim to compare the effects of calcipotriol and betamethasone in the murine psoriasis xenograft model. Twenty four patients with psoriasis were treated topically once daily for three weeks, whereas the grafted mice were treated for four weeks. Clinical responses were scored twice weekly and biopsies were taken at the end of each study to analyse for skin biomarkers by histology and immunohistochemistry. The results clearly demonstrate effects on both clinical signs and biomarkers. In the patient study the total clinical score was reduced significantly with both Daivobet® and calcipotriol. Both treatments reduced epidermal thickness, Ki-67 and cytokeratin 16 expression. T cell infiltration was significantly reduced by Daivobet® but only marginally by calcipotriol. Both treatments showed strong effects on the epidermal psoriatic phenotype. Results from the xenograft model essentially showed the same results. However differences were observed when investigating subtypes of T cells. The study demonstrates the feasibility of obtaining robust biomarker data in the psoriasis plaque test that correlate well with those obtained in other clinical studies. Furthermore, the biomarker data from the plaque test correlate with biopsy data from the grafted mice. PMID:20017943

  19. Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma

    PubMed Central

    Furnari, Frank B.; Cloughesy, Timothy F.; Cavenee, Webster K.; Mischel, Paul S.

    2016-01-01

    As tumours evolve, the daughter cells of the initiating cell often become molecularly heterogeneous and develop different functional properties and therapeutic vulnerabilities. In glioblastoma (GBM), a lethal form of brain cancer, the heterogeneous expression of the epidermal growth factor receptor (EGFR) poses a substantial challenge for the effective use of EGFR-targeted therapies. Understanding the mechanisms that cause EGFR heterogeneity in GBM should provide better insights into how they, and possibly other amplified receptor tyrosine kinases, affect cellular signalling, metabolism and drug resistance. PMID:25855404

  20. Mathematical model for calcium-assisted epidermal homeostasis.

    PubMed

    Kobayashi, Yasuaki; Sawabu, Yusuke; Kitahata, Hiroyuki; Denda, Mitsuhiro; Nagayama, Masaharu

    2016-05-21

    Using a mathematical model of the epidermis, we propose a mechanism of epidermal homeostasis mediated by calcium dynamics. We show that calcium dynamics beneath the stratum corneum can reduce spatio-temporal fluctuations of the layered structure of the epidermis. We also demonstrate that our model can reproduce experimental results that the recovery from a barrier disruption is faster when the disrupted site is exposed to air. In particular, simulation results indicate that the recovery speed depends on the size of barrier disruption. PMID:26953648

  1. The economics of satellite maintenance

    NASA Technical Reports Server (NTRS)

    Derocher, W. L., Jr.; Sosnay, R. G.

    1975-01-01

    The primary goal of the space transportation system - to reduce the cost of space programs while satisfying their mission requirements - can be enhanced by the proper choice of a satellite-maintenance concept. This paper develops the life-cycle costs of performing an automated satellite program during the shuttle era in three competitive modes: expendable, ground-refurbishable, and in-orbit maintainable. In-orbit maintenance is shown to be the most economic maintenance mode for both low- and high-earth orbits.

  2. Sirtuins, Tissue Maintenance, and Tumorigenesis

    PubMed Central

    Mohrin, Mary

    2013-01-01

    Aging is a degenerative process resulting in compromised tissue maintenance and increased susceptibility to diseases, such as cancer. Recent advancements support the notion that aging is a highly regulated process governed by evolutionarily conserved pathways. In mammals, tissue-specific adult stem cells (ASCs) persist throughout the lifetime to maintain and repair tissues. While reduced ASC self-renewal is thought to contribute to compromised tissue maintenance, increased self-renewal of cancer stem cells (CSCs) may lead to tumorigenesis. It is speculated that genetic regulators of aging, such as sirtuins, are likely to impinge upon the ASC compartments to regulate tissue maintenance and tumorigenesis. In this review, we discuss the emerging evidence linking sirtuins to normal and malignant ASC self-renewal, tissue maintenance, and tumorigenesis. PMID:24019997

  3. Avionics Maintenance Technology Program Standards.

    ERIC Educational Resources Information Center

    Georgia Univ., Athens. Dept. of Vocational Education.

    This publication contains statewide standards for the avionics maintenance technology program in Georgia. The standards are divided into the following categories: foundations, diploma/degree (philosophy, purpose, goals, program objectives, availability, evaluation); admissions, diploma/degree (admission requirements, provisional admission…

  4. Genetic variation and its maintenance

    SciTech Connect

    Roberts, D.F.; De Stefano, G.F.

    1986-01-01

    This book contains several papers divided among three sections. The section titles are: Genetic Diversity--Its Dimensions; Genetic Diversity--Its Origin and Maintenance; and Genetic Diversity--Applications and Problems of Complex Characters.

  5. Maintenance and Monitoring of BMPS

    EPA Science Inventory

    Two best management practice (BMP) sites in the Staten Island Bluebelt in Richmond Creek Watershed are Richmond Creek 5 (RC-5) and Richmond Creek 4 (RC-4). This presentation includes site description, briefing of initial monitoring activity, representative maintenance activity, ...

  6. Maintenance Downtime March 13, 2015

    Atmospheric Science Data Center

    2015-03-11

    ... Impact:  Due to Earthdata User Registration System (URS) maintenance scheduled Friday 3/13, users may expect potential downtime or degraded service for all subsetters requiring URS login authentication during this time. ...

  7. Managing Custodial and Maintenance Staffs.

    ERIC Educational Resources Information Center

    Fickes, Michael

    2001-01-01

    Presents some basic maintenance management techniques that can help schools meet their budgets, preserve staffing levels, meet productivity needs, and sustain quality services. Tips for staff recruitment, training, and retention are explored. (GR)

  8. Retroviral Transduction of Murine Primary T Lymphocytes

    PubMed Central

    Lee, James; Sadelain, Michel; Brentjens, Renier

    2016-01-01

    Summary In comparison to human T cells, efficient retroviral gene transfer and subsequent expansion of murine primary T cells is more difficult to achieve. Herein, we describe an optimized gene transfer protocol utilizing an ecotropic viral vector to transduce primary murine T cells activated with magnetic beads coated with agonistic anti-CD3 and CD28 antibodies. Activated T cells are subsequently centrifuged (spinoculated) on RetroNectin-coated tissue culture plates in the context of retroviral supernatant. Variables found to be critical to high gene transfer and subsequent efficient T cell expansion included CD3/CD28 magnetic bead to cell ratio, time from T cell activation to initial spinoculation, frequency of T cell spinoculation, interleukin-2 concentration in the medium, and the initial purity of the T cell preparation. PMID:19110621

  9. 33 CFR 127.401 - Maintenance: General.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) WATERFRONT FACILITIES WATERFRONT FACILITIES HANDLING LIQUEFIED NATURAL GAS AND LIQUEFIED HAZARDOUS GAS Waterfront Facilities Handling Liquefied Natural Gas Maintenance § 127.401 Maintenance: General. The...

  10. Myositis in a Child with Murine Typhus

    PubMed Central

    Seshadri, Sheshashree; Fergie, Jaime

    2014-01-01

    A 12-year-old boy presented with fever, lower extremity pain and weakness. Examination revealed paraparesis, thigh and calf tenderness. Labs showed high creatinine phosphokinase and Rickettsia typhi titers. This case illustrates endemic typhus should be considered in the differential diagnosis of myositis especially in areas with high prevalence of the disease. To our knowledge, this is the first reported case of myositis and paraparesis associated with a case of murine typhus. PMID:24757508

  11. Cone inputs to murine striate cortex

    PubMed Central

    Ekesten, Björn; Gouras, Peter

    2008-01-01

    Background We have recorded responses from single neurons in murine visual cortex to determine the effectiveness of the input from the two murine cone photoreceptor mechanisms and whether there is any unique selectivity for cone inputs at this higher region of the visual system that would support the possibility of colour vision in mice. Each eye was stimulated by diffuse light, either 370 (strong stimulus for the ultra-violet (UV) cone opsin) or 505 nm (exclusively stimulating the middle wavelength sensitive (M) cone opsin), obtained from light emitting diodes (LEDs) in the presence of a strong adapting light that suppressed the responses of rods. Results Single cells responded to these diffuse stimuli in all areas of striate cortex. Two types of responsive cells were encountered. One type (135/323 – 42%) had little to no spontaneous activity and responded at either the on and/or the off phase of the light stimulus with a few impulses often of relatively large amplitude. A second type (166/323 – 51%) had spontaneous activity and responded tonically to light stimuli with impulses often of small amplitude. Most of the cells responded similarly to both spectral stimuli. A few (18/323 – 6%) responded strongly or exclusively to one or the other spectral stimulus and rarely in a spectrally opponent manner. Conclusion Most cells in murine striate cortex receive excitatory inputs from both UV- and M-cones. A small fraction shows either strong selectivity for one or the other cone mechanism and occasionally cone opponent responses. Cells that could underlie chromatic contrast detection are present but extremely rare in murine striate cortex. PMID:19014590

  12. Differentiation of skin sensitizers from irritant chemicals by interleukin-1α and macrophage inflammatory protein-2 in murine keratinocytes.

    PubMed

    Son, Dain; Na, Yirang; Cho, Wan-Seob; Lee, Byoung-Hee; Heo, Yong; Park, Jae-Hak; Seok, Seung Hyeok

    2013-01-10

    The development of novel alternative testing methods is required to identify the sensitizing capacity of chemicals as a replacement for animal experimentation. We aimed to evaluate in vitro assays as screening tools for detecting skin sensitizers. The murine epidermal keratinocyte cell line HEL-30 was exposed to 16 relevant skin sensitizers and 6 skin irritants. The dose causing 75% cell viability (CV(75)) measured by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was chosen as a highest dose and three more doses (0.5×, 0.1×, and 0.01× of CV(75)) were tested. As parameters, levels of interleukin 1α (IL-1α), macrophage inflammatory protein 2 (MIP-2), IL-6, and IL-18 production were measured using 4 different doses. The accuracy of detecting sensitizers or irritants by IL-1α or MIP-2 alone was exactly same: 75% (12 out of 16) for sensitizers, 83% (5 out of 6) for irritants, and overall 77% (17 out of 22). However, combination of IL-1α and MIP-2 showed better accuracy: 94% (15 out of 16), 67% (4 out of 6), and overall 86% (19 out of 22). IL-6 and IL-18 could not differentiate sensitizers from irritants. This study suggests that the combination of pro-inflammatory cytokines IL-1α and MIP-2 in murine HEL-30 cells can be a reliable in vitro method for identifying chemicals that may act as skin sensitizers. PMID:23178550

  13. Zinc deprivation impairs growth factor-stimulated calcium influx into murine 3T3 cells associated with decreased cell proliferation.

    PubMed

    O'Dell, Boyd L; Browning, Jimmy D

    2011-06-01

    Zinc plays a critical role in growth, a process that depends primarily on cell proliferation. Murine fibroblasts, Swiss 3T3 cells, were used to explore the hypothesis that a critical role of zinc in cell proliferation relates to its function in calcium influx. Cells were deprived of zinc by an impermeant chelator, diethylenetriaminepentaacetate (0.6 mmol/L), and low-calcium status was achieved by using a low- (<5 μmol/L) calcium medium. Cells were stimulated by a composite of growth factors (GF): platelet-derived GF, insulin-like GF-I, and epidermal GF. GF stimulation of cell proliferation was assessed by the incorporation of tritiated thymidine and calcium influx by the increase in fluorescence of cells loaded with Fluo-4. Proliferation was dependent on both zinc and calcium and they interacted in this process. GF stimulated an immediate sharp increase in intracellular calcium, indicative of internal calcium release, which peaked within 1 min and decreased to an elevated plateau, a pattern typical of a store-operated calcium channel. The sustained calcium influx of zinc-deprived cells was markedly lower than that of supplemented cells. Verapamil, a calcium channel blocker, also depressed both cell proliferation and calcium influx. In summary, zinc deficiency impaired GF-stimulated calcium influx into murine fibroblasts in association with decreased cell proliferation. PMID:21508206

  14. A Dual Role for NOTCH Signaling in Joint Cartilage Maintenance and Osteoarthritis

    PubMed Central

    Liu, Zhaoyang; Chen, Jianquan; Mirando, Anthony; Wang, Cuicui; Zuscik, Michael J.; O’Keefe, Regis J.; Hilton, Matthew J.

    2015-01-01

    Loss of NOTCH signaling in postnatal murine joints results in osteoarthritis (OA), indicating a requirement for NOTCH during joint cartilage maintenance. Unexpectedly, NOTCH components are significantly up-regulated in human and murine post-traumatic OA, suggesting either a reparative or pathological role for NOTCH activation in OA. Here we investigated the potential dual role for NOTCH in joint maintenance and OA by generating two mouse models overexpressing the NOTCH1 intracellular domain within postnatal joint cartilage; one with sustained NOTCH activation that likely resembles pathological NOTCH signaling and one with transient NOTCH activation that more closely reflects physiological NOTCH signaling. Sustained NOTCH signaling in joint cartilage leads to an early and progressive OA pathology, while on the contrary, transient NOTCH activation enhances cartilage matrix synthesis and promotes joint maintenance under normal physiological conditions. Using RNA-seq, immunohistochemical, and biochemical approaches we identified several novel targets potentially responsible for NOTCH-mediated cartilage degradation, fibrosis, and OA progression, including components of the IL6/STAT3 and ERK/p38 MAPK pathways; factors that may also contribute to post-traumatic OA development. Collectively, these data demonstrate a dual role for the NOTCH pathway in joint cartilage and identify important downstream NOTCH effectors as potential targets for disease modifying osteoarthritis drugs (DMOADs). PMID:26198357

  15. Differential expression of SKALP/Elafin in human epidermal tumors.

    PubMed Central

    Alkemade, H. A.; Molhuizen, H. O.; van Vlijmen-Willems, I. M.; van Haelst, U. J.; Schalkwijk, J.

    1993-01-01

    Recently we described a new epidermal serine proteinase inhibitor, skin-derived antileukoproteinase (SKALP), also known as elafin. SKALP/elafin was found to be absent in normal human epidermis, but can be induced in vitro and in vivo under hyperproliferative conditions. Here we studied the expression of SKALP/elafin in several types of epidermal tumors (basal cell carcinoma, squamous cell carcinoma, Bowen's disease, actinic keratosis, and keratoacanthoma). Using immunohistochemical staining SKALP/elafin appeared to be differentially expressed in these tumors. Functional measurements of anti-proteinase activity, and Western blotting of tumor extracts confirmed our findings at the histological level. In well differentiated squamous cell carcinoma, SKALP/elafin messenger RNA was demonstrated by non-radioactive in situ hybridization. We conclude that SKALP/elafin is a marker for abnormal or disturbed squamous differentiation. A possible role of SKALP/elafin in the control of tumor cell invasion is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8256855

  16. Epidermal cooling during pulsed laser treatment of selected dermatoses

    NASA Astrophysics Data System (ADS)

    Nelson, J. Stuart; Anvari, Bahman; Tanenbaum, B. S.; Milner, Thomas E.; Kimel, Sol; Svaasand, Lars O.

    1996-01-01

    The clinical objective in laser treatment of selected dermatoses such as port wine stain (PWS), hemangioma and telangiectasia is to maximize thermal damage to the blood vessels, while at the same time minimizing nonspecific injury to the normal overlying epidermis. 'Dynamic' cooling of skin, whereby a cryogen is sprayed onto the surface for an appropriately short period of time (on the order of tens of milliseconds), may offer an effective method for eliminating epidermal thermal injury during laser treatment. We present theoretical and experimental investigations of the thermal response of skin to dynamic cooling in conjunction with pulsed laser irradiation at 585 nm. Computed temperature distributions indicate that cooling the skin immediately prior to pulsed laser irradiation with a cryogen spurt of tetrafluoroethane is an effective method for eliminating epidermal thermal injury during laser treatment of PWS. Experimental results show rapid reduction of skin surface temperature is obtained when using tetrafluoroethane spurts of 20 - 100 ms duration. Successful blanching of PWS without thermal injury to the overlying epidermis is accomplished.

  17. Mathematical morphologic analysis of aging-related epidermal changes.

    PubMed

    Moragas, A; Castells, C; Sans, M

    1993-04-01

    Fractographic techniques based on mathematical morphology were used to study aging-related epidermal changes in abdominal skin samples obtained from 96 autopsy cases. Three linear roughness indices were evaluated for the rete peg profile and the shrinkage effect on the basal layer and interface between the granular and horny layers. Elderly subjects had a 36.3% decrease in rete peg-related roughness index when compared with younger subjects. This roughness index has been corrected, with shrinkage due to skin elasticity taken into account. For females, fitting of a logistic decay function yielded a curve with right and left asymptotes and a steeper descent between 40 and 60 years. Half value time--i.e., the time when half rete peg profile flattening occurred--was 46.8 years. In contrast, males showed almost monotonical decay. Epidermal thickness measured between rete pegs showed the same exponential decline for both sexes, with values from 22.6 to 11.4 microns. Skin shrinkage in elderly subjects decreased 22% in superficial layers and only 6% in the lower epidermis. In both cases shrinkage had a linear relation with age, and no sex differences were found. PMID:8318130

  18. Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

    PubMed Central

    Kobayashi, Hiroshi; Kumagai, Kenichi; Gotoh, Akito; Eguchi, Takanori; Yamada, Hiroyuki; Hamada, Yoshiki; Suzuki, Satsuki; Suzuki, Ryuji

    2013-01-01

    In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP. PMID:23492901

  19. Hybrid Enhanced Epidermal SpaceSuit Design Approaches

    NASA Astrophysics Data System (ADS)

    Jessup, Joseph M.

    A Space suit that does not rely on gas pressurization is a multi-faceted problem that requires major stability controls to be incorporated during design and construction. The concept of Hybrid Epidermal Enhancement space suit integrates evolved human anthropomorphic and physiological adaptations into its functionality, using commercially available bio-medical technologies to address shortcomings of conventional gas pressure suits, and the impracticalities of MCP suits. The prototype HEE Space Suit explored integumentary homeostasis, thermal control and mobility using advanced bio-medical materials technology and construction concepts. The goal was a space suit that functions as an enhanced, multi-functional bio-mimic of the human epidermal layer that works in attunement with the wearer rather than as a separate system. In addressing human physiological requirements for design and construction of the HEE suit, testing regimes were devised and integrated into the prototype which was then subject to a series of detailed tests using both anatomical reproduction methods and human subject.

  20. Production of human epidermal growth factor using adenoviral based system

    PubMed Central

    Negahdari, Babak; Shahosseini, Zahra; Baniasadi, Vahid

    2016-01-01

    Epidermal growth factor (EGF), a growth factor involved in cell growth and differentiation, is a small polypeptide with molecular weight of approximately 6 kDa known to be present in a number of different mammalian species. Experimental studies in animals and humans have demonstrated that the topical application of EGF accelerates the rate of epidermal regeneration of partial-thickness wounds and second-degree burns. Due to its commercial applications, Human EGF (hEGF) has been cloned in several forms. In the present study, adenoviral based expression system was used to produce biologically active recombinant hEGF. The presence of secreted recombinant hEGF was confirmed by a dot blot and its expression level was determined by enzyme-linked immuno-sorbent assay. Moreover, biological activity of secreted hEGF was evaluated by a proliferation assay performed on A549 cells. For production of hEGF in a secretory form, a chimeric gene coding for the hEGF fused to the signal peptide was expressed using adenoviral based method. This method enables the production of hEGF at the site of interest and moreover it could be used for cell proliferation and differentiation assays in tissue engineering research experiments instead of using commercially available EGF. PMID:27051431

  1. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    PubMed Central

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-01-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (<32 weeks gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments1,2. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI3. In a previous study, we demonstrated that epidermal growth factor receptor (EGFR) plays an important role in oligodendrocyte development4. Here, we examine whether enhanced epidermal growth factor receptor (EGFR) signaling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioral recovery in the developing brain. Using an established model of very preterm brain injury, we demonstrate that selective overexpression of human (h)EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells (OPCs) and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioral deficits on white matter-specific paradigms. Inhibition of EGFR signaling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in OPCs at a specific time after injury is clinically feasible and applicable for the treatment of premature children with white matter injury. PMID:24390343

  2. Transcription Factor MafB Coordinates Epidermal Keratinocyte Differentiation.

    PubMed

    Miyai, Masashi; Hamada, Michito; Moriguchi, Takashi; Hiruma, Junichiro; Kamitani-Kawamoto, Akiyo; Watanabe, Hajime; Hara-Chikuma, Mariko; Takahashi, Kenzo; Takahashi, Satoru; Kataoka, Kohsuke

    2016-09-01

    Mammalian epidermis is a stratified epithelium composed of distinct layers of keratinocytes. The outermost cornified layer is a primary barrier that consists of a cornified envelope, an insoluble structure assembled by cross-linked scaffold proteins, and a surrounding mixture of lipids. Skin keratinocytes undergo a multistep differentiation process, but the mechanism underlying this process is not fully understood. We demonstrate that the transcription factor MafB is expressed in differentiating keratinocytes in mice and is transcriptionally upregulated upon human keratinocyte differentiation in vitro. In MafB-deficient mice, epidermal differentiation was partially impaired and the cornified layer was thinner than in wild-type mice. On the basis of transcriptional profiling, we detected reduced expression levels of a subset of cornified envelope genes, for example, filaggrin and repetin, in the MafB(-/-) epidermis. By contrast, the expression levels of lipid metabolism-related genes, such as Alox12e and Smpd3, increased. The upregulated genes in the MafB(-/-) epidermis were enriched for putative target genes of the transcription factors Gata3, Grhl3, and Klf4. Immunohistochemical analysis of skin biopsy samples revealed that the expression levels of filaggrin and MafB were significantly reduced in patients with human atopic dermatitis and psoriasis vulgaris. Our results indicate that MafB is a component of the gene expression program that regulates epidermal keratinocyte differentiation. PMID:27208706

  3. EFFECT OF PARACETAMOL ON MELANIZATION PROCESS IN HUMAN EPIDERMAL MELANOCYTES.

    PubMed

    Wrześniok, Dorota; Oprzondek, Martyna; Hechmann, Anna; Beberok, Artur; Otreba, Michał; Buszman, Ewa

    2016-01-01

    Paracetamol (acetaminophen) is commonly used as a drug of choice for treatment of pain and fever. Unlike non-steroidal anti-inflammatory drugs (NSAIDs) it does not cause gastrointestinal damage or untoward cardiorenal effects, however cutaneous adverse effects have been reported. It is known that paracetamol binds to melanin biopolymers, but the relation between the affinity of this drug to melanin and its toxicity is not documented. The aim of this work was to examine the impact of paracetamol on melanogenesis in cultured human normal epidermal melanocytes (HEMn-DP). The effect of paracetamol on cell viability was determined by WST-1 assay, melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that paracetamol induced concentration-dependent loss in melanocytes viability. The value of EC50 was found to be - 20.0 mM. The analyzed drug inhibited melanin biosynthesis in a concentration-dependent manner by decreasing the melanin content as well as the tyrosinase activity. The demonstrated inhibitory effect of paracetamol on melanization process in normal epidermal melanocytes in vitro may explain the potential role of melanin biopolymer in the mechanisms of undesirable side effects of this drug in vivo, as a result of its accumulation in pigmented tissues. PMID:27476283

  4. A Novel Role of RASSF9 in Maintaining Epidermal Homeostasis

    PubMed Central

    Lee, Chiou-Mei; Yang, Polung; Chen, Lih-Chyang; Chen, Chia-Chun; Wu, Shinn-Chih; Cheng, Hsiao-Yun; Chang, Yu-Sun

    2011-01-01

    The physiological role of RASSF9, a member of the Ras-association domain family (RASSF), is currently unclear. Here, we report a mouse line in which an Epstein-Barr virus Latent Membrane Protein 1 (LMP1) transgene insertion has created a 7.2-kb chromosomal deletion, which abolished RASSF9 gene expression. The RASSF9-null mice exhibited interesting phenotypes that resembled human ageing, including growth retardation, short lifespan, less subcutaneous adipose layer and alopecia. In the wild-type mice, RASSF9 is predominantly expressed in the epidermal keratinocytes of skin, as determined by quantitative reverse-transcription PCR, immunofluorescence and in situ hybridization. In contrast, RASSF9−/− mice presented a dramatic change in epithelial organization of skin with increased proliferation and aberrant differentiation as detected by bromodeoxyuridine incorporation assays and immunofluorescence analyses. Furthermore, characteristic functions of RASSF9−/− versus wild type (WT) mouse primary keratinocytes showed significant proliferation linked to a reduction of p21Cip1 expression under growth or early differentiation conditions. Additionally, in RASSF9−/− keratinocytes there was a drastic down-modulation of terminal differentiation markers, which could be rescued by infection with a recombinant adenovirus, Adv/HA-RASSF9. Our results indicate a novel and significant role of RASSF9 in epidermal homeostasis. PMID:21445300

  5. A novel role of RASSF9 in maintaining epidermal homeostasis.

    PubMed

    Lee, Chiou-Mei; Yang, Polung; Chen, Lih-Chyang; Chen, Chia-Chun; Wu, Shinn-Chih; Cheng, Hsiao-Yun; Chang, Yu-Sun

    2011-01-01

    The physiological role of RASSF9, a member of the Ras-association domain family (RASSF), is currently unclear. Here, we report a mouse line in which an Epstein-Barr virus Latent Membrane Protein 1 (LMP1) transgene insertion has created a 7.2-kb chromosomal deletion, which abolished RASSF9 gene expression. The RASSF9-null mice exhibited interesting phenotypes that resembled human ageing, including growth retardation, short lifespan, less subcutaneous adipose layer and alopecia. In the wild-type mice, RASSF9 is predominantly expressed in the epidermal keratinocytes of skin, as determined by quantitative reverse-transcription PCR, immunofluorescence and in situ hybridization. In contrast, RASSF9-/- mice presented a dramatic change in epithelial organization of skin with increased proliferation and aberrant differentiation as detected by bromodeoxyuridine incorporation assays and immunofluorescence analyses. Furthermore, characteristic functions of RASSF9-/- versus wild type (WT) mouse primary keratinocytes showed significant proliferation linked to a reduction of p21Cip1 expression under growth or early differentiation conditions. Additionally, in RASSF9-/- keratinocytes there was a drastic down-modulation of terminal differentiation markers, which could be rescued by infection with a recombinant adenovirus, Adv/HA-RASSF9. Our results indicate a novel and significant role of RASSF9 in epidermal homeostasis. PMID:21445300

  6. Epidermal inclusion cyst of the breast: A literature review

    PubMed Central

    PALIOTTA, ANNALISA; SAPIENZA, PAOLO; D'ERMO, GIUSEPPE; CERONE, GENNARO; PEDULLÀ, GIUSEPPE; CROCETTI, DANIELE; DE GORI, ANTONIETTA; DE TOMA, GIORGIO

    2016-01-01

    An epidermal inclusion cyst (EIC) of the breast is a rare, benign condition that may potentially be malignant. The present study conducted a systematic review of the literature in order to identify pathological hypotheses, clinical characteristics, and diagnostic and treatment options. A search for relevant studies was conducted through the Scopus, Embase and Medline databases during September 2014. The search term employed was ῾epidermal inclusion cyst breast᾽. Studies were selected if they contained adequate information regarding symptoms at presentation, diagnostic tools, pathology, characteristics, type of procedure performed and follow-up routines. A total of 35 papers describing 91 patients affected by EIC of the breast were identified. Following this, a total of 82 patients, including an additional case supplied from the present study, were selected for further analysis. EIC of the breast typically occurs during the fifth decade of life. A palpable mass of the breast was present in 65 (79%) patients. Ultrasonographic imaging was consistently utilized as a diagnostic tool in all the cases analyzed, whereas fine-needle aspiration cytology was used in 70% of the cases and mammography in 65%. No tumor recurrence was reported at a mean follow-up time of 53 months. The present study demonstrated that elliptical excision is the preferred treatment for EIC of the breast, with pathological analysis required to exclude malignancy. PMID:26870262

  7. Flexible pH-Sensing Hydrogel Fibers for Epidermal Applications.

    PubMed

    Tamayol, Ali; Akbari, Mohsen; Zilberman, Yael; Comotto, Mattia; Lesha, Emal; Serex, Ludovic; Bagherifard, Sara; Chen, Yu; Fu, Guoqing; Ameri, Shideh Kabiri; Ruan, Weitong; Miller, Eric L; Dokmeci, Mehmet R; Sonkusale, Sameer; Khademhosseini, Ali

    2016-03-01

    Epidermal pH is an indication of the skin's physiological condition. For example, pH of wound can be correlated to angiogenesis, protease activity, bacterial infection, etc. Chronic nonhealing wounds are known to have an elevated alkaline environment, while healing process occurs more readily in an acidic environment. Thus, dermal patches capable of continuous pH measurement can be used as point-of-care systems for monitoring skin disorder and the wound healing process. Here, pH-responsive hydrogel fibers are presented that can be used for long-term monitoring of epidermal wound condition. pH-responsive dyes are loaded into mesoporous microparticles and incorporated into hydrogel fibers using a microfluidic spinning system. The fabricated pH-responsive microfibers are flexible and can create conformal contact with skin. The response of pH-sensitive fibers with different compositions and thicknesses are characterized. The suggested technique is scalable and can be used to fabricate hydrogel-based wound dressings with clinically relevant dimensions. Images of the pH-sensing fibers during real-time pH measurement can be captured with a smart phone camera for convenient readout on-site. Through image processing, a quantitative pH map of the hydrogel fibers and the underlying tissue can be extracted. The developed skin dressing can act as a point-of-care device for monitoring the wound healing process. PMID:26799457

  8. Epidermal growth factor receptor family in lung cancer and premalignancy.

    PubMed

    Franklin, Wilbur A; Veve, Robert; Hirsch, Fred R; Helfrich, Barbara A; Bunn, Paul A

    2002-02-01

    Lung cancer, like many other epithelial malignancies, is thought to be the outcome of genetic and epigenetic changes that result in a constellation of phenotypic abnormalities in bronchial epithelium. These include morphologic epithelial dysplasia, angiogenesis, increased proliferative rate, and changes in expression of cell surface proteins, particularly overexpression of epidermal growth factor receptor (EGFR) family proteins. The EFGR family is a group of four structurally similar tyrosine kinases (EGFR, HER2/neu, ErbB-3, and ErbB-4) that dimerize on binding with a number of ligands, including EGF and transforming growth factor alpha. Epidermal growth factor receptor overexpression is pronounced in virtually all squamous carcinomas and is also found in > or = 65% of large cell and adenocarcinomas. It is not expressed in situ by small cell lung carcinoma. Overexpression of EGFR is one of the earliest and most consistent abnormalities in bronchial epithelium of high-risk smokers. It is present at the stage of basal cell hyperplasia and persists through squamous metaplasia, dysplasia, and carcinoma in situ. Recent studies of the effect of inhibitors of receptor tyrosine kinases suggest that patterns of coexpression of multiple members of the EGFR family could be important in determining response. Intermediate endpoints of such trials could include monitoring of phosphorylation levels in signal transduction molecules downstream of the receptor dimers. These trials represent a new targeted approach to lung cancer treatment and chemoprevention that will require greater attention to molecular endpoints than required in past trials. PMID:11894009

  9. Epidermal cell proliferation in guinea pigs with experimental dermatophytosis

    SciTech Connect

    Tagami, H.

    1985-08-01

    To elucidate the mechanisms underlying the self-healing process of experimental dermatophytosis produced in guinea pigs by an occlusive method with Trichophyton mentagrophytes, epidermal proliferative activity was evaluated by the in vivo tritiated thymidine-labeling technique performed at various intervals after the first and second infections. Determination of labeling indices disclosed that an increased epidermal proliferation correlated well with the severity of inflammatory changes, i.e., a peak activity was noted after 10 days in primary infection and at 2 days in reinfection, respectively, and was followed by subsequent spontaneous lesion clearance after 10 days. Application of a heat-killed spore suspension produced inflammatory changes with enhanced epidermopoiesis, similar to those induced by reinoculation of living spores, only in immune animals. The present results indicate that the dermatitic changes occurring in experimental dermatophytosis increase epidermopoiesis which facilitates elimination of the fungus from the stratum corneum and that host immune activity, particularly contact sensitivity to fungal antigen, exerts a crucial role to induce these changes.

  10. Growth of melanocytes in human epidermal cell cultures

    SciTech Connect

    Staiano-Coico, L.; Hefton, J.M.; Amadeo, C.; Pagan-Charry, I.; Madden, M.R.; Cardon-Cardo, C. )

    1990-08-01

    Epidermal cell cultures were grown in keratinocyte-conditioned medium for use as burn wound grafts; the melanocyte composition of the grafts was studied under a variety of conditions. Melanocytes were identified by immunohistochemistry based on a monoclonal antibody (MEL-5) that has previously been shown to react specifically with melanocytes. During the first 7 days of growth in primary culture, the total number of melanocytes in the epidermal cultures decreased to 10% of the number present in normal skin. Beginning on day 2 of culture, bipolar melanocytes were present at a mean cell density of 116 +/- 2/mm2; the keratinocyte to melanocyte ratio was preserved during further primary culture and through three subpassages. Moreover, exposure of cultures to mild UVB irradiation stimulated the melanocytes to proliferate, suggesting that the melanocytes growing in culture maintained their responsiveness to external stimuli. When the sheets of cultured cells were enzymatically detached from the plastic culture flasks before grafting, melanocytes remained in the basal layer of cells as part of the graft applied to the patient.

  11. The mitosis-differentiation checkpoint, another guardian of the epidermal genome.

    PubMed

    Gandarillas, Alberto; Molinuevo, Rut; Freije, Ana; Alonso-Lecue, Pilar

    2015-01-01

    The role of p53, the original "guardian of the genome", in skin has remained elusive. We have explored p53 function in human epidermal cells and demonstrated the importance of a mitosis-differentiation checkpoint to suppress potentially precancerous cells. This model places epidermal endoreplication as an antioncogenic mechanism in the face of irreparable genetic alterations. PMID:27308487

  12. In vitro transformation of Syrian hamster epidermal cells by N-methyl-N'-nitro-N-nitrosoguanidine

    SciTech Connect

    Sun, N.C.; Sun, C.R.Y.; Chao, L.; Fung, W.P.; Tennant, R.W.; Hsie, A.W.

    1981-05-01

    The selection of Syrian hamster epidermal cells which do not terminally differentiate has provided a quantitative focus assay for in vitro chemical transformation. One-day-old Syrian hamster epidermal cells plated at 5 x 10/sup 6//100-mm dish were treated for 5 hr with various concentrations of N-methyl-N-nitro-N'-nitrosoguanidine. After 4 weeks, the normal epidermal cells began to terminally differentiate to keratinized squamous cells and died, but transformed epidermal colonies grew to higher cell densities and appeared as darker areas against a lightly stained normal cell background. Transformed epidermal foci were isolated and subcultured for at least 15 passages, whereas normal epidermal cells could not be subcultured under the same conditions. The transformed cells assumed the typical cobblestone-like morphology of epithelial cells, retained desmosomes and tonofilaments, and were able to use citrulline in place of arginine. Argininosuccinate synthetase (EC 6.3.4.5) activity was significantly higher in the epidermal cells than in fibroblasts. The injection of 5 x 10/sup 6/ cells of two transformed epidermal cell lines into athymic nude mice resulted in the formation of tumors which were identified as keratinizing squamous carcinomas.

  13. The mitosis-differentiation checkpoint, another guardian of the epidermal genome

    PubMed Central

    Gandarillas, Alberto; Molinuevo, Rut; Freije, Ana; Alonso-Lecue, Pilar

    2015-01-01

    The role of p53, the original “guardian of the genome”, in skin has remained elusive. We have explored p53 function in human epidermal cells and demonstrated the importance of a mitosis-differentiation checkpoint to suppress potentially precancerous cells. This model places epidermal endoreplication as an antioncogenic mechanism in the face of irreparable genetic alterations.

  14. An Automated and Minimally Invasive Tool for Generating Autologous Viable Epidermal Micrografts

    PubMed Central

    Osborne, Sandra N.; Schmidt, Marisa A.; Harper, John R.

    2016-01-01

    ABSTRACT OBJECTIVE: A new epidermal harvesting tool (CelluTome; Kinetic Concepts, Inc, San Antonio, Texas) created epidermal micrografts with minimal donor site damage, increased expansion ratios, and did not require the use of an operating room. The tool, which applies both heat and suction concurrently to normal skin, was used to produce epidermal micrografts that were assessed for uniform viability, donor-site healing, and discomfort during and after the epidermal harvesting procedure. DESIGN: This study was a prospective, noncomparative institutional review board–approved healthy human study to assess epidermal graft viability, donor-site morbidity, and patient experience. SETTING: These studies were conducted at the multispecialty research facility, Clinical Trials of Texas, Inc, San Antonio. PATIENTS: The participants were 15 healthy human volunteers. RESULTS: The average viability of epidermal micrografts was 99.5%. Skin assessment determined that 76% to 100% of the area of all donor sites was the same in appearance as the surrounding skin within 14 days after epidermal harvest. A mean pain of 1.3 (on a scale of 1 to 5) was reported throughout the harvesting process. CONCLUSIONS: Use of this automated, minimally invasive harvesting system provided a simple, low-cost method of producing uniformly viable autologous epidermal micrografts with minimal patient discomfort and superficial donor-site wound healing within 2 weeks. PMID:26765157

  15. Epidermal Cyst of Parotid Gland: A Rarity and a Diagnostic Dilemma

    PubMed Central

    Ganesan, Anuradha; Nandakumar, Gautham Kumar

    2015-01-01

    Epidermal cysts are common skin lesions but they occur very rarely in the oral cavity, especially in the salivary glands. Very few cases have been reported in the literature and, here, we present one such rare case of epidermal cyst in the right parotid gland in a 62-year-old female patient. PMID:25628900

  16. Effects of Wnt3a on proliferation and differentiation of human epidermal stem cells

    SciTech Connect

    Jia Liwei; Zhou Jiaxi; Peng Sha; Li Juxue; Cao Yujing; Duan Enkui

    2008-04-11

    Epidermal stem cells maintain development and homeostasis of mammalian epidermis throughout life. However, the molecular mechanisms involved in the proliferation and differentiation of epidermal stem cells are far from clear. In this study, we investigated the effects of Wnt3a and Wnt/{beta}-catenin signaling on proliferation and differentiation of human fetal epidermal stem cells. We found both Wnt3a and active {beta}-catenin, two key members of the Wnt/{beta}-catenin signaling, were expressed in human fetal epidermis and epidermal stem cells. In addition, Wnt3a protein can promote proliferation and inhibit differentiation of epidermal stem cells in vitro culture. Our results suggest that Wnt/{beta}-catenin signaling plays important roles in human fetal skin development and homeostasis, which also provide new insights on the molecular mechanisms of oncogenesis in human epidermis.

  17. Nifedipine prevents sodium caprate-induced barrier dysfunction in human epidermal keratinocyte cultures.

    PubMed

    Uchino, Yoshihiro; Matsumoto, Junichi; Watanabe, Takuya; Hamabashiri, Masato; Tsuchiya, Takashi; Kimura, Ikuya; Yamauchi, Atsushi; Kataoka, Yasufumi

    2015-01-01

    Tight junctions (TJs) of the epidermis play an important role in maintaining the epidermal barrier. TJ breakdown is associated with skin problems, such as wrinkles and transepidermal water loss (TEWL). Clinical studies have reported that topical nifedipine is effective in reducing the depth of wrinkles and improving TEWL. However, it remains unknown whether nifedipine influences the TJ function in the epidermis. In the present study, we investigated the effect of nifedipine on epidermal barrier dysfunction in normal human epidermal keratinocytes (NHEKs) treated with sodium caprate (C10), a TJ inhibitor. Nifedipine reversed the C10-decreased transepithelial electrical resistance values as a measure of disruption of the epidermal barrier. Immunocytochemical observations revealed that nifedipine improved the C10-induced irregular arrangement of claudin-1, a key protein in TJs. Taken together, these findings suggest that nifedipine prevents epidermal barrier dysfunction, at least in part, by reconstituting the irregular claudin-1 localization at TJs in C10-treated NHEKs. PMID:26027835

  18. Vertebrate epidermal cells are broad-specificity phagocytes that clear sensory axon debris.

    PubMed

    Rasmussen, Jeffrey P; Sack, Georgeann S; Martin, Seanna M; Sagasti, Alvaro

    2015-01-14

    Cellular debris created by developmental processes or injury must be cleared by phagocytic cells to maintain and repair tissues. Cutaneous injuries damage not only epidermal cells but also the axonal endings of somatosensory (touch-sensing) neurons, which must be repaired to restore the sensory function of the skin. Phagocytosis of neuronal debris is usually performed by macrophages or other blood-derived professional phagocytes, but we have found that epidermal cells phagocytose somatosensory axon debris in zebrafish. Live imaging revealed that epidermal cells rapidly internalize debris into dynamic phosphatidylinositol 3-monophosphate-positive phagosomes that mature into phagolysosomes using a pathway similar to that of professional phagocytes. Epidermal cells phagocytosed not only somatosensory axon debris but also debris created by injury to other peripheral axons that were mislocalized to the skin, neighboring skin cells, and macrophages. Together, these results identify vertebrate epidermal cells as broad-specificity phagocytes that likely contribute to neural repair and wound healing. PMID:25589751

  19. Epidermal cell growth-dependent arylhydrocarbon-hydroxylase (AHH) activity in vitro.

    PubMed

    Thiele, B; Merk, H F; Bonnekoh, B; Mahrle, G; Steigleder, G K

    1987-01-01

    Cytochrome P-450-dependent arylhydrocarbon-hydroxylase (AHH) activity and inducibility by benzanthracene (BA) was measured in cultured guinea pig and human epidermal cells. Basal AHH-activity (AHHb) in guinea pig epidermal cells was much higher than in human epidermal cells. AHHb in guinea pig epidermal cells was directly related to the labeling index and decreased to the original level between the 5th and 7th day of cell culturing. On the other hand, the induction-ratio of AHH reached its maximum level when the number of cells began to rise (proliferation phase) and remained high at day 7 of the cell culture. These results suggest a cell growth dependent activity and inducibility of carcinogen-metabolizing enzymes, such as AHH, in isolated epidermal cells. PMID:3435181

  20. Epidermal Growth Factor and Epidermal Growth Factor Receptor: The Yin and Yang in the Treatment of Cutaneous Wounds and Cancer

    PubMed Central

    Bodnar, Richard J.

    2013-01-01

    Significance Epidermal growth factor (EGF) and EGF receptor (EGFR) play an essential role in wound healing through stimulating epidermal and dermal regeneration. The development of new therapies for enhancing wound healing has included the use of EGF. In addition, EGFR inhibitors (EGFRis) have become a therapeutic option for the treatment of cancer. Thus, therapies targeting EGF/EGFR are useful for the treatment of both cutaneous wounds and cancer. Recent Advances Identification of EGFR as a regulator of normal and pathological cell function has allowed for the development of EGFRis for the treatment of cancer and topical administration of EGF to enhance wound healing. Critical Issues The use of EGFRi has emerged as an option for metastatic cancers. These drugs induce dermatological toxicity, a papulopustular rash that is pruritic and painful; chronic use may negatively impact wound healing. Currently, there is no standard therapy to alleviate the side effects caused by EGFRi administration except to reduce or eliminate EGFRi usage. Therefore, side effects from these drugs should be taken into consideration on patients prone to develop chronic wounds and with cutaneous injuries. Future Directions There is a need for adjunctive treatment to eliminate dermatological toxicity from EGFRi use. The development of new downstream targets of EGFR may be a rational strategy to reduce potential cutaneous side effects and provide a better strategy for the treatment of cancer. Until then, the topical use of EGF could be used to ameliorate dermatological lesions caused by EGFRi. PMID:24527320

  1. TPX remote maintenance and shielding

    SciTech Connect

    Rennich, M.J.; Nelson, B.E.

    1994-09-01

    The Tokamak Physics Experiment machine design incorporates comprehensive planning for efficient and safe component maintenance. Three programmatic decisions have been made to insure the successful implementation of this objective. First, the tokamak incorporates radiation shielding to reduce activation of components and limit the dose rate to personnel working on the outside of the machine. This allows most of the ex-vessel equipment to be maintained through conventional ``hands-on`` procedures. Second, to the maximum extent possible, low activation materials will be used inside the shielding volume. This resulted in the selection of Titanium (Ti-6Al-4V) for the vacuum vessel and PFC structures. The third decision stipulated that the primary in-vessel components will be replaced or repaired via remote maintenance tools specifically provided for the task. The component designers have been given the responsibility of incorporating maintenance design and for proving the maintainability of the design concepts in full-scale mockup tests prior to the initiation of final fabrication. Remote maintenance of the TPX machine is facilitated by general purpose tools provided by a special purpose design team. Major tools will include an in-vessel transporter, a vessel transfer system and a large component transfer container. In addition, tools such as manipulators and remotely operable impact wrenches will be made available to the component designers by this group. Maintenance systems will also provide the necessary controls for this equipment.

  2. 18 CFR 367.81 - Maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Maintenance. 367.81... Expense Instructions § 367.81 Maintenance. (a) The cost of maintenance chargeable to the various operating... maintenance work. A list of work operations applicable generally to service company property is included...

  3. 49 CFR 193.2605 - Maintenance procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Maintenance procedures. 193.2605 Section 193.2605...: FEDERAL SAFETY STANDARDS Maintenance § 193.2605 Maintenance procedures. (a) Each operator shall determine... maintenance standards prescribed by this subpart. (b) Each operator shall follow one or more manuals...

  4. 14 CFR 91.405 - Maintenance required.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Maintenance required. 91.405 Section 91.405... AND GENERAL OPERATING RULES GENERAL OPERATING AND FLIGHT RULES Maintenance, Preventive Maintenance, and Alterations § 91.405 Maintenance required. Each owner or operator of an aircraft— (a) Shall...

  5. Acrolein increases 5-lipoxygenase expression in murine macrophages through activation of ERK pathway

    SciTech Connect

    Kim, Chae E.; Lee, Seung J.; Seo, Kyo W.; Park, Hye M.; Yun, Jung W.; Bae, Jin U.; Bae, Sun S.; Kim, Chi D.

    2010-05-15

    Episodic exposure to acrolein-rich pollutants has been linked to acute myocardial infarction, and 5-lipoxygenase (5-LO) is involved in the production of matrix metalloproteinase-9 (MMP-9), which destabilizes atherosclerotic plaques. Thus, the present study determined the effect of acrolein on 5-LO/leukotriene B{sub 4} (LTB{sub 4}) production in murine macrophages. Stimulation of J774A.1 cells with acrolein led to increased LTB{sub 4} production in association with increased 5-LO expression. Acrolein-evoked 5-LO expression was blocked by pharmacological inhibition of the ERK pathway, but not by inhibitors for JNK and p38 MAPK pathways. In line with these results, acrolein exclusively increased the phosphorylation of ERK among these MAPK, suggesting a role for the ERK pathway in acrolein-induced 5-LO expression with subsequent production of LTB{sub 4}. Among the receptor tyrosine kinases including epidermal growth factor receptor (EGFR) and platelet derived growth factor receptor (PDGFR), acrolein-evoked ERK phosphorylation was attenuated by AG1478, an EGFR inhibitor, but not by AG1295, a PDGFR inhibitor. In addition, acrolein-evoked 5-LO expression was also inhibited by inhibition of EGFR pathway, but not by inhibition of PDGFR pathway. These observations suggest that acrolein has a profound effect on the 5-LO pathway via an EGFR-mediated activation of ERK pathway, leading to acute ischemic syndromes through the generation of LTB{sub 4}, subsequent MMP-9 production and plaque rupture.

  6. Simultaneous Isolation of Three Different Stem Cell Populations from Murine Skin.

    PubMed

    Forni, Maria Fernanda; Ramos Maia Lobba, Aline; Pereira Ferreira, Alexandre Hamilton; Sogayar, Mari Cleide

    2015-01-01

    The skin is a rich source of readily accessible stem cells. The level of plasticity afforded by these cells is becoming increasingly important as the potential of stem cells in Cell Therapy and Regenerative Medicine continues to be explored. Several protocols described single type stem cell isolation from skin; however, none of them afforded simultaneous isolation of more than one population. Herein, we describe the simultaneous isolation and characterization of three stem cell populations from the dermis and epidermis of murine skin, namely Epidermal Stem Cells (EpiSCs), Skin-derived Precursors (SKPs) and Mesenchymal Stem Cells (MSCs). The simultaneous isolation was possible through a simple protocol based on culture selection techniques. These cell populations are shown to be capable of generating chondrocytes, adipocytes, osteocytes, terminally differentiated keratinocytes, neurons and glia, rendering this protocol suitable for the isolation of cells for tissue replenishment and cell based therapies. The advantages of this procedure are far-reaching since the skin is not only the largest organ in the body, but also provides an easily accessible source of stem cells for autologous graft. PMID:26462205

  7. Invasion of Herpes Simplex Virus Type 1 into Murine Epidermis: An Ex Vivo Infection Study.

    PubMed

    Rahn, Elena; Petermann, Philipp; Thier, Katharina; Bloch, Wilhelm; Morgner, Jessica; Wickström, Sara A; Knebel-Mörsdorf, Dagmar

    2015-12-01

    Herpes simplex virus type 1 (HSV-1) invades its human host via the skin or mucosa. We aim to understand how HSV-1 overcomes the barrier function of the host epithelia, and for this reason, we established an ex vivo infection assay initially with murine skin samples. Here, we report how tissue has to be prepared to be susceptible to HSV-1 infection. Most efficient infection of the epidermis was achieved by removing the dermis. HSV-1 initially invaded the basal epidermal layer, and from there, spreading to the suprabasal layers was observed. Strikingly, in resting stage hair follicles, only the hair germ was infected, whereas the quiescent bulge stem cells (SCs) were resistant to infection. However, during the growth phase, infected cells were also detected in the activated bulge SCs. We demonstrated that cell proliferation was not a precondition for HSV-1 invasion, but SC activation was required as shown by infection of aberrantly activated bulge SCs in integrin-linked kinase (ILK)-deficient hair follicles. These results suggest that the status of the bulge SCs determines whether HSV-1 can reach its receptors, whereas the receptors on basal keratinocytes are accessible irrespective of their proliferation status. PMID:26203638

  8. Hesperetin induces melanin production in adult human epidermal melanocytes.

    PubMed

    Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

    2015-06-01

    One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p < 0.01) and 1.1-fold (p < 0.01), respectively, and the corresponding increases in the case of 50 µM HSP were 1.9-fold (p < 0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable photoprotective substance if its capacity to increase melanin production in human melanocyte cultures could be reproduced on human skin. PMID:25765751

  9. Transcriptome Profiling of Developing Murine Lens Through RNA Sequencing

    PubMed Central

    Khan, Shahid Y.; Hackett, Sean F.; Lee, Mei-Chong W.; Pourmand, Nader; Talbot, C. Conover; Riazuddin, S. Amer

    2015-01-01

    Purpose Transcriptome is the entire repertoire of transcripts present in a cell at any particular time. We undertook a next-generation whole transcriptome sequencing approach to gain insight into the transcriptional landscape of the developing mouse lens. Methods We ascertained mouse lenses at six developmental time points including two embryonic (E15 and E18) and four postnatal stages (P0, P3, P6, and P9). The ocular tissue at each time point was maintained as two distinct pools serving as biological replicates for each developmental stage. The mRNA and small RNA libraries were paired-end sequenced on Illumina HiSeq 2000 and subsequently analyzed using bioinformatics tools. Results Mapping of mRNA and small RNA libraries generated 187.56 and 154.22 million paired-end reads, respectively. We detected a total of 14,465 genes in the mouse ocular lens at the above-mentioned six developmental stages. Of these, 46 genes exhibited a 40-fold differential (higher or lower) expression at one the five developmental stages (E18, P0, P3, P6, and P9) compared with their expression level at E15. Likewise, small RNA profiling identified 379 microRNAs (miRNAs) expressed in mouse lens at six developmental time points. Of these, 49 miRNAs manifested an 8-fold differential (higher or lower) expression at one the five developmental stages, as mentioned above compared with their expression level at E15. Conclusions We report a comprehensive profile of developing murine lens transcriptome including both mRNA and miRNA through next-generation RNA sequencing. A complete repository of the lens transcriptome of six developmental time points will be monumental in elucidating processes essential for the development of the ocular lens and maintenance of its transparency. PMID:26225632

  10. Redox-dependent regulation of epidermal growth factor receptor signaling.

    PubMed

    Heppner, David E; van der Vliet, Albert

    2016-08-01

    Tyrosine phosphorylation-dependent cell signaling represents a unique feature of multicellular organisms, and is important in regulation of cell differentiation and specialized cell functions. Multicellular organisms also contain a diverse family of NADPH oxidases (NOXs) that have been closely linked with tyrosine kinase-based cell signaling and regulate tyrosine phosphorylation via reversible oxidation of cysteine residues that are highly conserved within many proteins involved in this signaling pathway. An example of redox-regulated tyrosine kinase signaling involves the epidermal growth factor receptor (EGFR), a widely studied receptor system with diverse functions in normal cell biology as well as pathologies associated with oxidative stress such as cancer. The purpose of this Graphical Redox Review is to highlight recently emerged concepts with respect to NOX-dependent regulation of this important signaling pathway. PMID:26722841

  11. Epidermal Nerve Fiber Quantification in the Assessment of Diabetic Neuropathy

    PubMed Central

    Beiswenger, Kristina K.; Calcutt, Nigel A.; Mizisin, Andrew P.

    2008-01-01

    Summary Assessment of cutaneous innervation in skin biopsies is emerging as a valuable means of both diagnosing and staging diabetic neuropathy. Immunolabeling, using antibodies to neuronal proteins such as protein gene product 9.5, allows for the visualization and quantification of intraepidermal nerve fibers. Multiple studies have shown reductions in intraepidermal nerve fiber density in skin biopsies from patients with both type 1 and type 2 diabetes. More recent studies have focused on correlating these changes with other measures of diabetic neuropathy. A loss of epidermal innervation similar to that observed in diabetic patients has been observed in rodent models of both type 1 and type 2 diabetes and several therapeutics have been reported to prevent reductions in intraepidermal nerve fiber density in these models. This review discusses the current literature describing diabetes-induced changes in cutaneous innervation in both human and animal models of diabetic neuropathy. PMID:18384843

  12. Redox-dependent regulation of epidermal growth factor receptor signaling

    PubMed Central

    Heppner, David E.; van der Vliet, Albert

    2015-01-01

    Tyrosine phosphorylation-dependent cell signaling represents a unique feature of multicellular organisms, and is important in regulation of cell differentiation and specialized cell functions. Multicellular organisms also contain a diverse family of NADPH oxidases (NOXs) that have been closely linked with tyrosine kinase-based cell signaling and regulate tyrosine phosphorylation via reversible oxidation of cysteine residues that are highly conserved within many proteins involved in this signaling pathway. An example of redox-regulated tyrosine kinase signaling involves the epidermal growth factor receptor (EGFR), a widely studied receptor system with diverse functions in normal cell biology as well as pathologies associated with oxidative stress such as cancer. The purpose of this Graphical Redox Review is to highlight recently emerged concepts with respect to NOX-dependent regulation of this important signaling pathway. PMID:26722841

  13. Epidermal growth factor, from gene organization to bedside

    PubMed Central

    Zeng, Fenghua; Harris, Raymond C.

    2014-01-01

    In 1962, epidermal growth factor (EGF) was discovered by Dr. Stanley Cohen while studying nerve growth factor (NGF). It was soon recognized that EGF is the prototypical member of a family of peptide growth factors that activate the EGF receptors, and that the EGF/EGF receptor signaling pathway plays important roles in proliferation, differentiation and migration of a variety of cell types, especially in epithelial cells. After the basic characterization of EGF function in the first decade or so after its discovery, the studies related to EGF and its signaling pathway have extended to a broad range of investigations concerning its biological and pathophysiological roles in development and in human diseases. In this review, we briefly describe the gene organization and tissue distribution of EGF, with emphasis on its biological and pathological roles in human diseases. PMID:24513230

  14. Toxic epidermal necrolysis due to lamotrigine in a pediatric patient

    PubMed Central

    Barvaliya, Manish J.; Patel, Mahendra K.; Patel, Tejas K.; Tripathi, C. B.

    2012-01-01

    A 12-year-male child developed toxic epidermal necrolysis (TEN) probably due to lamotrigine. The patient was on antiepileptic therapy (sodium valproate and clonazepam) since 6–7 months, and lamotrigine was added in the regimen 1–2 months back. A serious cutaneous reaction is more likely to occur during the first 2 months of starting lamotrigine. The use of lamotrigine as an add-on to valproate may have precipitated the reaction. Other drugs were ruled out based on the incubation period of TEN. Drug interactions should be kept in mind with multiple antiepileptic therapies. The patient died because of the severity of reactions and delay in starting the treatment with steroids. One must be vigilant in early detection of the reaction. PMID:23326109

  15. A case report on toxic epidermal necrolysis with etoricoxib

    PubMed Central

    Kameshwari, J. S.; Devde, Raju

    2015-01-01

    Etoricoxib is a selective cyclo-oxygenase 2 (COX-2) enzyme inhibitor and is exploited for its analgesic activity in various disease conditions like osteoarthritis, gouty arthritis, acute pain including postoperative dental pain and primary dysmenorrhea, etc. Although highly efficacious in pain management the safety profile of this COX-2 inhibitor is yet to be established in a broader sense. Short-term clinical trials and postmarketing surveillance have shown a very rare incidence of very serious skin reactions like Steven Johnson syndrome or toxic epidermal necrolysis (TEN). In this case report, we summarize regarding a patient who developed TEN after treatment with etoricoxib for osteoarthritis that later resolved in 15 days after withdrawal and symptomatic treatment. PMID:25878388

  16. Spatiotemporal coordination of stem cell commitment during epidermal homeostasis.

    PubMed

    Rompolas, Panteleimon; Mesa, Kailin R; Kawaguchi, Kyogo; Park, Sangbum; Gonzalez, David; Brown, Samara; Boucher, Jonathan; Klein, Allon M; Greco, Valentina

    2016-06-17

    Adult tissues replace lost cells via pools of stem cells. However, the mechanisms of cell self-renewal, commitment, and functional integration into the tissue remain unsolved. Using imaging techniques in live mice, we captured the lifetime of individual cells in the ear and paw epidermis. Our data suggest that epidermal stem cells have equal potential to either divide or directly differentiate. Tracking stem cells over multiple generations reveals that cell behavior is not coordinated between generations. However, sibling cell fate and lifetimes are coupled. We did not observe regulated asymmetric cell divisions. Lastly, we demonstrated that differentiating stem cells integrate into preexisting ordered spatial units of the epidermis. This study elucidates how a tissue is maintained by both temporal and spatial coordination of stem cell behaviors. PMID:27229141

  17. Spatiotemporal coordination of stem cell commitment during epidermal homeostasis

    PubMed Central

    Rompolas, Panteleimon; Mesa, Kailin R.; Kawaguchi, Kyogo; Park, Sangbum; Gonzalez, David; Brown, Samara; Boucher, Jonathan; Klein, Allon M.; Greco, Valentina

    2016-01-01

    Adult tissues replace lost cells via pools of stem cells. However, the mechanisms of cell self-renewal, commitment, and functional integration into the tissue remain unsolved. Using imaging techniques in live mice, we captured the lifetime of individual cells in the ear and paw epidermis. Our data suggest that epidermal stem cells have equal potential to either divide or directly differentiate. Tracking stem cells over multiple generations reveals that cell behavior is not coordinated between generations. However, sibling cell fate and lifetimes are coupled. We did not observe regulated asymmetric cell divisions. Lastly, we demonstrated that differentiating stem cells integrate into preexisting ordered spatial units of the epidermis. This study elucidates how a tissue is maintained by both temporal and spatial coordination of stem cell behaviors. PMID:27229141

  18. The Phytotherapeutic Fenugreek as Trigger of Toxic Epidermal Necrolysis.

    PubMed

    Bentele-Jaberg, Nicoletta; Guenova, Emmanuella; Mehra, Tarun; Nägeli, Mirjam; Chang, Yung-Tsan; Cozzio, Antonio; French, Lars E; Hoetzenecker, Wolfram

    2015-01-01

    We describe the case of a 32-year-old woman who presented to the hospital with generalized painful exanthema, blisters and erosions 1 month after giving birth to a healthy girl. The patient's medical history was inconspicuous for comorbidities; however, it included the incidental intake of pain killers and a herbal preparation (fenugreek), which she took regularly over the last 4 weeks to improve lactation. Based on the clinical characteristics, we suspected toxic epidermal necrolysis (TEN), a severe cutaneous adverse drug reaction, which was confirmed by skin biopsy. The patient was treated with high-dose intravenous human immunoglobulins and was discharged 2 weeks after hospital admission in good condition. The allergological workup identified fenugreek as the most likely causative agent. Given the increased self-medication of freely available phytotherapeutics by patients in industrialized countries, herbal mixtures should be taken into consideration in the diagnostic workup of TEN. PMID:26138328

  19. [Wound treatment with autogenous epidermal cell expansion culture].

    PubMed

    Bonnekoh, B; Müller, R P; Mahrle, G; Steigleder, G K

    1988-11-11

    Sheets of autologous epidermal cells grown by expansion culture were used to cover small skin defects in seven patients with postoperative necroses, necroses due to temporal arteritis, varicose ulcers or after tangential excision of tattoos. Several transplantation techniques were used: backing of the cultured epithelia with vaseline gauze, Surfasoft, Adaptic, Silastic foil, culturing directly from Petriperm-foil. Meshed Silastic-foil proved to give the best support. Optimal take of the in-vitro epithelia (more than 80% of their surface area) was achieved only for fresh dermal wound-beds. The take was only moderate on chronic granulation tissue, but the transplants reduced the formation of fibrinous-necrotic material and favoured the formation of fresh granulation tissue. PMID:3181024

  20. Metolazone Associated Stevens Johnson Syndrome-Toxic Epidermal Necrolysis Overlap

    PubMed Central

    Chauhan, Ajay; Charaniya, Riyaz; Ghosh, Anindya; Tandon, Vaibhav

    2016-01-01

    Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe mucocutaneous disease with high mortality rate. It is characterised by severe necrosis and detachment of the epidermis. Drugs are the most common triggering agent for SJS/TEN. These are commonly reported with the use of aromatic antiepileptics, antiretrovirals, allopurinol, NSAID’S and sulfonamide antibiotics. Non antibiotic sulfonamides rarely cause SJS/TEN. Metolazone is a well known diuretic and is extensively used by clinicians. Although this drug is in market for last several decades, no case of SJS/TEN has been reported till date. We report a rare case of metolazone induced SJS/TEN overlap in a 55-year-old lady. PMID:27134890

  1. Interdependent epidermal growth factor receptor signalling and trafficking.

    PubMed

    Jones, Sylwia; Rappoport, Joshua Z

    2014-06-01

    Epidermal growth factor (EGF) receptor (EGFR) signalling regulates diverse cellular functions, promoting cell proliferation, differentiation, migration, cell growth and survival. EGFR signalling is critical during embryogenesis, in particular in epithelial development, and disruption of the EGFR gene results in epithelial immaturity and perinatal death. EGFR signalling also functions during wound healing responses through accelerating wound re-epithelialisation, inducing cell migration, proliferation and angiogenesis. Upregulation of EGFR signalling is often observed in carcinomas and has been shown to promote uncontrolled cell proliferation and metastasis. Therefore aberrant EGFR signalling is a common target for anticancer therapies. Various reports indicate that EGFR signalling primarily occurs at the plasma membrane and EGFR degradation following endocytosis greatly attenuates signalling. Other studies argue that EGFR internalisation is essential for complete activation of downstream signalling cascades and that endosomes can serve as signalling platforms. The aim of this review is to discuss current understanding of intersection between EGFR signalling and trafficking. PMID:24681003

  2. Effects of microgravity on epidermal development in the rat

    NASA Technical Reports Server (NTRS)

    Hoath, Steven B.

    1995-01-01

    The overall goal of this project was to investigate the effects of prolonged weightlessness on the development of the skin in the fetal and newborn rat. Specifically, we used the NASA microgravitational rat model to test the following hypotheses: (1) Exposure of the pregnant rat to microscopy during late gestation will diminish the transport of calcium across the placenta from the mother to the fetus leading to decreases in total epidermal and dermal calcium content; (2) Microgravity will lead to slowing of body growth and diminish the rate of formation of the outermost layer of the epidermis and the stratum corneum; and (3) Microgravity will lead to formation of a stratum corneum with decreased DC electrical resistance and increased permeability to tritiated water.

  3. Modulation of epidermal growth factor receptors by human alpha interferon.

    PubMed Central

    Zoon, K C; Karasaki, Y; zur Nedden, D L; Hu, R Q; Arnheiter, H

    1986-01-01

    Treatment of Madin-Darby bovine kidney (MDBK) cells with human interferon (IFN)-alpha 2 at 37 degrees C results in a dose-dependent inhibition of cell growth and a reduction of the subsequent binding of 125I-labeled epidermal growth factor (EGF) at 4 degrees C. Human IFN-beta and -gamma, which exhibit little antiviral and antiproliferative activities on MDBK cells, have little effect on cell growth or the binding of 125I-labeled EGF to these cells. The binding of EGF is decreased after exposure to IFN-alpha for greater than 8 hr. Scatchard analyses of the EGF binding data indicate that a 20-hr exposure period results in a decrease in the apparent number of cell-surface EGF receptors and a reduction in the affinity of EGF for its receptor. The rate of internalization of EGF by MDBK cells does not appear to be affected by IFN treatment. PMID:3095830

  4. Modulation of epidermal growth factor receptors by human alpha interferon.

    PubMed

    Zoon, K C; Karasaki, Y; zur Nedden, D L; Hu, R Q; Arnheiter, H

    1986-11-01

    Treatment of Madin-Darby bovine kidney (MDBK) cells with human interferon (IFN)-alpha 2 at 37 degrees C results in a dose-dependent inhibition of cell growth and a reduction of the subsequent binding of 125I-labeled epidermal growth factor (EGF) at 4 degrees C. Human IFN-beta and -gamma, which exhibit little antiviral and antiproliferative activities on MDBK cells, have little effect on cell growth or the binding of 125I-labeled EGF to these cells. The binding of EGF is decreased after exposure to IFN-alpha for greater than 8 hr. Scatchard analyses of the EGF binding data indicate that a 20-hr exposure period results in a decrease in the apparent number of cell-surface EGF receptors and a reduction in the affinity of EGF for its receptor. The rate of internalization of EGF by MDBK cells does not appear to be affected by IFN treatment. PMID:3095830

  5. Iron production maintenance effectiveness system

    SciTech Connect

    Augstman, J.J.

    1996-12-31

    In 1989, an internal study in the Coke and Iron Maintenance Department identified the opportunities available to increase production, by decreasing unscheduled maintenance delays from 4.6%. A five year front loaded plan was developed, and presented to the company president. The plan required an initial investment of $1.4 million and a conservative break-even point was calculated to be 2.5 years. Due to budget restraints, it would have to be self-funded, i.e., generate additional production or savings, to pay for the program. The program began in 1991 at number 2 coke plant and the blast furnaces. This paper will describe the Iron Production Maintenance Effectiveness System (ME), which began with the mechanical and pipefitting trades.

  6. Active maintenance of semantic representations.

    PubMed

    Nishiyama, Ryoji

    2014-12-01

    In research on verbal working memory, articulatory rehearsal, a maintenance mechanism for phonological representations, has undergone intensive and excellent study. Possible mechanisms for semantic representation have received less attention. However, several studies have reported a double dissociation in types of memory deficits (semantic memory difficulties vs. phonological memory difficulties). This suggests the separability of two maintenance mechanisms. The present study focused on this separability in individuals with normal memory abilities, using a dual-task interference paradigm. The results indicate a crossover interaction between memory and interference task effects: Preventing articulatory rehearsal more strongly disrupted the phonological memory task, whereas performing a tapping task that interfered with attentional control more strongly disrupted semantic memory. These results suggest that semantic representations are actively maintained by a mechanism other than phonological maintenance. PMID:24687734

  7. NASA Critical Facilities Maintenance Assessment

    NASA Technical Reports Server (NTRS)

    Oberhettinger, David J.

    2006-01-01

    Critical Facilities Maintenance Assessment (CFMA) was first implemented by NASA following the March 2000 overtest of the High Energy Solar Spectroscopic Imager (HESSI) spacecraft. A sine burst dynamic test using a 40 year old shaker failed. Mechanical binding/slippage of the slip table imparted 10 times the planned force to the test article. There was major structural damage to HESSI. The mechanical "health" of the shaker had not been assessed and tracked to assure the test equipment was in good working order. Similar incidents have occurred at NASA facilities due to inadequate maintenance (e.g., rainwater from a leaky roof contaminated an assembly facility that housed a spacecraft). The HESSI incident alerted NASA to the urgent need to identify inadequacies in ground facility readiness and maintenance practices. The consequences of failures of ground facilities that service these NASA systems are severe due to the high unit value of NASA products.

  8. Evolutionary origin and diversification of epidermal barrier proteins in amniotes.

    PubMed

    Strasser, Bettina; Mlitz, Veronika; Hermann, Marcela; Rice, Robert H; Eigenheer, Richard A; Alibardi, Lorenzo; Tschachler, Erwin; Eckhart, Leopold

    2014-12-01

    The evolution of amniotes has involved major molecular innovations in the epidermis. In particular, distinct structural proteins that undergo covalent cross-linking during cornification of keratinocytes facilitate the formation of mechanically resilient superficial cell layers and help to limit water loss to the environment. Special modes of cornification generate amniote-specific skin appendages such as claws, feathers, and hair. In mammals, many protein substrates of cornification are encoded by a cluster of genes, termed the epidermal differentiation complex (EDC). To provide a basis for hypotheses about the evolution of cornification proteins, we screened for homologs of the EDC in non-mammalian vertebrates. By comparative genomics, de novo gene prediction and gene expression analyses, we show that, in contrast to fish and amphibians, the chicken and the green anole lizard have EDC homologs comprising genes that are specifically expressed in the epidermis and in skin appendages. Our data suggest that an important component of the cornified protein envelope of mammalian keratinocytes, that is, loricrin, has originated in a common ancestor of modern amniotes, perhaps during the acquisition of a fully terrestrial lifestyle. Moreover, we provide evidence that the sauropsid-specific beta-keratins have evolved as a subclass of EDC genes. Based on the comprehensive characterization of the arrangement, exon-intron structures and conserved sequence elements of EDC genes, we propose new scenarios for the evolutionary origin of epidermal barrier proteins via fusion of neighboring S100A and peptidoglycan recognition protein genes, subsequent loss of exons and highly divergent sequence evolution. PMID:25169930

  9. Targeting epidermal lipids for treatment of Mendelian disorders of cornification

    PubMed Central

    2014-01-01

    Background Inherited ichthyoses or Mendelian disorders of cornification (MeDOC) are clinically heterogeneous disorders with high unmet therapeutic needs, which are characterized by skin hyperkeratosis and scaling. Some MeDOC types are associated with defects of the epidermal lipid metabolism, resulting in perturbed barrier permeability and subsequent epidermal hyperplasia, hyperkeratosis and inflammation. An example is the CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, an X-linked dominant multisystem MeDOC caused by mutations in the NSDHL (NAD(P)H steroid dehydrogenase-like protein) gene, which is involved in the distal cholesterol biosynthetic pathway. The skin manifestations of the CHILD syndrome have been attributed to two major mechanisms: deficiency of cholesterol, probably influencing the proper corneocyte membrane formation, and toxic accumulation of aberrant steroid precursors. Methods Here we addressed the efficacy of an ointment containing cholesterol and simvastatin, an agent inhibiting endogenous cholesterol synthesis in a compassionate-use treatment of three patients with CHILD syndrome. To test the specificity of this therapeutic approach, we applied the same topical treatment to two patients with other types of MeDOC with disturbed skin lipid metabolism. Results The therapy with simvastatin and cholesterol was highly effective and well-tolerated by the CHILD syndrome patients; only lesions in the body folds represented a therapeutic challenge. No improvement was noted in the patients with other types of MeDOC. Conclusions This therapy is inexpensive and accessible to every patient with CHILD syndrome, because both simvastatin and cholesterol are available worldwide. Our data provide initial evidence of the specificity of the therapeutic effect of the simvastatin-cholesterol ointment in CHILD syndrome in comparison to other types of MeDOC. PMID:24607067

  10. Maintenance of photovoltaic power systems. Revision 1. Maintenance manual

    SciTech Connect

    Hall, M.R.

    1985-06-01

    This publication establishes standard practices for inspection, testing, and maintenance of photovoltaic power systems at Department of the Navy installations. The practices and procedures are recommended to ensure reliable operation of the power systems. The manual covers photovoltaic-array, battery, voltage-regulator, inverter, and wiring subsystems. In addition, this manual provides a troubleshooting guide and self-study questions and answers.

  11. Novel Murine Dendritic Cell Lines: A Powerful Auxiliary Tool for Dendritic Cell Research

    PubMed Central

    Fuertes Marraco, Silvia A.; Grosjean, Frédéric; Duval, Anaïs; Rosa, Muriel; Lavanchy, Christine; Ashok, Devika; Haller, Sergio; Otten, Luc A.; Steiner, Quynh-Giao; Descombes, Patrick; Luber, Christian A.; Meissner, Felix; Mann, Matthias; Szeles, Lajos; Reith, Walter; Acha-Orbea, Hans

    2012-01-01

    Research in vitro facilitates discovery, screening, and pilot experiments, often preceding research in vivo. Several technical difficulties render Dendritic Cell (DC) research particularly challenging, including the low frequency of DC in vivo, thorough isolation requirements, and the vulnerability of DC ex vivo. Critically, there is not as yet a widely accepted human or murine DC line and in vitro systems of DC research are limited. In this study, we report the generation of new murine DC lines, named MutuDC, originating from cultures of splenic CD8α conventional DC (cDC) tumors. By direct comparison to normal WT splenic cDC subsets, we describe the phenotypic and functional features of the MutuDC lines and show that they have retained all the major features of their natural counterpart in vivo, the splenic CD8α cDC. These features include expression of surface markers Clec9A, DEC205, and CD24, positive response to TLR3 and TLR9 but not TLR7 stimuli, secretion of cytokines, and chemokines upon activation, as well as cross-presentation capacity. In addition to the close resemblance to normal splenic CD8α cDC, a major advantage is the ease of derivation and maintenance of the MutuDC lines, using standard culture medium and conditions, importantly without adding supplementary growth factors or maturation-inducing stimuli to the medium. Furthermore, genetically modified MutuDC lines have been successfully obtained either by lentiviral transduction or by culture of DC tumors originating from genetically modified mice. In view of the current lack of stable and functional DC lines, these novel murine DC lines have the potential to serve as an important auxiliary tool for DC research. PMID:23162549

  12. 14 CFR 91.1425 - CAMP: Maintenance, preventive maintenance, and alteration programs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false CAMP: Maintenance, preventive maintenance... RULES Fractional Ownership Operations Program Management § 91.1425 CAMP: Maintenance, preventive... have an inspection program and a program covering other maintenance, preventive maintenance,...

  13. 14 CFR 121.377 - Maintenance and preventive maintenance personnel duty time limitations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Maintenance and preventive maintenance personnel duty time limitations. 121.377 Section 121.377 Aeronautics and Space FEDERAL AVIATION..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty...

  14. 14 CFR 121.377 - Maintenance and preventive maintenance personnel duty time limitations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Maintenance and preventive maintenance personnel duty time limitations. 121.377 Section 121.377 Aeronautics and Space FEDERAL AVIATION..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty...

  15. 14 CFR 121.377 - Maintenance and preventive maintenance personnel duty time limitations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Maintenance and preventive maintenance personnel duty time limitations. 121.377 Section 121.377 Aeronautics and Space FEDERAL AVIATION..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty...

  16. 14 CFR 121.377 - Maintenance and preventive maintenance personnel duty time limitations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Maintenance and preventive maintenance personnel duty time limitations. 121.377 Section 121.377 Aeronautics and Space FEDERAL AVIATION..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty...

  17. 14 CFR 121.377 - Maintenance and preventive maintenance personnel duty time limitations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Maintenance and preventive maintenance personnel duty time limitations. 121.377 Section 121.377 Aeronautics and Space FEDERAL AVIATION..., Preventive Maintenance, and Alterations § 121.377 Maintenance and preventive maintenance personnel duty...

  18. Layer-by-layer assembly of epidermal growth factors on polyurethane films for wound closure.

    PubMed

    Kulkarni, Abhilash; Diehl-Jones, William; Ghanbar, Sadegh; Liu, Song

    2014-02-13

    To facilitate the healing of chronic wounds, growth factors such as epidermal growth factor need to be safely encapsulated for their sustained and effective delivery to the wound bed. Using a layer-by-layer assembly technique, epidermal growth factor is successfully encapsulated on the surface of poly(acrylic acid)-modified polyurethane film. The amount of encapsulated epidermal growth factor is controlled by adjusting the number of chitosan/epidermal growth factor bilayers. A controlled release of epidermal growth factor from the surface of polyurethane film for a period of five days is achieved with well-retained bioactivity (over 90%) as evidenced by a cell proliferation assay. In an in vitro cellular wounding assay, the cell gap covered with the epidermal growth factor-loaded polyurethane film closes at a rate more than twice as fast as that covered with a control polyurethane film. Fluorescent staining of F-actin reveals that the released epidermal growth factor induces differences in cytoskeletal organization, suggesting that stimulated cell migration also contributes to the close of the cell gap. PMID:24525716

  19. Irradiation Design for an Experimental Murine Model

    SciTech Connect

    Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

    2010-12-07

    In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

  20. Efficacy of Posaconazole in Murine Experimental Sporotrichosis

    PubMed Central

    Fernández-Silva, Fabiola; Capilla, Javier; Mayayo, Emilio

    2012-01-01

    We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology. PMID:22330929

  1. Reemergence of Murine Typhus in Galveston, Texas, USA, 2013

    PubMed Central

    Vohra, Rahat F.; Bouyer, Donald H.; Walker, David H.

    2015-01-01

    Twelve patients with murine typhus were identified in Galveston, Texas, USA, in 2013. An isolate from 1 patient was confirmed to be Rickettsia typhi. Reemergence of murine typhus in Galveston emphasizes the importance of vector control and awareness of this disease by physicians and public health officials. PMID:25695758

  2. Gloss, colour and grip: multifunctional epidermal cell shapes in bee- and bird-pollinated flowers.

    PubMed

    Papiorek, Sarah; Junker, Robert R; Lunau, Klaus

    2014-01-01

    Flowers bear the function of filters supporting the attraction of pollinators as well as the deterrence of floral antagonists. The effect of epidermal cell shape on the visual display and tactile properties of flowers has been evaluated only recently. In this study we quantitatively measured epidermal cell shape, gloss and spectral reflectance of flowers pollinated by either bees or birds testing three hypotheses: The first two hypotheses imply that bee-pollinated flowers might benefit from rough surfaces on visually-active parts produced by conical epidermal cells, as they may enhance the colour signal of flowers as well as the grip on flowers for bees. In contrast, bird-pollinated flowers might benefit from flat surfaces produced by flat epidermal cells, by avoiding frequent visitation from non-pollinating bees due to a reduced colour signal, as birds do not rely on specific colour parameters while foraging. Moreover, flat petal surfaces in bird-pollinated flowers may hamper grip for bees that do not touch anthers and stigmas while consuming nectar and thus, are considered as nectar thieves. Beside this, the third hypothesis implies that those flower parts which are vulnerable to nectar robbing of bee- as well as bird-pollinated flowers benefit from flat epidermal cells, hampering grip for nectar robbing bees. Our comparative data show in fact that conical epidermal cells are restricted to visually-active parts of bee-pollinated flowers, whereas robbing-sensitive parts of bee-pollinated as well as the entire floral surface of bird-pollinated flowers possess on average flat epidermal cells. However, direct correlations between epidermal cell shape and colour parameters have not been found. Our results together with published experimental studies show that epidermal cell shape as a largely neglected flower trait might act as an important feature in pollinator attraction and avoidance of antagonists, and thus may contribute to the partitioning of flower

  3. Gloss, Colour and Grip: Multifunctional Epidermal Cell Shapes in Bee- and Bird-Pollinated Flowers

    PubMed Central

    Papiorek, Sarah; Junker, Robert R.; Lunau, Klaus

    2014-01-01

    Flowers bear the function of filters supporting the attraction of pollinators as well as the deterrence of floral antagonists. The effect of epidermal cell shape on the visual display and tactile properties of flowers has been evaluated only recently. In this study we quantitatively measured epidermal cell shape, gloss and spectral reflectance of flowers pollinated by either bees or birds testing three hypotheses: The first two hypotheses imply that bee-pollinated flowers might benefit from rough surfaces on visually-active parts produced by conical epidermal cells, as they may enhance the colour signal of flowers as well as the grip on flowers for bees. In contrast, bird-pollinated flowers might benefit from flat surfaces produced by flat epidermal cells, by avoiding frequent visitation from non-pollinating bees due to a reduced colour signal, as birds do not rely on specific colour parameters while foraging. Moreover, flat petal surfaces in bird-pollinated flowers may hamper grip for bees that do not touch anthers and stigmas while consuming nectar and thus, are considered as nectar thieves. Beside this, the third hypothesis implies that those flower parts which are vulnerable to nectar robbing of bee- as well as bird-pollinated flowers benefit from flat epidermal cells, hampering grip for nectar robbing bees. Our comparative data show in fact that conical epidermal cells are restricted to visually-active parts of bee-pollinated flowers, whereas robbing-sensitive parts of bee-pollinated as well as the entire floral surface of bird-pollinated flowers possess on average flat epidermal cells. However, direct correlations between epidermal cell shape and colour parameters have not been found. Our results together with published experimental studies show that epidermal cell shape as a largely neglected flower trait might act as an important feature in pollinator attraction and avoidance of antagonists, and thus may contribute to the partitioning of flower

  4. Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients

    PubMed Central

    Bacchi, Carlos E.; Ciol, Heloísa; Queiroga, Eduardo M.; Benine, Lucimara C.; Silva, Luciana H.; Ojopi, Elida B.

    2012-01-01

    OBJECTIVE: Epidermal growth factor receptor is involved in the pathogenesis of non-small cell lung cancer and has recently emerged as an important target for molecular therapeutics. The KRAS oncogene also plays an important role in the development of lung cancer. The aim of this study was to evaluate the frequency of epidermal growth factor receptor and KRAS mutations in a population of Brazilian patients with non-small cell lung cancer. METHODS: A total of 207 specimens from Brazilian patients with non-small cell lung cancer were analyzed for activating epidermal growth factor receptor and KRAS somatic mutations, and their associations with clinicopathological characteristics (including age, gender, ethnicity, smoking habits, and histological subtype) were examined. RESULTS: We identified 63 cases (30.4%) with epidermal growth factor receptor mutations and 30 cases (14.6%) with KRAS mutations. The most frequent epidermal growth factor receptor mutation we detected was a deletion in exon 19 (60.3%, 38 patients), followed by an L858R amino acid substitution in exon 21 (27%, 17 patients). The most common types of KRAS mutations were found in codon 12. There were no significant differences in epidermal growth factor receptor or KRAS mutations by gender or primary versus metastatic lung cancer. There was a higher prevalence of KRAS mutations in the non-Asian patients. Epidermal growth factor receptor mutations were more prevalent in adenocarcinomas than in non-adenocarcinoma histological types. Being a non-smoker was significantly associated with the prevalence of epidermal growth factor receptor mutations, but the prevalence of KRAS mutations was significantly associated with smoking. CONCLUSIONS: This study is the first to examine the prevalence of epidermal growth factor receptor and KRAS mutations in a Brazilian population sample with non-small cell lung cancer. PMID:22666783

  5. Transforming growth factor alpha and epidermal growth factor levels in bladder cancer and their relationship to epidermal growth factor receptor.

    PubMed Central

    Mellon, J. K.; Cook, S.; Chambers, P.; Neal, D. E.

    1996-01-01

    We have examined levels of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) in neoplastic and non-neoplastic bladder tissue using a standard radioimmunoassay technique. Tumour samples had much higher TGF-alpha levels compared with EGF and TGF-alpha levels in malignant tissue were significantly higher than in benign bladder samples. There was, in addition, a difference in mean EGF levels from 'normal' bladder samples from non-tumour bearing areas of bladder in patients with bladder cancer compared with 'normal' bladder tissue obtained at the time of organ retrieval surgery. Levels of EGF and TGF-alpha did not correlate with levels of EGF receptor (EGFR) as determined by a radioligand binding method but levels of TGF-alpha > 10 ng gm-1 of tumour tissue did correlate with EGFR positivity defined using immunohistochemistry. These data suggest that TGF-alpha is the likely ligand for EGFR in bladder tumours. PMID:8605103

  6. Efficient nucleic acid delivery to murine regulatory T cells by gold nanoparticle conjugates.

    PubMed

    Gamrad, Lisa; Rehbock, Christoph; Westendorf, Astrid M; Buer, Jan; Barcikowski, Stephan; Hansen, Wiebke

    2016-01-01

    Immune responses have to be tightly controlled to guarantee maintenance of immunological tolerance and efficient clearance of pathogens and tumorigenic cells without induction of unspecific side effects. CD4(+) CD25(+) regulatory T cells (Tregs) play an important role in these processes due to their immunosuppressive function. Genetic modification of Tregs would be helpful to understand which molecules and pathways are involved in their function, but currently available methods are limited by time, costs or efficacy. Here, we made use of biofunctionalized gold nanoparticles as non-viral carriers to transport genetic information into murine Tregs. Confocal microscopy and transmission electron microscopy revealed an efficient uptake of the bioconjugates by Tregs. Most importantly, coupling eGFP-siRNA to those particles resulted in a dose and time dependent reduction of up to 50% of eGFP expression in Tregs isolated from Foxp3eGFP reporter mice. Thus, gold particles represent a suitable carrier for efficient import of nucleic acids into murine CD4(+) CD25(+) Tregs, superior to electroporation. PMID:27381215

  7. Efficient nucleic acid delivery to murine regulatory T cells by gold nanoparticle conjugates

    PubMed Central

    Gamrad, Lisa; Rehbock, Christoph; Westendorf, Astrid M.; Buer, Jan; Barcikowski, Stephan; Hansen, Wiebke

    2016-01-01

    Immune responses have to be tightly controlled to guarantee maintenance of immunological tolerance and efficient clearance of pathogens and tumorigenic cells without induction of unspecific side effects. CD4+ CD25+ regulatory T cells (Tregs) play an important role in these processes due to their immunosuppressive function. Genetic modification of Tregs would be helpful to understand which molecules and pathways are involved in their function, but currently available methods are limited by time, costs or efficacy. Here, we made use of biofunctionalized gold nanoparticles as non-viral carriers to transport genetic information into murine Tregs. Confocal microscopy and transmission electron microscopy revealed an efficient uptake of the bioconjugates by Tregs. Most importantly, coupling eGFP-siRNA to those particles resulted in a dose and time dependent reduction of up to 50% of eGFP expression in Tregs isolated from Foxp3eGFP reporter mice. Thus, gold particles represent a suitable carrier for efficient import of nucleic acids into murine CD4+ CD25+ Tregs, superior to electroporation. PMID:27381215

  8. An ES-Like Pluripotent State in FGF-Dependent Murine iPS cells

    PubMed Central

    Ungaro, Federica; Prigione, Alessandro; Chen, Hsu-Hsin; Welling, Maaike; Eijpe, Maureen; Mostoslavsky, Gustavo; Tesar, Paul; Adjaye, James; Geijsen, Niels; Broccoli, Vania

    2010-01-01

    Recent data demonstrates that stem cells can exist in two morphologically, molecularly and functionally distinct pluripotent states; a naïve LIF-dependent pluripotent state which is represented by murine embryonic stem cells (mESCs) and an FGF-dependent primed pluripotent state represented by murine and rat epiblast stem cells (EpiSCs). We find that derivation of induced pluripotent stem cells (iPSCs) under EpiSC culture conditions yields FGF-dependent iPSCs from hereon called FGF-iPSCs) which, unexpectedly, display naïve ES-like/ICM properties. FGF-iPSCs display X-chromosome activation, multi-lineage differentiation, teratoma competence and chimera contribution in vivo. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions. Characterization of the key molecular signalling pathways revealed FGF-iPSCs to depend on the Activin/Nodal and FGF pathways, while signalling through the JAK-STAT pathway is not required for FGF-iPS cell maintenance. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions. PMID:21209851

  9. Developing a 'thick skin': a paradoxical role for mechanical tension in maintaining epidermal integrity?

    PubMed

    Galletti, Roberta; Verger, Stéphane; Hamant, Olivier; Ingram, Gwyneth C

    2016-09-15

    Plant aerial epidermal tissues, like animal epithelia, act as load-bearing layers and hence play pivotal roles in development. The presence of tension in the epidermis has morphogenetic implications for organ shapes but it also constantly threatens the integrity of this tissue. Here, we explore the multi-scale relationship between tension and cell adhesion in the plant epidermis, and we examine how tensile stress perception may act as a regulatory input to preserve epidermal tissue integrity and thus normal morphogenesis. From this, we identify parallels between plant epidermal and animal epithelial tissues and highlight a list of unexplored questions for future research. PMID:27624830

  10. Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function

    PubMed Central

    Duchnik, Ewa; Maleszka, Romuald; Marchlewicz, Mariola

    2016-01-01

    The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part – stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transepidermal water loss and sebum excretion. The knowledge of biophysical skin processes may be useful for the implementation of prophylactic actions whose aim is to restore the barrier function. PMID:26985171

  11. Epidermal growth factor and kidney disease: a long-lasting story.

    PubMed

    Klein, Julie; Bascands, Jean-Loup; Buffin-Meyer, Bénédicte; Schanstra, Joost P

    2016-05-01

    Epidermal growth factor has been previously associated with kidney disease. In this issue of Kidney International, Betz et al. (2016) link urinary epidermal growth factor abundance with an increased risk of the development of diabetic nephropathy in a novel animal model of diabetic nephropathy and in a large cohort of patients with type 2 diabetes. Although the clinical value of these observations needs to be confirmed in further studies, these observations further strengthen the tight link between epidermal growth factor and kidney disease. PMID:27083276

  12. Vulvar Epidermal Inclusion Cyst as a Long-term Complication of Female Genital Mutilation.

    PubMed

    Victoria-Martínez, Ana Mercedes; Cubells-Sánchez, Laura; Martínez-Leborans, Lorena; Sánchez-Carazo, José Luis; de Miquel, Víctor Alegre

    2016-01-01

    We present a case report of a patient with epidermal inclusion cyst as a late complication of female genital mutilation (FGM). We describe the management of the patient, and a review of the literature. We report the clinical and pathological findings in a 37-year-old female patient from Nigeria, with a clitoral mass of 1 year duration. She declared to have an FGM since she was 5 years. The lesion was excised successfully with good cosmetic results. Histological examination revealed epidermal cyst with the presence of granular layer. An epidermal inclusion cyst can develop as a long-term consequence of FGM. PMID:26955127

  13. Vulvar Epidermal Inclusion Cyst as a Long-term Complication of Female Genital Mutilation

    PubMed Central

    Victoria-Martínez, Ana Mercedes; Cubells-Sánchez, Laura; Martínez-Leborans, Lorena; Sánchez-Carazo, José Luis; de Miquel, Víctor Alegre

    2016-01-01

    We present a case report of a patient with epidermal inclusion cyst as a late complication of female genital mutilation (FGM). We describe the management of the patient, and a review of the literature. We report the clinical and pathological findings in a 37-year-old female patient from Nigeria, with a clitoral mass of 1 year duration. She declared to have an FGM since she was 5 years. The lesion was excised successfully with good cosmetic results. Histological examination revealed epidermal cyst with the presence of granular layer. An epidermal inclusion cyst can develop as a long-term consequence of FGM. PMID:26955127

  14. A Case of Digital Myxoid Cyst Coexisting with Epidermal Inclusion Cyst

    PubMed Central

    Kim, Byung Soo; Jwa, Seung Wook; Suh, Sung Won; Kim, Sung Jun; Oh, Chang-Keun; Kwon, Kyung Sool

    2008-01-01

    A 62-year-old male developed a solitary asymptomatic nodule on the lateral aspect of the distal interphalangeal joint of the right great toe. Histopathologic findings demonstrated a myxoid cyst with a concomitant epidermal inclusion cyst. To the best of our knowledge, this is the first case of concurrent occurrence of digital myxoid cyst and epidermal inclusion cyst. Although the exact mechanism for developing a digital myxoid cyst and an epidermal inclusion cyst simultaneously at the same site is not explained, trauma might be a possible cause.

  15. Circassian Language Maintenance in Jordan

    ERIC Educational Resources Information Center

    Rannut, Ulle

    2009-01-01

    The central goal of this research is to explore the language policy aspects in Jordan by focusing on the Circassian language maintenance issues and to provide measures for language revitalisation in the current demographic, linguistic and political situation. Research is based on multiple sources of information, but primarily on the empirical data…

  16. Drive alignment pays maintenance dividends

    SciTech Connect

    Fedder, R.

    2008-12-15

    Proper alignment of the motor and gear drive on conveying and processing equipment will result in longer bearing and coupling life, along with lower maintenance costs. Selecting an alignment free drive package instead of a traditional foot mounted drive and motor is a major advancement toward these goals. 4 photos.

  17. Electrical Mechanical Maintenance. Instructor's Guide.

    ERIC Educational Resources Information Center

    Santa Clara County Superintendent of Schools, San Jose, CA.

    This instructor's guide describes the development of a sixteen-week postsecondary course in electrical mechanical maintenance. Following introductory sections that provide background information and a course summary, the third section describes the instructional model used in the course. Section 4 presents an overview of instructional media used…

  18. Maintenance of photovoltaic power systems

    NASA Astrophysics Data System (ADS)

    Hall, M. R.

    1984-08-01

    This publication establishes standard practices for inspection, testing, and maintenance of photovoltaic power systems at Dept. of the Navy installations. The practices and procedures are recommended to ensure reliable operation of the power systems. The manual covers photovoltaic-array, battery, voltage-regulator, inverter, and wiring subsystems. In addition, this manual provides a troubleshooting guide and self-study questions and answers.

  19. Maintenance of photovoltaic power systems

    SciTech Connect

    Hall, M.R.

    1984-08-01

    This publication establishes standard practices for inspection, testing, and maintenance of photovoltaic power systems at Department of the Navy installations. The practices and procedures are recommended to ensure reliable operation of the power systems. The manual covers photovoltaic-array, battery, voltage-regulator, inverter, and wiring subsystems. In addition, this manual provides a troubleshooting guide and self-study questions and answers.

  20. The Benefits of Health Maintenance.

    ERIC Educational Resources Information Center

    Rosenstein, Alan H.

    1987-01-01

    The article focuses on the merits of a comprehensive, medically-oriented health maintenance/risk assessment program, and suggests that such conditions as heart disease, cancer, and arteriosclerosis can be prevented or postponed through proper nutrition, weight control, exercise, smoking cessation, and stress management. (Author/CB)

  1. Afrikaans Language Maintenance in Australia

    ERIC Educational Resources Information Center

    Hatoss, Aniko; Starks, Donna; van Rensburg, Henriette Janse

    2011-01-01

    Changes in the political climate in the home country have resulted in the emigration of South Africans to English speaking countries such as Britain, Canada, Australia and New Zealand. Despite the scale of movement of the South African population, language maintenance in these diasporic contexts has received little consideration. This paper…

  2. Maintenance Sessions Prolong Cigarette Abstinence.

    ERIC Educational Resources Information Center

    Brandon, Thomas H.; And Others

    Recent smoking treatment programs have shifted emphasis from initial cessation rates to long-term abstinence, with aversion therapy and coping response training having had the most success. A smoking cessation treatment consisting of rapid smoking and behavioral counseling was supplemented with two maintenance treatments. After completing the…

  3. Avionics Maintenance Technology Program Guide.

    ERIC Educational Resources Information Center

    Georgia Univ., Athens. Dept. of Vocational Education.

    This program guide presents the avionics maintenance technology curriculum for technical institutes in Georgia. The general information section contains the following for both the diploma program and the associate degree program: purpose and objectives; program description, including admissions, typical job titles, and accreditation and…

  4. Locker Room Maintenance Made Easy.

    ERIC Educational Resources Information Center

    Theel, James

    1998-01-01

    Provides examples on ways to make locker room maintenance easier and their use more student-friendly. Improvements include use of indoor-outdoor carpeting with numerous floor drains to cut mildew buildup, adequate ventilation to reduce musty smells, better hot water management, ceramic tiles to reduce water-damage repair and painting needs, and…

  5. Laboratory Maintenance of Rickettsia rickettsii

    PubMed Central

    Beier-Sexton, Magda; Azad, Abdu F.

    2009-01-01

    This unit includes protocols for the laboratory maintenance of the obligate intracellular bacterium Rickettsia rickettsii, including propagation in mammalian cell cultures, as well as isolation, counting, and storage procedures. Regulations for working with R. rickettsii in biosafety level 3 containment are also discussed. PMID:19016440

  6. New Directions in Maintenance Simulation.

    ERIC Educational Resources Information Center

    Miller, Gary G.

    A two-phase effort was conducted to design and evaluate a maintenance simulator which incorporated state-of-the-art information in simulation and instructional technology. The particular equipment selected to be simulated was the 6883 Convert/Flight Controls Test Station. Phase I included a generalized block diagram of the computer-trainer, the…

  7. Maintenance Sourcebook: A Caretaker's Manual.

    ERIC Educational Resources Information Center

    Yeatts, G. Dewey; Stoverink, Al; Conry, Terry; Goulet, Nicole; Wilson, Joe; Ryan, Rob

    2002-01-01

    Discusses five areas of custodial maintenance caretaking in which facility managers need continual education: first aid and safety, hazardous materials, products and supplies, chemicals and their intended use, and cleaning procedures. Includes an annotated list of resources related to these areas. (EV)

  8. Checklist for School Maintenance Surveys.

    ERIC Educational Resources Information Center

    Maryland State Dept. of Education, Baltimore.

    This document is a simple 34-category checklist to be used by technicians conducting maintenance surveys. Categories includes: roadways & parking lots; site appearance; site utilities; exterior appearance; playground equipment; exterior structural conditions; gutters and downspouts; windows and caulking; sidewalks; entryways and exit doors; roof…

  9. Computer-Assisted School Maintenance

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2012-01-01

    At thousands of schools and universities, years of economic troubles have led to repeated budget cuts. The reductions typically fall disproportionately on maintenance departments, where cuts are viewed as less critical than those that directly affect classroom instruction. And so nearly every facility manager at an education institution faces a…

  10. Building Maintenance. Student Learning Guide.

    ERIC Educational Resources Information Center

    Palm Beach County Board of Public Instruction, West Palm Beach, FL.

    This student learning guide contains one module for completing a course in building maintenance. It is designed especially for use in secondary schools in Palm Beach County, Florida. The module covers one task, and consists of a purpose, performance objective, enabling objectives, learning activities keyed to resources, information sheets, student…

  11. Laboratory Maintenance of Acinetobacter baumannii.

    PubMed

    Jacobs, Anna C; Zurawski, Daniel V

    2014-01-01

    Acinetobacter baumannii has recently drawn great interest in the microbiology research community due to the increase in clinical antibiotic resistance of this organism, and persistence of this bacterial species in the hospital environment. This unit outlines protocols for the growth and maintenance of A. baumannii in the laboratory. PMID:25367273

  12. Dynamic Evolution of Squeezing Maintenance

    NASA Astrophysics Data System (ADS)

    Wan, Zhi-Long; Fan, Hong-Yi

    2016-08-01

    By virtue of the coherent state representation and solving Riccati equation we derive dynamic evolution operator for maintaining squeezing, i.e., we demonstrate that the final state keeps squeezing when the initial state is a squeezed vacuum state. The number-phase squeezing maintenance mechanism is also studied.

  13. Identification and analysis of the human murine putative chromatin structure regulator SUPT6H and Supt6h

    SciTech Connect

    Chiang, Pei-Wen; Wang, SuQing; Hillman, J.

    1996-06-15

    We have isolated and sequenced SUPT6H and Supt6h, the human and murine homologues of the Saccharomyces cerevisiae and Caenorhabditis elegans genes SPT6 (P using 1603 aa = 6.7 e-{sup 95}) and emb-5 (P using 1603 aa = 7.0 e-{sup 288}), respectively. The human and murine SPT6 homologues are virtually identical, as they share >98% identity and >99% similarity at the protein level. The derived amino acid sequences of these two genes predict a 1603-aa protein (human) and a 1726-bp protein (mouse), respectively. There were several known features, including a highly acidic 5{prime}-region, a degenerate SH2 domain, and a leucine zipper. These features are consistent with a nuclear protein that regulates transcription, whose extreme conservation underscores the likely importance of this gene in mammalian development. Expression of human and murine SPT6 homologues was analyzed by Northern blotting, which revealed a 7.0-kb transcript that was expressed constitutively. The SPT6 homologue was mapped to chromosome 17q11.2 in human by somatic cell hybrid analysis and in situ hybridization. These data indicate that SUPT6H and Supt6h are functionally analogous to SPT6 and emb-5 and may therefore regulate transcription through establishment or maintenance of chromatin structure. 23 refs., 3 figs.

  14. Topical application of the adenosine A2A receptor agonist CGS-21680 prevents phorbol-induced epidermal hyperplasia and inflammation in mice.

    PubMed

    Arasa, Jorge; Martos, Patricio; Terencio, María Carmen; Valcuende-Cavero, Francisca; Montesinos, María Carmen

    2014-08-01

    The nucleoside adenosine is a known regulator of immunity and inflammation that mediates, at least in part, the anti-inflammatory effect of methotrexate, an immunosuppressive agent widely used to treat autoimmune inflammatory diseases. Adenosine A2A receptors play a key role in the inhibition of the inflammatory process besides promoting wound healing. Therefore, we aimed to determine the topical effect of a selective agonist, CGS-21680, on a murine model of skin hyperplasia with a marked inflammatory component. Pretreatment with either CGS-21680 (5 μg per site) or the reference agent dexamethasone (200 μg/site) prevented the epidermal hyperplasia and inflammatory response induced by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 nmol/site) for three consecutive days. The histological analysis showed that both CGS-21680 and dexamethasone produced a marked reduction of inflammatory cell infiltrate, which correlated with diminished myeloperoxidase (MPO) activity in skin homogenates. Both treatments reduced the levels of the chemotactic mediators LTB4 and CXCL-1, and the inflammatory cytokine TNF-α, through the suppression of NFκB phosphorylation. The immunohistochemical analysis of the hyperproliferative markers cytokeratin 6 (CK6) and Ki67 revealed that while both agents inhibit the number of proliferating cells in the epidermis, CGS-21680 treatment promoted dermal fibroblasts proliferation. Consistently, increased collagen deposition in dermis was observed in tissue sections from agonist-treated mice. Our results showed that CGS 21680 efficiently prevents phorbol-induced epidermal hyperplasia and inflammation in mice without the deleterious atrophic effect of topical corticosteroids. PMID:24889129

  15. Novel MEK1 Mutation Identified by Mutational Analysis of Epidermal Growth Factor Receptor Signaling Pathway Genes in Lung Adenocarcinoma

    PubMed Central

    Marks, Jenifer L.; Gong, Yixuan; Chitale, Dhananjay; Golas, Ben; McLellan, Michael D.; Kasai, Yumi; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Solit, David; Levine, Ross; Michel, Kathrin; Thomas, Roman K.; Rusch, Valerie W.; Ladanyi, Marc; Pao, William

    2008-01-01

    Genetic lesions affecting a number of kinases and other elements within the epidermal growth factor receptor (EGFR) signaling pathway have been implicated in the pathogenesis of human non–small-cell lung cancer (NSCLC). We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this pathway that could contribute to lung tumorigenesis. We have identified in 2 of 207 primary lung tumors a somatic activating mutation in exon 2 of MEK1 (i.e., mitogen-activated protein kinase kinase 1 or MAP2K1) that substitutes asparagine for lysine at amino acid 57 (K57N) in the nonkinase portion of the kinase. Neither of these two tumors harbored known mutations in other genes encoding components of the EGFR signaling pathway (i.e., EGFR, HER2, KRAS, PIK3CA, and BRAF). Expression of mutant, but not wild-type, MEK1 leads to constitutive activity of extracellular signal–regulated kinase (ERK)-1/2 in human 293T cells and to growth factor–independent proliferation of murine Ba/F3 cells. A selective MEK inhibitor, AZD6244, inhibits mutant-induced ERK activity in 293T cells and growth of mutant-bearing Ba/F3 cells. We also screened 85 NSCLC cell lines for MEK1 exon 2 mutations; one line (NCI-H1437) harbors a Q56P substitution, a known transformation-competent allele of MEK1 originally identified in rat fibroblasts, and is sensitive to treatment with AZD6244. MEK1 mutants have not previously been reported in lung cancer and may provide a target for effective therapy in a small subset of patients with lung adenocarcinoma. PMID:18632602

  16. Potassium Balances in Maintenance Hemodialysis

    PubMed Central

    Choi, Hoon Young

    2013-01-01

    Potassium is abundant in the ICF compartment in the body and its excretion primarily depends on renal (about 90%), and to a lesser extent (about 10%) on colonic excretion. Total body potassium approximated to 50mmol/kg body weight and 2% of total body potassium is in the ECF compartment and 98% of it in the intracellular compartment.Dyskalemia is a frequent electrolyte imbalance observed among the maintenance hemodialysis patients. In case of hyperkalemia, it is frequently "a silent and a potential life threatening electrolyte imbalance" among patients with ESRD under maintenance hemodialysis. The prevalence of hyperkalemia in maintenance HD patients was reported to be about 8.7-10%. Mortality related to the hyperkalemia has been shown to be about 3.1/1,000 patient-years and about 24% of patients with HD required emergency hemodialysis due to severe hyperkalemia. In contrast to the hyperkalemia, much less attention has been paid to the hypokalemia in hemodialysis patients because of the low prevalence under maintenance hemodialysis patients. Severe hypokalemia in the hemodialysis patients usually was resulted from low potassium intake (malnutrition), chronic diarrhea, mineralocorticoid use, and imprudent use of K-exchange resins. Recently, the numbers of the new patients with advanced chronic kidney disease undergoing maintenance hemodialysis are tremendously increasing worldwide. However, the life expectancy of these patients is still much lower than that of the general population. The causes of excess mortality in these patients seem to various, but dyskalemia is a common cause among the patients with ESRD undergoing hemodialysis. PMID:23946760

  17. Sexual dimorphism of Murine Masticatory Muscle Function

    PubMed Central

    Daniels, David W.; Tian, Zuozhen; Barton, Elisabeth R.

    2008-01-01

    (1) Objective To determine if gender distinctions of force generating capacity existed in murine masticatory muscles. (2) Design In order to investigate the effect of sex on force generating capacity in this muscle group, an isolated muscle preparation was developed utilizing the murine anterior deep masseter. Age-matched male and female mice were utilized to assess function, muscle fiber type and size in this muscle. (3) Results Maximum isometric force production was not different between age-matched male and female mice. However, the rate of force generation and relaxation was slower in female masseter muscles. Assessment of fiber type distribution by immunohistochemistry revealed a threefold decrease in the proportion of myosin heavy chain 2b positive fibers in female masseters, which correlated with the differences in contraction kinetics. (4) Conclusions These results provide evidence that masticatory muscle strength in mice is not affected by sex, but there are significant distinctions in kinetics associated with force production between males and females. PMID:18028868

  18. Phase II trial of paclitaxel-carboplatin with intercalated gefitinib for untreated, epidermal growth factor receptor gene mutation status unknown non-small cell lung cancer

    PubMed Central

    Yang, Jianliang; Shi, Yuankai; Zhang, Xiangru; Xu, Jianping; Wang, Bin; Hao, Xuezhi; Li, Junling; Yan, Wang

    2014-01-01

    Background This study was conducted to evaluate the efficacy and safety of paclitaxel-carboplatin combined with intercalated gefitinib in patients with advanced, untreated, nonsquamous non-small cell lung cancer. Methods A total of 29 patients were enrolled in the study. All patients were Chinese, with a histology type of adenocarcinoma, without a smoking history, and as a result of the limited tissue sample, an epidermal growth factor receptor (EGFR) mutation test could not be performed. All patients received chemotherapy of paclitaxel-carboplatin every 21 days for four cycles, and gefitinib (250 mg/day) was administered on days eight to 17 of the chemotherapy cycle. If the patient responded to chemotherapy, maintenance therapy of 250mg of gefitinib could be administered daily. Results All of the 29 patients received at least one cycle of chemotherapy and gefitinib, and 25 patients received four cycles of therapy. Eighteen patients selected maintenance therapy with gefitinib. The objective response rate was 74.1% (95% confidence interval, 53.7% to 88.9%). No complete response was achieved. The median progression-free survival was 16 months, however, the median overall survival was not available by the conclusion of the study. The major adverse event was hematologic toxicity. Conclusions The regimen of paclitaxel-carboplatin combined with intercalated gefitinib showed a high response rate and a favorable safety profile. Gefitinib maintenance therapy was proven to be beneficial. This study proposes a good pattern of chemotherapy combined with EGFR tyrosine kinase inhibitors. PMID:26766992

  19. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells.

    PubMed

    Zhang, Hui-ming; Talbot, Mark J; McCurdy, David W; Patrick, John W; Offler, Christina E

    2015-09-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca(2+) levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane-microtubule inter-relationship is discussed. PMID:26136268

  20. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells

    PubMed Central

    Zhang, Hui-ming; Talbot, Mark J.; McCurdy, David W.; Patrick, John W.; Offler, Christina E.

    2015-01-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca2+ levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane–microtubule inter-relationship is discussed. PMID:26136268

  1. Effects of soap-water wash on human epidermal penetration.

    PubMed

    Zhu, Hanjiang; Jung, Eui-Chang; Phuong, Christina; Hui, Xiaoying; Maibach, Howard

    2016-08-01

    Skin decontamination is a primary interventional method used to decrease dermal absorption of hazardous contaminants, including chemical warfare agents, pesticides and industrial pollutants. Soap and water wash, the most common and readily available decontamination system, may enhance percutaneous absorption through the "wash-in effect." To understand better the effect of soap-water wash on percutaneous penetration, and provide insight to improving skin decontamination methods, in vitro human epidermal penetration rates of four C(14) -labeled model chemicals (hydroquinone, clonidine, benzoic acid and paraoxon) were assayed using flow-through diffusion cells. Stratum corneum (SC) absorption rates of these chemicals at various hydration levels (0-295% of the dry SC weights) were determined and compared with the results of the epidermal penetration study to clarify the effect of SC hydration on skin permeability. Results showed accelerated penetration curves of benzoic acid and paraoxon after surface wash at 30 min postdosing. Thirty minutes after washing (60 min postdosing), penetration rates of hydroquinone and benzoic acid decreased due to reduced amounts of chemical on the skin surface and in the SC. At the end of the experiment (90 min postdosing), a soap-water wash resulted in lower hydroquinone penetration, greater paraoxon penetration and similar levels of benzoic acid and clonidine penetration compared to penetration levels in the non-wash groups. The observed wash-in effect agrees with the enhancement effect of SC hydration on the SC chemical absorption rate. These results suggest SC hydration derived from surface wash to be one cause of the wash-in effect. Further, the occurrence of a wash-in effect is dependent on chemical identity and elapsed time between exposure and onset of decontamination. By reducing chemical residue quantity on skin surface and in the SC reservoir, the soap-water wash may decrease the total quantity of chemical absorbed in the

  2. Water Relations of Leaf Epidermal Cells of Tradescantia virginiana12

    PubMed Central

    Tomos, Alun Deri; Steudle, Ernst; Zimmermann, Ulrich; Schulze, Ernst-Detlev

    1981-01-01

    Water-relation parameters (cell turgor pressure [P], volumetric elastic modulus [ε] and hydraulic conductivity [Lp]) of individual leaf epidermal cells of Tradescantia virginiana have been determined with the pressure-probe technique. Turgor was 4.5 ± 2.1 [41] bar (mean ± sd; in brackets the number of cells) and ranged from 0.9 to 9.6 bar. By vacuum infiltration with nutrient solution, it was raised to 7.5 ± 1.5 [5] bar (range: 5.3-8.8 bar). There was a large variability in the absolute value of ε of individual cells. ε ranged from 40 to 360 bar; mean ± sd: 135 ± 83 bar; n = 50 cells. ε values of individual cells seemed to be rather independent of changes in cell turgor. A critical assessment of the errors incurred in determining ε by the technique is included. The half-times of water exchange of individual cells ranged from 1 to 35 seconds, which gave values of 0.2 to 11 × 10−6 centimeters per second per bar for Lp (mean ± sd: 3.1 ± 2.3 × 10−6 centimeters per second per bar; n = 39 cells). The large range in Lp and ε is believed to be due to the difficulties in determining the effective surface area of water exchange of the cells. Lp is not influenced by active salt pumping driven by respiration energy inasmuch as it was not altered by 0.1 millimolar KCN. The temperature dependence of Lp (T½) was measured for the first time in individual higher-plant cells. Lp increased by a factor of 2 to 4, when the temperature was increased by 10 C. The activation energy of water exchange was found to be between 50 and 186 kilojoules per mole. Within the large range of variation it was found that T½, Lp, and ε did not change under various experimental conditions (intact and excised tissue, water content and turgidity, age, etc.). Similar results were obtained for the epidermal cells of Tradescantia andersoniana. The measurements suggest that the entire epidermis would respond very rapidly (i.e. with a half-time of 1 to 30 s) to a demand for water from the

  3. Toxic epidermal necrolysis and hemophagocytic lymphohistiocytosis: a case report and literature review

    PubMed Central

    Sniderman, Jonathan D S; Cuvelier, Geoff D E; Veroukis, Stasa; Hansen, Gregory

    2015-01-01

    Key Clinical Message Diagnostic criteria for hemophagocytic lymphohistiocytosis should be reviewed early in critically ill patients with toxic epidermal necrolysis, multisystem dysfunction, and a deteriorating clinical trajectory. PMID:25767712

  4. Diversity of murine norovirus strains isolated from asymptomatic mice of different genetic backgrounds within a single U.S. research institute.

    PubMed

    Barron, Elyssa L; Sosnovtsev, Stanislav V; Bok, Karin; Prikhodko, Victor; Sandoval-Jaime, Carlos; Rhodes, Crystal R; Hasenkrug, Kim; Carmody, Aaron B; Ward, Jerrold M; Perdue, Kathy; Green, Kim Y

    2011-01-01

    Antibody prevalence studies in laboratory mice indicate that murine norovirus (MNV) infections are common, but the natural history of these viruses has not been fully established. This study examined the extent of genetic diversity of murine noroviruses isolated from healthy laboratory mice housed in multiple animal facilities within a single, large research institute- the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIAID-NIH) in Bethesda, Maryland, U.S. Ten distinct murine norovirus strains were isolated from various tissues and feces of asymptomatic wild type sentinel mice as well as asymptomatic immunodeficient (RAG 2(-/-)) mice. The NIH MNV isolates showed little cytopathic effect in permissive RAW264.7 cells in early passages, but all isolates examined could be adapted to efficient growth in cell culture by serial passage. The viruses, although closely related in genome sequence, were distinguishable from each other according to facility location, likely due to the introduction of new viruses into each facility from separate sources or vendors at different times. Our study indicates that the murine noroviruses are widespread in these animal facilities, despite rigorous guidelines for animal care and maintenance. PMID:21738664

  5. Endocervical Polyp With Florid "Epidermal Metaplasia": Report of a Previously Undescribed Phenomenon.

    PubMed

    Angra, Seema; McCluggage, W Glenn

    2016-09-01

    Endocervical polyps are common benign lesions which rarely result in diagnostic problems, although a variety of alterations occasionally complicate histologic interpretation. We report an unusual, and not previously described, finding of florid "epidermal" metaplasia with keratinization and extensive formation of skin appendages structures (sebaceous and sweat glands and hair follicles) within an endocervical polyp. The features closely resembled an epidermal inclusion cyst. We speculate on the possible pathogenesis of this rare phenomenon and review unusual findings in endocervical polyps. PMID:27167675

  6. Epidermal Cyst in the Scrotum Successfully Treated while Preserving the Testis: A Case Report

    PubMed Central

    Kondo, Takuya; Kawahara, Takashi; Matsumoto, Taro; Yamamoto, Yuko; Tsutsui, Miho; Ohtani, Masako; Ohtaka, Mari; Kumano, Yohei; Maeda, Yoko; Mochizuki, Taku; Mori, Kohei; Asai, Takuo; Kuroda, Shinnosuke; Takeshima, Teppei; Hattori, Yusuke; Teranishi, Jun-ichi; Miyoshi, Yasuhide; Yumura, Yasushi; Yao, Masahiro; Inayama, Yoshiaki; Uemura, Hiroji

    2016-01-01

    A 66-year-old male was referred to our hospital for further examination of a scrotal mass. Because of the risk of testicular cancer, we first clamped the vessels as a course of higher orchiectomy. Then, we approached the tumor through the scrotum and successfully resected it while preserving the testis. A histopathological diagnosis revealed an epidermal cyst. We herein report a rare case of an intrascrotal epidermal cyst successfully treated while preserving the testis. PMID:27194984

  7. Identification of Candidate Transcriptional Regulators of Epidermal Transfer Cell Development in Vicia faba Cotyledons.

    PubMed

    Arun-Chinnappa, Kiruba S; McCurdy, David W

    2016-01-01

    Transfer cells (TCs) are anatomically-specialized cells formed at apoplasmic-symplasmic bottlenecks in nutrient transport pathways in plants. TCs form invaginated wall ingrowths which provide a scaffold to amplify plasma membrane surface area and thus increase the density of nutrient transporters required to achieve enhanced nutrient flow across these bottlenecks. Despite their importance to nutrient transport in plants, little is known of the transcriptional regulation of wall ingrowth formation. Here, we used RNA-Seq to identify transcription factors putatively involved in regulating epidermal TC development in cotyledons of Vicia faba. Comparing cotyledons cultured for 0, 3, 9, and 24 h to induce trans-differentiation of epidermal TCs identified 43 transcription factors that showed either epidermal-specific or epidermal-enhanced expression, and 10 that showed epidermal-specific down regulation. Members of the WRKY and ethylene-responsive families were prominent in the cohort of transcription factors showing epidermal-specific or epidermal-enhanced expression, consistent with the initiation of TC development often representing a response to stress. Members of the MYB family were also prominent in these categories, including orthologs of MYB genes involved in localized secondary wall deposition in Arabidopsis thaliana. Among the group of transcription factors showing down regulation were various homeobox genes and members of the MADs-box and zinc-finger families of poorly defined functions. Collectively, this study identified several transcription factors showing expression characteristics and orthologous functions that indicate likely participation in transcriptional regulation of epidermal TC development in V. faba cotyledons. PMID:27252730

  8. Intercalated chemotherapy and erlotinib for non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations.

    PubMed

    Zwitter, Matjaz; Rajer, Mirjana; Stanic, Karmen; Vrankar, Martina; Doma, Andrej; Cuderman, Anka; Grmek, Marko; Kern, Izidor; Kovac, Viljem

    2016-08-01

    Among attempts to delay development of resistance to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor (EGFR), intercalated therapy has not been properly evaluated. In a phase II trial, 38 patients with EGFR mutated NSCLC in advanced stage were treated with 4 to 6 3-weekly cycles of intercalated schedule with gemcitabine (1250 mg/m2, days 1 and 4), cisplatin (75 mg/m2, day 2) and erlotinib (150 mg, days 5 - 15), followed by continuous erlotinib as maintenance. In addition to standard radiologic evaluation according to RECIST, PET/CT was done prior to treatment and at 6 months, using PERCIST as a method for assessment of response. The primary endpoint was progression-free survival (PFS). In general, tolerance to treatment was good, even among 8 patients with performance status 2-3 and 13 patients with brain metastases; grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. Complete response (CR) or partial response (PR) were seen in 15 (39.5%) and 17 (44.7%) cases, respectively. All cases of CR were confirmed also by PET/CT. Median PFS was 23.4 months and median overall survival (OS) was 38.3  months. After a median follow-up of 35 months, 8 patients are still in CR and on maintenance erlotinib. In conclusion, intercalated treatment for treatment-naive patients with EGFR activating mutations leads to excellent response rate and prolonged PFS and survival. Comparison of the intercalated schedule to monotherapy with TKIs in a randomized trial is warranted. PMID:27261103

  9. The Evidence Regarding Maintenance Tocolysis

    PubMed Central

    Elliott, John P.; Morrison, John C.

    2013-01-01

    Preterm delivery is a public health issue of major proportion. More than 12% of deliveries in the United States that occur at less than 37 weeks gestation preterm labor (PTL) represents the largest single reason for preterm birth (PTB). Attempts to prevent PTB have been unsuccessful. This paper of maintenance tocolytic therapy will examine the efficacy and safety of the drugs, both oral and subcutaneous, which have been utilized for prolongation of pregnancy following successful arrest of a documented episode of acute preterm labor. The evidence for oral tocolytics as maintenance therapy as well as parenteral medications for such patients is offered. Finally, the effects in the United States of the Food and Drug Administration (FDA) action on such medications are reported. PMID:23577034

  10. Mining Surveillance and Maintenance Dollars

    SciTech Connect

    MARTINEZ, R.

    2000-02-01

    Accelerating site cleanup to reduce facility risks to the workers, the public and the environment during a time of declining federal budgets represents a significant technical and economic challenge to U.S. Department of Energy (DOE) Operations Offices and their respective contractors. A significant portion of a facility's recurring annual expenses are associated with routine, long-term surveillance and maintenance (S&M) activities. However, ongoing S&M activities do nothing to reduce risks and basically spend money that could be reallocated towards facility deactivation. This paper discusses the background around DOE efforts to reduce surveillance and maintenance costs, one approach used to perform cost reviews, lessons learned from field implementation and what assistance is available to assist DOE sites in performing these evaluations.

  11. Orbital assembly and maintenance study

    NASA Technical Reports Server (NTRS)

    Gorman, D.; Grant, C.; Kyrias, G.; Lord, C.; Rombach, J.; Salis, M.; Skidmore, R.; Thomas, R.

    1975-01-01

    The requirements, conceptual design, tradeoffs, procedures, and techniques for orbital assembly of the support structure of the microwave power transmission system and the radio astronomy telescope are described. Thermal and stress analyses, packaging, alignment, and subsystems requirements are included along with manned vs. automated and transportation tradeoffs. Technical and operational concepts for the manned and automated maintenance of satellites were investigated and further developed results are presented.

  12. c-Rel in Epidermal Homeostasis: A Spotlight on c-Rel in Cell Cycle Regulation.

    PubMed

    Lorenz, Verena N; Schön, Michael P; Seitz, Cornelia S

    2016-06-01

    To maintain proper skin barrier function, epidermal homeostasis requires a subtly governed balance of proliferating and differentiating keratinocytes. While differentiation takes place in the suprabasal layers, proliferation, including mitosis, is usually restricted to the basal layer. Only recently identified as an important regulator of epidermal homeostasis, c-Rel, an NF-κB transcription factor subunit, affects the viability and proliferation of epidermal keratinocytes. In human keratinocytes, decreased expression of c-Rel causes a plethora of dysregulated cellular functions including impaired cell viability, increased apoptosis, and abnormalities during mitosis and cell cycle regulation. On the other hand, c-Rel shows aberrant expression in many epidermal tumors. Here, in the context of its role in different cell types and compared with other NF-κB subunits, we discuss the putative function of c-Rel as a regulator of epidermal homeostasis and mitotic progression. In addition, implications for disease pathophysiology with perturbed c-Rel function and abnormal homeostasis, such as epidermal carcinogenesis, will be discussed. PMID:27032306

  13. Sensitivity enhancement of a micro-scale biomimetic tactile sensor with epidermal ridges

    NASA Astrophysics Data System (ADS)

    Zhang, Yuhua

    2010-08-01

    A microscale biomimetic tactile sensor with epidermal ridges is proposed to enhance the sensitivity of force detection. Guided by the principles of the human tactile perception mechanism, specifically the epidermal ridges, artificial epidermal ridges made of polydimethylsiloxane (PDMS) were designed and placed on micro-fabricated metal strain gauge arrays. A polyimide layer was fabricated to facilitate attachment between the metal and PDMS, so that patterned copper could be deposited on the polyimide to function as the strain gauges. The aspect ratio of the artificial epidermal ridges was optimized using material stability calculations and finite element method (FEM) simulations, and the optimal structure obtained was 400 µm in width and 110 µm in height. Experiments verified the effectiveness of enhancing the sensitivity of such a tactile sensor with the artificial epidermal ridges, in that the outputs of the strain gauges were 1.8 times more sensitive than those of a tactile sensor without ridges. The proposed artificial epidermal ridges are readily applicable to any developed tactile sensors for performance enhancement.

  14. [A study of epidermal alterations induced by PCDF on experimental carcinogenesis].

    PubMed

    Hirose, R; Hori, M; Toyoshima, H; Shukuwa, T; Udono, M; Yoshida, H

    1991-05-01

    An effect of 2,3,4,7,8-pentachlorodibenzofuran (PCDF) as a promoter on a course of experimental skin carcinogenesis in mice by chemicals 20-methylcholanthrene (MC) has been proved by our previous studies. Details of ultrastructural epidermal alterations induced by MC and PCDF were observed and an attempt to differentiate benign tumor from malignant one in which a combined application of MC and PCDF on mice skin resulted was done electron microscopically. Four significant findings as follows were detected. First of all even the epidermal cells without tumor had some atypicality. Secondly both of benign tumor and normal-appeared skin without tumor had giant and round-shaped keratohyalin granules (KHGs) which show a tendency of less keratinization. Thirdly cytoplasmic projections of epidermal cells increased in number and sparse tonofilaments scattered in the cytoplasm of benign tumor. This is also an appearance of mucous metaplasia of keratinocytes as well as the form of KHGs mentioned above. Finally benign tumor had thick horny cells including numerous lipid droplets, and that is a sign of acceleration of epidermal turn over. Since epidermal cells have little chance to be exposed to carcinogens when they quickly keratinize, they rarely form a cancer. When epidermal cells have such tendency as less keratinization or more keratinization, they are supposed to be less sensitive to any stimuli of carcinogens, and consequently they incline to be benign tumor instead of malignant one. PMID:1916594

  15. Use of a novel epidermal harvesting system in resource-poor countries.

    PubMed

    Serena, Thomas; Francius, Adler; Taylor, Cristin; MacDonald, John

    2015-03-01

    The 2010 earthquake in Port-au-Prince, Haiti, highlighted the need for wound care in resource-poor countries. Subsequently, the University of Miami in Florida established one of the first interprofessional wound care centers located at Bernard Mevs Hospital in the central portion of Port-au-Prince, caring for patients with acute and chronic wounds. In 2012, the authors used a novel epidermal harvesting system (CelluTome Epidermal Harvesting System; Kinetic Concepts Inc, San Antonio, Texas) to harvest epithelium to be grafted on 7 patients at the Mevs Hospital with longstanding wounds. Epidermal microblisters were obtained from each patient's thigh using the CelluTome Epidermal Harvesting System. After 35 minutes, microblisters were raised using the device harvester, and an adhesive dressing was inserted into the harvester for transfer to the wound site. In patients with lower-extremity wounds, a 2-layer compression dressing was placed over epidermal grafts. Six of the 7 wounds improved or achieved complete closure in 4 weeks. One of the patients with a 2-year-old thigh wound failed to demonstrate improvement; this may have been secondary to an inability to adequately secure the graft. All donor sites healed without any visible scarring. The authors were able to conclude that epidermal grafting may represent a viable reconstructive option for patients in resource-poor countries. PMID:25658643

  16. Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF)

    PubMed Central

    He, Yonghua; Schmidt, Monica A.; Erwin, Christopher; Guo, Jun; Sun, Raphael; Pendarvis, Ken; Warner, Brad W.; Herman, Eliot M.

    2016-01-01

    Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother’s breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N’ terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform. PMID:27314851

  17. Acute Modulations in Permeability Barrier Function Regulate Epidermal Cornification

    PubMed Central

    Demerjian, Marianne; Hachem, Jean-Pierre; Tschachler, Erwin; Denecker, Geertrui; Declercq, Wim; Vandenabeele, Peter; Mauro, Theodora; Hupe, Melanie; Crumrine, Debra; Roelandt, Truus; Houben, Evi; Elias, Peter M.; Feingold, Kenneth R.

    2008-01-01

    Stratum corneum comprises corneocytes, derived from outer stratum granulosum during terminal differentiation, embedded in a lipid-enriched extracellular matrix, secreted from epidermal lamellar bodies. Permeability barrier insults stimulate rapid secretion of preformed lamellar bodies from the outer stratum granulosum, regulated through modulations in ionic gradients and serine protease (SP)/protease-activated receptor type 2 (PAR2) signaling. Because corneocytes are also required for barrier function, we hypothesized that corneocyte formation could also be regulated by barrier function. Barrier abrogation by two unrelated methods initiated a wave of cornification, assessed as TdT-mediated dUTP nick end-labeling-positive cells in stratum granulosum and newly cornified cells by electron microscopy. Because cornification was blocked by occlusion, corneocytes formed specifically in response to barrier, rather than injury or cell replacement, requirements. SP inhibitors and hyperacidification (which decreases SP activity) blocked cornification after barrier disruption. Similarly, cornification was delayed in PAR2−/− mice. Although classical markers of apoptosis [poly(ADP-ribose)polymerase and caspase (Casp)-3] remained unchanged, barrier disruption activated Casp-14. Moreover, the pan-Casp inhibitor Z-VAD-FMK delayed cornification, and corneocytes were structurally aberrant in Casp14−/− mice. Thus, permeability barrier requirements coordinately drive both the generation of the stratum corneum lipid-enriched extracellular matrix and the transformation of granular cells into corneocytes, in an SP- and Casp-14-dependent manner, signaled by PAR2. PMID:18156206

  18. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: An Update.

    PubMed

    Dodiuk-Gad, Roni P; Chung, Wen-Hung; Valeyrie-Allanore, Laurence; Shear, Neil H

    2015-12-01

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous reactions, predominantly drug induced. The mortality rates for SJS and TEN are as high as 30 %, and short- and long-term morbidities are very common. SJS/TEN is one of the few dermatological diseases that constitute a true medical emergency. Early recognition and prompt and appropriate management can be lifesaving. In recent years, our understanding of the pathogenesis, clinical presentation, and management of SJS/TEN has improved. Nevertheless, in 2015, there are still no internationally accepted management guidelines. This review summarizes up-to-date insights on SJS/TEN and describes a protocol for assessment and treatment. We hope these suggested guidelines serve as a practical clinical tool in the management of SJS/TEN. The classic manifestation of SJS/TEN consists of initial "flu-like" symptoms (malaise, fever, anorexia) in the prodromal phase, followed by cutaneous and mucous membrane (ocular, oral, and genital) inflammation and pain, and other systemic involvement. Symptoms usually begin 4-28 days after the onset of drug intake. Treatment is multidisciplinary and includes identification and withdrawal of the culprit drug, transfer to a specialist unit, supportive care, medical treatment, communication, and provision of appropriate information and emotional support. PMID:26481651

  19. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    NASA Astrophysics Data System (ADS)

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  20. The epidermal growth factor receptor pathway in chronic kidney diseases.

    PubMed

    Harskamp, Laura R; Gansevoort, Ron T; van Goor, Harry; Meijer, Esther

    2016-08-01

    The epidermal growth factor receptor (EGFR) pathway has a critical role in renal development, tissue repair and electrolyte handling. Numerous studies have reported an association between dysregulation of this pathway and the initiation and progression of various chronic kidney diseases such as diabetic nephropathy, chronic allograft nephropathy and polycystic kidney disease through the promotion of renal cell proliferation, fibrosis and inflammation. In the oncological setting, compounds that target the EGFR pathway are already in clinical use or have been evaluated in clinical trials; in the renal setting, therapeutic interventions targeting this pathway by decreasing ligand availability with disintegrin and metalloproteinase inhibitors or with ligand-neutralizing antibodies, or by inhibiting receptor activation with tyrosine kinase inhibitors or monoclonal antibodies are only just starting to be explored in animal models of chronic kidney disease and in patients with autosomal dominant polycystic kidney disease. In this Review we focus on the role of the EGFR signalling pathway in the kidney under physiological conditions and during the pathophysiology of chronic kidney diseases and explore the clinical potential of interventions in this pathway to treat chronic renal diseases. PMID:27374915

  1. Langerhans Cells Facilitate UVB-induced Epidermal Carcinogenesis

    PubMed Central

    Lewis, Julia M.; Bürgler, Christina D.; Freudzon, Marianna; Golubets, Kseniya; Gibson, Juliet F.; Filler, Renata B.; Girardi, Michael

    2015-01-01

    Ultraviolet B (UVB) light is considered the major environmental inducer of human keratinocyte DNA mutations, including within the tumor-suppressor gene p53, and chronic exposure is associated with cutaneous squamous cell carcinoma (SCC) formation. Langerhans cells (LC) comprise a dendritic network within the suprabasilar epidermis, yet the role of LC in UVB-induced carcinogenesis is largely unknown. Herein, we show that LC-intact epidermis develops UVB-induced tumors more readily than LC-deficient epidermis. While levels of epidermal cyclopyrimidine dimers (CPD) following acute UVB exposure are equivalent in the presence or absence of LC, chronic UVB-induced p53 mutant clonal islands expand more readily in association with LC which remain largely intact and are preferentially found in proximity to the expanding mutant keratinocyte populations. The observed LC facilitation of mutant p53 clonal expansion is completely αβ and γδ T-cell independent, and is associated with increased intraepidermal expression of interleukin (IL)-22 and the presence of group 3 innate lymphoid cells (ILC3). These data demonstrate that LC play a key role in UVB-induced cutaneous carcinogenesis, and suggest that LC locally stimulate keratinocyte proliferation and innate immune cells that provoke tumor outgrowth. PMID:26053049

  2. Epidermal Growth Factor Receptor in Prostate Cancer Derived Exosomes

    PubMed Central

    Kharmate, Geetanjali; Hosseini-Beheshti, Elham; Caradec, Josselin; Chin, Mei Yieng; Tomlinson Guns, Emma S.

    2016-01-01

    Exosomes proteins and microRNAs have gained much attention as diagnostic tools and biomarker potential in various malignancies including prostate cancer (PCa). However, the role of exosomes and membrane-associated receptors, particularly epidermal growth factor receptor (EGFR) as mediators of cell proliferation and invasion in PCa progression remains unexplored. EGFR is frequently overexpressed and has been associated with aggressive forms of PCa. While PCa cells and tissues express EGFR, it is unknown whether exosomes derived from PCa cells or PCa patient serum contains EGFR. The aim of this study was to detect and characterize EGFR in exosomes derived from PCa cells, LNCaP xenograft and PCa patient serum. Exosomes were isolated from conditioned media of different PCa cell lines; LNCaP xenograft serum as well as patient plasma/serum by differential centrifugation and ultracentrifugation on a sucrose density gradient. Exosomes were confirmed by electron microscopy, expression of exosomal markers and NanoSight™ analysis. EGFR expression was determined by western blot analysis and ELISA. This study demonstrates that exosomes may easily be derived from PCa cell lines, serum obtained from PCa xenograft bearing mice and clinical samples derived from PCa patients. Presence of exosomal EGFR in PCa patient exosomes may present a novel approach for measuring of the disease state. Our work will allow to build on this finding for future understanding of PCa exosomes and their potential role in PCa progression and as minimal invasive biomarkers for PCa. PMID:27152724

  3. Detergent-induced epidermal barrier dysfunction and its prevention.

    PubMed

    Okuda, Minehiro; Yoshiike, Takashi; Ogawa, Hideoki

    2002-12-01

    Various detergents are used as skin cleansing products. In some cases, skin cleanser removes not only dirt but also valuable skin lipids. Therefore, detergents may disrupt epidermal barrier function despite that using of detergents are required for good skin hygiene. Lipid supplements can reverse detergent-induced dysfunction of the skin barrier. Elevated transepidermal water loss (TEWL) and riboflavin penetration in 5% SLS-treated rat and human skin were reversed by supplementation of monoglyceride (MG), squalene (SQ), cholesterol ester (CE) and pseudo-ceramide (Cer2). MG and Cer2 achieved the best results. MG appears to inhibit elution of intercellular ceramides, since more ceramides remained when the detergent was supplemented with MG. Topical application of Cer2 is not effective for recovery from artificially induced barrier disruption, but supplemented Cer2 into skin cleanser has a beneficial effect for prevention of detergent-induced barrier disruption. In conclusion, the prevention of barrier disruption is most important matter for maintaining skin health and barrier function. Therefore, we think that Cer2-supplemented skin cleanser is useful for conservation of skin barrier function. PMID:12443839

  4. Kinetics of growth and differentiation of cultured human epidermal keratinocytes

    SciTech Connect

    Albers, K.M.

    1985-01-01

    A study was made of the interrelationship between replication and differentiation in cultures of human epidermal keratinocytes. Measures of both parameters were made using newly developed methods to quantify the rate at which keratinocytes replicate and the rate at which they withdraw from the cell cycle. Keratinocyte replication was measured by determining the cell doubling time, labeling index, and cell cycle duration. Cell cycle length was measured using a double label assay that determines the length of time between two successive phases of DNA synthesis. The first DNA synthesis phase was marked by labeling keratinocytes with /sup 14/C-thymidine. At the next round of DNA synthesis, cells were labeled with bromodeoxyuridine, a heavy analog of thymidine. The cell cycle length is given by the time required for the /sup 14/C-labeled DNA to become double labeled. To measure keratinocyte differentiation, the rate at which cells withdraw from the cell cycle was determined. To measure withdrawal, the percentage of cells labeled by a pulse of /sup 14/C-thymidine that failed to undergo a second cycle of DNA synthesis, as measured by bromodeoxyuridine incorporation, was determined. Cells which failed to undergo a second cycle of synthesis were considered to have differentiated and withdrawn from the cell cycle.

  5. Epidermal growth factor receptor inhibition in lung cancer: status 2012.

    PubMed

    Hirsch, Fred R; Jänne, Pasi A; Eberhardt, Wilfried E; Cappuzzo, Federico; Thatcher, Nick; Pirker, Robert; Choy, Hak; Kim, Edward S; Paz-Ares, Luis; Gandara, David R; Wu, Yi-Long; Ahn, Myung-Ju; Mitsudomi, Tetsuya; Shepherd, Frances A; Mok, Tony S

    2013-03-01

    Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing. PMID:23370315

  6. Toxic Epidermal Necrolysis in Polymedicated Patient Treated With Radiotherapy

    PubMed Central

    Pérez-Calderón, Remedios; Corrales-Vargas, Silvia; Jiménez-Ferrera, Gloria; Rodríguez-Nevado, Isabel; Díaz-Delgado, Mario

    2015-01-01

    Temozolomide is an oral alkylating agent indicated for the treatment of patients with glioblastoma multiforme concomitantly with radiotherapy and subsequently as monotherapy treatment. We report the case of a patient who developed toxic epidermal necrolysis (TEN) while she was being treated with chemoradiotherapy and several drugs. Cutaneous tests were performed with the drugs involved with negative result. Although the occurrence of TEN contraindicates suspected drug readministration, we based the decision to perform the controlled administration of temozolomide on the following reasons: (1) the poor prognosis of the underlying disease, (2) the lack of therapeutic alternatives, (3) the suspicion that other drugs taken by the patient simultaneously may be responsible (as anticonvulsants and trimethoprim sulfamethoxazole [TMP-SMX]), and (4) temozolomide was the first choice for treating the patient's disease. The administration of a cumulative dose of 60 mg of temozolomide caused a slight skin reaction. Given this result, we conducted controlled administration of other drugs involved. Dexamethasone, codeine, omeprazole and levetiracetam were well tolerated. However, TMP-SMX produced a similar reaction to that caused by temozolomide. In conclusion, we present the first case of TEN induced by temozolomide and TMP-SMX associated with cranial radiotherapy confirmed by controlled administration. Radiotherapy in combination with these drugs could have favored TEN, as some authors have postulated, but we cannot prove this. PMID:25729629

  7. Saccharin and Cyclamate Inhibit Binding of Epidermal Growth Factor

    NASA Astrophysics Data System (ADS)

    Lee, L. S.

    1981-02-01

    The binding of 125I-labeled mouse epidermal growth factor (EGF) to 18 cell lines, including HeLa (human carcinoma), MDCK (dog kidney cells), HTC (rat hepatoma), K22 (rat liver), HF (human foreskin), GM17 (human skin fibroblasts), XP (human xeroderma pigmentosum fibroblasts), and 3T3-L1 (mouse fibroblasts), was inhibited by saccharin and cyclamate. The human cells were more sensitive to inhibition by these sweeteners than mouse or rat cells. EGF at doses far above the physiological levels reversed the inhibition in rodent cells but not in HeLa cells. In HeLa cells, the doses of saccharin and cyclamate needed for 50% inhibition were 3.5 and 9.3 mg/ml, respectively. Glucose, 2-deoxyglucose, sucrose, and xylitol did not inhibit EGF binding. Previous studies have shown that phorbol esters, strongly potent tumor promoters, also inhibit EGF binding to tissue culture cells. To explain the EGF binding inhibition by such greatly dissimilar molecules as phorbol esters, saccharin, and cyclamate, it is suggested that they operate through the activation of a hormone response control unit.

  8. Epidermal NLRP10 contributes to contact hypersensitivity responses in mice.

    PubMed

    Damm, Anna; Giebeler, Nives; Zamek, Jan; Zigrino, Paola; Kufer, Thomas A

    2016-08-01

    The nucleotide binding and oligomerization domain-like receptor (NLR) protein NLRP10 is highly expressed in the epidermis and contributes to cell-autonomous responses against invasive bacteria. To investigate the role of NLRP10 in inflammatory responses of the skin we analyzed the effect of full-body and keratinocyte-specific depletion of NLRP10 in croton oil-induced irritant contact dermatitis (ICD) and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced contact hypersensitivity (CHS) in mice. Nlrp10(-/-) mice were phenotypically normal and skin repair after wounding was not affected by lack of NLRP10. Similarly, we did not detect a contribution of NLRP10 to the ICD response induced by croton oil. In contrast, Nlrp10(-/-) mice showed significantly reduced inflammation in the DNFB-induced CHS response as compared to control animals. Microscopic analysis revealed significantly reduced numbers of CD4(+) and CD8(+) T cells in the infiltrates of animals lacking NLRP10 expression after CHS challenge. Epidermis-specific deletion of Nlrp10 by keratin-14 promotor driven Cre-recombinase was sufficient to account for this phenotype, although lymphocyte recruitment seemed to be unaltered in animals lacking NLRP10 expression in keratinocytes. Taken together, we provide evidence that NLRP10 contributes to T-cell-mediated inflammatory responses in the skin and highlight a physiological role of NLRP10 in epidermal keratinocytes. PMID:27221772

  9. Genome-wide transcriptome analysis of human epidermal melanocytes

    PubMed Central

    Haltaufderhyde, Kirk D.; Oancea, Elena

    2015-01-01

    Because human epidermal melanocytes (HEMs) provide critical protection against skin cancer, sunburn, and photoaging, a genome-wide perspective of gene expression in these cells is vital to understanding human skin physiology. In this study we performed high throughput sequencing of HEMs to obtain a complete data set of transcript sizes, abundances, and splicing. As expected, we found that melanocyte specific genes that function in pigmentation were among the highest expressed genes. We analyzed receptor, ion channel and transcription factor gene families to get a better understanding of the cell signalling pathways used by melanocytes. We also performed a comparative transcriptomic analysis of lightly versus darkly pigmented HEMs and found 16 genes differentially expressed in the two pigmentation phenotypes; of those, only one putative melanosomal transporter (SLC45A2) has known function in pigmentation. In addition, we found 166 genes with splice isoforms expressed exclusively in one pigmentation phenotype, 17 of which are genes involved in signal transduction. Our melanocyte transcriptome study provides a comprehensive view and may help identify novel pigmentation genes and potential pharmacological targets. PMID:25451175

  10. Micro-fractional Epidermal Powder Delivery for Skin Vaccination.

    PubMed

    Jia, Feng; Liu, Shengwu; Wu, Mei X; Chen, Xinyuan

    2016-01-01

    Skin is a highly immunogenic site for vaccine delivery due to its richness of antigen-presenting cells. Several vaccines have been approved for skin delivery and in particular intradermal delivery in the last two decades. Yet intradermal delivery often causes frequent and severe local reactions, preventing the incorporation of adjuvants to further boost skin vaccination. Here we describe a novel skin delivery technology, called micro-fractional epidermal powder delivery or EPD, with minimized local reactions for improved skin vaccination. EPD is based on laser or microneedle treatment to generate microchannel arrays in the epidermis followed by topical application of powder vaccine-coated array patches to deliver vaccines into the skin via microchannels. Due to the fractional delivery, EPD significantly reduces vaccine/adjuvant-induced local reactions without compromising vaccine immunogenicity and adjuvant potency. EPD also eliminates needle injection-associated pain and is promising to improve vaccine stability due to the direct powder delivery. This chapter describes detailed methods for the advantageous EPD in preclinical animal models. PMID:27076332

  11. Designing a scrubber for maintenance

    SciTech Connect

    Mahlmeister, M.E.; Baron, E.S.; Watts, J.

    1996-12-01

    Under Round 4 of the U.S. Department of Energy`s (DOE) Clean Coal Technology program, New York State Electric & Gas Corporation (NYSEG), in partnership with Saarberg-Holter-Umwelttechnik (SHU), Consolidation Coal Company and Stebbins Engineering and Manufacturing Company, has retrofitted a formic acid enhanced forced oxidation wet limestone scrubber on Units I and 2 at the Milliken Steam Electric Station. Units I and 2 are 1950s vintage Combustion Engineering tangentially fired pulverized coal units, which are rated at nominal 150 MW each and operate in balanced draft mode. The Flue Gas Desulfurization (FGD) system for Unit 2 was placed into operation in January 1995 and the Unit I system in June 1995. The project incorporates several unique aspects: low pH operation; a ceramic tile-lined cocurrent/countercurrent, split module absorber; a wet stack supported on the roof of the FGD building; and closed loop, zero liquid discharge operation that produces commercial grade gypsum and calcium chloride brine. The project objectives include 98% SO{sub 2} removal efficiency while burning high sulfur coal, the production of marketable byproducts to minimize solid waste disposal, zero wastewater discharge, space-saving design, and minimization of maintenance requirements of a wet scrubber. The paper provides a brief overview of the project scrubber design relating to maintenance considerations. A discussion of the early results of the maintenance history is also provided. Repair techniques that have been developed and tested for ceramic tile lined modules are included. 1 fig.

  12. Demonstration of reliability centered maintenance

    SciTech Connect

    Schwan, C.A.; Morgan, T.A. )

    1991-04-01

    Reliability centered maintenance (RCM) is an approach to preventive maintenance planning and evaluation that has been used successfully by other industries, most notably the airlines and military. Now EPRI is demonstrating RCM in the commercial nuclear power industry. Just completed are large-scale, two-year demonstrations at Rochester Gas Electric (Ginna Nuclear Power Station) and Southern California Edison (San Onofre Nuclear Generating Station). Both demonstrations were begun in the spring of 1988. At each plant, RCM was performed on 12 to 21 major systems. Both demonstrations determined that RCM is an appropriate means to optimize a PM program and improve nuclear plant preventive maintenance on a large scale. Such favorable results had been suggested by three earlier EPRI pilot studies at Florida Power Light, Duke Power, and Southern California Edison. EPRI selected the Ginna and San Onofre sites because, together, they represent a broad range of utility and plant size, plant organization, plant age, and histories of availability and reliability. Significant steps in each demonstration included: selecting and prioritizing plant systems for RCM evaluation; performing the RCM evaluation steps on selected systems; evaluating the RCM recommendations by a multi-disciplinary task force; implementing the RCM recommendations; establishing a system to track and verify the RCM benefits; and establishing procedures to update the RCM bases and recommendations with time (a living program). 7 refs., 1 tab.

  13. Epidermal growth factor receptor tyrosine kinase inhibitors with conventional chemotherapy for the treatment of non-small cell lung cancer

    PubMed Central

    Gao, Yuan; Song, PingPing; Li, Hui; Guo, HongBo; Jia, Hui; Zhang, BaiJiang

    2016-01-01

    We report a Chinese male patient with advanced stage lung squamous cell carcinoma who developed brain metastases after responding to treatment comprising six cycles of conventional chemotherapy with docetaxel and cisplatin. The patient was then treated with oral erlotinib (150 mg/day) and whole-brain radiation therapy followed by four cycles of docetaxel and carboplatin chemotherapy. The patient then received gefitinib (250 mg/day) as a maintenance therapy until the end of the follow-up period. In this patient, progression-free survival, defined as the interval from the initiation of first-line chemotherapy to the cessation of erlotinib due to progressive disease or death from any cause, was 3 months. Overall survival, defined as the interval from the initiation of first-line chemotherapy to death from any cause, was 75 months. Erlotinib was well tolerated in combination with whole-brain radiation therapy and a favorable objective response rate was observed. Furthermore, targeted drug treatment warrants consideration in patients with a negative epidermal growth factor receptor mutation status and male patients with a history of smoking. PMID:26719713

  14. Icotinib combined whole brain radiotherapy for patients with brain metastasis from lung adenocarcinoma harboring epidermal growth factor receptor mutation

    PubMed Central

    Li, Jin-Rui; Zhang, Ye

    2016-01-01

    Background The brain is a metastatic organ that is most prone to lung adenocarcinoma (LAC). However, the prognosis of patients with brain metastasis remains very poor. In this study, we evaluated the efficacy of icotinib plus whole brain radiation therapy (WBRT) for treating patients with brain metastasis from epidermal growth factor receptor (EGFR)-mutated LAC. Methods All patients received standard WBRT administered to the whole brain in 30 Gy in 10 daily fractions. Each patient was also instructed to take 125 mg icotinib thrice per day beginning from the first day of the WBRT. After completing the WBRT, maintenance icotinib was administered until the disease progressed or intolerable adverse effects were observed. Cranial progression-free survival (CPFS) and overall survival (OS) times were the primary endpoints. Results A total of 43 patients were enrolled in this study. Two patients (4.7%) presented a complete response (CR), whereas 20 patients (46.5%) presented a partial response (PR). The median CPFS and OS times were 11.0 and 15.0 months, respectively. The one-year CPFS rate was 40.0% for the patients harboring EGFR exon 19 deletion and 16.7% for the patients with EGFR exon 21 L858R (P=0.027). Conclusions The concurrent administration of icotinib and WBRT exhibited favorable effects on the patients with brain metastasis. EGFR exon 19 deletion was predictive of a long CPFS following icotinib plus WBRT. PMID:27499937

  15. A returned traveller with persistent fever due to murine typhus.

    PubMed

    Ng, C P; Lo, C B; Wong, K K; Chung, C H

    2002-12-01

    Murine (endemic) typhus is a notifiable disease in Hong Kong, but its diagnosis can be difficult. We report a case of murine typhus in a middle-aged man who presented with persistent fever, headache, and skin rash 2 weeks after returning from a visit to China. The diagnosis of murine typhus requires a high index of suspicion for a febrile patient with a history of potential exposure to the disease vector (rat flea) in an endemic area. The importance of early recognition lies in the potential for early therapeutic intervention, leading to decreases in morbidity and duration of stay in hospital. PMID:12459604

  16. Effects of Nitrogen on Mesophyll Cell Division and Epidermal Cell Elongation in Tall Fescue Leaf Blades 1

    PubMed Central

    MacAdam, Jennifer W.; Volenec, Jeffrey J.; Nelson, Curtis J.

    1989-01-01

    Leaf elongation rate (LER) in grasses is dependent on epidermal cell supply (number) and on rate and duration of epidermal cell elongation. Nitrogen (N) fertilization increases LER. Longitudinal sections from two genotypes of tall fescue (Festuca arundinacea Schreb.), which differ by 50% in LER, were used to quantify the effects of N on the components of epidermal cell elongation and on mesophyll cell division. Rate and duration of epidermal cell elongation were determined by using a relationship between cell length and displacement velocity derived from the continuity equation. Rate of epidermal cell elongation was exponential. Relative rates of epidermal cell elongation increased by 9% with high N, even though high N increased LER by 89%. Duration of cell elongation was approximately 20 h longer in the high- than in the low-LER genotype regardless of N treatment. The percentage of mesophyll cells in division was greater in the high- than in the low-LER genotype. This increased with high N in both genotypes, indicating that LER increased with cell supply. Division of mesophyll cells adjacent to abaxial epidermal cells continued after epidermal cell division stopped, until epidermal cells had elongated to a mean length of 40 micrometers in the high-LER and a mean length of 50 micrometers in the low-LER genotype. The cell cycle length for mesophyll cells was calculated to be 12 to 13 hours. Nitrogen increased mesophyll cell number more than epidermal cell number: in both genotypes, the final number of mesophyll cells adjacent to each abaxial epidermal cell was 10 with low N and 14 with high N. A spatial model is used to describe three cell development processes relevant to leaf growth. It illustrates the overlap of mesophyll cell division and epidermal cell elongation, and the transition from epidermal cell elongation to secondary cell wall deposition. PMID:16666581

  17. Glucocorticoid receptors in murine erythroleukaemic cells

    SciTech Connect

    Hammond, K.D.; Torrance, J.M.; DiDomenico, M.

    1987-01-01

    Glucocorticoid receptors in murine erythroleukaemic cells were studied in relation to hexamethylene bisacetamide (HMBA) induced differentiation. Specific binding of dexamethasone was measured. A single class of saturable, high affinity binding sites was demonstrated in intact cells; with cell homogenates or fractions binding was low and could not be reliably quantified. Receptor binding in whole cell suspensions was lower in cells which had been treated with HMBA (36.5 +/- 8.2 pmol/g protein) than in untreated controls (87.9 +/- 23.6 pmol/g protein); dissociation constants were similar in treated (2.7 nM) and untreated cells (2.5 nM). Dexamethasone, hydrocortisone, corticosterone and progesterone competed with tritium-labelled dexamethasone for receptor binding sites; cortisone, deoxycorticosterone and oestradiol had little effect.

  18. 14 CFR 145.217 - Contract maintenance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Contract maintenance. 145.217 Section 145...) SCHOOLS AND OTHER CERTIFICATED AGENCIES REPAIR STATIONS Operating Rules § 145.217 Contract maintenance. (a) A certificated repair station may contract a maintenance function pertaining to an article to...

  19. 40 CFR 610.52 - Maintenance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Maintenance. 610.52 Section 610.52 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY RETROFIT DEVICES Test Procedures and Evaluation Criteria Durability Test Procedures § 610.52 Maintenance. (a) Maintenance during the durability...

  20. 49 CFR 260.39 - Maintenance standards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Maintenance standards. 260.39 Section 260.39... REHABILITATION AND IMPROVEMENT FINANCING PROGRAM Standards for Maintenance of Facilities Involved in the Project § 260.39 Maintenance standards. (a) When the proceeds of a direct loan or an obligation guaranteed...

  1. 49 CFR 260.39 - Maintenance standards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Maintenance standards. 260.39 Section 260.39... REHABILITATION AND IMPROVEMENT FINANCING PROGRAM Standards for Maintenance of Facilities Involved in the Project § 260.39 Maintenance standards. (a) When the proceeds of a direct loan or an obligation guaranteed...

  2. 14 CFR 145.217 - Contract maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Contract maintenance. 145.217 Section 145...) SCHOOLS AND OTHER CERTIFICATED AGENCIES REPAIR STATIONS Operating Rules § 145.217 Contract maintenance. (a) A certificated repair station may contract a maintenance function pertaining to an article to...

  3. 33 CFR 127.401 - Maintenance: General.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Maintenance: General. 127.401 Section 127.401 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... Waterfront Facilities Handling Liquefied Natural Gas Maintenance § 127.401 Maintenance: General. The...

  4. 49 CFR 192.749 - Vault maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Vault maintenance. 192.749 Section 192.749 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Maintenance § 192.749 Vault maintenance. (a) Each...

  5. 49 CFR 195.420 - Valve maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Valve maintenance. 195.420 Section 195.420 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... PIPELINE Operation and Maintenance § 195.420 Valve maintenance. (a) Each operator shall maintain each...

  6. 30 CFR 57.5066 - Maintenance standards.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Maintenance standards. 57.5066 Section 57.5066... Maintenance standards. (a) Any diesel powered equipment operated at any time in underground areas must meet the following maintenance standards: (1) The operator must maintain any approved engine in...

  7. 23 CFR 1.27 - Maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Maintenance. 1.27 Section 1.27 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GENERAL MANAGEMENT AND ADMINISTRATION GENERAL § 1.27 Maintenance... maintenance of projects shall be carried out in accordance with policies and procedures issued by...

  8. 49 CFR 37.203 - Lift maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Lift maintenance. 37.203 Section 37.203... DISABILITIES (ADA) Over-the-Road Buses (OTRBs) § 37.203 Lift maintenance. (a) The entity shall establish a system of regular and frequent maintenance checks of lifts sufficient to determine if they are...

  9. 47 CFR 87.69 - Maintenance tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Maintenance tests. 87.69 Section 87.69... Operating Requirements and Procedures Operating Requirements § 87.69 Maintenance tests. The licensee may make routine maintenance tests on equipment other than emergency locator transmitters if there is...

  10. 47 CFR 80.96 - Maintenance tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Maintenance tests. 80.96 Section 80.96... MARITIME SERVICES Operating Requirements and Procedures Operating Procedures-General § 80.96 Maintenance tests. Stations are authorized to engage in test transmissions necessary for maintenance of the...

  11. 49 CFR 260.39 - Maintenance standards.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Maintenance standards. 260.39 Section 260.39... REHABILITATION AND IMPROVEMENT FINANCING PROGRAM Standards for Maintenance of Facilities Involved in the Project § 260.39 Maintenance standards. (a) When the proceeds of a direct loan or an obligation guaranteed...

  12. 40 CFR 86.001-25 - Maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Maintenance. 86.001-25 Section 86.001...-Fueled and Methanol-Fueled Heavy-Duty Vehicles § 86.001-25 Maintenance. Section 86.001-25 includes text... engines. (2) Maintenance performed on vehicles, engines, subsystems, or components used to...

  13. 41 CFR 101-39.303 - Maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Maintenance. 101-39.303... Maintenance. In order to ensure uninterrupted operation of GSA Interagency Fleet Management System (IFMS) vehicles, safety and preventive maintenance inspections will be performed at regularly scheduled...

  14. 5 CFR 850.302 - Record maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Record maintenance. 850.302 Section 850... (CONTINUED) RETIREMENT SYSTEMS MODERNIZATION Records § 850.302 Record maintenance. (a) The retirement and..., for the initiation and maintenance of records, evidence, or other information described in this...

  15. 40 CFR 63.1655 - Maintenance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Maintenance requirements. 63.1655....1655 Maintenance requirements. (a) The owner or operator of an affected source must comply with the... maintenance plan for each air pollution control device associated with submerged arc furnaces, metal...

  16. Maintenance Staffing Guidelines For Educational Facilities.

    ERIC Educational Resources Information Center

    APPA: Association of Higher Education Facilities Officers, Alexandria, VA.

    The purpose of this publication is to provide a resource or guide for educational facilities in establishing or developing a maintenance trades organization that is sufficient to accomplish basic facilities maintenance functions. The guidelines are intended to suggest staffing levels for those routine facilities maintenance activities that are…

  17. 49 CFR 195.420 - Valve maintenance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Valve maintenance. 195.420 Section 195.420... PIPELINE Operation and Maintenance § 195.420 Valve maintenance. (a) Each operator shall maintain each valve..., inspect each mainline valve to determine that it is functioning properly. (c) Each operator shall...

  18. 49 CFR 195.420 - Valve maintenance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Valve maintenance. 195.420 Section 195.420... PIPELINE Operation and Maintenance § 195.420 Valve maintenance. (a) Each operator shall maintain each valve..., inspect each mainline valve to determine that it is functioning properly. (c) Each operator shall...

  19. 49 CFR 195.420 - Valve maintenance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Valve maintenance. 195.420 Section 195.420... PIPELINE Operation and Maintenance § 195.420 Valve maintenance. (a) Each operator shall maintain each valve..., inspect each mainline valve to determine that it is functioning properly. (c) Each operator shall...

  20. 49 CFR 195.420 - Valve maintenance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Valve maintenance. 195.420 Section 195.420... PIPELINE Operation and Maintenance § 195.420 Valve maintenance. (a) Each operator shall maintain each valve..., inspect each mainline valve to determine that it is functioning properly. (c) Each operator shall...